Changes to the MCC's qualifying examination.
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Canada↗
Biomedical subjects
D Ness
Publications and source records attributed to D Ness.
Muscle cell potassium, RNA and hydration in pregnancy and pre-eclampsia.
Thirty four pregnant women from 26 to 38 weeks gestation and 24 pregnant women with pre-eclampsia gave samples of muscle (rectus abdominis) at caesarean section. Muscle samples were analysed for H2O, K+, Mg2+ and Na+. Cell extracellular H2O was partitioned by the use of the Cl- space. Also protein, nucleic acids and Zn2+ were determined. From 26 to 38 weeks gestation the concentration of K+ per litre of cell water ([Ki]) slowly declined. The slope was significant. Points for patients with pre-eclampsia fell below the line and analysis of covariance showed that the two populations were different (P less than 0.001). Patients A-J were regarded clinically as severe pre-eclamptics. Points for these patients, in general, fell between 1 and 2 SDs below the normal line. Since other cations per litre of muscle cell water did not change, questions are raised. is the cation gap filled by amino acids or does vascular spasm cause a leakage of K+ from muscle cells? Does hypotonicity eventually develop leading to water intoxication? The low oncotic pressure in pre-eclampsia (shown here), the negative free water clearance could all favour increased cell hydration (some evidence for this is presented here towards term). Assessment of available information concerning creatinine excretion during normal pregnancy and K40, K42 studies together with our own rodent studies leads us to believe that a significant increase in muscle mass occurs, but such may not be the case in pre-eclampsia since the reduction in RNA and Zn2+ concentrations in muscle would suggest excessive protein degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdominal Muscles↗
Malnutrition in aboriginal children at Yalata, South Australia.
Comparative studies of body weight, height, intracellular water representing cell mass, and age, and plasma concentrations of albumin, vitamins, trace elements and iron stores in Aboriginal children aged 6 to 13.5 years, from two rural Aboriginal settlements and one rural Caucasian school (Hawker) provided evidence of significant deficits in one of the Aboriginal settlements (Yalata). Yalata Aboriginal children had lower body weights and heights for age and lower intracellular water values. Plasma albumin, zinc, iron, alpha-tocopherol, beta-carotene and retinol concentrations were lower relative to the normally grown Aboriginal children at Nepabunna. The latter children did not differ from rural Caucasian children for the parameters studied. The reasons for this poorer growth at Yalata may reside in poor nutrition, or repeated bowel infection in postnatal life leading to malabsorption, or both. Limited observational evidence suggests that Giardiasis has a high prevalence at Yalata, and it has been shown elsewhere that Giardiasis is capable of inducing malabsorption with resulting nutritional deficiencies.
Adolescent↗
HLA-JY328: mapping studies and expression of a polymorphic HLA class I gene.
The JY328 clone was identified in a human genomic library using cDNA corresponding to mRNA for HLA-B7 as a probe. The L/328 cell line was established by cotransformation of mouse Ltk- cells with the herpes thymidine kinase gene and clone JY328. On Northern blots, RNA from L/328 strongly hybridized to an HLA class I probe, and an antigen was recognized by an anti-HLA class I framework antibody on the cell surface. A DNA probe corresponding to a segment of intron 7 was developed by comparing the nucleotide sequence of clone JY328 with that of other HLA class I-type genes. Using the radiolabeled probe to screen Southern blots of DNA from families with siblings exhibiting intra-HLA recombinations, a restriction fragment length polymorphism was revealed--a 1.4 kb BstE II band not present in all individuals. A corresponding fragment was apparent in the base sequence of clone JY328. The occurrence of this band on Southern blots established that JY328 maps distinct from and centromeric to the HLA-C locus and near to the HLA-B locus. Antibody absorption studies and cytotoxicity tests indicated that the JY328 gene product was not an HLA-B antigen but that it did specifically absorb CW7-specific antibody. In sum, these results suggest a novel, polymorphic HLA class I gene which expresses a product serologically similar to HLA-Cw7 but which does not map within the corresponding locus.
Animals↗
A monoclonal antibody against HLA-A11 and A24.
A monoclonal IgG antibody was produced from a mouse immunized with an A11, A24; B27, B44 Epstein-Barr virus transformed B lymphoblastoid cell line. The antibody, A11.1M, by standard lymphocytotoxicity assay, reacts with all cells expressing HLA-A11 and -A24. Absorption studies with both A11+, A24- and A11-, A24+ platelets removed antibody reactivity against A11 and A24 lymphocytes. The shared antigenic determinant between A11 and A24, as defined by this antibody, A11.1M, represents a new "supertypic" determinant.
Animals↗
Effect of porcine relaxin and progesterone on rat, pig and human myometrial activity in vitro.
The in vitro effect of pure porcine relaxin on nonpregnant and pregnant myometrium before and after progesterone treatment was studied in the rat, pig and human. Myometrial strips from 45 rats, 30 pigs and 64 humans were studied. Porcine relaxin inhibited myometrial activity in the nonpregnant and pregnant rat until midpregnancy, when the sensitivity to it gradually decreased. By day 19 of rat pregnancy the myometrium was completely refractory to the inhibitory effect of porcine relaxin. Pretreatment of rat myometrial strips in vitro with progesterone increased their sensitivity to relaxin but did not overcome the refractory period in late pregnancy. In the pig, myometrial contractility was completely inhibited by porcine relaxin both in the nonpregnant state and throughout pregnancy (days 25-109). Progesterone was again synergistic, with relaxin in the pig inhibiting myometrial contractility. However, porcine relaxin had little or no effect on human myometrial contractility either in the nonpregnant state or during the pregnancies tested (28-42 weeks). Pretreatment of human myometrium with progesterone did not induce a response to porcine relaxin.
Animals↗
Muscle cell growth and the distribution of water and electrolyte in human pregnancy.
Ten normal pregnant women had muscle composition analyses (rectus abdominis) carried out at 39-40 weeks of pregnancy. Water, chloride (Cl), chloride space (ECV), non-chloride space (ICW), potassium (K), sodium (Na), magnesium (Mg) and zinc (Zn) determinations were carried out. Analyses for DNA (cell number), protein: DNA ratio (cell size), RNA and collagen were also performed. Similar analyses were performed on uterine muscle and placentae before and after perfusion with Earle's solution. Data from pregnant patients were compared with similar estimations carried out on rectus abdominis samples from 13 non-pregnant subjects undergoing gynaecological procedures. Muscle tissue and predicted muscle mass (MM) (which constitutes 40% of body weight) demonstrated that the gain in body K was due to the products of conception, that ICW decreased per unit weight in muscle (8%), ECV increased (41%) without a radical change in muscle water content (2%). Overall a 6 l gain in ECV and a 2 l gain in ICW can be accounted for during pregnancy. The results of this study indicate that added hydration excluding the products of conception (placenta, infant, uterus) is mainly extracellular. Intracellular Na concentration decreases (50%) and it is speculated that the cation gap is made up by H+ in the presence of extracellular alkalosis. Muscle cells diminish in size but cell number per gram is constant. Zinc content (Zn/DNA) decreases. Previous experimental work suggests that MM increases by about 10% during pregnancy and this information has been included in considerations but it remains to be shown to what extent total muscle cell numbers increase and as to whether such increased muscle growth remains following pregnancy.
Cell Division↗
Zinc content of red and white blood cells in aboriginal children.
Studies were carried out on erythrocyte, granulocyte and lymphocyte zinc content of aboriginal children at the La Grange settlement in the north-west area of the Kimberley. Forty-eight children, 34 boys and 14 girls between 6 and 13 years were studied. Only the boys were investigated for white blood cell (WBC) zinc. Twenty-five Caucasian children volunteered to give blood for control studies. Two approaches were made concerning zinc analyses, atomic absorption spectroscopy and proton induced x-ray emission. It was found that lymphocyte, granulocyte and erythrocyte zinc content were significantly reduced in aboriginal boys aged 6 to 13 years. Since the turnover of white blood cells is relatively fast, it follows that the zinc content of these cells may be a true index of current zinc status confirming previous observations.
Adolescent↗
Segregation and mapping analysis of polymorphic HLA class I restriction fragments: detection of a novel fragment.
An HLA-B7 complementary DNA clone was used as a hybridization probe to analyze the segregation pattern of polymorphic class I restriction fragments in several families whose HLA types had been determined by serological techniques. In one family in which a crossover in the HLA region had occurred, a specific genomic fragment was mapped with respect to the crossover. In another family, a novel genomic fragment present in one child and absent in all other family members was observed. With the exception of this novel fragment, all polymorphic class I fragments observed in this study segregated with a serologically defined parental haplotype, a result consistent with HLA linkage.
Chromosome Mapping↗
An HLA-B locus probe clarifies endonuclease polymorphism of major histocompatibility complex class I genes.
A DNA probe specific for the HLA-B locus has been isolated from a broadly cross-reactive HLA class I genomic clone. Locus specificity of the probe appears to be derived primarily from a stretch of approximately 180 nucleotides comprising the last (7th) intron of the original B7 gene. Use of the probe to analyze Southern blots of genomic DNA from unrelated individuals provides the first direct demonstration of intragenic localization of an HLA allele-specific restriction endonuclease site. Availability of this probe should make practicable the study of HLA-B locus restriction fragment length polymorphism as genetic markers of disease susceptibility, and should provide a model for developing probes specific for other HLA class I loci.
Cloning, Molecular↗
The effects of a new anti-hypertensive agent (endralazin) upon the general and coronary haemodynamics of the anaesthetized dog.
The effects of a new anti-hypertensive drug (endralazin) was studied in the intact anesthetized dog; in a dose of 150 millimicron/kg intravenously, the drug increased heart rate, respiratory rate, cardiac output and coronary sinus flow. Systemic blood pressure fell 60 min after the injection. The drug decreased calculated peripheral, pulmonary, and coronary vascular resistance,, amd maintained calculated cardiac efficiency. It also increased blood glucose, non-esterified fatty acid, lactate and pyruvate values, but did not influence cardiac usage of these substrates. There was evidence also of catecholamine release during the period of the study.
Anesthesia↗
The effects of captopril (SQ14,225) on the systemic and coronary haemodynamics of the intact anaesthetized dog.
1. The effects of Captopril (SQ14,225), an inhibitor of angiotensin-converting enzyme, given intravenously in a dose of 0.3 mg/kg ws studied in intact anaesthetized dogs. 2. The drug caused a decrease in systemic and pulmonary arterial mean pressures, an increase in cardiac output, and hence a decrease in calculated systemic and pulmonary vascular resistances. A sustained tachycardia also occurred. 3. A minor, transient increase in coronary sinus flow was recorded, with a sustained decrease in calculated coronary vascular resistance. 4. No change was found in cardiac oxygen metabolism nor in calculated cardiac efficiency. 5. The plasma renin values increased in the control animals and those given the drug.
Anesthesia↗
Effect of bilirubin on the fungicidal capacity of human neutrophils.
The effect of unconjugated bilirubin on the fungicidal capacity of human neutrophils was examined. Per cent Torulopsis glabrata killed in the presence of 1 x 10(-5) and 5 x 10(-5) M bilirubin was 72.7 +/- 2.5 and 40.9 +/- 7.2 respectively, compared to 81.4 +/- 4.1 in control (p less than 0.01 and p less than 0.001), respectively). This effect was not due to a concomitant inhibition of phagocytosis. The results suggest that jaundiced neonates may be more susceptible to fungal infections.
Adult↗
Production in vitro of murine antibody to a human histocompatibility alloantigen.
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Animals↗
Antifungal drugs and neutrophil chemotaxis.
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Amphotericin B↗
Neutrophil phagocytic and bactericidal dysfunction induced by bilirubin.
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Bilirubin↗
IgM-mediated, T cell-independent suppression of humoral immunity.
The immunological unreactive state occurring in (T,G)-A-L nonresponder mice after secondary antigen challenge was investigated. Syngeneic IgM anti-(T,G)-A-L antibody-containing plasma, transferred at the time of the time of primary challenge, induced persistent suppression of autologous specific antibody production. Removal of plasma IgM with goat anti-mu antisera removed the ability of the plasma to supress. The induction and maintenance of the suppressed state were not different in thymectomized or sham-thymectomized animals. Primed animals subjected to graft-vs-host reaction (GVHR) at the time of secondary challenge switched over to IgG production. Animals suppressed by passive antibody transfer reacted to GVHR, at the time of secondary challenge, with specific IgM but not IgG antibody production. Transfused normal spleen cells partially abrogated suppression only when (suppressed) hosts had been lethally irradiated. Spleen cells from antigen-plus-antibody suppressed donors, upon transfer to previously normal, syngeneic hosts, were less immunocompetent than spleen cells from untreated donors. These data are consistent with a model of IgM mediated, T cell-independent persistent suppression of humoral immunity.
Animals↗
The effects of an histamine H2-receptor agonist, impromidine (SK & F 92676) on the general and cardiac haemodynamics of the intact dog.
1. The effects of impromidine (16 nmol/kg intravenously) were studied in the general and coronary circulations of the intact anaesthetized dog. 2. The drug caused tachycardia, increased cardiac output and coronary sinus flow, and induced minor changes in systemic and pulmonary arterial pressures. 3. It increased left and right ventricular work, and decreased calculated resistance values in the greater and lesser circulations. Coronary vascular resistance fell, cardiac O2 extraction increases. 4. These changes were substantially prevented by treatment with cimetidine. 5. The action of an H2-receptor agonist then is associated with a general and coronary vasodilator response, with maintenance of calculated cardiac efficiency.
Animals↗