Melcher assumes reins of Senate aging committee.
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Biomedical subjects
Publications and source records attributed to H Weiss.
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The development of cancer in humans is considered as a multistep process ultimately leading to clinically detectable disease and further progression of the tumour. By use of cytometric techniques it has been possible to perform quantitative measurements and detect qualitative alterations in malignant tumours. This mainly applies to DNA aberrations and deviations in nuclear size and morphology. Such alterations may also be present for a long period prior to malignant, invasive growth, i.e. at a preneoplastic stage. A survey of available data on such preneoplastic changes is given. Since the type of aberrations is both dependent on the tissue of origin and the tumour type, this must always be taken into consideration. A particularly rapid expansion has taken place in the field of flow cytometry, where high resolution measurements of cellular DNA content as well as cell cycle distribution and other parameters can be performed shortly after sampling of the tissue. It is expected that cytometric methods will be used in future diagnostics of early cancerous growth in several organ systems, including the skin, the gastrointestinal tract, the urinary bladder, the breast and female genital organs.
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An apparent outbreak of fume fever was identified among six workers in an electronics instrument testing laboratory during a routine thermal evaluation of conductivity on electrical cable. The employees experienced characteristic symptoms of fume fever. Three employees required hospitalization; they demonstrated fever, leukocytosis with a left shift, and significant arterial-alveolar oxygen gradients, all of which resolved over several hours. To prevent future occurrences, an attempt was made to delineate the etiologic agent by exactly reproducing the circumstances of the event and analyzing for the evolution of metal fumes or pyrolysis products of polymers. The pertinent findings included overall poor ventilation in the laboratory and the development of significant chloride air contamination during the test. This latter finding raises the possibility that a chloropolymer contaminant was the etiologic agent.
The Fe/S protein of complex III is encoded by a nuclear gene, synthesized in the cytoplasm as a precursor with a 32 residue amino-terminal extension, and transported to the outer surface of the inner mitochondrial membrane. Our data suggest the following transport pathway. First, the precursor is translocated via translocation contact sites into the matrix. There, cleavage to an intermediate containing an eight residue extension occurs. The intermediate is then redirected across the inner membrane, processed to the mature subunit, and assembled into complex III. We suggest that the folding and membrane-translocation pathway in the endosymbiotic ancestor of mitochondria has been conserved during evolution of eukaryotic cells; transfer of the gene for Fe/S protein to the nucleus has led to addition of the presequence, which routes the precursor back to its "ancestral" assembly pathway.
Dimeric ubiquinol:cytochrome c reductase of Neurospora mitochondria was isolated as a protein-Triton complex and free of ubiquinol (Q). The enzyme was incorporated into phosphatidylcholine membranes together with Q. The effects of varying the molar ratio of Q to enzyme on the electron transfer from duroquinol (DHQ2) to the cytochromes c, c1 and b were studied. The rate of electron flow from DQH2 to cytochrome c was 15 times increased by Q and was maximal when one molecule of Q was bound to one enzyme dimer. The apparent Km value for DQH2 of the Q-free enzyme was 5 microM and of the Q-supplemented enzyme 25 microM. The pre-steady-state rate of electron transfer from DQH2 to cytochrome c1 was also 15 times increased by Q and was maximal with one Q molecule bound to one enzyme dimer. This effect of Q was inhibited by antimycin. The pre-steady-state rate of electron transfer from DQH2 to cytochrome b was 5 times decreased when Q was bound to the enzyme and this effect of Q was insensitive to myxothiazol. The H+/2e- stoichiometry with DQH2 as substrate of the Q-supplemented enzyme was 3.6. These results are interpreted in accordance with a Q-cycle mechanism operating in a dimeric cytochrome reductase. Each enzyme monomer catalyses a single electron transfer from the QH2-oxidation centre to the Q-reduction centre and the two monomers cooperate in the reduction of Q to QH2 at one Q-reduction centre. This centre contains two different binding sites for Q. DQH2 does not properly react at the QH2-oxidation centre. DQH2, however, binds to the loose Q-binding site of the Q-reduction centre and reduces the Q bound to the tight Q-binding site of the centre. The QH2 thus formed at the Q-reduction centre serves as electron donor for the QH2-oxidation centre.
Nine xeroderma pigmentosum (XP) patients were investigated. In comparison to a normal control group the XP patients had a reduced OKT-4 lymphocyte subpopulation, reduced response of lymphocytes to phytohemagglutinin in autologous serum, and diminished delayed hypersensitivity skin reaction. The possible contribution of ultraviolet irradiation to the observed immunologic alterations, and the link of these alterations to the susceptibility of patients for malignant transformation is discussed.
50 infants admitted during the years 1981 to 1985 for suspected hypertrophic pyloric stenosis were examined sonographically. A pyloric cockade of 14 mm or more in diameter is diagnostic. A diameter up to 10 mm can be considered normal, whereas values between 11 and 13 mm represent borderline cases, which need consideration of the clinical symptoms and repeated controls. Because of its accuracy sonography can replace X-ray examinations in most of the cases with suspected hypertrophic pyloric stenosis.
We have recently reported that a rise of platelet numbers in ITP can be induced by blockade of the RES with antibody-coated red blood cells. We now present a collaborative study in which 15 Rhesus-positive children with ITP (nine boys and six girls aged 1-15 years) were treated with low-dose anti-D. Ten patients had chronic ITP (duration 6-47 months), five had acute ITP. Doses of 28-50 micrograms anti-D/kg bodyweight per course were given intravenously. In all patients clinical signs of bleeding ceased and platelet counts were elevated. An excellent, good or fair response with platelet increments of greater than 100, 50-100, or 20-50 X 10(9)/l, respectively, was observed in 19, 7, and 12 out of 45 courses in chronic ITP, and in 4, 1, and 2 out of 8 courses in acute ITP. The platelet increase (greater than 40 X 10(9)/l) persisted for 10 to over 360 days in chronic ITP. There were no untoward side reactions. Haemoglobin values remained stable in all patients but laboratory signs of mild, compensated haemolysis ensued. The direct antiglobulin test became positive in all cases due to anti-D IgG. Previous therapy of patients with chronic ITP included high-dose immunoglobulins and prednisone. These regimens were both effective but remissions were short. We conclude that anti-D therapy is an effective and safe form of treatment in childhood ITP.
The effect of sulphur dioxide on the clearance of Listeria monocytogenes from normal and emphysematous hamsters was assessed by measuring the number of colony forming units recovered from whole lung homogenates. Continuous exposure to SO2 after intratracheal instillation of Listeria significantly altered the clearance of viable bacteria from the lungs of emphysematous but not normal hamsters. Preexposure of hamsters to SO2 for 2 weeks prior to respiratory infection had similar effects. The emphysematous hamsters exposed to SO2 had a lower average number of Listeria in the lungs after the first week of infection than control groups. This effect appears to result from the combined influence of the SO2, the Listeria infection, and the emphysematous condition within the lungs.
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