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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 199 records · Page 11Linked to original sources
PubMed1995

The revival of interest in mechanisms of bacterial pathogenicity.

1. After a long barren period, the study of bacterial pathogenicity is now one of the most popular subjects in microbiology. This is because bacterial diseases remain a major problem in public health despite the advent of antibiotics, and the subject is a fertile field for the application of genetics and molecular biology. 2. Pathogenicity is a multifactorial property. The biological requirements are abilities to: infect mucous surfaces; enter the host through those surfaces; multiply in the environment of the host; interfere with host defences; and damage the host. Each requirement has many facets all of which can be accomplished by a variety of processes. 3. The molecular determinants of the five requirements for pathogenicity can be identified and the relation between their structure and function obtained by a seven step procedure. Genetic manipulation and observations on organisms grown in vivo play major roles in this procedure. Other vital aspects are the availability of good animal models and the design of biological tests for virulence determinants in vitro that are pertinent to the situation in vivo. 4. A survey of the state of studies on bacterial pathogenicity has highlighted some areas of immense erudition and exposed others that need more attention in the future. Research is often at the highest level of molecular biology for: adherence to and entry of epithelial cells; interference with humoral and phagocytic defences; toxins; and direct induction of cytokines and inflammation. The major gaps are: the determinants of competition with commensals on mucous surfaces; spread into deeper tissues; the host supplied nutrients and metabolism underlying growth rate in vivo; the determinants of interference with the immune response in important chronic diseases and carrier states; the determinants of immunopathological reactions that cause damage in chronic disease; and the determinants of change from carrier to invasive state. Areas that are receiving some attention but are worthy of more are: moving through mucus to gain access to mucous surfaces; opportunistic infections; the determinants of mixed infections; and the determinants of host and tissue susceptibility to infection. 5. Current interest in the regulation of production of virulence determinants and the influence on it of environmental factors has raised speculation on the role these factors play in vivo. However, it has not yet provided much information on the host factors specifically involved in particular bacterial infections. The individualistic concept of community, as a relative latecomer to discussions of animal community, is sometimes misconstrued as holding that communities are random assemblages of organisms without biotic interactions among species. Nevertheless, it has increasingly been accepted as supported by studies of diverse taxa and habitats. However, many other ecologists continue to argue for integrated, biotically controlled and evolved communities.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

The Effects of Fat Distribution on Resting Energy Expenditure in Premenopausal Morbidly Obese Females.

BACKGROUND: upper body, or abdominal, distribution of body fat is associated with a number of metabolic and hormonal aberrations that could influence resting energy expenditure REE. The purpose of our study was to examine the effects of fat distribution on REE of 96 morbidly obese premenopausal females. METHODS: the study population consisted of three groups of study subjects, 32 with lower body fat distribution (LBD) and waist-to-hip circumference ratios WHR < 0.80, 20 with intermediate (INT) fat distribution and WHR between 0.80 and 0.85 and 34 females with upper body distribution of fat (UBD) and WHR > 0.85. Indices measured included: (1) REE; (2) maximal oxygen consumption during an exercise tolerance test (VO&inf2; max); (3) basal respiratory quotient (RO); (4) fasting blood glucose; and (5) serum cholesterol and triglycerides. RESULTS: we found that morbidly obese women who store fat abdominally (WHR > 0.80) have significantly (p < 0.01) higher REE (kcal per h per BSA) than those with lower body obesity. Levels of triglyceride and glucose of the UBD group were also higher than those of the LBD subjects, i.e. 35% and 23%, respectively. VO&inf2; max and RO were similar between the study groups, suggesting that the elevated REE of the patients with abdominal adiposity were likely not the result of their greater muscle mass or differences in substrate utilization. CONCLUSION: fat distribution affects REE in morbidly obese premenopausal females, and further research is needed to identify the various entities regulating REE in the morbidly obese.

Journal Article↗
PubMed1995

Breast self-examination: attitudes and practices among young women in Europe.

Breast self examination (BSE) is recommended for the early detection of breast cancer in the European Code against Cancer. Evidence from North America suggests that there is reasonable public awareness of its importance, but compliance with regular BSE is reported by only a minority of young women. Attitudes to and practice of BSE has rarely been studied outside North America. In the present study, attitudes to BSE were evaluated by questionnaire in a sample of 16,486 students aged 17-30 from 20 European countries. Frequency of BSE practice was reported by the 9,181 women in the sample. Information on public recommendations concerning BSE was obtained from cancer organizations in each country. The data were collected as part of the European Health Behaviour Survey, an international study on health beliefs and health behaviour. The results showed that BSE was recommended in 16 countries and 'breast awareness' in two, while two countries did not recommend self-examination. 54% of women reported as never having practiced BSE. Regular practice (monthly) was reported by only 8% of the sample, with another 36% reporting occasional BSE. Significant differences emerged between centres in different countries ranging from 6% to 15% reporting regular BSE. Attitude towards BSE was a significant predictor of BSE practice within each centre and across all centres combined. Attitudes towards BSE were significantly less positive in the two centres from countries without BSE recommendations than in the others, but levels of practice were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Fine needle aspiration techniques for the characterization of breast cancers.

Fine needle aspiration biopsy (FNAB) is a well established method for diagnosing breast lesions, including cancers. FNAB does not require surgery and uses only a small amount of material. FNAB can also be used to acquire material for special studies. This is especially useful with small tumors (< or = 1 cm) when most of the material is needed to make a histologic diagnosis. Immunostaining techniques can be used on FNABs to investigate proliferation by bromodeoxyuridine uptake or Ki-67 labeling. Immunostaining techniques can also be used to identify oncoprotein expression, such as of p53. Fluorescence in situ hybridization is a technique that can be used to gather cytogenetic information directly from interphase tumor cells and is well suited for use with FNAB material because the harvested nuclei are intact and no cumbersome dissociation processing is needed. Flow cytometric techniques can be applied to FNAB material to study DNA content and S-phase fraction. Material acquired by FNAB can also be analyzed by the polymerase chain reaction followed by mutation detection. In this report, the authors show the applicability of these various analytic approaches to FNAB material from primary breast cancers. They show that it is essential that the FNAB harvest is representative, ample, and well prepared for the success of these studies.

Biopsy, Needle↗
PubMed1994

Alloproliferative responses of purified CD4+ and CD8+ T cells to endothelial cells in the absence of contaminating accessory cells.

Human capillary endothelial cells (EC), unlike rodent, constitutively express MHC class II antigens, raising the question of whether they can cause direct stimulation of resting T cells. Although previous reports have demonstrated an alloproliferative response between cultured human EC and resting T lymphocytes, they have not stringently proven the absence of contaminating leukocytes in both stimulator and responder populations. Here, we have quantitated the number of contaminating leukocytes in serially passaged human umbilical vein endothelial cells (HUVEC) and have examined the ability of HUVEC and an EC line (EAhy.926) to cause allostimulation of positively selected CD4+ and CD8+ T cells. Contaminating CD45+ leukocytes were found in primary cultures at a mean level of 0.43 +/- 0.49%; by passages 3 and 4 there were less than 1/10,000 cells. CD4+ and CD8+ T cells were purified by positive selection on antibody-coated Dynabeads and residual DR+ cells were removed by complement-dependent lysis. They were shown to be depleted of monocytes by their failure to proliferate in response to OKT3 and PHA. Nevertheless, the same cells gave an unequivocal response to cytokine-treated, serially passaged HUVEC or EAhy.926 cells. The response of CD4+ but not CD8+ T cells was dependent upon pretreatment of HUVEC or EAhy.926 with human rIFN-gamma. Neither CD4+ nor CD8+ T cells responded to MHC class II-bearing fibroblasts or epithelial cells. The CD8+ T cells that recognized EC did not respond to spleen cells in an MLR. The results confirm that EC, unlike other non-bone-marrow-derived cells, have the ability to provide all the signals necessary for direct stimulation of resting allogeneic T cells.

Antigen-Presenting Cells↗
PubMed1994

Sialylation of lipopolysaccharide by CMP-NANA in viable gonococci is enhanced by low Mr material released from blood cell extracts but not by some UDP sugars.

Serum resistance of gonococci in most patients is due to sialylation of a Gal beta 1-4GlcNAc group on a conserved 4.5 kDa lipopolysaccharide (LPS) component by host cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) catalysed by a gonococcal sialyl transferase. This sialylation is enhanced by a low M(r) factor(s) which, like CMP-NANA, is released in diffusates from high M(r) fractions obtained from sonicates dialysed at 4 degrees C. Also, as shown here, this factor(s) is released when the sonicates are dialysed at 18-20 degrees C. The enhancement of sialylation, first demonstrated using enzymes in gonococcal extracts, has been shown to occur in live gonococci and hence probably to have a role in pathogenicity. Gonococci, emerging from lag phase and incubated for 2 h with CMP-14CNANA fixed up to 90% more radiolabel than controls when the second factor(s) was present; their LPS separated by SDS-PAGE contained more radiolabel than control samples and label was not detected in any other component. Fractions with enhancing activity absorbed maximally at about 260 nm but a mixture of UDP-galactose (UDP-Gal), UDP-N-Acetyl galactosamine (UDP-GalNAc), UDP-glucose (UDP-Glc) and UDP-N-Acetyl glucosamine (UDP-GlcNAc) showed no significant enhancing activity. The enhancing action of the low M(r) fractions was unaffected by incubation with beta-galactosidase.

Blood Bactericidal Activity↗
PubMed1994

Phytochrome transgenics: functional, ecological and biotechnological applications.

The phytochromes have important functions in regulating plant growth and development in response to signals perceived from the natural light environment. In particular, the phytochrome-mediated shade avoidance syndrome has major significance for competition between plants growing in natural dense communities. In recent years, the availability of DNA sequences coding for members of the phytochrome family has enabled the construction of transgenic plants that express these sequences to high levels. Introduced PHY genes expressed in heterologous or homologous hosts yield apoproteins that combine with chromophores and are physiologically functional. Physiological analysis of transgenic plants expressing introduced PHYA and PHYB coding sequences has contributed to understanding the functions of phytochromes A and B. Ecological experiments with transgenic PHYA expressers have provided a novel test of the adaptive plasticity hypothesis, and point the way to a transgenic programme to improve crop plants.

Adaptation, Physiological↗
PubMed1994

Primary and secondary liver/kidney microsomal autoantibody response following infection with hepatitis C virus.

Liver/kidney microsomal autoantibody type 1 (LKM-1), which characterizes a subtype of autoimmune hepatitis, is also found in some patients with chronic hepatitis C virus (HCV) infection. Whether HCV and LKM-1 are accidentally or causally related is unknown. This case report describes a child who became infected by HCV after liver transplantation for end-stage liver disease caused by alpha 1-antitrypsin deficiency. LKM-1 was detected by immunofluorescence, anti-microsomal reactivity by Western blotting, anti-HCV and anti-GOR by immunoenzymatic assays, and HCV RNA by polymerase chain reaction. Two weeks after HCV infection, immunoglobulin (Ig) M LKM-1 appeared, followed by IgG1 LKM-1, with titers increasing to 1/2560; antibodies to a 50-kilodalton liver microsomal protein appeared 2 months later. Sera from day 1 posttransplant became positive for HCV RNA. HCV RNA was also detected in a liver biopsy specimen obtained 3 months after surgery. The patient did not produce anti-HCV and anti-GOR antibodies throughout the study and had no histological evidence of hepatitis. The temporal relationship between HCV infection and LKM-1 production suggests that HCV may trigger a primary autoimmune response. The lack of liver damage attributable to autoimmunity or viral infection may be caused by immunosuppression.

Antibody Formation↗
PubMed1994

Mutagenicity of mono- and dinitropyrenes in the Salmonella typhimurium TM677 forward mutation assay.

Nitropyrenes are a group of widespread environmental pollutants, some of which are highly potent as bacterial and mammalian cell mutagens and as animal carcinogens. A quantitative bacterial forward mutation assay, based on resistance to 8-azaguanine (8-AG) in Salmonella typhimurium TM677, was employed as an alternative to reversion assays to reexamine the mutagenicity of 1-, 2-, and 4-nitropyrene (1-, 2-, and 4-NP) and 1,3-, 1,6-, and 1,8-dinitropyrene (1,3-, 1,6-, and 1,8-DNP) in the presence and absence of rat liver postmitochondrial supernatant (PMS). The major finding is that 2-NP, reported as a potent mutagen in the absence of PMS in bacterial reversion assays, was inactive in the absence of PMS in this assay. However, 2-NP was mutagenic in the presence of PMS. The implications of this observation with respect to sample purity and the metabolism of 2-NP are discussed. Without PMS the following minimum detectable mutagen concentration (MDMC) potency series expressed as nmol/ml was obtained: 1,8-DNP (0.5 x 10(-3)), 1,6-DNP (1.2 x 10(-3)), 1,3-DNP (2.3 x 10(-3)), 4-NP (0.2), 1-NP (0.2), 2-NP (> 1200), pyrene (> 1500). With PMS the potency series was: 1,6-DNP (0.7), 1,8-DNP (2.1), 4-NP (2.2), 2-NP (2.6), 1,3-DNP (3.7), 1-NP (4.6), pyrene (> 1500). With the exception of 2-NP, all the nitropyrenes were more mutagenic without PMS than with PMS. The greatest difference was observed with the dinitropyrenes, which were three orders of magnitude less potent in the presence of PMS. Pyrene, often reported as a bacterial mutagen in the presence of PMS, was nonmutagenic in this assay when a purified sample was tested.

Animals↗
PubMed1994

Hepatitis C and E in non-A non-B fulminant hepatic failure: a polymerase chain reaction and serological study.

A significant proportion of patients with fulminant hepatic failure have clinical, biochemical and histological features suggestive of acute viral hepatitis, without serological evidence of either hepatitis A or B. The contribution of hepatitis C to such cases of non-A non-B fulminant hepatic failure is presently uncertain while hepatitis E is well recognized as a cause of fulminant hepatic failure in endemic areas. Nested polymerase chain reaction for detection of both hepatitis C and E virus as well as two serological assays for anti-hepatitis C virus and anti-hepatitis E virus western blotting (both IgG and IgM) were performed on acute sera of 42 consecutive cases of non A, non B-fulminant hepatic failure and on convalescent sera of 17 of 20 patients who underwent orthotopic liver transplantation. Fresh liver tissue, obtained at the time of transplantation, was also studied by polymerase chain reaction in eight cases. Evidence of an acute hepatitis E virus infection (hepatitis E virus RNA amplified from serum by polymerase chain reaction or serum IgM positive to western blot) was found in eight patients. One patient had anti-HCV at presentation but assays on later sera proved negative. Convalescent sera and sera obtained after orthotopic liver transplantation were all negative to both anti-HCV assay systems, but HCV RNA was not found in either serum or liver tissue in any case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Botulinum toxin A for hyperkinetic facial lines: results of a double-blind, placebo-controlled study.

Previous work on patients with muscular dystonia has shown that small intramuscular doses of botulinum toxin A eliminated hyperkinetic facial lines for approximately 6 months. The purpose of this study was to determine the efficacy of botulinum toxin A injections in eliminating facial wrinkles in aesthetic surgery patients who do not have muscular dystonia. Eleven healthy subjects were studied in a double-blind fashion. On both sides of the face, 0.2 cc of either normal saline or botulinum toxin A was injected into the forehead or into the periorbital wrinkles (crow's feet). Documentation of results was made by photographs taken of the patients during repose and during facial animation before and after injection. Assessment of facial wrinkles was done from a grading system in which the patient and the facial plastic surgeon were asked to judge the severity of the wrinkles on a scale from 0 to 3, with 0 reflecting no facial wrinkles and 3 reflecting severe facial wrinkling. Nine of 11 subjects injected with botulinum toxin A noted a significant improvement in the severity of their facial wrinkles in comparison with the side of the face injected with saline, with a rating improvement of 2 points. Two of 11 subjects noted a moderate improvement, with a rating improvement of 1 point. No patient injected with saline reported an improvement in the severity of the facial wrinkles on the control side. There were no serious complications. Botulinum toxin A is an efficacious method of nonsurgically eliminating facial wrinkles and may play a role in the cosmetic enhancement of the aging face.

Adult↗
PubMed1994

Role of surface glycoproteins in influenza virus pyrogenicity.

Eleven H3N2, seven H1N1 and three H3N1 influenza virus reassortants of the pyrogenic A/Puerto Rico/8/34-A/England/939/69 clone 7a (H3N2) (A/7A) and poorly pyrogenic A/Fiji/15899/83 (H1N1) (A/Fiji) parents were analysed genetically for the parental origin of their genes and for their pyrogenicity in ferrets. All H3N2 reassortants were pyrogenic and produced significantly more fever than A/Fiji but differences in pyrogenicity between them could not be correlated with either single or constellations of genes. All H1N1 reassortants were poorly pyrogenic compared with A/7A but one (Am29) produced significantly more fever than A/Fiji. No correlation of the increased fever with inserted A/7A genes was evident in Am29 and, while mutations were detected in the H1 haemagglutinin of this reassortant using monoclonal antibodies, similar mutations were present in the other H1N1 reassortants which showed no increase in fever production. The three H3N1 reassortants were intermediate in their pyrogenicity, being more pyrogenic than A/Fiji and less pyrogenic than A/7A. Overall, these results support previous conclusions that the haemagglutinin and/or neuraminidase play a major role in the pyrogenicity of influenza virus.

Animals↗