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Biomedical subjects

J H Jackson

Publications and source records attributed to J H Jackson.

At least 55 records · Page 3Linked to original sources

Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke.

The mechanism by which cigarette smoking and asbestos exposure synergistically increase the incidence of lung cancer is unknown. We hypothesized that cigarette smoke and asbestos might synergistically increase DNA damage. To test this hypothesis we exposed isolated bacteriophage PM2 DNA to cigarette smoke and/or asbestos, and assessed DNA strand breaks as an index of DNA damage. Our results supported our hypothesis. 78 +/- 12% of the DNA exposed to both cigarette smoke and asbestos developed strand breaks, while only 9.8 +/- 7.0 or 4.3 +/- 3.3% of the DNA exposed to cigarette smoke or asbestos, respectively, developed strand breaks under the conditions of the experiment. Our experimental evidence suggested that cigarette smoke and asbestos synergistically increased DNA damage by stimulating .OH formation. First, significant amounts of .OH were detected by electron paramagnetic resonance (EPR) in DNA mixtures containing both cigarette smoke and asbestos, but no .OH was detected in mixtures containing cigarette smoke alone or asbestos alone. Second, the .OH scavengers, dimethylsulfoxide (DMSO), mannitol, or Na benzoate decreased both .OH detection by EPR and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. Third, the H2O2 scavenger, catalase, and the iron chelators, 1,10-phenanthroline and desferrithiocin, decreased both .OH detection and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. These latter findings suggest that iron contained in asbestos may catalyze the formation of .OH from H2O2 generated by cigarette smoke. In summary, our study indicates that cigarette smoke and asbestos synergistically increase DNA damage and suggests that this synergism may involve .OH production.

Asbestos↗

Dimethylthiourea decreases acute lung edema in phorbol myristate acetate-treated rabbits.

Treatment with dimethylthiourea (DMTU), a potent O2 metabolite scavenger, prevented neutrophil-mediated acute edema in lungs of rabbits given phorbol myristate acetate (PMA) and in isolated rabbit lungs perfused with neutrophils and PMA. DMTU-treated rabbits given PMA did not increase their lung weight-to-total body weight ratios (5.0 +/- 0.3) or lung lavage albumin concentrations (14 +/- 4.6 mg/dl) in comparison to untreated rabbits given PMA (6.6 +/- 0.5 and 60 +/- 10 mg/dl, respectively). Similarly, DMTU-treated isolated rabbit lungs perfused with neutrophils and PMA did not gain weight (0 g) or increase their lavage albumin concentrations (82 +/- 17 mg/dl) in comparison to untreated lungs perfused with neutrophils and PMA (71 +/- 3.1 g and 1,299 +/- 47 mg/dl, respectively). DMTU did not appear to decrease edema by preventing increases in pulmonary arterial pressures (PAP). First, treatment with DMTU did not decrease initial PAP increases in rabbits given PMA. Second, even though addition of DMTU attenuated PAP increases in isolated lungs perfused with neutrophils and PMA, DMTU-treated isolated lungs did not develop acute edema when subjected to mechanical increases in venous outflow pressures. The mechanism by which DMTU decreases lung edema is unclear but may involve scavenging of toxic O2 metabolites, since DMTU also decreased hydrogen peroxide (H2O2) and hydroxyl radical (OH) concentrations in in vitro mixtures containing neutrophils and PMA.

Acute Disease↗

Genetic analysis of spontaneous resistance to ampicillin in Neisseria gonorrhoeae.

Step-wise intrinsic resistance to ampicillin in Neisseria gonorrhoeae was analyzed genetically by DNA-mediated transformation experiments. A first-step ampicillin-resistant (Ampr1) mutant and a second-step ampicillin-resistant (Ampr2) mutant generated during sequential selection were used in these studies. Each selection step was accompanied by an approximate twofold increase in resistance. Four amp alleles were found to account for full resistance of the Ampr2 phenotype. All four amp alleles lie among a cluster of genes which code for ribosomal functions. This region has the map order rif str fus tet cam. First-step resistance was caused by two amp alleles, ampA2 and ampB1, neither of which independently caused detectable ampicillin resistance. Outcrossing of the ampA2 or the ampB1 mutation resulted in wild-type susceptibility to ampicillin. Mapping studies indicate that ampB1 lies between str and fus, whereas ampA2 lies to the right of cam. Second-step resistance required two mutations, ampC3 and ampD4, in addition to ampB1 and ampA2. Transformation of ampC3 to ampC3+ in an Ampr2 mutant resulted in the Ampr1 phenotype. Both ampC3 and ampD4 showed transformation linkage to rif and str. ampC3 was positioned at a site between rif and str. ampD4 apparently occupied a site, outside of the rif-str region, proximal to rif and distal to str. We postulate the gene order to be ampD rif ampC str ampB fus tet cam ampA.

Alleles↗

Dimethylthiourea consumption reflects H2O2 concentrations and severity of acute lung injury.

Even though dimethylthiourea (DMTU) effectively scavenges O2 metabolites in vitro, it is often unclear if scavenging of O2 metabolites is the mechanism by which DMTU decreases tissue injury in biological models. Since DMTU not only scavenges O2 metabolites but is also consumed in a dose-response manner following reaction with hydrogen peroxide (H2O2) in vitro, we wondered whether DMTU would also be consumed by O2 metabolites in biological systems and if DMTU consumption would then reflect O2 metabolite concentrations and O2 metabolite-mediated injury. Our results supported this possibility. We found that selected nonprotecting concentrations of DMTU were consumed in isolated rat lungs perfused with H2O2 and that the amounts of DMTU consumed reflected both the added amounts of H2O2 and the corresponding degrees of H2O2-induced acute edematous injury. DMTU consumption was relatively specific for reaction with H2O2 occurring in isolated lungs that were injured by H2O2 but not lungs injured by elastase, oleic acid, histamine, or a venous pressure challenge. Our results suggest that measurement of DMTU consumption may be useful for assessing the presence and toxicity of O2 metabolites and the specificity of the protective effects of DMTU in biological systems.

Animals↗

Intraluminal meconium calcification without distal obstruction.

Intraluminal meconium calcification of unknown mechanism is reported in three neonates who did not have distal intestinal obstruction. The condition was benign in all three cases and did not require surgical intervention. This new form of intra-abdominal calcification should be differentiated from other forms that invariably are due to surgical disorders.

Calcinosis↗

Characteristics of the isoelectric focusing procedure: importance of column size, pH, and protein-protein interactions.

Isoelectric focusing (IEF) on 110- and 440-ml columns can result in the loss of enzyme activity. Such losses can be reduced or eliminated by focusing on 20-ml columns. Artifacts which arise during the IEF procedure may result from protein-protein interaction or from the interaction of pH with other sources of artifacts. The reasons for greater loss of activity on large columns and the mechanism of artifacts due to pH and protein-protein interactions are discussed.

Adenylate Kinase↗

Hyperalimented lung diagnosed by perfusion scan.

Injection of radiopharmaceutical through a catheter may be useful in localizing its placement. A case is described in which a central venous line had punctured to superior vena cava, delivering hyperalimentation solution into the right pleural space.

Adult↗

[After care services for psychiatric patients: organizational problems and perspectives exemplified by the service area of Honolulu, Hawaii, USA--initial status, empirical results].

During the past decades much effort has been taken to encourage community - based treatment and service for mental patients, and to reduce the share of the large custodial institutions within mental health care systems. Both in the United States and in W-Germany (FRG) there has been a growing awareness that major inadequacies occur especially with providing community--based out-care for the seriously mentally ill. Much of these inadequacies refer to those released from the mental hospital with such needs as help to structure their everyday lives, adequate housing, nutrition, support for the families and neighborhoods involved, financial support, and further treatment. Part 1 delines the growing awareness of these problems with reference to the expectations of "reformists" both for the U.S. and the F.R.G. The paper then describes empirical data about the care given to patients released from the psychiatric hospital within a 90 days' period in the State of Hawaii, U.S.A. It also gives a structural description of agencies involved in the aftercare services, and relates this both to the empirical findings and reformists' views on aftercare needs.

Aftercare↗

The widened renal fossa sign on liver-spleen scintigraphy and adrenal disease.

A widened renal fossa on the posterior view during liver-spleen scintigraphy using technetium Tc 99m sulfur colloid raises the possibility of renal or extrarenal disease. We encountered four patients with prominent renal fossae on liver-spleen scans. They were subsequently found to have lesions involving the right adrenal gland. Potential adrenal disease should be considered in patients whose liver-spleen scans show widened renal fossae.

Adrenal Gland Diseases↗

Tubular colonic duplication--review of 1876-1981 literature.

Four cases of tubular colonic duplication are reported and 53 more are reviewed from 1876-1981 literature. Eighty percent of these patients had other anomalies, most notably genital and bladder duplications. Females outnumbered the males 37 to 20. Fifty per cent of patients of either sex had some form of fistulous communication. In no one was the anomaly incompatible with life. Based on the anatomy of distal ends of duplicated colon, the patients are divided in five groups, for each of which the incidence and nature of concomitant anomalies are tabulated. Because of their anatomic complexity, most patients with colonic duplication require clinical evaluation by multiple subspecialists. We have also suggested the sequence and extent to which they should be evaluated by radiologists.

Abnormalities, Multiple↗