Search PubMed⌕ Search

Biomedical subjects

T Chen

Publications and source records attributed to T Chen.

At least 307 records · Page 17Linked to original sources

Reversible inhibition of human thioredoxin reductase activity by cytotoxic alkyl 2-imidazolyl disulfide analogues.

The thioredoxin/thioredoxin reductase system is important for several aspects of the regulation of cellular proliferation by both intracellular and extracellular mechanisms. The effects of n-butyl 2-imidazolyl disulfide (III-2), 1-methylpropyl 2-imidazolyl disulfide (IV-2), and n-decyl 2-imidazolyl disulfide (VII-2) on purified human placental thioredoxin reductase activity were examined. The analogues were competitive inhibitors with DTNB for reduction by thioredoxin reductase, with Ki values for III-2, IV-2, and VII-2 being 3.3, 13.0, and 8.6 microM, respectively. The inhibition was noncompetitive with reduced nicotinamide adenine dinucleotide phosphate (NADPH). None of the analogues was a suicide substrate inhibitor of the flavoenzyme. III-2 and VII-2 were metabolized by thioredoxin reductase at about half the rate of DTNB, whereas IV-2 was not detectably metabolized. The second order rate constants for the reactions of III-2 and IV-2 with reduced GSH were 931 and 91 M-1 s-1, respectively. The lower reactivity of IV-2 with reduced GSH and the lack of the analogue's metabolism by thioredoxin reductase may be due to the more sterically hindered structure of this analogue. The 50% inhibitory concentrations (IC50 values) for the inhibition of serum-dependent cellular proliferation of Swiss 3T3 murine fibroblasts by III-2, IV-2, and VII-2 were 2.0, 3.5, and 4.0 microM, respectively. IV-2 was considerably more potent as an inhibitor of the thioredoxin-dependent cellular proliferation of Swiss 3T3 fibroblasts, showing an IC50 value of 60 nM. Thus, inhibition of cellular proliferation by alkyl 2-imidazolyl disulfide analogues may involve interaction with thioredoxin, thioredoxin reductase, or an alternative target that is redox-regulated by thioredoxin.

Animals↗

Dilation treatment for achalasia by Chen's soft (fibrous) dilator. An observation of 233 cases.

From May 1987 to January 1993, 233 patients with achalasia admitted to our hospital had been treated using a self-invented soft (fibrous) esophageal dilator, including 16 patients who failed in Heller's myotomy. 228 (97.85%) patients were dilated by way of mouth, 3 (1.29%) by way of stomach and 2 (0.86%) had had a transthoracic operation because of the rupture of the esophagus due to dilation. 19 (8.15%) came back to have the second dilation and 2 the third dilation. 73 (31.33%) cases were dilated in the out-patient department. In 97.85% of the patients, excellent and good results were obtained, through once, twice or thrice of dilation by way of mouth. No esophageal reflux or any sequela was seen after dilation.

Adolescent↗

Immunohistochemical localization of ubiquitin in gerbil hippocampus with induced tolerance to ischemia.

Using immunohistochemistry, we visualized the localization of ubiquitin in the gerbil hippocampus following 3 min of ischemia with or without pretreatment with 2 min of sublethal ischemia and 3 days of reperfusion. Ubiquitin immunoreactivity in the hippocampus disappeared 4 h after 3 min of ischemia both with and without pretreatment. The immunoreactivity in the CA3 and the dentate gyrus recovered by 24 h, but never recovered in the CA1, where delayed neuronal death takes place, without pretreatment. However, the pretreatment, which protects against CA1 neuronal damage, led to recovery of ubiquitin immunoreactivity in the CA1 by 48 h. Thus, recovery of ubiquitin may be a prerequisite to neuronal survival after ischemia and the role of ubiquitin in ischemic tolerance was suggested.

Animals↗

Interleukin-1 beta induces cytosolic PLA2 in parallel with prostaglandin E2 in rheumatoid synovial fibroblasts.

We investigated the temporal relationship between the increase in enzymatic activity and protein of a high molecular weight (100 kDa), cytosolic PLA2 (cPLA2) in interleukin-1 beta (IL-1 beta)-treated rheumatoid synovial fibroblasts (RSF). Both of these responses increased according to a similar time-course which correlates with PGE2 production by these cells. In contrast, 14 kDa, secreted PLA2 (sPLA2), which was also produced by RSF, was not affected by IL-1 beta treatment. These findings support that an augmentation of CPLA2 activity, caused by an induction of cPLA2 protein, rather than sPLA2, is temporally associated with increased PGE2 production in IL-1 beta-treated RSF.

Arthritis, Rheumatoid↗

Secretory phospholipase A2 inhibitors and calmodulin antagonists as inhibitors of cytosolic phospholipase A2.

Human cytosolic phospholipase A2 (cPLA2, 85 kDa) appears to be pharmacologically distinct from human secretory phospholipase A2 (sPLA2, 14 kDa). Marine natural products and PLA2 substrate and product analogs were potent inhibitors of human recombinant sPLA2 (r-sPLA2), whereas these compounds stimulated, weakly inhibited, or had no effect on cPLA2 activity from the human monocytic cell line U937. In contrast, within a series of seven reported calmodulin (CaM) antagonists tested, significant correlations among the rank order of potencies of these compounds as inhibitors of cPLA2, r-sPLA2, and a CaM-dependent phosphodiesterase were observed. The correlated inhibitory effects of the hydrophobic CaM antagonists on cPLA2 and sPLA2 may reflect a common feature (possibly a hydrophobic domain) shared by these two types of enzymes.

3',5'-Cyclic-AMP Phosphodiesterases↗

Determination of lead in urine by electrothermal atomic absorption spectrometry with probe atomization.

An automated graphite-probe atomizer was used for the direct analysis of diluted (2- to 12.5-fold) urine samples by electrothermal atomic absorption spectrometry (ETAAS). The method was applied successfully to the determination of Pb in reference materials, quality control urines and patient samples. The concentrations found were mainly in the range 7-93 micrograms dm-3 and agreed well with results obtained by an established ETAAS method, which involved chelation of Pb and solvent extraction into isobutyl methyl ketone. The detection limit, based on three times the standard deviation of the blank, was 4 micrograms dm-3 at 283.3 nm and 2 micrograms dm-3 at 217.0 nm. Although probe atomization removed chemical interferences for peak-area measurements, 10-20% suppression remained for some samples with peak-height measurements.

Chelating Agents↗

Therapy with parenteral pamidronate prevents thyroid hormone-induced bone turnover in humans.

Bisphosphonates have been shown to decrease bone turnover in a variety of high turnover states. We postulated that pamidronate (APD), a bisphosphonate, could prevent the increased bone turnover caused by thyroid hormone excess. Twenty-two male subjects were randomized to receive either placebo (group 1) or APD (30 mg, iv, daily for 2 days; group 2). Subsequently, all subjects received T3 (50 micrograms, twice daily, for 8 days). Biochemical indices of bone turnover were measured in blood and urine at baseline, after treatment with APD/placebo, and after treatment with T3. The urinary calcium/creatinine ratio (Uca/cr) fell significantly after treatment with APD, but not after treatment with placebo (group 1, 0.131 +/- 0.021; group 2, 0.040 +/- 0.013 mmol Ca/mmol Cr; P < 0.002). After treatment with T3, Uca/cr rose significantly in group 1, but not in group 2 (group 1, 0.275 +/- 0.042; group 2, 0.065 +/- 0.025 mmol Ca/mmol Cr; P < 0.05). Thus, APD prevented the rise in Uca/cr caused by treatment with T3. Similar results were obtained with urinary hydroxyproline and urinary pyridinoline cross-links. We conclude that 8 days of mild thyroid hormone excess in normal men increases bone turnover, and prior administration of APD prevents thyroid hormone-induced increases in bone resorption. APD may be useful in the prevention of thyroid hormone-induced osteopenia.

Adolescent↗

A randomized trial comparing 2.5 mEq/L calcium dialysate and calcitriol to 3.5 mEq/L calcium dialysate in patients on peritoneal dialysis.

Peritoneal dialysate containing 2.5 mEq/L of calcium has been used to prevent hypercalcemia when calcium-containing phosphate binders are given. However, worsening of hyperparathyroidism may result. Calcitriol used in conjunction with 2.5 mEq/L calcium dialysate is an attractive alternative, but has not been examined in a controlled trial. Eighteen patients were randomly assigned to either a control group (3.5 mEq/L calcium dialysate without calcitriol) or a study group (conversion to 2.5 mEq/L calcium dialysate with oral calcitriol, median dose 0.25 microgram/day). The initial mean serum calcium (9.9 vs 9.6 mg/dL), phosphate (5.4 vs 5.6 mg/dL), median n-terminal parathyroid hormone (PTH) levels (71 vs 55 pg/mL, normal < 25), and median 1,25 (OH)2 vitamin D levels (4 vs 5 pg/mL, normal 15-60 pg/mL) were not different in the two groups. After 8 weeks the serum calcium and phosphate were unchanged from baseline in both groups. The 9 patients who converted to 2.5 mEq/L calcium dialysate had an insignificant fall in the PTH level, not different from the control group. The median 1,25 (OH)2 vitamin D level rose from 4 to 23 pg/mL (p = 0.003) on calcitriol, but remained unchanged in the control group (5 pg/mL). The median doses of oral calcium (0.9 vs 1.1 g/day) and the frequency of serum calcium levels greater than 11 mg/dL (4/9 vs 3/9 patients, 10% vs 8% of all values) were similar in the study and control groups. Aluminum hydroxide was required intermittently for serum phosphate control in 3 patients on 2.5 mEq/L calcium dialysate and 4 on 3.5 mEq/L calcium dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[The long-term clinical results of laryngeal cancer treated with tracheo-pharyngeal anastomoses].

From 1978 to 1991, 90 cases of laryngeal cancer had been treated with reconstructive tracheo-pharyngeal anastomoses. Among these cases, 78 were male and 12 female; the sex ratio was 6.5:1, the youngest case was 35 years old, and the eldest 87. The clinical staging was as follows: Supraglottic cancer 41 cases (stage II 23, stage III 16, stage IV 2), glottic cancer 47 (stage II 15, stage III 27, stage IV 5), subglottic cancer 2 (stage II 1, stage IV 1). The 3, 5, 10 year-survival rates were 76.6%, 60.8% and 18.2% respectively. Decannulation was successful in 42 cases (46.7%). All patients could take food via mouth and speak without training.

Adult↗

[75 infantile palsy children treated with acupuncture, acupressure and functional training].

In treating infantile cerebral palsy (CP), 75 CP children were treated with a comprehensive meridian therapy including scalp and body acupuncture, acu-point injection and auriculo-point stimulation, supplemented with acu-pressure and massage, and functional training. A minimum of 10 times of treatment within twenty days, and a maximum of 120 times within a year was performed. The effect of the treatment was evaluated by appraising the children's performance of physical exercise and their social adaptability. The intelligence quotient (IQ) of 30 sick children that had been treated for 60 times (6 courses) was compared prior to and after treatment. It indicates that the treatment yielded a very positive improvement in the children's physical capability and an increase of their intelligence.

Acupuncture Points↗