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At least 307 records · Page 17Linked to original sources
PubMed1988

Organ-specific, carcinogenic dibenzo[c,g]carbazole derivatives: discriminative response in S. typhimurium TA100 mutagenesis modulated by subcellular fractions of mouse liver.

7H-Dibenzo[c,g]carbazole (DBC) has carcinogenic effects on mouse subcutaneous fibroblasts and liver; the N-methyl derivative (N-MeDBC) induces only sarcomas; 3-methyl- and 5,9-dimethyldibenzo[c,g]carbazole (3-MeDBC and 5,9-DMeDBC) are specific, potent hepatocarcinogens in mice. The mutagenicity in S. typhimurium TA100 of these 4 compounds was evaluated in relation to the concentration of mouse liver 9000 X g supernatant (S9) and to the proportions of microsomes and cytosol in the medium. Optimal mutagenicity of N-MeDBC was seen with a low concentration of S9 or microsomes; a 5-10 times higher concentration of the subcellular fraction was necessary to induce optimal mutagenicity of the hepatocarcinogens 3-MeDBC and 5,9-DMeDBC. Intermediate quantities were needed in the case of DBC, which is carcinogenic in both cell types. Whereas the presence of cytosol had an inhibitory effect on the mutagenicity of the sarcomagenic N-MeDBC, the cytosolic fraction was essential for optimal mutagenic expression by the 2 hepatocarcinogenic derivatives. The activating cytosolic fraction is not inducible. These experiments show that programmed modulation of the metabolic activation system in the Ames test can be used to study organ-specific chemical carcinogenesis. The results suggest that differences in the enzymatic composition of target tissues are a determining factor in the organ specificity of carcinogens such as DBC.

Animals↗
PubMed1997

Organ-specific autoimmunity.

The past year has seen advances in our understanding of the mechanisms that control the expression of organ-specific autoimmunity. Attempts to develop therapeutic strategies for the prevention of autoimmune disease have largely been based on deviation of the T-cell response away from an autoaggressive, pro-inflammatory Th1 response. Manipulation of the cytokine environment at the site of antigen uptake or presentation, the source of endogenous antigen, costimulatory molecules or peptides processed and presented has yielded interesting results.

Animals↗
PubMed1999

Organ-specific carcinogenicity of haloalkenes mediated by glutathione conjugation.

Several halogenated alkenes are nephrotoxic in rodents. A mechanism for the organ-specific toxicity to the kidney for these compounds has been elucidated. The mechanism involves hepatic glutathione conjugation to dihaloalkenyl or 1,1-difluoroalkyl glutathione S-conjugates, which are cleaved by gamma-glutamyltransferase and dipeptidases to cysteine S-conjugates. Haloalkene-derived cysteine S-conjugates are substrates for renal cysteine conjugate beta-lyases, which cleave them to form reactive intermediates identified as thioketenes (from chloroalkene-derived S-conjugates) or thionoacyl halides (from 1,1-difluoroalkyl S-conjugates). Alternatively, cysteine S-conjugates may be N-acetylated to excretable mercapturic acids. The formation of reactive intermediates by cysteine-conjugate beta-lyase may play a role in the target-organ toxicity and in the possible renal tumorigenicity of several chlorinated olefins widely used in many chemical processes.

Animals↗
PubMed2000

The promoter of rbcS in a C3 plant (rice) directs organ-specific, light-dependent expression in a C4 plant (maize), but does not confer bundle sheath cell-specific expression.

The small subunit of ribulose-bisphosphate carboxylase (Rubisco), encoded by rbcS, is essential for photosynthesis in both C3 and C4 plants, even though the cell specificity of rbcS expression is different between C3 and C4 plants. The C3 rbcS is specifically expressed in mesophyll cells, while the C4 rbcS is expressed in bundle sheath cells, and not mesophyll cells. Two chimeric genes were constructed consisting of the structural gene encoding beta-glucuronidase (GUS) controlled by the two promoters from maize (C4) and rice (C3) rbcS genes. These constructs were introduced into a C4 plant, maize. Both chimeric genes were specifically expressed in photosynthetic organs, such as leaf blade, but not in non-photosynthetic organs. The expressions of the genes were also regulated by light. However, the rice promoter drove the GUS activity mainly in mesophyll cells and relatively low in bundle sheath cells, while the maize rbcS promoter induced the activity specifically in bundle sheath cells. These results suggest that the rice promoter contains some cis-acting elements responding in an organ-specific and light-inducible regulation manner in maize but does not contain element(s) for bundle sheath cell-specific expression, while the maize promoter does contain such element(s). Based on this result, we discuss the similarities and differences between the rice (C3) and maize (C4) rbcS promoter in terms of the evolution of the C4 photosynthetic gene.

Base Sequence↗
PubMed1995

Organ-specific autoimmunity induced by adult thymectomy and cyclophosphamide-induced lymphopenia.

Autoimmune gastritis, a CD4+ T cell-mediated organ-specific autoimmune disease, can be induced by thymectomy of neonatal, but not of older, BALB/c mice. Here we have shown that autoimmune gastritis can also be induced in 6-8-week-old BALB/c mice by thymectomy combined with a single dose of cyclophosphamide (300 mg/kg). This treatment reduced the numbers of splenic T and B cells approximately 25-fold. However, by 8 days after treatment, the number of splenic lymphocytes had returned to normal adult levels. Approximately 50% of treated mice developed autoimmune gastritis after 10-12 weeks. These mice had mononuclear cellular infiltrates within the gastric mucosa and serum autoantibodies to the alpha and beta subunits of the gastric H+/K+ ATPase. Transgenic mice, expressing the gastric H+/K+ ATPase beta-subunit in the thymus (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419), did not develop autoimmune gastritis after the adult thymectomy/cyclophosphamide treatment. Thus a T cell response to the H+/K+ ATPase beta-subunit is likely to be required for the onset of gastritis. These observations suggest that pathogenic autoreactive T cells exist in the periphery of normal adult mice and that autoimmunity can be induced by the activation of these autoreactive T cells following transient lymphopenia. Cyclophosphamide-treatment of adult mice without thymectomy did not induce autoimmune gastritis, suggesting thymic regulation of these pathogenic T cells.

Aging↗
PubMed1986

Analysis of organ-specific effects on metastatic tumor formation by studies in vitro.

After entry into the blood, cells from disseminating malignant tumors are rapidly distributed to many organs, but they only grow to form metastases in certain sites. Clinical and pathologic observations on tumor metastasis in humans and in animals have confirmed that the distribution of these secondary neoplasms is related to the site and type of the primary neoplasm. Numerous studies now indicate that success or failure in producing metastatic deposits is influenced by interaction between the tumor cells and the microenvironment of the organ in which they lodge. In the present investigation, the mechanisms by which the microenvironmental conditions of specific organs may influence tumor cell survival and behavior and hence metastasis distribution were investigated in vitro with the use of spontaneous mouse mammary carcinomas from C3H/Avy mice. Some organs (lung, ovary) promoted the survival and the attachment of the tumor cells to the substratum, while others (liver, thyroid gland) consistently diminished survival of the tumor cells in the flask. These effects were shown to be due to soluble substances diffusing out of the organs, the dose dependency of which was demonstrated. It is known that in vivo murine mammary tumors develop metastases mainly in the lungs and occasionally in the kidneys or ovaries (if inoculated via the aorta). The effects of these same organs on tumor cells in vitro were thus in good agreement with the in vivo observations. The findings are compatible with the hypothesis that normal organs can usually suppress the formation of tumor metastases and that tumors that succeed in establishing metastases have evolved means of escaping the inhibitory effects of organs in which the deposits are found.

Animals↗
PubMedDate not supplied

Pathogenetic aspects of organ-specific autoimmunity.

In the last few years a great deal of information on the etiopathogenetic aspects of organ-specific autoimmune diseases (OSADS) has been obtained. It has been shown that genetic factors play an etiologic fundamental role. They are responsible for the dysregulation of the immune system and for the target organ susceptibility which favour the onset of the diseases. Putative environmental factors, such as viral infections, can act as initiating or precipitating events only in genetically predisposed individuals. Immunological mechanisms capable of triggering autoimmune responses have been demonstrated. Data obtained from experimental models and from humans suggest that the ongoing expansion of autoreactive T cells with specificity for autoantigens (AAgs) can be considered as the main immunological event capable of inducing and maintaining the target organ damage. These cells can activate different effector systems, i.e., autoantibody (AAb)-producing B cells, cells with cytotoxic activity, etc., by releasing different combinations of lymphokines. In overt diseases AAbs are directly involved in the pathogenesis of lesions due to autoimmune responses against functional molecules and cellular receptors. The pathogenesis of the common inflammatory destructive lesions of the target organs is more complex and not yet clarified. A large proportion of T cells present in the inflammatory infiltrates are apparently not directed to the AAgs. Most cells display cytolytic activity and may contribute to tissue damage by releasing lymphokines which activate other cells and cascade the process. Vicious cycles, i.e., upregulation of class II and I molecules, alterations of the cytokine network, etc., are supposed to be involved in the maintenance of target organ lesions.

Autoantibodies↗
PubMedDate not supplied

[An immunofluorescence study of the ontogenesis of mouse thyroid organ-specific antigens: relation to fate of foetal thyroid homografts in adult recipients (author's transl)].

A study of the development of organ specific thyroid antigens in mice showed that these antigens make their appearance on the 17th day of gestation. This causes an increase in the specific antigenicity of the thyroid and coincides with the critical stages at which the fate of a homograft of embryonic thyroid is seen to change: embryonic thyroid tissue from 15-16 day embryo grafted on an adult recipient is accepted but if taken from a 17 day embryo it is rejected.

Aging↗
PubMed1995

Organ-specific differences in the ratio of alternatively spliced chorismate synthase (LeCS2) transcripts in tomato.

The primary transcript of one of the two chorismate synthase genes (LeCS2) of tomato is differentially processed due to an alternative splicing of the third intron. A novel observation was made when the abundances of the two LeCS2-specific transcripts in different organs were analysed. The ratio of these two transcripts differs in RNA populations from different organs. Possible explanations for this finding and its potential physiological impact for plant metabolism are discussed.

Alternative Splicing↗
PubMedDate not supplied

[Structuro-functional organization of the SV40 virus chromosome. IV. Specific organization of regulatory sequences of the SV40 genome in the mini-chromosome].

Using previously described technique of hybridization end-labeling, we analysed nucleosomal organization of the regulatory region of SV40 minichromosome. We showed that DNAase II, in spite of certain specificity observed on the naked DNA, cut the minichromosome in a highly specific manner with the major hypersensitive site inside the enhancer. This hypersensitivity and that to micrococcal nuclease were not found when the chromosome of mature SV40 virions was tested.

Animals↗
PubMed2006

Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.

BACKGROUND: We isolated the human liver-specific organic anion transporter gene, LST-2 (OATP8/SLCO1B3), which is exclusively expressed in the basolateral membrane of the hepatocytes. In this study, we analyzed the transcriptional regulation of the LST-2 gene in hepatocyte-derived cells and the effect of bile acid. METHODS: Transcriptional activity of the LST-2 gene was measured using a human LST-2 promoter-luciferase reporter plasmid under various concentrations of bile acids. Electrophoresis mobility shift assays of farnesoid X receptor (FXR), hepatocyte nuclear factor (HNF) 1alpha, and HNF3beta were performed. RESULTS: Luciferase analysis showed that the 5'-flanking region from -180 to -20 bp is responsible for LST-2 transcriptional activity. By site-directed mutation analysis, it was revealed that the consensus binding sites for FXR, HNF1alpha, and HNF3beta play important roles in the transcriptional activity of the LST-2 gene. By electrophoresis mobility shift assay, we observed specific protein-DNA complexes of FXR, HNF1alpha, and HNF-3beta. Luciferase activity was increased fivefold when chenodeoxycholate or deoxycholate were added. Northern blot analyses revealed that the expression of LST-2 was increased by addition of chenodeoxycholate or deoxycholate in a dose-dependent manner. CONCLUSIONS: This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta. HNF1alpha and HNF3beta might contribute to its liver-specific expression, and FXR might play a role in its transcriptional activation by bile acids.

Bile Acids and Salts↗
PubMed2004

Cancer risk estimates for gamma-rays with regard to organ-specific doses Part II: site-specific solid cancers.

Part I of this study presented an analysis of the solid cancer mortality data for 1950-1997 from the Japanese life-span study of the A-bomb survivors to assess the cancer risk for gamma-rays in terms of the organ-specific dose for all solid cancers combined. Compared to earlier analyses, considerably more curvature in the dose-effect relation is indicated by these computations, which now suggests a dose and dose-rate effectiveness factor of about 2. The computations are extended here in order to explore the site-specific solid cancer risks for various organs. A computational method has been developed whereby the site-specific cancer risks are all simultaneously computed with global age and gender effect modifiers. This provides a more parsimonious representation with fewer parameters and avoids the large relative standard errors which would otherwise result. The sensitivity of site-specific risks to the choices of the neutron RBE is examined. The site-specific risk estimates are quite sensitive to the neutron RBE for the least shielded organs such as the breast, bladder and oesophagus. For the deeper lying organs, such as the gallbladder, pancreas and uterus, the impact of the neutrons is much lower. With an assumed neutron RBE of 35, which is in line with results on low neutron doses in major past studies on rodents and which corresponds approximately to the current ICRP radiation weighting factor for neutrons, the neutrons appear to contribute about 40% of the observed excess cancer risk in the breast, i.e. the organ that is closest to the body surface. However, this neutron contribution fraction is only about 10% for deeper lying organs, such as the colon.

Algorithms↗
PubMed1996

A prospective randomized study of end points of resuscitation after major trauma: global oxygen transport indices versus organ-specific gastric mucosal pH.

BACKGROUND: Gastric tonometry, as a method of organ-specific monitoring of the status of the splanchnic circulation, has demonstrated prognostic and therapeutic implications in critically ill patients. The experience with this method in patients with trauma has been limited. STUDY DESIGN: Fifty-seven patients were prospectively randomized into two groups: group 1, n = 30, normalization and maintenance of gastric mucosal pH (pHi) at or above 7.3 and group 2, n = 27, maintenance of oxygen delivery index of 600 or an oxygen consumption index of greater than 150. The groups had statistically similar injury severity scores, lactate levels, and base deficits. RESULTS: Of the 44 patients with pHi greater than 7.3 at 24 hours, three (6.8 percent) died of multiple organ dysfunction syndrome as compared with seven (53.9 percent) of 13 in whom pHi was not optimized, p = 0.006. Optimization times for oxygen delivery index, oxygen consumption index, lactate levels, and base excess were similar between survivors and nonsurvivors. The time for pHi optimization was significantly longer in nonsurvivors. Multiple organ dysfunction syndrome points were significantly higher in patients who did not have pHi optimized within 24 hours (6.08 compared with 2.5, p = 0.03). Optimization time for pHi was predictive of mortality on multiple regression. Persistently low pHi was frequently associated with systemic or intra-abdominal complications. It was the first finding in all the nonsurvivors at least 48 to 72 hours before death. CONCLUSIONS: Gastric mucosal pH may be an important marker to assess the adequacy of resuscitation. Monitoring of pHi may provide early warning for systemic complications in the postresuscitation period.

Adolescent↗
PubMedDate not supplied

Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds.

Panax ginseng C.A. Meyer has been the most highly recognized medicinal herb in the Orient. The prolonged administration of red ginseng extract significantly inhibits the incidence of hepatoma and also proliferation of pulmonary tumors induced by aflatoxin B(1) and urethane. Statistically significant anticarcinogenic effects were in aged or heat treated extracts of ginseng and red ginseng made by steaming in a 9 weeks medium-term anticarcinogenicity test using benzo[a]pyrene. In case-control studies, odds ratios (OR) of the cancer of lip, oral cavity and pharynx, larynx, lung, esophagus, stomach, liver, pancreas, ovary, and colorectum were significantly reduced. As to the type of ginseng, the ORs for cancer were reduced in user of fresh ginseng extract intakers, white ginseng extract, white ginseng powder, and red ginseng. In a cohort study with 5 years follow-up conducted in a ginseng cultivation area, ginseng users had a decreased relative risk (RR) compared with non-users. The relative risks (RRs) of ginseng users were decreased in gastric cancer and lung cancer. These findings strongly suggest that Panax ginseng C.A. Meyer cultivated in Korea has non-organ specific cancer preventive effects against various cancers. To investigate the active components for cancer prevention, several fractions of fresh and red ginseng and four semi-synthetic ginsenoside Rh(1), Rh(2), Rg(3) and Rg(5), the major saponin components in red ginseng, were prepared among the ginsenosides. By using Yun's model, Rg(3) and Rg(5) showed statistically significant reduction of lung tumor incidence and Rh(2) had a tendency to decrease the incidence. In conclusion, these results strongly suggested that Panax ginseng C.A. Meyer cultivated in Korea is a non-organ specific cancer preventive against human cancers and also indicated that the anticarcinogenicity or human cancer preventive effect of Panax ginseng is due to ginsenoside Rg(3), Rg(5) and Rh(2).

Anticarcinogenic Agents↗
PubMed1994

The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis.

We used the lung epithelial cell-specific surfactant protein B (SPB) gene promoter as a model with which to investigate mechanisms involved in transcriptional control of lung-specific genes. In a previous study, we showed that the SPB promoter specifically activated expression of a linked reporter gene in the continuous H441 lung cell line and that H441 nuclear proteins specifically protected a region of this promoter from bp -111 to -73. In this study, we further show that this region is a complex binding site for thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3 (HNF-3). Whereas TTF-1 bound two highly degenerate and closely spaced sites, HNF-3 proteins bound a TGT3 motif (TGTTTGT) that is also found in several liver-specific gene regulatory regions, where it appears to be a weak affinity site for HNF-3. Point mutations of these binding sites eliminated factor binding and resulted in significant decreases in transfected SPB promoter activity. In addition, we developed a cotransfection assay and showed that a family of lung-specific gene promoters that included the SPB, SPC, SPA, and Clara cell secretory protein (CCSP) gene promoters were specifically activated by cotransfected TTF-1. We conclude that TTF-1 and HNF-3 are major activators of lung-specific genes and propose that these factors are involved in a general mechanism of lung-specific gene transcription. Importantly, these data also show that common factors are involved in organ-specific gene expression along the mammalian foregut axis.

Animals↗
PubMed1996

Genetic predisposition to organ-specific endpoints of alcoholism.

Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z, and Omenn, G. S., Alcohol. Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum-likelihood modeling indicated that approximately 50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.

Aged↗
PubMed1991

Organ specificity of the antigens reacting with the 48-1 and S-1 antibodies in chimpanzees infected with hepatitis C virus.

48-1 and S-1 antibodies produced by lymphoblastoid cells transformed with Epstein-Barr virus were reported to be associated with infection by not only the hepatitis non-A, non-B (NANB) virus but also hepatitis delta virus. Appearance of the antigens reacting with these antibodies in the liver of chimpanzees was recently found to be a host response to alpha-interferon induced by infections of both viruses. To investigate organ specificity of these antigens, various organs obtained from chimpanzees with hepatitis C (NANB) were examined. In addition to the liver, the adrenals and spleen were found to be positive by immunofluorescence. The positive reactions of these three organs were also confirmed by radioimmunoassay. By electron microscopy, microtubular aggregates similar to those observed in the liver were detected in the adrenals, but not in the spleen. The results suggested that these antigens existed in the liver, adrenal, and probably spleen of chimpanzees infected with hepatitis C.

Adrenal Glands↗
PubMed2005

Organ-specific expression of Arabidopsis genome during development.

The development of complex eukaryotic organisms can be viewed as the selective expression of distinct fractions of the genome in different organs or tissue types in response to developmental and environmental cues. Here, we generated a genome expression atlas of 18 organ or tissue types representing the life cycle of Arabidopsis (Arabidopsis thaliana). We showed that each organ or tissue type had a defining genome expression pattern and that the degree to which organs share expression profiles is highly correlated with the biological relationship of organ types. Further, distinct fractions of the genome exhibited expression changes in response to environmental light among the three seedling organs, despite the fact that they share the same photo-perception and transduction systems. A significant fraction of the genes in the Arabidopsis genome is organized into chromatin domains exhibiting coregulated expression patterns in response to developmental or environmental signals. The knowledge of organ-specific expression patterns and their response to the changing environment provides a foundation for dissecting the molecular processes underlying development.

Arabidopsis↗