Biomedical subjects
Publications and source records attributed to C Moran.
A highly polymorphic (AT)nTm microsatellite located in a PRE1 SINE element in the 3'UTR of the soluble angiotensin binding protein (ABP1) gene has enabled the linkage mapping on the PiGMaP reference families of the ABP1 gene to porcine chromosome 16, to a region homologous with the short arm of human chromosome 5.
The PiGMaP and USDA porcine linkage maps for chromosomes 2 and 5 have been aligned by typing five USDA microsatellite markers from chromosomes 2 and 4 from chromosome 5 on the PiGMaP reference families. The markers in the two maps can be successfully aligned except for Sw395 on chromosome 2, which is the end-most marker in the USDA map 22 cM remote from the next marker, but which maps to a more central location and in the same position as Sw776 in the PiGMaP families. The mapping of four additional chromosome 5 markers has enabled amalgamation of the two previously separate PiGMaP linkage groups assigned to chromosome 5 and has more than doubled the length of its map. The USDA map of chromosome 5 is considerably shorter than the revised PiGMaP version, particularly between DAGK and Sw1071, where the corresponding lengths are 9 cM versus 33 cM.
Swine-specific sequence tagged (microsatellite) sites, STS and STMS, were assigned chromosomally by polymerase chain reaction analysis of a somatic cell hybrid panel. This study confirms the localization from genetic mapping of seven anonymous microsatellites and the genes ANPEP, ATP2, CGA, DAGK, FSHB, IFNG, IGF1, IL1B and SPP1. New assignment for the gene BNP1 to chromosome 6 is reported. The confirmed and the new assignments extend the information of the previously established linkage maps and provide framework loci on which to order additional informative markers.
The effect of infection on hepatic uptake and disposal of a continuous (180-min) intravenous glucose infusion (8 mg.kg-1.min-1) was examined in conscious, 54-h-fasted, chronically catheterized dogs. Thirty-six hours before a study, either infection was induced by implantation of an Escherichia coli-containing (INF; 2 x 10(9) organisms/kg body wt; n = 6) fibrinogen clot, or a sterile (SH; n = 6) clot was implanted into the peritoneal cavity. Hepatic glucose metabolism was assessed using tracer ([3-3H]glucose and [U-14C]glucose) and arteriovenous difference techniques. Infection increased the basal rate of glucose appearance (45%); glucose levels were not altered. In response to glucose infusion, average blood glucose levels increased to similar levels (140 +/- 9 vs. 147 +/- 11 mg/dl in INF and SH, respectively), whereas arterial insulin levels were higher in the infected group during the last hour of the glucose infusion (77 +/- 10 vs. 41 +/- 5 microU/ml in INF vs. SH). Infection impaired net hepatic glucose uptake (0.6 +/- 0.5 and 2.7 +/- 0.7 mg.kg-1.min-1 in INF and SH; P < 0.05). The liver remained a persistent lactate consumer (4.1 +/- 1.8 mumol.kg-1.min-1), whereas the sham group became a net producer of lactate (-3.8 +/- 1.3 mumol.kg-1.min-1). Infection decreased net hepatic glycogen deposition by 53%. In conclusion, infection impairs net hepatic glucose uptake and glycogen deposition despite an exaggerated increase in insulin levels.
The hairless mutation of mice was caused by insertion of a murine leukemia virus. Starting with sequences flanking the provirus, a series of overlapping clones surrounding the viral integration site were obtained. By using a combination of sequencing, PCR, and exon-trapping techniques, the hairless gene was identified. It encodes a predicted protein of 1182 amino acids, including a potential zinc-finger domain. The expression patterns of the gene closely reflect the phenotype of animals carrying the hairless mutation.
Nineteen cosmids have been mapped to pig chromosomes by fluorescence in situ hybridization. Two kinds of cosmid clones were isolated as potential physical and genetic markers for the pig genome. Anonymous cosmids were obtained by screening a commercial cosmid library and were localized to Chromosomes (Chrs) 1, 2, 6, 7, 8, 10, 11, 12, 13, and 14. Some of these cosmids were found to reveal RFLP type DNA polymorphism. Microsatellite-containing cosmid clones were isolated by screening a pig cosmid library with a (CA)10 probe and were regionally mapped to Chrs 2, 6, 7, 13, and 14. Ten of the 19 chromosomes in the pig were labeled with these probes. Two-color fluorescence in situ hybridization was used to increase the efficiency of the cosmid localizations.
The present study examined the association between volunteer emergency work experience, personality, and reactions to a past traumatic incident. Participants from randomly selected State Emergency Services and Volunteer Bushfire Brigade Units in New South Wales (Australia) completed four questionnaires. The data did not support the idea that emergency workers are hardier than most, or have particular coping styles. Length of volunteer emergency service was associated with both severity and length of reaction to a past traumatic incident. The number of emergency callouts and current general symptom severity were associated with severity of reaction to a past incident.
The effect of acute glucagon removal on glucose metabolism following long-term (70-hour) stress hormone infusion (day 3) was investigated in 20-hour-fasted conscious dogs. Stress hormone infusion increased arterial plasma glucagon, cortisol, epinephrine, and norepinephrine (approximately fivefold), as well as arterial plasma glucose (delta 82 +/- 16 mg/dL) and insulin (delta 26 +/- 5 microU/mL). After assessing basal glucose metabolism on day 3, the long-term glucagon infusion was discontinued (n = 6), and the remaining hormones were infused for an additional 180 minutes. Constant glycemia was maintained by an exogenous glucose infusion. In five dogs, the stress hormone infusion containing glucagon was continued for 180 minutes. Glucose production and gluconeogenesis were assessed using tracer and arteriovenous-difference techniques. Acute removal of glucagon decreased arterial plasma glucagon from 220 +/- 24 to 32 +/- 4 pg/mL and net hepatic glucose output (delta 1.6 +/- 0.3 mg/kg/min). Net hepatic handling of lactate, alanine, and glycerol was not altered. The efficiency of gluconeogenesis, on the other hand, was decreased by 40%. Liver biopsies taken following discontinuation of glucagon indicated that both 3H- and 14C-glucose accumulated in glycogen. The calculated rate of plasma glucose and gluconeogenic precursor diversion to glycogen increased by fivefold and fourfold, respectively. The increased gluconeogenic precursor diversion to glycogen accounted for 58% of the decrease in the efficiency of gluconeogenesis. In conclusion, acute removal of glucagon during stress hormone infusion decreased net hepatic glycogenolysis in the face of prevailing hyperglycemia and hyperinsulinemia, while having minimal effects on the gluconeogenic process per se.
Excision repair of pyrimidine dimers was examined at the genome overall in three strains of hairless (hr/hr) and congenic wild-type mice, as well as in the expressed H-ras gene in hairless mice. The assay used a pyrimidine dimer-specific endonuclease from Micrococcus luteus and alkaline agarose gel electrophoresis. From 0 to 25% of endonuclease-sensitive sites were removed at the genome level in either hairy or hairless mice but about 50% were removed in the H-ras gene in hairless mice by 24 h after exposure to 5.4 J/cm2 UV (290-400 nm) irradiation. No differences were observed in the repair capacity between hairy and hairless mice, thus eliminating defective DNA repair as the explanation for the greater susceptibility to UV carcinogenesis in hairless mice.
The impact of the absence of an increase in glucagon on the metabolic response to stress hormone infusion was investigated. We studied 11 conscious dogs fasted for 20 h before (day 0) and after (day 3) a 70-h stress hormone infusion containing glucagon, cortisol, epinephrine, and norepinephrine that increased their respective levels approximately sixfold. Five additional dogs were studied on day 0 and were then infused with the same stress hormone infusion but without glucagon. Glucose production and gluconeogenesis were assessed using tracer and arteriovenous difference techniques. The absence of an increase in glucagon during stress hormone infusion attenuated the increase in arterial plasma glucose concentration (delta 81 +/- 16 vs. delta 28 +/- 6 mg/dl) but did not significantly alter the increase in the rate of glucose appearance (delta 1.7 +/- 0.3 vs. delta 1.1 +/- 0.4 mg.kg-1.min-1). However, it eliminated the increase in net hepatic glucose output (delta 0.7 +/- 0.3 vs. delta 0.0 +/- 0.4 mg.kg-1.min-1) primarily because of an increase in hepatic glucose uptake. In addition, the stress hormone-induced increase in net hepatic gluconeogenic precursor uptake (delta 0.7 +/- 0.3 vs. delta 0.2 +/- 0.1 mg of glucose.kg-1.min-1) and the efficiency of gluconeogenesis (delta 0.19 +/- 0.07 vs. delta 0.01 +/- 0.05) were attenuated. Glucagon thus plays a pivotal role in the metabolic response to stress hormone infusion by sustaining gluconeogenesis through a stimulatory effect on the hepatic gluconeogenic precursor uptake as well as on the efficiency of gluconeogenesis within the liver.
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Twenty-four infants, 1 to 18 months-old, who were referred to four centers for suspected gastroesophageal reflux and whose esophageal pH after a standard formula meal given at 9 to 10 am (Ho-day 1) fulfilled the criterion of being < 4 for more than 5% of the time between H1 and H6, entered a double-blind placebo-controlled dose-response trial of metoclopramide (M). Twenty-four hours later (day 2), patients were randomly assigned to receive either placebo or a single 0.1, 0.2, or 0.4 mg/kg dose of metoclopramide, 30 min before the formula meal (n = 6/group) and the procedure was repeated. Metoclopramide plasma concentration was measured 1 h after dosing (C1h). On day 1, the time during which the esophageal pH was < 4 (time pH < 4), and five other parameters, were not significantly different in the treatment groups. On day 2, time pH < 4 (m(SD)) decreased from 33(13) to 30(33), 39(27), to 36(47), 42(15) to 18(13) and 48(25) to 31(46) min in the placebo, 0.1, 0.2, and 0.4 mg/kg metoclopramide groups, respectively. Possibly due to the large interindividual variability, no significant differences in parameters were observed between the different groups. None of the parameters correlated with the metoclopramide dose. Time pH < 4 expressed as the difference between day 1 and day 2, relative to day 1, decreased significantly as a function of C1h. No side effects were observed. A similar study should be performed after repeated dosing regimen.
The P-M system of transposition in Drosophila melanogaster is a powerful mutator for many visible and lethal loci. Experiments using crosses between unrelated P and M stocks to assess the importance of transposition-mediated mutations affecting quantitative loci and response to selection have yielded unrepeatable or ambiguous results. In a different approach, we have used a P stock produced by microinjection of the ry506 M stock. Selection responses were compared between transposition lines that were initiated by crossing M strain females with males from the "co-isogenic" P strain, and ry506 M control lines. Unlike previous attempts to quantify the effects of P element transposition, there is no possibility of P transposition in the controls. During 10 generations of selection for the quantitative trait abdominal bristle number, none of the four control lines showed any response to selection, indicative of isogenicity for those loci affecting abdominal bristle number. In contrast, three of the four transposition lines showed substantial response, with regression of cumulative response on cumulative selection differential ranging from 15% to 25%. Transposition of P elements has produced new additive genetic variance at a rate which is more than 30 times greater than the rate expected from spontaneous mutation.
An A in equilibrium with G transition in exon III is known to differentiate alleles A and B of the cattle beta-lactoglobulin (BLG) gene. A BLG exon III fragment containing the transition site was amplified by the polymerase chain reaction. Temperature gradient gel electrophoresis (TGGE) was then used to detect this transition and hence to genotype cattle: the AT base-pair in allele A was readily distinguished from the GC base-pair of allele B. TGGE can be used to detect any single base-pair substitution, and thus is a powerful method of detecting genetic variability.
This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.
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Adenocarcinomas of or in lung that clinically and pathologically mimic diffuse pleural mesotheliomas are rare. We reviewed selected clinical and pathologic features of 15 autopsy/surgical cases previously reported in the medical literature and of 15 additional cases from the files of the Armed Forces Institute of Pathology (AFIP). Ninety percent of the patients were men. The median age was 61 years. Sixty-three percent of the patients smoked, 17% of them had possible or definite occupational exposure to asbestos, and one patient had microscopically proven asbestosis. Most patients had chest pain, shortness of breath, or cough, and had unilateral pleural effusion in the chest x-ray. At thoracotomy or at autopsy, numerous nodules, plaques, or a continuous rind of tumor was present over the pleural surface. Microscopically, the tumors showed simplified glands, nests, cords, papillary, tubulopapillary or biphasic patterns of growth. The neoplasms contained mucin that stained with diastase-predigested periodic acid-Schiff (PAS), mucicarmine, and alcian blue (with or without hyaluronidase predigestion). All patients died with/of tumor, with a mean survival of 4.7 months for those reported in the medical literature and of 7 months for those in the AFIP files. These adenocarcinomas therefore mimic pleural mesothelioma not only in their clinical and gross and microscopic appearance, but also in their prognosis.