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Biomedical subjects

K Morrison

Publications and source records attributed to K Morrison.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clenbuterol increases stroke power and contractile speed of skeletal muscle for cardiac assist.

BACKGROUND: Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a beta2-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep. METHODS AND RESULTS: The following 4 groups were used: A (n=6), untrained controls; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240- microsec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (n=6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (n=6), clen+trained. In a terminal experiment, the mobilized LD was wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (DeltaP) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to <20% of their original values by 15 minutes because of fatigue (P<0.005). Group B was fatigue-resistant, with a DeltaP and stroke power at 60 minutes of 13 mm Hg (70% of initial) and 0.34 W/kg (39% of initial), respectively. The performance of group C was similar to that of controls. In group D, however, the muscles were stronger at all time points than in B, with a DeltaP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:DeltaP) and relaxation (-dP/dt:DeltaP) were significantly greater in group D than B. Protein analyses showed group D to have only a trend toward greater abundance of the fast isoforms of myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase (P>0.1). CONCLUSIOINS: ++Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.

Adrenergic beta-Agonists↗
PubMed1999

Drug administration in custody.

This paper describes the system for drug administration to prisoners in custody which has been developed at U Division, Kilmarnock in Strathelyde. The protocols agreed by the police surgeons in the area are described. The system is relevant to all police surgeons in their daily work, particularly with the advent of general practice cooperatives and the decline in personal carriage of all but the most acutely required drugs.

Journal Article↗
PubMed1999

The study of spontaneous GH secretion after 36-h fasting distinguishes between GH-deficient and normal adults.

OBJECTIVE: Within an appropriate clinical context, GH deficiency (GHD) in adults can only be diagnosed biochemically by provocative testing. The evaluation of IGF-I, IGFBP-3 and even of spontaneous GH secretion do not establish the diagnosis of adult GHD. In fact, remarkable overlaps between normal and GHD adults have been reported for all these parameters. On the other hand, it is well known that even short-term fasting stimulates GH secretion in normal subjects. The aim of our study was to determine the effects of 36 h fasting on 8-h diurnal GH, insulin and glucose levels as well as on basal IGF-I, IGFBP-3, acid-labile subunit (ALS), IGFBP-1, GHBP and free fatty acid (FFA) levels. SUBJECTS: We studied 9 GHD adults (GHD, 8 males, 1 female; age, mean +/- SEM: 37.6 +/- 2.3 years, body mass index (BMI): 24.5 +/- 1.0 kg/m2) and 20 age-matched normal subjects (NS) as controls (13 males, 7 females; age: 28.9 +/- 0.6 years, BMI: 21.6 +/- 0.4 kg/m2). STUDY DESIGN: In all subjects we studied the effects of 36 h fasting on 8-h daytime GH, insulin and glucose levels (assay every 30 min from 0800 h to 1600 h) as well as on basal IGF-I, IGFBP-3, ALS, IGFBP-1, GHBP and FFA levels. RESULTS: Before fasting, basal mean IGF-I, IGFBP-3 and ALS levels in GHD were lower (P < 0. 0001) than in NS. IGFBP-1, GHBP and FFA levels were similar in both groups. Before fasting mean GH concentration (mGHc) in GHD was lower (P < 0.05) than in NS (0.4 +/- 0.2 vs. 2.2 +/- 0.6 mu/l) but with a clear overlap between the 2 groups (range 0.4-0.8 vs. 0.4-6.8 mu/l). After fasting, both in GHD and NS basal IGF-I, IGFBP-3, ALS and GHBP levels did not change significantly. On the other hand, in both GHD and in NS IGFBP-1 was increased (P < 0.0001) to a similar extent, while FFA increased in NS more (P < 0.01) than in GHD. Fasting significantly increased mGHc in NS (12.0 +/- 1.2 mu/l, P < 0.0001) but not in GHD (0.6 +/- 0.2 mu/l). After fasting, no overlap was present between GHD and NS (0.4-1.6 vs. 2.4-20.8 mu/l, respectively). Mean glucose and insulin concentrations over 8 h in GHD and NS in basal conditions were similar and were reduced to the same extent in both groups. CONCLUSIONS: Our findings demonstrate that after short-term fasting, the study of spontaneous GH secretion distinguishes between GH-deficient adults and normal subjects; this phenomenon occurs before significant changes in IGF-I and IGFBP-3 levels. These results suggest that the assessment of spontaneous GH secretion could be useful for the diagnosis of adult GH deficiency only after short-term fasting.

Adult↗
PubMed1998

Sequence comparisons and functional studies of the proximal promoter of the carbonic anhydrase 3 (CA3) gene.

Carbonic anhydrase 3 (CA3) is a member of a gene family encoding proteins which catalyse the hydration of CO2 to generate protons and bicarbonate ions for cellular ion transport and pH homeostasis. In mouse embryos CA3 is expressed at high levels in notochord and skeletal muscle and here we demonstrate that this pattern of expression is the same in the developing human embryo. To investigate mechanisms controlling CA3 transcription, we have isolated and compared 2.8kb of sequence flanking exon 1 from the mouse and human genes. Several segments of high sequence identity >80% have been identified, the longest segments of which represent a proximal promoter region and a putative enhancer element. We have shown previously that in cultured cells the human 2.8kb promoter region imposes high level myogenic specific transcription of a reporter gene. However, we now show that while this promoter region directed muscle-specific expression in transgenic mouse embryos this was subject to position effects.

Animals↗
PubMed1998

Differential leukotriene constrictor responses in human atherosclerotic coronary arteries.

BACKGROUND: Leukotrienes are a class of biologically active lipids that have potent effects on the heart. To assess their role in coronary artery disease, we compared the contractile responses of leukotriene C4 (LTC4) and leukotriene D4 (LTD4) and their binding activity in both atherosclerotic and nonatherosclerotic human coronary arteries. We also studied expression of the enzymes that control their formation to understand how the 5-lipoxygenase (5-LO) pathway is activated in the coronary arteries. METHODS AND RESULTS: The capacity of leukotrienes to affect coronary vessel tone and the influence of atherosclerosis was tested in organ baths. Leukotriene receptors were examined by autoradiography, and antibody binding to the various enzymes responsible for their formation was assessed by use of immunocytochemistry. Nonatherosclerotic coronary artery ring segments were unresponsive to LTC4 and LTD4. In contrast, LTC4 and LTD4 induced concentration-dependent contractions in atherosclerotic coronary arteries. Specific [3H]-LTC4 but not LTD4 binding to atherosclerotic coronary artery was evident, with no evidence of specific binding of [3H]-leukotrienes to nonatherosclerotic coronary artery. High-resolution autoradiography identified specific [3H]-LTC4 binding sites to smooth muscle cell and to regions of intimal proliferation and plaque. Cells showing positive antibody binding to 5-LO, FLAP (5-lipoxygenase activating protein), and leukotriene A4 hydrolase were also present in the coronary arteries and had a similar distribution to macrophages. CONCLUSIONS: Atherosclerosis is associated with a specific leukotriene receptor(s) capable of inducing hyperreactivity of human epicardial coronary arteries in response to LTC4 and LTD4.

5-Lipoxygenase-Activating Proteins↗
PubMed1998

Colon carbonic anhydrase 1: transactivation of gene expression by the homeodomain protein Cdx2.

The homeodomain protein, Cdx2, has been implicated in the transcriptional regulation of genes expressed in the small intestine. In vitro studies of the carbonic anhydrase 1 (CA1) colon promoter implied that Cdx2 may also play a role in the regulation of colon-specific gene expression. The current work follows up this proposal by examining the ability of Cdx2 to transactivate gene expression in cultured cells mediated by CA1 promoter sequences. The results show that Cdx2 exerts a positive regulatory effect by binding to a motif 87 bp upstream of the CA1 TATA box; this motif appears to act as an enhancer since gene activation is independent of its orientation.

CDX2 Transcription Factor↗
PubMed1998

Relative induction of heat shock protein in coronary endothelial cells and cardiomyocytes: implications for myocardial protection.

OBJECTIVES: Induction of the 70 kd heat shock protein in the heart is known to exert a protective effect against postischemic mechanical and endothelial dysfunction. However, the exact site of induction and the mechanisms involved remain unknown. The aim of this study was to investigate the relative capacity of endothelial and myocardial cells to express the 70 kd heat shock protein in response to heat stress, as well as their significance. METHODS: (1) Postischemic recovery of cardiac mechanical and endothelial function was studied in isolated rat hearts with and without endothelial denudation with saponin. (2) Semiquantitative determination of induction of 70 kd heat shock protein by Western immunoblotting was performed in the whole cardiac homogenate, in isolated cardiac myocytes, and in coronary endothelial cells. (3) Immunocytochemistry was used to visualize the distribution of induction of 70 kd heat shock protein in both cell types. RESULTS: Postischemic recovery (percent preischemic value +/- standard error of the mean) of cardiac output in hearts from heat-stressed animals was significantly improved (66.7 +/- 6.9 vs 44.5 +/- 4.5 in the control group, p < 0.01). In heat-stressed hearts treated with saponin no improvement in the recovery of cardiac output was noted (44.7 +/- 6.9 in heat-stressed hearts vs 38.0 +/- 4.0 in heat-stressed, saponin-treated hearts, p = not significant). Endothelial function (as assessed by the vasodilatory response to the endothelium-dependent vasodilator 5-hydroxytryptamine) improved from 31.0 +/- 5.2 in the control group to 65.8 +/- 7.1 in heat-stressed hearts (p < 0.02 vs control) and dropped to -1.9 +/- 3.8 in heat-stressed hearts treated with saponin. Immunocytochemistry showed that only sections of hearts from heat-treated rats showed a strong specific reaction with heat shock protein antibody. The positive staining was seen in endothelial cells. Induction of 70 kd heat shock protein content in the whole cardiac homogenate from heat-stressed rats as measured by Western immunoblotting was 5.2 +/- 1.9 (vs 0.0 in non-heat-stressed rats, p < 0.0001) and dropped to 0.0 in heat-stressed hearts treated with saponin. The tentative amount of 70 kd heat shock protein was 18.1 +/- 7.8 in isolated endothelial cells from heat-stressed hearts and 2.3 +/- 2.3 in isolated cardiac myocytes (p < 0.01 vs endothelial cells). CONCLUSIONS: Coronary endothelial cells are the main site of induction of 70 kd heat shock protein in the heart and appear to contribute to the protective effects of heat stress on the recovery of mechanical and endothelial function.

Animals↗
PubMed1998

Susceptibility to spina bifida; an association study of five candidate genes.

Clues regarding candidate genes which influence susceptibility to spina bifida and anencephaly come from the identification of folate-associated risk factors and from studies of mouse mutants showing neural tube anomalies. On this basis we selected five candidate genes; CBS, MS, MTHFR, T (Brachyury) and BRCA1 for genetic analysis in 31 Dutch and 48 British NTD families. Ten polymorphisms, two for each gene, were used in transmission tests for disequilibrium (TDT). In six instances more than 50 transmissions from heterozygous parents could be examined. Using TDT we find evidence for an association between an allele at the T gene and liability to NTD in the embryo. Data from British and Dutch populations showed the same trend and in combination gave a chi 2TDT = 4.89, P = 0.03 (OR 2.39, CI 95% 1.02-5.61). No association, in either population group, was found for CBS, MS and MTHFR, the enzymes most directly associated with the known risk factors in folate metabolism. The possibility of complex genetic interactions was explored; the data show that a Gly919 MS variant occurs more frequently in combination with the MTHFR thermolabile variant in mothers of NTD offspring (OR 3.94, CI 95% 1.0-16.3).

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

Specificity of the hyaluronate lyase of group-B streptococcus toward unsulphated regions of chondroitin sulphate.

The purification and properties of a hyaluronate lyase secreted by Streptococcus agalactiae, which is believed to facilitate the invasion of host tissues by the organism, have been described previously [Pritchard, Lin, Willingham and Baker (1994) Arch. Biochem. Biophys. 315, 431-436]. The specificity of the limited cleavage of chondroitin sulphate by the enzyme is the subject of this report. To simplify the task, a chondroitin sulphate from the Swarm rat chondrosarcoma, which contains only 4-sulphated and unsulphated disaccharide repeats, was used in this study. Tetrasaccharides from an ovine testicular hyaluronidase digest of the chondroitin sulphate were isolated, identified and tested as substrates of the streptococcal hyaluronate lyase. Only tetrasaccharides with an unsulphated disaccharide at the reducing end were cleaved (by elimination at the N-acetylgalactosaminidic bond). Thus chondroitin sulphate chains are cleaved by the action of this lyase at every unsulphated disaccharide repeat, but release of unsaturated unsulphated disaccharides only occurs from sites where two or more sequential unsulphated disaccharide repeats are present. Analysis of the chondrosarcoma chondroitin sulphate showed that of approximately five unsulphated disaccharide repeats per chain, two are clustered. The ability of group-B streptococcal hyaluronate lyase to cleave chondroitin sulphate may allow the organisms to invade tissues more efficiently. The demonstrated specific and highly limited cleavage of chondroitin sulphate by this bacterial lyase promises to be a useful tool in the determination of chondroitin sulphate structure and variability.

Animals↗
PubMed1997

A use of self-instruction to extend the generalization of a self-instructed in-common discrimination.

Three typically developing preschool children were presented with an in-common sorting problem involving colored and marked shapes; the task was to see what two pictures had in common and to sort a deck of pictures according to that feature. The children failed to sort accurately. They were then taught to name the common features of any pair and to answer the question, "What are you looking for?" before sorting, to produce the form of a self-instruction (e.g., "I'm looking for blue triangles"). They still failed to sort accurately until they were taught to link their sorting to that potentially self-instructive answer. They then showed perfect accuracy in sorting and occasional spontaneous overt self-instructions, when told only, "Put here what these pictures have in common," across ever-changing pairs (much like the children of prior reports). The present report asks whether that finally correct performance would generalize to new stimuli. Accordingly, the children were probed with steadily changing sample pairs of three new stimulus sets-recombinations of the colored, marked shapes used in training; letters; and pictures. One child showed near-perfect generalization to all three of these new sets (like many children in prior reports). But the other two children showed near-perfect generalization to only two of the sets and not to the third Set-letters. Merely reintroducing the content-free question, "What are you looking for?" and acknowledging correct answers to it (i.e., self-instructions about letters) yielded largely accurate sorting of letter problems; this way of remediating failures of generalization had not been studied before. In general, sorting problems with two elements in common proved more difficult than those with one element in common; this difference diminished in the child told to self-instruct about letters after that self-instruction.

Child, Preschool↗
PubMed1996

The caudal-type homeobox protein Cdx-2 binds to the colon promoter of the carbonic anhydrase 1 gene.

Carbonic anhydrase 1 (CA1) is an abundant enzyme in colon epithelia. In the gastrointestinal tract, carbonic anhydrase is vital for NaCl resorption, alkalinization of gut contents, and absorption of short-chain fatty acids. The CA1 gene has two promoters, one of which is specifically active in colon epithelia and the other in erythroid cells. We are investigating the factors that regulate CA1 expression from the colon-specific promoter. Colon-specific deoxyribonuclease I hypersensitive sites (DHS) have been mapped close to the colon transcription initiation site (DHS6c) and in the upstream intron (DHS5c). Using electrophoretic mobility-shift assays to search the 650-bp region which contains DHS6c, we have identified sequences that bind a colon-specific factor (COF1) and by deletion analysis we have narrowed down the COF1-binding motif to a 17-bp sequence. A comparison of this motif with a protein-binding motif in the sucrase-isomaltase gene promoter, competition assays, and antibody studies indicate that COF1 is identical to the homeodomain protein Cdx-2. We propose that Cdx-2 plays an important role in the intestine-specific expression of CA1.

Animals↗
PubMed1996

Treatment of esophageal obstruction from mediastinal compressive tumor with covered, self-expanding metallic Z-stents.

BACKGROUND: Mediastinal malignancies may involve the esophagus, leading to esophageal stenosis and dysphagia. Rigid and self-expanding esophageal stents have been used for effective palliation, but their use in extrinsic, compressive lesions is controversial. METHODS: A retrospective review of self-expanding Gianturco-Rösch Z-stents that were successfully placed in 13 patients with malignant esophageal obstruction due to extrinsic lesions. RESULTS: All patients had an improvement in dysphagia of at least two dysphagia grades. The mean dysphagia grade fell from 3.15 to 0.62. Mean survival was 2.2 months. Early (within 48 hours) procedure-related complications occurred in 4 of 13 patients and consisted of minor, transient chest pain that resolved within 6 hours (3 patients) and endoscopic stent dislodgment into the stomach (1 patient). Late complications (> 48 hours) occurred in 2 patients and consisted of a partial proximal stent migration and the development of a benign stricture proximal to the stent. There was no procedural or stent related mortality. CONCLUSIONS: Esophageal obstruction and malignant dysphagia from extrinsic, compressive mediastinal malignancies can be effectively and safely palliated with self-expanding Gianturco- Rösch Z-stents.

Aged↗
PubMed1996

Prior radiation and chemotherapy increase the risk of life-threatening complications after insertion of metallic stents for esophagogastric malignancy.

BACKGROUND: Self-expanding metallic stents (SEMS) are effective in relieving the symptoms of obstructing esophagogastric malignancy. While complications with SEMS have been described, factors influencing such occurrence have not been defined. METHODS: Self-expanding Gianturco-Rosch Z-stents were placed successfully in 59 patients with obstructing esophagogastric malignancies. RESULTS: Early procedure-related complications occurred in 6 patients (10%) and were usually minor. Twenty-three late complications occurred in 22 patients (37.5%). Life-threatening complications occurred in 9 patients (15%), including gastrointestinal bleeding (7), perforation (1), and tracheoesophageal fistula (1) and contributed to all five deaths. Eight of 22 patients with prior radiation and/or chemotherapy (36.4%) had life-threatening complications compared to 1 of 37 (2.5%) without prior therapy (p = 0.001). Stent-related mortality occurred in 5 of 22 (23%) patients with prior therapy compared to none of the 37 without prior therapy (p = 0.005). Multivariate analysis confirmed the association between prior radiation and/or chemotherapy and life-threatening complications (p = 0.012; odds ratio, 32.63) and also an association with female gender (p = 0.032; odds ratio, 13.9). There was no association with tumor location or length, histologic type, age, prestent dysphagia grade, or previous surgical resection. CONCLUSION: Patients with prior radiation and/or chemotherapy have an increased risk of severe complications following placement of SEMS.

Adenocarcinoma↗
PubMed1996

Genetic mapping of the human homologue (T) of mouse T(Brachyury) and a search for allele association between human T and spina bifida.

We describe a genetic analysis of the human homologue (T) of the mouse T (Brachyury) gene; human T was recently cloned in our laboratory. The protein product of the T gene is a transcription factor crucial in vertebrates for the formation of normal mesoderm. T mutant Brachyury mice die in midgestation with severe defects in posterior mesodermal tissues; heterozygous mice are viable but have posterior axial malformations. In addition to its importance in development, T has intrigued geneticists because of its association with the mouse t-haplotype; this haplotype is a variant form of the t-complex and is characterized by transmission ratio distortion, male sterility and recombination suppression. We have identified a common polymorphism of human T by single strand conformation polymorphism (SSCP) and used this in mapping studies and to re-investigate the idea that human T is involved in susceptibility to the multifactorial, neural tube defect, spina bifida. Our mapping data show that human T maps to 6q27 and lies between two other genes of the t-complex, TCP1 and TCP10. These data add to the evidence that in man the genes of the t-complex are split into two main locations on the short and long arms of chromosome 6. We have used an allele association test which is independent of mode of inheritance and penetrance to analyse data from the spina bifida families. Using this test we find evidence for a significant (p = 0.02) association between transmission of the TIVS7-2 allele of the human T gene and spina bifida.

Alleles↗
PubMed1995

A novel cDNA with homology to an RNA polymerase II elongation factor maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11 (Tceb1l).

Few of the auxiliary factors that assist RNA polymerase II in the process of mRNA chain elongation have been identified. We have isolated a novel cDNA, Tceb1l, from mouse and human sources that encodes a 163-amino-acid protein and shows a significant level of identity with a recently identified RNA polymerase II transcription elongation factor, p15. Tceb1l is highly conserved throughout vertebrates and maps to mouse chromosome 11 and to the syntenic region of human chromosome 5q31. Tceb1l shows a restricted pattern of expression in the early mouse embryo, where it is absent from the neurectoderm; later Tceb1l is expressed in the caudal region of the neural tube, followed by widespread expression in many tissues, including the brain and spinal cord. These observations are consistent with Tceb1l being an RNA polymerase II elongation factor and suggest that Tceb1l/p15-like peptides may be a new family of proteins that influence RNA elongation.

Amino Acid Sequence↗