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Biomedical subjects

T Chen

Publications and source records attributed to T Chen.

At least 361 records · Page 20Linked to original sources

Combined chemoradiotherapy in limited-disease, inoperable non-small cell lung cancer.

Forty-three patients with limited-disease, inoperable non-small cell lung cancer received two intravenous courses of cyclophosphamide, Adriamycin, and cisplatin (CAP) chemotherapy over a 6-week period. This was followed by 5 weeks of combined chemoradiotherapy (CCRT) consisting of low weekly doses of CAP for 5 weeks plus 50 Gy continuous X ray therapy (XRT) to the primary tumor site. Chemotherapy was continued until disease progression occurred or until the total dose of Adriamycin reached 450 mg/m2, whichever came first. CCRT improved the response rate [complete response (CR) plus partial responses (PR)] from 25% after two courses of CAP alone to 65% after CCRT. Previous response to two courses of CAP influences response subsequent to CAP plus XRT. A pretherapy weight loss of 6% or greater had a significant adverse effect on both response and survival time. The median survival time for all patients was 50 weeks; patients whose disease responded to treatment survived significantly longer than patients with nonresponding disease. The median time until disease progression was 37 weeks. Twenty-seven patients relapsed. The first sites of relapse were local in 30% of the patients, distant in 56% of them, and both local and distant in 15%. Severe esophagitis occurred in 30% of the patients and was dose-limiting. The administration of CCRT resulted in an improved response rate compared with the rates reported in previous studies of chemotherapy or radiotherapy alone. Further improvement of the CCRT program is needed to increase long-term survival time and to decrease esophageal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Simultaneous chemotherapy-radiotherapy with prophylactic cranial irradiation for inoperable adeno and large cell lung carcinoma: a Southwest Oncology Group Study.

From September 1980 to March 1983, 30 cases were registered in a Southwest Oncology Group Study. Twenty-four cases were evaluable and constitute the basis for this report. Patients were diagnosed with adenocarcinoma or large cell lung carcinoma. Tumors were considered inoperable but able to be encompassed in a single radiotherapy (RT) port. Seventy-two percent of measured tumors were 4 cm in diameter or bigger (range 2 cm to 10 cm). RT was given initially to the primary lung tumor and ipsilateral hilar, mediastinal, and supraclavicular nodes, at 2 Gy per day; total dose was 44 Gy. The areas involved by tumor were boosted with 10 Gy more. Prophylactic cranial irradiation (PCI) was started at the same time with 15 treatments of 2.75 Gy. A 2-week rest period was instituted after the first 11 treatments. Chemotherapy (CT) was given from day 1 which consisted of 5-Flourouracil, 500 mg./M2, (bolus day 1 and 8) Vincristine, 1 mg./M2, and Mitomycin C, 5 mg./M2 both given on day 1. Cycles were repeated at 28 day intervals for 3 cycles and at 6 week intervals for 5 more cycles, or until progression, with persistent disease. Eight cases (33%) achieved complete response (CR), and 5 (21%) partial response (PR). Overall median survival was 37 weeks and 2 years survival was 8%. CR patients had the best chance for long-term survival. Relapses were evenly distributed between extra and intrathoracic sites, with the latter even between the inside and outside the RT field. No patient died with clinical evidence of metastasis to the brain (MB), although one was found to have MB at autopsy. Toxicity was severe in 7 cases (29%) and 2 deaths are considered toxicity related. When comparing these results to those from the literature, we found this protocol has achieved a slightly higher CR rate than what is expected with RT alone, without survival improvement. As CR patients have the best prognosis, simultaneous CT-RT might offer some promise, but at the expense of increased toxicity. PCI was effective in preventing or delaying MB, and thus deserves further investigation. We should caution that the study of possible long-term effects of PCI could not be assessed because of the short median survival of the patients. It is possible that a less aggressive time-dose fractionation to the brain might be as effective as the one used in this protocol.

Adenocarcinoma↗

CheA protein, a central regulator of bacterial chemotaxis, belongs to a family of proteins that control gene expression in response to changing environmental conditions.

During bacterial chemotaxis, the binding of stimulatory ligands to chemoreceptors at the cell periphery leads to a response at the flagellar motor. Three proteins appear to be required for receptor-mediated control of swimming behavior, the products of the cheA, cheW, and cheY genes. Here we present the complete nucleotide sequence of the Salmonella typhimurium cheA gene together with the purification and characterization of its protein product. The protein is a 73,000 Mr cytoplasmic constituent. Amino acid-sequence comparisons indicate that it belongs to a family of bacterial regulatory proteins including the products of the cpxA, dctB, envZ, ntrB, phoR, phoM, and virA genes. Each member of this family has a conserved domain of approximately equal to 200 residues within its C terminus. We have previously shown that another chemotaxis protein, CheY, represents a domain of protein structure that has been conserved within a second large family of bacterial regulatory proteins. Each protein of the CheA family seems to function as a regulator of a different CheY homologue. Although each pair of proteins appears to produce a specialized response to a distinct type of stimulus, the relationships in primary structure suggest that a similar molecular mechanism may be involved.

Amino Acid Sequence↗

Sequence requirements of Escherichia coli attTn7, a specific site of transposon Tn7 insertion.

Transposon Tn7 transposes at high frequency to a specific site, attTn7, in the Escherichia coli chromosome. We devised a quantitative assay for Tn7 transposition in which Tn7-end derivatives containing the cis-acting transposition sequences of Tn7 transpose from a bacteriophage lambda vector upon infection into cells containing the Tn7-encoded transposition proteins. We used this assay to identify a 68-base-pair DNA segment containing the sequences essential for attTn7 target activity. This segment is positioned asymmetrically with respect to the specific point of Tn7 insertion in attTn7 and lacks obvious homology to the sequences at the ends of Tn7 which participate directly in transposition. We also show that some sequences essential for attTn7 target activity are contained within the protein-coding sequence of a bacterial gene.

Base Sequence↗

Antiarrhythmic potential of chloroquine: new use for an old drug.

Amiodarone and chlorpromazine are phospholipase inhibitors which produce cytoplasmic inclusion bodies and have important electrophysiologic properties. Chloroquine also inhibits phospholipase activity, resulting in similar inclusion bodies, but electrophysiologic information about this drug is lacking. In this study, the cellular electrophysiologic effects of two doses of chloroquine were examined in sheep Purkinje fibres and ventricular muscle cells. Both concentrations produced a significant reduction in maximum velocity of upstroke of the action potential and prolongation of the action potential duration and refractory period in Purkinje fibres. These effects were observed in the absence of significant changes in threshold of stimulation or action potential amplitude and were partially reversible following washout of the lower drug concentration. In addition to these experimental data, clinical evidence of antiarrhythmic action was determined by administering 500 mg chloroquine daily over nine weeks to six subjects with frequent asymptomatic ventricular premature complexes. In four patients there was a reduction in ventricular ectopy, which recurred when the drug was discontinued, while a fifth patient reverted to sinus rhythm from atrial fibrillation previously resistant to other antiarrhythmic medication. Thus, chloroquine has important electrophysiologic properties. The underlying mechanism of this action remains unproven at the present time.

Action Potentials↗

Fractures and vertebral bone mineral density in patients with renal osteodystrophy.

We investigated the relationship of CT determined vertebral bone mineral density (BMD), type of renal osteodystrophy, N terminal PTH levels and fracture history in 31 dialysis patients. BMD for patients with bone biopsy documented osteitis fibrosa was 1.6 standard deviation (SD) above the normal value for age and sex matched controls, while those patients with low turnover osteodystrophy had a mean BMD 1.2 SD below normal (p less than 0.0001). Three patients with osteitis fibrosa who had previously been treated with prednisone had a low BMD (1.8 SD below normal, different than O, p = 0.0015). There was no correlation between BMD and time on dialysis (r = 0.1). An N terminal PTH level greater than 150 pg/ml was a sensitive (94%) and specific (100%) method of separating those patients with osteitis fibrosa from those with low turnover osteodystrophy, while BMD was much less useful in this differentiation. A low BMD was not predictive of fracture history but the type of renal osteodystrophy was. Patients with low turnover osteodystrophy had a fracture rate of 0.2 fractures/dialysis year in comparison to those with osteitis fibrosis who had 0.1 fractures/dialysis year. Patients with the former bone disease fractured mainly axial rather than appendicular bones in contrast to those patients with osteitis fibrosa. In conclusion we found that patients with osteitis fibrosa had increased BMD compared to normal while those with low turnover osteodystrophy had decreased BMD, but that the N terminal PTH level was a better predictor of the type of bone disease present than was BMD.

Adult↗

Excessive ATP degradation during hemodialysis against sodium acetate.

As the initial step in examining the metabolic basis for acetate intolerance, we have tested the hypothesis that excessive adenosine triphosphate (ATP) degradation occurs during hemodialysis against acetate dialysate (compared with the degree of degradation occurring during dialysis against bicarbonate dialysate). Seven patients undergoing long-term dialysis were infused with carbon 14--labeled 8-adenine, and their response to dialysis against acetate was compared with their response to dialysis against bicarbonate. The following changes were observed. During dialysis against acetate, the mean dialysate uric acid--to-creatinine ratio levels were significantly higher than the mean levels observed after dialysis against bicarbonate (p less than 0.001). The mean dialysate uric acid radioactivity--to-creatinine ratio and inosine, hypoxanthine, and xanthine radioactivity--to-creatinine ratio levels were significantly increased during dialysis against acetate (p less than 0.001). There was no significant change in plasma venous hypoxanthine level, but during dialysis against acetate, the arterial hypoxanthine levels (3.7 +/- 1.6 mumol/L) at 60 minutes were significantly higher than the levels observed after dialysis against bicarbonate (1.4 +/- 0.5 mumol/L) (p less than 0.01). These data provide evidence that excessive ATP degradation occurs during hemodialysis against acetate but not during hemodialysis against bicarbonate dialysate.

Acetates↗

Immunochemical probing of the N-terminus of the myosin heavy chain.

The reactivity of myosin subfragment 1 (S-1) towards site specific polyclonal anti-N-terminus antibodies was examined in competitive ELISA titrations. Tryptic digestion of S-1 and specifically the cleavage at the 25/50K junction greatly increased the accessibility of the N-terminus region to the antibodies. The binding of actin to S-1 did not change significantly the reactivity of either tryptic or intact S-1 towards anti-N-terminus antibodies. These results suggest the interdependence of the N-terminus and 25/50K junction regions on S-1.

Actins↗

Proteolysis and binding of myosin subfragment 1 to actin.

Rates of proteolytic cleavage of myosin subfragment 1 were measured in the absence and presence of different amounts of actin. The rates of tryptic digestion at the 50K/20K junction and papain digestion at the 25K/50K junction of the myosin head were progressively inhibited with increasing substoichiometric molar ratios of actin to myosin subfragment 1. The percentage inhibitions of digestion reactions corresponded precisely to the molar compositions of actin-subfragment 1 solutions and demonstrated that equimolar complexes of these proteins were responsible for the observed changes in the proteolysis of myosin heads.

Actins↗

Identification of a possible nucleotide binding site in CheW, a protein required for sensory transduction in bacterial chemotaxis.

CheW is an essential component of the system which mediates chemotaxis in Salmonella typhimurium and Escherichia coli. Here we report the nucleotide sequence of the cheW gene as well as the purification and characterization of the CheW protein. The DNA sequence predicts a protein of 18,000 molecular weight. The pure protein exhibits an apparent molecular weight of 18,000 during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Molecular sieve chromatography under nondenaturing conditions indicates a molecular weight of approximately 35,000, however. This result suggests that CheW is a homodimer. The predicted amino acid sequence between Thr-128 and Asp-160 fits a consensus exhibited by many proteins which bind purine nucleotides.

Amino Acid Sequence↗

Kinetics of procaterol auto-oxidation in buffered acid solutions.

The kinetics of procaterol (1) degradation in buffered acidic solutions (pH 4-6) was investigated using an HPLC procedure. The effect of temperature and ferric ions on the reaction rate was estimated. In acidic solutions, 1 undergoes pseudo first-order degradation with an induction period. The first-order rate constant for degradation increased and the induction period decreased with an increase in pH. Ferric ions catalyzed the degradation reaction and decreased the induction period. At pH 6, the activation energy of the reaction was 34.5 kcal/mol/deg. The results of this study indicate that 1 in solution is more stable at acidic pH, in the absence of heavy metal ions, and protected from air.

Bronchodilator Agents↗

The welfare effects of illegal immigration.

"This paper extends the work of Ethier on illegal immigration by examining the optimal level of enforcement for the labor-importing country in a two-country model and by considering the effects of allowing capital mobility. We derive a formula for the optimal level of enforcement against firms that hire illegal workers, and show that the presence of enforcement costs makes the policy less efficient than a wage tax. With capital mobility, foreign workers gain from an increase in enforcement in the home country because capital is driven out of the home country."

Demography↗

Long-term follow-up of lens changes with Scheimpflug photography in diabetics.

This study was designed to document and quantify changes in lens clarity over 24 months in a group of diabetic patients. One hundred thirty-four type I and type II diabetics of 3 months' to 45 years' duration with an average age of 53.5 +/- 7 years volunteered to participate in this prospective study. Patients were evaluated upon entry and at 6-month intervals. Scheimpflug lens photographs (Topcon SL45) were taken at each visit. All photographs were evaluated by densitometry which allowed quantification of the light scattering in the various lens layers. A significant and progressive (4-7% every 6 months) increase in light scattering was observed in the lens anterior superficial lens cortex over 24 months. The rate of change in lens clarity was similar in all patients regardless of the clinically observable lens change type (nuclear, cortical, posterior subcapsular, or mixed). Patients who were younger at enrollment, having diabetes of shorter duration and higher glycosylated hemoglobin values (a measure of long-term glucose control), were identified to be at greater risk of having increased densitometry values in the anterior superficial lens cortex. Only a few patients had significant changes in visual acuity during 24 months, and the correlation of superficial cortical lens clarity changes to clinical cataract formation and visual impairment remains to be established.

Adolescent↗