[Thyroid and adrenal diagnosis in obesity are not worth while].
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Biomedical subjects
Publications and source records attributed to J Müller.
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The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.
To determine the average diameter and the upper normal limit of the common bile duct in healthy man, 830 blood donors were examined by ultrasound. The mean diameter was 2.5 +/- 1.1 mm (SD) at the porta hepatis and 2.8 +/- 1.2 mm (SD) at the widest point, the regression coefficient between both diameters being r = 0.84. None of the healthy subjects had a diameter larger than 7 mm at any site, and in 95% of all subjects the diameters were less than 4 mm at both sites of measurement. The diameters were significantly correlated with age (r = 0.16) and weight (r = 0.11), but not with sex, height, and body surface area. In 73 patients with cholelithiasis and in 55 patients after cholecystectomy, all of whom lacked clinical or laboratory signs of biliary obstruction, the average diameters at the porta hepatis were 3.8 +/- 2.0 mm and 5.2 +/- 2.3 mm, and at the widest point 4.8 +/- 2.2 mm and 6.2 +/- 2.5 mm, respectively. It is concluded that a common bile duct with any sonographic diameter larger than 4 mm should be followed closely and evaluated further with clinical examinations such as intravenous cholangiography unless cholecystectomy has been performed.
Urinary RNA catabolites, especially modified nucleosides and nucleobases, have turned out to represent valuable new criteria for diagnosis and follow-up of malignancies. Here we show for the first time that multivariate analysis of urinary RNA catabolites can distinguish between tumor carriers and controls who, if examined by univariate procedures, would remain undifferentiated. Two such models have been demonstrated. We hope that a continuation of this work will support primary clinical diagnostic procedures, the control of therapy effects, and the long-term follow-up of patients, which should be regarded as special medical applications of the general principles of molecular biology.
The influence of a guinea pig lymphokine preparation on the oxidative metabolism of human and guinea pig granulocytes of various sources was investigated. A dose-dependent increase of the oxidative burst following lymphokine challenge was observed. It occurred in unstimulated guinea pig peripheral polymorphonuclear leukocytes (PMN) and in prestimulated PMN obtained from the peritoneal cavity after glycogen injection as well. The lymphokine effect on the oxidative metabolism is not species-restricted because the guinea pig lymphokine preparation elicits an oxidative burst in human PMN, too. The increase caused by lymphokines is nearly of the same order of magnitude as that obtained with zymosan.
NZB mice serve as a model for human systemic lupus erythematodes. T-cell abnormalities in this strain have previously been described. In this paper the cytotoxic T lymphocyte precursor (CTL-p) frequencies of NZB mice against H-2 allogeneic and H-2 syngeneic cells are investigated and compared with those of the normal strain BALB/c. The CTL-p frequency in NZB lymphocytes against H-2 allogeneic cells equals that in normal mouse strains (i.e. 1/7500). The NZB anti BALB/c response is in the same order of magnitude. No corresponding BALB/c anti NZB response was elicited. The results suggest abnormally high sensitivity of NZB CTL-p to helper signals.
A new bovine collagenic prosthesis (Solcograft P) was tested in animal experiments. In 45 dogs the infrarenal abdominal aorta was substituted. During a follow-up period of up to 18 months the functional rate amounted to 88%. Joint-crossing iliaco-femoral bypasses were implanted in 31 dogs, 5 times in both sides. For the new bovine collagenic graft the functional rate ran up to 83%, during a follow-up period of 9 months. A wound infection was observed twice in the inguinal region thus exacting the removal of the prosthesis. An aneurysm was not observed. In our opinion the satisfying results are due to the compliance of the new prosthesis which is similar to natural artery.
K+ Repletion for 48 h of rats previously kept on a low K+ diet for 2 weeks specifically increased the conversion of corticosterone into aldosterone and 18-hydroxycorticosterone by incubated capsular fractions of rat adrenal tissue. This increase in the activity of the final steps of aldosterone biosynthesis was not accompanied by an increase in capsular adrenal mitochondrial cytochrome P-450 concentration. By contrast, an increased corticosterone-induced absorbance change (BI) was consistently found in capsular adrenal mitochondria upon K+ repletion. In addition, a type I-like absorbance change was induced with 18-hydroxy-11-deoxycorticosterone but not with 18-hydroxycorticosterone. Therefore, K+ repletion of K+ depleted rats specifically increased the binding of corticosterone and possibly 18-hydroxy-11-deoxycorticosterone to the 18-methyl oxidase enzyme complex. Whether this increased binding was due to an increase in enzyme protein concentration or due to a better availability of the substrate to the enzyme, could not be decided from these experiments.
By means of the Simonson GVH-assay and the popliteal lymph node (PLN) assay, the T-cell reactivity of NZB mice against H-2 identical allogenic cells was investigated in vivo and compared to that of normal mice. None of the normal mice did react, but a highly significant NZB response could be demonstrated, which did not depend on differences in Mls antigens. These in vivo results extend previous findings of a T-cell hyperreactivity of NZB mice in primary in vitro reactions. They favour the possibility that the T-cell hyperreactivity might be relevant in vivo in facilitating autoimmune responses.
Two cell membrane leucocyte alloantigens were detected in pigs by simple direct agglutination tests. Family studies showed that the locus controlling these antigens was not identical, or in close linkage, with the SLA major histocompatibility complex, SLB leucocyte locus or with the A, E, and N blood group loci. In the studied population, the locus termed SLC (Swine Leucocyte C locus) has two alleles controlling mutually exclusive antigens SLC-1 and SLC-2. The frequency of SLC1 and SLC2 alleles is 0.10 and 0.90, respectively. The antigens have not been detected on erythrocytes and thrombocytes but are well determined on granulocytes, peritoneal macrophages, mononuclears from different sources (thymus, spleen, bone marrow, lymph nodes) and enriched T and B cells from peripheral blood.
A stereological study of the development of testicular volume, the germ cell population and the seminiferous tubules was carried out on testes from 50 boys between 0 and 18 years of age who had suffered from sudden unexpected death. Semi-thin sections (0.5 micrometer) of testicular tissue were prepared and examined by point and profile counting using a projection microscope. Testicular weight was recorded in 48 of the cases. Median volume of pairs of testes increased from 1.1 (range 0.3--1.9) to 3.0 cm3 (range 2.8--3.4) during the 0--10 year period, while the median of the total number of germ cells per boy was augmented from 13 x 10(6) (range 4.4--36 x 10(6)) to 83 x 10(6) (range 32--122 x 10(6)) during the same period. The median length of the seminiferous tubules per boy was 181 m (range 27--361) in the 0--1 year period and 411 m (range 277--660) in the group 5--10 years. Mean tubular diameter was unchanged during the first 10 years of life, whereas the mean nuclear diameter of the germ cells showed significant negative correlation to age in boys less than 10 years. After the age of 10 years a more marked growth of testicular volume, an increase in the number of germ cells and the diameter as well as the length of the seminiferous tubules were observed. Thus, the study showed that testicular size, the number of germ cells and the total length of the seminiferous tubules per boy increased not only in puberty but also during the first ten years of life.
Late steps of aldosterone biosynthesis, i.e., the conversions of corticosterone to 18-hydroxycorticosterone and aldosterone, are catalyzed by a mitochondrial cytochrome P-450. Resumption of potassium intake by potassium-depleted rats resulted within 2 days in a marked stimulation of these conversions, as reflected by increased production of aldosterone and 18-hydroxycorticosterone and decreased outputs of deoxycorticosterone, corticosterone, and 18-hydroxy-11-deoxycorticosterone by incubated capsular portions of the adrenal glands. The stimulation of aldosterone biosynthesis was accompanied by the appearance of a protein with a molecular weight of about 49,000 in the mitochondria of the zona glomerulosa but not of the inner zones of the adrenal cortex. Over 48 h of potassium repletion, the amount of this protein increased in parallel with the activity of the final steps of aldosterone biosynthesis. According to its molecular weight, its zone specificity, and the time course of its appearance, this protein might represent the steroid 18-methyl oxidase (cytochrome P-450CMO for corticosterone methyl oxidase) that catalyzes the conversion of corticosterone to 18-hydroxycorticosterone and aldosterone.
The urinary excretion of 5 modified and 2 unmodified RNA catabolites and of creatinine has been investigated in two children aged 71/2 and 6 years under different isocaloric diets over 5 days each (phase I-III) and compared with the excretion values during a 12-day and libitum food intake (phase 0). On a diet (phase I) extremely rich in nucleic acids (meat) there is only a slight increase of the modified RNA catabolites and a pronounced increase of creatinine in urine. On a protein-rich diet free from nucleic acids (phase II) the urinary RNA catabolites largely parallel the values seen under ad libitum food intake. On a diet virtually free of nucleic acids and protein (phase III) there is a markedly decreased excretion of modified RNA catabolites. It is concluded that modified RNA catabolites in the urine are mainly of endogenous origin. These "one-way catabolites" permit an assessment of the RNA turnover. Thus, they can serve as a new sensitive biochemical criterion for anabolic and catabolic situations, respectively.
Disodium chromoglycate, an antiasthmatic drug, which is effective in inhibiting mediator release from bronchial mast cells, failed to inhibit allergen-induced histamine release in vitro from actively sensitised basophils of grass pollen sensitive children and adults. In contrast, ketotifen, a drug that has been demonstrated in a number of placebo controlled studies to be of lower efficacy in vivo, inhibits histamine release. Our data support the concept that human basophils and mast cells respond differently to antianaphylactic drugs.
Mice and rabbits immunized intraperitoneally or intradermally with an ethanol-killed crude Candida albicans antigen and non-immunized controls were infected intravenously with C. albicans. The mortality rates clearly demonstrated immune protection, although the proportion of dead cells in the Candida immunization dose was inversely related to the degree of protection. Histopathological observations demonstrated distinct differences in the morphology of the fungal cells as well as in the host tissue reaction between the immunized and the non-immunized animals.
Cytoplasmic and mitochondrial malate dehydrogenases from pig and chicken were studied by chemical modification of amino groups, hybridization of immobilization. Determination of thermal stability was used to characterize the different species. Modification of amino groups was found to decrease thermal stability especially when neutralization of the positive charges occurred. Decreased thermal stability correlated with decreased reassociation of immobilized monomers and modification in the monomeric state completely inhibited reassociation. Thus some lysines seem to be implicated within the subunit contacts. Active monomers of the mitochondrial forms as demonstrated earlier (Jürgensen, S.R., Wood, D.C., Mahler, J.C. and Harrison, J.H. (1981) J. Biol Chem. 256, 2383-2388) were found to display unaltered kinetic properties. From hybridizations the mechanism of thermal denaturation of malate dehydrogenases was concluded to contain a rate-limiting cooperative transaction of both monomers within the dimer, as was found earlier for tetrameric lactate dehydrogenase (Müller, J. (1981) Biochim. Biophys. Acta 669, 210-215 and Müller, J. and Klein, C. (1981) Biochim. Biophys. Acta 671, 38-41).
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Alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1) was covalently bound to Sepharose beads. Kinetic measurements with the substrate p-nitrophenyl phosphate gave the following results. Effectiveness factors were decreasing with increasing bound activity, decreasing substrate concentration, and increasing particle radius of the beads. With decreasing effectiveness factors, the apparent Michaelis constants were decreasing. Preparations with high bound activities did not obey Michaelis-Menten kinetics at substrate concentrations much higher than the apparent Michaelis constants. The experimental results accorded quantitatively with the theory of diffusion limitation (Engasser, J.M. (1978) Biochim. Biophys. Acta 526, 301-310).