[Thrust injuries by children (author's transl)].
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Biomedical subjects
Publications and source records attributed to W Weber.
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Lecithin-cholesterol acyltransferase (EC 2.3.1.43) was purified 15 000-fold from human plasma. The active material was homogeneous in different gel electrophoretic systems but separated into three major bands with apparent pI values of 4.28, 4.33 and 4.37 in isoelectrofocusing. The apparent Mr of the enzyme is 67 000 +/- 2000. An antiserum prepared against the purified enzyme specifically inhibited the activity of lecithin-cholesterol acyltransferase in whole serum. Serum from a patient with familial deficiency of lecithin-cholesterol acyltransferase was substituted in vitro with the highly purified enzyme. The serum from this patient did not contain immunochemically detectable enzyme protein. Substitution of enzyme resulted in the following major changes. 1. Cholesteryl ester content in serum increased by 36-89 mg/100 ml depending on the experimental conditions. The enzyme-mediated formation of cholesteryl ester led to an increase of cholesteryl ester content in high-density and very-low-density lipoproteins and in low-density lipoproteins containing apoprotein-B. No increase occurred in fractions containing very large flattened structures and the abnormal lipoprotein-X and in lipoprotein-E. Incubation of isolated fractions with lecithin-cholesterol acyltransferase led to significant cholesterol esterification only in high-density lipoproteins. 2. The characteristic disc-shaped rouleaux-forming high-density lipoproteins of enzyme-deficient serum disappeared. Instead a single homogeneous population of high-density lipoproteins formed. The particles generated were spherical and had the electrophoretic properties, density (1.080 g/ml), diameter (12.5 nm) and apoprotein composition of normal high-density lipoproteins-2. 3. The concentration of spherical particles containing apolipoprotein E (density 1.040-1.080 g/ml) and the lamellar lipoprotein-X-like structures in the low-density lipoprotein fraction were not affected by the enzyme substitution. 4. A single homogeneous population of spherical lipoprotein-B particles of 26.5-nm diameter occurred at density 1.029 g/ml. The data suggest that the discoidal high-density lipoproteins are the major site of cholesteryl ester formation that apolipoprotein-E is not involved in an undirectional transport of newly formed cholesteryl ester from high-density lipoproteins to other lipoproteins and that lipoprotein-X and lipoprotein-E are not preferential substrates for the acyltransferase.
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Two groups of 16 patients each were studied during abdomino-surgical procedures. Patients of one group received an isotonic glucose solution to cover insensible water losses from the peritoneal cavity whilst patients of the other group were not treated with glucose. In these we found a significant increase in plasma osmolality and in mean corpuscular hemoglobin concentration of the red cells during anaesthesia and operation. The balance of osmotic free water was calculated from changes of plasma osmolality during the observation period. Calculating output as difference between known input and balance we found losses of osmotic free water amounting to approximately 4.5 ml per kilogram bodyweight per hour of operation in both groups. These losses are, in our opinion, identical with the insensible water loss from the peritoneum. Plasma sodium concentration in both groups showed decreasing tendency compared with plasma osmolality. This was partly due to dilution with increased extracellular glucose concentration and partly to an extra-intracellular shift of sodium (without net-water-flux). Plasma potassium concentration decreased in patients receiving glucose but increased in patients without glucose. Red cell potassium concentration decreased in both groups. Urin-to-plasma ratio of osmolality was equal in both groups in spite of a different water balance. Patients receiving glucose had higher urine outputs and therefore (with equal osmolar U/P ratio) a higher osmolar clearance and a higher free-water-reabsorption. It is demonstrated that under conditions as described the amount of free-water reabsorption and concomitantly a favourable effect on water balance during mild dehydration is mainly depending on osmolar clearance.
The polymorphism of apolipoprotein E (Apo E) in man is controlled by two codominant alleles, Apo E(n) and Apo E(d), at the Apo E-N/D locus and by two alleles, the dominant, Apo E4(+), and the recessive, Apo E4(o), at the Apo E4 locus. Frequency distribution analysis of Apo E phenotypes demonstrated a highly significant association between both systems (P approximately 1%). The Apo E4-(+) variant was about twice as frequent in phenotype Apo E-N (30.1%) than in phenotype Apo E-ND (16.4%). The phenotypic combination Apo E-D/-E4(+) was not observed. The segregation of Apo E phenotypes in informative matings is consistent with a close linkage of both loci. The results may be explained by different models. On the basis of the present data, these models cannot be distinguished by formal genetic criteria. (1) Haplotypes Apo E(n)/E4(+), Apo E(n)/E4(o), and Apo E(d)/E4(o) determine the different phenotypes, and a linkage disequilibrium exists of Delta = .0147 between the E-N/D and E4 loci. (2) The fourth haplotype, Apo E(d)/E4(+), exists, but the gene E4(+) is not expressed in coupling with Apo E(d). The four-haplotype model seems more attractive in view of Apo E-N/D polymorphism's quantitative character and of biochemical results, which show that phenotypes Apo E-N and Apo E-D differ in the apparent molecular weight (M(r)) of the respective major Apo E polymorphic form. Hence, the Apo E-N/D locus may control structural genes involved in the posttranslational modification of Apo E. (3) Finally, there may exist only one Apo E structural gene locus but with mutations at two sites susceptible to posttranslational modification.
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TransferrinC (TfC) subtypes were determined by isoelectric focusing (PAGIF) on samples from 90 carriers of the TFB and TfD alleles. In all cases of CB and CD heterozygotes only one of the two common subtypes of the TfC allele, TfC1 or TfC2, was observed. This is considered strong support for the hypothesis of two common alleles at the Tf locus. The different isofocusing patterns of rare B and D variants are compared with the results obtained after agarose gel electrophoresis (AGE).
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Streptomyces glaucescens, strain Tü 49 = ETH 22794, produces hydroxystreptomycin as well as the tetracenomycins, a mixture of several lipophilic antibiotics. The main component and the most active one is tetracenomycin C. Tetracenomycin C has a molecular formula C23H20O11 and is chemically related to tetracyclines and anthracyclinones. The pale yellow antibiotic is active against some gram-positive bacteria, especially against streptomycetes. Gram-negative bacteria and fungi are not inhibited. In considering the differences of biological activity and the functional groups of the molecule, tetracenomycin C is not a member of the tetracycline or anthracyclinone group of antibiotics.
Much progress has been made in allogeneic bone marrow transplantation for severe aplastic anemia (SAA) and acute leukemia (AL). In SAA it was shown that hemopoietic chimerism and apparently permanent cures can be achieved in the majority of patients by conditioning with cyclophosphamide followed by bone marrow transplantation (BMT) from an HLA-identical sibling. The previous transfusion history is crucial for failure or success: untransfused patients do very well while graft rejection is an enormous problem in most polytransfused ones. We have shown that most patients without HLA-identical sibling donors can be adequately helped as well. After conditioning with ALG followed by transfusion of haploidentical marrow and low dose androgens there is partial to complete autologous hemopoietic reconstitution in virtually all patients. This points to the fact that most of these patients have pluripotent hemopoietic stem cells that are intact, but apparently unable to differentiate to mature cells, because they are inhibited by autoimmune mechanisms. The results of BMT in patients with endstage leukemia are modest. New pilotstudies with early marrow grafts, i.e. for ANLL in first remission and for ALL in second remission indicate that with this type of approach potentially over 50% of all patients with HLA-identical siblings can be cured. We recommend that HLA-typing should be performed early in families with SAA and AL and that the possibility of a marrow graft should be seriously considered before the patients have endstage disease. Marrow grafts are technically simple but they may pose enormous problems such as graft versus host reaction (GvH), interstitial pneumonia, graft rejection and leukemic recurrence. Therefore, the procedure should only be performed in highly specialized centers with much knowledge and experience in the immunobiology of bone marrow transplantation.
A series of 229 patients with urogenital carcinomas were investigated for aberrant peptide hormone activities. Serum TSH and prolactin were frequently measured in elevated levels and showed some relation to the stage of disease. Ectopic production of beta-HCG was not observed in any of the cases, thyroid and steroid hormones did not exceed the normal ranges.
The long-term treatment of retrograde ejaculation disorders following retroperitoneal lymphadenectomy with the alpha-sympathomimetic, Midodrin, administered orally, led to improvements in the intensity of orgasm and the degree of erection. Normal ejaculation was induced in 7 out of 12 patients and emission of spermatozoa into the posterior urethra was restored in 3 out of 12 patients by a single intravenous injection of 25--30 mg Midodrin.
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