Emil Abderhalden: his contribution to the nutritional biochemistry of protein.
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Animal Nutritional Physiological Phenomena↗
Biomedical subjects
G Wolf
Publications and source records attributed to G Wolf.
Isoproterenol stimulates tubular DNA replication in mice.
The beta-adrenergic stimulant isoproterenol is a mitogen for cultured murine proximal tubular cells. The present study was undertaken to test whether isoproterenol has a similar effect on tubular replication in vivo. BALB/c mice were intraperitoneally injected with two different doses of isoproterenol in the presence or absence of beta 1 + 2-receptor antagonist propranolol. Proliferation of renal cells was evaluated by staining of tissue sections for proliferating cell nuclear antigen (PCNA). In addition, cDNA amplification for PCNA was performed in reverse-transcribed RNA isolated from renal cortex. Treatment of mice with 0.1 mg/g body weight isoproterenol for 24 h significantly increased PCNA staining of nuclei compared to controls. This response was completely blocked by propranolol. There was no light-microscopic evidence that the proliferative response was subsequent to ischaemia with tubular necrosis. Semiquantitative cDNA amplification revealed that isoproterenol also stimulated the RNA expression of the PCNA gene. This study shows for the first time that isoproterenol directly stimulates proliferation of mainly proximal tubular cells in vivo as detected by PCNA expression. Since proliferation and differentiation of tubular cells is pivotal for the recovery of renal function in many pathophysiological situations, beta-adrenergic-mediated mitogenesis may be important in the reparative processes surrounding tubular epithelium regeneration.
Adrenergic beta-Agonists↗
Transforming growth factor beta mediates the angiotensin-II-induced stimulation of collagen type IV synthesis in cultured murine proximal tubular cells.
BACKGROUND: Angiotensin II (Ang II) stimulates synthesis of type IV collagen in a cultured murine proximal tubular cell line (MCT cells). In addition, Ang II also induces the expression of TGF-beta1 in these cells. Since TGF-beta has well-known stimulatory effects on the transcription of various collagens, we tested whether the Ang-II-mediated stimulation of type IV collagen is due to induction of endogenous TGF-beta1 synthesis in MCT cells. RESULTS: A neutralizing monoclonal anti-TGF-beta1-3 antibody abolished the Ang II-stimulated release of type IV collagen in culture supernatants. The anti-TGF-beta1-3 antibody also partly blocked Ang-II-mediated incorporation of 3[H]proline into de novo synthesized collagens. Moreover, 5 microM TGF-beta1 antisense oligonucleotides, but not the same concentration of sense oligonucleotides, completely blocked Ang-II-stimulated 3[H]proline incorporation. MCT cells incubated with TGF-beta1 antisense phosphorothioate-modified oligonucleotides failed to synthesize TGF-beta1 protein after Ang II treatment as measured by a sandwich ELISA in culture supernatants. SDS-polyacrylamide electrophoresis of 3[H]proline-labelled collagens and comparison with standard collagens also demonstrated that the neutralizing anti-TGF-1-3 antibody abolished the Ang-II-mediated stimulation in type IV collagen. Semiquantitative cDNA amplification for collagen type alpha1 (IV) transcripts revealed that the anti-TGF-beta1-3 antibody abrogates the increase in mRNA after Ang II treatment. Transient transfection studies in MCT cells using murine collagen alpha1 (IV) enhancer/promoter constructs also demonstrated the suppressive effect of the neutralizing antibody on Ang-II-stimulated gene transcription. CONCLUSIONS: Our data collectively suggest that the Ang-II-mediated increase in type IV collagen in MCT cells is mediated by endogenous synthesis and autocrine action of TGF-beta1. These findings may be important in changes of the tubulointerstitial architecture during the progression of renal disease.
Angiotensin II↗
A history of vitamin A and retinoids.
This is a historical account of the recognition of human vitamin A deficiency from ancient Egypt to the present century, as well as history of the discovery of vitamin A and the functions of vitamin A and the retinoids.
History, 17th Century↗
Analysis of hard two-photon correlations measured in heavy-ion reactions at intermediate energies.
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Journal Article↗
High-fat, high-cholesterol diet raises plasma HDL cholesterol: studies on the mechanism of this effect.
Earlier work with human subjects showed that a low-fat, low-cholesterol diet lowered plasma high-density-lipoprotein-cholesterol (HDL-C) and the production rate of apolipoprotein A-I (apo A-I). More recent research with transgenic mice demonstrated that a high-fat, high-cholesterol diet raised plasma HDL-C and the production rate of apo A-I by a mechanism involving the regulation of translation of the apo A-I mRNA. The authors conclude that the rise induced in HDL-C by a high-fat, high-cholesterol diet is defensive and therefore, should not be interpreted as a desirable dietary change.
Apolipoprotein A-I↗
Function of the bone protein osteocalcin: definitive evidence.
Mice that lacked the genes for the bone protein osteocalcin were generated and were used to study the function of osteocalcin. These osteocalcin-deficient mutants had normal bones at birth but had increased bone density and thickness at 6 months. Their osteoblasts deposited more bone matrix than those of wild-type mice, though mineralization was not affected. Osteocalcin, therefore, was concluded to be a negative regulator of bone formation.
Animals↗
Leptin: the weight-reducing plasma protein encoded by the obese gene.
Leptin, the protein encoded by the recently cloned obese gene, has the properties of a hormone released by adipose tissue, regulating appetite and energy expenditure. Injected leptin reduces body weight and food intake in mice, and in obese, diabetic mice (with a mutated obese gene), it also reduces plasma insulin and glucose. Leptin release is stimulated by insulin; leptin appears to act on the hypothalamus by inhibiting the release of the neuropeptide Y.
Adipose Tissue↗
Nutritional and hormonal regulation of fatty acid synthase.
Fasting causes a decrease in the rate of synthesis of fatty acid synthase, the central enzyme in fatty acid synthesis, while refeeding carbohydrate increases synthesis. Insulin also increases the synthesis of fatty acid synthase, while glucagon causes a decline. The mechanism was shown to be transcriptional activation-mediated through a 2.1-kb stretch of the 5'-flanking sequence of the fatty acid synthase gene promoter that contains an insulin response element. These effects were confirmed by in vivo experiments with transgenic mice.
Animals↗
The mechanism of uptake of ascorbic acid into osteoblasts and leukocytes.
Ascorbic acid is taken up into osteoblast cells by a saturable, stereospecific, Na(+)-dependent transporter, accumulating ascorbic acid to a level 100-fold that in the medium. The ascorbic acid uptake rate correlated with intracellular hydroxyproline synthesis. A second, distinct mechanism has also been described for accumulation of ascorbic acid into neutrophils and myeloid leukemia cells. This appears to be Na(+)-independent and relies on the glucose transporter GLUT1 to ferry dehydroascorbic acid (DHA) into cells and then to trap it as ascorbic acid to a high concentration.
Animals↗
The regulation of retinoic acid formation.
Rat liver microsomal as well as cytosolic retinol dehydrogenases from cellular retinal-binding protein (CRBP)-retinal from CRBP-retinol. A cytosolic dehydrogenase transforms retinal into retinoic acid. Apo-CRBP and ethanol inhibit the cytosolic but not the microsomal retinol dehydrogenase, the latter being the primary enzyme in the rate-limiting step in retinoic acid synthesis.
Alcohol Oxidoreductases↗
Adipocyte differentiation is regulated by a prostaglandin liganded to the nuclear peroxisome proliferator-activated receptor.
Adipocyte differentiation and the homeostasis of fat cell number are regulated by a nuclear receptor protein, the peroxisome proliferator-activated receptor (PPAR gamma). The endogenous ligand is thought to be 15-deoxy-delta 12,14-prostaglandin J2-Thiazolidinedione, an antidiabetic drug, closely mimics the action of the prostaglandin, suggesting a regulatory role by the prostaglandin and PPAR gamma both in adipocyte differentiation and in glucose homeostasis.
Adipocytes↗
Angiotensin II is mitogenic for cultured rat glomerular endothelial cells.
Angiotensin II (Ang II) has growth-stimulatory properties on different renal cell types. However, possible growth effects of this vasoactive peptide on endothelial cells isolated from the glomerular microvasculature have not been formally investigated. Therefore, we isolated and characterized primary cultures of rat glomerular endothelial cells. We used a simple technique in which collagenase-treated glomeruli were sparsely plated in several 96-well culture plates and microscopically screened for cobblestone-like outgrowth. After two limiting dilutions, homogeneous cultures were obtained. Cells were characterized by positive staining for the endothelial markers factor VIII, CD 31, endothelial leukocyte adhesion molecule-1, and the lectin Bandeiraea simplificifolia. Ang II stimulated the synthesis and release of endothelin-1 in culture supernatants. Moreover, in contrast to syngeneic mesangial cells, glomerular endothelial cells expressed angiotensin-converting enzyme. Ang II stimulated a mild but significant proliferation of quiescent cells, as measured by [3H]thymidine incorporation and direct cell counting. This mitogenesis was transduced by losartan-blockade angiotensin type 1 receptors. Moreover, Ang II mediated phosphorylation of mitogen-activated protein kinase 2 and induction of transcripts for the immediate early gene Egr-1. Our results indicate that Ang II is a moderate mitogen for primary cultures of rat glomerular endothelial cells and activation of these metabolically active cells may play a role in the pathophysiology of several types of glomerulonephritis. Moreover, remodeling of glomerular endothelial cells by Ang II may be important in the progression of structural renal damage during the course of hypertensive injury.
Angiotensin II↗
Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.
To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.
Alprostadil↗
Intraoperative radiation therapy, endotracheal hyperthermia and IR-192-brachytherapy in patients with advanced thyroid cancer.
Tracheal stenosis due to infiltrative nonresectable thyroid cancer causes severe reduction in life quality. Palliative therapy, apart from tracheostomy is--up to now--intraluminal and/or external radiation. Good tumor control is achieved by local hyperthermia. A combined modality treatment (CMT) consisting of surgery, brachytherapy and intraoperative radiation, eventually combined with intraluminal NdYg-Laser-desobliteration was performed. An intraoperative radiation therapy (IORT)-protocol was designed for poorly differentiated non-anaplastic thyroid carcinoma. Out of 155 cases of differentiated thyroid tumors, 12 showed marked vascular and/or capsular invasion. Five entered the study (3 primarily local invasive tumors, 2 local recurring). IORT was administered after tumor surgery (4-10 Gy) and combined with postoperative percutaneous irradiation. The tumor control rate in the thyroid bed is 5/5, 1/5 developed mediastinal nodes, 1/5 with primary mediastinal tumor extend shows tumor progression. No specific complications occurred.
Adenocarcinoma, Follicular↗
[Bioavailability of morphine after oral administration as retard tablets].
The oral bioavailability of morphine following administration of a single dose of 30 mg morphine hydrochloride as Vendal retard film tablets (Lannacher Heilmittel) was investigated and compared with the bioavailability of morphine following administration of 30 mg morphine sulphate as Mundidol retard film tablets (Mundipharma). A randomized crossover study was conducted in 24 male, healthy volunteers. In 6 of them a pilot study with formulations containing 60 mg was conducted. Morphine and its metabolites were quantitated with an immunofluorimetric solid-phase assay (DELFIA). With regard to the following parameters the novel controlled-release formulation was statistically different from the reference formulation: area under the concentration-time curve, time to maximum and half value duration. After a single dose of the test formulation analgesic serum levels were maintained over a longer lasting period of time than after administration of the reference formulation. The maximal levels in serum and the elimination half life were not different. From the improved pharmacokinetic parameters of the novel controlled-release formulation an improved clinical efficacy can be expected.
Administration, Oral↗
A microplate assay for K-ras genotyping.
The paper presents a microplate hybridisation assay for the detection of codon 12 mutations of the K-ras protooncogene. Single-stranded target DNA, obtained from amplifying sample DNA with 5'-biotin and 5'-digoxigenin-labelled primers and subsequent strand separation, is hybridised with solid phase-fixed capture probes complementary to wild-type and mutated forms of K-ras. After stringent washing the duplex DNA is detected by an ELISA-like protocol incorporating photometric, fluorometric or luminometric detection. Application examples are shown in which the K-ras status was examined in peripheral blood cells, cell cultures, fresh and paraffin-embedded tumour tissue and in stool samples.
Codon↗
Randomized comparison of sitting and prone positions for stereotactic fine-needle aspiration breast biopsy.
In a prospective randomized study, 103 women had stereotactic biopsies performed either in the prone (n = 51) or sitting (n = 52) position. Questionnaires were administered before and after biopsy, to measure anxiety, pain and subjective experience in all patients. Vasovagal reactions were scored from 0 to 2 according to severity. There was no significant difference between biopsies performed in the sitting or the prone position with regard to overall tolerance. Significantly more patients biopsied in the prone position (15 of 51, 29 per cent) than in the sitting position (seven of 52, 13 per cent) would prefer premedication before a repeat biopsy (P = 0.04). Of the total patient group, three women fainted, one in the prone position and two others in the sitting position. Breast biopsies performed in the prone or sitting position are equally well tolerated. Somatic reactions such as fainting are not a major problem during breast biopsy; however, attention should be focused on patient care, including information given before the procedure.
Anxiety↗