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Biomedical subjects

T E Nash

Publications and source records attributed to T E Nash.

At least 109 records · Page 6Linked to original sources
PubMed1982

Chronic giardiasis: studies on drug sensitivity, toxin production, and host immune response.

UNLABELLED: We investigated a patient (W.B.) with chronic symptomatic Giardiasis despite seven separate courses of either quinacrine or metronidazole who was cured by combined quinacrine and metronidazole. After isolating Giardia lamblia from W.B., we cultured the trophozoites to make the following observations. In vitro drug testing showed that (a) W.B.'s organisms were not more drug resistant than three other isolates and that (b) W.B.'s organisms were more sensitive to combined quinacrine and metronidazole than to either drug alone. Isolates of Giardia lamblia from W.B. and 3 other patients did not produce detectable enterotoxin in four different assays. W.B. had normal levels of circulating immunoglobulins, detectable intestinal immunoglobulin A, circulating immunoglobulin G anti-Giardia lamblia antibodies, and lymphocyte responsiveness to solubilized giardia lamblia. However, monocytes-macrophages from W.B. exhibited reduced killing for Giardia lamblia compared with normal subjects. CONCLUSIONS: (a) The chronicity of our patient's infection was not due to the organism having unique properties of drug resistance. (b) Combined quinacrine and metronidazole, which cured our patient's chronic giardiasis, should be tried in patients in whom infection persists after single drug therapy. (c) The diarrhea in our patient was probably caused by a mechanism other than Giardia lamblia-induced secretion by currently recognized enterotoxins. (d) Reduced cellular cytotoxicity for Giardia lamblia may have contributed to the persistence of our patient's infection and should be suspected in other patients with chronic giardiasis.

Adult↗
PubMed1981

Infection with Schistosoma mekongi in Southeast Asian refugees.

Schistosoma mekongi is a newly recognized species of Schistosoma that is closely related to Schistosoma japonicum and is pathogenic to humans. Like the other forms of schistosomiasis in which the parasites reside in the mesenteric vasculature, S. mekongi infection has hepatosplenomegaly and portal venous hypertension as its most common serious sequelae. Schistosomiasis, although endemic in certain areas of Southeast Asia, has not been recognized as a health problem in Asian refugees who are currently entering the United States. In the present study 12 Laotian immigrants with S. mekongi infection were examined. The clinical, laboratory, and parasitologic findings in these patients are discussed. The diagnosis was made by examination of stool specimens in 11 patients and rectal biopsy specimens in one patient. All patients were asymptomatic, although the six youngest children had hepatomegaly. It is suggested that specific serologic tests may be useful in screening Asian refugees for infection with Schistosoma.

Adolescent↗
PubMed1981

IgG antibody to Giardia lamblia detected by enzyme-linked immunosorbent assay.

A sensitive, reproducible enzyme-linked immunosorbent assay using unfixed, intact Giardia lamblia trophozoites as antigen is described. Employing this assay, we demonstrated that 81% of 59 symptomatic giardiasis patients and 12% of 17 uninfected control subjects had circulating IgG antibodies to G. lamblia. Eleven out of 15 patients tested serially had detectable antibody from 2 wk to 15 mo after therapy for acute infection. The prevalence of antibody in 197 unselected individuals in the Washington, D.C. area was 14%. Specificity of the antibodies was demonstrated by the ability of live G. lamblia trophozoites, but not Entamoeba histolytica or Trichomonas vaginalis trophozoites, to absorb the antibody activity. High titers of antibody were detected in 5 out of 7 patients with recurrent infection. The enzyme-linked immunosorbent assay described here may help to further characterize the antibody response to infection with G. lamblia.

Adult↗
PubMed1981

Analysis and antigenic activity of a carbohydrate fraction derived from adult Schistosoma mansoni.

The antigenic constituents of a crude predominately carbohydrate trichloroacetic acid soluble fraction of adult Schistosoma mansoni (TCA-S-C) were determined by comparing the antibody levels in human infections with crude TCA-S-C and fractions obtained after DEAE chromatography. Antibodies were measured using ELISA tests employing poly(L-lysine)-coated and uncoated polystyrene plates as well as radioimmunoassays to the 2 active fractions. Two active materials were identified. Acute and early infected patients had high levels of antibody to the previously characterized purified gut-associated proteoglycan (GASP), whereas the heavily infected chronically exposed patients had elevated levels to another fraction, PSAP. IgG levels to PSAP correlated significantly with the egg excretion rate. Both the acute and early infected as well as the chronically exposed patients had raised levels of antibody to crude TCA-S-C but no correlation with egg excretion or acuteness of infection. Therefore, the measurement of antibodies to specific schistosome components unmasked clinically relevant correlations that were not apparent when crude fractions were used. The pattern of response was similar whether ELISA or radioimmunoassays were used, although the radioimmunoassays were found to be more sensitive and specific. Antibody levels to GASP significantly correlated with the immunofluorescent antibody titer to schistosome gut epithelial cells. PSAP was characterized as a polydisperse PAS-positive staining material composed primarily of substances(s) with an apparent m.w. ranging from 130,000 to 90,000. The composition of this material as revealed by earlier studies suggested that PSAP was a glycoprotein(s).

Animals↗
PubMed1980

Hepatic fibrosis in rabbits infected with Japanese and Philippine strains of Schistosoma japonicum.

Symmers' clay pipestem fibrosis of the liver was produced by Schistosoma japonicum infection in the rabbit. Gross and microscopic portal fibrosis and portal vascular lesions resembled those in hepatosplenic schistosomiasis in man. Portal obstruction caused dilation of portal-systemic collateral veins but only minimal portal hypertension. The rapidity of development and prevalence of Symmers' fibrosis were related to the intensity of the schistosome infection. A mixed macronudular and micronodular cirrhosis of the liver was also present in most animals with Symmers' fibrosis, and other differences from the disease in man were present as well. Hepatic fibrosis regressed after the 30th week of infection, as judged from gross and microscopic observations and from measurement of hepatic collagen. The prevalence of Symmers' fibrosis and cirrhosis also decreased after the 30th week in the less heavily infected rabbits. The S. japonicum-infected rabbit is an imperfect model of human Symmers' fibrosis, but the rabbit is the only experimental model available other than the schistosome infected chimpanzee. The rapid production of severe fibrosis without the use of hepatotoxic agents, and the reversibility of the lesions, make this model of general interest for the study of hepatic fibrosis.

Animals↗
PubMed1979

Isolation of a polysaccharide antigen from Schistosoma mansoni eggs.

A polysaccharide antigen was isolated from Schistosoma mansoni egg homogenates by the phenol procedure. The crude preparation (CPEA) contained at least two antigens. The more purified antigen (PEA) was isolated by sequential enzymatic treatment of CPEA with DNase, RNase, Pronase, and alpha-amylase. PEA was resistant to boiling, freezing and thawing, mild acid and alkali, and chloroform, but was destroyed with periodate. It gave a positive reaction with anthrone reagent. PEA was eluted in the wash fraction from a DEAE cellulose collumn and in the void volume of a Sephacryl 200 column. After immunoelectrophoresis and polyacrylamide electrophoresis there was little or no migration. Amino acid analysis failed to reveal ninhydrin-positive material in the a hydrolyzate of PEA. These resluts suggested that PEA is a neutral polysaccharide with a m.w. of more than 200,000 and contains no amino acids or hexosamine. Antibodies against PEA were detected in sera obtained from mice infected with S. mansoni. PEA is different from previously described antigens derived from schistosome eggs.

Animals↗
PubMed1978

Hepatic amebiasis in spider monkeys.

In the past, investigators have been able to produce hepatic amebiasis in laboratory animals only by direct introduction of parasites into the liver or its vasculature, or by other artificial manipulations. A natural model of human visceral amebiasis has been lacking. We document an extensive outbreak of amebic dystentery which took place in a colony of spider monkeys; severe hepatic abscesses occurred in many animals. The spider monkey is highly susceptible to infection with Entamoeba histolytica and could provide a valuable model for the study of the pathogenesis of invasive amebiasis.

Animals↗
PubMed1978

Antibody response to a polysaccharide antigen present in the schistosome gut. I. Sensitivity and specificity.

By using paraffin sections of adult schistosomes fixed in Rossman's fixative, specific human IgM and IgG antibodies to a polysaccharide present in the epithelial cells of the schistosome were measured by using indirect immunofluorescent techniques. Of the 49 patients, mostly infected with S. mansoni but a few infected with S. haematobium or S. japonicum, all had antibody present at a 1:8 dilution of serum. Specific IgM antibody was more sensitive than IgG, yielding 100% and 86% positivity respectively. The false positive rate was 3% in a panel of sera obtained from patients most of whom were infected with other parasites. Antibodies were detected by the 3rd week in experimentally infected animals. Unisexual infections also induced antibody production. As a diagnostic test, the measurement of antibody to the polysaccharide is an easily performed reliable test with high sensitivity and specificity.

Animals↗
PubMed1978

Antibody response to a polysaccharide antigen present in the schistosome gut. II. Modulation of antibody response.

Specific IgM and IgG antibody to a polysaccharide present in the epithelial cells of the gut of adult schistosomes was measured in four groups of infected patients: I) patients with documented acute schistosomiasis; II) Americans exposed to schistosomiasis within the preceding 0--4 years; III) chronically and heavily infected patients, mostly from Puerto Rico, without hepatomegaly or hepatosplenomegaly; and IV) heavily infected Brazilian children with hepatic or hepatosplenic schistosomiasis. Specific IgM and IgG titers were both highest in the acute Group I patients and lowest in the chronically infected Groups III and IV. Total IgG and IgM levels were compared to specific antibody titers. Immunoglobulin levels tended to follow specific antibody titers except in the chronically infected Groups III and IV in which total IgG rose to high levels. The decrease in specific antigen titers over the course of time occurred despite continued antigenic stimulation and suggests a modulation of the humoral response. The mechanism remains obscure.

Adult↗
PubMed1977

Uricosuric effects of niridazole.

Niridazole, an antischistosomal drug, caused a 44% decrease in the serum uric acid (SUA) concentration in 11 patients with schistosomiasis. The mean SUA (+/- SE) was 6.3 +/- 1.4 mg/100 ml at baseline and 3.5 +/- 1.5 mg/100 ml (p less than 0.01) on day 7 of treatment. There was a significant increase in the urinary uric acid/creatinine ratio, from 0.446 +/- 0.165 at baseline to 0.550 +/- 0.145 on day 3. There was no significant difference on day 7. The fractional clearance of uric acid rose from 7.2 +/- 6.8% to 13.9 +/- 17.3% (p less than 0.01), indicating a uricosuric effect. Oxypurine excretion was unchanged. In a separate study on 7 other patients, the SUA remained low for 4 to 7 days after the last dose. Niridazole, although not an organic acid, has uricosuric effects.

Creatinine↗
PubMed1977

Further purification and characterization of a circulating antigen in schistosomiasis.

Previous studies showed that an antigen found in the circulation of animals heavily infected with Schistosoma mansoni was extracted in a trichloroacetic acid soluble-chloroform insoluble fraction (TCA-S-C) of adult worms. Antigenic activity was destroyed by periodate treatment but remained unaltered after treatment with proteolytic enzymes, DNase, RNase, and lyophilization. In the present study, chromatography of TCA-S-C on a DEAE cellulose column revealed six substances, one of which was antigenic. After electrophoresis in agarose antigenic activity corresponded to a slower moving, toluidine blue-staining material. A faster moving, toluidine blue-staining substance seems to be responsible for the large 260 nm, absorbing peak. Analysis of a fraction containing only antigen revealed a large amount of carbohydrate, primarily N-acetylglucosamine and D-glucuronic acid but also galactase, glucose, N-acetylglucosamine, and trace amounts of other sugars. Amino acids accounted for about 11% of the weight of the antigen. The antigen appears to be a proteoglycan.

Animals↗
PubMedDate not supplied

Human cellular immune response to Giardia lamblia.

Human peripheral blood mononuclear cells (PBMC) from two individuals experimentally and one naturally infected with Giardia lamblia responded strongly (in an in vitro lymphocyte proliferation assay) to both heterologous and homologous (parasite origin) G. lamblia antigen stimuli. Proliferative responses to specific antigens as determined by T-cell blotting were due to Giardia T-cell epitopes mostly present in antigens lower than Mr 85,000 and 31,000 in isolates PM and GS/M-H7, respectively. Additionally, Il-2 production of PBMC respective to T lymphocyte subsets under antigen stimulation were determined in one selected patient. Proliferative and lymphokine responses could be associated with CD4+ PBMC depleted of CD8+ T cells and not with PBMC depleted of CD4+ T cells. These preliminary results suggest the initiation of larger studies addressing questions of cell-mediated immune response and the role of lymphokines in human giardiasis.

Animals↗
PubMedDate not supplied

The uptake and metabolism of cysteine by Giardia lamblia trophozoites.

The cysteine, cystine, methionine and sulfate uptake and cysteine metabolism of Giardia lamblia was studied. Initial experiments indicated that bathocuproine sulphonate (20 microM) added to Keister's modified TYI-S-33 medium supported the growth of G. lamblia at low L-cysteine concentration. This allowed the use of high specific activity radiolabeled L-cysteine for further studies. The analyses of L-cysteine uptake by G. lamblia indicate the presence of at least two different transport systems. The total cysteine uptake was non saturable, with a capacity of 3.7 pmoles per 10(6) cells per min per microM of cysteine, and probably represent passive diffusion. However, cysteine transport was partially inhibited by L-methionine, D-cysteine and DL-homocysteine, indicating that another system specific for SH-containing amino acids is also present. Cysteine uptake was markedly decreased in medium without serum. In contrast to cysteine, the uptake of L-methionine and sulfate were carried out by saturable systems with apparent Km of 71 and 72 microM, respectively, but the Vmax of the uptake of sulfate was six orders of magnitude lower than the Vmax of methionine uptake. Cystine was not incorporated into trophozoites. [35S]-labeled L-cysteine and L-methionine, but not [35S]sulfate, were incorporated into Giardia proteins, indicating that the parasite lacks the capacity to synthesize cysteine or methionine from sulfate. Neither cystathionine gamma lyase nor cystathionine gamma synthase activities was detected in homogenates of Giardia lamblia, suggesting that the transsulfuration pathway is not active and there is no conversion of methionine to cysteine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗