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R Chase

Publications and source records attributed to R Chase.

At least 19 recordsLinked to original sources

Effect of the Gulf War on infant and child mortality in Iraq.

BACKGROUND: Increased malnutrition and morbidity among Iraqi children after the onset of the Persian Gulf war have been reported by several fact-finding missions. The magnitude of the effect of the war and the economic embargo on child mortality remains uncertain, however. METHODS: We conducted a survey of 271 clusters of 25 to 30 households each, chosen as a representative sample of the Iraqi population. The households were selected and the interviews conducted by an international team of public health professionals independent of Iraqi authorities. In each household all women 15 to 49 years of age were interviewed, and the dates of birth and death of all children born on or after January 1, 1985, were recorded. RESULTS: The study population included 16,076 children, 768 of whom died during the period surveyed (January 1, 1985, to August 31, 1991). The age-adjusted relative mortality for the period after the war began, as compared with the period before the war, was 3.2 (95 percent confidence interval, 2.8 to 3.7). No material change in the relative risk was observed after adjustment for region of residence, maternal education, and maternal age. The increase in mortality after the onset of the war was higher among children 1 to less than 12 months old (relative risk, 4.1; 95 percent confidence interval, 3.3 to 5.2) and among those 12 to less than 60 months old (relative risk, 3.8; 95 percent confidence interval, 2.6 to 5.4) than among those less than 1 month old (relative risk, 1.8; 95 percent confidence interval, 1.4 to 2.4). The association between the war and mortality was stronger in northern Iraq (relative risk, 5.3) and southern Iraq (relative risk, 3.4) than in the central areas (relative risk, 1.9) or in Baghdad (relative risk, 1.7). CONCLUSIONS: These results provide strong evidence that the Gulf war and trade sanctions caused a threefold increase in mortality among Iraqi children under five years of age. We estimate that more than 46,900 children died between January and August 1991.

Child, Preschool

Synaptic innervation of the giant cerebral neuron in sated and hungry snails.

The giant cerebral neuron (GCN) is a serotoninergic cell that facilitates feeding behaviour in gastropod molluscs. We have examined the morphology of its cerebral arborizations after labelling them by intracellular injection of hexamminecobalt. Observations in the light microscope reveal extensive arborizations, with similar overall distributions, in the terrestrial snails Achatina fulica and Rumina decollata. All the major peripheral nerves terminate within the zone covered by the GCN arbor. In a sample of 370 synapses in which the GCN participated, the GCN was identified as the postsynaptic element in every case, thereby establishing the dendritic nature of the cerebral arborizations. A total of approximately 1,000 synapses contacts the GCN, with no evident regional differences in innervation density. The synaptic membrane of the presynaptic profile is characterized by an agglomeration of small clear vesicles and small dense vesicles. At nonsynaptic membranes there are agglomerations of larger dense and dense core vesicles, suggestive of nonsynaptic release. The dendrites of the GCN also contain vesicles. Starvation for five days (Rumina decollata) caused a significant increase in the proportion of curved synapses relative to flat synapses. This might be a plastic change allowing for a greater efficiency of transmission between sensory afferents and the GCN.

Animals

Stability of dendritic mass during aestivation.

In hot and dry weather, terrestrial snails withdraw into their shells and remain inactive for long periods of time. This phenomenon, known as aestivation, is the basis for our investigation of the effects of behavioral inactivity on neuronal structure. Several recent studies have shown that the level of afferent electrical activity is an important modifier of structure, even in adult animals. During aestivation, sensory stimulation (and therefore presumably afferent activity) is greatly reduced. We have tested the hypothesis that long-term behavioral inactivity causes a regression of dendrites. Two identified neurons of Achatina fulica were selected for study, the giant cerebral neuron (GCN) and RPall. The cells were viewed on 10-micron-thick sections after intracellular injection of hexamminecobalt chloride. They were reconstructed by using a video camera attached to a light microscope and a digitizing board resident in a microcomputer. Snails in the aestivated group were completely inactive for 8 weeks beginning at age 23 weeks. A quantitative analysis showed that there were no significant differences in either cell, in either the total mass of material or its distribution, comparing cells from the Aestivated snails and cells from the Younger snails (age 23 weeks) and the Older snails (age 33 weeks). These results suggest limits to the modifiability of neuronal structure.

Animals

The interactions of courtship, feeding, and locomotion in the behavioral hierarchy of the snail Helix aspersa.

Starvation both increased the number of snails that exhibited feeding (i.e., increased feeding proclivity) and decreased the latencies of response to a food stimulus (i.e., increased food arousal). Feeding inhibited locomotion, although starvation itself had no effect. Sexual arousal (the intensity of courtship) increased locomotion, but only in the absence of a mating partner. Sexual proclivity (the likelihood of a snail to court with conspecifics) had no effect on locomotion. In general, proclivity and arousal had different effects on behavior. Food deprivation did not alter the preference of sexually aroused snails for sexual stimuli over food stimuli Both starved and fed courting pairs responded to a food stimulus only during periods of low sexual arousal, although when not sexually aroused, starved snails usually increased the amount of time they spent in contact with a food stimulus. These results suggest that courtship can suppress feeding and that the expression of feeding behavior is dependent upon the occurrence of low levels of sexual arousal (time sharing).

Animals

"Central arousal" and sexual responsiveness in the snail, Helix aspersa.

In molluscs, a "central arousal" system is thought to positively modulate both an animal's level of activity and its behavioral responsiveness. This hypothesis is examined in Helix aspersa by testing the relationships between activity, feeding, and sexual behavior. Activity, feeding, and mating exhibit parallel daily rhythms. Snails are most active, and eat and mate most frequently, during scotophase and the first 3 h of photophase. Handling and injections of serotonin (5 x 10(-7) m/kg body wt) increase general activity. Inducing activity during late photophase increases food consumption, but it does not induce sexual activity. Moreover, serotonin and handling have no effect on sexual arousal; treated snails show no increase in genital eversion stage and require the same length of courtship as controls. If snails are sexually deprived, increasing activity in late photophase does increase copulation frequency, but snails do not copulate more frequently than do unhandled snails tested during early photophase. These results suggest that while manipulations thought to increase central arousal do increase activity and responsiveness to food stimuli, they do not directly affect sexual proclivity or sexual arousal. Moreover, the relationship between feeding and sexual behavior differs between Helix and Aplysia. This difference between the two species may be related to the differences in their reproductive strategies.

Animals

Dissociation of sexual arousal and sexual proclivity in the garden snail, Helix aspersa.

Sexual arousal (intensity of courtship) and sexual proclivity (tendency to court) in Helix aspersa can be reliably measured using externally observable correlates. Snails with sexual proclivity are significantly more likely to turn toward an anesthetized conspecific after contacting it than are sexually unreceptive snails. Sexual arousal can be inferred from the stage of a snail's genital eversion, which appears only during courtship. The higher the stage of the eversion, the shorter the time required to complete introductory courtship behavior and the higher the rate of successful copulation, the fewer the number of breaks and pauses during courtship, and the longer the time a snail will spend in contact with an anesthetized conspecific. Sexual proclivity has no effect on feeding or locomotory behavior; however, sexual arousal inhibits feeding and increases locomotor activity. Snails that were allowed daily contact with conspecifics required less time to complete introductory courtship behavior relative to snails that were isolated from conspecifics for 1 week. This suggests that daily contact increases sexual arousal. A greater percentage of isolated snails exhibited courtship behavior than did snails which had experienced daily conspecific contact. This suggests that isolation increases sexual proclivity. These differences indicate that sexual arousal is not merely due to an increase in sexual proclivity.

Animals

Interganglionic dendrites constitute an output pathway from the procerebrum of the snail Achatina fulica.

The procerebrum is an olfactory processing region that occupies approximately one-third of the total brain area in pulmonate gastropod molluscs. It has many unusual features, including a development separate from the rest of the brain and the absence of axons belonging to its intrinsic neurons. We have investigated the input and output pathways of the procerebrum in the terrestrial snail Achatina fulica by using hexamminecobalt chloride as a selective label. Both the tentacle nerve and the cerebropedal connective nerve contribute to a fine neural plexus that is distributed throughout the neuropile region of the procerebrum. The fibers from the tentacle nerve are predominantly presynaptic, whereas those from the cerebropedal connective are predominantly postsynaptic. The postsynaptic fibers (dendrites) were traced to two groups of nerve cells (total number, 20-25) near the ventral surface of the ipsilateral pedal ganglion. No evidence was obtained for any other numerically significant output pathway from the procerebrum. Since locomotion is known to be controlled by the pedal ganglion, these results provide an anatomical substrate for the strong influence of olfaction on locomotor behavior in snails. The pathway is unusual in that the dendrites are interganglionic and can be as long as 5 mm.

Animals

Doctor mom.

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Child Day Care Centers

The development of transmission at an identified molluscan synapse. I. The emergence of synaptic plasticities.

1. A monosynaptic, chemical synapse exists between two identified neurons in the subesophageal ganglia of the pulmonate mollusc, Achatina fulica. The snail undergoes a direct development, i.e., there is no intervening metamorphic period. The presynaptic (V2) and postsynaptic (RPr1) cells are two of the largest neurons found in the ganglia. The development of transmission at this synapse was studied from the last one-third of embryonic life to adulthood. 2. Synaptic transmission was studied by eliciting an action potential in V2 and recording the resultant excitatory postsynaptic potential (EPSP) in RPr1. In a train of repetitive stimuli, the ratio of the mean amplitude of the second EPSP to that of the first EPSP (EPSP2/EPSP1) is always greater than 1, indicating that short-term facilitation is present at all developmental ages studied. Following the initial short-term facilitation, embryonic synapses undergo a profound synaptic depression. Postembryonically there is a progressive increase in the amount of frequency facilitation with age, suggesting that the synapse shows a developmental trend towards an increased capacity for transmitter release. 3. In contrast to the progressive growth of frequency facilitation, the amplitude of the first EPSP in a series of responses (EPSP1) is not significantly related to age. 4. When transmitter release is reduced to approximately 25% of normal levels by a low-Ca2+/high-Mg2+ saline, the synaptic depression that is observed in the younger synapses disappears and is replaced by an adult-like frequency facilitation. 5. The adult synapse displays a phenomenon similar to posttetanic potentiation, which we refer to as the "retention of frequency facilitation." If an initial train of 150 stimuli at 0.2 Hz is followed by a second, identical train after an interval of 1 h, the postsynaptic response is greater during the second train than during the first. This phenomenon only becomes apparent in the second month after hatching, indicating that this separate synaptic plasticity develops at a different rate than does frequency facilitation.

Animals

The development of transmission at an identified molluscan synapse. II. A quantal analysis of transmission.

1. A quantal analysis of transmission at the identified molluscan synapse, V2-RPr1, was performed during development. The study was intended to determine the pre- and postsynaptic contributions to the marked changes in transmitter release described in the previous report. 2. The success of the quantal analysis was predicated on overcoming the problems associated with extending the quantal analysis technique to central synapses. This involved adopting the following strategies: 1) using a low-noise recording system coupled with electrical filtering; 2) establishing objective criteria for failures recognition; and 3) using three methods to determine the quantal content: amplitude histograms, failures analysis, and the coefficient of variation. 3. The correlation of the results obtained from an analysis of amplitude histograms and from failures analysis were highly significant (P less than 0.01) at all times studied. A similar significant correlation was observed between the failures method and the coefficient of variation methods. 4. The amplitude of the quantal unit declined progressively during development (range: 131-25 microV), in parallel with the decrease in the postsynaptic input resistance (range: 103-5 M omega). 5. At both frequencies of stimulation (0.02 and 0.2 Hz), there is an approximately 20-fold increase in quantal content over the period of the study. Frequency facilitation at the synapse is due to an increase in quantal content. 6. Possible structural correlates for the developmental increase in quantal content were discussed.

Aging

Evidence for differential DNA endoreplication during the development of a molluscan brain.

The DNA content of neurons in the cerebral ganglion of Achatina fulica was determined by the two-wavelength method of microspectrophotometry using Feulgen-stained sections. DNA measurements of mouse hepatocytes were used as a control of the methods. All sampled neurons with a nuclear diameter greater than 7 microns were polyploid. The shape of the frequency histogram of DNA contents is not compatible with an interpretation that assumes one or more simple duplications of the genome. It is suggested, instead, that the results are due to either the underreplication of some DNA sequences or the selective amplification of genes. Additional experiments using [3H]-thymidine autoradiography showed that the incidence of neuronal DNA synthesis is highest during the period of the animal's greatest growth and then declines rapidly near the onset of sexual maturity. The mesocerebrum incorporated greater amounts of [3H]-thymidine than the rest of the brain, whereas the procerebrum remained diploid throughout the course of the study.

Animals

Hepatitis B virus deoxyribonucleic acid in serum during hepatitis B e antigen clearance in corticosteroid-treated severe chronic active hepatitis B.

The relationship between hepatitis B virus deoxyribonucleic acid in serum and histologic activity was determined in 11 patients with corticosteroid-treated severe chronic active hepatitis B who underwent clearance of hepatitis B e antigen. All patients cleared hepatitis B virus deoxyribonucleic acid from the serum, and clearance preceded the loss of hepatitis B e antigen by 9-49 mo (mean 24 +/- 4 mo). Seropositivity for hepatitis B virus deoxyribonucleic acid was always associated with histologic features of chronic active hepatitis. Resolution of histologic activity followed the loss of hepatitis B virus deoxyribonucleic acid from the serum and it preceded clearance of hepatitis B e antigen in all patients. A transient elevation of serum aspartate aminotransferase activity occurred in 5 patients at the time that absence of hepatitis B virus deoxyribonucleic acid in serum was first demonstrated, and it was followed by resolution of histologic activity. The serum level of hepatitis B virus deoxyribonucleic acid slowly decreased or remained unchanged in all but 1 patient during long-term corticosteroid therapy. We conclude that hepatitis B virus deoxyribonucleic acid in serum is associated with histologic activity in corticosteroid-treated patients with severe chronic active hepatitis B. Disappearance of hepatitis B virus deoxyribonucleic acid from the serum precedes the loss of histologic activity and clearance of hepatitis B e antigen. Serum hepatitis B virus deoxyribonucleic acid levels usually do not increase during long-term corticosteroid therapy.

Adrenal Cortex Hormones

Autoradiographic evidence for receptor cell renewal in the olfactory epithelium of a snail.

The tentacles of the terrestrial snail Achatina fulica contain an epithelium at their tips which is specialized for olfaction. The histology of the snail's olfactory organ bears a striking resemblance to that of the olfactory mucosa in the nose of vertebrates, where the receptor cell population is known to undergo a continuous process of renewal. In the present experiments, [3H]thymidine was delivered as a single pulse that was determined to have a maximum duration of about 1 h. Thirty minutes after an injection of [3H]thymidine, presumptive precursor cells were found labeled within, or at the edges of, receptor cell lobules. At later survival times, label was seen over cells that were identified as receptors. The mean position of the labeled cells within the layer of receptor cells became progressively more superficial with increasing survival times, indicating an upward migration of newly differentiated cells. The labeling index in the snail is ca. 0.7%, compared to 0.9% in the mouse. The turnover time is about 45 days, compared to 30-45 days in the mouse.

Animals

Brain cells that command sexual behavior in the snail Helix aspersa.

Evidence is presented indicating that the mesocerebrum of the terrestrial snail, Helix aspersa, has a major role in the control of sexual behavior. Morphological and physiological results demonstrate a right-sided bias in the mesocerebrum that is consistent with the fact that sexual behavior is executed almost entirely on the animal's right side. Thus, the right lobe has 23% more neurons than the left lobe, and they are 24% larger. Excitatory synaptic inputs derive predominately from neurons on the right side. The axons of right-side mesocerebral neurons go to the right pedal ganglion almost without exception, and even the axons of left-side neurons travel mostly in right-side connective nerves. Direct evidence for a role of the mesocerebrum in commanding sexual behavior comes from experiments with electrical stimulation. Extracellular stimulation of the right mesocerebrum, but not the left mesocerebrum, resulted in movements of the "love dart" sac and the penis. Intracellular stimulation of neurons in the right mesocerebrum evoked measurable movements of either the dart sac or the penis, or both, in 17% of the cells tested. The latencies ranged between 5 and 50 s. In an intact animal, these movements would cause a release of the dart and an eversion of the penis. The motor effects were mediated through the right cerebropedal connective and the pedal nerve NCPD, with the motorneurons probably situated in the right pedal ganglion.

Animals

Cytotoxicity of combinations of prostaglandin D2 (PGD2) and antitumor drugs for B16 melanoma cells in culture.

Prostaglandin D2 (PGD2) is lethal to murine and human melanoma cells at high doses, but synchronizes cells at G1 at non-toxic doses (2.5 or 5 micrograms/ml). We tested the lethality to B16 mouse melanoma cells of combinations of PGD2 with anticancer drugs. The drugs selected were mostly those used in treating human melanoma: actinomycin D, Bleomycin, BCNU, cis-platin, melphalan, 5-fluorouracil, and 1-beta-D-arabinofuranosylcytosine (ara-C). PGD2 was combined with the drugs according to 3 different protocols: An asynchronous culture was given a long term (24 hr) exposure simultaneously to PGD2 + drug. Combinations with Bleomycin, ara-C or melphalan were additive or slightly antagonistic whereas PGD2 plus actinomycin D was significantly antagonistic. Cells synchronized in G1 by 24 hr PGD2 exposure were then given a short-term (2 hr) treatment with PGD2 + drug. Combinations with cis-platin, Bleomycin, BCNU or 5-fluorouracil were additive or slightly antagonistic, whereas melphalan and actinomycin D combinations were significantly antagonistic. Cells were released from a PGD2-induced G1 block and were exposed to drug at different times during cell progression. Actinomycin D was antagonistic when added immediately after release from the G1 block, but was significantly synergistic when added 10 to 12 hr later. The effect of the combinations cannot be explained by available cell cycle or biochemical information. The antagonism between PGD2 and several of the drugs resembles the "cytoprotective" effect of PGD2 towards various noxious agents.

Animals

In vitro activity of ketoconazole against herpes simplex virus.

The effects of ketoconazole alone and in combination with acyclovir and adenine arabinoside upon the replication of herpes simplex virus types 1 and 2 (HSV-1 and -2) were investigated by using a yield reduction assay. Ketoconazole demonstrated antiviral activity against HSV-1 and -2 and synergistic antiviral activity when it was combined with acyclovir. Combinations of ketoconazole with adenine arabinoside resulted in either interference or indifference. The effects of ketoconazole upon the protein synthesis of HSV-2-infected cells were also determined in an effort to define the mechanism of action for the antiviral activity of ketoconazole. There was no reduction of HSV proteins when compared with acyclovir. These findings suggest that further investigations of the use of ketoconazole for the treatment of HSV infections are warranted.

Acyclovir