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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 541 records · Page 30Linked to original sources
PubMed1982

Effect of isoniazid administration on selected rat and mouse hepatic microsomal mixed-function oxidases and in vitro [14C]acetylhydrazine-derived covalent binding.

The effect of isoniazid on selected microsomal mixed-function oxidase activities and on the microsomal metabolism of its own metabolite, acetylhydrazine, to a highly reactive compound which covalently binds to intracellular macromolecules was characterized in male C57BL6 mice and male Sprague-Dawley rats. In comparison with controls, isoniazid pretreatment of rats significantly increased the sp. act. of acetanilide 4-hydroxylase and the in vitro [14C]acetylhydrazine-derived covalent binding to hepatic microsomes but significantly decreased the sp. act. of benzo[a]pyrene hydroxylase and testosterone 16 alpha-hydroxylase. Isoniazid treatment of mice had no effect on any of these parameters except for a significant reduction in sp. act. of testosterone 7 alpha-hydroxylase. Thus the pathway of isoniazid metabolism leading to the formation of reactive metabolites of acetylhydrazine is enhanced by isoniazid pretreatment in rats but not in mice. The presence of similar routes of isoniazid metabolism in man may account for the 8.7-24% incidence of subclinical hepatocellular damage observed in patients receiving isoniazid alone in the chemoprophylaxis of tuberculosis.

Animals↗
PubMed1982

Habituation and sensitization of startle reflexes elicited electrically from the brainstem.

Repetitive elicitation of startle-like responses by electrical stimulation of the cochlear nucleus led to sensitization followed by habituation. In contrast, repetitive elicitation of startle-like responses by electrical stimulation of the reticular formation led only to sensitization. Since these different locations represent different points along the acoustic startle circuit, the data suggest that sensitization may be related to the motor side of reflex arcs, whereas habituation may be related to the sensory side.

Animals↗
PubMed1982

Characterization and solubilization of the specific binding sites for d-alpha-tocopherol from human erythrocyte membranes.

Previous work from our laboratory has demonstrated the presence of specific binding sites for d-alpha-tocopherol (vitamin E) in intact human erythrocytes [A. E. Kitabchi and J. Wimalasena, Biochim. biophys. Acta 684, 300 (1982)]. The binding was time, temperature and cell concentration dependent. To localize the binding sites, red blood cells were further fractionated; greater than 90% of the tocopherol binding sites were localized on membranes. The washed membrane fraction from normal human erythrocytes has specific binding sites for d-alpha-tocopherol with properties suggestive of protein receptors. Two binding sites with Ka values of 3.31 x 10(1)M-1 and 1.51 x 10(6)M-1 were demonstrated, and solubilized d-alpha-tocopherol binding site complexes were resolved to a major component with an Mr of 65,000 and a minor component with an Mr of 125,000.

Binding Sites↗
PubMed1982

Accelerated development of alcoholic cirrhosis in patients with HLA-B8.

To test whether the increased prevalence of HLA-B8 reported in patients with alcoholic cirrhosis is due to the antigen being a genetic marker of susceptibility to liver damage from alcohol, patients who had cirrhosis of comparable clinical and histological severity were investigated for HLA-B8 status and cumulative alcohol intake. Both male and female cirrhotics with HLA-B8 had been drinking greater than 40 g alcohol/day for a shorter period of time (16.6 +/- 1.4 men, and 9.4 +/- 2.0 years, women) than their counterparts without this antigen (23.7 +/- 1.7, p less than 0.005, and 15.8 +/- 2.0 years, p less than 0.05, respectively), but the mean daily alcohol intake was similar whether patients had HLA-B8 or not. These results suggest that genetic determinants linked to HLA-B8 enhance the rate of development of liver damage in those who drink potentially hepatotoxic amounts of alcohol.

Adult↗
PubMed1982

Evidence for the vivo compartmentation of amino acids between blood cells and plasma in man with liver disease during constant infusion of L (U-14C) tyrosine.

L (U-14C) tyrosine tracer was infused at a constant rate for 8 hrs in a series of five patients with liver disease on two occasions, the first when diet consisted of intravenous glucose, and the second when aminoacids were added. Plateau labelling of both plasma and intracellular blood cell free tyrosine was obtained by 6 hr of each infusion. However, the intracellular specific activities were on average 50% lower (p less than 0.05) when diet was glucose alone, and 54% lower (p less than 0.01) when glucose and aminoacids were given. Change in diet did not significantly affect these differences. The results provide evidence for significant in-vivo compartmentation of aminoacids between plasma and blood cells in man with liver disease, and indicate that whole blood cannot be used in the conventional measurement of whole body protein.

Amino Acids↗
PubMed1982

Opposite effects of N,N-dimethyltryptamine (DMT) and 5-methoxy-n,n-dimethyltryptamine (5-MeODMT) on acoustic startle: spinal vs brain sites of action.

The present studies examined the role of the spinal cord and the brain in mediating the effects of the hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on the acoustic startle response in the rat. Systemic administration of these agents, which distributes to both the brain and spinal cord, produced opposite effects, as DMT depressed and 5-MeODMT increased acoustic startle. However, when administered directly into the lateral ventricle in the forebrain (intraventricular administration) 5-hydroxytryptamine (5-HT), DMT and 5-MeODMT all depressed acoustic startle, DMT and 5-MeODMT being about equipotent in this regard. In contrast, when administered directly into the spinal cord subarachnoid space (intrathecal administration), 5-HT and 5-MeODMT increased startle, whereas DMT was without effect. In another series of studies, the effects of systemically-administered DMT and 5-MeODMT on the "startle" elicited by electrical stimulation of the nucleus reticularis pontis caudalis (RPC) were determined. Since the RPC is the last nucleus of the primary startle circuit before the spinal cord, agents which act downstream from the RPC (i.e., in the lower brainstem and spinal cord) would be expected to alter RPC-elicited "startle," while agents which act upstream from the RPC would be without effect. Given systemically, 5-MeODMT markedly increased RPC-elicited "startle" while DMT was without effect. These data indicate that DMT and 5-MeODMT are equipotent in depressing startle through actions in the brain. In contrast, the difference in the effects of DMT and 5-MeODMT on acoustic startle is related to the spinal excitatory effects of 5-MeODMT which DMT does not possess. From the present results it is suggested that the relative potencies of DMT and 5-MeODMT in other behavioral measures may relate to the role of brain (equipotent) or spinal (5-MeODMT more potent than DMT) sites of action for the various behaviors.

Acoustic Stimulation↗
PubMed1982

Nuclear magnetic resonance imaging techniques as developed modestly within a university medical center environment: what can the small system contribute at this point?

This paper describes a geometrically small NMR imaging system which has been developed and assembled within a university medical center environment. Consideration is given to the technical specifications and basic economics for the magnet system, NMR spectrometer, and computer configuration. Initial research objectives for the system are outlined which include (1) the signal-to-noise improvement potential of rotational gradient imaging, and (2) 19F tracer imaging considerations with a detailed discussion concerning the feasibility of in vivo NMR imaging of 19F-fluorodeoxyglucose (2-FDG and 3-FDG). Finally, potentially significant areas for research within the constraints of a small NMR imaging system are described.

Academic Medical Centers↗
PubMed1982

Clinical effects and metabolism of diazepam in patients with chronic liver disease.

1. After a fixed weight-related dose given intravenously, plasma diazepam concentrations were significantly lower in 11 cirrhotic patients than in controls matched for age and sex, in the 4 h after diazepam administration but not thereafter. 2. When measured at a single fixed time point, a greater proportion of the drug was in the unbound from in the plasma of cirrhotic patients, but non-bound diazepam concentrations were not significantly different in the two groups. 3. Several psychomotor tests showed that cirrhotic patients, although having significantly impaired liver function, did not as a group have increased sensitivity to diazepam compared with their matched controls. 4. Only those cirrhotic patients who at the time of drug administration had impaired cerebral function, as judged by baseline performance of psychomotor tests, showed increased sensitivity to the effects of intravenous diazepam. 5. Psychomotor tests, particularly the Reitan trail test, seem more useful than tests of liver function or drug metabolism for identifying those patients with liver cirrhosis at risk of excessive sedation after diazepam administration.

Adult↗
PubMed1982

Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas.

Expression of IgA by plasmacytomas occurs as a result of a DNA rearrangement that brings the variable region gene, VH, a few kilobases 5' to the constant region gene, C alpha. In this study, we show that the allelic nonexpressed C alpha gene also is rearranged in most plasmacytomas. Cloning, restriction mapping, heteroduplex analyses, and sequence analyses of the nonproductively rearrange C alpha genes from two plasmacytomas, M603 and M167, have demonstrated that the nonproductive rearrangement occurs within the alpha switching region, S alpha. In each case, the same DNA sequence has been joined to the 5' side of C alpha and we have termed this DNA "NIRD" (for nonimmunoglobulin rearranged DNA). Southern blotting analyses of genomic DNAs from various IgG-, IgM-, or IgA-producing plasmacytomas suggest that NIRD is rearranged in almost all plasmacytomas. However, NIRD rearranges to the S alpha region only in IgA-producing cells, not in IgM or IgG producers. Cytogenetic evidence has shown that T(12;15) translocations are common in murine plasmacytomas. Immunoglobulin heavy chain genes are located on chromosome 12, and the translocation breakpoint in plasmacytomas occurs near the immunoglobulin genes. NIRD has been mapped to chromosome 15 by Southern blotting analysis of mouse-hamster cell lines, suggesting that the nonproductively rearranged C alpha clones represent the T(12;15) translocations identified cytogenetically. Therefore, we have identified a region of DNA on chromosome 15 that is commonly rearranged in transformed mouse lymphocytes. We speculate on the significance of NIRD in neoplastic transformation of mouse lymphocytes.

Animals↗
PubMed1982

Tricyclic antidepressants vary in decreasing alpha 2-adrenoceptor sensitivity with chronic treatment: assessment with clonidine inhibition of acoustic startle.

1 Clonidine inhibition of the acoustic startle reflex in the rat was used as a behavioural measure of alpha 2-adrenoceptor sensitivity following acute or chronic administration of tricyclic antidepressants. 2 Chronic (14 day) administration of desipramine (10 mg/kg, i.p.) attenuated the depressant effect of clonidine (20 or 40 microgram/kg) on the startle reflex. 3 No change in response to clonidine was obtained after chronic treatment with two other tricyclic antidepressants, amitriptyline (10 mg/kg) or iprindole (5 mg/kg). 4 Acute administration of these tricyclics (1 h) did not modify the effect of clonidine on startle. 5 It is suggested that the development of alpha 2-adrenoceptor subsensitivity produced by chronic tricyclics may be unique to those compounds, such as desipramine, which are active in blocking the uptake of noradrenaline.

Animals↗
PubMed1982

Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure.

A controlled trial of 44 patients was undertaken to evaluate the use of dexamethasone (32 mg stat, 8 mg qds) in preventing, and intravenous mannitol (1 g/kg) in reversing the cerebral oedema of fulminant hepatic failure. Diagnosis of cerebral oedema was based on intracranial pressure recordings or the presence of defined clinical signs. Cerebral oedema developed in 34 patients with similar frequency in those treated with and without dexamethasone (16 of 21 and 18 of 23 respectively). In those 34 patients episodes of cerebral oedema resolved significantly more frequently in the 17 patients who received mannitol than in the 17 patients who did not (44 of 53 and 16 of 17 respectively, p less than 0.001). Dexamethasone did not affect survival but among patients who developed cerebral oedema those who received mannitol had a significantly better survival than those who did not receive it (47.1% and 5.9% respectively, p 0.008, Fisher's one-tail test).

Adolescent↗
PubMed1982

Fetus-in-fetu.

Explore the source record for details and available documents.

Abdominal Neoplasms↗
PubMed1982

Transposon Tn10: genetic organization, regulation, and insertion specificity.

Transposon Tn10 is a composite element in which two individual insertion sequence (IS)-like sequences cooperate to mediate transposition of the intervening material. The two flanking IS10 elements are not identical; IS10-right is responsible for functions required to promote transposition, and IS10-left is defective in transposition functions. We suggest that the two IS10 elements were originally identical in sequence and have subsequently diverged. IS10-right is compactly organized with structural gene(s), promoters, and sites important for transposition and (presumably) its regulation all closely linked and, in some cases, overlapping. IS10 has a single major coding region that almost certainly encodes an essential transposition function. A pair of opposing promoters flank the start of this coding region. One of these promoters is responsible for expression in vivo of transposon-encoded transposition functions. We propose that the second promoter is involved in modulation of Tn10 transposition. Genetic analysis suggests that transposon-encoded function(s) may be preferentially cis-acting. Insertion of Tn10 into particular preferred target sites is due primarily to the occurrence of a particular six-base pair target DNA sequence. The properties of this sequence suggest that symmetrically disposed subunits of a single protein may be responsible for both recognition and cleavage of target DNA during insertion.

Base Sequence↗
PubMed1982

A primary acoustic startle circuit: lesion and stimulation studies.

The latency of the acoustic startle reflex in the rat is 8 msec, measured from tone onset to the beginning of the electromyographic response in the hindleg. This extremely short latency indicates that only a few synapses could be involved in some primary acoustic startle circuit. Acoustic startle is being used as a model system for studying habituation, sensitization, prepulse inhibition, classical conditioning, fear or anxiety, and drug effects on behavior. The present study attempted to delineate a short latency acoustic startle circuit, since this would provide critical information for further study in all of these areas. Bilateral lesions of the ventral cochlear nucleus, which receives the primary auditory input, abolish acoustic startle. Electrical, single pulse stimulation of the ventral cochlear nucleus elicits startle-like responses with a latency of about 7 msec. Bilateral lesions of the dorsal and ventral nuclei of the lateral lemniscus, which receive direct input from the ventral cochlear nuclei, abolish acoustic startle. Electrical stimulation of these nuclei elicits startle-like responses with a latency of about 6 msec. Bilateral lesions of ventral regions of the nucleus reticularis pontis caudalis, which contain cell bodies that give rise to the reticulospinal tract, abolish acoustic startle. Electrical stimulation of these points elicits startle-like responses with a latency of about 5 msec. Reaction product from horseradish peroxidase iontophoresed into this area is found in the nuclei of the lateral lemniscus. In contrast, lesions of the dorsal cochlear nuclei, vestibular nuclei, nucleus reticularis pontis oralis, nucleus reticularis gigantocellularis, and dorsal regions of the nucleus reticularis pontis caudalis fail to abolish acoustic startle. Also, "startle" cannot be elicited electrically from these areas. The data suggest that a primary acoustic startle circuit in the rat consists of auditory nerve, ventral cochlear nucleus, nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal interneuron, lower motor neuron, and muscles. Hence, five synapses, plus the neuromuscular junction, are probably involved.

Acoustic Stimulation↗