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Biomedical subjects

S Madersbacher

Publications and source records attributed to S Madersbacher.

108 records · Page 6Linked to original sources
PubMed1993

Morphology of tissue destruction induced by focused ultrasound.

The effect of high-intensity focused ultrasound (HIFU) ablation on the morphology of prostatic, renal and testicular tissue was studied by light and electron microscopy. Specimens were obtained in 21 patients 1 h to 10 weeks after lesioning. Histological findings showed consistent coagulative necrosis with precisely defined, sharp margins to normal tissue. Lesion size and position correlated well with the assumed target zones, suggesting that HIFU permits therapeutic tissue ablation.

Humans↗
PubMed1993

Tissue ablation in benign prostatic hyperplasia with high-intensity focused ultrasound.

The safety and effectiveness of tissue ablation by coagulative necrosis with high-intensity focused ultrasound (HIFU) applied through a rectal probe to 36 patients with symptomatic benign prostatic hyperplasia (BPH) was investigated in a phase II clinical trial. Overall, HIFU treatment was well tolerated, the mean hospital stay being 1.1 days. Negative side effects were transient urinary retention in 32/36 patients, hematuria in 2 patients and hematospermia resolving after 3-4 weeks (n = 15). After 3 months the maximum flow rate/s (Qmax) increased from 9.0 +/- 3.9 to 14.4 +/- 7.0 ml/s, the median flow rate/s (QM90) from 4.9 +/- 2.4 to 7.6 +/- 4.17 ml/s; the postvoid residual volume decreased from 128 +/- 88 to 57 +/- 35 ml and the AUA symptom score from 25.5 +/- 5 to 13.2 +/- 4.4. In conclusion, it was shown that tissue ablation in patients with symptomatic BPH using HIFU is safe and dramatically reduces both obstructive and irritative symptoms and leads to a significant increase in uroflow and a decrease in postvoid residual volume.

Feasibility Studies↗
PubMed1993

[Antigenic determinants of human chorionic gonadotropin (hCG): identification of epitopes and determination of their biological functions, for use in immunometric test systems and development of a fertility regulating vaccine].

Analysing immunologically relevant structures of human chorionic gonadotropin (hCG), a glycoprotein hormone, has bearing on a variety of clinical features. These structures are of importance for the establishment of immunometric assays for the diagnosis and monitoring of pregnancy and hCG producing tumours. Moreover, the development of fertility regulating vaccines by the use of one of the subunits of hCG (hCG beta) or a synthetic peptide corresponding to the carboxyl-terminal peptide thereof (hCG beta CTP, beta 109-145) requires detailed knowledge of the antigenic properties of hCG. It appeared that 16 different antigenic epitopes are localized on the protein backbone of hCG and that the carbohydrate moieties do not contribute significantly to the immunological properties of this hormone. Reduced and carboxylmethylated subunits of hCG, i.e., hCG alpha and hCG beta, express only 1 alpha- and 2 beta-epitopes, the majority of antigenic determinants being destroyed by this chemical procedure. Epitopes of hCG are thus predominantly dependent on the intact tertiary or quaternary structure of the protein. The urinary low molecular weight fragment of hCG beta (hcG beta cf), a predominant molecular fraction in the urine of pregnant women or patients with various tumours expresses 7 out of 9 epitopes of hCG beta (beta 1- beta 7), whereas two antigenic determinants, beta 8 and beta 9, are localized on the hCG beta CTP.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Time-resolved immunofluorometry and other frequently used immunoassay types for follicle-stimulating hormone compared by using identical monoclonal antibodies.

The influence of assay design and quantification system on assay performance was investigated by developing, optimizing, and comparing a time-resolved immunofluorometric assay (IFMA), an immunoenzymometric assay (IEMA), an immunoradiometric assay (IRMA), and a competitive radioimmunoassay (RIA), all performed with the same monoclonal antibodies (MCA) directed against human follicle-stimulating hormone (hFSH). The lowest detection limit (2 ng/L for hFSH-I-3, corresponding to 2.5 mIU of 1st International Reference Preparation of hFSH 78/549 per liter), the widest measuring range (2-160,000 ng/L), and the greatest signal-to-noise ratio (13,000:1 at 160,000 ng/L) were obtained in the IFMA. For analysis of serum samples from 101 male (ages 2-91 years) and 99 female (ages 2-90 years) individuals at a single dilution, 100% of samples were within the measuring range of the IFMA, whereas only 87%, 55%, 32%, and 8% of the sera were for the IRMA, the IEMA evaluated with double-wavelength measurement, the conventional IEMA, and the competitive MCA-based RIA, respectively. These studies demonstrate clear advantages of the IFMA in sensitivity and assay range, which allows reliable and cost- and time-effective determination of hFSH in individuals from infancy to senescence.

Adolescent↗
PubMed1993

Does tumor-derived human chorionic gonadotropin act as a thyroid stimulator in vivo?

To evaluate in vivo the proposed intrinsic thyroid-stimulating hormone (TSH) activity (TSA) of human chorionic gonadotropin (hCG), we monitored over 0.5-1 years the thyroid status of eight patients with hCG-producing non-seminomatous testicular cancer. The patients' sera were analyzed for concentrations of hCG, free thyroxine (fT4), hTSH, and thyroxine-binding globulin (TBG). All patients had excessively high concentrations of hCG (1 x 10(5)-5 x 10(8) ng/L, mean: 1 x 10(7) ng/L) before polychemotherapy, which decreased under successful therapy to physiological values (< 240 ng/L). Although the serum concentrations of hCG varied by more than six orders of magnitude, we saw no changes and no correlation (P > 0.05) between the concentrations of hCG and the concentrations of fT4 and hTSH. Not even when hCG concentrations were greatest (> 5 x 10(7) ng/L) were any signs of hyperthyroidism observed: fT4 (3.5-13 ng/L) and hTSH (9-700 ng/L) were in the physiological range in all patients and remained so during chemotherapy. The results of this longitudinal study were confirmed in analyzing the data for all eight patients (total: 82 samples) cross-sectionally. Again, we found no correlation (P > 0.05) between the concentrations of hCG and fT4 or hCG and hTSH. We conclude that even excessive amounts of testicular tumor-derived hCG do not display any TSH-like activity in vivo.

Chorionic Gonadotropin↗
PubMed1992

Increased ELISA sensitivity using a modified method for conjugating horseradish peroxidase to monoclonal antibodies.

We investigated the importance of monoclonal antibody (MCA) purity and the input molar ratio of horseradish peroxidase (HRPO)/IgG used for MCA conjugation on various immunoenzymometric assay (IEMA) parameters. The sensitivity of IEMAs for human follicle stimulating hormone (hFSH), human chorionic gonadotropin (hCG) and the free alpha subunit of hCG (hCG alpha) could be increased up to 6-fold, whereas non-specific binding remained within tolerable limits (E less than 0.1), when MCAs purified by high performance liquid chromatography (HPLC) using a hydroxylapatite column (HPHT) were conjugated with an input molar HRPO/IgG ratio of four instead of the usual ratio of two.

Animals↗
PubMed1992

Free alpha-subunit, free beta-subunit of human chorionic gonadotropin (hCG), and intact hCG in sera of healthy individuals and testicular cancer patients.

To determine the serum concentrations of human chorionic gonadotropin (hCG), its free beta-subunit (hCG beta), and the free alpha-subunit (free alpha) common to all human glycoprotein hormones under physiological and pathological conditions, we developed monoclonal antibody-based immunoenzymometric assays. Free alpha-subunit was detected in the sera of all healthy individuals of both sexes; hCG was measurable in sera of 54% of the men, and 46% were positive for free hCG beta; in nonpregnant women, 69.5% were positive for hCG, 68.4% for the free beta-subunit. Pathological conditions, i.e., hCG-producing tumors, were studied in vitro and in vivo. In vitro, the concentrations of hCG, free hCG beta, and free alpha in tissue-culture supernates of a choriocarcinoma cell-line ("JAR") showed a parallel pattern during time-course analysis. In vivo, in long-term follow-up studies of 13 patients with testicular cancer, serum concentrations of the three analytes paralleled each other, whether the disease was in remission or not. Because of a selective increase of free hCG beta and free alpha in 27% of seminomatous tumor patients and in 13% of the nonseminomatous patients, the percentage of tumor-marker-positive sera was increased from 15% to 42% and 57% to 70%, respectively, by the additional measurement of free hCG beta and free alpha. Thus hCG, free hCG beta, and free alpha are physiologically present in a high percentage of the sera from healthy men, and the determination of free hCG beta and free alpha, although not of prognostic value, improves the diagnostic possibilities in patients with testicular cancer.

Choriocarcinoma↗
PubMed1990

[Immunometric tests system for glycoprotein hormones and their free subunits].

Highly specific sensitive immunoenzymometric assays were established for human glycoprotein hormones, the common free alpha-subunit of glycoprotein hormones and the free beta-subunit of human chorionic gonadotropin, using a large panel of monoclonal antibodies previously produced in our laboratory. The significance of serum levels of human chorionic gonadotropin and its free subunits under physiological conditions, as well as their prognostic value in human chorionic gonadotropin-producing tumours was determined in vitro and in vivo. These investigations revealed that all three analytes were present in the sera of the majority of normal individuals; moreover, the percentage of positive sera for these tumour markers in patients suffering from seminomatous and non-seminomatous testicular cancers was significantly elevated when two, or even better, all three parameters were determined.

Biomarkers, Tumor↗
PubMed1990

[Modulation of hCG synthesis by alpha tumor necrosis factor in JAR choriocarcinoma cells].

The tumour necrosis factor (TNF) stimulates in cultured JAR choriocarcinoma cells the biosynthesis of hCG, including the free alpha and beta chain and the holo-hCG. Although elevated serum TNF levels have been shown by Balkwill et al. (1987) in about 50% of tumour patients, we were unable to confirm these data in the 10 examined patients, who had a choriocarcinoma. Despite its excellent in-vitro action, INF could not be confirmed to exercise an influence on the regulation of hCG in choriocarcinoma patients.

Cell Line↗
PubMed1990

Monoclonal antibodies against the free subunits of human chorionic gonadotrophin.

Discordant results on body fluid levels of human chorionic gonadotrophin (hCG) free alpha- and beta-subunits under physiological and pathophysiological conditions, prompted us to raise a total of 260 monoclonal antibodies (MCA) against free hCG-alpha, free hCG-beta, holo-hCG, human follicle-stimulating hormone and bovine luteinizing hormone; 153 MCA recognizing the human alpha-subunit and 28 reacting with hCG-beta were extensively analysed for their intra- and inter-species cross-reactivity with homologous hormones, and for the compatibility of epitopes recognized by them. The immunological topography of free hCG-alpha and free hCG-beta was resolved by these MCA, and epitope maps were designed. Six antigenic determinants on the free alpha-chain (alpha 1-alpha 6), clustered in three spatially distinct domains, and seven epitopes on the surface of free hCG-beta (beta 1-beta 7), could be distinguished. Strikingly, three alpha-chain epitopes (alpha 4, alpha 5 and alpha 6) were shared between various species, which is in contradiction to the concept of immunological species-specificity of alpha-subunits. Three determinants were found to be present only on the free subunits but not on holo-hCG (alpha 6, beta 6 and beta 7), and only two determinants (beta 1 and beta 7) were hormone-specific for hCG. Based on this information, an immunoenzymometric assay for the free alpha-subunit of human glycoprotein hormones was established, with a sensitivity of 1.3 pg/well and a cross-reactivity with holo-hCG of less than 0.005%.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMedDate not supplied

Relationship between testosterone serum levels and lifestyle in aging men.

OBJECTIVE: The aim of this study was to evaluate the association between serum levels of testosterone and free testosterone to lifestyle in aging males. METHODS: Men between 45 and 85 years were assessed regarding body mass index (BMI), nicotine and alcohol consumption, stress level, physical and social activity, and sleeping quality by a self-administered questionnaire. In parallel, serum levels of testosterone (T), free testosterone (fT), LH, FSH, DHEA-S, E2 and SHBG were obtained. RESULTS: In total, 375 men with a mean age of 59.9 years (9.2 +/- SD) entered this study; 25.4% and 27.4% had hypogonadal testosterone or free testosterone serum levels, respectively. Nicotine consumption (smokers had higher levels of T and fT; p < 0.01), BMI (negative correlation to T; p < 0.01) and age (negative correlation to fT; p < 0.001) correlated with serum levels of testosterone or free testosterone. Physical and social activity, nicotine and alcohol consumption, stress level and sleep quality did not show a significant association with serum androgen levels. CONCLUSION: This prospective study of 375 men aged 45 to 85 years confirms the correlation between age, BMI and smoking with serum levels of testosterone and free testosterone, whereas the investigated variety of lifestyle factors did not show a significant association to serum androgen levels.

Age Factors↗
PubMedDate not supplied

Genetic polymorphisms of CYP1A1 and GSTM1 and lung cancer risk.

Susceptibility to lung cancer may, in part, be determined by interindividual differences in the cytochrome P450-catalysed bioactivation and the glutathione S-transferase-catalysed detoxification of procarcinogens. Therefore a lung cancer case-control study was set up to investigate the association of three polymorphisms of the CYP1A1 gene (CYP1A1*2A, CYP1A1*2B, CYP1A1*4) and GSTM1*0 genotype with lung cancer risk in Austrian Caucasians. Genomic DNA was isolated from the peripheral blood lymphocytes of 134 male lung cancer patients and 134 age-matched controls with nonmalignant conditions and PCR-based analyses were performed. There was no significant difference in risk between cases and controls, either for the CYP1A1*2A (OR=1.09, 95%CI=0.46-2.58), CYP1A1*2B (OR=1.09, 95%CL=0.46-2.58) or for the CYP1A1*4 polymorphism (OR=0.49, 95%CL=0.20-1.16). The prevalence of the GSTM1*0 genotype in the lung cancer group (47.8%) was comparable to that found in the control group (49.3%) and also had no effect on lung cancer risk (OR=0.94, 95%CL=0.54-1.57). Further, in a subgroup of male ever-smokers (n=126), no significant influence on the relative risk was found for these polymorphisms. Our results suggest that these investigated polymorphisms can not be considered as genetic susceptibility markers for lung cancer within the Austrian Caucasian population.

Adenocarcinoma↗