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Biomedical subjects

M R Elwell

Publications and source records attributed to M R Elwell.

At least 73 records · Page 4Linked to original sources

Proliferative lesions in the male reproductive system of F344 rats and B6C3F1 mice: incidence and classification.

The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program. The overall incidence of reproductive system neoplasms in male F344 rats was 81.5%. The most common neoplasms were interstitial cell adenoma of the testis (76.6%), adenoma/carcinoma of the preputial glands (2.9%), mesothelioma of the tunica vaginalis (1.5%), and adenoma of the prostate gland (0.3%). The combined incidence (0.1%) of 59 other rare neoplasms consisted of 18 different types that occurred with a frequency of 4 or less. In contrast to the rats, male B6C3F1 mice had a low overall incidence (0.6%) of neoplasms in reproductive organs. The most common neoplasm was the interstitial cell adenoma (0.4%). Thirty additional types of neoplasms were identified. Each of these uncommon neoplasms occurred at a frequency of 12 or less with an overall combined incidence of 0.2%. Morphological features are described for neoplasms in the rat and mouse, and criteria are presented for differentiation of testicular interstitial cell adenoma, prostatic adenoma, and mesothelioma from hyperplastic changes.

Adenoma↗

Epidemiology and characterization of leptospirosis at an urban and provincial site in Thailand.

Patients with FUOs at the Children's Hospital in Bangkok and the Chao Phya Abhai Bhu Bejhr Hospital in Prachinburi were screened for leptospirosis by blood and urine culture in addition to microagglutination testing of their serum. Animal populations in urban and periurban areas of Bangkok were surveyed for evidence of leptospira infection. Three rural sites near the Prachinburi Provincial Hospital were also surveyed. The rodents' and domestic animals' blood, urine, and/or kidney cell samples were cultured for leptospira. Sera from these animals were also tested for leptospira antibody. The bataviae serovar was the most commonly detected leptospiral agent in both man and animals. Presenting symptoms varied with age with children showing primarily fever, vomiting, headache, abdominal and generalized muscle pain and diarrhea whereas adults had fever, headache, anorexia, muscle pain and constipation. Blood samples from patients suspected of having leptospirosis were tested for antibody by the MAT and cultured in EMJH media. The following serogroups were identified: bataviae, autumanalis, javanica, hebdomadis, and pyrogens. Leptospirosis incidence in humans was much higher in the rainy/flooding year of 1983 compared to the relatively dry year of 1984. Results of our animal surveillance studies indicate that in addition to rats, which have previously been mentioned, dogs, bandicoots, cattle and pigs could be the source of human leptospirosis infection in both urban and provincial locations in Thailand.

Animals↗

An attempt to treat rabies encephalitis in monkeys with intrathecal live rabies virus RV 675. Brief report.

A highly attenuated rabies virus, RV 675, proved innocuous but immunogenic when injected intrathecally into monkeys by the lumbar route. Attempts to use this virus to modify the course of fatal rabies encephalitis in monkeys were inconclusive possibly because of the brief encephalitic illness. Further studies are indicated to investigate RV 675 as a candidate therapeutic agent for rabies encephalitis.

Animals↗

Morphology and classification of 96 primary cardiac neoplasms in Fischer 344 rats.

Ninety-six primary cardiac neoplasms were identified from 79,971 Fischer 344 (F344) rats used in chronic toxicity and carcinogenicity studies by the National Toxicology Program (NTP) and National Cancer Institute (NCI), for an overall incidence of 0.1%. Neoplasms were classified as: 60 endocardial schwannomas, 23 intramural schwannomas, eight atriocaval mesotheliomas, three paragangliomas, one pericardial mesothelioma, and one hemangioma. Metastases occurred in four rats with endocardial schwannoma. Histological appearance of the endocardial and intramural schwannomas was consistent with origin from nerve sheath. Two of six endocardial schwannomas available for immunohistochemical staining were weakly positive for S-100 antigen. The atriocaval mesotheliomas, while morphologically resembling adenocarcinoma, were positive for vimentin and keratin, indicating mesothelial origin. Seventy of the 96 cardiac neoplasms occurred in rats 2 years of age or older at time of death. There were no sex or treatment-related differences in the incidence of these neoplasms, with the exception of atriocaval mesothelioma, which was more common in males.

Animals↗

Anti-rabies virus IgM in serum and cerebrospinal fluid from rabid dogs.

An anti-rabies IgM antibody capture radio immunoassay was used to test serum and cerebrospinal fluid from 37 dogs held in quarantine for suspicion of rabies. Rabies was confirmed in dogs that died by mouse inoculation and subsequent examination of mouse brains by fluorescent antibody technique to detect rabies antigen. The mean counts per minute (CPM) of iodinated anti-rabies gamma globulin coupled IgM rabies antibody in CSF and serum from rabid dogs were significantly higher than in CSF and serum from non-rabid dogs. Mean CPM from rabid dogs was greater in CSF than in sera, in contrast with non-rabid dogs, from which mean cpm was higher in sera than CSF, suggesting that antibody may have been synthesized in the CSF. To evaluate this test further, a dog was infected by rabies virus, and serial serum and CSF specimens were collected until the time of death. IgM anti-rabies antibody developed in the CSF and serum 29 days following infection, and rose just before the dog died of rabies on day 34. The rabies MAC RIA is potentially useful as a diagnostic method in quarantined dogs with rabies-like illness. Perhaps more importantly, it may be applied to better understand the immunopathogenicity of rabies.

Animals↗

Pathology of toxic death in mice following intravenous injection of Rickettsia tsutsugamushi strain gilliam: examination by light and scanning electron microscopy.

The pathologic manifestations of the toxic death elicited by the iv injection of mice with Rickettsia tsutsugamushi strain Gilliam were examined by light and scanning electron microscopic techniques to ascertain the cause of death. Light microscopic examinations of hematoxylin and eosin-stained sections of organs suggested the presence of fluid in the lungs; this was confirmed by an increase in the weight of the lungs of moribund mice. Scanning electron microscopy of blood cells demonstrated a marked crenation of erythrocytes from these mice. Death appears to be the result of shock brought on by vascular collapse secondary to plasma leakage.

Animals↗

Japanese encephalitis virus immunoglobulin M antibodies in porcine sera.

A solid-phase enzyme-linked immunosorbent assay (ELISA) was developed for detection of porcine immunoglobulin (Ig)M antibodies to Japanese encephalitis virus (JEV). Antibodies in sera were captured onto the solid phase of Microtiter plates sensitized with mouse monoclonal antibodies to porcine mu heavy chain. Virus antigen binding to the lawn of IgM was quantitated by subsequent binding of peroxidase-labeled human hyperimmune anti-JEV IgG, which in the final step, catalyzed a substrate color change. In sucrose density-gradient fractionated sera from recently infected pigs, the peak of ELISA JEV IgM activity corresponded to the peak of 18-S, 2-mercaptoethanol-sensitive hemagglutination-inhibiting (HAI) antibody activity. Within 2 to 3 days, JEV-infected sentinel pigs developed high JEV IgM activity; this activity decreased within 2 weeks. Among specimens collected from 99 random swine at abattoirs in Thailand during a period of low JEV transmission, none of 25 JEV HAI-negative sera had JEV IgM activity, 7 of 74 JEV HAI-positive sera did have JEV IgM activity, and the remaining 67 sera had readily detectable JEV HAI antibodies, but lacked JEV IgM. The JEV IgM solid-phase ELISA was useful for rapidly diagnosing active or recent JEV infections in swine.

Animals↗

Serologic evidence of Hantaan-like virus in rodents and man in Thailand.

A serologic survey was conducted to determine the presence of antibody to Hantavirus in rodents in Thailand. Sera from over 300 rodents were tested by an immunofluorescent antibody method. Bandicota indica, a field rodent, was found to have a high incidence of infection (20-24%) in 2 locations. A Hantavirus was isolated from lung samples of B. indica. When sera were tested from humans living in Kanchanaburi and several locations in Bangkok, those people living in close proximity to the infected B. indica had greater than 30% prevalence of positive antibody titers.

Animals↗

Use of streptomycin and isoniazid during a tuberculosis epizootic in a rhesus and cynomolgus breeding colony.

An epizootic of tuberculosis occurred following the addition of new cynomolgus monkeys to a nonhuman primate breeding colony. A total of 5/47 cynomolgus and 51/148 rhesus became tuberculin positive (reactors). Mycobacterium tuberculosis was cultured from reactors which were euthanatized and monkeys which died spontaneously. The isolates were sensitive to the standard antitubercular agents. Rhesus reactors and their unweaned infants were quarantined and given streptomycin and isoniazid by intramuscular injection. Isoniazid was added to the drinking water quarantined and given streptomycin and isoniazid by intramuscular injection. Isoniazid was added to the drinking water of the remainder of the breeding colony to curtail the outbreak. Isoniazid toxicity was observed in both infants and adults with an overall incidence of 3%. Forty-eight rhesus reactors and their infants born before the outbreak were alive and healthy at the end of the treatment period. In addition, nine surviving infants were born during the 6 month treatment period. Tuberculin tests were still positive in many of the treated reactors following treatment. In this epizootic, the institution of quarantine and chemotherapy instead of euthanasia resulted in significant savings.

Animals↗

Doxycycline prophylaxis for experimental leptospira infection in non-human primates and hamsters.

Doxycycline was effective as a chemoprophylactic agent for experimental Leptospira infection in non-human primates and hamsters. Monkeys injected intraperitoneally with Leptospira bataviae, and receiving only diluent as treatment developed a leptospiremia during the first week and later leptospires were cultured from the cerebrospinal fluid and urine. Monkeys treated daily with oral doxycycline for 10 days beginning one day before infection had a shortened period of detectable leptospiremia, and organisms were never detected in the cerebrospinal fluid or urine. Even an oral dose of doxycycline 2 hours before infection and on day 7 prevented the later infection of the cerebrospinal fluid and urine. In hamsters, doxycycline treatment prevented deaths from acute Leptospira infection and when hamsters were treated daily for 4 or more days, renal infection was prevented. The results of animal studies, the susceptibility of LC0475 and the five other isolates to doxycycline in vitro, and lack of evidence for antibiotic resistance in culture suggests this antibiotic may be useful as a prophylactic drug for high risk groups and an effective treatment for leptospirosis in Thailand.

Animals↗

Acute toxoplasmosis in hamsters and mice: measurement of pathogenicity by fever and weight loss.

Infections with 4 strains of Toxoplasma gondii were studied in mice and hamsters. In mice, infections with strains RH, T-1, and T-45 were always fatal, but strain ts-4 infection was not (ie, the mice survived). In hamsters, the RH strain always gave rise to a fatal infection and the T-1 strain killed about 90% of the hamsters, but as many as 10(6) tachyzoites of the T-45 and ts-4 strains failed to cause fatal infection. The lesions of the ts-4 infection in hamsters were limited to mononuclear inflammation and a scar at the injection site. Also, only the ts-4 strain did not produce chronic infection in hamsters. To evaluate degrees of pathogenicity of the strains, percentages of mortality, survival time, and such subtle changes as fever and weight loss can be used.

Acute Disease↗

Immunity to toxoplasmosis in hamsters.

Protective immunity to Toxoplasma was studied in hamsters. Immunity developed in 2 to 3 weeks after vaccinations were performed. Vaccination with live RH, T-45, and ts-4 strains afforded the best protection against challenge exposure with the most pathogenic RH strain used. Even a killed-toxoplasma vaccine protected all hamsters against the slightly less pathogenic T-1 strain through 24 weeks, but it did not protect hamsters against challenge exposure with the RH strain. Both ts-4, a nonpersistent strain, and killed-toxoplasma vaccine provided protective immunity in hamsters that was not dependent upon premunition. Toxoplasma antibody titers in hamsters given the 2 vaccines were similar. However, there was a difference in the quality of immunity: fever and body weight loss were seen in hamsters vaccinated with the killed-toxoplasma vaccine after they were challenge exposed with T-1 strain, whereas these changes were rarely seen in hamsters given the live-toxoplasma vaccine and then challenge exposed with RH strain. Delayed-type hypersensitivity to Toxoplasma antigen always appeared before protective immunity and was detected in all hamsters by 4 days after vaccination with live-toxoplasma strains. Although the development of delayed-type hypersensitivity preceded protective immunity, it was not indicative that protective immunity was present or would develop.

Animals↗