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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 613 records · Page 34Linked to original sources
PubMed1986

Alcohol levels in trauma victims.

A group of 142 patients injured in motor vehicle accidents or assaults was investigated to ascertain patterns of alcohol usage and blood alcohol levels; 77% were positive for blood alcohol (range 0.01-0.492 g/dl; mean 0.212 g/dl). A correlation between alcohol levels and injury severity was found. In assaults, multiple injuries were associated with high alcohol levels because of less effective self-defence. Injured young pedestrians as well as injured occupants of motor vehicles showed alarmingly high alcohol levels. The increasing load placed on trauma services and the resultant burden to the taxpayer necessitates an urgent programme of public education designed to alter attitudes towards alcohol consumption.

Accidents, Traffic↗
PubMed1986

Clinical and biochemical aspects of the insulin autoimmune syndrome (IAIS).

A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 microU/ml (normal range less than 20 microU/ml) were detected which rose to peak levels of 2,460 microU/ml (normal range less than 300 microU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation). 125I-insulin added to the patient's serum was not bound to dextran-coated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C 18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 microU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit. We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.

Adult↗
PubMed1986

Bicycle accident injuries.

Bicycle accidents in 210 patients are analysed. Ages ranged from 1 to 59 years (mean 14.5 years) with a male predominance. In 52% of patients there was a head or facial injury, 6% being moderate to severe. Of the fractures 64% involved the upper limb, 32% being of the radius and ulna and 22% of the clavicle. The majority of abrasions and soft-tissue injuries involved the limbs.

Adolescent↗
PubMed1986

Cloning and expression of cDNA encoding mouse tyrosinase.

We have isolated a pigment cell-specific cDNA clone from a B16 mouse melanoma cDNA library by differential hybridization. The mRNA of isolated cDNA is highly expressed in B16 melanoma cells and in black mouse (C57BL/6) skin, but is not detectable in mouse neuroblastoma cells nor in K1735 mouse amelanotic melanoma cells. The protein sequence deduced from the nucleotide sequence of the cloned cDNA shows significant similarity to the entire region of Neurospora tyrosinase. To know the identity of cDNA, we transfected K1735 amelanotic melanoma and COS-7 cells with the cDNA carried in a simian virus 40 vector (pKCRH2). We confirmed that the isolated cDNA encodes mouse tyrosinase by immunofluorescence staining of transfected cells using two different anti-T4-tyrosinase monoclonal antibodies. Tyrosinase is composed of 513 amino acids with a molecular weight of 57,872 excluding a hydrophobic signal peptide of 24 amino acids.

Amino Acid Sequence↗
PubMed1986

Synthesis and maturation of recombinant human tumor necrosis factor in eukaryotic systems.

The biosynthesis of human tumor necrosis factor (hTNF) was studied. The amino-terminal extension of the hTNF precursor (26 kDa polypeptide) was not cleaved off in a cell-free system supplemented with dog pancreas microsomes. Correct maturation of pre-hTNF was nevertheless not restricted to the macrophage system: in the medium of a TNF-producing, transformed CHO cell line, a (weak) approximately 20 kDa, an approximately 18.5 kDa (doublet) and a 17 kDa TNF polypeptide, the latter corresponding to mature hTNF, were revealed by specific immunoprecipitation. Similar results were obtained with Xenopus laevis oocytes, injected with hTNF mRNA, except that the 20 kDa band was lacking. The results are discussed in relation to the secretion mechanism of hTNF.

Animals↗
PubMed1986

Evidence that expression of c-fos protein in amnion cells is regulated by external signals.

While c-fos expression is normally very low in certain cell types but transiently inducible by growth factors (e.g. in fibroblasts), other cells (e.g. amnion cells) exhibit an apparently constitutive expression in vivo. Here we show that in primary amnion cells c-fos protein expression rapidly drops to undetectable levels following plating in normal growth medium. However, c-fos expression is inducible by, and maintained at high levels in the presence of, dialyzed placenta- or embryo-conditioned medium. These observations suggest that c-fos expression in primary amnion cells is regulated by placenta- and embryo-derived factor(s), providing further evidence for the hypothesis that transcription of the c-fos gene may generally be controlled by external signals. We also show that proliferation of primary amnion cells is not dependent on a high c-fos expression, suggesting that the function of c-fos is more likely to be associated with other cellular functions in the differentiated amnion cell.

Amnion↗
PubMed1986

Expression of c-fos in NIH3T3 cells is very low but inducible throughout the cell cycle.

It has previously been shown that the c-fos proto-oncogene is rapidly and transiently induced following growth factor stimulation of quiescent NIH3T3 mouse fibroblasts. To investigate a possible role of c-fos in growth control mechanisms we have studied its expression and inducibility during the NIH3T3 cell cycle. Two major conclusions can be drawn from this analysis. First, expression of c-fos is not cell cycle-regulated, and is barely detectable in all phases of the cycle. Second, cells at different stages of the cell cycle (except for mitosis) are as sensitive to c-fos induction by growth factors as quiescent cells. These observations suggest that induction of the c-fos gene does not play a role during the continuous cycling of NIH3T3 cells, but they are fully compatible with the hypothesis that a function of c-fos may be associated with the induction of competence in fibroblasts. Through such a function c-fos may contribute to moving cells out of the quiescent state.

Animals↗
PubMed1986

Wounding a fibroblast monolayer results in the rapid induction of the c-fos proto-oncogene.

The c-fos gene has previously been shown to be transiently induced within minutes after the stimulation of mouse fibroblasts with growth factors. Induction of c-fos was observed specifically with competence factors (e.g., platelet-derived growth factor), not with progression factors (e.g., platelet-poor plasma), suggesting a role for c-fos in conferring competence on fibroblasts. To test this hypothesis we have analyzed c-fos expression in NIH 3T3 cells that were made competent in a different way, namely by wounding a confluent monolayer of cells. Using antibodies raised against either a synthetic fos peptide or a beta-galactosidase--fos fusion protein, we show in this study that in the majority of cells lining the wound c-fos protein is rapidly and transiently induced to high levels. No induction is observed in cells at a distance from the wound greater than approximately 5 cell layers. Induction is equally efficient in both serum-containing and serum-free medium, and is similar in cells that were deprived of fetal calf serum for 40 h prior to making the wound. Our observations support the hypothesis that c-fos may be involved in inducing the 'competent state' in fibroblasts and suggests an early role for c-fos in wound healing and tissue regeneration.

Animals↗
PubMed1986

Fluorescence of 3-keto-steroids in aqueous solution. Probes for steroid-protein interactions.

The physiologically important 3-keto-steroids are non-fluorescent or only weakly fluorescent in protic as well as in aprotic solvents. In contrast, the 4,6,8(14)-triene-3-one steroids are highly fluorescent in aqueous solution but they do not appreciably fluoresce in other solvents. Evidence is presented that the introduction of double bonds into the skeleton of the 3-keto-steroids leads to a decrease of the energy of the lowest pi-pi* state, bringing this level into the neighbourhood of the non-fluorescent n-pi* state. As a consequence, for two states of approximately the same energy, relatively small perturbations such as those due to solvent interactions, protein binding and micelle formation, will then determine whether a system will fluoresce (pi-pi* state lowest) or not (n-pi* state lowest). When the fluorescent 3-keto-steroids, having three conjugated double bonds, bind to proteins, the fluorescence intensity becomes almost zero, making these compounds useful as probes for steroid-protein interactions. This quenching of the fluorescence is explained by a decrease in energy of the n-pi* state relative to the pi-pi* state of th steroids due to hydrophobic interactions with the proteins.

Biophysical Phenomena↗
PubMed1986

Delayed effects of prolonged exercise on serum lipoproteins.

The delayed lipoprotein changes after a 3-hour running test were examined in 14 moderately trained young male subjects. Fasting blood samples were obtained one day before, immediately before, and one, two, and four days after the race. Nonfasting samples were collected immediately after, one, and three hours after exercise. Three hours after the race, the ratio of unesterified cholesterol to cholesteryl esters was significantly increased, and one and two days after the race it was significantly decreased compared to the preexercise value. The HDL2/HDL3 ratio, measured by density-gradient ultracentrifugation was one and three hours after the running significantly elevated. However, no redistribution of the HDL2/HDL3 cholesterol ratio determined by a precipitation method with polyanions was found at this time. One day postexercise HDL cholesterol rose significantly above the preexercise value, and this was associated with an elevation of the HDL3 subfraction. On the following day a significant increase of HDL2 cholesterol and the HDL2/HDL3 cholesterol ratio was found. The apolipoproteins A-I, A-II, and B, measured by radial immunodiffusion, did not change during the first hours and the first two days after the race. On the second postexercise day the Lp(a) lipoprotein rose significantly above the preexercise value. Compared with the preexercise level the LCAT activity was significantly elevated three hours after the race and significantly decreased two days later. The present study suggests that during the first few days after prolonged exercise a number of plasma lipoprotein changes take place that are similar to those observed after a period of physical training.

Adult↗
PubMed1986

Immunogenicity of recombinant hepatitis B vaccine in dialysis patients.

Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a geometric mean titer (GMT) of 180.7 IU/l after 3 vaccinations, whereas all of the 16 healthy controls, vaccinated 3 times with a 10-micrograms dose of the same vaccine batch, had specific antibodies higher than 10 IU/l (GMT 897.4 IU/l). Responses of patients were slightly higher than those of dialysis patients vaccinated in an earlier study with plasma-derived vaccine according to the same schedule. Results in 20 patients immunized 6 times intragluteally with 40 micrograms HBsAg/dose in monthly intervals were not better (at month 7, 65% showed anti-HBs concentrations greater than 10 IU/l; GMT = 126.6 IU/l), and 19 patients receiving 6 times 20 micrograms HBsAg monthly showed significantly lower responses (anti-HBs greater than 10 IU/l in 42% of vaccinees, GMT = 89.5 IU/l). The vaccine was tolerated well; side-effects were slight, and no serious adverse reactions were observed. In conclusion, recombinant hepatitis B vaccine is comparable to plasma-derived vaccine also in the case of dialysis patients; a 6-dose schedule does not seem to have much advantage compared to the conventional 3-dose regimen.

Adult↗
PubMed1986

Sulfonylurea therapy fails to diminish insulin resistance in type I-diabetic subjects.

To assess whether extrapancreatic effects of sulfonylureas in vivo are detectable in the absence of endogenous insulin secretion, insulin sensitivity was determined in six insulin-deficient type 1-diabetic subjects. Peripheral uptake and hepatic production of glucose and lipolysis were measured during hyperinsulinemia using the euglycemic clamp technique and 3-3H-glucose infusions twice, once during a period with glibornuride treatment (50 mg b.i.d.), and once without. Hepatic glucose production decreased in diabetic subjects during hyperinsulinemia (insulin infusion of 20 mU/m2 X min; plasma free insulin levels of 40 +/- 4 mU/l) from 2.9 +/- 0.6 mg/kg min to 0.2 +/- 0.1 mg/kg X min after 120 min, and plasma free fatty acid (FFA) concentrations decreased from 1.33 +/- 0.29 to 0.38 +/- 0.08 mmol/l. Hepatic production, peripheral uptake of glucose and plasma FFA concentrations before and during hyperinsulinemia were not influenced by pretreatment with glibornuride. Compared to 8 non-diabetic subjects, type 1-diabetics demonstrated a diminished effect of hyperinsulinemia on peripheral glucose clearance (2.4 +/- 0.04 vs 4.2 +/- 0.5 ml/kg X min, P less than 0.01), whereas hepatic glucose production and plasma FFA levels were similarly suppressed by insulin. The data indicate that sulfonylurea treatment did not improve the diminished insulin sensitivity of peripheral glucose clearance in type 1-diabetic subjects; insulin action on hepatic glucose production and lipolysis was unimpaired in diabetics and remained uninfluenced by glibornuride. Thus, extrapancreatic effects of sulfonylureas in vivo are dependent on the presence of functioning beta-cells.

Adult↗