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Biomedical subjects

S Kaplan

Publications and source records attributed to S Kaplan.

At least 361 records · Page 20Linked to original sources
PubMed1983

Biosynthesis of the photosynthetic membranes of Rhodopseudomonas sphaeroides.

The steady-state biosynthesis of the photosynthetic membrane (ICM) of Rhodopseudomonas sphaeroides has been reviewed. At moderate light intensities, 500 ft-c, preexisting ICM serves as the insertion matrix for newly synthesized membrane components. Whereas the bulk of the membrane protein, protein-pigment complexes, and pigments are inserted into preexisting ICM throughout the cell cycle, phospholipid is transferred from outside the ICM to the ICM only at the time of cell division. Because the site of cellular phospholipid synthesis is the cytoplasmic membrane, these results infer that despite the physical continuity of cytoplasmic membrane and ICM, there must exist between these membranous domains a "barrier" to the free diffusion of cellular phospholipid. The cyclical alternation in protein to phospholipid ratio of the ICM infers major structural and functional alternations, such as changes in the protein to lipid ratio of the membrane, specific density of the membrane, lipid structure within the membrane, and the rate of cyclic electron flow. When biochemical studies are correlated with detailed electron microscopic investigations we can further conclude that the number of photosynthetic units within the plane of the membrane can vary by nearly a factor of two over the course of the cell cycle. The average physical size of the photosynthetic units is constant for a given light intensity but inversely proportional to light intensity. The distribution of photosynthetic unit size classes within the membrane can be interpreted as suggesting that the "core" of the photosynthetic unit (reaction center plus fixed antenna complex) is inserted into the membrane coordinately as a structural entity. The variable antenna complex is, on the other hand, inserted independent of the "core" and randomly associates with both old and new core complexes. Finally, we conclude that there is substantial substructure to te distribution of photosynthetic units within the ICM, ie, they are highly ordered and exist in a defined spatial orientation to one another.

Bacterial Chromatophores↗
PubMed1983

Normal aortic root dimensions in premature infants.

Normal aortic root dimensions are established using 334 sequential echocardiograms in 111 average-gestational-age premature infants between 600-2500 g. The aortic roots increased in diameter from 0.53 cm +/- 0.04 cm for infants weighing 600-900 g to 0.80 +/- 0.08 cm for infants weighing between 2200-2500 g.

Aorta↗
PubMed1983

Morphologic changes in blast cells of children with acute lymphoblastic leukemia in relapse.

Relapse in children with acute lymphoblastic leukemia (ALL) on therapy may be due to development of a resistant clone of blast cells. Seven children who presented initially with the "common"-type, L1 lymphoblast relapsed with a morphologically different and more undifferentiated blast cell. All were male, with a median age of 12 years at initial presentation. One child who relapsed while off therapy was successfully reinduced and remains in hematologic remission on therapy. The remaining 6 children died within 10 months of relapse. Selection of a resistant clone of lymphoblasts by chemotherapy may be responsible for relapse in children with ALL and should be studied in hopes of controlling the disease.

Adolescent↗
PubMed1983

Glucose and insulin changes in infants and children undergoing hypothermic open-heart surgery.

Marked hyperglycemia was observed in patients undergoing hypothermic open-heart surgery. To evaluate potential mechanisms responsible for hyperglycemia, paired samples were evaluated for glucose and insulin levels in 3 groups of patients. Group 1 consisted of 8 patients less than 2 years of age undergoing cardiac surgery requiring total circulatory arrest; Group 2 consisted of 9 patients less than 2 years of age undergoing open-heart procedures but not requiring total circulatory arrest; Group 3 consisted of 10 patients greater than 2 years of age, none of whom required total circulatory arrest. All 3 groups had striking hyperglycemia during cardiac surgery and in the first few hours after the operation. Despite elevated glucose levels during surgery, insulin levels failed to increase proportionately in response to hyperglycemic stimulus. Subsequently, in a fourth group of 10 patients less than 2 years of age not undergoing total circulatory arrest, the amount of glucose infused was restricted and they did not have hyperglycemia. In children, osmotic diuresis resulting from hyperglycemia after open-heart surgery may be misinterpreted as an index of satisfactory cardiorenal performance. Accordingly, it is recommended that the diluent added to the pump blood prime solution contain no supplemental glucose; also, intraoperative fluid should consist of a balanced electrolyte solution but no glucose.

Cardiac Surgical Procedures↗
PubMed1983

A phase I trial of marcellomycin with a weekly dose schedule.

Marcellomycin, a new anthracycline antibiotic, was administered intravenously on a weekly schedule to 22 patients with advanced malignant solid tumors. Patients were treated at 6 dosage levels ranging from 5 to 30 mg/m2 weekly for 4 weeks. Courses were repeated after a 3-week rest period. Hematologic toxicity was dose-limiting but unpredictable. Of 10 patients treated with weekly doses of 27.5 mg/m2, 3 patients exhibited myelosuppression and 2 died in agranulocytosis. Moderate to severe nausea and vomiting occurred in 19 of 22 evaluable patients. Other toxic effects were non-acute and consisted of mild stomatitis, diarrhea, phlebitis and moderate fatigue in 1-3 patients each. In 17 patients evaluable for antitumor activity no partial or complete responses occurred. One patient with advanced breast cancer showed a mixed response. Marcellomycin given on a weekly dose schedule has unpredictable and erratic hematologic toxicity. The maximally tolerated dose appears to be between 27.5 and 30 mg/m2 weekly. However, no firm recommendations can be given for a dose level that results in tolerable, predictable and reversible toxicity.

Adult↗
PubMed1983

Identification of nitrogenase and carboxylase genes in the photosynthetic bacteria and cloning of a carboxylase gene from Rhodopseudomonas sphaeroides.

The presumptive genes for the ribulose 1,5-bisphosphate carboxylase large subunit and for nitrogenase-specific components from Rhodopseudomonas sphaeroides and several other photosynthetic bacteria were identified and located by interspecific probing. Restriction digests of R. sphaeroides genomic DNA were hybridized under stringent conditions to cloned DNA from Rhodospirillum rubrum (plasmid pRR2119 carrying the carboxylase gene) and Klebsiella pneumoniae (pSA30 carrying the nitrogenase genes). The nitrogenase probe hybridized with different signal intensities to several distinct HindIII, BglII, EcoRI, BamHI and PvuII fragments of R. sphaeroides 2.4.1.DNA. The carboxylase probe hybridized to only single R. sphaeroides 2.4.1.DNA fragments produced with all five restriction enzymes. A 3000-bp EcoRI-BamHI R. sphaeroides 2.4.1.DNA fragment carrying the presumptive gene for the large subunit of ribulose 1,5-bisphosphate carboxylase was cloned into pBR322 and positively identified by probing with a 32P-labeled internal PstI fragment of the Rhodospirillum carboxylase gene.

Carboxy-Lyases↗
PubMed1983

Differentiation of constrictive pericarditis and restrictive cardiomyopathy using digitized echocardiography.

Constrictive pericarditis and restrictive cardiomyopathy are difficult to distinguish at the bedside and occasionally at routine cardiac catheterization. Left ventricular diastolic function was studied by computer analysis of digitized M-mode echocardiograms in four patients with constrictive disease and three with restrictive disease, and the data were compared with those of normal subjects. The respective distinguishing echographic features of constrictive pericarditis and restrictive cardiomyopathy were as follows: the major filling period of the left ventricle was 78 +/- 9% of normal versus 128 +/- 4% (p less than 0.01), minimal left ventricular dimension to peak filling interval was 50 +/- 10 versus 110 ms (p less than 0.05) and the maximal rate of left ventricular posterior wall thinning was -4.9 versus -2.3 seconds-1 (p less than 0.05). This preliminary study suggests that it may be possible to accurately diagnose the two disease entities using this technique at the bedside and to avoid cardiac catheterization.

Adolescent↗
PubMed1983

Flow-independent improvement by diltiazem of ischemia-induced conduction delay in porcine hearts.

The calcium channel blocking agent, diltiazem, improves ischemia-induced conduction delays in the canine heart. It is not known, however, if the improvement of myocardial blood flow caused by diltiazem participates in this response. Accordingly, ischemia-induced conduction delay was measured during brief coronary artery occlusion before and after administration of diltiazem in nine anesthetized pigs with fixed heart rate. Acute coronary occlusion prolonged subendocardial (mean +/- standard error of the mean, 39.9 +/- 3.9 ms) and subepicardial (41.6 +/- 4.1 ms) conduction times (time to peak of the bipolar electrogram in each region) by 51 +/- 4 and 58 +/- 5%, respectively. Regional myocardial blood flow at the ischemic electrode sites was 0.006 +/- 0.002 ml/min per g and was unaffected by diltiazem. Intravenous diltiazem pretreatment (0.01, 0.1, 0.3 and 1.0 mg/kg) 5 minutes before coronary occlusion significantly reduced the ischemia-induced conduction delay in both subendocardial and subepicardial regions during coronary occlusion. The pigs in which ventricular fibrillation occurred within 10 minutes showed a significantly longer conduction delay than that observed in pigs in which ventricular fibrillation occurred later (greater than 10 minutes). Thus, the data suggest that the reduction of ischemia-induced conduction delay produced by diltiazem is independent of blood flow changes and, therefore, that diltiazem may have a beneficial antiarrhythmic action.

Animals↗
PubMed1983

Light-dependent regulation of the synthesis of soluble and intracytoplasmic membrane proteins of Rhodopseudomonas sphaeroides.

Cells of Rhodopseudomonas sphaeroides grown under saturating light conditions (30 W/m2) and then shifted to low light intensity (3 W/m2) required 2.5 h to adapt to the new lower light conditions. After the shift, cell growth, whole cell protein accumulation, and bacteriochlorophyll accumulation ceased immediately. Approximately midway into the adaptation period, bacteriochlorophyll synthesis commenced at a new, higher rate, which continued through the beginning of the low-light growth period until new steady-state levels were reached. Immediately after the downshift, the rate of cellular protein synthesis declined to 22% of its preshift rate. Pulse-labeling of protein throughout the adaptation period and comparison with a steady-state prelabel culture revealed that synthesis of two of the three light-harvesting proteins, as well as two additional high-molecular-weight photosynthetic membrane proteins, was derepressed three- to fivefold compared with bulk cellular protein. Finally, the synthesis of at least three soluble proteins showed light-dependent regulation after the light downshift. These results are discussed in terms of the light-dependent regulation of synthesis of the photosynthetic membrane macromolecular components and the division of protein synthesis between the photosynthetic membranes and the soluble cell phase.

Bacterial Proteins↗
PubMed1983

Immunochemical relationship of the major outer membrane protein of Rhodopseudomonas sphaeroides 2.4.1 to proteins of other photosynthetic bacteria.

Immunoblots of sodium dodecyl sulfate-polyacrylamide gels derived from outer membrane preparations of various strains of Rhodopseudomonas sphaeroides revealed polypeptides which cross-reacted with antibody directed against the major outer membrane protein of R. sphaeroides 2.4.1. Immunochemical quantitation of the major outer membrane protein of strain 2.4.1 showed approximately 5.5 x 10(4) molecules per cell whether cells were grown chemoheterotrophically or photoheterotrophically. Rhodospirillum rubrum outer membranes contained a cross-reactive protein, whereas the outer membranes derived from Rhodopseudomonas capsulata and Paracoccus denitrificans showed no cross-reaction with the antibody prepared against the major outer membrane protein from R. sphaeroides 2.4.1.

Bacterial Outer Membrane Proteins↗
PubMed1983

In vivo metabolic intermediates of phospholipid biosynthesis in Rhodopseudomonas sphaeroides.

The in vivo metabolic pathways of phospholipid biosynthesis in Rhodopseudomonas sphaeroides have been investigated. Rapid pulse-chase-labeling studies indicated that phosphatidylethanolamine and phosphatidylglycerol were synthesized as in other eubacteria. The labeling pattern observed for N-acylphosphatidylserine (NAPS) was inconsistent with the synthesis of this phospholipid occurring by direct acylation of phosphatidylserine (PS). Rather, NAPS appeared to be kinetically derived from an earlier intermediate such as phosphatidic acid or more likely CDP-diglyceride. Tris-induced NAPS accumulation specifically reduced the synthesis of PS. Treatment of cells with a bacteriostatic concentration of hydroxylamine (10 mM) greatly reduced total cellular phospholipid synthesis, resulted in accumulation of PS, and stimulated the phosphatidylglycerol branch of phospholipid metabolism relative to the PS branch of the pathway. When the cells were treated with a lower hydroxylamine dosage (50 microM), total phospholipid synthesis lagged as PS accumulated, however, phospholipid synthesis resumed coincident with a reversal of PS accumulation. Hydroxylamine alone was not sufficient to promote NAPS accumulation but this compound allowed continued NAPS accumulation when cells were grown in medium containing Tris. The significance of these observations is discussed in terms of NAPS biosynthesis being representative of a previously undescribed branch of the phospholipid biosynthetic sequence.

Hydroxylamine↗
PubMed1983

Effect of cerulenin on macromolecule synthesis in chemoheterotrophically and photoheterotrophically grown Rhodopseudomonas sphaeroides.

The antibiotic cerulenin causes the immediate cessation of phospholipid biosynthesis in both chemoheterotrophic and photoheterotrophic cultures of Rhodopseudomonas sphaeroides. Macromolecule biosynthesis in photoheterotrophic cells was unaffected by cerulenin for the first 2 h after antibiotic addition and then continued at a reduced rate for an additional 8 h. In contrast, macromolecule biosynthesis in chemoheterotrophic cells was severely affected by cerulenin within the first 2 h of treatment. Pulse-labeling of protein after cerulenin addition revealed that all subcellular fractions were equally affected by the action of cerulenin with chemoheterotrophic cell fractions more profoundly affected than those derived from photoheterotrophic cells. Protein insertion into the intracytoplasmic membrane of photoheterotrophic cells continued for up to 6 h after the onset of cerulenin treatment. Residual macromolecule synthesis was correlated with the presence of the photosynthetic membrane system under all conditions of growth.

Antifungal Agents↗
PubMed1983

Age-related changes in electrophysiological properties of canine Purkinje fibers: effect of ouabain.

Transmembrane potentials were recorded in Purkinje fibers obtained from dogs aged 1 day, 1 week, 2 weeks, 4 weeks and more than 1 year. After the initial impalements there was a time-dependent increase in diastolic potential. This hyperpolarization was more pronounced in the younger Purkinje fibers. Maximum diastolic potentials from 1-day-old puppies (-78.0 +/- 1.2 mV), after 10 min of continuous impalement, were significantly less negative than those for adults (-84.2 +/- 1.9 mV). Fibers from neonates exposed to ouabain do not depolarize as much as fibers from adults.

Action Potentials↗
PubMed1983

Phase II study of doxifluridine in advanced colorectal adenocarcinoma.

Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.

Adenocarcinoma↗
PubMed1982

The in vitro transcription-translation of DNA and RNA templates by extracts of Rhodopseudomonas sphaeroides. Optimization and comparison of template specificity with Escherichia coli extracts and in vivo synthesis.

A DNA-directed coupled transcription-translation system has been developed in cell-free extracts from the facultative phototroph, Rhodopseudomonas sphaeroides. The in vitro protein-synthesizing system was active when prepared from either chemoheterotrophically or photoheterotrophically grown cells. Optimal activity was dependent upon: use of extracts prepared freshly from early exponential phase cells, the method of cell breakage, and the length of preincubation of the extract (S-30), as well as the concentrations of S-30, template, and cations. The R. sphaeroides cell-free system was compared to one prepared from Escherichia coli. DNA templates tested included R. sphaeroides phage RS1 DNA and E. coli phages T4 and T7 DNA, as well as plasmids RSF1010, pBR322, pSL25 (a pBR322 derivative), and a chimeric plasmid of pSL25 and RSF1010. One RNA template, phage R17, was also employed to test translational fidelity. Transcriptional-translational specificity was observed between R. sphaeroides and E. coli and these observations are discussed in terms of differential gene expression among phylogenetically distinct groups of bacteria.

DNA, Bacterial↗