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Biomedical subjects

J M Best

Publications and source records attributed to J M Best.

At least 73 records · Page 4Linked to original sources

The dentist and the pediatric oncology patient.

As the survival rates for pediatric oncology patients continue to increase, more dentists will be faced with providing the necessary dental treatment to these complex dental problems. The dental resolution to the oral presentations of these disease conditions needs to be done in an understanding, supportive environment. The oral cavity and its relationship to both the child's positive self-image and quality of life presents the dental professional with a unique opportunity to enrich the human condition.

Child↗

Fetal infection after maternal reinfection with rubella: criteria for defining reinfection.

Five cases of asymptomatic maternal reinfection with rubella are described that occurred in England and Wales during 1985-8 and resulted in intrauterine infection. The criteria for diagnosing reinfection are described. In four cases the rubella contact was with the woman's own children. Two women had therapeutic abortions, rubella virus being recovered from the products of conception, and three were delivered of infants with congenitally acquired disease. Though the risks associated with maternal reinfection with rubella are very small and being measured in a prospective study, it is hoped that the recently introduced augmented programme of rubella vaccination will reduce rubella in the community and therefore this small risk still further.

Female↗

Growth of rubella virus in a glass bead propagator.

A glass sphere propagator with an air lift pump to circulate the medium, has been successfully used to produce large volumes of rubella virus. The system was productive, flexible and easy to operate.

Animals↗

Identification of immunogenic regions of the major coat protein of human papillomavirus type 16 that contain type-restricted epitopes.

We have identified regions of the major capsid protein, L1, of the human papillomavirus (HPV) type 16 (HPV-16 L1), that are recognized by five monoclonal antibodies (MAbs) raised to a bacterial fusion protein containing residues 172 to 375 of HPV-16 L1. All five MAbs recognized HPV-16-infected tissue sections by immunohistochemistry, but not sections infected with HPV-1a (cutaneous warts), HPV-6b or -11 (genital warts). MAbs 3D1, 5A4 and 1D6 also recognized HPV-2-infected sections (cutaneous warts); MAb 8C4 recognized only sections containing HPV-16. Four MAbs (8C4, 3D1, 1D6 and 5A4) recognized a synthetic peptide corresponding to residues 269 to 284 of HPV-16 L1; within this region a minimum antibody binding site was identified, a tripeptide 276 to 278. However the complete epitope appears to extend beyond these residues and beyond HPV-16 L1 (269 to 284). The fifth MAb, 1C6, recognized bacterial fusion proteins containing HPV-6b L1, -16 L1 or -18 L1 using immunoblots, yet appeared HPV-16-specific when tested on infected tissue sections. This MAb recognized five amino acids within a different region of HPV-16 L1 (residues 299 to 313).

Amino Acid Sequence↗

Prevalence of antibodies to herpes simplex virus types 1 and 2 in pregnant women, and estimated rates of infection.

There has been a recent increase in notifications of genital herpes but it is not known whether this has been reflected in the pregnant population. We have therefore carried out a study to determine the prevalence of herpes simplex antibodies in pregnant women and to estimate the incidence of primary infection. Sera were collected from 3533 women at antenatal clinics and tested for total antibodies to herpes simples virus (HSV), and if positive, for specific antibodies to HSV-2. Estimates of HSV-1 seroprevalence were derived from the HSV-2 seronegative population. HSV-1 seroprevalence was nearly 100% in black women born in Africa or the Caribbean and 60-80% in white, Asian and UK born black women. It was lower in women in non-manual employment. HSV-2 seroprevalence was related to age, rising from 0 at age 16 to 40% at age 35 in black women, and to about 10% in Asian and white women. The estimated incidence of primary HSV-2 infection during pregnancy, per 1000 pregnancies, was about 2.4 in Asian women, 5 in white women, and 20 in black women. Estimates of the incidence of neonatal infection were derived from these figures and compared to the nationally reported rates.

Adult↗

In vivo expression of rubella antigens on human leucocytes: detection by flow cytometry.

Flow cytometry has been used to detect in vivo expression of rubella antigens on human leucocytes. Sequential samples of peripheral blood were obtained from four volunteers with naturally acquired rubella and five persons immunised with RA27/3 rubella vaccine. Leucocytes were stained for rubella antigens using a pool of rubella monoclonal antibodies. Rubella antigens were detected on the leucocytes of all four volunteers with naturally acquired rubella between 1 and 13 days after onset of illness. Viral antigens were expressed more frequently on the monocyte (9-51%) than the lymphocyte (less than 1-4%) and granulocyte (less than 1-3%) populations. Among the vaccines, rubella antigens were detected on the leucocytes of four of the five volunteers between 5 and 12 days after immunisation. The expression of viral antigens was more transient and the proportion of cells exhibiting rubella-specific fluorescence considerably lower following vaccination (1-12%) than natural infection (9-51%). Our results demonstrate that flow cytometry provides a rapid and sensitive analytical technique for detecting viral antigens on leucocytes from infected persons. Leucocytes may play an important role in the pathogenesis of rubella infection.

Adult↗

Class-specific herpes simplex virus antibodies in sera and cervical secretions from patients with cervical neoplasia: a multi-group comparison.

Serum and cervical secretions were collected from patients with cervical dysplasia, carcinoma-in-situ (CIS), squamous cell carcinoma (cervical SCC), and controls with normal cervices, attending clinics within the West Lambeth Health District, London. Enzyme-linked immunosorbent assays were used to examine cervical secretory IgA (sIgA) and serum IgG and IgA antibodies to herpes simplex virus (HSV). Sexual and demographic factors were considered during data analysis, which involved fitting multiple linear or multiple logistic regressions to HSV antibody levels. Prevalence of sIgA-HSV and levels of serum antibodies to HSV in all groups were compared with those of gynaecology controls. Caucasian women with mild dysplasia had a significantly higher prevalence of sIgA-HSV. Serum IgG levels to HSV (IgG-HSV) were significantly elevated in women with mild dysplasia and severe dysplasia/CIS. Serum IgA levels to HSV1 (IgG-HSV1) were significantly higher in women with cervical SCC (after adjusting for smoking habits) and other genital tumours. Significantly higher levels of serum IgA to HSV2 (IgA-HSV2) were also found among Caucasian women with cervical SCC. The possible role of HSV as a co-factor in cervical carcinogenesis is discussed.

Antibodies, Viral↗

Maternal rubella at St Thomas' Hospital in 1978 and 1986: support for augmenting the rubella vaccination programme.

The effects of the rubella epidemics in 1978 and 1986 among patients attending antenatal clinics at St Thomas' Hospital were compared. Although many pregnant women who had been exposed to rubella-like illnesses were investigated in both 1978 (269) and 1986 (160), the number of cases of maternal rubella was substantially lower in 1986 (1) than in 1978 (17). Rubella vaccination of 11-14-year-old girls was introduced in the United Kingdom in 1970, but 10% of our patients were susceptible and only 36% gave a definite history of vaccination. Despite the smaller number of maternal rubella cases, substantial resources were expended on assessing patients who had been exposed to or who presented with rubella-like illnesses. In 1978 an intensification of the selective rubella vaccination campaign was recommended, but experience in the 1986 epidemic supports the view that the programme should be augmented by vaccination of preschool children with a combined measles, mumps, and rubella vaccine, with a view to rubella eradication.

Adolescent↗

Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid beta-oxidation in Leishmania mexicana amastigotes.

The biochemical mechanism of action of antimony (Sb) in pentavalent form complexed to gluconic acid (sodium stibogluconate)--the drug of choice for the leishmaniases--has been only slightly investigated. We recently reported that, in stibogluconate-exposed Leishmania mexicana amastigotes, there is a dose-dependent decrease in the ATP/ADP ratio [Berman et al., Antimicrob. Agents Chemother. 27, 916 (1985)]. To investigate mechanisms by which ADP phosphorylation to ATP might be inhibited, stibogluconate-exposed amastigotes were incubated with [14C]glucose, fatty acid, or acetate, and 14CO2 production was determined. In organisms exposed to 500 micrograms Sb/ml, formation of 14CO2 from [6-14C]glucose and [1-14C]palmitate was inhibited 69 and 67% respectively. In comparison, formation of 14CO2 from [1-14C]glucose and [2-14C]acetate was inhibited less than 15%. These results suggest that glucose catabolism via glycolytic enzymes and fatty acid beta-oxidation, but not glucose metabolism via the hexosemonophosphate shunt or the citric acid cycle, is specifically inhibited in stibogluconate-exposed Leishmania mexicana amastigotes. Inhibition of these pathways suggests a mechanism for the inhibition of ADP phosphorylation previously reported.

Acetates↗

Uptake, distribution, and oxidation of fatty acids by Leishmania mexicana amastigotes.

Fatty acid uptake, distribution, and beta-oxidation were investigated in Leishmania mexicana amastigotes. The uptake of radiolabeled palmitic, stearic, and oleic acids was similar, reaching 3-6 nmol/10(8) cells in 2 min and 8-12 nmol/10(8) cells in 60 min. The percent of radiolabeled fatty acid that was esterified in the form of triglycerides or phospholipids increased from less than 25% at 2 min to 65-86% at 60 min. The dehydrogenase(s) in an amastigote granule fraction were unusual in that the Vmax for long-chain substrates (0.95-1.6 delta Abs units/min-mg protein) approximated the Vmax for short-chain substrates (0.82-2.0 delta Abs units/min-mg protein), and the Km for long-chain substrates was high (approximately 250 microM), in contrast to data for a mammalian liver mitochondrial fraction. The high Vmax and Km for long-chain substrates suggest a biochemical mechanism for the postulated high utilization of fatty acids as an energy source for amastigotes. Although the primary anti-leishmanial agent, Sb in the form of Pentostam, inhibited oxidation of palmitic acid to CO2 by intact organisms, Sb did not significantly inhibit fatty acid uptake or esterification by organisms, or beta-oxidation by the granule fraction, and the mechanism of action of Sb remains unclear.

Acyl-CoA Dehydrogenase↗

Comparison of risk factors for cervical cancer in different populations.

The incidence of cervical cancer has been found to vary between populations. Risk factors of cervical cancer include early age at first marriage, multiple marriages and antibodies to herpes simplex virus type 2 (HSV-2). The interrelatedness of these risk factors was examined by comparing data collected from 428 cancer cases and 947 control women selected from 6 populations having standardized cervical cancer incidence rates varying from 9.3 to 85.1 per 100,000. Logistic regression analysis revealed that multiple marriages, early age at first marriage or pregnancy and HSV-2 antibodies were all associated with significant risk when all 3 factors were entered into the model. Cervical cancer incidence rates were best predicted by the occurrence of HSV-2 antibodies among control women. To further assess the relation between cervical cancer rates and HSV-2 antibody, 2,306 additional sera representing an 0.8% random sample of females over 9 years of age residing in the Republic of Panama were assayed for antibodies to the virus, and the occurrence of antibodies was correlated with invasive cervical cancer rates specific to each Province. Data from both the random sample and the other study populations yielded a linear relation between the occurrence of HSV-2 antibodies and the incidence of cervical cancer. An exception was found for women living in Herrera Province, Republic of Panama, who had a higher cancer rate than predicted by HSV-2 antibody occurrence. The data suggested that infection with HSV-2 is a co-variable of venereal factors, although a role for the virus in the genesis of a certain proportion of cervical cancers is not excluded.

Adult↗