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Biomedical subjects

L Shapiro

Publications and source records attributed to L Shapiro.

At least 271 records · Page 15Linked to original sources

A comparative study of a BCNU containing 4-drug program versus MOPP versus 3-drug combinations in advanced Hodgkin's disease: a cooperative study by the Cancer and Leukemia Group B.

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkin's disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3-drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4-drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3-drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4-drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Adult↗

Cell-cycle-associated rearrangement of inverted repeat DNA sequences.

Inverted repeat DNA sequences of Caulobacter crescentus have been isolated, characterized, and cloned in a bacteriophage lambda vector. Both whole populations and individual clones of these sequences were hybridized to restriction endonuclease-generated fragments of chromosomal DNA isolated from cells that were in different stages of the cell cycle. Some inverted repeat DNA sequences were observed to hybridize to different regions of the chromosomal DNA isolated from the morphologically and biochemically distinct swarmer cell and stalked cell populations. These results suggest that the inverted repeat sequences have the capacity to rearrange and thus be located at different sites on the genomes of the different cell types.

Bacteria↗

Flagellar hook and basal complex of Caulobacter crescentus.

Intact bacterial flagella possessing a membrane-free hook and basal complex were purified from Caulobacter crescentus CB15, as well as from mutants which synthesize incomplete flagella. The basal body consisted of five rings mounted on a rod. Two rings were in the hook-proximal upper set, and three rings (two narrow and one wide) were in the lower set. The diameters of the two upper rings differed, being 32 and 21 nm, respectively. The lower rings were all approximately 21 nm in diameter, although they varied significantly in width. During the normal course of the C. crescentus cell cycle, the polar flagellum with hook and rod was shed into the culture medium without the basal rings. Similarly, hooks with attached rods were shed from nonflagellate mutants, and these structures also lacked the basal rings. The hook structure was purified from nonflagellated mutants and found to be composed of a 70,000-molecular-weight protein component.

Bacteria↗

Deoxyribonucleic acid sequence homologies among bacterial insertion sequence elements and genomes of various organisms.

Plasmid and phage deoxyribonucleic acid (DNA) harboring bacterial insertion sequence (IS) elements IS1, IS2, and IS5 were characterized and used as probes to detect homologous sequences in various procaryotic and eucaryotic genomes. The hybridization method used permits the detection of sequences partially homologous to the elements. Hybridization of the IS-containing probes to each other revealed a region of limited homology between IS1 and IS2. Homologous sequences were then detected by computer analysis of the published IS1 and IS2 nucleotide sequences. The homologous sequence contains a tandemly repeated tetranucleotide sequence which resembles the repeated sequence at the hot spot for spontaneous mutations in the lacI gene (P. J. Farabaugh, U. Schmeissner, M. Hofer, and J. Miller, J. Mol. Biol. 126:847-863, 1978). Homology between the IS elements and various genomes was determined by hybridizing labeled DNA containing IS1, IS2, and IS5 sequences to Southern blots of chromosomal DNA cleaved with restriction endonucleases. IS1 and IS5 appear limited to the enteric bacteria, whereas IS2 sequences can also be detected in Pseudomonas putida, Pseudomonas aeruginosa, and Serratia marcescens. Bacteria which appear not to possess extrachromosomal elements, e.g., Caulobacter crescentus, did not show homology with any insertion sequences tested. In addition, sequences homologous to IS1, IS2, or IS5 were not detected in Saccharomyces cerevisiae, Dictyostelium discoideum, or calf thymus DNA.

Bacteria↗

Caulobacter cresentus mutant defective in membrane phospholipid synthesis.

To study the relationship between phospholipid synthesis and organelle biogenesis in the dimorphic bacterium Caulobacter crescentus, auxotrophs have been isolated which require exogenous glycerol or glycerol 3-phosphate for growth when glucose is used as the carbon source. Upon glycerol deprivation, net phospholipid synthesis ceased immediately in a glycerol 3-phosphate auxotroph which was shown to have levels of biosynthetic sn-glycerol 3-phosphate dehydrogenase (E.C. 1.1.1.8) activity 10 times lower than that of the wild type. In the absence of glycerol, the optical density of the culture continued to increase for the equivalent of one generation, although the cells did not divide. After the equivalent of one generation time, rapid cell death occurred. Cell death also occurred when phospholipid synthesis was inhibited by cerulenin. Although ribonucleic acid and protein syntheses continued at a reduced rate for the equivalent of one generation in mutant strains, a substantial decrease in the rate of deoxyribonucleic acid synthesis occurred immediately upon glycerol deprivation. Revertant strains had wild-type levels of glycerol 3-phosphate dehydrogenase activity and normal rates of phospholipid and macromolecular synthesis.

Bacteria↗

Sulcular exudate flow in gingival inflammation.

Sulcular exudate flow measurements were obtained from 45 subjects and compared to the clinical as well as histologic degrees of inflammation. The results of this investigation demonstrated no statistically significant difference between exudate flow and the clinical degree of inflammation while demonstrating a statistically significant difference between exudate flow and the clinical assessment of inflammation. It was proposed that current clinical indices do not accurately reflect the microscopic degree of gingival inflammation.

Gingival Crevicular Fluid↗

Galactose catabolism in Caulobacter crescentus.

Caulobacter crescentus wild-type strain CB13 is unable to utilize galactose as the sole carbon source unless derivatives of cyclic AMP are present. Spontaneous mutants have been isolated which are able to grow on galactose in the absence of exogenous cyclic nucleotides. These mutants and the wild-type strain were used to determine the pathway of galactose catabolism in this organism. It is shown here that C. crescentus catabolizes galactose by the Entner-Duodoroff pathway. Galactose is initially converted to galactonate by galactose dehydrogenase and then 2-keto-3-deoxy-6-phosphogalactonate aldolase catalyzes the hydrolysis of 2-keto-3-deoxy-6-phosphogalactonic acid to yield triose phosphate and pyruvate. Two enzymes of galactose catabolism, galactose dehydrogenase and 2-keto-3-deoxy-6-phosphogalactonate aldolase, were shown to be inducible and independently regulated. Furthermore, galactose uptake was observed to be regulated independently of the galactose catabolic enzymes.

Aldehyde-Lyases↗

Membrane phospholipid composition of Caulobacter crescentus.

The phospholipid composition of Caulobacter crescentus CB13 and CB15 was determined. The acidic phospholipids, phosphatidylglycerol and cardiolipin, comprise approximately 87% of the total phospholipids. Neither phosphatidylethanolamine nor its precursor phosphatidylserine was detected. The outer and inner membranes of C. crescentus CB13 were separated, and phospholipid analysis revealed heterogeneity with respect to the relative amounts of phosphatidylglycerol and cardiolipin in the two membranes. As has been shown to be the case for other bacterial membranes, the concentration of cardiolipin increases and phosphatidylglycerol decreases as cell cultures enter stationary phase.

Bacteria↗

Acute pulmonary edema in Plasmodium falciparum malaria.

This report describes a patient who developed acute pulmonary edema as a complication of Plasmodium falciparum malaria. Hemodynamic evaluation revealed a pulmonary artery wedge pressure of 3 mm Hg and a cardiac index of 4.6 liter per min per m2. The patient exhibited an acute decrease in serum colloid osmotic pressure from 25.1 mm Hg to 16.8 mm Hg. These findings suggest that pulmonary edema in this patient was the result of altered capillary membrane permeability.

Acute Disease↗

Clinical study of mianserin, imipramine and placebo in depression: blood level and MHPG correlations.

1. The clinical efficacy of mianserin, a tetracyclic compound, was compared with imipramine and placebo in 47 hospitalized depressed patients. 2. The clinical ratings showed that the three treatment groups improved equivalently during hospitalization. 3. Plasma levels of mianserin correlated with changes in the Hamilton Rating Scale for depression, total score and two of its factors (anxiety/somatization, and retardation) and the item 'late insomnia'. 4. Drowsiness was a more frequent side-effect among mianserin patients on day 4; no other side-effect distinguished the treatments. 5. No relationship between MHPG levels and treatment or treatment outcome were observed.

Adjustment Disorders↗

Desmoplastic trichoepithelioma.

Fifty examples of a distinctive clinicopathologic entity occurred in 49 patients who ranged in age from 8 to 70 (median 46) years. Forty-nine tumors were on the face, mainly the cheek, chin and forehead; most were present one to five years, and 85% of the patients were female. The growths varied in size from 3 to 8 mm; many were hard and annular, with a raised border and depressed nonulcerated center. Histologically, narrow strands of basaloid cells and epidermoid cyts infiltrated a fibrotic stroma. This tumor, which we have named desmoplastic trichoepithelioma, must be differentiated histologically from morphealike basal cell carcinoma, desmoplastic cutaneous metastasis, and certain benign adnexal neoplasms.

Adenoma↗

A pH-conditional mutant of Escherichia coli.

Mutants of Escherichia coli have been isolated that are able to grow on lactose at pH 7.0 but not at pH 8.1. One of these mutants was analyzed and shown to map in the Z region of the lactose operon. beta-Galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) activity in toluenized mutant cells at pH 8.0 was one-tenth that at pH 7.0. Enzyme purified to near homogeneity from the pH-conditional mutant similarly exhibited pH-conditional activity under conditions where wild-type enzyme was unaffected over a pH range of 6.0-8.0. The pH-conditional beta-galactosidase was used in vivo as a probe for intracellular pH. We show that an internal pH of approximately 7.8-8.0 is maintained through an external pH range of 5.9-7.8. The phenotype of pH-conditional mutants was defined on medium with lactose as the sole carbon source. Under such conditions the gene product itself, beta-galactosidase, is required to maintain intracellular pH, since such maintenance is clearly energy-dependent. Therefore, we were able to recover a pH-conditional mutant in a cytoplasmic gene product. We predict that with any phenotype independent of energy production, however, pH-sensitive mutants will be recovered only in surface elements.

Cytoplasm↗

Effect of carbon source and the role of cyclic adenosine 3',5'-monophosphate on the Caulobacter cell cycle.

The expression of cell cycle events in Caulobacter crescentus CB13 has been shown to be associated with regulation of carbohydrate utilization. Growth on lactose and galactose depends on induction of specific enzymes. Prior growth on glucose results in a delay in enzyme expression and cell cycle arrest at the nonmotile, predivisional stage. Dibutyryl cyclic adenosine 3',5'-monophosphate (AMP) was shown to stimulate expression of the inducible enzymes and, thus, the initiation of the cell cycle. beta-Galactosidase-constitutive mutants did not exhibit a cell cycle arrest upon transfer of cultures from glucose to lactose. Furthermore, carbon source starvation results in accumulation of the cells at the predivisional stage. The cell cycle arrest therefore results from nutritional deprivation and is analogous to the general control system exhibited by yeast (Hartwell, Bacteriol. Rev. 38:164-198, 1974; Wolfner et al., J. Mol. Biol. 96:273-290, 1975), which coordinates cell cycle initiation with metabolic state. Transfer of C. crescentus CB13 from glucose to mannose did not result in a cell cycle arrest, and it was demonstrated that this carbon source is metabolized by constitutive enzymes. Growth on mannose, however, is stimulated by exogenous dibutyryl cyclic AMP without a concomitant increase in the specific activity of the mannose catabolic enzymes. The effect of cyclic AMP on growth on sugars metabolized by inducible enzymes, as well as on sugars metabolized by constitutive enzymes, may represent a regulatory system common to both types of sugar utilization, since they share features that differ from glucose utilization, namely, temperature-sensitive growth and low intracellular concentrations of cyclic guanosine 3',5'-monophosphate.

Bacteria↗