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M Rotenberg

Publications and source records attributed to M Rotenberg.

At least 37 records · Page 2Linked to original sources
PubMed1991

Mutations within the Ddc promoter alter its neuron-specific pattern of expression.

The Drosophila dopa decarboxylase gene (Ddc) is expressed in a reproducible set of approximately 150 neurons, and in a subset of the glia of the third instar larva's central nervous system (CNS). Expression in this pattern requires a cell type-specific neuronal enhancer/glial repressor region located 1000 bp from the transcriptional start site, and specific sequences within the promoter. We have used mutagenesis in vitro and P-element-mediated transformation to examine the role of the promoter, particularly its major CNS activator sequence (element I), in the generation of the wildtype expression pattern. Immunohistological analysis of these transgenic strains demonstrates that particular deletion mutations shift the site of transgene expression to a set of neurons which do not express Ddc at detectable levels in wild-type larvae. Transgene expression in these strains may be driven by a previously undetected activator sequence. Our data also suggest that glial expression may be driven by the same activator sequences that drive expression in the hypoderm.

Animals↗
PubMed1990

Completed suicide at age 50 and over.

The authors present data abstracted from medical examiners' investigative reports of 246 completed suicides of persons over the age of 50 years classified into four age groups. The sample population conformed to epidemiologic studies with regard to sex distribution. With increasing age, more suicide victims were widowed, and significantly fewer were single, separated, or divorced. Violent methods of suicide were more prevalent and alcohol use and psychiatric histories less common with aging. Physical illness and loss became the most common definable precipitants to suicide, whereas job, financial, and family relationship problems became less frequent with increasing age. The indications for future research and intervention in primary care settings are discussed.

Aged↗
PubMed1989

Effect of phospholipids on the thermal stability of microsomal UDP-glucuronosyltransferase.

The GT2P isoform of microsomal UDP-glucuronosyltransferase from pig liver is a lipid-dependent enzyme. The data in the present work indicate that, in addition to regulation of activity, the thermal stability of the enzyme also is modulated by the acyl chain composition of phosphatidylcholines (PC) used to reconstitute the activity of pure enzyme. There was a reversible, temperature-dependent change in the state of the pure enzyme to an inactive form with onset at T greater than 38 degrees C, depending on the environment of the enzyme. The midpoint for the transition shifted from 39.8 degrees C for enzyme in a bilayer of distearoylphosphatidylcholine (DSPC) to 47.5 degrees C for enzyme in a bilayer of 1-stearoyl-2-oleoylphosphatidylcholine (SOPC). For all lipids, the transition from a catalytically active to an inactive form of the enzyme was associated with large compensating changes in H and S. Lipid-induced stabilization of the active form of UDP-glucuronosyltransferase at T greater than 37 degrees C was associated with decreases in delta H and delta S, but the decreases in delta S were larger, indicating that lipid-induced stabilization of the active form of the enzyme was entropic. The transition between the active and inactive forms of the enzyme was too rapid in either direction to measure in a standard spectrophotometer. In addition to reversible inactivation of the enzyme, there was a slower irreversible, temperature-dependent inactivation. The rate of this process depended on the acyl chains of the phosphocholines interacting with the enzyme. However, there was no obvious correlation between the structures of lipids that stabilized the different inactivation reactions.

Animals↗
PubMed1989

Regulation of UDP-glucuronosyltransferase by lipid-protein interactions. Comparison of the thermotropic properties of pure reconstituted enzyme with microsomal enzyme.

The temperature dependence of two kinetic properties of the GT2P isoform of microsomal UDP-glucuronosyltransferase was studied for enzyme in intact microsomes and for pure enzyme reconstituted into different types of lipid bilayers. The properties studied were the non-Michaelis-Menten kinetics of the enzyme and activity at Vmax(app). For enzyme in intact microsomes, the pattern of non-Michaelis-Menten kinetics was seen at all temperatures in the range tested (23 to 48 degrees C), and the slopes of the Hill plots of the data were constant across this range of temperatures. Although non-Michaelis-Menten kinetics were present for pure enzyme in bilayers of 1,2-dimyristoylphosphatidylcholine or 1,2-dipalmitoylphosphatidylcholine only in the gel phase (Hockman, Y., Kelley, M., and Zakim, D. (1983) J. Biol. Chem. 258, 6509-6519), it was not possible to reconstitute this pattern of kinetics for enzyme at T greater than 40 degrees C. For example, GT2P displayed Michaelis-Menten kinetics in bilayers of 1,2-distearoylphosphatidylcholine at 44 degrees C. For enzyme in microsomes, activities at Vmax(app) increased with increasing temperature in the range 23 to 48 degrees C, with a discontinuity in the slope of the Arrhenius plot at 34 degrees C. This thermotropic property also could not be reconstituted with pure GT2P. Instead, activities at Vmax(app) for GT2P reconstituted in 1,2-dioleoylphosphatidylcholine, 1,2-distearoylphosphatidylcholine, or 1,2-stearoyl oleoylphosphatidylcholine increased in the range 23 to 37 degrees C, but then decreased at T greater than 37 degrees C. The fall in activity at T greater than 37 degrees C was reversible, indicating that GT2P undergoes a reversible change at 37 degrees C to a less active form of the enzyme. The differences between pure, reconstituted GT2P and microsomal GT2P indicate that the thermotropic properties of the microsomal enzyme are not properties of the enzyme per se but depend on interactions between it and other components in the microsome. The data suggest, therefore, that the properties of GT2P in microsomes results in part from an organization of components in the microsomal membrane.

Animals↗
PubMed1987

Porphyrin-membrane interactions: binding or partition?

Porphyrins are photodynamic drugs employed in an experimental tumor-treatment modality in which cell membranes are one of the primary drug-action sites. To gain insight into the nature of the interaction of these drugs with those primary sites we have studied the affinity of porphyrins to the lipid moieties of biological membranes, at the molecular level. The association of porphyrins to large unilamellar liposomes, modeling the lipid regions of biological membranes was studied (at equilibrium) for deuteroporphyrin IX and protoporphyrin IX, at neutral pH and 37 degrees C, taking into account porphyrin aggregation. Two thermodynamic approaches were investigated: (i) Simple partition equilibria between the external aqueous phase and the lipid bilayer, for drug monomers and dimers. (ii) Binding equilibria of drug monomers and dimers to the lipid bilayer. Using two types of experimental design and processing the data according to the expectations of both approaches, three different models for the binding (differing in the participation assigned to the dimer) were considered. Our major findings are: (a) The data clearly do not fit with the expectations for simple partition equilibria, nor with binding models assuming direct participation of the dimers. (b) The data fit well with a binding process, in which the membrane binds the porphyrin monomers only, with the dimers participating indirectly through the aqueous dimerization equilibrium. (c) At 37 degrees C and neutral pH, for liposomes composed of phosphatidylcholine/cholesterol at molar ratios of 3:2, we found for both investigated species a binding constant of 2.3 x 10(4) M-1. (d) For each species the binding constant is independent of the initial and final states of drug aggregation in the aqueous phase.

Chemical Phenomena↗
PubMed1986

Calcification of intervertebral disks in I-cell disease.

I-cell disease (ICD) is associated with skeletal dysplasia. However, changes of the intervertebral disks had not been previously reported. We describe a child with clinical and laboratory evidence of ICD who had multiple intervertebral disk calcifications. Since an excessive degeneration of the cartilage had previously been found in ICD, we propose that this process may give rise to calcification of the intervertebral disks in patients with ICD.

Calcinosis↗
PubMed1985

Deuteroporphyrin-albumin binding equilibrium. The effects of porphyrin self-aggregation studied for the human and the bovine proteins.

The binding equilibrium of deuteroporphyrin IX to human serum albumin and to bovine serum albumin was studied, by monitoring protein-induced changes in the porphyrin fluorescence and taking into consideration the self-aggregation of the porphyrin. To have control over the latter, the range of porphyrin concentrations was chosen to maker dimers (non-covalent) the dominant aggregate. Each protein was found to have one high-affinity site for deuteroporphyrin IX monomers, the magnitudes of the equilibrium binding constants (25 degrees C, neutral pH, phosphate-buffered saline) being 4.5 (+/- 1.5) X 10(7) M-1 and 1.7 (+/- 0.2) X 10(6) M-1 for human serum albumin and for bovine serum albumin respectively. Deuteroporphyrin IX dimers were found to bind directly to the protein, each protein binding one dimer, with high affinity. Two models are proposed for the protein-binding of porphyrin monomers and dimers in a porphyrin system having both species: a competitive model, where each protein molecule has only one binding site, which can be occupied by either a monomer or a dimer; a non-competitive model, where each protein molecule has two binding sites, one for monomers and one for dimers. On testing the fit of the data to the models, an argument can be made to favour the non-competitive model, the equilibrium binding constants of the dimers, for the non-competitive model (25 degrees C, neutral pH, phosphate-buffered saline), being: 8.0 (+/- 1.8) X 10(8) M-1 and 1.2 (+/- 0.6) X 10(7) M-1 for human serum albumin and bovine serum albumin respectively.

Animals↗
PubMed1985

Increasing frequency of penicillin-resistant pneumococci: epidemiological aspects and case-control study.

At the Hadassah University Hospital, Mt. Scopus, Jerusalem, the frequency of patients with relatively penicillin-resistant pneumococci (RPRP) isolates has increased from 0.9 to 10.8% during the years 1979-82. Infants and children were particularly involved. Significantly more RPRP isolates were found in those less than 14 years old than in those who were older (P less than 0.005). The determination of susceptibility or relative resistance to penicillin was based on the disk sensitivity method, which remained unchanged throughout the study period. The minimal inhibitory concentration (MIC) to penicillin G was also determined for 20 RPRP isolates and was found to be in the range of relative resistance to penicillin (0.25 to 0.50 micrograms/ml) in all 20 isolates. A case-control study of 16 index patients examined antibiotic usage during the 60 days preceding pneumococcal isolation. Total antibiotic usage was high in both groups (18.8 vs. 8.8 days, P = 0.2); beta-lactam antibiotic usage was significantly higher in the RPRP group than in the control group (13.3 vs. 4.2 days, 0.01 less than P less than 0.02). General prescribing practices, even in nonisolated areas where there is no need for public health programs to dispense prophylactic antibiotics, may produce sufficiently high antibiotic exposures to aid the emergence of RPRP strains.

Age Factors↗
PubMed1984

Thermodynamics of porphyrin dimerization in aqueous solutions.

The dimerization equilibrium of deuteroporphyrin IX and of mesoporphyrin IX in aqueous solutions were studied by fluorimetric techniques over the 0.01-1 microM concentration range, where dimerization is the dominant aggregation process. Deuteroporphyrin IX was studied at several temperatures over the range 22-37 degrees C, and mesoporphyrin at 25 and 37 degrees C. The magnitudes determined for the dimerization equilibrium constants (25 degrees C, neutral pH, phosphate-buffered saline) are 2.3 X 10(6)M-1 and 5.4 X 10(6)M-1 for the deutero and meso derivatives respectively. The meso, deutero and haemato species tested show a similar temperature effect, namely dimerization decreasing with increasing temperature, indicating the involvement of a negative enthalpy change. Van't Hoff isochore of the dimerization constants determined for deuteroporphyrin IX was linear within the temperature range of 22-37 degrees C, allowing the calculation of the thermodynamic parameters. For deuteroporphyrin dimerization, those were found to be delta G0 = -36. 4kJ X mol-1; delta H0 = -46. 0kJ X mol-1 and delta S0 = -32.2J X K-1 X mol-1 (at neutral pH, 25 degrees C, phosphate-buffered saline), showing the process to be enthalpy-driven. Similar trends have been found for porphyrin species other than those studied here. Our data fit with a hypothesis giving a major role to the solvent in driving porphyrins to aggregate in aqueous solution. The magnitudes and directions of the energetic changes fit better with the expectation of the ' solvophobic force' theory predicting enthalpy-driven association, than with the classic hydrophobic bonding, predicting the association to be entropy-driven.

Deuteroporphyrins↗
PubMed1983

Transport theory for growing cell populations.

The partial differential equation that describes the growth of cell populations whose maturation rate is random is developed. The equation resembles that used in classical transport theory but mitotic boundary conditions and the restriction of the maturation rate to non-negative values brings out new features and new problems. This is a generalization of a previously published formulation in which cells could make transitions at random between only two maturation velocities: a characteristic velocity and zero. Growth rates, cycle time distributions and pulsed labeled mitotic curves are calculated for a simple choice of parameters. A numerical algorithm that is suited to the solution of the transport equation is given.

Biological Transport↗
PubMed1983

[Effects of subinhibitory concentrations of antibiotics on the virulence of group A hemolytic Streptococci].

We have investigated the influence of subinhibitory concentrations of chloramphenicol, erythromycin, penicillin G and gentamicin on the phagocytosis and the virulence in the mouse of strains of group A beta-haemolytic streptococci. In most cases, an increase of the phagocytosis and a decrease of the virulence were shown. The maximum effect have been observed in concentration ranging from 1/2 to 1/8 of the respective MIC. In one strain, the virulence was enhanced in the presence of 1/2 and 1/4 MIC of chloramphenicol and 1/2 of erythromycin, in spite of the fact that the phagocytosis was increased in these concentrations of drugs. The importance of hyaluronic acid as virulence factor has been investigated and discussed.

Anti-Bacterial Agents↗