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Biomedical subjects

M Deane

Publications and source records attributed to M Deane.

At least 37 records · Page 2Linked to original sources
PubMed1992

Adverse pregnancy outcomes in relation to water consumption: a re-analysis of data from the original Santa Clara County Study, California, 1980-1981.

Residents of a census tract that received drinking water from a well contaminated with solvents were previously shown to experience a spontaneous abortion rate over twice that occurring in an unexposed census tract. In addition, the rate of birth defects in the exposed tract was three times that in the unexposed tract. Surprisingly, increased tapwater consumption was associated with higher rates of spontaneous abortions in both the exposed and the unexposed tracts. Subsequent studies in this area have investigated the relation between spontaneous abortions and consumption of tapwater in more detail. In this report, data from the original study have been re-analyzed using methods comparable with those used in more recent studies. These results confirm the association between spontaneous abortions and reported cold tapwater consumption that was seen in the original study. The observed effect was not due to maternal risk factors, nor was it a function of consumption of bottled water. After controlling for bottled water, the odds ratio for consumption of tapwater was 3.4 (95% confidence interval = 0.6-19.4).

Abortion, Spontaneous↗
PubMed1992

Potential sources of bias and confounding in environmental epidemiologic studies of pregnancy outcomes.

Biases familiar to all epidemiologists take on new importance when studying spontaneous abortion because of the significance of the timing of exposure during gestation, and because the gestational age at which the pregnancy is recognized may be related to risk factors under study. In this paper, we systematically review the principal biases that might affect epidemiologic studies of pregnancy loss, in the context of a series of studies that found associations between adverse reproductive outcomes and prenatal use of tap or bottled water. These biases relate to availability of subjects for study, exposure opportunity, recall of exposure, recall of disease, and confounding. In one of the studies, the rate of bottled water use changed dramatically over the course of the study period, providing an opportunity to test indirectly for biased recall of exposure. We conclude that a less complete recall of water intake among women with normal pregnancies, as compared with those with spontaneous abortions, may have produced, or increased the magnitude of, the associations seen in these studies.

Bias↗
PubMed1991

Independent clonal origin of T- and B-cell clones in a composite lymphoma.

We present a detailed immunohistological and genotypic analysis of an unusual case in which a peripheral T-cell lymphoma, with features of Lennert's and angioimmunoblastic lymphoma, occurred after treatment of a low grade plasmacytoid lymphoma. By analysis of immunoglobulin and T-cell receptor genes, we show that the two diseases had an independent clonal origin at the level of lymphoid commitment. However, by employing a novel polymerase chain reaction-based technique for analysis of B-cell clonality, we show the persistence of a residual minor clonal B-cell population in the subsequent T-cell lymphoma. Only 2 previous cases of composite lymphoma involving B- and T-cell clones have been demonstrated by molecular analysis. This study underlines the immunophenotypic and genotypic heterogeneity of peripheral T-cell lymphomas and illustrates an unusual disease course in which a T-cell lymphoma has arisen in the context of, and perhaps as a consequence of, a B-cell lymphoma.

B-Lymphocytes↗
PubMed1991

Immunoglobulin gene 'fingerprinting': an approach to analysis of B lymphoid clonality in lymphoproliferative disorders.

Rearrangement of the immunoglobulin heavy chain (IgH) gene is widely exploited as a marker of B cell lineage and clonality in the pathology of lymphoproliferative disorders. We have developed a simple, polymerase chain reaction (PCR) based method for detecting IgH gene rearrangement which relies on the observation that by using a panel of PCR amplimers specific for each of the six heavy chain variable region families in conjunction with a common joining region amplimer, clonal rearrangement can be detected in over 90% of cases of B lymphoid malignancy. By using radiolabelled amplimers and exploiting the size heterogeneity resulting from independent IgH rearrangement events, we show that high resolution gel electrophoresis can be used to generate a 'fingerprint' representing the spectrum of B cell clonality in complex populations of B lymphocytes. The method effectively scans the entire IgH gene rearrangement repertoire and is capable of detecting rare clonal or oligoclonal B lymphoid cell populations. In normal bone marrow mononuclear cells, clonal IgH rearrangement could be readily detected at a sensitivity of 10(-3). We illustrate the application of the method in assessing the spectrum of B cell clonality occurring in an autoimmune condition. Hashimoto's thyroiditis, and in a malignant B cell disorder, chronic lymphocytic leukaemia. In addition, we explore the potential application of the technique in tracking minimal residual disease and for monitoring clonal evolution in acute lymphoblastic leukaemia.

B-Lymphocytes↗
PubMed1991

Preferential rearrangement of developmentally regulated immunoglobulin VH1 genes in human B-lineage leukaemias.

Immunoglobulin heavy chain (IgH) variable region (VH) genes are rearranged and expressed in a programmed manner during B-cell development. In common with foetal/pre-immune B-cells, malignant B-lymphoid populations preferentially use a restricted repertoire of developmentally regulated VH genes. By nucleotide sequence analysis of polymerase chain reaction amplified IgH genes, we have compared the repertoire of VH1 family genes that are rearranged in mature, CD5+ B chronic lymphocytic leukaemia (CLL) with that in immature, CD5-B-lineage acute lymphoblastic leukaemia (ALL). The results revealed a non-random pattern pf VH1 usage in which no single VH1 family member was common to each of these disease groups. The VH1 gene, 51P1, which underlies an auto-antibody associated cross-reactive idiotype, 'G6', frequently expressed on foetal B-cells, was preferentially rearranged in CLL (three of nine rearranged alleles). Another developmentally regulated VH1 gene, 20P3, accounted for more than half of the VH1 specific IgH gene rearrangements in ALL (five of nine VH1 alleles). Such developmentally restricted VH1 genes may distinguish discrete, although not necessarily exclusive, stages or compartments in B-lymphopoiesis from which each of these disease types arise.

B-Lymphocytes↗
PubMed1991

An improved method for detection of B-lymphoid clonality by polymerase chain reaction.

Several groups have recently described methods for the detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements in B-cell malignancies by polymerase chain reaction (PCR) gene amplification using variable region-(VH) and joining (JH) region-specific primers. The simplest methods utilize a single VH primer specific for sequences present in most VH regions corresponding to the third framework region (FR3). An alternative approach is to use a panel of VH family-specific primers specific for the first framework regions (FR1). In the course of nucleotide sequence analysis of IgH gene rearrangements amplified using a VH FR1 primer panel, these authors previously observed 3' VH region deletion and/or base mis-matches sufficient to prevent efficient priming from the VH FR3 primer target sequence in a significant minority of cases of B-lineage malignancy. An improved PCR method has therefore been developed by using a panel of seven VH FR1 family-specific primers incorporated in a single reaction. By using this method clonal IgH gene rearrangement is detected in 15 of 16 cases of B-lineage malignancy. Significantly, this series included four cases of B-lymphoma in which previous attempts to detect PCR clonal IgH gene rearrangements using a VH FR3 primer were unsuccessful. In two of these cases, nucleotide sequence analysis of the amplified DNA showed that failure to prime with the VH FR3 primer was likely to be attributable to insufficient homology with the target sequence. The use of the approach described in this paper should significantly improve the reliability of detection of B-lymphoid clonality by PCR.

Base Sequence↗
PubMed1991

Immunoglobulin heavy chain gene fingerprinting reveals widespread oligoclonality in B-lineage acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) of B-cell lineage typically arises as a monoclonal expansion of committed B-lymphocyte precursors that are arrested at an immature stage of differentiation. From Southern hybridization analysis of immunoglobulin heavy chain (IgH) genes in leukaemic blasts, the occurrence of a sizeable minority of patients displaying multiple (greater than two) rearranged heavy chain alleles has been widely reported. In at least some patients these data are consistent with the presence of oligoclonal populations of precursor B-cells. We have used a more sensitive, polymerase chain reaction based immunoglobulin gene 'fingerprinting' approach in the analysis of B-cell clonality in eight patients with common ALL which were apparently monoclonal on the basis of Southern blot analysis of their IgH genes. The results revealed an oligoclonal pattern of IgH gene rearrangement in half of the patients analysed, implying that oligoclonality at the level of B-cell commitment, as defined by IgH gene rearrangement, is much more widespread in this disease than has previously been recognized.

Alleles↗
PubMed1990

Immunoglobulin heavy chain variable region family usage is independent of tumor cell phenotype in human B lineage leukemias.

During B cell development, immunoglobulin heavy chain (IgH) variable region (VH) genes are rearranged and expressed in a programmed manner and accumulating evidence suggests recurrent utilization of developmentally restricted VH genes in malignant B lymphoid populations. We have used polymerase chain reaction gene amplification in conjunction with a panel of VH family-specific amplimers to directly compare the repertoire of VH region rearrangement in mature, CD5+ B cell chronic lymphocytic leukemia with that in immature, CD5 B lineage acute lymphoblastic leukemia. The results revealed a diverse pattern of VH family utilization common to both disease groups in which VH regions most proximal to the IgH joining locus were preferentially rearranged relative to their family sizes with recurrent utilization of several known developmentally restricted VH genes in close to germ-line configuration. These results indicate that biased VH family usage is independent of tumor cell phenotype in B lineage leukemias. This bias may reflect similar stages or compartments in normal B lymphopoiesis from which diverse types of B cell malignancy may arise. Moreover, since blast cells in acute lymphoblastic leukaemia do not express functional immunoglobulin, we infer that the tumor cell-associated VH family repertoire is determined through antigen-independent mechanisms.

Antigens, Differentiation↗
PubMed1990

Detection of immunoglobulin gene rearrangement in B lymphoid malignancies by polymerase chain reaction gene amplification.

Immunoglobulin heavy chain gene rearrangement serves as a marker of cell lineage and clonality in B lymphoproliferative disorders. We have used polymerase chain reaction (PCR) gene amplification to detect immunoglobulin gene rearrangements involving VH251, a heavy chain variable region preferentially utilized in B lymphoproliferative disorders. Using synthetic amplimers derived from VH251 and the heavy chain joining region, under conditions of high stringency, a homogeneous VH251-specific fragment of approximately 350 bp could be amplified from leukaemic DNA. Of 53 cases of B lineage acute lymphoblastic leukaemia screened for VH251 rearrangement by PCR, 10 were positive. A background level of VH251 rearrangement could also be amplified from normal peripheral blood and bone marrow DNA, but a VH251 rearranged leukaemic clone representing 0.01% of bone marrow mononuclear cells could be readily detected. The application of PCR to detect immunoglobulin gene rearrangement involving VH251 and potentially other preferentially utilized V regions provides a sensitive method both for tracking malignant B cells and for the study of normal B cell developmental pathways through which B lineage malignancies arise.

Blotting, Southern↗
PubMed1990

Observations on the haemopoietic response to critical illness.

Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM-CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis.

Adolescent↗
PubMed1989

Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981.

An epidemiologic study was conducted to investigate a suspected cluster of adverse outcomes of pregnancies conceived in 1980-1981 among women who resided in a census tract in Santa Clara County, California that was thought to be exposed to drinking water from a well contaminated by an organic solvent, trichloroethane. A comparison census tract that received water from a different source was selected on the basis of demographic comparability. The cluster was confirmed; the odds ratio for spontaneous abortion was 2.3 (95% confidence interval (Cl) 1.3-4.2) after adjustment by multiple logistic regression for maternal risk factors, including maternal age, alcohol consumption, smoking, and prior fetal loss. The relative risk for congenital malformations was 3.1 (95% Cl 1.1-10.4). Because of the lack of precise information on the timing and extent of contamination, the pattern of spontaneous abortion rates throughout the study period cannot be used to either support or refute a causal inference.

Abnormalities, Drug-Induced↗
PubMed1984

Epidemiological monitoring plan for geothermal developments.

In order to assure that geothermal developments in the Imperial Valley of California proceeded on an environmentally sound basis, The U.S. Energy Research and Development Administration contracted with the Lawrence Livermore Laboratory to conduct a comprehensive study of six aspects of the region and its potential problems: Air Quality Water Quality, Ecosystem Quality (Soil, Plants, Animals, etc.) Subsidence and Induced Seismicity, Health Effects, and Socio-Economic Effects which may result from the proposed development. This report of the possible health effects is designed to be repeated as geothermal developments progress. It includes both general health attributes and attributes which may be likely to be adversely affected by such developments and is focussed on two different populations, one likely to be affected and a second which is less likely to be affected. Such a design permits the easier identification of possible effects against a background of time-dependent processes in later phases of the study. This baseline study documents that before such developments, there were differences in health status of the two areas, which were chosen to maximize demographic comparability. It further identifies that odor, a possible problem associated with geothermal development, is currently present, and at times intense. Without such baseline monitoring, the likelihood is great that such effects in the future might be falsely ascribed to the geothermal development.

Adolescent↗
PubMed1982

A retrospective study of 275 cases of cutaneous malignant melanoma in the East Midland region.

A study of 275 cases of cutaneous malignant melanoma treated in one centre at Nottingham has shown no significant changes in survival rates since Bodenham published his figures 13 years ago. Early excision of a suspicious tumour followed by immediate frozen section is still the best approach and was found to be reliable way of confirming the diagnosis of malignancy in a pigmented lesion. A large percentage of patients with malignant melanoma develop their first metastases 5 years after the initial treatment. Therefore, the routine follow-up of patients with cutaneous malignant melanoma should be continued for at least 10 years.

England↗
PubMed1979

Severe malaria and glucose-6-phosphate-dehydrogenase deficiency: a reappraisal of the malaria/G-6-P.D. hypothesis.

Nigerian children with convulsions and Plasmodium falciparium parasitaemia above 100,000/microliter did not show a decreased frequency of glucose-6-phosphate-dehydrogenase (G.-6-P.D.) deficiency. A re-evaluation of earlier studies has led to the conclusion that clinical evidence of protection against falciparum malaria in G.-6-P.D.-deficient individuals is lacking. Evidence for the possible role of malaria in selecting for G.-6-P.D.-deficient genes consists solely of the geographical association of high frequencies of G.-6-P.D. deficiency with endemic malaria.

Child↗
PubMed1979

Frequency of blood group antigens in Nigerian children with falciparum malaria.

The frequencies of the following blood group antigens: A, B, O, M, N, S, s, U, Fya, FyB, Lea, Jsa and K have been determined in Nigerian children with severe falciparum malaria. The frequency distribution of M, N, S, s, U, Fya and Fyb were not significantly different in children with life-threatening falciparum malaria and controls. The frequencies of A, B, O, Lea, Jsa and K found in the children with severe malaria were similar to those previously reported for healthy adults in this population. The Duffy blood group antigens Fya and Fyb were virtually absent from both infected and control children. This finding is in variance with a Fya frequency of 23% reported by Worlledge et al. (1974) for healthy adults in this population.

ABO Blood-Group System↗