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Biomedical subjects

D R Hill

Publications and source records attributed to D R Hill.

At least 19 recordsLinked to original sources
PubMed1992

Amide bond replacements incorporated into CCK-B selective "dipeptoids".

This paper describes the chemical synthesis and CCK-B and CCK-A receptor binding affinities of a series of compounds in which the central amide bond of the CCK-B "dipeptoid" ligand tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,S*)]-[2-[[1-(hydroxymethyl)- 2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]carb amate (4) (CCK-B IC50 = 852 nM), and tricyclo[3.3.1.1(3,7)]dec-2-yl (R)-[1-(1H-indol-3-ylmethyl)-1-methyl- 2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamate (23) (CCK-B IC50 = 32 nM) is replaced by 11 different amide replacements. These replacements are the methyleneamino (CH2NH), the reverse amide (NHCO), the ester (COO), the N-methylamide (CONMe), the thioamide (CSNH), the N-acetylmethyleneamino (CH2NAc), the cis double bond (CHCH), the ethylene (CH2CH2), the thiolester (COS), the hydroxyethylene (CHOHCH2), and a 4,5-dihydro-1,3-thiazole. Most of the replacements have weaker affinity and reduced selectivity for the CCK-B receptor than the parent amide. However, this affinity can be improved by appending a fumarate side chain to the phenethyl group, e.g. tricyclo[3.3.1.1(3,7)]dec-2-yl-3-(1H-indol-3-yl-methyl)-3-methyl-4 ,9- dioxo-7-phenyl-5,13-dioxa-2,8-diazatetradec-10-enoate (36) (CCK-B IC50 = 38.8 nM). Replacement of the amide of compound 4 with a 4,5-dihydro-1,3-thiazole gives tricyclo[3.3.1.1(3,7)]dec-2-yl [1-[4,5-dihydro-4-(phenylmethyl)-2- thiazolyl]-2-(1H-indol-3-yl)ethyl]carbamate (5), which is selective for the CCK-A receptor (CCK-A IC50 = 125 nM, CCK-B IC50 = 2580 nM, ratio = 21). The methyleneamino and hydroxyethylene replacements, which have been used elsewhere as transition-state inhibitors of enzymes, are poor mimics of the amide in these CCK-B receptor ligands. Some of the steric, lipophilic, and hydrogen bonding properties of amide replacements incorporated into the simple amide, N-methylacetamide, have been quantified with the aid of molecular modeling. These data will contribute to the rational selection of amide bond replacements in other substrates.

Amides↗
PubMed1992

Autoradiographic visualization and characteristics of [125I]bradykinin binding sites in guinea pig brain.

The present study was undertaken to localize and characterize bradykinin (BK) binding sites in 10 microns serial sections of guinea pig brain by in vitro quantitative receptor autoradiography. Specific binding of [125I-Tyr8]bradykinin ([125I]BK) was localized in the medulla oblongata to the regions of the nucleus of the solitary tract (nTS), the area postrema (AP), the dorsal motor nucleus of the vagus (X) and the caudal subnucleus of the spinal trigeminal nucleus. No significant specific [125I]BK binding was seen in other brain regions. The specific binding (85-90% of total binding) was of high affinity and saturable with a KD of 73.5 +/- 9.9 pM and a Bmax of 27.8 +/- 1.9 amol per mm2 of tissue. In competition studies, the rank order of potencies was: BK greater than Met-Lys-BK greater than Lys-BK much greater than Des-Arg9-BK. The B2 receptor antagonist D-Arg0-Hyp3-Thi5,8-D-Phe7-BK inhibited [125I]BK binding with a Ki value of 3.5 +/- 1.5 nM while Des-Arg9-[Leu8]-BK, a B1 receptor antagonist did not significantly inhibit [125I]BK binding in concentrations up to 10 microM. Our finding of specific high affinity [125I]BK binding sites in the nTS, AP and the X is important because these brain areas are known to be involved in central cardiovascular regulation. Moreover, our results suggest that the specific [125I]BK binding sites in the guinea pig medulla are of the bradykinin B2 receptor type.

Animals↗
PubMed1992

Psychosocial interventions in adult patients with coronary heart disease and cancer. A literature review.

A growing body of evidence suggests that chronic medical illness is associated with an increased prevalence and incidence of psychiatric and psychological disturbances. The present literature review is based on two theses: first, that chronic illness is viewed as a stressor and is associated with increased psychological distress, and secondly, that interventions can minimize the distress. A review of the studies conducted with adult patients diagnosed either with coronary heart disease or cancer suggests that psychosocial interventions are, in general, efficacious in relieving self-reported psychological distress. The review also recommends psychosocial interventions for high-risk patients rather than all patients, and that researchers need to identify other outcomes such as health care costs, disability, days in hospital, morbidity, and mortality in order to convince policy makers that these interventions are worthwhile. Recommendations for future research are also discussed.

Adaptation, Psychological↗
PubMed1992

Capnocytophaga bacteremia in a patient with Hodgkin's disease following bone marrow transplantation: case report and review.

Capnocytophaga is a gram-negative, capnophilic, facultatively anaerobic bacillus that normally inhabits the oral cavity. We report the case of a patient who developed capnocytophaga bacteremia following autologous bone marrow transplantation for Hodgkin's disease, and we review other reported cases of capnocytophaga bacteremia in immunocompromised patients. In our case infection followed pretransplantation conditioning and was associated with severe oral mucositis and neutropenia. Antibiotic therapy resulted in clinical resolution of infection. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients (e.g., those undergoing bone marrow transplantation) especially in the presence of mucositis and gingival bleeding.

Adult↗
PubMed1992

Selected list of books and journals in allied health.

This list of 396 books and 77 journals is intended as a selection guide to be used in a library supporting allied health educational programs or allied health personnel in either an academic or health care setting. Due to the necessity of limiting the scope of coverage because of the large number and wide range of allied health professions and occupations, the recommended publications are focused primarily on the twenty-eight programs accredited by the Committee on Allied Health Education and Accreditation of the American Medical Association, plus physical therapy, dental allied health, medical secretarial, nutrition, and speech pathology/audiology. Books and journals are categorized by subject; the book list is followed by an author/editor index, and the subject list of journals is followed by an alphabetical title listing. Items suggested for initial purchase (194 books and 31 journals) are indicated by asterisks. To purchase the entire collection of books and journals (1992 subscriptions) would require an expenditure of about $22,800. The cost of only the asterisked items totals $10,850.

Allied Health Occupations↗
PubMed1992

Immunizations.

The protection of travelers against vaccine-preventable disease is an important part of pre-travel preparation. This review discusses immunizations that should be given as part of routine health maintenance, regardless of whether the individual is traveling. It also covers immunizations that may be required by a country as a condition for entry and those that are recommended because of a risk of acquiring a particular vaccine-preventable illness during travel. Prior to the administration of any of these vaccines, a careful health and immunization history and detailed travel itinerary should be obtained.

Communicable Disease Control↗
PubMed1991

Reduction of [125I]Bolton Hunter CCK8 and [3H]MK-329 (devazepide) binding to CCK receptors in the substantia nigra/VTA complex and its forebrain projection areas following MPTP-induced hemi-parkinsonism in the monkey.

Cholecystokinin (CCK) receptors were visualized autoradiographically using [125I]Bolton Hunter CCK8 ([125I]BHCCK8) in the fore- and midbrain of 3 monkeys rendered hemi-parkinsonian by unilateral intra-carotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). More specifically, CCK-A receptors were detected using [3H]MK-329 (devazepide), a peripheral-type (CCK-A) receptor antagonist. In the substantia nigra pars compacta, ipsilateral to the toxin infusion, where dopamine D2 receptors (labelled with [3H]sulpiride) were lost, there was a decrease in the binding of both [125I]BHCCK8 and [3H]MK-329. Binding of the two CCK ligands was also reduced in the ipsilateral nucleus accumbens and most medial part of the caudate nucleus, whereas 3H-sulpiride binding was increased in the lateral caudate nucleus and putamen. These results indicate that CCK-A receptors may be located on dopaminergic cells within the substantia nigra, which are lost in the parkinsonian brain, and may also be present on dopaminergic terminals within restricted regions of nigral/ventral tegmental area projection sites.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Gender differences in social support and physical health.

A large body of prospective data has accumulated linking social support to health, and most social scientists agree that low levels of support are associated with poor physical and mental health. Unfortunately, most of the research has been limited to White men. When women and people of color are included in the designs, the relationships between social support and physical health are more complicated. Prospective population-based studies provide evidence that low support is associated with increased risk of mortality in women. However, in several studies, results indicated that, for specific age groups, women with high social support have increased risk of mortality. Factors that may contribute to the observed gender differences in the social support-physical health relationship are discussed. Future research should include adequate numbers of women and more sophisticated measures of social support to move the field forward.

Adult↗
PubMed1991

Pre-travel health, immunization status, and demographics of travel to the developing world for individuals visiting a travel medicine service.

It is estimated that five million Americans will travel to the developing world over the next year. This study examines the demographic profile, past medical and immunization history, itinerary, and reason for travel of 2, 445 travelers to the developing world seen at a travel medicine service from 1984 through 1989. The travelers age ranged from three months to 85 years (mean age 43). A chronic medical condition was reported by 654 (27%). Four percent of all travelers were intolerant of sulfonamides, and 9% had contraindications to mefloquine for malaria prophylaxis. Many travelers were due to receive the primary series or updatings of routinely recommended immunizations: 43% for tetanus/diphtheria, 55% of those born after 1956 for measles, and 70% for polio if their travel itinerary included a polio risk. Most travel (71%) was for vacations, 13% was for teaching or study, 11% for business, and 5% for missionary activities. The median duration of travel was 21 days; 5% traveled for more than one year. While over 150 countries were visited, 52% of all travel was to 10 countries in East Africa, the Indian subcontinent, the Far East, and South America. Information about the epidemiology of travel to the developing world can help physicians and travel medicine services develop more effective preventive measures for travelers.

Adolescent↗
PubMed1991

Selected list of books and journals for the small medical library.

The current financial status of the health care industry is viewed both from its effect on the hospital library collection and the response of the hospital library to the financial crisis. Predecessors of this list have been intended as selection guides for a small or medium-size library in a hospital or comparable medical facility. As the prices of books and journals continue to soar, the secondary purpose as a core collection for a consortium of small hospital libraries or a network sharing library resources may eventually become its primary use. Books (607) and journals (140) are categorized by subject; the book list is followed by an author/editor index, and the subject list of journals by an alphabetical title listing. To purchase the entire collection of books and to pay for 1991 subscriptions would require about $77,700. The cost of only the asterisked items totals $29,300.

Forecasting↗
PubMed1990

Autoradiographic visualization of NK-3 tachykinin binding sites in the rat brain, utilizing [3H]senktide.

The autoradiographic distribution of the selective NK-3 tachykinin agonist [3H]senktide was investigated in rat brain. [3H]Senktide bound with high affinity (KD less than 2.5 nM) and high specificity (greater than 75%) to cerebral cortex and numerous subcortical sites, including the substantia nigra pars compacta. In addition, moderately dense binding was seen in the median but not the dorsal raphe nucleus, and this was disrupted by 5,7-dihydroxytryptamine (5,7-DHT)-induced destruction of 5-HT neurons. 5,7-DHT lesions did not affect the binding of [3H]senktide to forebrain regions, suggesting that 5-HT terminals are devoid of NK-3 receptors.

5,7-Dihydroxytryptamine↗
PubMed1990

Differentiation of central cholecystokinin receptor binding sites using the non-peptide antagonists MK-329 and L-365,260.

Cholecystokinin (CCK) receptor binding was measured in rodent and primate brain and spinal cord using 125I-Bolton Hunter CCK-8 (125I-BH-CCK) and the selective non-peptide CCK antagonists MK-329 and L-365,260. In homogenate binding studies, L-365,260 displayed nanomolar affinity for CCK-B receptors in the cerebral cortex of several species including man (pIC50 congruent to 8.2) but showed low affinity for CCK-A receptors in the rat pancreas (pIC50 congruent to 6.3). By contrast, the CCK-A antagonist MK-329 showed the reverse selectivity (cortex: pIC50 congruent to 6.9, pancreas: pIC50 = 9.6). In autoradiographs of rat and monkey brain. 125I-BH-CCK binding was localized regionally with high levels being detected in the cerebral cortex, basal ganglia and some mid- and hindbrain nuclei. Specific 125I-BH-CCK binding was also localized to the substantia gelatinosa of the rat, monkey and human spinal cord. L-365,260 inhibited binding to most areas of the brain, but in the rat medial nucleus tractus solitarii and the monkey nucleus tractus solitarii. dorsomedial nucleus and infundibular hypothalamic nuclei together with the dorsomedial aspects of the caudate nucleus, where CCK-A sites are present, L-365,260 failed to displace all 125I-BH-CCK binding. In the primate spinal cord, L-365,260 was a relatively weak inhibitor of 125I-BH-CCK binding (pIC50 congruent to 6.0) whereas MK-329 showed high affinity for the CCK-A sites present there (pIC50 congruent to 9.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Failure of omega-conotoxin to block L-channels associated with [3H]5-HT release in rat brain slices.

The effects of the mixed N- and L-type voltage-sensitive calcium channel (VSCC) antagonist, omega-conotoxin GVIA and the L-type VSCC agonist Bay K-8644 on calcium-dependent, potassium evoked release of [3H]5-hydroxtryptamine ([3H]5-HT) were investigated in slices of rat hippocampus. Bay K-8644 (1 microM) enhanced, whilst omega-conotoxin (10-30 nM) attenuated, but did not abolish, evoked release of [3H]5-HT. The facilitatory actions of Bay K-8644 on evoked release were unaffected by concentrations of omega conotoxin that significantly inhibited [3H]5-HT release. The experiments indicate that concentrations of omega-conotoxin which inhibit neurotransmitter release by blockade of N-type VSCC, may leave L-type calcium channel activity unaffected.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Ingestion of Giardia lamblia trophozoites by murine Peyer's patch macrophages.

Macrophages in Peyer's patches are important in the initiation of gastrointestinal immune responses to enteric pathogens. To examine their potential role in giardiasis, murine mononuclear cells were isolated from collagenase-treated Peyer's patches by their adherence to glass. These cells were incubated with Giardia lamblia trophozoites in the presence of nonimmune or immune (anti-Giardia antibody titer, greater than or equal to 1:1,024) mouse serum. Macrophages ingested trophozoites at low levels when they were incubated with nonimmune mouse serum. Ingestion was significantly increased at all time points (P less than 0.01) when cells and parasites were incubated in 5% immune mouse serum; the number of Giardia trophozoites ingested per 100 macrophages was 21.6 +/- 7.1 (standard error of the mean) at 1 h and increased to 59.0 +/- 16.4 at 8 h. Electron microscopy documented trophozoite destruction within macrophages. Association of G. lamblia with macrophages elicited an oxidative response; 50.9 +/- 3.6% of macrophages with trophozoites attached or ingested reduced the dye Nitro Blue Tetrazolium, compared with 13.0 +/- 5.2% for cells without associated trophozoites (P less than 0.04). These results demonstrate that macrophages are capable of ingesting G. lamblia in vitro and may play an important role in host defense in giardiasis.

Animals↗
PubMed1990

Lymphocyte proliferation in Peyer's patches of Giardia muris-infected mice.

Gastrointestinal immune events in giardiasis are important in controlling infection. In this study, Peyer's patch lymphocytes from mice infected with Giardia muris developed specific, proliferative responses to G. muris antigen. This proliferation correlated with clearance of infection. Further understanding of the gut immune response will be helpful in developing immunoprophylactic strategies in the control of giardiasis.

Animals↗