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S Chen

Publications and source records attributed to S Chen.

At least 1,135 records · Page 63Linked to original sources
PubMed1994

An efficient multiple-stage procedure for phase II clinical trials that have high response rate objectives.

Gehan's two-stage procedure is commonly used in phase II clinical trials to enable one to stop a trial early if the observed response rate in the first stage does not warrant further study and to obtain an adequate estimate of response rate if the trial passes the first stage. However, when the response rate of interest is relatively high (0.3 or more), Gehan's procedure can be inefficient since the trial may hardly be halted even though the actual response rate is low. In this paper, we extend Gehan's two-stage procedure to a more efficient multiple-stage procedure, which allows early termination of a phase II trial at multiple stages and provides precise estimate of the response rate if the trial reaches the final stage. The proposed multiple-stage procedure is suitable for phase II clinical trials that have high response rate objectives.

Clinical Trials, Phase II as Topic↗
PubMed1994

Measurements and analysis of fluid saturation-dependent NMR relaxation and linebroadening in porous media.

NMR T1, T2 and spectral linewidth measurements were conducted in rock samples with different saturations obtained by drainage experiments. Saturation dependent T1 was found to follow a power-law relationship and the inverse of linewidth to follow a linear dependence with saturation. These phenomena can be explained by considering that the fluids are distributed in different sized pores for different saturation states. A method is proposed for calculating wetting phase relative permeabilities using T1 data at various saturations.

Magnetic Resonance Spectroscopy↗
PubMed1994

Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer.

Hyperacute rejection of discordant xenografts occurs rapidly, precluding cellular infiltration. Thus the role of cellular rejection in discordant xenografts is debated. Using adoptive transfer of sensitized splenocytes and passive transfer of sensitized serum, we evaluated the influence of cellular and humoral elements on cellular infiltration and rejection in the guinea-pig-to-rat discordant xenograft model. Guinea-pig hearts were transplanted into Lewis rats. Pretransplant, rats underwent splenectomy and plasma exchange and were started on daily cobra venom factor injections. Xenografts rejected faster after adoptive (1, 2, 2 and 2 days) or passive (1, 1, 2 and 2 days) transfer than controls (4, 4, 4 and 4 days; p < 0.05). Macrophages and neutrophils were predominant in early prerejection specimens. Over time, cellular infiltrates were dominated by mononuclear cells. Natural killer cells were present in all groups, as were interleukin 2 receptor positive cells. Our data suggest that either sensitized serum or sensitized cells are capable of initiating an accelerated rejection characterized by cellular infiltration. Despite subtle differences, the population of infiltrating cells was similar in each group. Thus, although rejection may be initiated by either cellular or humoral influences, the ultimate result is the same. We have, therefore, established a small animal model to study cellular rejection in discordant xenografts. This model will help evaluate the role of cell subsets and xenoantibodies in xenograft rejection and will help determine the precise relationship between the two when hyperacute rejection is prevented.

Acute Disease↗
PubMed1994

Measurement of Ca2+ pump-mediated efflux in hypertension.

Ca2+ homeostasis has been a prominent research area in the study of hypertension. There is convincing evidence that hypertension in spontaneously hypertensive rats is characterized by enhanced Ca2+ influx in various cell types. It is, however, still unclear whether hypertension is associated with reduced or enhanced Ca2+ efflux. Reduced Ca2+ efflux would augment the effects of enhanced Ca2+ influx. However, enhanced Ca2+ extrusion may occur as an adaptive process to minimize the effects of Ca2+ overload. This question remains unanswered because of inconsistent results obtained using a variety of experimental techniques. In this article we have reviewed the research findings and discuss existing and possible new techniques to assess Ca2+ efflux in hypertension, with particular attention to vascular smooth muscle. We have focused mainly on studies using the spontaneously hypertensive rat and discuss its appropriateness as a model for essential hypertension.

Animals↗
PubMed1994

Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants.

To understand the mechanisms of mRNA transport in eukaryotes, we have isolated Saccharomyces cerevisiae temperature-sensitive (ts) mutants which accumulate poly(A)+ RNA in the nucleus at the restrictive temperature. A total of 21 recessive mutants were isolated and classified into 16 complementation groups. Backcrossed mRNA transport-defective strains from each complementation group have been analyzed. A strain which is ts for heat shock transcription factor was also analyzed since it also shows nuclear accumulation of poly(A)+ RNA at 37 degrees C. At 37 degrees C the mRNA of each mutant is characterized by atypically long polyA tails. Unlike ts pre-mRNA splicing mutants, these strains do not interrupt splicing of pre-mRNA at 37 degrees C; however four strains accumulate oversized RNA polymerase II transcripts. Some show inhibition of rRNA processing and a further subset of these strains is also characterized by inhibition of tRNA maturation. Several strains accumulate nuclear proteins in the cytoplasm when incubated at semipermissive temperature. Remarkably, many strains exhibit nucleolar fragmentation or enlargement at the restrictive temperature. Most strains show dramatic ultrastructural alterations of the nucleoplasm or nuclear membrane. Distinct mutants accumulate poly(A)+ RNA in characteristic patterns in the nucleus.

Biological Transport↗
PubMed1994

Gene transfer to human fetal pulmonary tissue developed in immunodeficient SCID mice.

Human fetal lung rudiments (8-12 weeks of development) undergo considerable growth upon microsurgical ectopic implantation in the xenograft-tolerant SCID mouse, and differentiate into a lung-like tissue that includes: (i) bronchial structures lined with pseudostratified, secretory, ciliated epithelium surrounded by smooth muscle and cartilage rings, (ii) submucosal glands, and (iii) alveolar sacs. Normal expression of the cystic fibrosis transmembrane conductance regulator (CFTR) protein was detected by immunostaining in those grafts, and similar differentiation was observed from either normal or cystic fibrosis (CF) fetal lung rudiments. Upon microinjection into human CF or normal lung grafts in SCID mice, beta-galactosidase-adenovirus gene constructs were efficiently transduced into epithelial and glandular cells. Such an in vivo replica of the human respiratory tissue may be a useful experimental model to study normal and pathologic lung development, and to assay candidate therapeutic gene constructs preclinically.

Adenoviridae↗
PubMed1994

Nuclear mRNA accumulation causes nucleolar fragmentation in yeast mtr2 mutant.

We have identified a set of genes that affect mRNA transport (mtr) from the nucleus to the cytoplasm of Saccharomyces cerevisiae. One of these genes, MTR2, has been cloned and shown to encode a novel 21-kDa nuclear protein that is essential for vegetative growth. MTR2 shows limited homology to a protein implicated in plasmid DNA transfer in Escherichia coli. PolyA+RNA accumulates within the nucleus of mtr2-1 in two to three foci at 37 degrees C. mRNA, tRNA, and rRNA synthesis continue as do pre-mRNA splicing, tRNA processing, and rRNA export at 37 degrees C. Under these conditions the polyA tail length increases, and protein synthesis is progressively inhibited. Nucleolar antigens also redistribute to two to three nuclear foci at 37 degrees C, and this redistribution depends on ongoing transcription by RNA polymerase II. Surprisingly, these foci coincide with the sites of polyA+RNA accumulation. Comparable colocalization and dependance on RNA polymerase II transcription is seen for the mtr1-1 mutant. The disorganization of the nucleolus thus depends on mRNA accumulation in these mutants. We discuss the possible functions of MTR2 and the yeast nucleolus in mRNA export.

Amino Acid Sequence↗
PubMed1994

Enhanced 45Ca2+ efflux in cultured vascular smooth muscle cells from spontaneously hypertensive rats.

Ca2+ efflux from cultured vascular smooth muscle cells (VSMC) consists of two mechanisms: one is dependent on extracellular sodium, mediated by the Na(+)-Ca2+ exchange (Na+o-dependent Ca2+ efflux), and the other is independent of extracellular sodium but is mediated by the Ca(2+)-pump (Na+o-independent Ca2+ efflux). In the present study we have compared these two Ca2+ effluxes in cultured aortic smooth muscle cells derived from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY). In the presence of 100 nmol/L angiotensin II both Na(+)-Ca2+ exchange and Ca(2+)-pump-mediated 45Ca2+ efflux were enhanced significantly in SHR compared to WKY. The cellular 45Ca content was found to be increased in SHR compared to WKY. When the data were expressed as the fraction of 45Ca2+ lost, defined as the ratio of 45Ca2+ lost over each time interval (5 sec) to total cellular 45Ca content during that period, Ca2+ efflux by both mechanisms was still higher in SHR. Our results suggest that the enhanced 45Ca2+ efflux in response to angiotensin II in SHR may be linked to greater Ca2+ uptake and possibly Ca2+ release from intracellular stores. An increase in intracellular [Ca2+]i may be compensated for by enhanced Ca(2+)-pump and Na(+)-Ca2+ exchange activities in VSMC in hypertension.

Angiotensin II↗
PubMed1994

Structural analysis of underivatized and derivatized aminophospholipids and phosphatidic acid by positive ion liquid secondary ion and collisionally induced dissociation tandem mass spectrometry.

This paper describes an approach for structurally analyzing aminophospholipids, including glycerophosphatidylethanolamine, glycerophosphatidylserine and their lyso analogues, and glycerophosphatidic acid by positive-ion liquid secondary-ion and four-sector tandem mass spectrometry. Polar head groups and the composition and position of the fatty acid chains in aminophospholipid species as well as diacyl and monoacyl phosphatidylethanolamine and their plasmalogen species can be characterized by collisionally induced dissociation of [M+H]+ ions of underivatized molecular species. Tandem mass spectrometry of [M+Na]+ and [M + 2Na-H]+ ions of 9-fluorenylmethyloxycarbonyl-derivatized glycerophosphatidylethanolamine and glycerophosphatidylserine induces fragmentation processes, but product ions are generally less structurally informative. Collisionally induced dissociation of [M + 2Na-H]+ ions of the molecular species of glycerophosphatidic acid not only yields information on the composition and position of fatty acid chains, but also allows the double bond location to be identified. This common positive-ion method is particularly effective in characterizing the molecular species of natural ethanolamine glycerophospholipids because of the advantage of a low detection limit. This approach also represents a useful alternative for the analysis of the molecular species from natural aminophospholipids by tandem mass spectrometry.

Amines↗
PubMed1994

Phase 2 study of prolonged administration of oral etoposide in combination with weekly cisplatin in advanced non-small cell lung cancer.

We administered chemotherapy consisting of a 21-day course of oral etoposide (50 mg/m2/day) and a 3-weekly dose of cisplatin (30-33 mg/m2/week) to 23 chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Six patients achieved a partial response (28.6%; 95% confidence interval, 11.3-52.2%), with a median response duration of 4 months and a median overall survival of 5 months. Besides alopecia, myelosuppression was the most significant drug-related toxicity. Observed side effects in 59 cycles of chemotherapy were granulocytopenia (< 1,000/microliters) in 23% of the treatment cycles, thrombocytopenia (< 75,000/microliters) in 25%, anemia (< 10 g/dl) in 64%, and nausea-vomiting (grades > or = 2) in 8%. Mild renal insufficiency (serum creatinine, 1.5-2.1 mg/dl) occurred in six patients. Three toxic deaths were observed during or immediately after cycle 1, and were related to granulocytopenia. We conclude that this regimen has modest activity in advanced NSCLC; but this therapeutic approach does not appear to produce a major improvement in the treatment of this disease. Thus, in advanced NSCLC, continued evaluation of new chemotherapeutic agents should remain the major emphasis of investigational therapy.

Administration, Oral↗
PubMed1994

The design of a zoom stand magnifier--a new low vision device.

A new stand magnifier has been designed for low vision patients and developed into a working instrument. This zoom magnifier has two ergonomic advantages over the currently available single lens magnifiers: it stays in focus (zooms) as the power is changed and it has a longer working space to allow both reading and writing with the same magnifier. This two-lens zoom magnifier contains a stationary plus lens and a movable minus lens. Using a symmetry condition, first order equations are presented and solved for the two lens powers. A family of three zoom magnifiers was designed--low, medium, and high power--each with a conveniently positioned sharp image with a 2-fold range of power and magnification. The equivalent viewing powers of the units (for a +2.50 D add) range from 6 to 23 D. The working spaces are approximately double that of comparable power single lens stand magnifiers.

Equipment Design↗
PubMed1994

Role of cyclic AMP-induced Cl conductance in aqueous humour formation by the dog ciliary epithelium.

1. The effects of isoprenaline, a forskolin derivative NKH-477, and dibutyryl cyclic AMP (db cyclic AMP) on the membrane potential, conductance and cell volume of the dog non-pigmented ciliary epithelium (NPE) were investigated by intracellular potential recording, nystatin-perforated patch clamp technique and videomicroscopic cytometry. 2. The resting membrane potential of NPE was about -70 mV in physiological saline and was depolarized by isoprenaline in a dose-dependent manner with an ED50 of about 3 nM. This depolarization was competitively antagonized by the beta-adrenoceptor antagonist, timolol (pA2 = ca. 9) and almost completely blocked by the Cl transport blocker, DIDS. 3. In single dissociated NPE cells, 10 microM isoprenaline induced an inward current and caused a concomitant decrease in cell volume. The reversal potential measurement indicated that this inward current was carried mainly by Cl ion. DIDS (10 microM) abolished both the current and cell volume decrease. 4. NKH-477 (10 microM) or db cyclic AMP (1 mM) also induced an inward current together with a cell volume decrease, the properties of which were similar to those caused by isoprenaline. 5. These results suggest that beta-adrenoceptor stimulation in NPE leads to an increased rate of aqueous humour production by increasing Cl- efflux via an elevation of cyclic AMP and this effect is efficiently blocked by timolol.

Animals↗
PubMed1994

Effect of lipopolysaccharide (LPS) chain length on interactions of bactericidal/permeability-increasing protein and its bioactive 23-kilodalton NH2-terminal fragment with isolated LPS and intact Proteus mirabilis and Escherichia coli.

The target-specific cytotoxicity for gram-negative bacteria and the endotoxin-neutralizing activity of the 55-kDa bactericidal/Permeability-increasing protein (BPI) and its bioactive 23-kDa NH2-terminal fragment depend on the strong attraction of BPI for the lipid A region of lipopolysaccharides (LPS). We have shown before that smooth gram-negative bacteria with long-chain LPS are more resistant to BPI (especially holo-BPI) than are rough strains. It has been suggested that the high BPI resistance of some gram-negative bacteria, such as Proteus mirabilis, might also reflect the structural diversity of lipid A. To explore this possibility, we compared the antibacterial activity and binding of natural and recombinant holo-BPI and a recombinant NH2-terminal fragment (rBPI-23) to an isogenic rough (Re-LPS chemotype) and a smooth (S-LPS chemotype) strain of P. mirabilis and to LPS isolated from the two strains. Holo-BPI and rBPI-23 were both potently active against the Re strain of P. mirabilis (90% lethal dose, 20 nM). In contrast, the smooth strain was > or = 100 times more resistant to holo-BPI but only 10 times more resistant to rBPI-23. rBPI-23 was also more potent against several Escherichia coli strains from clinical bacteremia isolates. Differences in the antibacterial potency of BPI toward the Re and S strains of P. mirabilis correlated with differences in the binding of holo-BPI and rBPI-23 to these bacteria. In contrast, the binding of biosynthetically (in vitro transcribed and translated) 35S-labeled holo-BPI and NH2-terminal fragment to isolated Re- and S-LPS from P. mirabilis in solution was similar. Moreover, in the Limulus amebocyte lysate assay, holo-BPI and rBPI-23 potently neutralized both forms of LPS with equal effectiveness. Together, these results strongly suggest that BPI recognizes Proteus lipid A and that the relative resistance of (smooth) P. mirabilis to holo-BPI is due to the inhibitory effect of long polysaccharide chains of tightly packed LPS in the envelope.

Antimicrobial Cationic Peptides↗
PubMed1994

Serological cross-reaction between Legionella spp. and Capnocytophaga ochracea by using latex agglutination test.

Cross-reactivity between Legionella spp. and Capnocytophaga ochracea was noted by latex agglutination tests (Serobact Legionella; Disposable Products, Adelaide, Australia). Four of 11 (36%) C. ochracea isolates agglutinated with latex reagents designed to identify Legionella pneumophila serogroups. C. ochracea isolated on buffered charcoal yeast extract media may give false-positive results in this Legionella latex agglutination assay.

Capnocytophaga↗