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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 487 records · Page 27Linked to original sources
PubMed1986

The role of spinal cord cyclic AMP in the acoustic startle response in rats.

Drugs thought to increase intracellular levels of cAMP were infused intrathecally into the subarachnoid space of the lumbar spinal cord, and the effects on the acoustic startle response in rats were measured. Intrathecal infusions of the cAMP analogs dibutyryl cAMP or 8-bromo cAMP (12.5-100 micrograms) produced marked, dose-dependent increases in startle amplitude compared to the infusion of artificial cerebrospinal fluid (CSF). Local infusions of dibutyryl cAMP at more rostral levels of the spinal cord or brain failed to mimic the excitatory effect seen following lumbar intrathecal infusion. No excitation of startle was seen following intrathecal infusion of cAMP itself, ATP, 5'-AMP, or dibutyryl cGMP. A weak excitation of startle was seen following intrathecal, but not intraventricular, infusion of the water-soluble adenylate cyclase activator forskolin 7-deacetyl-7-O-hemisuccinic acid (forskolin-DHA; 5.0-100 micrograms, in artificial CSF), whereas forskolin itself [0.01-200 micrograms, in dimethyl sulfoxide (DMSO)] was without consistent effect. Finally, intrathecal infusion of the selective phosphodiesterase inhibitor Rolipram (12.5-200 micrograms) produced a marked excitation of startle similar in magnitude to the effects produced by cAMP analogs. The excitatory effects of intrathecally infused dibutyryl cAMP, 8-bromo cAMP, forskolin-DHA, or Rolipram support a functional link between spinal cord cAMP and the acoustic startle reflex. Possible sites of cAMP action on startle are discussed.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Aneurysmal malformation of the extrahepatic portal vein.

Malformations of the extrahepatic portal vein are quite rare. A 6-cm aneurysmal malformation of the extrahepatic portal vein, thought to be congenital in origin, is described. An English language literature review yielded only six similar cases, each of which was associated with portal hypertension, primary hepatocellular disease, or both. The patient reported herein had cholelithiasis with chronic cholecystitis, but no primary liver disease or vascular disease. We believe this is the first report of such an anomaly.

Adult↗
PubMed1985

Genetic markers of the antigen-specific T cell receptor locus.

The restriction enzyme Eco RI reveals DNA cleavage sites that serve to distinguish the gene locus believed to encode the beta subunit of the major histocompatibility complex (MHC)-restricted, antigen-specific receptor of the T cell in BALB/c mice from that of SJL/J mice. A monoclonal antibody, KJ16-133, also distinguishes BALB/c and SJL/J, because it recognizes an allotypic marker present on a cell-surface heterodimer believed to function as the MHC-restricted, antigen-specific T cell receptor. This study has shown that these two markers cosegregate in a set of BALB/c X SJL/J recombinant inbred (RI) mouse strains, permitting the conclusion that they are linked to within 3 centimorgans of each other, and to the kappa locus on chromosome 6. The tight linkage between these independently derived, totally different T cell markers substantially strengthens the argument that they characterize the MHC-restricted antigen-specific receptor of the effector T cell.

Alleles↗
PubMed1985

Central noradrenergic involvement in yohimbine excitation of acoustic startle: effects of DSP4 and 6-OHDA.

It was previously shown that i.p. administration of the alpha 2-adrenergic antagonist yohimbine increased the magnitude of the acoustic startle response in rats. The purpose of the present study was to determine possible central noradrenergic involvement in yohimbine's effect on startle. Pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromo-benzylamine (DSP4; 50 mg/kg, i.p.; 1-2 days before testing) completely blocked the excitatory effect of yohimbine on startle. DSP4 reduced forebrain and spinal cord NE levels by 47% and 56%, respectively, without affecting forebrain or spinal serotonin (5-HT), or forebrain dopamine (DA). Pretreatment with the NE reuptake blocker desmethylimipramine (DMI; 20 mg/kg, i.p.; 30 min before DSP4) prevented the ability of DSP4 to block the yohimbine effect. DMI partially reversed the NE-depleting effects of DSP4. Neither bilateral adrenalectomy nor intravenously administered 6-hydroxydopamine (6-OHDA; 20 mg/kg; 1-2 days before testing) altered the excitatory effect of yohimbine, indicating that peripheral NE is not involved. 6-OHDA (2 X 200 micrograms) injected into the lateral ventricles blocked yohimbine's effect, and depleted NE by 95% (spinal cord) and 86% (forebrain), without affecting 5-HT in either region. 6-OHDA also depleted forebrain DA levels by 49%. Finally, intrathecal administration of 6-OHDA (20 micrograms; 14 days before testing) into the subarachnoid space of the lumbar spinal cord blocked the excitatory effect of yohimbine, and produced an extensive (94%) depletion of spinal cord NE. Intrathecal 6-OHDA did not alter spinal levels of 5-HT or forebrain levels of NE, 5-HT or DA. In summary, these data indicate that central descending NE neurons are necessary for yohimbine's excitatory effect on startle.

Animals↗
PubMed1985

Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms.

A human complementary DNA clone specific for the alpha-chain of the T-cell receptor and a panel of rodent X human somatic cell hybrids were used to map the alpha-chain gene to human chromosome 14 in a region proximal to the immunoglobulin heavy chain locus. Analysis by means of in situ hybridization of human metaphase chromosomes served to further localize the alpha-chain gene to region 14q11q12, which is consistently involved in translocations and inversions detectable in human T-cell leukemias and lymphomas. Thus, the locus for the alpha-chain T-cell receptor may participate in oncogene activation in T-cell tumors.

Animals↗
PubMed1985

Antagonism of apomorphine-enhanced startle by alpha 1-adrenergic antagonists.

The present study investigated the possible involvement of central noradrenergic neurons in mediating the excitatory effect of the dopamine agonist apomorphine on the acoustic startle response in rats. Experiment 1 assessed the effects of intraperitoneal (i.p.) administration of adrenergic antagonists on apomorphine-enhanced startle. The excitation of startle produced by apomorphine (1.0-3.0 mg/kg i.p.) was blocked by the alpha 1-adrenergic antagonists prazosin (0.03-1.0 mg/kg) and WB-4101 (1.0 mg/kg). Prazosin was very potent in this regard, having an ED50 of 0.03 mg/kg. Blockade of beta-adrenergic receptors with propranolol (20 mg/kg) or blockade of peripheral alpha-adrenergic receptors with phentolamine (10 mg/kg) failed to alter the effect of apomorphine. Prazosin did not block the enhancement of startle produced by other drugs (5-methoxy-N,N-dimethyltryptamine, strychnine), nor did it alter the entry of apomorphine into the brain. The alpha 1-adrenergic antagonists piperoxane (0.03 mg/kg), yohimbine (0.03 mg/kg) or RX781094 (0.07 mg/kg) markedly potentiated apomorphine excitation. These data indicated that specific blockade of central alpha 1-adrenergic receptors prevents apomorphine-enhanced startle. In contrast to the effects of alpha 1-adrenergic antagonists, Experiment 2 found that other drugs that produce an acute (clonidine, 0.040 mg/kg) or chronic (intraventricular 6-hydroxydopamine, 2 X 200 micrograms; DSP4, 50 mg/kg i.p.) disruption of noradrenergic transmission failed to affect apomorphine excitation. Thus, the ability of alpha 1-adrenergic antagonists to block apomorphine's excitation of startle cannot be explained by a simple dopamine-norepinephrine interaction. Alternative hypothesis are discussed.

Adrenergic alpha-Antagonists↗
PubMed1985

Cocaine: excitatory effects on sensorimotor reactivity measured with acoustic startle.

Cocaine (2.5-10 mg/kg) caused a dose-related increase in the amplitude of the acoustic startle reflex in rats. In contrast, procaine (5-40 mg/kg) caused a dose-related decrease in startle, indicating that the effects of cocaine could not be ascribed to its local anesthetic effects. Cocaine's excitatory effects were blocked by pretreatment with haloperidol (0.5 mg/kg) but not by cyproheptadine or prazosin. The excitatory effects of cocaine (10 mg/kg) were markedly attenuated by pretreatment with reserpine (5 mg/kg 24 and 18 h earlier) but not by alpha-methyl-p-tyrosine (100 mg/kg 1 h earlier). In contrast, comparably sized excitatory effects of d-amphetamine were blocked by alpha-methyl-p-tyrosine and greatly enhanced by pretreatment with reserpine. Neither pretreatment blocked excitatory effects of apomorphine on startle. The data indicate that cocaine increases startle by acting through reserpine-sensitive pools of dopamine and provide further support for the conclusion that acoustic startle is enhanced by activation of dopamine receptors.

Acoustic Stimulation↗
PubMed1985

Cocaine: effects on acoustic startle and startle elicited electrically from the cochlear nucleus.

Startle-like responses can be elicited by single pulse electrical stimulation of nuclei within the acoustic startle pathway. Compared with acoustically-elicited startle, this technique provides a method for localizing the ultimate sites of action of a drug that affects the acoustic startle response. Strychnine (1 mg/kg) increased both acoustically-elicited startle and startle elicited from the ventral cochlear nucleus (VCN), the first central nucleus in the acoustic startle pathway. In contrast, cocaine (10 mg/kg) increased acoustically-elicited startle but depressed VCN-elicited startle. These results suggest that cocaine increases startle by acting on sensory rather than final motor systems and are discussed in relation to the putative effect of cocaine on dopamine neurotransmission and the involvement of dopamine in sensorimotor reactivity.

Acoustic Stimulation↗
PubMed1985

Fear-enhanced acoustic startle is not attenuated by acute or chronic imipramine treatment in rats.

The effect of acute or chronic administration of imipramine on fear-enhanced startle (potentiated startle) in rats was investigated. Thirty male albino rats were initially given preliminary startle testing, assigned to one of three matched groups, and trained for potentiated startle by presenting ten light-shock pairings on each of 2 days. Subsequent startle testing following a single injection of 0, 5 or 10 mg/kg imipramine revealed that the degree of startle potentiation (increased responding in the presence of the light previously paired with shock) was similar across treatment conditions. A significant and comparable potentiation of startle was observed in animals treated chronically with saline or imipramine (10 mg/kg/day) for 21 days between training and testing. Potentiated startle was also observed in these animals on the next (22 nd) day after injection of an additional dose of the drug (10 mg/kg) 5 min prior to testing. Plasma levels of imipramine and its metabolite, desipramine, were relatively high after each of these treatments. Since previous studies have shown that potentiated startle is decreased by diazepam, the present findings suggest that the potentiated startle paradigm is a valid model for studying simple fear or anxiety rather than panic disorder.

Acoustic Stimulation↗
PubMed1985

Estrogen and thyroid-stimulating hormone (TSH) receptors in neoplastic and nonneoplastic human thyroid tissue.

Estrogen-binding receptors (ER) and thyroid-stimulating hormone (TSH) receptors were observed in the cytosol and in a membrane particulate fraction, respectively, in most neoplastic and nonneoplastic human thyroid tissues. Fourteen of 15 thyroid neoplasms and 6 of 15 nonneoplastic thyroid specimens had estrogen receptors (assuming the sensitivity of our estrogen receptor assay is 0.2 fmole/mg protein), and 14 of 15 thyroid neoplasms and 11 of 15 nonneoplastic thyroid specimens had a high affinity, low capacity TSH receptor. Neoplastic thyroid tissue had more ER (2.35 +/- 0.70/fmole/mg protein) than nonneoplastic thyroid tissue (0.57 +/- 0.181/fmole/mg protein) removed from the same patients (P less than 0.05). The Kd for ER did not differ in nonneoplastic (0.41 +/- 0.090 nM) and neoplastic (0.311 +/- 0.048 nM) thyroid tissue. The number of TSH receptors was comparable in neoplastic (0.609 +/- 0.191 pmole/mg protein) and in nonneoplastic (0.765 +/- 0.181 pmole/mg protein) thyroid tissue removed from the same patients who had the ER studies. The maximal adenylate cyclase response to TSH was greater in the neoplastic (147 +/- 26.9 pmole/mg protein/30 min) than in nonneoplastic thyroid tissue (32.8 +/- 6.69 pmole/mg protein/30 min) (P less than 0.001) suggesting a greater metabolic responsiveness of the neoplastic thyroid tissue to TSH. No correlation was evident, however, between the number of estrogen and TSH receptors in nonneoplastic and neoplastic thyroid tissue (r = 0.226). This study demonstrates that neoplastic human thyroid tissues have both estrogen receptors and TSH receptors. The neoplastic tissue also has a greater AC response to TSH than nonneoplastic thyroid tissue.

Adenocarcinoma↗
PubMed1985

Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis.

Sixty-four patients admitted with acute alcoholic hepatitis, with or without underlying cirrhosis, were randomized regardless of encephalopathy to receive a controlled diet either alone, or supplemented orally, nasogastrically, or intravenously as necessary, with 2000 kCal and 10 g nitrogen daily. Whether this came from a conventional protein source or a branched chain amino acid enriched formulation was also randomly determined. In the absence of renal failure, nitrogen intakes of 10 g or more daily were invariably associated with positive nitrogen balance, but complications of liver dysfunction prevented the attainment of significantly more positive balance in the supplemented groups than in controls. Neither in the series as a whole, nor in any identifiable subgroup of patients, was mortality affected by treatment. Changes in prothrombin time and in measured nutritional parameters during the study did not differ between supplemented and control groups, and the observed changes in midarm muscle circumference appeared to reflect changes in degree of fluid retention. Neither enteral nor parenteral branched chain amino acids showed any consistent effect upon encephalopathy.

Amino Acids, Branched-Chain↗
PubMed1985

Associative learning modifies startle reflexes at the lateral lemniscus.

Acoustic and electrical brain stimulation studies have revealed that the ventral nucleus of the lateral lemniscus is a specific site within the brain stem where a previously conditioned stimulus modulates a simple reflex, the acoustic startle response. Sixty rats were implanted with bilateral electrodes in the ventral cochlear nucleus (VCN), ventral acoustic stria (VAS), dorsal lateral lemniscus (DLL), ventral lateral lemniscus (VLL), or the nucleus reticularis pontis caudalis (RPC). Following recovery all rats were conditioned to be fearful of a light by pairing a light with a shock for 10 trials on each of 2 days. One day later, the rats were placed in cages equipped to measure startle responses. Startle was elicited either acoustically or electrically through the electrodes that had been implanted in various parts of the acoustic startle circuit. Startle was elicited in darkness or during a brief presentation of the ligh previously paired with the shock. In all groups, acoustic startle amplitude was significantly greater in the presence of the light than it was in darkness, which is consistent with previous data showing that fear increases startle. Startle elicited electrically from the VCN, VAS, and VLL was also significantly increased by the light. In contrast, startle elicited electrically in the DLL or the RPC was not affected by the light despite the fact that the same rats in the same test session had elevated acoustic startle amplitude in the presence of light. Thus, it seems that for the first time in a complex vertebrate, a locus has been found within the nervous system (the VLL) where a conditioned stimulus acts to alter neural transmission so as to affect behavior.

Acoustic Stimulation↗
PubMed1985

Clinical presentation of pyogenic liver abscess in the elderly.

The presenting features of seven elderly patients with pyogenic liver abscess were reviewed retrospectively. Symptoms of malaise, anorexia and abdominal pain referrable to intra-abdominal pathology were present in only 43% cases and physical examination was frequently unhelpful. Leucocytosis, hyperbilirubinaemia and raised alkaline phosphatase were of diagnostic value in the majority of patients. Chest and urinary tract infections were frequent predisposing conditions. Antibiotic therapy for four weeks is adequate in elderly patients if combined with drainage procedures.

Abdomen↗
PubMed1985

Predicting the risk of abdominal disease in Hodgkin's lymphoma. A multifactorial analysis of staging laparotomy results in 255 patients.

There were 425 consecutive patients treated for Hodgkin's disease at this Medical Center from 1943 to 1983. Of these, 255 patients underwent a staging laparotomy and had complete preoperative clinical records. Overall, 35% had a change in stage (24% were upstaged, 11% downstaged). Twenty-nine per cent of clinical stage I patients were upstaged; 31% of stage II patients were upstaged, while less than 1% were downstaged; and four per cent of stage III patients were upstaged while 44% were downstaged. The diagnostic laparotomy yielded involvement in the spleen in 71% of patients with abdominal involvement, in the periaortic lymph nodes in 41%, in the liver in 11%, and the bone marrow in seven per cent. Only 12% of the 135 patients with negative laparotomies subsequently relapsed in the abdomen after a mean follow-up of 4.8 years. A multifactorial analysis was performed to identify dominant factors predicting the risk for abdominal disease. The factors best predicting abdominal involvement in stage I and II patients were: antecedent symptoms (greater than or equal to 2, 1, 0; p less than 0.00001), histological type [nodular sclerosing (NS) less than lymphocyte-predominant (LP) less than mixed cellularity (MC) less than lymphocyte-depleted (LD); p = 0.0009], and sex (females less than males, p = 0.01). The clinical stage (I vs. II), the site of lymphoma presentation, and the age and race of the patient did not have significant predictive value for the risk of abdominal disease after the other factors were accounted for. A mathematical model was derived for identifying dominant prognostic factors for predicting the risk of abdominal disease in an individual patient setting. The lowest risk patients were asymptomatic females with NS histology (6%) or LP histology (8%), while the highest risk patients were men with multiple symptoms and either MC histology (85%) or LD histology (93%). This information can be useful in making clinical decisions in Hodgkin's lymphoma patients, especially those at an increased risk for surgery.

Hodgkin Disease↗
PubMed1985

Breakage on chromosome 2 brings the Ck gene to a region 3' of c-myc in a Burkitt's lymphoma line carrying a (2;8) translocation.

We have shown using in situ hybridization that the constant region of the kappa light chain immunoglobulin gene (Ck) is translocated from chromosome 2 to chromosome 8 in Burkitt's lymphoma cells with a (2;8) translocation. The Ck gene then ends up adjacent to and on the 3' side of c-myc. The breakpoint probably falls between the gene for the variable region of the kappa light chain (Vk) and the Ck gene.

Burkitt Lymphoma↗