Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 1,207 records · Page 67Linked to original sources

PubMed1999

Comparison of volatile generation in serine/threonine/glutamine-ribose/glucose/fructose model systems.

Thermal generation of volatiles in nine model reactions was studied and compared. Each of the model systems contained one amino acid and one monosaccharide. The amino acid was serine, threonine, or glutamine, and the monosaccharide was ribose, glucose, or fructose. More unsubstituted pyrazine was generated in serine-sugar systems than threonine-sugar systems. The formation of several furfuryl-substituted pyrazines and pyrroles was observed in some of the studied systems. Total pyrazines were generated more in glutamine-containing systems than in serine- and threonine-containing systems, and the reverse was true for generation of furfuryl-substituted compounds. Acetylpyrazine was generated in serine/threonine/glutamine-glucose and serine/glutamine-fructose systems.

Fructose↗

PubMed1999

Absence of mutations in the ATM gene in forty-seven cases of sporadic breast cancer.

Epidemiological evidence points to an increased risk of breast cancer in ataxia telangiectasia (AT) heterozygote women. Previous attempts to screen early onset or familial breast cancer patients failed to confirm an association. The issue of AT and late onset sporadic breast cancer remained unresolved. We screened 47 women who developed later onset, sporadic breast cancer for ataxia telangiectasia mutated (ATM) mutations. No mutations were found.

Adult↗

PubMed1999

New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis.

A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited typical malignant epithelial in morphology and were positive for alpha-fetoprotein (AFP). Flow cytometric analysis of the cell DNA content showed an aneuploid pattern, and its index was 1.5 as compared to that of normal human peripheral blood lymphocytes. Karyotypic analyses of G- and C-banding techniques revealed that all cells presented chromosome abnormalities in number and structure. The number of cell line MHCC97 chromosome ranged from 59 to 65 with a modal number of 60 and 61. At least two common chromosome markers, i(1q) and der(4)t(4;?)(4pter-->q35::?), were present in all cells, and deletion of Y chromosome also occurred in all cells. The subcutaneous and intrahepatic xenografts were formed and metastatic lesions in lungs were found after the cells were inoculated into nude mice. The rate of metastasis to lungs was 100% using orthotopic inoculation. Reverse transcription polymerase chain reaction products revealed positive expressions of integrin alpha5 and beta1, urokinase type plasminogen activator receptor (uPAR), vascular endothelial growth factor and nm23-H1 mRNAs of cell line MHCC97. Immunostaining of c-Met, uPAR showed strongly positive in both subcutaneous xenografts and lung metastatic lesions; while positive in xenografts and negative in metastatic lesions for integrin alpha5, beta1. E-cadherin and P53 was not expressed either in xenograft or in the metastatic lesions. PCR products of HBsAg and HBxAg were both positive. The cell line MHCC97 still retained some characteristic features of original tumour. Establishment of cell line MHCC97 should be beneficial to the studies of HCC metastatic mechanisms.

Adult↗

PubMed1999

Altered expression of the suppressors PML and p53 in glioblastoma cells with the antisense-EGF-receptor.

Gene amplification and enhanced expression of the epidermal growth factor receptor (EGFR) represent the major molecular genetic alteration in glioblastomas and it may play an essential role in cell growth and in the carcinogenic process. On the other hand, the nuclear suppressor proteins PML and p53 are also known to play critical roles in cancer development and in suppressing cell growth. Here we report that, in glioblastoma cells with defective EGFR function, the expressions of both promyelocytic leukaemia (PML) and p53 were altered. Cells that were transfected with the antisense-cDNA of EGFR were found to have more cells in G1 and fewer cells in S phase. In addition, the transfected cells were found to be non-responsive to EGF-induced cell growth. Interestingly, the expression of the suppressors p53 and PML were found to be significantly increased by immunohistochemical assay in the antisense-EGFR cells. Moreover, the PML expression in many of the cells was converted from the nuclear dot pattern into fine-granulated staining pattern. In contrast, the expressions of other cell cycle regulated genes and proto-oncogene, including the cyclin-dependent kinase 4 (cdk4), retinoblastoma, p16INK4a and p21H-ras, were not altered. These data indicate that there are specific inductions of PML and p53 proteins which may account for the increase in G1 and growth arrest in antisense-EGFR treated cells. It also indicates that the EGF, p53 and PML transduction pathways were linked and they may constitute an integral part of an altered growth regulatory programme. The interactions and cross-talks of these critical molecules may be very important in regulating cell growth, differentiation and cellular response to treatment in glioblastomas.

Brain Neoplasms↗

PubMed1999

Rigiscan versus snap gauge band measurements: is the extra cost justifiable?

Both RigiScan and the Snap Gauge band devices are used to objectively measure penile rigidity. The Snap Gauge band is the more simple and inexpensive of the two techniques. We investigated the correlation between the results obtained by both devices in order to evaluate whether the Snap Gauge band could be employed as the sole method of rigidity evaluation while not affecting the quality of diagnosis. Forty eight patients who were presented to our erectile dysfunction clinic used the two devices simultaneously, each according to the accepted protocols. Breakage of two and three strings of the Snap Gauge (good rigidity) correlated well with good tip and average rigidity as evaluated by the RigiScan. Snap gauge results also correlated with duration of erection, number of erections, the number of adequate erections, and the longest duration of erection measured by the RigiScan. Therefore, good rigidity according to the Snap Gauge test correlated well with the results of functional erections (number, rigidity, duration) as obtained by the RigiScan. The Snap Gauge band can be used to adequately evaluate penile rigidity. RigiScan measurements, which are more complicated and more expensive, should be reserved for selected patients in whom the results of the Snap Gauge band are inconclusive or when more detailed information is required.

Adult↗

PubMed1999

Hypertension is associated with a high risk of cancer.

To investigate the possible relationship between hypertension and cancer, a retrospective analysis was carried out using a database including 1225 cases, of which 552 were hypertensives and 673 normotensives. Seventy cases of cancers with different origins were found during a 17-year follow-up. Odds ratio (OR) for occurrence of cancer was calculated. It was shown that an age over 40 years, male sex, alcohol-taking, systolic and diastolic blood pressures (SBP/DBP) were the five risk factors for the occurrence of cancers, while occupation, smoking, body mass index, left ventricular hypertrophy, and antihypertensive medication had no effect on cancer incidence. Hypertensives were at a high risk of overall cancer incidence with OR 2.2 (P < 0.01). After stratification of age, OR for hypertensives aged 40-49 years old with SBP > or =140 mm Hg or DBP > or =90mm Hg was 3.18 and 2.98 (P < 0.01 respectively). The OR of cancer for non-alcohol taking male hypertensives with SBP < or =140 mm Hg or DBP > or =90 mm Hg were 3.6 (95%CI 1.37-9.68, P = 0.003) and 5.67 (95%CI 2.01-16.75, P < 0.001), 7.55 (95%CI 2.10-33.19, P < 0.001) and 7.80 (95%CI 2.14-33.79, P < 0.001) for non-alcohol taking female hypertensives with SBP > or =140 mm Hg or DBP > or =90 mm Hg. After adjustment of age, sex and alcohol taking, the OR of the cancer incidence was 3.45 (95%CI 1.30-9.01, P < 0.01) for male and 5.0 (95%CI 1.56-16.67, P < 0.01) for female hypertensives aged 40-49 years. Multiple logistic regression analysis shows that age over 40 years, male sex, alcohol-taking, and DBP were the four independent risk factors for cancers. It is concluded that hypertension is associated with a high risk of cancer.

Adult↗

PubMed1999

Cloning and sequencing of the gene encoding universal stress protein from Escherichia coli O157:H7 isolated from Jack-in-a-Box outbreak.

A gene encoding the universal stress protein (uspA) was cloned from Escherichia coli O157:H7 isolated from a Jack-in-a-Box outbreak. The nucleotide sequence was determined and the amino acid sequence predicted. The gene was found to be highly conserved and shared 97% homology with the same gene of E. coli K-12. Within an 800-base pair (bp) region sequenced, a 15-bp mismatch existed between E. coli K-12 and O157:H7, of which 11 base pairs were internal to the structural gene of uspA. However, only an area with a 4-bp mismatch caused an amino acid substitution, changing an alanine to an arginine at position 140.

Amino Acid Sequence↗

PubMed1999

The limitations of the instantaneous centre of rotation in joint research.

The limitations on the use of the instantaneous centre of rotation (ICR), as calculated from discrete displacement data, are often not fully appreciated. As a consequence, the concept of the ICR has been improperly applied in some instances. In this paper, the procedures used to compute the ICR are developed in detail, and the factors that affect the computed results are identified. With an example, it is shown that in addition to being path dependent, ICR location is also sampling increment size dependent. Therefore, it is not appropriate to consider the ICR as a rotation centre if the body is undergoing general planar (combined translation and rotation) motion because it does not uniquely characterize the movement.

Humans↗

PubMed1999

Escherichia coli nusG mutations that block transcription termination by coliphage HK022 Nun protein.

The Escherichia coli nusG gene product is required for transcription termination by phage HK022 Nun protein at the lambda nutR site in vivo. We show that it is also essential for Nun termination at lambda nutL. Three recessive mis-sense nusG mutations have been isolated that inhibit termination by Nun at lambda nutR. The mutations are ineffective in a lambda pL nutL fusion, even when lambda nutR replaces lambda nutL. The mutant strains support lambda growth, indicating that lambda N antitermination activity is not impaired. Transcription arrest by Nun in vitro is stimulated by NusG protein at both lambda nutR and lambda nutL. Mutant NusG protein fails to enhance transcriptional arrest by Nun at either site. The mutant protein, like the wild-type protein, suppresses transcriptional pausing by RNA polymerase and stimulates Rho-dependent termination. These results imply that the role of NusG in Nun termination may be distinct from its roles in other transcription reactions.

Bacterial Proteins↗

PubMed1999

In vivo post-translational processing and subunit reconstitution of cephalosporin acylase from Pseudomonas sp. 130.

Cephalosporin acylases are a group of enzymes that hydrolyze cephalosporin C (CPC) and/or glutaryl 7-amino cephalosporanic acid (GL-7ACA) to produce 7-amino cephalosporanic acid (7-ACA). The acylase from Pseudomonas sp. 130 (CA-130) is highly active on GL-7ACA and glutaryl 7-aminodesacetoxycephalosporanic acid (GL-7ADCA), but much less active on CPC and penicillin G. The gene encoding the enzyme is expressed as a precursor polypeptide consisting of a signal peptide followed by alpha- and beta-subunits, which are separated by a spacer peptide. Removing the signal peptide has little effect on precursor processing or enzyme activity. Substitution of the first residue of the beta-subunit, Ser, results in a complete loss of enzyme activity, and substitution of the last residue of the spacer, Gly, leads to an inactive and unprocessed precursor. The precursor is supposed to be processed autocatalytically, probably intramolecularly. The two subunits of the acylase, which separately are inactive, can generate enzyme activity when coexpressed in Escherichia coli. Data on this and other related acylases indicate that the cephalosporin acylases may belong to a novel class of enzymes (N-terminal nucleophile hydrolases) described recently.

Amino Acid Sequence↗

PubMed1999

Fluorescent phosphoinositide derivatives reveal specific binding of gelsolin and other actin regulatory proteins to mixed lipid bilayers.

Fluorescent derivatives of phosphatidyl inositol (PtdIns)-(4,5)-P2 were synthesized and used to test the effects of the PtdIns-(4, 5)-P2-regulated proteins gelsolin, tau, cofilin, and profilin on labeled PtdIns-(4,5)-P2 that was either in micellar form or mixed with phosphatidylcholine (PtdCho) in bilayer vesicles. Gelsolin increased the fluorescence of 7-nitrobenz-2-oxa-1,3-diazole (NBD)- or pyrene-labeled PtdIns-(4,5)-P2 and NBD-PtdIns-(3,4,5)-P3. Cofilin and profilin produced no detectable change at equimolar ratios to PtdIns-(4,5)-P2, while tau decreased NBD-PtdIns-(4,5)-P2 fluorescence. Fluorescence enhancement by gelsolin of NBD-PtdIns-(4, 5)-P2 in mixed lipid vesicles depended on the mole fraction of PtdIns-(4,5)-P2 in the bilayer. Specific enhancement of 3% NBD-PtdIns-(4,5)-P2 : 97% PtdCho was much lower than that of 10% PtdIns-(4,5)-P2 : 90% PtdCho, but the enhancement of 3% NBD-PtdIns-(4,5)-P2 could be increased by addition of 7% unlabeled PtdIns-(4,5)-P2. The gelsolin-dependent increase in NBD-PtdIns-(4, 5)-P2 fluorescence was reversed by addition of Ca2+ or G-actin. Significant, but weaker, fluorescence enhancement was observed with the gelsolin N-terminal domain (residues 1-160) and a peptide comprised of gelsolin residues 150-169. Fluorescence energy transfer from gelsolin to pyrene-PtdIns-(4,5)-P2 was much stronger with intact gelsolin than the N-terminal region of gelsolin containing the PtdIns-(4,5)-P2 binding sites, suggesting that PtdIns-(4,5)-P2 may bind near a site formed by the juxtaposition of the N- and C-terminal domains of gelsolin.

4-Chloro-7-nitrobenzofurazan↗

PubMed1999

A comparison among four regimens of itraconazole treatment in onychomycosis.

The purpose of this study was to compare the efficacy of different dosage regimens in the management of onychomycosis with itraconazole and to determine the results of a further 1-week intermittent pulse treatment in non-cured patients. In this study, 153 patients were randomly allocated to four groups. Patients in group A were treated with daily doses of 100 mg for 3 months in the case of fingernail onychomycosis and for 4 months in the case of toenail onychomycosis. Patients in the other groups received a intermittent pulse therapy, in which the drug was taken for 1 week, then discontinued for 3 weeks, three cycles for fingernail and four cycles for toenail infection. The daily doses were 400 mg (group B), 300 mg (group C) and 200 mg (group D). After therapy, non-cured patients were treated further with one cycle in which the daily dose was 400 mg. Patients were subsequently observed for 9 months and efficacy was assessed by mycological examination and the growth of unaffected nails. At the end of the therapy, the cure rates in the four groups were 19.1% (A), 15.2% (B), 18.9% (C) and 17.9% (D), and no significant differences were found between each of B, C, D and A. At the end of the study, the cure rates were 76.2%, 91.3%, 78.4%, 28.6% respectively. The group that received further treatment had a cure rate of 55.6% at the end of the first month and of 83.3% in the second month. Drug tolerability was equally good in the four groups. Intermittent pulse therapy with a daily dose of 400 mg had the highest cure rate. Treatment of improved but non-cured patients with a dose of 400 mg intermittent pulse therapy markedly increased the cure rate. All treatment regimens were well tolerated.

Adolescent↗

PubMed1999

Assessment of decisions in the treatment of Helicobacter pylori-related duodenal ulcer: a cost-effectiveness study.

AIMS: Many treatment trials for Helicobacter pylori have been reported but few have evaluated treatment in terms of both cost and effectiveness. It is important to find a therapy with a high eradication rate and low cost, especially in China. The aim of the study is to assess the efficiency of therapy for duodenal ulcers, including ulcer healing, H. pylori eradication and ulcer recurrence. METHODS: Ninety-six consecutive patients with duodenal ulcers and H. pylori infection were randomly allocated into two groups: AMT group (amoxycillin + metronidazole + tagamet); OA group (omeprazole + amoxycillin). Side-effects were recorded during the treatment period. Endoscopic examinations were repeated at the 7th or 8th week to assess ulcer healing. Patients were followed up for 6 months and repeat endoscopy was performed. Ulcer healing rate, H. pylori eradication rate and ulcer recurrence rate were compared. All costs were recorded and a cost-effectiveness analysis was conducted. RESULTS: In the AMT and OA groups, the ulcer healing rate was 83.7 and 93.5%, respectively (P = 0.27). The eradication rate of H. pylori was 65.1 and 69.6%, respectively and was significantly higher in patients with an ulcer diameter < or = 1 cm compared with those with an ulcer diameter > 1 cm, irrespective of treatment group. There was no difference in recurrence rate, duration of pain or the time lost because of the disease. Moderate or severe side-effects were found in 8.9% in AMT group and 6.5% in OA group. The cost of treatment for ulcer healing, H. pylori eradication and reduction in ulcer recurrence were all lower in the AMT group than in the OA group. Sensitivity analysis supported the result that AMT was more cost effective than OA. CONCLUSIONS: The AMT therapy was more effective and less costly than the OA therapy, especially in patients with H. pylori-related duodenal ulcers < 1 cm diameter.

Adolescent↗

PubMed1999

Long-term changes in connexin32 gap junction protein and mRNA expression following cocaine self-administration in rats.

Considerable evidence indicates a critical role for dopamine in the reinforcing effects of cocaine. Because dopamine has been shown to be a critical modulator of gap junction communication in both eye and brain, we sought to examine whether extended intravenous cocaine self-administration would affect the expression of gap junction channel-forming proteins (connexins). Using ELISA, Western analysis, immunohistochemistry, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and non-radioactive in situ hybridization, we demonstrate that withdrawal from chronic cocaine self-administration causes lasting changes in connexin32 (Cx32) expression in the nucleus accumbens and hippocampus at 2, 7 and 21 days after the last cocaine injection. A sustained decrease in Cx32 protein and mRNA levels is noted in areas that have been implicated in cocaine craving (i.e. nucleus accumbens and subfields of the hippocampal formation). A progressive increase in gap junction protein and mRNA expression is noted in areas that become hyperexcitable after chronic cocaine exposure (i.e. CA1 hippocampal neurons). We speculate that gap junction communication may be critically involved in reinforcement processes and neuroadaptive changes produced by drugs of abuse.

Animals↗

PubMed1999

Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study.

OBJECTIVES: To determine, in a prospective randomized, double-blind placebo-controlled study, the effect of 6 weeks of high-dose (5 g/day) orally administered nitric oxide (NO) donor L-arginine on men with organic erectile dysfunction (ED). PATIENTS AND METHODS: The study included 50 men with confirmed organic ED who were randomized after a 2-week placebo run-in period to receive L-arginine or placebo. A detailed medical and sexual history, O'Leary's questionnaire, a specially designed sexual function questionnaire and a sexual activity diary were obtained for each patient. All participants underwent a complete physical examination including an assessment of bulbocavernosus reflex and penile haemodynamics. Plasma and urine nitrite and nitrate (designated NOx), both stable metabolites of nitric oxide, were determined at the end of the placebo run-in period, and after 3 and 6 weeks. RESULTS: Nine of 29 (31%) patients taking L-arginine and two of 17 controls reported a significant subjective improvement in sexual function. All objective variables assessed remained unchanged. All nine patients treated with L-arginine and who had subjectively improved sexual performance had had an initially low urinary NOx, and this level had doubled at the end of the study. CONCLUSIONS: Oral administration of L-arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production. The haemodynamics of the corpus cavernosum were not affected by oral L-arginine at the dosage used.

Administration, Oral↗

PubMed1999

In situ detection of neuronal DNA strand breaks using the Klenow fragment of DNA polymerase I reveals different mechanisms of neuron death after global cerebral ischemia.

Ischemic cell injury in the brain may involve a cascade of programmed cell death. DNA damage may be either a catalyst or a consequence of this cascade. Therefore, the induction of DNA strand breaks in the rat brain following transient global ischemia was examined using (a) the Klenow labeling assay, identifying DNA single-strand breaks (SSBs) or double-strand breaks (DSBs) with protruding 5' termini, and (b) terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), detecting DNA DSBs with protruding 3' termini or blunt ends. Klenow-positive staining occurred within 2 h of reperfusion and increased with increasing durations of reperfusion. DNA damage detected with the Klenow labeling assay preceded that of TUNEL expression in the caudate putamen, reticular thalamus, thalamus, and cortex. However, in CA1, DNA SSBs were not detected until 72 h of reperfusion and occurred simultaneously with DSBs. Thus, the time course and fragmentation characteristics of DNA damage differ between the hippocampal CA1 and other selectively vulnerable brain regions. This distinct pattern suggests that the delayed neuronal death in CA1 following transient global ischemia may occur via an apoptotic mechanism different from that of other brain regions.

Animals↗

PubMed1999

hFE65L influences amyloid precursor protein maturation and secretion.

The amyloid precursor protein (APP) is processed in the secretory and endocytic pathways, where both the neuroprotective alpha-secretase-derived secreted APP (APPs alpha) and the Alzheimer's disease-associated beta-amyloid peptide are generated. All three members of the FE65 protein family bind the cytoplasmic domain of APP, which contains two sorting signals, YTS and YENPTY. We show here that binding of APP to the C-terminal phosphotyrosine interaction domain of hFE65L requires an intact YENPTY clathrin-coated pit internalization sequence. To study the effects of the hFE65L/APP interaction on APP trafficking and processing, we performed pulse/chase experiments and examined APP maturation and secretion in an H4 neuroglioma cell line inducible for expression of the hFE65L protein. Pulse/chase analysis of endogenous APP in these cells showed that the ratio of mature to total cellular APP increased after the induction of hFE65L. We also observed a three-fold increase in the amount of APPs alpha recovered from conditioned media of cells overexpressing hFE65L compared with uninduced controls. The effect of hFE65L on the levels of APPs alpha secreted is due neither to a simple increase in the steady-state levels of APP nor to activation of the protein kinase C-regulated APP secretion pathway. We conclude that the effect of hFE65L on APP processing is due to altered trafficking of APP as it transits through the secretory pathway.

Amyloid beta-Protein Precursor↗

PubMed1999

Molecular cloning of a cell cycle regulation gene cyclin H from ischemic rat brain: expression in neurons after global cerebral ischemia.

Gene expression plays an important role in determining the fate of neurons after ischemia. To identify additional genes that promote survival or execute programmed cell death in ischemic neurons, a subtractive cDNA library was constructed from hippocampus of rats subjected to global ischemia. With use of a differential screening technique, a cDNA was identified that was up-regulated after ischemia. The cDNA was found to have high homology with human cyclin H at both the nucleotide level (89%) and the amino acid level (93%). Northern blotting detected cyclin H mRNA in nonischemic and ischemic brains. In situ hybridization studies revealed that cyclin H message was found in hippocampal neurons in nonischemic brain. After ischemia, expression was increased primarily in the dentate gyrus and CA3 regions of hippocampus. Expression of cyclin H protein, detected by western blotting of hippocampal tissue, was increased after global ischemia, but expression of cyclins B1 and D1 and other related cell cycle genes (Cdk7 and Cdc2) was not increased. Cyclin H immunoreactivity was found exclusively within neurons. After ischemia, there was increased immunoreactivity within neurons in dentate gyrus, CA3, and cortex. Thus, cyclin H is expressed in normal postmitotic neurons and expression is increased in neurons that are ischemic yet survive. These results suggest that cyclin H may have functions in neurons other than cell cycle regulation, including other known functions such as DNA repair.

Amino Acid Sequence↗