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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.
J Mol Med (Berl) 2001
PMID:Natural zeolite clinoptilolite: new adjuvant in anticancer therapy. 1143 24

Enteropathogenic Escherichia coli (EPEC) is a major cause of infantile diarrhoea in a number of developing countries and is the prototype of pathogenic bacteria that cause attaching and effacing (A/E) intestinal lesions. A chromosomal pathogenicity island, termed the locus of enterocyte effacement (LEE), contains all the genes necessary for the A/E phenotype as well as genes for a type III secretion system and intimate adhesion. Genes in the LEE and genes involved in the synthesis of bundle-forming pili (BFP) are positively regulated by the plasmid-encoded regulator (Per) and comprise the per regulon. In order to identify factors that control the per regulon, we screened an EPEC genomic library for clones that modulate the expression of per. A plasmid clone that decreased the expression of per was isolated using a lacZ reporter gene fused to the per promoter. Subcloning revealed that YhiX, a putative AraC/XylR family transcriptional regulator, was the effector of per repression. Through downregulation of per, a plasmid overproducing YhiX reduced the synthesis of intimin, BfpA, Tir, and CesT, factors important for EPEC virulence. yhiX is located downstream of gadA, which encodes glutamate decarboxylase, an enzyme involved in acid resistance of E. coli. YhiX was found to be an activator of gadA, and the cloned yhiX gene increased production of glutamate decarboxylases (GAD) and activated the transcription of the gadA and gadB promoters. Therefore, yhiX was renamed gadX. Analysis of a gadX mutant grown in the different culture media with acidic and alkaline pH showed that regulation of perA, gadA and gadB by GadX was altered by the external pH and the culture media condition. Under conditions in which EPEC infects cultured epithelial cells, GadX negatively regulated perA expression, and the derepression in the gadX mutant increased translocation of Tir into epithelial cells relative to wild-type EPEC. DNA mobility shift experiments showed that purified GadX protein bound to the perA, gadA and gadB promoter regions in vitro, indicating that GadX is a transcriptional regulator of these genes. On the basis of these results, we propose that GadX may be involved in the appropriate expression of genes required for acid resistance and virulence of EPEC. Our data are consistent with a model in which environmental changes resulting from passage from the stomach to the proximal small intestine induce the functional effect of GadX on per and GAD expression in order to prevent inappropriate expression of the products of these two systems.
Mol Microbiol 2001 Sep
PMID:An activator of glutamate decarboxylase genes regulates the expression of enteropathogenic Escherichia coli virulence genes through control of the plasmid-encoded regulator, Per. 1155 93

Increased whole-body proteolysis with muscle protein net degradation has been suggested as one of the causes of weight loss in patients infected with human immunodeficiency virus (HIV). We studied the exchange rates of amino acids and energy substrates across the lower extremity in 16 HIV patients and 16 age-matched controls with similar body cell mass. The patients had either opportunistic infections or chronic diarrhea but no signs of clinical malnutrition. The following findings were obtained in the HIV patients: an augmented peripheral net release of arginine and lysine; an increase in both the negative arterial-venous difference and the efflux of the nitrogen contained in nonmetabolized amino acids; diminished export of 3-methylhistidine; lowered plasma and erythrocyte amino acid concentrations; reduced output of glycerol and furthermore; and neither a net release nor a net uptake of free fatty acids. The findings concerning nitrogen metabolism support the hypothesis that, in the presence of a reduction in protein breakdown, peripheral protein synthesis is severely depressed, making a slow protein wasting process likely to occur. The balances of glycerol and free fatty acids are due not only to the leg tissues but perhaps also in part to increased net retention of these substrates by skeletal muscle.
J Mol Med (Berl) 2001 Nov
PMID:Flux of amino acids and energy substrates across the leg in weight-stable HIV-infected patients with acute opportunistic infections: indication of a slow protein wasting process. 1171 71

Toxigenic Clostridium difficile is the etiologic agent of C. difficile-associated diarrhoea (CDAD), the most common cause of hospital-acquired infectious diarrhoea. The genes tcdA and tcdB, which encode for the toxin A and B proteins, are part of the pathogenicity locus (PaLoc) of toxigenic C. difficile. Genetic and virulence studies at the molecular level in C. difficile have been hindered by the lack of techniques for DNA manipulation in this species. We describe the electroporation of DNA fragments from a toxigenic isolate into a non-toxigenic strain of C. difficile. Using previously described methods of electroporation into Clostridium spp., the complete toxin B gene and polymerase chain reaction (PCR) fragments of the PaLoc were cloned and electroporated into a non-toxigenic strain of C. difficile. The resulting transformed clones were screened for the introduced gene fragments by PCR, which confirmed their presence. This is the first description of introduction of DNA into C. difficile by electroporation.
Mol Cell Probes 2001 Oct
PMID:Electroporation of DNA sequences from the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile into a non-toxigenic strain. 1173 2

Cryptosporidium parvum is an intracellular protozoan parasite causing intestinal malabsorption and diarrhea in humans. The infection is usually self-limiting, although persistent cryptosporidosis is observed in immunocompromised and malnourished individuals. As with other Apicomplexa, the life cycle of Cryptosporidium is thought to comprise a sexual phase, during which a motile microgamont fuses with a sessile macrogamont. The four sporozoites found within each oocyst (the infectious form excreted in the feces) are thought to be the product of a meiotic division taking place immediately following fertilization, but the existence of a meiotic cycle in this genus has not been tested experimentally. To substantiate the occurrence of meiotic recombination in this species, we performed a genetic cross between two distinct isolates of C. parvum co-infected in INF-gamma knockout mice. We found that mixed infections produced recombinant progeny characterized by multilocus genotypes comprising alleles inherited from each parental line. This observation represents the first demonstration of sexual recombination in this pathogen. Together with the occurrence of genetically heterogeneous infections, this finding suggests that outcrossing between genotypes may occur in nature. Experimental crosses among Cryptosporidium populations will facilitate mapping of clinically relevant genes, the delineation of Cryptosporidium species, and defining the taxonomical status of C. parvum subtypes and host-specific genotypes.
Mol Biochem Parasitol 2002 Jan
PMID:Experimental evidence for genetic recombination in the opportunistic pathogen Cryptosporidium parvum. 1175 86

Sierra Leone ranks at the bottom of the global World Bank Development Index based on multiple health and economic indices and lacks the resources to purchase HIV diagnostic kits. Our study has defined some common clinical features presenting HIV infection that could form clinical algorithms for the diagnosis and recognition of HIV infection by health workers in Sierra Leone. In a private clinic in Freetown, Sierra Leone, West Africa, 106 out of a total of 124 patients presenting with various symptoms and strong clinical suspicion of HIV infection within a two-year period (1999 and 2000), were deemed positive by two different ELISA tests. The prevalence of HIV infection seen in this private clinic in Freetown in 2000 was 14.89% as compared to 9.25% in 1999. The positive predictive value of our clinical diagnosis of HIV/AIDS infection was 85.5%. The male:female ratio of the patients in our series was 1:1.9, with a mean age of 39 years for males and 28 years for females. HIV infection was found in a cross-section of the population that we examined. Heterosexual contact appeared to be the major mode of transmission amongst our patients and there seemed to be a significant epidemiological risk of HIV infection amongst those who traveled to other countries in the West African sub region. Common clinical features in decreasing frequency were fever (92.5%), weight loss (84.1%), lymphadenopathy (78.3%), cough (48.1%), diarrhea (37.7%), candidiasis (32.1%) and body aches (30.1%).
Cell Mol Biol (Noisy-le-grand) 2001 Nov
PMID:The usefulness of defined clinical features in the diagnosis of HIV/AIDS infection in Sierra Leone. 1183 63

Toxigenic Clostridium difficile is the etiologic agent of C. difficile-associated diarrhea (CDAD), the most common cause of nosocomial diarrhea. Cross-infection between patients and transmission through the environment and medical personnel are important factors in the acquisition of CDAD. In order to understand differences in epidemiology and pathogenesis, a number of typing schemes have been developed. We will review the typing methods used to study the epidemiology of C. difficile infections and how they have evolved from a phenotypic identification to state of the art molecular methods, detecting genetic polymorphisms among strains. These molecular methods include PCR-based methods (arbitrarily primed-PCR [AP-PCR] and PCR ribotyping), restriction endonuclease analysis (REA) and pulse field gel electrophoresis (PFGE). The application, usefulness and feasibility of these methods are compared and discussed. Finally, the role of genomics as a tool to investigate CDAD is introduced.
Expert Rev Mol Diagn 2001 May
PMID:Molecular typing methods for the epidemiological identification of Clostridium difficile strains. 1190 1

Whipple's disease is a systemic infection, caused by the bacterium Tropheryma whipplei, with protean clinical manifestations characterized by fever, weight loss, diarrhea, polyarthritis, skin hyperpigmentation and adenopathy. For a long time, due to the inability to culture the causative organism, diagnosis was based on histologic examination of infected tissues, usually duodenal biopsies, which revealed diastase-resistant periodic acid-Schiff-positive staining. Now, PCR of various tissues or fluid is emerging as a way to diagnose Whipple's disease. However, the presence of T. whipplei DNA in saliva, gastric juice or duodenal biopsies of healthy individuals has led to questions regarding the specificity of the molecular techniques involved. After a series of failures, stable culture was achieved in 2000. Subsequently, the generation of rabbit polyclonal antibodies has led to the detection of the bacterium in tissues by immunohistology. However, culture and immunohistology are very recent techniques and are not yet widely used. Propagation of the bacterium will lead to extensive molecular knowledge of T. whipplei, which will help in the diagnosis and understanding of the epidemiology and pathogenicity of Whipple's disease.
Expert Rev Mol Diagn 2001 Sep
PMID:Molecular techniques in Whipple's disease. 1190 35

Guanylyl cyclase C (GC-C) was found to function as the principal receptor for heat-stable enterotoxins (STa), major causative factors in E. coli-induced secretory diarrhea. GC-C is enriched in intestinal epithelium, but was also detected in other epithelial tissues. The enzyme belongs to the family of receptor guanylyl cyclases, and consists of an extracellular receptor domain, a single transmembrane domain, a kinase homology domain, and a catalytic domain. GC-C is modified by N-linked glycosylation and, at least in the small intestine, by proteolysis, resulting in a STa receptor that is coupled non-covalently to the intracellular domain. So far two endogenous ligands of mammalian GC-C have been identified i.e. the small cysteine-rich peptides guanylin and uroguanylin. The guanylins are released in an auto- or paracrine fashion into the intestinal lumen but may also function as endocrine hormones in gut-kidney communication and as regulators of ion transport in extra-intestinal epithelia. They are thought to activate GC-C by inducing a conformational change in the extracellular portion of the homotrimeric GC-C complex, which allows two of the three intracellular catalytic domains to dimerize and form two active catalytic clefts. In the intestine, activation of GC-C results in a dual action: stimulation of Cl and HCO3 secretion, through the opening of apical CFTR Cl channels; and inhibition of Na absorption, through blockade of an apical Na/H exchanger. The principal effector of the GC-C effect on ion transport is cGMP dependent protein kinase type II, which together with GC-C and the ion transporters, may form a supramolecular complex at the apical border of epithelial cells.
Mol Cell Biochem 2002 Jan
PMID:Structure and function of the heat-stable enterotoxin receptor/guanylyl cyclase C. 1195 98

Enteropathogenic Escherichia coli (EPEC) is a major cause of paediatric diarrhoea and a model for the family of attaching and effacing (A/E) pathogens. A/E pathogens encode a type III secretion system to transfer effector proteins into host cells. The EPEC Tir effector protein acts as a receptor for the bacterial surface protein intimin and is involved in the formation of Cdc42-independent, actin-rich pedestal structures beneath the adhered bacteria. In this paper, we demonstrate that EPEC binding to HeLa cells also induces Tir-independent, cytoskeletal rearrangement evidenced by the early, transient formation of filopodia-like structures at sites of infection. Filopodia formation is dependent on expression of the EPEC Map effector molecule - a protein that targets mitochondria and induces their dysfunction. We show that Map-induced filopodia formation is independent of mitochondrial targeting and is abolished by cellular expression of the Cdc42 inhibitory WASP-CRIB domain, demonstrating that Map has at least two distinct functions in host cells. The transient nature of the filopodia is related to an ability of EPEC to downregulate Map-induced cell signalling that, like pedestal formation, was dependent on both Tir and intimin proteins. The ability of Tir to downregulate filopodia was impaired by disrupting a putative GTPase-activating protein (GAP) motif, suggesting that Tir may possess such a function, with its interaction with intimin triggering this activity. Furthermore, we also found that Map-induced cell signalling inhibits pedestal formation, revealing that the cellular effects of Tir and Map must be co-ordinately regulated during infection. Possible implications of the multifunctional nature of EPEC effector molecules in pathogenesis are discussed.
Mol Microbiol 2002 May
PMID:Co-ordinate regulation of distinct host cell signalling pathways by multifunctional enteropathogenic Escherichia coli effector molecules. 1204 91


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