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T E Nash

Publications and source records attributed to T E Nash.

At least 91 records · Page 5Linked to original sources
PubMed1985

Differences in excretory-secretory products and surface antigens among 19 isolates of Giardia.

The excretory-secretory (E-S) products and surface antigens of 19 isolates of Giardia were compared by reactivity of E-S products with antisera to homologous and heterologous organisms and by acrylamide gel electrophoresis of surface-labeled Giardia. Isolates could be divided into three broad groups on the basis of the previously reported DNA studies and the present studies. Group 1 consisted of five isolates with similar or highly cross-reactive E-S. These showed identical DNA banding patterns after endonuclease restriction analysis; four of five had identical surface antigens, and the remaining isolate showed a similar but different major surface antigen. Group 2 consisted of 11 isolates with moderate reactivity amongst themselves. DNA patterns showed some bands in common with group 1 organisms and themselves, but the surface-antigen molecular weight patterns were different. Group 3 consisted of three isolates with reactivity only amongst themselves. There were no DNA bands in common with group 1, and the molecular weights of the surface antigens were diverse. Surface-antigen differences are common among isolates of Giardia lamblia. These differences correlated to some degree with the DNA banding patterns observed after endonuclease restriction analysis and may result in altered virulence and host response.

Animals↗
PubMed1985

Severe giardiasis in a patient with cystic fibrosis.

A 20-year-old male patient with cystic fibrosis (CF) is described, who acutely developed hypoalbuminemia concurrently with giardiasis. Hypoalbuminemia could not be explained by the usual causes seen in patients with CF, but resolved with quinacrine therapy. Subsequently, asymptomatic giardiasis was sought but not found by either the string test or stool exam in any of 15 patients with pancreatic insufficiency who were examined in a prospective manner. Although pancreatic insufficiency is felt to be able to act synergistically with giardiasis to accentuate malabsorption, patients with pancreatic insufficiency per se are not necessarily at greater risk for colonization with Giardia.

Adult↗
PubMed1985

Comparison of four schistosome excretory-secretory antigens: phenol sulfuric test active peak, cathodic circulating antigen, gut-associated proteoglycan, and circulating anodic antigen.

Several carbohydrate-containing antigens of schistosomes have been characterized and tests for these antigens or for the corresponding antibodies are increasingly being used for the diagnosis and clinical analysis of human schistosomiasis. Phenol sulfuric active peak (PSAP) and cathodic circulating antigen (CCA) are 2 soluble glycoproteins found in adult worms of Schistosoma mansoni. These antigens have some similar characteristics including solubility in trichloroacetic acid and non-binding or weak binding to DEAE cellulose which suggests these 2 compounds to be identical. PSAP and CCA were therefore compared using radioimmunoassays employing monoclonal antibodies to CCA and radiolabeled PSAP as well as inhibitory assays using the original glycoproteins as inhibitors. By these criteria PSAP and CCA were found to be different glycoproteins. Using similar techniques, 2 anodic schistosome compounds, gut-associated proteoglycan (GASP) and circulating anodic antigen (CAA) were found to be identical. We now propose to call this later material GASCAP (gut-associated circulating anodic proteoglycan).

Animals↗
PubMed1984

Differentiation of schistosomes by species, strain, and sex by using cloned DNA markers.

We have detected species, strain, and sex-specific genetic markers for the genus Schistosoma by Southern blot analysis of its DNA using cloned DNA segments of the Schistosoma mansoni ribosomal gene as probes. Restriction analysis of DNA from eight different strains of S. mansoni, from Africa and the Caribbean, revealed that the predominant or major DNA fragment containing the ribosomal gene unit was the same in each but that low copy number or minor fragments containing the gene varied. It was shown that the detection of these minor fragments could serve as the basis for both strain differentiation and the analysis of individual differences within a strain. Analysis of the parents and progeny of a genetic cross revealed sex-linked markers and suggested that these markers are inherited in a Mendelian fashion. DNAs from the species Schistosoma haematobium and Schistosoma japonicum were also analyzed. Differences in the length of the major repeating unit of the ribosomal gene served to distinguish each species. Furthermore, an array of minor bands was detected in each species, suggesting that strains of S. haematobium and S. japonicum could be differentiated in the same manner as S. mansoni strains.

Animals↗
PubMed1984

Enzyme-linked immunosorbent assay for the detection of Giardia lamblia in fecal specimens.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of Giardia lamblia in human feces. The assay could detect between 37 and 375 trophozoites from cultures and between 12.5 and 125 cysts purified from human stool. Stool specimens were positive by ELISA in 36 (92%) of 39 patients with giardiasis; negative specimens came from patients with low numbers of parasites in their stool. In 10 patients stools became negative by ELISA after successful treatment. Stool specimens were positive by ELISA in three (2%) of 128 patients without demonstrable Giardia organisms in their stools; one positive specimen was from a child with IgA deficiency and diarrhea who responded clinically to metronidazole. The ELISA is a simple, sensitive, and specific diagnostic test for G lamblia that will be useful in diagnosis, in follow-up treatment, and in large-scale studies directed at defining the epidemiology and pathophysiology of G lamblia infection.

Antigens↗
PubMed1984

A case of schistosomiasis japonica: resolution of CAT-scan detected cerebral abnormalities without specific therapy.

A 28-year-old Marine Corps officer developed Katayama fever with central nervous system (CNS) manifestations 6 weeks after swimming on Leyte Island in the Philippines. Symptoms consisted of fever, nausea and vomiting, focal visual field deficits and mild confusion. CAT-scan of the patient's head initially revealed multiple lucencies and severe edema in the left frontal, parietal and occipital lobes. No schistosome eggs were found in the patient's stool, and therefore he was treated with a 10-week course of dexamethasone with resolution of all symptoms over 3 months. Repeat CAT-scan after symptoms cleared showed complete resolution of the focal abnormalities seen earlier. The diagnosis was subsequently established by positive serology and by finding eggs in the patient's stool and in tissue obtained by liver biopsy. This is the first report of CAT-scan-detected focal CNS lesions in a patient with acute schistosomiasis japonica, and resolution of the CNS abnormalities, temporally related to non-specific steroid treatment, is documented as well.

Adult↗
PubMed1984

Immune complex size determines the clearance rate of a circulating antigen in schistosome-infected mice.

Previous studies showed that the clearance rate of gut-associated proteoglycan (GASP), a specific excretory-secretory antigen, was enhanced in mice infected with low schistosome burdens compared to heavily infected and control mice. Because the size of immune complexes alters the clearance rate of antigens, in the present experiments the size of GASP-containing immune complexes was determined after injection of radiolabeled GASP into lightly and heavily infected and control mice. The size and amount of immune complexes were determined by sucrose density centrifugation, agarose electrophoresis, and (NH4)2SO4 precipitation. All three methods showed that lightly infected mice had larger and quantitatively more GASP-containing immune complexes than did heavily infected mice. The differences in clearance between lightly and heavily infected mice, therefore, appear to be due to the presence of smaller, and quantitatively less, immune complexes in the heavily infected mice.

Animals↗
PubMed1984

Delayed hypersensitivity granuloma formation around Schistosoma mansoni eggs in vitro. III. Granuloma formation and modulation in human Schistosomiasis mansoni.

An in vitro model of granuloma formation was used to study the cellular immune responses of Schistosoma mansoni-infected patients. The purposes of this study were to determine the relationship of granulomatous hypersensitivity to S. mansoni eggs in recent, well-defined infections and long-term chronic infections, and to determine the role of T cell subsets (OKT3, 4, and 8) defined by monoclonal antibodies in granulomatous hypersensitivity. Peripheral blood mononuclear cells obtained from patients with recent S. mansoni infections demonstrated increased granulomatous hypersensitivity responses in vitro when compared to peripheral blood mononuclear cells obtained from patients infected for 5 yr or more. The selective removal of infected for 5 yr or more. The selective removal of OKT3+ or OKT4+ cells reduced the ability of peripheral blood mononuclear cells to form granulomas in vitro. Positive selection for OKT4+ T cells produced optimal granulomatous hypersensitivity when compared to that produced by the unfractionated peripheral blood mononuclear cell population. OKT8+ cells demonstrated no ability to form granulomas in vitro. Selective removal of OKT8+ T cells produced variable results in the ability of the remaining peripheral blood mononuclear cells to form granulomas in vitro. These studies demonstrate the feasibility of investigating granulomatous hypersensitivity and immunoregulatory mechanisms operative in S. mansoni-infected patients by using in vitro technology.

Acute Disease↗
PubMed1983

Excretory-secretory products of Giardia lamblia.

The surface of Giardia lamblia strain WB was radioiodinated with either 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril (IODOGEN) or lactoperoxidase, and the labeled membrane components as well as the released excretory-secretory (E-S) products were identified. The surface of G. lamblia was easily labeled, and G. lamblia excretory-secretory (E-S) products were identified in the medium. Over 70% of the label on the cell surface was released over 24 hr. The major E-S product released was polydisperse (m.w. 225 to 94,000), protease VI and periodate-sensitive, chloroform-methanol insoluble, and failed to adhere to a series of carbohydrate-binding lectins or to diethylaminoethyl (DEAE) cellulose. Hydrophobicity was suggested by adherence to phenyl-Sepharose. The major E-S product of another G. lamblia isolate, Portland-1 (P-1), was antigenically different. A previous study showed that strain P-1 lacked a major antigenic component of strain WB. In the present study, this material was identified as the major secretory product of WB by crossed immunoelectrophoresis.

Animals↗
PubMed1982

Antigenic analysis of Giardia lamblia from Afghanistan, Puerto Rico, Ecuador, and Oregon.

The trophozoite antigens of Giardia lamblia to which host humoral and cellular immune responses are directed have not been identified. Therefore, we initiated studies to characterize these antigens in strains of G. lamblia from Afghanistan, Oregon, Ecuador, and Puerto Rico. By polyacrylamide gel electrophoresis, the electrophoretic mobility patterns of proteins of the four strains were similar; molecular weights of protein bands ranged between 12,000 and 140,000. The antigens which reacted with rabbit and anti-G. lamblia antisera by immunoelectrophoresis were also similar for the four strains. However, comparison by crossed immunoelectrophoresis showed the Oregon strain, which has been the longest in culture, lacked a set of anodic antigens and the single neutral antigen which were present in the other three strains. In addition, other minor antigen differences between the strains were detected by this technique. When we employed trophozoites from each strain as antigen in an enzyme-linked immunosorbent assay against 10 human antisera of various liters, we also detected some differences between the strains. Although polyacrylamide gel electrophoresis and immunoelectrophoresis revealed gross similarity among G. lamblia from widely differing geographic locations, subtle differences detected by crossed electrophoresis and enzyme-linked immunosorbent assay suggest the existence of potentially important antigenic differences among these strains.

Afghanistan↗
PubMed1982

Treatment of Schistosoma mekongi with praziquantel: a double-blind study.

Praziquantel is a newly developed drug effective in the treatment of schistosomiasis. In order to assess the efficacy and toxicity of praziquantel in the treatment of Schistosoma mekongi, 11 infected Laotian refugees, all belonging to a single extended family, were treated in a double-blind crossover trial with praziquantel and placebo. Initially, one group of five received praziquantel 60 mg/kg body weight in three divided doses orally while the remainder received an identically appearing placebo. Patients were evaluated clinically before, during and following therapy for 2 days. After 2.5 months the patients were re-evaluated and subjected to the opposite treatment, and final follow-up took place 5-7 months later. Three other patients were treated using an open protocol. All but one person was cured (91%). This patient failed to show a decrease in egg excretion 2.5 weeks after praziquantel therapy and was lost to follow-up thereafter. Side effects were common and consisted primarily of abdominal pain, malaise, and fever. These were generally mild and transient. No abnormal laboratory findings were associated with praziquantel therapy. At the final evaluation 6/6 patients with initial hepatomegaly showed a decrease in liver size.

Adolescent↗
PubMed1982

Schistosome infections in humans: perspectives and recent findings. NIH conference.

Approximately 200 million persons are infected with schistosomes. Of those infected, a small proportion develop serious chronic disease, usually after years of intensive exposure and infection. Schistosoma mansoni and Schistosoma japonicum reside in the mesenteric veins and produce liver fibrosis, which results in portal hypertension and bleeding esophageal varices but little hepatocellular dysfunction. Schistosoma haematobium resides primarily in the pelvic veins and produces mass lesions in the bladder and ureters, which lead to hydroureter and hydronephrosis. The intensity of infection is a major factor determining development of disease, but differences in worm strain and host response may also be important. In acute schistosomiasis there is an intense response to the parasite, which is suppressed as the infection becomes chronic. The marked inflammatory response seen in early and acute schistosomiasis becomes less intense and fibrotic lesions predominate. The recent advent of safe, effective, and easily administered chemotherapeutic reagents will aid in the control of schistosomiasis.

Animals↗
PubMed1982

Factors that modulate clearance and ultimate fate of a specific schistosome antigen (GASP) in schistosome infections.

To understand factors that modulate the amount and removal of antigen found in the circulation of schistosome-infected mice, a specific schistosome antigen, GASP, found in the circulation of infected animals, was radiolabeled with Bolton-Hunter reagent and injected into infected and control mice. The rates of clearance, levels of antigen binding, and the fate of the injected antigen were determined. Within 1 to 3 wk after injection, infected animals developed enhanced antigen clearance that paralleled the increase in antibody to GASP. Lightly infected animals showed faster clearance rates and increased antibody levels compared with heavily infected mice. The level of antibody in the sera, irrespective of the duration or intensity of infection, correlated with enhanced clearance. Heavily infected animals removed preformed immune complexes as rapidly as lightly infected mice. This indicates that the relative inability to clear antigen was not due to blockade of Kupffer cells. Circulating GASP antigen, determined by countercurrent electrophoresis, was detected in heavily infected animals in the presence of increased antibody, suggesting that circulating GASP was in immune complexes. Both free and complexed antigen were primarily cleared by the liver and then excreted in the urine as low m.w. nonantigenic products. With sensitive radioimmunoassays, GASP could not be detected in infected human or mouse urine.

Animals↗
PubMed1982

Human host response to Giardia lamblia. I. Spontaneous killing by mononuclear leukocytes in vitro.

To understand host resistance to Giardia lamblia infection, we investigated the capacity of human peripheral blood effector cells to kill G. lamblia trophozoites. Peripheral blood was obtained from 12 healthy, uninfected individuals without detectable IgG anti-G. lamblia antibody or known exposure to G. lamblia. Isolated mononuclear leukocytes (MNL), granulocytes, lymphocytes, and monocytes were cultured 16 hr with G. lamblia that had been pulsed with (3H)TdR while in log growth. MNL from all 12 individuals were spontaneously cytotoxic for G. lamblia. Specific cytotoxicity ranged from 13% at an E:T of 3:1 to 56% at an E:T of 100:1. Release of 3H directly correlated with a decrease in viable G. lamblia. In contrast to the uniform cytotoxicity by mononuclear cells, granulocytes and lymphocytes had no spontaneous cytotoxic activity for G. lamblia. MNL depleted of phagocytic or adherent cells lost all cytotoxic activity. Also, G. lamblia induced nonspecific MNL cytotoxicity to unrelated target cells. Finally, cytotoxicity against G. lamblia could be inhibited by adding unlabeled Trichomonas vaginalis, suggesting that this may be a more general mechanism of host defense against extracellular protozoa. We conclude that human peripheral blood monocytes-macrophages are spontaneously cytotoxic for G. lamblia and that this may be a major mechanism of host defense against this parasite.

Adult↗
PubMed1982

Identification and characterization of excretory-secretory products of Brugia malayi, adult filarial parasites.

Although E-S antigens may be particularly important for both the pathogenesis and immunodiagnosis of helminth infections, little is known about the immunochemistry or functional roles in human filarial infections. In the present paper, we have done some initial identification and characterization of E-S products of adult Brugia malayi by employing a combination of sensitive biochemical and immunochemical techniques. E-S products, collected by incubating B. malayi adults in vitro in a defined protein-free medium, were radiolabeled with 125I. SDS-polyacrylamide gel electrophoresis (PAGE) and autoradiography of labeled E-S products revealed 11 protein bands in the m.w. range of 10,000 to 70,000. Comparison of radiolabeled E-S products and adult somatic antigen (B.m.A) in SDS-PAGE indicated many common bands, and crossed immunoelectrophoresis and competitive Staph-A RIA confirmed the presence of most E-S antigens in B.m.A. Of the 11 E-S bands, two appeared to be derived from the surface of the adult worms and microfilariae as shown by SDS-PAGE and autoradiography of lodogen surface-labeled parasites; the presence of two host proteins in E-S was detected by crossed-line immunoelectrophoresis. The E-S antigens were highly immunogenic when tested both with rabbit antiserum raised against B.m.A and with a serum pool of patients with natural filarial infection.

Animals↗