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At least 955 records · Page 53Linked to original sources
PubMed1998

Human ARHGDIG, a GDP-dissociation inhibitor for Rho proteins: genomic structure, sequence, expression analysis, and mapping to chromosome 16p13.3.

GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activity of GTPases. We recently reported the identification of a new GDI for the Rho-related GTPases named RhoGDIgamma. This gene is now designated ARHGDIG by HUGO. Here, in a detailed analysis of tissue expression of ARHGDIG, we observe high levels in the entire brain, with regional variations. The mRNA is also present at high levels in kidney and pancreas and at moderate levels in spinal cord, stomach, and pituitary gland. In other tissues examined, the mRNA levels are very low (lung, trachea, small intestine, colon, placenta) or undetectable. RT-PCR analysis of total RNA isolated from exocrine pancreas and islets shows that the gene is expressed in both tissues. We also report the genomic structure of ARHGDIG. The gene spans over 4 kb and is organized into six exons and five introns. The upstream region lacks a canonical TATA box and contains several putative binding sites for ubiquitous and tissue-specific factors active in central nervous system development. Using FISH, we have mapped the gene to chromosome band 16p13.3. This band is rich in deletion mutants of genes involved in several human diseases, notably polycystic kidney disease, alpha-thalassemia, tuberous sclerosis, mental retardation, and cancer. The promoter structure and the chromosomal location of RhoGDIgamma suggest its importance and underscore the need for further investigation into its biology.

Base Sequence↗
PubMed1999

cDNA cloning and characterization of a human sperm antigen (SPAG6) with homology to the product of the Chlamydomonas PF16 locus.

Serum from an infertile male with high-titer anti-sperm antibodies was used to identify a novel human sperm antigen by screening of a testis expression library. The clone, initially designated Repro-SA-1 (HUGO-approved symbol SPAG6), was found to encode a sequence highly enriched in testis. The deduced amino acid sequence of the full-length cDNA revealed striking homology to the product of the Chlamydomonas reinhardtii PF16 locus, which encodes a protein localized to the central pair of the flagellar axoneme. The human gene encodes 1.8- and 2.8-kb mRNAs highly expressed in testis but not in prostate, ovary, spleen, thymus, small intestine, colon, peripheral blood leukocytes, heart, brain, placenta, liver, muscle, kidney, and pancreas. The gene was mapped to chromosome 10p11.2-p12. Antibodies raised against SPAG6 sequences localized the protein to the tails of permeabilized human sperm. Both the Chlamydomonas protein and SPAG6 contain eight contiguous armadillo repeats, which place them in a family of proteins known to mediate protein-protein interactions. The cloning of the human homologue of the Chlamydomonas PF16 locus provides a new avenue to explore the role of the axoneme central pair in human sperm function.

Algal Proteins↗
PubMed1993

Apparent rates of glutathione turnover in rat tissues.

Apparent first-order rate constants for glutathione (GSH) turnover were determined for 14 tissues in male Fischer 344 rats after intravenous injection of [35S]cysteine ([35S]Cys). Rate constants for glutathione turnover were estimated by nonlinear least-squares iterative minimization from the decrease in GSH specific activity 1-102 hr after administration of [35S]Cys. Tissue nonprotein sulfhydryl concentrations were determined by Ellman's assay and compared with GSH and Cys levels detected by high-performance liquid chromatography equipped with an electrochemical detector. Additionally, total radiolabeled [35S]GSH was determined by high-performance liquid chromatography equipped with a flow-through radioactivity detector. There were substantial differences in the apparent rates of GSH turnover between the various tissues examined. For example, both the liver and the kidney had rapid turnover rates with half-lives of 1-5 hr, while those for heart, skeletal muscle, and blood were much slower with half-lives of 68-118 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach = caecum > duodenum = small intestine = large intestine > colon > forestomach. [35S]GSH had a half-life in lung and skin of approximately 63 and 50 hr, respectively.

Animals↗
PubMed1996

Chemoprevention of lung cancer by isothiocyanates.

Naturally occurring and synthetic isothiocyanates are among the most effective chemopreventive agents known. A wide variety of isothiocyanates prevent cancer of various tissues including the rat lung, mammary gland, esophagus, liver, small intestine, colon, and bladder. Mechanistic studies have shown that the chemopreventive activity of isothiocyanates is due to favorable modification of Phase I and Phase II carcinogen metabolism, resulting in increased carcinogen excretion or detoxification and decreased carcinogen DNA interactions. In the majority of studies reported, the isothiocyanate must be present at the time of carcinogen exposure in order to observe inhibition of tumorigenesis. Our studies have focused on the naturally occurring isothiocyanates phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) as inhibitors of lung cancer. The carcinogens employed in these studies have been the major lung carcinogens in tobacco smoke- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP). Combinations of chemopreventive agents that inhibit tumorigenesis by NNK and BaP in rodents may be effective in addicted smokers. PEITC is an effective inhibitor of lung tumor induction by NNK in F-344 rats and A/J mice. BITC but not PEITC inhibits BaP induced lung tumorigenesis in A/J mice. PEITC is a selective inhibitor of the metabolic activation of NNK in the rodent lung, and studies in smokers who consumed watercress, a source of PEITC, indicate that the metabolic activation of NNK is also inhibited by PEITC in humans. Combinations of chemopreventive agents active against different carcinogens in tobacco smoke may be useful in the chemoprevention of lung cancer.

Animals↗
PubMed1993

Fate and effects of the surfactant sodium dodecyl sulfate.

Sodium dodecyl sulfate is the most widely used of the anionic alkyl sulfate surfactants. Its surface-active properties make it important in hundreds of household and industrial cleaners, personal care products, and cosmetics. It is also used in several types of industrial manufacturing processes, as a delivery aid in pharmaceuticals, and in biochemical research involving electrophoresis. SDS synthesis is a relatively simple process involving the sulfation of 1-dodecanol followed by neutralization with a cation source. Purification is accomplished through repeated extraction. It is available commercially in both broad-cut and purified forms. Although its environmental occurrence arises mainly from its presence in complex domestic and industrial effluents, SDS is also directly released in some applications (e.g., oil dispersants and pesticides). Although surfactants are known to significantly contribute to the toxicity of some effluents, no official water quality standards currently exist. Research has shown SDS to be highly biodegradable by a large number of naturally occurring bacteria, and degradation is generally reported to be > or = 90% within 24 hr. The process involves initial enzymatic sulfate liberation and conversion to dodecanoic acid, followed by either beta-oxidative shortening or elongation and desaturation. All surfactant properties are lost after initial sulfate hydrolysis. SDS can enhance absorption of chemicals through skin, gastrointestinal mucosa, and other mucous membranes. Thus, it is used in transepidermal, nasal, and ocular drug delivery systems and to enhance the intestinal absorption of poorly absorbed drugs; enhancement is concentration dependent. Human exposure is mainly through oral ingestion and dermal contact, although cases of respiratory exposure are known. The main sources of daily intake are ingestion of personal care products, residues on insufficiently rinsed utensils, and contaminated drinking water. Uptake, distribution, and excretion of SDS are all rapid. In fish, uptake in various tissues plateaus within 24-72 hr, with elimination occurring within < 24-48 hr; selective accumulation occurs in the hepatopancreas and gall bladder. In mammals, it is readily absorbed via the intestine, colon, and skin. Metabolism is similar in fish and mammals, proceeding from initial omega-oxidation to a carboxylic acid, then to beta-oxidation to butyric acid 4-sulfate, which is finally nonenzymatically desulfurated to gamma-butyrolactone and inorganic sulfate. SDS elicits both physical and biochemical effects on cells, with the membrane the primary target structure. Effects are concentration dependent and range from loss of barrier function and increased permeability to complete cell lysis. Hemolysis in mammals is pH dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Current concepts of competitive exclusion cultures for the control of salmonellae in domestic poultry.

Two defined competitive exclusion (CE) cultures (CF-I and CF-II) and a characterized CE culture (CF-III), which are composed of mixtures of nonpathogenic bacteria, were developed from anaerobic continuous-flow (CF) cultures that had been inoculated with cecal contents from adult chickens. After the primary CF cultures attained homeostasis, 13 bacteria (11 facultative anaerobes and 2 obligate anaerobes) representing 6 genera were isolated from CF-I; II bacteria (9 facultative anaerobes and 2 obligate anaerobes) representing 7 genera were isolated from CF-II; and 29 bacteria (15 facultative anaerobes and 14 obligate anaerobes) representing 14 genera were isolated from CF-III. Newly hatched chicks were treated orally with each primary CF culture; challenged on day 3 with Salmonella typhimurium; and cultured on day 10. Each culture significantly (p < 0.05) reduced salmonellae intestinal colonization and organ invasion. From the reconstituted CF-I and CF-II cultures, all organisms were isolated and their fermentation parameters and efficacy against salmonellae challenge were similar, if not identical, to the primary cultures. The CF-I and CF-II cultures satisfied the 5 requirements for defined CE cultures: 1) the primary CE culture must be efficacious; 2) all bacteria must be isolated and identified; 3) the fermentation parameters of the reconstituted CE culture must be similar to those of the primary culture; 4) all bacteria from the reconstituted culture must be isolated and identified; and 5) the efficacy of the reconstituted culture must be very similar to the primary culture. From these integrated studies, 3 mechanisms were demonstrated for preventing the enteric colonization of salmonellae in newly hatched chicks that were pretreated with CE cultures. First, the component organisms in the CE culture establish a normal enteric flora prior to salmonellae exposure. Second, the CE organisms compete with salmonellae for essential nutrients. Third, the CE organisms produce concentrations of volatile fatty acids at low pH levels that are bacteriostatic for salmonellae.

Animals↗
PubMed1984

The DNA repair host-mediated assay as a rapid and sensitive in vivo procedure for the determination of genotoxic factors present in various organs of mice. Some preliminary results with mitomycin C.

The DNA repair host-mediated assay, in which repairable DNA damage is determined in E. coli cells present in various organs of mice exposed to genotoxic agents, was further developed to broaden the range of organs under study and to simplify the procedure of assessing differential bacterial cell survival. A pair of derivatives of E. coli K-12 strain 343/113 was constructed which differed vastly in DNA repair capacity (uvr+/rec+ vs uvrB/recA), as a means of assessing DNA damaging effects; furthermore, the strains differed in their ability to ferment lactose (delta Lac vs Lac+), so that the individual survival of both strains could be determined on a single agar medium (containing neutral red as pH indicator), on which the strains had different colony colour morphology (red, Lac+ vs white, Lac- colonies). Finally, the strains were made streptomycin-dependent, to prevent uncontrolled growth of the bacterial cells within the various organs and also to inhibit contamination of the survival agar medium by representatives of the normal intestinal microflora. The experimental procedure consisted of injecting mixtures of stationary cells of the two strains (ca. 3-5 X 10(8) viable cells per mouse) both intravenously and orally into mice, either pretreated or subsequently treated with test chemicals. Ninety minutes after injection of the bacteria, the liver, spleen, lungs, kidneys, stomach, intestine, colon, and ca. 50 microliter blood, were removed, suspended in buffer, homogenized, and the survival of the two strains determined on neutral red agar supplemented with streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

The incidence of gastro-intestinal cancer in North Baden (West Germany) 1971--1977.

The incidences of the cancer of the oesophagus, stomach, small intestines, colon, and rectum for the years 1971--1977 in the regional district of North Baden, Federal Republic of Germany are presented and their relation to environmental factors are discussed briefly. The age specific incidence as well as the age standardized incidence and the sex ratios show remarkable differences due to the specific tumor localizations. The colon cancer incidence in the female population increases steeply during the period considered. The risk of developing rectal cancer also increases. The results of the pathoanatomic registry are well comparable with the data from clinical registries.

Adult↗
PubMedDate not supplied

Genetic factors in host resistance to urinary tract infection.

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearence from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to the Lpsd/Lpsd genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance of Escherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Animals↗
PubMed1985

Genetic factors in host resistance to urinary tract infection.

In patients with recurrent pyelonephritis, the pathogenetic events proceed through intestinal colonization, spread to the urinary tract and persistence, seemingly uninterrupted by host defense mechanisms. The factors responsible for the deficient bacterial clearance from the kidneys of these patients, and the genetic control, have not been identified. The susceptibility to colonization has been linked to an increased receptivity for attaching bacteria of the uroepithelia, and to an overrepresentation of the P1 blood group phenotype. To evaluate the role of defects in host defense for the susceptibility to pyelonephritis, experimental UTI in mouse strains with known deficiencies was used. A highly significant increase in susceptibility was noted for C3H/HeJ compared to C3H/HeN mice. The bacterial recovery was inversely correlated to the mitogenic response to LPS. Back-cross analysis revealed a linkage of susceptibility to the Lpsd/Lpsd genotype. In contrast, T and B lymphocyte and complement (C5) defects had little effect on the clearance of Escherichia coli from the kidneys. It is concluded that the inflammatory mechanisms induced by LPS are essential for resistance to experimental pyelonephritis.

Animals↗
PubMedDate not supplied

P-fimbriae of pyelonephritogenic Escherichia coli: significance for reflux and renal scarring-a hypothesis.

An experimental pyelonephritis model was developed in monkeys (Macaca fascicularis) using P-fimbriated Escherichia coli as the infecting organism. The relevant receptor molecules for P-fimbriae were also shown to be present in Macaca fascicularis. Atraumatic administration of P-fimbriated E. coli into the ureter induced a ureteritis followed by acute and chronic pyelonephritis. The decisive role of P-fimbriae as an adhesive virulence factor was proven by the receptor blockade of P-fimbriae-mediated bacterial adhesion by a synthetic receptor analogue (alpha-D-Galp-(1-4)-beta-D-Galp-1-OMe), which was administered into the ureter together with the challenge bacteria. On the basis of these and other findings, the role of reflux and pyelonephritis in relation to renal scarring is discussed in this paper. It is proposed that minor transitional vesicoureteral reflux together with the adhesive property of P-fimbriated E. coli and their ability to induce ureteritis might constitute an alternative mechanism to gross reflux by which bacteria ascend to the kidney. These findings and the fact that intestinal colonization with P-fimbriated E. coli coincides with the disease have opened up new prophylactic and therapeutic possibilities.

Adhesiveness↗
PubMed1999

Rectal Dieulafoy's lesion: report of a case and review of the literature.

Dieulafoy's lesion is an uncommon cause of gastrointestinal bleeding that occurs after rupture of an exposed submucosal artery. The vast majority of lesions are found in the stomach, but cases have been described in the esophagus, small intestine, colon, and rectum. We describe an elderly patient who presented with severe lower gastrointestinal bleeding caused by a rectal Dieulafoy's lesion. This is the first report of a rectal Dieulafoy's lesion treated successfully with endoscopic epinephrine injection followed by thermocoagulation. We review the physiopathology, clinical presentation, diagnosis, and treatment of this disease.

Aged↗
PubMed1987

A stomach oncofetal antigen recognized by monoclonal antibody GC302.

A monoclonal antibody, GC302, was established by fusing murine myeloma NS/1 cells with the splenocytes of a BALB/c mouse immunized with a human gastric cancer cell line, NU-GC-3. The serological specificity of GC302 was analyzed by an anti-mouse Ig mixed-hemadsorption (MHA) test on a panel of human cell lines, and an immunoperoxidase method using the frozen sections of tumors and normal tissues of adult and fetus. GC302 reacted with cancers of the stomach and colorectum but did not react with hepatocellular carcinomas, melanomas, or astrocytomas in the MHA tests. By the immunoperoxidase method, GC302 was found not to react with normal adult gastric mucosa, but to react with the mucosa in the fetal stomach, intestinal metaplasia, and almost all of the cancer of the stomach. GC302 also reacted with the normal mucosa of the intestine, colon, and rectum as well as with cancers of these origins. In normal liver sections, the antibody reacted with the bile ducts, but not with the hepatic cells. These results indicate that the antigen detected by GC302 is characterized as an oncofetal antigen in the stomach, and also as a differentiation antigen whose localization discriminates between the gastrointestinal tracts of the forgut origin and those of the midgut and hindgut origin. The molecular weight of the GC302 antigen was estimated to be ca. 40,000 by the Western blot analysis. Periodic acid treatment on the antigen suggested that the antigenic determinant is a carbohydrate.

Animals↗
PubMed2001

The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution.

Serotonin (5-hydroxytryptamine, 5-HT) receptor pre-mRNA is alternatively spliced in human tissue to produce three splice variants, h5-HT7(a), h5-HT7(b) and h5-HT7(d), which differ only in their carboxyl terminal tails. Using membranes from transiently and stably transfected HEK293 cells expressing the three recombinant h5-HT7 splice variants we compared their pharmacological profiles and ability to activate adenylyl cyclase. Using PCR on cDNA derived from various human tissues, the 5-HT7(a) and 5-HT7(b) splice variants were detected in every tissue examined. The h5-HT7(d) splice variant was detected in 13 of 16 tissues examined, with predominant expression in the heart, small intestine, colon, ovary and testis. All three h5-HT7 splice variants displayed high affinity binding for [3H]5-HT (pKd=8.8-8.9) in the presence and absence of 100 microM GTP and had similar binding affinities for all 17 ligands evaluated. In HEK293 cells expressing similar, high levels of receptor (approximately 10,000 fmol/mg protein), 5-CT (5-carboxamidotryptamine), 5-MeOT (5-methoxytryptamine) and 5-HT were full agonists while 8-OH-DPAT ((2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin) was a partial agonist with relative efficacy of approximately 0.8. Even at this high receptor level, EC50 values for stimulation of adenylyl cyclase were 10- to 50-fold higher than the Kd values, indicating a lack of spare receptors. No significant differences in coupling to adenylyl cyclase were observed between the three splice variants over a wide range of receptor expression levels. For antagonists, binding affinities determined by displacement of [3H]5-HT binding and by competitive inhibition of 5-HT-stimulated adenylyl cyclase activity were essentially identical amongst the splice variants. These studies indicate that the three human splice variants are pharmacologically indistinguishable and that modifications of the carboxyl tail do not influence coupling to adenylyl cyclase.

Adenylyl Cyclases↗
PubMed2006

Gastrointestinal manifestations in Hungarian scleroderma patients.

Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by fibrosis and destruction of the microvasculature. Increased deposition of collagen and other extracellular matrix components affects not only the skin but most of the internal organs including lungs, heart, kidneys and the gastrointestinal (GI) tract. Within the GI tract, esophageal involvements are most frequently seen features. However, abnormalities in the small intestine, colon and anorectum may also occur. A retrospective study was performed to investigate the frequency and clinical relevances of GI involvement in patients with SSc. Charts of altogether 246 SSc patients were reviewed. This patient population included 40 males and 206 females, with a mean age of 54.2 years. In general, 176 of 246 patients (71.5%) had GI symptoms. Esophageal involvement including gastro-esophageal reflux disease (GERD), aperistalsis, pseudodiverticuli, etc. was the most common (62.6%). In addition, diseases of the stomach (31.7%), dysfunctions of the colon and anorectum (11.4%), as well as sclerosis of the biliary tract and other pancreato-biliary disorders (9.8%) also occurred. Diarrhea and malabsorption resulted in cachexia and other secondary complications leading to death in two cases. Our results support that GI manifestations are rather common in SSc. Apart from the esophagus, other GI complications in SSc are usually mild, however, early recognition is necessary to improve quality of life.

Cohort Studies↗
PubMed2006

Efficacy of mangiferin against Cryptosporidium parvum in a neonatal mouse model.

The inhibitory activity of mangiferin (50 mg/kg/die and 100 mg/kg/die) on Cryptosporidium parvum was evaluated in a neonatal mouse model and its activity was compared with that of paromomycin (100 mg/kg/die). At 4 days of age, neonatal Swiss conventional outbred mice were experimentally infected by oral administration of 10(4) oocysts/animal of C. parvum and treated orally for 10 consecutive days, starting 7 days after the experimental infection. One group of mice was left untreated. To evaluate the efficacy of mangiferin, from euthanised mice, 3-mum-thick tissue sections of the intestine were stained with haematoxylin-eosin and periodic acid Schiff. Immunohistochemistry was also used by employing a monoclonal anti-C. parvum antibody. Oocysts were counted and results were expressed as mean oocysts number/intestine. Results obtained show that mangiferin at 100 mg/kg/die has a significant anticryptosporidial activity and that its activity is similar to that showed by the same dose (100 mg/kg/die) of paromomycin. However, both mangiferin and paromomycin were not able to completely inhibit intestinal colonization of C. parvum but only to reduce it. This reduction was calculated at over 80% for both mangiferin and paromomycin with respect to the untreated control. A significant activity was found also for mangiferin at 50 mg/kg/die only after the end of treatment.

Animals↗
PubMed2002

Efficacy of lactulose plus 13C-acetate breath test in the diagnosis of gastrointestinal motility disorders.

BACKGROUND: We designed a new method of measuring gastric emptying and orocecal transit time (OCTT) at the same time to assess the influence of gastric emptying upon OCTT. METHODS: Twenty-five dyspeptic patients (6 men, 19 women) with a mean age of 64.8 years (range, 25-80 years) were studied. The patients received a liquid test meal, containing 100 mg of 13C-acetate and 12g of lactulose, while they were in the sitting position after an overnight fast. Breath samples were collected at 10-min intervals of 120 min and both 13CO2 and hydrogen (H2) levels were measured. Subsequently, H2 concentrations were measured at 30-min intervals, for a total of 240 min. RESULTS: The results of gastric emptying were expressed as the time of peak 13CO2 excretion. OCTT was defined as the period between the ingestion of lactulose and a H2 peak rise of 5 ppm above the baseline value. The onset of H2 enrichment in the breath began at 90-110 min, whereas 13CO2 levels increased from the beginning, with peak enrichment values being reached after 60-80 min. OCTT was related to 13CO2 peak time. In 5 of the 25 patients, H2 breath enrichment in the 10-min sample was more than 5 ppm over the baseline value. All these 5 patients had double or triple peaks in serial breath H2 concentrations. CONCLUSIONS: The combination of the lactulose hydrogen breath test (LHBT) with the 13C-acetate breath test, which requires only breath samples, provides us with much information on the gastrointestinal tract; gastric emptying, OCTT, bacterial overgrowth in the small intestine, colonic fermentation, and oropharyngeal flora. The 13C-acetate breath test can be useful as an adjuvant test when LHBT is performed for measuring OCTT.

Acetates↗
PubMed2002

A massive hiatal hernia that mimics a congenital diaphragmatic hernia. An unusual presentation of hiatal hernia in childhood: report of a case.

A massive hiatal hernia containing the colon, intestine, and stomach with organoaxial volvulus is an uncommon entity in childhood. This clinical form of a hiatal hernia may mimic congenital diaphragmatic hernia and chest pathologies. In this paper, we describe a patient who presented with a massive hiatal hernia that mimicked a congenital diaphragmatic hernia, and discuss the pitfalls in diagnosing this clinical entity.

Adolescent↗