Biomedical subjects
W Peters
Publications and source records attributed to W Peters.
Syntheses of leukotriene analogs.
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Electron microscopic localization of chitin using colloidal gold labelled with wheat germ agglutinin.
The lectin wheat germ agglutinin (WGA) has a binding site which is able to bind a sequence of three N-acetyl-glucosamine residues. Therefore, it has a very strong affinity for the polymers of this sugar, especially chitin. Colloidal gold can be labelled with WGA and used as a specific electron-dense marker for the electron-microscopic localization of chitin. The specificity of the WGA-gold binding can be checked by competitive inhibition with 5-10 mM triacetyl chitotriose. The reliability of this method was tested in three species. In the formation zone of the radula of the snail, Biomphalaria glabrata Say, chitin or chitin precursors were localized in vesicles of the odontoblasts, outside the extremely long microvilli of odontoblasts and in the newly formed teeth. The inner peritrophic envelope of the earwig, Forficula auricularia L., is characterized by an orthogonal texture of bundles of microfibrils that are thought to contain chitin. The presence of chitin was proved using the present method. In the peritrophic membranes of the blowfly, Calliphora erythrocephala Meigen, it was possible to differentiate between chitin and glycoproteins which have N-acetylglucosamine residues.
Leishmania infecting man and wild animals in Saudi Arabia. 2. Leishmania arabica n. sp.
Leishmania arabica n. sp., found in the rodent Psammomys obesus in the Eastern Province of Saudi Arabia, is described. This parasite, which has also been found in a feral dog in the same area, is distinguished from the common species of the Eastern Province, L. major zymodeme LON-4, on the basis of its very distinctive isoenzyme profile (zymodeme LON-64) and kinetoplast DNA. It is morphologically indistinguishable from L. major. The new parasite has not been found in man to date and its vector is so far unknown.
Leishmania in the Old World: 5. Numerical analysis of isoenzyme data.
Numerical analysis of 59 zymodemes of Old World Leishmania, based on the enzyme profiles of 280 stocks, revealed several distinct clusters. Some of these clusters corresponded with traditional taxonomic groupings: L. major, L. tropica, L. aethiopica and L. donovani sensu lato, but hitherto unrecognized groups were also indicated. The analysis provided an overview of the interrelationships between the Leishmania zymodemes.
Leishmania in the Old World: 1. The geographical and hostal distribution of L. major zymodemes.
135 stocks of Leishmania major from man, reservoir hosts and sandflies were characterized using thin-layer starch-gel electrophoresis of 13 enzymes: MDH, 6PGD, GD, SOD, ASAT, ALAT, PK, PGM, ES, NH, PEPD, MPI, GPI. Homogeneity in this species was demonstrated by identical electrophoretic mobilities in nine enzymes. Polymorphism in four enzymes: 6PGD, GPI, PEPD, ES, gave six zymodemes among the collection. Stocks from sandflies and several species of burrowing rodents were indistinguishable from those from man in the same areas. Stocks of Leishmania from North-West India were identified as L. major. In some foci the distribution of zymodemes has some correlation with the presence of particular rodent reservoir hosts. The enzymic homogeneity of L. major throughout its geographical and host range appears to be correlated with the close association between L. major and sandflies of the subgenus Phlebotomus. The status of L. major as a distinct species is supported.
Leishmania in the Old World: 2. Heterogeneity among L. tropica zymodemes.
Isoenzyme profiles of 27 stocks of Leishmania tropica from widely separated geographical areas were compared with those of reference strains of L. tropica and L. major using starch-gel electrophoresis of 13 enzymes (GPI, GD, ES, PGM, PEPD, NH, ASAT, ALAT, PK, MPI, 6PGD, SOD, MDH). 18 zymodemes were seen. L. tropica showed considerable intraspecific variation which did not correlate with its epidemiological uniformity. Isolates from cases of cutaneous and visceral leishmaniasis and leishmaniasis recidivans were identified as L. tropica. Only one isoenzyme band was held in common with the enzyme profile of the L. major reference strain thus supporting the status of L. tropica as a separate species.
Leishmania in the Old World: 3. The distribution of L. aethiopica zymodemes.
Isoenzyme profiles of 28 stocks of Leishmania aethiopica were compared with those of reference strains of L. aethiopica, L. tropica and L. major using starch-gel electrophoresis of 13 enzymes (GPI, GD, ES, PGM, PEPD, NH, ASAT, ALAT, PK, MPI, 6PGD, SOD, MDH). 13 zymodemes were seen. L. aethiopica showed some infraspecific variation. Stocks from Phlebotomus longipes and Procavia habessinica were indistinguishable from those from man. Stocks from cases of diffuse cutaneous and cutaneous leishmaniasis were indistinguishable. Only one enzyme pattern was held in common with the L. tropica reference strain enzyme profile, and none with the L. major reference strain. The status of L. aethiopica as a separate species is supported.
Leishmania in the Old World: 4. The distribution of L. donovani sensu lato zymodemes.
Isoenzyme profiles of 67 stocks of Leishmania donovani sensu lato from across the Old World were compared with those of reference strains of L. donovani sensu stricto, L. infantum, L. major, L. tropica and L. aethiopica using starch-gel electrophoresis of 13 enzymes (GPI, GD, ES, PGM, PEPD, NH, ASAT, ALAT, PK, MPI, 6PGD, SOD, MDH). 12 zymodemes were seen. Isolates from man, Canis familiaris, Vulpes vulpes, Rattus rattus, Arvicanthis sp. and Phlebotomus martini were examined. Several zymodemes comprised stocks from man and C. familiaris, two of which also included wild animal isolates. Isolates from cases of post-kala-azar dermal leishmaniasis and visceral leishmaniasis were indistinguishable. L. donovani s.l., including L. donovani s.s. and L. infantum, formed a coherent group with a striking degree of enzymic homogeneity. Only one enzyme pattern was held in common with the L. tropica and L. aethiopica reference strains and two with the L. major reference strain enzyme profile.
Qinghaosu resistance in rodent malaria.
Resistance to qinghaosu (artemisinin) developed rapidly in a chloroquine-resistant line of Plasmodium yoelii (NS) passaged in mice, but was not produced in chloroquine-sensitive P. berghei. Development of resistance took place in an apparently stepwise fashion. After removal of drug selection pressure some resistance was lost which was regained rapidly within three passages when drug pressure was reapplied. The resistant QS line was cross-resistant to two reduced derivatives of artemisinin but not to propoxycarbonyl dihydroartemisinin or artesunate. No significant resistance was shown against primaquine, pyrimethamine, cycloguanil or pyrimethamine-sulphadoxine, but resistance to chloroquine was enhanced and marked resistance to quinine, mefloquine and amodiaquine was noted. It is suggested that the unusual cross-resistance pattern of the strain relates to changes in membrane characteristics.
Preliminary serological characterization of bovine viral diarrhoea virus strains using monoclonal antibodies.
Five monoclonal antibodies against the bovine viral diarrhoea (BVD) viral strain NADL were isolated and characterized by an indirect immunofluorescence assay. Extensive cross-reactions were detected when the antibodies were tested with 12 heterologous BVD and four hog cholera (HC) viral strains. One antibody reacted with all strains tested. Two antibodies were specific for cytopathogenic BVD viruses, but failed to react with HC virus. The other antibodies reacted to varying degrees with BVD and HC viral strains.
High dose chemotherapy in solid tumours in adults.
The available evidence suggests that if benefit is to be obtained from high dose chemotherapy regimens, it will be in patients whose tumours are either untreated or still responding to conventional therapy. In each of the diseases discussed in this chapter the optimum timing of the treatment regimen has still to be determined. Effective regimens have been found but it is probable that further improvements can be made. In small cell lung cancer initial high dose therapy followed by non-cross-resistant regimens may prove effective. In glioma studies with high dose therapy before irradiation are awaited and may offer the best means of exploiting this approach to treatment. In breast cancer some impressive responses have occurred but the category of patient likely to benefit has not yet been defined. In melanoma high dose treatment is likely to benefit only those patients with probable minimal disease after surgery.
The chemotherapy of rodent malaria, XL. The action of artemisinin and related sesquiterpenes.
Artemisinin (Qinghaosu), a poorly soluble sesquiterpene lactone derived from the plant Artemisia annua Linn., and a number of more soluble, semi-synthetic derivatives are rapidly-acting blood schizontocides against Plasmodium berghei and P. yoelii nigeriensis. An oily suspension of artemisinin given s.c. is more effective than aqueous suspensions. The activity is retained against lines resistant to primaquine, cycloguanil, pyrimethamine, sulphonamides, mefloquine and menoctone, but a highly chloroquine-resistant line is much less sensitive. Artemisinin has no causal prophylactic, gametocytocidal or sporontocidal action. Dihydroartemisinin causes the pigment of P. berghei to clump, but in a different fashion from the pigment changes induced by chloroquine or quinine, reflecting a different mode of action of the sesquiterpenes from that of these other antimalarials.
Plants as sources of antimalarial drugs: in vitro antimalarial activities of some quassinoids.
Fourteen quassinoids, obtained from simaroubaceous plants, were tested for in vitro antimalarial activity. All of these inhibited the incorporation of [3H]hypoxanthine into Plasmodium falciparum in vitro at concentrations below 0.41 microgram ml-1. The two most potent quassinoids, bruceantin and simalikalactone D, showed 50% inhibitory concentration values of 0.0008 and 0.0009 microgram ml-1, respectively. The results are compared with the antiamoebic, antileukemic, and cytotoxic activities of these compounds reported in the literature.
High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer.
Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.
Hemolysis induced by artemisinin and its derivatives in vitro.
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The chemotherapy of rodent malaria XLI. Causal prophylaxis. Part V. Effect of mefloquine on exoerythrocytic schizogony in Plasmodium yoelii yoelii.
Previous studies using mefloquine in rodents have suggested that this compound has no effect on pre-erythrocytic schizogony. In the present study, direct observations on 46-hour-old pre-erythrocytic schizonts of P. yoelii in the liver of rats have shown that mefloquine does induce recognizable changes in the peripheral, enzyme-containing vesicles but that these are insufficient to hinder the maturation of the parasites, thus confirming that this compound has no causal prophylactic value.
[The Danes show it again: fluorides are effective dental health aides].
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