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Biomedical subjects

J R Martin

Publications and source records attributed to J R Martin.

At least 163 records · Page 9Linked to original sources

Congenital contractural deformities of the fingers and arthropathy.

Four patients are described who presented with congenital finger contractures and arthropathy. There was synovial cell hyperplasia and giant cells but no inflammatory process. Radiographs showed flattening of the metacarpal and metatarsal heads and the proximal femoral ossification centres. In the oldest patient the process had subsided leaving slight contractures but severe impairment of hip mobility. In another the arthropathy was still prominent in the early teens. In a third, finger contractures had failed to respond to conservative or surgical measures.

Contracture↗

Increased ethanol consumption and blood ethanol levels in rats with portacaval shunts.

In a series of experiments, it was demonstrated that male rats with end-to-side portacaval shunts (PCS) consumed more ethanol and exhibited higher blood ethanol levels than sham-operated control animals in chronic tests with 2% ethanol and water ad libitum. Ethanol intake in the 6 h prior to blood sampling was 2-5 times and blood ethanol 10-50 times higher in PCS than control rats. These effects were not due to the feminization of male rats occurring after a PCS, since female PCS rats exhibited comparable increases of ethanol intake and blood ethanol. In both sexes ethanol elimination rate and alcohol dehydrogenase activity per total liver were lower after PCS than in control rats, explaining the disproportionate increase in blood ethanol relative to ethanol intake. Interestingly, ethanol intake was not abnormal in PCS rats fed a low-protein, low-tryptophan diet (corn) alone or as a supplement to the usual chow diet. Such dietary modulation of ethanol preference in this animal model of chronic liver dysfunction merits further attention.

Alcohol Drinking↗

Palm oil and pyrantel as child nutrition mass interventions in Papua New Guinea.

Two mass interventions in the local low energy-density diet were evaluated for safety, acceptability and nutritional efficacy in a four-group matched study of 896 Papua New Guinea children aged 12-54 months. A single dose of 125 mg of pyrantel pamoate and an 800 mg supply of red palm oil were given monthly at the regular child health clinics. Both were safe and highly accepted. Children given palm oil gained more weight than controls (P less than .05) in the first three study months, confirming a pilot study. However, weight gain after one year was 94% of standard, with no differences in anthropometry, morbidity or mortality between groups. The lack of demonstrable differences at one year is attributed to secular improvement in control group nutrition and to diffusion of palm oil supplies within the family. While pyrantel was an effective antihelminthic, further study is needed to define the nutritional role of mass worm treatment. Palm oil was economical and culturally popular; thus it should be an ideal import substitution. It is clinically useful where diets are of low energy-density. However, any simultaneous demonstration of its nutritional safety, acceptability as a sustained mass intervention must be carried out in an area where major child growth deficits remain and expropriation of the oil by other household members can be controlled.

Anthropometry↗

The effects of caffeine on physiological functions and mental performance.

Polygraphic monitoring of several physiological variables was done throughout an experiment investigating the effects of caffeine on mental performance. The experiment started with a mental maze learning task. Then the subjects were given the test beverages according to the group design (CC group (N = 16): 300 mg caffeine in decaffeinated coffee, DC group (N = 16): decaffeinated coffee, WW group (N = 8): warm water, and NB group (N = 8): no beverage). The experiment continued with a letter cancellation task which was followed by a second mental maze learning task. The caffeine treated subjects differed from the other groups by increased regularity of letter cancellation performance, as indicated by decreases in intraindividual variance. They also differed from the other groups by a slight but significant acrodermal vasoconstriction. No intergroup differences were obtained for mental maze learning, heart rate, respiration, muscle tension, and skin conductance. The results suggest therefore that the drug at this dose level improves behavioral routine and speed rather than cognitive functions and that the vegetative side effects are minimal.

Adult↗

Pharmacological characterization of apomorphine-induced hypothermia in the spontaneously hypertensive rat.

The dopamine agonist apomorphine was more potent in eliciting hypothermia in spontaneously hypertensive rats (SHRs) than in normotensive Wistar rats (NWRs), while normotensive Wistar-Kyoto rats (WKYs) were intermediate in response. Various drug interventions were attempted in an effort to explain the greater sensitivity of SHRs to apomorphine. Haloperidol produced abolition of apomorphine-induced hypothermia in SHRs but at greater doses than required for antagonism of the drug effect in WKYs and NWRs. Chronic hydralazine treatment that reduced the high blood pressure of SHRs failed to appreciably influence the magnitude of apomorphine-induced hypothermia, compared to the response in control SHRs that received no hydralazine. These findings suggested to us that the enhanced hypothermic effect of apomorphine in SHRs was entirely dopamine receptor-mediated and that it was also independent of the high blood pressure. We also found that chronic lithium treatment that had no influence upon apomorphine-induced hypothermia in WKYs and NWRs significantly reduced the drug effect in SHRs. Based on this finding, we suggest that the greater hypothermic effect induced by apomorphine in SHRs might be due to a supersensitivity of hypothermia-mediating dopamine receptors in the hypertensive strain.

Animals↗

Differential response to cholinergic stimulation in psychogenitically selected rat lines.

Male and female rats of two lines psychogenetically selected for bipolar extremes in shuttle box avoidance were evaluated for tremor, salivation, chromodacryoorhea, and hypothermia following treatment with the muscarinic cholinergic agonist oxotremorine. Roman Low-Avoidance (RLA/Verh) rats exhibited more pronounced oxotremorine-induced tremor, chromodacryorrhea, and hypothermia than Roman High-Avoidance (RHA/Verh) rats. There was a sex difference only for a chromodacryorrhea response, with females exhibiting a greater response following oxotremorine than males. In a subsequent experiment using female rats of both rat lines, it was demonstrated that pre-treatment with the cholinergic antagonist scopolamine blocked oxotremorine-induced tremor, salivation and chromodacryorrhea responses in both rat lines and reduced the hypothermic effect observed in RLA/Verh rats (but not the much weaker hypothermia found in RHA/Verh rats) after oxotremorine injection. Pretreatment with the peripherally active cholinergic antagonist methscopolamine significantly reduced oxotremorine-induced salivation and chromocacryorrhea and somewhat decreased tremor and hypothermic responses in both rat lines. These results stand in contrast to the results of earlier research in which RHA/Verh rats exhibited greater behavioral depression in a tunnel maze than RLA/Verh rats following cholinergic manipulations. In view of evidence that these rat lines do not differ in number of muscarinic brain receptors, the present results may be due to genetic differences in other aspects of cholinergic neurotransmitter function, differences in the function of other neurochemical systems, or differences in the absorption, distribution, or metabolism of oxotremorine.

Animals↗

Intra-axonal virus in demyelinative lesions of experimental herpes simplex type 2 infection.

Three-week-old mice which had been infected intracerebrally with herpes simplex virus type 2 (HSV-2) were examined electron-microscopically for the presence of intra-axonal virus in or near optic nerve and spinal cord demyelinative lesions. Acute lesions and their margins frequently contained a very small proportion of abnormal axons, and in a few of these mature virus particles, nucleocapsids, or other incomplete forms were found. A similar range of particle morphology was present in the cytoplasm of infected and degenerating glia. Axons containing similar particles were not identified in fibers in normal white matter surrounding demyelinative lesions. It is proposed that neuronal infection and axonal transport of virus may lead to foci of oligodendroglial infection, destruction and central nervous system (CNS) demyelination near to or remote from the cell bodies of infected neurons. In some instances, the topography of lesions could reflect a tract association. Anatomical features of nervous tissue could favor amplification of demyelination from a relatively minimal neuronal infection, with little evidence of tract degeneration. This hypothesis is consistent with the great predominance of demyelination relative to gray matter disease seen experimentally in non-fatal CNS infections with HSV-2. It would also explain the marked tendency for demyelinative lesions in at least certain CNS locations to be greatly elongated in the long axis of fiber tracts. This mechanism could be of importance in other animal models of virus-induced demyelination, and perhaps also in multiple sclerosis.

Animals↗

Tail pinch induced eating: psychogenetic comparison of Roman high- and low-avoidance rats.

Consummatory behavior elicited by mild tail pinch in the presence of solid food was studied in male Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats. RLA/Verh rats, characterized as the more emotional of the two rat lines, exhibited significantly shorter latencies to bite and eat solid food during tail pinch than the RHA/Verh rats. Treatment with 6, 12 and 24 mg/kg sodium pentobarbital prior to tail pinch failed to increase the elicited eating in either rat line.

Animals↗

Erythromycin uptake and accumulation by human polymorphonuclear leukocytes and efficacy of erythromycin in killing ingested Legionella pneumophila.

Studies were undertaken to demonstrate the efficacy of erythromycin in killing Legionella pneumophila organisms that have been ingested by human polymorphonuclear leukocytes. With use of an electron microscope-autoradiography method in conjunction with an antibiotic-uptake assay, it was shown that [3H]-labeled erythromycin A base penetrated into the cytoplasm of human polymorphonuclear leukocytes in concentrations up to 24 times higher than the extracellular drug level. Similar studies using [14C]benzyl penicillin revealed that this antibiotic penetrated human polymorphonuclear leukocytes very poorly. Removal of erythromycin from the extracellular environment resulted in rapid leakage of radioactivity from the cells; an assay for bioactivity showed that this material was unaltered drug. Human polymorphonuclear leukocytes were permitted to ingest L. pneumophila and were then treated with erythromycin A base. The erythromycin killed the ingested legionellae, as evidenced by bacterial plate counts and morphological destruction of ingested organisms. These data clearly demonstrate the efficacy of erythromycin in killing susceptible intracellular pathogens.

Erythromycin↗

The nervous system in genital herpes simplex virus type 2 infections in mice. Lethal panmyelitis or nonlethal demyelinative myelitis or meningitis.

Female mice were inoculated vaginally with the MS strain of herpes simplex virus type 2, and serially positive vaginal cultures were used to confirm infection. The proportion of mice infected and the mortality rate in infected mice decreased with increasing age. In mice 12 weeks old, clinical, neuropathologic, and virologic criteria defined four patterns of disease. Moribund mice had severe genital lesions, hindleg paralysis, and urinary and fecal retention, and most died during the second week of infection. These mice had a panmyelitis with a decreasing gradient of both viral antigen and lesions extending rostrally from the lumbosacral cord into the brain stem. Lesions were about equally distributed in gray and white matter and were characterized by neuronal loss and axonal demyelination, respectively. By contrast, mice with nonfatal infections had mild or no evident genital lesions and a small proportion had mild hindleg weakness. Of these, some mice had demyelinative lesions, particularly in the lower spinal cord but also at higher cord and brain stem levels, whereas others had leptomeningitis. Both of these groups had sacral sensory root abnormalities. A third group of survivors lacked both sensory root and central nervous system abnormalities. This report defines a broader spectrum of disease patterns following infection by a natural route than has been previously appreciated. It provides the first evidence that nonfatal herpes simplex virus type 2 infection by a peripheral route can produce central nervous system demyelination. It indicates that in aseptic meningitis with this agent, the route of virus spread to the central nervous system is neural and not hematogenous. Finally, the antigenic and pathologic observations presented here complement and confirm the virus isolation data and pathologic findings of others that genital herpes simplex virus type 2 infection causes ascending infection in the peripheral and central nervous system.

Aging↗

Two-way avoidance and acute shock stress induced alterations of regional noradrenergic, dopaminergic and serotonergic activity in Roman high- and low-avoidance rats.

Various brain regions of male RHA/Verh and RLA/Verh rats were dissected out and deep-frozen immediately after 30 min in a shuttle box involving a) no shock (control), b) 40 inescapable shocks or c) 40 avoidable shocks. The RHA/Verh rats used in the "c" category exhibited about 80-85% learned avoidance. 5-HT, 5-HIAA, NA, MHPG-SO4, DA, DOPAC and HVA levels were subsequently measured in selected regions. NA levels were considerably reduced in the hypothalamus and pons/medulla of both selected lines of rats after acute shock stress, supporting the results of numerous studies which have indicated that NA turnover is nonspecifically increased by all types of stress, at least in those regions. An increase in cortical MHPG-SO4 and a reduction in hypothalamic 5-HT seen after avoidance learning also occurred after shock stress in RHA/Verh rats. Whereas RLA/Verh rats showed an increased metabolism of 5-HT in the hypothalamus and pons/medulla after shock stress, RHA/Verh rats showed the opposite response in the hypothalamus after the same treatment. A reduction in 5-HT metabolism was also evident in RHA/Verh rats, after avoidance learning, in the cortex, hippocampus and hypothalamus. These results indicated, pending further studies regarding, for example, possible genetic differences in tryptophan uptake and utilization, that 5-HT probably plays at least a modulatory role in the reaction to stress, and in avoidance behavior. That role may be either active or passive, depending upon the emotional status of the subjects. In regard to the DA responses measured in striatum and hypothalamus of the two rat lines, some divergent inter-treatment tendencies, as well as some similarities, were seen in DA metabolism in both regions, but almost none of the differences were significant.

Animals↗

Familial hypertryptophanemia, tryptophanuria and indoleketonuria.

Two patients presenting with mental subnormality and severe emotional lability were examined for possible inborn errors of metabolism. Amino acid and organic acid analyses of their plasma and urine revealed a novel and grossly abnormal metabolism of tryptophan. Basal levels of plasma tryptophan were ten times that of controls and the 24-hour urinary excretion of tryptophan was up to 50 times greater than normal. Both patients excreted about 100 times the normal amounts of indoleacetic, indolelactic and indolepyruvic acids. Administration of oral antibiotic to one of the patients to eliminate intestinal bacteria did not result in any reduction in the excretion of the indoleic acids. The results are interpreted in terms of a possible congenital defect in the normal conversion of tryptophan to kynurenine.

Adult↗

Environmental and genetic effects on food-deprivation induced stomach lesions in male rats.

When Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats were individually housed in plastic cages with sawdust bedding and food-deprived (F-D) for 4-5 days, it was found that F-D RHA/Verh rats had more lesions than their unfasted controls and more lesions than F-D RLA/Verh rats. The lesions were mostly petechial in nature and located in the glandular portion of the stomach. Also, F-D RHA/Verh rats which were housed in the same room as the controls, as well as F-D RHA/Verh rats which were housed in a separate room with a strong food odor present, had more lesions than F-D RHA/Verh rats housed in the same separate room when there was no food odor, and when none of the rats present had access to food. When F-D RHA/Verh and F-D RLA/Verh rats were individually housed in metal cages with grid floors, however, a general increase in lesion scores resulted and differences between the two rat lines disappeared, as did differences among the room conditions. Also, many lesions were of an ulcerative nature and were located in the rumenal portion of the stomach. It was concluded that sensory (in this case olfactory, at least) and genetic factors are capable of playing roles in the induction of stomach lesions in rats, and that the type, extent and location of the lesions can depend upon whether or not the animals have access to sawdust bedding.

Animals↗

Alterations in ingestive behavior following experimental portacaval anastomosis in rats.

Following surgical construction of an end-to-side portacaval shunt (PCS), male rats exhibited exaggerated consumption of glucose, saccharin, saline, and ethanol solutions relative to sham-operated rats in 24-hr preference tests with water present. Spontaneous daily water intake was also increased, but daily food intake and body weight were decreased by PCS. The overconsumption of glucose, saccharin, and saline exhibited by rats with portacaval shunts was reduced, or eliminated, by providing a corn supplement to their diet, consistent with the view that the disturbance of amino acid balance may have contributed to this ingestive abnormality. In a series of short drinking tests, rats with portacaval shunts consumed more of both 10% glucose and 10% fructose (given in separate tests) than sham-operated rats and glucose intake was greater than fructose intake for both of these groups. However, neither surgical nor saccharide condition affected the duration of the first bout or the initial inter-bout interval, indicating that the relative satiating properties of these two monosaccharides were probably not altered by portacaval shunting.

Alcohol Drinking↗

Portacaval anastomosis in rats: effects on behavior and brain serotonin metabolism.

The behavior of male rats with chronic end-to-side portacaval shunts or control surgery were evaluated in a complex enclosed maze, an open-field arena, and a swim canal. Subsequently, serotonin and 5-hydroxyindoleacetic acid levels were measured for hypothalamus, striatum, hippocampus, and midbrain-medulla. Chronic portacaval anastomosis did not significantly alter any of the behavioral parameters evaluated in the diverse test situations studied, despite a significant elevation of 5-hydroxyindoleacetic acid levels in all brain regions analyzed and the elevation of serotonin levels in hypothalamus and midbrain-medulla.

Animals↗