Biomedical subjects

S Pan

Publications and source records attributed to S Pan.

At least 19 recordsLinked to original sources

PubMed2001

Role for tissue factor pathway in murine model of vascular remodeling.

Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay between TF and TFPI and the regulation of vascular thrombogenicity in a model of vascular remodeling. To determine the levels and pattern of vascular expression of TF and TFPI associated with vascular remodeling, a murine model of flow cessation was studied. TF activity of the arteries increased after ligation (P<0.05). Quantitative analysis of homogenates of remodeled carotid arteries revealed increased TF expression but unchanged TFPI expression compared with normal carotid arteries, resulting in enhanced TF activity. To determine the potential therapeutic role of TFPI in this thrombogenic state, mice were treated with intravascular adenoviral delivery of either murine TFPI (Ad-mTFPImyc) or a control adenovirus (Ad-DeltaE1). Overexpression of TFPI decreased vascular TF activity compared with viral control (P<0.01). Overexpression of TFPI inhibited neointimal formation (P=0.038), resulting in enhanced luminal area (P=0.001) 4 weeks after flow cessation. In this murine model of vascular remodeling, an imbalance between TF and TFPI expression is generated, resulting in increased TF activity. Overexpression of TFPI in this model inhibits vascular TF activity and results in attenuation of vascular remodeling associated with flow interruption.

Animals↗

PubMed2001

Factors influencing the induction of DT-diaphorase activity by 1,2-dithiole-3-thione in human tumor cell lines.

NAD(P)H:(quinone acceptor)oxidoreductase (DT-diaphorase) is a two-electron reducing enzyme that activates bioreductive antitumor agents and is induced by a wide variety of compounds including 1,2-dithiole-3-thione (D3T). We investigated factors influencing DT-diaphorase induction in fourteen human tumor cell lines. Four cell lines had basal DT-diaphorase activity that was increased by D3T treatment (group A), six cell lines had basal DT-diaphorase activity but the activity was not increased by D3T (group B), and four cell lines had low enzyme activity without, or with, D3T (group C). Two cell lines in group A and two cell lines in group B had a C to T polymorphism at base 609 in the NQO(1), DT-diaphorase gene, in one allele, while all four cell lines in group C were homozygous mutants. The base 609 mutant NQO(1) gene produces a protein with little enzyme activity. In group A, D3T increased NQO(1) mRNA and wild-type protein, and also increased mutant protein in the two heterozygous cell lines. In group B, the inducer slightly increased NQO(1) mRNA, did not increase the wild-type protein, but did increase the mutant protein in the two heterozygous cell lines. In group C, D3T increased NQO(1) mRNA as well as its mutant enzyme product. Transfection of the mutant NQO(1) gene into cells with two wild-type alleles did not alter DT-diaphorase activity. The results suggest that the lack of induction of DT-diaphorase activity is transcriptional in nature, that basal and induced expression of DT-diaphorase are regulated independently, and that mutant NQO(1) does not act as a dominant-negative to suppress DT-diaphorase activity.

Antineoplastic Agents↗

PubMed2001

Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase.

3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1. It was found that several compounds were potent inhibitors of HIV-1 with the most potent compound 24 exhibiting an IC90 = 32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC90s against several clinically meaningful mutant virus strains.

Anti-HIV Agents↗

PubMed2001

3,3a-Dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones are potent non-nucleoside reverse transcriptase inhibitors.

A series of unique 3,3a-dihydropyrano[4,3,2-de]quinazolin-2(1H)-ones and a 2a,5-dihydro-2H-thieno[4,3,2-de]quinazo-line-4(3H)-thione were found to be HIV-1 non-nucleoside reverse transcriptase inhibitors. One of these compounds, as the racemate, possessed an IC90 = 4.6 nM against wild-type virus in a whole cell antiviral assay and had an IC90 = 76 and 897 nM against the clinically significant K103N and K103N/L100I mutant viruses, respectively.

Binding Sites↗

PubMed2001

Early colonic carcinoma with extensive lymph node metastases: case report and review of literature.

An 81-year-old woman had an early carcinoma invading focally into the upper submucosa of the middle-transverse colon, which was accompanied by extensive lymph node metastases and resulted in a poor prognosis. Although her tumor was small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor enabled its earlier detection. To further study the exceptional lymph node metastases we studied the expression of intestinal trefoil factor and sialyl Tn antigen immunohistochemically on the resected specimen. Their simultaneous expression in lymph node metastasis further supports the aggressive nature of this tumor.

Adenocarcinoma↗

PubMed2001

Mining time dependency patterns in clinical pathways.

Clinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length of hospital stay of each patient. The development of clinical pathways is a lengthy process, and may require the collaboration among physicians, nurses, and staffs in a hospital. However, the individual differences cause great variances in the execution of clinical pathways. It calls for a more dynamic and adaptive process to improve the performance of clinical pathways. This paper reports a data mining technique we have developed to discover the time dependency pattern of clinical pathways for managing brain stroke. The mining of time dependency pattern is to discover patterns of process execution sequences and to identify the dependent relation between activities in a majority of cases. By obtaining the time dependency patterns, we can predict the paths for new patients when he/she is admitted into a hospital; in turn, the health care procedure will be more effective and efficient.

Algorithms↗

PubMed2001

Overexpression of Hp95 induces G1 phase arrest in confluent HeLa cells.

Xp95, a protein recently identified in Xenopus laevis, is potentially involved in progesterone-induced Xenopus oocyte maturation. In this study, we cloned a human homologue of Xp95, designated Hp95, and examined the effect of its overexpression on the growth properties of human malignant HeLa cells which have lost the contact inhibition of cell proliferation. We observed that although HeLa cells did not undergo G1 phase arrest at any stage after confluence, they were able to downregulate their G1 phase CDK activities in response to confluence. When Hp95 was overexpressed in HeLa cells by transfection with a constitutive or an inducible expression vector containing a full-length Hp95 transgene, HeLa cells became able to undergo G1 phase arrest and form a monolayer culture after confluence. However, the G1 phase CDK activities in these Hp95 overexpressing cells were not inhibited further as compared to control cells after confluence. These results indicate that the defects in HeLa cells that cause the loss of contact inhibition of cell proliferation are in components downstream of the G1 phase CDKs and that overexpression of Hp95 counteracts some of these defects.

Amino Acid Sequence↗

PubMed2001

Investigation of the extent of gastric metaplasia in the duodenal bulb by using methylene blue staining.

BACKGROUND AND AIMS: The existence of gastric metaplasia (GM) of the duodenal mucosa has been considered to be highly related to the recurrence of duodenal ulcers (DU). The aims of this study are to evaluate the usefulness of methylene blue staining in the detection of GM, and to clarify the relationship between GM and the deformity of the duodenal bulb. METHODS: Fifteen patients with healed DU and four patients with symptoms of dyspepsia without evidence of ulcers were enrolled into this endoscopic study. During each endoscopy, methylene blue was sprayed evenly on the duodenal bulb, and biopsies were taken from blue-stained and unstained areas. The existence and extent of GM were assessed histologically and grossly. The correlation between duodenal bulb deformity and the extent of GM was also studied. RESULTS: The mean score of methylene blue non-staining (MBNS) was 0, 1.30 +/- 0.15, and 3.00 +/- 0.00 in group A (non-ulcer patients), group B (patients with healed DU and with normal-shaped bulb) and C (patients with healed DU and with deformed duodenal bulb), respectively; showing significant differences among the groups (P < 0.05 in each). Both the existence and the grading of GM were higher in unstained specimens than in blue-stained specimens (100 vs 16.6%, P < 0.0001 and 3.62 +/- 0.09 vs 0.19 +/- 0.06, P < 0.001, respectively). CONCLUSIONS: Methylene blue non-staining can be applied to investigate the existence and extent of GM in the duodenal bulb accurately. The incidence of GM in the duodenal bulb was higher in patients with healed ulcers than in non-ulcer patients. Patients with deformed duodenal bulbs have a higher extent of GM than those without deformed duodenal bulbs.

Adult↗

PubMed2001

Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a prospective, randomized long-term study.

BACKGROUND: To assess the efficacy of adjuvant sclerotherapy after banding for the treatment of esophageal varices, a randomized trial was carried out of endoscopic variceal ligation (EVL) alone with sequential sclerotherapy versus sequential ligation-sclerotherapy (SLS) after banding with respect to variceal eradication, associated complications, and recurrence of varices. METHODS: One hundred patients qualified for this study. Fourteen patients were not included for the following reasons: 6 chose not to participate, 4 had fundal varices, and 4 had some form of cancer. Of the remaining 86 patients in the study, 42 underwent EVL alone and the other 44 SLS. Variceal ligation was begun in the region of the gastroesophageal junction, with subsequent ligatures applied cephalad 3 to 5 cm; ligation was repeated every 2 weeks until variceal obliteration. For SLS, ligation was also begun in the region of the gastroesophageal junction and repeated until varices were reduced to F1 size. Subsequently, these patients underwent sclerotherapy with between 6 and 8 mL of sodium tetradecyl sulfate (free hand technique). RESULTS: No significant differences were found between EVL alone and SLS with regard to variceal eradication, development of associated complications, and recurrent bleeding during a follow-up of 2 years. The probability of variceal recurrence requiring further treatment after 1 year was 14% for the SLS group and 26% for EVL group patients. Another year later, the probability of variceal recurrence was 24% and 45%, respectively, for the SLS and EVL groups. CONCLUSIONS: Because a significantly lower rate of variceal recurrence was found for SLS patients, sequential sclerotherapy followed by ligation to eradicate those varices too small to easily band may be a better procedure.

Combined Modality Therapy↗

PubMed2001

[Correlation between electroretinographic findings, clinical phenotypic and genotypic analysis in Duchenne and Becker muscular dystrophy].

OBJECTIVE: To explore the relationship between electrophysiological changes, clinical phenotype and genotype in Duchenne and Becker muscular dystrophy(DMD/BMD), to address the expression and roles of dystrophin and its isoforms on the retina, and to inquire into the molecular mechanism of the abnormal electroretinogram(ERG) on DMD/BMD patients with different genotype. METHODS: Gene deletions were screened by multiplex DNA amplification with eleven primers on twenty-two consecutive patients with DMD and BMD, and then, the ERG was tested according to international ERG standard. RESULTS: ERG phenotype was associated with the site of DMD gene defects rather than the severity of the phenotype. Patients with deletion in the central region of the gene had more severe changes in the scotopic ERG as compared to those with gene non-deletion. CONCLUSION: The ERG genotype-phenotype correlation suggests that DP260 may play the most important role in the retinal neurotransmission.

Adolescent↗

PubMed2001

[Intron 44 is not the most unstable intron in the "central deletion hot spot" of dystrophin gene].

OBJECTIVE: To understand the distributional characteristics of dystrophin gene deletion breakpoints in "central deletion hot spot" and analyze the instability of introns 44-51 after excluding the effect of intron's length. METHODS: Fifty-nine Duchenne/Becker muscular dystrophy(DMD/BMD) patients were detected by polymerase chain reactions with the primers to amplify exons 44-52 of dystrophin gene. The amount of actual breakpoints, expected breakpoints according to its length, and the ratios of actual breakpoints to expected values(A/E) for introns 44-51 were calculated respectively. RESULTS: In "central deletion hot spot", about 30.8% of breakpoints fell in intron 44, about 23.1%, 17.9%, 10.3%, 10.3% of breakpoints fell in introns 50,51, 45, 48, respectively. But the amount of actual breakpoints of intron 44 was less than that of expected breakpoints according to its length, the ratio of A/E was 0.7. The amount of actual breakpoints of introns 48, 50, 51, 45 were more than that of length expected value. The ratios of A/E were 2.7, 2.0, 1.9, 1.1, respectively. CONCLUSION: Intron 44 is more stable than the whole molecular region of "central deletion hot spot". Introns 48, 50 and 51 are comparatively instable in "central deletion hot spot".

Dystrophin↗

PubMed2001

Relationship of duodenal ulcer recurrence to gastric metaplasia of the duodenal mucosa and duodenal bulb deformity.

BACKGROUND AND PURPOSE: This study investigated changes in the severity of gastric metaplasia (GM) of the duodenal mucosa before and after ulcer healing and Helicobacter pylori eradication. It also investigated whether deformity of the duodenal bulb affects the severity of GM and the likelihood of ulcer recurrence. METHODS: Eleven patients were consecutively enrolled in this study. They all had duodenal ulcer(s) and H. pylori infection, for which they had received anti-H. pylori triple therapy during the active ulcer stage, and had all undergone serial endoscopic examinations during both the active ulcer and scarring ulcer stages, and at 1 year after ulcer healing. Duodenal biopsies were obtained at each endoscopy to identify the severity of GM. Duodenal ulcers were divided into three types by bulbar shape and GM was classified into four grades of severity. RESULTS: All 11 patients had increased GM severity just after ulcer healing. The 1-year follow-up study revealed that the GM was unchanged in six of eight patients with grade 3 GM severity at the scarring stage, while in the other two it regressed to grade 1 or 2; these two patients suffered ulcer recurrence. A markedly deformed bulb (type III) was found in three patients, of whom two had ulcer recurrence. CONCLUSION: Two characteristic conditions were found in patients with duodenal ulcer recurrence after H. pylori eradication: a markedly deformed bulb with grade 3 GM at the scarring stage, and a change in GM from high to low grade at or around the previous ulcer site after ulcer healing.

Adult↗

PubMed2000

Increased nondisjunction of chromosome 21 with age in human peripheral lymphocytes.

Fluorescence in situ hybridization (FISH) on binucleated cells with chromosome-specific DNA probes provides a convenient way to visualize reciprocal segregation patterns in daughter nuclei, and overcomes most problems related to the artefactual loss or gain of chromosomes that flaw chromosome preparations. In this study, FISH was employed to evaluate age- and sex-effects on spontaneous malsegregation, nondisjunction and loss of chromosome 21 in human lymphocytes after the first division in culture. A total of 68 healthy nonsmokers and nondrinkers of alcohol (37 males and 31 females) were grouped by age as Group I (0-10 years), Group II (20-30 years), Group III (40-50 years) and Group IV (60-70 years), with at least seven subjects per group and sex. FISH with a pericentric chromosome 21 specific DNA probe was carried out on binucleated lymphocytes, cytokinesis-blocked by cytochalasin B (6 microg/ml for 26 h) at 44 h after initiation of cultures. Linear regression analyses demonstrated a significant age-related increase in the frequency of micronuclei without chromosome 21 (MN-21)(r=0.73, p<0.001 in females; r=0.69, p<0.001 in males) in all binucleated cells, with a steeper slope in females (0.1758) than in males (0. 1241). Analysis using the 2x2 chi-square (chi(2)) test on the frequencies of MN-21 showed significant age-related differences in both males and females, except males in Group III and Group IV (p>0. 05). A significant sex-related difference was found only in subjects over 60 years (p<0.05), with females having more MN-21 (12.57 per thousand vs. 8.43 per thousand) than males. Loss of chromosome 21, occurring at mean levels of 0.38 per thousand in all binucleated cells and 0.24 per thousand in binucleated cells containing four FISH signals, was shown not to be age- or sex-related. A positive age-related increase in nondisjunction of chromosome 21 was shown in males (r=0.50, p<0.01), females (r=0.61, p<0.001) and all subjects (r=0.55, p<0.001) by linear regression analysis. An age effect was found only between children and adults (p<0.01 for females, p<0.05

Adolescent↗

PubMed2000

NFATz: a novel rel similarity domain containing protein.

Nuclear Factor of Activated T cell (NFAT) is a family of transcription factors that are important for the coordinate expression of various cytokines and immunoregulatory cell surface molecules in T cells and other types of cells in the immune system. In addition, analysis of gene disrupted mice revealed that some members of NFAT family are important for the development of myocardium, myocardial hypertrophy, and mesenchymal stem cells. NFAT family proteins have two conserved domains, the NFAT Homology Domain (NHD) and the Rel Similarity Domain (RSD). The RSD is DNA binding and AP-1 interacting domain which has structural similarity to the Rel Homology Region, the DNA binding domain of Rel family proteins. The NHD is a regulatory domain required for the Ca regulated translocation of NFAT. We report here the isolation and initial characterization of a novel RSD containing protein designated NFATz. NFATz has a RSD but no NHD. NFATz protein is localized in the nucleus without Ca signal. There is no detectable binding to a typical NFAT site even in the presence of AP-1, and it is not capable of activating transcription through the NFAT site. The chromosomal location determined by FISH revealed that NFATz and NFATx genes are in the same region.

Amino Acid Sequence↗

PubMed2000

Acrokeratosis paraneoplastica (Bazex syndrome) with adenocarcinoma of the colon: report of a case and review of the literature.

Acrokeratosis paraneoplastica is a rare disease and is uncommon even in patients with upper aerodigestive tract cancer. We report a 63-year-old man with a 1-month history of numerous pruritic lesions and vesicles on both feet. Although he had received local therapy, progressive dense scale formation involving both palms and both soles was found. Colonoscopy was performed because of hematochezia, and it revealed an early colon cancer. After the resection of the cancer, the skin lesions began to fall off dramatically. To the best of our knowledge, there is no report of acrokeratosis paraneoplastica associated with colon cancer in the literature. This is the first case report of acrokeratosis paraneoplastica associated with early colon cancer.

Acrodermatitis↗

PubMed2000

Pulmonary artery perfusion with protective solution reduces lung injury after cardiopulmonary bypass.

BACKGROUND: The inflammatory response and higher temperature of lung tissue during cardiopulmonary bypass can result in lung injury. This study was to evaluate the protective effect of pulmonary perfusion with hypothermic antiinflammatory solution on lung function after cardiopulmonary bypass. METHODS: Twelve adult mongrel dogs were randomly divided into two groups. The procedure was carried out through a midline sternotomy, cardiopulmonary bypass was established using cannulas placed in the ascending aorta, superior vena cava, and right atrium near the entrance of the inferior vena cava. After the ascending aorta was clamped and cardioplegic solution infused, the right lung was perfused through a cannula placed in the right pulmonary artery with 4 degrees C lactated Ringer's solution in the control group (n = 6) and with 4 degrees C protective solution in the antiinflammation group (n = 6). Antiinflammatory solution consisted of anisodamine, L-arginine, aprotinin, glucose-insulin-potassium, and phosphate buffer. Plasma malondialdehyde, white blood cell counts, and lung function were measured at different time point before and after cardiopulmonary bypass; lung biopsies were also taken. RESULTS: Peak airway pressure increased dramatically in the control group after cardiopulmonary bypass when compared with the antiinflammation group at four different time points (24 +/- 1, 25 +/- 2, 26 +/- 2, 27 +/- 2 cm H2O versus 17 +/- 2, 18 +/- 1, 17 +/- 1, 18 +/- 1 cm H2O; all p < 0.01). Pulmonary vascular resistance increased significantly in the control group than in the antiinflammation group at 5 and 60 minutes after cardiopulmonary bypass (1,282 +/- 62 dynes x s x cm(-5) versus 845 +/- 86 dynes x s x cm(-5) and 1,269 +/- 124 dynes x s x cm(-5) versus 852 +/- 149 dynes x s x cm(-5), p < 0.05). Right pulmonary venous oxygen tension (PvO2) in the antiinflammation group was higher than in the control group at 60 minutes after cardiopulmonary bypass (628 +/- 33.3 mm Hg versus 393 +/- 85.9 mm Hg, p < 0.05). The ratio of white blood cells in the right atrial and the right pulmonary venous blood was lower in the antiinflammation group than in the control group at 5 minutes after the clamp was removed (p < 0.05). Malondialdehyde were lower in the antiinflammation group at 5 and 90 minutes after the clamp was removed (p < 0.01 and p < 0.05, respectively). Histologic examination revealed that the left lung from both groups had marked intraalveolar edema and abundant intraalveolar neutrophils, whereas the right lung in the control group showed moderate injury and the antiinflammation group had normal pulmonary parenchyma. CONCLUSIONS: Pulmonary artery perfusion using hypothermic protective solution can reduce lung injury after cardiopulmonary bypass.

Animals↗

PubMed2000

Role of the TATA binding protein-transcription factor IIB interaction in supporting basal and activated transcription in plant cells.

The TATA binding protein (TBP) and transcription factor IIB (TFIIB) play crucial roles in transcription of class II genes. The requirement for TBP-TFIIB interactions was evaluated in maize cells by introducing mutations into the Arabidopsis TBP (AtTBP2) within the C-terminal stirrup. Protein binding experiments indicated that amino acid residues E-144 and E-146 of AtTBP2 are both essential for TFIIB binding in vitro. Activation domains derived from herpes simplex viral protein VP16, the Drosophila fushi tarazu glutamine-rich domain (ftzQ), and yeast Gal4 were tested in transient assays. TBP-TFIIB interactions were dispensable for basal transcription but were required for activated transcription. In general, activated transcription was more severely inhibited by TBP mutation E-146R than by mutation E-144R. However, these TBP mutations had little effect on activity of the full-length cauliflower mosaic virus 35S and maize ubiquitin promoters, thus demonstrating that strong TBP-TFIIB contacts are not always required for transcription driven by complex promoters.

Animals↗

PubMed2000

Ticlopidine-induced severe cholestatic hepatitis.

We report a case study of an 86-year-old female patient with severe cholestatic hepatitis who was undergoing treatment with oral ticlopidine 250 mg daily for coronary artery disease. The patient had nausea and vomiting and was jaundiced after taking ticlopidine for 6 weeks. She was admitted to the hospital for further evaluation. Ultrasound and endoscopic retrograde cholangiopancreatography eliminated the presence of biliary obstruction. Results from a liver biopsy showed a histopathologic picture consistent with cholestatic hepatitis. Ticlopidine-induced cholestatic hepatitis has been reported 32 times in the foreign literature. This is the first reported severe cholestatic hepatitis (total bilirubin up to 43 mg/dl) case in Taiwan. Ticlopidine-related blood dyscrasia is a renowned adverse drug effect; liver function should be monitored in patients receiving ticlopidine therapy.

Aged↗