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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 163 records · Page 9Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

A balance of tastes. Chefs & dietitians roundtable discussion.

The demands from foodservice customers for healthier foods that also taste good have compelled chefs & dietitians to break off their traditional separation of powers & begin forming working partnerships. These new partnerships are producing menus that strike a balance just as new--a balance between the preferences & priorities of both professions. It means a combining of two different but not incompatible perspectives that magnifies both the pleasure & the benefit of the good food they serve. In recognition of these new partnerships, FM convened the first roundtable with chefs & dietitians, all of whom are on the leading edge of this emerging trend. Excerpts of their discussion reflect striking similarities in opinion--as well as differences still to be reconciled.

Diet, Vegetarian↗

On the foundation and structure of medical informatics.

The authors from China and the United States take medical informatics from theory to practice by improving its research, application, and dissemination and by expanding its educational potential. We built a theoretical model and discussed its definition, approach, foundation, principles, and structure. Medical informatics is the interdisciplinary study of information science applied to medicine and health care. Its developing approach is transplantation. The foundation of medical informatics has "building blocks" of knowledge. They are: information procedure models; information classification principles; information processing methodologies; and functional hierarchical principles of information systems. The structure of medical informatics includes the main knowledge branches and their logical relations. There are four big branches: computer tools and systems methods; engineering equipment and methods; medical fields information systems; and health care management systems. Based on the investigation of the professional status (its theory and application, and its forms and the contents) of medical informatics, it can be seen that this new discipline is becoming mature.

China↗

Ultrastructure of parvalbumin-immunoreactive neurons in the CA1 area of the rat hippocampus following a kainic acid injection.

Non-pyramidal neurons which contain the calcium-binding protein parvalbumin (PV) were examined, at the ultrastructural level, in the CA1 area of the normal hippocampus and following a unilateral intracerebroventricular kainic acid (KA) injection. Many degenerating PV-immunoreactive (IR) neurons were identified in the ipsilateral strata oriens and pyramidale at 3 days post-lesion and some were seen in stratum oriens of the contralateral CA1 area. A few PV-IR neurons remained resistant to the effects of KA. A chronic, almost total loss of PV-IR terminals was detected around the soma of the ipsilateral CA1 pyramidal neurons. However, the PV-IR terminals around the axon initial segments of the CA1 pyramidial neurons remained intact at all post-lesion survival times in both ipsilateral and contralateral tissue. The examination of serial ultrathin sections established the origin of the PV-IR terminals around the axon initial segments to be the KA-resistant PV-IR neurons in stratum pyramidale. This data provides evidence for the loss of non-pyramidal neurons following a KA lesion together with evidence for a surviving inhibitory circuit that could, if functional, provide a very strong inhibitory control of pyramidal neurons.

Animals↗

Congenital diaphragmatic hernia: the hidden morbidity.

It is often thought that survivors of congenital diaphragmatic hernia (CDH) have an isolated problem related to lung hypoplasia, and little data exist regarding the extrapulmonary problems of high-risk CDH patients who do survive. In 1990, the authors began a multidisciplinary follow-up clinic for CDH patients. Members of the program include representatives from the departments of surgery, pulmonary medicine, development, nursing, and nutrition. Since this program began, the authors have followed up on 33 infants who survived after treatment of high-risk CDH, ie, those who were symptomatic within 6 hours of birth. Twenty patients were treated with extracorporeal membrane oxygenation (ECMO). Neurological problems were common in these patients: seven children (21%) required hearing aids, and seven others had abnormal results with brain-stem auditory evoked response (BAER) testing. Extraaxial fluid collections or enlarged ventricles were present on head computed tomography scans of 10 children, and four children had clinical seizure activity. Fifteen patients had developmental delays, which improved rapidly once the children began to thrive. Six patients required eyeglasses or had strabismus, and one patient is congenitally blind. There were a variety of problems related to growth and nutrition, with six patients needing fundoplications, and 13 patients below the fifth percentile for weight. Of 10 patients with patch repairs, two had recurrent hernias. Six others required surgery for bowel obstruction. Eleven patients had pectus excavatum, usually mild, and four had mild to moderate degrees of scoliosis. There were undescended testicles in five boys, vesicoureteral reflux in two patients, and kidney stones in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroencephalography↗

Fetal liver length in diabetic pregnancy.

OBJECTIVES: Our purpose was to investigate whether liver size is increased in the fetuses of pregnant women with diabetes and whether there is any relationship between fetal liver size and maternal glycemic control. STUDY DESIGN: Eighty pregnant women with diabetes had ultrasonographic measurement of fetal liver length made at 18, 28, and 36 weeks' gestation. Twenty-four obese, nondiabetic women were studied at 36 weeks as controls. RESULTS: Fetal liver length measurements were significantly greater than normal by 18 weeks' gestation (12% above normal mean values; p < 0.001) and increased further (19%, p < 0.02) by 36 weeks. In the obese controls liver length was increased 9% and was significantly lower than in the diabetic subjects (p < 0.001). CONCLUSIONS: Fetal liver size in increased in pregnant women with diabetes and cannot be explained solely by maternal obesity. The major increase in liver size occurs early in pregnancy but appears to be modifiable by glycemic control later in gestation.

Adult↗