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Biomedical subjects

Y Hong

Publications and source records attributed to Y Hong.

At least 109 records · Page 6Linked to original sources
PubMed1999

Rac homologues and compartmentalized phosphatidylinositol 4, 5-bisphosphate act in a common pathway to regulate polar pollen tube growth.

Pollen tube cells elongate based on actin- dependent targeted secretion at the tip. Rho family small GTPases have been implicated in the regulation of related processes in animal and yeast cells. We have functionally characterized Rac type Rho family proteins that are expressed in growing pollen tubes. Expression of dominant negative Rac inhibited pollen tube elongation, whereas expression of constitutive active Rac induced depolarized growth. Pollen tube Rac was found to accumulate at the tip plasma membrane and to physically associate with a phosphatidylinositol monophosphate kinase (PtdIns P-K) activity. Phosphatidylinositol 4, 5-bisphosphate (PtdIns 4, 5-P2), the product of PtdIns P-Ks, showed a similar intracellular localization as Rac. Expression of the pleckstrin homology (PH)-domain of phospholipase C (PLC)-delta1, which binds specifically to PtdIns 4, 5-P2, inhibited pollen tube elongation. These results indicate that Rac and PtdIns 4, 5-P2 act in a common pathway to control polar pollen tube growth and provide direct evidence for a function of PtdIns 4, 5-P2 compartmentalization in the regulation of this process.

Amino Acid Sequence↗
PubMed1999

Sequences downstream of the RNA initiation site of the HTLV type I long terminal repeat are sufficient for trans-activation by human cytomegalovirus immediate-early proteins.

Human T cell leukemia virus type I infection is associated with a low incidence of morbidity in the form of adult T cell leukemia and neurologic disease, suggesting that there are other factors determining the pathogenic outcome of infection. We found that HCMV could infect various human cell lines known to be susceptible to HTLV-I infection, including T cell lines already harboring HTLV-I, and that HCMV infection could highly activate gene expression from the HTLV-I LTR. In addition, the coexpression of IE1 and IE2 genes of HCMV increased transcription from the HTLV-I LTR. The deletion analysis indicated that the entire U3 region is not required, but that the 216-bp region from +101 to +316 is sufficient for activation of the LTR by IE1 and IE2. These results suggest that HCMV IE proteins may affect the level of HTLV-I gene expression in coinfected individuals by interacting with HTLV-I LTR sequences.

Antigens, Viral↗
PubMed1999

Tumorigenicity of mouse thymoma is suppressed by soluble type II transforming growth factor beta receptor therapy.

Many types of tumor cells overexpress transforming growth factor beta (TGF-beta), which is believed to promote tumor progression. We hypothesized that overexpression of the extracellular region of the type II TGF-beta receptor (soluble TbetaRII) would compete for or block TGF-beta binding to TbetaRs on immune cells, preventing TGF-beta-mediated immunosuppression and consequently resulting in the eradication of tumor cells. We tested this in the mouse thymoma cell line EL4, which has been reported to suppress cellular immunity by secreting a large amount of TGF-beta. Transduction of EL4 with recombinant retrovirus encoding soluble TbetaRII resulted in the secretion of heterogeneously glycosylated, 25 to 35 kDa truncated TbetaRII. Inoculation of 1 x 10(4) to 5 x 10(4) soluble TbetaRII-modified EL4 cells (EL4/Ts, EL4 cells transduced with recombinant retrovirus encoding soluble TbetaRII and neomycin resistance gene) s.c. to mice showed reduced tumorigenicity, as indicated by lower overall tumor incidence (7%, 1 of 14; P < 0.001) compared with unmodified EL4 (100%, 9 of 9) or vector-modified EL4 cells (EL4/neo, EL4 cells transduced with recombinant retrovirus encoding neomycin resistance gene; 100%, 4 of 4). Administration of mitomycin C-treated EL4/Ts cells (1 x 10(6)) after EL4 inoculation (1 x 10(4)) reduced tumor incidence from 100% (5 of 5 in mice inoculated with mitomycin C-treated EL4/neo) to 40% (4 of 10, P < 0.05), indicating that supply of soluble TbetaRII could actually block TGF-beta-mediated tumorigenesis. In vitro tumor cytotoxicity assays revealed 3-5-fold higher cytotoxic activity with lymphocytes from EL4/Ts-bearing mice compared with those from EL4- or EL4/neo-bearing mice, indicating that the observed tumor rejection was mediated by restoration of the tumor-specific cellular immunity. These data suggest that expression of soluble TbetaRII is an effective strategy for treating highly progressive tumors secreting TGF-beta.

Animals↗
PubMed1999

The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis.

Expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of Tumor Necrosis Factor Alpha (TNF). While murine C127 cells containing the bovine papillomavirus type 1 (BPV-1) genome were reported to exhibit increased TNF sensitivity, the gene(s) responsible was not identified. The BPV-1 E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. BPV-1 E6 was introduced into C127 cells (PBE6) by retroviral infection and stable clones were isolated. These cells showed increased apoptosis in response to TNF, as measured by several criteria. TNF-induced apoptosis in PBE6 cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A2 was activated. We also provide evidence that BPV-1 E6 mediated-sensitization of cells to TNF-induced apoptosis can occur in the absence of p53.

Animals↗
PubMed1999

Evidence of a major locus for lipoprotein lipase (LPL) activity in addition to a pleiotropic locus for both LPL and fasting insulin: results from the HERITAGE Family Study.

A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal tau s) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.

Adolescent↗
PubMed1999

Total body fat and abdominal visceral fat response to exercise training in the HERITAGE Family Study: evidence for major locus but no multifactorial effects.

The familial etiology of the response in total fat mass (FM) and abdominal visceral fat (AVF) to 20 weeks of exercise training was investigated in families participating in the HERITAGE Family Study. AVF (measured by computed tomographic scanning) and FM (measured by underwater weighing techniques) were assessed at baseline (in a sedentary state) and after 20 weeks of exercise training. The response AVF (AVFdelta) and response FM (FMdelta) were computed as the simple delta values (posttraining - baseline) and adjusted for the effects of sex, generation, and a polynomial in age using multiple regression analysis. To index the AVF response independently of the response in FM and the initial level of visceral fat, the AVFdelta was also adjusted for age and baseline AVF (AVFB) and FMdelta. Familial correlation analysis was used to investigate the multifactorial familial effects (polygenic and/or familial environmental), and segregation analysis was used to search for major gene effects. For the age-adjusted AVFdelta, a putative recessive locus accounting for 18% of the variance (q2 = 1%) was detected. Adjusting AVFdelta for AVFB and FMdelta slightly increased the percentage of variance accounted for (to 26%, q2 = 3%) but did not radically alter the pattern of the parameter estimates. For FMdelta, a putative dominant locus accounting for 31% of the variance (q2 = 49%) was noted. In conclusion, the results were consistent across methods in suggesting that there is little evidence of a multifactorial heritability for either AVFdelta or FMdelta. Rather, the familial etiology of the response to exercise training appears to be primarily due to putative major genes (a recessive locus for AVFdelta and a dominant locus for FMdelta). In addition, a pleiotropic/oligogenic system underlying these variables was inferred. That is, the putative loci for FMdelta and/or AVFB also may impact the AVFdelta, with an additional independent major locus effect on AVFdelta after the former influences have been removed.

Abdomen↗
PubMed1999

Towards obtaining ES cells in the marine fish species Sparus aurata; multipassage maintenance, characterization and transfection.

Animal Embryonic-Stem (ES) cells represents a unique tool in animal genetic manipulation. Though putative ES cells from several species have been reported, only those from mice proved successful. In this work, a long-term embryonic cell culture, derived from the commercial fish (Sparus aurata), is reported. These cells have been in vitro characterized for totipotency and transfected with a GFP plasmid.

Animals↗
PubMed1999

A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development.

BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.

Adult↗
PubMed1999

Implications of body fat distribution in an older twin population.

BACKGROUND: As people age, fat becomes preferentially deposited in the abdominal region over the periphery, and such changes are thought to be associated with adverse metabolic outcomes. We were interested in whether body mass index (BMI) and waist-hip ratio (WHR) are differentially associated with fasting insulin levels, triglycerides, and blood pressure (systolic and diastolic) in an older population. We were also interested in whether these associations change after controlling for genetic influences. METHODS: Data were obtained as part of the Swedish Adoption/Twin Study of Aging. All blood samples and anthropometric measures were assessed from 1989-1991 except insulin, which was assessed from 1986-1988. The sample contains 263 twin pairs (97 monozygotic and 166 dizygotic), 56% women, average age 65 years. RESULTS: In men and women, WHR and BMI were significantly associated with all the metabolic variables except for diastolic blood pressure. When BMI's association with the metabolic variables was assessed independent of WHR, it remained significantly associated with all metabolic variables except diastolic blood pressure in men and triglycerides in women. When WHR's association with the metabolic variables was assessed independent of BMI, it did not remain significantly associated with any of the metabolic variables in men and remained significantly associated with insulin and diastolic pressure in women. After controlling for genetic effects, the relationship between WHR and the metabolic variables became nonsignificant. However, BMI remained significantly associated with systolic blood pressure and triglycerides in men, independent of WHR. CONCLUSION: The results suggest that overall body fat is important to consider in relation to these metabolic parameters in older individuals. The results also suggest that BMI may share associations with blood pressure and triglycerides beyond those that can be attributed to familial influences.

Adipose Tissue↗
PubMed1999

Multiple functions of human papillomavirus type 16 E6 contribute to the immortalization of mammary epithelial cells.

The E6 proteins from cervical cancer-associated human papillomavirus (HPV) types such as HPV type 16 (HPV-16) induce proteolysis of the p53 tumor suppressor protein through interaction with E6-AP. We have previously shown that human mammary epithelial cells (MECs) immortalized by HPV-16 E6 display low levels of p53. HPV-16 E6 as well as other cancer-related papillomavirus E6 proteins also binds the cellular protein E6BP (ERC-55). To explore the potential functional significance of these interactions, we created and analyzed a series of E6 mutants for their ability to interact with E6-AP, p53, and E6BP in vitro. While there was a similar pattern of binding among these E6 targets, a subset of mutants differentiated E6-AP binding, p53 binding, and p53 degradation activities. These results demonstrated that E6 binding to E6-AP is not sufficient for binding to p53 and that E6 binding to p53 is not sufficient for inducing p53 degradation. The in vivo activity of these HPV-16 E6 mutants was tested in MECs. In agreement with the in vitro results, most of these p53 degradation-defective E6 mutants were unable to reduce the p53 level in early-passage MECs. Interestingly, several mutants that showed severely reduced ability for interacting with E6-AP, p53, and E6BP in vitro efficiently immortalized MECs. These immortalized cells exhibited low p53 levels at late passage. Furthermore, mutants defective for p53 degradation but able to immortalize MECs were also identified, and the immortal cells retained normal levels of p53 protein. These results imply that multiple functions of HPV-16 E6 contribute to MEC immortalization.

Animals↗
PubMed1999

Genetic effects for plasma factor VII levels independent of and in common with triglycerides.

BACKGROUND: Coagulation factor VII has been demonstrated as a potential risk factor for cardiovascular disease. Both genes and non-genetic factors are related to plasma levels of factor VII. However, the extent to which genetic effects influence variability in plasma factor VII levels is unknown. Further, increased levels of plasma factor VII are associated with serum triglycerides, yet the reason for this association is not fully understood. METHODS AND RESULTS: Quantitative genetic analyses were applied to evaluate the relative importance of genetic and different environmental influences on plasma factor VII levels and to test the significance of genetic and environmental factors in common to factor VII and triglycerides in 215 pairs of middle-aged and elderly twins, of whom 104 were reared apart and 120 were women. Genetic influences were found to account for 57% of the individual differences in plasma factor VII levels, whereas shared-rearing and residual-familial environmental factors were not significant. Furthermore, a significant genetic correlation of 0.38 was found between factor VII and triglycerides, but the environmental correlation between these two measures was not significant. Genetic factors in common to factor VII and triglycerides explain about 7% of the total variance for factor VII. CONCLUSION: The present study suggests that there are substantial genetic influences on plasma factor VII levels. Furthermore, genetic effects explain the phenotypic association between factor VII and triglycerides.

Aged↗
PubMed1999

[Extract of cemental matrix enhance periodontal cells bind to the root surface].

OBJECTIVE: To investigate whether the extract of cemental matrix can enhance periodontal cells binding to the root surfaces. METHODS: Healthy human gingiva and periodontal ligament were acquired from patients, then gingival fibroblasts and periodontal cells were cultured in vitro. On the other hand, extract of cemental matrix was separated and clarified from healthy teeth which were extracted because of orthodontic treatment. Finally, the effects of cementum matrix with different concentration and different time on the attachment of gingival fibroblast and periodontal cells to root surface were observed. RESULTS: The extract of cemental matrix could enhance the initial attachment of human gingival fibroblasts (HGF) and human periodontal cells (HPC) to the surface of root, and such effects were strengthened with increasing density and time. The optimal concentration of extract of cell attachment 10 micrograms/ml, and the attachment was also proportional to the incubation time, reaching near maximal levels at 2 hours, furthermore, the extract of cemental matrix was more effective in promoting the attachment of human periodontal cells than that of gingival fibroblasts. CONCLUSION: The extract of cemental matrix can enhance the initial attachment of HGF and HPC on the root surface.

Cell Adhesion↗
PubMed1998

Cholinergic cell expression in the developing rat medial septal nucleus in vitro is differentially controlled by GABAA and GABAB receptors.

The early appearance and relative abundance of GABAergic neurons in basal forebrain cholinergic nuclei like the medial septum suggest that the maturation of the later developing cholinergic neurons in these nuclei may be controlled by GABA. To examine this possibility, the effects of both exogenous GABA and specific GABA receptor agonists, as well as that of endogenous GABA on the phenotypic expression and survival of the cholinergic neurons in primary cultures from the fetal rat medial septum, were studied. Treatment of these cultures for six days with GABA significantly decreased the enzymatic activity of choline acetyltransferase (EC 2.3.1.6) (ChAT) in a dose-dependent manner. This response to exogenous GABA was blocked by bicuculline, mimicked by muscimol and slightly potentiated by saclofen. Consistent with this latter observation, the GABAB receptor agonist, baclofen, dose-dependently increased septal ChAT activity. However, while the effect of baclofen on cholinergic expression was lost in the absence of glia, the suppressive effects of GABA or muscimol were more marked. Acetylcholinesterase (EC 3.1.1.7) (AChE) expression in mixed neuronal-glial cultures, was, like ChAT activity, increased or decreased in intensity with the inclusion of baclofen or muscimol, respectively. Although the number of AChE positive neurons in muscimol-treated cultures was significantly lower than that in controls, no changes in neither neuronal nor general cell viability were noted. Finally, as GABAA or GABAB receptor antagonists bicuculline and picrotoxin or saclofen, when applied alone to mixed cultures, increased or decreased ChAT activity, respectively, it appears that endogenous GABA, tonically released in the developing septum, may, via specific receptor types, differentially control the biochemical maturation of the cholinergic neurons.

Acetylcholinesterase↗
PubMed1998

Kinetic analysis of the interaction of actin-depolymerizing factor (ADF)/cofilin with G- and F-actins. Comparison of plant and human ADFs and effect of phosphorylation.

The thermodynamics and kinetics of actin interaction with Arabidopsis thaliana actin-depolymerizing factor (ADF)1, human ADF, and S6D mutant ADF1 protein mimicking phosphorylated (inactive) ADF are examined comparatively. ADFs interact with ADP.G-actin in rapid equilibrium (k+ = 155 microM-1.s-1 and k- = 16 s-1 at 4 degreesC under physiological ionic conditions). The kinetics of interaction of plant and human ADFs with F-actin are slower and exhibit kinetic cooperativity, consistent with a scheme in which the initial binding of ADF to two adjacent subunits of the filament nucleates a structural change that propagates along the filament, allowing faster binding of ADF in a "zipper" mode. ADF binds in a non-cooperative faster process to gelsolin-capped filaments or to subtilisin-cleaved F-actin, which are structurally different from standard filaments (Orlova, A., Prochniewicz, E., and Egelman, E. H. (1995) J. Mol. Biol. 245, 598-607). In contrast, the binding of phalloidin to F-actin cooperatively inhibits its interaction with ADF. The ADF-facilitated nucleation of ADP.actin self-assembly indicates that ADF stabilizes lateral interactions in the filament. Plant and human ADFs cause only partial depolymerization of F-actin at pH 8, consistent with identical functions in enhancing F-actin dynamics. Phosphorylation does not affect ADF activity per se, but decreases its affinity for actin by 20-fold.

Actin Depolymerizing Factors↗
PubMed1998

GFP expression in Drosophila tissues: time requirements for formation of a fluorescent product.

We analyzed the acquisition of fluorescence of a GFP fusion protein expressed from gene constructs designed to regulate either the time of translation of the protein or the time of gene transcription. Both gene constructs expressed a fusion protein with wild-type GFP appended to the N-terminus of the Bicoid (Bcd) transcription factor. One gene construct, P[gfp-bcd] expressed an mRNA that was initially translated at the time of egg deposition. GFP-Bcd fluorescence could first be detected in anterior nuclei in the embryo at syncytial blastoderm stage, within 1.5-2.5 h after translation commenced. The second gene construct, P[hs-gfp-bcd], utilized the hsp70 promoter to regulate the induction of gene expression. In larval salivary glands, GFP-Bcd fluorescence could first be detected in nuclei after a 40-min recovery period following a 10-min heat shock induction of gene expression. These estimates of the time required for the acquisition of a fluorescent GFP product in Drosophila tissues are less than suggested by previously published reports.

Animals↗
PubMed1998

In vivo chiro-inositol metabolism in the rat: a defect in chiro-inositol synthesis from myo-inositol and an increased incorporation of chiro-[3H]inositol into phospholipid in the Goto-Kakizaki (G.K) rat.

We report our comparative studies of myo- and chiro-[3H]inositol distribution in control nondiabetic Wistar and spontaneous nonobese insulin-resistant Type II diabetic G.K. rat tissues following 78-h labeling period. From various tissue extracts, free inositols, inositol phosphates, and inositol phospholipids were isolated and analyzed. Our findings demonstrate (1) a significant difference in the metabolism of myo- and chiro-inositol in normal Wistar and G.K. rats, (2) a severe defect in conversion of myo-[3H]inositol to chiro-[3H]inositol at the inositol phospholipid level of insulin-sensitive tissues of the G.K. rat, (3) an increased incorporation of myo-[3H]inositol into purified inositol phospholipids of the G.K. rat consistent with a decreased conversion to chiro-[3H]inositol, (4) the presumed presence of a pathway which incorporates chiro-[3H]inositol into inositol phospholipids, and which is overactive in the G.K. rat compared to the Wistar rat, and (5) no or minimal conversion of chiro-[3H]inositol to myo-[3H]inositol.

Animals↗