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Biomedical subjects

H R Smith

Publications and source records attributed to H R Smith.

At least 73 records · Page 4Linked to original sources
PubMed1999

The natural killer gene complex genetic locus Chok encodes Ly-49D, a target recognition receptor that activates natural killing.

Previously, we established that natural killer (NK) cells from C57BL/6 (B6), but not BALB/c, mice lysed Chinese hamster ovary (CHO) cells, and we mapped the locus that determines this differential CHO-killing capacity to the NK gene complex on chromosome 6. The localization of Chok in the NK gene complex suggested that it may encode either an activating or an inhibitory receptor. Here, results from a lectin-facilitated lysis assay predicted that Chok is an activating B6 NK receptor. Therefore, we immunized BALB/c mice with NK cells from BALB.B6-Cmv1(r) congenic mice and generated a mAb, designated 4E4, that blocked B6-mediated CHO lysis. mAb 4E4 also redirected lysis of Daudi targets, indicating its reactivity with an activating NK cell receptor. Furthermore, only the 4E4(+) B6 NK cell subset mediated CHO killing, and this lysis was abrogated by preincubation with mAb 4E4. Flow cytometric analysis indicated that mAb 4E4 specifically reacts with Ly-49D but not Ly-49A, B, C, E, G, H, or I transfectants. Finally, gene transfer of Ly-49DB6 into BALB/c NK cells conferred cytotoxic capacity against CHO cells, thus establishing that the Ly-49D receptor is sufficient to activate NK cells to lyse this target. Hence, Ly-49D is the Chok gene product and is a mouse NK cell receptor capable of directly triggering natural killing.

Animals↗
PubMed1999

Characterization of enteroaggregative Escherichia coli isolated from outbreaks of diarrhoeal disease in England.

Twenty-two strains of enteroaggregative Escherichia coli (EAggEC), isolated from four outbreaks of diarrhoeal disease in England, were examined for a range of phenotypic attributes including the ability to produce fimbriae, haemolysins and siderophores, and cell-surface properties such as surface charge and hydrophobicity. Strains of EAggEC isolated from two of these outbreaks belonged to a diverse range of serotypes and were heterogeneous in phenotype. Strains of EAggEC isolated from the other two outbreaks belonged predominantly to serotypes 086:H34 and 098:H-, respectively. Only two strains expressed fimbriae and two strains produced an 18 kDa membrane associated protein (MAP), suggesting that EAggEC express a range of adhesion mechanisms to produce the cell arrangement recognized as the 'stacked brick' formation. The possible explanation for the diversity of EAggEC serotypes is discussed.

Bacterial Outer Membrane Proteins↗
PubMed1999

Reactivation of cutaneous leishmaniasis after surgery.

Cutaneous leishmaniasis (CL) is caused by a parasite from the genus Leishmania. Infection is transmitted to humans from the bite of sandflies. We describe an 85-year-old man who developed CL on his face after recent cutaneous surgery in that site. The case is also unusual because the most likely source of exposure to the infection occurred over 50 years previously. Polymerase chain reaction, slit-skin smear, serology and the leishmanin test were not helpful in diagnosis, which was confirmed by histopathological demonstration of the parasite.

Aged↗
PubMed1999

Dermatological adverse effects with the antimalarial drug mefloquine: a review of 74 published case reports.

Mefloquine is a relatively new antimalarial drug which has been associated with a wide variety of adverse effects, including skin reactions. In order to evaluate the range and frequency of mefloquine's dermatological effects, we searched the scientific literature for published case reports of such effects. We found 74 case reports, published between the years 1983 and 1997. Pruritus and maculopapular rash are the dermatological effects most commonly associated with mefloquine: their approximate frequency is 4-10% for pruritus, and up to 30% for nonspecific maculopapular rash. Adverse effects associated less commonly with mefloquine include urticaria, facial lesions and cutaneous vasculitis. One case of Stevens-Johnson syndrome and one fatal case of toxic epidermal necrolysis occurred. Appropriate primary studies of mefloquine use should be carried out to elucidate the epidemiology and aetiology of dermatological and other adverse effects of the drug.

Adult↗
PubMed1999

Bullous pemphigoid developing during systemic therapy with chloroquine.

Bullous pemphigoid has been reported to be induced or precipitated by systemic therapy with several drugs, including penicillamine, captopril, frusemide and ampicillin. We report an African male patient with sarcoidosis who was prescribed chloroquine for progressive dyspnoea. After 3 months he developed generalized pruritus which evolved into a widespread bullous eruption with acral targetoid lesions resembling erythema multiforme. The histological and immunofluorescence findings were diagnostic of bullous pemphigoid. The atypical clinical features of this case resemble the phenotype that has been noted in previous reports of drug-induced bullous pemphigoid.

Antirheumatic Agents↗
PubMed1999

A study of infectious intestinal disease in England: microbiological findings in cases and controls.

A study was undertaken to identify the microorganisms and toxins in stool specimens associated with infectious intestinal disease (IID) among cases in the community and presenting to general practitioners (GPs) and in asymptomatic controls. Population based cohorts were recruited from practice lists in 70 practices and followed for 26 weeks (cohort component). Seven hundred and sixty-one cases of IID identified from the cohorts, 2893 cases who presented to GPs in 34 of the practices (GP component), and age/sex matched control subjects (555 and 2264, respectively) submitted stool specimens by post for comprehensive microbiological examination. Campylobacter spp (12.2% of stools tested), rotavirus group A (7.7%), and small round structured virus (SRSV) (6.5%) were the organisms most commonly detected in the GP component. SRSV was identified in 7.0% of cases in the community cohort. No target microorganisms or toxins were identified in 45.1% and 63.1% of cases in the two components. Aeromonas spp, Yersinia spp, and some enterovirulent groups of Escherichia coli were detected as frequently in controls as in cases. The higher frequency of detection of campylobacter, salmonella, and rotavirus among cases who presented to GPs than among those in the community suggests that those pathogens cause more severe illness. No enteropathogens were detected from a large proportion of cases although comprehensive standard methods were used to seek them.

Case-Control Studies↗
PubMed1998

Genetic control of natural killing and in vivo tumor elimination by the Chok locus.

The molecular mechanisms underlying target recognition during natural killing are not well understood. One approach to dissect the complexities of natural killer (NK) cell recognition is through exploitation of genetic differences among inbred mouse strains. In this study, we determined that interleukin 2-activated BALB/c-derived NK cells could not lyse Chinese hamster ovary (CHO) cells as efficiently as C57BL/6-derived NK cells, despite equivalent capacity to kill other targets. This strain-determined difference was also exhibited by freshly isolated NK cells, and was determined to be independent of host major histocompatibility haplotype. Furthermore, CHO killing did not correlate with expression of NK1.1 or 2B4 activation molecules. Genetic mapping studies revealed linkage between the locus influencing CHO killing, termed Chok, and loci encoded within the NK gene complex (NKC), suggesting that Chok encodes an NK cell receptor specific for CHO cells. In vivo assays recapitulated the in vitro data, and both studies determined that Chok regulates an NK perforin-dependent cytotoxic process. These results may have implications for the role of NK cells in xenograft rejection. Our genetic analysis suggests Chok is a single locus that affects NK cell-mediated cytotoxicity similar to other NKC loci that also regulate the complex activity of NK cells.

Alleles↗
PubMed1998

Expression of membrane-associated proteins by strains of enteroaggregative Escherichia coli.

Certain strains of enteroaggregative Escherichia coli express an outer membrane-associated protein, involved with the adhesion of these bacteria to HEp-2 cells. Strains of enteroaggregative E. coli hybridising with DNA probes for aggregative adhesion, diffuse adhesion and aggregative adhesion fimbriac II expressed an outer membrane-associated protein of 18 kDa regulated by magnesium ions. Strains hybridising with the aggregative adhesion probe only expressed a 20-kDa outer membrane-associated protein regulated by calcium and magnesium. The present study describes two populations of enteroaggregative E. coli which appear to adhere to HEp-2 cells by expressing antigenically distinct, negatively charged membrane-associated proteins.

Animals↗
PubMed1998

Brain imaging. Functional consequences of ethanol in the central nervous system.

In recent years, sophisticated methods have been developed to view structure and function within the living brain. Functional imaging methods are used to visualize dynamic chemical processes that are linked to brain activity. Increased neural activity, for example, leads to greater glucose and oxygen consumption and greater regional rates of blood flow to meet elevated energy demands. Mapping these changes provides quantitative visual descriptions of localized changes in brain activity that result from behavioral or pharmacological manipulations. This chapter first describes several current methods and how they are used to study the effects of alcohol on brain function. In the second part, the effects of acute intoxication are discussed with emphasis on the complex nature of alcohol's effects in the central nervous system, which depend on dose, time since administration, and environmental context. In the final part, the functional consequences of long-term exposure to alcohol as well as diseases associated with chronic alcoholism are reviewed.

Alcohol Drinking↗