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Biomedical subjects

U Thiel

Publications and source records attributed to U Thiel.

At least 19 recordsLinked to original sources

[European Association of Urology guidelines on urinary and male genital tract infections].

Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.

Disease Notification↗

Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin.

During continuous ambulatory peritoneal dialysis (CAPD) the peritoneal immune cells, mainly macrophages, are highly compromised by multiple factors including oxidative stress, resulting in a loss of functional activity. One reason for the increase of inflammatory reactions could be an imbalance in the thiol-disulfide status. Here, the possible protective effects of the antioxidant flavonoid complex silymarin and its major component silibinin on the cellular thiol status were investigated. Peritoneal macrophages from dialysis fluid of 30 CAPD patients were treated with silymarin or silibinin up to 35 days. A time-dependent increase of intracellular thiols was observed with a nearly linear increment up to 2.5-fold after 96 hours, reaching a maximum of 3.5-fold after 20 days of culture. Surface-located thiols were also elevated. The stabilization of the cellular thiol status was followed by an improvement of phagocytosis and the degree of maturation as well as significant changes in the synthesis of IL-6 and IL-1ra. Furthermore, the treatment of peritoneal macrophages with flavonoids in combination with cysteine donors resulted in a shortened and more efficient time course of thiol normalization as well as in a further increased phagocytosis. In addition, GSH-depletion in thiol-deficient media simulating CAPD procedures led to intracellular thiol deficiency similar to the in vivo situation. It is concluded that treatment with milk thistle extracts silymarin and silibinin alone or, more effectively in combination with cysteine donors, provide a benefit for peritoneal macrophages of CAPD-patients due to a normalization and activation of the cellular thiol status followed by a restoration of specific functional capabilities.

Acetylcysteine↗

Evidence of a defective thiol status of alveolar macrophages from COPD patients and smokers. Chronic obstructive pulmonary disease.

In increasing numbers of pulmonary diseases an association with a loss of intracellular thiols, mainly glutathione, is postulated. Therefore, the quantitative measurement of thiols within different viable cells is a possible metabolic parameter for cellular function and defense capacity of all pulmonary immune cells including alveolar macrophages (AM), that are highly compromised by oxidative stress. In this study the cellular thiol content was determined using fluorochrom conjugated chloromethyl derivatives (5-chloromethylfluorescein diacetate, CMFDA) in flow cytometry. The procedure was evaluated in vitro using biochemical techniques for glutathione quantification. Based on this approach, AM obtained from bronchoalveolar lavage (BAL) of smokers and patients with chronic obstructive pulmonary disease (COPD) showed a significant thiol deficiency compared to a nonsmoker/non-COPD group. The cellular thiol expression of AM from smokers and COPD patients reached only 50 and 53% of the control group. Lowest thiol concentrations (47% of control) were detected within the smoker(+)/COPD(+) group. This intracellular thiol deficiency significantly correlated with reduced lung function (FEV(1), PaO(2)). With regard to the tightly regulated thiol metabolism of immune cells, these results imply the onset of functional disturbances in thiol deficient AM. The determination of the cellular thiol content of AM, obtained from BAL by flow cytometry, presents a simple and reliable tool to monitor the effect of therapeutic measures focusing on the stabilization of the cellular thiol status.

Aged↗

Diphospho-myo-inositol phosphates during the life cycle of Dictyostelium and Polysphondylium.

The intracellular amounts of diphospho-myo-inositol phosphates and InsP6 were determined in Dictyostelium discoideum AX2 throughout the life cycle, including exponential growth, starvation, differentiation, sporulation and spore germination. Similar experiments were performed with the closely related species Polysphondylium pallidum under conditions resulting in microcyst formation. A distinct accumulation of these compounds is observed during the early starvation phase of the cell population before the onset of the actual differentiation program. When exponentially growing D. discoideum cells were shifted to starvation conditions, a 25-fold accumulation of 5,6-bis-PP-InsP4 within 3 h was observed. In P. pallidum, the 5,6-bis-PP-InsP4 pool rises around 20-fold within 8 h during the formation of microcysts from vegetative cells. Finally, the diphosphoinositol phosphates are deposited in spores or microcysts and are degraded when spores or microcysts germinate at low cell density.

Animals↗

Membrane-bound proteindisulfide isomerase (PDI) is involved in regulation of surface expression of thiols and drug sensitivity of B-CLL cells.

The proteindisulfide isomerase (PDI), a multifunctional cytoplasmic enzyme with additional chaperone activity, has been shown recently, using monoclonal antibodies, to be located on the membrane of mature human B lymphocytes and B cell chronic lymphocytic leukemia (B-CLL) cells. Here, evidence is presented that this antigen exhibits catalytic activity as measured by the reductive degradation of insulin (release of A chain molecules) on intact B cells in patients suffering from B-CLL, as well as on JVM 13 cells (B-CLL cell line). More than 98% of these cells exhibited PDI activity which could be inhibited by bacitracin and also by monoclonal and polyclonal antibodies to PDI. Interestingly, surface PDI expression was strongly correlated in our study with protein-bound membrane SH groups. These surface protein thiols were specifically determined by using low concentrations of the chloromethyl-derivative based fluorescent probe 5-(and6)-(((4-chloromethyl)-benzoyl)amino)-tetramethyl-rhodamine (CMTMR) at low temperature in the presence of sodium azide in flow cytometry. The highest PDI and SH expression was found on B lymphocytes, particularly B-CLL cells. The mean fluorescence intensity (MFI) of CMTMR-positive B cells in the B-CLL line was up to 10-fold higher than that of controls, indicating a strong elevation of cell membrane-located protein thiols on malignant B cells. The link between PDI and SH expression on cell surfaces points to a functional interaction between the two. Treatment with bacitracin resulted in a strong inhibition of PDI and a dramatic increase in surface protein thiol expression of B-CLL cells. Similar effects could be observed by cell treatment with anti-PDI antibodies, indicating that this enzyme system plays a crucial role in the regulation of protein-bound SH groups. Interestingly, artificially induced protein thiol expression led to significantly higher cellular resistance to the cytostatic drugs chlorambucil, vinblastin, and cisplatin in vitro as measured by cell growth. These data suggest for the first time a regulatory effect of PDI on the surface protein thiol status of B cells. The increased expression of PDI may play a crucial role in SH-mediated protection and drug resistance in malignant B lymphocytes.

B-Lymphocytes↗

Alterations in structure and cellular localization of molecular forms of DP IV/CD26 during T cell activation.

Dipeptidyl peptidase IV (DP IV, CD26), known as an activation marker of T lymphocytes, is a proline-specific protease thought to be involved in the regulation of the immune response. The physiological role of dipeptidyl peptidase IV in the immune system and the molecular events of lymphocyte activation mediated by this enzyme are only partly established. Former results suggested the occurrence of different molecular forms of DP IV in distinct human sources. As yet it has been unknown whether DP IV from human hematopoietic cells also appears in different forms and whether similar structural modifications are involved in functional processes of the regulation of the immune response. Here we describe that lymphocytic DP IV/CD26 occurs in various molecular forms and that some of them are associated with the activation process. In cell lysates of mitogen-activated lymphocytes at least 5 enzymatically active DP IV forms and up to 11 immunoreactive molecular forms of this enzyme with isoelectric points between pH 3.5 and 5.9 were discernible. Corresponding analyses of soluble and membrane cell fractions of human lymphocytes showed significant differences in the staining pattern of molecular DP IV structures. After mitogenic stimulation a special molecular form of DP IV arises in the membrane, which was originated either from the soluble part of the cell (translocation) or represents a new synthesized form. Particularly, changes of molecular DP IV forms after mitogenic stimulation strongly suggest that special forms/epitopes of this enzyme are directly involved in the process of lymphocyte activation and growth. Importantly, different monoclonal DP IV antibodies partly define different molecular forms of DP IV. Moreover, the pattern of immunostaining and enzymatic staining (Gly-Pro-beta-methoxynaphthylamide) also reveals drastic differences. These data strongly suggest a direct relationship between the expression/recognition of special DP IV epitopes and the contradictory functional effects of monoclonal DP IV antibodies found by us and other groups.

Cells, Cultured↗

Structures of diphospho-myo-inositol pentakisphosphate and bisdiphospho-myo-inositol tetrakisphosphate from Dictyostelium resolved by NMR analysis.

Diphospho-myo-inositol phosphates (PP-InsP5 and bis-PP-InsP4) were isolated from Dictyostelium in order to clarify the precise positional isomerism by two-dimensional 1H/31P-NMR analysis. The diphosphorylated inositol phosphates are 4-PP-Ins(1,2,3,5,6)P5 and 4,5-bis-PP-Ins(1,2,3,6)P4 or their corresponding enantiomers. The vicinal arrangement of the diphospho groups with its steric and electrostatic constraints possibly qualifies bis-PP-InsP4 as a metabolite with high phosphate-group-transfer potential in phosphotransferase reactions.

Animals↗

The detection, purification, structural characterization, and metabolism of diphosphoinositol pentakisphosphate(s) and bisdiphosphoinositol tetrakisphosphate(s).

A new class of inositol phosphates containing energy-rich pyrophosphoryl residues has been characterized. D/L-1-Diphosphoinositol pentakisphosphate(s) and D/L-bis-(1,4)-diphosphoinositol tetrakisphosphate(s) are present as soluble ionic species in the cytosol of amoebae (Dictyostelium discoideum) at concentrations in the range of 0.05-0.25 mM. These compounds are rapidly metabolized in intact cells and can be synthesized in cell lysates from myo-inositol hexakisphosphate in the presence of ATP. Their phosphomonoester groups have predicted C-O-P bond energies of between 3.3 and 4 kcal mol-1; however, the bond energies of the P-O-P links in their diphosphate moieties are 6.6 kcal mol-1 and hence similar to the equivalent bonds in ADP, indicating a potential role for these compounds as phosphate donors in phosphotransferase reactions. Compounds with similar chromatographic properties are found in a variety of mammalian cell types.

Animals↗

Induction of protein disulphide-isomerase and immunoglobulins by pokeweed mitogen in human lymphocytes.

The Protein disulphide-isomerase (PDI, EC 5.3.4.1, Thiol-proteindisulphide oxidoreductase, EC 1.8.4.2) is thought to regulate the sulfhydryl status of cells and to catalyze thiol/disulphide exchange reactions involved in the post-translational processing of disulphide containing secretory proteins. The aim of the present investigations was to study the possible function of this enzyme in differentiation of B lymphocytes and immunoglobulin synthesis. Non-adherent human mononuclear cells or purified T cells were cultured in presence and absence of Pokeweed mitogen over 3, 5 and 7 days. Monoclonal antibodies and a rabbit polyclonal antiserum specific for human liver PDI were produced to determine the concentration of PDI by an ELISA technique and cytoplasmic immunofluorescence. After PWM stimulation, both, the cellular content of PDI as well as that of immunoglobulin, particularly IgM, have been found to be induced in a time dependent manner with a 2-3 fold increase in comparison to unstimulated cells. The specific induction of PDI in human B lymphocytes was also confirmed in Western blotting. Our findings suggest that PDI plays a critical role in the final stages of B cell differentiation and immunoglobulin synthesis by activated B cells and plasma cells, respectively.

Antibodies, Monoclonal↗

[Immunochemical determination of human thiol protein disulfide oxidoreductase in cell and tissue homogenates by competitive EIA].

Different monospecific antisera against thiol-protein disulfide oxidoreductase (TPO, EC 1.8.4.2, protein-disulfide isomerase, EC 5.3.4.1) were raised in rabbits by immunization with purified human TPO and characterized by means of Laurell and immunoblot techniques. A competitive anti-TPO-EIA with insolubilized TPO has been used to determine this enzyme in cells and tissue homogenates. The assay shows a sensitivity of 1.2 ng/ml and a specificity of about 99%. The TPO content in relation to the total protein was found to be: in pancreas 0.65%, liver 0.45%, spleen 0.12%, placenta 0.16%, tonsils 0.06% and lymph nodes 0.03%.

Blotting, Western↗

[Percutaneous catheter dilatation of benign ureteral stenoses: indications, technic, results].

From June 1984 to December 1986 twenty-one benign ureteral stenoses were treated. After percutaneous nephropyelostomy an antegrade dilatation was performed by means of balloon catheters or increasing size of angiographic catheters. Subsequently an ureteral splinting with a F-12-catheter and a glucocorticoid therapy was followed. 13 strictures (61.9%) were treated successfully and in 3 cases (14.3%) an improvement of the obstruction and kidney function was obtained. In 5 patients (23.8%) the dilatation failed, in 2 of whom a nephrectomy was done. The failures occurred in cases with actinic and scarred-fibrotic strictures. The technical procedure, advantages and disadvantages of both dilatation methods were described. Treatment was complicated in 2 patients by the development of nephrolithiasis due to infection and in 2 further patients by acute pyelonephritis. Auxiliary measures of the dilatation therapy are a sufficient diuresis and an effective antibiotic therapy. In conclusion, the results are more dependent on the cause of stricture, than on the duration of disease and the used dilatation technique.

Adult↗

[Percutaneous nephropyelostomy--indications, complications, and various aspects of clinical use].

During almost 3 years in 100 patients the percutaneous nephropyelostomy was used as method of the supravesical discharge of urine 109 times. The X-ray-aimed puncture was performed on the basis of the fine needle puncture technique by means of a puncture set which we developed ourselves. When a urinary retention is present, the number of targets is great (96%), the rate of complications small. In 12 systematically exposed kidneys limited subcapsular haematomas were found, once a small perirenal haematoma. In one case a breaking off of the wire occurred. In 2 cases a septicaemia appeared, 4 punctures failed. Following the PNS 3 kidneys had to be exposed due to tamponage of the renal pelvis (2) and perforation of the renal pelvis, respectively. The percutaneous nephropyelostomy is a measure for the temporary or permanent supravesical discharge of the urine which is little stressing for the patient and simply to be performed. It represents a secure and effective alternative for the operative nephrostomy in patients with obstruction of the urinary tract of every genesis.

Adult↗

[Therapy of bladder calculi--trends and results of a mainly transurethral oriented clinic].

From 1975 to 1985 519 patients with urinary calculi were treated in the Urologic Clinic of the Berlin-Buch Hospitals. 57.6% of them were treated by lithotripsy and TUR-P, 14.8% by lithotripsy alone, 11.8% by stone removal and transvesical adenomectomy and 15.8% by suprapubic cystotomy only. The diagnosis of the four forms of therapy is described. The trend in the conception of treatment goes to the treatment of calculi transurethrally in combination with the simultaneous removal of the obstruction of the outflow from the urinary bladder. Since October 1985 the electrohydraulic lithotripsy has been used. Up to 1985 in 218 patients urinary calculi were crushed by means of the device Urat-1. In 190 patients (87.3%) the lithotripsy was carried out in combination with other therapeutic measures, in 153 (70.2%) a transurethral resection of the prostate gland and in 28 patients (12.9%) other transurethral interventions were performed. Postoperatively, in 7 patients complications occurred (3.2%), perforations of the urinary bladder were not seen. Taking into consideration the whole number of patients, it is reported on the advantages of the use of the electrohydraulic lithotripsy by means of the apparatus Urat-1 as an uncomplicated technique easily to be learned, which excellently may be combined with simultaneous transurethral interventions.

Aged↗

[Morphology and diagnosis of acquired bladder deformities].

Acquired displacements of the urinary bladder refer to intrapelvic pathological anatomy. These alterations of the bladder are predominantly detected via an initial radiologic study with intravenous urography or suprapubic pelvic ultrasonography. According to their clinical incidence displacements of the bladder can occur in: pelvic space-occupying lesions; displacements in musculo-fascial defects of supporting structures as well as in extirpation cavities of the small pelvis; extrapelvic space-occupying lesions. Herniation, prolapse and descensus of the bladder can be accurately diagnosed by correct examination via intravenous urography. The diagnostics of pelvic and extrapelvic pathogenetic causes require the complex application of all methods of diagnostic imaging, the value of which is determined by clinical diagnosis and by the choice of an appropriate therapy.

Abscess↗