Biomedical subjects
Publications and source records attributed to D Crawford.
The results of percutaneous endoscopic gastrostomy in 25 patients who required enteral alimentation when feeding by mouth was not possible is reported. The procedure was successful on 30 occasions, with a low incidence of major complications. Endoscopic gastrostomy is a simple, less expensive alternative to surgical gastrostomy with a lower morbidity and mortality.
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Four human subjects recorded their wake-up and to-sleep times for one year each. The data were plotted to display individual circadian rhythms and the data were analyzed statistically. First, individuals had characteristic patterns in which visible changes in the patterns were observed mainly when time zones were changed because of travel. Second, the months with the latest wake-up and latest to-sleep times concentrated around the winter solstice; the months with the earliest wake-up and earliest to-sleep times concentrated around the fall equinox. Third, new moon versus full moon days were not different. Fourth, one-hour changes between standard and daylight savings time in the USA were reflected by near one-hour changes in two subjects, but not in a third. Fifth, weekend delays in wake-up time (0.8-1.6 hours), weekend delays in to-sleep time (0.1-0.5 hours), and shorter weekend awake time (0.8-1.3 hours) were observed. Sixth, throughout the year, wake-up times were close to the time of sunrise, but to-sleep times were several hours past sunset.
Ribonuclease inhibitor (RNH) is a protein that binds tightly to ribonucleases in cells and may be essential in the control of mRNA degradation and gene expression. The human RNH gene has been regionally localized to chromosome band 11p15 by in situ hybridization. A human placental cDNA was used to construct a 600-bp probe, which was then radiolabeled with tritium for in situ hybridization to human metaphase chromosomes. Localization of the RNH gene to 11p15, and possibly to 11p15.5, adds to a large number of genes assigned to this band, including 10 structural genes. This chromosomal region also represents an evolutionarily conserved syntenic group in the owl monkey, mouse, rat, and cow. Thus, regional assignment of RNH could facilitate the understanding of this gene and its association with ribonucleases, and perhaps extend a conserved syntenic region in mammalian genomes.
A randomized prospective controlled trial was carried out comparing the value of immediate ultrasound examination with conventional management (selective ultrasound examination) in patients with acute abdominal symptoms. Immediate ultrasound led to earlier establishment of a final diagnosis but did not shorten the duration of in-patient care. Selective ultrasound improved diagnostic yield compared to immediate ultrasound and is believed to be the better option. It implies that a prompt but selective ultrasound service should be available for in-patients in the acute specialties.
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We report the sequence of the cDNAs representing five independent splice forms of human placental RNase inhibitor (RI) mRNA. RI mRNAs differ principally in the 5'-untranslated region, which may include or lack a 68-nucleotide (nt) exon inserted at a splice site located only 20 nt upstream from the initiator AUG. At least three other exons may also abut the same splice site. This unusual and variable feature of the mRNA would suggest that secondary structure in the region of the start codon may differ among RI messages. A single copy of the RI gene exists in the human genome.
Besides being toxic, oxidants can induce pathophysiological effects in mammalian cells. For example they can stimulate rather than inhibit cell growth. Since oxidants are ubiquitous they may represent 'natural' tumour promoters. Our work with xanthine/xanthine-oxidase as an extracellular source of active oxygen (AO) and promotable (clone 41) and non-promotable (clone 30) mouse epidermal cells JB6 allows insights into the mechanism of action of oxidant promoters. We found that AO stimulated the growth only of promotable clone 41 after an initial period of moderate inhibition while it was strongly cytostatic for non-promotable clone 30. Active oxygen induced larger amounts of DNA-strand breaks and poly ADP-ribosylation of chromosomal proteins in non-promotable cells. In addition, AO was capable of inducing the growth- and differentiation-related proto-oncogenes c-fos and c-myc in promotable and non-promotable JB6 cells. We speculate that these genes can exert their functions only in the promotable clone 41 because the general cytostatic effects of AO are moderate. A possible explanation for the differences between these 2 clones was discovered when we compared the constitutive activities, protein concentrations and mRNA levels for the antioxidant enzymes catalase (CAT), Cu,Zn-superoxide dismutase (SOD) and glutathione-peroxidase (GPx). We found that CAT and SOD (but not GPx) levels were 2-3-fold higher in the promotable clone 41. We propose that promotable cells possess a superior antioxidant defence which protects them from excessive cytostatic effects of AO.
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Hardwood dust can cause dermatitis, respiratory disease, allergies and nasal cancer in humans. A major concern with animal hardwood bedding is its dust content and its possible effects on animals and animal technicians. Previous reports on the quality control of rodent bedding did not specify sample size or shake time for measuring bedding particle size and dust content. These variables could alter particle size analyses. In an effort to more accurately characterize bedding particle size and dust content, 50g and 100g samples of hardwood bedding were shaken for 0.5, 1, 2, 3, 4, or 5 minutes in a portable sieve shaker containing U.S. standard sieves (Nos. 8, 20, 30 and 50) to determine optimum sample size and shake time. Significant differences (P less than 0.05 or greater) were observed in the percent of bedding retained on a No. 8 sieve when 50g and 100g samples were taken for 30 seconds or for 1 minute. Samples shaken for 2 or more minutes did not show any statistical differences in the percent of bedding which was retained on or passed through the different sieves. Major differences occurred in the percent of bedding which was retained or passed through the different sieves, when the shake time was varied from 0.5 to 5 minutes. These results indicated that 0.5 or 1 minute was definitely not enough time to accurately measure bedding particle size and dust content and that the sample size and shake time must be consistent in order to accurately compare the particle size and dust content of different shipments of bedding or to compare bedding from different vendors.(ABSTRACT TRUNCATED AT 250 WORDS)
mRNA molecules encoding a number of inflammatory cytokines, as well as certain proto-oncogenes, contain a conserved UA-exclusive sequence in the 3' untranslated region that confers message instability in vivo. This sequence may comprise a critical regulatory element, governing the level of these mRNA molecules, and determining the efficiency with which they are translated. Through the use of a double-label RNAse assay, we have determined that lysates prepared from mouse macrophages selectively degrade mRNA molecules containing the 3' untranslated UA sequence found in the mRNA encoding human cachectin/TNF. The degree of instability is dependent upon the number of copies of inserted UA sequence present in the target mRNA molecule (a Xenopus beta-globin mRNA). mRNAs containing randomly generated UA sequences are more labile than unmodified globin mRNA, but less susceptible to degradation than mRNAs containing the authentic cachectin-derived sequence. mRNA molecules containing synthetic UG-exclusive sequences are normally stable or protected in vitro. The destruction of UA-containing mRNA is inhibited by random adenylate/uridilate copolymers, but not by guanylate/uridilate copolymers. Boiling or proteinase K treatment destroys the selective nucleolytic activity of macrophage lysates. We propose that the nuclease measured here may serve to regulate cellular levels of mRNA molecules encoding cachectin, other inflammatory cytokines, and certain proto-oncogene products.
In light of recent studies implicating low catalase activities in the pathogenesis of the cancer-prone disease xeroderma pigmentosum (XP) we have measured catalase activity, protein levels, and mRNA concentrations in six XP fibroblast strains and three normal controls. Only one XP strain of complementation group A (XP1223) possessed significantly lower catalase by all three criteria. The other five XP strains (two XP variants, two strains of complementation group D, and one strain of complementation group C) possessed catalase levels which fell into the range of the interindividual variations of normal controls. We further assessed the total enzymatic antioxidant defense status by measuring the levels of copper, zinc, and manganese superoxide dismutase and glutathione peroxidase. None of these enzymes showed significant deviations from controls in XP cells. Our results do not support the notion that a deficient enzymatic antioxidant defense facilitates the establishment of a prooxidant state in XP upon exposure to near-UV. However, they do not argue against the participation of active oxygen in near-UV-induced carcinogenesis in XP.
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The purpose of this study was to identify the toxicologic effects produced by methyl carbamate in F344 rats and B6C3F1 mice. Administration of methyl carbamate by gavage five times a week for 13 weeks to male (50, 100, 200, 400, or 800 mg/kg) and female (62.5, 125, 250, 500, or 1000 mg/kg) rats resulted in dose-related lesions in the liver characterized by proliferative changes in hepatocytes consisting of foci of cellular alteration and frequent mitoses with atypical forms. Toxic alterations consisted of focal hepatocellular necrosis, pigmentation of Kupffer's cells, and the presence of basophilic inclusions resembling nucleoli in the cytoplasm of hepatocytes. Other toxic effects observed in rats were weight loss, testicular hypoplasia, bone marrow hyperplasia, and excessive pigmentation of the spleen. The survival of male and female rats was reduced following administration of the highest dose of methyl carbamate. In contrast to these findings, administration of the chemical to male (93.75, 187.5, 375, 750, or 1500 mg/kg) and female (125, 250, 500, 1000, or 2000 mg/kg) mice five times a week for 13 weeks resulted only in weight loss and inflammatory changes of the liver. The proliferative nature of the hepatic lesions observed in rats suggests that the compound is potentially hepatocarcinogenic.