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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 505 records · Page 28Linked to original sources
PubMed1985

Spinalization unmasks clonidine's alpha 1-adrenergic mediated excitation of the flexor reflex in rats.

Clonidine exerts alpha 2-adrenergic mediated depressant effects on most behaviors measured in a normal animal. However, in the spinal-transected (spinalized) animal, clonidine apparently facilitates the flexor reflex through a stimulation of spinal alpha 1-adrenoceptors. The purpose of the present study was to determine if spinalization per se causes the shift in clonidine's profile from an alpha 2- to an alpha 1-adrenergic agonist. The hindlimb flexor reflex was elicited by electrical pulses delivered through electrodes implanted subcutaneously in the hindpaw and was measured with a force transducer and polygraph. In contrast to an alpha 2-adrenergic mediated inhibition of the flexor reflex in intact rats, clonidine produced an alpha 1-adrenergic mediated increase in flexor reflex amplitude in spinalized rats. Because decerebration did not alter the depression due to clonidine, and intraventricular (but not intrathecal) administration of oxymetazoline mimicked the effect of clonidine, the depressant effects of alpha 2-adrenergic agonists are mediated through alpha 2-adrenergic receptors localized in the brainstem. Alternate methods for inducing a functional spinal transection (spinal block with intrathecal procaine; spinal ligation) indicated that the shift in clonidine's effect from inhibition of the flexor reflex to excitation occurred immediately following spinalization. Spinal ligation did not produce alpha 1-adrenergic supersensitivity at 15 min or 2 hr after transection, as measured by alterations in [3H]prazosin receptor binding or behavioral responses to clonidine. Thus, the shift in clonidine's effects from alpha 2-adrenergic mediated inhibition of the flexor reflex in intact rats to alpha 1-adrenergic mediated excitation in spinalized rats results because spinal transection unmasks clonidine's alpha 1-adrenergic stimulatory effect. Other conditions under which clonidine exerts alpha 1-adrenoceptor mediated excitatory effects on behavior are discussed.

Adrenergic alpha-Agonists↗
PubMed1985

"Bull's eye" or "target" lesions of the stomach secondary to carcinoma of the lung.

Three patients with radiographically demonstrated "bulls eye" or "target" lesions of the stomach were found to have gastric metastases from carcinoma of the lung. In two of the three patients, upper gastrointestinal radiography was performed because of gastrointestinal bleeding. Awareness of this association may facilitate earlier recognition of the primary site or earlier recognition of metastatic disease in similar cases. The radiographic appearance of the lesions in these patients is presented, along with a discussion of the pathogenesis of these lesions.

Adult↗
PubMed1984

Use of a direct high performance liquid chromatography method for multiple testosterone hydroxylations in studies of microsomal monooxygenase activities.

A high performance liquid chromatography method is described for separation of the products of testosterone monooxygenation . The method involves direct injection onto a reverse phase octadecylsilane column of the supernatant from incubations containing as little as 25 micrograms microsomal protein. Isocratic elution with formate buffer/acetonitrile and detection at 254 nm permits the separation and simultaneous quantitation of multiple discrete testosterone-derived peaks on the chromatogram. The production of the eight major oxygenated testosterone metabolites in hamster liver microsomes was determined. This profile was altered uniquely after pretreatment with either phenobarbitone, beta-naphthoflavone, rifampicin or pregnenolone 16 alpha-carbonitrile. These changes reflected analogous dissimilar effects of the enzyme inducers on the metabolism of the exogenous cytochrome P-450 substrates aldrin, acetanilide, benzo[alpha]pyrene and ethylmorphine. Therefore, the testosterone assay provides a sensitive and effective method for separating and quantitating testosterone monooxygenation products and may offer a single alternative to the use of multiple exogenous substrates for categorizing and defining the metabolic activity of cytochromes P-450.

Acetanilides↗
PubMed1984

Comparison of substrate specificity of myosin kinase and cyclic AMP-dependent protein kinase.

A series of synthetic peptides corresponding to the amino-terminal region of chicken gizzard myosin light chain (Mr 20 000) have been tested for their capacity to act as substrates for the cAMP-dependent protein kinase. The 18-residue peptide, K6AKTTK11 K12R13PQRATS19NVFS , was stoichiometrically phosphorylated on serine-19 by the cAMP-dependent protein kinase. This is the same residue phosphorylated by the myosin light chain kinase. The cAMP-dependent protein kinase phosphorylated this peptide with an apparent Km of 120 microM and Vmax of 0.29 mumol . min .-1 mg-1. The Km is 17-fold higher and the Vmax 10-fold lower than the corresponding values obtained with this peptide as substrate for the myosin light chain kinase. The kinetics of phosphorylation of shortened peptides corresponding to this 18-residue sequence together with those of another related sequence, RPQRAKAKTTKATSNVFS , indicated that the myosin light chain kinase had a relatively stronger dependence on lysine residues, whereas the cAMP-dependent protein kinase depends more on arginine residues. Although both the cAMP-dependent protein kinase and the myosin light chain kinase phosphorylate the same serine in the myosin light chain peptides, these enzymes are influenced by different nearby basic residues.

Amino Acids↗
PubMed1984

Systemic-pulmonary shunting and hemoptysis in a benign intrathoracic teratoma.

Hemoptysis as a presenting symptom in benign intrathoracic teratoma is rare, but we have documented one such case and discuss the various possibilities of why such a problem should arise. The bleeding was secondary to systemic-pulmonary artery shunting, caused at least in part by extensive pleural adhesions. The exact cause of the adhesions was not determined but possibilities include previous infection or trauma. The tumor was successfully removed surgically.

Adolescent↗
PubMed1984

Diazepam blocks fear-enhanced startle elicited electrically from the brainstem.

Startle-like responses were elicited electrically from the ventral cochlear nucleus (VCN) in darkness or in the presence of a light that had previously been paired with shocks. These startle-like responses were potentiated by the light and potentiation was selectively decreased by diazepam in a dose-related fashion (0.625 to 2.5 mg/kg). The benzodiazepine antagonist RO15-1788 attenuated the effect of diazepam. The data indicate that potentiation of electrically elicited startle behaves like acoustically elicited startle, providing further evidence that electrical elicitation of startle is a viable experimental technique.

Animals↗
PubMed1984

Genetically engineered poxviruses: a novel approach to the construction of live vaccines.

Gene splicing techniques have been used to modify the smallpox vaccine virus thus providing a generic approach for the construction of live vaccines directed against a variety of heterologous infectious disease agents. The technique involves translocating a particular gene from an infectious agent into the genetic material of the smallpox vaccine virus. This unique foreign gene, selected because it contains the information essential for the synthesis of an antigen important in immunity to that particular infectious disease agent, is now expressed under the regulation of the engineered smallpox vaccine virus. On immunization with this live recombinant vaccine, the body is fooled into thinking that it was infected by the foreign infectious disease agent and mounts a defensive attack resulting in immunity to that particular infectious agent. Three examples of this approach are provided. Thus, smallpox vaccine viruses were engineered to express genes encoding the hepatitis B virus surface antigen (HBsAg), the herpes simplex virus glycoprotein D (HSV-gD) and the haemagglutinin (HA) from influenza virus. These foreign gene products when synthesized in vitro under vaccinia virus regulation were shown to be antigenic by a variety of serological tests. When these recombinant vaccinia viruses were inoculated into laboratory animals, the heterologous gene products elicited the production of specific antibodies thus demonstrating that they were immunogenic. Serum neutralizing antibodies were demonstrated to be present for both influenza and herpes simplex viruses. Additional studies in mice showed that a recombinant smallpox vaccine virus expressing a gene from herpes simplex virus effectively protected the mice when subsequently challenged with what would normally be lethal doses of infectious herpes simplex virus.

Animals↗
PubMed1984

Prospective study of nasogastric feeding via East Grinstead or Viomedex tubes compared with oral dietary supplementation in patients with cirrhosis.

Forty-seven patients with alcoholic hepatitis and/or cirrhosis were randomised to receive nutritional supplementation by oral sip feeding or by nasogastric infusion administered via either an East Grinstead or a Viomedex nasoenteric tube. The three groups were well matched for severity and complications of liver disease. Patients fed by the nasogastric route attained their daily target dietary intake significantly more often than did those supplemented orally, but the consequent improvement in their nitrogen balance was not significant. There were no significant differences between nasogastric and sip feeding, or between the types of tube studied, in the frequency with which vomiting, diarrhoea or variceal bleeding occurred, but Viomedex tubes required reinsertion significantly less frequently than did the East Grinstead type.

Journal Article↗
PubMed1984

Strychnine increases acoustic startle amplitude but does not alter short-term or long-term habituation.

Theories of habituation have included an increase in postsynaptic inhibition as one possible mechanism underlying response decrement following repetitive stimulus presentation. In this study, the glycine antagonist strychnine (1.0 mg/kg, ip, 10 min pretreatment) was used to investigate the involvement of glycinergic neurons in the development and/or expression of short-term (within-session) habituation (Experiment 1) and long-term (between-sessions) habituation (Experiments 2 and 3) of the acoustic startle response in rats. Over a range of eliciting-stimulus intensities (95, 105, and 115 dB) and interstimulus intervals (3, 7, 13, and 27 s), strychnine markedly increased startle amplitude, relative to water injection, whereas it failed to attenuate the rate of within-session habituation (Experiment 1). In Experiment 2, rats that were exposed to daily sessions of startle-eliciting stimuli for 4 days and then tested on the fifth day showed lower overall levels of startle amplitude, relative to rats that had not received prior habituation training. Strychnine injected prior to the test session again increased startle amplitude but did not block the expression of between-sessions habituation. In Experiment 3, rats that were injected with either strychnine or water prior to each of three daily habituation training sessions and subsequently tested on Day 4 showed similar between-sessions habituation, relative to untrained rats that had received daily injections in the animal room. In summary, strychnine increased startle amplitude without affecting either within-session or between-sessions habituation of acoustic startle. These results emphasize the need to discern between drug effects on response amplitude per se and effects on response habituation. Furthermore, the data indicate that a buildup of inhibition in glycinergic neurons does not explain either within-session or between-sessions habituation of acoustic startle in rats. These results are discussed in light of current theories of habituation.

Acoustic Stimulation↗
PubMed1984

Granular cell myoblastoma of the esophagus.

Granular cell myoblastoma, a rare, but generally benign tumor, is being encountered with increasing frequency in the digestive tract. Seventy-two cases have been described in the esophagus; we report two additional cases. A follow-up, available in 13 patients (including ours), reveals a low likelihood of malignant transformation or recurrence after surgical removal. Guidelines for the management of these tumors are presented.

Adult↗
PubMed1984

Effects of guanabenz on gastrointestinal absorption of hydrochlorothiazide.

The pharmacokinetics of guanabenz (16 mg) and hydrochlorothiazide (25 mg), administered separately and as a fixed-combination tablet (guanabenz 16 mg/hydrochlorothiazide 25 mg), were compared in a randomized three-period crossover study in 24 healthy men. Plasma concentrations were monitored for 48 h after each administration. No statistically significant differences between the two formulations were noted in mean plasma concentrations or the rate and extent of absorption of guanabenz. The relative bioavailability (Fr) of the combination tablet compared with guanabenz alone was 96%; thus the two formulations were bioequivalent with respect to guanabenz. For hydrochlorothiazide, mean plasma concentrations were similar for 3 h after administration but were higher for the combination tablet than for hydrochlorothiazide alone from 4 through 48 h (p less than 0.05). A significant increase in the extent, but not the rate, of absorption of hydrochlorothiazide was observed for the combination tablet (mean Fr, 120%), which is not considered clinically significant. We propose that this increase may have been due to increased systemic availability of hydrochlorothiazide in the presence of guanabenz, an alpha-adrenergic agonist, which may have delayed intestinal transport of hydrochlorothiazide, resulting in enhanced gastrointestinal absorption.

Adult↗
PubMed1984

An affinity technique for the isolation of Clostridium perfringens type C from man and pigs in Papua New Guinea.

Necrotising enteritis caused by Clostridium perfringens type C (CwC) is an important cause of morbidity and death in highland regions of Papua New Guinea (PNG) and the organism is readily isolated from clinical cases. Although detected in fluorescent antibody stains of faecal cultures, CwC has previously only once been isolated from normal people or from pigs in PNG. The difficulty results from the greater numbers of the much more common Cl. perfringens type A (CwA) which is morphologically and culturally indistinguishable from CwC. Separation of CwC from the more numerous CwA has been achieved by utilising their antigenic dissimilarity. Silicate beads covered with specific antibody to CwC added to a mixed culture bound CwC cells while most of the unbound cells were washed away. When the beads were plated out type C organisms were recovered. In laboratory tests CwC was isolated from mixtures with CwA where the type A organisms predominated by one million to one. With this system type C organisms have been isolated from human and pig faeces from PNG.

Animals↗
PubMed1984

Antibodies to alcohol altered liver cell determinants in patients with alcoholic liver disease.

Circulating antibodies reacting specifically with hepatocytes isolated from ethanol pretreated rabbits have been demonstrated by two techniques - induced cytotoxicity and immunofluorescence. In the cytotoxicity assay antibodies were found in seven of 19 (39%) of patients with alcoholic fatty liver (with or without fibrosis), six of 13 (46%) of those with alcoholic hepatitis, 15 of 36 (43%) of those with cirrhosis, and seven of 14 patients (50%) of those with hepatitis and cirrhosis. In the immunofluorescence studies, nine of 15 sera induced a granular pattern of fluorescence on the ethanol pretreated hepatocytes; two sera which induced significant cytotoxicity did not induce immunofluorescence. No ethanol related antibodies were found in normal individuals or in patients with other types of acute or chronic liver disease. These results show that antibodies directed against ethanol altered liver cell determinants are present in the serum of 43% of patients with alcoholic liver disease, and suggest a mechanism whereby chronic alcohol consumption may, by inducing antigenic changes in hepatocyte membranes, trigger a cell damaging immune reaction.

Adult↗
PubMed1984

c-myc Gene activation and chromosomal translocation.

Burkitt's lymphoma cells are characterized by the presence of specific chromosomal translocation bringing the immunoglobulin and the c-myc proto-oncogenes into the proximity of each other. Different translocations involve each of the three immunoglobulin loci but the breakpoint with respect to the c-myc gene is shown to be very variable. In t8/14 the breakpoint occurs upstream from the c-myc gene whilst in the variant lymphomas it occurs downstream from the gene. Possible ways in which the translocation affects the c-myc gene are discussed.

Animals↗