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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smooth pursuit eye movement dysfunction is a psychophysiological and genetic marker for schizophrenia seen in 50-80% of patients and in about 40% of their first-degree relatives. In this study, we qualitatively assessed the smooth pursuit eye movements of 33 psychiatric patients (including 32 diagnosed with schizophrenia) and 30 control subjects in the Port Moresby area of Papua New Guinea. Brief case histories of each patient were also reviewed. Using a conservative estimate of smooth pursuit dysfunction, we found that 42% of the psychiatric patients had the marker, compared to 10% of the controls. Specific eye movement abnormalities were also much more common among the patients. A patient who had previously 'run amok' and another who was a cargo cultist had smooth pursuit dysfunction; a patient whose psychotic symptoms may have been due to cerebral malaria did not have the marker. Highland and coastal patients were similar in their expression of the marker. This study, the first of its kind done outside of large-scale, urbanized societies, provides further evidence for a common biological basis for schizophrenia in biologically and culturally diverse populations worldwide.
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PMID:Eye movements and schizophrenia in Papua New Guinea: qualitative analyses with case histories. 959 73

This study was undertaken to attempt to identify correlations between microsporidial seroprevalence data in man, clinical diseases and groups of people at the risk of HIV/AIDS infection. Groups of patients were selected according to the predilection of members of the genus Encephalitozoon for nervous and kidney tissue. Female prostitutes and alcohol and intravenous drug abusers were selected as groups at risk of HIV/AIDS infections. A total of 401 samples of human sera were examined for the presence of antimicrosporidial IgG antibodies by ELISA test with a titre of 600 considered borderline positivity. The highest occurrence of antimicrosporidial antibodies was found in the groups of alcohol abusers (16% from 43 patients), intravenous drug abusers (11% from 9 patients) and prostitutes (10% from 80 women) for E. cuniculi antigen and in the groups of psychiatric patients (14% from 44 patients), malaria patients (11% from 38 patients) and alcohol abusers (7% from 43 patients) for E. hellem antigen. The occurrence of specific antibodies of the six examined diagnostic units (glomerulonephritis chronica, pyelonephritis chronica, schizophrenia, dementia, multiple sclerosis and cerebral stroke) was statistically significant only in patients with pyelonephritis chronica and dementia (p < 0.05). No cases of microsporidial infection were found among the female prostitutes by parasitological examination, although one case of giardiasis was identified. Sera of patients with high anti-E. cuniculi and anti-E. hellem antibodies (titres in ELISA of 600 and above) were confirmed by Western blot using E. cuniculi and E. hellem polypeptides, respectively. These results suggest that the examined patients could show residual antibodies from past or latent infections.
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PMID:The serological surveillance of several groups of patients using antigens of Encephalitozoon hellem and E. cuniculi antibodies to microsporidia in patients. 968 20

Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission and play roles in many cognitive processes. They are under intense research as potential targets of drugs used to treat neurodegenerative diseases and neurological disorders such as Alzheimer's disease and schizophrenia. Invertebrate nAChRs are targets of anthelmintics as well as a major group of insecticides, the neonicotinoids. The honey bee, Apis mellifera, is one of the most beneficial insects worldwide, playing an important role in crop pollination, and is also a valuable model system for studies on social interaction, sensory processing, learning, and memory. We have used the A. mellifera genome information to characterize the complete honey bee nAChR gene family. Comparison with the fruit fly Drosophila melanogaster and the malaria mosquito Anopheles gambiae shows that the honey bee possesses the largest family of insect nAChR subunits to date (11 members). As with Drosophila and Anopheles, alternative splicing of conserved exons increases receptor diversity. Also, we show that in one honey bee nAChR subunit, six adenosine residues are targeted for RNA A-to-I editing, two of which are evolutionarily conserved in Drosophila melanogaster and Heliothis virescens orthologs, and that the extent of editing increases as the honey bee lifecycle progresses, serving to maximize receptor diversity at the adult stage. These findings on Apis mellifera enhance our understanding of nAChR functional genomics and provide a useful basis for the development of improved insecticides that spare a major beneficial insect species.
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PMID:The nicotinic acetylcholine receptor gene family of the honey bee, Apis mellifera. 1706 16

The genetic basis of complex diseases is expected to be highly heterogeneous, with complex interactions among multiple disease loci and environment factors. Due to the multi-dimensional property of interactions among large number of genetic loci, efficient statistical approach has not been well developed to handle the high-order epistatic complexity. In this article, we introduce a new approach for testing genetic epistasis in multiple loci using an entropy-based statistic for a case-only design. The entropy-based statistic asymptotically follows a chi(2) distribution. Computer simulations show that the entropy-based approach has better control of type I error and higher power compared to the standard chi(2) test. Motivated by a schizophrenia data set, we propose a method for measuring and testing the relative entropy of a clinical phenotype, through which one can test the contribution or interaction of multiple disease loci to a clinical phenotype. A sequential forward selection procedure is proposed to construct a genetic interaction network which is illustrated through a tree-based diagram. The network information clearly shows the relative importance of a set of genetic loci on a clinical phenotype. To show the utility of the new entropy-based approach, it is applied to analyze two real data sets, a schizophrenia data set and a published malaria data set. Our approach provides a fast and testable framework for genetic epistasis study in a case-only design.
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PMID:An entropy-based approach for testing genetic epistasis underlying complex diseases. 1799 8

Four of the most disabling human diseases are syphilis, malaria, schizophrenia, and manic-depressive illness. The history of the development of treatments for these seemingly unrelated disorders intersects at several points. Treatment of tertiary cerebral syphilis (general paresis) by inducing fever with malaria led to a Nobel Prize. Although attempts to synthesize quinine, a plant product effective against malaria, failed, these efforts encouraged industrial organic chemists to synthesize many useful substances, including dyes, antibiotics, and antihistamines. The aniline-derived dye methylene blue was a member of a new class of polycyclic chemicals, the phenothiazines. Efforts to modify phenothiazines to find an antimalarial agent also failed but led to novel antiemetic-sedative antihistamines, including promethazine, promazine, and eventually chlorpromazine--the first effective treatment for schizophrenia and mania. Chlorpromazine has antipsychotic and antimanic properties, and it revolutionized the therapeutics of psychotic illnesses.
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PMID:Neurosyphilis, malaria, and the discovery of antipsychotic agents. 1880 5

The breadth and scope of new information makes difficult a selection of topics to be included in a limited review of highlights of the year. Admittedly, the choices are idiosyncratic. The eight topics presented here are (1) structural and copy number variants in the human genome; (2) progress in defining genetic factors in the etiology of schizophrenia; (3) microRNAs in central nervous system development and function; (4) progress in elucidation of risk factors for complex common disorders through large scale association studies; (5) epigenetics and the epigenomic era; (6) reprogramming of somatic cell nuclei to generate pluripotent stem cells; (7) new concepts regarding factors involved in sexual differentiation; and (8) Duffy blood group antigens: new concepts, and new discoveries on the role of these antigens in malaria and HIV-AIDS.
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PMID:The year in human and medical genetics. Highlights of 2007-2008. 1915 14

Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1) the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2) some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects.
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PMID:Kynurenine pathway metabolites in humans: disease and healthy States. 2208 78

Methylene blue has been widely used since the late 19th century in biomedical research, and was the lead compound in several important clinical areas, including therapeutics for malaria and schizophrenia. The photodynamic therapy (PDT) of cancer and, more recently, of microbial infection (photodynamic antimicrobial chemotherapy (PACT)) has also employed methylene blue and its congeners, among other chemical types, due to the low human toxicities and efficient photosensitising properties of the group. However, little work has been carried out in terms of derivative and structure-activity development, most reports covering standard, commercially available compounds. This review deals with the evolution of phenothiazinium photosensitisers for both PACT and PDT use.
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PMID:The development of phenothiazinium photosensitisers. 2504 68

Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.
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PMID:Palladium-catalysed transannular C-H functionalization of alicyclic amines. 2688 89

S-Palmitoylation is a uniquely reversible and biologically important post-translational modification as it plays an essential role in a variety of cellular processes including signal transduction, protein-membrane interactions, neuronal development, lipid raft targeting, subcellular localization and apoptosis. Due to its association with the neuronal development, it plays a pivotal role in a variety of neurodegenerative diseases, mainly Alzheimer's, Schizophrenia and Huntington's disease. It is also essential for developmental life cycles and pathogenesis of Toxoplasma gondii and Plasmodium falciparum, known to cause toxoplasmosis and malaria, respectively. This depicts the strong biological significance of S-Palmitoylation, thus, the timely and accurate identification of S-palmitoylation sites is crucial. Herein, we propose a predictor for S-Palmitoylation sites in proteins namely SPalmitoylC-PseAAC by integrating the Chou's Pseudo Amino Acid Composition (PseAAC) and relative/absolute position-based features. Self-consistency testing and 10-fold cross-validation are performed to evaluate the performance of SPalmitoylC-PseAAC, using accuracy metrics. For self-consistency testing, 99.79% Acc, 99.77% Sp, 99.80% Sn and 1.00 MCC was observed, whereas, for 10-fold cross validation 97.22% Acc, 98.85% Sp, 95.80% Sn and 0.94 MCC was observed. Thus the proposed predictor can help in predicting the palmitoylation sites in an efficient and accurate way. The SPalmitoylC-PseAAC is available at (biopred.org/palm).
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PMID:SPalmitoylC-PseAAC: A sequence-based model developed via Chou's 5-steps rule and general PseAAC for identifying S-palmitoylation sites in proteins. 3059 78


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