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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 217 records · Page 12Linked to original sources
PubMed1993

Distraction of the frontal bone outside the cranial plane: a rabbit model.

Distraction of the frontal bone outside the cranial plane using the Ilizarov principle was performed in 17 22-week-old New Zealand white rabbits. Five rabbits had frontal bone osteotomy only and were in the control group; 5 rabbits were placed in the sham control group and had frontal bone osteotomy plus application of a customized headgear appliance; and 7 rabbits were placed in the experimental group, which underwent frontal bone osteotomy application of the headgear and distraction. The frontal bone was elevated 1 mm every other day for a period of 8 weeks, and the animals were then killed. Cephalometry was performed both preoperatively and at the end of the 8-week period. Histological examination of the skulls was also performed. The experimental group showed a significantly elevated frontal bone compared to the sham control group (p < 0.05). Callous bone filled the distracted segment, which united the frontal bone with the cranial plane. Therefore, frontal bone advancement by distraction osteogenesis is possible using this rabbit model.

Animals↗
PubMed1993

Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on haemodynamic parameters, transcapillary fluid balance, diuresis and atrial peptides.

The effects of Ringer's acetate (RAc) infusion with different temperatures, 18 degrees C compared to 36 degrees C, were studied in 20 healthy volunteers. An infusion volume of 20% of the estimated extracellular volume was given over 45 min. Before and after the RAc infusion, interstitial colloid osmotic pressure and interstitial fluid hydrostatic pressure were measured on the lateral part of the thorax and in the lower leg. Blood sampling and pressure measurements were performed through a cannula placed in the left radial artery, and arterial oxygen saturation was measured by pulse oximetry. Atrial peptides ANF (99-126) and ANF (1-98) in plasma were measured as indicators of volume loading. Cold RAc infusion increased mean arterial pressure from 82 (s.d. +/- 7) to 96 (s.d. +/- 9) mmHg (10.9-12.8 kPa) at the end of the infusion with a simultaneous fall in heart rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The arterial oxygen saturation during the infusion of cold RAc was higher than during warm RAc infusion. Cold infusion produced the expected haemodilution with a fall in erythrocyte volume fraction (EVF) from 0.39 (+/- 0.03) to 0.33 (+/- 0.03) and a fall in plasma colloid osmotic pressure (COPp) from 21.7 (+/- 1.1) mmHg to 15.0 (+/- 1.3) mmHg (2.9-2.0 kPa). Warm infusion induced a nearly identical haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (+/- 2.3) mmHg to 8.9 (+/- 2.7) mmHg (1.5-1.2 kPa) after warm infusion while cold infusion gave no changes. The changes in interstitial fluid hydrostatic pressure were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Alpha 2-chimerin, an SH2-containing GTPase-activating protein for the ras-related protein p21rac derived by alternate splicing of the human n-chimerin gene, is selectively expressed in brain regions and testes.

n-Chimerin (alpha 1-chimerin) is a brain GTPase-activating protein (GAP) for the ras-related p21rac. We now report the occurrence of another form of chimerin, termed alpha 2-chimerin. This is the product of an alternately spliced transcript of the human n-chimerin gene encoding an N-terminal SH2 (src homology 2) domain in addition to the phorbol ester receptor and GAP domains. alpha 1- and alpha 2-chimerin mRNAs were expressed differently. In the rat brain, only alpha 1-chimerin mRNA was expressed in cerebellar Purkinje cells, although both alpha 1- and alpha 2-chimerin mRNAs occurred in neurons in the cerebral cortex, hippocampus, and thalamus. Only alpha 2-chimerin RNA was expressed in rat testes, in early pachytene spermatocytes. A 45-kDa SH2-containing chimerin corresponding to the alpha 2 form was purified from rat brain. As with Escherichia coli 45-kDa recombinant alpha 2-chimerin, purified brain alpha 2-chimerin exhibited racGAP activity which was stimulated by phosphatidylserine. The recombinant SH2 domain bound several 32P-labelled phosphoproteins of PC12 cells, whose phosphorylation increased in response to trophic factors, including nerve growth factor. To examine the relationships of alpha 1- and alpha 2-chimerin transcripts, human genomic DNA clones were characterized. In alpha 2-chimerin mRNA, a 3' splice acceptor site within exon 1 of alpha 1-chimerin mRNA was used, replacing its 5' untranslated region and N-terminal coding sequence. The single human n-chimerin gene was mapped to chromosome 2q31-q32.1, colocalizing with the CRE-BP1 transcription factor gene (2q32). It contained several splice junctions conserved with the sequence-related protein kinase C and bcr genes. alpha 2-Chimerin is only the second SH2-containing GAP and the first example of an SH2 domain generated by alternate splicing.

Alternative Splicing↗
PubMed1993

Haemoccult does not reduce the need for colonoscopy in surveillance after curative resection for colorectal cancer.

Patients who had undergone curative resection for colorectal cancer were studied to compare the efficacy of faecal occult blood detection (Haemoccult test) with colonoscopy in the detection of metachronous tumours. Fifty nine patients were studied and both Haemoccult testing and colonoscopy were successfully completed in 54 patients. In 37 patients, both tests were negative. One patient with a positive Haemoccult test had no colonoscopic abnormality and remains alive and well two years later. There were, however, 16 patients with negative Haemoccult tests in whom an abnormality was found on colonoscopy. In four patients, one Dukes's A cancer and seven tubulovillous adenomas were found--all neoplastic lesions that would have been missed if surveillance had been by Haemoccult alone.

Aged↗
PubMed1993

Cerebral blood flow and evoked potentials during reoxygenation with 21 or 100% O2 in newborn pigs.

The effects of resuscitation with 21 or 100% O2 on cerebral blood flow (CBF) and somatosensory evoked potentials (SEPs) were studied in 19 newborn pigs anesthetized with pentobarbital sodium. They were ventilated with 8% O2 until base excess reached -20 mmol/l and then were randomly reoxygenated with 21% O2 (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2. Mean duration of hypoxemia in the two groups was 57 +/- 6 (SE) and 59 +/- 6 min, respectively. CBF determined by radioactive microspheres was significantly increased in all areas in both groups after 5 and 20 min of reoxygenation. At 5 min of reoxygenation forebrain O2 uptake (CMRo2) had increased significantly compared with baseline values in the 21% O2 group (2.5 +/- 0.1 to 3.2 +/- 0.2 ml.100 g-1.min-1) but not in the 100% O2 group. There were, however, no significant differences between the two groups in CBF or CMRo2 at any time, and by 60 min of reoxygenation both had returned to baseline levels. SEPs were not significantly different in the two groups. We conclude that, as judged by CBF, CMRo2, and SEP, 21% O2 is not inferior to 100% O2 when hypoxemic newborn pigs are reoxygenated.

Animals↗
PubMed1993

Effect of hypoxemia and hypovolemia on retinal and choroidal blood flow in the newborn piglet.

The effect of hypoxemia and/or hypovolemia on ocular blood flow was studied in paralyzed and mechanically ventilated newborn piglets with the isotope-labelled microsphere method. Twenty-six piglets were studied in four different groups. One group of piglets (n = 6) was made hypoxemic by breathing 10% O2, a second group (n = 7) and a third group (n = 7) were studied during hypoxemia (10% O2), followed by hypovolemia (bleeding 20 and 30% of estimated blood volume, respectively). A fourth group of piglets (n = 6) was made hypovolemic by bleeding 20% of estimated blood volume. Hypoxemia resulted in a 2- to 3-fold increase in retinal blood flow (RBF), while hypovolemia did not change RBF, not even when preceded by a period of hypoxemia. In the case of choroidal blood flow (ChBF), the increase caused by hypoxemia was only 10-40%. Although ChBF decreased significantly during hypovolemia, no significant correlation between mean arterial blood pressure and ChBF was found. The results indicate that autoregulation is normally seen in RBF, but probably not in ChBF. However, during hypoxemia autoregulation was found neither in RBF nor in ChBF.

Animals↗
PubMed1993

Effect of nimodipine on cerebral and organ blood flow in normal and posthypoxemic newborn piglets.

Using the isotope-labelled microsphere method, blood flow to the brain, the heart and the kidneys were studied in newborn piglets during nimodipine infusion. Twenty piglets were studied in two different groups. Group 1 (n = 8) was kept normoxic and given a continuous nimodipine infusion (15 micrograms/kg/min). Group 2 (n = 12) was made hypoxemic by breathing 10% O2 for 10 min followed by an identical nimodipine infusion as group 1. In spite of a significant systemic hypotension, nimodipine infusion alone significantly increased blood flow in the brain stem and right cardiac ventricle at 30-60 min of infusion, while blood flow to cerebellum, cerebrum and the left cardiac ventricle did not change. Blood flow to the kidneys decreased significantly. In posthypoxemic piglets nimodipine infusion gave almost similar flow patterns, however, the changes appeared at an earlier time. We conclude that in spite of a significant reduction in blood pressure, cerebral and cardiac blood flow is preserved both in normal and posthypoxemic animals even at high doses of nimodipine. However, because of the decreased blood flow to the kidneys further dose-response studies are needed before clinical use in asphyctic newborns.

Animals↗
PubMed1993

Split-calvaria osteoplastic rotational flap for anterior fossa floor repair after tumor excision. Technical note.

A split-calvaria osteoplastic rotational flap to repair the anterior fossa floor after tumor excision was devised and tested clinically. At surgery, the flap is outlined between the glabella and the vertex. After the pericranium between the glabella and the flap's anterior pole is elevated to form its pedicle, a full-thickness craniotomy is performed to expose the diploic aspect of the bone graft donor site (when the graft is relatively wide, bifrontal craniotomies may be advantageous). The diploic space is split in situ, taking care to protect the pedicle and its attachments to the osseous segment. Linear osteotomies in the outer table are created to mobilize the flap. With the flap rotated frontally, the craniotomy is completed. After tumor extirpation, the margins of the osseous segment of the flap are shaped to conform to the defect of the anterior fossa floor. Transverse osteotomies are performed so that the graft's convex curve conforms to that of the anterior fossa floor. The flap is then rotated into position. Follow-up evaluation in two patients at 22 and 30 months demonstrated bone integrity of the anterior fossa floor with graft preservation. Transient postoperative cerebrospinal fluid (CSF) rhinorrhea, which occurred in Case 1, was avoided in Case 2 by placing the osseous segment of the graft coplanar with the bone floor of the fossa. Neither patient had late meningitis or CSF rhinorrhea. The split-calvaria osteoplastic rotational flap may represent an advance toward the ideal reconstruction of the anterior cranial fossa floor.

Brain Neoplasms↗
PubMed1993

Transplacental and nonplacental clearances, metabolism and pharmacodynamics of labetalol in the fetal lamb after direct intravenous administration.

Labetalol has been previously shown to cause significant maternal and fetal metabolic effects in pregnant sheep after maternal administration. To investigate these observations further, the present study describes the pharmacokinetics, metabolism and pharmacodynamics of labetalol in the fetal lamb after direct fetal i.v. bolus (4 mg) administration. The fetal total body clearance of labetalol (50.45 +/- 1.37 ml m-1 kg-1), which was significantly higher than that previously determined in the ewe, was composed of transplacental and nonplacental CLs of 23.4 +/- 8.99 ml m-1 kg-1 and 27.05 +/- 10.36 ml m-1 kg-1, respectively. The maternal to fetal plasma labetalol area under the curve ratio was 0.031 +/- 0.002 and the CLmp and CLmn were 7.27 +/- 2.11 ml m-1 kg-1 and 30.5 +/- 5.94 ml m-1 kg-1, respectively. Labetalol concentrations in fetal tracheal fluid were consistently higher than that in fetal plasma. The glucuronide conjugate of labetalol was found in the amniotic fluid at up to 20 times the free drug concentration but the oxidative metabolite, 3-amino-1-phenyl-butane, was not detected in plasma or amniotic fluid samples. The fetal effect of labetalol was characterized by an acute lactic acidosis. The calculated hind limb arteriovenous lactate flux showed a net output of lactic acid equal to 3.85 +/- 2.05 g from the hind limb over 24 h after labetalol administration. Although the fetal exposure to labetalol in this study was roughly 4 times that after a 100-mg maternal bolus administration, the magnitude of fetal lactic acidosis was not significantly different in these studies. The clinical implications of the observations made in this study remain to be investigated.

Animals↗
PubMed1992

Developmental regulation and neuronal expression of the mRNA of rat n-chimaerin, a p21rac GAP:cDNA sequence.

Human n-chimaerin is a GTPase-activating protein (GAP) for p21rac and a phorbol ester receptor. We have isolated rat n-chimaerin cDNA and investigated the cellular and developmental pattern of mRNA expression in the brain. There is extensive sequence conservation with human n-chimaerin in the coding region and the first 400 nucleotides of the 3'-untranslated region (UTR) (90% and 83% identity respectively). The rat cDNA encodes an additional 35 N-terminal amino acids compared with the reported human cDNA, which has a 5'-UTR sequence inversion and a 41-nucleotide deletion including the putative initiator methionine. The rat cDNA encodes a 334-amino acid protein (38200 M(r), pI 8.04) with 97% amino acid sequence identity with the human protein, after correction of the human 5'-DNA sequence. n-Chimaerin mRNA was detectable in embryonic rat brain at day 15 and increased in amount postnatally from birth to 20 days, coincident with cellular differentiation and synaptogenesis. n-Chimaerin mRNA is restricted to neurons, with highest concentrations in hippocampal pyramidal cells, granule cells of the dentate gyrus and cortical neurons. In the cerebellum the mRNA was detected only in Purkinje neurons. The pattern and specificity of mRNA expression suggests an important role for n-chimaerin in neuronal signal-transduction mechanisms.

Amino Acid Sequence↗
PubMed1992

Diversity and versatility of GTPase activating proteins for the p21rho subfamily of ras G proteins detected by a novel overlay assay.

The p21ras superfamily, involved in diverse processes including cell growth and intracellular trafficking, possesses intrinsic GTPase activity and cycles between GTP-bound active and GDP-bound quiescent states. This intrinsic activity, which results in down-regulation, is accelerated by GTPase activating proteins (GAPs). Other proteins regulating the GDP/GTP cycle include exchange proteins and dissociation inhibitors. The p21s rho, rac, and cdc42Hs constitute a subfamily implicated in cytoskeletal organization. BCR and n-chimaerin are prototypes of a new GAP family for these p21s. To investigate proteins modulating GTP hydrolysis of the three p21s, we developed a novel overlay assay applicable to tissue extracts. Diverse GAPs with different specificities were identified in all rat tissues. Brain contained rac1 GAPs of 45, 50, 85, 100, and 150 kDa. The p50 and p150 GAPs also act on rhoA and cdc42Hs and are ubiquitous, while the p45-GAP, n-chimaerin, is brain- and testis-specific and acts preferentially on rac1; the p100 GAP acts on both rac1 and cdc42Hs and is brain-specific. A new class of p21-interacting proteins was also identified. This diversity, versatility, and tissue specificity of GAPs may be required for fine control of the down-regulation of GTP-bound p21s and the suggested specific downstream effects of individual GAPs, which could involve "cross-talk" between GAPs and p21s.

Blotting, Western↗
PubMed1992

Identification and quantitation of an oxidative metabolite of labetalol in sheep: pharmacokinetic and metabolic implications.

A sensitive and selective assay has been developed for the identification and quantitation of 3-amino-1-phenyl butane (3-APB), a metabolite of labetalol, in biological fluids using electron impact gas chromatography/mass-selective detection. Samples were extracted with n-hexane, derivatized with heptafluorobutyric anhydride and chromatographed on a cross-linked fused-silica capillary column. A positive EI spectrum was obtained using a mass-selective detector. Identification of the metabolite was accomplished using an authentic standard; quantitation was performed in the selected ion monitoring mode using ions m/z 345 (M+) and 132. The assay was linear over the calibration range of 0.5-1000 ng of the analyte and the intra-sample coefficients of variation were less than 12% in all cases. The absolute recovery of 3-APB following extraction from urine and bile was found to be 102.9 +/- 4.9% and 98.3 +/- 1.45% (mean +/- SEM) respectively. The minimum quantitation limit of the assay was 0.5 ng ml-1 (approximately 2 pg injected). Application of the assay in a pharmacokinetic-pharmacodynamic study of labetalol in sheep is demonstrated. The metabolite was detected in urine and bile samples obtained from adult non-pregnant sheep following labetalol administration. The cumulative amount of 3-APB excreted in urine over 24 h was found to be 71.55 micrograms in one animal following a 100 mg dose of labetalol. Evidence for biliary excretion, glucuronidation and sulfation of 3-APB was also found.

Animals↗
PubMed1992

The T-cell receptor zeta chain contains a GTP/GDP binding site.

In a search for nucleotide binding proteins associated with the T-cell receptor (TCR)-CD3 complex, a novel labeling technique involving introduction of [alpha-32P]GTP or [alpha-32P]ATP into permeabilized cells followed by in situ periodate oxidation was developed. To test the method we first demonstrated that p21ras and other classical GTP binding proteins could be labeled in a GTP-specific manner. In human T lymphocytes the TCR zeta chain was found to be specifically labeled by GTPoxi but not by ATPoxi or CTPoxi. Labeling kinetics and competition experiments demonstrated that zeta had a capacity to bind GTP and GDP but not GMP or ATP. Proteolytic cleavage experiments identified lysine 128 as the GTP crosslinking site. This result was confirmed by studies using oligonucleotide-directed mutagenesis. Lysine residues 128, 135 and 149 were each replaced by arginine and glycine 134 by valine and mutated proteins were expressed in CHO cells. Labeling of mutants K128R and G134V was abrogated whereas mutant proteins K135R and K148R could still be specifically crosslinked to GTP. We conclude that Lys128 and Gly134 are part of a GTP/GDP binding site suggesting that zeta is a unique GTP/GDP binding structure.

3T3 Cells↗
PubMed1992

The human heat-shock genes HSPA6 and HSPA7 are both expressed and localize to chromosome 1.

HSPA6 is a member of the human heat-shock protein gene family, encoding a basic 70-kDa protein, with unique induction characteristics (Leung et al., 1990, Biochem. J. 267: 125-132). Hybridization analyses with a somatic cell hybrid DNA panel localized the gene to chromosome 1q. The highly related HSPA7 DNA sequence (Voellmy et al., 1985, Proc. Natl. Acad. Sci. USA 82: 4949-4953) colocalized. Both HSPA6 and HSPA7 represent functional genes, as determined by analyses of mRNA from heat-shocked human cells using specific oligonucleotides, although their pattern of expression differed. Neither mRNA was detected in the absence of heat stress. A BamHI polymorphism in the HSPA7 gene was present in a predominantly Asian population.

Base Sequence↗