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Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 793 records · Page 44Linked to original sources
PubMed2000

[Effect of tea polyphenols and tea pigments on inducing the activity of phase II detoxicating enzymes and on the chemoprevention of liver precancerous lesions].

In order to elucidate the chemoprevention mechanism of tea, the regulative effect of tea polyphenols and tea pigments on phase II enzyme, glutathions S-transferase (GST) activity and its isoenzymes in Wistar rat were studied. Rat liver precancerous lesions were initiated with diethylnitrosamine (DEN), promoted with partial hepatectomy and carbon tetrachloride. The rats were killed after 8 weeks of treatment. Liver cytosol GST activities were tested. The GST 1-1, 1-2, 3-3 and Pi isoenzymes were detected with Western Blot method. The results showed that the activities of GST increased greatly in the tea polyphenol and tea pigment groups, while the activities were decreased in positive control group. Both tea polyphenold and tea pigments increased the activities of classes GST alpha (GST1-1, 1-2) and GST mu(GST3-3). The increase of GST alpha was more in tea polyphenol group, and the increase of GST mu was more in tea pigment group. Both tea polyphenols and tea pigments inhibited the over expression of GST Pi in the rats treated with DEN/PH/CCl4. The study indicated that tea polyphenols and tea pigments modulated phase II enzymes effectively, thus inhibited the occurrence and development of the precancerous lesions of rat liver.

Animals↗
PubMed2000

A novel alpha-helix-liked metallohelicate series and their structural adjustments for the isomorphous substitution.

A novel metallohelical motif is well designed and synthesized by mimicking the alpha-helical fold structure of protein. The 1D helical structures of [Cd(CH2(COO)2)(SC(NH2)2)2]n (I) and [Zn(CH2(COO)2) (SC(NH2)2)2]n (II) are primarily induced and stabilized by the multiple long-range intrahelix hydrogen bonds. Malonate dianion acts as a bidentate ligand coordinated with metal ions to form the backbone of the helix, and thiourea molecules that bend into the helical turn are involved in the intrahelix hydrogen-bond system. The metal ion occupations in the helix of I and II can be freely substituted by simply controlling the initial ratio of those two metal ions. Single crystals of three mixed metal ion complexes of [Cd0.77Zn0.23(CH2(COO)2)(SC(NH2)2)2]n (III), [Cd0.50Zn0.50(CH2(COO)2)(SC(NH2)2)2]n (IV), and [Cd0.21Zn0.79(CH2(COO)2)(SC(NH2)2)2]n (V) were synthesized from systems with an initial Cd/Zn mole ratio of 1:1 for III, 1:2 for IV, and 1:8 for V. They are isomorphous as confirmed by X-ray characterization. When the metal ion is substituted, the multiple intrahelix hydrogen interaction motifs of the coordination polymer structure are self-adjusted to sustain their 1D helical motifs.

Journal Article↗
PubMed2000

4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes modified for extended conjugation and restricted bond rotations.

Five new, constrained, aryl-substituted 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) dyes (3f,g and 4h-j) were prepared and investigated to see if they have more favorable fluorescence characteristics than the unconstrained systems 2 that were prepared in previous studies. Dye types 3 and 4 have relatively rigid conformations caused by the heteroatom (3f and 3g) or ethylene bridge (4h-j) linkers that preclude free rotation of the substituted-benzene molecular fragments. In the event, the new dye types 3 and 4 have longer lambda(max abs) (620-660 nm) and lambda(max)(fluor) (630-680 nm) values than compounds 2. They also exhibit higher extinction coefficients (>100 000 M(-1) cm(-1), except for 3g). Their fluorescent quantum yields are high (up to 0.72 for 4j), with the exception of compound 3g, which has a quantum yield of only 0.05. The redox properties of dyes 3 and 4 have also been examined.

Boron Compounds↗
PubMed2000

Involvement of spinal protein kinase C in induction and maintenance of both persistent spontaneous flinching reflex and contralateral heat hyperalgesia induced by subcutaneous bee venom in the conscious rat.

To further study the roles of spinal protein kinase C (PKC) in induction and maintenance of both the persistent spontaneous nociception and the contralateral heat hyperalgesia induced by subcutaneous (s.c.) bee venom injection, the effects of intrathecal (i.t.) treatment with a PKC inhibitor, chelerythrine chloride (CH), were evaluated in conscious rats. Pre-treatment i.t. with CH at three doses of 0.01, 0.1 and 1 nmol produced a dose-dependent suppressive effect on the flinching reflex with the inhibitory rates of 39, 48 and 59%, respectively, when compared with the pre-saline control group. Post-treatment i.t. with the drug at the highest dose used (1 nmol) also resulted in a 42% suppression of the flinching reflex compared with the control. Moreover, pre-treatment i.t. with CH at three doses of 0.01, 0.1 and 1 nmol also produced 12, 22 and 48% inhibition of the contralateral heat hyperalgesia in the pre-saline control group. Post-treatment i.t. with the drug at the highest dose used (1 nmol) also resulted in a 35% reversal effect on the established contralateral heat hyperalgesia. The present result suggests that activation of PKC in the spinal cord contributes to the induction and maintenance of both peripherally-dependent persistent spontaneous pain and contralateral heat hyperalgesia which is dependent upon central sensitization.

Animals↗
PubMed2000

Contralateral heat hyperalgesia induced by unilaterally intraplantar bee venom injection is produced by central changes: a behavioral study in the conscious rat.

In a previous study, we found that subcutaneous (s.c.) intraplantar injection of bee venom unilaterally could produce bilateral heat hyperalgesia. However, the bee venom-induced heat hyperalgesia identified in the injection site was presumed to be different from that identified in the contralateral hindpaw, since the former co-existed with the mechanical hyperalgesia while the latter did not. The aim of the present study was to testify whether the contralateral heat hyperalgesia identified in the bee venom model was a consequence of central changes. The radiant heat and von Frey-type filaments were applied to both the injection site and the contralateral pawpad of conscious rats prior to and 4 h after s.c. bee venom injection. After confirmation of the development of primary heat and mechanical hyperalgesia and contralateral heat hyperalgesia following s.c. bee venom, the sciatic nerve of the injection side was transected. After axotomy, the bee venom-induced heat hyperalgesia in the non-injected hindpaw was not altered at all compared with that prior to axotomy. Moreover, intrathecal pre-treatment with either N-methyl-D-aspartate (NMDA) or non-NMDA receptor antagonist could prevent the development of the contralateral heat hyperalgesia. The present results suggest that central sensitization contributes to development of the bee venom-induced contralateral heat hyperalgesia and activation of both NMDA and non-NMDA receptors in the spinal cord is involved in the processing.

Animals↗
PubMed2000

Unfolding and disassembly of the chaperonin GroEL occurs via a tetradecameric intermediate with a folded equatorial domain.

The chaperonin GroEL is a homotetradecamer in which the subunits (M(r) 57 000) are joined through noncovalent forces. This study reports on the unfolding and disassembly of GroEL in guanidine hydrochloride and urea. Kinetic and equilibrium measurements were made using amide hydrogen exchange/mass spectrometry, light scattering, and size-exclusion chromatography. Hydrogen exchange in GroEL destabilized in 1.8 M GdHCl (the unfolding midpoint is 1.2 M GdHCl) shows that the apical and intermediate domains unfold 3.1 times faster than the equatorial domain. Light scattering measurements made under the same conditions show that disassembly of the native GroEL tetradecamer occurs at the same rate as unfolding of the equatorial domain. This study of the kinetics of GroEL unfolding and disassembly demonstrates the existence of an intermediate that was identified as a tetradecamer with the apical and intermediate domains unfolded. Although this intermediate was easily detected in dynamic unfolding measurements, its population in equilibrium measurements at the midpoint for GroEL unfolding was too small to be detected. This study of GroEL unfolding and disassembly points to features that may be important in the folding and assembly of the GroEL macroassembly.

Amino Acid Sequence↗
PubMed2000

Care and outcomes of elderly patients with acute myocardial infarction by physician specialty: the effects of comorbidity and functional limitations.

PURPOSE: Whether patients with acute myocardial infarction who are treated by cardiologists have better outcomes than patients treated by generalist physicians is controversial. Because some of the survival benefit associated with cardiology care may be due to baseline differences in patient characteristics, we evaluated how differences in case-mix of comorbid illness and functional limitations may explain the association between specialty care and survival. MATERIALS AND METHODS: We examined the records of 109,243 Medicare beneficiaries hospitalized for myocardial infarction from 1994 to 1995 from the national Cooperative Cardiovascular Project to evaluate the association of physician specialty with 30-day and 1-year mortality. We assessed the extent to which this relation was mediated by differences in the use of guideline-supported therapies (aspirin, beta-blockers, reperfusion, angiotensin-converting enzyme inhibitors) or differences in the clinical characteristics of the patients. RESULTS: Patients who had board-certified cardiologists as attending physicians had the least number of comorbid conditions, whereas patients who had general practitioners or internal medicine subspecialists as attending physicians usually had the most comorbidities. Cardiologists had the greatest use of most guideline-supported therapies, and general practitioners had the lowest use. After adjustment for severity of myocardial infarction, clinical presentation, and hospital characteristics, patients treated by cardiologists were less likely to die within 1 year (relative risk [RR] = 0.92, 95%, confidence interval [CI]: 0.89 to 0. 95), and patients cared for by other general practitioners were more likely to die within 1 year (RR = 1.09, 95% CI: 1.03 to 1.14), than patients cared for by general internists. After adjusting for additional measures of comorbid illness and functional limitations, the 1-year survival benefit associated with cardiology care was attenuated relative to internists (RR = 0.97, 95% CI: 0.94 to 1.0), and the excess mortality associated with general practitioners decreased (RR = 1.05, 95% CI: 1.00 to 1.11). After further adjustment for the use of guideline-supported therapies, both differences in 1-year survival between patients treated by cardiologists or general practitioners were not significantly different from those of patients treated by internists. CONCLUSION: Studies comparing outcomes by physician specialties that do not adjust adequately for differences in patient characteristics may attribute more benefit than is appropriate to specialists who treat patients who have fewer comorbid conditions. Some of the remaining benefit-at least among patients with myocardial infarction-may be attributable to greater use of recommended therapies.

Activities of Daily Living↗
PubMed2000

Are beta-blockers effective in elderly patients who undergo coronary revascularization after acute myocardial infarction?

BACKGROUND: Although randomized clinical trials have demonstrated that beta-blocker therapy is effective in reducing mortality after acute myocardial infarction (AMI), many of these studies excluded patients who undergo coronary revascularization. However, the clinical practice guidelines established by the American College of Cardiology and the American Heart Association recommend that beta-blocker therapy be considered for patients who underwent successful revascularization after AMI. METHODS: Using data from the Cooperative Cardiovascular Project, we compared the initiation of beta-blocker therapy at discharge in patients aged 65 years or older who underwent coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) during their hospitalization for AMI with that of patients who did not undergo revascularization. We then examined whether beta-blocker therapy was associated with lower 1-year mortality between revascularized and nonrevascularized groups. RESULTS: After excluding patients with contraindications to beta-blocker therapy, 84 457 patients remained in the study sample. Of these, 8482 patients underwent CABG, and 13 997 patients underwent PTCA. After adjusting for demographic and clinical factors, we found that these patients were less likely to initiate beta-blocker therapy after CABG (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.41-0.47) or PTCA (OR, 0.89; 95% CI, 0.85-0.93) relative to the nonrevascularized group. After adjusting for potential confounders, beta-blockers were significantly associated with lower 1-year mortality in patients who underwent CABG (hazard ratio [HR], 0.70; 95% CI, 0.55-0.89) or PTCA (HR, 0.86; 95% CI, 0.74-1.00), similar to that of the non-revascularized group (HR, 0.83; 95% CI, 0.80-0.87). CONCLUSIONS: Therapy after AMI with beta-blockers appears to be as effective in reducing 1-year mortality for elderly patients who have undergone CABG or PTCA as for a nonrevascularized group. Our findings suggest that routine use of beta-blockers should be considered for patients who undergo revascularization after AMI.

Adrenergic beta-Antagonists↗
PubMed2000

Germline BRCA1 and HMLH1 mutations in a family with male and female breast carcinoma.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, predisposing to the development of colorectal cancer and other tumor types such as endometrial, small bowel, stomach, ovary and urinary tract carcinoma, while most investigators find no association between HNPCC and cancer of the breast. We have identified hMLH1 mutations in 2 Amsterdam-criteria HNPCC families where both male and female gene carriers were affected with breast cancer. To investigate whether these breast cancers were caused by other genetic factors, we analyzed the 2 breast cancer susceptibility genes BRCA1 and BRCA2. In one family we did not find any mutation in the breast cancer genes, while in the other, a BRCA1 mutation segregated in the breast cancer cases. Hereditary breast cancer, and in particular BRCA1 tumors, display discrete histo-pathological and immunohistological characteristics. The tumor from a woman with both hMLH1 mutations and a BRCA1 mutation exhibited typical BRCA1 histology, e.g., grade 3 invasive ductal carcinoma with dense lymphocytic infiltration, and immunohistology, estrogen receptor (ER) negative, progesterone receptor (PgR) negative, strongly p53 positive, c-erbB-2 negative and highly Ki67 positive (>50% stained cells). The histology of the breast tumor from the man with both one hMLH1 mutation and a BRCA1 mutation was a grade 2 invasive ductal carcinoma without any special BRCA1 features. Immunohistology was also different. This might merely reflect a true difference in male breast tumor progression vs. female. We cannot exclude that the combined effect of BRCA1 and hMLH1 dysfunction has a bearing on tumor progression.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Quantitative measurement of motor and somatosensory impairments after mild (30 min) and severe (2 h) transient middle cerebral artery occlusion in rats.

We tested the hypothesis that mild and severe ischemic cell damage are reflected in neurological and functional recovery after stroke. Rats were subjected to either 30 min or 120 min of middle cerebral artery occlusion or sham operation. Neurological and functional tests including, gross neurological score, and rotarod and adhesive removal tests were performed at various time points up to 21 days after stroke. Significant differences between groups of animals were detected using the rotarod and adhesive removal test. A significant correlation between lesion volume and adhesive removal test was detected in rats subjected to 30 min of ischemia. Our data indicate that quantitative rotarod and adhesive removal tests measure different aspects of functional recovery after stroke, and both are useful in characterizing functional recovery from an ischemic insult.

Animals↗
PubMed2000

Expression of Bcl-2 protects against photoreceptor degeneration in retinal degeneration slow (rds) mice.

The retinal degeneration slow or rds gene encodes rds/peripherin, an integral membrane glycoprotein in the outer segments of rod and cone photoreceptors. Mice homozygous for a null mutation in rds fail to develop outer segments and undergo subsequent degeneration of photoreceptors by the apoptotic pathway. Mutations in the human RDS gene are responsible for several forms of inherited blindness including autosomal-dominant retinitis pigmentosa and macular degeneration. Here, we examined the effects of ectopic Bcl-2 expression in transgenic photoreceptors on the rate of retinal degeneration in rds mutant mice. We observed an approximately twofold preservation of photoreceptors compared with nontransgenic rds mutant mice at 3 months. Immunoblot analysis showed similar levels of Bcl-2 in 2-, 3-, and 4-week-old transgenic mice. Expression of Bcl-2 in the rds mouse did not lead to outer segment formation and did not induce cell death. These results suggest that Bcl-2 expression may be an effective therapeutic strategy in humans with mutations in RDS or other genes that affect the integrity of photoreceptor outer segments.

Animals↗
PubMed2000

Kinetics and mechanism of the citrate synthase from the thermophilic archaeon Thermoplasma acidophilum.

The kinetics and mechanism of the citrate synthase from a moderate thermophile, Thermoplasma acidophilum (TpCS), are compared with those of the citrate synthase from a mesophile, pig heart (PCS). All discrete steps in the mechanistic sequence of PCS can be identified in TpCS. The catalytic strategies identified in PCS, destabilization of the oxaloacetate substrate carbonyl and stabilization of the reactive species, acetyl-CoA enolate, are present in TpCS. Conformational changes, which allow the enzyme to efficiently catalyze both condensation of acetyl-CoA thioester and subsequently hydrolysis of citryl-CoA thioester within the same active site, occur in both enzymes. However, significant differences exist between the two enzymes. PCS is a characteristically efficient enzyme: no internal step is clearly rate-limiting and the condensation step is readily reversible. TpCS is a less efficient catalyst. Over a broad temperature range, inadequate stabilization of the transition state for citryl-CoA hydrolysis renders this step nearly rate-limiting for the forward reaction of TpCS. Further, excessive stabilization of the citryl-CoA intermediate renders the condensation step nearly irreversible. Values of substrate and solvent deuterium isotope effects are consistent with the kinetic model. Near its temperature optimum (70 degrees C), there is a modest increase in the reversibility of the condensation step for TpCS, but reversibility still falls short of that shown by PCS at 37 degrees C. The root cause of the catalytic inefficiency of TpCS may lie in the lack of protein flexibility imposed by the requirement for thermal stability of the protein itself or its temperature-labile substrate, oxaloacetate.

Acetyl Coenzyme A↗
PubMed2000

Markedly decreased binding of vincristine to tubulin in vinca alkaloid-resistant Chinese hamster cells is associated with selective overexpression of alpha and beta tubulin isoforms.

Vinca alkaloids are among a number of cytotoxic agents which target tumor cell microtubules. Studies described herein document the basis for one form of acquired resistance to these plant alkaloids involving an alteration of tubulin in a variant (DC-3F/VCRd-5L) of DC-3F Chinese hamster cells. Our results revealed a markedly decreased binding of [(3)H]vincristine (VCR) to tubulin extracted from this variant compared to tubulin extracted from wild-type DC-3F cells. This was quantitated as a 10- to 15-fold decrease in on-rate in the presence of GTP for the [(3)H]VCR associating with tubulin in cell-free cytosol and a 10-fold increase in off-rate for GTP-dependent dissociation of the [(3)H]VCR-tubulin complex. Quantitative RT-PCR and nucleotide sequencing of poly(A)(+) RNA also carried out with variant and wild-type DC-3F cells documented a different pattern of relative expression, but no base pair differences in the open reading frame of the three alpha and beta tubulin isoforms detected in each cell type. This was accounted for by selective overexpression of one alpha tubulin (alphaII) and two beta tubulin (betaI and betaIV) isoforms in the variant cells. These results would appear to provide an underlying basis for the large decrease in [(3)H]VCR binding by tubulin in these variant Chinese hamster cells and a major component of their acquired resistance to this vinca alkaloid.

Animals↗
PubMed2000

Intracerebral transplantation of bone marrow with BDNF after MCAo in rat.

We tested the hypothesis that a composite graft of fresh bone marrow (BM) along with brain-derived neurotrophic factor (BDNF), transplanted into the ischemic boundary zone (IBZ) of rat brain, facilitates BM cells to survive and differentiate, and improves functional recovery after middle cerebral artery occlusion (MCAo). The fresh BM was harvested from adult rats injected with bromodeoxyuridine (BrdU) as a tracer. Rats (n=37) were subjected to 2h of MCAo, received grafts at 24h and were sacrificed at 7days after MCAo. Test groups consisted of: (1) control - MCAo alone (n=9); (2) injection of phosphate buffered saline (n=4); (3) transplantation of BM (n=8); (4) injection of BDNF (n=7); and (5) transplantation of BM with BDNF (n=9) into the IBZ. Immunohistochemistry was used to identify cells derived from the BM stem cells. Behavioral tests (rotarod motor test; adhesive-removal somatosensory test) were performed before and 7days after MCAo. The data indicate that intracerebral grafting of a combination of BM with BDNF enhances differentiation of BM cells and significantly improves motor recovery of rotarod (P<0.05) and adhesive-removal (P<0.05) tests. We anticipate that BM along with neurotrophic factors may provide a powerful autoplastic therapy for human neurological injury and degenerative disorders.

Animals↗
PubMed2000

Ionizing radiation exposure results in up-regulation of Ku70 via a p53/ataxia-telangiectasia-mutated protein-dependent mechanism.

Genome damaging events, such as gamma-irradiation exposure, result in the induction of pathways that activate DNA repair mechanisms, halt cell cycle progression, and/or trigger apoptosis. We have investigated the effects of gamma-irradiation on cellular levels of the Ku autoantigens. Ku70 and Ku80 have been shown to form a heterodimeric complex that can bind tightly to free DNA ends and activate the protein kinase DNA-PKcs. We have found that irradiation results in an up-regulation of cellular levels of Ku70, but not Ku80, and that this enhanced level of Ku70 accumulates within the nucleus. Further, we uncovered that the postirradiation up-regulation of Ku70 utilizes a mechanism that is dependent on both p53 and damage response protein kinase ATM (ataxia-telangiectasia-mutated); however, the activation of DNA-PK does not require Ku70 up-regulation. These findings suggest that Ku70 up-regulation provides the cell with a means of assuring either proper DNA repair or an appropriate response to DNA damage independent of DNA-PKcs activation.

Antigens, Nuclear↗
PubMed2000

A poly(N-isopropylacrylamide-co-N-acryloxysuccinimide-co-2-hydroxyethyl methacrylate) composite hydrogel membrane for urease immobilization to enhance urea hydrolysis rate by temperature swing*

A composite membrane made of cross-linked poly(N-isopropylacrylamide-co-N-acryloxysuccinimide-co-2-hydroxyethyl methacrylate) (p(NIPAAm-NAS-HEMA)) hydrogel on polyester nonwoven support has been synthesized. The composite membrane shows temperature-responsive properties similar to conventional PNIPAAm hydrogels beads, which reversibly swells below and de-swells above the lower critical solution temperature of PNIPAAm (around 32 to 33 degrees C). Diffusion of urea through the membrane was temperature-dependent with the effective diffusion coefficient at 20 degrees C being 18 times that at 60 degrees C. Urease was immobilized directly to the membrane by forming covalent bonds between its amino groups and the succinimide ester groups of the membrane. Membrane prepared with NIPAAm to NAS molar ratio of 9, and then reacted in pH 7 buffer with 6 mg of urease gave the best immobilized enzyme, where 0.102 mg protein and 5.71 U activity per cm(2) membrane, and 55% relative specific activity could be obtained. There was negligible internal mass transfer resistance for this preparation judging from the calculated effectiveness factor. Urease shows enhanced thermal stability after immobilization with the first-order inactivation rate constant at 70 degrees C decreased to 1/8 of that of free urease. Membrane-immobilized urease could be utilized in a two-compartment membrane reactor with temperature swing to substantially enhance urea hydrolysis rate. The best operating condition of the membrane reactor was with temperature cycling between 60 to 20 degrees C and with temperature change every 10 min, where concentration of product ammonia after 3 h reaction increased 3.8-folds when compared with isothermal operation at 60 degrees C.

Journal Article↗
PubMed2000

Synthesis and characterization of superporous hydrogel composites.

Recently, we synthesized superporous hydrogels which swell fast with high swelling ratios for development of gastric retention devices. Due to their superabsorbent nature, superporous hydrogels are too mechanically weak for gastric retention application. The mechanical strength of superporous hydrogels was substantially increased by making superporous hydrogel composites. The composite materials used were hydrophilic particulate materials commonly used as disintegrants in pharmaceutical tablets. In this study, Ac-Di-Sol was used as a model composite material. Addition of Ac-Di-Sol resulted in significant improvement in the properties of superporous hydrogels. The dried superporous hydrogels maintained interconnected channels even after drying in the air. Thus, the swelling kinetics and the swelling ratio were not affected by air drying, which normally would have resulted in partial or total collapse of the interconnected pores. The presence of Ac-Di-Sol also increased the mechanical strength substantially. Scanning electron microscopic examination showed that the composite material increased the physical crosslinking density which provided high mechanical strength and prevented polymer chains from collapsing during air drying. The superporous hydrogel composites possess properties suitable for gastric retention.

Chemical Phenomena↗