Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The circumsporozoite (CS) protein of malaria parasites is a major surface protein of the sporozoite stage. In the process of investigating the immunogenicity of this protein in the Plasmodium vivax complex, we found that a monoclonal antibody (mAb) directed against the CS protein of isolates of P. vivax recognizes New World monkey hepatocytes and human hepatoma cells HepG2A16 in Western blot and by immunoelectron microscopy. The mAb NVS3 binds to the amino acid sequence AGDR, which is also shared with the alpha 3 domain of the human and primate major histocompatibility complex class I. In addition, in vitro experiments suggest that the binding of the mAb NVS3 to hepatocytes from Saimiri monkey enhances the invasion or development of malaria sporozoites. These results form the basis for investigating the relationships between parasite surface proteins and host-cell receptors.
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PMID:A monoclonal antibody directed against the sporozoite stage of Plasmodium vivax binds to liver parenchymal cells. 142 5

Antibodies to Plasmodium falciparum sporozoites were detected in children aged 6 months to 9 years, and in adults, in a holendemic village near Yekepa, Liberia, by enzyme linked immunosorbent assay (ELISA) using the recombinant circumsporozoite protein R32tet32 or by inhibition of sporozoite invasion (ISI) of hepatoma cells. Both assays were significantly correlated with each other and showed that anti-sporozoite antibodies increase with age. ISI was more sensitive than ELISA and demonstrated significantly increased anti-sporozoite antibodies at age 5-6 years, when young children show partial clinical resistance to malaria. These results suggest that anti-sporozoite antibodies, as measured by ISI, may contribute to protection against malaria.
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PMID:Age-dependent occurrence of protective anti-Plasmodium falciparum sporozoite antibodies in a holoendemic area of Liberia. 269 66

A case-control study was carried out to explore possible risk factors of primary hepatocellular carcinoma (PHC) in Taiwan. One hundred thirty-one PHC patients and 207 hospital control patients were interviewed and blood samples were collected for blood type and hepatitis B virus (HBV) infection marker tests. Eighty-three percent of the PHC patients were found to be hepatitis B surface antigen (HBsAg) positive as compared with 21.0% of the control patients with an odds ratio (OR) of 21.5. Hepatitis B e antigen (HBeAg) positive status increased the risk of PHC. No significant association was observed between erythrocyte genetic markers and PHC, except c of the Rh system, which was significantly lower in the PHC cases. As compared with the control patients, the PHC patients had a higher proportion with a history of liver diseases and more siblings affected with liver diseases. However, the variables such as cigarette smoking, alcohol drinking, peanut consumption, frequent intake of raw fish, heart diseases, peptic ulcer, malaria, hypertension, diabetes, color blindness, G-6-PD deficiency, surgical operation, blood transfusion, and liver diseases of parents and children were not found to be associated with PHC.
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PMID:A case-control study of primary hepatocellular carcinoma in Taiwan. 284 88

The circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum may be the most promising target for the development of a malaria vaccine. In this study, proteins composed of 16, 32, or 48 tandem copies of a tetrapeptide repeating sequence found in the CS protein were efficiently expressed in the bacterium Escherichia coli. When injected into mice, these recombinant products resulted in the production of high titers of antibodies that reacted with the authentic CS protein on live sporozoites and blocked sporozoite invasion of human hepatoma cells in vitro. These CS protein derivatives are therefore candidates for a human malaria vaccine.
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PMID:Expression of Plasmodium falciparum circumsporozoite proteins in Escherichia coli for potential use in a human malaria vaccine. 298 25

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of Plasmodium falciparum were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.
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PMID:Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum. 298 26

DL-alpha-difluoromethylornithine and DL-alpha-monofluoromethyldehydroornithine methyl ester, inhibitors of ornithine decarboxylase, blocked exoerythrocytic schizogony of Plasmodium berghei in mice and in cultured human hepatoma cells. These effects were reversed by exogenous administration of the polyamine, spermidine. The antimalarial drug, primaquine, the side chain of which is structurally analogous to a natural polyamine, did not enhance the activity of alpha-difluoromethylornithine or alpha-monofluoromethyldehydroornithine methyl ester. These results extend previous observations that polyamines influence the malaria parasite's schizogony outside the red blood cell but not within it.
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PMID:Plasmodium berghei: inhibitors of ornithine decarboxylase block exoerythrocytic schizogony. 299 Sep 89

Several lines of evidence have emphasized the importance of the malaria circumsporozoite (CS) protein as a factor in sporozoite invasion of the hepatocyte; however, the specific mechanism of cell recognition and invasion has not been explained. In this study we present evidence that a highly conserved region of the CS protein immediately adjacent to the repeat region, the N1 region, specifically recognizes receptors on the human hepatoma cell line HepG2-A16 under conditions where invasion by sporozoites can occur. Peptides consisting of sequences from the repeat region or of the more extensive N2 region showed no such specific association. Antibody against the N1 peptide could inhibit sporozoite invasion in vitro. Covalent coupling of radiolabeled N1 peptide to HepG2-A16 cells identified two hepatic cell proteins to be closely associated with the peptide. We suggest that these proteins could act as receptors or mediators, via the N1 region of the CS protein, for the P. falciparum sporozoite in the process of invasion of the hepatocyte.
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PMID:Synthetic peptides from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium knowlesi recognize the human hepatoma cell line HepG2-A16 in vitro. 302 19

A specific DNA probe was used to study the effect of recombinant rat, mouse, and human gamma-interferon (gamma-IFN) on the course of sporozoite-induced malaria infections. In mice and rats infected with sporozoites of Plasmodium berghei, mouse and rat gamma-IFN's strongly inhibited the development of the exoerythrocytic forms in the liver liver cells of the hosts, but not the development of the erythrocytic stages. The degree of inhibition of the exoerythrocytic forms was proportional to the dose of gamma-IFN administered, but was independent of the number of sporozoites used for challenge. A 30 percent reduction in the development of exoerythrocytic forms in rat liver was achieved when 150 units (about 15 nanograms of protein) of rat gamma-IFN were injected a few hours before sporozoite challenge; the reduction was 90 percent or more with higher doses of gamma-IFN. The effect was less pronounced if the gamma-IFN was administered 18 hours before or a few hours after challenge. Human gamma-IFN also diminished the parasitemia in chimpanzees infected with sporozoites of the human malaria parasite Plasmodium vivax. The target of gamma-IFN activity may be the infected hepatocytes themselves, as shown by in vitro experiments in which small doses of the human lymphokine inhibited the development of exoerythrocytic forms of Plasmodium berghei in a human hepatoma cell line. These results suggest that immunologically induced interferon may be involved in controlling malaria infection under natural conditions.
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PMID:Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. 308 18

In endemic areas, malaria-infected mosquitoes may feed upon humans who possess antibodies against malaria sporozoites. Therefore, we examined the effect that ingested anti-sporozoite antibodies have upon Plasmodium falciparum sporogony within Anopheles stephensi mosquitoes. Anti-sporozoite antibodies (IgG) traversed the midgut into the hemocoel within 3 hr following ingestion and, depending upon the titer, persisted for 6-24 hr. When fed to infected A. stephensi at 12 days postinfection (p.i.), anti-sporozoite antibodies bound to sporozoites in the hemocoel, but not to sporozoites residing in the salivary glands of the same mosquitoes. Anti-sporozoite antibodies also bound to developing oocysts when fed to infected A. stephensi at 5 days p.i. Oocysts in mosquitoes that had been fed anti-sporozoite antibodies on Day 5 p.i. produced significantly more sporozoites than did oocysts in nonimmune-fed (Day 5 p.i.) mosquitoes. In addition, the sporozoites from Day 5 immune-fed mosquitoes were significantly more infective to cultured human hepatoma cells than were sporozoites from nonimmune-fed controls. Use of hetereologous immune feedings at Day 5 p.i. did not result in an enhanced production of sporozoites, suggesting that enhancement is related to the specificity of the antibody and is not merely a nutritional effect.
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PMID:Plasmodium falciparum: ingested anti-sporozoite antibodies affect sporogony in Anopheles stephensi mosquitoes. 329 24

Ethiopia is a country of 45 million people in northeast Africa. With a stagnant, agriculture-based economy and a per capita gross national product of $110 in 1984, it is one of the world's poorest nations. 70% of the children are mildly to severely malnourished, and 25.7% of children born alive die before the age of 5. Life expectancy is 41 years. The population is growing at the rate of 2.9%/year, but only 2% of the people use birth control. After the 1974 revolution, the socialist government nationalized land and created 20,000 peasant associations and kebeles (urban dwellers' associations), which are the units of local government. The government has set ambitious goals for development in all sectors, including health, but famine, near famine, forced resettlement programs, and civil war have prevented any real progress from being made. The government's approach to health care is based on an emphasis on primary health care and expansion of rural health services, but the Ministry of Health is allocated only 3.5% of the national budget. Ethiopia has 3 medical schools -- at Addis Ababa, Gondar, and the Jimma Institute of Health Sciences. Physicians are government employees but also engage in private practice. A major problem is that a large proportion of medical graduates emigrate. Ethiopia has 87 hospitals with 11,296 beds, which comes to 1 bed per 3734 people. There are 1949 health stations and 141 health centers, but many have no physician, and attrition among health workers is high due to lack of ministerial support. Health care is often dispensed legally or illegally by pharmacists. Overall, there is 1 physician for 57,876 people, but in the southwest and west central Ethiopia 1 physician serves between 200,000 and 300,000 people. In rural areas, where 90% of the population lives, 85% live at least 3 days by foot from a rural health unit. Immunization of 1-year olds against tuberculosis, diphtheria-pertussis-tetanus, poliomyelitis, and measles is 11, 6, 6, and 12% respectively. Infectious diseases dominate the medical scene in Ethiopia. In 1984, tuberculosis accounted for 11.2% of hospital admissions and 12.2% of deaths. The leading cause of childhood mortality in 1984 was diarrhea (45%). Malaria, trypanosomiasis, schistosomiasis, leishmaniasis, and meningococcal meningitis are endemic. Intestinal parasitism is rampant, and the nationwide prevalence of leprosy is 3/1000. Venereal diseases were the 9th most common cause of hospital outpatient visits in 1984, but AIDS is rare. The leading noninfectious diseases are rheumatic and syphilitic heart disease, hypertension, diabetes mellitus, hepatoma, and elephantiasis. Ethiopia has the highest number of cases of nonfilarial elephantiasis -- an estimated 350,000 cases -- in the world. Aside from a large influx of money, the most necessary changes to improve the health system are lowering the salaries of doctors and nurses, reorienting physician training toward primary health care, increasing the quality of existing health services, more efficient management, and better coordination between the Ministry of Health and the voluntary organizations.
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PMID:Health and medical care in Ethiopia. 271 Jan 85


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