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Biomedical subjects

G Wolf

Publications and source records attributed to G Wolf.

At least 145 records · Page 8Linked to original sources
PubMed2000

The oxidation of 9-cis-retinol: a possible synthesis pathway for 9-cis-retinoic acid.

A short-chain alcohol dehydrogenase has been discovered that oxidizes 9-cis- and 11-cis-retinol to their corresponding aldehydes. The gene for this enzyme was sequenced and appears to be expressed with highest efficiency in the retinal pigment epithelium of the eye, as well as in human liver and mammary gland and in mouse liver and kidney. Because 9-cis-retinol occurs in liver, it may be a precursor of 9-cis-retinoic acid.

Alcohol Oxidoreductases↗
PubMed2000

Cellular retinoic acid-binding protein II: a coactivator of the transactivation by the retinoic acid receptor complex RAR.RXR.

Cellular retinoic acid-binding protein (CRABP) appears in vertebrate organisms in two isoforms, CRABPI and II, with distinct distribution and functions. CRABPII, when combined with its retinoic acid (RA) ligand, interacts specifically with the liganded RA receptor complex (RAR.RXR), which is bound to the RA response elements of particular genes in order to greatly activate their expression. Thus, liganded CRABPII acts as a coactivator for RAR.RXR.

Animals↗
PubMed2000

Retinoic acid induces the degradation of the leukemogenic protein encoded by the promyelocytic leukemia gene fused to the retinoic acid receptor alpha gene.

Acute promyelocytic leukemia (APL) cells carry a mutated gene that is the result of a translocation in which the retinoic acid receptor alpha (RAR alpha) gene is fused to the promyelocytic leukemia (PML) gene, coding for a fusion protein, PML/RAR alpha. Its presence is the single event that causes APL in transgenic mice. All-trans-retinoic acid (atRA) induces the proteolytic degradation of PML/RAR alpha by ubiquitination and proteolysis. RAR alpha itself is also degraded by atRA treatment, a process representing a possible feedback mechanism to turn off RAR alpha's stimulation of transcription.

Antineoplastic Agents↗
PubMed2000

Increased expression of CD40 ligand (CD154) on CD4+ T cells as a marker of disease activity in rheumatoid arthritis.

OBJECTIVES: The interaction between the activation induced surface glycoprotein CD40L (ligand) (CD154) on CD4+ T cells and its receptor CD40, which is expressed on various cell types, plays a crucial part in numerous cell mediated and humoral immune reactions that may be of pathogenetic importance in rheumatoid arthritis (RA). To further evaluate the pathogenetic role of CD40L in RA, expression of CD40L and various other T cell activation antigens as well as costimulatory molecules was investigated on CD4+ T cells in RA by flow cytometry. METHODS: Two colour flow cytometry was used to determine the percentage of CD4+ T cells expressing CD40L, CD69, CD25, HLA-DR, CD39, CD27 and CD28 in peripheral blood (PB) of 62 RA patients in comparison to 20 healthy controls (HC). Disease activity was assessed by clinical, laboratory and radiological examination. Status of clinical remission of RA was evaluated according to the ACR preliminary criteria for complete clinical remission of RA. RESULTS: CD40L was expressed on > 10% of CD4+ T cells in 29% of RA patients thus defining a CD40L(high+) patient group. Disease activity as estimated by C reactive protein, rheumatoid factor and status of clinical remission of disease (p = 0.049) was higher in this subgroup than in the RA CD40L(low+) group. Expression of CD69, CD25, and HLA-DR was significantly increased in both RA patient groups in comparison with HC. However, the percentage of CD39+ CD4+ T cells was increased only in the RA CD40L(high+) subgroup (versus HC p = 0.019, versus RA CD40L(low+) p = 0.044). Furthermore, expression of CD40L and CD39 on CD4+ T cells correlated positively as estimated by Spearman rank correlation (p<0.001). The percentage of CD4+ T cells lacking the costimulatory molecules CD27 (p = 0.002) and CD28 (p = 0.026) was increased in RA CD40L(low+) patients in comparison with HC. CONCLUSIONS: These data suggest that increased expression of CD40L on CD4+ T cells in RA indicates prolonged and increased activation of CD4+ T lymphocytes and is associated with active disease and possibly an unfavourable prognosis. Whether this phenotypically defined RA CD40L(high+) subgroup will preferentially respond to an anti-CD40L antibody treatment remains to be elucidated.

Adult↗
PubMed2000

Endolacrimal laser assisted lacrimal surgery.

AIMS: To utilise the improved optical qualities of newly developed lacrimal endoscopes and newly miniaturised laser fibres for diagnostic visualisation and laser surgery of the lacrimal system. METHODS: A KTP laser (wavelength 532 nm, 10 W energy) was used for laser assisted dacryocystorhinostomy (DCR) with endolacrimal visualisation in 26 patients. Bicanalicular silicone intubation was placed in all patients for at least 3 months. RESULTS: After 3-9 months of follow up, the silicone tube in all 21 patients who underwent KTP laser DCR are still patent, three patients have eye watering in extremely cold weather and two required a conventional DCR. CONCLUSIONS: The KTP laser generates enough power to open the bony window in DCR surgery. Precise endolacrimal visualisation via a specially designed miniendoscope is essential for surgical success.

Dacryocystorhinostomy↗
PubMed2000

Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis.

The response to glomerular and tubulointerstitial cell injury in most forms of renal disease includes changes in cell number (proliferation and apoptosis) and cell size (hypertrophy). These events typically precede and may be responsible for the accumulation of extracellular matrix proteins that leads to a decrease in renal function. There is increasing evidence showing that positive (cyclins and cyclin-dependent kinases) and negative (cyclin-dependent kinase inhibitors) cell cycle regulatory proteins have a critical role in regulating these fundamental cellular responses to immune and nonimmune forms of injury. Data now show that altering specific cell cycle proteins affects renal cell proliferation and improves renal function. Equally exciting is the expanding body of literature showing novel biological roles for cell cycle proteins in the regulation of cell hypertrophy and apoptosis. With increasing understanding of the role for cell cycle regulatory proteins in renal disease comes the hope for potential therapeutic interventions.

Animals↗
PubMed2000

Management of acute surgical orbital haemorrhage: an otorhinolaryngological and ophthalmological perspective.

This retrospective report describes the management and outcome of seven patients who suffered an acute surgical orbital haemorrhage (ASOH), secondary to a surgical procedure performed on either the sinuses, orbits or eyelids. All patients but one recovered their pre-operative vision. A management plan is outlined on how to assess and tackle this complication, so that the ENT surgeon may be better prepared to meet such an acute surgical emergency, should it arise.

Adult↗
PubMed2000

Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection.

BACKGROUND: Curative resection of pancreatic adenocarcinoma is the only clinical parameter related to a favorable prognosis while other clinicopathological parameters fail. To evaluate whether angiogenesis, vascular endothelial growth factor (VEGF) or certain tumor proteases, e.g., cathepsin B (CTSB) and L (CTSL), are factors of prognostic relevance, we investigated their expression in patients with long- and short-term survival after curative resection (RO) because of pancreatic adenocarcinoma. METHODS: Twenty-nine tissue samples from patients with adenocarcinoma of the pancreas were examined. The patients were selected in a long-term survival group with a survival > or = 24 mo (n = 18) and a shortterm survival group of patients, who died within 8 mo after surgery because of their malignancy (n = 11). The microvessel quantification was performed immunohistochemically using a monoclonal anti-CD34 antibody. VEGF, CTSB, and CTSL expressions was studied using polyclonal antibodies (PAbs). RESULTS: The median microvessel density (MVD) was 75 (range 39-182). MVD correlated significantly with the survival time after surgery (p = 0.0132) but not with clinicopathological parameters. In cancer cells, VEGF was positive in 82.8% and showed significant correlation with the MVD (p = 0.0002) and survival time (p = 0.0395). Positive immunoreactivity could be obtained for 96.5% for CTSB and 84.2% for CTSL. Expression of both proteases correlated significantly with the survival time after surgery (CTSB p = 0.0002, CTSL p = 0.0001). Furthermore, CTSB expression correlated with invasion of the perineural space. Thus, a short postoperative survival correlated with a high MVD, and highly expressed VEGF, CTSB, and CTSL. No significant correlation between MVD, VEGF, as well as CTSL and clinicopathological parameters was found. For routinely assessed markers (e.g., TNM-stage, UICC-stage, and so on) no significant correlation with survival time was found in this small group of patients. CONCLUSION: These findings indicate that the MVD, VEGF, CTSB, and CTSL are prognostic factors after curative resection, whereas other parameters (TNM, UICC, and so on) failed to show prognostic relevance in our group of patients. Furthermore, the correlation between MVD and VEGF underlines the importance of this growth factor for angiogenesis and tumor growth. The correlation between CTSB and perineural invasion demonstrates the involvement of cathepsins in local tumor invasion.

Adenocarcinoma↗
PubMed1999

In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.

In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.

Animals↗
PubMed1999

Tyramide signal amplification in brain immunocytochemistry: adaptation to electron microscopy.

The tyramide signal amplification (TSA) technique is well-established in light microscopic immunohistochemistry and in situ hybridization to improve the signal-to-noise ratio. The present study deals with its adaptation to the electron microscopic level using the pre-embedding technique and a modified protocol. The outcome of immunolabeling of most of the antigens tested in brain tissue, including endothelial and neuronal nitric oxide synthase, glial fibrillary acidic protein, and isolectin B4, was greatly improved. If signal amplification is required, the TSA-technique proved to be reliable with high specificity and good ultrastructural resolution.

Antibody Specificity↗
PubMed1999

Peroxynitrite mediated damage and lowered superoxide tolerance in primary cortical glial cultures after induction of the inducible isoform of NOS.

The effect of the induction of i-NOS in primary glial cultures was studied with respect to the protein levels of reactive oxygen species (ROS) scavenging enzymes and the cytotoxicity of nitric oxide (.NO) formation at different levels of artificially generated superoxide. Stimulation of the cultures by bacterial lipopolysaccharides and gamma-interferon resulted in an induction of i-NOS exclusively in microglial cells. Among the ROS scavenging enzymes superoxide dismutase (Cu/Zn- and Mn-isoform), glutathione peroxidase and catalase only mitochondrial Mn-SOD was found to be upregulated in the course of i-NOS induction (Western blots). Although .NO formation did not affect cell viability at physiological levels of superoxide over a time period of 4 days, it caused an oxidative load particularly in microglial cells as observed by monitoring the oxidation of dichloro-dihydrofluorescein, an indicator for the formation of peroxynitrite and ROS. Elevated levels of superoxide, generated either intracellularly by paraquat or extracellularly via xanthine oxidase and hypoxanthine, resulted dose-dependently in a larger decline of cell viability in the .NO forming cultures compared to controls (release of lactate dehydrogenase, citrate synthase, stainability by propidium iodide, and tetramethylrhodamine). NOS-inhibitors reduced the degree of cell damage to that seen for control cultures, indicating an ONOO--/.NO mediated mechanism of cell damage. Our data support the concept that i-NOS catalyzed .NO-formation leads to an ONOO--mediated increased oxidative load. At physiological levels of superoxide and within a wide range of higher superoxide levels this nitrosative stress is well balanced in cultured glial cells by protective mechanisms.

Animals↗
PubMed1999

Urokinase plasminogen activator receptor (CD87) expression of tumor-associated macrophages in ductal carcinoma in situ, breast cancer, and resident macrophages of normal breast tissue.

UNLABELLED: Macrophages concentrate urokinase-type plasminogen activator (uPA) at the cell surface by expressing urokinase receptors (uPAR) in order to focus the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. This study examines the uPAR levels of tumor-associated macrophages (TAM) of invasive breast carcinomas, of TAMs from ductal carcinoma in situ (DCIS) and of macrophages derived from normal (non-tumor) breast tissue. TAMs from invasive breast carcinomas (n = 30), from DCIS (n = 12), and macrophages from normal breast tissue (n = 30) were cultured and immunocytochemically phenotyped by using a panel of antibodies. Urokinase receptor levels were determined by Western blot analysis and in cell-free supernatants by enzyme-linked immunosorbent assay. Urokinase receptor cell surface fluorescence intensity was determined by FACS and by confocal laser scan microscopy. Urokinase-receptor mRNA was detected by in situ hybridization. TAMs of invasive breast carcinomas and of DCIS possess significantly elevated uPAR levels compared with macrophages derived from normal breast tissue. CONCLUSIONS: activated macrophages with elevated uPAR levels belong to inflammatory areas in close vicinity of infiltrating and non-infiltrating (DCIS) tumor cells. Blood monocytes that possess elevated uPAR-levels may be selectively recruited from the bloodstream to inflammatory sites close to carcinoma cells, and/or breast cancer and precursor lesions may induce elevated uPAR-levels in TAMs by paracrine interactions.

Breast Neoplasms↗
PubMed1999

Angiotensin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells.

Tubulointerstitial fibrosis is a common end-point of many chronic renal diseases and contributes to the permanent loss of renal function. There is increasing evidence that the profibrogenic cytokine transforming growth factor TGF-beta plays an essential role in this process by inducing the production of extracellular matrix proteins by tubular cells through an autocrine mechanism. We have previously demonstrated that the vasopeptide angiotensin (ANG) II induces TGF-beta transcription and synthesis in cultured murine proximal tubular cells (MCT cell line). Since the overall effects of TGF-beta on a distinct target cell may also depend on the expression of specific cell surface receptors, the present study was undertaken to test the hypothesis that ANG II modulates expression of TGF-beta receptors in MCT cells. ANG II stimulated protein expression of TGF-beta receptor type II, but not that of type I, in MCT cells as detected by immunofluorescence and western blotting of cell lysates. This stimulated receptor expression was also reflected in an overall increase in specific binding of 125I-labeled TGF-beta1 to intact MCT cells. Coincubation with ANG II and an AT1 receptor antagonist abolished this increase in 125I-labeled TGF-beta1 binding. Furthermore, ANG II also increased steady-state mRNA expression for TGF-beta receptor type II. This stimulation was transduced through AT1 receptors and was independent of TGF-beta released into the culture medium. Transient transfection studies using various length enhancer/promoter elements of the human TGF-beta receptor type II linked to the CAT gene revealed that AP1 sites are a necessary prerequisite for ANG II induced transcriptional activity. ANG II had no effect on TGF-beta receptor types I or II protein or on mRNA expression in syngeneic mesangial cells. Our results provide for the first time convincing evidence that ANG II upregulates TGF-beta receptor type II expression on proximal tubular cells. Since this subtype of receptor is primarily engaged in the initial binding of TGF-beta, an increased receptor expression may result in amplification of the TGF-beta effects on tubular cells. Interference with an activated renin-angiotensin system could therefore counteract the profibrogenic effects of TGF-beta by abolishing ANG II induced expression of TGF-beta receptor type II.

Angiotensin II↗
PubMed1999

[Staging of breast carcinoma. Value of diagnostic imaging].

In women with breast cancer, staging of the tumor plays an important role and often is considered to be the most prognostic and therapeutic factor. The most widely used staging system is based on the pathologic TNM classification. In recent years conservative therapies such as preoperative chemo- or radiotherapy are used more often with limited tissue evaluation resulting in insufficient or even inaccurate staging data. Tumor size as well as nodal involvement is decisive in selecting a treatment method and assessing the response. Thus, more accurate preoperative in vivo staging is necessary. This article therefore gives an overview of the different imaging modalities (mammography, ultrasonography, magnetic resonance imaging, and nuclear medicine) used for breast cancer staging. Furthermore, results of these methods are compared critically with the pathohistologic staging.

Breast↗
PubMed1999

Angiotensin converting-enzyme inhibitor treatment reduces glomerular p16INK4 and p27Kip1 expression in diabetic BBdp rats.

AIMS/HYPOTHESIS: Renal hypertrophy occurs early in diabetes mellitus and precedes the development of glomerulosclerosis and tubulointerstitial fibrosis. We have previously shown that cultured mesangial cells exposed to high glucose are arrested in the G1-phase of the cell cycle and undergo cellular hypertrophy. High glucose-mediated induction of p27Kip1, an inhibitor of cyclin-dependent kinases, is essential in this process. Further investigations have also shown that p27Kip1 and p21Cip1, other cyclin-dependent kinase inhibitors, are up regulated in the kidneys of mice with Type I (insulin-dependent) as well as Type II (non-insulin-dependent) diabetes mellitus. Our study was undertaken to test a potential effect of short-term treatment with the angiotensin-converting enzyme inhibitor enalapril on the glomerular expression of the cyclin-dependent kinase inhibitors p16INK4, p21Cip1, and p27Kip1 in BBdp rats, an autoimmune model of Type I diabetes. METHODS: We evaluated p16INK4, p21Cip1, and p27Kip1 protein expression in isolated glomeruli by western blots. We also assessed p27Kip1 positive glomerular cells by immunohistochemistry. RESULTS: Glomerular expression of all three cyclin-dependent kinase inhibitors were stimulated in BBdp rats compared with non-diabetic BBdr animals. Enalapril treatment for 3 weeks, started after the onset of diabetes, reduced the glomerular expression of p16INK4 and p27Kip1 but not of p21Cip1. Enalapril also prevented the increase in kidney weights observed in BBdp rats but had no effect on systolic blood pressure or glucose concentrations. CONCLUSION/INTERPRETATION: Our data show that enalapril attenuates the glomerular expression of cyclin-dependent kinase inhibitors in diabetes and suggest a molecular mechanism of how angiotensin-converting enzyme inhibitors prevent renal hypertrophy in diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Randomized in vitro and in vivo evaluation of different biopsy needles and devices for breast biopsy.

In an experimental study (in vitro and in vivo) we evaluated the efficacy of various biopsy needles/devices for breast biopsy. In vitro, biopsies of five human cadaveric breast specimens were performed using 33 different needles/devices ranging from 14 to 20-gauge. Of these 33 needles/devices, 22 optimally performing needles were selected for the in vivo study. In the clinical part of the study, 44 breast lesions were randomly biopsied with each of the 22 needles/devices under stereotactic guidance. Tissue specimens were analysed quantitatively and qualitatively. Several automatic long-throw guns (Acecut, Asap, Biopty, Magnum) obtained greater tissue areas and had a better histopathologic score than the conventional type of a side-notch needle like Trucut, an aspiration needle like Surecut, or an end-cut needle like Autovac. The automatic long-throw guns performed better than the short-throw Monopty gun. Regardless of needle size (14-20-gauge), breast biopsies should be routinely performed with automated long-throw side-notch guns (Acecut, Asap, Biopty, Magnum).

Adult↗
PubMed1999

Three-dimensional partial zona dissection for preimplantation genetic diagnosis and assisted hatching.

OBJECTIVE: To develop a new approach to partial zona dissection of oocytes and embryos for facilitating preimplantation genetic sampling and assisted hatching. DESIGN: Controlled clinical study. SETTING: Preimplantation genetic diagnosis and IVF program, Reproductive Genetics Institute/IVF Illinois, Chicago, Illinois. PATIENT(S): Three hundred forty patients undergoing IVF in whom preimplantation genetic diagnosis or assisted hatching was required. INTERVENTION(S): Three-dimensional partial zona dissection and conventional partial zona dissection were performed, with the use of a simple microneedle, on embryos before preimplantation genetic sampling or on day 3 of embryo development before ET. MAIN OUTCOME MEASURE(S): Pregnancy rate, implantation rate, and ease of preimplantation genetic sampling. RESULT(S): A pregnancy rate of 42% and an embryo implantation rate of 17.6% were obtained in the group in which three-dimensional partial zona dissection was performed, compared with a pregnancy rate of 33% and an implantation rate of 14.7% in the control group, which underwent conventional partial zona dissection. Preimplantation genetic sampling can be performed without distortion of the blastomere configuration in the embryo. CONCLUSION(S): Three-dimensional partial zona dissection is a safe and simple mechanical means of creating an opening sufficient for the atraumatic removal of material from oocytes and embryos for preimplantation genetic diagnosis and assisted hatching.

Dissection↗