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Biomedical subjects

N Grossman

Publications and source records attributed to N Grossman.

At least 19 recordsLinked to original sources
PubMed1991

Smoking and movement disorders in psychiatric patients.

Previous studies have suggested that tardive dyskinesia may occur more frequently in patients who smoke. Further evidence of an interaction between smoking and movement disorders includes the low lifetime exposure to cigarettes found in Parkinson's disease patients. In this study 126 patients with chronic psychiatric illnesses were blindly evaluated for tardive dyskinesia, neuroleptic-induced parkinsonism, and akathisia. Patients who smoked received significantly higher doses of neuroleptics but did not have significantly more frequent or more severe tardive dyskinesia or parkinsonism. Female smokers did have significantly more akathisia. These results are discussed with regard to interactions between smoking, central dopaminergic tone, and the psychopathology of extrapyramidal syndromes. The effect of smoking on neuroleptic blood levels as well as clinical symptomatology is also discussed.

Adult↗
PubMed1990

Salmonella O antigen-specific oligosaccharide-octyl conjugates activate complement via the alternative pathway at different rates depending on the structure of the O antigen.

Artificial Salmonella serogroup B, D or Cl-specific glycolipids were prepared by covalently linking oligosaccharides corresponding to two O-antigen repeating units, obtained by phage enzyme hydrolysis of native O-antigenic polysaccharides, to octyl residues. Sheep erythrocytes coated with the artificial glycolipids were studied for their ability to consume C3, when incubated in C4- deficient guinea pig serum. Salmonella C1 (0-6,7) glycolipid-coated erythrocytes consumed C3 40% more efficiently than Salmonella D (0-9,12) glycolipid-coated erythrocytes, and 10-times more efficiently than Salmonella B (0-4,12) glycolipid-coated erythrocytes. These results resemble C3 consumption by Salmonella C1, D, and B cells and by sheep erythrocytes coated with purified lipopolysaccharides of these O-specificities. The results prove directly that in a particulate system C3 activation via the alternative pathway depends on the structural properties of the O-antigenic side chain. Structures as small as octasaccharides, or as two O-antigenic repeating units, are sufficient for triggering C3 activation, but the magnitude of activation depends on the nature of the monosaccharides. Apparently, neither the core oligosaccharide nor Lipid A of lipopolysaccharide are required for C3 activation via the alternative pathway.

Animals↗
PubMed1989

Termination of DNA replication is required for cell division in Escherichia coli.

The correlation between termination of DNA replication and cell division in Escherichia coli was studied under conditions in which DNA replication was slowed down without inducing SOS functions. The experimental system used involved amino acid starvation of synchronized cells in the presence of methionine. The results further support the essential correlation between termination of DNA replication and initiation of division processes.

Cell Division↗
PubMed1989

Apparent minimal size required for cell division in Escherichia coli.

The experiments described in this report were designed to find out whether there is a minimal size threshold for cell division or for DNA replication in Escherichia coli. Cells with decreasing size (or mass) were obtained by successive amino acid starvations. Following two starvations, the cells were at least 30% smaller than unstarved newborn cells. The results suggest that this size is below a minimal size threshold for cell division but not for initiation of DNA replication.

Amino Acids↗
PubMed1987

Lipopolysaccharide size and distribution determine serum resistance in Salmonella montevideo.

The survival of Salmonella montevideo during serum treatment depends on the presence of an O antigen (O-Ag) associated with the lipopolysaccharide molecule. In this organism, the O antigen is a polysaccharide composed of 0 to more than 55 subunits, each containing 4 mannose residues together with glucose and n-acetylglucosamine. We used a mutant strain of S. montevideo that requires exogenous mannose for the synthesis of O-Ag. Lipopolysaccharide (LPS) was prepared from these cells grown under three different conditions where the availability of exogenous mannose was regulated such that the average number of O-Ag units per LPS molecule, the percentage of LPS molecules bearing long O-Ag side chains, and the percentage of lipid A cores bearing O-Ag were all varied. These changes in LPS profiles were monitored on sodium dodecyl sulfate-polyacrylamide gels, and cells with different LPS profiles were tested for their ability to survive treatment with pooled normal human serum. Survival in serum was associated with LPS that contained an average of 4 to 5 O-Ag units per LPS molecule, and 20 to 23% of the LPS molecules had more than 14 O-Ag units per LPS molecule. Serum survival was less clearly associated with the percentage of lipid A cores covered with O-Ag. We propose, based on these data and on previous work, that the O-Ag polysaccharide provides the cell protection from serum killing by sterically hindering access of the C5b-9 complex to the outer membrane and that a critical density of long O-Ag polysaccharide is necessary to provide protection.

Antigens, Bacterial↗
PubMed1986

C3b binding, but not its breakdown, is affected by the structure of the O-antigen polysaccharide in lipopolysaccharide from Salmonellae.

Bacteria whose lipopolysaccharide contains O-antigen side chains activate complement via the alternative pathway. We have shown previously that three strains of Salmonella, differing in the chemical structure of their O-antigens, consumed C3 to different extents when incubated in C4-deficient guinea pig serum. Moreover, sheep erythrocytes coated with lipopolysaccharide purified from these strains mimicked whole cells in C3 consumption, proving that lipopolysaccharide alone could account for these results. We have now measured the deposition of 125I-C3 in this system, and found that C3 deposition parallels C3 consumption in rate and extent, and differs for surfaces bearing different O-antigens, whether tested with bacteria or with erythrocytes coated with purified lipopolysaccharide. We have also examined the fate of C3 on these Salmonellae by measuring the size and quantity of 125I-C3 breakdown fragments by SDS-PAGE, and have determined the kinetics of conversion of C3b to iC3b by using conglutinin, a molecule that binds specifically to iC3b. There is no difference in breakdown of C3b deposited on cells with different O-antigens: all show partial conversion to iC3b and C3dg as indicated by 68,000, 44,000, and 41,000 m.w. bands on reduced SDS gels. Furthermore, for all strains, the Ka of conglutinin binding to iC3b is similar (0.49 to 0.69 X 10(8) M-1), as is the rate of generation of iC3b and the final ratio of iC3b:C3b + iC3b (0.62 to 0.72). We therefore postulate that the fine structure of the O-antigen in lipopolysaccharide determines the magnitude of alternative pathway activation on the bacterial surface by affecting the rate and extent of C3b deposition, but not the rate and extent of breakdown of C3b.

Antigens, Bacterial↗
PubMed1986

C3 binds preferentially to long-chain lipopolysaccharide during alternative pathway activation by Salmonella montevideo.

We studied the population of LPS molecules on Salmonella montevideo that bind C3 during alternative pathway activation in serum. LPS molecules of Salmonella are composed of lipid A:core oligosaccharide (one copy per molecule), substituted by an O-polysaccharide (O-PS) side chain, which is a linear polymer of 0 to greater than 60 O-antigen repeat units containing mannose. A mutant of S. montevideo called SL5222 that inserts galactose only into core oligosaccharide and mannose only into O-antigen subunits was grown with [3H]mannose and [14C]galactose, so that LPS molecules bearing large numbers of O-antigen subunits have high 3H to 14C ratios, whereas molecules with few O-antigen subunits have lower 3H to 14C ratios. Double-labeled SL5222 was incubated in C8-deficient (C8D) serum or C8D serum with 2 mM Mg++Cl2 and 10 mM ethylene glycoltetraacetic acid (MgEGTA C8D). LPS molecules with covalently attached C3 were identified by binding to anti-C3. LPS molecules that bound C3 under both incubation conditions had O chains seven to eight times longer than the average LPS molecule. SL5222 was then grown in suboptimal concentrations of mannose in order to decrease the number of LPS molecules with long O-PS side chains. C3 attached to progressively shorter chain molecules of LPS as the mannose input was lowered, but still chose the longest available molecules. This finding and recently published observations indicate that C3 can bind to LPS molecules with short O-PS side chains. We postulate that preferential attachment of C3 to long-chain LPS in SL5222 results because long-chain LPS molecules sterically hinder shorter chain LPS molecules from macromolecules. This study provides direct proof that the O-PS of LPS sterically hinders access of large molecules to the outer membrane and indicates that the LPS coat of these bacteria functions as a barrier against large protein molecules.

Antigens, Bacterial↗
PubMed1986

Effect of TMB-8 on histamine release from isolated rat mast cells.

TMB-8 was capable of complete inhibition of the histamine release induced by antigen, compound 48/80, and the ionophore A23187 (2 microM). The effective concentrations for 50% inhibition (IC50) were 1.2 X 10(-4) M for antigen, 1.6 X 10(-4) M for compound 48/80 both in the absence and in the presence of calcium, and 0.7 X 10(-4) M for the ionophore. The inhibitory action was not affected by increased calcium concentration in the medium from 1 to 2m M. The presence of glucose in the medium counteracted the inhibition by TMB-8 and, for low concentrations of the ionophore (0.25 microM), TMB-8 caused a pronounced enhancement of the histamine release. Our results indicate that TMB-8 primarily exerts its effects by interference with oxidative metabolism rather than by affecting the intracellular calcium availability.

Animals↗
PubMed1984

Complement activation via the alternative pathway by purified Salmonella lipopolysaccharide is affected by its structure but not its O-antigen length.

Salmonellae, the lipopolysaccharide of which differ in the chemical structure of their O-antigenic side chains, were previously shown to activate C3 at differential rates via the alternative pathway. We wanted to test whether lipopolysaccharide isolated from these strains yields identical results, and also the effect of the polysaccharide chain length, which varies from 0 to 40 or more repeating units in a single strain. Lipopolysaccharide was purified from the above strains, hydrolyzed (0.1 N NaOH, 56 degrees C, 30 min), and used to coat sheep erythrocytes to different densities, and C3 activation in C4-deficient guinea pig serum was measured. C3 activation was proportional to lipopolysaccharide density and time, and the relative rates and extents of activation by this bacteria-free system were the same as for the original bacteria. Activation was reduced 10 to 15% when the serum was preabsorbed with strains either containing or lacking O-antigen side chain, suggesting augmentation by antibody; however, even after multiple absorptions, activation varied with O-antigen structure as expected. This differential activation was not due to differences in the average length of the O-antigenic polysaccharide chains, because the size was similar for all three lipopolysaccharides. Moreover, the extent of activation by lipopolysaccharide that had been fractionated on a column of Sephadex G-200 was independent of the polysaccharide chain length for lengths greater than 3 repeating units. The results prove that C3 activation by lipopolysaccharide via the alternative pathway is sensitive to slight variations in the chemical structure, but not to large variations in length of the O-antigen polysaccharide side chain of lipopolysaccharide.

Animals↗
PubMed1983

Puberty gingivitis in insulin-dependent diabetic children. I. Cross-sectional observations.

This cross-sectional study examined the gingivitis occurring at puberty in a population of insulin-dependent juvenile diabetics. Seventy-seven children between the ages of 6 and 15 years were examined for gingivitis levels, stages of pubertal maturation and blood levels of glucose and glycosylated hemoglobin. Bacterial plaque was sampled from one or more approximal tooth surfaces of every subject and cultured under anaerobic and aerobic conditions on nonselective and selective media. The total cultivable flora and percentage of certain presumptive periodontopathic bacteria were determined. Before puberty, children with "high" levels of glycosylated hemoglobin also had higher gingivitis levels than children with "normal" metabolic control of diabetes. During puberty, the level of gingivitis increased independently from both fasting blood glucose levels and per cent glycosylated hemoglobin. The microbiota of marginal plaque was predominantly composed of facultatively anaerobic bacteria. The percentages of Capnocytophaga sp and Actinomyces naeslundii were statistically higher at the onset of puberty, suggesting that a specific bacterial shift in the microbial composition of marginal plaque occurs in response to host changes in juvenile diabetic children at this age period.

Adolescent↗
PubMed1983

Salmonellae activate complement differentially via the alternative pathway depending on the structure of their lipopolysaccharide O-antigen.

Differences in the O-antigen polysaccharide structure of lipopolysaccharide were previously shown to affect the rate of phagocytosis of Salmonellae strains by the murine macrophage-like cell line J774. Phagocytosis required a serum factor(s) that is labile to heat (56 degrees C for 30 min) and to zymosan treatment, which indirectly suggested the participation of C. We now show, using guinea pig serum, that these bacteria activate C3 at different rates, and this activation is proportional to the later rate of phagocytosis. Activation is predominantly via the alternative pathway, because C4 is not consumed and the reaction proceeds equally well in the serum of C4-deficient guinea pigs. Because the extent of activation of C3 and the subsequent rate of phagocytosis are inversely proportional to virulence, we propose that virulence of a strain may be influenced by the ability of the polysaccharide structure of its lipopolysaccharide to activate the alternative pathway of C, destining it for subsequent phagocytosis.

Animals↗
PubMed1983

Thyroid indexes.

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Humans↗
PubMed1982

Changes in cell dimensions during amino acid starvation of Escherichia coli.

Electron microscopic analysis was used to study cells of Escherichia coli B and K-12 during and after amino acid starvation. The results confirmed our previous conclusion that cell division and initiation of DNA replication occur at a smaller cell volume after amino acid starvation. Although during short starvation periods, the number of constricting cells decreased due to residual division, it appears that during prolonged starvation, cells of E. coli B and K-12 were capable of initiating new constrictions. During amino acid starvation, cell diameter decreased significantly. The decrease was reversed only after two generation times after the resumption of protein synthesis and was larger in magnitude than that previously observed before division (F. J. Trueba and C. L. Woldringh, J. Bacteriol. 142:869-878, 1980). This decrease in cell diameter correlates with synchronization of cell division which has been shown to occur after amino acid starvation.

Amino Acids↗
PubMed1980

Initiation of deoxyribonucleic acid replication in Escherichia coli B: uncoupling from mass/deoxyribonucleic acid ratio.

In Escherichia coli growing at different rates, the ratio of cell mass to the number of chromosome origins tended to be constant at the time of the initiation of deoxyribonucleic acid (DNA) replication. This observation led to the assumption that the initiation event is controlled in some way by cell mass, e.g., by a growth-dependent synthesis of an initiator or dilution of a repressor. We have now found that the initiation of DNA synthesis can be uncoupled from cell mass. We used a synchronous culture of newly divided cells of E. coli B which was obtained by the membrane elution technique (C.E. Helmstetter, J. Mol. Biol. 24: 417-427, 1967) and was starved for an amino acid. Upon restoration of the amino acid, the cells not only divided at a size that was smaller than normal, but also initiated DNA replication long before they could increase their masses to reach the expected ratio of mass/DNA presumably required for initiation.

Acetates↗