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Biomedical subjects

G Wolf

Publications and source records attributed to G Wolf.

At least 271 records · Page 15Linked to original sources
PubMed1997

Prostaglandin E2 stimulates expression of matrix metalloproteinase 2 in cultured rat mesangial cells.

Prostaglandins of the E-series have been demonstrated to reduce extracellular accumulation of collagens in some models of glomerulonephritis. This effect is partially due to reduction of collagen formation by mesangial cells. The potential effects of prostaglandins on the expression of collagen degrading enzymes in mesangial cells are largely unknown. Since rat mesangial cells generate a matrix metalloproteinase 2 (MMP-2) that specifically degrades collagen type IV, the effects of prostaglandin E2 (PGE2) on transcription, steady-state mRNA levels, extracellular enzyme activity and protein concentration of this proteinase were evaluated. Mesangial cells (MC) were incubated with PGE2 (2 microM) for different time-periods (1 to 48 hr), and steady-state mRNA levels of MMP-2 were determined by Northern blotting. PGE2 increased MMP-2 mRNA levels beginning at one hour of incubation and remained elevated up to 24 hours. Nuclear run off experiments revealed that the PGE2-induced increase in mRNA expression for MMP-2 is due to stimulated gene transcription. Western blot analysis and zymography revealed that MMP-2 protein production and enzyme activity was also enhanced by PGE2. The cAMP analogue 8-bromo-cAMP increased MMP-2 mRNA levels, suggesting that PGE2-induced generation of intracellular cAMP plays a role in MMP-2 induction in MC. These studies demonstrate that PGE2 stimulates the transcription, protein formation and enzyme activity of MMP-2 in cultured rat MC. This effect may contribute to the prostaglandin mediated reduction of extracellular collagen deposition in glomerulonephritis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Overexpression of aminopeptidase A abolishes the growth promoting effects of angiotensin II in cultured mouse mesangial cells.

Angiotensin II (Ang II) has diverse effects on the glomerular tuft such as regulation of glomerular hemodynamics and stimulation of mesangial cell growth, and may be one pivotal factor in the progression of renal disease. In order to locally inactivate Ang II, we overexpressed aminopeptidase A (E.C. 3.4.11.7; ATA), a peptidase involved in the conversion of Ang II into angiotensin III, in a mouse mesangial cell line (MMC) that normally does not exhibit this enzyme. Stable transfections were selected in medium containing G418. ATA-overexpressing clones ATA5 and ATA21 revealed mRNA, protein, and enzyme activity in contrast to wild-type MMCs or mock-transfected Neo3 cells (stably transfected with expression vectors without ATA cDNA). There was no difference in the binding of Ang II to its putative receptors in all cell lines. Ang II increased intracellular inositol 1,4,5-triphosphate (IP3) in Neo3, but not in ATA5 and ATA21 cells. In contrast to MMCs and Neo3 cells, Ang II failed to stimulate proliferation in ATA5 and ATA21 clones as measured by [3H] thymidine incorporation and direct cell counts. However, ATA5 and ATA21 revealed a mitogenic response not different from MMCs after stimulation 2% or 10% of fetal calf serum. Treatment of ATA5 and ATA21 with 0.1 mM of the ATA-inhibitor amastatin or an ATA-inhibiting specific monoclonal antibody restored the proliferative effect of Ang II, suggesting that surface activity of ATA is involved in the attenuated mitogenesis in these cell. Our study demonstrates that it is feasible to overexpress Ang II-degrading enzymes in cultured mesangial cells and that this overexpression attenuated some effect of exogenous Ang II. These experiments are a first step toward the development of novel strategies to selectively antagonize locally generated Ang II in the kidney.

Aminopeptidases↗
PubMed1997

Serotonin acts as a radical scavenger and is oxidized to a dimer during the respiratory burst of activated microglia.

Serotonin (5-HT) is known to be readily oxidized and to act as a scavenger of reactive oxygen species produced, e.g., in the presence of peroxidase and H2O2 or during the respiratory burst of phagocytes. One major oxidation product formed under these conditions, the 5-HT dimer 5,5'-dihydroxy-4,4'-bitryptamine (DHBT), was suggested to have neurotoxic properties and to contribute to neuronal damage in neurodegenerative disorders. It is shown in the present study that the luminol-enhanced chemiluminescence signal measured after stimulation of the respiratory burst activity of cultivated rat microglial cells by the addition of phorbol 12-myristate 13-acetate is suppressed by 5-HT in a dose-dependent manner. During this process, 5-HT is oxidized to DHBT. Neither the intraventricular injection of DHBT nor the addition of DHBT to cultured astrocytes, neurons, or PC-12 cells was found to cause measurable cytotoxic effects. It is concluded that extracellular 5-HT locally released from platelets and 5-HT nerve endings at sites of brain damage or inflammation, through its suppressant effect on the release of reactive oxygen species during the respiratory burst of activated microglia, may contribute to attenuate secondary tissue damage in the CNS.

Animals↗
PubMed1997

[Endoscopic detection of cerebrospinal fluid fistulas with a fluorescence technique. Report of experiences with over 925 cases].

BACKGROUND: For more than 35 years intrathecal fluorescein has been used for identification of cerebrospinal fluid leaks. Whereas some authors apply this technique routinely and with excellent results, significant complications have also been reported, sparking considerable controversy. At the Graz University ENT Department intrathecal sodium fluorescein has been routinely used for more than 25 years and is considered a significant help. MATERIAL AND METHODS: In a retrospective study data of 925 patients who underwent a diagnostic fluorescein test during the period from 1970-1995 at our department were evaluated. The techniques of preparation and intrathecal application of sodium fluorescein are described, as are the techniques of endoscopic diagnostic and intraoperative identification of fluorescein stained CSF. RESULTS: There were three complications during 925 fluorescein tests that resulted in grand mal seizures after suboccipital application. Since 1990, we have discontinued the use of suboccipital punctures, and in more than 250 consecutive cases since then we have not seen any complications. Side effects and complications reported in literature are attributable to three main factors; application of too large quantities of fluorescein, of unsuitable fluorescein preparations, and of excessively high concentrations of fluorescein. False positive results are not possible with this technique; false negative findings can be present in 1-7 percent of cases, however. CONCLUSION: Our results demonstrate that the use of intrathecal fluorescein can be an extremely helpful diagnostic technique involving minimal risk.

Adolescent↗
PubMed1997

[Surgical occlusion of cerebrospinal fistulas of the anterior skull base using intrathecal sodium fluorescein].

BACKGROUND: For more than 25 years, intrathecal 5% sodium fluorescein has been routinely used at the University ENT Hospital at Graz during surgical closures of CSF leaks of the anterior skull base. Especially with endoscopic approaches, this technique has been of significant help in identifying and localizing dural defects. No fluorescein-related complications occurred in the series reported. MATERIAL AND METHODS: In a retrospective study, indications, techniques, and results of surgical closures of CSF leaks of the anterior skull base are reviewed. During 5 1/2 years from 1990-1995, 72 patients with CSF-rhinorrhea were operated on at our department, 69 of whom had sodium fluorescein applied intrathecally. In 41 patients strictly endoscopic techniques were applied, in 22 patients an external approach was chosen and in 9 cases combined approaches were used. Defects in the roof of the ethmoid, the lamina cribrosa, and in the sphenoid sinus almost exclusively were approached endoscopically. Defects in the posterior table of the frontal sinus, especially when located laterally, were approached from externally or via combined endonasal and external routes. The causes of the CSF leaks, their localization, and the surgical approaches chosen are analysed and the surgical techniques described in detail. RESULTS: The direct coronal CT of the paranasal sinuses/anterior skull base proved to be significantly better in detecting lesions compared to axial CT images (82% vs. 53%). In all cases intrathecal fluorescein allowed for a precise localization of the defect(s). There were no fluorescein related complications in this series. In one patient with massive frontobasal chip fractures and substantial dural defect, a rhinosurgical closure was not successful. Two patients developed recurrent fistulae after several months and years respectively. One of these patients had to be operated 3 times until permanent closure was achieved. Two patients had to be revised because of mucoceles of the frontal sinuses, in both cases the initial closure of the dural defect proved to be tight. CONCLUSION: Our results demonstrate that with exception of defects of the posterior lateral table of the frontal sinus, CSF leaks of the rhinobasis can be closed safely endoscopically. After a follow-up from 19-65 months, the overall success rate for 72 CSF leaks was at 94.5%. When applied correctly, the fluorescein technique proves to be an extremely helpful technique for diagnosis and surgery of CSF leaks.

Adolescent↗
PubMed1997

Mammography in women undergoing hormone replacement therapy. Possible effects revealed at routine examination.

PURPOSE: A retrospective study of screen-film mammographs was performed in 960 postmenopausal women to evaluate the possible effects of hormonal replacement therapy on the breast parenchymal pattern. MATERIAL AND METHODS: Screen-film mammographs of 754 women (mean age 51.4 years) who had undergone hormonal replacement therapy (estrogen, gestagen; mean duration 2.4 years) were compared with findings in 206 women who had not received hormonal replacement therapy (mean age 52.3 years). Mastopathic changes were analyzed according to a 4-grade scale and the incidence of circumscribed lesions (such as fibroadenomas, cysts and malignancies) was further evaluated. RESULTS: In the treated women we found moderate mastopathic changes in 47.2%, intermediate changes in 2.4%, and extensive proliferations in 0.7%. For the untreated women the corresponding figures were 33.5%, 4.8%, and 1.4%. In the treated patients fibroadenomas were apparent in 3.9%, cystic lesions in 3.3%, and malignant lesions in 1.4%. In the untreated women fibroadenomas were evident in 11.6%, cystic lesions in 7.2%, and malignant lesions in 2.4%. CONCLUSION: Mastopathic changes might increase under hormonal replacement therapy. However, the higher incidence of circumscribed lesions in the untreated women might be due to the higher number of symptomatic women who sought examination. We also speculate as to whether the increased density of the breast parenchyma in the treated women might cause a higher number of mammographically undedectable lesions.

Breast↗
PubMed1997

Neuropeptides responding to leptin.

Leptin, the circulating protein that inhibits food intake and energy expenditure, was thought to function through inhibition of the hypothalamic neuropeptide Y (NPY), a stimulator of food intake. However, mouse mutants lacking NPY are normal, suggesting that alternative neuromodulators of food intake must exist. Recently, melanocortin, a neuropeptide acting on the hypothalamic receptor melanocortin4-R, was discovered in mice, controlling energy regulation. This receptor is antagonized by the "agouti" protein in the mutant obese agouti mouse.

Animals↗
PubMed1997

A new uncoupling protein: a potential component of the human body weight regulation system.

A mitochondrial protein that uncouples the respiratory chain from oxidative phosphorylation and generates heat is found in brown adipose tissue (BAT) of rodents. Although humans have little BAT, a second uncoupling protein has been discovered that is widely distributed in human tissues. It is induced in mice by a high-fat diet and in mice with obese mutations, and may play a role in human body weight regulation.

Adipose Tissue, Brown↗
PubMed1997

Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking.

Shc and insulin receptor substrate 1 (IRS-1) are cytoplasmic substrates of tyrosine kinase receptors that engage, localize, and activate downstream SH2 enzymes. Each contains a phosphotyrosine-binding (PTB) domain that is structurally unrelated to SH2 domains. We have designed high-affinity, cellular inhibitors of the Shc PTB domain by incorporating nonnatural, phosphatase-resistant amino acids into short peptides. None of the inhibitors bind the IRS-1 PTB domain, consistent with distinct specificities for domains. The best inhibitor of the Shc domain was introduced by electroporation into Rat1 fibroblasts that express human insulin receptors. Insulin-stimulated phosphorylation of Shc was inhibited, with no effect on IRS-1, and downstream effects on mitogen-activated protein kinase and DNA synthesis were both inhibited. The PTB domain inhibitor had less influence on epidermal growth factor-induced effects and essentially no impact on serum- or phorbol ester-induced effects. The inhibitor did not affect insulin internalization and its degradation. We conclude that the PTB domain of Shc is critical for its phosphorylation by the insulin receptor, that Shc is an important mediator of insulin's mitogenic effects, and that Shc is not central to insulin receptor cycling in these cells. PTB domains can be inhibited selectively in cells and represent potential targets for drug discovery.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Differentiation of benign and malignant breast lesions: MR imaging versus Tc-99m sestamibi scintimammography.

PURPOSE: To compare the accuracies of magnetic resonance (MR) imaging and scintimammography in differentiating benign from malignant breast lesions. MATERIALS AND METHODS: MR imaging was performed in 66 women with 75 lesions during intravenous administration of gadopentetate dimeglumine. Planar and single photon emission computed tomographic (SPECT) scintimammography were performed (with 740 MBq technetium-99m sestamibi administered intravenously) in all 66 patients with 75 lesions and in 64 patients with 73 lesions, respectively. MR imaging and scintimammographic studies were independently evaluated by using signal intensity measurements versus time or focal tracer uptake to differentiate benign from malignant lesions. Histopathologic proof was obtained in 63 lesions. Twelve lesions were monitored with follow-up. RESULTS: MR imaging was false-negative in one and false-positive in nine lesions. Planar scintimammography was false-negative in 10 and false-positive in six lesions. SPECT scintimammography was false-negative in four and false-positive in 10 lesions. Sensitivities and specificities for malignancy were, respectively, 96% and 82% for MR imaging, 62% and 88% for planar scintimammography, and 83% and 80% for SPECT scintimammography. CONCLUSION: Both MR imaging and scintimammography are useful in the evaluation of breast cancer. MR imaging is more sensitive and as specific as scintimammography.

Adult↗
PubMed1997

Coaxial technique: approach to breast core biopsies.

PURPOSE: To assess the feasibility of the coaxial core breast biopsy technique performed under stereotactic and ultrasound (US) guidance in vitro and in vivo. MATERIALS AND METHODS: Biopsies were performed in vitro and in vivo with a coaxial technique. In vitro, the true needle-tip deviation was measured with a breast phantom on a stereotactic device with alteration of x and y axes. In vitro US studies were performed to evaluate the optimal technique for harvesting sufficient material for histologic work-up. In 205 patients, coaxial biopsy was performed in 210 suspicious lesions under US (61 lesions) or stereotactic (patient in the sitting position, n = 67; patient in the prone position, n = 82) guidance. In addition, the coaxial system was used for preoperative localization. Surgery and histologic work-up were performed in all cases. RESULTS: In vitro, the true needle-tip deviation was found to be less than indicated on the stereotactic device. A factor was introduced to correct this error. For US guidance, angulation or rotation of the coaxial needle within the lesion proved to be the best technique to increase the size of histologic specimen. Of the 210 lesions, 112 were benign and 98 were malignant. Agreement between biopsy results and final postsurgical histologic analysis was found in 205 cases (98%). CONCLUSION: The coaxial breast biopsy technique is an accurate, simple, and time-saving method performed under stereotactic or US guidance.

Adult↗
PubMed1997

High glucose stimulates expression of p27Kip1 in cultured mouse mesangial cells: relationship to hypertrophy.

Hypertrophy of mesangial cells is an early hallmark of diabetic nephropathy. We have previously shown that murine mesangial cells (MMC), cultured in high-glucose medium, are arrested in the G1 phase of the cell cycle and undergo hypertrophy. This study was undertaken to test whether high glucose-containing medium influences the expression of p27Kip1, an inhibitor of G1 phase active cyclin-dependent kinases (CDK). Incubation of MMC, in the absence of other factors for 48-96 h, in medium containing high D-glucose (450 mg/dl), stimulated p27Kip1 protein expression but failed to influence mRNA abundance. These effects were independent of the osmolarity of the medium. High glucose-stimulated expression of p27Kip1 involved activation of protein kinase C and was partly dependent on induction of transforming growth factor-beta (TGF-beta). Immunoprecipitation experiments revealed that only small amounts of p27Kip1 protein from MMC grown in high-glucose medium preferentially associates with CDK2 but not with CDK4. The p27Kip1 antisense, but not missense, oligonucleotides inhibited high glucose-stimulated total protein synthesis and facilitated G1 phase exit. Our data showed for the first time that expression of p27Kip1 protein is pivotal in mesangial cell hypertrophy induced by high ambient glucose. These findings may be important in the deciphering of molecular processes causing diabetic glomerular hypertrophy.

Animals↗
PubMed1997

Angiotensin II inhibits inducible nitric oxide synthase in tubular MCT cells by a posttranscriptional mechanism.

Expression of the inducible isoform of nitric oxide synthase (iNOS) and generation of nitric oxide (NO) have been recently described, in addition to mesangial and medullary thick ascending limb cells, in proximal tubular cells, including MCT, a mouse proximal tubular epithelium cell line. Because vasoconstrictors may interfere with the induction of iNOS and the subsequent generation of NO, in the study presented here, whether exogenous angiotensin II (ANG II) influences bacterial lipopolysaccharide (LPS)/gamma-interferon (gamma-IF)-stimulated NO synthesis and iNOS protein and mRNA expression in MCT cells was tested. LPS/gamma-IF readily stimulated nitrite synthesis in MCT cells, as one measured parameter of NO synthesis. Coincubation of cells with 10(-9)-10(-6) M ANG II attenuated this LPS/gamma-IF-stimulated induction of nitrite. This effect was reversed by the AT1-receptor blocker losartan, but not by an AT2-receptor antagonist, indicating signal transduction through AT1-receptors. Western blot analysis applying a specific monoclonal antibody generated against mouse iNOS revealed that 10(-8)-10(-6) M ANG II significantly reduced LPS/gamma-IF-induced iNOS protein expression. However, ANG II had no effect on LPS/gamma-IF-induced iNOS mRNA as assessed by Northern blots. Moreover, transient transfection studies using a chimeric gene construct, in which iNOS regulatory elements are linked to the CAT reporter gene, showed no effect of ANG II on the LPS/gamma-IF-stimulated transcriptional activity. The study presented here demonstrates that ANG II influences LPS/gamma-IF-stimulated NO generation in MCT cells, most likely at a posttranscriptional level, by influencing iNOS protein expression. Whether proximal tubular cells in vivo express iNOS remains to be established, but this study suggests a mechanism for how iNOS activity is influenced by ANG II in cultured proximal tubular cells.

Angiotensin II↗
PubMed1997

Nitric oxide and nitric oxide synthase: biology, pathology, localization.

Nitric oxide (NO) has opened a new and vigorous field of biological and clinical experimentation as evidenced presently by about one hundred original publications every week. Being a biological signal under physiological conditions, NO may be < > to pathologically affected tissues. Major insights into the biology and pathology of this unorthodox biomolecule have come from the histochemical analysis of NO synthase (NOS) and its molecular isoforms that are responsible for the formation of NO. Immunocytochemistry as well as NADPH-diaphorase histochemistry are most widely used to visualize NOS in various tissues. There are several constraints regarding specificity and sensitivity of the techniques used and, therefore, apparent discrepancies in the literature concerning the cellular and subcellular distribution of NOS and its isoforms. Despite such inconsistencies there is a wealth of data that has an important impact on further investigation of NO-mediated processes underlying a vast number of NO-mediated physiological and pathological mechanisms.

Animals↗
PubMed1997

Renal tubular hypertrophy induced by angiotensin II.

Cellular processes leading to renal tubular hypertrophy may contribute to the development of progressive renal disease. Angiotensin II (ANG II) is a prime agent that has been linked to the progression of renal disease by a host of mechanisms, including the induction of tubular epithelial hypertrophy and stimulation of extracellular matrix biosynthesis. All components of a functional renin-angiotensin system reside within the renal tubule. Epithelial cells exhibit distinct patterns of growth behavior after stimulation with ANG II (namely, hypertrophy of proximal tubule segments and proliferation of more distal segments). The hypertrophic action of ANG II is mediated through high-affinity AT1-receptors, involves activation of pertussis-toxin sensitive G1 proteins, and depends on a decrease in intracellular cAMP. In addition, ANG II induces sequential activation of MAP kinases and S6 kinase, and leads to activation of early immediate genes and the modulation of a series of cyclins and cyclin-dependent kinases. There is also compelling evidence that the ANG II-induced epithelial hypertrophy and the stimulated-synthesis of collagen type IV are mediated by increased transcription and production of TGF-beta. ANG II-mediated inhibition of protein degradation may further increase protein content. The hypertrophic response to ANG II is greater in medium with high glucose concentration. Blockade of the action of ANG II prevents the renal hypertrophy and the tubulointerstitial fibrosis in animal models of chronic renal diseases (independent of changes in systemic or glomerular hemodynamics), in part through interception of ANG II-mediated induction of TGF-beta expression.

Angiotensin II↗
PubMed1997

[Iodine and thyroid hormone metabolism in pregnancy].

The influence of pregnancy on thyroid function as well as important interactions of pregnancy and thyroid disorders are of high clinical importance. During the last decade knowledge of these issues greatly influenced clinical aspects and basic science. Because of the increasing frequency of thyroid disorders during pregnancy, knowledge of these issues is important in order to diagnose, treat and manage all patients exposed to these problems.

Female↗