Biomedical subjects
Publications and source records attributed to R H Cypess.
Adult mice were administered the common parasite Toxocara canis or lead or both. The parasite clearly altered mouse performance on tests of exploration, activity, learning, and motor coordination; behavioral effects in mice receiving lead alone were less general. Consequence of Toxocara administration appeared attenuated in animals receiving both agents. Parasite larvae were found in the central nervous system in all infected mice.
Ingestion of palatable and unpalatable solutions was measured in adult mice in which had been administered the common parasite of the dog, Toxocara canis alone, or in combination with lead. In addition, response to hot plate and susceptibility to electroconvulsive seizure were also measured. Results from the palatability test indicated that either lead or Toxocara may alter the mouse's mode of interacting with its environment. However, the two agents in combination interacted in their effects on consummatory behavior. Results from the hot plate and ECS measures were less clear with respect to how lead and/or Toxocara influence temperature reactivity and seizure susceptibility. Histological examination of the CNS in parasite infected animals revealed Wallerian Type degeneration of fiber pathways including the corpus callosum, olfactory tract, and cerebellar penduncles.
An automated fluorescent immunoassay technique (FIAX; International Diagnostic Technology, Santa Clara, Calif.) has been developed for the quantitation of circulating antibodies in dogs infected with Dirofilaria immitis. Two groups of sera, group I consisting of 77 samples and group II consisting of 126 samples, were obtained from experimentally infected microfilaremic dogs, known negative controls, and clinically diagnosed cases of occult dirofilariasis. Antibody against a partially purified trichloroacetic acid-soluble extract of a soluble somatic extract of D. immitis was measured by FIAX and by an enzyme-linked immunosorbent assay (ELISA). A standard curve was drawn from four samples with known FIAX titers and fluorescent signal unit values. The standard curve was used to determine titers of unknown samples. The correlation coefficients determined in the analysis of log10 ELISA and log10 FIAX values were r = 0.9057 and r = 0.8976 in groups I and II, respectively. Eighty-three percent of the titer values calculated by FIAX in group I were within one dilution, and 95% were within two dilutions, of those titers obtained by ELISA. In group II, 79 and 96% of the values obtained by FIAX were within one and two dilutions, respectively, of those obtained by ELISA. FIAX proved to be a reproducible and convenient assay for the measurement of serum antibody in dogs experimentally infected with Dirofilaria.
Blood samples were obtained during a lead screening program from 100 children aged 1-6 years in Allegheny County, Pennsylvania, to determine whether there was any association between specific forms of pica and infection with Toxocara canis, the principal cause of visceral larva migrans in the United States, or elevated blood lead levels. Significant associations were found between: 1) feces, soil, or grass pica and Toxocara infection; 2) paint or plaster pica and elevated blood lead; and 3) dog ownership and Toxocara infection. These findings suggest that an accurate pica history may be useful in identifying potential health problems in children.
The chronology of the antibody response to Dirofilaria immitis was measured in 2 groups of experimentally infected Beagle dogs. An enzyme-linked immunosorbent assay (ELISA), using a semipurified, adult D immitis-derived antigen was used to quantitate antibody levels. Group A consisted of 4 dogs inoculated once with D immitis infective larvae, 4 dogs inoculated twice with D immitis infective larvae, and 4 noninoculated dogs. Group B consisted of 26 dogs which were all infected with D immitis; however, 16 of these were given daily prophylactic concentrations of diethylcarbamazine (DEC) beginning 5 days before inoculation. Significant levels of antibody were demonstrable 16 weeks after inoculation of group A dogs and remained significantly increased throughout the study. There were no significant differences in antibody levels in dogs inoculated once or twice. Nontreated and diethylcarbamazine-treated dogs in group B developed significant antibody titers 11 weeks after inoculation. Significant differences in antibody titers between treated and nontreated dogs were first observed 13 weeks after inoculation; these differences remained for the duration of the investigation. There was no apparent correlation between antibody levels and either adult worm numbers or microfilaria counts.
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The enzyme-linked immunosorbent assay (ELISA) using Toxocara canis larva-specific antigens was used to confirm a presumptive clinical diagnosis of visceral larva migrans in patients whose serum specimens were submitted to the Center for Disease Control. The clinical and epidemiological characteristics of patients with diagnostic ELISA titres (greater than or equal to log2 5) were compared with patients who had less or no detectable antibody. The typical patient with serologically confirmed toxocaral visceral larva migrans was about five years of age and resided in the southern half of the USA. Clinical findings were likely to include leucocytosis, eosinophilia, an increased anti-A or anti-B isohaemagglutinin titre, and an elevated serum IgG level. Pica, as ascertained by a physician questionnaire, was not a consistent finding and both sexes were nearly equally represented.
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Sera from ICR/CD mice were assayed by radial immunodiffusion following oral infection and challenge with Heligmosomoides polygyrus larvae. Infection of these mice was found to alter the concentrations and classes of immunoglobulins, as well as the levels of antiparasitic antibody. Challenge of single- or multiple-infected mice with viable larvae resulted in the appearance of anti-H. polygyrus IgA and IgG in the serum. The kinetics of the detection for both of these antibody classes were consistent with an anamnestic response to an antigen isolated from adult nematodes. There also appeared to be an association in resistant mice of serum IgA levels with early and late events in the life cycle of the parasite.
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Seven of 10 patients with visceral larva migrans (VLM) had serum precipitating antibodies specific for larval antigens of Toxocara canis as determined by double diffusion in agar. Such antibodies were absent in 114 normal adults and 25 patients with collagen disease. Precipitation of ascarid components by C-reactive protein resulted in false-positive reactions, but this precipitation was readily prevented by appropriate absorption of sera before testing. A more sensitive assay, the enzyme-linked immunosorbent assay, revealed high titers of antibodies to larvae of Toxocara in all patients with VLM; the log2 titer ranged from 9 to 14. Five of eight household relatives of these patients and four children who had had VLM two to four years before testing had titers of 6-12. Of the 114 normal adults, 105 had titers of 0-2; nine had titers of 3-8. Of the 25 patients with collagen disease, 23 had titers of 0, and two had titers of 4 and 6, respectively. Additional studies of those patients indicated that infection with Toxocara can be distinguished serologically from ascariasis, filariasis, and trichinellosis.
Extensive demographic data concerning homicide victims and perpetrators in Allegheny County, 1966-1974, were obtained retrospectively from the records of the County Coroner's Office and Police Department. Analysis revealed that the demographic characteristics describing perpetrators and victims were essentially identical. Rates of homicide peaked in the young adult years of life. The race ratio (B/W) among victims was 18.7 for males and 6.7 for females, while sex ratio (M/F) was 5.4 for blacks and 1.9 for whites. An inverse relationship between the rate of homicide and socioeconomic status was present among both black and white races. The majority of victims were killed by a spouse, relative, or friend (66%), usually in familiar locations, i.e., residence or place of work (60%), and usually during an alteration (68%). Shooting was the method used to perpetrate 61% of the killings, most of which were by means of a handgun. An increasing trend of homicide was noted, particularly for the type perpetrated by shooting.
Radial immunodiffusion analysis was performed on intestinal perfusates from ICR/CD1 mice following oral infection and challenge with viable Heligosomoides polygyrus larvae. Infection of these mice resulted in an alteration in the amount and class of immunoglobulins, as well as anti-parasitic antibody. Specific IgA peaked at 3 days post-infection and then showed a gradual decline until day 21. This rapid elevation in IgA levels was temporally associated with early events in the parasite life cycle, and the increase in IgA was significantly higher in mice infected twice with H. polygyrus prior to challenge. Differences in both the concentrations and kinetics of specific IgA and IgG1 were also observed in the perfusates from these mice when compared to those noted for animals infected only once.
Monkeys infected with 2.0 larvae/g body weight died 31-41 days post-infection (PI): two of three monkeys infected with 1.0 larva/g body weight became moribund and were sacrificed at 50 days, but six of six monkeys infected with 1.0 larva/g body weight were healthy 225 days PI. Periorbital and facial edema and eosinophilia were observed in all groups during the second week PI, and myalgia and stiffening of joints was observed during the third week. High numbers of encyse, biceps brachii and deltoideus. Adult worms were recovered from the intestine 49 days PI. The morphological changes were essentially similar to those seen in humans and a generalized lymphoid hyperplasia was not observed. Thus, rhesus monkeys develop trichinosis which show similarities clinically, pathologically and morphologically to human disease.
The recent development of a sensitive and specific test (Enzyme-linked immunosorbent assay) for Toxocara canis infection has made it possible to study the epidemiology of this parasite in man. Antibody to Toxocara was measured in veterinarians, kennel workers, nurses, laboratory technicians, and clerical personnel in an animal hospital (Animal Medical Center, New York, NY) in order to determine the risk of infection in persons with varying degrees of occupational and home exposure to pet dogs. Antibodies were found in 8 (11 per cent) of 73 employees, and the prevalence and intensity of antibody was not statistically associated with either job exposure or dog ownership. However, antibody was not detected in any of the 14 employees who denied both past and present dog ownership. Additional studies using larger numbers of sera are required to determine the significance of these findings.
This paper presents the site-specific cancer mortality, 1953-1966, for men employed in by-product coke plants in Allegheny County, Pa. Approximate relative risks, which take into account race, age, and calendar years of follow-up, have been calculated for various work areas of the coke plant. The major findings are: 1. As indicated previously by Lloyd and Redmond, men with five or more years at the coke ovens have an excess risk of dying from lung cancer and kidney cancer. 2. Cancers of the digestive system are significantly elevated in nonoven workers. Cancers of two sites, the colon and pancreas, account for the total excess in cancers of the digestive system. 3. Cancers of the buccal cavity and pharynx appear high in nonoven workers, although the number of deaths involved is small. These observations clearly indicate the need to consider nonoven as well as oven workers when evaluating cancer hazards in the coke plant.
Mitogen-stimulated lymphocytes recently have been shown to release colony-stimulating activity (CSA), a stimulator of granulopoiesis in vitro. Whether CSA release is a result of specific antigen-lymphocyte interactions has been investigated by determining the ability of spleen lymphocytes isolated from Trichinella spiralis and Bacille Calmette Guerin (BCG) infected mice to release CSA. Lymphocytes were incubated with different antigens to obtain conditioned media (CM). Conditioned media prepared from Trichinella-sensitized lymphocytes incubated with Trichinella antigen (CM-1) resulted in a fourfold increase in the number of colonies from murine marrow cultured in methylcellulose as compared to controls. The addition of Trichinella antigen to either nonsensitized or BCG-sensitized lymphocytes did not stimulate CSA release. Similar results were obtained with lymphocytes from BCG-infected mice. Liquid cultures stimulated with CM resulted in an increase in 3h-thymidine incorporation and cell numbers. Using CM-1 to stimulate marrow from Trichinella-infected mice resulted in a three- to fourfold increase in the number of eosinophils present after 4 days. All other CMs tested stimulated only neutrophil production...