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Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 721 records · Page 40Linked to original sources

[The expression and distribution of Smad 2 in human tooth germ].

OBJECTIVE: To investigate the expression of Smad 2 gene in human tooth germ,and the possible function of Smad 2 during human tooth germ development. METHODS: Immunohistochemical staining on prepared specimens of different stages of developing human tooth germ. RESULTS: Smad 2 expression had specific temporal-spatial pattern during tooth germ development, which was similar to TGF-beta. CONCLUSION: The expression of Smad 2 gene in tooth germ was detected in different stages of human tooth germ. The results suggest that Smad 2, one of the intracellular downstream molecules of TGF-beta, and as an inductive signal mediating epithelial-mesenchymal interaction, may regulate the differentiation of ameloblast and odontoblast cells, and modulate dentinogenesis and amelogenesis.

English Abstract↗

Food insecurity in Canadian households.

OBJECTIVES: This article examines the prevalence of food insecurity in Canada, the characteristics of people most likely to live in households lacking sufficient funds for food, and several related health problems. DATA SOURCE: The data are from the cross-sectional household component of the 1998/99 National Population Health Survey and the Food Insecurity Supplement to that survey. ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate the percentage of Canadians experiencing food insecurity and the prevalence of five selected health outcomes among people who were and were not food insecure. Multivariate logistic regression was used to assess the association of several socio-demographic and economic factors with food insecurity and to determine the association of food insecurity with the selected health outcomes. MAIN RESULTS: In 1998/99, 10% of Canadians, or about 3 million people, were living in food-insecure households. Low-income households, households depending on social assistance, lone-parent families headed by women, tenants, children, and Aboriginal people had significantly high odds of experiencing food insecurity. Food insecurity was significantly associated with poor/fair health, multiple chronic conditions, obesity, distress and depression.

Adolescent↗

Heart disease, family history and physical activity.

OBJECTIVES: This article examines the association of family history of heart disease and leisure-time physical activity with incident heart disease. DATA SOURCE: The data are from the 1994/95, 1996/97 and 1998/99 longitudinal household components of Statistics Canada's National Population Health Survey. This study is based on information provided by 9,255 respondents aged 20 or older who reported that, in 1994/95, they were free of diagnosed heart disease and in good health. ANALYTICAL TECHNIQUES: Multiple logistic regression was used to estimate the association of family history and physical activity with a new diagnosis of heart disease, while controlling for age, sex, educational attainment, smoking, high blood pressure, diabetes, and body mass index. MAIN RESULTS: When family history and other risk factors were taken into account, people who, in 1994/95, engaged in regular physical activity at a moderate level or beyond had lower odds of receiving a new diagnosis of heart disease than did sedentary individuals. People with a family history of heart disease who regularly participated in at least moderate physical activity had lower odds of developing heart disease than did their sedentary counterparts.

Adult↗

Starting and sustaining physical activity.

OBJECTIVES: This article examines factors associated with starting or sustaining physical activity during leisure time. DATA SOURCE: The data are from the longitudinal household components of the National Population Health Survey. The sample consisted of 11,026 respondents who were aged 20 and older in 1994/95. ANALYTICAL TECHNIQUES: Multiple logistic regression was used to identify variables that independently predicted the adoption or maintenance of leisure-time physical activity. MAIN RESULTS: Among people who had been inactive in 1994/95, the two-year incidence of starting at least moderate physical activity by 1996/97 or 1998/99 was 24 cases per 100 person-years. For people who had been at least moderately active in 1994/95, the two-year incidence of ceasing to maintain that level of activity was 32 cases per 100 person-years. Many predictors of starting or sustaining activity were the same: sex, age, educational attainment, smoking, and sense of mastery. However, some factors were significant for one sex only. For instance, overweight and the presence of children were deterrents for women, but not for men. Social involvement and smoking status were significant for men, but not for women.

Adult↗

[Serapharmacological effect of kangxian ruangan granula on the proliferation of hepatic stellate cells].

OBJECTIVE: To investigate the antifibrotic mechanism of kangxian ruangan granula (KXRGG) at cellular level. METHOD: HSC were isolated from the normal rats by enzyme digestion and density gradient centrifugation, cultured, identified and subcultured. The medicated sera were prepared to incubated with the subcultured HSC. Sodium chloride sera and colchicines sera were taken as control groups. HSC viability was observed by 3H-proline; cell proliferation was measured with 3H-TdR incorporation and MTT colorimetric assay. RESULT: KXRGG medicated serum had no effect on the cellular shape and elevated 3H-proline incorporation (P < 0.01). Drug serum obviously inhibited 3H-TdR incorporation and MTT transformation (P < 0.01), and the latter had a drug concentration-dependent tendency. CONCLUSIONS: KXRGG can elevate cellular viability and has no toxic effect. The formula can inhibit the proliferation of HSC, which may be one of the cellular mechanisms of its antifibrotic action.

Animals↗

[Analysis of tendency of false and inferior species from Chinese medicinal materials markets].

OBJECTIVE: To offer information on the supervision by analysing the change of origin of false and inferior species from Chinese medicinal materials (CMM) markets. METHOD: 750 cases false and inferior species from Hubei province were compared classifiedly. RESULTS: In recent ten years, distributive characteristics of false and inferior species from CMM markets is as follows. First, false and inferior species from prepared medicinal herb increase, so do with man-made adulteration and poisonous species. Second, false and inferior species increase in rural area, country fairs, individual clinics and medicine booths. Last, extracted products are sold and used as certified products. CONCLUSION: CMM country fairs, outlying rural area, individual clinics and private medicine booths are the center of further supervision hereafter.

Consumer Product Safety↗

Long-term results of ammonia removal and transformation by biofiltration.

In this paper, long-term (>8 month) results of ammonia removal in biofilters was studied. Compost was used as the biofilter medium and activated carbon as an added material. The ammonia removal was normally >95% at influent ammonia concentrations of 20-500ppmv. According to the test results, the influent ammonia concentration should be <200ppmv (0.1570g ammonia/kg media per day) so that the effluent concentration of ammonia is <1.0mg/m(3) (the emission standard of China), and the biofiltration system can achieve good long-term performance. In the biofiltration system utilized in this study, the shortest retention time that the system could attain was 0.532min. However, the retention time can be decreased further without decreasing the ammonia removal efficiency. Countercurrent flow is favorable, as it enhances the moisture retention ability of the media. In the bioreactors, ammonia can be converted into the nitrate. The bioreactors have a stratification phenomenon for ammonia removal over the biofiltration depth, which implies that different parts of the bioreactor play different roles in the ammonia removing process.

Air Pollution↗

Temperature-sensitive mutants of p53 homologs.

Two homologs of the p53 tumor suppressor, p63 and p73 have recently been discovered. These proteins have activities similar to p53 in cell culture but have distinct developmental functions in vivo. We found that temperature-sensitive mutants of certain p63 and p73 isoforms can be created by single amino acid substitutions of an alanine residue corresponding to alanine 135 of murine p53. The mutants (p63gamma-Pro167, p73alpha-Leu156 and p73beta-Ile156) can be controlled by temperature shift between 32 degrees C and 39 degrees C. They can be stably expressed in p53-null H1299 cells at 39 degrees C, become transcriptionally activated at 32 degrees C, and induce expression of p53-responsive genes MDM2 and p21WAF1. Activation of p73beta-Ile156 in H1299 cells inhibits cell division but induces significant increase in cell size (hypertrophy), whereas activation of p73alpha-Leu156 and p63gamma-Pro167 induces apoptosis. These mutants may be useful tools for gaining further insight to the functions of p53 homologs.

Amino Acid Sequence↗

Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation.

Translation initiation is one of the key events regulated in response to mitogenic stimulation and nutrient availability, tightly coupled to mammalian cell cycle progression and growth. FKBP12-rapamycin-associated protein (FRAP; also named mTOR or RAFT1), a member of the ataxia telangiectasia mutated (ATM)-related kinase family, governs a rapamycin-sensitive membrane-to-cytoplasm signaling cascade that modulates translation initiation via p70 S6 kinase (p70(s6k)) and eIF-4E binding protein 1 (4E-BP1). Our studies reported here reveal a surprising regulatory mechanism of this signaling, which involves cytoplasmic-nuclear shuttling of FRAP. By using leptomycin B (LMB), a specific inhibitor of nuclear export receptor Crm1, we show that FRAP is a cytoplasmic-nuclear shuttling protein. Inhibition of FRAP nuclear export by LMB coincides with diminished p70(s6k) activation and 4E-BP1 phosphorylation. Further investigation by altering FRAP's nuclear shuttling activity with exogenous nuclear import and export signals has yielded results that are consistent with a direct link between nuclear shuttling of FRAP and mitogenic stimulation of p70(s6k) activation and 4E-BP1 phosphorylation. Furthermore, by using a reporter system, we provide evidence suggesting that nuclear shuttling of FRAP regulates mitogen-stimulated rapamycin-sensitive translation initiation. These findings uncover a function for the nucleus in the direct regulation of the protein synthesis machinery via extracellular signals.

Adaptor Proteins, Signal Transducing↗

Founder's Award, Society for Biomaterials. Sixth World Biomaterials Congress 2000, Kamuela, HI,May 15-20, 2000. Really smart bioconjugates of smart polymers and receptor proteins.

Over the past 18 years we have been deeply involved with the synthesis and applications of stimuli-responsive polymer systems, especially polymer-biomolecule conjugates. This article summarizes our work with one of these conjugate systems, specifically polymer-protein conjugates. We include conjugates prepared by random polymer conjugation to lysine amino groups, and also those prepared by site-specific conjugation of the polymer to specific amino acid sites that are genetically engineered into the known amino acid sequence of the protein. We describe the preparation and properties of thermally sensitive random conjugates to enzymes and several affinity recognition proteins. We have also prepared site-specific conjugates to streptavidin with temperature-sensitive polymers, pH-sensitive polymers, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed in this article.

Acrylamides↗

Primitive hematopoietic stem cell function in vivo is uniquely high in the CXB-12 mouse strain.

Bone marrow cells (BMCs) from CXB-12/HiaJ (CXB-12) mice had 14 times the total long-term repopulating ability found in the best of 11 other CXB recombinant inbred (RI) lines. BMCs from each RI line donor were mixed with genetically marked standard competitor BMCs from the BALB/cByxC57BL/6 F1 (CByB6F1) hybrid, the mice used to produce the RI lines, and the mixtures repopulated lethally irradiated CByB6F1 recipients. Percentages of donor-type erythrocytes and lymphocytes measured the actual long-term repopulating functions of the donor RI lines relative to the standard competitor. CXB-12 BMCs repopulated better after 3 or 6 months than after 1 month, suggesting that the most primitive precursors were involved. Compared to CByB6F1 standard competitor cells, CXB-12 cells repopulated 3 to 12 times as well, with their advantage increasing when higher doses of cells were transplanted, probably because of hybrid resistance of the recipient against low doses. This was far better than expected, because F1 cells normally function 2 to 3 times as well as cells from an inbred strain. In competitive dilution, the advantage resulted from 2 factors: more precursor cells and more function per precursor. In the model that best fit the data, CXB-12 donors had 2.4 times the concentration of hematopoietic stem cells (HSCs) as the CByB6F1 standard, and each HSC repopulated 1.4 times as well. CXB-12 mice did not have elevated erythrocyte and lymphocyte numbers in blood and marrow and did not have unusually elevated concentrations of colony-forming unit spleen, cobblestone colonies, and long-term colony-initiating cells in marrow.

Age Factors↗

Induction of cyclin-dependent kinase 5 in the hippocampus by chronic electroconvulsive seizures: role of [Delta]FosB.

The transcription factor DeltaFosB is induced in the hippocampus and other brain regions by repeated electroconvulsive seizures (ECS), an effective antidepressant treatment. The unusually high stability of this protein makes it an attractive candidate to mediate some of the long-lasting changes in the brain caused by ECS treatment. To understand how DeltaFosB might alter brain function, we examined the gene expression profiles in the hippocampus of inducible transgenic mice that express DeltaFosB in this brain region by the use of cDNA expression arrays that contain 588 genes. Of the 430 genes detected, 20 genes were consistently upregulated, and 14 genes were downregulated, by >50%. One of the upregulated genes is cyclin-dependent kinase 5 (cdk5). On the basis of its purported role in regulating neuronal structure, we studied directly whether cdk5 is a true target for DeltaFosB. Upregulation of cdk5 immunoreactivity in the hippocampus was confirmed by Western blotting in the DeltaFosB-expressing transgenic mice as well as in rats treated chronically with ECS. Chronic ECS treatment also increased, in the hippocampus, the phosphorylation state of tau, a microtubule-associated protein that is a known substrate for cdk5. A 1.6 kb fragment of the cdk5 promoter was cloned, and activity of the promoter was found to be increased after overexpression of DeltaFosB in cell culture. Moreover, mutation of the single consensus activator protein-1 site contained within the cdk5 promoter fragment completely abolished activation of the promoter by DeltaFosB. Together, these results suggest that cdk5 is one target by which DeltaFosB produces some of its physiological effects in the hippocampus and thereby mediates certain long-term consequences of chronic ECS treatment.

Animals↗

Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme.

The CCR4-NOT transcriptional regulatory complex affects transcription both positively and negatively and consists of the following two complexes: a core 1 x 10(6) dalton (1 MDa) complex consisting of CCR4, CAF1, and the five NOT proteins and a larger, less defined 1.9-MDa complex. We report here the identification of two new factors that associate with the CCR4-NOT proteins as follows: CAF4, a WD40-containing protein, and CAF16, a putative ABC ATPase. Whereas neither CAF4 nor CAF16 was part of the core CCR4-NOT complex, both CAF16 and CAF4 appeared to be present in the 1.9-MDa complex. CAF4 also displayed physical interactions with multiple CCR4-NOT components and with DBF2, a likely component of the 1.9-MDa complex. In addition, both CAF4 and CAF16 were found to interact in a CCR4-dependent manner with SRB9, a component of the SRB complex that is part of the yeast RNA polymerase II holoenzyme. The three related SRB proteins, SRB9, SRB10, and SRB11, were found to interact with and to coimmunoprecipitate DBF2, CAF4, CCR4, NOT2, and NOT1. Defects in SRB9 and SRB10 also affected processes at the ADH2 locus known to be controlled by components of the CCR4-NOT complex; an srb9 mutation was shown to reduce ADH2 derepression and either an srb9 or srb10 allele suppressed spt10-enhanced expression of ADH2. In addition, srb9 and srb10 alleles increased ADR1(c)-dependent ADH2 expression; not4 and not5 deletions are the only other known defects that elicit this phenotype. These results suggest a close physical and functional association between components of the CCR4-NOT complexes and the SRB9, -10, and -11 components of the holoenzyme.

Adenosine Triphosphatases↗

Characterization of the rat DNA fragmentation factor 35/Inhibitor of caspase-activated DNase (Short form). The endogenous inhibitor of caspase-dependent DNA fragmentation in neuronal apoptosis.

Nuclear changes, including internucleosomal DNA fragmentation, are classical manifestations of apoptosis for which the biochemical mechanisms have not been fully elucidated, particularly in neuronal cells. We have cloned the rat DNA fragmentation factor 35/inhibitor of caspase-activated DNase (short form) (DFF35/ICAD(S)) and found it to be the predominant form of ICAD present in rodent brain cells as well as in many other types of cells. DFF35/ICAD(S) forms a functional complex with DFF40/caspase-activated DNase (CAD) in the nucleus, and when its caspase-resistant mutant is over-expressed, it inhibits the nuclease activity, internucleosomal DNA fragmentation, and nuclear fragmentation but not the shrinkage and condensation of the nucleus, in neuron-differentiated PC12 cells in response to apoptosis inducers. DFF40/CAD is found to be localized mainly in the nucleus, and during neuronal apoptosis, there is no evidence of further nuclear translocation of this molecule. It is further suggested that inactivation of DFF40/CAD-bound DFF35 and subsequent activation of DFF40/CAD during apoptosis of neuronal cells may not occur in the cytosol but rather in the nucleus through a novel mechanism that requires nuclear translocation of caspases. These results establish that DFF35/ICAD(S) is the endogenous inhibitor of DFF40/CAD and caspase-dependent apoptotic DNA fragmentation in neurons.

Amino Acid Sequence↗

A novel MDM2 anti-sense oligonucleotide has anti-tumor activity and potentiates cytotoxic drugs acting by different mechanisms in human colon cancer.

MDM2 is over-expressed in several human tumors. Its product is a negative-feedback regulator of p53, which interferes with the control of cell proliferation and apoptosis, interacting not only with p53 but also with retinoblastoma (Rb) and E2F. Moreover, mutations in the ARF-Ink4a locus may also allow MDM2 to override p53 functions. In this study, we have used a novel oligonucleotide anti-sense MDM2, with mixed-backbone structure and demonstrate that it causes inhibition of MDM2 expression, induction of both p53 and p21/WAF1 expression and a dose-dependent, growth-inhibitory effect in human GEO colon-cancer cells. We also show that anti-sense MDM2 has a co-operative growth-inhibitory effect with different classes of cytotoxic drugs acting by different mechanisms. Moreover, anti-sense MDM2 induces apoptosis and markedly enhances the apoptotic activity of different cytotoxic drugs. Finally, we show that anti-sense MDM2 has anti-tumor activity in vivo in nude mice bearing GEO xenografts and potentiates the anti-tumor effect of cytotoxic drugs. Indeed, despite the short treatment period, the combination of anti-sense MDM2 and cytotoxic drugs causes a marked delay in tumor growth and prolongation of mice survival, lasting several months after treatment cessation. The anti-tumor effect is associated with inhibition of MDM2 expression in tumor specimens of animals treated with anti-sense MDM2, alone or in combination with a cytotoxic drug. Our results provide the rationale for development of a novel mixed-backbone anti-sense MDM2 into a clinical setting in therapeutic combination strategies with conventional cytotoxic drugs.

Animals↗

Stimulation of the mitogen-activated protein kinase cascade and tyrosine phosphorylation of the epidermal growth factor receptor by hepatopoietin.

Hepatopoietin (HPO) is a novel human hepatotrophic growth factor, which specifically stimulates proliferation of cultured primary hepatocytes in vitro and liver regeneration after liver partial hepatectomy in vivo. Recently, the identification of the mitogenic effect of HPO on hepatoma cell lines and the existence of HPO-specific receptors indicate that HPO acts via its specific cell surface receptor. However, the molecular mechanism of HPO action is not fully elucidated. In this report, we examined the signal transduction events induced by HPO in hepatoma cell line (HepG2). Our results demonstrated that HPO induces phosphorylation of mitogen-activated protein kinase kinase and mitogen-activated protein kinase (MAPK) in a rapid and transient manner. HPO stimulates tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Furthermore, we observed that both MAPK activation and the mitogenic effect of HPO on HepG2 cells were completely blocked by AG1478, a specific inhibitor of EGFR tyrosine kinase activity. However, the effects of HPO were not antagonized by an EGFR-blocking antibody, mAb528, which blocks the interaction between epidermal growth factor and EGFR, indicating that stimulation of tyrosine phosphorylation of EGFR by HPO was not mediated by epidermal growth factor. In contrast, genistein, a general tyrosine kinase inhibitor, significantly attenuated the tyrosine phosphorylation of EGFR in response to HPO. In conclusion, our results suggest that tyrosine phosphorylation of EGFR may play a critical role in MAPK activation and mitogenic stimulation by HPO.

Enzyme Inhibitors↗

Mouse pseudouridine synthase 1: gene structure and alternative splicing of pre-mRNA.

Evidence for the alternative splicing of the message for mouse pseudouridine synthase 1 (mPus1p) was found when several expressed sequence tag clones were completely sequenced. The genomic DNA for the MPUS1 gene (6.9 kb) was cloned from a mouse genomic library; the gene contains seven exons, of which three are alternatively spliced. In addition, one of the internal exons (exon VI) is unusually large. RNase protection analysis confirmed that several alternatively spliced messages were present in mouse tissues and cells in culture. A Western blot of total cellular protein from mouse tissues and cultured cells was reacted with an antibody specific for mPus1p; at least three proteins were detected. One protein corresponds to the predicted molecular mass of mPus1p (44 kDa) and is the most abundant. The two other isoforms, one 2 kDa larger and one 7 kDa smaller than mPus1p, were differentially expressed. The cDNA species for the three isoforms were cloned into expression plasmids; the proteins were synthesized in vitro and tested for pseudouridine synthase activity. The two isoforms, one containing an insert of 18 amino acids in a region of the enzyme assumed to be critical for activity, and the other, which has a deletion of the protein coding potential of two exons, were both inactive on tRNA substrates that mPus1p modifies.

Alternative Splicing↗