Biomedical subjects

J Chai

Publications and source records attributed to J Chai.

At least 19 recordsLinked to original sources

PubMed2005

Painful small-fiber neuropathy in Sjogren syndrome.

Of 20 consecutive patients with Sjögren neuropathy, 16 (80%) presented with burning feet and 12 (60%) with non-length-dependent sensory symptoms. Leg and thigh skin biopsies, performed in 13 patients, including 7 with normal electrophysiology, showed either reduced epidermal nerve fiber (ENF) density or abnormal morphology. ENF loss was frequently non length dependent, suggesting that patients with this disorder commonly have a small-fiber sensory neuronopathy rather than a "dying-back" axonopathy.

Adult↗

PubMed2005

Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B.

Rebamipide accelerates healing of gastric ulcers and gastritis but its actions on gastric cancer are not known. Survivin, an anti-apoptosis protein, is overexpressed in stem, progenitor, and cancer cells. In gastric cancer, increased and sustained survivin expression provides survival advantage and facilitates tumor progression and resistance to anti-cancer drugs. Aurora-B kinase is essential for chromosome alignment and mitosis progression but surprisingly its role in gastric cancer has not been explored. We examined in human gastric cancer AGS cells: (1) survivin expression, (2) localization of survivin and Aurora-B, (3) cell proliferation, and (4) effects of specific survivin siRNA and/or rebamipide (free radical scavenging drug) on survivin and Aurora-B expression and cell proliferation. Survivin and Aurora-B are strongly expressed in human AGS gastric cancer cells and co-localize during mitosis. Survivin siRNA significantly reduces AGS cell viability. Rebamipide significantly downregulates in AGS cell survivin expression, its association with Aurora-B and cell proliferation. Rebamipide-induced downregulation of survivin is at the transcription level and does not involve ubiquitin-proteasome pathway.

Alanine↗

PubMed2005

Characterization of SSU and LSU rRNA genes of three Trypanosoma (Herpetosoma) grosi isolates maintained in Mongolian jirds.

Trypanosoma (Herpetosoma) grosi, which naturally parasitizes Apodemus spp., can experimentally infect Mongolian jirds (Meriones unguiculatus). Three isolates from A. agrarius, A. peninsulae, and A. speciosus (named SESUJI, HANTO, and AKHA isolates, respectively) of different geographical origin (AKHA from Japan, and the others from Vladivostok), exhibited different durations of parasitaemia in laboratory jirds (2 weeks for HANTO, and 3 weeks for the others). To assess the genetic background of these T. grosi isolates, their small (SSU) and large subunit (LSU) ribosomal RNA genes (rDNA) were sequenced along with those of 2 other Herpetosoma species from squirrels. The SSU rDNA sequences of these 3 species along with available sequences of 3 other Herpetosoma trypanosomes (T. lewisi, T. musculi and T. microti) seemed to reflect well the phylogenetic relationship of their hosts. Three isolates of T. grosi exhibited base changes at 2-6 positions of 2019-base 18S rDNA, at 5-29 positions of 1817/1818-base 28Salpha rDNA, or 1-5 positions of 1557-1559-base 28Sbeta rDNA, and none was separated from the other 2 isolates by rDNA nucleotide sequences. Since base changes of Herpetosoma trypanosomes at the level of inter- and intra-species might occur frequently in specified rDNA regions, the molecular analysis on these regions of rodent trypanosomes could help species/strain differentiation and systematic revision of Herpetosoma trypanosome species, which must be more abundant than presently known.

Animals↗

PubMed2005

A 5-year prospective study on small diameter screw-shaped oral implants.

Alveloar ridges of limited dimensions could preclude the placement of dental implants of the regular dimension. Smaller diameter implants - narrow platform (NP) implants were commercially available to address this issue. The aim of the study was to determine the 5-year clinical performance of 3.3 mm diameter NP implants. Twenty-three machined screw-shaped NP implants were placed in nine patients (six males; three females) between 18 and 70 years of age. Clinical and radiographic examinations were performed annually for 5 years. Recognized implant success criteria was used. The criteria were based on the mean marginal alveolar bone loss, the placement of prosthesis of satisfactory appearance, and the absence of implant mobility, peri-implant radiolucency, pain, discomfort or infection. One implant failed at abutment connection. The remaining 22 implants were restored and functioned successfully according to the criteria. The mean marginal alveolar bone loss during the first year was 0.41 +/- 0.17 mm. The mean marginal alveolar bone loss between the second and fifth year was 0.03 +/- 0.06 mm. The success rate of NP implants according to a well-established set of criteria was 96%.

Adult↗

PubMed2005

Retrospective survival analysis of 3-unit fixed-fixed and 2-unit cantilevered fixed partial dentures.

To evaluate the cumulative survival (CS) rates of fixed partial dentures (FPDs) retained by full-veneer retainers, and those of resin-bonded FPDs provided by graduating dental students for the replacement of a single missing tooth. In 168 patients, 61 3-unit fixed-fixed FPDs and 25 2-unit cantilevered FPDs retained by full-veneer retainers, and 77 3-unit fixed-fixed resin-bonded FPDs and 47 2-unit cantilevered resin-bonded FPDs, were examined for their retention and integrity. The periodontal health, endodontic status and coronal tissues of all abutment teeth were also evaluated. The survival rates of these various designs were analysed with the Kaplan-Meier method. The mean age of all FPDs was 31 months. At 48 months after their insertion, 3-unit FPDs retained by full-veneer retainers had a CS rate of 82%, followed by 2-unit resin-bonded FPDs at 81%, 2-unit FPDs retained by full-veneer retainers at 77%, and 3-unit resin-bonded FPDs at 63%. No significant difference was found between the four designs (P>0.05). Up to both 48 and 60 months, the most common causes of failure were endodontic for FPDs retained by full-veneer retainers, and dislodgement for resin-bonded FPDs. The 3-unit fixed-fixed FPDs retained by full-veneer retainers had the most favourable prognosis after 48 months for replacing a single missing tooth, but the difference between designs was not statistically significant.

Bicuspid↗

PubMed2005

Reduced expression of epidermal growth factor receptor related protein in gastric cancer.

OBJECTIVES: The recently cloned epidermal growth factor receptor related protein (ERRP) has been proposed to be a negative regulator of the epidermal growth factor receptor (EGFR). Because of the causal involvement of EGFR and its ligands in gastric cancer growth, we investigated expression of ERRP and cell proliferation in human gastric cancer. METHODS: We examined ERRP expression and localisation in surgical specimens of gastric cancers from 47 patients versus non-malignant gastric mucosa and determined their relationship to cell proliferation and differentiation. We also examined expression of ERRP by western blotting in three different gastric cancer cell lines. To further determine the functional properties of ERRP, we examined the effect of ERRP on epidermal growth factor (EGF) induced EGFR phosphorylation essential for its activation in MKN-28 gastric cancer cells. RESULTS: ERRP expression was dramatically reduced in gastric cancers (34% of all specimens positive) compared with non-malignant gastric mucosa (66% of specimens positive). Expression of ERRP in cancer cells inversely correlated with cell proliferation and grade of malignancy. Cell lines derived from metastatic gastric cancers had reduced ERRP expression compared with cell lines derived from a non-metastatic cancer. Exogenous ERRP protein markedly inhibited EGF induced EGFR phosphorylation in gastric cancer cells providing a novel molecular mechanism of its action. CONCLUSIONS: Our data indicate that downregulation of ERRP could play an important role in gastric cancer differentiation and progression. ERRP is a negative regulator of tumour cell proliferation and may exert its inhibitory effect, in part, by attenuating EGFR activation.

Adult↗

PubMed2005

Prevalence of malnutrition and risk factors in geriatric patients of a convalescent and rehabilitation hospital.

OBJECTIVES: To investigate the prevalence and risk factors of malnutrition in geriatric patients admitted to a convalescent and rehabilitation hospital. DESIGN: Cross-sectional study. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 120 patients (aged 60 years or older) referred to Tung Wah Eastern Hospital. MAIN OUTCOME MEASURES: Anthropometric, biochemical, and haematological parameters were measured for nutritional assessment. Malnutrition was defined as a body mass index of lower than 18.5 kg/m(2) and serum albumin level of lower than 35 g/L. The clinical outcomes of patients were also recorded. The predictive value of the Chinese Mini Nutritional Assessment as a nutritional screening tool was assessed. Potential risk factors associated with malnutrition were evaluated according to established protocols. RESULTS: The mean age of patients was 80.3 years (standard deviation, 7.4 years), and the mean body mass index was 21.9 kg/m(2) (standard deviation, 4.4 kg/m(2)). The prevalence of malnutrition was 16.7%. The age distribution of malnourished patients (mean, 86.2 years; standard deviation, 7.0 years; n=20) was significantly different to those nourished (mean, 79.1 years; standard deviation, 6.9 years; n=100) [P=0.0001]. Mortality was also higher in malnourished patients (25%) than nourished patients (4%) [P=0.001]. Based on the Chinese Mini Nutritional Assessment, 16.9% of patients were classified as malnourished (cut-off value, 18.5). The Chinese Mini Nutritional Assessment was useful as a screening tool to exclude patients who were not malnourished, ie it had a high negative predictive value (95%). Being totally dependent for the performance of activities of daily living, living in a home for the elderly, and being chair- or bed-bound posed a significantly increased risk of malnutrition. The presence of mental depression (geriatric depression scale score of 8 or higher), moderately or severely impaired cognitive function (abbreviated mental test score of lower than 7), or polypharmacy (five medications or more) did not significantly affect risk of malnutrition. CONCLUSIONS: Malnutrition was common in the geriatric patients studied and was associated with an increased mortality. The Chinese Mini Nutritional Assessment was a useful screening tool to exclude malnutrition. Significant risk factors of malnutrition were total dependence, living in a home for the elderly, and being chair- or bed-bound.

Age Factors↗

PubMed2004

Incidence of deep vein thrombosis after varicose vein surgery.

BACKGROUND: Varicose vein surgery is generally considered to have little risk of postoperative deep vein thrombosis (DVT). This prospective study examined the incidence of DVT in patients undergoing varicose vein surgery. METHODS: Lower leg veins were assessed before operation by duplex ultrasonography in 377 patients, and reassessed 2-4 weeks after surgery, and again at 6 and 12 months. Patients were instructed to contact a physician if symptoms consistent with DVT occurred before the scheduled follow-up appointment. Preoperative prophylaxis (a single dose of subcutaneous heparin) was left to the discretion of the vascular surgeon. RESULTS: DVT was detected in 20 (5.3 per cent) of the 377 patients. Of these, only eight were symptomatic and no patient developed symptoms consistent with pulmonary embolus. Eighteen of the 20 DVTs were confined to the calf veins. Subcutaneous heparin did not alter the outcome. No propagation of thrombus was observed and half of the DVTs had resolved without deep venous reflux at 1 year. CONCLUSION: The incidence of DVT following varicose vein surgery was higher than previously thought, but these DVTs had minimal short- or long-term clinical significance.

Adolescent↗

PubMed2004

Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action?

Clinical and experimental data indicate that rebamipide accelerates ulcer healing, improves scar quality, and prevents ulcer recurrence. However, the mechanisms responsible for these rebamipides' actions are not fully elucidated. We studied, using gene expression microarray analysis, which of the ulcer healing genes are activated by rebamipide treatment. Normal rat gastric epithelial cells (RGM1) were treated with either vehicle or rebamipide. Gene expression was determined using Affymetrix rat genome U34A gene chip arrays and data were analyzed using the GeneSpring program. Activation of some of the genes and protein translation were also examined by RT/PCR and Western blotting. Rebamipide significantly upregulated the proangiogenic genes encoding vascular endothelial growth factor (VEGF), by 7.5-fold, heparin binding epidermal growth-like factor (HB-EGF), by approximately 5-fold, fibroblast growth factor receptor-2 (FGFR2), by 4.4-fold, and cyclooxygenase-2 (Cox2), by 9.3-fold, as well as growth promoting genes, e.g., insulin growth factor-1 (IGF-1), by 5-fold. RT/PCR and Western blotting demonstrated that Cox2 mRNA and protein were upregulated; the latter, approximately 6-fold. Treatment of rat gastric mucosal endothelial cells with rebamipide stimulated in vitro angiogenesis by approximately 240% (vs. controls, P < 0.001). Conclusions are as follows. (1) Rebamipide activates in gastric epithelial RGM-1 cells a genetic program that promotes angiogenesis and signals cell growth and tissue regeneration. (2) In addition, rebamipide treatment directly stimulates angiogenesis in gastric microvascular endothelial cells. Thus rebamipide has two separate and distinct mechanisms of proangiogenic action: one through activation in gastric epithelial cells of proangiogenic growth factor genes and the second a direct angiogenic action on microvascular endothelial cells.

Alanine↗

PubMed2002

Serum response factor: discovery, biochemistry, biological roles and implications for tissue injury healing.

Serum response factor (SRF) is a transcription factor, which binds to a serum response element (SRE) associated with a variety of genes including immediate early genes such as c-fos, fosB, junB, egr-1 and -2, neuronal genes such as nurr1 and nur77 and muscle genes such as actins and myosins. By regulating expression of these genes, SRF controls cell growth and differentiation, neuronal transmission as well as muscle development and function. SRF can be activated by a variety of agents, including serum, lysophosphatidic acid (LPA), lipopolysaccharide (LPS), 12-O-tetradecanoylphorbol-13-acetate (TPA), cytokines, tumor necrosis factor-alpha (TNFalpha), agents that increase intracellular Ca2+, T-cell virus1 activator protein, hepatitis B virus activator proteins pX, activated oncogenes and protooncogenes as well as extracellular stimuli such as antioxidant and UV light. SRF itself is regulated by both cellular signal transduction pathways and interaction with other transcription factors e.g. Sp1, ATF6 and myogenic regulatory factors. Its biological function is best elucidated for myocardium. Specific cardiac SRF transgenesis demonstrated that overexpression of SRF caused hypertrophic cardiomyopathy in mouse and the mouse died of heart failure within 6 months after birth. Other transgenic data suggested that sufficient SRF was needed for embryogenesis and early development. Since SRF is important regulator of numerous genes involved in cell growth and differentiation, including muscle and neural components, SRF may also play a crucial role in tissue injury and ulcer healing, e.g. healing of gastrointestinal ulcers.

Animals↗

PubMed2002

Expression of serum response factor in normal rat gastric mucosa.

Serum response factor (SRF) is a transcription factor that is involved in cell proliferation, muscle and neuron development and maintenance. Its expression in gastric mucosa remains unknown. In this study we demonstrated that SRF is expressed in normal rat gastric tissue as two isoforms and localized mainly to smooth muscle cells of muscularis mucosae and its extensions into the lamina propria, to muscularis propria, and musculature of the vascular system. To a lesser extent, SRF is also expressed in the gastric epithelium of the mucosal neck area (proliferative zone) and in the endothelial cells of microvessels. These data suggest that the main role of SRF in normal gastric tissue is to maintain muscular support and contraction and possibly epithelial regeneration.

Animals↗

PubMed2001

Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding.

Apoptosis is primarily executed by active caspases, which are derived from the inactive procaspase zymogens through proteolytic cleavage. Here we report the crystal structures of a caspase zymogen, procaspase-7, and an active caspase-7 without any bound inhibitors. Compared to the inhibitor-bound caspase-7, procaspase-7 zymogen exhibits significant structural differences surrounding the catalytic cleft, which precludes the formation of a productive conformation. Proteolytic cleavage between the large and small subunits allows rearrangement of essential loops in the active site, priming active caspase-7 for inhibitor/substrate binding. Strikingly, binding by inhibitors causes a 180 degrees flipping of the N terminus in the small subunit, which interacts with and stabilizes the catalytic cleft. These analyses reveal the structural mechanisms of caspase activation and demonstrate that the inhibitor/substrate binding is a process of induced fit.

Amino Acid Sequence↗

PubMed2001

Early postnatal cardiac changes and premature death in transgenic mice overexpressing a mutant form of serum response factor.

Serum response factor (SRF) is a key regulator of a number of extracellular signal-regulated genes important for cell growth and differentiation. A form of the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced the binding activity of SRF protein to the serum response element and reduced the capability of SRF to activate the atrial natriuretic factor promoter that contains the serum response element. Cardiac-specific overexpression of dmSRF attenuated the total SRF binding activity and resulted in remarkable morphologic changes in the heart of the transgenic mice. These mice had dilated atrial and ventricular chambers, and their ventricular wall thicknesses were only 1/2 to 1/3 the thickness of that of nontransgenic mice. Also these mice had smaller cardiac myocytes and had less myofibrils in their myocytes relative to nontransgenic mice. Altered gene expression and slight interstitial fibrosis were observed in the myocardium of the transgenic mice. All the transgenic mice died within the first 12 days after birth, because of the early onset of severe, dilated cardiomyopathy. These results indicate that dmSRF overexpression in the heart apparently alters cardiac gene expression and blocks normal postnatal cardiac growth and development.

Age of Onset↗

PubMed2001

Seroprevalence of Borna disease virus in domestic animals in Xinjiang, China.

To investigate the animals infected with Borna disease virus (BDV) in Xinjiang, China, we examined for BDV antibodies in the sera from groups of 20 horses, sheep and cattle, and from 165 wild rodents (18 species) by ELISA and immunoblot. The serological study disclosed the presence of antibodies to both BDV-p24 and -p40 in the horses (20%) and sheep (25%), whereas no apparent positive reaction was detected either in cattle or rodents. The results suggested that BDV is prevalent in horses and sheep in the district investigated.

Animals↗

PubMed2001

Structural basis of caspase-7 inhibition by XIAP.

The inhibitor of apoptosis (IAP) proteins suppress cell death by inhibiting the catalytic activity of caspases. Here we present the crystal structure of caspase-7 in complex with a potent inhibitory fragment from XIAP at 2.45 A resolution. An 18-residue XIAP peptide binds the catalytic groove of caspase-7, making extensive contacts to the residues that are essential for its catalytic activity. Strikingly, despite a reversal of relative orientation, a subset of interactions between caspase-7 and XIAP closely resemble those between caspase-7 and its tetrapeptide inhibitor DEVD-CHO. Our biochemical and structural analyses reveal that the BIR domains are dispensable for the inhibition of caspase-3 and -7. This study provides a structural basis for the design of the next-generation caspase inhibitors.

Apoptosis↗

PubMed2001

A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.

X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP. Here we show that XIAP associates with the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspase-9, which becomes exposed after proteolytic processing of procaspase-9 at Asp315. Supporting this observation, point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9, or deletion of the linker peptide, prevented caspase-9 association with XIAP and its concomitant inhibition. We note that the N-terminal four residues of caspase-9 linker peptide share significant homology with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3 domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9 activity by disrupting the interaction of the linker peptide of caspase-9 with BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two conserved peptides, one from Smac and the other one from caspase-9, has opposing effects on caspase activity and apoptosis.

Amino Acid Motifs↗

PubMed2001

The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity.

PURPOSE: To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX). METHODS: Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.) or 0.5 mg/kg MTX (i.v.), either alone or 30 min after 25 mg/kg DRZ (i.p.) weekly for up to 12 weeks. Animals treated with DXR alone either died (n = 2) or were killed (n = 3) at a cumulative dose of 10 mg/kg. The severity of cardiac lesions (cytoplasmic vacuolization and myofibrillar loss) were graded semiquantitatively by light microscopy on a scale of 0 to 3. RESULTS: Cardiac lesions were observed in all SHR given DXR or MTX alone, and were attenuated in those given DRZ prior to either DXR (mean lesion scores 2.7 vs 1.5; P < 0.05) or MTX (mean lesion scores 2.0 vs 1.25; P < 0.05). Cardioprotection was also demonstrated by monitoring serum levels of cardiac troponin T (cTnT), which were elevated in all animals receiving DXR or MTX alone. These elevations were attenuated in SHR given the combination of DXR and DRZ (mean values 0.79 ng/ml vs 0.24 ng/ml; P < 0.05) and MTX and DRZ (mean values 0.19 ng/ml vs 0.04 ng/ ml; P < 0.05). Biochemical studies have shown that both DXR and MTX form potentially cardiotoxic complexes with iron. ADR-925 (the hydrolysis product of DRZ) and other chelators (EDTA, diethylenetriaminepentaacetic acid and desferrioxamine) removed Fe(III) from its complex with MTX or DXR. CONCLUSIONS: The present study showed that DRZ significantly attenuates the cardiotoxicity induced by DXR and MTX, and that this protective activity can be assessed by morphological evaluation of cardiac tissues and by monitoring the concentrations of cTnT in serum.

Animals↗

PubMed2001

Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.

The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional alpha helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins.

Amino Acid Sequence↗