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Biomedical subjects

Y Ke

Publications and source records attributed to Y Ke.

At least 19 recordsLinked to original sources
PubMed2001

Human cutaneous fatty acid-binding protein induces metastasis by up-regulating the expression of vascular endothelial growth factor gene in rat Rama 37 model cells.

Human cutaneous fatty acid-binding protein (C-FABP) gene is capable of inducing the metastatic phenotype when overexpressed in nonmetastatic rat Rama 37 cells. However, the mechanism of how it induces metastasis is not clear. Northern and slot blot analyses revealed that expression of the endogenous vascular endothelial growth factor (VEGF) gene was increased by 3.8-5.2-fold in the C-FABP-transfected cells (pSV-CFABP-R37) and in their metastatic sublines (e.g., Met-1) when compared with that in the nonmetastatic control transfectant pSV-R37 cells generated by transfection of only plasmid DNA. Higher levels of VEGF immunoreactive protein were also secreted from the malignant C-FABP-expressing cells. Reverse transcription-PCR detected two VEGF transcript isoforms, VEGF(164) and VEGF(188), in both the nonmetastatic control transfectant pSV-R37 cells and the malignant metastatic Met-1 cells. Chick chorioallantoic membrane assays showed that the conditioned medium of the control pSV-R37 cells possessed only very weak angiogenic activity, whereas conditioned media from the metastatic C-FABP transfectants and their sublines were strongly angiogenic and could be inhibited by antibodies to VEGF. Transfection of VEGF(164) cDNA in an expression vector into nonmetastatic Rama 37 cells produced a cell clone (R37-VEGF-2) that expressed high levels of VEGF. Inoculation of R37-VEGF-2 cells into syngeneic Wistar Furth rats produced metastases in a significant number (Fisher's exact test, P < 0.01) of animals (18 of 31 animals), whereas the control, vector alone-transfected R37-PSV cells produced no metastases (0 of 30 animals). Immunocytochemical methods demonstrated a strong positive staining for VEGF and an increased microvessel density in the primary tumors produced from PSV-VEGF-2 cells in comparison with tumors produced from control transfectants. Immunocytochemical staining for factor VIII detected a 3.5-fold increase in microvessel density of the primary tumors produced by PSV-VEGF-2 cells when compared with that of the primary tumors developed from the control pSV-R37 cells. Therefore, we suggest that overexpression of the C-FABP gene in the original transfectants induces metastasis through up-regulation of expression of the VEGF gene in this rat Rama 37 model system, and thus VEGF may play a crucial role in this particular metastatic cascade.

Animals↗
PubMed2001

African origin of modern humans in East Asia: a tale of 12,000 Y chromosomes.

To test the hypotheses of modern human origin in East Asia, we sampled 12,127 male individuals from 163 populations and typed for three Y chromosome biallelic markers (YAP, M89, and M130). All the individuals carried a mutation at one of the three sites. These three mutations (YAP+, M89T, and M130T) coalesce to another mutation (M168T), which originated in Africa about 35,000 to 89,000 years ago. Therefore, the data do not support even a minimal in situ hominid contribution in the origin of anatomically modern humans in East Asia.

Africa↗
PubMed2001

Exercise decreases cytosolic aconitase activity in the liver, spleen, and bone marrow in rats.

Effects of strenuous exercise on cytosolic aconitase activity (CAA) were investigated in this study. Female Sprague-Dawley rats were randomly assigned to four groups: S1 (Sedentary), S2 (Sedentary + L-NAME [N-nitro-l-arginine methyl ester]), E1 (Exercise), and E2 (Exercise + L-NAME). Rats in the E1 and E2 groups swam for 2 h/day for 3 months. L-NAME (an inhibitor of NOS) in drinking water (1 mg/ml) was administered to rats in the S2 and E2 groups for the same period. At the end of the third month, the CAA in the liver, spleen, and bone marrow cells was measured. In the exercise group (E1), CAA in the liver, spleen, and bone marrow cells was 19.99 +/- 1.49, 1.61 +/- 0.13, and 0.59 +/- 0.09 mU/mg protein, respectively. These values were significantly lower than the corresponding sedentary values in the S1 group (33.96 +/- 1.38, 3.96 +/- 0.19, and 3.20 +/- 0.18 mU/mg protein) (P < 0.01, 0.001, and 0.001, respectively). The treatment of L-NAME led to a significant increase in tissue CAA in the sedentary rats (S2). Also, the significantly higher CAA in the liver, spleen, and bone marrow cells was found in the exercised rats treated with L-NAME (E2) (29.50 +/- 1.27, 2.89 +/- 0.25, and 1.34 +/- 0.20 mU/mg) than without L-NAME (E1) (P < 0.01, 0.01, 0.05, respectively). However, the values in the E2 group were still significantly lower than those in the S1 group (P < 0.05, 0.01, and 0.001, respectively). This indicates that L-NAME treatment can partly recover the decreased CA in tissues in the exercised rats. These results provide evidence for the existence of the increased activity of IRP1 (iron regulatory protein 1) that is probably induced by the increased nitric oxide production in the strenuously exercised rats.

Aconitate Hydratase↗
PubMed2001

Rethinking the role of ceruloplasmin in brain iron metabolism.

For more than three decades, it has been widely accepted that ceruloplasmin plays an important role in iron efflux from mammalian cells, including brain cells, via the activity of ferroxidase. However, in light of recent findings, this view might not be completely accurate and the role of ceruloplasmin in brain iron metabolism may need to be re-evaluated. Based on recent studies, we propose in this article that the role of ceruloplasmin in iron uptake by brain neuronal cells might be more important than its role in iron release from the cells. A possible explanation of why the absence of ceruloplasmin induces excessive iron accumulation in neurons in aceruloplasminemia (ceruloplasmin gene mutations) was also discussed.

Animals↗
PubMed2001

Human papillomavirus type 16 is an important infectious factor in the high incidence of esophageal cancer in Anyang area of China.

To investigate the potential role of human papillomavirus (HPV) infection in the pathogenesis of esophageal carcinomas in the Anyang area of China, we have evaluated specimens collected by balloon cytology examination from volunteers in two regions with significantly different incidences of esophageal carcinoma. 138 donors were from a village in a county with an esophageal carcinoma (EC) age-adjusted mortality rate of 132x10(5), the remaining 68 were resident in a second village from another county with an EC mortality rate of 52x10(5). Specimens were evaluated using both polymerase chain reaction (PCR) amplification and in situ hybridization (ISH) protocols. PCR results showed that the prevalence of the human papillomavirus type 16 (HPV-16) E6 gene in the high incidence area was 1.9-fold higher than that of the low incidence area (72 and 37%, respectively, P < 0.01). Moreover, the positive rate corresponded with pathology grade. Similar results were obtained with the HPV-16 E7 gene. As the cells undergoing cytopathological progress, the HPV-16 E6 positive rate was increased, in both villages. In contrast to HPV-16 E6 and E7, detection of the HPV L1 gene was consistently lower, and its prevalence decreased with increasing dysplasia grades (P < 0.05). By ISH analyses, the expression rate of HPV-16 E6 in the specimens collected from the high incidence area was 2.2-fold higher than those from the low incidence area (49 versus 22%, respectively; P < 0.05), and transcription of the E6 gene paralleled cytopathology. HPV-18 was also detected in 17 and 15% of the specimens from the high and low incidence areas, respectively, but most of these samples were also simultaneously HVP-16 positive. These results suggest that HVP-16 plays a causative role in the high incidence of esophageal cancer in the Anyang region of CHINA:

China↗
PubMed2001

Increased nitric oxide is one of the causes of changes of iron metabolism in strenuously exercised rats.

This study was carried out to investigate the possible role of increased nitric oxide (NO) production in the development of the low iron status in strenuously exercised rats. Female Sprague-Dawley rats were randomly assigned to four groups: sedentary (S1), sedentary + nitro-L-arginine methyl ester (L-NAME; S2), exercise (E1), and exercise + L-NAME (E2). Animals in the E1 and E2 groups swam for 2 h/day for 3 mo. L-NAME in the drinking water (1 mg/ml) was administrated to rats in the S2 and E2 groups for the same period. At the end of third month, hematological indexes and nitrite and nitrate (NOx) contents in the plasma and non-heme iron and NOx levels in the liver, spleen, and bone marrow cells were measured. Three months of exercise induced a significant increase in NOx content and a decrease in iron level both in plasma and tissues. Treatment with L-NAME, an inhibitor of NO synthase (NOS), led to a significant decrease in NOx and an increase in iron level both in plasma and tissues in the exercised rats. The E2 group had a significantly lower NOx content as well as a higher iron level both in plasma and tissues than the E1 group. However, the iron contents in the plasma and tissues of the E2 group were still significantly lower than those found in S1. No difference was found in NOx levels between E2 and S1. These findings showed that exercise was associated with elevation in NOx and reduction in iron in plasma and the tissues. Treatment with L-NAME was able to completely inhibit the effect of exercise on NOx as well as partly recover the decreased iron contents in plasma and tissues resulting from exercise. This suggests that the increased production of NO might be one of the causes of the lower iron status in exercised rats.

Animals↗
PubMed2001

Skin reflectance in the Han Chinese and Tibetan populations.

Genetic and environmental factors are involved in the determination of skin pigmentation in humans. With the recent development of statistical and genetic tools in mapping complex traits in humans, it is becoming feasible to utilize such methods in identifying genes involved in skin pigmentation. Furthermore, the use of new portable reflectance spectroscopy instruments such as the Photovolt ColorWalk colorimeter allows researchers to measure skin reflectance of a large number of subjects with ease and accuracy. We used a new portable instrument (Photovolt ColorWalk) to study the skin reflectance of 372 Han Chinese and 274 Tibetan individuals to establish background reflectance measurements of unexposed skin of the inner upper arm in these two populations. In addition, we explored the effect of various factors such as age and gender on skin reflectance.

Adolescent↗
PubMed2000

Assessment of GABA concentration in human brain using two-dimensional proton magnetic resonance spectroscopy.

A quantitative method to assess in vivo brain gamma-aminobutyric acid (GABA) levels is proposed using a J-resolved, two-dimensional (2D) magnetic resonance spectroscopy (MRS) technique. Localized, J-resolved 2D MR spectra were obtained from a 12-cm(3) voxel in the occipital lobe of 36 healthy volunteers (18 male and 18 female, age: 25.1+/-4.8 years). Based on phantom measurements, a GABA resonance peak located at 2.94 ppm, 7.45 Hz, in J-resolved 2D MRS overlaps the least with other resonance peaks which arise from N-acetylaspartate, choline, creatine, glutamate and glutamine. Measurements of this resonance peak yield in vivo GABA concentrations of 1.01+/-0.36 micromol/cm(3) for male and 1.16+/-0.43 micromol/cm(3) for female volunteers, without correction for T1 and T2 relaxation effects. These results are in good agreement with previously reported data and suggest that, with further development, 2D MRS may provide a practical means to estimate the concentration of this important neurotransmitter.

Creatine↗
PubMed2000

Heat shock protein expression independently predicts clinical outcome in prostate cancer.

Heat shock proteins (hsps) occupy a central role in the regulation of intracellular homeostasis, and differential expression of individual hsps occurs in a broad range of neoplastic processes. This study was performed to test the hypothesis that the particular patterns by which individual hsps become specifically modulated in human prostate cancers are correlated with behavioral phenotype and hence may be of value in determining the most appropriate clinical management of individual patients. Monoclonal antibodies specific for each hsp protein were used to assess expression of hsp27, hsp60, and hsp70 in formalin-fixed, paraffin wax-embedded, archival tissue specimens of early prostatic adenocarcinomas (pT1-2N0M0) removed at radical prostatectomy (n = 25) and in advanced cancers (n = 95) identified at transurethral resection of prostate (TURP). These findings were compared with similar data from control prostates (n = 10) removed at primary cystectomy for urinary bladder neoplasia not involving the prostate and also at TURP for benign prostatic hyperplasia (n = 50). Western blotting of whole cell lysates derived from established human prostatic epithelial cell lines PNT2, LNCaP, DU145, and PC3 was compared with expression of hsps by the primary human tissues. This study found that early in situ neoplastic transformation of normal prostatic epithelium was consistently associated with loss of hsp27 expression and that the level of hsp27 expression by individual prostate cancers was correlated with their Gleason grade. In advanced cancers, hsp27 expression was invariably associated with poor clinical outcome (P = 0.0001). Data from cell lines supported the primary tissue findings, with elevated hsp27 expression only in aggressive malignant cell lines and androgen-insensitive cell lines. Expression of hsp60 was significantly increased in both early and advanced prostate cancer when compared with nonneoplastic prostatic epithelium (P < 0.0001), as well as in malignant prostate cancer cell lines. Expression of hsp70 was unaltered in early prostate cancers when compared with nonneoplastic prostatic epithelium but showed a diminished expression in morphologically advanced cancers (P = 0.0029). No consistent correlation was found between levels of hsp60 or hsp70 expression and phenotypic behavior of individual primary prostatic cancers. Thus, patterns of hsp expression have been confirmed to be specifically and consistently modulated in both early and advanced human prostate cancers. Whereas absence of hsp27 is a reliable objective marker of early prostatic neoplasia, reexpression of this protein by an individual invasive prostatic carcinoma invariably heralds poor clinical prognosis. Because this protein has been shown to alter the balance between proliferation and apoptosis, understanding the mechanism(s) by which individual hsps regulate intracellular homeostasis may assist in explaining some key processes that occur during evolution of human prostate cancers. We suggest that hsp27 expression provides novel diagnostic and prognostic information on individual patient survival which, if obtained at the time of primary diagnosis, would assist in determining tumor-specific management strategies. Development of techniques to therapeutically modulate hsp27 expression raises the possibility of novel targeted approaches to regulate this homeostatic mechanism, thus allowing better control over tumor cell proliferation and hence patient survival.

Adenocarcinoma↗
PubMed2000

A myosin I isoform in the nucleus.

A nuclear isoform of myosin I beta that contains a unique 16-amino acid amino-terminal extension has been identified. An affinity-purified antibody to the 16-amino acid peptide demonstrated nuclear staining. Confocal and electron microscopy revealed that nuclear myosin I beta colocalized with RNA polymerase II in an alpha-amanitin- and actinomycin D-sensitive manner. The antibody coimmunoprecipitated RNA polymerase II and blocked in vitro RNA synthesis. This isoform of myosin I beta appears to be in a complex with RNA polymerase II and may affect transcription.

3T3 Cells↗
PubMed2000

Effect of fatty acids on the mycelial growth and polysaccharide formation by Ganoderma lucidum in shake flask cultures.

Fatty acids were added into the media to investigate their effects on the mycelial growth and polysaccharide formation by Ganoderma lucidum. The experiments were carried out in freely suspended cultures or immobilized cultures using shake flasks. The results indicate that the extent of stimulation or inhibition were associated with the types and levels of fatty acids. Oleic acid at the level of 0.15 g/100 ml led to a significant increase in cell concentration from 0.20 to 0.46 g/100 ml in a suspended culture and palmitic acid was of great advantage to polysaccharide production. In contrast, linoleic acid (0.1 g/100 ml) drastically suppressed both mycelial growth and polysaccharide formation. In immobilized cultures with fatty acids, the stimulation of mycelial growth remained the same level, but the enhancement of polysaccharide production became less. In addition, the growth of G. lucidum in the pattern of immobilization might be beneficial to the production of mycelia and polysaccharide.

Journal Article↗
PubMed2000

Modulating effect of estrogen and testosterone on prostatic stromal cell phenotype differentiation induced by noradrenaline and doxazosin.

BACKGROUND: Noradrenaline (NA) has been shown to enhance expression of the contractile phenotype of human prostatic stromal cells in tissue culture. This study examined the possibility that changing levels of sex hormones in elderly men with BPH may modulate the differentiating effect of NA and hence the efficacy of alpha(1)-adrenoceptor-blocking drugs. METHODS: Confluent, quiescent stromal cell cultures from 6 different patients were treated with combinations of 20 microM NA, 1 microM doxazosin, 0.1 microM beta-estradiol, and 0.1 microM testosterone, over a period of 10 days. Harvested cells were labelled with fluorescein-conjugated antisera to alpha-smooth muscle actin and myosin to identify cells of contractile phenotype which were thereafter analyzed flow-cytometrically. RESULTS: NA increased mean immunoexpression of both actin and myosin. Enhancement of myosin expression was highly significant (P </= 0.02). This effect was incompletely opposed by doxazosin. Neither estradiol nor testosterone influenced mean expression of contractile filaments and did not significantly enhance or inhibit the effects of NA or doxazosin. However, both sex hormones exhibited a differentially powerful effect on cell lines from individual patients. The expression of myosin increased by NA was further elevated by addition of estradiol in four of the cell lines and by testosterone in three. CONCLUSIONS: The data suggest that levels of estrogens and androgens, either alone or in combination, are unlikely to predict the development of obstructive symptoms in patients with BPH or their response to doxazosin. Nevertheless, prostatic stromal cells from individual patients may be exceptionally sensitive to both sex hormones, with enhanced modulation towards a contractile phenotype. Since alpha- and beta-subtypes of the estrogen receptor are differentially expressed between the stroma and epithelium of the early fetal prostate, it is likely that interaction between sex hormones and noradrenaline is an important factor in determining the phenotypic composition of prostatic stroma at this early stage of development, and possibly predisposition to BPH during later adult life.

Actins↗
PubMed2000

Internal loop/bulge and hairpin loop of the iron-responsive element of ferritin mRNA contribute to maximal iron regulatory protein 2 binding and translational regulation in the iso-iron-responsive element/iso-iron regulatory protein family.

Iron-responsive elements (IREs), a natural group of mRNA-specific sequences, bind iron regulatory proteins (IRPs) differentially and fold into hairpins [with a hexaloop (HL) CAGUGX] with helical distortions: an internal loop/bulge (IL/B) (UGC/C) or C-bulge. C-bulge iso-IREs bind IRP2 more poorly, as oligomers (n = 28-30), and have a weaker signal response in vivo. Two trans-loop GC base pairs occur in the ferritin IRE (IL/B and HL) but only one in C-bulge iso-IREs (HL); metal ions and protons perturb the IL/B [Gdaniec et al. (1998) Biochemistry 37, 1505-1512]. IRE function (translation) and physical properties (T(m) and accessibility to nucleases) are now compared for IL/B and C-bulge IREs and for HL mutants. Conversion of the IL/B into a C-bulge by a single deletion in the IL/B or by substituting the HL CG base pair with UA both derepressed ferritin synthesis 4-fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding observed for the oligomers. Since the engineered C-bulge IRE was more helical near the IL/B [Cu(phen)(2) resistant] and more stable (T(m) increased) and the HL mutant was less helical near the IL/B (ribonuclease T1 sensitive) and less stable (T(m) decreased), both CG trans-loop base pairs contribute to maximum IRP2 binding and translational regulation. The (1)H NMR spectrum of the Mg-IRE complex revealed, in contrast to the localized IL/B effects of Co(III) hexaammine observed previously, perturbation of the IL/B plus HL and interloop helix. The lower stability and greater helix distortion in the ferritin IL/B-IRE compared to the C-bulge iso-IREs create a combinatorial set of RNA/protein interactions that control protein synthesis rates with a range of signal sensitivities.

Animals↗
PubMed2000

Identification of the messenger RNA for human cutaneous fatty acid-binding protein as a metastasis inducer.

Using our recently developed systematic differential display and complete comparison of gene expression approaches combined with other methods, we have identified a large number of mRNAs that are expressed differentially between benign and malignant human cells. One such mRNA that is common to prostate and breast carcinoma cell lines encodes the human cutaneous fatty acid-binding protein (C-FABP). Northern and slot blot analyses confirm that the expression levels of C-FABP mRNA in the malignant prostate and breast carcinoma cell lines are 4.9+/-0.9- to 16.9+/-2.1-fold higher than those expressed in the benign cell lines. A similar difference between the benign and malignant cell lines was also detected at the protein level. In situ hybridization experiments have detected overexpression of the mRNA for C-FABP in human prostate carcinoma tissues. Transfection of a C-FABP expression construct into the benign, nonmetastatic rat mammary epithelial cell line Rama 37 and inoculation of the C-FABP expression transfectants into syngeneic Wistar-Furth rats produce a significant number (P < 0.05) of animals with metastases (6 of 26 animals), whereas the control transfectants generated by the vector alone yield no such metastases. Measurements of mRNA and protein levels with Northern and Western blotting show that C-FABP is not expressed in the control transfectant cells produced by the vector alone but is highly expressed in the pool of C-FABP transfectants and-the sublines established from their metastases. Immunocytochemical staining with antibodies to C-FABP shows that C-FABP is not expressed in the primary tumors developed from the control transfectants that have failed to metastasize, but it is expressed in both the primary tumors developed from the C-FABP transfectants and their metastases. Reinoculation of the sublines established from metastases in syngeneic rats has produced a higher proportion (50%) of animals (7 of 14 animals) with metastases than that obtained in the first-round inoculations, indicating that the metastatic clones have been preferentially selected from the original pool of metastatic and nonmetastatic transfectant clones. These results have demonstrated that elevated expression of C-FABP can induce metastasis and that metastatic capability has been transferred in a genetically dominated manner in this Rama 37 model. Thus, we suggest that C-FABP is a metastasis-inducing gene, and under suitable conditions, it may induce metastasis of some human cancers.

Animals↗
PubMed2000

Bovine and human insulin activate CD8+-autoreactive CTL expressing both type 1 and type 2 cytokines in C57BL/6 mice.

CD8+ T cells down-regulate a variety of immune responses. For example, porcine and human insulin do not stimulate Abs in C57BL/6 mice because CD8+ T cells inhibit CD4+ helper T cells. By contrast, bovine insulin induces Ab in C57BL/6 mice, and removal of CD8+ T cells does not alter this response. This raises the question of whether porcine, but not bovine, insulin activates CD8+ T cells or whether both insulins activate CD8+ T cells but CD4+ helper T cells are differentially inhibited by them. In this study, we show that insulin-specific CD8+ CTL can be cultured from C57BL/6 mice primed with either bovine or human insulin in CFA. Thus, exogenous Ags, besides OVA, induce CD8+ CTL when administered in an adjuvant, suggesting this is a typical response. These CTL are H-2Kb restricted and produce IL-5, IL-10, IFN-gamma, and small amounts of IL-4, which is distinct from IFN-gamma and TNF-alpha that are typically secreted by virus-specific CTL. Moreover, the CTL primed with either bovine or human insulin recognize an A-chain peptide that is identical to the mouse insulin sequence. That foreign proteins, which are closely related to self-proteins, activated autoreactive, CD8+ T cells in vivo is a novel finding. It raises the possibility that self-reactive CTL may be activated by cross-reacting Ags and once activated they might participate in autoimmunity. These results also suggest that down-regulation of insulin-specific responses by autoreactive CD8+ T cells is most likely due to the differential sensitivity of bovine and human insulin-specific CD4+ T cells.

Amino Acid Sequence↗
PubMed2000

Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses.

Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans. Recently, we reported that noscapine binds stoichiometrically to tubulin and promotes microtubule polymerization. Noscapine causes growth arrest of tumor cells in mitosis and induces apoptosis of tumor cells in vitro. Previous experiments also showed that noscapine has potent antitumor activity in mice when administered parenterally or by gastric lavage. Here, we report that the anti-mitotic effect was specific to noscapine since closely related compounds did not inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to be effective in reducing the growth of the lymphoma and increasing the survival of tumor-bearing mice when administered in the drinking water. It is noteworthy that, noscapine showed little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral noscapine did not inhibit primary immune responses, which are critically dependent upon proliferation of lymphoid cells. Thus, our results indicate that noscapine has the potential to be an effective chemotherapeutic agent for the treatment of human cancer.

Alkaloids↗
PubMed2000

Multiple origins of Tibetan Y chromosomes.

The genetic origin of Tibetans was investigated using Y chromosome markers. A total of three populations were studied, two from central Tibet speaking central Tibetan and one from Yunnan speaking Kham. Two dominant paternal lineages (>80%) were identified in all three populations with one possibly from central Asia (YAP+) and the other from east Asia (M122C). We conclude that Tibetan Y chromosomes may have been derived from two different gene pools, given the virtual absence of M122C in central Asia and YAP+ in east Asia, with drift an unlikely mechanism accounting for these observations.

Alu Elements↗