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R S Cohen

Publications and source records attributed to R S Cohen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Projections of ventromedial hypothalamic neurons to the midbrain central gray: an ultrastructural study.

Ventromedial hypothalamic projections to the midbrain central gray may be involved in the mediation of female reproductive behavior. In order to demonstrate and examine projections of the ventromedial nucleus in the midbrain central gray, in the rat, electrolytic lesions were placed in the ventromedial nucleus and the midbrain central gray was examined for ultrastructural signs of degeneration at various intervals, i.e. 27.5 h and two, four, six and eight days following the lesions. The fine structure of the midbrain central gray of unlesioned animals was also examined to characterize its normal morphology and to establish a baseline with which to compare the effects of the lesion. In unlesioned animals, the neuropil of midbrain central gray contained several synaptic types, with axodendritic synapses appearing to be the most predominant. Dendrites contained well-preserved microtubules. Synaptic endings contained many clear, round vesicles and some contained dense-cored vesicles as well. Neuropil synapses were both asymmetric and symmetric. Cell bodies were characterized by light cytoplasm and had asymmetric and symmetric synapses on their surface. Following electrolytic lesions in the ventromedial nucleus, various types of degenerative patterns were seen in the midbrain central gray, including electron-dense, flocculent, watery, and pinocytotic degeneration. Specific characteristics of degeneration included shrunken, dense axons and endings, clumped synaptic vesicles, abnormally large, dark mitochondria, membranous sacs of various sizes, swollen endings with reduced numbers of synaptic vesicles, and endings and processes containing large numbers of coated vesicles. Some of these signs were already evident at 27.5 h following the lesion. In addition, degenerating postsynaptic processes and cell bodies were seen in the midbrain central gray. At 27.5 h survival time, degenerating dendritic processes often appeared swollen, devoid of microtubules, and contained enlarged mitochondria. At longer survival times neuronal degeneration was observed in the midbrain central gray, characterized by electron-dense cell bodies and pycnotic nuclei. Both degenerating pre- and postsynaptic elements appeared to be engulfed by glial processes. Control lesions in non-hypothalamic regions which project to the midbrain central gray, i.e. nucleus gigantocellularis and pontine reticular formation and in a non-projecting region, i.e. parietal cortex, were performed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Transneuronal degeneration in the midbrain central gray following chemical lesions in the ventromedial nucleus: a qualitative and quantitative analysis.

In the preceding experiments with electrolytic lesions of the ventromedial nucleus of the hypothalamus, we showed pre- and postsynaptic degeneration in the midbrain central gray of the rat. The postsynaptic degeneration seen may indicate a transneuronal effect of the ventromedial nucleus on the midbrain central gray. Electrolytic lesions, however, destroy afferent endings and fibers in passage, so that the postsynaptic degeneration seen in the midbrain central gray may be due to retrograde degeneration of midbrain central gray afferents to the ventromedial nucleus or due to degeneration of fibers in passage. In order to distinguish among these possibilities, chemical, i.e. kainic acid and N-methyl aspartate, lesions were made in the ventromedial nucleus and the ultrastructure of the midbrain central gray and cerebral cortex was examined at various intervals following the lesions. Both of these excitotoxins have been shown to destroy neurons, sparing afferent terminals and fibers in passage. Animals receiving kainic acid lesions in the right ventromedial nucleus were allowed to survive for one week, and animals receiving N-methyl aspartate lesions in the right ventromedial nucleus were permitted to survive for four, eight, and 20 days. Midbrain central gray tissue of unlesioned animals served as a control for both kainic acid and N-methyl aspartate lesions. In addition, other control animals received injections of the same amount of N-methyl aspartate in the right parietal cortex and were permitted to survive for four and eight days. For each of the above injection and survival conditions, the left cortex and subdivisions of the midbrain central gray were removed and processed for electron microscopy. Animals receiving ventromedial hypothalamic lesions with both kainic acid and N-methyl aspartate showed signs of pre- and postsynaptic degeneration. A quantitative analysis (General Linear Model Procedure) of degeneration was performed on the cortex and midbrain central gray of animals receiving N-methyl aspartate lesions in the ventromedial nucleus and cortex, and several parameters were measured. Animals receiving ventromedial hypothalamic lesions and surviving for eight and 20 days show significantly higher ratios of degenerating presynaptic elements to total presynaptic elements, degenerating postsynaptic elements to total postsynaptic elements, and degenerating total elements to total elements, in the midbrain central gray than in the cortex. Furthermore, the ratio of degenerating postsynaptic elements to total postsynaptic elements is larger than the other ratios.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Periodic interactions of heat shock transcriptional elements.

The activity of some genes is known to be a periodic function of the amount of DNA between the binding sites of its regulatory proteins. The period observed is close to 10.5 base pairs (bp), that is, one turn of the B form of the DNA helix. Such periodicity is also seen in the cooperative binding of phage lambda and lac repressors. These periodic phenomena have been attributed to a requirement for a unique rotational alignment in forming essential contacts between the bound proteins. Here we report a strong periodic dependence of the transcription of a cloned Drosophila melanogaster heat shock gene on the amount of DNA inserted between its two heat shock consensus elements. In addition, we find a similar periodicity for insertions just 3' to the proximal heat shock element. Consistent with the torsional flexibility of DNA, these periodic effects are seen for short insertions, up to approximately 80 bp, but not for much longer ones. We conclude that maximal transcription requires rotationally unique contacts between proteins bound to the two heat shock elements and also requires correct alignment of additional sites of DNA-protein binding downstream of the proximal element.

Animals↗
PubMed1988

Estrogen-induced alterations in synaptic morphology in the midbrain central gray.

Axons of ventromedial hypothalamic (VMH) neurons have been previously shown to terminate in the midbrain central gray (MCG) (Chung et al. 1984, 1986). Since VMH synapses in this region may be involved in the mediation of estrogen-induced lordosis behavior, we examined the effect of estrogen on the morphology of synapses in the MCG. Ovariectomized adult female rats were given daily subcutaneous injections of estradiol benzoate (10 micrograms) or the vehicle control and after 20 days of injection, only the estrogen-treated rats showed the lordosis response. A quantitative analysis of MCG tissue from these animals demonstrates morphological changes in various synaptic parameters with estrogen treatment including: 1) an increase in the mean number of dense-cored vesicles and an increase in the number of terminals containing dense-cored vesicles, 2) an increase in the length of postsynaptic densities (PSDs), 3) an increase in the number of PSDs showing perforations, 4) an increase in the number of synapses, and 5) an increase in the number of synapses with positive synaptic curvature. No alterations in the number of subjunctional bodies were observed. The dense-cored vesicles may contain an estrogen-induced trophic factor which may function in maintaining the integrity of postsynaptic processes and cells in the MCG with which VMN endings contact (Chung et al. submitted) and/or which induces morphological changes in postsynaptic structures which facilitate the effects of estrogen on lordosis behavior.

Animals↗
PubMed1988

Effect of booster blood transfusions on oxygen utilization in infants with bronchopulmonary dysplasia.

To assess the impact of booster transfusions on oxygen utilization in infants with bronchopulmonary dysplasia, we noninvasively measured oxygen consumption (VO2) and the variables of systemic oxygen transport (SOT) before and 24 hours after transfusion therapy in 10 oxygen-dependent infants with bronchopulmonary dysplasia. The infants had been born with a mean gestational age of 27.6 weeks and a mean birth weight of 0.88 kg. Study weight averaged 1.24 +/- 0.35 kg, and study age averaged 5.5 +/- 2.4 weeks. Requirements for fractional concentration of inspired oxygen averaged 0.41 +/- 0.15 to maintain an oxygen saturation of 0.93 +/- 0.02. The VO2 was measured by means of a commercially available analyzer through a flow-through circuit and pump connected to a hood or in line with the ventilator. Cardiac output was calculated by means of pulsed Doppler ultrasonography. Oxygen saturation was measured by means of transcutaneous pulse oximetry. The coefficient of oxygen utilization was calculated as VO2/SOT. Transfusion consisted of packed erythrocytes (10 ml/kg). Oxygen utilization fell in all subjects after transfusion (p less than 0.01), but it fell more substantially in subjects with higher coefficients of oxygen utilization (r = -0.80, p less than 0.01), suggesting a physiologic benefit in selected patients, particularly those with higher levels of oxygen utilization. There was also a significant increase in overall systemic oxygen transport (p less than 0.01) and decrease in VO2 (p less than 0.02). Hemoglobin levels alone did not correlate with overall systemic oxygen transport, VO2, or level of oxygen use before transfusion, and thus did not predict which subjects would have a physiologic benefit from transfusion as reflected by falls in oxygen utilization.

Blood Transfusion↗
PubMed1987

Inositol trisphosphate-induced calcium release in brain microsomes.

The effects of different ionic media on Ca2+ uptake and release in isolated brain microsomes were investigated. KCl (100 mM) provided the best medium for Ca2+ uptake in the presence of ATP. The effect of myo-inositol 1,4,5-trisphosphate (IP3) on Ca2+ release was examined and was maximum at 0.2 microM. IP3-induced Ca2+ release was dependent on extramicrosomal free Ca2+ concentration with maximal release at 5.0 microM free Ca2+. Replacement of KCl by sucrose or NaCl did not show any response to IP3. Electron microscopy showed that the microsomal fraction consisted of characteristic endoplasmic reticulum-derived vesicular profiles and were free of mitochondria or plasma membrane contamination. Our results support the concept that the endoplasmic reticulum is the target for IP-3 induced mobilization of Ca2+ in the cell.

Adenosine Triphosphate↗
PubMed1987

Lipoprotein metabolism in a rat model of diet-induced adiposity.

Obesity in humans is associated with decreased plasma levels of high density lipoprotein (HDL), but the mechanisms effecting this relationship have not been established. Four treatment groups were used to develop a range of moderate adiposity: rat pups were raised in litters of 4 or 14 and fed from weaning diets of 6 or 24% fat (wt/wt) for 15-17 wk. Lipoproteins from plasma and from a recirculating in situ liver perfusion system were then separated and analyzed, lipoprotein lipase (LPL) activity was assayed in samples of adipose tissue and skeletal muscle and body composition and cholesterol concentrations of various tissues were determined. There was little effect of the diet or litter size treatments on plasma lipids or lipoprotein profiles. Compared to the marked changes in lipid and lipoprotein metabolism that have been observed in severely obese animal models, there was generally little effect of the treatments used to produce this model of moderate diet-induced adiposity. Adiposity was unrelated to plasma total cholesterol and triglycerides. While fatness was positively, although weakly, correlated with plasma levels of several HDL components, including HDL cholesterol, there were no consistent treatment effects on these measures. Plasma HDL levels and adiposity were unrelated to hepatic HDL production or tissue LPL activities. A review of the literature suggests that differences in plasma HDL responses to adiposity in humans and in experimental animals may be due to inherent species differences in lipoprotein metabolism.

Adipose Tissue↗
PubMed1987

Biochemical and immunocytochemical characterization and distribution of phosphorylated and nonphosphorylated subunits of neurofilaments in squid giant axon and stellate ganglion.

Monoclonal antibodies to squid neurofilament (aNFP) and intermediate filament (aIFA) proteins were used as probes for the biochemical and immunocytochemical analyses of neurofilament structure and distribution in the squid giant axon and stellate ganglion. On Western blots the aNFP antibody stained exclusively the 220 kDa and high-molecular-weight (HMW) components of neurofilaments in the giant axon, whereas the aIFA antibody primarily labeled the 60 kDa protein in the giant axon and the 60 and 65 kDa proteins in the stellate ganglion. Dephosphorylation of axoplasmic proteins by alkaline phosphatase resulted in a decrease in the molecular weights of both the 220 kDa and HMW neurofilament proteins and a concomitant loss of reactivity with the aNFP antibody on Western blots. This indicated that the aNFP antibody is specific for a phosphorylated epitope in the neurofilament. Increased dephosphorylation of the 220 kDa protein led to an enhanced immunostaining of the resultant 190 kDa polypeptide by the aIFA antibody, suggesting that the phosphorylated epitope may mask the conserved epitope recognized by aIFA. Light and electron microscopic immunocytochemical studies show intense labeling by the aNFP antibody in the giant axon. In contrast, the aIFA antibody labeled the glial cells around the giant axon intensely, while labeling of the giant axon itself was considerably less than that with the aNFP antibody. Since the 60 kDa protein in axoplasm is intensely stained by the aIFA antibody on Western blots, the relatively low amounts of labeling seen on semithin and thin sections of the giant axon by this antibody may be due to the masking of the 60 kDa protein by in situ fixed axoplasmic proteins. However, the aIFA antibody intensely labeled glial cells within the stellate ganglion and "islands" of filaments and nuclear membranes within ganglion cells. No reactivity for either antibody was seen in synapses. The aNFP antibody specifically labeled "beadlike" portions and cross-bridges on the axonal neurofilaments, suggesting that these components consist of the 220 kDa and HMW proteins. In contrast, the aIFA antibody labeled relatively smooth filaments in ganglion and glial cells. These data suggest that the 65 kDa protein represents the squid glial filament protein and that the 60 kDa protein found in axoplasm represents the low-molecular-weight subunit in the axonal neurofilament. The latter appears to be formed and/or organized in "islands" of filaments within ganglion cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Increased immunoreactive erythropoietin in cord plasma and neonatal bilirubin production in normal term infants after labor.

The purpose of this investigation was to compare immunoreactive erythropoietin levels in umbilical cord plasma and neonatal bilirubin production in infants born of normal women who delivered with or without labor. Two groups of term (38 to 42 weeks) singleton pregnancies were compared: 1) those delivered by repeat elective cesarean section without prior labor (N = 17), and 2) those delivered vaginally or by cesarean section after labor (N = 24). None of the infants was asphyxiated, and there was no difference in Apgar scores between the no-labor and labor groups. The cord plasma erythropoietin levels were lower in the infants of women who had repeat elective cesarean section without labor than in those whose mothers had labor before delivery (Wilcoxon rank sum test, P less than .025). The median erythropoietin for the no-labor group was 22.9 mU/mL compared with 38.8 mU/mL for the labor group. The pulmonary excretion rate of carbon monoxide (VeCO), an index of bilirubin production, for the no-labor group was 14.3 +/- 6.2 SD microL/kg per hour compared with 18.0 +/- 4.9 SD microL/kg per hour for the labor group (P less than .05). The hemoglobin concentration for the no-labor group was 16.0 +/- 1.5 SD g/dL compared with 17.7 +/- 2.2 SD g/dL for the labor group (P less than .05). The VeCO correlated with the hemoglobin concentration (N = 32, r = 0.37, P less than .05). The results of the present study suggest that labor is normally associated with increases in the cord plasma erythropoietin level.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗
PubMed1985

Immunocytochemical localization of actin in dendritic spines of the cerebral cortex using colloidal gold as a probe.

Immunocytochemical localization of actin in rat cerebral cortex embedded in the resin LR White was performed using 5 nm colloidal gold as a probe. Antigenicity is maintained throughout the embedding procedure and the low electron opacity of LR White permits fine filamentous structures to be visualized. Control experiments included incubating the sections with normal goat serum or mouse IgG instead of the primary antibody, preadsorbing the antibody with actin from bovine muscle or liver acetone powder, and heat treating the primary antibody. Immunoreactive actin was identified primarily in dendritic spines, particularly in the postsynaptic density (PSD), the subsynaptic web, and the spine apparatus and endothelial and smooth muscle cells of blood vessels. Within dendritic spines, actin which is labeled in the PSD is in continuity with the filaments of the subsynaptic web. These filaments, in turn, are in continuity with the spine apparatus and/or the spine membranes adjacent to the PSD. The PSD may therefore function like other submembranous filamentous arrays which communicate events occurring at the membrane, in this case, the postsynaptic membrane, to the underlying cytoskeletal network, i.e., the subsynaptic web of the spine. It is also suggested that the actin present in the spine may play a role in changes in spine shape and synaptic curvature. Some actin was also seen in the presynaptic process in association with synaptic vesicles, the filamentous network that is contiguous with the synaptic vesicle membrane, and the presynaptic dense projections. Actin may be involved in dynamic processes in the presynaptic ending which include vesicle translocation.

Actins↗
PubMed1985

Freeze-fracture analysis of synaptogenesis in glomeruli of mouse olfactory bulb.

The relationship between intramembranous particle (IMP) aggregates appearing on the extracellular leaflet (E-face) of the postsynaptic membrane and postsynaptic densities was examined by electron microscopy during mouse olfactory bulb development. During prenatal development the IMP aggregates first increased in size and then decreased in size to the adult level, while the length of the postsynaptic densities tended to increase to a plateau. Concomitant with the size change, the shape of the IMP aggregates appeared to change during development from small, round clusters to large, anastomotic aggregations. Some of the IMP aggregates appeared to have a particle-free area in their centre. As development proceeded, the overall IMP density increased. The density of particles measuring 7-11 nm remained unchanged throughout prenatal life and decreased in the adult. These particles may be involved in stabilization of initial contacts and maintenance of mature synapses, rather than representing receptors or ion channels which would be expected to increase during development. The density of particles smaller than 7 nm increased prenatally, decreased at birth, then increased in the adult. These particles may represent two or more different macromolecules, one important in synaptogenesis, the other important in adult synapses.

Aging↗
PubMed1985

Separate regulatory elements for the heat-inducible and ovarian expression of the Drosophila hsp26 gene.

We have constructed and transformed into the D. melanogaster germ line a series of hsp26 deletion variants. We show that the region -728 to +14 contains all of the cis-acting sequences necessary for the developmental and heat-inducible transcription of hsp26. Sequences upstream of -341 are not required for heat-inducible expression but are required for ovarian expression. Conversely, sequences between -351 and -53 are unnecessary for ovarian expression but are needed for maximal heat-inducible expression. We conclude that most, or all, of the cis-acting regulatory sequences required for hsp26 gene expression during oogenesis are physically separable from those required for heat-inducible expression. These results suggest that different trans-acting factors bind at different regulatory sites in the 5'-flanking region of the gene, thus activating its transcription.

Animals↗
PubMed1985

Use of sodium nitroprusside in neonates: efficacy and safety.

Sodium nitroprusside was administered to 58 neonates, including 11 with severe respiratory distress syndrome, 15 with persistent pulmonary hypertension of the newborn, 28 with clinical shock, three with systemic hypertension, and two with pulmonary hypoplasia, all refractory to conventional intensive therapy. Nitroprusside was infused at 0.2 to 6.0 micrograms/kg/min for periods of 10 minutes to 126 hours. Infants with severe respiratory distress syndrome had increased PaO2 and decreased PaCO2 or peak inspiratory pressure, and nearly all (82%) survived. Infants with persistent pulmonary hypertension of the newborn had variable responses; improvement did not correlate with survival, but survival (47%) was identical to that in an earlier series of infants given tolazoline. Infants in shock had improved perfusion, urine output, and serum bicarbonate levels, and these responses were significantly related to survival. Hypertension was controlled in all three hypertensive infants. Adverse effects were very uncommon. Toxic effects were not observed. Sodium nitroprusside is effective and can be used safely in circulatory disorders in the neonate.

Bicarbonates↗
PubMed1985

Bilirubin production after supplemental oral vitamin E therapy in preterm infants.

The purpose of this investigation was to determine the influence of early vitamin E supplementation on the rate of heme catabolism (bilirubin production) in healthy preterm infants. Bilirubin production was estimated from the concentration of carbon monoxide in "end-tidal" gas. Serum vitamin E, hemoglobin, and bilirubin levels were determined by standard techniques. Thirty infants received supplementation with vitamin E or placebo in a double-blind, randomized fashion. Infants were studied on day 1 of life prior to therapy, and on days 3 and 7 postnatally. Results showed that in both placebo-supplemented and vitamin E-supplemented groups, vitamin E levels were significantly higher on days 3 and 7 compared with day 1. Bilirubin production was not significantly different on day 3 compared with day 1 in either group, but was significantly lower in both groups by day 7 compared with day 1. There were no significant differences in hemoglobin and serum bilirubin levels between the two groups at any point in time. In conclusion, although vitamin E supplementation significantly raises vitamin E levels, placebo-supplemented premature infants also achieve vitamin E sufficiency and a decrease in bilirubin production by day 7 of age.

Bilirubin↗