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T L Chen

Publications and source records attributed to T L Chen.

At least 145 records · Page 8Linked to original sources
PubMed1989

Hemodynamic response to ketamine and diazepam in dogs with acute cardiac tamponade.

Induction of anesthesia may produce a significant hazard to patients with critical cardiovascular status. Ketamine has been advocated as the drug of choice for maintaining cardiovascular performance during induction of anesthesia in high-risk surgical patients. There is no detailed information on the use of ketamine in patients with acute cardiac tamponade. The purpose of this study was to assess the safety of ketamine in acute cardiac tamponade in dogs. Sixteen dogs were studied and a Swan-Ganz catheter was inserted through the right external jugular vein to measure hemodynamic parameters. Data obtained before tamponade was used as the control, then, tamponade was accomplished by infusing a mixture of saline and blood from the same dog through a catheter into the pericardial sac. Ketamine, 2 mg/kg intravenously resulted in an improvement of cardiac output from 1.2 +/- 0.5 L/min to 2.2 +/- 0.3 L/min (p less than 0.05). The addition of diazepam 0.3-0.5 mg/kg blunted the ketamine-induced cardiostimulation and resulted in a fall in cardiac output from 2.2 +/- 0.3 L/min to 1.7 +/- 0.2 L/min (p less than 0.05). Five dogs with intrapericardial pressure above 10 mmHg did not respond to ketamine. Diazepam did not blunt any more to these decompensated dogs. This study demonstrated that ketamine plays a beneficial role in acute cardiac tamponade as a safe induction agent. Limitation still existed when using ketamine in dogs with high intrapericardial pressure because they showed only negative inotropic effect during decompensation. Diazepam inhibited the cardiostimulant effects of ketamine in dogs with tamponade, but could not elicit a negative inotropic effect during decompensation. The practical application of ketamine and diazepam in patients with acute cardiac tamponade could be determined by evaluation of intrapericardial pressure through a needle-transducer kit.

Acute Disease↗
PubMed1989

Quin2-induced metaphase arrest in stamen hair cells can be reversed by 1,2-dioctanoylglycerol but not by 1,3-dioctanoylglycerol.

Elicitor molecules of the polyphosphoinositide cycle, inositol 1,4,5-trisphosphate (InsP3) and 1,2-diacylglycerol (1,2-DAG) play roles in the entry of calcium into the cytosol and in the elevation of protein kinase C activity, respectively. We have treated stamen hair cells of the spiderwort plant, Tradescantia virginiana, with a solution of quin2 (50 microM) or its acetoxymethyl ester, quin2-AM (50 microM) and have retarded the normally predictable rate of progression through metaphase. Metaphase arrest persists for longer than 80 min after treatment with this Ca2+-chelator, and, shortly thereafter, the cells revert to interphase without dividing. Reversal of metaphase arrest results from treatments with calcium chloride (100 microM) after 5 to 8 min or with 1,2-DAG (i.e., 60 micrograms/ml 1,2-dioctanoylglycerol) after 7 to 11 min. In control experiments, metaphase arrest could not be reversed by treatment with either magnesium sulfate or 1,3-dioctanoylglycerol. Anaphase onset was observed in these control cells after post-treatment with calcium chloride (after 4-9 min) or with 1,2-dioctanoylglycerol (after 7-13 min). The treatment of stamen hair cells in very early prophase with H-7, (i.e., 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride), a potent protein kinase C inhibitor, extends the duration of metaphase significantly. Neither H-8 nor HA-1004, less active protein kinase C inhibitors in this class of molecules, alter the duration of metaphase to a significant extent. These results suggest that in cells arrested in metaphyase by quin2, calcium translocation plays a role in the sequence of events which culminate in anaphase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines↗
PubMed1989

Acute graft-versus-host disease: a clinical report and analysis of risk factors.

Of the 31 cases of allogeneic bone marrow transplantation performed in the past 4 years at the National Taiwan University Hospital, 25 evaluable cases were retrospectively studied for incidence, severity, and risk factors of acute graft-versus-host disease (GVHD). The incidence was 60% (15/25) with the proportion of severe form (greater than or equal to grade II) being 53% (8/15). Skin involvement was the most common (13/15), gut the second (5/15), and liver the third (4/15). Most of the diagnosis of skin disease were confirmed by biopsy. Acute GVHD accounted for 3 deaths directly and was the next most common cause of death in post-transplant patients. The long-term survival rate for cases with grade 0-I disease was 65%, and that for those with grade II-III disease was 38%. Multivariate linear regression analysis of risk factors associated with severe form GVHD showed that the diagnosis of aplastic anemia was the most significant factor. Total lymphoid irradiation with or without plasmapheresis in aplastic anemia might contribute to the occurrence of severe acute GVHD.

Acute Disease↗
PubMed1988

Determination of busulfan in human plasma by gas chromatography with electron-capture detection.

A simple and highly sensitive gas chromatographic method has been developed for the determination of busulfan in human plasma. After extraction of plasma specimens (clinical or spiked) with ethyl acetate, busulfan and the internal standard [1,8-bis(methanesulfonyloxy)octane] were derivatized with 2,3,5,6-tetrafluorothiophenol to yield compounds monitored by a 63Ni electron-capture detector. Sample recoveries from extraction and derivatization were greater than 78 and 91%, respectively. The limit of quantitation was 0.01 microgram/ml (0.04 microM) in 1 ml of plasma with a linear relationship over the 0.01-1.0 micrograms/ml (0.04-4 microM) concentration range. The method has been applied to analyze the plasma versus time profile of busulfan in human subjects following administration of an oral dose of 4 mg/kg per day as a marrow ablative chemotherapy for bone marrow transplantation.

Biological Availability↗
PubMed1988

Polypeptide growth factors in bone matrix.

The presence of many types of polypeptide growth factors in the mineralized extracellular matrix of bone is now well established. These factors are generally referred to as bone-derived growth factors (BDGFs), and are similar, or possibly identical, to the following species; platelet-derived growth factor (PDGF); acidic and basic forms of fibroblast growth factor (aFGF, bFGF); transforming growth factor beta (TGF-beta); and insulin-like growth factor 1 (IGF-1). Several osteoinductive factors, such as bone morphogenetic protein (BMP) and osteogenin, a skeletal growth factor (SGF), and osteoblast-derived BDGFs, have also been identified. Complete description of the biological functions of these BDGFs which are relevant to bone will ultimately require specific bioassays involving specific cell types in vitro, as well as in vivo animal implant models. Studies with primary rat osteoblast-like cells exposed either to mixed BDGFs, pure TGF-beta, or heparin-purified PDGF, aFGF, or bFGF from bovine bone have shown a general dose-dependent mitogenic effect. Phenotypic changes which accompany the BDGF-induced wave of proliferation include: decreased osteocalcin secretion and a reduction in 1,25-(OH)2 vitamin D3-stimulated osteocalcin synthesis; reduced alkaline phosphatase specific activity; decreased cyclic AMP responsiveness to parathyroid hormone (PTH); and increased collagen synthesis. Bone exhibits the most complex spectrum of growth factor activities of any tissue yet described. In bovine bone powder free of blood and cartilage contamination, the volume concentration of mitogens is up to 20 times greater than that in serum. Bone cells and other indigenous cell types must be considered as possible sources of the BDGFs, in addition to sequestration from blood. Mechanisms for the unmasking or release of BDGFs from the mineralized matrix that result in local action on osteoblasts, endothelial cells, and other target cells are undoubtedly important for the development and maintenance of bone tissue.

Animals↗
PubMed1988

Gangliosides suppression of murine lymphoproliferation and interleukin 1 production.

Studies were carried out to determine whether inhibition of gangliosides on lymphoproliferation was related to interleukin (IL)-1. The results showed that gangliosides, GM1 and GT1b were able to inhibit the proliferation of spleen lymphocytes from C57BL/6J mice in dose-dependent fashion, whereas asialo-GM1 was not inhibitory. However, gangliosides, GM1 and asialo-GM1 did not suppress the production of IL-1 in Salmonella typhosa lipopolysaccharide (LPS)-induced peritoneal adherent cells. Various types of LPS including S. enteritidis, S. minnesota and Escherichia coli 055:B5 were used to stimulate the production of IL-1 in adherent cell cultures. The IL-1 production was not affected by gangliosides, GD1a and GD1b. Although GT1b suppressed IL-1 production of human monocytes to 82% of control level it did not, however, affect the IL-1 production of murine adherent cells. Thus, the inhibitory mechanism of gangliosides on murine immune cells remains unclear, and warrants further study.

Animals↗
PubMed1988

Immunological and biochemical strategies for the identification of brain tumor-associated antigens.

Various strategies have been used to identify and characterize the antigens associated with human brain tumors. These approaches have included the raising of polyclonal and monoclonal antibodies against tumor antigens and, more recently, efforts toward the direct biochemical identification of such proteins. This review summarizes the progress made in this area, suggests reasons for the broad antigenic cross-reactivity and heterogeneity revealed by these studies, and proposes additional methods for deciphering the complex antigenic composition of human brain tumors.

Antibodies, Monoclonal↗
PubMed1987

Mitotic progression in stamen hair cells of Tradescantia is accelerated by treatment with ruthenium red and Bay K-8644.

The normally predictable duration of metaphase in stamen hair cells from the spiderwort, Tradescantia virginiana, is shortened significantly by treatment during prometaphase with either ruthenium red or Bay K-8644. Ruthenium red is an inhibitor of Ca2+ translocation and Bay K-8644 is a Ca2+-channel agonist. Their action on mitotic progression appears to involve a rise in the cytosolic Ca2+ level that in turn has a pronounced effect on the duration of metaphase. The timing of addition of ruthenium red for accelerated progression through metaphase is less critical than that for Bay K-8644 which will promote metaphase progression only if added 0 to 12 min after nuclear envelope breakdown. In contrast, ruthenium red can be added at any time from approximately 10 min prior to nuclear envelope breakdown up to 25 min afterward. A reduction of extracellular Ca2+ is sufficient by itself to prolong the duration of metaphase in stamen hair cells, but the duration of metaphase by ruthenium red or Bay K-8644 is significantly shortened in identical solutions with Ca2+ buffered at levels greater than 1 microM. Metaphase progression rates with either agent are independent of changes in extracellular Mg2+ levels. Correlated with the precocious entry into anaphase was rapid formation of the spindle and a marked reduction in spindle rotation during metaphase. Interestingly, we observed a modest increase in the rate of anaphase chromosome separation, but the appearance of cell plate vesicles at the site of incipient cell plate formation occurred normally approximately 19 min after anaphase onset. Similarly, the initial appearance of cell plate vesicles in Bay K-8644 was normal, approximately 19 min after the onset of anaphase. These results further implicate shifts in cytosolic Ca2+ in the regulation of mitotic events.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

High-performance liquid chromatographic assay for taxol in human plasma and urine and pharmacokinetics in a phase I trial.

Taxol is a unique antineoplastic agent which appears to exert its cytotoxic action as a result of interference with microtubular structure and function. Clinical development of this drug will be facilitated by the availability of sensitive and specific methods for its quantitation in biological fluids. We have developed a reverse-phase high-performance liquid chromatographic assay for taxol capable of detecting concentrations as low as 50 nM, which can be automated using readily available equipment. With this assay we have performed pharmacologic studies of taxol during the conduct of a phase I trial of this compound at The Johns Hopkins Oncology Center. Following a 60- to 360-minute infusion, the plasma disappearance is biexponential, with harmonic mean alpha half-life and beta half-life values of 16.2 minutes and 6.4 hours, respectively. Volumes of distribution for the theoretical central compartment (VDc) and at steady state (VDss) were 8.6 and 67.1 L/m2. Mean plasma clearance was 253 ml/minute/m2. Urinary clearance was 29.3 ml/minute/m2 and 5.9% +/- 8.8% of the drug was identified in 48-hour urine collections. No metabolites have been identified. Over the 18-fold dose range studied, there was no evidence of nonlinearity or dose-dependent behavior. A rough correlation between area under the plasma disappearance curve and hematologic toxicity was observed.

Alkaloids↗
PubMed1986

Hormonal responses to 1,25-dihydroxyvitamin D3 in cultured mouse osteoblast-like cells--modulation by changes in receptor level.

The level of 1,25(OH)2D3 receptors in cultured mouse osteoblast-like (OB) cells is modulated by the rate of cell proliferation. We have studied two 1,25(OH)2D3-induced bioresponses to ascertain whether the changes in receptor levels during growth in culture alter cell responsiveness. Nuclear receptor levels were high (127 fmol/100 micrograms DNA) in rapidly dividing (log) cells and low (25 fmol/100 micrograms DNA) in quiescent (confluent) cells. The bioresponses we studied were induction of 25(OH)D3-24-hydroxylase activity (24-hydroxylase) and inhibition of collagen synthesis. The basal levels of 24-hydroxylase were low and similar in cells at log growth phase and confluence. At a maximal induction dose of 13 nM, 1,25(OH)2D3 induced a three-fold rise in enzyme activity at long growth phase, but only caused less than two-fold rise at confluence. The half-maximal dose (ED50) was slightly shifted from 0.6 nM to 0.8 nM. Daily measurement of 1,25(OH)2D3 receptor levels and maximal induction of 24-hydroxylase activity throughout the culture cycle showed a strong correlation between receptor abundance and enzyme induction. The basal level of collagen synthesized by cells in log growth phase was approximately 5% and increased to approximately 8% at confluence. Maximal inhibition of collagen synthesis by 1,25(OH)2D3 reached 80% of control levels in log cells, but was only 40% of control in confluent cells. The ED50 was approximately 0.1 nM in the log cells and increased to approximately 1 nM at confluence. Daily assay of 1,25(OH)2D3 receptor levels and 1,25(OH)2D3 responses during the culture cycle indicated a correlation between changes in receptor level and the extent of inhibition of collagen synthesis. These changes in bioresponse at various growth phases did not occur in rat OB cells where the 1,25(OH)2D3 receptor levels were independent of cell proliferation. The results indicate that cell proliferation rate, via change in receptor levels, determines the magnitude and sensitivity of the cellular responses to 1,25(OH)2D3.

Animals↗
PubMed1986

The effects of 1,25-dihydroxyvitamin D3 and dexamethasone on rat osteoblast-like primary cell cultures: receptor occupancy and functional expression patterns for three different bioresponses.

The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and dexamethasone to regulate collagen and osteocalcin synthesis and induction of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) activity were studied in rat osteoblast-like cell primary cultures. In this culture system, the basal levels of collagen and osteocalcin synthesis increased with rising cell density in culture. At maximal doses, both 1,25-(OH)2D3 (8.1 nM) and dexamethasone (130 nM) reduced collagen synthesis to about 50% of the control levels, 1,25-(OH)2D3 affected osteocalcin synthesis in a biphasic manner: stimulatory at low doses, which peaked near 0.33 nM to reach 3- to 5-fold the basal level, followed by a gradual return to the basal level at higher concentrations. Dexamethasone had only a slight stimulatory effect on osteocalcin. 1,25-(OH)2D3 also induced 24-hydroxylase activity in rat osteoblast-like cells, while dexamethasone had no effect on the enzyme. Induction of enzyme activity achieved a 4- to 6-fold rise, but required higher concentrations of 1,25-(OH)2D3 to achieve maximal levels (16 nM). The half-maximal doses (ED50) of 1,25-(OH)2D3 required for each bioresponse were different. The approximate ED50 for the inhibition of collagen synthesis was near the Kin (0.4 nM; apparent dissociation constant of receptor nuclear internalization), while the ED50 for osteocalcin synthesis (0.08 nM) was below the Kin, and the ED50 for 24-hydroxylase induction (20 nM) was greater than the Kin. The ED50 for dexamethasone on collagen synthesis (20 nM) was about 5-fold higher than the Kin (4 nM) of dexamethasone receptor binding. The potencies of various vitamin D3 metabolites in all three functional responses followed their abilities to compete for the 1,25-(OH)2D3 receptor, indicating that these actions were 1,25-(OH)2D3 receptor mediated. In summary, these studies explored bone cell bioresponses to 1,25-(OH)2D3 and dexamethasone and examined the relationship between receptor occupancy and functional expression. Each action exhibited a different dose-response pattern, implying that different levels of control are required for each individual response.

Animals↗
PubMed1986

Dexamethasone increases 1,25-dihydroxyvitamin D3 receptor levels and augments bioresponses in rat osteoblast-like cells.

Glucocorticoids increase the level of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in primary cultures of rat calvarial osteoblast-like (OB) cells. The present study investigated how this dexamethasone (DEX) up-regulation of 1,25-(OH)2D3 receptors modulates three 1,25-(OH)2D3 bioresponses: inhibition of collagen synthesis, stimulation of osteocalcin synthesis, and induction of 25-hydroxyvitamin D3-24-hydroxylase activity. Pretreatment of OB cells with 13 nM DEX for 24 h doubled the 1,25-(OH)2D3 receptor level without changing receptor affinity for 1,25-(OH)2D3 to study bioresponses. After DEX treatment to increase the 1,25-(OH)2D3 receptor level, the magnitude and sensitivity of all three 1,25-(OH)2D3 bioresponses were enhanced. The maximal 1,25-(OH)2D3 inhibition of collagen synthesis was increased by DEX pretreatment compound to control values: 30 to 50% (1 day treatment) and 50 to 70% (2 day treatment). The sensitivity to 1,25-(OH)2D3, as measured by reduction of the half-maximal inhibitory dose (ED50), was increased 50%. This potentiation of 1,25-(OH)2D3 inhibitory action on collagen synthesis was still evident after correction for the inhibitory effect on collagen synthesis by DEX alone. The maximal stimulation of osteocalcin by 1,25-(OH)2D3 was also enhanced from 2- to 3-fold in controls to over 4- to 5-fold by DEX pretreatment. Similarly, the ED50 of the response was reduced 50%. For the induction of 25-hydroxyvitamin D3-24-hydroxylase activity, DEX doubled the enzyme activity over that seen with 1,25-(OH)2D3 alone, but only slightly affected the sensitivity of the enzyme induction. In conclusion, after DEX up-regulation of 1,25-(OH)2D3 receptor levels, there was a general potentiation of 1,25-(OH)2D3 bioresponses in rat OB cells. However, the detailed patterns of the augmented responses were different for each of the three biological functions we studied.

Animals↗