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Biomedical subjects

D Dawson

Publications and source records attributed to D Dawson.

At least 181 records · Page 10Linked to original sources

Influence of induction of anaesthesia with midazolam on the neuro-endocrine response to surgery.

The effect of midazolam, for induction of anaesthesia, on the glycaemic and adrenocortical responses to lower pelvic surgery in female patients has been studied and compared with a comparable group of patients receiving thiopentone. Although midazolam has been shown to obtund adrenaline and noradrenaline release to electrical or surgical stress in the rat and dog, there was no blunting of the glycaemic response to surgery in man. Plasma cortisol levels in response to surgery and anaesthesia were comparable in the two groups of patients.

Adult↗

A semiquantitative probe for radiation-induced normal tissue damage at the molecular level.

Sheep antibodies to bovine type I collagen were employed in the immunohistochemical detection of type I collagen in lung tissue sections of irradiated LAF1 mice. A video image digitizing system was developed to estimate collagen levels, by assigning a numerical value (0-63) to each of approximately 53,800 picture elements (pixels) in the microscope field, according to the collagen-dependent fluorescence intensity at each locus. For lungs harvested 52 weeks subsequent to graded doses of 60Co gamma radiation between 0 and 10 Gy, a dose-dependent increase in type I collagen was observed in the alveolar walls. A reproducible increase was evident for doses as low as 5 Gy: doses of 7 to 10 Gy elicited type I collagen levels significantly elevated with respect to those of age-matched controls. These results are consistent with a role for type I collagen in the development of radiation-induced pulmonary fibrosis. The assay system developed here will be used to explore the role of connective tissue macromolecules in the development of radiation pneumonitis and fibrosis.

Animals↗

The influence of Yaa on anti-DNA responses of B6-lpr mice.

The anti-DNA autoantibody responses of mice congenic for lpr and the Y-linked autoimmune accelerator (Yaa) genes were studied to evaluate genetic interactions in murine autoimmunity. Male B6-lpr, + mice failed to generate significant anti-DNA responses in comparison to B6-+, + mice. In contrast, B6-lpr mice bearing Yaa (B6-lpr, Yaa) had markedly increased IgG anti-DNA levels in comparison to both B6-+, + and B6-lpr, + mice. To determine whether anti-DNA levels reflected the overall B-cell response to lpr and Yaa, total IgG and IgM levels were also determined. This analysis demonstrated that the increase in IgG anti-DNA produced by mice with the Yaa gene was far greater than the increase in total IgG. Taken together, these results indicate that an impaired anti-DNA response related to one gene-determined mechanism for the development of autoimmunity does not preclude the response to another. Furthermore, it appears that the polyclonal B-cell activation during murine autoimmunity may be associated with the preferential expression of certain autoantibodies.

Age Factors↗

Mobile elements bounded by C4A4 telomeric repeats in Oxytricha fallax.

A novel family of micronuclear elements termed telomere-bearing elements (TBEs) is described. All 1900 family members are eliminated during macronuclear development. We conclude that they are transposons, first because the members are moderately conserved in sequence and probably dispersed in the genome. Second, in two cases, sequence comparison of the termini and flanks of the element with the corresponding empty site indicate that elements cause 3 bp target duplications (AAT) upon insertion; the 3 bp are part of the 5 bp target sequence, AATGA. Lastly, both elements carry 77 or 78 bp inverted terminal repeats. The tip of each inverted terminal repeat is the 17 bp telomere-like sequence 5' C1A4C4A4C4. At least half of the elements have these 17 bp or an extremely similar sequence. One possible pathway for transposition into new micronuclear sites starts in the developing macronucleus with excision to create a free linear form to which telomeres are added, followed by a low frequency of movement to the micronucleus, and insertion into the germ-line micronuclear DNA.

Animals↗

The nucleotide sequence of the Escherichia coli K12 nusB (groNB) gene.

The nusB (groNB) gene product of Escherichia coli plays a pivotal role in allowing bacteriophage lambda N protein to function as an antiterminator of mRNA transcription and in modulating host gene expression. In addition it is essential for bacterial viability since mutations in it result in a cold-sensitivity phenotype for growth. We have previously cloned the nusB gene and shown it to code for a 14,500-Mr protein. Here we present the primary DNA sequence of the nusB gene. From the sequence we deduce that it codes for a slightly basic protein (21 basic as opposed to 20 acidic amino acids) composed of 139 amino acids with a cumulative 15,689-Mr. The predicted N-terminal amino acid sequence as well as the overall amino acid composition agrees well with that of the purified protein.

Amino Acid Sequence↗

Elimination of germ-line tandemly repeated sequences from the somatic genome of the ciliate Oxytricha fallax.

The ciliated protozoa exhibit nuclear dimorphism. The genome of the somatic macronucleus arises from the germ-line genome of the micronucleus following conjugation. We have studied the fates of highly repetitious sequences in this process. Two cloned, tandemly repeated sequences from the micronucleus of Oxytricha fallax were used as probes in hybridizations to micronuclear and macronuclear DNA. The results of these experiments show: (1) the cloned repeats are members of two apparently unrelated repetitious sequence families, which each appear to comprise a few percent of the micronuclear genome, and (2) the amount of either family in the macronuclei from which our DNA was prepared is about 1/15 that found in an equal number of diploid micronuclei. Most, if not all, of the apparent macronuclear copies of these repeats can be accounted for by micronuclear contamination, which strongly suggests that these sequences are eliminated from the macronuclei and have no vegetative function.

Cell Nucleus↗

Telomeric properties of C4A4-homologous sequences in micronuclear DNA of Oxytricha fallax.

The hypotrichous ciliated protozoan Oxytricha fallax has both macronuclei and micronuclei. The short DNA molecules of the macronucleus are terminated with repeats of the octanucleotide C4A4. Micronuclear DNA carries a family of long sequence blocks, which share a consensus restriction map and have homology with the C4A4 repeats. Each block contains a 3 to 6 kb subregion, which is refractory to all restriction enzymes tested and includes the C4A4 homology. We conclude that these refractory sequences are at DNA termini because Sau 3A fragments containing them fail to ligate to form circles, and they are rapidly degraded by Bal 31 nuclease. These terminal C4A4-homologous sequence blocks likely represent micronuclear chromosomal telomeres. Possible relationships between these sequences, internal micronuclear C4A4 repeats, and macronuclear DNA termini are discussed.

Animals↗

The Collaborative Lipid Research Clinics Program Family Study. II. Response rates, representativeness of the sample, and stability of lipid and lipoprotein levels.

The Collaborative Family Study (1975-1978), the third phase of the Lipid Research Clinics Program Population Studies, covers 2405 probands and 15,693 of their relatives from nine North American communities. This sample was examined for participation differences across race, sex, locality, educational level, and reason for selection. The participation rates were somewhat lower for blacks, younger age groups, and subjects with lower educational levels. The probands' reason for selection into the study had little impact on the participation of probands or relatives. Moreover, based on information gathered at earlier examinations on eligible Family Study probands, the cornary risk factor profile appeared to be similar among participants and nonparticipants . The available longitudinal lipid data on probands indicated general consistency in lipid levels within subjects over short periods of time, in cholesterol even more so than in triglycerides. Among age strata, the younger subjects showed the least intrapersonal stability, especially for triglycerides.

Adolescent↗

HLA in two islands of French Polynesia.

The HLA-A, B, and C antigens of 243 individuals from two Polynesian islands, Maiao and Hiva Oa, have been characterized. 328 haplotypes were defined by family analysis. Most frequent antigens were A2, A11, Aw24, A26 , Aw34 ; Bw38, Bw39 , Bw48 , Bw55 , Bw56 , Bw60 ; Cwl, Cw3, and Cw4. Several other antigens were present at low frequency or were present on only one island. New variants of Bw22 and B40 were found. Despite an overall similarity in antigens of the two islands, the combination of HLA-A, B and C antigens on the haplotype were distinctive. Of 328 total haplotypes identified, 65 were unique. Thirteen of these (20%) were present on both islands. Twenty-eight (43%) were unique to Hiva Oa and 24 (37%) were unique to Maiao . Significant, positive linkage disequilibrium values (delta) for HLA-A, B and HLA-B, C antigens were also different for the two populations.

Alleles↗

Rare internal C4A4 repeats in the micronuclear genome of Oxytricha fallax.

Approximately 20,000 different short, linear, macronuclear DNA molecules are derived from micronuclear sequences of Oxytricha fallax after conjugation. These macronuclear DNAs are terminated at both ends by 20 base pairs of the sequence 5'-dC4A4-3'. Sequences homologous to this repeat (C4A4+) are also abundant in the micronuclear chromosomes, but most reside at their telomeres. Here we show that nontelomeric C4A4 clusters of 20 base pairs or longer exist in only a few hundred copies per micronuclear genome. This demonstrates that nearly none of the 20,000 sequence blocks of micronuclear DNA destined to be macronuclear DNA molecules can be flanked by full-length (20-base pair) C4A4 clusters, and therefore C4A4 repeats must be added to most, if not all, macronuclear telomeres during macronuclear development. Six internal micronuclear C4A4+ loci were cloned, and their structural relationships with macronuclear and micronuclear sequences were examined. The possible origins and functions of these rare, micronuclear internal C4A4 loci are discussed.

Animals↗

Modified-self-induced modulation of the immune response to herpes simplex virus: effect on antibody formation, cytotoxic T lymphocyte induction, and survival.

C3H/HeJ mice were injected i.v. with soluble herpes simplex virus (HSV) envelope antigens coupled to syngeneic splenocytes 7 days before challenge i.p. with either soluble HSV antigens in complete Freund's adjuvant or infectious HSV. Fourteen days post challenge, and anti-HSV antibody hyporesponsiveness was observed in the HSV modified-self pretreated animals that was 50% or less than the control response. Both forms of HSV challenge were equally effective. This unresponsiveness was specific for HSV when compared with a concomitant response to chicken red blood cell (CRBC) challenge. Challenge with infectious HSV afforded us the opportunity to investigate the effect of HSV modified-self pretreatment on the induction of HSV-specific cytotoxic T lymphocytes (CTL). In vitro restimulation of in vivo-primed splenocytes with infectious HSV generated HSV-specific CTL. The degree of HSV-specific CTL response was found to be variable in animals that received the HSV modified-self pretreatment with respect to control animals. Survival was significantly greater in HSV modified-self pretreated mice after infectious HSV challenge than in control animals.

Animals↗

Intracerebral hemorrhage and oral amphetamine.

Four patients suffered intracerebral hemorrhages following the oral or nasal use of amphetamine or related compounds. Two of these patients had abnormal-appearing cerebral blood vessels on angiography. Review of previously reported cases showed that intracerebral hemorrhage may occur in patients using the drug for the first time and for nonrecreational purposes.

Administration, Intranasal↗

Lack of association between Alzheimer's disease and histocompatibility antigens.

The present report describes the distribution of histocompatibility antigens in 52 patients with Alzheimer's disease. No significant associations were observed between this illness and particular HLA types before or after statistical correction for multiple comparisons. These findings are discussed in terms of the difficulties inherent in the clinical diagnosis of Alzheimer's disease and with regard to the choice of suitable control populations.

Aged↗

Chronic psychiatric patients in the community.

A feasibility study is presented which describes a cohort of 102 chronic psychiatric patients. The cases were selected on the criterion of four or more new admissions to psychiatric services in the Hamilton-Wentworth region during the year 1977. The group was predominately in the age 20-39 year range and both sexes were represented about equally. The diagnostic labels were personality disorder, schizophrenia, depression and alcoholism in descending order of frequency. The large majority were socially isolated and had contact with social agencies and the police. Seven deaths occurred in the cohort during the year of study.

Adult↗

Micronuclear DNA sequences of Oxytricha fallax homologous to the macronuclear inverted terminal repeat.

The macronucleus of the protozoan Oxytricha fallax is generated from a micronucleus following conjugation. While the micronucleus contains high molecular weight DNA, the macronucleus contains only short linear DNA molecules which all end in the same 20 bp inverted terminal repeat (Ma-ITR). The Ma-ITR was radioactively labeled and purified for use as a probe in hybridizations to micronuclear and macronuclear DNA. Sequences homologous to the Ma-ITR were detected in micronuclear DNA. The copy number of the repeat in the micronuclear genome is approximately that required to encode the macronuclear DNA termini. The micronuclear copies are found embedded in repeated long sequence blocks.

Animals↗