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Biomedical subjects

J R Goldsmith

Publications and source records attributed to J R Goldsmith.

At least 19 recordsLinked to original sources

The insulin hypoglycemia-induced inhibition of gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: roles of vasopressin and corticotropin-releasing factor.

Insulin-induced hypoglycemia (IIH) profoundly inhibits the activity of the hypothalamic GnRH pulse generator. The aim of this study was to determine the role of vasopressin and CRF in this response. Ovariectomized rhesus monkeys with chronically implanted recording electrodes in the mediobasal hypothalamus and with intracerebroventricular (icv) cannulas in the lateral ventricle were placed in primate chairs, and blood samples were taken every 10 min. Pulse generator activity was monitored electrophysiologically by detecting characteristic increases in hypothalamic multi-unit activity (MUA volleys) and by attendant LH pulses measured in peripheral blood. Arginine vasopressin (AVP) infused via the i.c.v. cannula (50 micrograms/60 microliters.h) in eight monkeys failed to decrease pulse generator activity, as measured by the frequency of MUA volleys, but decreased mean serum LH concentrations (P < 0.001) while increasing serum cortisol levels (P < 0.02). Central administration of an AVP antagonist ([deamino-Pen1, O-Me-Tyr2-Arg8] vasopressin) in four monkeys at a rate (180 micrograms/60 microliters.h) that had previously been found to block the aforementioned effects of coadministered AVP failed to prevent the IIH-induced inhibition of GnRH pulse generator activity and LH secretion in the same animals. On the other hand, a CRF antagonist, [D-Phe12,Nle21,38,C alpha MeLeu37] rat CRF-(12-41), infused i.c.v. at a rate of 500 micrograms/60 microliters.h in four monkeys, delayed the inhibition of pulse generator frequency in response to IIH. These results suggest that AVP does not mediate the hypoglycemia-induced inhibition of GnRH pulse generator frequency in the rhesus monkey, but that CRF may be involved in this response.

Animals

Radiocesium body burdens in immigrants to Israel from areas of the Ukraine, Belarus and Russia near Chernobyl.

Of the 500,000 immigrants from the former Soviet Union who came to Israel during 1990-1993, about 100,000 are estimated to have come from radiocontaminated areas near Chernobyl. These people were subject to chronic uptake of environmental radiocesium over protracted periods. During October-November 1991, a joint Israeli-Canadian investigation measured radiocesium body burdens in immigrants to Israel from the Ukraine, Belarus, and the southern Russian republic in order to provide factual information on radiocesium levels to concerned immigrants and to relate the body burdens to the geographic area of residence before coming to Israel. Assessments were made of 137Cs body burdens in 1,228 volunteer men, women, and children. These measurements were accompanied by medical assessments based on clinical histories and examinations. Radiocesium levels were strongly dependent on the duration of residence in Israel, with the highest levels being found in the most recent immigrants. The maximum level, extrapolated back to the time of leaving the former Soviet Union, was estimated to be about 0.83 kBq (10.3 Bq kg-1). Of the most recent immigrants from the Kiev region (< 101 days in Israel), only 15% had back extrapolated body burdens > 50 Bq, whereas 53% of those coming from Gomel and other towns in the contaminated zones (> 3.7 x 10(10) Bq km-2 of radiocesium) had detectable levels > 50 Bq. People coming from the latter region had significantly higher body burdens as compared to those from the former, in accordance with the higher degree of ground radiocesium contamination reported for the latter region. Women and children showed considerably lower total radiocesium content in comparison to men. All radiocesium body burdens at the time of measurement were too low to be of health concern.

Adolescent

Health effects in a casual sample of immigrants to Israel from areas contaminated by the Chernobyl explosion.

We analyzed questionnaire and physician examination data for 1560 new immigrants from the former USSR divided into three groups by potential exposure to Chernobyl radiation. Two groups were chosen according to soil contamination by cesium-137 at former residences, as confirmed by our findings in a 137Cs body burden study. The third group consisted of "liquidators," persons who worked at the Chernobyl site after the disaster. Liquidators had greater self-reported incidences of symptoms commonly accepted as acute effects of radiation exposure, increases in prevalence of hypertension, and more health complaints. Excesses of bronchial asthma and health complaints were reported in children from the more exposed communities. Asthma prevalence in children potentially exposed in utero appears to be increased eightfold. Older adults from more exposed areas had more hypertension as assessed by history and measurements. These findings suggest the possible association of radiation exposure with several nonmalignant effects.

Adolescent

Factors affecting long-term sick leave in an industrial population.

Factors affecting long-term absenteeism for non-accident-related sickness leave in a large, remotely located factory (Dead Sea Industry, Israel) were evaluated. About 10% (89 persons) of the workers were found to be on sick leave for more than 20 days/year. This group was designated as high absence workers (HAW). Most of the sickness absence were for repeated short-term leaves due to intercurrent diseases, rather than for continuous periods related to a major or single illness. Average cumulative duration of sick leave in this group was 54 days/year. The average number of spells was 11 per year (4.9 days/spell). There were significantly more HAW among skilled (relative risk, R.R. = 1.6) workers or shift workers (R.R. = 1.3), compared to white collar workers. There were significantly fewer HAW among workers 35-49 years of age (7.6%) than among younger (12.5%) or older workers (13.8%). Except for possible hearing loss in one worker, no occupationally related illness was identified. Sixty-six percent of the HAW took many sick leaves, over 20 days during the year following the study year, and 52% of this group took over 20 days in the preceding year (usually for minor diseases or complaints). This pattern of long-term sickness absence indicates that various socio-economic factors determine HAW to a greater extent than immediate occupational risks or health problems.

Adult

Neural analogue of long-term sensitization training produces long-term (24 and 48 h) facilitation of the sensory-to-motor neuron connection in Aplysia.

1. An in vitro analogue of long-term sensitization training was used to gain insights into the mechanisms and time course of the memory for long-term sensitization in Aplysia. The analogue, consisting of four blocks of shocks, was delivered to peripheral nerves of the isolated pleural-pedal ganglia, which contain the sensory neurons and motor neurons that mediate the tail withdrawal reflex. 2. Long-term facilitation of the connections between the sensory neurons and motor neurons was produced by the conjoint stimulation of two peripheral nerves, P8 and P9. Long-term facilitation, however, was not observed after conjoint stimulation of three nerves, P7, P8, and P9. 3. The preparation was viable and stable (no changes in the amplitudes of excitatory postsynaptic potentials (EPSPs) and membrane properties in controls) for at least 48 h. Moreover, the long-term facilitation persisted for at least 48 h. 4. We observed no significant long-term changes in the resting membrane potentials of the sensory and motor neurons or in the input resistance of the motor neurons 24 and 48 h after the conjoint stimulation of nerves P8 and P9. Thus changes in these biophysical properties do not appear to contribute to the expression of long-term facilitation. 5. The finding that conjoint stimulation of three nerves, P7, P8, and P9, produced no long-term facilitation raised the possibility that stimulation of nerve P7 alone might produce long-term inhibition that opposes the facilitatory effects induced by conjoint stimulation of nerves P8 and P9. Stimulation of nerve P7 alone, however, had no long-term inhibitory effect on the EPSPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Fiberglass or silica exposure and increased nephritis or ESRD (end-stage renal disease).

The U.S. multiplant cohort mortality study of workers producing manufactured mineral fibers is finding increasing mortality from nephritis and/or nephrosis. We examine other data sets to see if similar effects can be identified. In a case-referent study among Michigan patients with end-stage renal disease (ESRD), men with exposures to silica have elevated odds ratio for ESRD. In a California occupational mortality study based on 1979-81 data, a number of the construction trades, farmers, and farm laborers show excess mortality for renal disease. The highest mortality ratio is found in the category including insulation workers. This ratio remains significantly elevated when adjusted for estimated exposures to smoking, alcohol, and for socio-economic status. California mortality data from 20 years earlier (1959-61) fail to show much excess renal disease in construction workers, but do for farmers. In Singapore, granite workers with a long-term exposure to silica have excess excretion of albumin and similar compounds compared to less exposed controls, leading to the presumption that silica exposure can lead to silica nephrotoxicity. Balkan nephropathy has been associated with consumption of well water high in silica. In the Negev of Israel, dust storms are a vehicle for increasing respiratory uptake of silica. The Beduin, thought to be a population with maximal exposures, have higher rates of ESRD than do Jews in the age groups over 60 years. Although high blood concentrations of silica are found in persons with renal failure, the close association with elevated creatinine has been interpreted as evidence that the buildup of silica is due to renal failure, rather than vice-versa.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies

Bag cell extract inhibits tail-siphon withdrawal reflex, suppresses long-term but not short-term sensitization, and attenuates sensory-to-motor neuron synapses in Aplysia.

The peptides released from the bag cells (bag cell peptides, BCPs) in Aplysia californica are responsible for eliciting or modulating a repertoire of behaviors preceding and accompanying egg laying. Our interest was in determining to what extent behaviors that can occur simultaneously with egg laying are modulated. To address this issue, we examined the effects of an extract (bag cell extract, BCE) that contained BCPs, as well as egg-laying hormone (ELH), an identified BCP, on both the tail-siphon withdrawal reflex and the ability of that reflex to exhibit sensitization, a simple form of nonassociative learning. In addition, we examined the ability of BCE, as well as the individual BCPs, to modulate a component of the circuitry of the reflex. Behavioral experiments indicated that BCE inhibited the baseline withdrawal reflex and suppressed long-term sensitization of the reflex while leaving short-term sensitization unaffected. These effects were not observed in animals receiving an extract of a control ganglion or in animals receiving ELH, and therefore may be attributed to the actions of one or more BCPs, but presumably not to ELH alone. Electrophysiological experiments revealed that BCE also attenuated the monosynaptic EPSP elicited in tail motor neurons by tail sensory neurons. In subsequent experiments in which the BCPs were individually applied, only one BCP, beta-BCP, significantly attenuated the EPSPs. This effect was independent of narrowing of the presynaptic action potential. Taken together, these results suggest a novel behavioral modification attributed to BCPs, inhibition of the tail-siphon withdrawal reflex, and suggest a possible locus of action and peptide candidate for this effect. In addition, these experiments raise the possibility that BCPs may exert a long-lasting effect (> 24 hr), selectively blocking a simple form of long-term memory.

Action Potentials

Nuclear installations and childhood cancer in the UK: mortality and incidence for 0-9-year-old children, 1971-1980.

Data on cancer incidence and mortality in the vicinity of nuclear installations in England and Wales have been published, covering the period 1959-1980. Several age classes and a number of cancer sites have been included. Systematic analysis has so far been limited to cancer mortality. This suggests that childhood leukemia is unusually frequent near some types of installations and the excess is greater for years 0-9 than for later ages. In the earlier decade, 1959-1969, there was questionable consistency of incidence reporting. This report uses the incidence and mortality data only for the period 1971-1980; leukemia and non-leukemia cancer data for those 0-9 years are analyzed, and consistency of incidence reporting is evaluated by comparing incidence and mortality. For comparison with reported data for grouped local authority areas (LAAs) near to 21 different installations, two sources of expected incidence are used. The first is based on regional data, and the second is based on a group of LAAs similar in location, urban/rural character and population size. Effectiveness of treatment of acute lymphocytic leukemia (ALL, the principal type among 0-9-year-old children) has improved in recent decades and this has decreased the case fatality rate, and increased the relevance of incidence data. No significant differences in the mortality/incidence ratio were found when comparing areas near installations with their matched reference areas. Although some standardized incidence ratios (SIRs) are low in comparison areas, these are a reflection of the small numbers in the denominator. Low and high SIRs are observed in both installation and comparison areas. Excluding the populations near Sellafield and Dounreay, the installations of which include nuclear reprocessing and which are reported elsewhere, children living near one of a group of six installations have significantly increased leukemia incidence. One hundred sixty-five cases were observed for the combined population group, whereas 133.6 were expected on the basis of regional data and 141.9 on the basis of comparison areas. The operations of these installations include nuclear research, nuclear fuel production, nuclear weapons manufacture, and radio-isotopic reagent manufacture and marketing. No evidence of any increase of leukemia incidence is found for populations surrounding nuclear power installations, nor in coastal communities possibly affected by Sellafield discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

Child

Involvement of protein kinase C in serotonin-induced spike broadening and synaptic facilitation in sensorimotor connections of Aplysia.

1. Plasticity at the connections between sensory neurons and their follower cells in Aplysia has been used extensively as a model system to examine mechanisms of simple forms of learning. Earlier studies have concluded that serotonin (5-HT) is a key modulatory transmitter and that it exerts its short-term actions via cAMP-dependent activation of protein kinase A. Subsequently, it has become clear that other kinase systems such as protein kinase C (PKC) also may be involved in the actions of 5-HT. 2. Application of phorbol esters, which activate PKC, produced a slowly developing spike broadening but had little effect on excitability (a process known to be primarily cAMP dependent). Moreover, the effects of phorbol esters and 5-HT on spike duration were not additive, suggesting that they may share some common mechanisms. 3. The protein kinase inhibitor staurosporine suppressed both 5-HT-induced slowly developing spike broadening and, under certain conditions, facilitation of transmitter release. Staurosporine did not inhibit 5-HT-induced enhancement of excitability. The effectiveness of staurosporine on spike broadening was dependent on the time at which spike broadening was examined after application of 5-HT. Staurosporine appeared to have little effect on spike broadening 3 min after application of 5-HT, whereas it inhibited significantly 5-HT-induced spike broadening at later times. The staurosporine-insensitive component of 5-HT-induced spike broadening may be mediated by cAMP. 4. The results suggest that the activation of PKC plays a key role in components of both 5-HT-induced spike broadening and facilitation of synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids

Perspectives on what we formerly called threshold limit values.

From the point of view of an epidemiologist with experience in community air quality standards, occupational health standards, radiation standards, and water quality standards, reasons are given for discarding the assumption that occupational health protection should be based on threshold concepts. The weakness of worker health protection based on prescription of maximal exposure levels is noted, regardless of whose judgement is used for such levels.

Air Pollutants, Occupational

Neural and molecular bases of nonassociative and associative learning in Aplysia.

A model that summarizes some of the neural and molecular mechanisms contributing to short- and long-term sensitization is shown in Figure 14. Sensitizing stimuli lead to the release of a modulatory transmitter such as 5-HT. Both serotonin and sensitizing stimuli lead to an increase in the synthesis of cAMP and the modulation of a number of K+ currents through protein phosphorylation. Closure of these K+ channels leads to membrane depolarization and the enhancement of excitability. An additional consequence of the modulation of the K+ currents is a reduction of current during the repolarization of the action potential, which leads to an increase in its duration. As a result, Ca2+ flows into the cell for a correspondingly longer period of time, and additional transmitter is released from the cell. Modulation of the pool of transmitter available for release (mobilization) also appears to occur as a result of sensitizing stimuli. Recent evidence indicates that the mobilization process can be activated by both cAMP-dependent protein kinase and protein kinase C. Thus, release of transmitter is enhanced not only because of the greater influx of Ca2+ but also because more transmitter is made available for release by mobilization. The enhanced release of transmitter leads to enhanced activation of motor neurons and an enhanced behavioral response. Just as the regulation of membrane currents is used as a read out of the memory for short-term sensitization, it also is used as a read out of the memory for long-term sensitization. But long-term sensitization differs from short-term sensitization in that morphological changes are associated with it, and long-term sensitization requires new protein synthesis. The mechanisms that induce and maintain the long-term changes are not yet fully understood (see the dashed lines in Fig. 14) although they are likely to be due to direct interactions with the translation apparatus and perhaps also to events occurring in the cell nucleus. Nevertheless, it appears that the same intracellular messenger, cAMP, that contributes to the expression of the short-term changes, also triggers cellular processes that lead to the long-term changes. One possible mechanism for the action of cAMP is through its regulation of the synthesis of membrane modulatory proteins or key effector proteins (for example, membrane channels). It is also possible that long-term changes in membrane currents could be due in part to enhanced activity of the cAMP-dependent protein kinase so that there is a persistent phosphorylation of target proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Follow-up of schoolchildren in the vicinity of a coal-fired power plant in Israel.

This study was carried out in the framework of a health monitoring system set up in the vicinity of a 1400 megawatt coal-fired power plant in Israel. Second- and fifth-grade school children were followed up every 3 years; they performed pulmonary function tests (PFT), and their parents filled out American Thoracic Society-National Heart and Lung Institute health questionnaires. Among the cohort of second graders (in 1983) living in the area expected to be most polluted, a significant increase in the prevalence of part of the respiratory symptoms (such as cough and sputum, wheezing with and without cold and wheezing accompanied by shortness of breath) was evident in 1986. The prevalence of asthma among fifth graders in this area doubled (p = 0.0273) compared with prevalence when they were second graders. Among the children from the older cohort (fifth graders in 1983) living in this community, a similar although milder trend could be observed, especially in regard to an increased prevalence of asthma in 1986 compared with 1983 (13.9% versus 8.1%). Annual increases in PFT in the four groups of children (boys and girls from both cohorts) were found to be higher in the community expected to be polluted (especially in the younger cohort) compared with the two other communities. The discrepancy between the increased prevalence of respiratory symptoms and diseases and the higher annual increase in PFT among children from the expected more polluted community may be partly attributable to differential annual increase in height and to different distribution of background variables (such as socioeconomic status, passive smoking, heating, and respiratory diseases among parents) in the three communities.

Air Pollution

Preventability of neonatal cold injury and its contribution to neonatal mortality.

When the body temperature of a small neonate falls below 35 degrees C, lassitude can be noted; severe derangements of cardiovascular, renal, hepatic, immunological, and hematological systems may also occur depending in part on the duration and severity of hypothermia. Diagnosis requires a low-reading thermometer, lacking which the diagnosis can be suspected, but most often is missed. Fatal cases of diagnosed cold injury commonly have terminal pneumonia or sepsis. Prevention involves identification and home visits to high-risk infants; intensive care of those with the diagnosis at Soroka Hospital Medical Center has reduced the case-fatality rate from 30% in 1971 to 3% in 1988-1989. During the same period in our region, the proportion of neonatal deaths occurring in winter months of December, January, and February has dropped from 55 to 27%. The expected proportion is 25%. We hypothesize that excess neonatal mortality during winter months, especially due to pneumonia and sepsis or sudden infant death syndrome (SIDS) is an indicator of missed cold injury syndrome. A preliminary evaluation was made form U.S. data by state, provided by the National Center for Health Statistics, which records no fatalities from cold injury during 1986. Contrasted with this are 26 cold injury deaths in Israel for 1977-1980. In the U.S., though, excess winter neonatal deaths in 1986 from SIDS, pneumonia, and sepsis are reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Cold Temperature