The Diabetes Intervention Study (DIS): a cooperative multi-intervention trial with newly manifested type II diabetics: preliminary results.
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Adult↗
Biomedical subjects
S Fischer
Publications and source records attributed to S Fischer.
[Results of protein-sparing modified fasting in hyperlipoproteinemias].
We investigated the influence of a PSMF on body weight, body composition, blood lipids, physical working capacity, and nitrogen balance in obese HLP patients. During 4 weeks, 12 patients were treated by PSMF (approximately 340 kcal/d) under health resort conditions. At the same time, they daily exercised on a bicycle with an intensity of 80% of their physical working capacity estimated by an exercise load. The therapeutic regimen induced a significant weight loss (10.1 kg in the mean). Evidently, the patients diminished their body fat only as could be shown by estimations of total body water. Triglycerides, total cholesterol, and LDL-cholesterol also decreased significantly, while HDL-cholesterol remained unchanged. In spite of the weight reduction, the physical working capacity significantly increased from 57.8 to 93.2 kgm. Measurements of total nitrogen excretion with urine gave evidence of the protein saving effect of the therapy. Thus, PSMF--representing an effective therapeutic procedure--can be recommended to be used in obese HLP patients, proceeded that contraindications have been taken into consideration carefully.
Body Weight↗
Stimulation of tyrosine phosphorylation in lectin treated human lymphocytes.
Large increases in tyrosine phosphorylation have been detected in subcellular matrixes isolated from lectin treated human lymphocytes. In lectin stimulated cells proteins of molecular weight 105, 75, 58 and 35 kDa contained phosphotyrosine (P-tyr) whereas non-stimulated cells had no 105 and low levels of P-tyr in proteins of 75, 58 and 35 kDa. In stimulated cells increased tyrosine kinase activity was also shown using gastrin as substrate. In both stimulated and non-stimulated cells the 58 kDa phosphoprotein was the most heavily labelled, after partial proteolysis of the 58 kDa different phosphopeptides were generated. A peptide with a sequence analogous to the autophosphorylated tyrosine site of pp60src inhibited tyrosine phosphorylation in stimulated cells. The lymphocyte system provides a useful tool to study normal tyrosine protein kinases and their role in cellular proliferation.
Detergents↗
Identification of a 58,000 daltons phosphoprotein with tyrosine protein kinase activity in a murine lymphoma cell line.
A very high level of tyrosine protein kinase (TPK) activity has been recently detected in a murine lymphoma, induced by Moloney murine leukemia virus. A major endogenous substrate for tyrosine phosphorylation in vitro is a protein of Mr 55-60,000 (p58) associated with the detergent insoluble matrix of LSTRA cells; in the present work p58 was solubilized, isolated by anion exchange chromatography and then precipitated by antiphosphotyrosine antibodies. Through these steps of isolation, TPK activity was measured by the use of a simplified gastrin phosphorylation assay. It is demonstrated that the TPK activity copurifies with p58, which leads to the conclusion that p58 bears itself the enzymatic activity. Although functionally similar to other enzymes of this group, this newly characterized TPK does not seem to be closely related to one of the previously documented TPK. This suggests either that this protein is the product of a so far unrecognized cellular TPK gene or that it derives from a rearrangement of one of the previously described TPK genes.
Animals↗
Uptake, release and metabolism of docosahexaenoic acid (DHA, c22:6 omega 3) in human platelets and neutrophils.
Exogenous DHA is converted by human platelets to 14- and 11- HDHE and by human neutrophils mainly to 7- HDHE . Human platelets prelabeled with 14C-DHA, 14C-EPA and 14C-AA and stimulated with thrombin release and metabolize DHA only in trace amounts as compared to EPA and AA. 14C-DHA is incorporated into the 2-position of platelet phospholipids and occurs predominantly in phosphatidylethanolamine. DHA and EPA were also incorporated by dietary means into phospholipids of platelets and neutrophils. In resting platelets free DHA as well as free AA and EPA are not detectable. In platelets stimulated ex vivo with thrombin DHA is not significantly released which is in contrast to EPA and AA. After stimulation, 14- HDHE is found only in trace amounts as compared to 12-HETE and 12- HEPE . In DHA enriched neutrophils formation of HDHEs cannot be demonstrated after stimulation with ionophore A 23187. We conclude that even after dietary enrichment of DHA in phospholipids of platelets and neutrophils the level of free DHA and/or formation of HDHEs might be too low to substantially affect arachidonic acid metabolism and related functions of these cells.
Adult↗
Hybrid character of a large neurofilament protein (NF-M): intermediate filament type sequence followed by a long and acidic carboxy-terminal extension.
The sequence of the amino-terminal 436 residues of porcine neurofilament component NF-M (apparent mol. wt. in gel electrophoresis 160 kd), one of the two high mol. wt. components of mammalian neurofilaments, reveals the typical structural organization of an intermediate filament (IF) protein of the non-epithelial type. A non-alpha-helical arginine-rich headpiece with multiple beta-turns (residues 1-98) precedes a highly alpha-helical rod domain able to form double-stranded coiled-coils (residues 99-412) and a non-alpha-helical tailpiece array starting at residue 413. All extra mass of NF-M forms, as a carboxy-terminal tailpiece extension of approximately 500 residues, an autonomous domain of unique composition. Limited sequence data in the amino-terminal region of this domain document a lysine- and particularly glutamic acid-rich array somewhat reminiscent of the much shorter tailpiece extension of NF-L (apparent mol. wt. 68 kd), the major neurofilament protein. NF-M is therefore a true intermediate filament protein co-polymerized with NF-L via presumptive coiled-coil type interactions and not a peripherally bound associated protein of a filament backbone built exclusively from NF-L. Along the structurally conserved coiled-coil domains the two neurofilament proteins show only approximately 65% sequence identity, a value similar to that seen when NF-L and NF-M are compared with mesenchymal vimentin. The highly charged and acidic tailpiece extensions of all triplet proteins particularly rich in glutamic acid seem unique to the neurofilament type of IFs. They could form extra-filamentous scaffolds suitable for interactions with other neuronal components.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Evaluation of a computerized drug review system: impact, attitudes, and interactions.
A study was carried out across 11 psychiatric and mental retardation, and developmental disabilities facilities to investigate the impact of a computerized drug prescription monitoring system on clinicians' prescribing behavior, knowledge of pharmacotherapy, attitudes toward computers, and the relationships between their attitudes and changes in their prescribing practices. The results document that surveillance systems can improve prescribing practices. The tangible feedback provided by the exception report, although in the form of a surveillance mechanism, also increased user acceptance to computer technology. However, the findings also suggest that user acceptance is not necessarily required to see positive effects, which in environments where clinical and fiscal accountability are paramount, may override some clinicians' concerns. Attention to human factors components may help to alleviate some negativism.
Attitude↗
Influence of acute tubular necrosis on first cadaver kidney transplant function.
Prolonged cold storage following intracellular electrolyte flushing increases the probability of significant acute tubular necrosis after cadaver kidney transplantation. The renal function of primary cadaver kidney grafts was compared in 68 recipients who required dialysis and 92 who did not require dialysis during the first week after transplantation. All kidneys were retrieved from beating-heart cadaver donors by our center, flushed with ice-cold intracellular electrolyte solution and cold-stored until transplantation at our hospital. Recipients requiring dialysis during the first week after transplantation received kidneys with a significantly longer cold storage time (27.4 plus or minus 10.2 versus 23.2 plus or minus 7.6 hours) and had significantly higher 1-month serum creatinine nadirs (2.1 plus or minus 1.3 versus 1.5 plus or minus 0.6 mg./dl.). Actuarial kidney graft survivals and serum creatinine levels 1 to 5 years after grafting were not significantly different. Acute tubular necrosis following primary cadaver kidney transplantation does not adversely affect long-term function of kidney grafts flushed with intracellular electrolyte solution and cold-stored until transplantation.
Acute Kidney Injury↗
Polycationic polypeptides: a possible model for the penetration-enhancing factor in the invasion of host cells by Toxoplasma gondii.
The effect of polycationic polypeptides (polylysine, polyarginine and polyhistidine) on the invasion of mammalian cells and plant protoplasts by Toxoplasma gondii was studied. In JM cells, a human lymphoblastoid cell line with T cell characteristics, all polycationic polypeptides used increased the invasion rate in a concentration-dependent manner. This effect and the morphological changes revealed by electron microscopy resembled the action of the penetration-enhancing factor previously described by E. Lycke and co-workers. Plant protoplasts of Catharanthus roseus, which are resistant to T. gondii invasion, showed the same morphological changes in the presence of polycationic polypeptides as observed for JM cells, but were not invaded.
Animals↗
Arachidonic acid and eicosapentaenoic acid metabolism in platelets and vessel walls.
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Animals↗
SCH 370 (clotrimazole-betamethasone dipropionate) cream in patients with tinea cruris or tinea corporis.
The safety and efficacy of SCH 370 (1 percent clotrimazole/0.05 percent betamethasone dipropionate) cream was compared with each of its individual components in 331 patients with tinea cruris or tinea corporis. The study was a multicentered, randomized, double-blind, parallel-groups design. The patients received one of three treatments applied twice a day for two weeks and returned for a follow-up visit two weeks after the last application. Total signs and symptoms scores of infections were evaluated at baseline, once between days three to five, and after weeks one, two, and four. Culture and potassium hydroxide preparations were done at baseline and weeks two and four. SCH 370 cream demonstrated more rapid therapeutic activity than the antifungal agent alone, resulting in significantly better clinical results in early treatment and in midtreatment. As expected with a steroid, betamethasone dipropionate achieved relief of inflammatory signs and symptoms early in the course of treatment, but SCH 370 was superior from one week on in the patients with tinea cruris and at post-treatment in the patients with tinea corporis. Mycologically, SCH 370 cream and clotrimazole were comparable at the end of the study and results were significantly better than those for betamethasone dipropionate. All three treatments were safe with no reports of unexpected or serious adverse experiences.
Adult↗
[Results of linseed oil and olive oil therapy in hyperlipoproteinemia patients].
Only few informations exist on the effect of different oils and the transformation of these precursor fatty acids to prostaglandins in patients with hyperlipoproteinemia. Therefore we investigated the impact of linseed oil and olive oil intake resp. on serum lipoprotein levels, platelet aggregation and fatty acid pattern of serum phospholipids and triglycerides resp. in patients with primary hypercholesterolemia (HC) (n = 13) and hypertriglyceridemia (HTG) (n = 16). The probands were randomly admitted to a 4 week test period with 30 ml olive or linseed oil intake. After linseed or olive oil intake all lipid fractions did not change significantly. Olive oil significantly reduced the platelet aggregation only in patients with HTG, whereas linseed oil failed to influence aggregation. After linseed oil intake there was a significant increase in linolenic and also in eicosapentaenoic acid content of phospholipids in patients with HTG. In contrast to HTG in HC linseed oil only increased significantly the linolenic acid fraction. Our data suggest, that the response of serum lipoproteins, fatty acids and platelet aggregation on modifications in dietary fats depends on the type of lipoprotein disorder.
Adult↗
Fatty acid composition and action of serum lipoproteins on the PGI2-formation after various oil diets in hyperlipoproteinemia.
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Dietary Fats↗
[Diagnostic problems of spinal tumors in childhood and adolescence].
In evaluation of the clinical-neurological symptoms of 59 children and juveniles with spinal space occupations, 43 of whom were operated on, the differential-diagnostic particularities especially with respect to the early symptoms are discussed. On the basis of representations of individual cases, the importance of metrizamide myelography and spinal computer tomography for the pre-operative diagnosis is pointed out.
Adolescent↗
Tyrosine phosphorylation in human T lymphoma cells.
A high level of tyrosine protein kinase (TPK) has been recently detected in the murine lymphoma LSTRA. The main substrate for tyrosine phosphorylation in this cell line is a Mr 55 000 protein associated with the insoluble matrix of the cell. These findings prompted the search for TPK activities in human lymphoid cells. Three human T lymphoma cell lines (i.e. Molt. 4, JM, and Ke 37) and control lymphocytes were examined. After in vitro phosphorylation of detergent insoluble extracts from human T lymphoma cells, 2 major phosphotyrosine containing proteins with Mr 55 000 and 35 000 can be detected in all three T lymphoma lines, whereas an additional species with Mr 78 000 is present only in the Ke 37 cell line. Similar size proteins are weakly phosphorylated in normal lymphocytes. Tyrosine phosphorylation in these proteins proceeds actively at 0 degrees C, and is dramatically stimulated by Mn++ ions. Partial proteolysis mappings of the Mr 55 000 phosphoproteins from murine and human lymphomas revealed a strong homology among these molecules. The function of this protein in transformed lymphocytes is discussed.
Animals↗
[Simple procedures for the determination of hemoglobin F and hemoglobin A2: radial immunodiffusion and column chromatography with commercial kits].
Two commercially available laboratory kits for the determination of HbF and HbA2 with radial immunodiffusion and chromatography in microcolumns have been compared with standard methods. The two kits can be recommended for diagnostic routine laboratories. They are easy to perform and the results were found to be in excellent agreement with those of the alkali denaturation method and electrophoresis with elution of HbA2. The two kits are time-saving, although the reagents and other materials are more expensive.
Chromatography↗
Thromboxane A3 (TXA3) is formed in human platelets after dietary eicosapentaenoic acid (C20:5 omega 3).
Platelet-rich plasma of subjects, who had ingested cod liver oil containing 10% eicosapentaenoic acid (C20:5 omega 3), the precursor of trienoic prostanoids, was stimulated ex vivo with collagen. Formation of thromboxane B3, the hydrolysis product of non-aggregatory thromboxane A3, from endogenous eicosapentaenoic acid was demonstrated by combined capillary gas chromatography-mass spectrometry. Concomitantly platelet aggregation in platelet-rich plasma upon low doses of collagen and associated thromboxane B2 formation from endogenous arachidonic acid were reduced. We conclude that both the formation of inactive thromboxane A3 as well as the reduction of thromboxane A2 may contribute to the reduced platelet reactivity after dietary eicosapentaenoic acid.
Blood Platelets↗
In vivo and in vitro effects of nafazatrom (Bay g 6575), an antithrombotic compound, on arachidonic acid metabolism in platelets and vascular tissue.
Nafazatrom, given acutely to male volunteers, had no effect on platelet aggregation, associated thromboxane B2 (TXB2) formation or the evaluated hormonal, renal and cardiovascular parameters. Only slight increases in plasma levels of 6-keto-PGF1 alpha and in platelet counts were observed. However, a marked influence of nafazatrom on arachidonic acid metabolism in certain in vitro systems was found. Prostaglandin synthesis by rabbit kidney cortex microsomes was significantly enhanced, PGI2 being stimulated the most. In normal human platelets arachidonic acid metabolism was not influenced significantly by nafazatrom which was taken up by the platelets in a dose-dependent manner. In contrast, in platelets with a high peroxide level probably due to depletion of reducing cofactors, 12-hydroperoxy-eicosatetraenoic acid was transformed to 12-hydroxy-eicosatetetraenoic acid by nafazatrom, while the formation of TXB2 was stimulated. These findings suggest that nafazatrom may act as a reducing cofactor for the hydroperoxidase involved in the cyclooxygenase- and lipoxygenase-pathways of arachidonic acid metabolism.
6-Ketoprostaglandin F1 alpha↗