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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 415 records · Page 23Linked to original sources

Development of an enzyme immunoassay for rat soluble interleukin-2 receptors.

This study describes the development of a sandwich enzyme immunoassay (ELISA) for rat soluble IL-2 receptors (sIL-2R) using a combination of monoclonal antibodies reactive with different epitopes on the rat IL-2R. Coating plates with NDS61 and NDS64 monoclonal antibodies produced similar dose-response curves when incubated with a standard sIL-2R preparation followed by biotinylated OX39, streptavidin-alkaline phosphatase and the substrate. Although normal rat serum inhibited the assay, the effects were more profound when NDS64 was used as the capture antibody and subsequent development of the assay was performed using NDS61. The intra- and interassay variations were typically less than 5%. This assay will be valuable for monitoring immune activation status in a variety of experimental models.

Animals↗

Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Blood Pressure↗

Smoking among New Zealand adolescents 1960-93.

AIM: To examine the prevalence of smoking among New Zealand youth from the 1960's to the 1990's to determine whether smoking among the young is increasing or decreasing. METHOD: Major surveys of smoking among adolescents were reviewed and analysed to identify trends in smoking over time. Using data from the Dunedin and Christchurch longitudinal studies of child development, it was also possible to examine recent cohort changes in uptake of smoking. RESULTS: Evidence suggests that by the 1990's about one in every five 15 year-olds had smoked in the last month, while about one in every ten smoked daily. This represents a significant decline from very high levels of smoking in the 1970's, and appears to have occurred among boys and girls, European and Maori, although perhaps less so among adolescent girls. CONCLUSION: Despite some community perceptions to the contrary, there have been significant declines in smoking among adolescents over the last three decades. Overall, the data present a somewhat encouraging view of smoking among New Zealand youth. However, further inroads into smoking in this age group may well depend upon greater restrictions of access to cigarettes and overcoming barriers to the implementation of school based educational programmes.

Adolescent↗

Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment.

The major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response is important in the clearance of viral infections in humans. After influenza A infection, a peptide from the matrix protein, M58-66, is presented in the context of the MHC allele HLA-A0201 and the resulting CTL response is detectable in most HLA-A0201 subjects. An initial study suggested that M58-66-specific CTL clones show conserved T cell receptor (TCR) alpha and beta gene segments. We have addressed the significance of this observation by determining the expression of V beta 17 during the development of M58-66-specific CTL lines in 21 unrelated HLA-A0201 subjects, and analyzing TCR usage by M58-66-specific CTL clones. TCR V beta 17 was the dominant V beta segment used and CD8 V beta 17 expansion correlated with M58-66-specific lysis. Limiting dilution analysis from five subjects showed the M58-66 CTL precursor frequency to vary between 1/54,000 and less than 1/250,000, and that up to 85% of the matrix peptide (M58-66)-specific CTL used the V beta 17 gene segment. The M58-66 specific CTL response was dependent on previous viral exposure and specific V beta 17 expansion, as it was not found in cord blood, despite a readily expandable V beta 17+ CD8+ T cell subpopulation. Sequence analysis of 38 M58-66-specific V beta 17 transcripts from 13 subjects revealed extensive conservation in the CDR3 region including conservation of an arginine-serine motif. To test the dependence of this CTL response on the V beta 17 gene segment, peripheral blood lymphocytes were depleted of CD8+ TCR V beta 17+ cells, before the generation of M58-66-specific CTL. In most cases such depletion blocked or severely reduced the generation of the M58-66-specific response, and under limiting dilution conditions could abolish M58-66-specific CTL precursors. These studies reveal the dependence of this natural human immune response on a particular TCR gene segment.

Alleles↗

Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase.

Two classes of protein tyrosine kinases (PTK) are utilized by the T cell antigen receptor (TcR)/CD3 complex for initiation of the signaling cascade, the Src-family PTK p56lck and p59fyn, and the Syk-family PTK p70zap and p72syk. In addition, the CD45 phosphotyrosine phosphatase (PTPase) is required for the induction of tyrosine phosphorylation by the TcR/CD3, presumably by positively regulating Src-family PTK. Here we report that CD45 also regulates the Syk-family PTK p70zap (or ZAP-70). In CD45-negative T cells, p70zap was constitutively phosphorylated on tyrosine and co-immunoprecipitated with the TcR-zeta chain. In resting wild-type CD45-positive cells, p70zap was mainly unphosphorylated, but it was rapidly phosphorylated on tyrosine upon treatment of the cells with anti-CD3 or PTPase inhibitors. Finally, p70zap co-distributed with CD45 in intact T cells, and tyrosine phosphorylated p70zap was dephosphorylated by CD45 in vitro. These findings suggest that CD45 plays an important role, direct or indirect, in the regulation of p70zap and its function in TcR/CD3 signaling.

Cell Line, Transformed↗

Characterization of a t(10;11)(p13-14;q14-21) in the monoblastic cell line U937.

Previous analysis of the monoblastic cell line U937 has shown that several sublines contain a rearranged chromosome arm 11q. In order to determine the true nature of the rearrangement, fluorescence in situ hybridization (FISH) was carried out with various combinations of single copy anonymous markers, clones containing genes, a chromosome 10 paint, and an 11 centromere specific sequence. The rearrangement was deduced to be a reciprocal translocation between chromosomes 10 and 11 described as t(10;11)(p13-14;q14-21). The breakpoint on chromosome 11 is telomeric to the INT2 gene and the pHS11 probe at 11q13, and centromeric to the marker D11S36 localized to 11q14.3-q22.1 and the MLL gene at 11q23. Similar translocations have been reported in various acute leukemias, principally of the monocytic lineage, and also in T-cell precursor acute lymphocytic leukemias. Further characterization of the genetic rearrangements in U937 may lead to the isolation of genes important in leukemogenesis and provide an in vitro system for their study.

Chromosome Mapping↗

From rodent glial precursor cell to human glial neoplasia in the oligodendrocyte-type-2 astrocyte lineage.

With only a few exceptions, the precursor cells representing the normal counterparts of human tumours are unknown. The comparative lack of information about the lineages involved in tissue development, and difficulties in growing many human tumors in a manner suitable for cellular biological analysis, together often make it difficult to study the differences between normal and tumor cells and to develop many of the model systems that would be useful in the study of human cancer. By applying techniques previously utilized to study glial progenitor cells, we have isolated a human glioblastoma multiforme (GBM)-derived population that expresses many properties otherwise uniquely expressed by oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (for Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, and generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, 1H-NMR analysis of amino acid composition demonstrated a striking conversation of types and quantities of free amino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible, and our results indicate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. In addition, the highly diagnostic 1H-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibility of eventual non-invasive identification of tumors of this lineage.

Animals↗

Potential of cervical electrosurgical excision procedure for diagnosis and treatment of cervical intraepithelial neoplasia.

The aim of this study was to evaluate the diagnostic potential, treatment efficacy, specimen adequacy, and acute complication rate associated with electrosurgical excision procedure (EEP) of the cervix for the management of cervical intraepithelial neoplasia (CIN). Analysis was performed retrospectively on 153 consecutive patients who underwent EEP under colposcopic guidance. Patients with negative endocervical curettage (ECC), adequate colposcopy, and biopsy-proven CIN were considered candidates for therapeutic EEP, whereas patients with a positive ECC, inadequate colposcopy, or cytology two or more grades discordant from the biopsy results underwent diagnostic EEP. Histopathologic specimens were graded as adequate, suboptimal, or inadequate. Diagnostic EEP was performed in 85 cases, and the remaining 68 procedures were performed primarily for treatment. Specimens were graded as adequate in 83%, suboptimal in 13%, and inadequate in 4% of the diagnostic EEP's. Specimen adequacy correlated most strongly with operator experience (P < 0.05). Four patients were found to have microinvasive or invasive cervical carcinoma. Complications occurred in 7% of the EEPs performed. Most consisted of immediate or delayed hemorrhage. In conclusion, EEP is a safe, well-tolerated procedure which is acceptable as both a therapeutic and diagnostic tool in the management of CIN when performed by an experienced operator. We recommend that initial EEP procedures should be performed for therapeutic indications, since adequacy of EEP specimens correlated with the level of operator experience.

Adult↗

Outcome of the Vaginal Infections and Prematurity Study: results of a clinical trial of erythromycin among pregnant women colonized with group B streptococci.

OBJECTIVE: Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight (< 2500 gm) and preterm (< 37 completed weeks) birth. STUDY DESIGN: In a double-blind clinical trial, 938 carriers of group B streptococci were randomized to receive erythromycin base (333 mg three times a day) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy. RESULTS: Pregnancy outcomes were available for 97% of randomized women; 14% of subjects withdrew from the trial. Birth weight < 2500 gm occurred in 8.6% of the erythromycin and 6.1% of the placebo recipients (relative risk 1.4, 0.9 to 2.2, p = 0.16). Preterm delivery occurred in 11.4% of women randomized to erythromycin and in 12.3% randomized to placebo (relative risk 0.9, 95% confidence limits 0.6 to 1.3, p = 0.65). Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance. CONCLUSIONS: In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight. Greater than anticipated complicating factors, including spontaneous clearance of the organism, use of nontrial antibiotics, and density of colonization, may have resulted in population sizes too small to detect a benefit of treatment. Future studies should take these factors into account in determining sample sizes.

Adult↗

Strange-male-induced pregnancy disruption in mice: reduction of vulnerability by 17 beta-estradiol antibodies.

It is well-established that novel males can disrupt early pregnancy in house mice. Inseminated female C57BL mice were either left undisturbed or each exposed indirectly to a novel HS male through a wire-mesh grid during days 1-6 of pregnancy. Varied dosages of antibodies to 17 beta-estradiol were administered to females exposed to males. Vehicle-treated females exposed to novel males showed fewer litters than did nonexposed controls. Male-exposed females given 1 ml daily of the antibody showed rates of pregnancy comparable to those observed in controls. These data suggest that estrogen levels might play a role in strange-male-induced pregnancy disruptions, converging with evidence implicating estrogens in stress-induced pregnancy blocks.

Animals↗

Predicting resting blood pressure at eighteen years: the Dunedin Study.

PURPOSE: To examine the value of repeated blood pressure screening during childhood, and exercise testing in adolescence, for predicting resting blood pressure at eighteen years. METHOD: Regular measures of blood pressure and other variables in a birth cohort from 7 to 18 years. Cardiovascular responses to exercise testing at 15 and 18 years. RESULTS: The best predictors of resting blood pressure at 18 years were body size at 18 years and resting blood pressure at 15 years. Neither exercise and recovery blood pressures at 15 years, nor the way blood pressure had tracked through childhood, added importantly to the prediction. CONCLUSION: We question the value of screening for hypertension during childhood, either by regular resting measures or by exercise testing in adolescence.

Adolescent↗

A comparison of the chest radiograph and computerised tomography in assessing lung changes in acute spinal injuries--an assessment of their prevalence and the accuracy of the chest X-ray compared with CT in their assessment.

Lung function in patients following an acute spinal injury is frequently much more compromised than may be expected from the level of injury and the chest radiograph appearance. Experimental evidence in anaesthetised patients and subsequently our own experience with patients with acute spinal injuries suggested that in paralysed patients lung changes were frequent and that in many spinal patients large pleural effusions and lung consolidation could be present without the usual associated chest radiograph changes being recognised. This study was performed to assess the prevalence of chest pathology and the sensitivity of the chest radiograph in portraying it. Sixty patients (50 males, 10 females, 31 cervical, 29 thoracic or thoracolumbar; 15 incomplete, 45 complete; ages 17-66, mode 22 years) with spinal injuries from a variety of causes were assessed with a supine chest radiograph and three computerised tomography axial cuts at standardised locations through the thorax. The chest radiograph agreed with the computerised tomography in only 12 patients (six normal, six abnormal). The chest radiograph suggested that there were 19 normals but computerised tomography only showed 12. In a total of 35 patients, the chest radiograph significantly underestimated the degree of change and in 13 the chest radiograph suggested greater pathology than was shown on computerised tomography. Thirteen of the 20 patients with cervical lesions but no chest trauma had lung changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Incisor stability in patients with anterior rotational mandibular growth.

The aim of this study was to investigate stability and patterns of relapse tendency in 42 children in whom mandibular incisors had been proclined as part of orthodontic treatment. All patients were selected on the basis of their predicted anterior rotational mandibular growth pattern. Results were based on study casts and standardized cephalometric profile radiographs, registered before and after active treatment as well as after a postretention period. Results demonstrate the clinical acceptability of the treatment principle employed in that the majority of the treatment changes were maintained well after the cessation of retention. There was, however, a general tendency to slight crowding in the mandibular incisor region in connection with bite deepening and reduction in intercanine distance. The reliability of prediction of mandibular rotation using the morphological criteria method is discussed.

Adolescent↗