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H H Chen

Publications and source records attributed to H H Chen.

At least 19 recordsLinked to original sources

The rubella virus nonstructural protease recognizes itself via an internal sequence present upstream of the cleavage site for trans-activity.

The substrate requirement for rubella virus protease trans-activity is unknown. Here, we analyzed the cleavability of RV P200-derived substrates varying in their N-terminal lengths (72-475 amino acids) from the cleavage site by the RV protease trans-activity. Only substrates with at least 309 amino acid residues N-terminal to the cleavage site were able to undergo cleavage. Further, rubella sequence was found to be necessary in the N-terminal region of the substrate, whereas a heterologous sequence C-terminal to the cleavage site was tolerated. These results demonstrated a requirement for residues located between amino acids 994-1102 of the RV P200 polyprotein, besides its cleavage site for RV protease trans-activity. This region overlaps with the starting site of the essential cis-protease activity of RV P200 polyprotein. This is a novel observation for a viral protease of the family Togaviridae.

Binding Sites↗

Membrane bioreactor application in wastewater re-use from the effluent of Bali primary WWTP, northern Taiwan.

Two MBR pilot systems were constructed and tested in the Bali Primary WWTP. The pilot study shows that two MBR systems, i.e. the Green-MenBio system (MBR-1) and the Bio-MF system (MBR-2), can both fulfill the requirement of wastewater reclamation standard. The MBR-2 system is more economical compared with MBR-1 system. The cost of US dollars 0.10-0.16/m3 is estimated to reclaim the effluent of primary WWTP in Taiwan. The Bali Primary WWTP has the capacity of 1,320,000 cmd which is the biggest in Taiwan. The domestic wastewater of partial Taipei City and Taipei County are collected and transported to the Bali Primary WWTP. The effluent of the Bali Primary WWTP is then discharged into the ocean through two 3.8 m marine outfalls. The AO processes are installed in both MBR systems. More than 90% of the NH3-N can be removed through the AO and membrane processes. The outflow of the MBR systems (without RO) can reach the quality of COD <30 mg/l, BOD <10 mg/l, SS <5 mg/l, NH3-N <3 mg/L. The outflow of the MBR system is proposed to transport 40 km south to the Taoyuan County where four new industrial parks are to be constructed. Part of the reclaimed water is to be used on irrigation and another portion is to be sent to the industries after RO treatment.

Aerobiosis↗

Cycloheximide enhances maintenance of methamphetamine-induced conditioned place preference.

Accrued evidence demonstrated the necessity of protein synthesis at acquisition, consolidation and expression stages in conditioning/learning tasks, while the underlying mechanisms of the maintenance of memory remained less explored. This study was designed to characterize the maintenance of methamphetamine-induced conditioned place preference, a drug-induced learning and memory. In addition, cycloheximide, a protein synthesis inhibitor, was used to examine the involvement of protein synthesis in the maintenance of such place preference memory. We found that the maintenance of the rapidly-established methamphetamine (2 mg/kg, i.p.) -induced conditioned place preference could be long-lasting and even over fifty days under the present protocol of extinction. Moreover, it was of interest to note the undulating expression of this conditioned place preference throughout the extinction protocol. Most importantly, as the methamphetamine-induced conditioned place preference was acquired and expressed by mice, the saline-pretreated control mice underwent numbers of intermittent extinction across a long-term retention test period, while cycloheximide-pretreated mice exhibited unaltered methamphetamine-induced conditioned place preference throughout the same retention test period. Taken together, we conclude that [1] methamphetamine-induced conditioned place preference could last for a long period of time, and such place preference memory is reluctant to extinguish even animals' repeated exposure to the previous conditioned environment at a drug-free status, and [2] blockade of protein synthesis may enhance the maintenance of the methamphetamine-induced conditioned place preference.

Animals↗

Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice.

Ovarian hormones were well documented to modulate the dopamine release in the central dopaminergic systems. The dopamine-releasing effects in the nucleus accumbens, a major target of the mesolimbicortical dopaminergic system, were closely associated with the reinforcing effects of two psychomotor stimulants, cocaine and methamphetamine. This study aimed to examine the sex differences in the cocaine- and methamphetamine-reinforcing behavior, conditioned place preference. In addition, the modulating effects of estradiol and progesterone on methamphetamine-induced conditioned place preference were investigated in both sexes of adult gonadectomized mice. There was no sex difference in the sensitivity to the cocaine (5 mg/kg)-induced conditioned place preference. However, female mice exhibited a more potent methamphetamine (1 mg/kg)-induced conditioned place preference than did male mice. Moreover, pretreatment with estradiol for two consecutive days before the beginning of the conditioning and throughout the four daily conditionings (0.47 microg/day for totally six days) effectively facilitated methamphetamine-induced conditioned place preference in gonadectomized female mice, but not in gonadectomized male mice. Progesterone, under a similar treatment regimen (0.47 microg/day for six consecutive days), did not alter the methamphetamine-induced conditioned place preference in either sex of gonadectomized mice. Taken together, we conclude that the facilitating effects of estradiol on methamphetamine-induced conditioned place preference could be sex-dependent with an eminent sensitivity associated with the adult female mice.

Animals↗

The Swedish Two-County Trial of mammographic screening: cluster randomisation and end point evaluation.

BACKGROUND: The Swedish Two-County Trial has been criticised on the grounds of the cluster randomisation and alleged bias in classification of cause of death. PATIENTS AND METHODS: In the Two-County Trial, 77 080 women were randomised to regular invitation to screening (active study population, ASP) and 55 985 to no invitation (passive study population, PSP), in 45 geographical clusters. After approximately 7 years, the PSP was invited to screening and the trial closed. We analysed data using hierarchical statistical models to take account of cluster randomisation, and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties. We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP. RESULTS: Taking account of the cluster randomisation there was a significant 30% reduction in breast cancer mortality in the ASP. Conservatively, assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality, there was a significant 27% reduction in mortality in the ASP. Ignoring classification of cause of death, there was a significant 13% reduction in all-cause mortality in breast cancer cases in the ASP. CONCLUSIONS: Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer. The criticisms of the Swedish Two-County Trial are unfounded.

Adult↗

Anti-leukemic immunity against U937 cells in uremic patients.

To examine anti-tumor immunity in uremic patients undergoing regular hemodialysis, we designed this study using in vitro mononuclear cell (MNC) cultures, with human leukemic U937 cells as the target. MNC were collected and cultured from uremic subjects and age- and gender-matched healthy controls. Conditioned media from the cultures (MNC-CM) were collected after stimulation with various concentrations of phytohemagglutinin (PHA). The proliferation-inhibiting and differentiation-inducing activities of the PHA-MNC-CM on U937 cells were evaluated. The growth inhibition activity of uremic patients' PHA-MNC-CM was lower than that of controls. The differentiation-inducing effects were evaluated by morphological scoring, superoxide production, and monocyte-associated antigen expression (CD14 and CD68). All three parameters demonstrated that the differentiation-inducing effect of MNC-CM increased with increasing doses of PHA. These effects, however, were significantly less in uremic patients compared to controls at higher doses of PHA. The levels of TNF-alpha and IFN-gamma in PHA-MNC-CM increased in a PHA dose-dependent manner and were much higher in the controls. We conclude that the capacity of MNC from uremic hemodialysis patients to produce anti-leukemic immunity is significantly lower than that of healthy controls.

Aged↗

Direct evidence for neutrino flavor transformation from neutral-current interactions in the Sudbury Neutrino Observatory.

Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.

Journal Article↗

Measurement of day and night neutrino energy spectra at SNO and constraints on neutrino mixing parameters.

The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.

Journal Article↗

Humoral response to p53 in human colorectal tumors: a prospective study of 1,209 patients.

p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/microL), low (10-76 U/microL) and high (>76 U/microL). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] = 3.4; 95% CI = 1.1-10.5), the rectum (OR = 2.9; 95% CI, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p = 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.

Adult↗

Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle.

Cdc6p and the origin recognition complex (ORC) are essential for assembly of a pre-replicative complex (preRC) at origins of replication, before the initiation of DNA synthesis. In the absence of Cdc6p, cells fail to initiate DNA replication and undergo a "reductional" mitosis, in which the unreplicated chromosomes are randomly segregated to the spindle poles. We show here that the cells harboring a mutation in the essential Cdc6p Walker A-box arrest in late mitosis, probably at anaphase. This cell cycle block requires either the three Cdc28p phosphorylation sites within the N terminus of Cdc6p or a short region (aa 8-17) that contains a Cy (Cyclin) interaction sequence. These same two Cdc6p mutants that allow a reductional mitosis are defective in binding Cdc28p kinase. In addition to Cdc6p, ORC also binds to cyclin-dependent kinases (CDKs). Interestingly, Sic1p, a CDK inhibitor protein, blocked the S phase-specific Cdc28p-Clb5p kinase from interacting with ORC, but did not prevent the G(1)-specific Cdc28p-Cln2p kinase-ORC interaction. We suggest that ORC, Cdc6p, and Sic1p bind to different CDKs in a cell cycle-dependent manner to temporally regulate events that (i) allow preRC formation after mitosis, (ii) prevent mitosis before DNA replication can occur, and (iii) promote initiation of DNA replication.

Amino Acid Sequence↗

Measurement of the rate of nu(e) + d --> p + p + e(-) interactions produced by (8)B solar neutrinos at the Sudbury Neutrino Observatory.

Solar neutrinos from (8)B decay have been detected at the Sudbury Neutrino Observatory via the charged current (CC) reaction on deuterium and the elastic scattering (ES) of electrons. The flux of nu(e)'s is measured by the CC reaction rate to be straight phi(CC)(nu(e)) = 1.75 +/- 0.07(stat)(+0.12)(-0.11)(syst) +/- 0.05(theor) x 10(6) cm(-2) s(-1). Comparison of straight phi(CC)(nu(e)) to the Super-Kamiokande Collaboration's precision value of the flux inferred from the ES reaction yields a 3.3 sigma difference, assuming the systematic uncertainties are normally distributed, providing evidence of an active non- nu(e) component in the solar flux. The total flux of active 8B neutrinos is determined to be 5.44+/-0.99 x 10(6) cm(-2) s(-1).

Journal Article↗

Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats.

Previous reports have demonstrated that exogeneous administration of glial cell line-derived neurotrophic factor (GDNF) reduces ventral mesencephalic (VM) dopaminergic (DA) neuron damage induced by 6-hydroxydopamine (6-OHDA) lesioning in rats. Recent studies have shown that 1,25-dihydroxyvitamin D(3) (D3) enhances endogenous GDNF expression in vitro and in vivo. The purpose of present study was to investigate if administration of D3 in vivo and in vitro would protect against 6-OHDA-induced DA neuron injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for 8 days and then lesioned unilaterally with 6-OHDA into the medial forebrain bundle. Locomotor activity was measured using automated activity chambers. We found that unilateral 6-OHDA lesioning reduced locomotor activity in saline-pretreated animals. Pretreatment with D3 for 8 days significantly restored locomotor activity in the lesioned animals. All animals were sacrificed for neurochemical analysis 6 weeks after lesioning. We found that 6-OHDA administration significantly reduced dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanilic acid (HVA) levels in the substantia nigra (SN) on the lesioned side in the saline-treated rats. D3 pretreatment protected against 6-OHDA-mediated depletion of DA and its metabolites in SN. Using primary cultures obtained from the VM of rat embryos, we found that 6-OHDA or H(2)O(2) alone caused significant cell death. Pretreatment with D3 (10(-10) M) protected VM neurons against 6-OHDA- or H(2)O(2)-induced cell death in vitro. Taken together, our data indicate that D3 pretreatment attenuates the hypokinesia and DA neuronal toxicity induced by 6-OHDA. Since both H(2)O(2) and 6-OHDA may injure cells via free radical and reactive oxygen species, the neuroprotection seen here may operate via a reversal of such a toxic mechanism.

Animals↗

Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality.

BACKGROUND: The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so-called "service screening") faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties. METHODS: In the group of subjects ages 20--69 years, there were 6807 women diagnosed with breast carcinoma over a 29-year period in 2 counties in Sweden and 1863 breast carcinoma deaths. All patients were classified from patient charts based on their screening status (i.e., whether they had been invited to undergo screening and whether they actually had undergone screening). The number of women who lived in the 2 counties during the 29-year study period was provided by the Central Bureau of Statistics. Breast carcinoma-specific mortality was compared across three time periods: 1) 1968--1977, when no screening was taking place because mammography had not been introduced; 2) 1978--1987, the approximate period of the Two-County randomized controlled trial of screening in women ages 40--74 years; and 3) 1988--1996, when all women in the 2 counties ages 40--69 years were invited to undergo screening (service screening). When comparing breast carcinoma mortality in screened women with that in women diagnosed before screening was introduced, a correction for self-selection bias was incorporated to prevent overestimation of the benefit of screening. RESULTS: The mortality from incident breast carcinoma diagnosed in women ages 40-69 years who actually were screened during the service screening period (1988--1996) declined significantly by 63% (relative risk [RR] = 0.37; 95% CI, 0.30--0.46) compared with breast carcinoma mortality during the time period when no screening was available (1968--1977). The mortality decline was 50% (RR = 0.50; 95% CI, 0.41--0.60) when breast carcinoma mortality among all women who were invited to undergo screening (nonattendees included) was compared with breast cancer mortality during the time period when no screening was available (1968--1977). The reduction in mortality observed during the service screening period, adjusted for selection bias, was 48% (RR = 0.52; 95% CI, 0.43--0.63). No significant change in breast carcinoma mortality was observed over the three time periods in women who did not undergo screening. This group included women ages 20--39 years because these individuals were never invited to undergo screening, and women ages 40--69 years who did not undergo screening (not invited during the randomized trial or invited during the second and third time periods but declined). CONCLUSIONS: Regular mammographic screening resulted in a 63% reduction in breast carcinoma death among women who actually underwent screening. The policy of invitation to organized screening with mammography appears to have reduced breast carcinoma mortality by 50% in these 2 counties.

Adult↗

Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.

The effects of a common industrial solvent, trichloroethylene (TCE), which was once used as an anesthetic agent but its in vivo mechanism is still unknown, on convulsant-induced seizures in mice were examined. Pretreatment with TCE (250-2000 mg/kg, i.p.) significantly increased pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, bicuculline (BIC)-, strychnine (STY)-, 4-aminopyridine (4-AP)- and N-methyl-D-aspartate (NMDA)-induced convulsion thresholds and lethal doses. However, the increase in convulsion thresholds and lethal doses was much greater for GABAergic antagonists (PIC, BIC, and PTZ) than non-GABAergic convulsants (STY, 4AP, and NMDA) following 2000 mg/kg TCE administration. Pre-treatment of mice with disulfiram (an inhibitor of CYP 4502E1) but not 4-methyl pyrazole (an inhibitor of alcohol dehydrogenase) significantly prolonged the time required for TCE (5000 mg/kg, i.p.) to induce the loss of righting reflex. These results suggest that acute exposure to TCE differentially alters the susceptibility to chemically induced convulsions in mice. The anticonvulsive effect of TCE may be predominantly mediated by GABA(A) receptors. In addition, TCE appears to exert a direct anesthetic effect.

Animals↗

Terminal transferase-dependent PCR (TDPCR) for in vivo UV photofootprinting of vertebrate cells.

Terminal transferase-dependent PCR (TDPCR) is a versatile, sensitive method for detecting DNA lesions such as those generated by the footprinting agents commonly used to detect in vivo protein-DNA interactions. Data similar to those obtained by ligation-mediated PCR (LMPCR) are obtained, but one advantage of TDPCR is that no special enzymes are needed other than terminal deoxynucleotide transferase, T4 DNA ligase, and thermostable DNA polymerases. A detailed TDPCR protocol is given for using UV photofootprinting to detect in vivo footprints and chromatin fine structure in vertebrate cells. One version of the protocol makes use of nonradioactive labeling by near-infrared fluorochromes and detection by a LI-COR DNA sequencing instrument. Sensitivity similar to that of (32)P-labeling is obtained, but with superior band resolution and quantitation.

Animals↗

Prospective study comparing wounds closed with tape with sutured wounds in colorectal surgery.

HYPOTHESIS: To test the efficacy of adhesive paper tape in the closure of clean-contaminated wounds following elective colorectal resection. DESIGN: A prospective, nonrandomized controlled study. SETTING: A medical center that offers a mixture of primary, secondary, and tertiary care services. PATIENTS: The group undergoing skin closure with paper tape (PT group) consisted of 150 patients. The group undergoing skin closure with interrupted suture (IS group) also comprised 150 patients. All 300 patients underwent elective colorectal resection in 1997. MAIN OUTCOME MEASURES: The duration of skin closure, wound complication rate, and cosmetic appearance of the scar at 6 months after operation were compared using the chi(2)test or t test. RESULTS: The mean +/- SD average duration of skin closure was 116 +/- 23 seconds for the PT group and 457 +/- 64 seconds for the IS group (P<.01). The wound complication rate was 3.3% (3 cases with wound infection; 2 with wound separation) for the PT group and 3.3% (5 cases with wound infection) for the IS group (P = 1.0). No significant differences were found between the narrowest width (mean +/- SD, 2.2 +/- 0.9 mm vs 2.3 +/- 1.0 mm) and widest width (mean +/- SD, 4.7 +/- 2.0 mm vs 4.3 +/- 1.8 mm) of scar formation between the 2 groups at 6 months after the operation. Ninety-eight percent of patients in the PT group reported satisfaction with their scar, compared with 92% in the IS group (P =.03). CONCLUSION: Compared with the traditional suture method, paper tape closure in the treatment of clean-contaminated wounds was less time consuming and produced greater patient satisfaction with no increased rate of wound complications.

Adhesives↗

In silico mining of EST databases for novel pre-implantation embryo-specific zinc finger protein genes.

Progress in the understanding of early mammalian embryo development has been severely hampered by scarcity of study materials. To circumvent such a constraint, we have developed a strategy that involves a combination of in silico mining of new genes from expressed sequence tags (EST) databases and rapid determination of expression profiles of the dbEST-derived genes using a PCR-based assay and a panel of cDNA libraries derived from different developmental stages and somatic tissues. We demonstrate that in a random sample of 49 independent dbEST-derived zinc finger protein genes mined from a mouse embryonic 2-cell cDNA library, more than three-quarters of these genes are novel. Examination of characteristics of the human orthologues derived from these mouse genes reveals that many of them are associated with human malignancies. Expression studies have further led to the identification of three novel genes that are exclusively expressed in mouse embryos before or up to the 8-cell stage. Two of the genes, designated 2czf45 and 2czf48 (2czf for 2-cell zinc finger), are zinc finger protein genes coding for a RBCC protein with a RFP domain and a protein with three C2H2 fingers, respectively. The third gene, designated 2cpoz56, codes for a protein with a POZ domain that is often associated with zinc finger proteins. These three genes are candidate genes for regulatory or other functions in early embryogenesis. The strategy described in this report should generally be applicable to rapid and large-scale mining of other classes of rare genes involved in other biological and pathological processes. Mol. Reprod. Dev. 59:249-255, 2001.

Animals↗

Associations of defecography and physiologic findings in male patients with rectocele.

This study evaluated the incidence and physiological findings in male patients with rectoceles. All defecographic studies were evaluated by a single colorectal surgeon. After diagnosis of rectocele in male patients, the patient's history, symptoms, and physiologic tests (anal manometry, pudendal nerve terminal motor latency [PNTML], assessment and electromyography [EMG]) were studied. A prominent rectocele was defined as one that did not empty during defecography and was associated with outlet obstructive syndrome. Forty (17%) rectoceles were diagnosed in 234 male patients with evacuatory disorders who underwent defecography. Rectoceles were anterior in 19 (48%) and posterior in 21 (52%) patients. The main complaint was constipation with difficult defecation in 33 (83%), followed by rectal pain in 5 (13%), rectal prolapse in 1 (3%), and incontinence in 1 (3%). Previous prostatic surgery had been performed in 16 (40%) patients. The mean age and duration of symptoms were 72.4 years (range, 30-88) and 10.3 years (range, 0.5-70), respectively. Excessive straining during evacuation was noted in 73%, unilateral or bilateral pudendal neuropathy in 24.5%, paradoxical puborectalis contraction in 49% and abnormal EMG in 11% of patients. Higher resting pressures with a mean 3.9 cm high pressure zone were noted in 29% of patients. The accompanying findings in defecography were, non-relaxing or partially relaxing puborectalis muscle (66%), perineal descent (65%), intussusception (23%), and sigmoidocele (15%). None of the patients underwent surgery for rectocele alone. In conclusion, rectocele is uncommon in males; it rarely appears as an isolated dysfunction as it is often associated with functional disorders of the pelvic floor. There is a frequent association between rectocele and prostatectomy. Clinical significance and therapeutic strategy remain unknown.

Adult↗