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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 181 records · Page 10Linked to original sources
PubMed1996

Allotypes of complement components C4, C3, C2 and BF in the populations of Tasmania and northeast England.

The distribution of four serum complement component polymorphisms (BF, C2, C3 and C4) were examined in two geographically separated populations, one from Tasmania (Australia) and the other from northeast England. The differences in genotypic frequencies between them at all 4 loci are not statistically significant (p > 0.05). When C4 haplotypes were investigated, only one (C4A4-C4B2) exhibited significant linkage disequilibrium (p = 0.0006 after correction, p = 0.01), and this was only observed in Tasmanians. The English population exhibited a larger number of alleles across the four loci used in this study than the Tasmanian, and this may well reflect a bottle-neck effect and the greater relative isolation of the population of the island State of Australia. Overall, the findings confirm the close relationship between immigrants from the British Isles to Tasmania.

Complement C2↗
PubMed1995

The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing.

The origin recognition complex (ORC) is a six protein assembly that binds S. cerevisiae origins of replication and directs DNA replication throughout the genome and transcriptional silencing at the yeast mating-type loci. Here we report the cloning of the genes encoding the 120 kDa (ORC1), 62 kDa (ORC3), and 56 kDa (ORC4) subunits of ORC and the reconstitution of the complete complex after expression of all six subunits in insect cells. Orc1p is related to Cdc6p and Cdc18p, which regulate DNA replication and mitosis, and to Sir3p, a regulator of transcriptional silencing. The N-terminal region of Orc1p is highly related to Sir3p, and studies of Orc1p/Sir3p chimeric proteins indicate that this domain is dedicated to the transcriptional silencing function of ORC.

Amino Acid Sequence↗
PubMed1995

Pulmonary hypoplasia and fetal breathing in preterm premature rupture of membranes.

Forty-eight patients with premature rupture of membranes prior to 24 weeks gestation (PPROM) were studied to investigate whether there was any difference in fetal breathing movements in those fetuses that did or did not develop pulmonary hypoplasia. The diagnosis of pulmonary hypoplasia was made on the basis of ultrasound measurement of fetal lung length. A control group of fetuses with intact membranes and normal pregnancies at the same gestation was also studied. The group that developed pulmonary hypoplasia had significantly less breathing movements than those that did not develop pulmonary hypoplasia and controls. This reduction in breathing movements may contribute to the development of pulmonary hypoplasia.

Female↗
PubMed1995

Purification, characterization, and partial amino acid sequence of a G protein-activated phospholipase C from squid photoreceptors.

Invertebrate visual transduction is thought to be initiated by photoactivation of rhodopsin and its subsequent interaction with a guanyl nucleotide-binding protein (G protein). The identities of the G protein and its target effector have remained elusive, although evidence suggests the involvement of a phospholipase C (PLC). We have identified a phosphatidylinositol-specific PLC from the cytosol of squid retina. The enzyme was purified to near-homogeneity by a combination of carboxymethyl-Sepharose and heparin-Sepharose chromatography. The purified PLC, identified as an approximately 140-kDa protein by sodium dodecyl sulfate-polyacrylamide gels, hydrolyzed phosphatidylinositol 4,5-bisphosphate (PIP2) at a rate of 10-15 mumol/min/mg of protein with 1 microM Ca2+. The partial amino acid sequence of the protein showed homology with a PLC cloned from a Drosophila head library (PLC21) and lesser homology with Drosophila norpA protein and mammalian PLC beta isozymes. Reconstitution of purified squid PLC with an AlF(-)-activated 44-kDa G protein alpha subunit extracted from squid photoreceptor membranes resulted in a significant increase in PIP2 hydrolysis over a range of Ca2+ concentrations while reconstitution with mammalian Gt alpha or Gi 1 alpha was without effect. These results suggest that cephalopod phototransduction is mediated by G alpha-44 activation of a 140-kDa cytosolic PLC.

Amino Acid Sequence↗
PubMed1995

A fundamental problem of consent.

A consultant anaesthetist gave a diclofenac suppository for postoperative pain to a patient having four teeth extracted under general anaesthesia in the dental surgery. He did not seek the patient's specific consent preoperatively for use of the suppository but told her afterwards what he had done. Charged before the professional conduct committee of the General Medical Council with failure to obtain informed consent and assault, the anaesthetist was found guilty of serious professional misconduct and admonished. This decision has far reaching implications and has caused great concern.

Adult↗
PubMed1995

Comparison of left and right vertebral artery intracranial diameters.

BACKGROUND: The vertebral artery is vulnerable to mechanical injury, especially in the region of the first and second cervical vertebrae, with resultant thrombus and/or emboli formation, often found at the vertebro-basilar junction. Such vascular injuries and associated neurological insults have been documented repeatedly in the literature as following cervical spine manipulation, when movements of the head and neck can cause compression and/or stretching of the vertebral artery and alterations in its blood flow. This has particular clinical relevance if a patient has a hypoplastic vertebral artery. Such persons may be considered at risk as regards vascular accidents following manipulation of the cervical spine. The aim of this study was to measure and compare the intracranial diameters of the left and right vertebral arteries in groups of black and white male and female South African subjects. METHODS: Cadaver material from 58 specimens was processed for light microscopy, and measurements of inner (lumen only) and outer (lumen, tunica intima, and tunica media) diameters taken and compared, using the t-test. RESULTS: Data analysis revealed a significant difference between the left and right vertebral artery intracranial diameters in the white female group only (N = 8). CONCLUSIONS: Such a statistically significant difference implies a difference of biological importance and it is suggested that this particular group of subjects may be a high-risk group as regards vascular accidents following cervical spine manipulation.

Black People↗
PubMed1995

Loss of hilar somatostatin neurons following tetanus toxin-induced seizures.

A loss of inhibitory interneurons has been reported in the hippocampus following seizure activity in various animal models of epilepsy and in human epileptic tissue. The question of whether particular populations of inhibitory neurons are similarly affected by the chronic block of inhibition that results after tetanus toxin injections directly into the brain has not previously been addressed. In the present study a unilateral intrahippocampal injection of tetanus toxin into the ventral hippocampus was used to produce a chronic epileptic syndrome characterised by brief seizures that recurred intermittently for 6-8 weeks. The results reveal, for the first time, the morphological changes in somatostatin interneurons following tetanus toxin-induced seizures in the rat. A bilateral short-term increase in immunoreactivity of somatostatin neurons is present 1 week after injection. This is accompanied by an increased intensity of somatostatin-immunoreactive axon terminals in the outer molecular layer of the dentate gyrus, which is more marked on the contralateral side. A chronic and significant loss of somatostatin-immunoreactive neurons was noted in the hilus of the dentate gyrus 2 months later. The significance of the chronic loss of the hilar somatostatin neurons in the control of excitatory activity in the dentate gyrus and whether the acute morphological changes are due to a direct action of the toxin on release mechanisms or as a result of seizure activity are discussed.

Animals↗
PubMed1995

The survival and growth of ovine afferent lymph dendritic cells in culture depends on tumour necrosis factor-alpha and is enhanced by granulocyte-macrophage colony-stimulating factor but inhibited by interferon-gamma.

An in vitro culture system is described which allows an analysis of the signals responsible for the survival, growth and functional maturation of afferent lymph dendritic cells (ALDC), a subpopulation of migrating dermal dendritic cells involved in antigen carriage and presentation to T-cells. Purified ALDC survived and grew for up to 30 days in lymph node conditioned medium and survived 14 days in recombinant ovine (rov) TNF-alpha whereas none were detected after 24 h in rov GM-CSF, rov IFN-gamma or rh M-CSF. However, when rov GM-CSF was added to cultures along with rov TNF-alpha, increased numbers of ALDC compared with input numbers (growth) were recorded on Days 14 and 21. In contrast, when 50-200 units ml-1 of rov IFN-gamma were added to cultures of ALDC along with TNF-alpha or rov TNF-alpha plus rov GM-CSF, cell survival and growth was inhibited. Antibody blocking studies confirmed the cytokine specificity of these effects. ALDC cultured in rov TNF-alpha or rov TNF-alpha plus rov GM-CSF retained MHC Class-II and ov CD-1 antigen expression and accessory function for autologous ov CD-4 T-cell proliferation, although at reduced levels compared with freshly isolated cells. Neither fresh nor cultured ALDC expressed coagulation factor XIIIa.

Animals↗
PubMed1995

Quantitation of ultraviolet light-absorbing fractions of the cornea.

This study attempts to measure the quantitative contribution of major chemical fractions of the whole bovine cornea to ultraviolet (UV) absorption between 240 and 300 nm, with special attention to the biologically significant range of 290-300 nm. The cornea was divided into water-insoluble, nonprotein small water-soluble, water-soluble protein, and lipid-soluble fractions. The insoluble fraction (largely collagen) was solubilized by enzymatic digestion. Solutions of individual fractions equivalent to a constant mass of fresh cornea were scanned for absorption from 240 to 300 nm. The sum of the absorbances of the individual fractions closely approximated the absorbance of whole corneas at all wavelengths examined. The extinction coefficients of the lipid and water-soluble fractions were several times greater than that of the insoluble fraction throughout the studied spectrum. Yet, because of its large mass (75% of cornea dry weight), the insoluble fraction accounted for 40-50% of UV absorbance between 240 and 280 nm. However, in the range of 290-300 nm, the water-soluble plus lipid-soluble fractions accounted for 60-65% of the total absorption, with the water-soluble proteins alone accounting for 40-45% of the total. The soluble proteins comprised only approximately 17% of the cornea's dry weight. The special contribution of the water-soluble proteins to absorption was attributed to their relatively high tryptophan content (approximately 1.6% by weight). A 54-kDa protein, identified by others as tryptophan-rich, tumor-associated aldehyde dehydrogenase, accounted for approximately 30% of the total soluble protein mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1995

The traditional humoral food habits of pregnant Vietnamese-Australian women and their effect on birth weight.

Vietnamese-Australian women have infants with lower birth weight than Australian-born women. Traditional humoral food habits, based on ancient Chinese medicine, are more likely to be followed during life changes like pregnancy. These food habits may influence maternal energy intake, weight gain and therefore infant birth weight. This study determined the proportion of pregnant Vietnamese women in southwestern Sydney who practise traditional humoral food habits, and their effect on birth weight. A cohort of 113 pregnant Vietnamese-born women were questioned on smoking status, height, weight, parity, food practices and demographics. Dietary intake was measured in each trimester. Known risk factors and infant birth weights were collected from medical records for participants and nonresponders. Fifty-seven per cent practised the traditional food habits. There were no differences in energy intake or weight gain between the two groups. After adjusting for confounders, birth weight was estimated to be 3257 g (95 per cent confidence interval (CI) 3205 to 3309) and 3272 g (CI 3211 to 3333) for the infants of traditional and nontraditional women respectively. Following humoral food habits does not appear to affect birth weight. Women who choose to follow these traditions should not be discouraged from doing so.

Adolescent↗
PubMed1995

Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

Aspergillus fumigatus↗
PubMed1995

Retreatment for relapse following desipramine discontinuation in dysthymia.

OBJECTIVE: It is an accepted yet unproven belief that prior favorable response to an antidepressant medication predicts good response to the same antidepressant during a subsequent depressive episode. The authors studied desipramine retreatment for dysthymic patients who had responded to desipramine during acute and continuation treatment and then subsequently relapsed after discontinuation of desipramine. METHOD: The subjects were 12 patients who had pure dysthymia or dysthymia with major depression who relapsed while taking placebo during maintenance treatment. Each patient received open desipramine treatment at a dose equal to or greater than that received during the continuation phase. RESULTS: Eleven (91.7%) of the 12 relapsed patients achieved full remission after an average of 4.7 weeks (range = 2-8 weeks, median = 4 weeks) of desipramine retreatment, a significant response rate. CONCLUSIONS: Positive response to desipramine strongly predicts favorable response to retreatment for depressive relapse following desipramine discontinuation.

Adult↗
PubMed1995

Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation.

STUDY OBJECTIVE: To determine whether alterations of platelet reactivity occur during obstructive sleep apnea (OSA) and, if so, whether therapy with nasal-continuous positive airway pressure (N-CPAP) alters this reactivity. DESIGN: Patients with suspected moderate to severe OSA had blood drawn for spontaneous platelet aggregation (sAGG) and activation (sACT) measurements at hourly intervals during diagnostic polysomnography (PSG) and, in those with confirmed OSA, on a separate night during which N-CPAP was applied. SETTING: Tertiary care center sleep laboratory. PATIENTS: Six patients with OSA had matched blood samples drawn on both diagnostic and N-CPAP treatment nights. Five patients without confirmed OSA served as controls. INTERVENTIONS: N-CPAP was applied to those patients with OSA and pressures adjusted with goals of eliminating apneas; N-CPAP was then maintained through the night. MEASUREMENTS AND RESULTS: sACT and sAGG were measured using flow cytometric determination of P-selectin expression using a monoclonal antibody. Platelet aggregation was assessed by measuring the proportion of platelets larger than resting platelets by light scatter techniques. Mean values for sACT and sAGG were higher on the diagnostic night compared with treatment night (p = 0.001 and p = 0.003, analysis of variance, respectively). The mean baseline supine sACT compared with completion supine sACT for both diagnostic and N-CPAP nights also revealed significant differences (mean = 16.6 +/- 3.5% vs 36.9 +/- 7.5%, p = 0.04; and 11.9 +/- 3% vs 39.5 +/- 9.1%, p = 0.04). Platelet activation during sleep in five subjects without OSA resembles that found in patients with OSA during N-CPAP. CONCLUSIONS: Increased platelet sACT and sAGG occur during sleep in patients with OSA. This effect is greatly reduced by N-CPAP.

Adult↗