[New biochemical aspects of diabetes: receptor problems and insulin mutations].
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Biomedical subjects
Publications and source records attributed to H Müller.
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Helix-coil transitions of double-stranded RNA from reovirus and infectious bursal disease virus were measured optically in aqueous medium of different ionic strengths. In RNA from reovirus four transitions and in RNA from infectious bursal disease virus two transitions were resolved and evaluated quantitatively. The ionic strength dependence of their midpoint temperatures dTm/dlog[Na+] were 13.5 +/- 0.3 degrees C for reovirus RNA and 14.9 +/-0.7 degrees C for infectious bursal disease virus RNA. The midpoint temperatures extrapolated to 1 M ionic strength were 102.9, 104.3, 105.6, and 108.8 +/- 0.3 degrees C for reovirus RNA, and 108.8 +/- 1.8 and 109.6 +/- 1.0 degrees C for infectious bursal disease virus RNA. The G + C content of the regions in reovirus RNA melting in the different transitions were determined from the spectrum of the hypochromicity. The quantitative interpretation of the data is carried out on the basis of the ion condensation theory. It is estimated for double-stranded RNA of 100% G + C, that dTm/dlog[na+] = 8.4 degrees C. The two-dimensional dependence Tm = Tm (ionic strength, G + C content) is given. The ionic strength dependence in different double-stranded RNAs is correlated to the spacing of the phosphate backbone, secondary structure, and tertiary structure.
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The in vivo and in vitro development of the zona pellucida as well as the vitelline membrane surface of oocytes isolated from juvenile mice aged between 8 and 30 days p.p. were investigated by scanning electron microscopy. In vivo a consistent development of the zona pellucida surface can be observed, namely the formation of a fibrous network like structure interspersed with numerous pores. After enzymatic removal of the zona pellucida the surface of the vitelline membrane was studied. In "normal" oocytes with intact germinal vesicles, microvilli were distributed over the entire oocyte surface in all age groups investigated. After resumption of meiosis in vitro a characteristic differentiation on the vitelline membrane occurs. A glabrous polar region appears in primary oocytes and a glabrous polar body in secondary oocytes. The same differentiation in surface organization could be observed in the in vivo precociously matured oocytes.
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The hypothesis that there is prostaglandin-mediated hypercalcaemia associated with the Walker carcinosarcoma in the rat was tested by measuring PGE production during the development of the hypercalcaemia, and determining the effects of inhibition of prostaglandin synthesis on serum calcium concentration. Parathyroid hormone (PTH) activity was estimated by the determination of the serum concentration of immunoreactive PTH. There was a 3-fold increase in the urinary excretion of 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid (PGE-M), a major urinary metabolite of the E prostaglandins from basal levels. Treatment with indomethacin, a potent inhibitor of prostaglandin synthesis, did not lower serum calcium concentrations with two different doses (1·6 mg/kg/day orally and 5 mg/kg/day i.m.); effective inhibition of prostaglandin synthesis was demonstrated by the suppression of PGE-M excretion rates below basal levels. Serum concentrations of immunoreactive PTH were not significantly altered by either tumour growth or indomethacin. Dexamethasone (0·5 mg/kg/day i.m.) attenuated both the increased urinary excretion of PGE-M and the rise in serum calcium concentration, suggesting that one or several lipoxygenase products might be the actual mediators of the hypercalcaemia. We conclude that the hypercalcaemia in the rat with Walker carcinosarcoma is probably not mediated by E-prostaglandins and probably not by any other product of the cyclo-oxygenase pathway. The increased PGE turnover may be considered as a biochemical marker of tumour load, but not as an indicator of a prostaglandin-mediated hypercalcaemia.
The human kidney contains two types of alkaline phosphatase (AP) isoenzymes: a hepatic type of AP and an intestinal-like AP. Intestinal-like AP, measured by immunotitration techniques, is a minor component (1 to 4%) of the total AP activity. It is found only in the particle-free fraction (cytoplasm) and is located, with immunofluorescent techniques, in some of the proximal convoluted tubules. Urinary AP activity is found after high-speed centrifugation in the supernatant (x 100,000g), as well as in the sediment, and may be extracted from the sediment after solubilization with n-butanol. Both types of these renal isoenzymes contribute to urinary AP activity. Biochemical characterization (effect of inhibitors, thermostability, denaturing with urea, and so on) revealed that urinary intestinal-like AP and renal intestinal-like AP are identical. Both, however, have been distinguished as multiple forms of AP from the small intestine. Most of the urinary AP activity of healthy persons (22 volunteers) was found in the sediment and consisted of liver-type AP. Urinary AP of patients with diseases, after application of potentially nephrotoxic drugs or during rejection episodes of renal allografts, contains little sediment activity, but it contains increased amounts of urinary intestinal-like AP.
1. Isolated rat kidneys were perfused with a modified Krebs-Henseleit medium at constant pressure. 2. When prostaglandin F2 alpha (PGF2 alpha) was infused into these kidneys at 0.1 mumol/l (final concentration) PGF2 alpha-derived prostaglandin E2 (PGE2) could be identified by high-performance liquid chromatography and combined gas chromatography-mass spectrometry. 3. The extent of this conversion of PGF2 alpha into PGE2 during passage through the kidney is dependent on the salt history of the rats from which the kidneys were taken for perfusion: kidneys from rats kept on normal diet converted 10%, those from rats on a low sodium diet 5% and those from rats kept on a high sodium diet 11%. 4. These differences in conversion can account for the different increases in renin release after PGF2 alpha infusion in these groups.
Endometrical nuclei, prepared from rabbits subjected to different hormonal treatments, were used for the cell-free synthesis of RNA. Optimal conditions for the incorporation of [3H]UMP into RNA are described, leading to the synthesis of relatively undegraded RNA molecules. Under these conditions there is virtually no initiation of new RNA chains in vitro, and RNA chain elongation is inhibited up to 60% by low concentrations of alpha-amanitin and up to 90% by actinomycin D. The synthesis of RNA is slightly inhibited in the presence of Hg-CTP and monothioglycerol, but newly synthesized mercurated RNA can be efficiently separated from endogenous RNA upon chromatography on sulfhydryl-Sepharose under stringent conditions. The RNA synthesized in vitro by endometrial nuclei from pseudopregnant rabbits contains RNA sequences transcribed from the uteroglobin gene, as demonstrated by hybridization to an excess of purified preuteroglobin cDNA. In endometrial cells from pseudopregnant animals the number of RNA polymerase II molecules transcribing the uteroglobin gene is 12-fold higher than in control animals, demonstrating that at least part of the hormonally induced accumulation of preuteroglobin mRNA is due to an increased rate of transcription of the uteroglobin gene.
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Fourteen patients (six males and eight females) have been treated with chronic hemofiltration three times weekly for three to 27 months with the post-dilution technique. All patients had previously been on regular dialysis treatment. Patients were selected for hemofiltration because of dialysis-resistent hypertension (eight), symptoms of dialysis discomfort (five), hypertriglyceridemia (five) and polyneuropathy (seven). Hypertension improved in six of eight patients, symptoms of dialysis discomfort markedly diminished in all five patients, hypertriglyceridemia did not change consistently, polyneuropathy improved in six of seven patients. Balance studies of Na, Ca and Mg revealed a positive correlation to fluid balance. Phosphate, BUN, creatinine and uric acid increased. Loss of amino acids and protein is negligible. Hormone studies showed a decrease of T3, T4 and TSH though the pituitary-thyroid axis is intact, possibly indicating a decreased TRH activity. Vitamin D remained unchanged, PTH levels increased, possibly related to a diminished excretion of phosphate and diminished intake of calcium, respectively, during hemofiltration treatment as compared to hemodialysis.
Bovine papilloma virus (BPV) appears to be the etiological agent of common equine connective tissue tumors. We investigated the physical state of the viral DNA within such tumors and found no indication for integration into the host genome. The BPV genomes were present as free circular episomes. Two equine sarcoids were shown to contain multiple copies of free circular BPV type 1 (BPV-1) DNA. When the tumors were digested with several single-cut restriction enzymes, there were only form III BPV-1 DNA sequences could be revealed. One of the sarcoids contained, apart from wild-type BPV-1 DNA, a class of smaller BPV-1 circular DNA molecules bearing a deletion of approximately 9% of the BPV-1 genome. This deletion is located in the physical map between the relative units 0 and 0.32.
The chromosome set of the lesser kudu, Tragelaphus imberbis, consists of 38 elements in both sexes. In contrast to most other members of the bovid subfamily Tragelaphinae, both the X and the Y chromosomes are compound, having fused with identical autosomes from ancestors presumed to have higher chromosome numbers. From a comparison of the unusual sex chromosomal rearrangements that have occurred in this family, a hypothetical lineage has been derived. This family tree and the details of various banding studies in the lesser kudu are described.
Strain C 2653 have proved to be applicable with good success as a live vaccine to treat avian encephalomyelitis. The virus is excreted by immunised animals up to roughly three weeks from immunisation and absorbed by non-immunised animals. Propagation and excretion of the immunisation virus will bring about sufficient immunity of the entire herd, within something between four and eight weeks from immunisation. Something between two and four per cent of the individuals in one herd are treated by crop instillation, which works well in cases of floor keeping. Yet, contact of all animals with the immunisation virus cannot be ensured, if the same technique is applied to animals kept in cages. Administration of the vaccine in pressure compensating vessels of the cage nipple lines or valve-operated drinking grooves in floor-keeping fowl houses will increase the amount by vaccine needed by the factor of 2.5, as compared to crop instillation, but the entire stock will be immunised in a shorter period of time, with 80 per cent of man-hours being saved. Application to floor-kept animals can be further simplified, which was demonstrated by the experimental prototype of a new drug proportioning device. Five times more vaccine will be needed, as compared to crop instillation, but that higher quantity is offset by more savings in man-hours.
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In 1978 353 premature and mature newborns were admitted to our neonatal and intensive care unit. 34 children developed bacterial infections. B-streptococci were the offending organisms in 6 cases, pneumococci in 1 case, 5 of these 7 infections were of the early-onset type, 2 of the late-onset type. The early-onset type disease manifests itself by respiratory distress and shock. It is transmitted vertically from mother to child before or during birth. 3 of our 5 affected children died. The late-onset type disease occurs after 5-10 days, is transmitted as horizontal, mostly nosocomial infection, and presents as sepsis with meningitis or - as in one of our cases - with osteomyelitis. In addition to the 7 sick infants 8 of the 353 admitted newborns were colonized without signs of disease. Early diagnosis, therapy, and prophylaxis of these infections present still unsolved problems.
Epidural injection of small doses of opiates causes a reduction of pain in the lower parts of the body. The use of epidural opiate-analgesia for surgical anesthesia, combined with controlled ventilation (oxygen-nitrous oxide), was investigated in 170 patients undergoing surgery, especially long lasting gynaecological operations. Haemodynamic monitoring demonstrated a constant cardiovascular situation, underlining the sufficiency of analgesia. Blood gas analyses for one hour after the operation revealed no signs of respiratory depression. The epidural opiate-analgesia outlasted the intraoperative period, covering even the postoperative phase.