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Biomedical subjects

H Xie

Publications and source records attributed to H Xie.

At least 55 records · Page 3Linked to original sources
PubMed2001

Low concentration N-methyl-N'-nitro-N-nitrosoguanidine activates DNA polymerase-beta expression via cyclic-AMP-protein kinase A-cAMP response element binding protein pathway.

Ultraviolet light (UV), ionizing-radiation or alkylating agents are known as carcinogens, mostly because of their ability to damage DNA directly. However, they may also play a diverse role in activating the signal pathways and altering the gene expression. We have shown previously that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of 0.2 microM can increase the transcription of DNA polymerase-beta gene, which has a cyclic AMP response element (CRE) motif in its promoter. Using the CRE report vector, we show here, such treatment can stimulate the CRE-driven gene expression by approximately 1.5-fold compared with control. Consistent with it, the proportion of ser-133 phosphorylated CRE binding protein (CREB), the related transcription factor was 2.08-fold higher versus control in vero cells after 60 min of MNNG treatment. Although CREB has many putative kinases for its phosphorylation, such as p38 mitogen-activated protein kinase (p38 MAPK), Ca(2+)/calmodulin-dependent protein kinase Pi (CaMK Pi) and protein kinase C (PKC), we found the protein kinase A (PKA) was activated and its activation peaked when cells were treated for 60 min (with arbitrary activity unit of 11.03+/-2.80 and 0.86+/-0.43 in treatment and control, respectively), this phasic character was similar to that of the CREB phosphorylation. We also determined the intracellular cyclic AMP (cAMP) levels and it was found that the cAMP concentration was elevated after 60 min treatment (1.53-fold higher). However, to our surprise, we did not find any accompanying cAMP elevation in cells treated by MNNG for 30 min, in which PKA was activated significantly. These findings, together with other observations, suggest that cAMP-PKA-CREB signaling pathway mediates the low concentration MNNG induced pol-beta expression. In addition to elevated cAMP, there might exist a cAMP-independent PKA activation manner in this course.

Animals↗
PubMed2001

MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes.

Viability-promoting genes such as BCL2 play an important role in human cancer but do not directly cause aggressive tumors. BCL2 transgenic mice develop lymphoma at low frequency, hindering studies of tumorigenesis and its inhibition in the presence of such gene products. MCL1 is a member of the BCL2 family that is highly regulated endogenously and that promotes cell viability and immortalization when introduced exogenously. Mice expressing an MCL1 transgene in hematolymphoid tissues have now been monitored for an extended period and were found to develop lymphoma with long latency and at high probability (more than 85% over 2 years). In most cases, the disease was widely disseminated and of clonal B-cell origin. A variety of histologic subtypes were seen, prominently follicular lymphoma and diffuse large-cell lymphoma. MCL1 thus sets the stage for the development of lymphoma as does BCL2, disease occurring with high probability and recapitulating a spectrum of subtypes as seen in human patients. These findings with the transgene underscore the importance of the normal, highly regulated pattern of MCL1 expression, in addition to providing a model for studying tumorigenesis and its inhibition in the presence of a viability promoting BCL2 family member. (Blood. 2001;97:3902-3909)

Animals↗
PubMed2001

A humanized monoclonal antibody constructed from intronless expression vectors targets human hepatocellular carcinoma cells.

An anti-human hepatocellular carcinoma (HCC) monoclonal antibody, hHP-1, was genetically humanized from a murine monoclonal antibody. In this study, a concept of positional template approach was applied to design the amino acid sequence of hHP-1's variable region, and synthetic DNA fragments for protein expression were produced through overlapping PCR from single strand oligonucleotides. Synthetic DNA fragments and human antibody constant region cDNA were used to construct two CMV promotor-based expression vectors for the antibody light and heavy chains, in which the variable region was connected directly to the constant region without an intron sequence. Completely assembled humanized antibody was successfully expressed in mammalian cells as IgG1 kappa molecules and purified using protein A affinity column. The immunogenicity of the hHP1 was estimated by the amino acid sequence and determined through a HAMA (human anti-murine antibody) serum reaction assay. Results indicated that the immunogenicity of hHP-1 was significantly reduced. In vitro binding activity assay showed that the hHP-1 had retained its binding function to a human HCC SMMC-7721 cell-line, without cross binding to other human normal tissues. Immunofluorescence staining showed that hHP-1 had a strong binding activity to SMMC cells. A competitive binding assay showed that the relative binding activity of hHP-1 was approximately 25% binding activity of the original murine antibody. Our results indicate that a humanized antibody could be produced using intronless vectors and expressed as a complete IgG1 kappa antibody. Hence we believe that hHP-1 could be a potential candidate for HCC treatment.

Amino Acid Sequence↗
PubMed2001

Role of hydrogen bonding in the interaction between a xylan binding module and xylan.

NMR studies of the internal family 2b carbohydrate binding module (CBM2b-1) of Cellulomonas fimi xylanase 11A have identified six polar residues and two aromatic residues that interact with its target ligand, xylan. To investigate the importance of the various interactions, free energy and enthalpy changes have been measured for the binding of xylan to native and mutant forms of CBM2b-1. The data show that the two aromatic residues, Trp 259 and Trp 291, play a critical role in the binding, and similarly that mutants N264A and T316A have no affinity for the xylose polymer. Interestingly, mutations E257A, Q288A, N292A, E257A/Q288A, E257A/N292A, and E257A/N292A/Q288A do not significantly diminish the affinity of CBM2b-1 for the xylose polymers, but do influence the thermodynamics driving the protein-carbohydrate interactions. These thermodynamic parameters have been interpreted in light of a fresh understanding of enthalpy-entropy compensation and show the following. (1) For proteins whose ligands are bound on an exposed surface, hydrogen bonding confers little specificity or affinity. It also displays little cooperativity. Most specificity and affinity derive from binding between the face of sugar rings and aromatic rings. (2) Loss of hydrogen bonding interactions leads to a redistribution of the remaining bonding interactions such that the entropic mobility of the ligand is maximized, at the expense (if necessary) of enthalpically favorable bonds. (3) Changes in entropy and enthalpy in the binding between polysaccharide and a range of mutants can be interpreted by considering changes in binding and flexibility, without any need to consider solvent reorganization.

Actinomycetales↗
PubMed2001

A simple automated continuous-flow-equilibration method for measuring carbon monoxide in seawater.

A simple, robust, low-maintenance method using air-segmented continuous-flow equilibration was developed and automated to measure carbon monoxide (CO) in natural waters precisely and accurately. Finely regulated flows of CO-free air and of seawater or standard water were pumped into a glass coil, forming discrete gas/liquid segments. The partially CO-equilibrated gas effluent was injected into a Trace Analytical reduction analyzer for CO detection. A semiempirical mass-balance model was established for predicting and optimizing the performance of the CO extractor. The optimized gas and water flow rates were approximately 1.2 and approximately 14 mL min(-1), respectively, giving a response time of less than 15 min and a CO-extraction yield of approximately 80%. The analytical blank, precision, and accuracy were, respectively, 0.02 nM, +/-2.5% (at the approximately 1 nM level), and better than 5%. Two extractors can be interfaced to one detector at 4-6 samples per hour for each extractor. Coupled with a continuous surface-water sampler, the system was successfully applied to monitoring the diurnal variation of CO concentration in Sargasso Sea surface waters.

Automation↗
PubMed2001

Evidence for synergy between family 2b carbohydrate binding modules in Cellulomonas fimi xylanase 11A.

Glycoside hydrolases often contain multiple copies of noncatalytic carbohydrate binding modules (CBMs) from the same or different families. Currently, the functional importance of this complex molecular architecture is unclear. To investigate the role of multiple CBMs in plant cell wall hydrolases, we have determined the polysaccharide binding properties of wild type and various derivatives of Cellulomonas fimi xylanase 11A (Cf Xyn11A). This protein, which binds to both cellulose and xylan, contains two family 2b CBMs that exhibit 70% sequence identity, one internal (CBM2b-1), which has previously been shown to bind specifically to xylan and the other at the C-terminus (CBM2b-2). Biochemical characterization of CBM2b-2 showed that the module bound to insoluble and soluble oat spelt xylan and xylohexaose with K(a) values of 5.6 x 10(4), 1.2 x 10(4), and 4.8 x 10(3) M(-1), respectively, but exhibited extremely weak affinity for cellohexaose (<10(2) M(-1)), and its interaction with insoluble cellulose was too weak to quantify. The CBM did not interact with soluble forms of other plant cell wall polysaccharides. The three-dimensional structure of CBM2b-2 was determined by NMR spectroscopy. The module has a twisted "beta-sandwich" architecture, and the two surface exposed tryptophans, Trp 570 and Trp 602, which are in a perpendicular orientation with each other, were shown to be essential for ligand binding. In addition, changing Arg 573 to glycine altered the polysaccharide binding specificity of the module from xylan to cellulose. These data demonstrate that the biochemical properties and tertiary structure of CBM2b-2 and CBM2b-1 are extremely similar. When CBM2b-1 and CBM2b-2 were incorporated into a single polypeptide chain, either in the full-length enzyme or an artificial construct comprising both CBM2bs covalently joined via a flexible linker, there was an approximate 18-20-fold increase in the affinity of the protein for soluble and insoluble xylan, as compared to the individual modules, and a measurable interaction with insoluble acid-swollen cellulose, although the K(a) (approximately 6.0 x 10(4) M(-1)) was still much lower than for insoluble xylan (K(a) = approximately 1.0 x 10(6) M(-1)). These data demonstrate that the two family 2b CBMs of Cf Xyn11A act in synergy to bind acid swollen cellulose and xylan. We propose that the increased affinity of glycoside hydrolases for polysaccharides, through the synergistic interactions of CBMs, provides an explanation for the duplication of CBMs from the same family in some prokaryotic cellulases and xylanases.

Actinomycetales↗
PubMed2001

Spinocerebellar ataxia type 1 in China: molecular analysis and genotype-phenotype correlation in 5 families.

BACKGROUND: Twelve genetic types of autosomal dominant hereditary ataxia have been recently identified and the genes responsible for most of them cloned. Molecular identification of the type of ataxia is important to determine the disease prevalence and its natural history in various populations. OBJECTIVES: To perform molecular analysis of 75 Chinese families affected with spinocerebellar ataxia (SCA) and to evaluate the spectrum of mutations in these genes and the correlation between genotypes and phenotypes in Chinese patients. SETTING: Neurogenetics Unit, China-Japan Friendship Hospital, Beijing, China. METHODS: One hundred nine patients from 75 kindreds diagnosed as having autosomal dominant SCA, 16 patients with sporadic SCA or spastic paraplegia, 280 control chromosomes of the Chinese population, and 120 control chromosomes of the Sakha population were selected for this study. We conducted detailed mutational analysis by direct sequencing of polymerase chain reaction products amplified from genomic DNA. RESULTS: Spinocerebellar ataxia type 1 (SCA1) was identified in 5 families with 12 studied patients. All affected family members were heterozygous for a CAG repeat expansion in the SCA1 gene containing 51 to 64 trinucleotide repeats. Normal alleles had 26 to 35 repeats. Spinocerebellar ataxia type 1 accounted for 7% of the studied Chinese families with ataxia. In addition, we determined the frequency of a single vs double CAT interruption in 120 control chromosomes of the Siberian Sakha population, which has the highest known prevalence of SCA1, and compared this with 280 control chromosomes from the Chinese populations. The results show that 64.7% of the Siberian normal alleles contain a single CAT interruption, whereas 92% of the Chinese had more than 1 interruption. CONCLUSIONS: Spinocerebellar ataxia type 1 is responsible for 7% of affected families in the Chinese population. A correlation between the prevalence of SCA1 and the number of CAT interruptions in the trinucleotide chain suggests that a CAT-to-CAG substitution may have been the initial event contributing to the generation of expanded alleles and influencing relative prevalence of SCA1.

Adult↗
PubMed2001

Characterization for didodecyldimethylammonium bromide liquid crystal film entrapping catalase with enhanced direct electron transfer rate.

Direct electrochemistry for catalase (CAT) embedded in the liquid crystal film of didodecyldimethylammonium bromide (DDAB) was investigated at pyrolytic graphite (PG) electrode by voltammetric methods. The reduction reaction involved the redox couple in CAT, i.e. FeIII/FeII couple. The electron transfer between the incorporated CAT and PG electrode was found to be greatly enhanced by DDAB. The heterogeneous electron transfer rate constant k(s) was fitted as 3.0 +/- 0.4 s(-1) using the nonlinear regression analysis of the square wave voltammograms at a series of pulse heights. The pH dependence of the formal potential for CAT in DDAB film was 57 mV/pH, which suggested one-proton-transfer together with a one-electron reaction. Visible absorption and reflectance-absorbance infrared (RAIR) spectra inferred the similar heme environment of CAT in DDAB film to its native status. Circular dichroism (CD) results indicated DDAB affected slightly on the second structure of CAT.

Animals↗
PubMed2001

Matrix metalloproteinase activities of turkey (Meleagris gallopavo) bile.

The bile from turkey (Meleagris gallopavo) gall bladders was found to contain substantial matrix metalloproteinase (MMP) activities using gelatin, collagen, and casein substrate zymography, [3H]labeled collagen degradation assays, and gelatin-agarose affinity purification. Five major bands corresponding to approximate M(w) of 64, 60, 46, 40 and 36 kDa showed gelatinolytic activities. On incubation with p-aminophenylmercuric acetate or thimerosal, the densities of both the 64- and 46-kDa bands decreased with increasing intensities of the 60- and 40-kDa bands. Both the 64- and 60-kDa bands showed collagenolytic activities whereas the caseinolytic activities appeared as diffuse bands corresponding to M(w) of approximately 60, 40 and 36 kDa. Using [3H]collagen as substrate, the bile enzymes showed both a time and concentration-dependent degradation, which could be inhibited by the MMP inhibitors such as EDTA, phenanthroline, and N-[(2R)-2-(hydroxyamido carbonylmethyl)-4-methylpentanonyl]-L-tryptophan methylamide, but not by serine and cysteine protease inhibitors like trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, phenylmethylsulfonyl fluoride or leupeptin. Both 60- and the 40-kDa gelatinolytic bands showed affinity adsorption to a gelatin-agarose matrix. The physiological roles of bile MMPs are not clear, but their involvement in the digestive functions of birds are likely.

Animals↗
PubMed2001

An application of the thresholds of change model to the analysis of mental health data.

The threshold of change model (TCM) is a statistical technique for analyzing ordered stages of change variables. TCM focuses on the thresholds that separate the ordered stages, and the effects of explanatory variables are evaluated in terms of raising or lowering the thresholds. TCM also allows the explanatory variables to exert differential influence on each threshold. In this paper, we use TCM to analyze the data from a clinical trial that compared assertive community treatment (ACT) with standard case management (SCM) for patients with co-occurring severe mental illness and substance use disorder. Endpoint data (36-month follow up) were used for this analysis. The response variable is the recoded Substance Abuse Treatment Scale with three ordered levels (engagement/persuasion, active treatment, and recovery/relapse prevention), and hence two thresholds. The explanatory variables are gender and group (ACT vs. SCM). The results indicate that gender exerts constant and significant effects on both thresholds. The group effect is somewhat mixed: ACT lowers the first threshold (active treatment), but raises the second threshold (recovery/relapse prevention).

Adolescent↗
PubMed2001

Does competitive employment improve nonvocational outcomes for people with severe mental illness?

The authors examined the cumulative effects of work on symptoms, quality of life, and self-esteem for 149 unemployed clients with severe mental illness receiving vocational rehabilitation. Nonvocational measures were assessed at 6-month intervals throughout the 18-month study period, and vocational activity was tracked continuously. On the basis of their predominant work activity over the study period, participants were classified into 4 groups: competitive work, sheltered work, minimal work, and no work. The groups did not differ at baseline on any of the nonvocational measures. Using mixed effects regression analysis to examine rates of change over time, the authors found that the competitive work group showed higher rates of improvement in symptoms; in satisfaction with vocational services, leisure, and finances; and in self-esteem than did participants in a combined minimal work-no work group. The sheltered work group showed no such advantage.

Adult↗
PubMed2001

Ethnic differences in dietary intakes, physical activity, and energy expenditure in middle-aged, premenopausal women: the Healthy Transitions Study.

BACKGROUND: Menopause is a time of increased risk of obesity in women. The effect of menopause in African American women, in whom obesity is already highly prevalent, is unknown. OBJECTIVE: We compared dietary intakes and energy expenditure (EE) between middle-aged, premenopausal African American and white women participating in a longitudinal study of the menopausal transition. DESIGN: Dietary intakes by food record, EE by triaxial accelerometer, physical activity by self-report, and body composition by dual-energy X-ray absorptiometry were compared in 97 white and 52 African American women. Twenty-four-hour and sleeping EE were measured by whole-room indirect calorimetry in 56 women. RESULTS: Sleeping EE (adjusted for lean and fat mass) was lower in African American than in white women (5749 +/- 155 compared with 6176 +/- 75 kJ/d; P = 0.02); however, there was no significant difference in 24-h EE between groups. Reported leisure activity over the course of a week was less in African American than in white women (556 +/- 155 compared with 1079 +/- 100 kJ/d; P = 0.02), as were the daily hours spent standing and climbing stairs. Dietary intakes of protein, fiber, calcium, magnesium, and several fatty acids were significantly less in African Americans, whereas there were no observed ethnic differences in intakes of fat or carbohydrate. Body fat within the whole group was positively correlated with total, saturated, and monounsaturated fat intakes and inversely associated with fiber and calcium intakes. Fiber was the strongest single predictor of fatness. CONCLUSION: Ethnic differences in EE and the intake of certain nutrients may influence the effect of menopausal transition on obesity in African American women.

Absorptiometry, Photon↗
PubMed2001

Sutureless liver repair and hemorrhage control using laser-mediated fusion of human albumin as a solder.

BACKGROUND: Major liver trauma has a high mortality because of immediate exsanguination and a delayed morbidity from septicemia, peritonitis, biliary fistulae, and delayed secondary hemorrhage. We evaluated laser soldering using liquid albumin for welding liver injuries. METHODS: Fourteen lacerations (6 x 2 cm) and 13 nonanatomic resection injuries (raw surface, 8 x 2 cm) were repaired. An 805-nm laser was used to weld 53% liquid albumin-indocyanine green solder to the liver surface, reinforcing it by welding a free autologous omental scaffold. The animals were heparinized and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, 16 soldering repairs were evaluated acutely at 3 hours. Eleven animals were evaluated chronically, two at 2 weeks and nine at 4 weeks. RESULTS: All 27 laser mediated-liver repairs had minimal blood loss compared with the suture controls. No dehiscence, hemorrhage, or bile leakage was seen in any of the laser repairs after 3 hours. All 11 chronic repairs healed without complication. CONCLUSION: This modality effectively seals the liver surface, joins lacerations with minimal thermal injury, and works independently of the patient's coagulation status.

Animals↗
PubMed2001

Converting day treatment centers to supported employment programs in Rhode Island.

OBJECTIVE: The purpose of the study was to compare vocational and nonvocational outcomes of clients of two community mental health centers that underwent conversion from day treatment programs to supported employment programs with outcomes of clients of a center that delayed conversion until after the study was completed. METHODS: As part of a statewide effort in Rhode Island to convert day treatment programs to supported employment programs, the authors assessed 127 day treatment clients with severe mental illness in three community mental health centers. Two of the centers converted to supported employment, and one continued its rehabilitative day program. Participants were assessed prospectively for 30 to 36 months, with special attention to vocational and social outcomes. RESULTS: Former day treatment clients in the converted centers attained higher rates of competitive employment than those in the comparison group (44.2 percent and 56.7 percent versus 19.5 percent). Other employment outcomes also improved, and hospitalization rates and overall social functioning were unchanged. CONCLUSIONS: This study supports findings of previous studies suggesting that replacing rehabilitative day treatment programs with supported employment programs yields improvements in employment outcomes without adverse effects.

Adolescent↗
PubMed2001

Six-month outcomes for patients who switched to olanzapine treatment.

OBJECTIVE: This study evaluated the outcomes of patients in a community mental health center who switched from treatment with another antipsychotic to olanzapine treatment. It also sought to determine whether simultaneous access to case management and psychosocial rehabilitation and olanzapine leads to enhanced functional improvement. METHODS: Six-month outcomes for a consecutive series of 104 patients who switched from a conventional antipsychotic medication to olanzapine were evaluated. Forty-nine patients in the same treatment program who continued to take conventional antipsychotics were also monitored as a reference group. Outcomes of the group receiving olanzapine were compared with their own baseline status and with outcomes of the reference group. RESULTS: At six months, patients in the olanzapine group demonstrated significant improvement over baseline across multiple measures of symptoms and psychosocial function. Compared with the reference group, the olanzapine group was more symptomatic at baseline and demonstrated significantly greater improvement at follow-up on the Brief Psychiatric Rating Scale and all subscales; Mini Psychiatric Rating Scale negative symptom, disorganization, anxiety, depression, and medication side effects items; and Clinical Global Improvement scale and Case Manager's Rating Scale-Plus illness factors. There was a trend toward superior improvement in psychosocial functioning among patients in the olanzapine group that achieved significance when patients in acute relapse at baseline were excluded. CONCLUSIONS: Olanzapine is effective in managing markedly to severely ill patients with psychotic disorders in a community mental health center. Simultaneous treatment with olanzapine, case management, and psychosocial rehabilitation leads to enhanced functional improvement among nonrelapsing patients.

Adult↗
PubMed2001

Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice.

AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.

Animals↗
PubMed2001

Family treatment and medication dosage reduction in schizophrenia: effects on patient social functioning, family attitudes, and burden.

The effects of 2 family intervention programs (supportive family management [SFM], including monthly support groups for 2 years; or applied family management [AFM], including 1 year of behavioral family therapy plus support groups for 2 years), and 3 different neuroleptic dosage strategies (standard, low, targeted) on social functioning of patients with schizophrenia. their relatives' attitudes, and family burden were examined. AFM was associated with lower rejecting attitudes by relatives toward patients and less friction in the family perceived by patients. Patients in both AFM and SFM improved in social functioning but did not differ, whereas family burden was unchanged. Medication strategy had few effects, nor did it interact with family intervention. The addition of time-limited behavioral family therapy to monthly support groups improved family atmosphere, but did not influence patient social functioning or family burden.

Adult↗