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Biomedical subjects

D A Harrison

Publications and source records attributed to D A Harrison.

At least 73 records · Page 4Linked to original sources

Spinal anaesthesia for urological surgery. A survey of failure rate, postdural puncture headache and patient satisfaction.

A survey was conducted on 100 consecutive patients who underwent spinal anaesthesia in our urology operating theatres. Details of the spinal technique were recorded in the operating theatre. In 25% of patients, more than one attempt at subarachnoid puncture was required and 16% of this group went on to require general anaesthesia. The patients were visited between 24 and 48 h postoperatively by one of the authors. On questioning, 24% of patients reported a headache, which had the characteristics associated with dural puncture; 62% of these headaches were described as moderate or severe and lasted between 12 and 24 h. Patients were significantly (p < 0.05) more likely to develop a postdural puncture headache if more than one attempt at subarachnoid puncture was made.

Aged↗

The RNA polymerase II 15-kilodalton subunit is essential for viability in Drosophila melanogaster.

A small, divergently transcribed gene is located 500 bp upstream of the suppressor of Hairy-wing locus of Drosophila melanogaster. Sequencing of a full-length cDNA clone of the predominant 850-nucleotide transcript reveals that this gene encodes a 15,100-Da protein with high homology to a subunit of RNA polymerase II. The RpII15 protein is 46% identical to the RPB9 protein of Saccharomyces cerevisiae, one of the smallest subunits of RNA polymerase II from that species. Among those identical residues are four pairs of cysteines whose spacing is suggestive of two metal-binding "finger" domains. The gene is expressed at all developmental stages and in all tissues. Two deletions within the RpII15 gene are multiphasic lethal deletions, with accumulation of dead animals commencing at the second larval instar. Ovary transplantation experiments indicate that survival of mutant animals to this stage is due to the persistence of maternal gene product throughout embryogenesis and early larval development. The RpII15 gene product is thus necessary for viability of D. melanogaster.

Amino Acid Sequence↗

Functional specificity of jejunal brush-border pteroylpolyglutamate hydrolase in pig.

To determine the functional specificity of intestinal brush-border pteroylpolyglutamate hydrolase (PPH), we compared the regional location of in vivo hydrolysis of pteroyltriglutamate (PteGlu3) with the location of activity and immunoreactivity of the enzyme in the pig. After in vivo incubations, PteGlu3 hydrolytic products were recovered from intestinal segments in the jejunum but not from the ileum. Brush-border PPH activity in fractionated mucosa was 10-fold greater in the jejunum than in the ileum, whereas the activity of intracellular PPH was increased in the distal ileum. Antibodies to purified brush-border PPH identified a major protein band at 120 kDa and a minor protein band at 195 kDa in solubilized jejunal brush border. Immunohistochemistry identified the enzyme only on the brush-border surface of the jejunum, whereas an immunoblot of solubilized brush-border membranes identified brush-border PPH in the jejunum but not in the ileum. The parallel of the regional location of in vivo hydrolysis of PteGlu3 with the location of brush-border PPH activity and immunoreactivity demonstrates the functional specificity of this enzyme in folate digestion.

Animals↗

The gypsy retrotransposon of Drosophila melanogaster: mechanisms of mutagenesis and interaction with the suppressor of Hairy-wing locus.

We have used the yellow gene of Drosophila melanogaster as a model system in which to study the molecular mechanisms by which the gypsy retrotransposon causes mutant phenotypes that can be reversed by nonallelic mutations at the suppressor of Hairy-wing locus. This gene encodes a 109,000 dalton protein that contains an acidic domain and 12 copies of the Zn finger motif, which are characteristic of some transcription factors and DNA binding proteins. The suppressible y2 allele is caused by the insertion of the gypsy element at -700 bp from the start of transcription of the yellow gene, resulting in a phenotype characterized by mouth parts and denticle belts in the larvae, and by bristles in the adults, that show wildtype coloration, but mutant wings and body cuticle in the adult flies. This phenotype is the result of the interaction of gypsy sequences homologous to mammalian enhancers with tissue-specific yellow transcriptional regulatory elements located upstream from the gypsy insertion site and responsible for the expression of the yellow gene in the mutated tissues. This interaction is dependent on the binding of the su(Hw) protein to the specific gypsy sequences involved in the induction of the mutant phenotype.

Amino Acid Sequence↗

Vasculature of various locations of canine gastrointestinal tract responds differently to intravenous isoproterenol.

In this study we investigated the relative vascular response of different locations of the gastrointestinal tract to continuous intravenous infusion of isoproterenol (0.1 microgram kg-1 min-1 for 10 min). The vascular response of some nonsplanchnic organs was also examined. Blood flow of the arteries was measured by electromagnetic flowmetry and that of the tissues by 15-micron microspheres. Isoproterenol increased (P less than 0.05) blood flow of the axillary artery (+52%), and the superior mesenteric artery (+45%), but not that of the inferior mesenteric artery. In the nongastrointestinal tissues, isoproterenol increased (P less than 0.05) the blood flow of the left (+46%), and right ventricle (+85%), and the skeletal muscle (+100%). In the gastrointestinal tract, isoproterenol increased (P less than 0.05) blood flow in the esophagogastric junction (+505%) and antrum (+1511%) only, but not in the gastric body or in any location of the small or large intestine. The drug also caused a large fall in resistance in the esophagogastric junction (-74%) and antrum (-94%), and a small, but significant fall in the duodenum, jejunum, and in the mid-small intestine. It had no significant effect on vascular resistance in the gastric body, ileum, or colon. In those locations of the gastrointestinal tract where isoproterenol caused an increase in blood flow, this effect was confined to the combined mucosal plus submucosal layer, and the drug had no effect on the muscularis. These data suggest that different locations of the gastrointestinal tract respond differently to the same circulating concentration of isoproterenol. The mechanism of this difference in response merits further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The Drosophila su(Hw) gene, which controls the phenotypic effect of the gypsy transposable element, encodes a putative DNA-binding protein.

Homozygous mutations at the suppressor of Hairy-wing [su(Hw)] locus reverse the phenotype of gypsy-induced alleles in a number of genes located throughout the Drosophila genome. To understand the molecular basis of this phenomenon, the su(Hw) locus was isolated by chromosomal walking from a cloned homeo-box-containing sequence. The exact location of the gene was determined by Southern analysis of the DNA alterations associated with several su(Hw) alleles. A 9.5-kb KpnI-SalI fragment, where all the DNA changes associated with su(Hw) mutations were mapped, was able to rescue the su(Hw) mutant phenotype after P-element-mediated germ-line transformation. This DNA fragment encodes a 3.3-kb RNA that is expressed in all stages of Drosophila development; the size or abundance of this RNA is affected in several su(Hw) alleles tested. This transcript encodes a protein that contains a highly acidic region and 12 repeats of the 'Zn finger' domain characteristic of some DNA-binding and transcription-activating proteins, supporting the hypothesis that the su(Hw) locus might encode a transcription factor that plays a role in the expression of the gypsy element.

Alleles↗

The Drosophila melanogaster suppressor of Hairy-wing protein binds to specific sequences of the gypsy retrotransposon.

Mutations at the suppressor of Hairy-wing [su(Hw), 3-54.8] locus reverse the phenotype of second-site mutations induced by the gypsy transposable element in Drosophila melanogaster. This gene encodes a protein with a predicted molecular weight of 109,000 that contains an acidic domain and 12 copies of the DNA-binding 'Zn finger' motif. The su(Hw) protein was overexpressed in Escherichia coli and Drosophila cells, and partially purified. It was shown to interact specifically in vitro with a 367-bp DNA fragment that contains 12 copies of the sequence PyPuTTGCATACCPy located in the 5'-untranslated region of gypsy, between the 5' long terminal repeat (LTR) and the first ATG initiation codon. This sequence shows striking homology to some mammalian transcriptional enhancer elements, supporting a role for the su(Hw) protein in the control of gypsy transcription. In addition, the su(Hw) protein is present at approximately 100-200 sites on Drosophila polytene chromosomes, suggesting that it also interacts in vivo with DNA and might be involved functionally in the regulation of normal cellular genes.

Animals↗

Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.

Algorithms↗

Lymphangiography, ultrasonography, and computed tomography in Hodgkin's disease and non-Hodgkin's lymphoma.

Findings from histologic analysis, lymphangiography, ultrasonography, and computed tomography were reviewed for 54 cases of Hodgkin's disease and 18 cases of non-Hodgkin's lymphoma. All patients were classified as clinical stage 1 or 2 disease at the time of the imaging studies. The ultrasound and computed tomography studies identified only 30 to 40% of the truly positive patients. This low sensitivity contrasts with lymphangiography, which identified 95% of the truly positive Hodgkin's disease patients and 70% of the patients with abdominal spread of non-Hodgkin's lymphoma. Many errors in interpretation were attributable to location and distribution of disease in these patients and the differing patterns of spread in Hodgkin's disease and non-Hodgkin's lymphoma. The evidence indicates that when findings are positive on computed tomography or ultrasound, no other study is necessary. In stage 1 or 2 lymphoma, non-Hodgkin's patients with negative noninvasive findings and all Hodgkin's patients, regardless of their noninvasive findings, should undergo lymphangiography.

Abdomen↗

Computational analysis of models for cotransport.

The order of substrate interaction with a cotransport carrier is studied by numerically fitting theoretical models to empirical data for a Na+-D-glucose pathway. Our analysis is based on a least-squares minimization routine developed at CERN, and uses data derived from tracer flux of substrate under equilibrium exchange conditions. Random, Ordered mirror, and Ordered glide models are considered and the applicability of both Random and Glide systems to the experimental observations is demonstrated. A more detailed study of the Glide model provides an estimation of the relative values of the individual rate constants describing each kinetic step in the mechanism. We argue that parameterization of competing models can result in tests which will distinguish between them, even when these contain many unknowns in the proposed structure of the kinetic mechanism. The essence of this means of model discrimination is the ability to find a single set of parameter values that fits a variety of experimental observations. The ability to obtain numerical estimates of obtain numerical estimates of individual rate constants is also a useful tool in investigation of the kinetic fine structure of the carrier. For the data at hand we conclude that a complete parameterization of the Glide model cannot be attained, possibly due to a heterogeneity in the temperature at which the experiments have been performed. Three solutions to the Glide model are presented, each of which corresponds to a fit of the Glide model to a subset of the experimental data.

Biological Transport↗

Work in progress: detection of deep venous thrombosis with 99mTc-sulfur colloid.

Scintigrams of the leg were obtained following antecubital venous injection of 99mTc-sulfur colloid (SC) in 25 patients with suspected deep venous thrombosis. Contrast venograms were taken following the scan in all cases. Of 14 patients with confirmed deep venous thrombosis, 11 had positive scans. Of 11 patients with normal venograms, 10 had negative scintigrams. The simplicity of 99mTc-SC venography and its high rate of accuracy (84% in this series) suggest that it may be useful as a relatively noninvasive means of identifying deep venous thrombosis of the leg.

Adult↗

Maffucci's syndrome.

A case is reported of Maffucci's Syndrome with multiple enchondromata involving the left ring finger and subcutaneous haemangiomata in the left thenar eminence, treated by surgical excision.

Adult↗