Diagnostic value of prostatic specific antigen in hirsute women

Determination of prostatic specific antigen (PSA) in female tissues has become available recently. The expression of PSA gene is under androgenic regulation. Therefore, hyperandrogenemic states, such as polycystic ovary syndrome (PCOS), are expected to be presented with the higher levels of PSA. The current study aimed at evaluating PSA levels in hirsute women presumed to have PCOS or idiopatic hirsutism (IH). Thirty-three patients with PCOS, 40 patients with IH, and 20 healthy control subjects were enrolled in the study. Beside basal hormonal evaluation, total PSA (tPSA), and free PSA (fPSA) were determined in all subjects. Average level of tPSA was the highest in PCOS patients (0.099+/-0.267 ng/ml) when compared with IH and control subjects (p<0.05 and p<0.001, respectively). Besides, mean fPSA levels were found to be significantly higher in patients with PCOS than healthy controls (0.033+/-0.070 vs 0.010+/-0.001 ng/ml; p<0.05). Both total and free PSA levels were found to be higher in 73 hirsute women than in control subjects (p<0.01 and p<0.05, respectively). Women with hyperandrogenemia tended to have higher tPSA than women without hyperandrogenemia (p<0.01). PSA is likely to be used to discriminate hyperandrogenemic hirsutism. If more sensitive assays become available, PSA might be used as a diagnostic criteria for hirsutism and even for some diseases which have hirsutism as a component.     

A ras-related protein is phosphorylated and translocated by agonists that increase cAMP levels in human platelets.

The antigenicity of platelet proteins was assayed against various monoclonal antibodies (mAbs) that recognize specific epitopes of the ras-encoded p21 protein. mAb M90, which detects the region of p21 protein within amino acids 107-130 and inhibits its GTP-binding activity, strongly reacted with a 22-kDa protein present in the particulate fraction of human platelets. Other mAbs against ras-encoded proteins, including Y13-259, which efficiently detects ras proteins from a variety of organisms, did not recognize the platelet 22-kDa protein. Transfer of the platelet 22-kDa protein to nitrocellulose paper showed that the protein binds [alpha-32P]GTP. Moreover, preincubation of the transferred protein with mAb M90 drastically reduced its GTP-binding activity. Treatment of platelets with iloprost, a prostacyclin analog, caused (i) a time-dependent increase of a 24-kDa protein that is recognized by mAb M90 in particulate and cytosolic fractions and (ii) the gradual decrease of the 22-kDa protein from the particulate fraction. When platelets were labeled with 32P and then treated with iloprost, the 24-kDa protein was found to be phosphorylated. The 32P-labeled 24-kDa protein was specifically immunoprecipitated by mAb M90. These results suggest that appearance of the 24-kDa protein results from phosphorylation of the 22-kDa protein, which shifts its mobility to a higher molecular mass area.     

The effect of short-term glycemic regulation with gliclazide and metformin on postprandial lipemia.

AIM: Exaggerated postprandial lipemia is now accepted as an independent risk factor in atherogenesis in type 2 diabetes mellitus. We investigated if better glycemic control improves fasting and postprandial lipid profile in type 2 diabetic patients in the short-term. METHODS: Thirty-two type 2 diabetic patients were studied before and after desired glycemic regulation with gliclazide and metformin. Basal levels of glucose, total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, insulin, and C-peptide were evaluated at fasting state. Afterwards, patients were given a standard 400-kcal mixed meal as a breakfast, contaning 35 % fat. At the 2nd and the 4th hours after the breakfast, postprandial glucose, triglyceride, insulin, and C-peptide levels were determined again. RESULTS: Significant decrease was observed in total cholesterol levels after better glycemic regulation (p<0.05). Besides, triglyceride levels decreased significantly from 175.36+/-17.85 mg/dl to 138.73+/-14.93 mg/dl at fasting state (p<0.05), from 197.26+/-20.85 mg/dl to 154.15+/-14.61 mg/dl at the 2nd hour after mixed meal (p<0.05), and from 209.63+/-28.54 mg/dl to 155.63+/-15.68 mg/dl (p<0.05) at the 4th hour after the mixed meal, when better glycemic profile was provided. Area under curve for triglyceride levels decreased significantly with the better glycemic regulation (p<0.01). CONCLUSIONS: Improved glycemic regulation can lower the raised fasting and postprandial triglyceride levels which are important atherosclerotic risk factors in diabetic patients even in short-term. Since this improvement in triglyceride levels comes early, diabetic patients can be evaluated for fasting and postprandial triglyceride levels in the first month of therapy.     

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis (“flesh-eating disease”). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the ΔmtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.     

Twenty-four hour 17-hydroxyprogesterone response to adrenocorticotropine in adrenal incidentalomas: augmented response after adrenalectomy in two patients

The current study aimed to investigate the midterm (24 hour) response of 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulphate (DHEA-S) to synthetic high-dose adrenocorticotropin (ACTH) in adrenal incidentalomas (Al). Seventeen patients with Al and 40 age- and sex-matched controls received synthetic ACTH (tetracosactide, 1000 microg, IM). Plasma, 17-OHP and DHEA-S were collected in basal conditions and after 1, 4, 6, 8 and 24 hours. (HPA) axis was also evaluated using circadian serum cortisol, urinary free cortisol and over-night 2 mg dexamethasone suppression. Basal plasma 17-OHP levels did not differ among the groups. However, the increment in plasma 17-OHP in patients both in terms of peak [13.76 +/- 2.52, 4.77 +/- 0.30ng/ml, mean +/- S.E.M, p < 0.001] and area under the curve [190 +/- 46, 96.75 +/- 32 ng/ml/h, p < 0.001] were significantly higher than that of the controls. Stimulated 17OH-P levels never reached 9.1 ng/ml in controls. Sixty-five (11/17) % of the patients were found to have exaggerated response. Three of the patients were found to have subclinical Cushing's syndrome and interestingly, two augmented their 17-OHP response to ACTH after unilateral adrenalectomy and normalisation of their HPA axis. Basal DHEA-S levels of the patients were significantly lower [99.21 +/- 45, 230.18 +/- 34 microg/dl, p < 0.01] and stayed persistently lower than that of the controls. Evidence of a heterozygous 21 hydroxylase deficiency, as indicated by the exaggerated 17-OHP response to ACTH, has been widely reported in Al patients. However, to our knowledge to date there is no report on augmented 17-OHP response to ACTH after adrenalectomy. Possible reasons for the augmentation were discussed.     

Relationship between thyroid autoimmunity and Yersinia enterocolitica antibodies.

It has previously been proposed that subclinical Yersinia enterocolitica infection may play a role in autoimmune thyroid disease (AITD). In this study, we investigated the relationship between the thyroid autoantibodies and the antibodies that produced against different serotypes of Y. enterocolitica. A total of 215 subjects were included into the study (65 newly diagnosed Graves' disease [GD], 57 Hashimoto's thyroiditis [HT], 53 nontoxic diffuse goiter [NTDG], and 40 subjects for control group [CG]). Thyroid receptor antibodies (TRAb), thyroid and agglutinating antibodies against Y. enterocolitica serotype O:3, O:5, O:8, O:9 were measured in the blood samples. The highest incidence of Y. enterocolitica antibody positivity was measured in GD (53.8% for O:3, 29.2% for O:5, 44.6% for O:8, and 40% for O:9) and followed by HT. In patients with GD, TRAb levels were also higher than in patients with HT, NTDG, and CG. There was no difference between NTDG and CG in respect to the titer levels and the positivity of both TRAb and Y. enterocolitica antibodies. There was also a weak linear correlation between TRAb level and the titer of antibodies against Y. enterocolitica antigens. It can be concluded that Y. enterocolitica infection may play a role in etiology of GD in Turkey.     

The Phenotypic Characterization of A13/BACii, a Novel Bovine Chondrocytic Cell Line with Differentiation Potential

In cartilage research bovine articular cartilage is used as an alternative to human tissue. However, animal material is subject to availability and primary cultures undergo senescence, limiting their use. Here we report the immortalization of primary bovine chondrocytes, which could be used as a surrogate for freshly isolated chondrocytes. Chondrocytes were isolated from cartilage explants and immortalized using 1.0 μg/ml benzo[alpha]pyrene. For 3-dimensional culture, chondrocytes were resuspended in 0.5% low-melt agarose at high density (HD) and cultured for 24 h prior to determining changes in expression profile and morphology. A13/BACii chondrocytes acquired a 'flat' irregular morphology and a foetal-like cell volume (1,509.59 ± 182.04 μm(3)). The human cell line C-20/A4 showed a statistically similar volume and length to A13/BACii. Two-dimensional-cultured A13/BACii expressed elevated levels of type I collagen (col1), reduced levels of type II collagen (col2) compared to freshly isolated chondrocytes and an overall col2 to col1 expression ratio (col2:col1) of 0.11 ± 0.01. Upon 3-dimensional encapsulation, there was a significant rise in col2 expression in both A13/BACii and C-20/A4, suggesting a capacity for redifferentiation in both cell lines with a return of col2:col1 values of A13/BACii to values previously observed in primary chondrocytes. A13/BACii chondrocytes expressed aggrecan, matrix metalloproteinase (MMP)-3, MMP-9 and MMP-13, further supporting indications of the differentiated phenotype. Here we report the creation of a novel chondrocytic cell line and demonstrate its strong potential for redifferentiation upon HD 3-dimensional encapsulation, providing an alternative to conventional dedifferentiated cell lines and primary culture.     

Iloprost-induced translocation of a 23-kDa protein that is recognized by a Gs alpha antiserum.

We have observed that iloprost, a prostacyclin analog, causes the translocation of a 23-kDa protein from the membrane to the cytosol of human platelets. This 23-kDa protein is recognized by a Gs alpha (alpha subunit of stimulatory guanine nucleotide binding regulatory protein) antiserum but is not ADP-ribosylated by cholera toxin. The translocation of the Gs alpha-related protein might be an important part of the complex chain of events resulting in agonist-induced desensitization.