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L D Hendricks

Publications and source records attributed to L D Hendricks.

At least 37 records · Page 2Linked to original sources

Visceral leishmaniasis in the German shepherd dog. II. Pathology.

Three German shepherd dogs were inoculated with Leishmania chagasi and three with Leishmania donovani and the infection was followed for 82 days. All infected dogs developed splenomegaly and lymphadenomegaly. In lymph nodes there was a reduction in lymphocyte population in paracortical areas, extensive proliferation of macrophages in paracortical areas and medullary cords, follicular hyperplasia, and increased numbers of plasma cells. The spleen had decreased numbers of lymphocytes in periarteriolar lymphoid sheaths, proliferation of macrophages in these regions, follicular hyperplasia, and enlargement of the red pulp with clusters of macrophages and plasma cells. The morphology of the tonsil was similar to the lymph nodes. Clusters of macrophages, often containing Leishmania spp, were present in liver, bone marrow, lung, and the intestines. The morphologic changes in lymph nodes and spleen were suggestive of a suppressed cell-mediated immunity and an active humoral immunity. The German shepherd dog may be a useful laboratory model for the study of immunopathologic changes in visceral leishmaniasis.

Animals↗

Antileishmanial activity of liposome-encapsulated meglumine antimonate in the dog.

Experimental infections of Leishmania donovani in mixed-breed dogs were induced to determine the antileishmanial efficacy of liposome-encapsulated meglumine antimoniate ( LEMA ). Each dog was inoculated IV with 1.0 +/- 0.2 X 10(8) amastigotes of a Khartoum strain of L donovani/kg of body weight. The antileishmanial agents ( LEMA or unencapsulated meglumine antimoniate ) were given once daily, IV, for 1, 4, or 10 consecutive days beginning the 12th day after inoculation. The dogs were killed 3 or 4 days after completion of therapy, and parasites in the spleens were quantified. A single injection of LEMA (0.61 mg of Sb/kg of body weight) resulted in 89% suppression and 4 consecutive daily injections of LEMA (1.94 mg of Sb/kg/day) resulted in 95.8% suppression of splenic parasites. The dose of LEMA that would give 50% suppression ( SD50 ) was estimated as approximately 0.029 mg of Sb/kg. The SD50 for unencapsulated drug was estimated as approximately 24 mg of Sb/kg. The liposome-encapsulated drug was estimated to be more than 700 times more efficacious than the unencapsulated drug. Seemingly, liposomes can markedly reduce the drug dosage required for equivalent treatment of visceral leishmaniasis in dogs.

Animals↗

Evaluation of promastigote and amastigote antigens in the indirect fluorescent antibody test for American cutaneous leishmaniasis.

Leishmania braziliensis panamensis promastigotes, temperature-induced in vitro-cultivated amastigotes, Vero cell-derived amastigotes, and rodent lesion-derived amastigotes were evaluated as antigens in the indirect immunofluorescent antibody (IFA) test for American cutaneous leishmaniasis. Test sensitivity was determined using sera from 34 U.S. soldiers with leishmaniasis diagnosed by demonstrating parasites in their skin lesions. Sera were collected from 3 to 24 months after exposure to Leishmania. Positive IFA reactions among patient sera were 82% with promastigotes or lesion amastigotes, 79% with in vitro amastigotes, and 76% with Vero cell amastigotes (P = N.S.). Positive titers ranged from 1:8 to 1:128 using all antigens. Test specificity was determined with 30 sera from healthy individuals. False positive reactions ranged from 0-5% depending on the antigen and all titers were less than or equal to 1:8. Test cross-reactivity was assessed with 47 sera from patients with other diseases. Depending on the antigen, cross-reactions occurred with sera from patients with Chagas' disease, lupus erythematosus, malaria, toxoplasmosis and amebiasis. None of the antigens cross-reacted with sera from patients with viral hepatitis, coccidioidomycosis, syphilis, schistosomiasis, and trichinosis. In replicate experiments, 99-100% of the sera varied no more than +/- 1 titer dilution. As sensitivity, specificity, cross-reactivity, and reproducibility of the four antigens were statistically similar, promastigotes, which can be easily and economically cultured in large numbers in vitro are recommended for use in the IFA test for American cutaneous leishmaniasis.

Adult↗

Identification of Leishmania spp. by multiple isozyme analysis.

Biochemical data as enzyme profiles which were obtained by cellulose acetate electrophoresis (CAE) are reported on 44 Leishmania isolates. These enzyme profiles contain data from 25 enzyme systems. Calculations from the CAE data on average polymorphism indicated that Leishmania species/types or groups can be expected to be about 25% polymorphic, which suggests that isolate pairs which have profiles about 75% or more identical should be considered samples from the same species/type, and isolates that are significantly less than 75% identical are therefore samples from different species/types. There were five major groupings of isolates according to enzyme profiles, which were for the most part consistent with groupings of the genus based on other criteria: braziliensis, mexicana, donovani, tropica and hertigi profiles. Within these groups there were natural subgroups of isolates among which there was 75% or more allozyme or allomorph (genetic) identity. The braziliensis profile group had two subgroups: panamensis and braziliensis or guayanensis, and the mexicana profile group had three subgroups: mexicana, amazonensis and peruviana. There was an indication that an L. d. infantum isolate might be different from the other L. donovani isolates, and that the L. tropica isolates could be samples from more than one group. The data reported here are consistent with previously reported CAE data, but suggest that isozyme analysis of Leishmania isolates leading to identification should be based on data from many enzyme systems rather than just a few.

Humans↗

The specificity of purine base and nucleoside uptake in promastigotes of Leishmania braziliensis panamensis.

Promastigotes of Leishmania braziliensis panamensis absorbed the purines adenine, hypoxanthine, adenosine and inosine by a combination of diffusion and mediated components. When the uptake rates for these substrates were corrected for diffusion and compared, the purine bases adenine and hypoxanthine were transported at a significantly slower rate than the purine nucleosides adenosine and inosine. Competitive interactions among those purines tested confirmed the presence of mediated and diffusion components and suggested that three transport loci may be operating (Fig. 6). The first transport locus, designated Locus 1, transported inosine, Locus 2, the purine bases hypoxanthine and adenine and Locus 3, adenosine. In addition, adenine and hypoxanthine inhibited the uptake of one another competitively. A comparison of Ki values derived from double reciprocal plots of labelled hypoxanthine and adenine uptake in the presence of the unlabelled substrates as inhibitors suggested that adenine has a greater affinity for the transport locus.

Adenine↗

American cutaneous leishmaniasis.

A lesion of New World leishmaniasis, evident on the palm of the hand, a rare and unusual location, is described. Routine investigations for bacteria and mycobacteria were misleading. Specific culture for Leishmania led to the correct diagnosis. Successful treatment was achieved with a pentavalent antimonial (sodium stibogluconate). The authors suggest various patient management precautions for patients with active lesions.

Adult↗

Susceptibility of clinically sensitive and resistant Leishmania to pentavalent antimony in vitro.

Standard courses of pentavalent antimonials frequently fail to cure cutaneous, mucocutaneous, and visceral leishmaniasis, and characteristically fail to cure diffuse cutaneous disease. We have determined the in vitro sensitivity of clinical isolates of Leishmania to pentavalent antimony to determine if inherent drug resistance of the parasite is responsible for treatment failures in human beings. Intracellular amastigotes resulting from promastigote-initiated infection of human macrophages were exposed to pentavalent antimony for 6 days at 34.5-35 degrees C. Amastigotes from clinically sensitive simple cutaneous lesions exhibited a range of in vitro sensitivity. Four strains were greater than or equal to 90% eliminated and two strains were 70-75% eliminated in vitro by concentrations of antimony (15-20 micrograms Sb/ml), comparable to peak achievable serum levels in humans. Amastigotes from initially clinically resistant simple cutaneous lesions showed a wider range of sensitivities. Five strains were greater than or equal to 90% eliminated, but one strain was only 40% eliminated and another strain was completely insensitive in vitro. The clinically resistant diffuse cutaneous strain was 61% eliminated. The techniques described herein permit determination of the in vitro antimicrobial susceptibility of Leishmania from all major human forms of leishmaniasis. The data from this series indicate that in a minority of initially resistant cases parasite resistance to the drug may be contributing to clinical resistance, and use of non-antimonial drugs might be recommended for future therapy.

Animals↗

Interactions between macrophagelike cells and Leishmania braziliensis in vitro.

The interaction between macrophagelike cells (P388D murine tumor cells) and Leishmania braziliensis panamensis promastigotes was studied in vitro under various conditions by light and electron microscopy. When the macrophagelike cells and L braziliensis promastigate were incubated together for 2 minutes, 90% of the promastigotes were attached to the macrophagelike cells by the tip of the flagella. The macrophagelike cells did not form pseudopods or aggregated microfilaments around the inserted flagellum. After a 5-minute incubation period, the parasites attached to the macrophagelike cells did not show preferred orientation. At this time, numerous pseudopods and aggregated microfilaments of the macrophagelike cells were seen around the invading parasites. When the relationship between the cytochalasin B-treated promastigotes and the macrophagelike cells were examined, no interaction of the promastigote flagella with macrophagelike cells was observed at 2 minutes. After a 5-minute incubation period, 50% of the attached parasites adhered to a macrophagelike cell without any particular orientation. When the interaction between the promastigotes and cytochalasin B-treated macrophagelike cells were examined, the cytochalasin B-treated cells showed fewer pseudopods than the untreated cells, and the number of parasites attached to them was reduced considerably after a 5-minute incubation period. This data demonstrated, for the first time, that the mode of entry by Leishmania promastigotes into macrophagelike cells is dependent on the activation of the macrophagelike cells following the attachment of Leishmania promastigotes.

Animals↗

Cutaneous leishmaniasis associated with jungle training.

In November 1977, 627 soldiers belonging primarily to the First Battalion, 82nd Airborne Division, stationed at Fort Bragg, were sent to the Canal Zone, Panama, for jungle warfare training. A medical surveillance program incorporating pre- and post-evaluations over a 6-month period with dermatologic examinations, questionnaires, and serologic tests was established. Ten cases of cutaneous leishmaniasis (1.6/100 men) were diagnosed by positive Leishmania culture. The demonstrated lack of sensitivity and specificity of the indirect fluorescent antibody test and the direct agglutination test render these serological methods useless as diagnostic screening methods in the early stages of this disease.

Adolescent↗

Experimental infection of Mystromys albicaudatus with Leishmania braziliensis: pathology.

Thirty-four Mystromys albicaudatus were injected intradermally with Leishmania braziliensis promastigotes and examined and killed during a 12-week period. All animals developed single cutaneous lesions at the sites of inoculation that began as a papular thickening in the dermis and progressed to a 2.0 cm crateriform ulcer. The histopathology of these lesions was characterized by granuloma formation and diffuse infiltrates of lymphocytes and plasma cells. Parasites were most frequently observed in vacuolated macrophages immediately underlying the necrotic debris of the ulcer. Histiocytes in which amastigotes were not identified were noted in aggregates at the margins of the inflammation. Russell's bodies were observed at 6 weeks post-infection, and discrete lymphocytic infiltrates bordered the inflammation at 12 weeks post-infection. It is suggested that M. albicaudatus is an excellent model of American cutaneous leishmaniasis.

Animals↗