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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 181 records · Page 10Linked to original sources

Effect of ivermectin on Caenorhabditis elegans larvae previously exposed to alcoholic immobilization.

First-stage larvae of Caenorhabditis elegans were immersed in 0.15% 1-phenoxy-2-propanol to induce temporary paralysis, including the suppression of pharyngeal pumping. Subsequent addition of ivermectin (to give 50 micrograms/ml) induced coiling and prolonged immobilization of such larvae, as also of control larvae (previously immersed only in water). The results suggest that ingestion of drug by means of pharyngeal pumping is not a prerequisite for the uptake of ivermectin at levels sufficient for antinematodal action.

Animals↗

Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest.

OBJECTIVE: To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest. DESIGN: Population-based case-control study. SETTING: Seattle and suburban King County, Washington. PARTICIPANTS: A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF EXPOSURE: Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake. RESULTS: Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6). CONCLUSION: Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.

Adult↗

Assembly of Alzheimer-like, insoluble filaments from brain cerebrosides.

Amphiphiles are molecules which contain a polar head and a hydrophobic tail. When the head contains a chiral center, amphiphiles, incubated in the presence of some di- and trivalent metal ions, have been shown to form large fibrous molecular aggregates. In this study, naturally occurring brain cerebroside was tested to determine if it had sufficient amphiphilic properties to form similar supramolecular structures. When galactocerebroside was heated in the presence of magnesium, it was able to form tubules, vesicles and filaments. The filaments included long fibrils that aggregated into dense bundles and short fibrils that were associated to form smaller bundles. These fibrils were shown to be resistant to solubilization in boiling SDS in the presence of reducing agents. This is the first report of a naturally occurring glycolipid being able to form filaments. Since their structural and physical properties are similar to the paired helical filaments of Alzheimer's disease, they may serve as an experimental model for their assembly.

Alzheimer Disease↗

Comparison of echocardiographic variables between type I diabetics and normal controls.

This report compares echocardiographic estimates of systolic and diastolic function and ventricular dimensions in type I diabetics and normal controls. A random sample of 60 diabetics selected from a central hospital diabetic clinic was compared with a sample of 40 nondiabetic controls, and matched to the diabetics by age, gender, and blood pressure. Simple comparisons showed that diabetics had a higher mean resting heart rate (HR) (p < 0.001) and a slower diastolic early filling phase (maximal rate of increase in left ventricular dimension in early diastole [v/dtmax], p = 0.08; time from end-systole until dv/dtmax [ES-dv/dtmax], p = 0.03), which were explained by differences in HR and other factors. Resting HR was significantly associated with several echocardiographic variables, but the slope relating resting HR to ventricular dimension was more negative in diabetics than in controls (end-diastolic diameter, p < 0.008; end-systolic diameter, p < 0.005), and the ratio of systolic to diastolic duration was significantly (p < 0.01) less positive in diabetics. The association of resting HR to duration of isovolumic diastole was positive in diabetics and negative in controls (p < 0.02). Among diabetics, those with higher resting HR had more retinopathy (p < 0.05), microalbuminuria (p < 0.05), smaller ventricles (p < 0.01), and longer isovolumic diastole (p < 0.05). Poorer diabetic control was associated with poorer systolic (fractional shortening, p < 0.05) and diastolic (dv/dtmax, p < 0.05; ES-dv/dtmax, p < 0.05) function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Transgene-mediated auxin overproduction in Arabidopsis: hypocotyl elongation phenotype and interactions with the hy6-1 hypocotyl elongation and axr1 auxin-resistant mutants.

Transgenic Arabidopsis thaliana plants constitutively expressing Agrobacterium tumefaciens tryptophan monooxygenase (iaaM) were obtained and characterized. Arabidopsis plants expressing iaaM have up to 4-fold higher levels of free indole-3-acetic acid (IAA) and display increased hypocotyl elongation in the light. This result clearly demonstrates that excess endogenous auxin can promote cell elongation in a whole plant. Interactions of the auxin-overproducing transgenic plants with the phytochrome-deficient hy6-1 and auxin-resistant axr1-3 mutations were also studied. The effects of auxin overproduction on hypocotyl elongation were not additive to the effects of phytochrome deficiency in the hy6-1 mutant, indicating that excess auxin does not counteract factors that limit hypocotyl elongation in hy6-1 seedlings. Auxin-overproducing seedlings are also qualitatively indistinguishable from wild-type controls in their response to red, far-red, and blue light treatments, demonstrating that the effect of excess auxin on hypocotyl elongation is independent of red and blue light-mediated effects. All phenotypic effects of iaaM-mediated auxin overproduction (i.e. increased hypocotyl elongation in the light, severe rosette leaf epinasty, and increased apical dominance) are suppressed by the auxin-resistant axr1-3 mutation. The axr1-3 mutation apparently blocks auxin signal transduction since it does not reduce auxin levels when combined with the auxin-overproducing transgene.

Arabidopsis↗

Mutagenicity of benzo[a]pyrene and dibenzopyrenes in the Salmonella typhimurium TM677 and the MCL-5 human cell forward mutation assays.

The mutagenicity of benzo[a]pyrene (B[a]P), dibenzo[ae]pyrene (DB[ae]P), dibenzo[ah]pyrene (DB[ah]P), dibenzo[ai]pyrene (DB[ai]P), and dibenzo[al]pyrene (DB[al]P) was measured in quantitative forward mutation assays with bacteria (Salmonella typhimurium TM677) and a metabolically competent cell line derived from human B-lymphoblastoid cells (MCL-5) that contained activity for five cytochrome P450s and microsomal epoxide hydrolase found in human liver. DB[al]P and B[a]P, both potent animal carcinogens, were the most mutagenic substances in both assays. DB[al]P was nearly 50-fold more potent than B[a]P in human cells, but only 60% more mutagenic in Salmonella. The carcinogenic isomer DB[ah]P, though nonmutagenic in bacteria, was active in human cells. The following mutagenic potency series, expressed as the minimum detectable mutagen concentration (MDMC) in nmol/ml, was obtained with Salmonella in the presence of rat liver postmitochondrial supernatant (PMS): DB[al]P (3.7), B[a]P (5.8), DB[ae]P (6.9), DB[ai]P (14.9), DB[ah]P (> 100). None of the compounds were mutagenic in the absence of PMS. In human MCL-5 cells the potency series was: DB[al]P (3.1 x 10(-4)), B[a]P (1.5 x 10(-2)), DB[ae]P (2.5 x 10(-2)), DB[ah]P (0.5), DB[ai]P (3.2). The human cell assay thus exhibited over a 10,000-fold range between the most mutagenic and least mutagenic compound, whereas in the bacterial assay there was only a corresponding four-fold difference if the nonmutagenic DB[ah]P was excluded. The results were discussed in terms of their concordance with animal carcinogenicity studies.

Benzo(a)pyrene↗

Late-onset hepatic failure: clinical features, serology and outcome following transplantation.

A further series of 41 adult patients with late-onset hepatic failure was investigates with respect to aetiological factors, particularly hepatitis C and E, which have been identified since our earlier report of this condition. The increased use of transplantation and its impact on survival overall is assessed. Comparison is made with 64 patients admitted over the same period with fulminant hepatic failure of non-A, non-B aetiology. Screening for the hepatitis viruses revealed three cases of hepatitis A and one case of Epstein Barr virus hepatitis. There were no cases of hepatitis C or hepatitis E virus detected by enzyme immunoassay and reverse transcriptase/polymerase chain reaction techniques, although three patients had positivity for IgG anti-hepatitis E virus, demonstrating previous exposure. Serum autoantibodies in a titre greater than or equal to 1:40 were present in 29% of samples tested and in three cases, titres of SMA or ANF were greater than 1:320. In a further five cases, a potentially hepatotoxic agent had been given within 3 months of the onset of symptoms, leaving the majority of patients (29) with no identifiable cause for their disease. The frequency of symptoms, however, including nausea, abdominal discomfort with the subsequent development of ascites, encephalopathy and renal impairment suggest a similar disease process in these patients. Analysis of liver biopsy material showed similar patterns on all cases of map-like necrosis with nodular regeneration and without other additional features of aetiological significance. Differences in clinical and histological changes for the non-A, non-B fulminant hepatic failure comparison group reflect the tempo of disease process rather than the nature and cause of the liver damage. The introduction of transplantation has led to a marked improvement in survival (39% overall in the earlier series). In the 21 patients in whom transplantation was carried out, the 1-year actuarial survival is currently 55%. Treatment of late-onset hepatic failure with corticosteroids and the use of Prostaglandin E1 and interferon in individual cases has been disappointing, and the emphasis in management should be placed on teh early referral of such patients to a centre offering transplantation.

Adolescent↗

A serum-sensitive, sialyltransferase-deficient mutant of Neisseria gonorrhoeae defective in conversion to serum resistance by CMP-NANA or blood cell extracts.

A stable, sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62 totally defective in CMP-NANA-dependent lipopolysaccharide (LPS) sialylation was isolated by insertion mutagenesis with transposon Tn 1545-delta 3 and screened for unlabelled colonies following incubation with CMP-14C-NANA. In contrast to the parental strain which became serum resistant on incubation with CMP-NANA or blood cell extracts, the mutant, JB1, remained serum sensitive. French press extracts of strain F62 catalysed LPS sialylation, but corresponding extracts of the mutant were inactive. Five LPS components were detected by SDS-PAGE in the parental strain. Five components of the same Mr were also found in the mutant. Three identical components were detected by Western blotting using MAb 3F11, which recognizes the Gal beta 1-4GlcNAc groups in the conserved LPS components of F62 which can be sialylated. The mutant, JB1, is therefore deficient in the sialyltransferase that is essential for both LPS sialylation and conversion of serum-sensitive gonococci to serum resistance by either CMP-NANA or blood cell extracts. No evidence was obtained for an LPS sialylation pathway by blood cell extracts that is independent of CMP-NANA.

Antibodies, Monoclonal↗

Tobacco smoking in young adults from 21 European countries: association with attitudes and risk awareness.

Information concerning tobacco smoking was obtained in a survey of 16,483 students aged 18-30 years from 21 European countries. Belief in the benefits to health of not smoking were also assessed. Risk awareness was measured in terms of knowledge of the links between smoking and disease. The overall age-adjusted prevalence of smoking was 33.1% in men and 29.0% in women, but wide variations were observed across country samples. Significant sex differences were found in only a minority of cases. The inclusion of respondents who stated that they had sometimes smoked in the past substantially reduced variations in prevalence across country samples. Beliefs in the health benefits of not smoking were consistently associated with smoking behaviour. Awareness of the link between smoking and lung cancer was uniformly high, but awareness of the role of smoking in heart disease varied considerably across country samples, and averaged only 64.4% in men and 62.9% in women. In the majority of countries, risk awareness was greater among smokers than non-smokers. The results suggest that in this selected sector of the population of young adults in Europe, sex differences in smoking are relatively minor, robust associations between attitudes and smoking behaviour can be identified, and there are major gaps in risk awareness.

Adolescent↗

Constitutive expression of major histocompatibility complex class II antigens on monocytes and B cells correlates with disease in simian immunodeficiency virus-infected rhesus macaques.

Constitutive host factors that influence progression to AIDS are understood poorly. In the macaque model for AIDS, 35 animals infected with simian immunodeficiency virus (SIV) were analyzed for major histocompatibility complex class II antigen expression on blood monocytes and B cells by immunostaining and flow cytometry. Expression varied widely between animals but was constant with time. Level of expression and the proportion of monocytes and B cells that expressed class II were not affected by SIV infection. Significantly more animals developed AIDS in the group with low class II expression than in the group with high expression (P < .001). Progression to disease was faster in animals that expressed poorly (P < .01), and opportunistic pathogens were more common (P < .05). Thus, the constitutive level of class II antigen expression may be a useful prognostic indicator for human immunodeficiency virus disease in humans and may be an important factor in the design of vaccine trials.

AIDS Vaccines↗

Evaluation of a nurse-based hypertension management program: screening, management, and outcomes.

This article reports the experience of patients with elevated blood pressure scheduled to be seen in a nurse-based hypertension management program in a large multispecialty group practice. The hypertension management program is a screening and follow-up program designed to improve the measurement and management of patients' blood pressure with standardized protocols. The cohort for this study of the effectiveness of the hypertension management program consisted of 200 patients with elevated blood pressure (140 referred directly for management and counseling, 60 entered through screening). At entry, only 17% of the patients had blood pressure within controlled limits (< 140/90 mm Hg). One year after entry in the management phase of the program, systolic pressure had decreased an average of 6.20 mm Hg (P < 0.01), and 44% of patients had blood pressure within controlled limits (P < 0.001). These results suggest that the use of standardized screening techniques using multiple measurements helps to ensure that patients will not be unnecessarily treated. Furthermore, patients who entered the program successfully lowered their blood pressure and maintained the reduction over time.

Blood Pressure↗

Sarcoid myopathy in a patient with human immunodeficiency virus infection.

Although neither sarcoidosis nor HIV infection is rare, only eight patients with both diseases have been described. None of the eight had sarcoid myopathy. We describe a patient who had HIV infection and decreased CD4+ T-lymphocytes as well as sarcoidosis with muscle involvement. During 3 years of observation, primary sarcoidosis remitted and myopathic symptoms were controlled with prednisone. No opportunistic infections occurred during more than 3 years of prednisone therapy.

Adult↗

Correct processing of the kiwifruit protease actinidin in transgenic tobacco requires the presence of the C-terminal propeptide.

A 355 cauliflower mosaic virus promoter and a tapetum-specific promoter were used to direct the synthesis in tobacco of preproactinidin and a derivative that lacked a C-terminal extension. Preproactinidin was processed into a form that migrated identically on protein gels with mature actinidin extracted from kiwifruit. This protein was proteolytically active in vitro, and high-level accumulation of this protein appeared to be detrimental to plant growth. Plants expressing an actinidin cDNA construct that lacked the sequence encoding the C-terminal propeptide were phenotypically normal but accumulated N-proactinidin, which was proteolytically active in vitro but did not self-cleave to mature actinidin. In transgenic tobacco, the C-terminal extension of actinidin is therefore required for correct processing.

Base Sequence↗