Biomedical subjects
Publications and source records attributed to G Wolf.
A protein has been isolated from rat liver cytosol that specifically binds alpha-tocopherol. It does not occur in other tissues. Its amino acid sequence has been determined and it was found to have great homology with 11-cis-retinaldehyde-binding protein of the retina. This tocopherol-binding protein may be defective in a certain type of familial vitamin E deficiency syndrome.
Fumonisins, mycotoxins found on corn and other grains, can act as carcinogens. Recent studies have shown that fumonisin B1 stimulates cell proliferation due to inhibition of sphinganine N-acyl-transferase, an important rate limiting enzymatic step in sphingolipid biosynthesis. Subsequent accumulation of free sphingoid bases in the cell can act as tumor promoters.
Diet and the effect of hormones were studied in transgenic mice bearing a part of the promoter of the gene for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. The domains of the gene promoter involved in tissue specificity, development, and response to diet were identified by analysis of expression of the mutated gene. Important differences were uncovered between results from earlier cell culture experiments and the results from more physiologic responses of the transgenic animals.
Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-beta. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF-beta, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-beta antibody, but not normal rabbit IgG, significantly reduced the high glucose-stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-beta antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-beta 1 mimicked the effects of high glucose. Furthermore, the anti-TGF-beta antibody significantly reduced the increase in mRNA levels encoding alpha 2(I) and alpha 1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-beta activation. We postulate that the interception of the glomerular activity of TGF-beta may be an effective intervention in the management of diabetic nephropathy.
Magnetic resonance images of the sphenoid sinus in 401 patients under 15 years old were reviewed to establish normal age-related standards. T1-weighted sagittal and T2-weighted axial scans were evaluated for bone marrow conversion, development of pneumatization, spatial enlargement and septation of the sphenoid sinus. The sphenoid sinus had a uniformly low signal intensity (red bone marrow) on T1-weighted images in all children less than 4 months old. Signal intensity changes from hypointense to hyperintense (bone marrow conversion) started at the age of 4 months. Onset of pneumatization was observed in 12% of the patients at age 13-15 months. By age 43-48 months, 85% of the patients showed pneumatization of the anterior part of the sphenoid bone. Pneumatization was complete in all patients older than 10 years. Enlargement of the sinus showed a characteristic profile in each dimension. Median septation was observed irregularly with age, with a maximum of 77%. Septum variants were noticed between 4.5% and 20%. Because paediatric sinus disease is a challenging problem in children, these results may be useful as baseline standards of normal age-related development of the sphenoid sinus during childhood.
The possible role of prostaglandin E2 (PGE2) on the formation of collagens and fibronectin in cultured rat mesangial cells (MC) was studied. The effect of exogenous PGE2 was analyzed by the measurement of steady-state mRNA levels of the extracellular matrix components and by the secretion of these matrix components into cell culture supernatants. PGE2, in a dose-dependent manner, reduced mRNA levels of alpha 1(I) and alpha 1(III) procollagens but had little effect on alpha 1(IV) procollagen and fibronectin mRNA. In addition to its role on mRNA levels, PGE2 reduced the secretion of all studied collagen types into the cell culture supernatants. To evaluate a possible role of intracellular cAMP in the mediation of the PGE2 effects, MC were incubated with the cAMP analogue 8-bromo-cAMP (8brcAMP). In contrast to PGE2, 8brcAMP (1 mM) had no effect on mRNA expression of procollagen Types I and III over the studied time period (1 to 48 h). Furthermore, 8brcAMP stimulated collagen secretion into the cell supernatant after 48 h of incubation. These data demonstrate that PGE2 reduces mRNA levels of procollagen Types I and III in cultured MC, although the biosynthesis of all studied extracellular matrix components is inhibited. These alterations seem to be independent of intracellular cAMP, because the cAMP analogue 8brcAMP does not mimic the PGE2 effects on steady-state mRNA expression and collagen secretion of the studied extracellular matrix components.(ABSTRACT TRUNCATED AT 250 WORDS)
This study assessed the effects of exogenous isoproterenol on the proliferation of the proximal tubular cell lines MCT and LLC-PK1. Both cell lines express beta-adrenergic receptors as demonstrated by Scatchard analysis of binding data, receptor-cross linking studies, and mRNA expression for beta 2-adrenergic receptors. Isoproterenol (10(-7) M) for 15 min stimulated the formation of intracellular cAMP in MCT cells (controls, 8.0 +/- 0.7; isoproterenol, 12.6 +/- 0.89 fmol of cAMP/microgram of protein; P < 0.01). This effect was blocked by the beta-receptor antagonist propranolol (10(-6) M). Isoproterenol, in a dose-dependent manner, also induced proliferation in MCT and LLC-PK1 cells, as measured by [3H]thymidine incorporation and direct cell counts. Time-course experiments demonstrated maximal mitogenesis 48 h after a single dose of 10(-7) M isoproterenol. This mitogenic effect was mimicked by a stable cAMP analog or cholera toxin, but not by a cGMP analog, indicating that the isoproterenol-mediated growth effects are likely caused by cAMP. These results provide evidence that isoproterenol is a mitogenic growth factor for cultured proximal tubular cells. These findings may be important in the growth mechanisms involved in the proliferative remodeling of injured tubules after acute renal failure.
A perflubron emulsion is being developed as a contrast agent to enhance lymph nodes on computed tomography (CT) images. The emulsion is administered by percutaneous injection into the drainage field of the lymph nodes to be imaged. A series of preclinical studies was conducted to investigate the efficacy of the perflubron emulsion for enhancement of lymph nodes on CT images. The effects of dose (0.10 to 0.50 mL), application of massage, and route of administration were investigated in healthy New Zealand white rabbits. Results of these studies demonstrated that doses as low as 0.15 mL were efficacious for consistent enhancement of axillary lymph nodes on CT images after subcutaneous injections in the forepaw. Application of massage to the injection site decreased the time for maximum nodal enhancement from approximately 7 days to 2 days postinjection. A pilot study conducted in 18 healthy, male volunteers indicated dose-related enhancement of axillary lymph nodes on CT images following subcutaneous injections of the emulsion in the hand. Other than mild, transient injection-site discomfort, no clinically significant side effects were observed. These data demonstrate that the perflubron emulsion is safe and can enhance axillary lymph nodes on CT images following injections in the hand.
The activity of reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) was examined histochemically in the rat cerebellar cortex at the light and electron microscopical level. Different staining patterns were observed depending on the technique used. Electron dense reaction product was seen on distinct membrane portions of the endoplasmic reticulum including the nuclear envelope in most of the neurons and in endothelial cells. Electron microscopically no activity staining was seen in glial cells, including Bergmann cells. The addition of the detergent Triton X-100, usually applied in the light microscopical diaphorase histochemistry, led to a striking diminution in membrane staining. In such preparations inspected electron microscopically formazan formed small granules which were evenly distributed over the cytoplasm.
The recent discovery of the identify of nitric oxide synthase with the reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) has powerfully stimulated the anatomical localization of sites of nitric oxide synthesis in the nervous system. In the present study the widely used light microscopical technique for NADPH-d staining was adapted to the electron microscopical level by applying the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl)tetrazolium chloride (BSPT) which produces an electron-dense reaction product, BSPT-formazan. Predominantly membranes of the endoplasmic reticulum were stained. Apart from singular heavily labeled neurons, a majority of nerve cells, light microscopically "unstained", shows sporadically formazan deposits, and, likewise, but regionally different, a few astroglial cells. Lesions induced by the glutamate agonists quinolinic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) display surviving neurons, which are predominantly stained for NADPH-d. Astroglial cells within lesioned areas exhibit increased amounts of reaction product, apparently as a consequence of enzyme induction.
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1'-Hydroxyeugenol- and epoxy-Z-coniferyl alcohol esters from Coreopsis species as well as synthetic derivatives of these natural compounds were examined as lipoxygenase inhibitors and as LDL (low density lipoprotein)-stabilizing agents. Most of the compounds displayed inhibitory activity on the formation of leukotrienes (LTB4 and LTC4) in a cellular (RBL-1 cells) assay as well as in a cell-free 5-lipoxygenase assay at concentrations of 4-24 mumol/l. No effect of selected compounds was observed on mammalian lipoxygenases with other specificity (12- and 15-lipoxygenase). The more lipophilic derivatives also effectively reduced Cu(2+)-mediated oxidation of LDL. The findings are discussed on the base of structure-activity relationships.
Due to unstable angina pectoris coronary arteriography was performed in a 57 year-old female, showing diffuse 3-vessel disease; aortocoronary bypass surgery was recommended. During routine pre-operative examination hypercalcemia, as well as an elevated value of parathormone were observed. Ultrasonography of the parathyroid glands showed two enlarged cranial glands. In a simultaneous surgical procedure 4 bypass grafts were performed and 4 hyperplastic parathyroid glands were removed, one of which was re-operated as an autotransplantation in the left musculus adductor magnus. Histological examination showed water clear cell hyperplasia of the parathyroid glands. Though the patient had suffered from stomach and duodenal ulcers and nephrolithiasis over several years, primary hyperparathyroidism was diagnosed only after angiographically proven coronary artery disease.
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The term Border disease (BD) refers to a clinical condition of newborn lambs that results from congenital infection by a pestivirus (family: flaviviridae), occurring during the first one-half of gestation. The most prominent clinical features are tonic-clonic tremors and hairy fleece ("hairy shaker" symptomatology). Moreover early transplacental infection often causes fetal death, abortion or stillbirth and teratogenic disorders. In Germany there are only few reports on clinical cases of BD, however in sheep antibodies have been found frequently in different regions of the country. Similar to the situation with bovine viral diarrhea/mucosal disease (BVD/MD) the existence of persistently infected sheep is proven. As permanent carriers and initiators of clinically apparent as well as more commonly clinically inapparent infections persistently infected animals are of great epidemiological importance. As a new method for the diagnosis of persistently Border disease Virus (BDV) infected sheep flow cytometry is presented. This special procedure of immunofluorescence has the overall advantage of rapid and reliable detection of pestivirus-infected cells by a highly conserved viral epitope (p 80/125). All biotypes of pestiviruses (non cytopathic = ncp and cytopathic = cp isolates) are recognized equally well by monoclonal antibodies (mAb) which provides some advantage compared to conventional techniques because most virus isolates from sheep belong to the ncp biotype.
In Germany, Transfusion Medicine belongs to various medical disciplines. We would like to demonstrate our model of interdisciplinary collaboration in stem cell transplantation. Since 1989 we performed 339 leukaphereses in 53 patients. On average we got 1.4 x 10(8) MNC/kg body weight from one single apheresis procedure. To observe graft quality we measured the content of CD34-positive cells and the amount of CFU-GM. Despite diagnosis and therapeutical regimen the content of CD34+ cells was found to be 3.3% (0-20). The proliferation was 21.7 GM-CFU per 1 x 10(5) MNC seeded (0-393). The results of the first 17 transplantations showed a fast haematological recovery (WBS 1.0 Gpt/l after 9 days Plt 20 Gpt/l after 11 days). Close collaboration of Transfusion Medicine and Haematology leads to optimization of stem cell transplantation.