The Correlation between the Inhibition of Drug Resistance and Synergism in Streptomycin and Penicillin.
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Biomedical subjects
Publications and source records attributed to M Klein.
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The mononuclear peripheral blood cells from eight patients with chronic myelocytic leukaemia (CML) were incubated in cell suspension culture in the presence of the phorbolester 12-O-tetradecanoylphorbol 13-acetate (TPA). TPA caused the treated cells to adhere and to acquire morphological and functional features characteristic of macrophage-like cells. Using isoelectric focusing distinct changes in the isoenzyme profiles of carboxylic esterase, acid phosphatase, hexosaminidase and lactate dehydrogenase were detected in the TPA-exposed cells. Besides an increase in the number and staining intensity of isoenzymes of all enzymes, TPA triggered the new expression of a monocyte-specific esterase isoenzyme isoenzyme and of the tartrate-resistant acid phosphatase isoenzyme. The latter two isoenzymes represent further parameters of the monocyte/macrophage complex. The results indicate that immature leukaemic cells arrested along the granulocytic cell axis retain the ability to transform to macrophages.
The need to acquire a better knowledge of the main biological problems induced by microgravity implies--in addition to human experimentation--the use of animal models, and primates seem to be particularly well adapted to this type of research. The major areas of investigation to be considered are the phospho-calcium metabolism and the metabolism of supporting tissues, the hydroelectrolytic metabolism, the cardiovascular function, awakeness, sleep-awakeness cycles, the physiology of equilibrium and the pathophysiology of space sickness. Considering this program, the Centre d'Etudes et de Recherches de Medecine Aerospatiale, under the sponsorship of the Centre National d'Etudes Spatiales, developed both a program of research on restrained primates for the French-U.S. space cooperation (Spacelab program) and for the French-Soviet space cooperation (Bio-cosmos program), and simulation of the effects of microgravity by head-down bedrest. Its major characteristics are discussed in the study.
Using an aqueous extraction followed by ultrafiltration through Amicon Diaflo membranes, two ovine pineal fractions were obtained, which contain immunoreactive neurophysin. The presence of neurophysin was monitored by radioimmunoassay, employing an antiserum raised against pituitary bovine neurophysin and selected because it reacts with neurophysins of many other mammals. From 50 g of wet ovine pineal glands 552 micrograms of immunoreactive neurophysins were obtained. About 5% of these immunoreactive neurophysins are eluted from three different Sephadex columns with an elution volume corresponding to Mr above 10,000 between bovine serum albumin and pituitary neurophysin. The remaining 95% of ovine immunoreactive pineal neurophysin (Mr 10,000) shares immunological and physico-chemical properties with highly purified bovine pituitary neurophysin used as a reference. From the results of gel filtration and affinity chromatography on LVP-Sepharose it was concluded that ovine pineal gland may contain a neurophysin precursor molecule in addition to the neurophysin Mr 10,000.
An Ethiopian immigrated to Israel and gave a positive test result for human immunodeficiency virus. Soon after, he was thrice admitted to hospital in 3 months for severe pneumonia. Acquired immunodeficiency syndrome was diagnosed, as was hyperreactive malarial splenomegaly (HMS). Thereafter, during maintained proguanil treatment for HMS, the patient remained well for 16 months. Then, after another pneumonic illness, pneumococcal vaccine was administered. Proguanil was maintained for another 10 months and, despite declining CD4 cell counts, good health continued for a further 18 months.
Extensive apoptosis or programmed cell death (PCD) of both hematopoietic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic syndromes (MDS) cancels the high birth-rate resulting in ineffective hematopoiesis and has been demonstrated as the probable basis for peripheral cytopenias in MDS by our group. It is proposed that factors present in the microenvironment are inducing apoptosis in all the cells whether stromal or parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46 MDS patients and eight normal individuals were examined for the presence of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) and one cellular component, macrophages, by the use of monoclonal antibodies immunohistochemically. Results showed the presence of TNF-alpha and TGF-beta in 41/46 and 40/46 cases of MDS respectively, while only 15 cases showed the presence of GM-CSF. Further a significant direct relationship was found between the degree of TNF-alpha and the incidence of PCD (p= 0.0015). Patients who showed high PCD also had an elevated TNF-alpha level. Thus, the expression of high amounts of TNF-alpha and TGF-beta and low amounts of the viability factor GM-CSF may be responsible for the high incidence of PCD leading to ineffective hematopoiesis in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-alpha drugs such as pentoxifylline.
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Phosphorus nuclear magnetic resonance spectroscopy enables the energy metabolism of skeletal muscles to be studied non-invasively in vivo. Relative concentrations of phosphocreatine (PCr), inorganic phosphate (iP), monophosphoric sugars (mP) and ATP, as well as intracellular pH values, are directly accessible through the spectra. The striated muscle is continuously studied at rest, during exercise and during recovery. Exercise-induced changes in pH and mP provide indirect information on glycogenolysis and glycolysis. The speed of PCr resynthesis during post-exercise recovery and the PCr/iP ratio values at rest excellently reflect mitochondrial oxidative phosphorylations. Phosphorus NMR spectroscopy therefore is of interest not only to study the impact, through hypoxia, on muscle energy metabolism of such pathologies as cardiac or respiratory failure, or to study various acquired metabolic muscular diseases, but also and above all, to detect and locate muscular enzyme deficiencies involving glycogenolysis, glycolysis or mitochondrial metabolism, thereby pointing to the diagnosis of congenital, and mainly metabolic, myopathies.
New applications of the NMR-MOUSE (mobile universal surface explorer) to non-destructive quality control of elastomers are reported. One example concern the thermal aging of fast clutches which was probed by measurements of 1H transverse relaxation time. Novel methodological developments show that 1H double-quantum filtered NMR signals can be generated in the inhomogeneous fields of the NMR-MOUSE for characterization of residual dipolar couplings. This technique was applied to characterize reference natural rubber samples with different crosslink density and carbon black and silica fillers.
Substantial evidence supports an association of particulate matter (PM) with cardiorespiratory illnesses, but little is known regarding characteristics of PM that might contribute to this association and the mechanisms of action. The Atlanta superstation sponsored by the Electric Power Research Institute as part of the Aerosol Research and Inhalation Epidemiology Study (ARIES) study is monitoring chemical composition of ambient particles by size fraction, as well as a comprehensive suite of other pollutants, at a site in downtown Atlanta during the 25-month period, August 1, 1998-August 31, 2000. Our investigative team is making use of this unique resource in several morbidity studies, called the "Study of Particulates and Health in Atlanta (SOPHIA)". The study includes the following components: (1) a time series investigation of emergency department (ED) visits for the period during which the superstation is operating; (2) a time series investigation of ED visits during the 5 years prior to implementation of the superstation; and (3) a study of arrhythmic events in patients equipped with automatic implantable cardioverter defibrillators (AICDs) for the period January 1, 1993-August 31, 2000. Thirty-three of 39 Atlanta area EDs are participating in the ED studies, comprising over a million annual ED visits. In this paper, we present initial analyses of data from 18 of the 33 participating EDs. The preliminary data set includes 1,662,713 ED visits during the pre-superstation time period and 559,480 visits during the superstation time period. Visits for four case groupings--asthma, chronic obstructive pulmonary disease (COPD), dysrhythmia, and all cardiovascular diseases (CVDs) combined--have been assessed relative to daily air quality indices, controlling for long-term temporal trends and meteorologic variables, using general linear models, generalized estimating equations and generalized additive models. Single-pollutant models predicting case visitation rates using moving averages of 0-, 1-, and 2-day lagged air quality variables were run. For the pre-superstation period, PM10 (24-h), ozone (8-h), SO2 (1-h), NO2 (1-h) and CO (1-h) were studied. For the first 12 months of superstation operation, the following air quality variables of a priori interest were available: ozone (8-h), NO2 (1-h), SO2 (1-h), CO (1-h), and 24-h measurements of PM10, coarse PM (PM 2.5-10 microm), PM2.5, polar VOCs, 10-100 nm particulate count and surface area, and in the PM2.5 fraction: sulfates, acidity, water-soluble metals, organic matter (OM), and elemental carbon (EC). During the pre-superstation time period, statistically significant, positive associations were observed for adult asthma with ozone, and for COPD with ozone, NO2 and PM10. During the superstation time period, the following statistically significant, positive associations were observed: dysrhythmia with CO, coarse PM, and PM2.5 EC; and all CVDs with CO, PM2.5 EC and PM2.5 OM. While covariation of many of the air quality indices limits the informativeness of this analysis, the study provides one of the first assessments of PM components in relation to ED visits.
The amino acid composition of the proteins in selected body fractions of chickens and the 15N-excess of amino acids isolated from them resulting from a feeding experiment with long-term labelling with 15NH4-acetate supplied orally are given. The amino acid spectra of feathers, breast and leg muscles are characterised by differences in the content of individual amino acids specific for the organs, the composition of the proteins, however, is independent of the protein content of the ration and the age of the animals. The sarcoplasmatic and myofibrillar proteins also have typical amino acid patterns, which--with the exception of the histidine content--are neither influenced by the extraction of the proteins from the breast or leg muscles nor by the energy level of the feeding or the age of the animals. There are no significant differences in the metabolisation of the main protein fraction of the breast and leg muscles. The oral supply of 15N ammonium acetate to broilers predominantly labels the non-essential amino acids so that the derived kinetic data chiefly represent the metabolism of the non-essential amino acids.
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Pertussis toxin (PT), an oligomeric exotoxin of Bordetella pertussis containing five dissimilar subunits, is considered to be an essential immunogen in acellular and component pertussis vaccines against whooping cough. A rapid single-step procedure for isolating PT subunits was developed using reverse-phase high-performance liquid chromatography. Recoveries of individual subunits were 75% (S1), 70% (S2), greater than 90% (S3), greater than 90% (S4), and 50% (S5), as judged by SDS-PAGE and amino acid analysis. Lyophilized subunits were solubilized in urea followed by step-wise dialysis to remove the urea. All subunits were inactive in histamine sensitization, lymphocytosis, and hemagglutination assays. However, purified S1 retained residual NAD-glycohydrolase and ADP-ribosyltransferase activity. A partially active holotoxin could be generated by mixing the five individual subunits. All subunits were immunogenic in rabbits and mice. Monospecific antisera raised in both animal species were able to neutralize the PT-mediated clustering of Chinese hamster ovary cells, but active immunization of mice with single subunits failed to protect them in the intracerebral challenge assay. These subunit preparations therefore retained neutralizing determinants, but did not contain protective epitopes.
73 women suffering from primary carcinoma of the fallopian tube underwent surgical excision of their tubes. The tissue was embedded in paraffin and investigated for HER-2 oncogene amplification with a quantitative polymerase chain reaction method. DNA could be extracted and successfully prepared in 65/73 samples. None of the tissue samples exhibited amplified the HER-2 oncogene. Data suggest that the HER-2 oncogene does not play a role in tumor transformation and progression in fallopian tube carcinomas. This contrasts with observations in ovarian carcinomas, with which fallopian tube carcinomas share many clinical, histological and biochemical similarities.
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