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Biomedical subjects

N Cox

Publications and source records attributed to N Cox.

At least 73 records · Page 4Linked to original sources
PubMed1993

Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod, Russia.

Children aged 7-14 years in Novgorod, Russia, were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period. Schools were randomly assigned as a whole to one of the preparations. In the first year, the vaccines were bivalent, containing types A (H3N2) and A (H1N1) components. In the second year, the vaccines also contained a type B component. In the first year, all viruses isolated were type A (H3N2); in the second, about three-quarters of the isolates were type B and the rest type A (H1N1). During both years, the vaccines protected the vaccinated children. Where significant differences existed, the live attenuated vaccine was more protective than the inactivated. Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staff and unvaccinated children, suggesting that viral transmission had been reduced by the vaccine.

Adolescent↗
PubMed1993

Influenza A virus haemagglutinin polymorphism: pleiotropic antigenic variants of A/Shanghai/11/87 (H3N2) virus selected as high yield reassortants.

Genetic reassortment of the A/Shanghai/11/87 (H3N2) variant of influenza A virus with A/PR8/34 (H1N1) virus [the standard donor of high yield (hy) genes for influenza vaccine viruses] resulted in the isolation of two reassortants with differing H3 haemagglutinin (HA) phenotypes, X-99 and X-99a. The two HA phenotypes were derived from individual subpopulations of the H3N2 wild-type virus during the reassortment event. The HA mutants and their respectively derived reassortants (identical in RNA genotype) differed in antigenicity, replication characteristics, yield in chick embryos and haemagglutinin gene sequence. Despite antigenic differences in reactions to polyclonal rabbit antisera of 60%, both X-99 and X-99a, the hy reassortants, were equally immunogenic and protective in BALB/c mice to challenge by parental wild-type virus. Differences in HA phenotype were related to a Ser to Ile change at amino acid position 186. These findings emphasize the polymorphism of influenza virus strains as well as the need for caution in selection of vaccine strains from among antigenically distinct viral subpopulations.

Amino Acid Sequence↗
PubMed1993

Human papillomavirus DNA in glandular lesions of the uterine cervix.

AIMS: To assess the role of human papillomavirus in the pathogenesis of adenocarcinoma in situ, endocervical glandular dysplasia (a presumed precursor of adenocarcinoma) and endocervical glandular epithelial giant cell change. METHODS: Viral detection was carried out using an in situ hybridisation technique on paraffin wax sections. Biotinylated probes for human papillomavirus types 6/11, 16/18, 31/33/35 were used with a colorimetric detection system. RESULTS: Nine out of 21 (43%) cases of adenocarcinoma in situ contained human papillomavirus types 16/18, one of which was also positive for 31/33/35. Ten cases of glandular dysplasia and four cases of glandular epithelial multinucleation did not react with the probes used. CONCLUSIONS: These results indicate that while adenocarcinoma in situ is strongly associated with human papillomavirus infection, endocervical glandular dysplasia and glandular epithelial multinucleation are probably not associated with the virus.

Adenocarcinoma↗
PubMed1992

Importance sampling. I. Computing multimodel p values in linkage analysis.

In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. We propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of our method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation.

Diabetes Mellitus, Type 2↗
PubMed1991

Comparative study of intra-articular pressure dynamics in joints with acute traumatic and chronic inflammatory effusions: potential implications for hypoxic-reperfusion injury.

It has been proposed that the process of hypoxic-reperfusion injury contributes to the persistence of synovitis in the inflamed human joint. The generation of pathological, exercise induced, intra-articular pressure leading to occlusion of the synovial microcirculation is central to this mechanism. However, acute traumatic inflammatory joint effusions rarely result in chronic synovitis, suggesting that either the basic hypothesis is incorrect, or that joints with acute traumatic effusions show different intra-articular pressure dynamics. In this study the intra-articular pressure was measured at rest and during isometric exercise in five patients with acute traumatic joint effusions and in nine patients with chronic inflammatory joint effusions. The generation of intra-articular pressure in the patients with acute traumatic effusions was significantly lower at rest (mean 2.0 v 19.6 mm Hg) and during exercise (mean 13.7 v 222.5 mm Hg) than in the patients with chronic effusions. This was due to reflex muscular inhibition around the joint, which inhibited the pathological generation of intra-articular pressure. This difference in the ability to generate intra-articular pressure might mitigate against hypoxic-reperfusion injury in joints with acute traumatic effusions, thereby explaining the paradoxical clinical observation that patients with acute traumatic inflammatory joint effusions rarely develop chronic synovitis.

Acute Disease↗
PubMed1991

Genetic factors in autoimmune thyroid disease analyzed by restriction fragment length polymorphisms of candidate genes.

Possible genetic effects on the development of autoimmune thyroid disease were studied by analysis of restriction fragment length polymorphisms (RFLPs) of candidate genes. Peripheral blood leukocyte DNA was obtained from 65 caucasian patients with Graves' disease, 63 caucasian patients with Hashimoto's thyroiditis, and 65 caucasian controls. RFLP analysis was carried out on genomic DNA, using probes for DR beta, DQ alpha, DQ beta, DP alpha, DP beta, T-cell receptor TCR alpha, and thyroid peroxidase. The methodology allowed HLA-DR and DQ typing and provided information on specific RFLP patterns related to T cell receptor (TCR)alpha, DP alpha and -beta, and -beta, and thyroid peroxidase. HLA-DR3 frequency was significantly increased in patients with Graves' disease, as reported previously by others, but neither DNA-derived subtype of DR3 was differentially increased. HLA-DQw2 was also present in increased frequency because of its linkage disequilibrium with HLA-DR3. It is uncertain whether the primary susceptibility is with DQ, DR, or another nearby locus. Susceptibility was not related in these studies to genetic loci recognized in these studies involving DQ alpha, DP, TCR, or thyroid peroxidase. A significant linkage disequilibrium between DR3 and a specific DX alpha RFLP was observed in Graves' disease, but is believed to be representative of a generalized linkage disequilibrium between DR3 and DX alpha, rather than a specific abnormality in Graves' disease. Previous studies indicating association with specific TCR RFLPs could not be reproduced. The relative risk for carriers of HLA-DR3 subtype A in this study was 7.37-fold. RFLP analysis offers the possibility of investigating linkage in a variety of candidate genes as well as established genetic relationships for potentially important subtypes. While the significant relationship with HLA-DR3/DQw2 was reconfirmed, the involvement of other genes or haplotypes could not be established.

DNA↗
PubMed1990

Characterization of an rRNA gene-specific cDNA probe: applications in bacterial identification.

Discontinuous DNA complementary to Escherichia coli 16S + 23S ribosomal RNA was synthesized by random oligonucleotide priming using reverse transcriptase. cDNA generated from native or denatured rRNA template was labelled by incorporation of either [alpha-32P]dCTP or digoxigenin-labelled dUTP during synthesis, followed by template hydrolysis. The specific activity of the radiolabelled cDNA was 10(7)-10(8) c.p.m. (micrograms rRNA template)-1 with 60-92% incorporation after 5 h. The length of the reverse transcript was between 20 and 1140 nucleotides and was unaffected by exclusion of primer. The cDNA probe could detect 3 pg rRNA by quantitative slot blot. In the non-radiolabelling digoxigenin system 3 micrograms template gave 0.5-2.0 micrograms cDNA after 24 h with a length of between 100 and 1225 bases. This probe could detect 50 pg rRNA. Probes were evaluated in the comparison of Pasteurella haemolytica biotypes by hybridization to Southern blots of restriction-endonuclease-digested total DNA. The digoxigenin-labelled probe was used to identify clinical isolates of Campylobacter jejuni to demonstrate its potential use in laboratories requiring high-sensitivity detection without the use of radioisotopes.

Alkaline Phosphatase↗
PubMed1990

Comparative in situ hybridisation study of juvenile laryngeal papillomatosis in Papua New Guinea and Australia.

A comparative study of cases of juvenile laryngeal papillomatosis from Papua New Guinea (n = 3) and Brisbane, Australia (n = 9) was carried out. In situ hybridisation reactions for human papillomavirus (HPV) types 6 and 11 occurred in 11 cases. All three cases from Papua New Guinea and eight from Australia gave positive signals. A negative reaction was observed in one Australian case. The intensity of the reaction was strong in seven cases, moderate in one, and weak in three. An equivocal reaction was also noted with probes for types 16 and 18, and types 31, 33, and 35 in two cases from Australia and one from Papua New Guinea. It is concluded that as similar staining patterns and intensities occurred in cases from both areas, the aetiology is the same. The equivocal reactions noted in three cases were probably due to cross hybridisation rather than multiple infection.

Child↗
PubMed1990

Enhanced platelet reactivity in cats experimentally infected with feline infectious peritonitis virus.

Platelet function was evaluated in six specific-pathogen-free cats prior to and following intraperitoneal inoculation with feline infectious peritonitis virus (FIPV). By 4 days post-inoculation, platelet samples from five of six cats responded with irreversible platelet aggregation to threshold concentrations of adenosine diphosphate (ADP). This was accompanied by enhanced platelet 14C-serotonin release (greater than 10%) in two cats. Compared to one of six baseline samples, five of five post-inoculation samples exhibited microaggregate formation in response to 20 microM epinephrine. Enhanced platelet 14C-serotonin release did not accompany these responses. Enhanced platelet responses to ADP and epinephrine were also observed on day 11 post-inoculation and day 16 (when one cat died) or 21 (the end of the study). Platelet 14C-serotonin release in response to 20 microM epinephrine increased markedly in three of five cats on day 21. Enhanced collagen-induced platelet responses were not demonstrated. Although the mechanism for the enhanced platelet responses observed on day 4 was unknown, a direct effect on the virus on platelets, mononuclear inflammatory cells, and endothelial cells must be considered.

Adenosine Diphosphate↗
PubMed1990

Polymorphisms of GLUT2 and GLUT4 genes. Use in evaluation of genetic susceptibility to NIDDM in blacks.

The liver/islet (GLUT2) and muscle/adipose tissue (GLUT4) glucose-transporter gene products, membrane proteins that facilitate glucose uptake into cells, are important molecules for normal carbohydrate metabolism. Recent isolation of the genes encoding these proteins provides a means to assess the role of possible defects that might contribute to impaired glucose-stimulated insulin secretion or impaired insulin-mediated glucose uptake, both prominent phenotypic features of non-insulin-dependent diabetes (NIDDM). A GLUT2 cDNA clone was isolated from a human liver cDNA library to search for polymorphisms at this locus in American Blacks. Three highly polymorphic sites were identified, one of which (EcoRI-Hae III) appears to be due to an insertion and/or deletion of 200 base pairs of DNA. Significant linkage disequilibrium between these sites over approximately 30 kilobases of genomic DNA suggested that these polymorphisms could be in linkage disequilibrium with mutations at this locus if they exist. A GLUT4 cDNA clone was also utilized to search for polymorphisms at this locus, but only one previously described polymorphism was observed. GLUT2 and GLUT4 cDNA probes were used to evaluate DNA polymorphisms in genomic DNA from American Blacks with NIDDM. The allelic, genotypic, and haplotypic frequencies of the DNA polymorphisms at these loci did not differ from the frequencies in nondiabetic subjects. Because no associations with NIDDM were found, it appears unlikely that mutations at these loci contribute in a major way to the genetic susceptibility to NIDDM observed in American Blacks.

Alleles↗
PubMed1989

Effect of sucralfate and cimetidine on rheumatoid patients with active gastroduodenal lesions who are taking nonsteroidal anti-inflammatory drugs. A pilot study.

In a pilot study, 26 rheumatoid arthritic patients taking continuous, stable dosage regimens of nonsteroidal anti-inflammatory drugs and with developed gastric and duodenal lesions were administered sucralfate 1 g four times per day (14 patients) or cimetidine 400 mg twice daily (12 patients) in a single-blind regimen for six weeks. Eleven of the patients given sucralfate and eight of the patients taking cimetidine had improved lesion scores. The lesion score of 10 of the 14 patients taking sucralfate and four of the 12 patients taking cimetidine improved by 50 percent or better (not significant). The antrum and body of the gastric mucosa and the mucosa of the duodenum synthesized prostanoids and thromboxane A2, and there was no significant difference in the synthesis of individual prostanoids at entry to the trial in the groups assigned to sucralfate or cimetidine. After six weeks of administration of sucralfate, prostaglandin E2 (PGE2) synthesis by the antrum and body, but not the duodenum, was significantly greater than observed in the biopsy specimens at entry despite continuation of non-steroidal anti-inflammatory drug therapy. After six weeks of cimetidine treatment, no change in PGE2 synthesis was noted in any biopsy specimens when compared with the synthesis at entry. No change in the synthesis of PGF2 alpha, 6-oxo-PGF1 alpha, or thromboxane B2 was noted in gastric or duodenal biopsy specimens in any treatment group. Sucralfate and cimetidine administration resulted in improved gastroduodenal lesion scores in rheumatoid arthritic patients continuing with nonsteroidal anti-inflammatory drug therapy.

Aged↗
PubMed1989

Segregation and linkage analyses of bipolar and major depressive illnesses in multigenerational pedigrees.

Data were collected on six large multigenerational pedigrees, four ascertained through a proband with major depression and two ascertained through a proband with a bipolar form of illness. Diagnoses were made using the SADS-L structured interview and Research Diagnostic Criteria (RDC). Complex segregation analyses were conducted on the bipolar and the major depression pedigree sets using a model allowing for both major locus and polygenic inheritance; in these analyses a variety of diagnostic schemes and assumptions concerning the lifetime population prevalence were examined. Linkage analyses on standard markers were conducted using parameters for transmission of susceptibility to illness derived from the segregation analyses. Results of the segregation analyses were quite sensitive to the diagnostic and prevalence assumptions. In the pedigrees ascertained through probands with a bipolar form of illness, we were unable to discriminate between major gene and polygenic inheritance. The data were compatible with Mendelian major gene transmission of susceptibility to illness when bipolar and schizoaffective manic diagnoses were considered as affected and the lifetime population prevalence was between 0.04 and 0.06. Outside this narrow prevalence range, or when additional diagnoses, such as major depression or hypomania, were included as expressions of liability to disease, major gene transmission of susceptibility to disease could be rejected. Similarly, in the pedigrees ascertained through probands with major depression, it was not generally possible to discriminate between major gene and polygenic transmission of susceptibility to illness. For a diagnostic scheme including only major depression as a manifestation of susceptibility to illness, there was a narrow range of lifetime population prevalence values (female prevalence ranging from 0.20 to 0.25, male prevalence set to 1/2 female prevalence) which yielded results compatible with major gene transmission. Linkage analyses for all markers yielded negative or inconclusive results. In one bipolar pedigree a lod score of 1.65 was found with a marker in chromosome 1 recommending further studies of this chromosome.

Adult↗
PubMed1989

Spontaneous intracorneal haemorrhage.

We describe the unusual complication of spontaneous intracorneal haemorrhage in a patient who used an extended-wear contact lens. This was severe enough to cause corneal blood staining and ulceration which required surgical intervention.

Aged↗
PubMed1989

Evaluation of antithrombin-III activity as a coindicator of disseminated intravascular coagulation in cats with induced feline infectious peritonitis virus infection.

Six adult specific-pathogen-free cats were inoculated intraperitoneally with a cell culture-adapted strain of feline infectious peritonitis virus. Plasma samples were evaluated for antithrombin-III (AT-III) activities at post-inoculation days (PID) 0, 4, and 11 and at termination on PID 16 (1 cat) or 21 (5 cats). Other hemostatic values evaluated were activated partial thromboplastin times, prothrombin times, thrombin times, fibrinogen, platelet counts, and fibrin/fibrinogen degradation products. Antithrombin-III activity remained within normal or above normal range (89 to 246%) in all cats, with the exception of one cat on PID 4 (AT-III, 70%). Mean baseline AT-III activity for 6 cats at PID 0 was 123%. Mean AT-III activity on PID 4, 11, and 16 or 21 was 98, 162, and 130%, respectively. On PID 4 and 16 or 21, results of coagulation screening tests indicated that all cats had disseminated intravascular coagulation. Histologically, cats also had severe fibrinonecrotizing thrombovasculitis.

Acute Disease↗
PubMed1987

A new optical treatment for oscillopsia.

A simple optical device (spectacles plus contact lens) enabling viewing of the real world with either partial or almost-complete retinal image stabilisation has been tested in patients with oscillopsia caused by nystagmus. The device gave a useful improvement in vision in two of 14 patients. Reasons for success and failure were clear and are discussed. Obvious contraindications include severe optic atrophy, titubation and dementia. Net benefit is also unlikely if there is a good null point or area to the nystagmus, or if acuity (corrected but unstabilized) is 6/9 or better. It is not suitable for the treatment of oscillopsia caused by failure of the vestibulo-ocular reflex.

Adult↗