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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 559 records · Page 31Linked to original sources

Hormonal factors and melanoma in women.

The effect of exogenous hormones and reproductive factors on the risk of melanoma in women was investigated in a case-control study. Data from 91 women, aged from 15 to 81 years, and 91 matched controls were analysed in relation to use of oral contraceptives (OC), parity, age at the birth of the first child, and calculated length of ovulatory life. When potential confounding factors (including pigmentary characteristics and the lifetime exposure to sunlight were taken into account, there was no increase in risk of melanoma in relation to OC use, parity, or age at the birth of the first child. An unexplained association between melanoma and ovulatory life of greater length than 20 years was observed. The general findings of this study suggest that neither hormonal nor reproductive factors increase the risk of melanoma in women.

Adolescent↗

Common acquired naevi and the risk of malignant melanoma.

The relationship between common acquired naevi and malignant melanoma of the skin was assessed in a case-control study. IN 183 patients and 183 controls matched for sex, age and area of residence, there was a strong association between the presence of pigmented naevi on the arms and melanoma. In comparison with persons having no naevi on the arms, the crude relative risk of melanoma was 28.0 when naevi were present. After adjusting for hair colour, propensity to sunburn and lifetime sun exposure, the final risk estimate was 30.1. Family history did not appear to be a determinant of disease independent of the above risk factors.

Arm↗

The genetic susceptibility to insulin-dependent diabetes mellitus: combined segregation and linkage analysis.

We report a combined segregation and linkage analysis of a Danish sample of 216 insulin-dependent diabetes mellitus (IDDM) nuclear families: of these 216, twenty multiplex families were haplotyped regarding HLA-DR and -B markers. The analysis was conducted using the computer program COMBIN, which includes a modifier to absorb family resemblance that is additional to the effect of the major locus that is assumed linked to a marker locus, eg, within the HLA region. The initial analysis could clearly reject a dominant major locus but could not discriminate between other models with or without modifier. However, after adding supplementary information on population associations between HLA and IDDM together with the identity-by-descent (IBD) distribution to the analysis, a final model was identified. This invokes an additive major locus, linked to HLA with recombination not significantly different from 0, a disease gene frequency of 0.217, plus a dominant modifier. From this model it can be predicted that about 0.15% of the general population is at 100% risk of IDDM, about 5% is at intermediate risk (approximately 10%), while the remaining population has a risk of 0. The model predicts recurrence risks compatible with empirically estimated values. Particularly strong, positive haplotype associations were found for the DR3,B8, DR3,B18, and DR4,B15 haplotypes, but detailed analyses showed that neither these particular haplotypes nor the DR3 and DR4 haplotypes in general could entirely explain the HLA-associated susceptibility. The DR2 haplotypes showed a strong negative association. The results are discussed in the light of available data on the epidemiology of IDDM in order to provide a framework for further epidemiological studies.

Diabetes Mellitus, Type 1↗

Frequency of cancer among insulin-treated diabetic patients in Denmark.

The total prevalent population of insulin-treated diabetic subjects (1499 patients) in Fyn County, Denmark, was followed for 8 1/2 years (beginning 1 July 1973). All cases of cancer diagnosed during this period were identified by a record cross-check with the Danish Cancer Registry. In total, 45 and 37 cancer cases were identified among male and female patients, respectively, corresponding with observed/expected ratios of 1.37 (p = 0.03) and 1.08 (p = 0.65), respectively. Specified for site, a significant excess of cancer of the pancreas was found (six cases observed vs 2.4 expected, p = 0.02), but the excess was reduced by excluding cases where the cancer patient had diabetes as an early sign. Overall, no indications were found of an association between diabetes and cancer, whether in general or regarding particular cancer types.

Adolescent↗

Relative mortality of type 1 (insulin-dependent) diabetes in Denmark: 1933-1981.

The relative mortality of Type 1 (insulin-dependent) diabetes in Denmark during the period 1933-1981 was studied using a modification of Cox's regression model on the basis of two patient populations, ascertained in different ways and independently of each other. Initial analysis showed that the two groups could be combined completely into one common analysis. Relative mortality was the same for both sexes. The additional variables studied were age at diagnosis, current age, calendar year at diagnosis and calendar time during follow-up. All these interrelated variables were accounted for in the analysis. The analysis showed that relative mortality decreased with increasing age at diagnosis; increased from 1933 to a maximum in about 1965, after which it decreased; increased with increased duration of diabetes to a maximum at 15-25 years, after which it declined.

Adolescent↗

Riboflavin-responsive ethylmalonic-adipic aciduria.

A patient presenting with a condition resembling Reye's syndrome was found to have a urinary organic acid excretion pattern similar to those previously described in a single patient with ethylmalonic-adipic aciduria. The present patient responded clinically to riboflavin supplementation and his fibroblasts, when cultured in riboflavin-depleted medium, showed an abnormal reduction in the rate of butyrate oxidation.

Adipates↗

Excessive excretion of beta-alanine and of 3-hydroxypropionic, R- and S-3-aminoisobutyric, R- and S-3-hydroxyisobutyric and S-2-(hydroxymethyl)butyric acids probably due to a defect in the metabolism of the corresponding malonic semialdehydes.

A new metabolic disorder characterised by the excessive excretion of beta-alanine, 3-hydroxypropionic acid, R- and S-3-amino- and 3-hydroxyisobutyric acids and S-2-(hydroxymethyl)butyric acid is probably due to deficient activities of malonic, methylmalonic and ethylmalonic semialdehyde dehydrogenases. These dehydrogenation reactions could be mediated by one enzyme, or by enzymes with a common subunit, and both R- and S-methylmalonic semialdehydes seem to be equally affected. The patient is now aged 4 years and has developed normally. He has a persistent gross hypermethioninaemia which is probably unrelated to the other biochemical abnormalities.

Alanine↗

A biochemical study on mothers of children with congenital neurodevelopmental abnormalities.

A biochemical study has been undertaken on the mothers of children with a major neurodevelopmental disability, without known etiology (study group), and an appropriate control group. Two hundred seventy-four mothers were studied, 137 in each group. Social and environmental details were recorded in each of the two major groups. Biochemical studies included the assay of plasma and urinary amino acids and appropriate screening tests for carbohydrate and organic acid abnormalities. To introduce an element of standardization and also to enhance the opportunities for identifying possible biochemical heterozygote states, a 50-g protein mean was given to all subjects approximately three-quarters of an hour before blood and urine samples were taken. Difference of means tests on 22 amino acids revealed 9 significant t values at the 0.05 level and all means were significantly lower in the study groups. Because of the differences noted a discriminant analysis was carried out which demonstrated an extremely high proportion of correctly classified subjects (98%) when biochemical parameters were used to attempt to classify subjects into the study or control group.

Amino Acids↗

Sunburn and malignant melanoma.

We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations.

Adolescent↗

Glutaric aciduria type I misdiagnosed as Leigh's encephalopathy and cerebral palsy.

Two cases are reported of boys who suffer epileptic seizures only after playing video games. It is suggested that the amount of time the patient spends in front of the screen before the seizure is important, and also that video games trigger electrocortical activity far more efficiently than either television or intermittent photic stimulation.

Amino Acid Metabolism, Inborn Errors↗

Vasoactive intestinal peptide inhibits insulin-stimulated glucose transport in rat adipocytes.

Patients with tumors secreting vasoactive intestinal peptide (VIP) often develop hyperglycemia and glucose intolerance. Although VIP has been reported to increase glucose output by the liver, the concentration required for this effect greatly exceeds that observed clinically. We therefore investigated the effects of VIP on insulin-stimulated glucose transport in isolated adipocytes. Inhibition of insulin action was observed at a concentration of 1 ng/ml VIP with half-maximal inhibition at approximately 20 ng/ml. 125I-VIP bound to specific high-affinity sites on the adipocytes. Fifty percent inhibition of binding occurred at a concentration of unlabeled VIP of approximately 10 ng/ml and was not affected by insulin, glucagon, or growth hormone. As we have observed previously with glucagon and catecholamines, inhibition of insulin action by VIP was observed only when accumulation of adenosine in the incubation medium was prevented by addition of adenosine deaminase. Under these conditions VIP markedly increased cellular cAMP levels. A good correlation was observed among VIP binding, inhibition of insulin-stimulated glucose transport, and cellular concentrations of cAMP. The results suggest that inhibition of insulin action in adipose tissue contributes to the hyperglycemic effect of VIP. Together, with our published findings on glucagon and catecholamines, these results support the hypothesis that counterregulatory hormones inhibit insulin action by increasing cellular concentrations of cAMP.

Adenosine Deaminase↗

A study of sweat sodium and chloride; criteria for the diagnosis of cystic fibrosis.

Retrospective analysis of sodium and chloride results from sweat tests carried out in Bristol and Sheffield has shown that misdiagnosis of cystic fibrosis (false negatives and false positives) is considerably less if sodium and chloride are both measured. In patients with cystic fibrosis the chloride concentration is usually higher than the sodium, whereas in normal subjects the reverse usually occurs. This observation is particularly useful when borderline results (50-70 mmol/L) are obtained.

Adolescent↗

Cloned allospecific human helper T cell lines induce an MHC-restricted proliferative response by resting B cells.

To analyze helper T (Th) cell-induced B cell proliferation in man, we have cloned allospecific Th cells, grown them as long-term IL 2-dependent T cell lines (TCL), and analyzed their phenotypic and functional properties. The two TCL described in this report, A-7 and A-57, are both composed exclusively of T3+, T4+, T8- T cells blasts. In proliferative assays, with a panel of x-irradiated allogeneic stimulator cells, A-7 was found to proliferate in response to DR3-bearing cells, whereas A-57 responds to DR2-positive stimulators. Both TCL are capable of providing MHC-restricted polyclonal help for allogeneic B cells, as measured in the reverse hemolytic plaque assay. Of greater interest, x-irradiated A-7 and A-57 cells are capable of inducing a proliferative response by allogeneic B cells that is absolutely MHC restricted at the inductive (Th-APC) level. Thus, x-irradiated A-7 cells only trigger proliferation by DR3+ B cells, whereas A-57 cells selectively activate DR2+ B cells. In contrast, after antigen-specific activation, x-irradiated A-7 and A-57 cells can recruit a significant proliferative response by allogeneic B cells bearing "irrelevant" DR antigens. The possibility that Th-induced B cell proliferation may be restricted at the effector (Th-B cell) level was addressed by fractionating B cell populations into "activated" and "resting" subsets by discontinuous Percoll density gradient centrifugation and further purification by employing a monoclonal antibody directed against an antigen expressed on activated B cells (4F2). These studies demonstrate that activated B cells are readily and nonspecifically recruited to proliferate by activated Th cells, whereas optimal proliferative responses by resting B cells require MHC restricted Th-B cell interaction.

Antibodies, Monoclonal↗

A Cox regression model for the relative mortality and its application to diabetes mellitus survival data.

A Cox-type regression model for the ratio between the mortality in a cohort and that in a reference population is introduced. By means of the model it is possible to include in the survival analysis both individual (possibly time-dependent) characteristics for the study cohort and changing trends in the mortality in the reference population. This is particularly relevant in long-term follow-up studies where there may be considerable changes in the mortality in the reference population. Estimation procedures in the model are discussed and large-sample properties of the estimators are outlined. The model is applied to the analysis of two sets of data concerning the survival among insulin-dependent diabetics in Denmark.

Adolescent↗

A monoclonal-antibody enzyme immunoassay for detection of hepatitis B surface antigen with use of a biotin-avidin system.

In this solid-phase two-site enzyme immunoassay for hepatitis B surface antigen (HBsAg), three monoclonal anti-HBs are used: 5D3 (IgM) is immobilized on plastic beads; 5C3 (IgG2a) and 5C 11 (IgG1), labeled with biotin, are used as the first conjugate. Horseradish peroxidase covalently linked to avidin is the second conjugate. First, serum or plasma is incubated with the antibody-coated bead and biotin-labeled antibodies, simultaneously, at 45 degrees C for 1 h ("stat" procedure), 3 h ("standard" procedure), or 18 h ("overnight" procedure), during which HBsAg forms a complex with the solid-phase antibody and the biotinylated antibodies. The enzyme-conjugated avidin is then bound to the biotin on the antigen-antibody complex at 45 degrees C for 15 min ("stat") or 30 min (standard and overnight procedures). The beads are incubated with enzyme-substrate solution (H2O2 and o-phenylenediamine). Color developed is measured at 492 nm. All procedures satisfied third-generation HBsAg tests required by the FDA Office of Biologics, being sensitive both to ad and ay subtypes in subnanogram amounts. The assay is reactive with adw2, adw4, adr, ayw2, ayw3, and ayr subtypes and can detect viral determinants in HBsAg-anti-HBs immune complex form. Thus it provides a sensitive, simple, and reproducible alternative to radioimmunoassay.

Antibodies, Monoclonal↗