Germline mutations of BRCA1 and BRCA2 genes in Turkish breast, ovarian, and prostate cancer patients

Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC–OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC–OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC–OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC–OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management.     

Increased complement classical and mannan-binding lectin pathway activities in schizophrenia

Schizophrenia is a severe mental disorder, with worldwide prevalence of 1-1.5%. Immunological research in schizophrenia indicates that infectious or autoimmune processes might play a role in the etiopathogenesis. The complement system is a major mediator of innate immune defence against infection and contributes to many functions of the immune system including inflammation, opsonization and cell lysis. Mannan-binding lectin (MBL) activates the complement system via the lectin pathway. Inherited MBL deficiency, common in most human populations, predisposes to infectious and autoimmune diseases. We measured total complement activity (CH50), C4 activity (C4 CH50), MBL level and the activities of MBL-associated serine proteases, MASP-1 and MASP-2 in sera of 45 schizophrenic patients and in 62 healthy volunteers. We found that schizophrenic patients and healthy volunteers have statistically similar MBL levels and MASP-1 activity. However, MBL-bound MASP-2 activity and therefore MBL and MASP-2-mediated complement activation capacity is increased in schizophrenic patients compared with healthy volunteers (P<0.01). The increase was accompanied by increased CH50 (P<0.02) and C4 CH50 (P<0.02). Our results support the idea that complement system alterations may be involved in schizophrenia.     

Analysis of the monocyte chemoattractant protein 1 -2518 promoter polymorphism in Korean patients with alopecia areata

Monocyte chemoattractant protein-1 (MCP-1) levels are increased in scalp lesions of patients with alopecia areata (AA), suggesting a role in the development of AA. Recently, a biallelic A/G polymorphism in the MCP-1 promoter at position -2518 has been found, influencing the level of MCP-1 expression in response to an inflammatory stimulus. We investigated whether the presence of these polymorphisms were associated with AA in Korean population. 145 Korean patients with AA, 246 healthy subjects without clinical evidence of AA were screened for genotype with a PCR-based assay. In the AA patients the frequency of the A and G alleles was 40.3 and 59.7%, respectively and the distribution of the A/A, A/G and G/G genotypes was 19.3, 42.1 and 38.6%, respectively. Amongst the controls the frequency of the A and G alleles was 39.8 and 60.2%, and the distribution of the A/A, A/G, G/G genotypes in the same group was 17.5, 44.7 and 37.8%, respectively. There was no significant difference in the allele frequencies and genotype distributions between the patients and the controls (p=0.889, p=0.848, respectively). Our data indicates that no association exists between the -2518A/G polymorphism of the MCP-1 gene and susceptibility to alopecia areata.     

Role of catecholaminergic neurones of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats

Several findings suggest that catecholaminergic neurones in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. The present study sought to determine the effects of lesions of these neurones on the cardiovascular responses induced by changes in circulating volume. All experiments were performed in male Wistar rats (320-360 g). Medullary catecholaminergic neurones were lesioned by microinjection of anti-dopamine beta-hydroxylase-saporin (6.3 ng in 60 nl; SAP rats, n = 14) into the CVLM, whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n = 15). Two weeks later, rats were anaesthetized (urethane, 1.2 g kg(-1), i.v.), instrumented for measurement of mean arterial pressure (MAP), renal blood flow (RBF) and renal vascular conductance (RVC), and infused with hypertonic saline (HS; 3 m NaCl, 0.18 ml (100 g body weight)(-1), i.v.) or an isotonic solution (volume expansion, VE; 4% Ficoll, 1% of body weight, i.v.). In sham rats, HS induced sustained increases in RBF and RVC (155 +/- 7 and 145 +/- 6% of baseline, at 20 min after HS). In SAP rats, RBF responses to HS were blunted (125 +/- 6%) and RVC increases were abolished (108 +/- 5%) 20 min after HS. Isotonic solution increased RBF and RVC in sham rats (149 +/- 10 and 145 +/- 12% of baseline, respectively, at 20 min). These responses were reduced in SAP rats (131 +/- 6 and 126 +/- 5%, respectively, at 20 min). Pressor responses to HS were larger in SAP rats than in sham rats (17 +/- 5 versus 9 +/- 2 mmHg, at 20 min), whereas during VE these responses were similar in both groups (6 +/- 3 versus 4 +/- 6 mmHg, at 20 min). Immunohistochemical analysis indicates that microinjections of anti-DbetaH-saporin produced extensive destruction within the A1/C1 cell groups in the CVLM. These results suggest that catecholaminergic neurones mediate the cardiovascular responses to VE or increases in plasma sodium levels.     

The changes of skin temperature on hands and feet during and after T3 sympathicotomy for palmar hyperhidrosis

Unilateral thoracic sympathectomy in patients with palmar hyperhidrosis causes a skin temperature drop in the contralateral hand. A cross-inhibitory effect by the post-ganglionic neurons innervating hands is postulated as a mechanism of contralateral vasoconstriction. The purpose of our study was to evaluate whether this cross-inhibitory effect also occurs in the feet. Twenty patients scheduled for thoracoscopic sympathicotomy due to palmar hyperhidosis were studied. Right T3 sympathicotomy was performed first, followed by left T3 sympathicotomy. The thenar skin temperatures of both hands and feet were continuously monitored using a thermometer and recorded before induction of anesthesia, during the operation, 4 hr after and 1 week later. Following right T3 sympathicotomy, the skin temperature of the ipsilateral hand gradually increased, however the skin temperature of the contralateral hand gradually decreased. Immediately after bilateral sympathicotomy, the skin temperature differences between hands and feet increased, but these differences decreased 1 week later. Our results show that cross-inhibitory control may exist in feet as well as in the contralateral hand. Thus, the release of cross-inhibitory control following T3 sympathicotomy results in vasoconstriction and decrease of skin temperature on the contralateral hand and feet. One week later, however, the temperature balance on hands and feet recovers.     

Collagen birefringence in skin repair in response to red polarized-laser therapy

We use the optical path difference (OPD) technique to quantify the organization of collagen fibers during skin repair of full-thickness burns following low-intensity polarized laser therapy with two different polarization incidence vectors. Three burns are cryogenerated on the back of rats. Lesion L(parallel) is irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction. Lesion L(perpendicular) is irradiated using the electric field vector of the polarized laser radiation aligned perpendicularly to the aforementioned orientation. Lesion C is untreated. A healthy area labeled H is also evaluated. The tissue samples are collected and processed for polarized light microscopy. The overall finding is that the OPD for collagen fibers depends on the electric field vector of the incident polarized laser radiation. No significant differences in OPDs are observed between L(parallel) and H in the center, sides, and edges of the lesion. Lesions irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction show higher birefringence, indicating that collagen bundles in these lesions are more organized.