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M L Chance

Publications and source records attributed to M L Chance.

At least 37 records · Page 2Linked to original sources
PubMed1995

Complement-mediated lysis and infectivity for mouse macrophages and sandflies of virulent and attenuated Leishmania major promastigotes varying in expression of the major surface protease and lipophosphoglycan.

The infectivity to mouse macrophages and sandflies, the expression and enzymatic activity of the major surface glycoprotein (gp63), the developmental modification of lipophosphoglycan (LPG) and three metacyclogenesis markers (promastigote body size, lectin agglutination and complement resistance) were compared in four related Leishmania major promastigote lines. The lines, which differed in their virulence for BALB/c mice, were examined in both logarithmic and stationary phase. Although the two non-virulent lines were unable to survive and multiply within the macrophages, they were better at attaching to the macrophages and infecting sandflies than the two virulent lines, which were highly infective for macrophages. Except for the higher resistance of the attenuated parasites to complement-mediated lysis, there were no clear differences between the metacyclogenesis markers of the four lines. The amount and enzymatic activity of surface gp63 was relatively high in the attenuated promastigotes and this appears to be related to a higher expression of gp63 genes. In terms of LPG, cells of all the lines had approximately twice the number of galactose and mannose residues per molecule when in logarithmic phase than when in stationary phase. LPG of the virulent lines also contained approximately twice the mannose and galactose residues of the attenuated line. Although L. major gp63 could therefore be important for promastigote survival in the sandfly and for the resistance to complement-mediated lysis, there was no apparent correlation between gp63 expression and promastigote survival in the macrophage. A very elongated LPG could be necessary for the survival and proliferation of the parasite in macrophages.

Animals↗
PubMed1995

New developments in the chemotherapy of leishmaniasis.

Several significant advances in the chemotherapy of leishmaniasis have occurred in the last 10 years. Some of these advances have arisen due to the greater awareness of the pharmacokinetic properties of drugs, such as the pentavalent antimonials, while others have resulted from the introduction of drugs new to the treatment of leishmaniasis, such as aminosidine which can be used both systemically and topically against cutaneous leishmaniasis. The most encouraging advance is the use of lipid-associated amphotericin B; very short treatments with these preparations have been shown to be effective. Other studies have shown the usefulness of combination therapy and the use of immune modulators. A number of biochemical pathways in Leishmania, such as those associated with purine and sterol metabolism, are known to be distinct from those of the mammalian hosts. These have been exploited in the search for the rational choice of anti-leishmanial agents.

Antiprotozoal Agents↗
PubMed1993

Effects of sinefungin on growth and sterol composition of Leishmania promastigotes.

The S-adenosylmethionine analogue sinefungin was tested in vitro against promastigotes of various strains of Leishmania. The IC50 values for the Leishmania mexicana, Leishmania major, and Leishmania donovani strains used were of the order of 10 ng/ml but the Leishmania amazonensis strain tested was more resistant to the drug, the IC50 value being 6 micrograms/ml. Sterol profiles, in which 24-alkyl (C28) sterols predominated, were relatively unaffected by sinefungin. Incorporation of label derived from either [methyl-2H3]methionine or [methyl-14C]methionine into sterols was not appreciably affected by treatment at a growth-inhibiting concentration of sinefungin. It was concluded that sinefungin had only a limited effect on sterol production at the 24-transmethylation step and it is unlikely that this is the primary cause of cell death.

Adenosine↗
PubMed1993

Cutaneous leishmaniasis due to Leishmania aethiopica, on Mount Elgon, Kenya.

A survey of cutaneous leishmaniasis was carried out on the slopes of Mount Elgon, Kenya, including a detailed study of two villages in which cases were known to occur. The disease appeared to be restricted to altitudes between 1750 and 1900 metres, which coincides with an escarpment region. Vector sandflies were not found in houses and transmission appeared to be predominantly associated with caves found in the escarpment region. The parasites which were isolated were identified as Leishmania aethiopica.

Adolescent↗
PubMed1993

Studies on the Phlebotomus fauna of Mount Elgon, Kenya.

In a study of sandflies in 229 of 237 caves found on the slopes of Mount Elgon, Kenya, the Phlebotomus (Larroussius) species P. pedifer and P. elgonensis were found distributed at different altitudes. The females of these two species, which were the only ones of the genus Phlebotomus encountered in the study, were morphologically indistinguishable using existing techniques at the time. On the basis of the morphological identification of the males, however, P. pedifer occurred mainly at the lower altitudes (1750-1900 m) while P. elgonensis predominated at higher altitudes (2300-2600 m). The man-biting activities and the presence of promastigotes in the guts of female sandflies were restricted to lower altitudes (below 1900 m), i.e. the area of maximum distribution of P. pedifer and of cases of cutaneous leishmaniasis. This supports the suggestion that P. pedifer is a vector of cutaneous leishmaniasis on Mount Elgon.

Altitude↗
PubMed1992

Synergism in vitro of lovastatin and miconazole as anti-leishmanial agents.

The antifungal drug miconazole and the cholesterol-lowering agent lovastatin (mevinolin) were used in combination to assess their potency as anti-leishmanial agents. The drug combination was synergistic, being more potent in terms of inhibition of promastigote proliferation, macrophage infection and amastigote numbers. In promastigote cultures the effect was more marked in Leishmania amazonensis than L. donovani. Analysis of the sterol compositions of both promastigote and amastigote cultures revealed the inhibition of sterol 14 alpha-demethylation by miconazole and showed some apparent evidence of inhibition of sterol biosynthesis by lovastatin.

Animals↗
PubMed1992

Effects of long-term in vitro cultivation on the virulence of cloned lines of Leishmania major promastigotes.

The virulences of several clones from a single Leishmania major strain were studied in BALB/c mice. Clones showed the same pattern of infectivity and virulence two months after cloning as the parental population. After prolonged in vitro culture, however, it was apparent that two types of virulent clones existed: although the level of virulence remained stable in some clones, in others, such as C-11, it progressively decreased, as in the parental population. The progressive loss in virulence in a continuously cultured mixed population was probably due to selection, as the initial mixture of a stable virulent clone and a stable avirulent clone eventually yielded a totally avirulent promastigote population. After cultivation for 12 months, neither clone C-11 nor the parental population produced lesions in inoculated mice but virulent parasites were recovered from the inguinal nodes of the mice, possibly as a result of selection in vivo for virulent parasites.

Animals↗
PubMed1992

Antileishmanial drug targeting through glycosylated polymers specifically internalized by macrophage membrane lectins.

Antileishmanial chemotherapy is hampered by the location of the parasite within the phagolysosome of the macrophage, which restricts the bioavailability of many potentially useful antileishmanial drugs. In this study, the possibility of using antileishmanial drugs targeted to the infected macrophages by means of a chemical linkage to a neutral mannose-substituted poly-L-lysine carrier molecule was explored. The study was performed in an in vitro model with Leishmania donovani-infected murine macrophages. The antileishmanial activities of various synthetic constructs were compared with those of the free drugs and the pentavalent antimonial Pentostam, which was used as the positive control. The 50% effective dose of allopurinol riboside linked to the mannosylated poly-L-lysine was below 7.5 x 10(-6) M, while it was up to 3 x 10(-4) M for the free drug, indicating that the drug bound to the polymer was 50 times more active than the free drug. Control experiments with other constructs (e.g., allopurinol riboside linked to the mannose-free polymer) confirmed that the enhancement of activity was indeed achieved by means of the mannose homing device.

Animals↗
PubMed1991

Molecular approaches applied to the analysis of sympatric sandfly populations in endemic areas of western Venezuela.

To understand the epidemiology of cutaneous and mucocutaneous leishmaniasis in three distinct endemic foci of Tachira state, Western Venezuela, we aim to improve vector identification methods by developing species-specific sandfly DNA probes. These probes will be able to distinguish between sympatric sandfly populations thereby providing epidemiological data for determining the significance of individual sandfly groups related to their vectorial capacity.

Animals↗
PubMed1987

Cloning of a gene encoding the immunodominant surface antigen of Leishmania donovani promastigotes.

This study describes the characterisation of externally oriented surface peptides of both morphological forms of Leishmania donovani, the causative agent of visceral leishmaniasis (kala-azar). Using 125I surface labelling techniques and peptide extraction in the detergents Triton X-100 and Triton X-114, a major iodinable promastigote peptide at 63 kDa or 65 kDa (depending on detergent used) was identified. This peptide was demonstrated to be the immunodominant membrane peptide of L. donovani and was strongly recognised by human sera from parasitologically confirmed cases of kala-azar. This peptide was not demonstrated on the surface of tissue amastigotes, although in vitro translations of poly(A+) RNA from both promastigotes and amastigotes demonstrated that both forms possessed mRNA that directs the synthesis of a 63 kDa peptide. It is suggested therefore that in amastigotes this peptide may be a processed antigen. We also report the isolation of a recombinant cDNA clone in the bacteriophage vector lambda gt10 which encodes a 63 kDa polypeptide that is recognised by human kala-azar sera. It is proposed that this surface peptide could be used in a specific immunodiagnostic test for leishmaniasis.

Animals↗
PubMed1984

Quantitative and ultrastructural studies on the uptake of drug loaded liposomes by mononuclear phagocytes infected with Leishmania donovani.

This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony gluconate after i.v. administration to mice infected with Leishmania donovani. It was demonstrated that entrapment within liposomes greatly altered the kinetics of uptake of the drug. We were also able to show that liposomes composed of sphingomyelin, stearylamine and cholesterol were marginally better than any other preparation in delivering entrapped drug to liver and spleen. X-ray microanalytical studies on the uptake of liposomes by Kupffer cells infected with L. donovani have indicated that internalised liposomes probably fuse with parasitophorous vacuoles, transferring their contents into the immediate locality of the leishmanial parasites. It is proposed that this is the way in which liposome entrapped antileishmanial agents have an enhanced therapeutic effect over free drug therapy.

Animals↗
PubMed1982

[Ecology of a focus of cutaneous leishmaniasis in the Thiès region (Senegal, West Africa). 6. Characterization and typing of the strains of Leishmania isolated].

The authors studied the characterisation and typing of Leishmania strains isolated in the Keur-Moussa focus from human lesions (4 strains), from the digestive tract of Phlebotomus duboscqi (I strain) and from the rodents Mastomys erythroleucus (2 strains) and Tatera gambiana (2 strains). They used the following criteria: amastigote measurements, kinetoplast ultrastructure, pathogenicity in mice and hamsters, isoenzymes, kinetoplast and nuclear DNA buoyant densities and the Adler test. The results demonstrated that all the strains isolated from the various hosts and the Central Asian Leishmania major strains tested were identical according to these criteria. In addition the four human strains isolated in other regions of Senegal were also identical to those of the Keur-Moussa focus.

Animals↗
PubMed1980

The isolation and identification of leishmanial parasites from domestic dogs in the Machakos District of Kenya, and the possible role of dogs as reservoirs of kala-azar in East Africa.

Two out of 288 sick and emaciated dogs from homesteads in the Machakos District of Kenya, where human kala-azar cases existed, were found to be infected with leishmaniasis. The leishmanial strain isolated from one of the dogs was characterized enzymologically and serologically and found to be identical with strains isolated from human kala-azar cases and Phlebotomus martini. The significance of these findings is discussed in terms of the general epidemiology of visceral leishmaniasis in Kenya.

Animals↗
PubMed1979

Biochemistry of intraerythrocytic parasites III. Biochemical taxonomy of rodent Babesia.

Biochemical methods were investigated for use in taxonomic studies on Babesia. The techniques used were variation in the mobility of parasite enzymes on starch gels after electrophoresis and the measurement of the buoyant density of the DNA of the parasites. The study was carried out on four rodent species of Babesia (B. microti, B. rodhaini, B. hylomysci and B. muratovi) as well as two human isolates of Babesia believed to be of rodent origin. In addition a related piroplasm of rodents, Anthemosoma garnhami, was also investigated. The results indicate that biochemical methods would be of value in taxonomic studies on Babesia.

Animals↗