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Biomedical subjects

W Chin

Publications and source records attributed to W Chin.

13 recordsLinked to original sources

Chloroquine-resistant Plasmodium falciparum from East Africa: cultivation and drug sensitivity of the Tanzanian I/CDC strain from an American tourist.

A strain of Plasmodium falciparum, designated Tanzanian I/CDC, from an American tourist returning from Tanzania, was isolated in vitro and in the Aotus monkey. Clinically, the infection showed a late recrudescent pattern of chloroquine resistance. In 2 inoculated Aotus monkeys, the infection recrudesced after a dose of chloroquine (40 mg/kg) curative for sensitive P. falciparum strains in the Aotus monkey. In 4 ,dditional monkeys two primary infections and one of the recrudescent parasitaemias were cured with a 100 mg/kg dose of chloroquine; the second recrudescent parasitaemia was cured with an additional 40 mg/kg dose of chloroquine. The 48 h in-vitro chloroquine-sensitivity test demonstrated that the Tanzanian I/CDC strain had a pattern of chloroquine resistance similar to a reference resistant strain, the Vietnam-Oak Knoll (FVO). These studies reinforce reports which suggest that chloroquine-resistant malaria is being transmitted in East Africa.

Blood

The enzyme-linked immunosorbent assay (ELISA) for malaria. I. The use of in vitro-cultured Plasmodium falciparum as antigen.

Using the Panama II strain of Plasmodium falciparum obtained from continuous in vitro culture as antigen, the micro enzyme-linked immunosorbent assay (ELISA) was used to test serum samples from 50 persons from the southeastern United States and serum specimens collected weekly from four non-immune and nine semi-immune patients infected with P. falciparum. None of the 50 sera from the United States had ELISA antibody titers greater than 1:80. The nine semi-immune patients had rapid ELISA antibody responses (titers greater than 1:2560) following patent parasitemia. ELISA titers remained elevated despite disappearance of patent parasitemia, and declined gradually following curative antimalarial therapy. The ELISA responses observed in the four non-immune patients were more variable, though positive titers appeared rapidly with patent parasitemia. Maximum titers were lower than those observed in semi-immune patients. These results demonstrate that P. falciparum obtained from continuous in vitro culture is an excellent antigen for the micro-ELISA test for malaria. However, further assessments of the ELISA are needed to identify the conditions associated with positive responses.

Adolescent

Plasmodium fragile and Macaca mulatta monkeys as a model system for the study of malaria vaccines.

Pladmodium fragile and the Macaca mulatta monkey are presented as a model system for the study of malarial vaccines. Four animals were immunized with culture-grown P. fragile merozoites and subsequently challenged with culture-produced parasites. One animal failed to develop a detectable parasitemia following primary challenge. Two other immunized animals had primary infections which were short-term. the parasitemias in these three monkeys following secondary challenge were short-term and the immunity was apparently sterilizing. The fourth immunized monkeys had recrudescences of the primary and secondary infection but differed markedly from the four control animals. Indirect fluorescent antibody titers increased as a result of the immunization and were indicative of the level of immunity. Because of the many similarities to the human-P. falciparum model system, the P. fragile-M. mulatta system appears to be particularly well suited for a number of malaria vaccine studies.

Animals

The continuous cultivation of Plasmodium fragile by the method of Trager-Jensen.

Using the Trager-Jensen method, a second malaria species, Plasmodium fragile, a simian counterpart to the human malaria P. falciparum, has been cultivated successfully. The average growth rate every 3--4 days was 5-fold and the average number of merozoites observed was 14. To date, only rhesus monkey red blood cells (RBC) would support the long-term cultivation of this parasite. Short-term observations indicate that RBC from the squirrel monkey (Saimiri sciureus) may support growth but human RBC of each of the four major AB-O types failed to support growth of the parasite. Availability of the P. fragile-rhesus monkey model would allow for a second parasite-host system for the in vitro and in vivo study of the immunologic responses of the falciparum-like parasite in a more natural host.

Animals

Studies on the West African I strain of Plasmodium falciparum in Aotus trivirgatus monkeys.

The West African I strain of Plasmodium falciparum was isolated from a commercial airline pilot who had an overnight stay in Nigeria. Once established in the Aotus trivirgatus griseimembra monkey, the parasite produced high parasitemias and readily infected mosquitoes. Anopheles freeborni and An. maculatus mosquitoes transmitted the infection to additional animals. Infected salivary glands were also seen in An. culcifacies. Comparative infectivity studies indicated the most susceptible mosquito to be An. freeborni, followed by An. culicifacies, An. maculatus, and An. balabacensis balabacensis. Only 2 An. albimanus mosquitoes were infected out of 450 examined. The one A. t. trivirgatus monkey inoculated with this strain had very low levels of parasitemia.

Animals

Protein bound carboxyl-methyl ester as a precursor of methanol formation during oxidation of dimethylnitrosamine in vitro.

Protein modification with dimethylnitrosamine was studied in vitro in the presence of hamster liver microsomal fraction. Incorporation of radioactive methyl groups from dimethylnitrosamine into the exogenously added protein was dependent on the microsomal mixed function oxidase system. The methylation yielded chemically labile and stable products. The former was completely hydrolyzed by the mild alkaline treatment, pH 7.4, 100 degrees C, for 5 min and the hydrolytic product was identified as methanol indicating that the activated methyl groups from dimethylnitrosamine were incorporated into a protein as a carboxyl-methyl ester. Thus, it is suggested that methanol, recovered as one of the products during the biodegradation of dimethylnitrosamine [8], is derived, at least in part, from protein carboxyl-methyl ester which is unstable under physiological conditions.

Animals

Studies on the Santa Lucia (El Salvador) strain of Plasmodium falciparum in Aotus trivirgatus monkeys.

The Santa Lucia strain of Plasmodium falciparum was isolated from El Salvador, Central America, and established in Aotus trivirgatus monkeys. Transmission from monkey to monkey via the bites of infected Anopheles freeborni, A. maculatus, and A, albimanus mosquitoes was obtained in 20 of 27 attempts. Prepatent periods in the monkeys ranged from 17 to 46 days with a mean of 24.3 days. Parasitemias and mortality were higher following sporozoite inoculation into animals which had been previously infected with P. vivax than in those with no previous malaria experience. Monkeys previously infected with P. vivax and P. cynomolgi had lower maximum parasitemias than those previously infected with P. vivax only.

Animals

Reduced antibody-dependent cell-mediated cytotoxicity in systemic lupus erythematosus.

The peripheral blood mononuclear cells from twenty-three patients with SLE were studied. They showed a reduction in antibody-dependent cell-mediated cytotoxicity. This reduction was significantly related to disease activity. No correlations were found with other clinical features. Some of the possible explanations for this finding are discussed.

Adult

The use of exchange transfusions: a potentially useful adjunct in the treatment of fulminant falciparum malaria.

Fulminant falciparum malaria with greater than 500,000/mm3 parasites in the peripheral blood portends a poor prognosis. We recently managed a patient who had greater than 1.2 million/mm3 parasitized erythrocytes in her peripheral blood, following initially inadequate antimalarial therapy, with exchange transfusion in addition to conventional chemotherapy. This patient recovered from her disease despite severe cerebral involvement and acute failure. We feel that exchange transfusion was a useful adjunct and should be considered in patients with life threatening falciparum malaria when conventional measures fail to control the disease.

Adult