Search PubMed⌕ Search

Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 199 records · Page 11Linked to original sources
PubMed1998

Wetland systems for bioregenerative reclamation of wastewater: from closed systems to developing countries.

Results are presented from constructed wetland systems designed to treat wastewater in Akumal, Quintana Roo, Mexico, which was developed after prior experience with the Biosphere 2 closed ecological system wetland systems. These systems illustrate the congruity of needs in advanced life support systems and in solving social and environmental problems in developing countries. For sustainable food production for life support, closed ecological systems need to bioregenerate and recycle nutrient-rich wastewater. Developing countries need low-tech ecologically engineered systems that minimize requirements for capital, nonrenewable energy, and technical expertise. Biosphere 2's surface flow wetlands covered 41 m2 and treated the wastewater from eight inhabitants, laboratories, and domestic animals during the 1991-1993 closure experiment. The Mexican wetlands are subsurface flow wetlands using limestone gravel as substrate. Two wetland systems treat sewage from 40 people and cover 131 m2. During the initial year of operation, the wetlands in Akumal reduced BOD 86%, TSS 39%, total P 80%, total N 75%, and coliform bacteria 99.85%. Phosphorus uptake in the limestone gravel was around 6 mg/kg. High biodiversity, with 70 plant species, was maintained in the Akumal constructed wetlands 1.5 years after planting. The Shannon diversity index was 4.7 (base 2). Plant diversity was slightly less than tropical forest ecosystems of the region, but far greater than biodiversity in natural mangrove wetlands.

Arizona↗
PubMed1998

General practitioner experience of clinical self audit.

OBJECTIVE: To record the experience of 87 general practitioners who undertook a two phase clinical self-audit of their recording of risk factors for cancer and cardiovascular disease and the acceptability of the audit process to them. METHOD: Participants were members of two Victorian Divisions of General Practice, one rural and one metropolitan. Each practitioner completed a clinical self-audit with a pre and post audit questionnaire. The post audit questionnaire was a repeat of the pre audit questionnaire with the addition of specific questions to measure their experience of the audit process. OUTCOME MEASURES: Likert scale and qualitative response. RESULTS: The results indicate that general practitioners thought the process was sound and taught them something about their actual rather than perceived practice, but were wary of sampling techniques and whether the audit reflected the recording of risk factors rather than preventive practice. CONCLUSION: The potential of clinical self audit in Australian general practice is highlighted particularly in the light of Practice Assessment as a compulsory component of vocational registration.

Adult↗
PubMed1998

Common dilemmas in managing hypertension.

BACKGROUND: Undertaking a blood pressure measurement is a common occurrence in general practice. Excellent guidelines for the management of hypertension are available to all Australian general practitioners. There are, however, variants of primary hypertension that present management dilemmas, such as: is it ever safe to stop medication, the role of ambulatory blood pressure monitoring, and refractory or isolated systolic hypertension. OBJECTIVE: To provide management guidance on some of the difficult dilemmas that may occur in relation to blood pressure control in everyday practice while recognising the limitations of the application of scientific evidence to the individual presenting patient. DISCUSSION: Recommendations are given for the withdrawal of antihypertensive medication in a select group of patients. Ambulatory blood pressure monitoring is recommended for the patient with labile or refractory hypertension and where 'white coat' hypertension is suspected. Management advice is given for the very old, the asymptomatic middle-aged man, and refractory and isolated systolic hypertension.

Adult↗
PubMed1998

Transferrin in normal and neoplastic endocervical tissues: distribution and receptor expression.

OBJECTIVE: Our recent studies showed that lactoferrin seems to be down-regulated in endocervical adenocarcinomas. We extended those studies to examine the expression of transferrin (Tf) and its receptor (TfR) in endocervical carcinogenesis and any relationship to the expression of lactoferrin, steroid receptors and the proliferative index. STUDY DESIGN: A retrospective study was performed using sections prepared from paraffin-embedded, formalin-fixed surgical specimens of normal endocervix, endocervical adenocarcinoma and cervical adenocarcinoma in situ. Standard immunohistochemical techniques were used to localize Tf and its receptor in the normal and malignant endocervix. In situ detection of mRNA for Tf and the TfR was also performed. The relative intensity of the immunoreaction was estimated using digital computer image analysis. Statistical significance was tested by Student's t test. RESULTS: No differences in the relative staining intensity for Tf and TfR proteins were noted between normal and neoplastic glands. However, quantitation revealed that a greater number of malignant glands stained positive for TfR than observed in the normal endocervix. Expression of Tf and TfR did not correlate with the expression of steroid receptors and lactoferrin or with the rate of proliferation. CONCLUSION: We have demonstrated the expression of Tf and its receptor by both normal and malignant endocervical glands. The increased number of malignant endocervical glands expressing TfR may indicate a special requirement for Tf and the iron that it carries. Our data provide evidence for the existence of a Tf, TfR autocrine or paracrine circuit involved in the regulation of normal and abnormal endocervical physiology.

Adenocarcinoma↗
PubMed1998

A flow-cytometric equivalent of the Kleihauer test.

BACKGROUND AND OBJECTIVES: The Kleihauer slide test is in general use to screen obstetric patients for possible fetomaternal haemorrhage. Since 1993, Rh(D)-negative patients have been tested in our laboratory by a flow-cytometric method detecting Rh(D)-positive fetal cells, a method which offers improved sensitivity and accuracy. We report another flow-cytometric method of broader application which quantitates cells according to haemoglobin F (HbF) content. MATERIALS AND METHODS: The red cells are fixed with glutaraldehyde and permeabilized by exposure to Triton X-100. A polyclonal sheep antibody to HbF is incubated with the cells followed by a fluorescein-labelled anti-sheep antibody. RESULTS: Quantitation of the percentage of fetal cells following a FMH can be achieved irrespective of the blood groups of either mother or infant, and the presence of maternal F cells need not interfere since the intensity of staining is usually less than that of fetal cells. Two of 19 transfusion-dependent patients with beta-thalassaemia have been found to have red cells indistinguishable from fetal cells on the basis of HbF content, but these patients also have been found to give positive results by the Kleihauer test. CONCLUSIONS: The flow-cytometric method may serve to replace the traditional Kleihauer test since it appears to offer improved accuracy and objectivity.

Erythrocytes↗
PubMed1997

A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines.

A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-alpha, or TNFR1 were observed. However, a nonsignificant trend toward inhibition of mitogen-induced TNF-alpha production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (at this dose) in asymptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type of study.

Adult↗
PubMed1997

Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca2+ permeability, conductance, and gating of human alpha4beta2 nicotinic acetylcholine receptors.

A mutation (S247F) in the channel-lining domain (M2) of the alpha4 nicotinic acetylcholine receptor (AChR) subunit has previously been linked genetically to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To better understand the functional significance of this mutation, we characterized the properties of mutant and wild-type human alpha4beta2 AChRs expressed in Xenopus oocytes. Both had similar expression levels and EC50 values for ACh and nicotine. Substantial use-dependent functional upregulation was found for mutant alpha4beta2 AChRs, but not for wild type. Mutant AChR responses showed faster desensitization, slower recovery from desensitization, less inward rectification, and virtually no Ca2+ permeability as compared with wild-type alpha4beta2 AChRs. Addition of the alpha5 subunit restored Ca2+ permeability to the mutant alpha4beta2alpha5 AChRs. At -80 mV, wild-type alpha4beta2 AChR single channel currents exhibited two conductances, each with two mean open times (gamma1 = 17 pS, tau1 = 3.7 msec, and tau2 = 23.4 msec; gamma2 = 28 pS, tau1 = 1.9 msec, and tau2 = 8.1 msec). In contrast, mutant AChRs exhibited only one conductance of 11 pS, with tau1 = 1.9 msec and tau2 = 4.1 msec. The net effect of the mutation is to reduce AChR function. This could result in the hyperexcitability characteristic of epilepsy if the mutant AChRs were part of an inhibitory circuit, e.g., presynaptically regulating the release of GABA. In the minority of AChRs containing the alpha5 subunit, the overall functionality of these AChRs could be maintained despite the mutation in the alpha4 subunit.

Acetylcholine↗
PubMed1997

Chromosomal abnormalities in low grade chondrosarcoma and a review of the literature.

In this study, cytogenetic analysis of two low-grade chondrosarcomas revealed relatively simple chromosomal complements with structural rearrangements involving chromosomes 1, 6, and 12 [46,XY,add(16)(q24)[3]/46,XY,t(1;20)(q21;q11),t(6;17)(q23;q23)[3]/46,XY, t(4;14)(q12;q24),t(5;6)(q12;p21) [2] and 45,XY,t(12;16)(q13;q24),-14[17]/44,idem,add(4)(p16),-17,[2] respectively]. Previously published reports of chondrosarcoma have revealed structural abnormalities of chromosomes 1, 6, 9, 12, and 15 as common. Also, a correlation between the simplicity or complexity of the abnormalities seen and histologic grade has been suggested. The findings of the current study support these earlier observations.

Chondrosarcoma↗
PubMed1997

Chromosomal anomalies in a case of proliferative myositis.

Proliferative myositis, a reactive lesion similar to proliferative fasciitis and nodular fasciitis, has only been cytogenetically described in one other report to date. This previously described case showed trisomy 2. Cytogenetic analysis and fluorescence in situ hybridization (FISH) of a proliferative myositis lesion in the present study did not reveal trisomy 2 but the following clonal translocation was observed: 46,XX,t(6;14)(q23;q32).

Chromosomes, Human, Pair 14↗
PubMed1997

Socioeconomic determinants of health. The contribution of nutrition to inequalities in health.

Social class differences in health are seen at all ages, with lower socioeconomic groups having greater incidence of premature and low birthweight babies, heart disease, stroke, and some cancers in adults. Risk factors including lack of breast feeding, smoking, physical inactivity, obesity, hypertension, and poor diet are clustered in the lower socioeconomic groups. The diet of the lower socioeconomic groups provides cheap energy from foods such as meat products, full cream milk, fats, sugars, preserves, potatoes, and cereals but has little intake of vegetables, fruit, and wholewheat bread. This type of diet is lower in essential nutrients such as calcium, iron, magnesium, folate, and vitamin C than that of the higher socioeconomic groups. New nutritional knowledge on the protective role of antioxidants and other dietary factors suggests that there is scope for enormous health gain if a diet rich in vegetables, fruit, unrefined cereal, fish, and small quantities of quality vegetable oils could be more accessible to poor people.

Adult↗
PubMed1997

Crystal structure of nitrile hydratase reveals a novel iron centre in a novel fold.

BACKGROUND: Nitrile hydratases are unusual metalloenzymes that catalyze the hydration of nitriles to their corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and they contain one iron atom per alphabeta unit. We have determined the crystal structure of photoactivated iron-containing nitrile hydratase from Rhodococcus sp. R312 to 2.65 A resolution as a first step in the elucidation of its catalytic mechanism. RESULTS: The alpha subunit consists of a long N-terminal arm and a C-terminal domain that forms a novel fold. This fold can be described as a four layered structure, alpha-beta-beta-alpha, with unusual connectivities between the beta strands. The beta subunit also contains a long N-terminal extension, a helical domain, and a C-terminal domain that folds into a beta roll. The two subunits form a tight heterodimer that is the functional unit of the enzyme. The active site is located in a cavity at the subunit-subunit interface. The iron centre is formed by residues from the alpha subunit only-three cysteine thiolates and two mainchain amide nitrogen atoms are ligands. CONCLUSIONS: Nitrile hydratases contain a novel iron centre with a structure not previously observed in proteins; it resembles a hybrid of the iron centres of heme and Fe-S proteins. The low-spin electronic configuration presumably results in part from two Fe-amide nitrogen bonds. The structure is consistent with the metal ion having a role as a Lewis acid in the catalytic reaction.

Binding Sites↗
PubMed1997

Chlorella virus SC-1A encodes at least five functional and one nonfunctional DNA methyltransferases.

Chlorella virus SC-1A encodes at least six DNA methyltransferases (MTases): four N6-methyldeoxyadenine (m6A) MTases, M x CviSI (TGCmA), M x CviSII (CmATG), M x CviSIII (TCGmA) and M x CviSIV (GmATC), one 5-methyldeoxycytosine (m5C) MTase, M x CviSV (approximately RCmCG), and one nonfunctional m5C MTase, M x CviSVI, which is homologous to the MTase M x CviJI [RGmC(T/C/G)] produced by another chlorella virus IL-3A. Genes encoding three of the SC-1A m6A MTases (M x CviSI, M x CviSII, and M x CviSIII) and the nonfunctional m5C MTase were cloned and sequenced. Neither M x CviSI nor M x CviSIII genes hybridized to genes for their respective isomethylomers, M x CviRI and M x CviBIII, from other chlorella viruses. However, the M x CviSII gene hybridized strongly to its M x CviAII isomethylomer gene from virus PBCV-1. Like the prototype chlorella virus PBCV-1, the SC-1A genome contains inverted terminal repeats, one of which is adjacent to the nonfunctional m5C MTase. The three cloned m6A MTase genes are distributed throughout the approx. 345 kb SC-1A genome.

Amino Acid Sequence↗
PubMed1997

Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression.

The incidence of cervical adenocarcinomas in young women over the last two decades has increased. Even with increasing knowledge of the role of human papillomavirus in the etiology of adenocarcinoma of the cervix, there is a paucity of data concerning the genetic and epigenetic factors that contribute to the histologic features and biologic behaviors of these tumors. Lactoferrin is a basic glycoprotein found in human milk, secondary granules of neutrophils, and many body secretions, and it has been associated with carcinogenesis of the endometrium, breast, and lymphoid systems. In this study, we examined the expression of lactoferrin in normal human endocervical epithelium and in cervical adenocarcinomas in relation to proliferative index, steroid receptor status, p53 protein expression, and apoptosis. Immunohistochemical and in situ studies demonstrated that lactoferrin protein and mRNA were strikingly downregulated upon neoplastic transformation of the endocervix as early as in adenocarcinoma in situ when compared with the prominent expression exhibited by the normal cervical epithelium. Furthermore, neoplastic transformation of endocervical epithelial cells was accompanied by a pronounced stimulation of proliferation and a substantial reduction in the expression of the estrogen and progesterone receptors and p53 but little or no change in the number of apoptotic cells. In conclusion, we identified lactoferrin as a novel cancer-specific marker of endocervical adenocarcinomas that may be useful in the early detection of the disease, prediction of prognosis, and the development of new therapeutic modalities.

Adenocarcinoma↗
PubMed1997

Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature.

Tumor-specific chromosomal abnormalities have been identified in several histologic subtypes of sarcomas. Characterization of recurrent chromosomal abnormalities has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of osteosarcoma, the most common primary malignant bone tumor, are relatively rare. In this study, 73 osteosarcoma specimens from 51 patients were cytogenetically analyzed following short-term culture. Clonal chromosomal abnormalities were detected in 47 and included one haploid specimen, 18 near-diploid specimens, 17 near-triploid, 8 near-tetraploid, 1 near-hexaploid, and 2 specimens with multiple clones of different ploidy levels. Examination of the present data and previously published data (111 clonally abnormal osteosarcoma specimens) reveals that chromosomal bands or regions 1p11-13, 1q10-12, 1q21-22, 11p15, 12p13, 17p12-13, 19q13, and 22q11-13 are most frequently rearranged and the most common numerical abnormalities are +1, -9, -10, -13, and -17. Partial or complete loss of the long arm of chromosome 6 also was seen in all cases of the present study and all previously published cases describing structural abnormalities of 6q. Parosteal osteosarcoma, a prognostically favorable osteosarcoma subtype, was characterized by the presence of a ring chromosome accompanied by no or few other abnormalities. Complex karyotypes were seen nearly exclusively in the high-grade lesions. These findings indicate that specific chromosomal bands and/or regions are nonrandomly involved in osteosarcoma and may provide useful clinical information.

Adolescent↗
PubMed1997

The prognostic significance of T cell receptor beta gene rearrangements and idiotype-reactive T cells in multiple myeloma.

Clonal T cell populations with idiotype specificity are present in the peripheral blood of a proportion of patients with multiple myeloma. We have identified the presence of both T cell subpopulations with a specificity for autologous immunoglobin fragments and T cell receptor beta gene rearrangements in peripheral blood samples of patients with myeloma. T cell receptor beta gene rearrangements were detected in 38 of 119 patient samples (32%) and were more common in progressive disease (70%), than at diagnosis (25%) or in stable disease (23%). The 38 patients who had T cell receptor beta gene rearrangements detected at any time had a better overall survival (median not yet achieved) than the patients who never had rearrangements detected (median 45 months, n = 49; chi2 = 6.2, P < 0.01). All 12 patients with T cell receptor beta gene rearrangements at diagnosis are still alive whereas the median survival for 28 patients with a germline configuration at diagnosis was 40 months (chi2 = 5.8, P > 0.01). The presence of T cell receptor beta gene rearrangements even conferred a survival advantage during progressive disease (median survival 44 months vs 19 months; chi2 = 8.7, P < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin fragments demonstrated idiotype-reactive T cells in the peripheral blood of five out of 15 patients all of whom had T cell gene rearrangements. The remaining 10 patients had neither idiotype-reactive T cells nor a detectable T cell receptor beta gene rearrangement in concurrent samples. Thus in patients with myeloma there was a good correlation between the presence of T cell receptor beta gene rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell receptor beta gene had a significantly better prognosis.

Aged↗