Biomedical subjects

Feng Jin

Publications and source records attributed to Feng Jin.

At least 37 records · Page 2Linked to original sources

PubMed2004

Association of the HTR6 polymorphism C267T with late-onset Alzheimer's disease in Chinese.

Serotonergic neurotransmitter system has been implicated in the pathogenesis of Alzheimer's disease (AD). 5-Hydroxytryptamine (5-HT)(6) receptor is mainly expressed in the brain areas involved in cognitive processes. And 5-HT(6) receptor gene (HTR6) variants may be a genetic risk factor for late-onset Alzheimer's disease (LOAD). To assess whether HTR6 increases the risk for LOAD, we carried out an association study between the HTR6 polymorphism C267T and sporadic LOAD in Mainland Chinese. An association of C/T genotype with LOAD (OR = 2.10, P = 0.014) was observed. And no statistical difference was found between cases and controls after stratification for APOE epsilon4 status. These data suggest that the HTR6 polymorphism C267T possibly involved in the susceptibility to LOAD as an APOE epsilon4-allele independent risk factor of LOAD.

Aged↗

PubMed2004

Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase gene and Alzheimer's disease in Chinese.

A polymorphism (T/C) in intron 2 of the cholesterol 24-hydroxylase (CYP46) gene has recently been reported to be associated with the risk for late-onset Alzheimer's disease (LOAD). To investigate possible involvement of the CYP46 gene and apolipoprotein E (APOE) gene polymorphisms in the manifestation of LOAD, we analyzed 99 sporadic LOAD patients and 113 healthy controls of China. We found an obvious association between CYP46 TT genotype and LOAD (OR = 2.98, 95% CI 1.64-5.44, P < 0.001). A clear increase of the risk to develop LOAD was also observed in subjects carrying both the CYP46 TT genotype and the APOE epsilon4-allele (OR = 12.94, 95% CI 4.26-39.32, P < 0.001). Our data reveal that the polymorphism of CYP46 intron 2 is implicated in the susceptibility to LOAD and a strong synergistic interaction between CYP46 TT homozoygots and APOE epsilon4 carrier status on the risk of LOAD.

Aged↗

PubMed2004

[Detection of P504S (alpha-methylacyl-CoA racemase) in prostatic adenocarcinomas].

OBJECTIVE: To evaluate the specificity and sensitivity of the monoclonal antibody P504S (AMACR) in detection of prostatic adenocarcinomas. METHODS: 150 cases, including prostatic adenocarcinomas (n = 105), benign prostatic hyperplasia (BPH, n = 42) and atypical small acinar proliferation (ASAP, n = 3), were studied by immunohistiochemical analysis of P504S. The clinical data, HE, PSA and CK34betaE12 staining slides were reviewed in all of the cases. RESULTS: P504S was strongly and diffusely positive (> or = +++) in 97.1% cases of prostatic adenocarcinomas and focally positive (+) in 2 cases, regardless of Gleason score, age and serum PSA. However, P504S was also positive in high grade PIN that surrounded adenocarcinomas (n = 24) and weakly positive (+) in benign prostatic hyperplasia that surrounded adenocarcinomas (8 out of 82 cases). In 42 cases of BPH, 10 cases (23.8%) show (+) staining, and 1 case (2.4%) shows (++) staining. P504S was negative in entire 8 cases of basal cell hyperplasia (BCH) and in 3 cases of ASAP. CONCLUSION: P504S (AMACR), a recently established positive marker for prostatic adenocarcinomas, has good sensitivity (97.1%) and specificity (86.0%). It is crucial to correlate the P504S staining pattern with the findings of HE, PSA and CK34betaE12 (or p63) staining, as well as clinical information to reach a correct diagnosis.

Adenocarcinoma↗

PubMed2004

Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world.

Several lines of evidence suggest that patterns of genetic variability in the human angiotensinogen gene (AGT) contribute to phenotypic variability in human hypertension. The A(-6) promoter variant of AGT is associated with higher plasma angiotensinogen levels and increased risk of essential hypertension. The geographic distribution of the A(-6) variant leads to the intriguing hypothesis that the G(-6) promoter variant has been selectively advantageous outside Africa. To test these hypotheses, we investigated the roles of population history and natural selection in shaping patterns of genetic diversity in AGT, by sequencing the entire AGT gene (14400 bp) in 736 chromosomes from Africa, Asia, and Europe. We found that the A(-6) variant is present at higher frequency in African populations than in non-African populations. Neutrality tests found no evidence of a departure from selective neutrality, when whole AGT sequences were compared. However, tests restricted to sites in the vicinity of the A(-6)G polymorphism found evidence of a selective sweep. Sliding-window analyses showed that evidence of the sweep is restricted to sites in tight linkage disequilibrium (LD) with the A(-6)G polymorphism. Further, haplotypes carrying the G(-6) variant showed elevated levels of LD, suggesting that they have risen recently to high frequency. Departures from neutral expectation in some but not all regions of AGT indicate that patterns of diversity in the gene cannot be accounted for solely by population history, which would affect all regions equally. Taken together, patterns of genetic diversity in AGT suggest that natural selection has generally favored the G(-6) variant over the A(-6) variant in non-African populations. However, important localized effects may also be present.

Africa↗

PubMed2004

Effect of mitogen-activated protein kinase signal transduction pathway on multidrug resistance induced by vincristine in gastric cancer cell line MGC803.

AIM: To investigate the correlation between mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells. METHODS: Western blot was used to analyze the expression of MDR associated gene in transient vincristine (VCR) induced MGC803 cells, which were treated with or without the specific inhibitor of MAPK, PD098059. Morphologic analysis of the cells treated by VCR with or without PD098059 was determined by Wright-Giemsa staining. The cell cycle analysis was performed by using flow cytometric assay and the drug sensitivity of MGC803 cells which were exposed to VCR with or without PD098059 was tested by using MTT assay. RESULTS: Transient exposure to VCR induced P-gp but not MRP1 or GST-pi expression in MGC803 cells and the expression of P-gp was inhibited by PD098059. Apoptotic bodies were found in the cells treated with VCR or VCR+PD098059. FCM results indicated that more MGC803 cells showed apoptotic phenotype when treated by VCR and PD098059 (rate: 31.23%) than treated by VCR only (rate: 18.42%) (P<0.05). The IC(50) (284+/-13.2 mug/L) of MGC803 cells pretreated with VCR was 2.24-fold as that of negative control group (127+/-17.6 mug/L) and 1.48-fold as that of the group treated with PD098059 (191+/-27.9 mug/L). CONCLUSION: This study shows that the expression of P-gp can be induced by transient exposure to VCR and this induction can be prevented by PD098059, which can block the activity of MAPK. MAPK signal transduction pathway may play some roles in modulating MDR1 expression in gastric cancer.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Pharmacokinetic model of target-mediated disposition of thrombopoietin.

Thrombopoietin, TPO, a 353 amino acid cytokine, is a primary regulator of platelet production that was cloned recently. A target-mediated (platelet receptors) pharmacokinetic model was developed to characterize the disposition of TPO. Receptor-mediated endocytosis was assigned as the major elimination pathway in the model. A nonspecific binding compartment was also incorporated into the model. TPO concentration vs time profiles from a published phase 1 and 2 clinical trial were used to apply this model. Noncompartmental analysis demonstrated that TPO exhibits nonlinear kinetics. The proposed model captured the concentration-time profiles relatively well. The first-order internalization rate constant was estimated as 0.1 h(-1). The endogenous binding capacity was estimated as 164.0 pM. The second-order binding association constant (k(on)) was 0.055 h(-1).pM(-1) and the first-order dissociation constant (k(off)) was estimated as 2.5 h(-1), rendering the equilibrium dissociation constant K(d) as 45.5 pM. This model may be relevant to other therapeutic agents with receptor-mediated endocytotic disposition.

Biological Availability↗

PubMed2004

A novel human gene (WDR25) encoding a 7-WD40-containing protein maps on 14q32.

Members of the large family of WD-repeat proteins are involved in diverse functions such as RNA-procession, signal transduction, vesicular trafficking, cytoskeletal assembly, and cell cycle control. By large-scale-sequencing analysis of a human fetal brain cDNA library, we isolated a novel human cDNA encoding a 7-WD40-repeat protein. This cDNA is 2004 bp in length and it codes for a 544-amino-acid protein. We term it human WD40-repeat-containing gene 25 (WDR25) and this gene shows significant similarity with human pre-mRNA splicing factor 17. The WDR25 gene is mapped to chromosome 14q32 and contains seven exons. RT-PCR analysis shows that the WDR25 gene is widely expressed in human tissues and the expression levers in heart, muscle, testis, ovary, uterus, and prostate are relatively high.

Amino Acid Motifs↗

PubMed2004

Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*).

We have isolated a novel cDNA from the human fetal brain cDNA library with homology to the Mg2+ -dependent serine/threonine protein phosphatase 2C (PP2C) family. The cDNA is 3055 bp in length, and the predicted coding region encodes a 360-amino-acid protein, which shows 99% identity to the PP2C epsilon from rat and mouse. Then we term it human PP2C epsilon gene. The gene is mapped to chromosome 3q26.1 and contains 4 exons. RT-PCR analysis shows that the PP2C epsilon is widely expressed in human tissues and the expression levels in heart, placenta, lung, liver, kidney, and pancreas are relatively high.

Amino Acid Sequence↗

PubMed2004

Molecular cloning and characterization of SGT1.2, a novel splice variant of Homo sapiens SGT1.

SGT1.2, a novel splice variant of Homo sapiens SGT1 was isolated from a human fetal brain cDNA library. This cDNA is 1404 bp and contains an open reading frame from 68 to 1165 encoding a putative protein of 365 amino acids (SGT1.2) that share 90% identities to Homo sapiens SGT1, suppressor of G2 allele of SKP1 at protein level. RPS-BLAST searching revealed that SGT1.2 have a TPR domain, a p23 domain, a SGS domain and a CS domain. According to the search of the human genome database, SGT1.2 was mapped to human chromosome 13q14.13. Reversed transcription-polymerase chain reaction analysis indicated that it widely expressed in human adult tissues.

Alternative Splicing↗

PubMed2004

Cloning, characterization and expression of CDK5RAP1_v3 and CDK5RAP1_v4, two novel splice variants of human CDK5RAP1.

Two novel splice variants of CDK5RAP1, named CDK5RAP1_v3 and CDK5RAP1_v4, were isolated through the large-scale sequencing analysis of a human fetal brain cDNA library. The CDK5RAP1_v3 and CDK5RAP1_v4 cDNAs are 1923bp and 1792bp in length, respectively. Sequence analysis revealed that CDK5RAP1_v4 lacked 1 exon, which was present in CDK5RAP1_v3, with the result that these cDNAs encoded different putative proteins. The deduced proteins were 574 amino acids (designated as CDK5RAP1_v3) and 426 amino acids (CDK5RAP1_v4) in length, and shared the 420 N-terminal amino acids. RT-PCR analysis showed that human CDK5RAP1_v3 was widely expressed in human tissues. The expression level of CDK5RAP1_v3 was relatively high in placenta and lung, whereas low levels of expression were detected in heart, brain, liver, skeletal muscle, pancreas, spleen, thymus, small intestine and peripheral blood leukocytes. In contrast, human CDK5RAP1_v4 was mainly expressed in brain, placenta and testis.

Alternative Splicing↗

PubMed2004

Characteristic beta-globin gene cluster haplotypes of Evenkis and Oroqens in north China.

Haplotype frequencies of the beta-globin gene cluster were estimated for 114 Evenkis and 81 Oroqens from northeast China, and their characteristics were compared with those in Japanese, Koreans, and three Colombian Amerindian groups of South America (Wayuu, Kamsa, and Inga tribes). A major 5' subhaplotype (5' to the delta-globin gene) was + - - - - in Evenkis, whereas + - - - -, - + + - +, and - + - + + were the major subhaplotypes in Oroqens. One possible candidate for an ancestral 5' subhaplotype, - - - - -, was found in one Evenki (0.5%) and three Oroqen chromosomes (2.0%). They were observed as heterozygous forms for + ---- and -----. Major haplotypes were +-----+, + -----+-, and + - - - - + + in Evenkis, whereas they were +-----+,-++-+-+, +----+-, and -+-++-+ in Oroqens. The lowest Nei's genetic distance values of Evenkis or Oroqens based on the 5' subhaplotype frequency distributions were observed in relation to the Wayuu or Koreans, respectively, but those of Evenkis and Oroqens based on the haplotype frequency distributions were found in relation to Koreans.

Asian People↗

PubMed2004

[Effect of PKC inhibitor on P-gp expression and drug-resistance in MGC803 cells].

BACKGROUND & OBJECTIVE: It is showed that there is close relationship between multidrug resistance (MDR) and protein kinase C signal transduction system, but the mechanism remains unclarified. The aim of this study was to investigate the correlation between protein kinase C (PKC) signal transduction system and mdr1 gene in human gastric cancer cell line through studying the effect of vincristine (VCR) and a selective inhibitor of PKC, myr-psiPKC on MGC803 cells. METHODS: Western blot analysis was used to analyze the expression of P-glycoprotein (P-gp), which was encoded by mdr1, in transient VCR induced MGC803 cells, which were treated with or without myr-psiPKC. Cell cycle analysis was performed using flow cytometry and MTT assay was used to investigate the drug susceptibility of MGC803 cells which were exposed to VCR with or without myr-psiPKC. RESULTS: High level of P-gp expression was detected in the MGC803 cells after transient exposure to VCR, and its expression was down-regulated when the same VCR induced MGC803 cell line was incubated with myr-psiPKC. FCM results indicated that more MGC803 cells showed significantly higher level of apoptotic phenotype when treated with VCR and myr-psiPKC (ratio 31.23%), than those treated with only VCR (ratio 18.42%). The IC(50) (284.0+/-13.2 ng/ml) to VCR of MGC803 cells pretreated with VCR exhibited 2.24-fold of negative control group (127.0+/-17.6 ng/ml) and 1.33-fold of the group (212.0+/-30.4 ng/ml) treated with myr-psiPKC. CONCLUSION: The expression of P-gp can be induced by transient exposure to VCR and this induction can be inhibited by myr-psiPKC, which blocks the activity of PKCalpha and beta. PKC signal transduction system may play certain roles in modulating mdr1 expression in gastric cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

[Human genetics of physical performance].

Development of human molecular genetics gradually revealed that certain people seem to have congenital capacity in physical performance, and this capacity may correlate with genes. Recently, more and more evidences have shown that genes control some physical characters, such as extreme motion, muscle strength, endurance, ductility, fatigue recovery, and VO2max, ect. The development of spaceflight in China and nation defence urgently require appearance of this study, and its application will help to find physically potential individuals in advance and save large amount of money in the later systematic training.

Exercise↗

PubMed2004

[Association between genetic factor and physical performance].

Correlation study between physical performance and gene has become a hot topic. Evidences have indicated that human capacity is partially influenced by genetic factors. Since 2000, the genetic studies of locomotion have progressed rapidly. More than 70 genetics markers associated with physical performance have been studied, such as VO(2max) (maximal oxygen uptake), muscle strength and lactate threshold. This research could be used to detect the special individual in spaceflight project and national defense project. Obviously, genetic detection of the special individual at early stage will save time and fund as compared with traditional training system. The present paper is to summarize some major international studies on aerobic exercise related genes and loci. We expect that the present article may provide helpful information to promote the project in China.

Humans↗

PubMed2003

Association study between late-onset Alzheimer's disease and the transferrin gene polymorphisms in Chinese.

To investigate the possible involvement of the transferrin (TF) gene polymorphism in the manifestation of Alzheimer's disease (AD), we analyzed the TF and apolipoprotein E (APOE) genotypes of 67 sporadic late-onset AD patients and 131 normal elderly controls in the Chinese population. Our data showed that the TF C1 homozygosity carriers had an increased risk of AD in subjects > or =75 years of age, showing that homozygosity for the TF C1 allele was associated with an approximately three-fold increased risk (OR=3.57, 95% CI, 1.24-10.27, P=0.014). No synergic effects were found between the APOE epsilon 4 allele and TF gene polymorphisms.

Age Factors↗

PubMed2003

Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans.

We have analyzed eight Y-chromosomal binary markers (YAP, RPS4Y(711), M9, M175, LINE1, SRY(+465), 47z, and M95) and three Y-STR markers (DYS390, DYS391, and DYS393) in 738 males from 11 ethnic groups in east Asia in order to study the male lineage history of Korea. Haplogroup DE-YAP was found at a high frequency only in Japan but was also present at low frequencies in northeast Asia, including 2.5% in Korea, suggesting a northern origin for these chromosomes. Haplogroup C-RPS4Y(711) was present in Korea and Manchuria at moderate frequencies: higher than in populations from southeast Asia, but lower than those in the northeast, which may imply a northern Asian expansion of these lineages, perhaps from Mongolia or Siberia. The major Y-chromosomal expansions in east Asia were those of haplogroup O-M175 (and its sublineages). This haplogroup is likely to have originated in southern east Asia and subsequently expanded to all of east Asia. The moderate frequency of one sublineage in the Koreans, haplogroup O-LINE1 (12.5%), could be a result of interaction with Chinese populations. The age of another sublineage, haplogroup O-SRY(+465), and Y-STR haplotype diversity provide evidence for relatively recent male migration, originally from China, through Korea into Japan. In conclusion, the distribution pattern of Y-chromosomal haplogroups reveals the complex origin of the Koreans, resulting from genetic contributions involving the northern Asian settlement and range expansions mostly from southern-to-northern China.

Asian People↗

PubMed2003

A novel splice variant of human gene GDPD1 is mainly expressed in human ovary and small intestine.

Glycerophosphodiester phosphodiesterase (GDPD) is a glycerol metabolizing enzyme that has been previously identified in Escherichia coli, Haemophilus influenzae, Bacillus subtilis and Borrelia hermsii. It has been also reported that there is putative protein containing GDPD domain in Mus musculus, but not in Homo sapiens. SMART analysis showed that our predicted protein and three others of the same gene also comprise this domain. Because the gene has not been named, we termed it GDPD1 and accordingly termed our splice variant GDPD1_v1 after acquiring the agreement of HUGO. RT-PCR experiment revealed that our splice variant of the gene is mainly expressed in human ovary and small intestine, basically conforming to the result of serial analysis of gene expression.

Alternative Splicing↗

PubMed2003

[Associated genes for dementia of the Alzheimer type].

Dementia of the Alzheimer type (AD) is the leading cause of dementias for the elders. It is a progressively neurodegenerative disorder characterized by global cognitive decline. While most of the rare early-onset AD can be explained by mutations in APP gene and presenilin genes,the genetic etiology of the more common late-onset AD is only partly explained by the APOE-epsilon4 genotype. But the APOE-epsilon4 allele is neither necessary nor sufficient to cause disease and it can only account for less than one-half of the genetic variance of AD. Thus, more genes involved in AD are our special attention.

English Abstract↗