Biomedical subjects
Publications and source records attributed to D D Smith.
There is an irreducible uncertainty in the prediction of human behavior because the dynamics of the brain, as a self-organizing system consisting of many millions of elements, are inherently indeterminate. Thus the Laplacian ideal of universal laws relating knowable causes to predictable effects cannot be realized in psychology.
Kittens are the principal disseminators of Toxoplasma gondii. They can shed greater than 10(8) oocysts in the feces after initial infection with bradyzoites in tissue cysts. Thereafter, most kittens develop protective immunity and do not shed oocysts again if they are reinfected. Bradyzoites of a T gondii mutant, designated T-263, were used to vaccinate kittens. Their use did not result in oocyst shedding, but successfully prevented 84% (31/37) of the kittens from shedding oocysts when challenge exposed with a normal isolate of T gondii. Vaccination of outdoor-roaming cats and kittens would be a useful public health measure to prevent transmission of toxoplasmosis near homes, on farms, and in zoos. It is anticipated that several years will be required for a lyophilized bradyzoite vaccine to be ready for licensing and possible commercial availability.
The nonapeptide oxytocin (OXT) has been shown to facilitate female sexual receptivity when infused into the cerebral ventricles or the basal forebrain. Various selective antagonists have been used to block other behavioral effects of centrally administered OXT. In this study we compared the effects of equal doses of uterotonic, antidiuretic (V2) or vasopressor (V1) antagonists in blocking the facilitative effects of a simultaneous infusion of OXT into the basal forebrain. Ovariectomized (OVXed) animals were implanted with chronic cannulas in the basal forebrain. All animals were then given 0.5 micrograms estradiol benzoate daily for 3 days before testing. On the fourth day animals were tested to 8-10 mounts with a sexually vigorous male before and 20, 40 and 90 min after infusions of 500 ng OXT alone or in combination with a uterotonic, V2 or a V1 antagonist analogue. OXT significantly increased lordosis responding 20 and 40 min after its infusion into the medial preoptic area and anterior hypothalamus when compared to the receptivity of normal saline vehicle infused animals. The uterotonic antagonist significantly blocked the facilitation seen after OXT. The V1 and V2 antagonists at equal doses had no effect on the OXT-induced facilitation of lordosis postures. The V1 antagonist itself facilitated sexual receptivity 90 min after infusion. The facilitative effect of OXT on receptivity appears to be mediated by central uterotonic receptors, while central vasopressor receptors may serve an inhibitory role.
Human synoviocytes were stimulated for 48 hours or 72 hours with cytokines (recombinant interleukin-1 beta and/or recombinant tumor necrosis factor alpha) in the presence or absence of selected nonsteroidal antiinflammatory drugs. The drugs were tested at subtherapeutic and clinically therapeutic levels, as follows: piroxicam 0.3 pM to 3 X 10(6) pM, sodium salicylate 30 nM to 3 X 10(6) nM, and indomethacin 3 pM to 3 X 10(6) pM. At low concentrations, all 3 drugs showed significant enhancement of prostaglandin E2 (PGE2) secretion (piroxicam, salicylate greater than indomethacin). At high, clinically therapeutic concentrations, all drugs showed suppression of PGE2 secretion (indomethacin greater than piroxicam greater than salicylate). The enhancement of PGE2 secretion may be partially responsible for the flare of arthralgia or arthritis frequently seen after termination of drug therapy.
In the mammalian liver the distribution of ammonia-detoxifying enzymes, glutamine synthetase (GS) and carbamoylphosphate synthase I (ammonia) (CPS-I), is mutually exclusive in that these enzymes are expressed in two distinct populations of hepatocytes that are zonally demarcated in the liver acinus. In the present study we examined the distribution of GS and CPS-I in pancreatic hepatocytes to ascertain if the expression of these two genes in these hepatocytes is also mutually exclusive. Multiple foci of hepatocytes showing no clear acinar organization develop in the adult rat pancreas as a result of a change in the differentiation commitment after dietary copper deficiency. Unlike liver, GS and CPS-I are detected by immunofluorescence in all pancreatic hepatocytes. In situ hybridization revealed that all pancreatic hepatocytes contain GS and CPS-I mRNAs. The sizes of these two mRNAs in pancreas with hepatocytes are similar to those of the liver. The concomitant expression of GS and CPS-I genes in pancreatic hepatocytes may be attributed, in part, to the absence of portal blood supply to the pancreas vis-à-vis the lack of hormonal/metabolic gradients as well as to possible matrix homogeneity in the pancreas.
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This study investigated the postschool vocational and community adjustment of recent special education graduates from a southwestern metropolitan school district. Sixty-four students with learning disabilities (LD) who had attended self-contained classes at 12 high schools were randomly selected. A questionnaire, administered either via the telephone or in person, was the source of data. Thirty-eight of the LD sample were in competitive employment. In general, the LD students received very few community services. For the most part, they received no agency support after graduation. Most of the LD subjects lived with parents or other relatives and most had a driver's license and car. Implications for postsecondary services and future research are discussed.
Incubation of plasma from the red-eared turtle with glass beads in the presence of the kininase inhibitor 1,10-phenanthroline resulted in activation of the kallikrein-kinin system and generation of bradykinin-like immunoreactivity. The immunoreactive material comprised a single molecular form that was purified to homogeneity by reverse phase HPLC. The primary structure of the peptide was determined by automated Edman degradation and fast atom bombardment mass spectrometry. The amino acid sequence of the turtle kinin Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg contains the substitution Thr for Ser at position 6 compared with mammalian bradykinin. [Thr6] bradykinin was synthesized using solid phase methodology, and bolus injections of the peptide into the left atrium of the anaesthetized turtle produced rapid vasodilation. A dose-dependent increase in blood flow in the left aortic arch was accompanied by a decrease in peripheral vascular resistance, so that systemic blood pressure did not change. The data suggest that the kallikrein-kinin system may play an important physiological role in the regulation of cardiovascular function in reptiles.
Twenty previously healthy individuals were accidentally exposed to high concentrations of chlorine gas in 1975. Pulmonary function tests were performed on these individuals on several occasions over the next 12 years. On average, each subject was followed up for 8.5 years and 13 of the 20 exposed persons were tested 12 years following the exposure. Pulmonary function tests obtained one day following the accident were most notable for the high prevalence of airflow obstruction and air trapping. Over the ensuing years, the airflow obstruction persisted; however, the high prevalence of air trapping resolved. Of note, the prevalence of a low residual volume consistently increased during the follow-up period (p less than 0.001) and at year 12, 67 percent of those tested had residual volumes below 80 percent of their predicted value. We also found that five of 13 subjects tested at year 12 had an increase in airway reactivity (greater than 15 percent decline in FEV1) to inhaled methacholine. Those individuals with reactive airways were older (p = 0.004) and had more marked airflow obstruction (p = 0.03) and air trapping (p = 0.03) immediately following the exposure. These data suggest that exposure to high concentrations of chlorine gas may result in long-term pulmonary complications that are characterized by a reduced residual volume. Unfortunately, these data preclude us from determining whether the chlorine exposure led to the development of airway reactivity or the presence of reactive airways accounted for the air trapping that was observed following the exposure to chlorine gas.
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The membrane-bound (particulate) form of methane monooxygenase from Methylococcus capsulatus (Bath) has been solubilised using the non-ionic detergent dodecyl-beta-D-maltoside. A wide variety of detergents were tested and found to solubilise membrane proteins but did not yield methane monooxygenase in a form that could be subsequently activated. After solubilisation with dodecyl-beta-D-maltoside, enzyme activity was recovered using either egg or soya-bean lipids. Attempts to further purify the solubilized methane monooxygenaser protein into its component polypeptides were unsuccessful and resulted in complete loss of enzyme activity. The major polypeptides present in the solubilised enzyme had molecular masses of 49 kDa, 23 kDa and 22 kDa which were similar to those seen in crude extracts [Prior, S. D. & Dalton H. (1985) J. Gen. Microbiol. 131, 155-163]. Studies on substrate and inhibitor specificities indicated that the membrane-associated and solubilised forms of methane monooxygenase were quite similar to each other but differed substantially from the well-characterised soluble methane monooxygenase found in cells grown in a low copper regime and synthesised independently of the particulate methane monooxygenase.
Asbestosis is commonly associated with abnormalities of gas transport but since most asbestos workers are smokers and smokers also commonly have abnormalities in P(A-a)O2, the actual specificity and sensitivity of the P(A-a)O2 has been unknown. The P(A-a)O2 was measured at rest and exercise in 92 asbestos-exposed patients. These patients were divided into five groups based on their x-ray and pulmonary function status; normal, CAO, CAO and pleural disease, pleural disease alone and asbestosis with or without CAO. The P(A-a)O2/VO2(mm Hg)/L of O2 was the most discriminatory measurement of gas transport between groups, with mean values of 14.45 +/- 9.24 for normal, 19.04 +/- 10.52 for CAO, 16.85 +/- 8.94 for CAO and pleural disease and 34.07 +/- 21.54 for asbestosis with or without CAO. The P(A-a)O2/VO2 was of high specificity if greater than 35 mm Hg/L of O2 with only two out of 65 patients without asbestosis being considered abnormal. It was of low sensitivity in that only nine out of 27 patients with asbestosis would be detected if this were the sole criterion for diagnosis.
To investigate the oocyst-induced cycle with a 21+ day prepatent period, 32 cats were fed 5 x 10(5) to 2 x 10(7) sporulated oocysts of Toxoplasma gondii and necropsied between 4 hr and 41 days thereafter. The presence of the earliest stages in 7 cats was tested in mice. The tissues of 25 cats were studied histologically; 17 were bioassayed by feeding them to cats to determine, by the length of the prepatent period, whether bradyzoites were present. Based on previous studies, a short (3-10 days) prepatent period indicated that bradyzoites were present in an oral inoculum and a long (greater than 21 days) prepatent period indicated the presence of tachyzoites only. Tissues from 14 cats were also bioassayed in mice for the presence of bradyzoites, using their resistance to pepsin as indicator. Six were studied by both methods. Based on these criteria, tachyzoites predominated in extraintestinal organs during the first 14 days after infection. They were found as early as 4 hr in mesenteric lymph nodes where their number reached 10(4) after 6 and 9 days; they were present after 1 day in all levels of the small intestine and after 6 days in the liver, lung, and blood. Bradyzoites were first detected 10 days after oocyst feeding; they predominated by the third week of infection and were present up to 41 days. Enteroepithelial stages were found histologically only in 2 cats, 24 and 41 days after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitochondrial glutamine synthetase (EC 6.3.1.2) is the primary ammonia-detoxifying enzyme in avian liver and is therefore analogous in function to carbamoyl-phosphate synthetase I (ammonia) (EC 6.3.4.16) in mammalian liver. In mammalian liver, glutamine synthetase is cytosolic and its distribution is restricted to a few hepatocytes around the terminal venules. These cells do not express carbamoyl-phosphate synthetase I. Using immunocytochemistry, we show here that there is little or no zonation of glutamine synthetase in avian liver. Rather, it is broadly distributed to most hepatocytes, much like carbamoyl-phosphate synthetase I in mammalian liver. In situ hybridization with a cloned glutamine synthetase cDNA probe showed the distribution of glutamine synthetase mRNA in both mammalian and avian liver to correspond to the distribution of immunoreactive protein. Neither glutamine synthetase nor carbamoyl-phosphate synthetase I and ornithine transcarbamoylase (EC 2.1.3.3) are strictly zoned in liver of the Texas tortoise or of an Argentine tree frog, both of which possess a complete urea cycle but which may also rely on glutamine synthetase for ammonia detoxication. These latter results suggest that the mutually exclusive expression of either carbamoyl-phosphate synthetase I or glutamine synthetase may be unique to mammalian liver.
Estimates are obtained of the fraction of ingested or inhaled 239+240Pu transferred to blood and tissues of a reproducing herd of beef cattle, individuals of which grazed within fenced enclosures for up to 1064 d under natural conditions with no supplemental feeding at an arid site contaminated 16 y previously with Pu oxide. The estimated (geometric mean [GM]) fraction of Pu transferred from the gastrointestinal tract to blood serum was about 5 x 10(-6) (geometric standard error [GSE] = 1.4) with an approximate upper bound of about 2 x 10(-5). These results are in reasonable agreement with the value of 1 x 10(-5) recommended for human radiation protection purposes by the International Commission on Radiological Protection (ICRP) for insoluble Pu oxides that are free of very small particles. Also, results from a laboratory study by Stanley (St75), in which large doses of 238Pu were orally administered daily to dairy cattle for 19 consecutive days, suggest that aged 239+240Pu at this arid grazing site may not be more biologically available to blood serum than fresh 239+240Pu oxide. The estimated fractions of 239+240Pu transferred from blood serum to tissues of adult grazing cattle were: femur (3.2 X 10(-2), 1.8; GM, GSE), vertebra (1.4 X 10(-1), 1.6), liver (2.3 X 10(-1), 2.0), muscle (1.3 X 10(-1), 1.9), female gonads (7.9 X 10(-5), 1.5), and kidney (1.4 X 10(-3), 1.7). The blood-to-tissue fractional transfers for cattle initially exposed in utero were greater than those exposed only as adults by a factor of about 4 for femur (statistically significant) and of about 2 for other tissues (not significant). The estimated (GM) fraction of inhaled Pu initially deposited in the pulmonary lung was 0.34 (GSE = 1.3) for adults and 0.15 (GSE = 1.3) for cattle initially exposed in utero (a statistically significant difference), which may be compared with the expected fraction of 0.11 at the study site using the ICRP lung model for humans.
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An enzyme-linked immunosorbent assay (ELISA) for Bordetella pertussis-specific immunoglobulin (Ig)A antibody in serum was used to demonstrate B. pertussis infection. The upper limit of normal for the assay (mean + 3 SD) was established by testing sera that had been collected from a group of healthy blood donors. All 13 patients with clinical whooping cough from whom B. pertussis was isolated and 25.7% of 218 adults, who were aged 18-81 years, who were referred to a consultant physician for the investigation of a persistent cough, had elevated levels of IgA to B. pertussis. The study confirms the B. pertussis IgA ELISA as a sensitive test for the diagnosis of B. pertussis infections and that these infections cause respiratory illness, in particular, persistent cough in adults.