Search PubMed⌕ Search

Biomedical subjects

S H Smith

Publications and source records attributed to S H Smith.

At least 91 records · Page 5Linked to original sources

Immunosuppressive effects of 8,9-epoxyhexahydrocannabinol (EHHC).

8,9-Epoxyhexahydrocannabinol (EHHC)-treated mice showed an inhibition of both humoral and cell-mediated immunity. The hemolytic plaque forming assay was employed to determine both the IgM and IgG antibody response. The effect of EHHC on IgM antibody production was measured in BDG1 male mice given X 10(8) sheep erythrocytes i.p. followed 24 and 48 hours later by i.p. injections of EHHC. EHHC produced a dose-dependent inhibition of plaque forming cells (PFC)/10(6) spleen cells and PFC/spleen on days 3, 4 and 5 after antigen administration. On day 4 the ED50 for PFC/10(6) spleen cells and PFC/spleen was 28 and 18 mg/kg, respectively. Peak response to IgG antibody production was observed on day 9. EHHC (100 mg/kg) administered i.p. 48 hours after antigen produced a 58 and 46% suppression of PFC/10(6) leucocyte on days 7 and 9, respectively. CDF1 male mice received 100 microng of Cornybacterium parvum in the left footpad. Two days after sensitization, EHHC was administered in doses of 0.75 to 50 mg/kg i.p. A challenge dose of 100 microng of Cornybacterium parvum was injected into the right footpad on day 6 and footpad swelling was measured 24 hours later by mercury displacement. EHHC at a dose of 0.78 mg/kg produced a 95% inhibition of the delayed-type hypersensitivity response. These studies showed that EHHC inhibits both the humoral and cellular arm of the immune response.

Animals↗

Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. III. IBT's study.

Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No.2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel stran rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River stain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.

Abnormalities, Drug-Induced↗

Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures.

The drug 9-beta-d-arabinofuranosyladenine (ara-A) significantly suppressed the formation of herpes simplex virus type 1-induced syncytia in BHK-21/4 cells at concentrations as low as 0.1 mug/ml. Optimal activity was noted when the drug was added before initiation of viral deoxyribonucleic acid (DNA) synthesis (3.5 h postinfection). The deaminated derivative of ara-A, 9-beta-d-arabinofuranosylhypoxanthine (ara-H), was at least 10 times less effective in suppressing the development of herpes simplex virus-induced syncytia. The replication of herpes simplex virus was measured by assaying fluids and cells from infected drug-treated cultures by using a plaque production technique. Ara-A at drug levels of >10 < 32 mug/ml completely blocked the replication of infectious virus particles. Ara-H was less effective than ara-A in reducing the replication of virions. Rates of host and viral DNA synthesis were monitored by pulse labeling herpes simplex virus-infected synchronized KB cells with [(3)H]thymidine and subsequently separating viral from cellular DNA in CsCl density gradients. During synthetic (S) phase, ara-A or ara-H at concentrations ranging from 3.2 to 32 mug/ml selectively inhibited viral DNA synthesis. At 3.2 mug of ara-A per ml, viral DNA synthesis was reduced 74% although total cellular DNA synthesis was unaffected. Increasing concentrations of ara-A produced increasing temporal delays in the maximal rate of host DNA synthesis. This time shift was not observed in cells treated with ara-H.

Antiviral Agents↗

Selective inhibition of nuclear DNA synthesis by 9- -D-arabinofuranosyl adenine in rat cells transformed by Rous sarcoma virus.

The drug, 9-beta-D-arabinofuranosyl adenine, selectively inhibits the synthesis of nuclear DNA without affecting extrachromosomal DNA synthesis in rat cells transformed by Rous sarcoma virus (B-mix K-44/6). The inhibition was linear with respect to drug concentration over the range of 37-600 muM. Mitosis and total synthesis of DNA per cell were also depressed. DNA synthesis was determined by measurement of [(3)H]thymidine incorporation into DNA. Covalently-closed circular DNA was extracted by the Hirt procedure and separated from residual chromosomal DNA by buoyant density gradient ultracentrifugation in CsCl-propidium diiodide. On the basis of buoyant density and sedimentation velocity centrifugation, the covalently-closed circular DNA formed in the presence of the drug was indistinguishable from that formed in its absence.

Adenine↗

Computed tomography on invasive thymoma.

We report a case of invasive thymoma invading and occluding the superior vena cava in which the diagnosis was only made by the computed tomography (CT) study. Correlation of CT and autopsy findings of invasive thymoma were made in order to emphasize the usefulness of CT study in the evaluation of thymoma and its relationship with vascular structures.

Humans↗

Development of persistent intestinal infection and excretion of Lawsonia intracellularis by piglets.

Challenge experiments using Lawsonia intracellularis as oral inocula have established its aetiological role in porcine proliferative enteropathy. Thirty piglets, in four groups, were weaned at 21 days of age and inoculated orally at 24 days. Six piglets were challenged with 1.0 x 10(8) L intracellularis strain 916/91 (NCTC 12657) passaged 12 times in vitro, six with 5.0 x 10(8) of the same strain, seven with 3.0 x 10(8) L intracellularis strain LR 189/5/83, passaged nine times, and 11 controls were dosed with sucrose-potassium glutamate buffer. An immunofluorescence assay for L intracellularis was applied to faecal smears and a polymerase chain reaction (PCR) incorporating L intracellularis-specific primers was applied to extracts of bacterial DNA derived from the faeces samples. Up to five pigs in each challenge group excreted detectable L intracellularis in faeces, in samples taken between two and 10 weeks after challenge. Some of the pigs had up to 7 x 10(8) L intracellularis g-1 faeces. The average weight gains of the higher dose challenge groups were moderately below those of the control pigs between three and nine weeks after challenge; diarrhoea was also observed in six pigs, two to four weeks after challenge. Numerous L intracellularis were detected in the intestines of all the pigs challenged with strain LR 189/5/83 and two of the pigs challenged with 916/91, but not in other tissues.

Animals↗

Listerial myocarditis in cardiac transplantation.

Clinical signs of heart failure developed in two cardiac transplant recipients and were interpreted initially as graft rejection. Morphologic examination of explanted hearts revealed myocarditis with abscess formation and necrosis consistent with a bacterial process; Listeria monocytogenes was isolated from myocardial tissue in the first case and from blood in both. The first patient also developed signs of meningoencephalitis, but the second had no signs of infection outside the heart. Antimicrobial therapy and retransplantation were successful in eradicating listeriosis. The differential diagnosis of heart failure in cardiac transplant recipients includes infectious myocarditis due to L. monocytogenes.

Adult↗

Reproductive and teratologic studies with isoflurane.

The volatile anesthetic, Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), was investigated at anesthetic concentrations to determine its effects on reproduction in rats treated prior to mating, on fetal development in rats and rabbits when administered during various stages of gestation, and on fetal survival in rats treated during late pregnancy. No adverse reproductive effects were observed, and no evidence of teratogenic activity was obtained. Fetal survival was low in rats exposed during late pregnancy but whether or not this finding is related to Isoflurane exposure requires confirmation.

Animals↗