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Biomedical subjects

C Law

Publications and source records attributed to C Law.

At least 55 records · Page 3Linked to original sources

Reduction of radiation cytotoxicity by human apurinic endonuclease in a radiation-sensitive Escherichia coli mutant.

Ionizing radiation produces a variety of DNA damage through active oxygen species such as the superoxide radical (O2.-), the hydroxyl radical (OH.), and hydrogen peroxide (H2O2). The removal of alkylation-induced apurinic (AP) sites and 3'-blocking deoxyribose fragments by exonuclease III (xth) and endonuclease IV (nfo) has been well demonstrated in E. coli. Very little information on the repair of radiation-induced DNA damage by human apurinic endonuclease is available. We examined the biological roles of the human AP endonuclease in the repair of radiation-induced DNA damage. An expression vector was constructed with human APE cDNA and transformed into radiation-sensitive E. coli mutants (xth- and nfo-). The radiation cytotoxicity was assayed by cell survival curves. Expression of human AP endonuclease in E. coli confirmed that AP endonuclease could complement exonuclease III functionally to diminish radiation cytotoxicity. In contrast, AP endonuclease was not able to increase resistance to H2O2, owing to a poor 3'-termini repair. We also tested whether AP endonuclease is a limiting factor for radiation cytotoxicity by using a plasmid nicking assay. Cell extracts from mutant cells with or without AP endonuclease expression were added to irradiated supercoiled plasmid DNA. The inability to convert supercoiled plasmid DNA to relaxed or linear forms suggested that there were large accumulations of AP sites in the mutant cell extracts. The AP endonuclease activities estimated from the plasmid nicking assays are 20-fold lower in the cell extracts of AP endonuclease-deficient mutant than in AP endonuclease-expressing cells. Therefore, AP endonuclease is a limiting step of base excision repair for the radiation-sensitive E. coli mutant, BW528. Our results conclude that AP endonuclease is responsible for the removal of AP sites from gamma-radiation-induced base damage in E. coli.

DNA Repair↗

Sexually transmitted diseases and enteric infections in the male homosexual population.

There are certain special considerations in the management of sexually transmitted diseases (STDs) in homosexual men, with the impact of human immunodeficiency virus (HIV) infection on the presentation, diagnosis, and management of certain STDs just becoming apparent recently. Rectal and pharyngeal gonorrhea are usually asymptomatic and also more difficult to treat. The serological diagnosis of syphillis may be unreliable in acquired immunodeficiency syndrome (AIDS) patients, and HIV-seropositive homosexual men may be at risk of accelerated progression to neurosyphilis, despite treatment with benzathine penicillin. Chlamydia trachomatis is infrequently detected in patients with proctitis so therapy should be directed only at culture-positive cases. Herpes simplex is usually severe and persistent in immunosuppressed patients and may be further complicated by the development of acyclovir-resistance. Concurrent HIV infection may be associated with increased infectivity of homosexual chronic hepatitis B carriers, but milder hepatic injury and reduced efficacy of hepatitis B vaccines and immodulatory or antiviral agents. Although there is some concern regarding the possibility of increased risk of anal cancer in homosexual men, conservative management of human papilloma-virus-associated conditions is advised. The carriage of Entamoeba histolytica in this group is rarely associated with any deleterious effects and treatment should be directed only at symptomatic patients in whom other enteric pathogens have been excluded.

Homosexuality↗

Trichinosis in the Canadian Arctic: report of five outbreaks and a new clinical syndrome.

Trichinosis is a serious but understudied medical problem in the Arctic. Forty-nine consecutive cases in the Inuit population of northeastern Canada are described. Most developed the disease after eating raw walrus, and the clinical presentation of most of these cases differed from previously reported descriptions of classic trichinosis due to Trichinella spiralis. Unlike the classic syndrome of a brief period of diarrhea followed by fever, myalgia, muscle weakness, and edema, the most common presentation in these cases was a prolonged diarrhea without fever and with brief muscle symptoms. High peripheral eosinophilia, high Trichinella antibody serotiters, and little direct or indirect evidence of muscle invasion in many of those with the chronic diarrheal presentation suggest a new clinical syndrome due to a different species of Trichinella seen in the Arctic or to reinfection with Trichinella.

Animals↗

Gastrointestinal viral infections in homosexual men who were symptomatic and seropositive for human immunodeficiency virus.

Gastrointestinal viruses, predominantly rotaviruses and adenoviruses, were detected by enzyme-linked immunosorbent assay, electron microscopy, or cell culture in greater than 50% of two groups of homosexual men with symptomatic human immunodeficiency virus (HIV) infection, who did (54%) or did not (50%) have diarrhea. Lower detection rates were observed in HIV-seronegative (15%) and asymptomatic HIV-seropositive (16%) men. In the patients with diarrhea, 95% of the isolates of virus were found in the most immunosuppressed patients, those patients with AIDS-related complex or opportunistic infections associated with AIDS. High excretion rates of these viruses are probably associated with both anal-oral transmission and immunosuppression. These viruses apparently cause acute episodes or relapses of diarrhea in some patients but may be co-pathogens or noncontributory to chronic diarrhea in others.

AIDS-Related Complex↗

Characteristics influencing informed consent on a congenital malformations registry.

Maryland law requires that all babies born with "sentinel birth defects" be reported to the State Department of Health, but mothers may deny consent for further contact. Consent was not strongly related to maternal age, race, or self-reported data on exposures, smoking, and drugs but was much less likely if the infant was dead. Selection bias in congenital malformations research may lead to underrepresentation of lethal defects, but self-reported data appear to be unbiased.

Adult↗

Arctic trichinosis presenting as prolonged diarrhea.

We describe an outbreak of trichinosis after the consumption of raw walrus meat in 10 Inuit inhabitants of a northern community. During the presentation of the illness, diarrhea was found in all subjects and was the dominant symptom in 8 of the 10 cases. Myalgia (60%) and muscle weakness (50%) were much less prominent complaints. The diarrhea was characteristically prolonged, lasting up to 14 wk (average 5.8 wk), as opposed to comparatively short episodes of myalgia (average 5.4 days) and muscle weakness (average 4.5 days). Prolonged diarrhea with little or no muscle symptomatology in an epidemic form represents a previously unrecognized clinical presentation of trichinosis. It remains to be determined whether this new clinical presentation is related to variant biological behavior of arctic Trichinella, to previous exposure to the parasite, or to other factors.

Adult↗

Three cases of schistosomiasis mekongi from northern Laos.

Three cases of intestinal schistosomiasis acquired in northern Laos are reported. All three patients swam regularly for many years in the Mekong River near the cities of Vientiane and Luang Prabang. Morphology of the eggs found on rectal biopsy indicated infection with Schistosoma mekongi. One patient had severe portal hypertension with bleeding esophageal varices requiring a splenorenal shunt; studies of her liver biopsy showed S. mekongi eggs and periportal fibrosis. A second patient had abnormal liver function tests, and a third patient was asymptomatic. In two of the three cases, no schistosome eggs were found on stool examination, and the diagnosis was made by rectal biopsy. The implications of this new focus of infection are discussed.

Adult↗

Giardia lamblia infections in Mongolian gerbils: an animal model.

Mongolian gerbils were susceptible to infection with Giardia lamblia cysts from patients. Inoculation of gerbils with 5 x 10(3) cysts each resulted in an infection characterized by the intermittent release of cysts for up to 39 days. The mean number of cysts released per gerbil in a 2-hr period was 8.8 x 10(2) (range, 0-5 x 10(3)). The highest number of trophozoites found in the intestine was on day 15 after infection, when the mean number of trophozoites per gerbil was 6.36 x 10(6). Administration of cysts from different patients to gerbils resulted in a similar pattern of cyst release during the first 30 days of infection. Mongolian gerbils were also susceptible to infection with cultured trophozoites (Portland 1 strain). The pattern of cyst release and the number of trophozoites in the intestines of orally and duodenally inoculated gerbils were similar. Gerbils were protected against reinfection with G. lamblia for up to eight months after primary infection.

Animals↗

Analytical survey of N-nitroso contaminants in pesticide products.

1. Levels of N-nitroso dialkylamines in dinitroaniline derivatives were high (up to 153 mg/kg) in the past, but have been decreased considerably in current production, due to process changes. 2. Butralin and pendimethalin contain significant amounts of N-nitroso parent compounds. 3. Most dimethylamine salts of phenoxyalkanoic acids presently contain low or non-detectable levels of NDMA. 4. Quaternary ammonium compounds contain NDMA levels up to 16.8 mg/kg. 5. Two morpholine derivatives appear to contain N-nitrosomorpholine. 6. The triethanolamine salt of dinoseb contains over 200 mg/kg N-nitrosodiethanolamine. 7. A large number of amides, carbamates, organophosphates, triazines, urea derivatives and miscellaneous nitrogen-containing pesticides do not contain N-nitrosamines above 1 mg/kg. 8. Most N-nitroso contaminants in pesticides can be avoided by simple process changes and the elimination of nitrite salts in the formulation.

Chromatography, Gas↗

Dogs and intestinal parasites: a public health problem.

The stools of 239 stray dogs were examined for intestinal parasites. Of the helminths found, Toxocara canis (43.5%), tapeworms (25.5%), Ascaris species (21.3%) and hookworms (12.5%) were the commonest. Of the protozoans found, Isospora species and Entamoeba coli were the most prevalent. An unusual feature of the present study was the finding of Ascaris species. The importance of the high prevalence of intestinal parasites in dogs, the close contact of humans with dogs' excreta and the possible role of this environmental pollution in the spread of human disease are discussed.

Animals↗

Acute arterial occlusions of the small vessels of the hand and forearm: treatment with regional urokinase therapy.

PURPOSE: Arterial occlusions of the small vessels of the forearm and hand may have the same consequences as arterial occlusions in the distal lower extremity. There is limited reported experience with the regional thrombolytic therapy in this setting. The authors reviewed their experience with thrombolytic therapy in acute and subacute arterial occlusions of the distal upper extremity to further clarify its role. MATERIALS AND METHODS: Twelve patients with acute or subacute arterial occlusions of the forearm and hand who had ischemic digits and were treated with regional urokinase infusion were identified retrospectively. Their medical and radiology records were reviewed. RESULTS: All 12 patients demonstrated angiographic improvement and 11 patients demonstrated clinical improvement after treatment. Tissue necrosis in four patients led to partial amputation of one digit in two patients and three digits in two patients. Three of these patients had category III ischemia at presentation. The level of resulting amputation was altered in all but one patient. Vasospasm was noted frequently but responded to vasodilators. No significant complications occurred. CONCLUSIONS: When therapeutic alternatives are limited to anticoagulation and expectant amputation, regional urokinase infusion can optimize distal runoff, obviate or improve the options for distal surgical bypass, and limit tissue loss.

Acute Disease↗