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Biomedical subjects

V A Brown

Publications and source records attributed to V A Brown.

36 records · Page 2Linked to original sources

Use of highly polymorphic DNA probes for genotypic analysis following bone marrow transplantation.

The use of DNA markers known as restriction fragment length polymorphisms is a sensitive and informative method of distinguishing patient and allogeneic donor cells after bone marrow transplantation. To apply the test, it is necessary in each case to find DNA probes that display patient-specific and donor-specific bands in Southern transfer hybridization. We have isolated a set of 12 cloned DNAs from highly polymorphic loci by which siblings can usually be distinguished. With just four of these probes, we can expect to distinguish the genotypes of the recipient and a sibling donor in more than 99% of cases (except between identical twins). The availability of many highly polymorphic probes also allows selection of an optimal probe for each case, one that can detect both the patient and donor-specific bands in a single hybridization with maximum resolution and sensitivity. We have applied these probes to the analysis of cells from peripheral blood and bone marrow after transplantation and demonstrated their usefulness in confirming engraftment of donor cells or graft rejection, and in detecting mixed lympho-hematopoietic chimerism.

Base Sequence↗

Assessment of techniques for measuring contrast sensitivity in children.

Contrast sensitivity was measured in 10 children aged from 3 to 11 years using 4 psychophysical techniques in order to establish the best method of measurement for clinical use. Of the four methods, staircase, ascending continuous, modified Von Bekesy and two-alternate forced-choice, the staircase was selected as the most appropriate clinical technique and monocular contrast sensitivity functions of normal children were measured.

Child↗

Towards an epidemiology of health: a basis for planning community health programs.

Raising the quality of life of a community is the ultimate goal of most health promotion programs. Yet such programs are commonly restricted to reducing known risks to health. It is suggested that this linkage of health promotion to disease prevention is self-defeating, and that health promotion needs community recognition and a suitable methodology of its own. To this end the traditional epidemiology of disease is extended to a potential epidemiology of health. A five-part analysis of health issues is then suggested as a basis for planning and evaluating community health programs.

Australia↗

Abnormalities in the expression of the leucocyte-common antigen in chronic lymphocytic leukaemia.

The surface glycoproteins of lymphocytes isolated from patients suffering from B cell chronic lymphocytic leukaemia (B-CLL) have been studied by radioactive labelling with impermeable probes and with MoAb. Several features not found in normal B cells have been observed. The abnormalities found in the expression of polypeptides of the leucocyte common (L-C) antigen, identified by appropriate MoAb, have been examined in detail. It has been shown by both biochemical analysis and MoAb binding that this group of polypeptides can, within a panel of B-CLL patients, range from a typical B cell pattern to the pattern resembling that normally found in T cells. The T lymphocyte profile is correlated with a poor prognosis (MVA C rating) and in the one patient where a change in the glycoprotein profile towards that of the T cell was observed, the change coincided with a clinical deterioration. The biological significance of the molecular diversity is discussed.

Antigen-Antibody Reactions↗

Surface glycoproteins as markers of the cellular status of B chronic lymphocytic leukaemia lymphocytes.

The phenotype of B CLL cells is investigated with respect to their surface glycoproteins. These glycoproteins are identified by vectorial tritiation followed by 1 and 2 dimensional gel electrophoresis, and by lectin and MoAb binding using immunoprecipitation and flow cytometry. The profiles of the CLL cells are compared with those of normal B cells, prepared from tonsils, and T cells from peripheral blood. The CLL cells show many similarities with T cells, particularly the expression of glycoproteins which bind the MoAbs gpL 115, F10-44-2 and EZB 52, and a complex set of binding sites for Helix pomatia lectin. The significance of these observations in terms of the cellular origins of the leukaemic lymphocytes is discussed.

Antibodies, Monoclonal↗

Feto-maternal consequences of high-dose glucose infusion during labour.

The effects on the fetus of high doses of glucose given to the mother in labour to correct maternal ketonuria were investigated. Three groups of patients were compared: one group received 1 litre of 10% (w/v) glucose intravenously over 1 h, the second group received 1 litre of 0.9% sodium chloride solution intravenously over 1 h and the final group had no supplementary infusion. It was observed that whereas glucose administration rapidly corrected maternal ketonaemia, there was a significant fall in pH and a rise in lactate in fetal blood. These effects were not observed in the other two groups. It was concluded that the use of high doses of intravenous glucose in labour should be avoided.

Adult↗

The value of antenatal cardiotocography in the management of high-risk pregnancy: a randomized controlled trial.

The value of routine regular antenatal cardiotocography (CTG) in the management of high-risk pregnancy was assessed in a prospective randomized controlled study of 353 patients. All patients had a weekly CTG trace during the last 6 weeks of pregnancy and according to the random allocation the tracings were concealed from, or available to, the clinicians. Other methods of assessing fetal welfare were available to both groups. There was no significant difference between the concealed and revealed groups in the timing and mode of delivery, birthweights, Apgar score and neonatal morbidity. No apparent effect from the routine use of antenatal CTG in high-risk pregnancy was shown.

Adolescent↗

From Ottawa, Uppsala, and Alma-Ata to Canberra, Australia: a rationale for a degree in health.

The paper describes the principles of curriculum design applied in establishing the Degree of Bachelor of Applied Science in Health Education in Canberra, Australia in 1979. The design was based explicitly on three major initiatives in health planning and policy in the last decade: (i) the recommendations to the Canadian Government proposed by Lalonde in 1974, commonly called the Health Field Concept; (ii) the World Health Organization definition of Health, first stated in 1948, and reissued at Uppsala in 1977; and (iii) the World Health Organization policy statement from the Alma-Ata Seminar in 1978, which included social planning and legislative action among the legitimate concerns of health services. The authors, who are at present teaching the integrated units of the degree, describe the principal components, namely content, theoretical principles, professional skills and methods of knowledge integration which they are using to develop graduates who may be considered wither health educated or health educators. In either case, the program is intended to produce people who can provide a health development arm for, on the one hand, social planning and social change, and on the other, health-care services.

Australia↗

The retroverted gravid uterus and its effect on the outcome of pregnancy.

Among 1954 pregnant women who booked before the end of the 14th week of gestation the uterus was retroverted in 220 (11.2%). The incidence of bleeding in early pregnancy and spontaneous abortion was significantly higher in the retroverted group. Only three patients (1.4%) with a retroverted gravid uterus developed acute retention of urine. Patients with retroverted uteri did not have a higher incidence of previous infertility, nor any increase in the incidence of common obstetric abnormalities.

Abortion, Spontaneous↗

A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7.

Although cystic fibrosis (CF) is among the most common inherited diseases in Caucasian populations, the basic biochemical defect is not yet known. CF is inherited as an autosomal recessive trait apparently due to mutations in a single gene, whence the efforts made to identify the genetic locus responsible by linkage studies. Two markers have recently been identified that are genetically linked to CF: one is a genetic variation in serum level of activity of the enzyme paraoxonase, and the other is a restriction fragment length polymorphism (RFLP) identified with a randomly isolated DNA probe. We report here that the genetic locus DOCRI-917 defined by the cloned DNA probe is located on chromosome 7.

Chromosome Mapping↗

Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots.

Haemophilia A is a common disorder of blood coagulation caused by a deficiency of factor VIII. It is inherited as an X-linked recessive trait, and one-third of all cases are thought to result from de novo mutations. The clinical severity of haemophilia A varies markedly among different families and a subset of the patients with severe disease develop antibodies against factor VIII, called inhibitors. Because of this heterogeneity, it is likely that many different molecular lesions result in haemophilia A. Indeed, of the nine mutations described to date, all appear to be unique changes. However in this study of 83 patients with haemophilia A we have identified two different point mutations, one in exon 18 and one in exon 22, that have recurred independently in unrelated families. Each mutation produces a nonsense codon by a change of CG to TG, and each occurred de novo on the X-chromosome donated by the maternal grandfather. These observations strongly support the view that CpG dinucleotides are mutation hotspots.

Base Composition↗