Biomedical subjects

J Schubert

Publications and source records attributed to J Schubert.

At least 127 records · Page 7Linked to original sources

PubMed1999

Possibility of improving the acceptance rateof early detection testing for prostate cancerwith a one-step test for prostate-specific antigen in whole blood.

In order to increase the acceptance rate of early detection testing for prostate cancer, a qualitative prostate-specific antigen (PSA) one-step test has been developed. Determining the PSA level with this test system takes 10 min. The blood samples of 190 men were tested in this qualitative assay, which uses 50 microl of EDTA whole blood and in which the results are ascertained visually. Parallel samples were tested in serum-based, quantitative assays (Abbott Imx, EIA). The findings of the two kinds of assays were compared and evaluated regarding their correspondence (<4.0 and > or = 4.0 ng/ml). For the 74 blood samples in which the quantitative assay showed PSA levels <4.0 ng/ml, the PSA one-step test showed 83.8% correct negative results (corresponds to diagnostic specificity). For the 116 samples in which the classic assay showed PSA levels > or = 4.0 ng/ml, the one-step test showed 90.5% correct positive results (sensitivity). The noted deviations appear especially around the cut-off value of 4.0 ng/ml, i.e. within the PSA concentration range of 3.0 < 4.0 and 4.0 < 5.0 ng/ml. The qualitative PSA one-step test presented here demonstrates good reproducibility. It can be conducted by the patient and is easy to use. The test offers a simple, feasible method for early detection programs for prostate cancer.

Humans↗

PubMed1999

Multifocality in renal cell carcinoma: A bilateral event?

OBJECTIVES: The major disadvantage of nephron-sparing surgery for renal cell carcinoma is the risk of local recurrence. This is most likely a manifestation of undetected small additional tumors in the renal remnant. To define more clearly the incidence and nature of unilateral and bilateral multifocal tumors, an autopsy study was undertaken. MATERIALS AND METHODS: In a series of 14,793 autopsies from 1985 to 1995, 260 renal cell carcinomas were found. In all cases of renal cell carcinoma a search for small renal lesions was performed in the apparently normal-appearing portion of the kidneys. Every kidney was serially and systematically cut (5 mm) to probe for intraparenchymal lesions. RESULTS: Of the 260 renal cell carcinomas 36 cases (13.85%) had multifocal malignant and/or benign nodules. The number of the additional nodules ranged from 2 to 18. 12% of the malignant multifocal carcinomas were limited to the ipsilateral kidney and 88% were bilateral. The average size of the multifocal renal lesions was 8.7 x 9.0 x 9.5 (range 3-23) mm. Renal cell carcinomas with low stage and good grading have a higher incidence of multifocal nodules. No significant difference was found with regard to metastasized and nonmetastasized renal cell carcinomas. In 38.1% of all chromophilic renal cell carcinomas additional nodules were found. CONCLUSIONS: Multifocality in renal cell carcinomas cannot be predicted reliably, although the papillary histological pattern, good grading and low staging seems to be associated with a higher incidence of multifocality. Nearly 90% of the multifocal nodules were bilateral.

Autopsy↗

PubMed1999

Biosynthesis of glycosylphosphatidylinositols in mammals and unicellular microbes.

Membrane anchoring of cell surface proteins via glycosylphosphatidylinositol (GPI) occurs in all eukaryotic organisms. In addition, GPI-related glycophospholipids are important constituents of the glycan coat of certain protozoa. Defects in GPI biosynthesis can retard, if not abolish growth of these organisms. In humans, a defect in GPI biosynthesis can cause paroxysmal nocturnal hemoglobinuria (PNH), a severe acquired bone marrow disorder. Here, we review advances in the characterization of GPI biosynthesis in parasitic protozoa, yeast and mammalian cells. The GPI core structure as well as the major steps in its biosynthesis are conserved throughout evolution. However, there are significant biosynthetic differences between mammals and microbes. First indications are that these differences could be exploited as targets in the design of novel pharmacotherapeutics that selectively inhibit GPI biosynthesis in unicellular microbes.

Animals↗

PubMed1999

Interphase cytogenetic diagnosis of bladder cancer on cells from urine and bladder washing.

In order to determine the value of fluorescence in situ hybridization (FISH) in the diagnosis and follow-up of bladder cancer interphase cytogenetics was performed on cells from urine and bladder washings. 50 ml of urine or bladder washings were collected. FISH was carried out using centromere probes for chromosomes 7, 8, 9 and 12 according to standard protocols. In each case 100 cell nuclei were analysed. Fifty-four samples from urine and 67 samples from bladder washing were analysed by FISH in comparison with results obtained by conventional cytology. Sensitivity of detection of tumor cells by FISH was 68.5% in urine and 63% in bladder washings regardless of tumor stage and grade. Sensitivity obtained by conventional cytology was 50% in urine and 77.3% in bladder washings. FISH on cells from urine samples is an effective complement to the standard urine cytology. Using centromere probes this approach is characterized by high specificity and sensitivity in tumors with T-category higher than pTa and grade higher than G1.

Carcinoma, Transitional Cell↗

PubMed1999

Determination of telomerase activity in multifocal renal cell carcinoma.

In a consecutive series of 245 patients with renal cell carcinoma (RCC) all nephrectomy specimens were examined regarding the presence of additional multifocal lesions. Therefore, 3-mm step sections were performed and investigated by macroscopical and histopathological examination. Twenty-six multifocal tumors were found in 19 specimens by this procedure. In order to characterize the biological activity of these multifocal lesions in more detail, their telomerase activity was analyzed. Fourteen of the 23 investigated multifocal tumors (60.9%) displayed telomerase activity. In three cases the tissue probes were too small for further investigations. Telomerase activity was also detected in 10 out of 15 (66.7%) matched primary renal cell carcinomas. In contrast, all corresponding normal kidney cortex tissues used as control were telomerase negative. From our results we conclude, that small tumor lesions of RCC must be expected to have a malignant potential similar to that of primary carcinomas. Hence, nephron-sparing surgery cannot be routinely carried out even in patients with small tumors.

Carcinoma, Renal Cell↗

PubMed1998

Method for analysis of exhaled air by microwave energy desorption coupled with gas chromatography-flame ionization detection-mass spectrometry.

A method for chemical analysis of volatile constituents in exhaled air of mechanically ventilated patients is described. Exhaled substances are adsorbed and concentrated onto activated charcoal, desorbed by microwave energy and transferred into a gas chromatograph for separation without prior cryofocusing. Substances are identified by flame ionisation detection and mass spectrometry. This method yields reproducible results and is well suited for clinical studies.

Acetylene↗

PubMed1998

Human and mouse Gpi1p homologues restore glycosylphosphatidylinositol membrane anchor biosynthesis in yeast mutants.

Glycosylphosphatidylinositol (GPI) represents an important anchoring molecule for cell surface proteins. The first step in its synthesis is the transfer of N-acetylglucosamine (GlcNAc) from UDP to phosphatidylinositol (PI). The products of three mammalian genes, PIG-A, PIG-C and PIG-H, have previously been shown to be involved in the putative enzymic complex. Here we report the cloning of human and mouse cDNAs encoding a fourth participant in the GlcNAc transfer reaction which are homologues of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Gpi1 proteins. To provide evidence for their function, these proteins were expressed in GPI1-disrupted yeast strains. In Sacch. cerevisiae, where GPI1 disruption results in a temperature-sensitive phenotype and abolishes in vitro GlcNAc-PI synthesis, restoration of growth could be demonstrated in a temperature-dependent manner. In addition, in vitro GlcNAc-PI synthetic activity was again detectable. In Schiz. pombe, gpi1+ disruption is lethal. Using random spore analysis, we were able to show that the mammalian GPI1 homologues can rescue haploids harbouring the lethal gpi1+::his7+ allele. Our data demonstrate that the genes identified are indeed involved in the first step of GPI biosynthesis, and allow conclusions about a specific function for Gpi1p in stabilizing the enzymic complex. The finding that, despite a low degree of identity, the mammalian Gpi1 proteins are able to participate in the yeast GlcNAc-PI synthetic machinery as heterologous components further demonstrates that GPI biosynthesis has been highly conserved throughout evolution.

Amino Acid Sequence↗

PubMed1998

Ceramic coagulation tip for interstitial thermoablation of the prostate: first experiments.

A direct electrically heated ceramic coagulation tip for interstitial thermoablation has been developed. Both the coagulation tip and a laser system (Medilas 4060) were tested in vitro to compare their efficacies. We have obtained coagulation necroses of similar sizes. The electrical coagulation tip as opposed to laser coagulation is a new therapeutic option for the therapy of high risk patients with symptomatic benign prostatic hyperplasia. Because of the materials used and the principle of heating involved, certain economic and safety advantages over the laser system are offered.

Animals↗

PubMed1998

[Sleep deprivation and subsequent sleep phase advance stabilizes the positive effect of sleep deprivation in depressive episodes].

Approximately 60% of patients with major depression disorder show a beneficial response to total sleep deprivation (TSD), but the positive effect of TSD is short, and naps or the following night's sleep destroy it. Various methods have been tried to stabilize the positive sleep-deprivation effect. A consecutive 1-week advance in the sleep phase stabilized mood in more than 50% of the sleep-deprivation responders. We examined 40 male patients with major depression who in addition to medical treatment took part in a phase advance study to prove possible synergistic effects. About 60% of the patients showed positive mood stabilization after 1-week of treatment when the patients were sleep-deprivation responders. These results support data from other groups.

Adult↗

PubMed1998

[The VATER syndrome from the urologic viewpoint].

Duplications of the bladder is uncommon and rarely occurs as isolate anomaly. Two cases of complex malformations from the VACTERL-association are reported. The study of urogenital duplications in cases from the literature are described.

Abnormalities, Multiple↗

PubMed1998

[Lymphocyte transformation test (LTT) as a model for evaluating cytokine-induced immunomodulation in renal cell carcinoma].

We investigated the immunomodulatory capacity of cytokines produced by renal cell carcinoma in vitro by analyzing their effects on mitogen-induced T-lymphocyte blast cell transformation. All of the tested 70 cell cultures, derived from 70 tumor areas in 33 patients, had immunomodulatory capacity. In addition to suppression in the lymphocyte transformation test (max. 44/70; 63%) there was also superinduction (max. 37/70; 53%). We found no significant correlation with the stage and grade of primary tumors. However, the suppression of mitogen-induced T-lymphocyte blast cell transformation was significant in multifocal tumors (0.08% TCM, P < 0.001) and non-significant in metastatic tumors. The production of the assayed cytokines IL-6, IL-10, IL-11, and TGF beta 1 was variable and there was no significant correlation to the immunomodulatory capacity of the tumors.

Carcinoma, Renal Cell↗

PubMed1998

In vitro stimulation of renal tubular p-aminohippurate transport by dexamethasone in rat kidneys and in intact kidney tissue of patients suffering from renal cell carcinoma.

The aim of this study was to test whether or not the accumulation of p-aminohippurate (PAH) can be increased in intact human renal cortical slices obtained from tumor-bearing kidneys of patients suffering from renal cell carcinoma (RCC). Tissue slices were incubated for 24 h in Williams medium E containing 0.01-50 microM dexamethasone. Thereafter slices were placed in PAH-containing Cross-Taggart medium and PAH uptake into kidney tissue was measured for 2 h. In both rat and human renal tissue slices, PAH uptake capacity increased significantly in a concentration-dependent manner after 24 h of incubation in dexamethasone-containing medium (rat, 136%; man, 156%). The stimulatory effect was already significant after 12 h of incubation. In additional experiments it was shown that incubation in triiodothyronine (T3)-containing medium has different effects: in man, T3 does not influence the PAH accumulation capacity of renal cortical slices whereas in rats PAH accumulation is significantly lower after 24 h of incubation with T3. Thus stimulation of tubular transport capacity can be performed in vitro in human renal cortical slices. Discrepancies between the effects of dexamethasone and T3 indicate different modes of action of the two hormones at the cellular level.

Aged↗

PubMed1998

Bilateral renal cell carcinoma in a horseshoe kidney: preoperative assessment with MRI and digital subtraction angiography.

Renal cell carcinoma in a horseshoe kidney is an unusual entity. To our knowledge, only 123 cases have been published to date. We report the first bilateral case of two clear-cell carcinomas in an asymmetrically fused kidney. Optimum preservation of renal function after radical tumor removal requires accurate preoperative imaging. Since the vascular supply in fusion anomalies is extremely variable, angiography is mandatory. Magnetic resonance imaging was most suitable to predict the tumor extent and localization, because it simultaneously gave the most comprehensive anatomical overview of the malformation.

Adenocarcinoma, Clear Cell↗

PubMed1998

Evaluation of microvessel density by computerised image analysis in human renal cell carcinoma. Correlation to pT category, nuclear grade, proliferative activity and occurrence of metastasis.

A high microvessel density is suspected to favour tumour progression and the occurrence of metastasis. To elucidate the significance of abundant vessels for the behaviour of human renal carcinomas, the microvessel density of 110 renal cell carcinomas was correlated to pT category, nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival interval. The microvessels were quantified using CD31 immunostaining of endothelial cells and computer-aided image analysis. The rules for reproducible microvessel counting, as defined by Weidner, were strictly observed. A statistically significant relationship between the microvessel density and nuclear grade, proliferative activity, occurrence of metastasis and relapse-free survival was found; only for tumour size could no such relation be seen. Perplexingly, there is a diminution of microvessel density in association with increasing nuclear grade, proliferative activity, relapse-free survival interval and frequency of metastasis. This finding is contradictory to the hypothesis that an increasing microvessel density indicates a worsening prognosis.

Antibodies↗

PubMed1998

Comparative evaluation of the use of immunoblots and of IgG avidity assays as confirmatory tests for the diagnosis of acute EBV infections.

BACKGROUND: Despite the availability of several different markers for Epstein--Barr virus (EBV) serology, the EBV status of some patients cannot be resolved from a single serum sample with routine testing. To avoid the requirement of follow-up samples, supplementary tests have to be used in these cases. OBJECTIVE: To evaluate the usefulness of avidity and immunoblot assays as supplementary tests for the diagnosis of acute EBV infections. STUDY DESIGN: Three groups of samples for which a definite diagnosis on the EBV status could not be obtained with the routine serological tests were further examined by an EBV IgG avidity assay, by an immunoblot based on a lysate of EBV infected cells, and by a second immunoblot based on recombinant EBV antigens. The three groups consisted of 38 samples with negative/borderline EB nuclear antigen 1 (EBNA-1) antibodies, negative/borderline EBV IgM and positive EBV IgG; 10 samples with indeterminate EBNA-1 and/or EBV IgM assays because of control antigen reactions; and 4 samples with positive EBV IgM results that were not plausible. RESULTS: The avidity assay differentiated between acute and past infections for all samples. In contrast, some cases remained unresolved with both the recombinant and the lysate immunoblot. Two samples were incorrectly classified with the lysate immunoblot. Interpretation of the lysate immunoblot banding patterns was complicated when anticellular antibodies were present. CONCLUSION: Avidity testing appears to be the confirmatory method of choice to differentiate between acute and past EBV infections.

Acute Disease↗

PubMed1998

Impact of CYP2E1 genotype in renal cell and urothelial cancer patients.

Genetic polymorphisms of enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several drugs, precarcinogens and solvents to reactive metabolites. In the present study, we investigated the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients from two German regions, Jena and Halle, different with respect to their environmental pollution degree in comparison with healthy controls from the same regions. DNA of peripheral white blood cells was isolated both from 224 renal cell/urothelial cancer patients and 304 controls. We focussed on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphisms were identified as RFLP's by amplification of the appropriate DNA fragment and subsequent digestion with the restriction enzymes PstI, RsaI and DraI. In Jena as well as in Halle, the frequency distributions of the PstI/RsaI, DraI and combined DraI + PstI/RsaI genotypes showed no significant differences between controls and renal cell/urothelial cancer patients. We did not find significant differences between Jena and Halle. 86.2% of all subjects with a homozygote PstI/RsaI genotype also carried a heterozygote DraI genotype, whereas 5.1% of the subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. Renal cell cancer as well as urothelial cancer risk was not elevated in patients with heterozygote DraI, PstI/RsaI and combined DraI + PstI/RsaI genotypes (odds ratios slightly insignificantly increased). Interestingly enough, an association between these polymorphisms and renal cell cancer risk was found in the female subgroup but not in the male subgroup. The basis of these sex-specifically increased risks are different frequencies concerning heterozygote and homozygote genotypes in controls and cancer patients. In controls, the heterozygote genotype frequency was lower in females than in males. In renal cell cancer patients, the results were quite the contrary. Summing up, our results demonstrate an lack between CYP2E1 genetic polymorphism and renal cell/urothelial cancer risk.

Carcinoma, Renal Cell↗

PubMed1998

[3D and color Doppler ultrasound evaluation of cystic space-occupying lesion near the head of the pancreas].

AIM: Differential diagnosis of cystic lesions in the abdomen may be very difficult. We present the clinical manifestation and the diagnostic steps of a rare case of an aneurysm of the gastroduodenal artery mimicking a cystic lesion. We also discuss the imaging methods we used to verify the diagnosis such as colour Doppler sonography and 3D-sonography. METHOD AND PATIENT: A 42-year old woman with chronic pancreatitis was admitted to our hospital after an extended diagnostic program (sonography, computed tomography and laparoscopy) with the diagnosis of a pancreatic pseudocyst with vascular erosion. Using conventional sonography we found a cystic lesion of 5 x 5 cm diameter with parietal deposits between pancreas and coeliac trunk. After colour Doppler sonography we found an arterial jet in the cystic tumor; initially the source of the jet seemed to be the hepatic artery. We referred the patient to our department of radiology with the diagnosis of hepatic artery aneurysm. The aneurysm was confirmed by the angiography and was embolised with coils in the same session. However, the source of the aneurysm was not the hepatic, but the gastroduodenal artery. By postangiographical 3D-sonography we could clearly reconstruct the relation of the aneurysm to the gastroduodenal artery. CONCLUSION: Colour Doppler sonography should be the first imaging tool for clarifying cystic lesions in the abdomen. 3D-sonography is a reliable and useful method to identify visceral vessels of the abdomen. Nowadays the "gold standard" angiography should preferably be used as a therapeutic procedure.

Adult↗

PubMed1998

31P-magnetic resonance spectroscopy (31P-MRS) of human allografts after renal transplantation.

BACKGROUND: 31P-Magnetic resonance spectroscopy (31P-MRS) can be used as a non-invasive tool for measuring the relative intracellular concentrations of several phosphorus metabolites in different organs. Various pathological conditions are characterized by different metabolic patterns. We studied the value of 31P-MRS after renal transplantation with both an uneventful and a clinically complicated course. METHODS: We determined the relative concentrations of phosphate-containing metabolites in renal allografts of humans with 31P-MRS (1.5 Tesla) in the first few weeks after transplantation; 18 patients with an uneventful clinical course and 10 patients who required dialysis after transplantation were examined. Six patients with a stable allograft function 2-3 months after transplantation served as controls. RESULTS: In patients with primary allograft function, we found a significant correlation between the phosphomonoester/phosphodiester-ratio (PME/PDE) (r = 0.66, r < 0.01) and the time after transplantation, but no correlation between the nucleoside triphosphate (beta-NTP)-concentration (r = -0.11) and the time course. In the patients with primary or early allograft dysfunction caused by histologically proven rejection (n=5), we found a low beta-NTP compared to patients with an uncomplicated clinical course (0.09+/-0.01 vs 0.15+/-0.03), but no differences in the PME/PDE ratio (0.73+/-0.21 vs 0.80+/-0.21). In contrast, the PME/PDE ratio was lowered in three patients with delayed graft function caused by acute tubular necrosis (0.45+/-0.07 vs 0.80+/-0.21), but the beta-NTP concentration was not reduced (0.15+/-0.003 vs 0.15+/-0.03). The 31P-MR spectrum of two patients with cyclosporin A damage was not altered compared to the controls. CONCLUSIONS: 31P-MRS can be used in patients in the early period after renal transplantation. A significant correlation between the PME/PDE ratio and the time course but no change in the beta-NTP concentration was found in patients with primary allograft function in the first 4 weeks after renal transplantation. Different patterns of 31P-MR spectra were observed depending on the different causes of primary and early transplant dysfunction.

Adult↗