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Biomedical subjects

A Kelly

Publications and source records attributed to A Kelly.

At least 145 records · Page 8Linked to original sources

Sero-epidemiology of toxocariasis in school children.

The seroprevalence of toxocariasis was investigated in 2129 school children ranging in age from 4 to 19 years. Infection, as measured by titre, was found to be high compared to values obtained from children in other countries, with 31% having a titre of > or = 1:50 and 3.1% having titres of > or = 1:800. Relationships between seroprevalence and host factors including age, sex and location, and risk factors including geophagia, thumbsucking and pet ownership were explored. Age was found to be a significant factor in relation to infection with Toxocara. Males were significantly more infected than females, as were the inhabitants of rural schools versus urban schools. The percentage of seropositive children varied widely from school to school. Geophagia and pet ownership were found to be significantly associated with toxocariasis. Logistic regression analysis was used to model the relative contribution of these factors to infection with Toxocara. While this analysis identified factors which were highly significantly associated with Toxocara titre, the odds ratios were generally low indicating the low specificity of the model.

Adolescent↗

Isolation of a human allo-peptide presented by HLA-B51 molecules.

Recent studies have demonstrated directly that alloreactive mouse CTL recognize peptides presented by MHC class I molecules. However, there is no direct evidence that human alloreactive CTL recognize peptides presented by HLA class I molecules. We have isolated an HLA-B51 alloreactive CTL clone, 2B3, that did not kill the TAP defective cell lines T2 and .174, whereas it killed the TAP-positive cell line T1 and .174 cells transfected with TAP genes. These findings suggested that this clone recognizes a TAP-dependent allo-peptide. We attempted to isolate the human allo-peptide recognized by the 2B3 clone from HLA-B51 molecules. A naturally occurring HLA-B*5101 binding peptide isolated from T1 cells was recognized by the 2B3 clone. The peptide was also isolated from HLA-B*5101 molecules purified from C1R-B*5101 cells. In the present study, we directly demonstrated that a human alloreactive CTL clone recognizes peptide presented by HLA class I molecules.

Antigen Presentation↗

Small area variation in the utilization of mental health services: implications for health planning and allocation of resources.

OBJECTIVE: To determine the variables associated with utilization of mental health services and to develop a planning model to predict service utilization that incorporates these factors. METHOD: A regression analysis of service utilization and demographic characteristics was used to assess the relative importance of alternative service, supply of psychiatrists and demographics in explaining variations of services use. A model using socioeconomic factors was applied to the population to predict need. RESULTS: The percentage of divorced males was the only factor significantly and positively correlated with the utilization of hospital inpatient and provincial psychiatric beds. Predicted need exceeds utilization in 7 out of 10 areas for all services. CONCLUSIONS: Small area variations in inpatient psychiatric utilization is correlated with community characteristics, not supply of psychiatrists or utilization of alternative services. A model has been developed using census data to allocate resources according to need.

Adult↗

Nurse practitioners.

The department of health is keen to explore the potential of the nurse practitioner to substitute some areas of health care for the more expensive medical practitioner. The RCN has developed a specialist course for nurse practitioners. But as yet there is no clear definition of the role or educational status of the nurse practitioner. This professional briefing examines the issues, and suggests that attempts to define a specific nurse practitioner discipline and role limits its potential, and the potential for the development of current community nursing practitioners.

Humans↗

Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments.

The HLA-DM genes encode an unconventional HLA (human leukocyte antigen) class II molecule that is required for appropriate binding of peptide to classical HLA class II products. In the absence of DM, other class II molecules are unstable upon electrophoresis in sodium dodecyl sulfate and are largely associated with a nested set of peptides derived from the invariant chain called CLIP, for class II-associated invariant chain peptides. DMA and DMB associated and accumulated in multilaminar, intracellular compartments with classical class II molecules, but were found infrequently, if at all, at the cell surface. Thus, DM may facilitate peptide binding to class II molecules within these intracellular compartments.

Animals↗

Characteristics of women with a family history of ovarian cancer. II. Follicular phase hormone levels.

BACKGROUND: Although there is a basis for linking pituitary or ovarian hormones with experimentally induced ovarian cancer, establishing their role in women is complicated because the usual case-control methods cannot be applied. In this study, hormonal levels in women with a family history of ovarian cancer (FOC) and who are at higher risk for the disease are compared with women without such a history. METHODS: The authors studied 106 unrelated women (FOC patients) with at least one primary or two second-degree relatives with ovarian cancer compared with 116 age- and residence-matched controls without a family history of ovarian cancer (FOC control subjects). All women were premenopausal, between the ages of 25 and 49 years, not currently using oral contraceptives, and had blood drawn during the early follicular phase for gonadotropins, estradiol (E2), and CA-125. RESULTS: Women with a family history of ovarian cancer and control subjects did not differ significantly in follicle stimulating hormone (FSH) levels, E2, or CA-125. Patients with a family history of ovarian cancer had significantly lower luteinizing hormone (LH) levels compared with control subjects and produced more E2 and FSH relative to their level of LH. The ratios of LH to E2 and LH to FSH were correlated with the enzymatic activity of galactose-1-phosphate uridyl transferase, which was shown previously to differ between FOC patients and control subjects. CONCLUSION: Lower LH and higher E2 are reported in women with breast, endometrial, and ovarian cancer (before surgery). The authors speculate that these observations reflect greater LH binding and estradiol production in ovaries at risk for these cancers--the ovarian cortical hyperplasia postulated in older gynecologic literature as the precursor to estrogen dependent neoplasia.

Adult↗

Genomic organization of HLA-DMA and HLA-DMB. Comparison of the gene organization of all six class II families in the human major histocompatibility complex.

The genomic nucleotide sequences of HLA-DMA and HLA-DMB have been determined and their gene organizations have been compared with other human class II genes. The following features were found to be highly conserved throughout all human class II families. (i) All alpha genes are composed of 5 exons and all beta genes of 6 exons. (ii) The intron-exon boundary classes of exons 1-4 (alpha genes) and exons 1-5 (beta genes) are 100% conserved. Only the last boundary class which falls within the cytoplasmic domain appears to be variable. (ii) The size of exon 3 (membrane proximal domain) is also 100% conserved except for DMA (-1 codon) and DMB (+1 codon). The position and a possible functional implication of this deletion/insertion are discussed. Our findings confirm and extend the evidence based on sequence homology that DMA and DMB are different from typical class II genes suggesting that they may originate from a time prior to the divergence of the main class II genes. In addition we have identified various new repeat sequences within class II genes. Analysis of their classification and distribution reveal single and multiple repeat mediated recombination events. One of these events seems to have partially replaced exon 1 in DPA2. The possibility of this event causing DPA2 to become a pseudogene is discussed.

Amino Acid Sequence↗

Homozygous human TAP peptide transporter mutation in HLA class I deficiency.

Human lymphocyte antigen (HLA) class I proteins of the major histocompatibility complex are largely dependent for expression on small peptides supplied to them by transporter associated with antigen processing (TAP) protein. An inherited human deficiency in the TAP transporter was identified in two siblings suffering from recurrent respiratory bacterial infections. The expression on the cell surface of class I proteins was very low, whereas that of CD1a was normal, and the cytotoxicity of natural killer cells was affected. In addition, CD8+ alpha beta T cells were present in low but significant numbers and were cytotoxic in the most severely affected sibling, who also showed an increase in CD4+CD8+ T cells and gamma delta T cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Long-term pain: less common after laparoscopic than open cholecystectomy.

Persistent symptoms after cholecystectomy are common, occurring in up to 40 per cent of patients. Severe pain persists in 10 per cent of cases. A total of 450 patients were studied, 200 after open cholecystectomy and 250 after the laparoscopic operation. Patient notes were reviewed and a postal questionnaire was circulated. Responses were obtained from 155 patients (77.5 per cent) undergoing open cholecystectomy and 205 (82.0 per cent) having the laparoscopic operation. Mean (s.d.) follow-up was 32(23) months after open cholecystectomy and 15(7) months after the laparoscopic procedure. Right upper quadrant pain was more common after open cholecystectomy (9.7 versus 3.4 per cent, P < 0.05). Indigestion and heartburn were equally prevalent in the two groups. Some 59.4 per cent of patients were free from symptoms after open cholecystectomy compared with 63.4 per cent following the laparoscopic operation; there was symptomatic improvement in 30.3 and 31.7 per cent respectively. Symptoms were the same or worse in 10.3 per cent of patients after open cholecystectomy compared with 4.9 per cent after the laparoscopic operation (P < 0.05). Patients report significantly less right upper quadrant pain after laparoscopic than after open cholecystectomy.

Cholecystectomy↗

Cloning and characterization of human phosphatase inhibitor-2 (IPP-2) sequences.

cDNA clones similar to rabbit muscle phosphatase inhibitor-2 (IPP-2) were isolated from human libraries. On Northern blots two transcripts of approximately 2kbp and approximately 4kbp were detected in all tissues tested. Analysis of cDNA sequences showed that the longer transcripts were similar to the shorter clones but contained extended 3' ends. The human nucleotide sequence was highly homologous (94% identity) to the rabbit IPP-2 sequence and encoded a peptide of 205 amino acids. IPP-2 sequences were highly conserved throughout vertebrates. Southern hybridization results were consistent with the existence of a family of related IPP-2 sequences in the human genome. Most of these are likely to be pseudogenes, since all of the cDNA clones examined could have originated from a single gene. By in situ hybridization IPP-2 sequences were mapped to several different human chromosomes. We sequenced one gene located in the major histocompatibility complex (MHC) on Chromosome (Chr) 6 that contained the entire coding region of IPP-2.

Amino Acid Sequence↗

Cloning of the region between HLA-DMB and LMP2 in the human major histocompatibility complex.

The human MHC is one of the most extensively mapped regions of the human genome. Almost all of the class II region of the MHC has already been cloned in cosmids but a gap remained between the DMB and LMP2 genes. Previously, screening of several complete cosmid libraries had failed to bridge this gap, which may contain novel antigen processing or presentation genes. We constructed cosmid libraries from two different sources in order to clone the region: (a) a library with fourfold coverage made from flow-sorted human chromosome 6 DNA and (b) a library derived from a yeast artificial chromosome clone spanning the region. Using this saturation approach, cosmid clones were eventually isolated over the region of interest. A single bacteriophage P1 clone was also obtained spanning the region. The YAC, cosmid, and P1 physical maps were consistent and the distance between the DMB and LMP2 genes was measured as 70 kb. It is not clear why DMB to LMP2 is infrequently represented in cosmid libraries, but the clones that we have obtained will now enable us to search for new coding sequences.

Bacteriophage P1↗

High dosages of gonadotropins are associated with poor pregnancy outcomes after in vitro fertilization-embryo transfer.

OBJECTIVE: To compare the pregnancy outcomes during IVF-ET when different dosages of hMG are used after follicular phase suppression with leuprolide acetate (LA). DESIGN: Retrospective chart review. SETTING: Hospital-based IVF-ET program. PATIENTS: From January 1990 to December 1992, 264 cycles reached ET after LA downregulation and gonadotropin stimulation. RESULTS: Higher doses of gonadotropins, as measured by both average daily dose and total dose per cycle, were associated with lower clinical pregnancy rates. This effect was independent of age, basal FSH level, endometrial thickness, maximal E2 levels, number of eggs retrieved, and embryos transferred. CONCLUSION: High dosages of exogenous gonadotropins are associated with lower pregnancy rates in IVF-ET.

Adult↗

Clonality of CD3 negative large granular lymphocyte proliferations determined by PCR based X-inactivation studies.

AIMS: To examine persistent CD3-large granular lymphocytosis (LGL) cases for clonality, both by lineage specific (T cell receptor) and lineage independent (X-inactivation) molecular methods; and to find out whether X-inactivation studies are more appropriate than gene rearrangement studies for this subset of LGL disorders. METHODS: Patients were selected who had LGL of more than six months' duration and identified as CD3- by immunophenotyping. T cell receptor studies and, where possible, X-inactivation studies of the phosphoglycerate kinase (PGK) gene were carried out. Analysis of subpopulations was carried out on cases heterozygous for PGK by the use of a polymerase chain reaction (PCR) method for X-inactivation. RESULTS: Of 17 CD3- LGL cases studied, all were found to be germline for beta, gamma, and delta T cell receptor studies, and immunoglobulin heavy chain genes. However, six of these were analysed by X-inactivation of the PGK gene and two cases gave clonal band patterns but only within the CD3- subpopulation. CONCLUSIONS: Clonal analysis by the lineage independent method of X-inactivation allows clonal expansion undetected by T and B cell specific markers to be identified. It is therefore a more appropriate method for the analysis of CD3- LGL. This has implications for diagnosis in CD3- LGL disorders.

Adult↗

Novel genes in the human major histocompatibility complex class-II region.

Recent studies have identified a number of new genes mapping to the class-II region of the human major histocompatibility complex. Functionally these can be grouped into three broad categories: those encoding the new class-II-related genes DMA and DMB; those involved in aspects of class-I antigen-processing and presentation, and those with no apparent association with the immune system. There is evidence that further factors involved in class-II antigen presentation are located in the DMB to DQB1 interval.

Antigen Presentation↗

Results of day-case surgery for lumbar disc prolapse.

Microdiscectomy for lumbar disc prolapse on a day-patient basis was introduced by our department in 1985 and first reported in 1987, but has not been generally adopted in the United Kingdom. We now report our experience of the first 100 patients with lumbar disc prolapse treated by day-case microdiscectomy. Post-operative assessment was in the out-patient clinic and by subsequent postal questionnaire (average follow-up 37 months, range 3-64 months). Complications were few and are described. Only three patients developed a recurrent disc prolapse. Patient feedback was favourable and the majority (85%) said that, if necessary, they would be prepared to have the operation again on a day-case basis. For selected patients, lumbar microdiscectomy is a suitable procedure for day-case surgery.

Activities of Daily Living↗