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Biomedical subjects

T Jin

Publications and source records attributed to T Jin.

At least 73 records · Page 4Linked to original sources

Induction of donor-specific T cell anergy by portal venous injection of allogeneic cells.

The mechanisms behind tolerance induction by portal venous (pv) injection of allogeneic cells are investigated. When a hematopoietic stem cell (HSC)-enriched population of BALB/c bone marrow was pv injected into C57BL/6 mice, the response of the T cells in the B6 mice to BALB/c alloantigens in mixed lymphocyte reaction (MLR) decreased until day 4 after the injection. Neither clonal deletion of V beta 11+ T cell nor donor-specific suppressor activity was observed. When recipient T cells were separated into CD4+ and CD8+ cells, only the CD8+ cell population showed donor-specific tolerance. The donor cells were trapped and retained in the host liver. MHC class I antigens were highly expressed on the trapped cells whereas class II antigens or B7 costimulatory molecules were not. The tolerance to BALB/c alloantigens in MLR was obtained also by the pv injection of Meth A, a BALB/c-derived sarcoma cell line. However, tolerance was not induced by the pv injection of B7-transfected Meth A cells. In addition to MLR, tolerance was also observed in DTH responses, and this was also due to the unresponsiveness of CD8+ cells to the donor alloantigens. However, the BALB/c-specific DTH responses were not suppressed after the pv injection of B7-transfected Meth A cells. These results strongly suggest that the tolerance induced by pv injection of allogeneic cells is due to clonal anergy generated by the absence of costimulatory signals in the interaction between donor-specific CD8+ T cells and donor hematopoietic cells trapped in the host liver.

Adoptive Transfer↗

Nucleotide sequence of a 5423 base pairs fragment of the LsNPV genome and comparison with the AcNPV genome.

A 5423 bp fragment of LsNPV genome was sequenced, in which PDV-E66 gene and another four ORFs were found. The PDV-E66 gene of LsNPV was compared with the PDV-E66 gene of AcNPV, and a 51.9% nucleotide sequence homology and 38.8% amino acid sequence homology were found between the two genes. Two conserved late transcriptional motifs TAAG were found in LsNPV PDV-E66 gene, similar to those in AcNPV PDV-E66. The LsNPV PDV-E66 ORF is 204 base pairs shorter than the AcNPV PDV-E66 ORF at the 5' end. This is agreement with the fact that the N-terminus of the AcNPV PDV-E66 mature protein is 69 amino acids interior to the N-terminus predicted by the AcNPV PDV-E66 ORF. The 5' regulatory region of ORF1 contains early (CGTGC) and late (TAAG) transcriptional initiation motifs and ORF1 is predicted to encode a protein with 114 amino acid residues. The 5' regulatory region of ORF2 which can encode a protein with 115 amino acid residues contains only an early transcriptional initiation motif. Compared with all the genes from AcNPV and other baculoviruses, ORF1 and ORF2 have no homologous genes. It is suggested that ORF1 and ORF2 may be two novel baculovirus genes. ORF3 (PDV-E66 gene), ORF5 and an incomplete ORF, ORF6-part, have homologous regions in the AcNPV genome. ORF3, ORF5, ORF6-part are linked together in LsNPV genome, but their homologous regions are separated by about 58 kb fragment in the AcNPV genome. This fact indicates that the organization of the above genes in LsNPV is different from that of AcNPV. ORF4 is included in ORF6-part and can encode a 48 amino acid residues polypeptide, but ORF4 and ORF6-part are located on different DNA strands.

Amino Acid Sequence↗

Serum Calmodulin Activity in Male Lead-exposed Workers.

Serum calmodulin (CaM) activity was studied in 75 lead-exposed and 21 non-exposed male workers. The lead-exposed workers were divided into groups with low blood lead (BPb < 50 µg/dL) and high blood lead (BPb>/=50 µg/dL). The concentrations of lead, calcium, magnesium, copper, zinc, and free erythrocytic protoporphyrin (FEP) in blood were determined. Serum samples were heated in a water bath (100 degrees C) for 3 minutes and centrifuged for 15 minutes at 4 degrees C (18,000 x g). The supernatants obtained were used to measure CaM activity. The results showed that: 1) Average blood lead concentrations in workers with both low and high levels of exposure were significantly higher than those in controls (p < 0.05). 2) Serum CaM activity in the high-exposure group (31.09 +/- 7.84 µg/dL) was significantly lower than that in controls (78.11 +/- 15.13 µg/dL, p < 0.05). The biological threshold of BPb inhibition of CaM activity was less than 50 µg/dL. 3) Multiple correlation analysis showed a negative dose-response relationship between BPb and CaM activity. The stepwise regression procedure indicated that lead had negative, and calcium and magnesium positive, effects on serum CaM activity. The regression equation was Y = 66.1383 - 1.0857 X&inf1; + 2.9676 X&inf2; + 5.2222 X&inf3; (Y:CaM; X&inf1;:Pb; X&inf2;: Ca; X&inf3;:Mg). These results of the first such study carried out in male lead-exposed workers suggest that lead can inhibit CaM activity in humans.

Journal Article↗

The caudal homeobox protein cdx-2/3 activates endogenous proglucagon gene expression in InR1-G9 islet cells.

The proglucagon gene is expressed in a highly cell-specific manner in islet and enteroendocrine cells. DNA sequences within the proximal proglucagon G1 promoter region bind the homeobox protein cdx-2/3, and cdx-2/3 activates the proglucagon promoter in fibroblasts. We show here that cdx-2/3 activates the proglucagon promoter in both islet (InR1-G9) and enteroendocrine (STC-1 and GLUTag) cell lines. Furthermore, transfected cdx-2/3 increased the levels of endogenous proglucagon mRNA transcripts in both transient and stable transfections of InR1-G9 islet cells. The cdx-2/3-dependent induction of endogenous proglucagon mRNA transcripts in stable islet lines was associated with a corresponding increase in the transcriptional activity of proglucagon promoter-luciferase plasmids. An amino-terminally truncated cdx-2/3 derivative containing the homeodomain and carboxy-terminal region of the molecule inhibited both the cdx-2/3 activation of the proglucagon promoter and the induction of endogenous proglucagon mRNA transcripts. These observations demonstrate that cdx-2/3, acting through the proximal G1 element, is a major transcriptional determinant of cell-specific proglucagon gene expression in pancreatic islet cells.

Animals↗

Cumulative lead exposure in relation to mortality and lung cancer morbidity in a cohort of primary smelter workers.

OBJECTIVES: The purpose of this study was to determine the mortality and cancer incidence of long-term lead smelter workers at a primary smelter. METHODS: A cohort of 3979 workers employed for at least 1 year during 1928-1979 and a subcohort of 1992 workers employed in lead-exposed departments (lead only workers) was formed. The expected mortality in 1955-1987 and cancer incidence in 1958-1987 were calculated relative to the county rates, specified for cause, gender, 5-year age groups, and calendar year. A cumulative blood-lead index was used for the dose-response analyses. RESULTS: The lung cancer incidence of the total cohort [standardized incidence ratio (SIR) 2.8, 95% confidence interval (95% CI) 2.1-3.8] and the group with the highest exposure (SIR 3.1, 95% CI 2.0-4.6) was high. Similar risk estimates were observed with a latency of 15 years. The workers hired before 1950 had higher lung cancer risk estimates (SIR 3.6, 95% CI 2.6-5.0) than the workers hired later (SIR 1.3, 95% CI 0.6-2.6, no latency period). The risk estimates for lung cancer were further elevated in the subcohort of lead-only workers (SIR 5.1, 95% CI 2.0-10.5 in the highest exposed subgroup; latency period of 15 years). No excesses of other malignancies were noted. CONCLUSIONS: The increased relative risks were probably mainly due to interactions between lead and other carcinogenic exposures, including arsenic. Further study is required concerning such possible interactions before a role in the induction of lung cancer can be ascribed to lead.

Aged↗

[Constituent analysis of the essential oil in leaves of Torreya nucifera].

The constituents of the essential oil in leaves of Torreya nucifera (L.) Sieb. et Zucc. (EOLTN) in China were firstly analysed by GC-MS-DS. 68 of the 71 separated constituents in EOLTN were identified. The total contents of identified constituents accounted for 96.364% of EOLTN.

Bicyclic Monoterpenes↗

Lipobeads: a hydrogel anchored lipid vesicle system.

A new vesicle system is described that combines complementary properties of liposomes and polymeric beads. 'Lipobeads' consist of a lipid bilayer shell anchored on the surface of a hydrogel polymer cores which acts like a cytoskeleton. Anchoring is provided by fatty acids covalently attached to the surface of the hydrogel. These hydrophobic chains drive spontaneous assembly of a lipid bilayer shell around the modified hydrogel bead when exposed to a suspension of liposomes. The bilayer is stable and acts as a permeability barrier to compound loaded by prior absorption into the polymer core. Lipid mobility in the shell is similar to that found in other unanchored lipid bilayers. The system has potential application in drug delivery and for functional reconstitution of membrane proteins.

Acylation↗

Nephrotoxic impact of multiple short-interval cadmium-metallothionein injections in the rat.

The cadmium-metallothionein (CdMT) injection model was used to examine whether multiple short-interval injections of CdMT, instead of a single dose, could better reproduce the features of chronic exposure to inorganic cadmium. Male Wistar rats were given an initial CdMT dose and four subsequent doses subcutaneously at 2-h intervals. A control group, given saline, was compared with a low dose group (0.2 + 4 x 0.1 mg Cd/kg b.w.) and high dose group (0.4 + 4 x 0.1 mg Cd/kg b.w.). Nephrotoxic effects were seen at the high dose. A marked proteinuria began 6-12 h after the first injection and extended to day 9. A progressive, unreversed calciuria appeared at 6 h and reached its maximum at day 13. This was a marked increase in duration compared with the transient peaks of proteinuria and calciuria observed in previous single dose studies. The unreversed calciuria and the marked proteinuria are suggestive of residual tubular damage, which may be irreversible. In conclusion, the model with multiple short-interval CdMT injections more closely reproduces the situation in long-term exposure to inorganic cadmium, compared to the single dose models previously employed.

Animals↗

Protection against cadmium-metallothionein nephrotoxicity in streptozotocin-induced diabetic rats: role of increased metallothionein synthesis induced by streptozotocin.

Protection against the development of nephrotoxicity following the administration of cadmium-metallothionein (CdMT) at a dose of 0.4 mg Cd per kg body weights was studied in streptozotocin (STZ)-induced diabetic rats. Six groups of Wistar male rats were used (Groups A and B, Groups A1 and C, and Groups A2 and D were injected intraperitoneally with STZ at doses of 0, 50 and 100 mg/kg, respectively, and then 6 days later, Groups B, C and D were injected subcutaneously with CdMT). Proteinuria, albuminuria and transferrinuria were observed after the administration of CdMT, and a dose-related decrease following the increased STZ dose was seen in Groups B, C and D. The concentrations of metallothionein (MT) and zinc (Zn) in liver and kidney were dose-dependently increased in Groups B, C and D. Induction of increased MT synthesis in liver and kidney as the result of the STZ treatment was observed in this study. In particular, a remarkable increase in liver MT concentration was induced by STZ, and transport to the kidney of MT synthesized in liver may perhaps explain the protection against cadmium nephrotoxicity in STZ-induced diabetic rats.

Animals↗

Cadmium-metallothionein nephrotoxicity is increased in genetically diabetic as compared with normal Chinese hamsters.

To investigate the extra susceptibility of diabetics to some nephrotoxic agents, adult normal and diabetic Chinese hamsters (6-7 animals in each group) were injected subcutaneously with different doses of cadmium-metallothionein (Cd-MT) equivalent to 0.0, 0.1 or 0.25 mg Cd/kg body weight and the first 24 hr urinary outputs were collected. Several days prior to exposure to the Cd-MT the diabetic hamsters were hyperglycaemic, and plasma insulin levels and body weights were elevated in some of the diabetics. The higher dose of Cd-MT caused significant spillage of N-acetyl-beta-glucosaminidase (U-NAG) activity and protein into the urine of both normal and diabetic animals. The higher dose of Cd-MT was more toxic to the diabetic kidneys because U-NAG levels were higher in the diabetics (2.5-fold higher than normal). U-Cd levels were proportional to the injected Cd-MT dose. U-Zn levels were not consistently affected by the injected Cd-MT although it had contained small amounts of Zn. Therefore, genetic diabetes in the Chinese hamster appears to increase susceptibility to acute cadmium-MT nephrotoxicity. The mechanisms underlying this need to be further investigated.

Acetylglucosaminidase↗

Activation of proglucagon gene transcription through a novel promoter element by the caudal-related homeodomain protein cdx-2/3.

The proglucagon gene is expressed in a highly restricted tissue-specific manner in the A cells of the pancreatic islet and the L cells of the small and large intestines. The results of previous experiments indicate that cell-specific expression of the proglucagon gene is mediated by proteins that interact with the proximal G1 promoter element. We show here that the G1 element contains several AT-rich subdomains that bind proteins present in islet and enteroendocrine cell extracts. Electrophoretic mobility shift assay experiments using specific antisera identified the homeobox protein cdx-2/3 (which designates the same homeobox protein called cdx-2 for mice and cdx-3 for hamsters) as a major component of the G1-Gc2 complex in islet and intestinal cells. Mutations of the Gc element that decreased cdx-2/3 binding also resulted in decreased proglucagon promoter activity in islet and intestinal cell lines. The finding that cdx-2/3 mediates activation of the proglucagon promoter in both islet and enteroendocrine cells is consistent with the common endodermal lineage of these tissues and provides new insight into the coordinate regulation of genes expressed in both pancreatic and intestinal endocrine cell types.

Animals↗

Proglucagon gene expression is induced by gastrin-releasing peptide in a mouse enteroendocrine cell line.

The proglucagon gene is expressed in a cell-specific manner in the A cells of the islets and the L cells of the intestine; however, the physiological factors that regulate proglucagon gene expression are not well understood. Although insulin inhibits proglucagon gene transcription in the islets, peptides that stimulate proglucagon gene expression have not been identified. We show here that gastrin-releasing peptide (GRP) induces proglucagon messenger RNA transcripts in STC-1 enteroendocrine cells. The GRP induction of proglucagon gene expression was dose dependent, detectable by 4 h after GRP treatment, and sustained, i.e. detectable after a 24-h GRP incubation. GRP also induced the transcriptional activity of rat proglucagon promoter-luciferase plasmids in transfected STC-1 cells. The GRP induction of proglucagon promoter activity was attenuated, but not eliminated, after deletion of 5'-flanking sequences containing the proglucagon gene cAMP response element (CRE). A mutation in the CRE previously shown to abrogate cAMP responsiveness and CRE-binding protein binding was associated with a reduction in the transcriptional response to GRP. The proglucagon CRE also conferred GRP responsiveness to a truncated proglucagon promoter in STC-1 cells. These observations identify GRP as a peptide activator of proglucagon gene expression and provide evidence linking the proglucagon gene CRE to the physiological control of proglucagon gene expression.

Animals↗

Identification of the genes in multicopy plasmids affecting ompC and ompF expression in Escherichia coli.

Osmoregulation of the porin genes, ompF and ompC of Escherichia coli, occurs at the level of transcription through the action of EnvZ and OmpR proteins as well as at the level of translation through micF antisense RNA. In this study, we used a genetic screening approach to identify new genes which interfere with the expression of ompC or ompF. Using an E. coli genomic library in pUC19, we identified three clones whose products altered expression of ompC and ompF in response to medium osmolarity. One clone carrying the secB gene was found to block ompC and inhibit ompF expression. One clone carrying gcvA, a transcriptional regulator for the gvcA operon, was found to block ompF expression at high osmolarity and elevate ompC expression at low osmolarity. One clone carrying rbsR, a repressor for the rbs operon, was found to block ompF expression at both low and high osmolarities and elevate ompC expression at low osmolarity. These results suggest that ompF and ompC expression is associated with other physiological regulating systems in addition to osmoregulation.

Base Sequence↗

The suppression of age-related accumulation of lipid peroxides in rat brain by administration of Rooibos tea (Aspalathus linearis).

The protective effects of Rooibos tea (RT), Aspalathus linearis, against damage to the central nervous system (CNS) accompanying aging were examined by both the thiobarbituric acid reaction (TBA) and magnetic resonance imaging (MRI) methods in brains of chronically RT-treated rats. Ad libitum administration of RT was begun with 3-month-old Wistar female rats and continued for 21 months. The contents of TBA reactive substances (TBARS) in the frontal cortex, occipital cortex, hippocampus and cerebellum in 24-month-old rats after administration with water were significantly higher than those in young rats (5 weeks old). However, no significant increase of TBARS was observed in RT-administered aged rats. When MR images of the brains of 24-month-old rats with and without RT as well as 5-week-old rats were taken, a decrease of the signal intensity was observed in the cerebral cortex, hippocampus and cerebellum in MR images of aged rats without RT, whereas little change of the signal intensity was observed in MR images of the same regions of 24-month-old rats treated with RT, whose images were similar to those of young rats. These observations suggested that (1) the age-related accumulation of lipid peroxides in the brain was closely related to the morphological changes observed by MRI, and (2) chronic RT-administration prevented age-related accumulation of lipid peroxides in several regions of rat brain.

Administration, Oral↗

Conductance change in phospholipid bilayer membrane by an electroneutral ionophore, monensin.

Monensin is a polyether antibiotic ionophore and is considered an electroneutral Na/H antiporter. Its addition, however, increased the conductance of phospholipid bilayer membrane, and this increase was observed only when the medium contained Na+. Analysis of the current-voltage curve suggested that the increase was due to the formation and the translocation of an univalently charged species. The conductance at zero external voltage was proportional to the second power of monensin concentration and increased with the decrease in pH of the medium. Modified monensin whose terminal carboxyl was esterified showed much larger increase (ca. 100 times) in conductance than intact monensin. We concluded that the complex between the dimer of protonated monensin and Na+ contributed to the electrogenic transport of monensin. This complex bears a +1 charge, which is consistent with the analysis of current-voltage curves. Contrary to the conductance, the Na+ transfer rate of liposomal membrane measured with 23Na-NMR was proportional to the monensin concentration, meaning that the electrogenic component contributes little to the total monensin-mediated Na+ transport in the present system. It should be noted that this electrogenic component may change the membrane potential.

Electric Conductivity↗

The proglucagon gene upstream enhancer contains positive and negative domains important for tissue-specific proglucagon gene transcription.

The gene encoding proglucagon is restricted in expression to the central nervous system, endocrine pancreas, and intestine. Transgenic experiments indicate that the proglucagon gene upstream enhancer (GUE) element is a principal determinant of both the tissue specificity and the relative level of proglucagon gene transcription. We have now sequenced the rat proglucagon GUE and analyzed the transcriptional properties of proglucagon-luciferase fusion genes (that contain 5'- and 3'-deletions in the GUE) after transfection of islet (InR1-G9) and enteroendocrine (STC-1 and GLUTag) cell lines. The GUE contains both positive and negative elements that are recognized differentially in islet vs. intestinal cell lines. The transcriptional properties of the GUE sequences were more similar in cell lines of intestinal (STC-1 and GLUTag) compared with islet (InR1-G9) phenotypes. The electrophoretic mobility shift assay was used to identify specific domains of the GUE that interacted with nuclear proteins from islet and intestinal cells. Several GUE sequences recognized proteins present in both fibroblast and endocrine cell lines. In contrast, electrophoretic mobility shift assay experiments also identified 1) GUE-protein complexes common to both islet and intestinal cell lines and 2) GUE-protein complexes specific to either islet or intestinal lineages. One of the GUE subdomains, designated GLUE1, displayed enhancer-like activity in InR1-G9 and GLUTag, but not BHK, cell lines. Taken together, these observations demonstrate that the proglucagon GUE is comprised of multiple positive and negative domains that likely function in a combinatorial fashion to regulate islet and intestinal-specific proglucagon gene transcription.

Animals↗

Transmembrane signaling. Mutational analysis of the cytoplasmic linker region of Taz1-1, a Tar-EnvZ chimeric receptor in Escherichia coli.

Taz1-1 is Tar-EnvZ chimeric receptor that is able to induce ompC-lacZ expression in response to aspartate. Previous studies indicated that aspartate binding to the receptor domain of the Taz1-1 receptor modulated the ratio of kinase and phosphatase activities of the cytoplasmic signaling domain. The 80-residue segment of chemoreceptors that is located between the second transmembrane domain and the signaling domain was defined as the linker region. The Taz1-1 chimeric receptor contains 43 amino acid residues of the Tar linker region. In order to understand further the function of the linker region in transmembrane signaling, site-directed random mutagenesis was carried out on the conserved Ala231 in the linker region. Substitution mutations with Val, Glu, Gly, Thr, Lys and His gave the locked "off-mode" form (low ompC-lacZ expression), and substitution mutations with Ile and Leu resulted in the locked "on-mode" form (constitutive ompC-lacZ expression). All the mutant Taz1-1 receptors still retained both OmpR kinase and phospho-OmpR phosphatase activities. Interestingly Taz1N6, a kinase defective mutant, was able to complement with Taz1H1, a phosphatase defective mutant, carrying an off-mode mutant at position 231 to restore Asp-inducible ompC-lacZ expression, but not with Taz1H1 carrying an on-mode mutation. These results suggest that the residue at position 231 in Taz1-1 plays a key role in signal transduction.

Amino Acid Sequence↗