PubMed Health⌕ Search

Biomedical subjects

S Leng

Publications and source records attributed to S Leng.

12 recordsLinked to original sources

Allylnitrile: generation from cruciferous vegetables and behavioral effects on mice of repeated exposure.

The objective of the present study was to examine the possible generation of allylnitrile from commonly consumed cruciferous vegetables, and to determine the long-term behavioral effects of its oral administration at levels comparable to or greater than human dietary exposures. On the basis of gaschromatographic and mass spectrometric analyses, allylnitrile generation was observed in eight out of twelve vegetables, broccoli, broccoli (young stems and leaves), brussels sprouts, cabbage, cauliflower, chinese cabbage, komatsuna and kaiware-daikon (young stems and leaves). The daily dietary intake of allylnitrile was estimated to be at least 0.12 micromol/kg body weight for Japanese, based on its generation from the vegetables, broccoli, cabbage, cauliflower and Chinese cabbage and their daily dietary consumption. Mice received oral doses of 2, 20, 200, 500 and 1,100 micromol/kg allylnitrile once a day, 5 days per week for 13 weeks. Mice in the lower dosage groups of 2, 20 and 200 micromol/kg exhibited no behavioral changes. Mice dosed at the level of 500 micromol/kg showed restlessness, and one of them displayed alteration in tail hanging. These abnormalities were seen around seven days following the beginning of the treatment period. Animals in the highest dosage group elicited behavioral abnormalities, and their degree increased with increasing dosage. These results suggest that allylnitrile intake levels through daily vegetable consumption is below the level producing behavioral abnormalities.

Administration, Oral↗

Drosophila Pax-6/eyeless is essential for normal adult brain structure and function.

A role for the Pax-6 homologue eyeless in adult Drosophila brain development and function is described. eyeless expression is detected in neurons, but not glial cells, of the mushroom bodies, the medullar cortex, the lateral horn, and the pars intercerebralis. Furthermore, severe defects in adult brain structures essential for vision, olfaction, and for the coordination of locomotion are provoked by two newly isolated mutations of Pax-6/eyeless that result in truncated proteins. Consistent with the morphological lesions, we observe defective walking behavior for these eyeless mutants. The implications of these data for understanding postembryonic brain development and function in Drosophila are discussed.

Age Factors↗

Ethanol and gene expression in brain.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol-administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine D2-receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.

Alcoholism↗

Cloning and characterization of T-cell lymphoma invasion and metastasis 2 (TIAM2), a novel guanine nucleotide exchange factor related to TIAM1.

TIAM1 is a guanine nucleotide exchange factor that was identified in a screen for genes that increase the invasiveness of T lymphoma cell lines (Habets et al., 1994, Cell 77(4): 537-549). We have identified a gene, T-cell lymphoma invasion and metastasis 2 (HGMW-approved symbol TIAM2), with significant identity to the carboxyl-terminal region of the TIAM1 and mapped it to 6q25. TIAM2 is expressed as an approximately 3.3-kb transcript in cerebrum and as an approximately 4.4-kb transcript in the cerebellum and testis. The approximately 4. 4-kb message encodes a longer form of the approximately 3.3-kb mRNA predicted protein, and both contain homology to the Dbl-homologous region (70%) and Pleckstrin-homologous (54%) regions of TIAM1. We have purified TIAM2 and shown it to have GDP-GTP exchange activity. In situ hybridizations demonstrate TIAM2 expression in the E13.5 telencephalon of mouse embryos and in the cerebral cortex, hippocampus, and ependyma of adult mouse brains.

Amino Acid Sequence↗

The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23.

Bardet-Biedl Syndrome (BBS) is a heterogeneous, autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, syndactyly and/or polydactyly, short stature, and hypogenitalism and is caused by mutations at a number of distinct loci. Using a positional cloning approach for identifying the BBS4 (chromosome 15) gene, we identified and cloned an unconventional myosin gene, myosin IXA (HGMW-approved symbol MYO9A). Since mutations in unconventional myosins are known to cause several human diseases, and since mutations of unconventional myosin VIIa cause retinal degeneration, we evaluated myosin IXA as a candidate for BBS. We exploited PCR-based techniques to clone a 8473-nt cDNA for myosin IXA. A 7644-bp open reading frame predicts a protein with all the hallmarks of class IX unconventional myosins. Human Northern blot analysis and in situ hybridization of mouse embryos reveal that myosin IXA is expressed in many tissues consistent with BBS. Intron/exon boundaries were identified, and myosin IXA DNA and RNA from BBS4 patients were evaluated for mutation.

Amino Acid Sequence↗

[Molecular cloning of a cDNA encoding an antigenic polypeptide containing repeat units of Spirometra erinaceieuropaei plerocercoid].

AIM: To study the gene structure encoding some antigenic polypeptides of plerocercoid of Spirometra erinaceieuropaei (SEP). METHODS: A cDNA library constructed from SEP was immunoscreened using mouse anti-SEP polyclonal antibody. The gene structure was analyzed by computer after the insert of positive clone was subcloned and the nucleotide sequences of the insert were determined. The length of mRNA hybridized with cDNA was detected by Northern blotting. RESULTS: A cDNA clone of 1,084 bp encoding an antigenic polypeptide was isolated. The clone contained one open reading frame composed of 828 bp encoding 276 amino acids. The open reading frame contained tandem repeating unit of 123 bp which appeared 5 times in this clone. The 41 amino acids deduced from 123 bp repeating unit consisted of 53.7% of hydrophobic amino acid residues. In Northern blot assay of poly (A)+RNA, a strong band of about 1.1 kb and a weak band of about 1.7 kb were found in the plerocercoids but no band was found in the adult worms. CONCLUSION: The repeating element derived from the plerocercoids may be associated with the migration of the plerocercoids in the host tissue. The polypeptides with repeating element may act as evasive antigens of the parasite to escape from the destruction of host immune reactions.

Amino Acid Sequence↗

Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-infected fibroblasts after treatment with IFN-gamma or when virion host shutoff functions are disabled.

Herpes simplex virus (HSV)-specific CD8+ CTL cloned from individuals infected with HSV-2 efficiently lyse HSV-infected EBV-transformed B lymphoblastoid cells; however, these same CTL fail to lyse infected dermal fibroblasts. By 3 h after infection (early), class I MHC expression is reduced to less than 20% of that in uninfected fibroblasts, and expression is further reduced to less than 1% of the level in uninfected cells between 6 and 18 h after infection (late). We used an HSV-2 mutant that lacked the virion host shutoff (vhs) function to demonstrate that vhs plays a role in the loss of class I expression. While fibroblasts infected with this mutant are lysed by CTL that recognize virion proteins presented early as a consequence of introduction into the cytoplasm by the infecting virus, they are resistant to lysis by CTL that recognize viral proteins that must be synthesized de novo to be presented as class I Ags. Fibroblasts infected with a mutant that lacks the transporter-associated protein inhibitor ICP47 and is partially vhs defective are sensitive to CTL lysis. Pretreatment of fibroblasts with IFN-gamma prior to HSV infection sustained the level of class I expression for longer periods after infection, and these fibroblasts, infected with wild-type HSV-2, were partially sensitive to lysis by HSV-specific CTL. Taken together, these results suggest that the combined effects of the HSV-2 vhs and ICP47 gene products are to block Ag presentation by class I MHC. However, this effect can be transiently counteracted by IFN-gamma providing an early role for CD8+ CTL in the cellular immune response to HSV-2.

Antigen Presentation↗

Excitation and sensitization of the heat response induced by a phorbol ester in canine visceral polymodal receptors studied in vitro.

To clarify the possible involvement of protein kinase (PK) C activation in the excitation and sensitization of polymodal receptors (PMRs), the effects of phorbol 12,13-dibutyrate (PDBu) on PMRs were studied in canine testis-spermatic nerve preparations in vitro. Application of PDBu (10(-7), 10(-6), AND 10(-5) M) for 5 min evoked a significant increase in the ongoing activity of the PMRs within 15 min. PDBu (10(-8) to 10(-5) M) significantly augmented the subsequent heat responses of the PMRs. Staurosporine (10(-6) M), a PK inhibitor, attenuated the effect of PDBu on heat responses. These data suggest that activation of PKC contributes to the activities of PMRs.

Alkaloids↗

Characterization of the hepatitis C virus E2/NS1 gene product expressed in mammalian cells.

Truncated and full-length versions of the hepatitis C virus protein domain encoding a presumptive envelope glycoprotein designated E2/NS1 were stably expressed in CHO cell lines. Characterization of the processing events involved in the maturation of E2/NS1 revealed that a high-mannose form resident in the endoplasmic reticulum was the most abundant form detected intracellularly. The ionophore carboxyl cyanide m-chlorophenyl-hydrazone was used to show that the E2/NS1 glycoprotein resided in the endoplasmic reticulum. The full-length form of E2/NS1 appeared to be cell-associated and could not be detected as a secreted product. C-terminal truncated molecules could be detected in the extracellular media as fully processed glycoproteins containing terminal sialic acid additions. These truncated glycoproteins are predicted to be biologically relevant targets of the host immune response and are therefore potential subunit vaccine candidates.

Animals↗

Stimulatory effect of retinoic acid on GH gene expression: the interaction of retinoic acid and tri-iodothyronine in rat pituitary cells.

We have previously demonstrated that retinoic acid (RA) as well as thyroid hormone stimulates GH gene expression. To clarify the relationship between the action of RA and thyroid hormone, pituitary-specific gene expression was investigated further in rat pituitary cells. Rat clonal pituitary cells, GH3, were treated with RA with or without tri-iodothyronine (T3) for up to 3 days. After treatment with 10-1000 nmol RA/l with or without 0.1-10 nmol T3/l, medium was collected for radioimmunoassay and cells were subjected to RNA extraction, and GH and prolactin gene expression was analysed using 32P-labelled rat GH and rat prolactin cDNA probes respectively. The data demonstrated the dose-responsive manner of the stimulatory effects of RA and T3 on GH secretion with T3-depleted media. The action of RA was additive to that of T3 for GH secretion when maximum effective doses of RA or T3 were used. Using dot blot and Northern gel analysis, it was shown that RA increased GH mRNA levels in T3-depleted media, and that this action of RA was additive to that of T3 on the induction of GH mRNA levels. In contrast, neither RA nor T3 stimulated the secretion of prolactin and prolactin mRNA levels in these cells. Our results indicate that RA stimulates GH mRNA increment and GH secretion in T3-depleted media, and that the stimulatory effect of RA is additive to the maximum effective dose of T3.

Animals↗

Association between metabolic gene polymorphisms and susceptibility to peripheral nerve damage in workers exposed to n-hexane: a preliminary study.

Chronic exposure to n-hexane may result in peripheral neuropathy. 2,5-Hexanedione (2,5-HD) has been identified as a toxic metabolite of n-hexane. The CYP2E1, CYP1A1 and GST genes are involved in the formation of 2,5-hexanedione from n-hexane as well as the elimination of 2,5-HD-formed electrophile, and these genes are highly polymorphic in the general population. A nested case-control study in an industrial cohort was conducted to evaluate the associations between polymorphisms in these metabolic genes and n-hexane-induced peripheral nerve damage. The study subjects included 22 cases, who worked in a printing factory with symptoms of peripheral nerve damage, and 163 controls, who came from the same factory of cases. DNA was extracted from blood samples and genotyping was conducted for CYP2E1 Pst, CYP2E1 Dra, CYP2E1 Ins96, CYP1A1 Msp, GSTT1 null, GSTM1 null and GSTP1 105V. Unconditional logistic regression was applied to estimate the odds ratio and 95% confidence intervals. There were no significant differences between the two groups regarding age, sex, smoking and alcohol status. A significant association between Dra polymorphism and peripheral nerve damage was found. The frequency of CYP2E1 Dra homozygous mutation in the case group (18.2%) was higher than that in the control group (3.7%, p=0.015). Individuals with homozygote genotype (CC) of CYP2E1 Dra had a significantly higher risk of peripheral nerve damage compared with those with DD genotype (adjusted OR=?.58, 95% CI=1.32-23.65) after n-hexane exposure duration, sex, age, smoking and alcohol status were adjusted. No significant association was found that CYP2E1 Pst, CYP2E1 Ins96, CYP1A1 Msp, GSTT1, GSTM1, GSTP gene polymorphisms associated with the susceptibility of peripheral nerve damage. These findings suggested that CYP2E1 gene might increase the susceptibility to n-hexane-induced peripheral damage.

Adult↗