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M Tendler

Publications and source records attributed to M Tendler.

At least 19 recordsLinked to original sources

Vaccination in murine schistosomiasis with adult worm derived antigens--II. Protective and immune response in inbred mice.

Previous work in our laboratory, mainly focused the prospects of achieving resistance against Schistosoma mansoni infection with adult worm-derived antigens in the form of a soluble extract (SE). This extract obtained by incubation of living adult schistosomes in saline, contains a large number of distinct molecules and was actually shown to be significantly protective in different outbred animals models such as Swiss mice and rabbits. It thus appeared worthwhile to investigate the potential protective activity of SE in different inbred strains of mice, known to be highly susceptible to the infection. Herein we present data showing that DBA/2 mice, once immunized with SE acquire significant levels of resistance to a S. mansoni cercarial challenge. In addition, preliminary studies on the immune system of immunized animals revealed that, injection of SE caused no general imbalance of B or T cell responses.

Animals

A 14-kDa Schistosoma mansoni polypeptide is homologous to a gene family of fatty acid binding proteins.

The complete nucleotide sequence encoding a Schistosoma mansoni protein termed Sm14 was determined from cDNA clones propagated in bacteriophage lambda gt11 in Escherichia coli. The 14.8-kDa protein bears significant homologies with a family of related polypeptides which bind hydrophobic ligands. Members of this group of cytosolic proteins were originally identified based on their affinity for long chain fatty acids. The purified recombinant protein exhibited an affinity to fatty acids, in contrast to a mutant lacking 16 N-terminal amino acids. Immunofluorescence experiments show that tubercles, which are structures located on the dorsal surface of adult male schistosome and known to contain lipids, are stained using antibodies raised to the beta-galactosidase fusion protein. A regular staining pattern is also evident in the muscle layers as well as in the body of the parasite. As the schistosome cannot synthesize fatty acids de novo and is dependent on the uptake of lipids from serum, the available data support a role for Sm14 in the transport of fatty acids.

Animals

Vaccination in murine schistosomiasis with adult worm-derived antigens: variables influencing protection in outbred mice.

Previous studies have shown that both permissive (mouse) and partially permissive (rabbit) hosts develop high levels of resistance against Schistosoma mansoni infection after vaccination with a multiple antigen extract (SE) obtained by incubation of living adult worms in saline, plus bacterial adjuvant. To investigate variables influencing SE-induced protection in murine schistosomiasis, a series of distinct vaccination protocols were performed focussing on the immunization dose, carrier systems, route, site and amplitude of challenge infection, and time between immunization and challenge. In addition, a new approach was adopted to evaluate SE protective activity, by means of population analysis of worm burden frequency distributions in a large scale study of vaccination in outbred Swiss mice. Distinct curves of frequency and a drastic difference in worm burden distribution of frequencies from SE-vaccinated x non-vaccinated mice were found. It was shown that SE could generate 75% mean protection in outbred mice even in the absence of adjuvant. In addition SE immunization was also able to induce full protection against lethal infection. SE-induced protection could be modulated by such parameters as dose of SE immunization/challenge interval, and route of cercariae injection. These data show that SE yields very high protective activity in outbred mice, and may provide a further insight for rational design of a vaccine in experimental schistosomiasis.

Animals

Schistosoma mansoni-New Zealand rabbit model: resistance induced by infection followed by active immunization with protective antigens.

In previous studies, rabbits immunized with adult worm antigens released from fresh adult schistosomes incubated in saline media showed a significant level of protection against challenge parasites. Focusing on the rabbit-Schistosoma mansoni model, concomitant immunity was investigated. A peculiar form of response to cercarial infection was observed: rabbits subjected to percutaneous infection and similar reinfections at different times after primary infection killed schistosomula from the challenge infection as well as established parasites from the primary infection. In this study the challenge infection stimulus was replaced by active immunization with an adult worm-derived protective antigenic mixture. The results show that immunization of New Zealand rabbits with an adult worm antigenic extract is capable of inducing a response that results in a significant reduction of the mean worm burden of the primary infection earlier than did homologous infection, as compared to worm reduction due to a second infection.

Animals

The diagnosis of bacteriuria during pregnancy.

Three diagnostic tests, Nitur, Urobact, and Uricult, were evaluated in the detection of bacteriuria in 865 pregnant women. As reference method agar culture was performed. Heavy growth (greater than 10(5) CFU/ml) of urinary tract bacteria was considered a true positive result and demonstrated in 58 (6.7%) of the women, 14 of whom had gram-negative rods. The sensitivity of the nitrite test was extremely low (0.13). The test gave negative results in eight of 17 specimens yielding heavy growth of Escherichia coli or Proteus mirabilis. Although the Urobact test was highly sensitive as regards gram-negative infection, it had an unacceptably low (0.27) predictive value in positive tests. The sensitivity of the Uricult test was low (0.35) in this study. The predictive value (0.50) of a positive test result may be acceptable, since just over half of the false positive results were explainable by moderate growth of urinary tract pathogens (10(4)-10(5) CFU/ml). It is argued that semi-quantitative urine culture may be preferable to the rapid diagnostic methods studied for the screening of bacteriuria in pregnant women.

Agar

Curative and protective activity in rabbits after reinfection with Schistosoma mansoni: a new model of immunity?

New Zealand rabbits were infected on day 1 and challenged on days 15, 30, and 60 with 1,000 Schistosoma mansoni cercariae/animal/infection. Challenged and control rabbits were perfused 60 days after each infection, corresponding to days 75, 90, and 120 after the first exposure. No decrease in number of adult schistosomes occurred in animals reinfected 15 days after primary infection, but, when the rabbits were challenged 30 and 60 days after the first infection, worm burden reduction of 61.4% and 92.6%, respectively, was observed as compared to infection controls. These data indicate that rabbits submitted to reinfection are able to kill the worms from their primary infection, besides being protected against challenge parasites.

Animals

Distribution of Langerhans cells in Swiss Webster mouse skin.

The pattern of surface density and distribution of Langerhans Cells (LC) in the Swiss Webster (SW) albino mouse is reported. LC were demonstrated using ATP-Pb and their densities evaluated in the skin of anterior and posterior foot-pads, tail, abdomen, back and ear. Cells were counted using a light microscope with a drawing tube by projecting 0.01 mm2 areas at 150X magnification. The distribution and density of LC were quite different in the various regions of SW mouse skin.

Animals

Effects of ketanserin, a 5-HT2-receptor antagonist, on the blood flow response to temperature changes in the diabetic foot.

We studied the effect of ketanserin, a relatively specific antagonist for 5-hydroxytryptamine2-serotonergic receptors, on the total blood flow to the foot of patients with diabetes using a computerized pulse volume plethysmograph and a temperature controlled foot chamber. Ketanserin was administered intravenously as a bolus of 10 mg over four minutes followed by a constant infusion at the rate of 5 mg/hr. Saline infusion served as a control in each subject. Sixteen patients with type II diabetes and two patients with type I diabetes were studied. Mean age was 58.5 +/- 1.6 years and mean duration of diabetes was 10 +/- 2 years. Basal blood flow (mean +/- SEM, mL/100 mL/min) at room temperature was 3.77 +/- 0.99 with saline and 12.07 +/- 1.81 with ketanserin. At 38 to 40 degrees C, the values were 4.84 +/- 1.09 and 16.93 +/- 1.83. Reactive hyperemia was measured following three minutes of arterial occlusion; at 38 to 40 degrees C the flow rate was 20.67 +/- 2.45 with saline and 30.86 +/- 3.02 with ketanserin, while at 8 to 10 degrees C the corresponding values were 15.63 +/- 2.01 and 27.16 +/- 2.03. All differences between saline and ketanserin had a P less than .01. Venous distensibility (vol% at 50 mm Hg) at 8 to 10 degrees C was 0.55 +/- 0.05 with saline and 0.90 +/- 0.15 with ketanserin, P less than .05. Our findings are consistent with the hypothesis that serotonin is involved in the limitation of blood flow to the foot in diabetes and that ketanserin may play a potential role in therapy.

Adult

Schistosome motility in saline media.

The authors observed the motility of 1067 worms used as a biological parameter indicating the vitality of the parasites, to define the survival time of S. mansoni males and females in 0,85% NaCl and PBS. Among the worms observed in 0,85% NaCl the mean time of survival in minutes was 204 for males and 240 for females and in PBS it was 267 min. for males and 344 min. for females. All the tested differences (media, sex; sex for saline group; sex for PBS group) were significant at a 0.0001 level.

Animals