Biomedical subjects

Georg Schatzl

Publications and source records attributed to Georg Schatzl.

At least 19 recordsLinked to original sources

PubMed2006

Correlation of leukocytospermia with clinical infection and the positive effect of antiinflammatory treatment on semen quality.

OBJECTIVE: To investigate the correlation between leukocytospermia, bacteriospermia, and clinical signs of infection and to evaluate antiinflammatory therapy. DESIGN: Prospective nonrandomized study. SETTING: Andrologic clinic at university hospital. PATIENT(S): A total of 56 patients were evaluated, and 12 of them received further treatment with a Cox-2 inhibitor. INTERVENTION(S): Semen analysis and clinical investigation were done according to World Health Organization guidelines. Serum levels of leukocytes, C-reactive protein (CRP), and prostate-specific antigen (PSA) were measured from blood samples. MAIN OUTCOME MEASURE(S): Sperm concentration, leukocyte concentration, serum leukocyte count, CRP, PSA, bacterial growth. RESULT(S): Leukocytospermia (>1 x 10(6)/mL) was present in 60.7% of the semen samples, significant pathogenic bacterial growth was detectable in 35.7%, and 14.3% of the samples fulfilled the criteria for ejaculate signs of infection. All serum parameters were within the normal range. In abacterial leukocytospermia, treatment with a Cox-2 inhibitor decreased leukocytospermia from 5.5 x 10(6)/mL to 1.0 x 10(6)/mL (P=.001) and increased sperm concentration from 22.5 x 10(6)/mL to 48.0 x 10(6)/mL (P=.02). CONCLUSION(S): There was no evidence of an immune response in the peripheral blood system. In abacterial leukocytospermia, treatment with a Cox-2 inhibitor seems to be able to reduce leukocytospermia and increase sperm count.

Adult↗

PubMed2005

Value of counting white blood cells (WBC) in semen samples to predict the presence of bacteria.

OBJECTIVES: To investigate the correlation between the presence of white blood cells (WBC) without the use of specific stain to differentiate leukocytes and the presence of bacteria in semen samples of infertile men. METHODS: A total of 143 semen samples of men who attended an andrologic clinic for the evaluation of fertility were investigated using routine semen analysis (according to WHO laboratory guidelines) and bacterial culture. RESULTS: WBC were found in 43.4% (62/143). There were no WBC in 56.6% (81/143) of the samples (group I) while WBC were found in 43.4% (62/143) of the samples (group II). Pathogenic bacteria were detected in 48.2% (39/81) in group I and in 54.9% (34/62) in group II, all in all Bacteriospermia was present in 51.1% (73/143). The most common bacteria were Ureaplasma urealyticum, Enterococcus faecalis and Escherichia coli (23.8%, 16.8%, and 7.0% of samples, respectively). The sensitivity/specificity for detecting bacteria was 0.47/0.60 at a cut-off level of 0.25 Mio/mL WBC and 0.16/0.84 at a cut-off level of WBC 1 Mio/mL, representing likelihood ratios of 1.16 and 1.04, respectively. The greatest ratio between sensitivity and specificity (0.37/0.72) was found at a cut-off level of 0.5 Mio/mL WBC, with a likelihood ratio of 1.29. CONCLUSIONS: Counting WBC instead of a specific stain for the detection of leukocytes has only a poor sensitivity/specificity for the detection of bacteria.

Cell Count↗

PubMed2005

Reoperation, myocardial infarction and mortality after transurethral and open prostatectomy: a nation-wide, long-term analysis of 23,123 cases.

OBJECTIVE: To analyse long-term rates of reoperation, myocardial infarction and mortality after transurethral (TURP) and open prostatectomy (open PE) in a nation-wide analysis. MATERIAL AND METHODS: Patients who underwent TURP (n=20,671) or open PE (n=2452) in Austria between 1992 and 1996 entered this study and were followed for up to 8 years. Actuarial cumulative incidences of reoperation (TURP, urethrotomy, bladder neck incision), myocardial infarction and death after 1, 5 and 8 years were calculated. Data were provided by the Austrian Health Institute (OBIG). RESULTS: Actuarial cumulative incidences of a secondary TURP after primary TURP at 1, 5 and 8 years were 2.9%, 5.8% and 7.4%; the respective numbers after open PE 1.0%, 2.7% and 3.4%. The overall incidence of a secondary endourological procedure (TURP, urethrotomy, bladder neck incision) within 8 years was 14.7% after TURP and 9.5% after open PE. The 8 years incidence of myocardial infarction was identical after TURP (4.8%) and open PE (4.9%). In parallel, mortality rates at 90 days (TURP: 0.7%; open PE: 0.9%), one year (2.8% vs. 2.7%), 5 years (12.7% vs. 11.8%) and 8 years (20% vs. 20.9%) was identical after TURP and open PE. CONCLUSIONS: This large-scale, contemporary, nation-wide analysis confirms the higher reoperation rate after TURP compared to open PE. We observed no excess risk of myocardial infarction or death after TURP compared to open PE.

Actuarial Analysis↗

PubMed2005

Constant decline in sperm concentration in infertile males in an urban population: experience over 18 years.

OBJECTIVE: To investigate semen quality in infertile men from an urban population over an 18-year period. DESIGN: Retrospective study. SETTING: Andrology clinic at a city university hospital. PATIENTS: A total of 9,327 men were referred to the clinic for infertility investigation. After excluding those with azoospermia, 7,780 samples were evaluated. INTERVENTION(S): Semen samples were analyzed within half an hour of production using computer-automated semen analysis and phase microscopy. MAIN OUTCOME MEASURE(S): Sperm concentration, morphology, and motility; semen pH and leukocyte concentration; and patient age. RESULT(S): The median patient age over the study period was 31.6 years, with an increase from 30.8 years in 1986 to 34.4 years in 2003. The median sperm concentration was 10.25 million/mL for the entire period, with a decline from 27.75 million/mL in 1986 to 4.60 million/mL in 2003. The median proportion of normally shaped spermatozoa was 15%, and the proportion of motile spermatozoa was 21%. The pH increased from 7.4 in 1986 to 7.9 in 2003, and the median leukocyte concentration was 1.50 million/mL. CONCLUSION(S): A constant decline in median sperm concentration was found in the infertile men. The reason for this remains unclear, although the high pH and leukocyte concentration indicates the involvement of infection.

Adult↗

PubMed2005

Polymorphism in ARE-I region of prostate-specific antigen gene associated with low serum testosterone level and high-grade prostate cancer.

OBJECTIVES: To examine the impact of polymorphism in the androgen-responsive element I region of the prostate-specific antigen (PSA) gene on the serum testosterone level and Gleason score in patients with newly diagnosed, untreated prostate cancer (PCa). High-grade PCa is associated with a low serum testosterone level, and the testosterone level has been negatively correlated with the expression of PSA. METHODS: Endocrine factors (including testosterone, follicle-stimulating hormone, and luteotropic hormone), PSA level, prostate volume, and Gleason score were measured in 134 patients with untreated, biopsy-verified PCa. PSA polymorphism was determined by polymerase chain reaction-based methods using DNA from peripheral blood samples. RESULTS: Patients with the PSA G/G genotype had lower serum testosterone levels (3.5 +/- 1.2 ng/mL) than those with the A/A genotype (4.3 +/- 1.6 ng/mL) or the A/G genotype (4.4 +/- 1.5 ng/mL). The PSA level in the A/A and A/G genotype groups were significantly lower than that in the G/G genotype group (18.2 +/- 55.0 ng/mL versus 20.5 +/- 27.6 ng/mL, P = 0.013). In a multiple logistic regression model, the odds ratio for the G/G polymorphism was significantly increased for Gleason score (odds ratio 2.4, 95% confidence interval 1.6 to 10.4; P = 0.02) and serum testosterone level (odds ratio 0.44, 95% confidence interval 0.36 to 0.94; P = 0.01) relative to genotypes A/A and A/G. CONCLUSIONS: Our results showed that the PSA G/G genotype is associated with a greater Gleason score and serum PSA level but lower serum testosterone level and could be considered a risk factor for a poor outcome of PCa.

Adult↗

PubMed2005

Treatment of testicular cancer: influence on pituitary-gonadal axis and sexual function.

OBJECTIVES: To investigate the influence of treatment for testicular cancer on the pituitary-gonadal axis and sexual function in long-time survivors after unilateral orchiectomy. METHODS: Blood was drawn from patients treated for testicular cancer during routine oncologic follow-up for measurement of luteinizing hormone, follicle-stimulating hormone, sexual hormone-binding globulin, testosterone, and bioavailable testosterone. Sexual function was evaluated using the International Index of Erectile Function 15-item (IIEF-15) questionnaire. Patients were grouped according to treatment: group 1 followed a surveillance strategy, group 2 received two cycles of carboplatin monotherapy, and group 3 underwent cisplatin, etoposide, and bleomycin chemotherapy. RESULTS: No statistically significant difference was found in the serum hormonal levels among the three groups, and all hormonal levels were within the 95% confidence range, except for follicle-stimulating hormone. The median serum testosterone level was 3.5 ng/mL in group 1, 3.9 ng/mL in group 2, and 4.2 ng/mL in group 3. In group 1, the median IIEF-15 score was 64.0, and the median Erectile Function (EF) domain score was 28. The median scores in groups 2 and 3 were 62.5 for IIEF-15 and 27.5 for EF and 65.0 for IIEF-15 and 30.0 for EF, respectively. No correlation was found between testosterone level and IIEF-15 or EF score. CONCLUSIONS: None of the treatments investigated had a significant influence on the serum hormonal levels in long-time survivors of testicular cancer. Patients undergoing chemotherapy have no greater risk of developing a hormonal disorder than those following a surveillance strategy, and therapy for testicular cancer is not a risk factor for erectile dysfunction.

Adult↗

PubMed2005

The impact of age, body mass index and testosterone on erectile dysfunction.

PURPOSE: Erectile dysfunction (ED) may be associated with low serum total testosterone (T), low serum bioavailable testosterone (BAT) and high body mass index (BMI) in aging men. MATERIALS AND METHODS: A total of 675 workers (age range 45 to 60 years old) were entered into this study. Investigations were performed directly at their place of work. Exclusion criteria were abnormal urogenital status, antihypertensive drugs, medication possibly affecting the endocrine function and a history of previous pelvic trauma. T and sex hormone-binding globulin were measured with commercially available assays, and BAT was calculated from T and sex hormone-binding globulin. BMI was assessed and every individual completed a self-administrated questionnaire for erectile function (International Index of Erectile Function [IIEF-5]). RESULTS: T and BAT showed a significantly negative correlation with age and BMI. Each additional year of increase in age caused a decrease in the IIEF-5 score of 0.195 (p <0.001). Increase in BMI by 1 kg/m reduced IIEF-5 by 0.141, independent of age (p =0.005). Multiple logistic regression analyses confirmed the influence of increased age and higher BMI on the risk of ED. The corresponding odds ratio for ED was 1.082 (p <0.001) and 1.076 (p <0.001), respectively. These data indicate an increase in ED risk by 8.2% per year and by 7.6% per kg/m BMI. Severe cases of ED (IIEF-5 score 7 or less) were significantly associated with a decrease in T and BAT. Individuals with low BAT (1 ng/ml or less) had a 3 times higher risk of severe ED compared with men with BAT greater than 1 ng/ml (odds ratio 3.045, 95% CI 1.088 to 8.522, p =0.034). The result of the multiple logistic regression analysis was adjusted to age and BMI, and did not show a significant influence on the incidence of severe ED. CONCLUSIONS: BMI contributes strongly to ED. Low T or BAT are only relevant if IIEF-5 questionnaire results in severe ED.

Age Factors↗

PubMed2003

Reduced circulating androgen bioactivity in patients with prostate cancer.

BACKGROUND: Previous studies on immunoreactive androgen levels in serum have revealed equivocal associations with the risk of prostate cancer (CaP). The aim of this study was to compare serum biological androgen activity between men with newly diagnosed CaP and age-matched men with benign prostatic hyperplasia (BPH). METHODS: Caucasian men with newly diagnosed, untreated CaP (n = 101) and age-matched patients with BPH (n = 103) were investigated. Serum androgen bioactivity (ABA) levels were measured using a recently developed recombinant cell bioassay. RESULTS: In comparison to men with BPH, CaP patients with Gleason score >or=8 (n = 16) had lower serum ABA (P < 0.05), and patients with Gleason score or=8 (P = 0.07) displayed suppressed ABA levels in relation to serum testosterone. As the entire group, men with CaP (n = 101) had significantly lower serum ABA than age-matched men with BPH (n = 103): median 3.0 nM (range, 0.8-6.4 nM) versus 3.2 nM (range, 0.8-7.9 nM) testosterone equivalents, respectively (P < 0.005). By contrast, serum immunoreactive testosterone and SHBG concentrations and free androgen indices did not differ significantly between the two groups. CONCLUSIONS: Patients with CaP have lower serum ABA than controls with BPH, and men with low or high Gleason score display suppressed circulating ABA-to-testosterone ratio. These features may reflect interaction between variables such as the degree of tumor differentiation and tumor volume with androgen metabolism.

Aged↗

PubMed2003

Serum androgen levels in men: impact of health status and age.

OBJECTIVES: To investigate the impact of health status on androgen levels in men and to assess the age-related changes in androgen levels. METHODS: Sera were obtained from 526 men (age 20 to 89 years) participating in a health screening project and 35 men selected according to the SENIEUR protocol, which excludes those with underlying disease. The health screening project participants were divided into two groups: healthy men (n = 133; group 1) and the remainder (n = 393; group 2). The total testosterone and sex hormone-binding globulin levels were quantified, and the amount of free testosterone (cfT) was calculated. RESULTS: The lowest annual declines in androgen level were observed in group 3 (testosterone 0.2%; cfT 0.4%), followed by group 1 (testosterone 0.4%; cfT 0.8%) and group 2 (testosterone 0.8%; cfT 0.9%). Body mass index and levels of cholesterol, triglycerides, and glucose correlated negatively (P <0.01) with testosterone and cfT. Decade-adjusted reference values (mean +/- 2 standard deviations) for testosterone and cfT were defined. The proposed lower testosterone reference value declined gradually from 3.1 ng/mL (20 to 29 years) to 1.7 ng/mL (70 years or older). CONCLUSIONS: In this cross-sectional study, serum androgens declined in aging men, and the extent of this decrease correlated with health status. A fixed, non-age-adjusted reference value does not adequately reflect this and might lead to a false diagnosis of androgen deficiency, particularly in elderly men. The clinical value of age-related reference values, however, needs to be determined in prospective studies.

Adult↗

PubMed2003

The natural history of lower urinary tract symptoms over five years.

OBJECTIVES: To assess the natural history of lower urinary tract symptoms (LUTS) in a cohort of previously untreated men over five years. METHODS: Men participating in a health-screening project completed the International Prostate Symptom Score (IPSS) in 1996. In 2001, men older than 45 years with no prostate surgery or LUTS-specific medication before 1996 completed the IPSS plus a questionnaire on several aspects of LUTS. At the same time, all men underwent a health examination in 1996 and 2001. RESULTS: A total 456 men aged 52+/-12 years (range: 40-84) at baseline completed the 5-year follow-up. Mean IPSS increased from 4.6 to 5.5 (+20%; p<0.0001) and the IPSS-Ql from 0.8 to 1.1 (+38%; p<0.0001) over five years. Progression of IPSS and IPSS-Ql were highly correlated. No change of IPSS was reported by 19%, a worsening by 50% and an improvement by 31%. Not all aspects of LUTS progressed in a similar pattern, storage symptoms had a higher tendency to improve over time. Medical therapy was initiated in 7%, 39% and 67% of those with mild, moderate or severe LUTS at baseline, respectively. In a multivariate analysis age and degree of being bothered by LUTS were independent predictors for initiation of therapy. CONCLUSIONS: This 5-year longitudinal study of men without previous LUTS treatment demonstrates the slow nature of the disease's progression. Not all aspects of LUTS progress in a similar pattern. Initiation of therapy is influenced by patient age and by the degree of being bothered by LUTS.

Adult↗

PubMed2003

Associations of serum testosterone with microvessel density, androgen receptor density and androgen receptor gene polymorphism in prostate cancer.

PURPOSE: We investigate potential associations of serum testosterone with microvessel density, androgen receptor expression and AR gene polymorphism in men with untreated prostate cancer. MATERIAL AND METHODS: Serum luteinizing hormone, follicle-stimulating hormone, estradiol and testosterone were determined in men with newly diagnosed prostate cancer. The number of tumor vessels per 0.46 mm. and androgen receptor density (as the percent positive nuclei) were quantified immunohistochemically on prostate cancer areas of prostate biopsy specimens. Polymorphisms within the AR gene (number of CAG repeats) were determined by polymerase chain reaction and restriction fragment length polymorphism analysis using DNA from peripheral blood. RESULTS: The 39 men entered into this study were grouped into 16 with low (3 ng./ml. or less, group 1) and 23 with normal (greater than 3 ng./ml., group 2) serum testosterone. Mean prostate specific antigen +/- SD was significantly lower in group 1 than in group 2 (18.8 +/- 11.1 versus 27.2 +/- 12.2 ng./ml., p = 0.03). Mean Gleason score (7.4 +/- 1.3 versus 6.0 +/- 1.2, p = 0.01), androgen receptor density (96.6% +/- 2.8% versus 84.8% +/- 7.2%, p = 0.03) and tumor vessel density (63.0 +/- 30.8/0.46 versus 39.0 +/- 22.9/0.46 mm.2, p = 0.007) were significantly higher in group 1 than in group 2. The number of CAG repeats within the AR gene did not correlation with serum androgen. CONCLUSIONS: Low serum testosterone in men with newly diagnosed prostate cancer is associated with higher tumor microvessel and androgen receptor density as well as with higher Gleason score, suggesting enhanced malignant potential.

Aged↗

PubMed2002

C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils.

We have recently shown that resting human mast cells (MCs) produce tissue-type plasminogen activator (t-PA) without simultaneously expressing plasminogen activator inhibitor 1 (PAI-1). In the present study we have identified the anaphylatoxin rhC5a as a potent inducer of PAI-1 expression in human MCs and basophils. In primary human skin MCs and primary blood basophils, exposure to rhC5a was followed by an increase from undetectable to significant levels of PAI-1. In addition, rhC5a induced a concentration- and time-dependent increase in PAI-1 antigen in the MC line HMC-1 and the basophil cell line KU-812 and increased the expression of PAI-1 mRNA in HMC-1. In conditioned media of HMC-1 treated with rhC5a, active PAI-1 could be detected. A simultaneous loss of t-PA activity in conditioned media from the same cells indicated that rhC5a-induced PAI-1 was capable of inhibiting the enzymatic activity of coproduced t-PA. Correspondingly, the levels of t-PA-PAI-1 complexes increased in rhC5a-treated cells. When HMC-1 cells were incubated with pertussis toxin or anti-C5a receptor antibodies, the effect of rhC5a on PAI-1 production was completely abolished. Treatment of C5a with plasmin resulted in loss of its ability to induce PAI-1 production in MCs. Considering the suggested role for MCs and components of the complement system in the development of cardiovascular diseases, we hypothesize that MCs, by producing t-PA in a resting state and by expressing PAI-1 when activated by C5a, might participate in the modulation of the balance between proteases and protease inhibitors regulating tissue injury and repair in such disease processes.

Antigens, CD↗

PubMed2002

Association of polymorphisms within androgen receptor, 5alpha-reductase, and PSA genes with prostate volume, clinical parameters, and endocrine status in elderly men.

BACKGROUND: The aim of this study was to assess the impact of polymorphisms of three genes within the androgen pathway on prostate volume, clinical parameters, and endocrine status. METHODS: Elderly men with lower urinary tract symptoms underwent clinical and endocrine work-up. In parallel, polymorphisms within the 5alpha-reductase gene (SRD5A2 V89L and A49T), the androgen receptor gene (AR; number of CAG repeats), and the prostate specific antigen (PSA) gene (A --> G substitution at position-158) were determined by polymerase chain reaction and restriction-length polymorphism analysis by using DNA from peripheral blood. RESULTS: A total of 190 men (66.5 +/- 9.2 yr) were analyzed. The number of CAG repeats within the AR and the PSA polymorphism revealed no associations to clinical and endocrine parameters. Individuals carrying the mutated SRD5A2 A49T allele (5.3% of the total population) had larger prostates (54.1 vs. 39.3 ml), higher PSA levels (12.2 vs. 4.3 ng/ml), and a 35% reduction in prostatic stroma/epithelial cell ratio. Men with the mutated SRD5A2 V89L gene had lower testosterone levels. CONCLUSIONS: In contrast to prostate cancer, polymorphisms within AR and PSA genes do not seem to be of importance for benign prostatic hyperplasia. Polymorphisms within the 5alpha-reductase gene are interesting biomarkers for the development of benign prostatic hyperplasia and benign prostatic enlargement.

Aged↗

PubMed2002

DNA profiles and numeric histogram classifiers in nephrogenic adenoma.

BACKGROUND: The malignant potential of nephrogenic adenoma is still a matter of controversy and therapeutic regimens of this morphologic entity range from partial, even total cystectomy to watchful waiting. The objective of the current study was to evaluate several robust image cytometry-DNA histogram classifiers and to search among those for factors that separate a biologically nonaggressive metaplastic lesion from lesions with increased malignant potential. METHODS: The study included bladder irrigation specimens, 23 preceding transurethral resection of nephrogenic adenoma and 24 preceding resection of papillary bladder carcinoma. Feulgen-stained nuclei were imported to a static image analysis system, and densitometric data were interpreted by two different software programs. Histograms were described numerically by DNA index, 2c deviation index, and by 5c/9c-exceeding and euploid polyploidy rates. In addition, an interpretation algorithm based on a dual parameter analysis with an integrated automatic threshold was used. RESULTS: The numeric classification of DNA histograms of patients suffering from nephrogenic adenoma resulted in DNA indices between 0.91 and 1.15. The 2c deviation indices ranged from 0.03 to 0.43, and the 5c exceeding rates ranged from 0.0 to 1.58. None of the measurements showed nuclei exceeding 9c. The p25-75 ranges of 2c deviation indices in nephrogenic adenoma and papillary urothelial carcinoma did not overlap. These findings might be explained by minor proliferative activity in nephrogenic adenoma. Euploid polyploidy rates less than 5% confirm this explanation. Risk analysis documented high risk only for those patients with nephrogenic adenomas who had proven transitional cell carcinoma in their history. CONCLUSIONS: DNA estimation by image cytometry of urinary bladder irrigation specimens appears able to separate papillary bladder lesions. The method detects those lesions with higher malignant potential but is limited in separating entities with low malignant potential. Comparison of the discriminative power of robust numeric DNA classifiers reveals the 2c deviation index superior to the widely used DNA index and the 5c exceeding rate in this material.

Adenoma↗

PubMed2002

Vitamin D receptor gene polymorphism and prostate cancer risk.

BACKGROUND: 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts antiproliferative effect on prostatic cells, mediated through the vitamin D receptor. In a case-control study, we examined whether the vitamin D receptor (VDR) gene polymorphism in exon 9 could affect prostate cancer susceptibility. METHODS: One hundred ninety newly diagnosed prostate cancer patients and 190 age-matched men with benign prostatic hyperplasia (BPH), in whom the presence of prostate cancer was excluded clinically or histologically, were recruited for this study. The VDR TaqI polymorphism was investigated by polymerase chain reaction (PCR) following restriction fragment length polymorphism using DNA from lymphocytes. Depending on the presence or absence of the TaqI restriction site at the third position of codon 352, patients were classified as TT, Tt, or tt. RESULTS: The frequency of the tt genotype was not significantly different between prostate cancer patients (18%) and controls (12%; P = 0.07). The odds ratio (OR), calculated relative to individuals with the TT genotype was 1.76 (95% confidence limit (CL) = 0.90-3.45). After stratification for Gleason score and prostate specific antigen levels in a case-case comparison (n = 190), no significant associations with the VDR genotypes were detectable either. CONCLUSIONS: In this case-control study of Austrian Caucasians, no statistically significant association of the VDR TaqI polymorphism and prostate cancer risk was found.

Aged↗

PubMed2002

Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis.

OBJECTIVES: To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy (RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. METHODS: Patients with PCa before RP (n = 49), those who underwent TURP for BPH (n = 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n = 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. RESULTS: No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P = 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P = 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P = 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P < 0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. CONCLUSIONS: Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH.

Aged↗

PubMed2002

Polymorphic CAG repeats in the androgen receptor gene, prostate-specific antigen polymorphism and prostate cancer risk.

As the development of prostate cancer is androgen-dependent, it has been hypothesized that variation in transcriptional activity by the androgen receptor (AR) related to polymorphic CAG repeats in exon 1, influences prostate cancer risk. The AR regulates gene transcription by binding to androgen-response elements (AREs) in target genes, such as the prostate-specific antigen (PSA). In the ARE-I sequence of the PSA gene an adenine to guanine polymorphism is described. It has been hypothesized that the AR binds the two PSA alleles (A and G) with differing affinities and may, thereby, differentially influence prostate cancer risk. To examine the role of the polymorphisms in the AR and PSA genes in prostate cancer susceptibility, we conducted a case-control study of Austrian Caucasians with 190 newly diagnosed prostate cancer patients and 190 age-matched control men with benign prostatic hyperplasia (BPH). The polymorphisms were determined by polymerase chain reaction (PCR)-based methods using DNA from peripheral white blood cells. Logistic regressions were performed to calculate odds ratios (OR) and confidence limits (CL) and to control for possible confounders. Our data provide no evidence for an association between prostate cancer and CAG repeat length. However, we found a significant influence of the ARE-I PSA polymorphism on prostate cancer risk, when calculating the combination of the A/G and G/G genotypes relative to subjects with the A/A genotype (OR = 0.63; 95% CL 0.39-0.99; P = 0.048), suggesting that the G allele has a protective effect. In a case analysis according to Gleason score, the PSA G/G genotype was significantly more frequent in patients with Gleason score >7 (35.1%) than in patients with Gleason score <7 (21.5%), providing evidence that the PSA G/G genotype is associated with more advanced disease at time of diagnosis. However, the ambivalent role of the PSA during prostate carcinogenesis needs further investigation.

Aged↗

PubMed2002

Detection of novel CD antigens on the surface of human mast cells and basophils.

BACKGROUND: Mast cells (MC) and basophils are effector cells of allergic reactions. Growth and function of these cells are regulated by a network of cytokines, other ligands, and respective cell surface membrane receptors. METHODS: In the present study, we examined the expression of novel CD antigens on human lung MC, skin MC, blood basophils, the MC line HMC-1, and the basophil cell line KU-812. Expression of surface antigens was analyzed by monoclonal antibodies (mAbs) and indirect immunofluorescence staining techniques. RESULTS: Primary MC were found to react with mAbs against KIT (CD117), the signal regulatory protein SIRP-alpha (CD172a), and the ectoenzyme E-NPP3 (CD203c). Human basophils were found to express large amounts of E-NPP3 and lower levels of Siglec-5 (CD170), CXCR4 (CD184) and SIRP-alpha. The HMC-1 cell line was recognized by mAbs against SIRP-alpha, CXCR4, endothelial protein C receptor (CD201) and E-NPP3. KU-812 cells were found to react with mAbs against E-NPP3, CXCR4 and glycophorin C (CD236R), but did not react with mAb against endothelial protein C receptor. Most of the other CD antigens tested disclosed negative results. CONCLUSIONS: In summary, our data provide further evidence that MC and basophils express a unique composition of surface antigens. The use of novel CD antibodies may help to isolate MC and basophils and to study their functional properties.

Antibodies, Monoclonal↗