Search PubMed⌕ Search

Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 73 records · Page 4Linked to original sources

[Scheuermann disease as predisposition of later spinal disease and its effect on expert assessment in occupational disease examinations].

The Scheuermanns disease is an illness of which the fluoride stage is described as a disorder in growth of the vertebral-intervertebral disk borderline. This stage of the illness ends with the finish of bone growth. Depending on the advanced alterations of the spinal column segments or of the statics of the spinal column up to that point, in later stages of life there will be a higher rate of diskopathies of the lumbar vertebrae and later on of the cervical vertebrae where it often causes arthrosis of the swivel joints. I.e. Morbus Scheuermann is a predisposition for the beginning of diskopathies and has to be added to the differential diagnostic investigation considerations for the examination of causality of the occupation diseases subparagraph 2108 to 2110. We find it justified that the Scheuermanns disease has to be included into the accompanying leaflet as a relevant pre-illness. The thorakal as well as the lumbarthorakal or lumbar manifestation has to be a competitive cause of vocational connection brought under discussion. That is the reason why all the more a preference of the expected segments is required as far as an essential partial cause with a vocational influence with the judgement is discussed. The same also applies to the judgement in a sense of deterioration.

Eligibility Determination↗

Upregulation of PKC delta- and downregulation of PKC alpha-mRNA and protein by phorbol ester in human T84 cells.

Protein kinase C (PKC) family members are downregulated by chronic activation at the protein level in most cell types. In T84 human epithelia] cells 12-O-tetradecanoyl phorbol 13-acetate (TPA) caused persistent translocation of PKC delta to the membrane compartment and a 400% increase of PKC delta-mRNA after 24 h. In contrast, PKC alpha protein was completely downregulated and its mRNA was decreased to 60% of control levels after 24 h. This is the first report of PKC delta-mRNA upregulation by TPA which was previously only shown for PKCbeta. In view of the antimitogenic actions of PKC delta this pattern of regulation may serve to preserve growth control even in the presence of chronic cell activation.

Animals↗

Jejunal brake.

Explore the source record for details and available documents.

Adipose Tissue↗

Restricted geographical extension of the association of a glucagon receptor gene mutation (Gly40Ser) with non-insulin-dependent diabetes mellitus.

A mutation within the glucagon receptor gene (GRG) at codon 40 (Gly40Ser) was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM) in France and Sardinia. Since the frequency of the mutation, about 5% in the French and 8% in the Sardinian group was higher than that of any of the candidate gene mutations described so far, it appeared to be relevant to determine the prevalence within different populations. While a single mutation has not been found recently either in a Japanese, a Finnish or a Dutch cohort, but only in a British study in 2.2% of NIDDM patients, in this study we investigated the association of this mutation with NIDDM in 104 German patients by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). None of the German NIDDM patients had a Gly40Ser mutation. The results indicate that the mutation plays little role in susceptibility to NIDDM in this German region, and also indicate the genetic heterogeneity in NIDDM, and further emphasize the importance of studies in different ethnic groups.

Aged↗

Activation of human platelet protein kinase C-beta 2 in vivo in response to acute hyperglycemia.

Protein kinase C (PKC) is known to be activated in experimental model systems by elevated glucose and may play an important role in the pathogenesis of diabetic complications. Since there is no information about its role in humans in vivo we investigated the activation of PKC in human thrombocytes during infusion of glucose and insulin in normal controls and in 19 NIDDM patients by determining membrane and cytosol levels of PKC beta 2 using immune blots. In the 27 subjects investigated (8 controls, 19 NIDDM) membrane-associated levels of PKC beta 2 increased significantly after 60 and 150 min (p < 0.005). In controls an increase of membrane and of cytosolic PKC beta 2 occurred upon elevation of glucose by 5.5 mmol/L or more and the membrane association persisted for at least 60 min. In NIDDM glucose was elevated by 7.5-10 mmol/L during infusions. Increases of both membrane and cytosolic PKC beta 2 (< 20%-300%) occurred in 10 NIDDM patients suggesting that both, translocation and increased synthesis of PKC beta 2 were stimulated by glucose. Nine other patients showed no alteration (i.e. < 20%) of PKC beta 2. The 2 groups were similar regarding parameters of diabetes control, baseline glucose and glucose elevation during the test. However, the PKC beta 2 responsive group had lower levels of serum triglycerides (1.39 +/- 0.19 vs. 2.32 +/- 0.34 g/L; p = 0.038). To assess whether absolute levels of PKC were altered in human diabetes, platelet levels of PKC alpha, beta 1 and beta 2 were determined in 22 controls and 25 NIDDM subjects with poorly controlled diabetes (HbA1c = 9.8 +/- 0.36%). Cytosolic levels of PKC alpha were significantly decreased by 27% compared to controls in NIDDM but there was no change of PKC beta 1 or PKC beta 2. We conclude that 1. acute elevation of glucose by 5.5 mmol/L or more can activate PKC beta 2 translocation in controls and NIDDM patients in vivo irrespective of parameters of metabolic control. 2. NIDDM patients differ in their PKC beta 2-responses to glucose and 3. poor metabolic control leads to moderate downregulation of PKC alpha suggesting continued activation.

Adult↗

Widespread expression of a new putative hormone extrusion pump: NG-TRA transporter protein in human and rat tissue.

In 1991 Becker and co-workers isolated a new ATP-dependent transporter from a neuroblastomaXglioma-hybrid-cell line, called NG-TRA. This protein was proposed to represent a hormone extrusion pump. To gain further insight into its significance we studied the expression of NG-TRA in human and rat tissues and compared the nucleotide sequences derived from both species using reverse transcription PCR, subcloning and nucleotide sequencing. A 97% sequence homology was found between the original and the human subcloned fragments, derived from thyroid and colon carcinoma tissue, while the rat subcloned fragments, derived from brain cortex and heart muscle, showed a 25 amino acid deletion at the 3'end compared with both the original and human subclones. Expression of NG-TRA at the mRNA level was found in all tissues studied except blood and fat tissue, and additionally rat lung tissue. We conclude that NG-TRA is a widely expressed protein consistent with a general function in diverse species.

ATP-Binding Cassette Transporters↗

Effect of intestinal resection on human small bowel motility.

BACKGROUND: Few data are available on adaptive changes of human small bowel motility after intestinal resection. AIM: To characterise jejunal motility after extensive and limited distal intestinal resection. METHODS: Seven patients with a short bowel syndrome after total ileal and partial jejunal resection (residual jejunal segments between 60 and 100 cm) and six patients with limited distal ileal resection (resected segment between 30 and 70 cm) underwent ambulatory 24 hour jejunal manometry 15 (6-24) months after the operation. Normal values were obtained from 50 healthy subjects. Fasting motility and the motor response to a 600 kcal solid meal were analysed visually and by a computer program. RESULTS: Limited ileal resection did not result in changed jejunal motility. After extensive distal resection, patients had a significantly shorter migrating motor complex (MMC) cycle and a significantly shorter duration of the postprandial motor response compared with controls (p < 0.005). Intestinal resection had no influence on jejunal contraction frequency and amplitude and did not lead to any abnormal motor pattern. CONCLUSION: Extensive distal resection of the small intestine produces distinct abnormalities of fasting and postprandial motility in the intestinal remnant. The shortening of digestive motility and the increased frequency of MMC cycling could contribute to malabsorption and diarrhoea in the short bowel syndrome.

Adult↗

Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.

OBJECTIVE: Transforming growth factor-beta (TGF-beta) is a potent inducer of extracellular matrix production and of fibrogenesis and has been associated with the occurrence of diabetic micro- and macrovascular complications. Our aim was to determine whether circulating levels of TGF-beta 1 are altered in NIDDM and, if so, whether they are correlated with blood glucose and show an association with diabetic complications. RESEARCH DESIGN AND METHODS: Plasma levels of TGF-beta 1 were determined by enzyme-linked immunosorbent assay in 44 NIDDM patients and 28 control subjects of comparable age and weight and were correlated with parameters of metabolic control and the occurrence of micro- and macrovascular complications. RESULTS: TGF-beta 1 was significantly elevated in NIDDM (7.9 +/- 1.0 ng/ml), as compared with control subjects (3.1 +/- 0.4 ng/ml, P < 0.001) and correlated with glycosylated hemoglobin (r2 = 0.42; P < 0.001). Thrombocyte levels of TGF-beta 1 were similar in control subjects (54 +/- 7 pg/ml, n = 16) and diabetic patients (61.6 +/- 18 pg/ml, n = 13; P = 0.357). Elevated TGF-beta 1 levels were associated with retinopathy and neuropathy. CONCLUSIONS: We conclude that plasma levels of TGF-beta 1 are elevated in NIDDM patients and may be related to average blood glucose. Preliminary data suggest that they may contribute to the occurrence of diabetic complications.

Aged↗

Ambulatory 24-hour jejunal motility in diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Whether small-bowel motility is abnormal in the irritable bowel syndrome (IBS) is a controversy at present. The aim of our study was to compare ambulatory long-term jejunal motility in 35 IBS patients with predominant diarrhea to normal values obtained in 50 healthy controls. METHODS: Twenty-four-hour motility was recorded in the proximal jejunum with a portable datalogger and tube-mounted miniature pressure sensors. Fasting motility in the waking (W) and sleeping (S) state and the motor response to a standardized evening meal of 600 kcal underwent visual and computer-aided analysis. RESULTS: Fasting motility in patients showed migrating motor complex (MMC) cycles of normal length and composition. Uninterrupted runs of discrete clustered contractions during phase II (W) occurred in 57% of patients and 52% of controls but had a significantly longer duration in patients (33 +/- 5 versus 19 +/- 7 min; p < 0.005). During phase II (W) IBS patients had an increase in aborally propagated contractions (41 +/- 2% versus 35 +/- 2%; p < 0.01) and higher contraction amplitudes (26.3 +/- 0.8 versus 23.0 +/- 0.5 mm Hg; p < 0.01). Similar differences were obtained during postprandial motility (47 +/- 3% versus 39 +/- 3%; p < 0.01, and 25.9 +/- 0.9 versus 23.8 +/- 0.05 mm Hg; p < 0.02). In three patients (8.6%) disturbed aboral migration of phase III and irregular burst activity, manometric features of chronic idiopathic intestinal pseudo-obstruction, were identified. Whereas 57% of patients had an entirely normal 24-h manometry, 43% had at least one finding not present in any healthy control. CONCLUSION: Small-intestinal motility is frequently but not universally abnormal in diarrhea-predominant IBS. The abnormal manometric findings are heterogeneous and range from subtle quantitative changes to severe qualitative abnormalities resembling chronic idiopathic intestinal pseudo-obstruction in a small subset of patients.

Adult↗

[TNF-alpha level in the vitreous body. Increase in neovascular eye diseases and proliferative diabetic retinopathy].

BACKGROUND: Deficient retinal capillary perfusion results in angioneogenesis of the eye. Its extension depends on the degree of ischemia. Mild stages are restricted to the retina, while marked ischemia results in neovascularization of the iris (rubeosis iridis). The neovascularization may be induced by the release of growth factors into the vitreous. Tumor necrosis factor alpha seems to be an important angiogenetic growth factor. PATIENTS AND METHODS: The patients were divided up into three groups with different retinal stages of ischemia, as judged by the extension of new vessel formation of the eye: a control group without angioneogenesis, a diabetes group with less severe to moderate angioneogenesis of patients with proliferative diabetic retinopathy and a rubeosis group with massive angiogenesis (rubeosis iridis) resulting from different causes. TNF-alpha was determined by immunological methods. RESULTS: The TNF-alpha level of vitreous in rubeosis (25.8 pg/ml; n = 6) was 2-fold elevated compared to controls (13.1 pg/ml; n = 10; p < 0.05) and 1.4-fold elevated compared to the diabetes group (18.2 pg/ml; n = 17). The values ranged from unmeasurable values to 41.25 pg/ml. Within the rubeosis group similar changes were observed independently of the causes of ischemia. There was no correlation between TNF-alpha-levels in the diabetes group and serum creatinine. CONCLUSIONS: 1. TNF-alpha is upregulated in ischemia. 2. TNF-alpha seems to be a mediator of angiogenesis in the eye. 3. Changes in diabetes may be secondary to local ischemia rather than being specific for diabetic retinopathy.

Adult↗

Diabetic microvascular complications and growth factors.

Diabetes mellitus is associated with typical patterns of long term vascular complications which vary with the organ involved. The microvascular kidney disease (Olgemoller and Schleicher, 1993) is characterized by thickening of the capillary basement membranes and increased deposition of extracellular matrix components (ECM), while loss of microvessels with subsequent neovascularisation is predominant in the eye and peripheral nerves. On the other hand macrovascular disease is characterized by accelerated atherosclerosis. These complications are dependent on long term hyperglycemia. Specific biochemical pathways linking hyperglycaemia to microvascular changes were proposed: the polyol pathway (Greene et al., 1987), non-enzymatic glycation of proteins (Brownlee et al., 1988), glucose autooxidation and oxidative stress (Hunt et al., 1990), hyperglycemic pseudohypoxia (Williamson et al., 1993) enhanced activation of protein kinase C by de novo-synthesis of diacyl glycerol (Lee et al., 1989; DeRubertis and Craven 1994) and others. These pathways are not mutually exclusive (Larkins and Dunlop, 1992; Pfeiffer and Schatz, 1992). They may be linked to alterations in the synthesis of growth factors particularly since atherosclerosis and angioneogenesis are associated with increased proliferation of endothelial and smooth muscle cells. Increased synthesis of ECM components is stimulated by growth factors like transforming growth factor beta (TGF beta) (Derynck et al., 1984) and insulin-like growth factor I (IGF-I) (Moran et al., 1991). This review will summarize some of the recent evidence for an involvement of growth factors in diabetic vascular complications and will attempt to assign their emergence in the sequence of events leading to vascular complications.

Animals↗

Overexpression of calcium/calmodulin-dependent protein kinase II in insulinoma cells by use of a retroviral vector.

The manner in which increasing intracellular calcium levels lead to insulin exocytosis is not known. Possibly the signal is mediated by activation of calcium/calmodulin-dependent protein kinase II (CaM Kin II). In this work the establishment of an insulinoma cell line stably overexpressing CaM Kinase II subtype delta 2 by an ecotropic retroviral transduction system is described.

Calcium-Calmodulin-Dependent Protein Kinase Type 2↗