Risk of acute cellular rejection after azathioprine withdrawal in stable renal allograft recipients on cyclosporine, azathioprine, and prednisone.
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Adult↗
Biomedical subjects
G Roy
Publications and source records attributed to G Roy.
Helicobacter pylori infection and insulin-dependent diabetes mellitus.
Helicobacter pylori is associated with different diseases: duodenal ulcer, rosacea, ischaemic heart disease and gastric cancer. Given the abnormal immunological response and the high prevalence of gastrointestinal symptoms in diabetic patients, we conducted a study on H. pylori prevalence among these patients. We designed a case control study of a population-based cohort. Eighty insulin-dependent diabetes mellitus (IDDM) patients with an average age (24.05 +/- 8.3 years), and 100 control subjects (25 +/- 7.1 years) were selected to verify the seroprevalence of Helicobacter pylori in these populations. One serum sample was obtained from each subject for evaluation of antibodies against Helicobacter pylori, parietal cells (APA) and pancreatic islets cells (ICA). The seroprevalence of H. pylori among IDDM patients aged less than 24 years was significantly higher than among control subjects; the corresponding rate among IDDM aged greater than 24 years was significantly lower than among control subjects. Antibodies against parietal cells (APA) and islet cells (ICA) among H. pylori positive diabetic patients were significantly higher than among H. pylori negative diabetic patients. IDDM patients were subdivided on the basis of the evolutive course of diabetes. Seroprevalence of H. pylori as well as prevalence of ICAs decreased with IDDM duration. Nevertheless, no variation in the prevalence of APAs during the course of diabetes was observed. We observed an association between the seroprevalence of Helicobacter pylori and the duration of IDDM. The seroprevalence of H. pylori and ICA decreased with the evolutive course of diabetes mellitus among IDDM. The prevalence of ICA and APA in IDDM H. pylori positive subjects was higher than among controls.
Adolescent↗
Induction of thyroid tumours in (C57BL/6N x C3H/N)F1 mice by oral administration of kojic acid.
The tumorigenicity of kojic acid (KA), which is widely used for food and cosmetics in Japan, was examined in B6C3F1 mice. Female and male animals were divided into three groups and given 0, 1.5 and 3.0% KA containing food from the age of 6 weeks. At sacrifice after 20 months, thyroid weights were significantly increased in both sexes of mice receiving KA, especially in the male groups. The enlarged thyroid glands histologically featured diffuse hyperplasia and follicular adenomas, the incidences of the latter being 65% and 87%, respectively in 1.5% and 3.0% KA-treated males, significantly higher than the control value of 2%. In the females, the figures were 2%, 8% and 80% in the 0%, 1.5% and 3.0% KA groups, respectively. The serum free T3 levels in the 3.0% KA animals of both sexes at month 6 were significantly lower than in the controls. On the other hand, their serum TSH levels were higher, although the differences disappeared at later time points. In conclusion, continuous administration of high dose of KA induces thyroid adenomas in male and female B6C3F, mice, presumably by a mechanism involving decrease in serum free T3 levels and increased TSH.
Adenoma↗
ABC transporters in Leishmania and their role in drug resistance.
ABC transporters have been found in several parasitic protozoa including Leishmania. At least two Leishmania ABC transporters are involved in drug resistance. One is PgpA, which is involved in resistance to arsenic and antimony-containing compounds. Antimonials are the drug of choice against Leishmania infections. Transfection and biochemical studies suggest that PgpA recognizes metals conjugated to thiols. The second ABC transporter is closely related to mammalian P-glycoproteins and confers resistance to anticancer drugs by a mechanism that remains to be elucidated. Additional ABC transporters are likely to be present in Leishmania and these are discussed in relation to the phenomenon of antimony resistance.
Journal Article↗
Characterization of a chloride-selective channel from rough endoplasmic reticulum membranes of rat hepatocytes: evidence for a block by phosphate.
We have characterized the conduction and blocking properties of a chloride channel from rough endoplasmic reticulum membranes of rat hepatocytes after incorporation into a planar lipid bilayer. Our experiments revealed the existence of a channel with a mean conductance of 164 +/- 5 pS in symmetrical 200 mm KCl solutions. We determined that the channel was ten times more permeable for Cl- than for K+, calculated from the reversal potential using the Goldman-Hodgkin-Katz equation. The channel was voltage dependent, with an open probability value ranging from 0.9 at -20 mV to 0.4 at +60 mV. In addition to its fully open state, the channel could also enter a flickering state, which appeared to involve rapid transitions to zero current level. Our results showed a decrease of the channel mean open time combined with an increase of the channel mean closed time at positive potentials. An analysis of the dwell time distributions for the open and closed intervals led to the conclusion that the observed fluctuation pattern was compatible with a kinetic scheme containing a single open state and a minimum of three closed states. The permeability sequence for test halides determined from reversal potentials was Br- > Cl- > I- approximately F-. The voltage dependence of the open probability was modified by the presence of halides in trans with a sequence reflecting the permeability sequence, suggesting that permeant anions such as Br- and Cl- have access to an internal site capable of controlling channel gating. Adding NPPB to the cis chamber inhibited the channel activity by increasing fast flickering and generating long silent periods, whereas channel activity was not affected by 50 microM DNDS in trans. The channel was reversibly inhibited by adding phosphate to the trans chamber. The inhibitory effect of phosphate was voltage-dependent and could be reversed by addition of Cl-. Our results suggest that channel block involves the interaction of HPO2-4 with a site located at 70% of the membrane span.
Animals↗
Quantitative reverse transcriptase polymerase chain reaction for measuring the N-methylpurine-DNA glycosylase mRNA level in rodent cells.
A modified quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) procedure was developed for measuring mRNA concentration, in rodent cells, of the N-methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair protein responsible for the removal of N-alkylpurines and ethenoadducts of adenine, guanine, and cytosine from DNA. The method, applicable for quantitation of any mRNA, is based on the standard approach of comparing the relative amounts of PCR products of the experimental mRNA and a known amount of an exogenous reference RNA which is nearly identical to the experimental RNA. However, unlike in the earlier procedures in which deletion or insertion sequences were added to the reference RNA template, which may affect the efficiency of PCR but are needed to generate different size PCR products, experimental and reference RNAs yield PCR products of the same size in the new method. However, prior digestion with EcoRI allows separation of the two products because a unique EcoRI site was created in the reference RNA vector by point mutations. The QRT-PCR procedure is particularly useful for studying expression of the MPG gene whose mRNA level is very low and difficult to quantitate by Northern blot analysis. The number of MPG mRNA molecules/cell in late log-phase cultures varied from about 6 to 30 in several rodent lines. The SSV-NRK rat cell line has 6 +/- 0. 2 molecules/cell, while mouse NIH3T3 cells have about 30 +/- 1 molecules/cell. If the mRNA level is indicative of the level of the active MPG enzyme, these results may imply a variation in the capacity of various lines to remove the cytotoxic and mutagenic adducts from DNA.
3T3 Cells↗
Efflux systems and increased trypanothione levels in arsenite-resistant Leishmania.
The mechanism of resistance to the metal arsenite has been studied and compared in L. mexicana, L. tropica, and L. tarentolae selected in a step by step manner for arsenite resistance. Amplification of the ABC transporter gene pgpA was found to be a frequent resistance mechanism in all species. Transfection of pgpA genes into different species indicated that both the origin of the pgpA gene and the recipient strain into which the gene is transfected seem important for resistance. An increase in the levels of trypanothione was also correlated with metal resistance in different Leishmania species. The mechanism used to increase the levels of trypanothione seems to differ, however, between the different species. This study points to a key role of transporters and thiol levels in metal resistance in Leishmania.
ATP-Binding Cassette Transporters↗
Evaluation of donor skin disinfection methods.
BACKGROUND: Because most bacteria isolated from contaminated platelet concentrates are thought to originate from the donor's skin, the efficacy of four methods of skin disinfection was compared. STUDY DESIGN AND METHODS: Contact plates were used for antecubital skin cultures after they were demonstrated to be easier to use and at least as sensitive as a swab system. One antecubital fossa of each subject was disinfected by a standard method, the use of a povidone-iodine swabstick containing 0.75-percent available iodine followed by the use of a povidone-iodine swabstick containing 1-percent available iodine. The other arm was disinfected with either a 70-percent isopropyl alcohol scrub followed by an ampoule of 2-percent iodine tincture (Group 1; n = 126); a green-soap sponge followed by a 70-percent isopropyl alcohol swab, used for donors who are allergic to iodine (Group 2; n = 30); or a 0.5-percent chlorhexidine gluconate and 70-percent isopropyl alcohol sponge followed by an ampoule of 0.5-percent chlorhexidine gluconate and 70-percent isopropyl alcohol (Group 3; n = 40). Contact plate cultures were done before and after disinfection, and colonies counted after a 48-hour 37 degrees C incubation period. RESULTS: Similar numbers of bacteria grew from both antecubital fossae of the same subject before disinfection (p = 0.71). Compared to the standard povidoneiodine method, isopropyl alcohol and tincture of iodine resulted in significantly less bacterial growth (p < 0.001), the green soap and isopropyl alcohol method resulted in significantly more bacterial growth (p < 0.001), and the chlorhexidine gluconate and isopropyl alcohol method resulted in similar amounts of bacterial growth (p > 0.3). CONCLUSION: Isopropyl alcohol scrub followed by iodine tincture is more efficacious than povidone-iodine as measured by contact plate cultures. For donors who are allergic to iodine, chlorhexidine gluconate and isopropyl alcohol is more efficacious than green soap and isopropyl alcohol.
1-Propanol↗
Perinatal care of a woman with the prenatal diagnosis of a massive fetal neck tumour (cervical teratoma).
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Adult↗
Characterization of stable RNAs from the resected intestinal tissues of individuals with either Crohn's disease or ulcerative colitis.
Circular RNAs reminiscent of viroids and the human hepatitis delta virus have been proposed as possible nonconventional pathogens responsible for Crohn's disease and ulcerative colitis, two inflammatory bowel diseases. Consequently, RNA was extracted from various areas of intestinal tissues from individuals with either Crohn's disease or ulcerative colitis as well as several appropriate control diseases, and analyzed by two-dimensional gel electrophoresis. No circular viroid-like RNAs (< 1500 nucleotides) were detected, confirming a previous report that was limited to the investigation of small RNAs (< 300 nucleotides). However, three small, unusually stable, linear RNAs were shown to be associated to both Crohn's disease and ulcerative colitis tissues: a specific 28S ribosomal RNA cleavage product characterized previously; a 5.8S ribosomal RNA conformer; and a fragment homologous to transcripts from DNA CpG islands. The two last RNAs were detected prior to visible morphological tissue alterations, suggesting that they are produced early during the inflammation and that they have value as molecular diagnostic tools for the inflammatory bowel diseases. The potential cellular mechanisms producing these RNAs and their involvement in inflammatory bowel disease are discussed.
Colitis, Ulcerative↗
Effect of 17 beta-estradiol, retinoic acid and tamoxifen upon primary and transplanted thyroid tumor in B6C3F1 mice fed an iodine deficient diet.
This study was aimed to establish TSH dependent, transplantable thyroid tumor (TT) in B6C3F1 (BCF1) mice. In addition, transplanted TT was examined for its growth in mice given 17 beta-estradiol (E2), retinoic acid (RA), tamoxifen (TAM), T3 and T4. Both sexes of BCF1 mice were observed for 12 months under IDD and distilled water (DW), starting at 4 weeks of age. Groups of mice received an i.p. injection of radioactive iodine (131I) once at a dose of 60 mu Ci/head and/or given 0.25 mg E2 pellet s.c. One piece of induced pituitary or thyroid tumor was individually dissected aseptically and s.c. grafted under the fat pad of one site of the neck in the same strain of mice at 5 weeks of age. All mice were sacrificed between 7.5 to 13.5 months after grafting the tumors depending on the experiments. The transplantability of both pituitary and thyroid tumor was 100% in IDD mice, but TT was about 50% with a combined treatment of IDD plus E2. A supplement of thyroid hormones of T3 or T4 in mice with IDD completely inhibited the growth of in situ or grafted thyroid tumors. The growth of in situ thyroid gland was significantly promoted by the oral administration of RA in both sexes, whereas the growth of transplanted TT was significantly increased by RA in the female, but not in the male. Oral administration of TAM proved inhibitory upon in in situ and transplanted TT in the male, but not in the female. Thyroid tumor induced by IDD could grow only in mice with IDD and was partially regulated of its growth by RA and TAM.
Animals↗
Gene disruption of the P-glycoprotein related gene pgpa of Leishmania tarentolae.
Transfection of pgpA into Leishmania confers resistance to arsenite and antimonials. By gene targeting mediated by homologous recombination the two alleles of the pgpA gene of a L. tarentolae wild-type cell were disrupted sequentially with the neomycin and hygromycin phosphotransferase genes. This pgpA null mutant showed an increased sensitivity to arsenite and antimonite. In addition, the L. tarentolae pgpA null mutant exhibited a decreased intracellular survival inside murine macrophages. The observed phenotypes were reverted to levels not statistically different than wild-type when an intact pgpA gene was introduced into the null mutant. Disruption of the pgpA chromosomal locus in an arsenite resistant mutant indicated that PgpA is not essential for resistance to oxyanions, although it might be required in the early steps of selection when resistance is being established.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling.
The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.
Animals↗
Thioesterase and protein deacylase activities of porcine pancreatic phospholipase A2.
The thioesterase activity of porcine pancreatic phospholipase A2 has been investigated with non-phospholipid substrates. The acyl-CoA hydrolase activity towards acyl-CoA derivatives is specific for long chain fatty acids (14 C, 16 C) but is unable to hydrolyze short chain acyl-CoA compounds (below 8 C). The same enzyme also shows protein deacylase activity liberating [3H]palmitic acid from [3H]palmitoyl-acyl carrier protein.
Acyltransferases↗
Volume-sensitive chloride channels blocked by neuroprotective drugs in human glial cells (U-138MG).
Glial cell swelling in hypotonic media activates an anionic channel that was found previously to be permeable to amino acids. It is possible that the same channel is also activated when glial cells swell in pathologic conditions, like ischemia or hypoxia, and it could be partly responsible for the release of glutamate appearing in such conditions. Many drugs have been developed to block glutamate release during ischemia. Six of these drugs were tested on human glial cells (U-138MG) in vitro to determine if they could block the swelling-activated anionic channels. Three of them, phenytoin, lidocaine, and flunarizine, had no effect. The other three could block the anionic channels: riluzole, nizofenone, and BW1003C87. Such blocking was reversible and the half inhibition concentration (IC50) of each of these drugs was within that observed for their inhibition of glutamate release by various authors. An important advantage of these three drugs is their capacity to inhibit glutamate release after the beginning of ischemia. It is concluded that the volume-sensitive anionic channel could be partly responsible for glutamate release during a cerebral ischemia.
Cell Line↗
Childhood renal tumours with intravascular extension.
OBJECTIVE: To assess whether pre-operative chemotherapy reduces operative morbidity in children with intravascular extension of renal tumours. PATIENTS AND METHODS: Thirty children with intravascular extension of their renal tumour, treated in 10 different centres in the UK, were reviewed retrospectively. RESULTS: Twenty-nine patients had nephroblastoma and one child had clear cell sarcoma (favourable histology in 23, unfavourable histology in six). Patients were classified into stage II (17 patients), stage III (three patients) and stage IV (10 patients). Ultrasonography had been performed in 29 patients and had correctly diagnosed intravascular extension in 11 (40%); computed tomography (CT) was accurate in 93% of patients. A pre-operative diagnosis was made accurately in 24 patients, with caval extension in 18 and atrial extension in six. Nine patients underwent primary surgery, whilst 21 had pre-operative chemotherapy followed by delayed nephrectomy. In the latter group, the intravascular thrombus diminished in 16 patients. Five patients died, one from tumour rupture and four from extensive or progressive tumour disease; the overall 2-year survival was 83%. Unfavourable histology did not adversely affect survival, and patients having pre-operative chemotherapy appeared to have a better outcome. CONCLUSION: CT remains the best imaging modality to assess intravascular tumour extension. Pre-operative chemotherapy is recommended for patients with intra-caval extension of tumour. Those with intra-atrial extension or with hepatic vein obstruction (Budd-Chiari syndrome) may require a cardiopulmonary bypass and primary surgery.
Adenocarcinoma, Clear Cell↗
Influence of paternal (252) Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F(1) offspring of mice.
Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with (252) Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or three months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F(1) generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by (252) Cf neutron irradiation.
Animals↗
Formation of extrachromosomal circular amplicons with direct or inverted duplications in drug-resistant Leishmania tarentolae.
Selection for methotrexate resistance in Leishmania spp. is often associated with amplification of the H locus short-chain dehydrogenase-reductase gene ptr1 as part of extrachromosomal elements. Extensive sequences are always coamplified and often contain inverted duplications, most likely formed by the annealing of inverted repeats present at the H locus. By gene targeting mediated by homologous recombination, several repeated sequences were introduced in the vicinity of ptr1. Selection for methotrexate resistance in these transfectants led to ptr1 amplification as part of small circles with direct or inverted duplications whether the integrated sequences consisted of direct or inverted repeats. Hence, for a region to he amplified in L. tarentolae during drug selection, a drug resistance gene is required and must be flanked by (any) homologous repeated sequences. The distance between these repeats and their orientation will determine the length of the amplicon and whether it contains direct or inverted duplications.
Animals↗