Biomedical subjects
Publications and source records attributed to C C Smith.
Tetrahydrohomopteroate, which inhibits the growth of Streptococcus faecium (Streptococcus faecalis ATCC 8043), replaces folate as a growth factor in chlorguanide triazine-resistant strains of this organism.
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The treatment with ganciclovir of two non-compromised patients who required hospitalisation with acute cytomegalovirus (CMV) infection is described. Ganciclovir has rarely been used in such circumstances but, in four previously reported patients and in the patients described here, a rapid response to therapy was seen. In contrast to previous reports, relatively short courses of treatment (3-5 days) were given to our patients. The drug was well tolerated in each case and may have a role to play in the treatment of severe acute CMV infection in the normal host.
The effect of supplemental ascorbic acid and alpha-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22-55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella Typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P less than 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P less than 0.01) to 26% of control. Addition of ascorbic acid and alpha-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.
Indications of possible health effects of residue organics in drinking water have been sought using short-term tests of mutagenic and transforming activity. Ten percent or less of the total organic material in drinking water has been identified; the remainder is believed to include thousands of unknown nonvolatile compounds. Residual organics were concentrated from drinking water from representative U.S. cities by reverse osmosis followed by liquid-liquid extraction [yielding the reverse osmosis concentrate-organic extract (ROC-OE) fraction] and sorption-desorption on XAD-2 resin. Samples of these residue organics were provided by the Environmental Protection Agency for bioassay. They were examined for mutagenic activity by using Salmonella tester strains (primarily TA98 and TA100) and for transforming activity by using mouse fibroblasts (BALB/3T3 clone 1-13). City-specific patterns of dose-dependent bacterial mutagenesis and of bacterial toxicity were observed for these samples and for subfractions generated by sequential extractions with hexane, ethyl ether, and acetone. Mutagenic effects were essentially independent of a microsome activation system prepared from liver of Aroclor 1254-induced rats. On the basis of strain-specific effects in mutagenesis and differential distributions of mutagenic activity during liquid-liquid extraction, at least some of the active compounds are thought to be acidic, frameshift mutagens. The ROC-OE fraction of a New Orleans sample transformed BALB/3T3 cells in replicate experiments. By comparison with the bacterial mutagenesis data, cell transformation is a relatively sensitive method for detecting possible mutagenic and carcinogenic activity in this sample. The appropriateness of these systems for the assay of complex mixtures and the degree to which reverse osmosis concentrates contain the unaltered organic compounds in the original samples are discussed.
Vaccinia virus recombinants containing the herpes simplex virus (HSV) gene for glycoprotein D type 1 (gD-1) under control of an early (VP176) or late (VP254) vaccinia virus promoter or for HSV glycoprotein type 2 (gD-2) under control of the early promoter (VP221) were studied for their ability to induce protective immunity to HSV-2 in the guinea pig model of cutaneous recurrent disease and the mouse model of fatal disease. Titers of HSV-specific neutralizing antibody were similar in the two groups of immunized animals, but HSV-specific T cell responses were significantly higher in VP176-immunized than in VP254-immunized animals, as determined by lymphoproliferation (P less than .005) and delayed-type hypersensitivity (P less than .01) responses. The reduced responses correlated with poor expression of the gD protein and its impaired processing in infected antigen-presenting cells (splenic adherent and epidermal cells). VP176 immunization protected against primary (P much less than .001) and recurrent (P much less than .001) cutaneous HSV-2 lesions and ganglionic latency (62% protection) in the guinea pig and against zosteriform skin lesions and fatal disease in the mouse. Immunization with VP254 was not protective. In guinea pigs VP221 did not protect against primary HSV-2 cutaneous disease but did reduce the proportion of animals with recurrent disease (P less than .05). This partial protection appears to be associated with the role of type-specific antigenic determinants in gD-2 immunoregulation.
It has been argued that surgery is a form of psychological stress, and that the response to it should therefore be modifiable by psychological means. To test this hypothesis, we assessed the effect of preoperative relaxation instructions on endocrine, cardiovascular, and subjective responses in 21 patients undergoing minor abdominal surgery. Controls (N = 19) received general procedural information. In the relaxation group only, there was a significant increase in cortisol and adrenaline concentration from immediately before induction of anesthesia to immediately after surgery. Noradrenaline values were unaffected by relaxation. In contrast, relaxation reduced state-anxiety on the preoperative day and the two postoperative days; maximal peroperative systolic and diastolic blood pressures were also reduced. The results are consistent with previous evidence that adrenaline and cortisol responses to surgery are greater in less anxious patients.
The cell density in the Nucleus Basalis in six patients with clinical and histological evidence of Alzheimer's disease and reduced choline acetyltransferase activity in frontal and temporal cortex was found to be in approximately 50% of the cell count in five control subjects.
There are conflicting reports of platelet function abnormalities in diabetic patients without vascular complications. We have studied in vitro platelet aggregation, using platelet rich plasma and whole blood techniques, in 18 patients with uncomplicated insulin-dependent diabetes and a matched group of 24 non-diabetic subjects. In addition we measured plasma beta-thromboglobulin levels in these groups, as an index of in vivo platelet activation, and compared the indices of in vitro and in vivo platelet function before and after maximal bicycle exercise. Before exercise plasma beta-thromboglobulin levels and platelet sensitivities to ADP, collagen or adrenaline, as assessed by both methods of platelet aggregation, were the same in diabetic and control subjects. Both groups showed similar increases in beta-thromboglobulin levels and in platelet sensitivity to all agonists in whole blood following exercise. Using platelet rich plasma there were no changes in platelet sensitivity in either group after exercise. In non-diabetic subjects, increases in noradrenaline levels after exercise correlated with increases in platelet sensitivity to adrenaline in whole blood. This was not observed in the diabetic group. Abnormalities of platelet function, using the techniques described here, are not present in diabetic patients who do not have clinical evidence of vascular disease.
In order to test the effect of stress on injection-site blood flow and blood glucose control, 16 C-peptide negative patients were studied on a stress day, when a 30-min Stroop Colour-Word Test was completed, and a control day, when a cartoon was shown. Unmodified insulin was injected subcutaneously into the thigh before the test, and injection-site blood flow measured throughout the experiment with a thermal clearance probe. Blood glucose and plasma free insulin, glucagon, growth hormone, cortisol, and catecholamines were measured at intervals before, during, and after stress. Patients showed a significant overall rise in injection-site blood flow with the Stroop test from 4.1 (SD 1.6) to 5.2 (1.8) ml 100-g-1 min-1 (increase 38.1 (37.8) %, p less than 0.001). There was no overall significant difference between stress and control days in blood glucose or plasma free insulin levels, with differences in mean blood glucose levels during stress between the 2 days varying from -4.2 mmol l-1 to +6.3 mmol l-1 in individual patients. The increase in injection-site blood flow with stress correlated significantly with the increase in plasma free insulin concentration both during (r = 0.55) and after stress (r = 0.71). Differences in blood glucose concentration between stress and control day for each patient showed strong correlation with differences in plasma free insulin both during (r = -0.73) and after stress (r = -0.79). Differences in counter-regulatory hormones occurred but correlated poorly with blood glucose difference. Thus, stress affects the blood flow at the injection site, and this in turn affects insulin absorption. Most of the blood glucose response to stress is explained by changes in free insulin concentration.
We have characterized the estrous cycle by obtaining vaginal smears, and quantitating estradiol (E), progesterone (P), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) plasma levels at different phases of the estrous cycle in Lewis (LEW/N) and Fischer (F344/N) rats. Comparison of the duration of the component phases of estrous showed LEW/N metestrous to be significantly longer than in F344/N rats while diestrous and estrous were significantly shorter; proestrous was identical. E levels in LEW/N rats were significantly greater than in F344/N rats only in the estrous phase of the cycle. P levels were significantly greater in LEW/N rats in all phases. LH and FSH levels in the two strains did not differ. Elevated E and P levels would be expected to be associated with increased corticosterone through inhibition of the glucocorticoid negative-feedback pathway. The data reported suggest that other modulating factors in corticotropin-releasing-factor synthesis/release could be overriding both the E and P effects upon hypothalamic-pituitary-adrenal axis responsiveness.