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Biomedical subjects

H R Smith

Publications and source records attributed to H R Smith.

At least 55 records · Page 3Linked to original sources

A comparison of the behavioral effects of the repeated administration of PTT, 2beta-propanoyl-3beta-(4-tolyl)tropane and cocaine.

In the present study the effects of the repeated administration of the novel tropane analog PTT (2beta-propanoyl-3beta(4-tolyl)tropane) on spontaneous locomotor activity were compared to those of cocaine. Previous reports describing the in vivo effects of PTT have focused solely on its acute effects following a single administration. In Experiment 1, PTT (1.0, 3.0 mg/kg), cocaine (30 mg/kg), or vehicle were administered intraperitoneally to male Sprague-Dawley rats daily for 10 consecutive days and locomotor activity was assessed. In Experiment 2, the locomotor effects of PTT (1.0 mg/kg) and cocaine (15 mg/kg) were assessed following 5 days of drug exposure to either PTT (1.0, 3.0 mg/kg) or cocaine (30 mg/kg) and 18 days of withdrawal. In both paradigms, PTT (1.0, 3.0 mg/kg) and cocaine (30 mg/kg) produced marked increases in locomotor activity acutely and an augmented response to drug challenge following repeated exposure, indicative of behavioral sensitization. These data indicate that, despite differences in the pharmacological profiles of PTT and cocaine, both drugs produce behavioral sensitization. These data are consistent with previous reports in the literature describing the effects of the repeated administration of other dopamine reuptake inhibitors and suggest that the development of behavioral sensitization is a uniform characteristic of this class of drugs.

Animals↗

Nonstochastic coexpression of activation receptors on murine natural killer cells.

Murine natural killer cells (NK) express lectin-like activation and inhibitory receptors, including the CD94/NKG2 family of receptors that bind Qa-1, and the Ly-49 family that recognizes major histocompatibility complex class I molecules. Here, we demonstrate that cross-linking of NK cells with a new specific anti-Ly-49H mAb induced NK cell cytotoxicity and cytokine production. Ly-49H is expressed on a subset of NK cells and can be coexpressed with Ly-49 inhibitory receptors. However, unlike Ly-49 inhibitory receptors, Ly-49H is not detectable on naive splenic CD3(+) T cells, indicating that Ly-49H may be an NK cell-specific activation receptor. In further contrast to the stochastically expressed Ly-49 inhibitory receptors, Ly-49H is preferentially expressed with the Ly-49D activation receptor, and expression of both Ly-49H and Ly-49D is augmented on NK cells that lack receptors for Qa-1 tetramers. On developing splenic NK1.1(+) cells, Ly-49D and Ly-49H are expressed later than the inhibitory receptors. These results directly demonstrate that Ly-49H activates primary NK cells, and suggest that expression of Ly-49 activation receptors by NK cells may be specifically regulated on NK cell subsets. The simultaneous expression of multiple activation receptors by individual NK cells contrasts with that of T cell antigen receptors and is relevant to the role of NK cells in innate immunity.

Animals↗

Irritant thresholds in subjects with colophony allergy.

The factors which determine individual susceptibility to the development of allergic contact dermatitis (ACD) are not well defined. Since it is known that the presence of skin irritation is well-documented as a promoter of sensitization, the sensitivity to irritation of subjects with ACD has been compared with a normal control group. Whilst 78% of those with a positive patch test reaction to the contact allergen colophony (colophonium) responded to a concentration of no higher than 2.5% sodium lauryl sulfate (SLS), only 44% of the matched control group reacted at this level of SLS. Thus, the results are consistent with the hypothesis that individuals with enhanced susceptibility to skin irritation are also more liable to develop allergic skin reactivity.

Adolescent↗

Descriptive epidemiology of hand dermatitis at the St John's contact dermatitis clinic 1983-97.

For 15 years, hand dermatitis accounted for a quarter of patients seen in this clinic. The highest proportion occurred in women aged 17-30 years. Overall, the male to female ratio was 0.8, which contrasts with population-based studies. Catering was most frequently associated with occupational hand dermatitis. Other frequent occupational associations included metalworking, hairdressing, healthcare and mechanical work.

Adult↗

An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5alpha and EQ1.

AIMS: To examine Escherichia coli strains EQ1, DH5alpha, BLR and BL21 for known pathogenic mechanisms. METHODS AND RESULTS: Using specific DNA probes, the strains were shown not to carry the genes encoding invasion, various adhesion phenotypes or expression of a range of enterotoxins. The strains were unable to express long-chain lipopolysaccharide and were susceptible to the effects of serum complement. Using a BALB/c mouse model, the strains were shown to be unable to survive in selected tissues or to persist in the mouse gut. Using a chick model, strains EQ1, BLR and BL21 invaded livers but not spleens; only strain EQ1 persisted in the chick gut. In Merino sheep, only strain EQ1 was detected 6 d post-infection. CONCLUSIONS: Escherichia coli strains EQ1, DH5alpha, BLR and BL21 did not carry the well-recognized pathogenic mechanisms required by strains of E. coli causing the majority of enteric infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Escherichia coli strains EQ1, DH5alpha, BLR and BL21 were considered to be non-pathogenic and unlikely to survive in host tissues and cause disease.

Animals↗

Characterization of a tropane radioligand, [(3)H]2beta-propanoyl-3beta-(4-tolyl) tropane ([(3)H]PTT), for dopamine transport sites in rat brain.

PTT (2beta-propanoyl-3beta-[4-tolyl] tropane) is a tropane analog relatively selective for dopamine transporters in binding and uptake assays in vitro, with long-acting psychostimulant properties in vivo. To explore its utility in binding to dopamine transporters, [(3)H]PTT was synthesized and assayed for binding in rat striatal membranes and by in vitro autoradiography. In membranes, binding of [(3)H]PTT was saturable to a single class of binding sites with a K(D) value of 3 nM. The pharmacology of [(3)H]PTT binding in striatal membranes was consistent with that of a ligand selective for dopamine transporters, with dopamine-selective compounds being significantly more potent in displacing [(3)H]PTT binding than those for 5-HT or norepinephrine transporters. Although the ability of various transporter inhibitors to displace both [(125)I]RTI-55 and [(3)H]PTT binding correlated significantly with each other, there was a better correlation of inhibitor potencies versus [(3)H]PTT binding and dopamine uptake than versus [(125)I]RTI-55 binding and dopamine uptake. The differences in correlations were most noticeable for compounds relatively selective at the 5-hydroxytryptamine (serotonin) transporter. The autoradiographic distribution of [(3)H]PTT binding in coronal sections was consistent with the known distribution of the dopamine transporter, with high levels of binding evident in caudate nucleus, nucleus accumbens, and olfactory tubercle. Moderate densities of [(3)H]PTT binding were also observed in substantia nigra pars compacta, and ventral tegmental area, as well as in the anterior cingulate cortex and portions of the hypothalamus. In addition, nonspecific binding was less than 5% of total binding. Thus, [(3)H]PTT provides an accurate and convenient marker for the dopamine transporter.

Animals↗

Sarcoidosis and dermatomyositis in a patient with hemoglobin SC. A case report and literature review.

Although sarcoidosis has occasionally been associated with hemoglobinopathies, its association with dermatomyositis is extremely rare. A 24 y/o African American male with hemoglobin SC disease developed proximal weakness. He had heliotrope rash, muscle weakness, elevated serum CK, myositis by EMG, and no malignancy. A muscle biopsy confirmed dermatomyositis. Two years later, he was hospitalized with constitutional and respiratory symptoms and parotid enlargement. Chest X-ray and CT scan showed diffuse micronodular infiltration in both lungs and mediastinal lymphadenopathy. A transbronchial lung biopsy revealed non-caseating granulomata consistent with sarcoidosis. AFB and fungal stains and cultures were negative. Thus, in this case, sarcoidosis developed after or in association with dermatomyositis. A review of world's literature showed five other non-identical cases of dermatomyositis associated with sarcoidosis.

Adult↗