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)

Gangliosides are known to be suitable targets for immune attack against cancer but they are poorly immunogenic. Active immunization with ganglioside/BCG or liposome vaccines results in moderate titer IgM antibody responses of short duration. Covalent attachment of poorly immunogenic antigens to immunogenic proteins is a potent method for inducing an IgG antibody response. GD3, a dominant ganglioside on malignant melanoma, was modified by ozone cleavage of the double bond in the ceramide backbone, an aldehyde group introduced and used for coupling via reductive amination to epsilon-amino-lysyl groups of proteins. Utilizing this method, GD3 conjugates were constructed with: 1. Synthetic multiple antigenic peptide (MAP) constructs expressing 4 repeats of a malaria T-cell epitope; 2. Outer membrane proteins (OMP) of Neisseria meningitidis; 3. Cationized bovine serum albumin; 4. Keyhole limpet hemocyanin (KLH); and 5. Polylysine. In addition, conjugates containing only the GD3 oligosaccharide were synthesized. All constructs were tested for antigenicity using anti-GD3 antibody R24, and for immunogenicity in mice. Serum antibody levels were analyzed by ELISA and immune thin-layer chromatography. Results in the mouse show a significant improvement in the IgM antibody response and a consistent IgG response against GD3 using GD3-KLH conjugates. Other carrier proteins and the use of GD3 oligosaccharide were significantly less effective. If improved immunogenicity and clinical benefit with conjugate vaccines can be demonstrated in patients with melanoma, this approach may be applicable to patients with other tumors of neuroectodermal origin, including gliomas, glioblastomas, astrocytomas, and neuroblastomas.
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PMID:Ganglioside conjugate vaccines. Immunotherapy against tumors of neuroectodermal origin. 808 40

Control of falciparum malaria has become almost impossible in many areas due to the development of resistance to chloroquine and other antimalarial drugs. Verapamil and a number of unrelated compounds which chemosensitise multi-drug resistant cancer cells also enhance chloroquine susceptibility in Plasmodium falciparum. Chloroquine is accumulated to lower levels in resistant plasmodia, hence the reversal of chloroquine resistance has been attributed to the ability of chemosensitising agents to increase the amount of chloroquine accumulated by the resistant parasite. We have conducted a detailed examination of the effect of verapamil on chloroquine sensitivity and its relationship to chloroquine accumulation. The ability of verapamil to increase steady-state chloroquine accumulation was found to be totally insufficient to explain the increase in chloroquine sensitivity caused by the drug. In contrast, when chloroquine accumulation was increased by raising the pH gradient, the corresponding shifts in sensitivity to chloroquine could be accurately predicted. These results were confirmed with other classes of chemosensitisers and we conclude that an alternative mechanistic explanation is required to completely explain the reversal of chloroquine resistance in P. falciparum.
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PMID:Relationship of global chloroquine transport and reversal of resistance in Plasmodium falciparum. 818 26

The pteridine derivative BIBW-22 (4-[N-(2-hydroxy-2-methyl-propyl)-ethanolamino]-2,7-bis(cis-2,6-di methyl-morpholino)-6-phenylpteridine), which had been developed for the treatment of multidrug-resistant cancer and binds to P-glycoprotein, was tested against chloroquine resistant Plasmodium falciparum strains in culture. Based on the result that BIBW-22 enhanced rather than lowered chloroquine resistance in vitro, it is concluded that chloroquine resistance in malaria parasites may not be mechanistically linked to the multidrug-resistant phenotype of chloroquine resistant P. falciparum.
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PMID:Chloroquine resistance in Plasmodium falciparum is not reversed by BIBW-22, a compound reversing the multidrug resistance phenotype in mammalian cancer cells. 824 Mar 91

Resistance to quinoline containing drugs, particularly chloroquine (CQ), is a major impediment to the successful chemotherapy and prophylaxis of malaria. CQ-resistant parasites fail to accumulate as much drug as their sensitive counterparts and two major hypotheses have been proposed to account for this phenomenon. CQ-resistant parasites are thought to maintain lower intracellular drug levels by means of an active efflux system, similar to that found in multi-drug resistant cancer cells, despite major differences in both the genetic and biochemical manifestations of drug resistance in the two cell types. Alternatively, CQ-resistance could be linked to a defective CQ uptake mechanism, possibly an impaired acidification process in the food vacuole of the resistant parasite. These two theories are discussed in detail in the following review. The potential of pharmacological intervention to override these resistance mechanisms is also discussed.
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PMID:Malaria chemotherapy: resistance to quinoline containing drugs in Plasmodium falciparum. 824 75

The use of reversing agents to overcome drug resistance is a potential new treatment strategy for both malaria and cancer. Laboratory studies have raised questions about the safety of this therapeutic approach, but data in humans are lacking. We therefore assessed the toxic potential of reversing agent therapy in Thai patients receiving quinine (17 mg/kg given over 4.5 hr) for falciparum malaria by serial measurements of the QTc interval, an electrocardiographic (ECG) marker of the effect of quinine. Six patients were randomly assigned to receive intravenous quinine alone while another six received one intramuscular injection of 12.5 mg of the reversing agent prochlorperazine (PC; compazine, stemetil) 2.5 hr after the quinine infusion had begun. Compared with baseline values at 2.5 hr, there was prolongation of the QTc interval 30, 60, 90, and 120 min after PC was injected (P < 0.05) but no further lengthening with quinine alone (P > 0.2). Prochlorperazine alone did not lengthen the QTc interval in six healthy volunteers. Neither total nor free quinine plasma levels increased after PC was injected, suggesting that ECG changes may have been due to PC-induced intracellular accumulation of quinine. Although only minor quinine ECG effects were amplified by the reversing agent PC in this study, resistance-reversing therapy could potentiate more serious drug effects. The possibility that more serious toxic effects could be produced by this therapeutic approach should be investigated further.
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PMID:Amplification of quinine cardiac effects by the resistance-reversing agent prochlorperazine in falciparum malaria. 825 Jan 6

Increasing numbers of immunocompromised people are travelling abroad to areas where the risks of some infections are increased. HIV positive people respond reasonably well to most vaccines when asymptomatic but response is less predictable when symptomatic disease is present. Generally, live vaccines should be avoided in all stages of HIV disease. Patients with anatomic or functional asplenia are at particular risk of severe sepsis due to encapsulated bacteria and from malaria. They should be immunised against the pneumococcus, meningococcus, and haemophilus and should avoid travel to areas where the probability of malaria transmission is high. Patients receiving cancer chemotherapy or transplant recipients on long-term immunosuppression should avoid live virus vaccines but may benefit from bacterial polysaccharide vaccines such as the pneumococcal vaccine. All patients with potentially impaired immunity should be assessed on an individual basis in terms of the risks and benefits involved in travel and available prophylactic measures. Immunisations useful in their native regions can be reviewed at the same time. Such travellers should carry a physician's letter and contact address in case of medical problems encountered abroad.
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PMID:The immunocompromised traveller. 833

The author is a General Practitioner who worked at the Chogoria Hospital on the eastern slopes of Mount Kenya over the period 1984-86. The rural hospital of 350 beds has an outpatient facility and a large community health department which runs 30 outlying dispensaries. 6 doctors complement a total staff of about 300 Kenyans. The author served as the Director of the community health department in 1985 and 1986. He has since returned to work at the hospital and describes changes which seem to have taken place during his 5-year absence. Over the duration, the population of Nairobi seems to have grown and become more active. Schools are burgeoning with children and the growing population is exercising even greater pressure upon available public services. The community health department's outreach efforts to distribute contraceptives has, however, helped reduce the rate of population growth. Sections briefly describe conditions with malaria, HIV, mycobacteria, women's health, anaesthesia, surgery, and pediatrics. In general, severe infections diseases remain problematic; degenerative diseases are a relative rarity; and oesophageal, stomach, and liver cancers are common, while colonic cancer is unknown.
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PMID:Other people's practices. Kenya. 833 85

Adjuvant research has improved the ability of biotechnology to generate novel vaccines. Numerous strategies for enhancing the immunogenicity of synthetic peptides and proteins have been identified. This overview focuses on adjuvant development and vaccine delivery systems that provide new tools for amplifying the effectiveness of ongoing malaria and AIDS vaccine development programs. In addition, some of the complex challenges and issues that have become associated with the delivery of modern vaccines in man are outlined. As adjuvant research continues to open new opportunities in vaccine development, there is renewed expectation that further generations of safe and potent vaccines will be possible against a broad spectrum of infectious agents and cancer.
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PMID:Novel adjuvant strategies for experimental malaria and AIDS vaccines. 836 43

Epstein-Barr virus (EBV) type 2 is considered to be a much less potent transformer of lymphocytes than type 1. However, type-2 EBV may be involved in the pathogenesis of non-Hodgkin's lymphomas (NHLs) arising in immunocompromised patients, i.e., subjects with malaria or HIV-1 infection. To determine whether type-2 EBV may also play a role in Hodgkin's disease (HD) developing in immunocompromised patients, we characterized EBV subtypes in EBV-positive HD samples from 10 HIV-1-positive patients as well as from a control population of 24 HIV-1-negative patients. Type-2 EBV was detected in 5/10 HD samples from the HIV-1-positive group (1 case showed concomitant type-1 EBV positivity), but only in 1/20 HD samples from the HIV-1-negative group, indicating that, during HIV-1-induced immunodepression, type-2 EBV may be pathogenetically involved also in HD, as previously reported for HIV-associated NHLs.
Int J Cancer 1993 Jul 30
PMID:Subtypes of Epstein-Barr virus in HIV-1-associated and HIV-1-unrelated Hodgkin's disease cases. 839 80

In a study of the disease pattern of the elderly in Rwanda, all patients aged 60 or more, hospitalized in a one-year period at the Medical Department, University Hospital, Butare, were examined prospectively. One hundred and ninety-two patients were included; most were subsistence farmers having a mainly vegetarian diet and living in large families. Infections (37.5% of the patients) and liver cirrhosis (31.8%) were the problems most frequently encountered. Primary hepatocellular cancer was diagnosed in 5.7% of the patients and was the most frequent malignancy. The hospitalized elderly occupied 17.5% of the available beds in the Medical Department. Their disease pattern was different from that of younger patients, making heavier demands on the medical resources. Malaria and upper intestinal inflammation were less frequent in the elderly; liver cirrhosis, primary hepatocellular cancer, pneumonia, prostatic cancer, cardiovascular pathology, chronic renal pathology and chronic lung disease were more prevalent. Several age-related conditions frequently observed in industrialized countries (e.g. coronary heart disease, stroke, gallstones, renal cysts, dementia) were rare. The study thus illustrates the concept of 'secondary aging': to the primary changes induced by the aging process, additional alterations are added which depend upon the environment and the lifestyle, resulting in a varying disease pattern. Health policies thus must take into account that the demographic transition in developing countries may result in a pattern of diseases different from that seen in industrialized countries; care must be taken when transposing data obtained from elderly populations in industrialized countries.
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PMID:The disease pattern of elderly medical patients in Rwanda, central Africa. 841 4


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