Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy

Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.     

Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.

We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.     

Growth hormone deficiency,aortic dilation,and neurocognitive issues in Feingold syndrome 2

We report three patients with Feingold 2 syndrome with the novel features of growth hormone deficiency associated with adenohypophyseal compression, aortic dilation, phalangeal joint contractures, memory, and sleep problems in addition to the typical features of microcephaly, brachymesophalangy, toe syndactyly, short stature, and cardiac anomalies. Microdeletions of chromosome 13q that include the MIR17HG gene were found in all three. One of the patients was treated successfully with growth hormone. In addition to expanding the phenotype of Feingold 2 syndrome, we suggest management of patients with Feingold 2 syndrome include echocardiography at the time of diagnosis in all patients and consideration of evaluation for growth hormone deficiency in patients with short stature.     

The genotoxic effects of hepatitis B virus to host DNA

Chronic viral hepatitis is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma throughout the world. Hepatitis B virus (HBV) has mutagenic effects on somatic cells. HBV may be showing these mutagenic effects through its viral proteins or through integrating into host DNA. The aim of this study was to determine whether HBV has a genotoxic effect on host DNA or not. Peripheral blood lymphocytes of 31 chronic HBV patients and 20 chronic HBV carriers were cultured in order to make cytogenetic evaluation by observing chromosome breakage and cytological evaluation by the micronucleus (MN) test. Their results were compared with 20 healthy controls. For each individual, 100 metaphase chromosome spreads were analysed. Around 190-1091 binucleated cells were observed and MN were scored for each individual. Our results showed significantly higher frequencies of chromosome breaks in chronic HBV patients and in HBV carriers than in the control group. There was no difference in MN scores among HBV patients, HBV carriers and healthy carriers. Based on our data, we conclude that chronic HBV patients and carriers have chromosomal instability and that HBV carriers are as affected as patients because of their same chromosome breakage levels.     

Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.     

A novel NPHS1 mutation associated with temporary elevation of maternal serum alfa-fetoprotein and late onset of proteinuria

International Urology and Nephrology -     

Pain during sexual activity and ejaculation following hernia repair: A retrospective comparison of transabdominal preperitoneal versus Lichtenstein repair

Pain during sexual activity and ejaculation are the unspoken long-term complications of groin hernia repair. Laparoscopic surgical techniques are associated with decreased post-operative pain and earlier return to daily activities, but its effect on these complications is unclear. This study aims to investigate the effect of transabdominal preperitoneal repair (TAPP) on de-novo pain during sexual intercourse and ejaculation and to compare with open repair. For this reason, two groups were determined according to the surgical technique: the Lichtenstein repair and the TAPP groups and a questionnaire was sent to the patients a minimum of 6 months following the surgery. A total of 317 patients included, as 115 in TAPP and 202 in Lichtenstein repair group. No significant difference was observed concerning pre-operative pain during sexual activity and ejaculation in both groups (p = .75, p = .56). Following the surgery, the number of patients experiencing painful sexual activity was significantly higher in the Lichtenstein repair group compared to the TAPP group (19.3% vs. 11.3%, respectively, p = .03). The post-operative painful ejaculation rate was also significantly lower for the TAPP group (p = .04). The lower rates of post-operative dysejaculation and pain during sexual activity can be achieved with the advantage of laparoscopic surgery.     

Evaluation of Sexual Dysfunction in Patients Undergoing Hemodialysis Treatment

Aim

In this study. it was aimed to determine the prevalence of sexual dysfunction (SD) and the factors that may affect the occurrence of SD in patients receiving hemodialysis treatment.

Methods

The sample of the study consists of 49 patients (20 females. 29 males) receiving treatment in the hemodialysis unit of a university hospital. The data of the study were collected through a general information form including socio-demographic characteristics and risk factors. Female Sexual Function Index (FSFI). International Assessment Form for Erectile Function (IIEF) and Quality of Life Scale (SF-36).

Results

In our study. SD was detected in all patient groups. While the most affected area was seen to be orgasmic function and the least affected area was sexual desire in famales. the most affected area was found to be orgasmic function and the least affected area was erectile dysfunction in males. Such factors as age. profession. having a child. working status and duration of hemodialysis were found to affect occurrence of SD. There was a relationship between all sub-dimensions of sexual function and quality of life in male and female subjects.

Conclusion

In conclusion. sexual dysfunction is commonly encountered in patients undergoing hemodialysis treatment. In these patients. psychosocial factors as well as disease-related factors have an effect on SD. Therefore. SD should be evaluated together with disease-related factors as well as psychosocial factors in patients undergoing hemodialysis treatment.

     

Differences between cytokine release from bronchial epithelial cells of asthmatic patients and non-asthmatic subjects: effect of exposure to diesel exhaust particles

BACKGROUND: Recent evidence suggests that the airways of asthmatics are more susceptible to adverse effects of air pollutants than the airways of non-asthmatics, but the underlying mechanisms are not clear. METHODS: We have cultured bronchial epithelial cells (HBEC) from biopsies of atopic mild asthmatic patients and non-atopic non-asthmatic subjects, and investigated constitutive and diesel exhaust particles (DEP)-induced release of several pro-inflammatory mediators. RESULTS: HBEC of asthmatic patients constitutively released significantly greater amounts of IL-8, GM-CSF and sICAM-1 than HBEC of non-asthmatic subjects. RANTES was only released by HBEC of asthmatic patients. Incubation of the asthmatic cultures with 10 micrograms/ml DEP significantly increased the release of IL-8, GM-CSF and sICAM-1 after 24 h. In contrast, only the higher concentrations of 50-100 micrograms/ml DEP significantly increased the release of IL-8 and GM-CSF from HBEC of non-asthmatics. CONCLUSIONS: These results suggest that the increased sensitivity of the airways of asthmatics to air pollutants such as DEP may, at least in part, be a consequence of greater constitutive and pollutant-induced release of specific pro-inflammatory mediators from their bronchial epithelial cells.     

Herpes simplex type 2 neutralization antibodies in patients with cancers of urinary bladder,prostate, and cervix

In the blood samples obtained from a total of 68 patients with cancers of the urinary bladder, prostate, and cervix, who applied to the Departments of Urology, Obstetrics, and Gynecology of Hacettepe Medical Faculty, neutralizing antibodies were sought for against herpes simplex type 2 by neutralization test. The same test was applied to 35 control patients with no known malignancies. In contrast to the presence of the antibody in 62.86% of the control subjects, this ratio was 90.70% in patients with cancer of the urinary bladder, 87.50% in those with prostatic carcinoma, and 88.89% in those with cancer of the cervix.