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Biomedical subjects

J Morrison

Publications and source records attributed to J Morrison.

At least 19 recordsLinked to original sources

Inhibition of binding of bacteria to amniochorionic membranes by amniotic fluid.

The immunological composition of amniotic fluids is shown to be of such a lower order of activity that its role in fetal protection may be limited. Also, amniotic fluids were found not to have classical antibiotic activity. Amniotic fluids (25/31), however, were found to inhibit, by 27.5% to 88.2%, three target bacteria from binding to discs of amniochorionic membranes. This inhibition is also demonstrable with the monosaccharides alpha-D(+)-fucose, D(+)-galactose, alpha-D-glucose, alpha-D-lactose and bovine serum albumin-lactose conjugate, whereas other glycoconjugates enhanced bacterial binding. This demonstrates that the test bacteria bind to the amniochorionic membranes using bacterial lectins. In intraamniotic infection bacterial lectins may be complexed by amniotic fluid glycoconjugates which prevent the bacteria from binding to the amniochorionic membranes. This would explain asymptomatic infection and in the absence or reduced levels of the glycoconjugates the bacteria would bind to the amniochorionic membranes giving rise to symptomatic infection.

Amnion

A critical role for conserved residues in the cleft of HLA-A2 in presentation of a nonapeptide to T cells.

The peptide binding cleft of the class I human histocompatibility antigen, HLA-A2, contains conserved amino acid residues clustered in the two ends of the cleft in pockets A and F as well as polymorphic residues. The function of two conserved tyrosines in the A pocket was investigated by mutating them to phenylalanines and of a conserved tyrosine and threonine in the F pocket by mutating them to phenylalanine and valine, respectively. Presentation of influenza virus peptides and of intact virus to cytolytic T lymphocytes (CTLs) was then examined. The magnitude of the reduction seen by the mutation of the two tyrosines in the A pocket suggests that hydrogen bonds involving them have a critical function in the binding of the NH2-terminal NH3+ of the peptide nonamer and possibly of all bound peptide nonamers. In contrast, the mutations in the F pocket had no effect on CTL recognition.

Amino Acid Sequence

Assessment of global and regional left ventricular performance at rest and during exercise after thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II Study.

Global and regional left ventricular performances were evaluated with equilibrium radionuclide angiocardiography in patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial at the time of hospital discharge. Studies at rest were available in 1,162 (69%) of the invasive and 1,150 (69%) of the conservative strategy patients, and exercise studies in 1,133 (67%) of the invasive and 1,145 (69%) of the conservative patients. Repeat studies were performed at the time of 6-week follow-up. Global and regional ejection fraction at rest were both comparable in patients assigned to each of the treatment strategies. However, at the time of hospital discharge patients in the invasive strategy had normal exercise responses more frequently (29.7 vs 25.8% p = 0.01), greater peak exercise LV ejection fraction (54.8 +/- 13.8% vs 53.1 +/- 14.1%, p = 0.004), greater exercise--rest change in LV ejection fraction (3.7 +/- 6.7% vs 2.7 +/- 7.2%, p less than 0.001) and greater peak exercise infarct zone regional ejection fraction (53.2 +/- 31.1% vs 50.3 +/- 33.0%, p less than 0.001) than patients assigned to the conservative strategy. At 6-week follow-up these differences between treatment strategies were no longer evident. When data were restricted to those collected at comparable work loads, similar differences in hospital discharge exercise performance between invasive vs conservative strategy patients were observed. Thus, there is a small transient difference in exercise global and regional LV performance associated with an invasive as opposed to conservative strategy after thrombolytic therapy. These differences are noted at the time of hospital discharge but not at 6 weeks, and are unlikely to confer clinical benefit.

Chi-Square Distribution

Identification of the nonamer peptide from influenza A matrix protein and the role of pockets of HLA-A2 in its recognition by cytotoxic T lymphocytes.

Influenza matrix peptide 58-66 is shown to be the optimal nonamer for binding to HLA-A2 and presentation to cytotoxic T lymphocytes (CTL). If titered out to 2 x 10(-10) - 4 x 10(-10) M in CTL-mediated lysis assays and to 3 x 10(-9) M in an HLA-A2 assembly-stabilization assay in cell lysates. The peptide was shown to make probable contacts with its carboxy terminus close to residue 116 in the floor of the cleft of HLA-A2, close to the F pocket. The side chain of the amino-terminal amino acid was unimportant, but its free amino and carbonyl groups in the A pocket appeared important in optimizing peptide presentation. The B pocket probably accommodates the side chain of residue 2 (isoleucine) and was shown to be critical in peptide presentation.

Amino Acid Sequence

Child developmental delay and socio-economic disadvantage in Australia: a longitudinal study.

Socio-economic inequalities in adult and child health in Australia have been an issue of national concern. While a large body of data has discussed adult health, there have been relatively few Australian reports of socio-economic inequalities in child health. This occurs in a context where there have been increases in the proportion of Australian children living in poverty and where there has been an increased interest in child developmental delay as an indicator of child health status. This paper reports the result of a longitudinal study of pregnancy outcomes and one indicator of child health, namely child developmental delay. Three indicators of socio-economic status (chronic socio-economic disadvantage, mother's education, family income) were used to predict child developmental delays observed some 5 1/2 years after the study commenced. Mothers who had the lowest socio-economic status (using any of the indicators) had substantially higher rates of children manifesting developmental delays.

Australia

Vasculitic and encephalitic complications associated with Coccidioides immitis infection of the central nervous system in humans: report of 10 cases and review.

Six cases of apparent and four cases of histopathologically confirmed vasculitis of the central nervous system (CNS), including one case of histopathologically documented vasculitis with encephalitis associated with coccidioidal meningitis (CM), are presented. Vasculitic complications included changes in mental status as well as stroke-like findings of aphasia, hemianopsia, and hemiparesis. Seven patients died. Vasculitic complications were unanticipated and often abrupt in onset, and delayed therapeutic intervention was characteristic. The diagnosis of vasculitis/encephalitis due to Coccidioides immitis infection must be based on clinical judgment, since serum antibody titers, cerebrospinal fluid findings, and initial radiological studies are not always helpful. Institution of both intravenous and intracisternal administration of amphotericin B and possibly concomitant intravenous administration of dexamethasone may be warranted in situations in which the association of C. immitis with CNS vasculitis or encephalitis appears likely before serologic or cultural confirmation of C. immitis infection involving the CNS is available.

Adult

Determination of the structural domain of ApoAI recognized by high density lipoprotein receptors.

There is good evidence that high density lipoprotein (HDL) interacts with high affinity sites present on hepatocytes. The precise nature of the ligand recognized by putative HDL receptors remains controversial, although there is a consensus that apolipoprotein AI (apoAI) is involved. This suggestion would be strengthened if a biologically active site demonstrating a high affinity for the receptor could be isolated. Cyanogen bromide fragments (CF) of apoAI (CF1-CF4) were complexed with phospholipid, and their ability to associate with the receptor was compared in various binding studies. Careful analysis of the concentration-dependent association of 125I-labeled dimyristoyl phosphatidylcholine (DMPC) recombinants to rat liver plasma membranes revealed high and low affinity binding components. As all DMPC recombinants displayed the low affinity binding component, it was postulated that this interaction was independent of the protein present in the particle and may well represent a lipid-lipid or lipid-protein association with the membranes. Only 125I-labeled CF4.DMPC displayed a high affinity binding component with similar Kd and Bmax (8 x 10(-9) M, 1.6 x 10(-12) mol/mg plasma membrane protein) to that of 125I-labeled AI.DMPC (7 x 10(-9), 1.4 x 10(-12) mol/mg plasma membrane protein). Similarly, egg yolk phosphatidylcholine complexes containing CF4 (CF4.egg PC) showed higher affinity binding than CF1-egg yolk phosphatidylcholine complexes confirming the results obtained with DMPC complexes. Furthermore, ligand blotting studies showed that only 125I-labeled CF4.DMPC associated specifically with HB1 and HB2, two HDL binding proteins recently identified in rat liver plasma membranes. We conclude that a region within the carboxyl-terminus of apoAI is responsible for the interaction with putative HDL receptors present in rat liver plasma membranes.

Amino Acids

Bronchial hyperreactivity in children with Marfan syndrome.

Marfan syndrome is known to have pulmonary manifestations such as pneumothorax. There have been few previous studies of pulmonary function tests and none of bronchial hyperreactivity. Therefore, pulmonary function tests were performed in 11 children with Marfan syndrome and 11 normal children. Bronchial responsiveness was tested in ten of the Marfan patients by methacholine challenge test and response to bronchodilator. Because of disproportionate length of legs in Marfan patients, an "ideal" standing height was calculated from sitting height. Pulmonary function tests, as absolute values or as percent predicted based on "ideal" height, were not different in Marfan patients and normals, although a few individual patients had abnormal function (mostly airway obstruction and hyperinflation). Response to methacholine challenge was positive on forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25 and 75% VC (FEF25-75%), and FEF50%, in 37.5%, 60%, and 70% of tests respectively. A significant response to bronchodilators was obtained in 40% of patients as measured by FEV1, in 90% by FEF25-75% and in 100% by FEF50%. Pulmonary function tests after bronchodilator were significantly higher when compared with values before the bronchodilator as well as with the baseline before methacholine. Therefore, most if not all patients with Marfan syndrome had hyperreactive airways in this relatively small group of patients. Even though only one patient had a diagnosis of asthma, six more had subtle symptoms. It is concluded that tests for bronchial hyperreactivity could be part of the routine investigation in Marfan syndrome. Further studies on larger numbers of patients are still needed.

Adolescent

The mental health of women 6 months after they give birth to an unwanted baby: a longitudinal study.

This study reports a longitudinal prospective study of the impact of an unwanted pregnancy on the mental health of the mother. Data are derived from a Brisbane, Australian sample of 8556 mothers who were enrolled at their first clinic visit (mean gestation 18 weeks) and then interviewed again some 3-5 days after the birth and when the baby was 6 months of age. Standard scales of mental health were administered on each of these occasions and mothers whose babies were unwanted were compared with the rest of the sample. The results indicate that mothers of unwanted children have somewhat higher rates of anxiety and depression than the comparison group, but that the magnitude of the mental health differences between the two groups: (a) diminishes over the period of the follow-up, (b) may be partly attributable to the prior poor mental health of women giving birth to an unplanned and unwanted baby, (c) is such that relatively few women who give birth to an unwanted baby experience mental health problems. The paper considers the implications of these results for health planners, notes the absence of contrary data and the need to acknowledge that these results may reflect situational factors which are characteristic of but not necessarily limited to Brisbane.

Adolescent

The influence of paternal height and weight on birth-weight.

Analysis of 5,989 couples, for whom fathers' and mothers' heights and weights were recorded, showed that paternal height had a significant influence (p less than 0.0007) on birth-weight while paternal body mass index (Quetelets Index) had no significant effect (p greater than 0.05). Depending upon mother's height, the average effect of father's height (ranging from 165 cm to 184 cm) on birth-weight was up to 152 g, with a greater effect where the mother was taller (up to 235 g) and a lesser effect where the mother was shorter (confirming the effect of maternal constraint). The significance of these findings lies more with the need to consider this effect as an important variable in statistical analysis involving birth-weight than in its immediate obstetrical implications.

Analysis of Variance

Characterization of the discoidal complexes formed between apoA-I-CNBr fragments and phosphatidylcholine.

The structure, composition, and physico-chemical properties of lipid-protein complexes generated between dimyristoylphosphatidylcholine (DPMC) and the CNBr fragments of human apoA-I were studied. The fragments were separated by high performance liquid chromatography and purified on a reversed-phase column. The complexes with DMPC were isolated on a Superose column; their dimensions were obtained by gradient gel electrophoresis and by electron microscopy. The secondary structure of the protein in the complexes was studied both by circular dichroism and by attenuated total reflection infrared spectroscopy. The fragments 1 and 4 of apoA-I, containing, respectively, two and three amphipathic helices, recombined with the phospholipid to generate discoidal particles with sizes similar to that of apoA-I- and apoA-II-DMPC complexes. The infrared measurements indicated that in all complexes the apolipoprotein helical segments were oriented parallel to the phospholipid acyl chains and that the protein was located around the edges of the discs. Computer modelling of the complexes based on energy minimization techniques proposed a model for these particles in agreement with the dimensions measured experimentally. In conclusion, we propose that apoA-I and its longest CNBr fragments are able to generate discoidal particles with DMPC, with apolipoprotein helical segments oriented parallel to the acyl chains of the phospholipids.

Apolipoprotein A-I