Rook's Textbook of Dermatology, 9th edn. Christopher Griffiths, Jonathan Barker, Tanya Bleiker, Robert Chalmers, Daniel Creamer, eds. Publisher: Wiley-Blackwell, 2016; 4696 pp. ISBN: 978-1118441190. Price £522.50.

http://ift.tt/2rgzDYG

Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and Spine Density in the Adult Mouse Motor Cortex

Abstract

Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic branching and spine densities in layer 2/3 cortical pyramidal neurons. These effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser scanning microscopy to measure the spine turnover rate of adult mouse motor cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine remodeling after 4 days. Our results suggest relevant control functions of glial as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for more selective and targeted plasticity enhancing strategies.

http://ift.tt/2qizhmS

Localization and distribution of gonadal proteins in the oviparous lizard Sceloporus aeneus (Squamata: Phrynosomatidae)

Publication date: Available online 14 May 2017
Source:Acta Histochemica
Author(s): Antonio-Rubio Nivia Rocio, Villagrán-SantaCruz Maricela, Moreno-Mendoza Norma
Among vertebrates, several specific proteins are involved in the function and development of gonads. Several genes such as SOX9, FOXL2, DDX4, IFITM3, and DPPA3, are active during embryonic differentiation and maintain their expression in adult tissues, playing important roles in the function and development of the line cell, where these are produced. Among reptiles, molecular mechanisms for sex differentiation have been analyzed in turtles, crocodiles, and some lizards, while in adult stages such studies are scarce. The aim of this study was to locate and analyze the distribution of important gonadal proteins in adult and embryonic ovaries and testes of the oviparous lizard Sceloporus aeneus (Squamata: Phrynosomatidae). Adult specimens and embryos of the lizard S. aeneus were collected in Milpa Alta, a suburb located Southwest of Mexico City. Expression of gonadal proteins was analyzed using immunofluorescent staining and confocal microscopy. Our results showed that SOX9 is located in Sertoli cells of embryonic and adult testes. FOXL2 is expressed in follicular cells of adult ovaries. DDX4 and IFITM3 are located in germ line cells as well as in follicular cells of adult ovaries. DPPA3 was observed in somatic and germ line cells of adult and embryonic gonads. Our observations show that important molecules of vertebrate ovaries and testes are conserved in S. aeneus and it is suggested that these may have a similar role during gonadal development and function.



http://ift.tt/2pASGjY

Editorial Board ((ofc))

Publication date: May 2017
Source:Acta Histochemica, Volume 119, Issue 4





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What We Know About Stage II and III Colon Cancer: It’s Still Not Enough

Abstract

The introduction of oxaliplatin as adjuvant treatment for stage III colon cancer in 2004 has been the last practice changing progress in adjuvant treatment for patients with early colon cancer. Since then, many prognostic and predictive biomarkers have been studied, but only DNA mismatch repair status has been validated as having an important prognostic value. Accordingly, TNM and clinical-pathological patterns, such as pT4 lesions and lymph node sampling <12 nodes, are the main factors that guide physicians' choice regarding adjuvant treatment. More recently, many biomarkers showed promising results: POLE, ErbB2, CDX2, SMAD4, BRAF and KRAS. In addition to these, immune-contexture, molecular classification, and gene signatures could become new ways to better classify colon cancer patients with more discriminatory power than TNM. The aim of this review is to report the state-of-the-art of prognostic and predictive factors in the adjuvant setting and which of these could modify clinical practice and maybe replace TNM classification.

http://ift.tt/2r7MIHx

Therapeutic effect of microneedling and autologous platelet-rich plasma in the treatment of atrophic scars: A randomized study

Summary

Background

New treatments and techniques were being added over the last few years to treat atrophic scars with variable results and adverse effects.

Aim of the work

The aim of this study was to evaluate and compare the therapeutic efficacy and safety of microneedling, autologous platelet-rich plasma, and combination of both procedures in the treatment of atrophic scars.

Patients and methods

This study included 90 patients with atrophic scars and were classified randomly into three groups: I: 28 patients treated with microneedling, one session every 4 weeks; II: 34 patients treated with intradermal injection of platelet-rich plasma, one session every 2 weeks; and III: 28 patients treated with alternative sessions of each microneedling and platelet-rich plasma, 2 weeks between each session, for a maximum of six sessions.

Results

There was a statistically significant improvement in the appearance of atrophic scars, with reduction in the scores associated with the clinical evaluation scale for atrophic scarring in all groups, but the improvement was more obvious in group III.

Conclusions

Although a single treatment may give good results, combination between skin needling and platelet-rich plasma is more effective, safe with less number of sessions in all types of atrophic scars.

http://ift.tt/2rg9TeQ

The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: A randomized placebo-controlled study

Summary

Background

Hair is an essential part of a woman's appearance and attractiveness. This is reflected in the predominantly psychological morbidity that can be associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss.

Objective

To evaluate the efficacy and safety of autologous platelet-rich plasma in the treatment of female pattern hair loss.

Materials and methods

Thirty female patients with female pattern hair loss were randomly assigned to receive autologous PRP injection into a selected area, and another area was injected with normal saline as a placebo. Sessions were performed weekly for a maximum total of four sessions. Patients were followed up 6 months after the end of last session. The outcome was assessed both subjectively and objectively.

Results

There was a statistical significant difference between PRP and placebo areas (P<.005) regarding both hair density and hair thickness as measured by a folliscope. The hair pull test became negative in PRP-injected areas in 25 patients (83%) with average number of three hairs. Global pictures showed a significant improvement in hair volume and quality together with a high overall patient satisfaction in PRP-injected sites, and these results were maintained during the 6-month follow- up.

Conclusion

Platelet-rich plasma injections can be regarded as an alternative for the treatment of female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio.

http://ift.tt/2qhGp35

Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity

Summary

Objectives

To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function.

Methods

A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption.

Results

Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption).

Conclusions

Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.

http://ift.tt/2qHTlQZ

Therapeutic effect of microneedling and autologous platelet-rich plasma in the treatment of atrophic scars: A randomized study

Summary

Background

New treatments and techniques were being added over the last few years to treat atrophic scars with variable results and adverse effects.

Aim of the work

The aim of this study was to evaluate and compare the therapeutic efficacy and safety of microneedling, autologous platelet-rich plasma, and combination of both procedures in the treatment of atrophic scars.

Patients and methods

This study included 90 patients with atrophic scars and were classified randomly into three groups: I: 28 patients treated with microneedling, one session every 4 weeks; II: 34 patients treated with intradermal injection of platelet-rich plasma, one session every 2 weeks; and III: 28 patients treated with alternative sessions of each microneedling and platelet-rich plasma, 2 weeks between each session, for a maximum of six sessions.

Results

There was a statistically significant improvement in the appearance of atrophic scars, with reduction in the scores associated with the clinical evaluation scale for atrophic scarring in all groups, but the improvement was more obvious in group III.

Conclusions

Although a single treatment may give good results, combination between skin needling and platelet-rich plasma is more effective, safe with less number of sessions in all types of atrophic scars.

http://ift.tt/2rg9TeQ

The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: A randomized placebo-controlled study

Summary

Background

Hair is an essential part of a woman's appearance and attractiveness. This is reflected in the predominantly psychological morbidity that can be associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss.

Objective

To evaluate the efficacy and safety of autologous platelet-rich plasma in the treatment of female pattern hair loss.

Materials and methods

Thirty female patients with female pattern hair loss were randomly assigned to receive autologous PRP injection into a selected area, and another area was injected with normal saline as a placebo. Sessions were performed weekly for a maximum total of four sessions. Patients were followed up 6 months after the end of last session. The outcome was assessed both subjectively and objectively.

Results

There was a statistical significant difference between PRP and placebo areas (P<.005) regarding both hair density and hair thickness as measured by a folliscope. The hair pull test became negative in PRP-injected areas in 25 patients (83%) with average number of three hairs. Global pictures showed a significant improvement in hair volume and quality together with a high overall patient satisfaction in PRP-injected sites, and these results were maintained during the 6-month follow- up.

Conclusion

Platelet-rich plasma injections can be regarded as an alternative for the treatment of female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio.

http://ift.tt/2qhGp35

Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity

Summary

Objectives

To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function.

Methods

A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption.

Results

Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption).

Conclusions

Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.

http://ift.tt/2qHTlQZ

Management of Massive Hemoptysis with Oren Friedman

http://sfaki.blogspot.com/2017/05/management-of-massive-hemoptysis-with.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Mismatch repair cancer syndrome (MMRCS) : Multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity.

http://sfaki.blogspot.com/2017/05/mismatch-repair-cancer-syndrome-mmrcs.html

Haematologica. 2010 May; 95(5): 699–701.

doi:  10.3324/haematol.2009.021626

PMCID: PMC2864372

Constitutional mismatch repair-deficiency syndrome

Katharina Wimmer1 and Christian P. Kratz2

1 Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

2 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. E-mail: ta.ca.dem-i@remmiw.anirahtak

Katharina Wimmer, PhD, is Associate Professor at the Department for Medical Genetics, Molecular and Clinical Pharmacology, Medical University Innsbruck. She is supervising the onco-genetic laboratory for the diagnostics of cancer predisposition syndromes which are also her main research interest. Christian P. Kratz, M.D. is an investigator in the Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics at the National Cancer Institute, National Institutes of Health. His research focuses on individuals with inherited cancer predispositions.

Author information ▼ Copyright and License information ►

See "Constitutional mismatch repair deficiency and childhood leukemia/lymphoma – report on a novel biallelic MSH6 mutation" on page 841.

This article has been cited by other articles in PMC.

The mismatch repair (MMR) machinery contributes to genome integrity and the MLH1, MSH2, MSH6 and PMS2 genes play a crucial role in this process. MMR corrects single base-pair mismatches and small insertion-deletion loops that arise during replication. Moreover, the MMR system is involved in the cellular response to a variety of agents that damage DNA1 and in immunoglobulin class switch recombination.2 Heterozygous germline mutations in MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome (LS), an autosomal dominant cancer syndrome associated with hereditary non-polyposis colorectal cancer (HNPCC), endometrium carcinoma and other malignancies, occurring on average in the fourth and fifth decade of life. Notably, LS associated tumors display somatic loss of the remaining wild type MLH1, MSH2, MSH6 or PMS2 allele and evidence of microsatellite instability (for review see 3).

In contrast to individuals with LS who harbor a heterozygous mutant MMR gene allele, rare cases with biallelic deleterious germline mutations in MMR genes leading to constitutional mismatch repair-deficiency (CMMR-D) have been recognized since 1999.4,5 This cancer syndrome is characterized by a broad spectrum of early-onset malignancies and a phenotype that resembles neurofibromatosis type 1. In this issue of Haematologica, Ripperger and colleagues report on a patient with CMMR-D caused by a novel MSH6 mutation leading to a T-cell lymphoma and colonic adenocarcinoma at six and 13 years of age, respectively. In addition, they review 26 leukemia and/or lymphoma cases reported previously.6

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The clinical presentation and tumor spectrum of CMMR-D

Our knowledge of the CMMR-D syndrome originates primarily from the medical literature; consequently, potential publication bias must be kept in mind as we interpret these reports. Table 1 summarizes the malignancies observed in 89 reported6–11 and 3 unreported cases of CMMR-D. Neoplasms can be divided into four groups: (1) hematologic malignancies (reviewed in 6); (2) brain tumors; (3) LS-associated tumors; and (4) other malignancies. Notably, 31 out of the known 92 CMMR-D patients developed more than one malignancy, and in 19 cases the second or third neoplasm was an LS-associated tumor.

Table 1.

List of malignancies in 92 CMMR-D patients.

In some cases of CMMR-D, areas of skin hypo-pigmentation have been reported.12–15 However, signs reminiscent of neurofibromatosis type 1 (NF1), in particular café-aulait macules (CALMs), are much more common and were observed in the majority of the reported cases (63/92). There are only 2 patients explicitly reported to lack CALMs or other signs of NF1.9,13 Interestingly, several reports stress that CALMs in patients with CMMR-D differ from typical NF1-associated CALMs in that they vary in their degree of pigmentation, have irregular borders, and may display a segmental distribution. Other features of NF1 found in CMMR-D patients include skinfold freckling, Lisch nodules, neurofibromas and tibial pseudarthrosis. Hence, it is not surprising that a number of CMMR-D cases were initially diagnosed as having NF1. It has been speculated that the NF1-like clinical features in CMMR-D result from germline mosaicism arising early during embryonic development. The identification of a truncating NF1 mutation in the blood of one patient16 and data supporting the notion that the NF1 gene is a mutational target of MMR deficiency17 are in line with this assumption. However, extensive mutation analysis in other CMMR-D patients has not confirmed this theory (see 8,12,18 and papers cited therein).

Péron et al.2 have shown in 3 CMMR-D patients that constitutional PMS2 deficiency leads to impaired immunoglobulin class switch recombination characterized by increased serum IgM concomitant with decrease or absence of IgG2, IgG4, and IgA. Of note, one CMMR-D patient initially presented with a primary immunodeficiency,2 and patients with biallelic MSH2 and MSH6 mutations also show IgG2 and/or IgA deficiency 15,19,20. It remains to be seen whether defective IgA and IgG production is a common feature of CMMR-D. Fortunately, severe bacterial infections have not been reported to occur at high frequencies in persons with CMMR-D.

Go to:

Genotype-phenotype correlation of CMMR-D

A review of the literature suggests that the clinical features in patients with biallelic germline mutations of MLH1 or MSH2 differ from those with biallelic germline mutations of MSH6 or PMS2 (Table 2). Hematologic malignancies appear to occur more frequently in patients with MLH1 or MSH2 mutations than in patients with mutations of MSH6 or PMS2. In contrast, the latter group appears to have a higher prevalence of brain tumors. Furthermore, tumors tend to develop earlier in MLH1 or MSH2 mutation carriers than in patients with a mutation of MSH6 or PMS2. Patients with biallelic mutations in MSH6 or PMS2 are more likely to survive their first tumors and develop a second malignancy. Overall, the prevalence of LS-associated tumors is higher in patients with biallelic MSH6 or PMS2 mutations than in biallelic MLH1 or MSH2 mutation-positive individuals (Table 2). These factors facilitate the clinical diagnosis of CMMR-D in patients with mutations of MSH6 or PMS2 and may at least partly explain the preponderance of PMS2 mutations in published cases.

Table 2.

Differences in the overall tumor spectrum and age of malignancy onset between carriers of biallelic MLH1/MSH2 and MSH6/PMS2 mutations, respectively.

Go to:

Strategies for clinical and subsequent molecular diagnosis of CMMR-D

In view of the wide tumor spectrum that overlaps with Lynch and Turcot syndrome but also includes hematologic malignancies and embryonic tumors such as neuroblastoma, Wilms tumor and rhabdomyosarcoma (Table 1), CMMR-D should be considered in the differential diagnosis in all patients with malignancies (except clearly NF1-associated tumors) who show one or more of the following features: (1) CALMs and/or other signs of NF1 and/or hypo-pigmented skin lesions; (2) consanguineous parents; (3) family history of LS-associated tumors; (4) second malignancy; and (5) sibling with childhood cancer. It is important to note that especially in patients with PMS2 mutations, the family history will often not fulfill the Amsterdam or revised Bethesda criteria for LS.

Typically, confirmation of the diagnosis involves the analysis of microsatellite instability (MSI) and/or immunohistochemistry (IHC), followed by mutation analysis. MSI analysis follows current protocols used for LS-screening; however, this analysis may be unreliable in CMMR-D related brain tumors.7,11,21 IHC is a useful technique employed in patients with CMMR-D associated neoplasms including brain tumors and guides subsequent mutation analysis in the four MMR-genes. In general, a truncating mutation in PMS2 or MSH6 will result in isolated loss of these proteins, whereas a mutation in MLH1 or MSH2 will lead to concurrent loss of MLH1/PMS2 or MSH2/MSH6, respectively, since MLH1 and MSH2 are the obligatory partners in the formation of MLH1/PMS2 and MSH2/MSH6 heterodimers. Notably, in the case of an underlying missense mutation, IHC may show normal results. As CMMR-D patients constitutively lack the expression of one of the MMR genes, IHC detects loss in both neoplastic and non-neoplastic tissues. Conveniently, expression loss of one of the MMR genes can be demonstrated in blood lymphocytes (e.g. by Western blot 2). Similarly, it has been shown that MSI can be determined in normal non-neoplastic tissue of CMMR-D patients by analyzing DNA samples that are diluted to approximately 0–3 genome equivalents per PCR-reaction.22 Nonetheless, standardized procedures for the detection of MMR expression loss and MSI in non-neoplastic tissue from CMMR-D patients have not been developed to date. The diagnosis of CMMR-D should be confirmed by gene-specific mutation analysis. Reliable methods for all four MMR genes including PMS2 are now available.12 Mutation analysis will facilitate identification and surveillance of heterozygous and homozygous individuals in the wider family, and allow for informed decision-making about prenatal or pre-implantation genetic diagnosis.

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Treatment and surveillance of the patient and counseling of relatives

Genetic counseling should be offered to the parents prior to testing of the affected child, and should include information on the potential 25% recurrence risk and on the clinical consequences of a possible heterozygous mutation in both parents. Predictive testing following the established interdisciplinary counseling guidelines should be offered to all family members once a mutation has been identified. Heterozygous family members should be followed according to current LS-guidelines.23

Because of the wide spectrum of malignancies in CMMR-D patients, defining recommendations for surveillance of affected patients remains a challenge. Early diagnosis of CMMR-D and subsequent cancer screening at regular intervals may increase the likelihood of detecting associated cancers, such as colon cancer or brain tumors, at an operable stage. In theory, this screening could include regular exams such as: (1) clinical evaluation; (2) blood tests with full blood count and carcinoembryonic antigen (CEA); (3) magnetic resonance imaging of the brain; (4) endoscopic examination of the gastrointestinal tract; and (5) endometrial sampling and transvaginal ultrasound for endometrial and ovarian cancer. However, these recommendations rest only on clinical judgment and do not represent a standard of care. To date there is no available evidence to support any of these recommendations or to provide guidance on the optimal frequency of such tests. Likewise, there is currently no information available regarding the optimal treatment of CMMR-D patients. Several reports stress that careful attention should be given to the possibly increased cyto-toxicity and reduced efficacy of chemotherapeutic agents due to constitutionally impaired mutation repair, and the high risk of a second malignancy 6,8,14,15.

Reports such as the article by Ripperger and colleagues are valuable in increasing awareness and knowledge of the syndrome in the clinical community. Nevertheless, systematic studies are needed in order to better define the phenotype of MMR-D. Data related to cancer screening, treatment and outcome should be collected and evaluated systematically to provide a basis for recommendations on how to manage patients with CMMR-D.

Go to:

Footnotes

( Related Original Article on page 841)

We thank Drs. Anne Durandy and Johannes Zschocke for their helpful comments on the manuscript. Dr. Kratz's work was supported by the Intramural Research Program of the US National Cancer Institute.

No potential conflict of interest relevant to this article was reported.

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References

1. Jiricny J. The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol. 2006;7(5):335–46. [PubMed]

2. Peron S, Metin A, Gardes P, Alyanakian MA, Sheridan E, Kratz CP, et al. Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. J Exp Med. 2008;205(11):2465–72. [PMC free article] [PubMed]

3. Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003;21(6):1174–9. [PubMed]

4. Ricciardone MD, Ozcelik T, Cevher B, Ozdag H, Tuncer M, Gurgey A, et al. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Res. 1999;59(2):290–3. [PubMed]

5. Wang Q, Lasset C, Desseigne F, Frappaz D, Bergeron C, Navarro C, et al. Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Res. 1999;59(2):294–7. [PubMed]

6. Ripperger T, Beger C, Rahner N, Sykora KW, Bockmeyer CL, Lehmann U, et al. Constitutional mismatch repair deficiency and childhood leukemia/lymphoma - report on a novel biallelic MSH6 mutation. Haematologica. 2009 Dec 16; [Epub ahead of print] [PMC free article] [PubMed]

7. Giunti L, Cetica V, Ricci U, Giglio S, Sardi I, Paglierani M, et al. Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome. Eur J Hum Genet. 2009;17(7):919–27. [PMC free article] [PubMed]

8. Peters A, Born H, Ettinger R, Levonian P, Jedele KB. Compound heterozygosity for MSH6 mutations in a pediatric lymphoma patient. J Pediatr Hematol Oncol. 2009;31(2):113–5. [PubMed]

9. Sjursen W, Bjornevoll I, Engebretsen LF, Fjelland K, Halvorsen T, Myrvold HE. A homozygote splice site PMS2 mutation as cause of Turcot syndrome gives rise to two different abnormal transcripts. Fam Cancer. 2009;8(3):179–86. [PubMed]

10. Toledano H, Goldberg Y, Kedar-Barnes I, Baris H, Porat RM, Shochat C, et al. Homozygosity of MSH2 c.1906G-->C germline mutation is associated with childhood colon cancer, astrocytoma and signs of Neurofibromatosis type I. Fam Cancer. 2009;8(3):187–94. [PubMed]

11. Wimmer K, Etzler J. Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? Hum Genet. 2008;124(2):105–22. [PubMed]

12. Etzler J, Peyrl A, Zatkova A, Schildhaus HU, Ficek A, Merkelbach-Bruse S, et al. RNA-based mutation analysis identifies an unusual MSH6 splicing defect and circumvents PMS2 pseudogene interference. Human Mut. 2008;29(2):299–305. [PubMed]

13. Rahner N, Hoefler G, Hogenauer C, Lackner C, Steinke V, Sengteller M, et al. Compound heterozygosity for two MSH6 mutations in a patient with early onset colorectal cancer, vitiligo and systemic lupus erythematosus. Am J Med Genet A. 2008;146A(10):1314–9. [PubMed]

14. Scott RH, Homfray T, Huxter NL, Mitton SG, Nash R, Potter MN, et al. Familial T-cell non-Hodgkin lymphoma caused by biallelic MSH2 mutations. J Med Genet. 2007;44(7):e83. [PMC free article] [PubMed]

15. Scott RH, Mansour S, Pritchard-Jones K, Kumar D, MacSweeney F, Rahman N. Medulloblastoma, acute myelocytic leukemia and colonic carcinomas in a child with biallelic MSH6 mutations. Nat Clin Pract Oncol. 2007;4(2):130–4. [PubMed]

16. Alotaibi H, Ricciardone MD, Ozturk M. Homozygosity at variant MLH1 can lead to secondary mutation in NF1, neurofibromatosis type I and early onset leukemia. Mutat Res. 2008;637(1–2):209–14. [PubMed]

17. Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, Liskay RM, et al. Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type. Hum Genet. 2003;112(2):117–23. [PubMed]

18. Auclair J, Leroux D, Desseigne F, Lasset C, Saurin JC, Joly MO, et al. Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation. Hum Mutat. 2007;28(11):1084–90. [PubMed]

19. Ostergaard JR, Sunde L, Okkels H. Neurofibromatosis von Recklinghausen type I phenotype and early onset of cancers in siblings compound heterozygous for mutations in MSH6. Am J Med Genet A. 2005;139:96–105. discussion 96. [PubMed]

20. Whiteside D, McLeod R, Graham G, Steckley JL, Booth K, Somerville MJ, et al. A homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple cafe-aulait spots. Cancer Res. 2002;62(2):359–62. [PubMed]

21. Bougeard G, Charbonnier F, Moerman A, Martin C, Ruchoux MM, Drouot N, et al. Early onset brain tumor and lymphoma in MSH2-deficient children. Am J Hum Genet. 2003;72(1):213–6. [PMC free article] [PubMed]

22. Felton KE, Gilchrist DM, Andrew SE. Constitutive deficiency in DNA mismatch repair. Clin Genet. 2007;71(6):483–98. [PubMed]

23. Vasen HF, Moslein G, Alonso A, Bernstein I, Bertario L, Blanco I, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer) J Med Genet. 2007;44(6):353–62. [PMC free article] [PubMed]

Articles from Haematologica are provided here courtesy of Ferrata Storti Foundation

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Technology: Nucleic acid detection — it's elementary with SHERLOCK!

http://ift.tt/2qlkpCh

The evolutionary significance of polyploidy

Polyploidy occurs frequently but is usually detrimental to survival; thus, few polyploids survive in the long term. Here, evidence linking the short-term evolutionary success of polyploids to environmental upheaval is reviewed and possible longer-term evolutionary benefits of polyploidy are discussed.

http://ift.tt/2pA930t

Hypophysis. From outgrowth, to ocular disorder to pituitary gland.

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http://ift.tt/2rh4WTS

Hermaphroditism: an obsolete diagnosis?

Related Articles

Hermaphroditism: an obsolete diagnosis?

Hormones (Athens). 2017 Jan;16(1):104-106

Authors: Tranoulis A, Michala L

PMID: 28500834 [PubMed - in process]

http://ift.tt/2rhhgDR

The male bride: a story of Sexual Female-to-Male Transformation at marriage from the Hellenistic period, recorded by Phlegon of Tralles.

Related Articles

The male bride: a story of Sexual Female-to-Male Transformation at marriage from the Hellenistic period, recorded by Phlegon of Tralles.

Hormones (Athens). 2017 Jan;16(1):101-103

Authors: Barouti K, Markantes GK, Armeni AK, Vasileiou V, Georgopoulos NA

PMID: 28500833 [PubMed - in process]

http://ift.tt/2rhoDLF

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

Related Articles

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

Hormones (Athens). 2017 Jan;16(1):92-98

Authors: Uppal S, Jee YH, Lightbourne M, Han JC, Stratakis CA

Abstract
BACKGROUND: Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella.
METHODS/RESULTS: The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC.
CONCLUSION: We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

PMID: 28500832 [PubMed - in process]

http://ift.tt/2rhmnE0

Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control.

Related Articles

Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control.

Hormones (Athens). 2017 Jan;16(1):84-91

Authors: Shimon I, Saeger W, Wildemberg LE, Gadelha MR

Abstract
OBJECTIVE: To present two female patients with acromegaly inadequately controlled with long-acting octreotide who were subsequently treated with the multireceptor-targeted somatostatin analogue pasireotide that over-suppressed IGF-1 levels.
METHODS: We report two patients who failed surgery and received long-acting octreotide 20-30 mg/month as part of two double-blind, Phase III clinical trials. After 6-12 months of octreotide treatment, both patients remained inadequately controlled and were switched to long-acting pasireotide 40 mg/month as part of a crossover extension phase.
RESULTS: During the core phase of the studies the patients received octreotide 20-30 mg/month, but GH and IGF-1 levels remained above normal. They were switched to pasireotide 40 mg/month after 6 and 12 months, according to the study protocols. After crossover, GH and IGF-1 decreased and normalized, but continued treatment led to further reduction of IGF-1 to below the normal; these reduced levels mildly increased following pasireotide dose reduction to 20 mg/month. Tumour volume was reduced and the clinical signs and symptoms of acromegaly also improved.
CONCLUSION: These patients achieved long-term biochemical control, tumour volume reduction and improvement of clinical signs/symptoms after switching from octreotide to pasireotide. IGF-1 over-suppression is observed in a few patients and requires dose adjustment of pasireotide.

PMID: 28500831 [PubMed - in process]

http://ift.tt/2qiO0MT

Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism.

Related Articles

Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism.

Hormones (Athens). 2017 Jan;16(1):75-83

Authors: Khoshi A, Sirghani A, Ghazisaeedi M, Mahmudabadi AZ, Azimian A

Abstract
OBJECTIVE: Subclinical hypothyroidism (SCH) is defined as high levels of TSH in the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays a key role in thyroid hormone synthesis, variations in the TPO gene can change the enzyme structure and result in the production of anti-TPO antibodies. The aim of this study was to examine the relationship between the Asn698Thr (A2095C) and Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients with SCH.
DESIGN: In this study, 150 individuals (75 cases and 75 controls), aged 19-75 years, were selected randomly by a clinician. The thyroid function tests included were FT3, FT4, TSH and anti-TPO antibodies using ELISA. The TPO gene polymorphisms were examined by PCR-RFLP.
RESULTS: Anti-TPO levels in the experimental group was significantly increased (P=0.020). The A2095C genotype frequency in the experimental and control groups were 37.3% vs 34.7% for the AA healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively (P=0.001). The A2173C genotype frequency in the experimental and control groups were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC, respectively (P <0.001). The increased anti-TPO antibodies were significantly associated with the A2173C polymorphism (P=0.035). The findings showed that the chance (odds ratio) of developing subclinical hypothyroidism in individuals who had C alleles was 1.5 and 5.6-fold higher than in individuals without these alleles in the A2095C and A2173C regions, respectively.
CONCLUSIONS: Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in patients with SCH can be helpful for prediction of overt hypothyroidism.

PMID: 28500830 [PubMed - in process]

http://ift.tt/2rhnlQO

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice.

Related Articles

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice.

Hormones (Athens). 2017 Jan;16(1):62-74

Authors: Hatzidis A, Hicks JA, Gelineau RR, Arruda NL, Monteiro De Pina I, O'Connell KE, Seggio JA

Abstract
OBJECTIVE: Both the consumption of high-fat diets and exercise are known to produce alterations in metabolism and behavior. This study focuses on the effects of a change to a low-fat diet from a high-fat diet and voluntary exercise on obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J mice.
DESIGN: Mice were initially given either a high-fat diet or regular chow, along with a cage with a running-wheel to mimic exercise, or one without, to determine to what extend exercise affects these symptoms. Then half of the mice given a high-fat diet were switched to regular chow to ascertain if the switch in diet would improve type-2 diabetic-like and obesity symptoms.
RESULTS: Wheel-running alone produced an improvement in insulin in mice continuously fed a high-fat diet (p=0.006), but running-wheels did not produce any further improvements in mice with regular chow replacement (p=0.999) or in controls (p=0.996). Replacement of a high-fat diet with regular chow led to physiological improvements in insulin (p=0.012) and leptin (p <0.001), glucose tolerance (p <0.001), and obesity (p <0.001), more so than exercise alone. Mice consuming a high-fat diet without a wheel exhibited reduced home-cage activity compared to controls after the diet switch (p=0.030), while no reduction was found in running-wheel activity between high-fat diet and regular chow consuming mice after switching diets (p=0.516).
CONCLUSIONS: These results suggest that exercise is only partially beneficial to improving health outcomes in mice consuming a high-fat diet, whereas incorporating a better diet, even without exercise, improves quality of health and can suppress T2DM symptoms and related conditions more so than exercise alone.

PMID: 28500829 [PubMed - in process]

http://ift.tt/2rgUBaP

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women.

Related Articles

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women.

Hormones (Athens). 2017 Jan;16(1):54-61

Authors: Polovina SP, Miljic D, Zivojinovic S, Milic N, Micic D, Popovic Brkic V

Abstract
OBJECTIVE: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients.
MATERIALS AND METHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb.
RESULTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, BMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854).
CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

PMID: 28500828 [PubMed - in process]

http://ift.tt/2rhaqy4

Psychological vulnerability to stress in carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Related Articles

Psychological vulnerability to stress in carriers of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Hormones (Athens). 2017 Jan;16(1):42-53

Authors: Kyritsi EM, Koltsida G, Farakla I, Papanikolaou A, Critselis E, Mantzou E, Zoumakis E, Kolaitis G, Chrousos GP, Charmandari E

Abstract
OBJECTIVE: Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) demonstrate increased secretion of cortisol precursors following ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic corticotropin-releasing hormone (CRH) secretion. Both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression. We performed an endocrinologic and psychological evaluation in carriers of 21-OHD and matched control subjects.
DESIGN: We recruited 29 parents of children with classic CAH (14 males, 15 females; age (mean±SD): 41.8±5.7 yr), and hence 21-OHD carriers, and 13 normal subjects (5 males, 8 females; age: 43.8±6.1 yr). All subjects underwent a formal ovine (o) CRH stimulation test with measurement of ACTH, cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, which was preceded by determination of 24-hour urinary free cortisol (UFC) excretion. Psychometric assessment was performed by administering the State-Anxiety (STAI 1) and Trait-Anxiety (STAI 2) Inventory, Beck Depression Inventory, Symptom Checklist-90R and Temperament and Character Inventory.
RESULTS: Carriers of 21-OHD had significantly higher 17-OHP concentrations following oCRH stimulation and higher STAI 1 (47.6±5.6 vs. 43.3±5.4, P=0.023) scores than control subjects. Mean 24-hour UFC concentrations were positively correlated with paranoid ideation (r=0.435; P=0.023) and psychoticism (r=0.454; P=0.017). Stepwise multiple linear regression analysis revealed that the single independent predictor of STAI 1 was peak stimulated 17-OHP concentrations (β: 0.055, SE: 0.023, R2: 0.290, P=0.031).
CONCLUSIONS: Carriers of 21-OHD may be predisposed to the development of anxiety disorders.

PMID: 28500827 [PubMed - in process]

http://ift.tt/2r69uiO

Serum kisspeptin concentrations are negatively correlated with body mass index in adolescents with anorexia nervosa and amenorrhea.

Related Articles

Serum kisspeptin concentrations are negatively correlated with body mass index in adolescents with anorexia nervosa and amenorrhea.

Hormones (Athens). 2017 Jan;16(1):33-41

Authors: Bacopoulou F, Lambrou GI, Rodanaki ME, Stergioti E, Efthymiou V, Deligeoroglou E, Markantonis SI

Abstract
OBJECTIVE: To measure, for the first time, serum kisspeptin concentrations in adolescent females with anorexia nervosa (AN) and associated amenorrhea, and investigate potential correlations of kisspeptin with anthropometric, bone and hormonal data.
DESIGN: Setting: University Adolescent Medicine Center.
PARTICIPANTS: Females aged 12-20 years with typical or atypical AN (based on DSM-5 diagnostic criteria) and controls.
INTERVENTIONS: Measurement of body mass index (BMI), whole body/lumbar spine bone mineral density and serum concentrations of kisspeptin, follicle stimulating hormone, luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine, estradiol (E2), 17-hydroxyprogesterone.
MAIN OUTCOME MEASURES: Kisspeptin serum concentrations and correlations between kisspeptin and AN-related anthropometric, bone and hormonal changes.
RESULTS: Participants included 37 females, 22 with AN (typical AN group=17, atypical AN group=5) and 15 in the control group. All typical AN patients had secondary amenorrhea. Wide inter-subject variation (101.9-709.1 ng/L) in kisspeptin levels was observed with no significant differences among study groups; there was a trend toward higher concentrations in the atypical AN group. Adolescents with typical AN had significantly lower BMI (P<0.001), lumbar spine z-score (P=0.016), serum E2 (P<0.001), LH (P=0.016), PRL (P=0.034) and TSH (P=0.045) than controls. They also had lower BMI (P=0.009) and TSH (P=0.027) than girls with atypical AN. An inverse correlation between BMI and serum kisspeptin was noted in the typical AN group (r=-0.60, P=0.012).
CONCLUSIONS: Serum kisspeptin concentrations overlapped between patients and controls; in typical anorexic adolescents kisspeptin concentrations were negatively correlated with BMI. Future studies are needed to explore kisspeptin physiology in AN.

PMID: 28500826 [PubMed - in process]

http://ift.tt/2qHOb7B

Which type 2 diabetes mellitus patients should be screened for subclinical Cushing's syndrome?

Related Articles

Which type 2 diabetes mellitus patients should be screened for subclinical Cushing's syndrome?

Hormones (Athens). 2017 Jan;16(1):22-32

Authors: Cansu GB, Atılgan S, Balcı MK, Sarı R, Özdem S, Altunbaş HA

Abstract
OBJECTIVE: Diabetes or impaired glucose tolerance are common in patients with Cushing's syndrome (CS). In this study we investigated the incidence of subclinical Cushing's syndrome (SCS) in type 2 diabetic patients with poor and good metabolic control and the relationship between blood glucose and cortisol levels.
DESIGN: A total of 400 type 2 diabetes mellitus (T2DM) patients (Group A, HbA1c ≥8%, n=250; Group B, HbA1c ≤6.5%, n=150) were included in the study. Biochemical tests followed by the 1 mg dexamethasone suppression test (DST) were performed. If post-DST cortisol levels were above 1.8 μg/dl (non-suppressed group), the 2 mg DST test was performed for 2 days. Among the patients, post-DST cortisol of at least 1.8 μg/dL and midnight serum cortisol levels of at least 7.5 μg/dL confirmed the diagnosis of CS.
RESULTS: While SCS was observed in 5 patients (2%) in Group A, no case was observed in group B. There was a statistically significant difference between groups for basal cortisol and post-DST cortisol results (p<0.001 and p<0.001, respectively). Microvascular complication rates were higher in the non-suppressed group (p=0.007). Post-DST cortisol levels had a positive correlation with the number of complications and HbA1c levels (respectively r=0.213, p<0.001, and r=0.191, p<0.001). Multivariate regression analysis revealed that durations of DM, HbA1c level, and post 1 mg DST cortisol levels were associated with the number of complications.
CONCLUSIONS: This study shows the presence of SCS in a notable number in T2DM patients having poor metabolic control. Screening with 1 mg and 2 mg DST of T2DM patients with poor metabolic control who are also obese and hypertensive and have microvascular complications may be an appropriate method for detection of SCS.

PMID: 28500825 [PubMed - in process]

http://ift.tt/2qHJef0

Vitamin D and aspects of female fertility.

Related Articles

Vitamin D and aspects of female fertility.

Hormones (Athens). 2017 Jan;16(1):5-21

Authors: Voulgaris N, Papanastasiou L, Piaditis G, Angelousi A, Kaltsas G, Mastorakos G, Kassi E

Abstract
The role of vitamin D in female reproduction has been intensively examined over the last few decades. A large body of evidence suggests that vitamin D might have beneficial effects on metabolic/hormonal parameters of PCOS and endometriosis, while it appears to be associated with IVF outcomes. However, due to the heterogeneity among observational and interventional studies, no cause-effect relationship has yet been established. The aim of this review is to analyze recent in vitro animal and human studies which examined the association of vitamin D with disease entities affecting female fertility potential. Recent research data strongly imply that vitamin D is implicated in female reproduction and might represent a beneficial and inexpensive therapeutic approach, in combination with first-line medical treatments, to female infertility.

PMID: 28500824 [PubMed - in process]

http://ift.tt/2qHwogC

Hypophysis. From outgrowth, to ocular disorder to pituitary gland.

Related Articles

Hypophysis. From outgrowth, to ocular disorder to pituitary gland.

Hormones (Athens). 2017 Jan;16(1):99-100

Authors: Laios K, Androutsos G, Piagkou M, Moschos MM

PMID: 28500835 [PubMed - in process]

http://ift.tt/2rh4WTS

Hermaphroditism: an obsolete diagnosis?

Related Articles

Hermaphroditism: an obsolete diagnosis?

Hormones (Athens). 2017 Jan;16(1):104-106

Authors: Tranoulis A, Michala L

PMID: 28500834 [PubMed - in process]

http://ift.tt/2rhhgDR

The male bride: a story of Sexual Female-to-Male Transformation at marriage from the Hellenistic period, recorded by Phlegon of Tralles.

Related Articles

The male bride: a story of Sexual Female-to-Male Transformation at marriage from the Hellenistic period, recorded by Phlegon of Tralles.

Hormones (Athens). 2017 Jan;16(1):101-103

Authors: Barouti K, Markantes GK, Armeni AK, Vasileiou V, Georgopoulos NA

PMID: 28500833 [PubMed - in process]

http://ift.tt/2rhoDLF

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

Related Articles

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

Hormones (Athens). 2017 Jan;16(1):92-98

Authors: Uppal S, Jee YH, Lightbourne M, Han JC, Stratakis CA

Abstract
BACKGROUND: Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella.
METHODS/RESULTS: The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC.
CONCLUSION: We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

PMID: 28500832 [PubMed - in process]

http://ift.tt/2rhmnE0

Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control.

Related Articles

Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control.

Hormones (Athens). 2017 Jan;16(1):84-91

Authors: Shimon I, Saeger W, Wildemberg LE, Gadelha MR

Abstract
OBJECTIVE: To present two female patients with acromegaly inadequately controlled with long-acting octreotide who were subsequently treated with the multireceptor-targeted somatostatin analogue pasireotide that over-suppressed IGF-1 levels.
METHODS: We report two patients who failed surgery and received long-acting octreotide 20-30 mg/month as part of two double-blind, Phase III clinical trials. After 6-12 months of octreotide treatment, both patients remained inadequately controlled and were switched to long-acting pasireotide 40 mg/month as part of a crossover extension phase.
RESULTS: During the core phase of the studies the patients received octreotide 20-30 mg/month, but GH and IGF-1 levels remained above normal. They were switched to pasireotide 40 mg/month after 6 and 12 months, according to the study protocols. After crossover, GH and IGF-1 decreased and normalized, but continued treatment led to further reduction of IGF-1 to below the normal; these reduced levels mildly increased following pasireotide dose reduction to 20 mg/month. Tumour volume was reduced and the clinical signs and symptoms of acromegaly also improved.
CONCLUSION: These patients achieved long-term biochemical control, tumour volume reduction and improvement of clinical signs/symptoms after switching from octreotide to pasireotide. IGF-1 over-suppression is observed in a few patients and requires dose adjustment of pasireotide.

PMID: 28500831 [PubMed - in process]

http://ift.tt/2qiO0MT

Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism.

Related Articles

Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism.

Hormones (Athens). 2017 Jan;16(1):75-83

Authors: Khoshi A, Sirghani A, Ghazisaeedi M, Mahmudabadi AZ, Azimian A

Abstract
OBJECTIVE: Subclinical hypothyroidism (SCH) is defined as high levels of TSH in the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays a key role in thyroid hormone synthesis, variations in the TPO gene can change the enzyme structure and result in the production of anti-TPO antibodies. The aim of this study was to examine the relationship between the Asn698Thr (A2095C) and Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients with SCH.
DESIGN: In this study, 150 individuals (75 cases and 75 controls), aged 19-75 years, were selected randomly by a clinician. The thyroid function tests included were FT3, FT4, TSH and anti-TPO antibodies using ELISA. The TPO gene polymorphisms were examined by PCR-RFLP.
RESULTS: Anti-TPO levels in the experimental group was significantly increased (P=0.020). The A2095C genotype frequency in the experimental and control groups were 37.3% vs 34.7% for the AA healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively (P=0.001). The A2173C genotype frequency in the experimental and control groups were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC, respectively (P <0.001). The increased anti-TPO antibodies were significantly associated with the A2173C polymorphism (P=0.035). The findings showed that the chance (odds ratio) of developing subclinical hypothyroidism in individuals who had C alleles was 1.5 and 5.6-fold higher than in individuals without these alleles in the A2095C and A2173C regions, respectively.
CONCLUSIONS: Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in patients with SCH can be helpful for prediction of overt hypothyroidism.

PMID: 28500830 [PubMed - in process]

http://ift.tt/2rhnlQO

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice.

Related Articles

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice.

Hormones (Athens). 2017 Jan;16(1):62-74

Authors: Hatzidis A, Hicks JA, Gelineau RR, Arruda NL, Monteiro De Pina I, O'Connell KE, Seggio JA

Abstract
OBJECTIVE: Both the consumption of high-fat diets and exercise are known to produce alterations in metabolism and behavior. This study focuses on the effects of a change to a low-fat diet from a high-fat diet and voluntary exercise on obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J mice.
DESIGN: Mice were initially given either a high-fat diet or regular chow, along with a cage with a running-wheel to mimic exercise, or one without, to determine to what extend exercise affects these symptoms. Then half of the mice given a high-fat diet were switched to regular chow to ascertain if the switch in diet would improve type-2 diabetic-like and obesity symptoms.
RESULTS: Wheel-running alone produced an improvement in insulin in mice continuously fed a high-fat diet (p=0.006), but running-wheels did not produce any further improvements in mice with regular chow replacement (p=0.999) or in controls (p=0.996). Replacement of a high-fat diet with regular chow led to physiological improvements in insulin (p=0.012) and leptin (p <0.001), glucose tolerance (p <0.001), and obesity (p <0.001), more so than exercise alone. Mice consuming a high-fat diet without a wheel exhibited reduced home-cage activity compared to controls after the diet switch (p=0.030), while no reduction was found in running-wheel activity between high-fat diet and regular chow consuming mice after switching diets (p=0.516).
CONCLUSIONS: These results suggest that exercise is only partially beneficial to improving health outcomes in mice consuming a high-fat diet, whereas incorporating a better diet, even without exercise, improves quality of health and can suppress T2DM symptoms and related conditions more so than exercise alone.

PMID: 28500829 [PubMed - in process]

http://ift.tt/2rgUBaP

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women.

Related Articles

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women.

Hormones (Athens). 2017 Jan;16(1):54-61

Authors: Polovina SP, Miljic D, Zivojinovic S, Milic N, Micic D, Popovic Brkic V

Abstract
OBJECTIVE: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients.
MATERIALS AND METHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb.
RESULTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, BMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854).
CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

PMID: 28500828 [PubMed - in process]

http://ift.tt/2rhaqy4

Unilateral Hearing Loss in Children: Impact and Solutions

This course is an edited transcript of a Phonak webinar on AudiologyOnline.Learning OutcomesAfter this course learners will be able to:Describe the types of unilateral hearing loss.Describe the use cases of the Sky V, CROS II, and Roger Focus.Describ

http://ift.tt/2pMm2YP

Issue Information - TOC

http://ift.tt/2pNabZO

Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: If you are planning a pregnancy, currently pregnant, or in the postpartum period, it's important to stay up to date on the latest guidelines on thyroid disease and pregnancy. Read More….

We welcome your feedback and suggestions. Let us know what you want to see in this publication.

Feedback & Suggestions

The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.

http://ift.tt/2pMyrvT

Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: If you are planning a pregnancy, currently pregnant, or in the postpartum period, it's important to stay up to date on the latest guidelines on thyroid disease and pregnancy. Read More….

We welcome your feedback and suggestions. Let us know what you want to see in this publication.

Feedback & Suggestions

The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.

http://ift.tt/2pMyrvT

Variant in a common odorant-binding protein gene is associated with bitter sensitivity in people

Publication date: 30 June 2017
Source:Behavioural Brain Research, Volume 329
Author(s): Iole Tomassini Barbarossa, M. Hakan Ozdener, Melania, Latisha Love-Gregory, Makedonka Mitreva, Nada A. Abumrad, M. Yanina Pepino
Deeper understanding of signaling mechanisms underlying bitterness perception in people is essential for designing novel and effective bitter blockers, which could enhance nutrition and compliance with orally administered bitter-tasting drugs. Here we show that variability in a human odorant-binding protein gene, OBPIIa, associates with individual differences in bitterness perception of fat (oleic acid) and of a prototypical bitter stimulus, 6-n-propylthiouracil (PROP), suggesting a novel olfactory role in the modulation of bitterness sensitivity.



http://ift.tt/2qhAjQd

Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics

Publication date: 15 July 2017
Source:European Journal of Pharmaceutical Sciences, Volume 105
Author(s): Weiwei Lin, Jianmei Zhang, Yanmeng Liu, Ruijun Wu, Haisong Yang, Xiaobo Hu, Xiaomei Ling
Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and treatment are not sufficient so far. The purpose of this study is to develop biomarkers and therapeutic targets for diagnosis and better understanding of AD. As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF-MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD hippocampus by using label free nano-LC-MS/MS. Thus, pathogenesis of AD was involved with increasing of choline, decreasing of ACh, enhancement of GSTs and increasing of glutamate which led to oxidative stress and excitotoxity. Effects of donepezil and a natural medicine were evaluated through metabolomics and proteomics. In summary, proteomic and metabolomic analysis on constructed AD rat model were performed through rapid, sensitive and high resolution LC-MS methods to reveal candidate biomarkers. The data suggested that GSTs have great value as therapeutic targets. This study provided valuable information for the diagnosis mechanism and drug discovery of AD.

Graphical abstract

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“Ziziphus oxyphylla”: Ethnobotanical, ethnopharmacological and phytochemical review

Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Rizwan Ahmad, Niyaz Ahmad, Atta Abbas Naqvi
Ethnopharmacological relevanceZiziphus oxyphylla (ZO) is distributed mainly in tropic and warm temperate regions in the world. Pakistan owns six (06) indigenous species of genus Ziziphus out of which ZO is widely used for traditional treatment of different ailments such as diabetes, jaundice and liver diseases.Aim of the studyThe present review aims to provide in-depth and comprehensive literature overview, regarding botanical, chemical and biological characteristics of the plant alongwith phytochemical isolation and mechanistic studies to support its folklore and traditional uses.Materials and methodsThe literature search and relevant information were collected through authentic resources using data bases such as Google Scholar, PubMed, Web of Science, Scopus and Science Direct, peer reviewed articles, books and thesis.Results and discussionThe phytochemical characterization as well as color tests confirmed the presence of diverse chemical groups presents in the plant such as alkaloids, flavonoids, phenolic compounds and tannins. In-vivo and in-vitro pharmacological activities for the crude extracts and its fractions revealed potent antinociceptive, anti-inflammatory, antipyretic, antioxidant, antibacterial as well as acetyl choline esterase and lipoxygenase inhibitory activity. Majority of the isolated compounds belonged to class of Cyclopeptide alkaloids for which the genus is already very famous. Compounds from alkaloids and flavonoids chemical class were isolated and evaluated with a role as antioxidant, antidiabetic, anti-glycation and advanced glycation end products inhibitors. No toxicity was observed during cytotoxicity (MRC-5 cell lines), insecticidal and brine shrimp lethality studies.ConclusionThe review article supports the folklore uses of this plant in the aforementioned diseases. The plant due to its diverse biological nature may be further studied for mechanistic studies, its anticancer effects as well as its potency and toxicity studies for safe use in human beings.

Graphical abstract

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The prevalence of food allergy and other allergic diseases in early childhood in a population-based study: HealthNuts age 4-year follow-up

The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse.

http://ift.tt/2qHb7no

Signature of the Sleeper Cell: A Biomarker of HIV Latency Revealed

Publication date: Available online 13 May 2017
Source:Trends in Immunology
Author(s): Satish K. Pillai, Steven G. Deeks
HIV establishes a reservoir in latently infected T cells, and this reservoir has long hampered curative approaches. A recent study by Descours et al. identifies CD32a as a marker of latently infected T cells, potentially opening the way to the development of strategies that directly target this critical HIV reservoir.



http://ift.tt/2qi7O4N

Evaluation of behavioral change after adenotonsillectomy for obstructive sleep apnea in children with autism spectrum disorder

Publication date: June 2017
Source:Research in Developmental Disabilities, Volume 65
Author(s): Emi Murata, Ikuko Mohri, Kumi Kato-Nishimura, Jiro Iimura, Makoto Ogawa, Masaya Tachibana, Yuko Ohno, Masako Taniike
Background and objectiveObstructive sleep apnea (OSA) may affect daily cognitive functioning in children. The aims of our study were two-fold. The first aim was to detect, using the Child Behavior Checklist (CBCL), whether adenotonsillectomy (AT) for the treatment of OSA improved the behavior of children with autism spectrum disorder (ASD). The second aim was to identify characteristics for behavioral improvement following the treatment of OSA in these children with ASD.MethodsThe behaviors of ASD children aged 5–14 years diagnosed as having OSA (n=30) were evaluated using CBCL before and after AT. CBCL evaluation of ASD children without OSA at two time points with the same interval served as a control (n=24). We statistically examined the two groups. In addition, we conducted a paired t-test to assess changes in CBCL Tscores between the improved group and unchanged/deteriorated group to identify characteristics that may affect behavioral changes following OSA treatment.ResultsAfter AT, T-scores of the CBCL scales were significantly improved in the OSA group, but no change was observed in the control. A paired t-test revealed that the improved group had significantly higher scores on the CBCL pre-AT than the unchanged/deteriorated group in ASD children with OSA after OSA treatment.ConclusionsBehavioral problems were significantly improved following AT in ASD children with OSA. Early detection and treatment of children with OSA is essential to prevent behavioral problems and to support mental development.



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Acquisition of Who-question Comprehension in German Children with Hearing Loss

Publication date: Available online 13 May 2017
Source:Journal of Communication Disorders
Author(s): Eva Wimmer, Monika Rothweiler, Martina Penke
For children with sensorineural hearing loss the ability to understand wh-questions might be particularly challenging because they often have only restricted access to spoken language input during optimal periods of language acquisition. In previous research it has been suggested that this restricted input during critical stages in language acquisition might lead to syntactic deficits that persist into adolescence. In this study we want to pursue this issue by investigating the comprehension of wh-questions in German children with bilateral sensorineural hearing loss. We report results of a who-question comprehension task in a group of 21 3- to 4-year-old German hard-of-hearing children compared to a group of age-matched children with normal hearing. The group data and individual performance patterns suggest that the syntactic comprehension difficulties observed in some, but not all, of the children with hearing loss reflect a delay in the acquisition of who-question comprehension rather than a persistent syntactic deficit. Follow-up data elicited from a subgroup of children confirmed this supposition.



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Heart murmur detection based on Wavelet Transformation and a synergy between Artificial Neural Network and modified Neighbor Annealing methods

Publication date: Available online 13 May 2017
Source:Artificial Intelligence in Medicine
Author(s): Gholamhossein Eslamizadeh, Ramin Barati
Early recognition of heart disease plays a vital role in saving lives. Heart murmurs are one of the common heart problems. In this study, Artificial Neural Network (ANN) is trained with Modified Neighbor Annealing (MNA) to classify heart cycles into normal and murmur classes. Heart cycles are separated from heart sounds using wavelet transformer. The network inputs are features extracted from individual heart cycles, and two classification outputs. Classification accuracy of the proposed model is compared with five multilayer perceptron trained with Levenberg-Marquardt, Extreme-learning-machine, back-propagation, simulated-annealing, and neighbor-annealing algorithms. It is also compared with a Self-Organizing Map (SOM) ANN. The proposed model is trained and tested using real heart sounds available in the Pascal database to show the applicability of the proposed scheme. Also, a device to record real heart sounds has been developed and used for comparison purposes too. Based on the results of this study, MNA can be used to produce considerable results as a heart cycle classifier.



http://ift.tt/2rfxT21

Augmentation of the infraorbital rim in orthognathic surgery

Mid-face augmentation via a Le Fort I osteotomy is a commonly performed operation. Advancement of the upper jaw and associated structures (nose, lower cheek areas) can certainly improve function as well as facial aesthetics and harmony. Often, in patients with severe mid-face deficiency, hypoplasia of the maxilla extends all the way up to the infraorbital rims. The receding infraorbital rim contributes to the negative vector of the globes. In patients with this level of mid-face hypoplasia, while advancing the maxilla at the Le Fort I level satisfies all of the requirements for orthognathic surgery, the deficient infraorbital rim remains unchanged and can actually accentuate the negative vector of the globes.

http://ift.tt/2qklk6h

Epigenetics and immunotherapy: The current state of play

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant. Importantly, recent studies on the role of epigenetics in immune evasion have exposed a key role for epigenetic modulators in augmenting the tumour microenvironment and restoring immune recognition and immunogenicity. Epigenetic drugs such as DNA methyltransferase and histone deacetylase inhibitors can reverse immune suppression via several mechanisms such as enhancing expression of tumour-associated antigens, components of the antigen processing and presenting machinery pathways, immune checkpoint inhibitors, chemokines, and other immune-related genes. These discoveries have established a highly promising basis for studies using combined epigenetic and immunotherapeutic agents as anti-cancer therapies. In this review, we discuss the exciting role of epigenetic immunomodulation in tumour immune escape, emphasising its significance in priming and sensitising the host immune system to immunotherapies through mechanisms such as the activation of the viral defence pathway. With this background in mind, we highlight the promise of combined epigenetic therapy and immunotherapy, focusing on immune checkpoint blockade, to improve outcomes for patients with many different cancer types.



http://ift.tt/2pzIM2h

Molecular cloning and characterization of DNGR-1 in rhesus macaques

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Wen-Rong Yao, Lei Yu, Dong Li, Gui-Bo Yang
DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain family 9 member A (CLEC9A), is a promising target for immunological therapeutics and vaccination against tumors and viruses. However, little is known about its property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA, and found that its coding region could encode a 241-amino acid polypeptide with 91.7% sequence identity and similar antigenicity to that of humans. Both free and cell surface rhesus macaque DNGR-1 expressed in vitro could bind to apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to pyroptotic cells stimulated with PMA and LPS. We also demonstrated that rhesus macaque DNGR-1 mRNA was present in all the examined tissues, with the highest in lymph nodes, spleen, blood, and thymus. The expression of DNGR-1 that is highly similar to that of humans warranted the usefulness of rhesus macaques in testing human therapeutics and vaccines targeting DNGR-1, especially those for HIV/AIDS.



http://ift.tt/2qkn0fK

Epigenetics and immunotherapy: The current state of play

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant. Importantly, recent studies on the role of epigenetics in immune evasion have exposed a key role for epigenetic modulators in augmenting the tumour microenvironment and restoring immune recognition and immunogenicity. Epigenetic drugs such as DNA methyltransferase and histone deacetylase inhibitors can reverse immune suppression via several mechanisms such as enhancing expression of tumour-associated antigens, components of the antigen processing and presenting machinery pathways, immune checkpoint inhibitors, chemokines, and other immune-related genes. These discoveries have established a highly promising basis for studies using combined epigenetic and immunotherapeutic agents as anti-cancer therapies. In this review, we discuss the exciting role of epigenetic immunomodulation in tumour immune escape, emphasising its significance in priming and sensitising the host immune system to immunotherapies through mechanisms such as the activation of the viral defence pathway. With this background in mind, we highlight the promise of combined epigenetic therapy and immunotherapy, focusing on immune checkpoint blockade, to improve outcomes for patients with many different cancer types.



http://ift.tt/2pzIM2h

Molecular cloning and characterization of DNGR-1 in rhesus macaques

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Wen-Rong Yao, Lei Yu, Dong Li, Gui-Bo Yang
DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain family 9 member A (CLEC9A), is a promising target for immunological therapeutics and vaccination against tumors and viruses. However, little is known about its property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA, and found that its coding region could encode a 241-amino acid polypeptide with 91.7% sequence identity and similar antigenicity to that of humans. Both free and cell surface rhesus macaque DNGR-1 expressed in vitro could bind to apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to pyroptotic cells stimulated with PMA and LPS. We also demonstrated that rhesus macaque DNGR-1 mRNA was present in all the examined tissues, with the highest in lymph nodes, spleen, blood, and thymus. The expression of DNGR-1 that is highly similar to that of humans warranted the usefulness of rhesus macaques in testing human therapeutics and vaccines targeting DNGR-1, especially those for HIV/AIDS.



http://ift.tt/2qkn0fK

Application of metabolomics in sarcoma: from biomarkers to therapeutic targets

Publication date: Available online 13 May 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Li Min, Edwin Choy, Chongqi Tu, Francis Hornicek, Zhenfeng Duan




http://ift.tt/2rfedva

A novel pathogenic variant in the FZD6 gene causes recessive nail dysplasia in a large Iranian kindred

Publication date: Available online 13 May 2017
Source:Journal of Dermatological Science
Author(s): Javad Mohammadi-asl, Mohammad Reza Pourreza, Aliasgar Mohammadi, Ameneh Eskandari, Sima Mozafar-Jalali, Mohammad Amin Tabatabaiefar
BackgroundNail disorder nonsyndromic congenital (NDNC) is a very rare clinically and genetically heterogeneous disease inherited both in recessive or dominant modes. FZD6 is a component of Wnt-FZD signaling pathway in which recessive loss-of-function variants in the corresponding genes could lead to nail anomalies.ObjectiveA large multiplex family with NDNC was referred for genetic counselling. Thorough genetic evaluation was performed.MethodsPCR-Sanger sequencing was carried out for the coding exons and exon-intron boundaries of the FZD6 gene. Co-segregation analysis, in silico evaluation and computational protein modeling was accomplished.ResultsA homozygous 1bp deletion variant, c.1859delC (p.Ser620Cysfs*75), leading to a truncating protein was found in the patient. Parents were heterozygous for the variant. The variant was found to be co-segreagting with the phenotype in the family. Computational analysis and protein modeling revealed its pathogenic consequence by disturbing the cytoplasmic domain structure and signaling through loss of phosphorylation residues. The variant met the criteria of being pathogenic according to the ACMG guideline.ConclusionsThis is the first report of the genetic diagnosis of NDNC in Iran. We also report a novel pathogenic variant. The study of the FZD6 gene is recommended as the first step in the diagnostic routing of the autosomal recessive NDNC patients with enlarged nails.



http://ift.tt/2r6pW2L

Fluorogenic Kinetic Assay for High-Throughput Discovery of Stereoselective Ketoreductases Relevant to Pharmaceutical Synthesis

Publication date: Available online 13 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yen-Chi Thai, Anna Szekrenyi, Yuyin Qi, Gary W. Black, Simon J. Charnock, Wolf-Dieter Fessner
Enantiomerically pure 1-(6-methoxynaphth-2-yl) and 1-(6-(dimethylamino)naphth-2-yl) carbinols are fluorogenic substrates for aldo/keto reductase (KRED) enzymes, which allow the highly sensitive and reliable determination of activity and kinetic constants of known and unknown enzymes, as well as an immediate enantioselectivity typing. Because of its simplicity in microtiter plate format, the assay qualifies for the discovery of novel KREDs of yet unknown specificity among this vast enzyme superfamily. The suitability of this approach for enzyme typing is illustrated by an exemplary screening of a large collection of short-chain dehydrogenase/reductase (SDR) enzymes arrayed from a metagenomic approach. We believe that this assay format should match well the pharmaceutical industry's demand for acetophenone-type substrates and the continuing interest in new enzymes with broad substrate promiscuity for the synthesis of chiral, non-racemic carbinols.

Graphical abstract

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Application of In-vitro Screening Methods on Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitors

Publication date: Available online 13 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yue Wu, Zhensheng Jiang, Qidong You, Xiaojin Zhang
Anemia resulting from the reduced expression of erythropoietin (EPO) is a common complication of patients with chronic kidney diseases (CKD). Hypoxia inducible transcription factor-α (HIF-α), which adapts cellular hypoxia condition, regulates the expression of many downstream genes including the EPO gene. Hypoxia inducible transcription factor prolyl hydroxylase 2 (HIF-PHD2), as the key regulator of hypoxia response, is function of hydroxylating specify proline residues of HIF-α, which may lead to the degradation of HIF-α and eventually cause disenabling the expression of erythropoietin. Therefore, it is valid to improve anemia by inhibiting HIF-PHD2. In-vitro screening plays a vital role in searching for novel small molecule HIF-PHD2 inhibitors, thus, this review classified in-vitro screening methods which are used to hit novel HIF-PHD2 inhibitors.

Graphical abstract

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External pelvic and vaginal irradiation vs. vaginal irradiation alone as postoperative therapy in women with early stage uterine serous carcinoma: Results of a National Cancer Database analysis

Publication date: Available online 13 May 2017
Source:Brachytherapy
Author(s): Ankit Modh, Charlotte Burmeister, Adnan R. Munkarah, Mohamed A. Elshaikh
PurposeAdjuvant treatment in early stage uterine serous carcinoma (USC) usually consists of chemotherapy with vaginal brachytherapy (VB), pelvic external beam radiation therapy (EBRT), or combination. We compared survival outcomes across these various radiation treatment modalities using the National Cancer Database.Methods and MaterialsThe National Cancer Database was queried for adult females with histologically confirmed International Federation of Gynecology and Obstetrics 1988 Stage I–II USC diagnosed from 2003 to 2013 treated definitively with hysterectomy, adjuvant chemotherapy, and radiation therapy. χ² tests were used to assess differences by radiation type (VB, pelvic EBRT, and EBRT + VB) and various clinical variables. Kaplan–Meier and log-rank test methods were used to evaluate survival outcomes. Risk factors related to overall survival were identified by univariate and multivariate analysis.ResultsWe identified 1336 patients with USC who met our inclusion criteria. Most patients were treated with VB (66%) compared with EBRT (21%) or combination EBRT + VB (13%). The proportion of patients who received EBRT (including EBRT + VB) was higher for those who did not have a lymph node dissection or with fewer dissected lymph nodes. Patients treated with VB alone had longer 5-year survival rates (84% [95% confidence interval: 80, 90]) than those treated with EBRT (75% [95% confidence interval: 69, 80]) (p < 0.001). On multivariate analysis, the presence of lymphovascular space invasion (hazard ratio, 2.48; p < 0.001) and the absence of a lymph node dissection (hazard ratio, 2.24; p = 0.047) were independent predictors of overall survival.ConclusionsThis large hospital-based study suggests that VB alone may be sufficient for adjuvant radiation treatment in women with USC treated with adjuvant chemotherapy and who underwent an adequate surgical staging.



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Synthesis of a ternary Ag/RGO/ZnO nanocomposite via microwave irradiation and its application for the degradation of Rhodamine B under visible light

Abstract

Reduced graphene oxide supporting plasmonic photocatalyst (Ag) on ZnO has been synthesized via a facile two-step microwave synthesis using RGO/ZnO and AgNO₃. First step involves fabrication of RGO/ZnO via microwave irradiation. The nanocomposites were characterized by X-ray diffraction analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. Ag/RGO/ZnO shows enhanced photoactivity under visible light for the degradation of Rhodamine B. Enhanced charge separation and migration have been assigned using UV-vis diffuse reflectance spectra, photoluminescence spectra, electrochemical impedance spectra, and TCSPC analysis. The improved photoactivity of Ag/RGO/ZnO can be ascribed to the prolonged lifetime of photogenerated electron–hole pairs and effective interfacial hybridization between RGO and Ag with ZnO nanoparticles. Ag nanoparticles can absorb visible light via surface plasmon resonance to enhance photocatalytic activity.

http://ift.tt/2pyzR0W

Light absorption of biomass burning and vehicle emission-sourced carbonaceous aerosols of the Tibetan Plateau

Abstract

Carbonaceous aerosols over the Tibetan Plateau originate primarily from biomass burning and vehicle emissions (BB and VEs, respectively). The light absorption characteristics of these carbonaceous aerosols are closely correlated with the burning conditions and represent key factors that influence climate forcing. In this study, the light absorption characteristics of elemental carbon (EC) and water-soluble organic carbon (WSOC) in PM_2.5 (fine particulate matter smaller than 2.5 μm) generated from BB and VEs were investigated over the Tibetan Plateau (TP). The results showed that the organic carbon (OC)/EC ratios from BB- and VE-sourced PM_2.5 were 17.62 ± 10.19 and 1.19 ± 0.36, respectively. These values were higher than the ratios in other regions, which was primarily because of the diminished amount of oxygen over the TP. The mass absorption cross section of EC (MAC_EC) at 632 nm for the BB-sourced PM_2.5 (6.10 ± 1.21 m².g⁻¹) was lower than that of the VE-sourced PM_2.5 (8.10 ± 0.98 m².g⁻¹), indicating that the EC content of the BB-sourced PM_2.5 was overestimated because of the high OC/EC ratio. The respective absorption per mass (α/ρ) values at 365 nm for the VE- and BB-sourced PM_2.5 were 0.71 ± 0.17 m².g⁻¹ and 0.91 ± 0.18 m².g⁻¹. The α/ρ value of the VEs was loaded between that of gasoline and diesel emissions, indicating that the VE-sourced PM_2.5 originated from both types of emissions. Because OC and WSOC accounts for most of the carbonaceous aerosols at remote area of the TP, the radiative forcing contributed by the WSOC should be high, and requires further investigation.

http://ift.tt/2qjuTSU

Clinical and Pathological Characteristic of Metastatic Malignant Mesothelioma Initially Diagnosed by Lymph Node Biopsy

Publication date: Available online 13 May 2017
Source:Pathology - Research and Practice
Author(s): Xiang-Lan Zhu, Li-Min Gao, Fen Li, Wei-ping Liu, Wen-Yan Zhang, Gan-Di Li, Xiu-Hui Zhang, Min Chen, Xiao-Yu Liu, Sha Zhao
BackgroundIt is a great challenge for pathologists to initially diagnose metastatic malignant mesothelioma (MM) by the lymph node biopsy without any history of primary MM. Because the onset of MM is hidden and the metastatic MM in lymph node is relatively uncommon. Besides, morphologic and immuohistochemestry features of MM are similar to other tumors.MethodsIn order to improve the initial diagnositic accuracy of metastatic MM from LN biopsy and to reduce or avoid the possibility of missed diagnosis or misdiagnosis, we had collected the clinical and pathological data of the metastatic MM cases in our department, and summarized the characteristics of morphological, immunohistochemical and fluorescence in situ hybridization (FISH) results.ResultsSeven patients (4 males and 3 females) with 21–73 year-old had been included in our study. Six cases showed serous cavity effusion, serosal thickening and systemic multiple lymph node enlargement. The "moderate, nice" tumor cells were arranged in variable patterns. Mitosis was hardly to be found and necrosis was absent. Four immunohistochemical staining panels and FISH detection had been used for diagnosis and differential diagnosis of MM. All cases expressed broad-spectrum epithelial markers and at least 2 mesothelial-cell-origin markers. None were positive for specific-tissue-origin markers, and all cases were diagnosed of malignancy according to immunohistochemical markers and detection of pl6 gene deletion.ConclusionIt is necessary for us to keep our awareness of metastatic MM in lymph node. Correct diagnosis of MM metastasis by lymph node biopsy were based on detailed understanding of the clinical manifestation and the image data, careful observation of morphologic characteristics, and properly using immunohistochemical markers or FISH detection if necessary for diagnosis and differential diagnosis.



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