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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 253 records · Page 14Linked to original sources

Retinal, choroidal and total ocular blood flow response to hypercarbia during spontaneous breathing and mechanical ventilation.

The effect of hypercarbia on ocular blood flow was studied in the newborn piglet with the isotope-labeled microsphere method. Blood flow measurements were made during spontaneous breathing and during paralyzation (pancuronium) and mechanical ventilation. Retinal blood flow increased from 0.40 +/- 0.07 (mean +/- SEM) ml/min/g at baseline levels to 0.91 +/- 0.17 ml/min/g at a PaCO2 level of 11.0 kPa during spontaneous ventilation. A similar response was observed during paralyzation and mechanical ventilation (0.89 +/- 0.15 ml/min/g at a PaCO2 of 11.1 kPa). For choroidal blood flow, however, the increase caused by hypercarbia during spontaneous ventilation (16.14 +/- 3.69 to 29.15 +/- 3.22 ml/min/g) was significantly reduced when the animals were paralyzed and mechanically ventilated (15.99 +/- 2.99 to 23.51 +/- 3.41 ml/min/g). Since choroidal blood flow accounts for 60-80% of oxygen delivery to the retina, paralyzation and mechanical ventilation may significantly reduce oxygen delivery to the retina during hypercarbia.

Animals↗

Effect of different phototherapy lights on retinal and choroidal blood flow.

The response of retinal (RBF) and choroidal (ChBF) blood flow to illumination with light with different spectra was investigated in spontaneously breathing newborn piglets. After 1 h in complete darkness, the animals were exposed to blue, white or green light in such a manner that equal energy was delivered to the eye. RBF and ChBF showed different flow responses. After 60 min exposure to blue light, RBF increased from 0.22 +/- 0.01 ml/min/g at baseline to 0.32 +/- 0.03 ml/min/g (+/- SEM) (p less than 0.03). Apart from this increase, RBF did not change significantly during any of the experimental settings. ChBF, on the other hand, was significantly affected by illumination. Thus, at 120 min of light exposure all three types of light decreased ChBF significantly from baseline (darkness) levels. Blue light decreased ChBF (mean +/- SEM) from 13.78 +/- 0.84 to 7.61 +/- 0.67 ml/min/g (p less than 0.01), white light from 17.43 +/- 1.86 to 9.86 +/- 1.07 ml/min/g (p less than 0.01), and green light from 14.13 +/- 1.64 to 8.31 +/- 1.30 ml/min/g (p less than 0.02). The results indicate that light is an important modulator of ChBF and to a certain extent also RBF. Further, the results suggest that ChBF and RBF are regulated differently.

Animals↗

A multicentre controlled clinical trial of high-volume fresh frozen plasma therapy in prognostically severe acute pancreatitis.

Fresh frozen plasma (FFP) has been proposed as a specific therapy for acute pancreatitis. It may replenish important circulating proteins, particularly the naturally occurring anti-protease system. To investigate this potential therapy, 72 patients with predicted severe disease were selected from 301 admissions with acute pancreatitis using the modified Glasgow prognostic scoring system. They were randomised within 6 h of diagnosis to receive FFP (8 units daily for 3 days) or a similar volume of colloid control as part of their intravenous fluid therapy. Clinical progress was monitored and specific blood proteins were measured on days 1, 3 and 7. FFP therapy significantly increased the day 3 concentrations of some of the acute phase proteins (C1-reactive protein P less than 0.02, D-dimer P less than 0.05 and fibrinogen P less than 0.05) as well as some proteins which showed a fall in circulating concentration during the early stages of the disease (alpha 2 macroglobulin P less than 0.001, antithrombin III P less than 0.01 and fibronectin P less than 0.001). However, there was no significant difference between the two groups in terms of clinical outcome. Mortality was 20% in patients who received FFP and 18% in the colloid control group. Despite the ability of FFP therapy to supplement circulating concentrations of several potentially useful proteins during acute pancreatitis, it does not appear to improve clinical outcome.

Acute Disease↗

Agricultural pilot safety in Australia: a survey.

Agricultural flying is one of the most hazardous forms of aviation. The incidence of death and injury among agricultural pilots in Australia is over one hundred times the national average for work-related injury. As with most forms of aviation, the pilot's awareness of and attitude toward risk are important factors in accident prevention. However, it is difficult for others to monitor and regulate agricultural flying activity, and responsibility for safety tends to fall largely on the pilot. A 1988 survey of agricultural pilots in Australia, carried out on behalf of the Civil Aviation Authority, showed that: 1) over 50% regularly exceed regulated flying hours; 2) 90% fly on application when tired; 3) there is a systematic relation between accidents and exposure to risk; 4) pilots perceive the main factor contributing to accidents is the pilot. The practical challenge for aviation medicine is to improve occupational safety by assisting pilots to monitor their own capabilities and performance.

Accidents, Aviation↗

Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor.

A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint-cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid-dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain.

Amino Acid Sequence↗

Risk for systemic embolization of atrial fibrillation without mitral stenosis.

The risk for systemic embolization was studied in 272 patients without mitral stenosis or prosthetic valves who were referred to the echocardiography laboratory with atrial fibrillation (AF). During a mean follow-up period of 33 months (range less than 1 to 83), 27 (10%) patients had a systemic embolic event, which was cerebral in 23 patients (85%) and peripheral in 4 (15%). In the analysis of individual variables, the risk of embolization was increased by female sex, underlying heart disease and left atrial size greater than or equal to 4.0 cm, but not by age, hypertension or type of AF (paroxysmal vs chronic). In multivariable analysis, left atrial size greater than or equal to 4.0 cm was the single strongest predictor of increased risk for embolization (p less than 0.001), but female sex (p = 0.014) and underlying heart disease (p = 0.027) also contributed. When each of these 3 factors was assigned 1 point in a risk score, embolic events were found to occur in none (0%) of 24 patients with a risk score of 0, in 2 (3%) of 83 patients with a risk score of 1, in 13 (11%) of 118 patients with a risk score of 2 and in 12 (26%) of 47 patients with a risk score of 3. The score allows patients with AF and without mitral stenosis to be stratified into high-, medium- and low-risk groups for systemic embolization. Such information could be useful in decision making for anticoagulation in patients with AF.

Aged↗

Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro.

Carboxypeptidase E (CPE), which cleaves C-terminal amino acid residues and is involved in neuropeptide processing, is itself subject to intracellular processing. Human CPE cDNA was isolated and sequence comparisons were made with those of a previously isolated brain cDNA (M1622) encoding rat CPE and of other human carboxypeptidases (M and N). Human (2.5 kb) and rat (2.1 kb) CPE cDNAs approximated to the size of their respective mRNAs; additional sequences were located in putative 5' and 3' untranslated regions of human CPE mRNA. There is 79% sequence similarity between human and rat CPE cDNAs, with greater similarity (89%) over the coding region and short sections of the non-coding sequence. The predicted 476-amino acid-residue sequences of human and rat preproCPEs are highly conserved (96% identity), with lower degree of similarity of the N-terminal signal peptide (76%). Human CPE showed 51% and 43% sequence similarity to human CPN and CPM respectively, with discrete regions of divergence dispersed between the highly conserved mechanistically implicated regions. Antiserum generated from a fusion protein, synthesized in Escherichia coli from constructs of the human cDNA, recognized an approx. 50 kDa membrane protein and a smaller soluble protein in rat and human brain preparations, corresponding to the two forms of native CPE. Human CPE mRNA transcripts directed the synthesis in reticulocyte lysate of a 54 kDa translation product, which in the presence of dog pancreas microsomal membranes was co-translationally processed with cleavage, insertion into membranes and glycosylation. Three processed forms were generated, the largest (56 kDa) and smallest (52 kDa) being equally glycosylated. The membrane association of the processed translation products and of native brain membrane CPE, detected immunologically, was resistant to moderate alkali but not pH 11.5 extraction. These results are consistent with secondary-structure predictions that CPE is a peripheral membrane protein. The dissimilar regions of human carboxypeptidases may provide information on sequences responsible for their different cellular disposition.

Amino Acid Sequence↗

The human heat-shock protein family. Expression of a novel heat-inducible HSP70 (HSP70B') and isolation of its cDNA and genomic DNA.

The human heat-shock protein multigene family comprises several highly conserved proteins with structural and functional properties in common, but which vary in the extent of their inducibility in response to metabolic stress. We have isolated and characterized a novel human HSP70 cDNA, HSP70B' cDNA, and its corresponding gene sequence. HSP70B' cDNA hybrid-selected an mRNA encoding a more basic 70 kDa heat-shock protein that both the major stress-inducible HSP70 and constitutively expressed HSC70 heat-shock proteins, which in common with other heat-shock 70 kDa proteins bound ATP. The complete HSP70B' gene was sequenced and, like the major inducible HSP70 gene, is devoid of introns. The HSP70B' gene has 77% sequence similarity to the HSP70 gene and 70% similarity to HSC70 cDNA, with greatest sequence divergence towards the 3'-terminus. The HSP70B' gene represents a functional gene, as indicated by Northern-blot analysis with specific oligonucleotides, hybrid-selected translation with a specific 3' cDNA sequence and S1 nuclease protection experiments. In contrast with HSP70 mRNA, which is present at low concentrations in HeLa cells and readily induced by heat or CdCl2 treatment in both fibroblasts and HeLa cells, HSP70B' mRNA was induced only at higher temperature and showed no basal expression. The differences in patterns of induction may be due to the special features of the promoter region of the HSP70B' gene.

Adenosine Triphosphate↗

Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene.

A novel human brain complementary DNA sequence encodes n-chimaerin, a 34,000 Mr protein. A single cysteine-rich sequence CX2CX13CX2CX7CX7C in the N-terminal half of n-chimaerin shares almost 50% identity with corresponding sequences in the C1 regulatory domain of protein kinase C. The C-terminal half of n-chimaerin has 42% identity with the C-terminal region (amino acid residues 1050 to 1225) of BCR, the product of the breakpoint cluster region gene involved in Philadelphia (Ph') chromosome translocation. n-Chimaerin mRNA (2.2 x 10(3) base-pairs) is specifically expressed in the brain, with the highest amounts being in the hippocampus and cerebral cortex. The mRNA has a neuronal distribution and is expressed in neuroblastoma cells, but not in C6 glioma or primary astrocyte cultures. The similarity of two separate regions of n-chimaerin to domains of protein kinase C and BCR has intriguing implications with respect to its evolutionary origins, its function in the brain and potential phorbol-ester-binding properties.

Amino Acid Sequence↗

Methyl-tert-butyl-ether for treating bile duct stones: the British experience.

Methyl-tert-butyl-ether (MTBE), infused via a nasobiliary catheter, was used to treat 33 patients with bile duct stones in nine units around Britain. MTBE contributed to success in 12 (36 per cent) cases: seven passed stones spontaneously during MTBE infusion and five had partial stone dissolution allowing subsequent endoscopic extraction. MTBE was non-contributory in 21 (64 per cent) cases: four passed stones after MTBE was stopped, six were treated by subsequent endoscopic techniques without evidence of dissolution, seven underwent surgery, and four were treated conservatively (with one death). In at least ten of the 21 cases in which MTBE was non-contributory, pigment stones were present. Forty-two complications occurred in 26 (79 per cent) patients. The efficacy of MTBE for treating bile duct stones might be improved by better methods of instillation and, since success may be related to technique, the use of MTBE should be restricted to units familiar with this chemical.

Cholelithiasis↗

Evaluation of herniography in the diagnosis of an occult abdominal wall hernia in symptomatic adults.

Outpatient herniography as a means of confirming or refuting the presence of an occult abdominal wall hernia was performed in 50 symptomatic patients, including 13 who had previously undergone hernia repair. Altogether 30 occult hernias were detected in 27 patients, only one of which was considered to be unrelated to the presenting symptoms. On the basis of herniography, 17 patients were spared surgical exploration and, of these 17, 16 obtained a good result. One further patient with a clinically apparent hernia on one side but with contralateral symptoms was spared unnecessary surgery because the contralateral side was radiologically normal. There was one false negative and no false positive examinations. There were three minor complications: two cases of sigmoid colon puncture and one of abdominal wall haemorrhage (all managed conservatively). There were two technical failures. These results support the Scandinavian experience that herniography has a useful role in the management of patients who may have occult hernias as the underlying cause of abdominal wall symptoms.

Abdominal Pain↗

Cerebral blood flow during experimental epidural bleeding in swine.

Regional cerebral blood flow (rCBF) was studied during an aggressive epidural bleed, using a ventilated swine model. rCBF, regional organ blood flow and cardiac output were measured using the radioactive microsphere technique. Blood flows were measured prior to the start of bleeding (Stage 1), when intracranial pressures had reached a plateau and supratentorial perfusion pressure was reduced by about 50% (Stage 2), and at isoelectric EEG (Stage 3). Supratentorial rCBF did not change significantly between stages 1 and 2 while rCVR decreased, implying autoregulatory activity. Cerebral ischaemia developed between stages 2 and 3 when rCBF values fell to levels between 20 and 50% of control values. Infratentorial rCBF changes were similar but less marked, so that adequate brain stem perfusion was maintained below the upper mesencephalon. The left temporal and left parietal cortex and upper mesencephalon suffered a greater reduction in rCBF than other regions, due to proximity to the haematoma and tentorial herniation. The supratentorial perfusion pressure at stage 2 was 60 mm Hg associated with a haematoma volume of 6% of the intracranial volume (ICV). The infratentorial perfusion pressure never fell below 60 mm Hg. The Cushing response was absent when the EEG became isoelectric. This is tentatively ascribed to the absence of hypoxia, because mechanical ventilation was used. Instead systemic arterial hypotension accompanied bleeding in this ventilated model. This hypotension was due to falling cardiac output and peripheral vasodilation.

Animals↗

Mood changes, obstetric experience and alterations in plasma cortisol, beta-endorphin and corticotrophin releasing hormone during pregnancy and the puerperium.

The relationships between mood change, obstetric experience and alterations in plasma cortisol, beta-endorphin (beta-EP) and corticotrophin-releasing hormone (CRH) were examined in a prospective study of 97 primiparous Australian women. Psychological measures were administered between the 28th week of pregnancy and the 3rd postnatal month, including the Profile of Mood States (POMS) and the Montgomery Asberg Depressive Rating Scale (MADRS). Blood samples were collected for cortisol, beta-EP and CRH assay on most of these occasions and during labour. Factor analysis was used to identify key subsets of psychological variables for use in the subsequent analyses. 'Mood disturbance' and 'tiredness' factors peaked at 38 weeks' gestation, while 'difficulty falling asleep' was greatest around the time of birth. Cortisol, beta-EP and CRH concentrations rose significantly as pregnancy advanced and peaked at birth; plasma CRH correlated with plasma cortisol (r = 0.54) and beta-EP (r = 0.32). Women with the highest 'mood disturbance' and MADRS depression scores at 28 weeks' gestation received significantly more pain relief during labour. Those women whose mood deteriorated from 38 weeks' gestation to postnatal day 2 had larger falls in plasma beta-EP after delivery (p less than 0.01) than those women whose mood improved or remained constant. Women in this mood-deteriorated subgroup also had significantly higher MADRS depression scores at 3 months (p less than 0.01). Mild antenatal depression (MADRS greater than 13) occurred in 5.2% of women and mild postnatal depression in 4.7%. Overall, these data suggest a role for circulating CRH in the regulation of maternal cortisol secretion and significant relationships between maternal postnatal mood states and beta-EP and between antenatal mood states and obstetric events.

Adult↗

Keratin 8 of simple epithelia is expressed in glia of the goldfish nervous system.

The intermediate filament protein composition in glial cells of goldfish optic nerve differs from that found in glial cells of the goldfish spinal cord and brain. Brain and spinal cord glial cells contain glial fibrillary acidic protein (GFAP), whereas glial cells in the optic nerve contain ON3. The ON3 protein of the goldfish optic nerve was recently identified as the goldfish equivalent to the mammalian type II keratin 8 protein. In addition to the ON3 protein, the goldfish optic nerve also contains a 48-kDa protein. Immunoblotting experiments suggest that this protein is equivalent to the mammalian type I keratin 18 protein, which typically pairs with keratin 8 to form filaments. We show that these proteins are not specific to the optic nerve. The ON3 and 48-kDa proteins of the goldfish optic nerve share common antigenic properties with the predominant keratin pair expressed in the goldfish liver. These proteins are also expressed at low levels in the goldfish brain and spinal cord. In addition RNase protection assays and Northern blots indicate that the mRNA for the ON3 protein in optic nerve is identical to the message found in other goldfish tissues. The expression of ON3 was also examined in cultured glial cells from goldfish spinal cord and optic nerve and cultured fibroblast cells. Analysis of intermediate filament protein expression in cultured glial cells taken from goldfish spinal cord demonstrated the absence of GFAP in these cells and the expression of ON3. This protein was also the predominant intermediate filament protein of cultured optic nerve glial cells and fibroblasts. The differences in the expression of intermediate filament proteins in mammals and lower vertebrates are discussed. In addition, we discuss how the expression of a simple epithelial keratin pair in glial cells of the goldfish optic nerve may be associated with this system's capacity for continuous growth and regeneration.

Animals↗

Two brothers with heart defects and limb shortening: case reports and review.

Two male Arab sibs are reported with congenital heart disease and skeletal malformations. Other published case reports sharing some features in common with these brothers are considered. However, clinical and radiological features in these boys are distinct enough to represent a new cardioskeletal syndrome.

Abnormalities, Multiple↗