Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 19 recordsLinked to original sources

PubMed1992

Expression of c-fos mRNA in acute and kindled cocaine seizures in rats.

In situ hybridization for c-fos mRNA was performed on brain sections (a) from rats after an acute cocaine-induced seizure or from saline-injected controls and (b) from rats after their first cocaine-kindled seizure, as well as from rats that had not yet developed cocaine-kindled seizures (but were exposed to the same amount of cocaine as those that did exhibit convulsions) and from saline-injected controls. Increased expression of c-fos mRNA was observed in animals demonstrating cocaine-induced seizures acutely or following pharmacological kindling. Rats that experienced acute seizures after cocaine (65 mg/kg) showed pronounced increase in expression of c-fos mRNA in the dentate gyrus of the hippocampus and olfactory bulb. Increases were also observed in several other limbic cortical regions, as well as the striatum and ventromedial hypothalamic nucleus (VMH). In rats that were injected daily with an initially subconvulsive dose of cocaine-HCl (40 mg/kg), the cocaine-kindled seizures induced elevations in c-fos mRNA in the same brain regions as with an acute cocaine-induced seizure with the single exception of the VMH. These findings not only suggest the involvement of limbic, cortical and striatal structures in the cocaine-induced seizure, but also raise the possibility that alterations in the proto-oncogene c-fos and its subsequent impact on gene expression could play a role in the changes in neural excitability associated with cocaine-induced kindling.

Animals↗

PubMed1992

Cholesterol-related counseling by registered dietitians in northern California.

BACKGROUND: An estimated 40 million Americans have serum cholesterol levels that warrant medically supervised dietary intervention. Although registered dietitians are expected to play an important role in treating these patients, current treatment practices in the community are largely unknown. METHODS: A questionnaire concerning treatment practices was mailed to all 377 registered dietitians listed in the directories of the American Dietetic Association for two large California districts. Number of patients seen and length and content of dietary counseling were ascertained for three types of patients: (a) hypercholesterolemic outpatients without heart disease, (b) hypercholesterolemic outpatients who have heart disease, and (c) inpatients with myocardial infarction. RESULTS: A return rate of 59% (n = 252) was obtained for the questionnaire. A total of 44% of the registered dietitians counseled hypercholesterolemic patients in any of the categories surveyed. About 30% of the respondents counseled hypercholesterolemic outpatients without heart disease. They saw an average of 4.9 such patients a week, spent an average of 53 min in an initial session, and usually did not see the patient again in follow-up. Fewer than 10% of patients had as many as four sessions. About 27% of the respondents saw hypercholesterolemic outpatients with heart disease, averaging 3.5 such contacts per week. The reported practices were similar to those provided to noncardiac outpatients. About 22% of registered dietitians worked with hospitalized myocardial infarction patients. They spent an average of a total of 41 min over 2.5 visits with each patient. CONCLUSION: Currently, outpatient registered dietitian counseling for hypercholesterolemia appears to be limited in both the number of patients reached and the duration of the counseling. Further research into the impact of, barriers to, and efficacy of alternative delivery methods of dietary counseling is needed.

Adult↗

PubMed1992

Quantitative autoradiography of 3H-paroxetine binding sites in rat brain.

The use of 3H-paroxetine as a ligand for quantitative autoradiography of serotonin (5-HT) transport sites was optimized, and the distribution of 3H-paroxetine binding sites in rat brain was studied. Under the conditions described, 3H-paroxetine binding in forebrain sections was of high affinity and saturable, with a Kd of 0.18 +/- 0.02 nM (mean +/- SEM) and Bmax of 268 +/- 12 fmol/mg of protein (n = 3). Nonspecific binding was 10.7% +/- 1.0 of the total binding (n = 8). The distribution of 3H-paroxetine binding sites closely matched the regional distribution of 5-HT nerve terminals and cell bodies. The highest concentrations of 3H-paroxetine binding sites were found in the dorsal raphe nucleus (563 +/- 55 fmol/mg tissue, n = 4), and high densities of binding were also found in the locus coeruleus, medial forebrain bundle, substantia nigra, several limbic structures (amygdala, hippocampus, hypothalamus, olfactory tubercle, septum, and thalamus), and components of the visual relay system (superior colliculus and the lateral geniculate body). Although lesioning of 5-HT neurons with p-chloroamphetamine (PCA) drastically eliminated 3H-paroxetine binding in most regions of the rat brain, significant binding remained in the raphe nuclei and medial forebrain bundle suggesting that 3H-paroxetine binding in these regions was to presynaptic sites on cell bodies or axons relatively resistant to PCA.

Animals↗

PubMed1992

Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19).

Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.

Animals↗

PubMed1992

Matching patient need for pressure sore prevention with the supply of pressure redistributing mattresses.

The authors have conducted a series of pressure sore prevalence surveys within one health district over a 4-year period. Additional surveys of the availability and deployment of pressure redistributing (PR) bed mattresses have also been made within the same district. The prevalence of pressure sores increased from 6.8% (1986) to 14.2% (1989) while the available stocks of PR mattresses increased from 69 (1987) to 186 (1989). Our results appear to question the common assumption that successful pressure sore prevention can be achieved through expanding the stocks of PR mattresses. Five possible reasons why the increase in mattress provision was matched with an increased prevalence of pressure sores are forwarded. The use of measures of prevalence rather than incidence rates to monitor the effects of clinical initiatives is discussed.

Beds↗

PubMed1992

Intrinsic factors associated with pressure sores in elderly people.

As a preliminary to a larger, prospective study of intrinsic factors associated with pressure sore development in a population of elderly hospital in-patients, this retrospective study of patients who had participated in an earlier, unrelated study was completed. The results of biochemical and haematological analyses from admission, together with details of nursing care, were obtained from medical and nursing notes, and analysed in relation to the condition of the pressure areas of each patient, which had been documented by a single observer throughout the period of study. The relationships between intrinsic factors such as serum protein concentration and systolic blood pressure, and the presence of, or tendency to develop pressure sores is examined and discussed in the light of a need for more specific and sensitive risk assessment tools.

Aged↗

PubMed1992

Tolerance to adenosine's accentuation of ethanol-induced motor incoordination in ethanol-tolerant mice.

Our previously published reports have provided data that have supported a functional correlation between ethanol-induced changes in the characteristics of adenosine receptor, adenosine uptake and release in the brain, and ethanol-induced motor incoordination. The present data demonstrated a cross-tolerance between ethanol and adenosine further supporting the hypothesis that brain adenosine modulates the motor impairing effects of ethanol. Mice that received (-)-N6-cyclohexyladenosine (CHA) [0.25 mg/kg/day, intraperitoneally (ip)] for 10 days exhibited marked attenuation (cross-tolerance) to acute ethanol-induced motor incoordination compared with chronic saline (ip) controls. The attenuation of acute ethanol-induced motor incoordination was essentially same in animals that received CHA (25 ng/5 microliters/day for 10 days) by the intracerebroventricular (icv) route as opposed to the controls that chronically received artificial cerebral spinal fluid by the same route. Similarly, tolerance was exhibited to acute CHA (0.125 mg/kg ip and 12.5 ng/5 microliters icv) by animals fed liquid ethanol (19.5 g/kg/24 hr) for 10 days compared with none in the pair-fed sucrose controls. Scatchard plots using cerebellar tissue homogenates from animals given chronic CHA or chronic ethanol indicated no change in Bmax and/or Kd values for CHA binding when compared with CHA binding in tissues from their respective controls. However, a lack of any change in the binding characteristics cannot rule out the involvement of adenosine receptors in the observed cross-tolerance between ethanol and CHA. The results may suggest desensitization of adenosine A1 receptors due to chronic CHA and ethanol as an alternate possible explanation in the development of cross-tolerance between adenosine (CHA) and ethanol.

Adenosine↗

PubMed1992

Endomysial antibody: is it the best screening test for coeliac disease?

The sensitivities and specificities of the IgA and IgG antigliadin antibody and the IgA antireticulin antibody have been compared with the recently described endomysial antibody directed against the basement membrane of smooth muscle in monkey oesophagus. One hundred and seventeen patients with adult coeliac disease (21 untreated), 84 patients with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis (comprising the disease control group), 47 normal controls and a miscellaneous group of 29 patients, who were selected because of a positive reticulin staining pattern, were investigated. These results were correlated with the degree of abnormality of the intestinal mucosa in patients with adult coeliac disease. Endomysial antibodies were found in all patients with untreated coeliac disease and subtotal villous atrophy and in 47% of patients on a non-strict gluten free diet. One patient on a strict gluten free diet was positive and had partial villous atrophy while all patients in disease control groups were negative. Results were variable with the antireticulin and antigliadin antibodies. Sensitivity and correlation with subtotal villous atrophy in the untreated patients was 100%. It is concluded that the endomysial antibody is superior to other current antibody tests and should be used in preference for the diagnosis of coeliac disease.

Adolescent↗

PubMed1992

Expression of receptors for atrial natriuretic peptide on the murine bone marrow-derived stromal cells.

Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [125I]ANP binding assays and Northern blot analyses. The binding of [125I] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [125I]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [125I]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [125I]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow.

Animals↗

PubMed1992

Pulling together: building a community debriefing team.

1. Research shows that many emergency workers are affected physically and emotionally by critical incident stress. 2. Debriefings conducted by trained team members are an effective method to mitigate the impact of critical incident stress. A debriefing is a structured, time-limited group intervention. 3. Cooperation among community agencies is essential for the development and effective functioning of a critical incident stress debriefing team. 4. Several teams in Illinois have organized to form a Critical Incident Stress Debriefing Network. The Illinois network is part of an international organization composed of critical incident stress debriefing providers.

Adaptation, Psychological↗

PubMed1991

Use of anion-exchange chromatography and chromatofocusing to reveal the structural and functional heterogeneity of topoisomerase II in a HL-60 cell line resistant to multi-drug treatment.

Fractionation of nuclear extracts from a multi-drug-resistant subclone of the human promyelocytic subline HL-60 by anion-exchange chromatography and chromatofocusing resolves at least two different subtypes of topoisomerase II, which are not identical to the known alpha- and beta-forms of the enzyme because both forms are contained in each subtype. The two subtypes are present in about equal proportions and differ remarkably with respect to the optimum of reaction and sensitivity to m-amsacrine and orthovanadate. Both subtypes are highly insensitive to etoposide inhibition in vitro.

Amsacrine↗

PubMed1991

Expression of c-fos mRNA in rat brain after intracerebroventricular administration of corticotropin-releasing hormone.

Expression of the proto-oncogene c-fos is known to increase in rat brain following various types of seizures. Measuring c-fos mRNA or protein levels was shown to be a good cellular marker for neurons activated during central nervous system (CNS) excitation. In this study, we used in situ hybridization analysis of c-fos mRNA to determine brain regions activated by a peptide that has been closely linked to stress responsivity and kindling-like seizure activity. Corticotropin-releasing hormone (CRH) was injected into the left lateral ventricle of rats and produced the late onset of seizures between 1.5-5 h after its administration. Rats were sacrificed at various time points after the administration of CRH or sterile water, and c-fos mRNA levels were determined. In the preseizure state, CRH increased c-fos unilaterally in several cerebral cortical structures (most prominently in the dorsal endopiriform nucleus and in the piriform and insular cortices). CRH-induced seizures increased c-fos bilaterally in the same cortical regions, and in addition, in the hippocampus and olfactory bulb. The data are congruous with the hypothesis that intracerebroventricularly (i.c.v.) administered CRH elicits a rapid kindling-like response.

Animals↗

PubMed1991

Angiotensin II-induced phosphatidylcholine hydrolysis in cultured vascular smooth-muscle cells. Regulation and localization.

In cultured vascular smooth-muscle cells (VSMC), angiotensin II (AngII) induces a biphasic, sustained increase in diacylglycerol (DG) of unclear origin. To determine whether hydrolysis of phosphatidylcholine (PC) is a possible source of DG, we labelled cellular PC with [3H]choline, and measured the formation of intra- and extra-cellular [3H]choline and [3H]phosphocholine after stimulation with AngII. AngII induced a concentration-dependent release of choline from VSMC that was significant at 2 min and was sustained over 20 min. In contrast, accumulation of choline inside the cells was very slight. AngII also increased the formation of [3H]myristate-labelled phosphatidic acid, and, in the presence of ethanol, of [3H]phosphatidylethanol, characteristic of a phospholipase D (PLD) activity. Extracellular release of choline was partially inhibited by removal of extracellular Ca2+ (54 +/- 9% inhibition at 10 min) or inhibition of receptor processing by phenylarsine oxide (79 +/- 8% inhibition at 20 min). The protein kinase C activator phorbol myristate acetate also stimulated a large release of choline after a 5 min lag, which was unaffected by the Ca2+ ionophore ionomycin, but was additive with AngII stimulation. Down-regulation of protein kinase C by a 24 h incubation with phorbol dibutyrate (200 nM) decreased basal choline release, but had no effect on AngII stimulation. We conclude that AngII induces a major PC hydrolysis, probably mainly via PLD activation. This reaction is partially dependent on Ca2+ and is independent of protein kinase C, and appears to be mediated by cellular processing of the receptor-agonist complex. Our results are consistent with a preferential hydrolysis of PC from the external leaflet of the plasmalemma, and raise the possibility that PC hydrolysis occurs in specialized 'signalling domains' in VSMC.

Angiotensin II↗

PubMed1991

Rupture of the left ventricular free wall following mitral valve replacement for mitral stenosis: a cause of complete (fatal) or contained (false aneurysm) cardiac rupture.

Complete or incomplete left ventricular free wall rupture is a known complication of mitral valve replacement. Complete free wall rupture may result in fatal bleeding, whereas incomplete rupture may result in the formation of a pseudoaneurysm with survival possible. Two necropsy patients are described illustrating both of these complications. Proposed mechanisms for injury to the left ventricular free wall are reviewed.

Aged↗

PubMed1991

A humanized monovalent CD3 antibody which can activate homologous complement.

The rat monoclonal antibody (mAb) YTH12.5, specific for the CD3 antigen complex on human T cells has been modified in order to improve its efficacy in human therapy. With the aim of rendering it less immunogenic, it has been humanized using the method of framework grafting. During this process sequence analysis of the YTH12.5 VL gene indicated that it was of the lambda subclass, however, it was markedly dissimilar from previously published rat and mouse V lambda gene sequences and may represent a new V lambda gene family. The humanization of this light chain represents the first successful reshaping of a lambda light chain V region. To improve the effector function of the antibody we have created a monovalent form (1 Fab, 1 Fc) using a novel method involving the introduction of an N-terminally truncated human IgG1 heavy chain gene into cells producing the humanized CD3 mAb. Comparison of the mono- and bivalent humanized mAb in a complement-mediated cell lysis assay revealed that the monovalent antibody mediated lysis of human T cell blasts whereas the bivalent form did not. The availability of a humanized, complement-fixing CD3 mAb may improve opportunities for human therapy, in the management of organ rejection, autoimmunity and the treatment of T cell lymphoma.

Amino Acid Sequence↗

PubMed1991

Mononeuropathy in sickle cell anemia: anatomical and pathophysiological basis for its rarity.

Peripheral neuropathy is a rare complication of sickle cell disease. We report a young black woman with sickle cell anemia who developed a proximal median mononeuropathy in the setting of sickle cell crisis. The clinical and electrodiagnostic features are consistent with an ischemic mechanism from the sickling process. The pathophysiological basis for the rarity of this complication may be related to the rich anastomotic microvasculature of peripheral nerve and the unique large size of the capillaries of this vascular network.

Adult↗

PubMed1991

Early anti-HBs antibody response to accelerated and to conventional hepatitis B vaccination regimens in healthy persons.

A significantly higher prevalence of a protective concentration of anti-HBs was achieved at 1 and 2 months among 132 healthy medical students who received an accelerated vaccination schedule with a recombinant hepatitis B vaccine (Engerix-B) than among 120 medical students who received a conventional regimen. With the accelerated schedule, however, 60% students at 1 month and 27% at 2 months were still unprotected (anti-HBs titre less than 10.0 IU/l). Additional passive immunisation should therefore continue to be offered if the accelerated schedule is adopted for post-exposure prophylaxis.

Adult↗

PubMed1991

Regional expression of c-fos mRNA in rat brain during the evolution of amygdala kindled seizures.

The biochemical alterations eliciting the growth and spread of afterdischarge and accompanying the evolution of behavioral seizure stages in electrical kindling are not known. In situ hybridization for c-fos mRNA was used to map potential brain structures recruited during the evolution of major seizures from electrical kindling of the amygdala in rats. Two different patterns of c-fos induction were observed in the earliest stages of kindling (stages 1 and 2). A unilateral cortical distribution included the insular, temporal, perirhinal and parietal cortices and the amygdala. No changes in the hippocampus were noted in this group. The second distribution pattern was limited to the hippocampus (either unilateral or bilateral) and amygdala (unilateral) with no changes in the cortical areas. The afterdischarge durations were significantly (2 fold) longer in the 'hippocampal' group as compared to the 'cortical' group. In the later stages of kindling (stages 4 and 5) the distribution of c-fos mRNA was uniformly bilateral and involved a combination of the hippocampal and cortical distributions observed in the earlier stages and including the amygdala bilaterally as well. The induction of c-fos mRNA appears to provide a map of two different routes in the sequential pathways involved in the evolution of kindled seizures; it may also ultimately prove to be an important component of the kindling process itself. Additionally, c-fos mRNA was elevated bilaterally in the inferior colliculus of animals exhibiting running fits with their seizures. The inferior colliculus was previously shown by others to be involved in running fits accompanying convulsions.

Amygdala↗