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Biomedical subjects

S Tan

Publications and source records attributed to S Tan.

At least 127 records · Page 7Linked to original sources
PubMed1996

Crystal structure of a yeast TFIIA/TBP/DNA complex.

The X-ray crystal structure of the transcription factor IIA (TFIIA) in complex with the TATA-box-binding protein (TBP) and TATA-element DNA is presented at 2.5 A resolution. TFIIA is composed of a beta-barrel and a four-helix bundle motif that together have a boot-like appearance. The beta-barrel extends the TBP beta-sheet and bridges over the DNA major groove immediately upstream of the TATA box. The four-helix bundle contributes substantially to the surface of the complex available for interaction with additional transcription factors.

Amino Acid Sequence↗
PubMed1996

Mapping nucleosome position at single base-pair resolution by using site-directed hydroxyl radicals.

A base-pair resolution method for determining nucleosome position in vitro has been developed to com- plement existing, less accurate methods. Cysteaminyl EDTA was tethered to a recombinant histone octamer via a mutant histone H4 with serine 47 replaced by cysteine. When assembled into nucleosome core particles, the DNA could be cut site specifically by hydroxyl radical-catalyzed chain scission by using the Fenton reaction. Strand cleavage occurs mainly at a single nucleotide close to the dyad axis of the core particle, and assignment of this location via the symmetry of the nucleosome allows base-pair resolution mapping of the histone octamer position on the DNA. The positions of the histone octamer and H3H4 tetramer were mapped on a 146-bp Lytechinus variegatus 5S rRNA sequence and a twofold-symmetric derivative. The weakness of translational determinants of nucleosome positioning relative to the overall affinity of the histone proteins for this DNA is clearly demonstrated. The predominant location of both histone octamer and H3H4 tetramer assembled on the 5S rDNA is off center. Shifting the nucleosome core particle position along DNA within a conserved rotational phase could be induced under physiologically relevant conditions. Since nucleosome shifting has important consequences for chromatin structure and gene regulation, an approach to the thermodynamic characterization of this movement is proposed. This mapping method is potentially adaptable for determining nucleosome position in chromatin in vivo.

Animals↗
PubMed1996

Gastric intramucosal pH and multiple organ injury: impact of ischemia-reperfusion and xanthine oxidase.

OBJECTIVES: To determine if gastric intramucosal pH is affected by hepatoneteric ischemia-reperfusion. We additionally proposed to determine if changes in gastric mucosal hydrogen ion concentration are associated with liver and lung injury following hepatoenteric ischemia-reperfusion. Finally, we hypothesized that gastric intramucosal pH is influenced by xanthine oxidase, an oxidant-generating enzyme released after hepatoenteric ischemia-reperfusion. DESIGN: Randomized, controlled, animal study. SETTING: University-based animal research facility. SUBJECTS: Thirty-six New Zealand white male rabbits (2 to 3 kg). INTERVENTIONS: Anesthetized rabbits were randomly assigned to one of four groups (n = 9 per group): a) sham-operated group; b) sham-operated group pretreated with sodium tungstate (xanthine oxidase inactivator); c) aorta occlusion group; and d) aorta occlusion group pretreated with sodium tungstate. Descending thoracic aorta occlusion was maintained for 40 mins with a 4-Fr Fogarty embolectomy catheter, followed by 2 hrs of reperfusion. MEASUREMENTS AND MAIN RESULTS: Gastric tonometry was performed after completion of the surgical preparation (30-min equilibration) and at 30, 60, 90, and 120 mins of reperfusion. Plasma alanine aminotransferase activity was determined at 120 mins of reperfusion to assess hepatic injury. Bronchoalveolar lavage of the right lung was performed after 120 mins of reperfusion, and the protein content was determined as a measure of pulmonary alveolar-capillary membrane compromise. Descending thoracic aorta occlusion resulted in a significant decrease in gastric intramucosal pH as compared with sham-operated rabbits (p < .001). The change in gastric mucosal hydrogen ion concentration was significantly associated with plasma alanine aminotransferase activity (r2 = .48, p < .01) and bronchoalveolar protein content (r2 = .51, p < .01). Xanthine oxidase inactivation significantly improved gastric intramucosal pH after aortic occlusion and reperfusion (p < .001), with a concomitant attenuation of the release of plasma alanine aminotransferase (p < .05) and accumulation of bronchoalveolar protein (p < .05) during reperfusion. CONCLUSIONS: Gastric intramucosal pH was significantly decreased after hepatoenteric ischemia-reperfusion. Furthermore, an increase in gastric intramucosal hydrogen ion concentration was associated with a concomitant increase in tissue injury, a presumed harbinger of multiple organ failure. Gastric intramucosal pH values improved during reperfusion after xanthine oxidase inactivation, concomitant with attenuation of hepatic and pulmonary injury. Gastric tonometry is an important clinical tool that can provide critical insight into the pathogenesis of multiple organ injury after hepatoenteric ischemia-reperfusion. Gastric tonometry may aid in the rapid assessment of pharmacologic interventions designed to attenuate multiple organ injury in similar clinical settings (e.g., trauma, shock, major vascular surgery).

Animals↗
PubMed1996

Lung injury after hepatoenteric ischemia-reperfusion: role of xanthine oxidase.

Oxidant stress plays a major role in the pathophysiologic processes associated with ischemia-reperfusion injury. Xanthine oxidase (XO) is often implicated as a significant source of oxidants and increases in the circulation after hepatoenteric ischemia-reperfusion. We hypothesized that pulmonary injury is associated with hepatic ischemia-reperfusion resulting from descending thoracic aorta occlusion-reperfusion (AoOR). We also proposed that this remote pulmonary injury is attenuated through inactivation of circulating and tissue XO by tungstate, implicating an XO-dependent mechanism. Aortic occlusion was established in rabbits (standard or tungstate diet) for 40 min by 2 h reperfusion. Sham operated rabbits (standard or tungstate diet) served as controls. Hepatic reperfusion injury, as manifested by release of the hepatocellular enzyme alanine aminotransferase (ALT), was markedly increased after AoOR. Suprarenal-infrahepatic occlusion failed to increase ALT release. Tungstate pretreatment significantly (p < 0.05) reduced XO activity and ameliorated liver and intestinal injury (p < 0.05). Lung injury, manifested by increased bronchoalveolar lavage (BAL) protein concentration, BAL lactate dehydrogenase (LDH) activity and increased lung edema was significantly associated with liver injury (p < 0.05) and circulating XO activity (p < 0.001). XO inactivation significantly decreased BAL protein concentration, BAL LDH activity, and lung edema (p < 0.05). We conclude that remote pulmonary injury is significantly influenced by the extent of liver injury and circulating XO activity.

Administration, Oral↗
PubMed1996

Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia.

The antioxidants, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water soluble analog of vitamin E) and ascorbic acid (AA), protect the heart from ischemia-reperfusion injury. We hypothesized that maternal infusion of Trolox and AA, would reduce the fetal bradycardia and myocardial damage observed in fetal hypoxia and increase the total antioxidant activity in fetal plasma. Either i.v. saline (control group) or Trolox + AA (drug group) was randomly administered to 29-d-old pregnant rabbits. Fetal hypoxia was induced by uterine ischemia. Fetal heart rate, plasma CK-MB activity, and plasma total radical antioxidant potential (TRAP) were measured in different sets of animals. Fetal heart rate in the drug group was higher than in the control group for the first 35 min (p < 0.05 at every 5-min interval). Fetal bradycardia (<60 beats/min) occurred after 39 min (median) in the drug group, and 29 min in the control group (p < 0.05). After 50 min of hypoxia, plasma CK-MB was lower in the drug group, 1204 +/- 132 U/L (mean +/- SEM), than in the control group, 2633 +/- 233 U/L (p < 0.05). TRAP was higher in the drug group, 3.01 +/- 0.15 mM (Trolox equivalent concentration), than in the control group, 1.48 +/- 0.27 mM (p < 0.05). Higher TRAP levels (> or = 2.0 mM) were associated with lower CK-MB levels (<2500 U/L) (p < 0.05). Administration of Trolox and AA to the mother has a beneficial effect on fetal myocardial damage after fetal hypoxia, and a small beneficial effect on fetal bradycardia during hypoxia. The beneficial effect may be due to the augmentation of fetal plasma antioxidants from maternal antioxidant pretreatment.

Animals↗
PubMed1996

[A study on activity of beta-glucuronidase in serum and secretion from upper respiratory tract in patients with head and neck malignant tumors].

Beta-glucuronidase (beta-GD) activity in serum and upper respiratory tract (URT) secretion in patients with head and neck malignant tumors (HNMT) was studied. Subjects included 40 HNMT patients, 40 healthy volunteers and 40 patients with benign tumors of the head and neck region. The results showed that there was no statistically significant difference of serum beta-GD level among the three groups. The same was true for URT secretion between the normal control and benign tumor groups. beta-GD level in URT secretion was higher in HNMT group than in other groups (P < 0.001). Using healthy subjects' average beta-GD level plus two standard difference as positive standard, the sensitivity, reliability and specificity of the test were 85.0%, 92.5% and 100% respectively. beta-GD levels were higher in patients with advanced tumors and metastases. One year follow-ups of six patients showed that beta-GD level change in URT secretion was in accordance with clinical manifestations. These results suggest that assay of beta-GD level in URT secretion can be used as a valuable supplimental parameter in early diagnosis of HNMTs, their clinical staging, evaluation of therapeutic effectiveness and detection of recurrence and metastases. In addition, this method has the advantage of easy, prompt, result specificity, sensitivity and reliability.

Adult↗
PubMed1996

[Determination of puerarin in gegen ginlian tablets by RP-HPLC].

A quantitative method was developed for the determination of puerarin in Gegen Qinglian Tablets by reversed phase HPLC. Chromatographic conditions included column ODS-C18, column temperature: 35 C, UV detector: 250 nm, mobile phase: EtOH-H2O (23:77), flow rate: 1 ml/min. The number of theoretical plates calculated for puerarin peak was no less than 2000. The standard curve was linear in the concentration range of 5-80 micrograms/ml, and the correlation coefficient was 0.9999. The average recovery and the relative standard deviation were 97.6% and 1.8% respectivily.

Chromatography, High Pressure Liquid↗
PubMed1995

Structure of serum response factor core bound to DNA.

The human serum response factor is a transcription factor belonging to the MADS domain protein family with members characterized from the plant and animal kingdoms. The X-ray crystal structure of the serum response factor core in a specific-recognition DNA complex shows that the functions of DNA binding, dimerization and accessory-factor interaction are compactly integrated into a novel protein unit. The intrinsic and induced conformation of the serum response element DNA is the principal DNA feature recognized in the specific complex.

Amino Acid Sequence↗
PubMed1995

Dissection of transcription factor TFIIF functional domains required for initiation and elongation.

TFIIF is unique among the general transcription factors because of its ability to control the activity of RNA polymerase II at both the initiation and elongation stages of transcription. Mammalian TFIIF, a heterodimer of approximately 30-kDa (RAP30) and approximately 70-kDa (RAP74) subunits, assists TFIIB in recruiting RNA polymerase II into the preinitiation complex and activates the overall rate of RNA chain elongation by suppressing transient pausing by polymerase at many sites on DNA templates. A major objective of efforts to understand how TFIIF regulates transcription has been to establish the relationship between its initiation and elongation activities. Here we establish this relationship by demonstrating that TFIIF transcriptional activities are mediated by separable functional domains. To accomplish this, we sought and identified distinct classes of RAP30 mutations that selectively block TFIIF activity in transcription initiation and elongation. We propose that (i) TFIIF initiation activity is mediated at least in part by RAP30 C-terminal sequences that include a cryptic DNA-binding domain similar to conserved region 4 of bacterial sigma factors and (ii) TFIIF elongation activity is mediated in part by RAP30 sequences located immediately upstream of the C terminus in a region proposed to bind RNA polymerase II and by additional sequences located in the RAP30 N terminus.

Amino Acid Sequence↗
PubMed1995

A phase II trial of high-dose mitoxantrone, carboplatin, and cyclophosphamide with autologous bone marrow rescue for recurrent epithelial ovarian carcinoma: analysis of risk factors for clinical outcome.

Despite high initial response rates to platinum-based chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in the hematologic malignancies and lymphomas with high-dose therapy and bone marrow transplantation (BMT) when used early, suggesting that this therapy may also be of value in ovarian carcinoma. As a prelude to the use of high-dose chemotherapy with BMT early in the management of advanced ovarian carcinoma, we evaluated a new high-dose regimen in patients with relapsed/refractory ovarian carcinoma to define toxicities and responses. Thirty patients were treated, of whom 20 were platinum resistant and 22 had > 1 cm maximum diameter disease. They received mitoxantrone (75 mg/m2), carboplatin (1500 mg/m2), and cyclophosphamide (120 mg/kg), followed by an autologous BMT. Overall, 89% responded, with clinical complete responses seen in 88 vs 47% (P = 0.06) of platinum-sensitive vs -resistant disease. There was only one early death (3.3%) due to Aspergillus pneumonia. Median survival for all 30 patients was 29 months, and at 3 years 23% are alive without disease. There was a 10.1- vs 5.1-month progression-free survival for patients with platinum-sensitive versus -resistant disease, and at a median follow-up of 12 months, 80% of the platinum-sensitive patients are alive. This regimen is safe, and for platinum-sensitive disease appears superior to other salvage therapies. Its use should be explored earlier in the management of advanced ovarian carcinoma.

Adult↗
PubMed1995

Xanthine oxidase inactivation attenuates postocclusion shock after descending thoracic aorta occlusion and reperfusion in rabbits.

"Declamping shock" is observed after aortic crossclamping, with hypovolemia, hypotension, and metabolic acidemia invariably present. We hypothesized that oxidants derived from xanthine oxidase influence the resuscitative interventions required to maintain baseline hemodynamic and acid-base status after aortic occlusion and reperfusion in rabbits. We also hypothesized that inactivation of xanthine oxidase with sodium tungstate could reduce systemic injury as assessed by the release of lactate dehydrogenase and alkaline phosphatase. To test these hypotheses, we established aortic occlusion in rabbits (n = 10, standard diet; n = 8, tungstate diet) for 40 minutes by inflation of a 4F Fogarty catheter in the descending thoracic aorta followed by 2 hours of reperfusion. Sham-operated rabbits (n = 10, standard diet; n = 9, tungstate diet) served as controls. Tungstate-pretreated rabbits required significantly less Ringer's solution (28%), phenylephrine (68%), and sodium bicarbonate (30%) during reperfusion (p < 0.005). Lactate dehydrogenase and alkaline phosphatase release during reperfusion was significantly attenuated by tungstate pretreatment (p < 0.05). Tungstate pretreatment resulted in plasma xanthine oxidase activities significantly lower than those in the sham group administered a standard diet (p = 0.007). Resuscitation requirements and systemic injury were reduced by inactivation of xanthine oxidase in a rabbit model that simulates the situation of human thoracic aorta operations.

Acid-Base Equilibrium↗
PubMed1995

A comparative study of family functioning among Vietnamese and Cambodian refugees.

This study was designed to determine the extent of family problems among a clinic population of Cambodian and Vietnamese refugees, and to identify similarities and differences between the two groups. All 107 patients with adolescent children from a total clinic population of 298 were interviewed using a semistructured questionnaire, results were tabulated, and statistical methods were applied. The types of problems with children described by parents were classified into the dimensions of communication, personal behaviors, school performance, social behaviors, and antisocial behaviors. There were significantly more problems described by Vietnamese parents as compared with Cambodian parents. Vietnamese parents reported significantly more dissatisfaction with life in the United States. For both ethnic groups, parents' relationships with their adolescent children were a major source of concern and had a major impact on parents' perceptions of their own health. Yet, there were important ethnic differences between these refugee groups in how patients perceived their problems.

Acculturation↗
PubMed1995

Circulating xanthine oxidase in human ischemia reperfusion.

Reactive oxygen species (ROS) generated from xanthine oxidase (XO) play an important role in ischemia-induced injury. We hypothesize that XO and xanthine dehydrogenase (XDH) are released into the circulation with ischemia reperfusion to the human liver and intestine. Blood was drawn from a patient, before and at intervals after an aortic cross-clamp procedure. Plasma was incubated in the presence of xanthine, with NAD+ (for XD +XO) and without NAD+ (for XO). The amount of urate formed was quantified using a high-performance liquid chromatograph (HPLC). The calculated XDH+XO and XO activity increased from 1.88 and 1.66 microU/mg protein, respectively, before the cross clamp to 3.77 and 3.11 microU/mg, respectively, 7 minutes after reperfusion to the superior mesenteric, celiac, and right renal artery beds. The release of a significant biological source of ROS may explain the damage to lung or heart observed after ischemia to the human liver and intestine.

Aged↗
PubMed1995

Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase.

Reactive oxygen species play an important role in pathogenesis of a variety of pathological processes, e.g., ischemia-reperfusion, acute viral infections, thermal injury, hepatic diseases, and acute lung injury. Xanthine oxidase (XO) may be a significant source of these cytotoxic oxygen species. We tested the hypothesis that hepatic ischemia-reperfusion releases xanthine dehydrogenase + XO (XDH + XO) into the circulation and that circulating XO damages isolated perfused lung. Isolated liver + lung preparation was perfused with Krebs-Henseleit buffer to minimize confounding effects of circulating neutrophils. In one group, livers were rendered globally ischemic for 2 h and then reperfused (I/R). In another group, livers were pretreated with allopurinol and perfused with buffer containing additional allopurinol (I/R + Allo). After 2 h of ischemia, an isolated lung was connected to liver, and liver + lung preparation was reperfused in series for 15 min. Liver reperfusion was terminated, and lung was recirculated with liver effluent for 45 min. Capillary filtration coefficient (ml.min-1.cmH2O-1.100 g lung dry wt-1) was 2.0 +/- 0.3 and 1.9 +/- 0.4 in control and I/R + Allo lungs, respectively, and 9.0 +/- 1.2 in I/R lungs (P < 0.001). Lung wet-to-dry weight ratio in control and I/R + Allo lungs was 8.6 +/- 0.3 and 9.1 +/- 0.5, respectively, and 14.9 +/- 1.1 in I/R lungs (P < 0.01). Control and I/R + Allo bronchoalveolar lavage protein content was < 1.0 mg/ml compared with 32.6 +/- 8.4 mg/ml in I/R group.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMed1995

Borrelia burgdorferi in eastern Virginia: comparison between a coastal and inland locality.

In Virginia, Borrelia burgdorferi was more prevalent in a site along the Atlantic Ocean, near Maryland, than in an inland site near Williamsburg and Yorktown. At the coastal site on Assateague Island, B. burgdorferi was isolated from 4.2% of 475 animals sampled, including four species of small mammals. Serologic tests indicated that 25-37% of the small rodents assayed had been exposed to B. burgdorferi. Immunofluorescence antibody assays specific for B. burgdorferi showed spirochete infection in Ixodes scapularis and Dermacentor variabilis but not in other species of ticks also examined from this site. At another coastal site (Parramore Island), no evidence of Peromyscus leucopus was found, no immature specimens of I. scapularis were collected, and no isolations were made from numerous raccoons or small mammals sampled. Borrelia burgdorferi infection was found in one I. cookei nymph, but not in numerous specimens of I. scapularis or other tick species from this locality. At the inland site between Williamsburg and Yorktown, B. burgdorferi was isolated from two small mammal species and antibodies to B. burgdorferi were found in only 7-10% of the small mammals sampled. Ixodes scapularis were less abundant at this locality than at the Assateague Island site. Borrelia burgdorferi spirochetes were found in I. scapularis and a single nymph of Amblyomma americanum, but not in any of numerous specimens of four other species. Infection with B. burgdorferi was found in 20% of unfed adult I. scapularis from vegetation, but in only 0.2% of numerous adults from hunter-killed deer. Infection in immature ticks was much lower than at Assateague Island. Borrelia burgdorferi may be more prevalent along the Atlantic coast than in inland areas. Isolations, seroprevalence, immature I. scapularis densities, and spirochete infection rates in ticks were higher at the Assateague Island site than the Williamsburg/Yorktown site. Consequently, the risk of human exposure to Lyme disease may be higher in some parts of the coastal area than elsewhere in Virginia. Overall, B. burgdorferi is less intense in Virginia than in the northeastern United States.

Animals↗
PubMed1995

[Placental tissue histomorphometry in hydrops fetalis].

Placentae from 10 hydrops fetalis with hemoglobin Bart's disease were studied by tissue volumetry on the relative percentage of placental proper to its components, the surface area of villi and villi capillaries, and by comparing with 6 placentae from premature deliveries of 30-36 weeks. The placental weight, volume, percentage of placental proper and the villi volume, as well as the surface area of villi were significantly increased as compared with the controls. The relatively decreased volume percentage of intervillous space volume and surface area of villi capillaries resulted in a reduction of maternal-fetal exchanging surface area. We suggest careful prenatal scanning for Thalassemia and avoiding marriage between local peoples to reduce the incidence of hemoglobin Bart's disease.

Anthropometry↗