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Biomedical subjects

T L Chen

Publications and source records attributed to T L Chen.

At least 127 records · Page 7Linked to original sources
PubMed1991

Dexamethasone and 1,25-dihydroxyvitamin D3 modulation of insulin-like growth factor-binding proteins in rat osteoblast-like cell cultures.

Using the method of Western ligand blot, we have found that the major form of insulin-like growth factor-binding protein (IGF-BP) secreted by rat osteoblastic-like cells in culture is a 31-kDa protein that is immunologically identical to BP-2, the binding protein originally identified in conditioned medium of Buffalo rat liver cells (BRL-3A). Two minor forms of IGF-BPs with apparent mol wt of 24 kDa (BP-24) and 42 kDa (BP-42) have also been identified. The amount of IGF-BPs in serum-free conditioned medium increased 3-fold on day 3 compared to the day 1 level. We also studied the modulation of IGF-BPs by dexamethasone (DEX), 1,25-dihydroxyvitamin D [1,25-(OH)2D3], and insulin-like growth factor-I (IGF-I). DEX coordinately reduced the level of IGF-BPs in a dose- and time-dependent manner, which resulted in less than 10% of the BP-2 remaining at 100 nM. In contrast, 1,25-(OH)2D3 at 100 nM enhanced the amount of BP-2 by 1-fold. In combined treatments, 1,25-(OH)2D3 at 10 nM was unable to antagonize the inhibitory effect of DEX in the dose range of 1-10 nM. IGF-I, at 1 and 10 nM, proved to be a potent stimulator of all IGF-BPs, and at 10 nM, it completely reversed the inhibition by 100 nM DEX. Although the roles of IGF-BPs have not been clearly defined in bone cells, they are capable of modulating the biological actions of IGFs in other cell culture systems. Modulation of the IGF-BP level by DEX, 1,25-(OH)2D3, and IGF-I suggests important roles for these binding proteins in altering IGF-I action in rat osteoblast-like cell cultures.

Animals↗
PubMed1991

Further characterization of insulin-like-growth factor binding proteins in rat osteoblast-like cell cultures: modulation by 17 beta-estradiol and human growth hormone.

Insulin-like growth factors (IGF-I and IGF-II) are endocrine and autocrine factors affecting bone growth and metabolism. Binding proteins for IGFs (IGFBPs) are synthesized by the target tissues of IGF actions. Thus, IGFBPs may act as modulators for the biological functions of IGFs. We have characterized the rat IGFBPs (rIGFBPs) and studied their regulation by 17 beta-estradiol (beta E2) and human GH (hGH) in rat osteoblast-like (ROB) cell cultures. ROB cells were prepared from 19- to 20-day fetal rat calvariae by sequential collagenase digestion and studies were performed on the serum and phenol red-free conditioned medium of confluent cultures. [125I]IGF-I ligand blots showed that the major rIGFBP in the ROB is a nonglycosylated protein of 31 kilodaltons. This protein was immunoprecipitated by a specific antibody to rIGFBP-2 and messenger RNA for rIGFBP-2 was detected by RNA hybridization indicating that the rIGFBP-2 is the major rIGFBP of ROB. A minor band at 24 kilodaltons is likely to be the rat homologue of the newly isolated inhibitory IGFBP-4. The predominant glycosylated adult form of rIGFBPs of rat serum, rIGFBP-3, was undetectable. When cultures were treated with beta E2 for 2 days, there was a dose-dependent biphasic response which showed an inhibition of the rIGFBP-2 at low doses of 10(-11) to 10(-9) M and a stimulation at 10(-6) M. These changes in rIGFBP-2 parallel the changes in the endogenous IGF-I level. rIGFBP-2 level was not affected by 17 alpha-estradiol at the same concentration range. hGH, on the other hand stimulated the levels of rIGFBP-2 and rIGFBP-4 at doses ranging from 10(-11) to 10(-9) M without changing the IGF-I secretion. The alteration of the rIGFBPs by beta E2 and hGH suggests a role for these hormones in bone by modulating the biological functions of IGFs via their binding proteins.

Animals↗
PubMed1991

[Photic maculopathy by low energy laser beam. A case report].

The authors report a case of photic maculopathy that developed in a 30-year-old laboratory worker after repeated, consecutive exposure to low energy He-Ne laser. Pigmented foveal change and a small central scotoma in the right eye with window defect on fluorescein angiography characterized this maculopathy. Photochemical damage is considered to be the cause of the maculopathy.

Adult↗
PubMed1990

A unified model of eukaryotic chromosomes.

A revised model of DNA packaging into chromosomes is presented. Its features are consistent with observed structural dimensions and the molecular periodicities related to transcription, replication and matrix attachment domains. The transitions between euchromatic, heterochromatic and metaphase states are explained simply. Molecular and physical properties of chromosomal bands, and their correlation with specific DNA sequence motifs are discussed.

Animals↗
PubMed1990

Patterns of failure of aspirin treatment in symptomatic atherosclerotic carotid artery disease.

Over a 24-month period, 291 patients were consecutively admitted to the West Haven Veterans Administration Medical Center with new ischemic neurological symptoms. Of these, 90 patients (31%) developed ischemic neurological symptoms while taking aspirin (aspirin treatment failure). Of those in whom aspirin treatment failed, 66 patients had ischemic symptoms in the distribution of the carotid artery. Aspirin treatment failed in 21 patients with severe carotid stenosis (greater than 75% stenosis). Eleven of these 21 patients had cerebral infarctions while taking aspirin, and 7 of these 11 infarcts occurred without the prior warning of transient ischemic attacks. Aspirin treatment failed in 45 patients with lesser degrees of carotid stenosis. Transient ischemic attack without permanent ischemia was the most common manifestation of failure in these patients. Infarction occurred in only 12 of these 45 patients and in only 4 patients did infarction occur without warning. We conclude that patients with symptomatic high-grade carotid stenosis (greater than 75%) in whom aspirin treatment failed are likely to suffer an infarct without warning as the first sign of treatment failure (P less than 0.033). We suggest that this subgroup of patients should be considered for alternative forms of therapy.

Aged↗
PubMed1990

Recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) enhances healing and strength of granulation skin wounds.

A new animal model to study secondary intention wound healing and the effects of topically applied rhTGF-beta 1 was developed. A time course study was performed of full thickness 6 mm punch wounds placed on the backs of anesthetized pigs and treated once with either 3% methylcellulose or rhTGF-beta 1 in 3% methylcellulose or left untreated. Wounds receiving rhTGF-beta 1 had enhanced tensile strength at days 4 and 7 compared to controls. Studies of the response on days 4 and 7 to graded doses of rhTGF-beta 1 showed that a dose of 250 or 2500 ng rhTGF-beta 1 gave a similar enhanced wound strength, while 25 ng rhTGF-beta 1 had no effect. Blood flow to treated granulating wounds as measured by 141Ce microspheres indicate an increase in flow in wounds treated with 250, 500 or 2500 ng rhTGF-beta 1 compared to controls. These results indicate a possible use for rhTGF-beta 1 in enhancing wound healing clinically.

Animals↗
PubMed1990

Accelerated healing of ulcer wounds in the rabbit ear by recombinant human transforming growth factor-beta 1.

A dermal ulcer wound-healing model was established in rabbit ear to examine the effects of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) in wound healing. Histomorphometric examination of the wounds indicate a biphasic healing response 7 days after a single application of rhTGF-beta 1 at the time of wounding. Statistically significant healing occurred at 5-100 ng but not at higher doses of 500 or 1000 ng rhTGF-beta 1/wound. Enhanced collagen synthesis as determined by [3H]proline incorporation occurred at 15 and 25 ng and was significantly depressed at 500 ng rhTGF-beta 1/wound. Multiple doses of 100 ng rhTGF-beta 1 applied to the wound at the time of wounding and for 3 days after wounding provided results comparable to the single application of growth factor. Delaying treatment 24 hr after wounding did not enhance wound healing compared with vehicle. Our findings suggest that rhTGF-beta 1 can be a valuable growth factor to improve the healing of ulcer wounds.

Animals↗
PubMed1990

Microvascular perfusion and resistance in extracorporeal cardiopulmonary bypass under hypothermia with high-dose narcotic anesthesia--animal model.

Microvascular perfusion of the liver, kidney (cortex and medulla), pancreas and spleen was measured by laser-Doppler flowmetry under hypothermia in extracorporeal cardiopulmonary bypass, to determine the effectiveness of high-dose fentanyl in improving the microcirculation of these visceral organs. Twenty-four mongrel dogs in two groups were monitored by arterial catheter, Swan-Ganz catheter and laser-Doppler flowmeter. Cardiopulmonary bypass was carried out to induce hypothermia to 20 degrees C through the cannulation of inferior vena cava and aorta. Microvascular perfusion was measured by either needle or suturable probes of laser-Doppler flowmeter in liver, kidney (cortex and medulla), pancreas and spleen. With high-dose of fentanyl (100 micrograms/kg), decrease of microvascular perfusion in liver, pancreas and kidney (cortex and medulla) was less than the control group, especially at 20 degrees C. Notably, the trend of these changes had its unique pattern in each organ due to their own specific anatomical and physiological characteristics, while spleen did not show significant difference in both groups. In summary, high-dose of fentanyl improved the hepatic, renal and pancreatic microvascular perfusion, in agreement with our previous observation, might protect the function of these visceral organs from the damage of microvascular ischemia under hypothermia in the extracorporeal cardiopulmonary bypass.

Anesthesia↗
PubMed1990

Evaluation of systemic hemodynamic effects on post-transplant perfusion to renal allograft.

Hemodynamic parameters and post-transplant renal perfusion were evaluated in 24 cadaver kidney transplantation. Cardiac output (CO), systemic vascular resistance (SVR) and mean arterial pressure (MAP), were continuously monitored in each patient via a transesophageal Doppler cardiac output monitor and radial arterial catheter. Seventeen were well perfused (Group 1) after releasing vascular clamps. Six among group 1 presented as the clinical picture of acute tubular necrosis. Seven were poorly perfused (Group 2). Post-anastomotic CO significantly increased in group 1, and decreased in group 2. SVR significantly decreased in group 1, and increased in group 2. MAP were not significantly different between group 1 and 2. Treatments based on hemodynamic derangement were initiated as soon as it was detected. Correction of CO was associated with the improvement of post-anastomotic renal perfusion, while SVR and MAP were not. Among the 7 poorly perfused kidneys, 5 became well perfused before leaving the operating room. The remaining 2 resumed their hemodynamic stability and renal function a few days later after oral captopril was administered. Two among the 6 acute tubular necrosis resumed renal function as long as hemodynamic stability was restored. Our study demonstrates that hemodynamic parameters are parallel to renal perfusion status. Restoration of hemodynamic derangement not only improves renal perfusion but also renal function. It is concluded that hemodynamic instability and graft ischemic time contribute to the variation of post-transplant perfusion to renal allograft. Non-invasive cardiac output monitor is a safe and reliable monitor which we recommend to be used during the operation of kidney transplantation.

Adult↗
PubMed1990

Comparison of continuous epidural infusion of fentanyl and fentanyl-bupivacaine for post cholecystectomy pain control.

Epidural narcotics has been shown to produce profound and long-lasting analgesia. It has been suggested that lipid-soluble narcotics such as fentanyl, because of their short transit time in the CSF, are less likely to be associated with delayed respiratory depression and side effects. We tried to combine low concentrations of fentanyl with bupivacaine to minimize side effects and to see if synergistic effect existed. Forty ASA physical status I or II patients who present for cholecystectomy were included in the trial. Before surgery a thoracic epidural catheter was inserted and pain control began when patients became fully awake and complained of pain in the recovery room after surgery. Patients were randomized in a double-blind fashion to one of four groups. Patients in group I were given epidural infusions of fentanyl 0.001%; patients in group 2 received fentanyl 0.001% mixed with bupivacaine 0.1%; patients in group 3 received fentanyl 0.0005%; patients in group 4 received fentanyl 0.0005% mixed with bupivacaine 0.1%. A continuous epidural infusion of these drugs began at a rate of 10 mL/h after a 5-mL bolus of the solution. Pain relief was assessed with visual analogue pain scale. Respiratory rates, vital signs, and mental status were assessed hourly. Except the group 3, the degree of analgesia achieved was similarly satisfactory in all other groups. There was no respiratory depression developed in either group. Motor block was minimal or absent in all groups. The incidence of nausea and pruritus was significant less in group 3 and group 4. In conclusion, the continuous infusion of dilute bupivacaine with fentanyl provides synergistic analgesia with minimal side effects.

Analgesia, Epidural↗
PubMed1989

SINEs and LINEs cluster in distinct DNA fragments of Giemsa band size.

By in situ hybridization, short interspersed repeated DNA elements (SINEs), exemplified by Alu repeats, are located principally in Giemsa-light human metaphase chromosome bands. In contrast, the L1 family of long interspersed repeats (LINEs) preferentially cluster in Giemsa-dark bands. These SINE/LINE patterns also generally correspond to early and later replication band patterns. In order to provide a molecular link between structurally visible chromosome bands and a framework of interspersed repeats, we investigated patterns of SINE and LINE hybridization using pulse-field gel electrophoresis (PFGE). Interspersed SINEs and LINEs hybridize with high intensity to specific size fragments of 0.2-3 megabase pairs (Mb). Using appropriate restriction enzymes and pulse-field conditions, a number of fragments were delineated that were either SINE or LINE rich, and were mutually exclusive. Control studies with a human endogenous retroviral repeat that is related in sequence to the major LINE family, delineated a subset of fragments of 0.07-0.4 Mb with unequal intensity. Thus these less numerous repeats also appear to cluster selectively in DNA domains that are larger than a chromosome loop (60-120 kb). In summary, PFGE studies independently confirm the clustering of interspersed repeats on contiguous DNA loops. Selective clustering of repeat motifs may contribute to special structural or functional properties of large chromosome domains, such as chromatin extension/condensation or replication characteristics. In some cases the DNA fragments defined by these repeats approach the size of tandem satellite arrays.

Animals↗
PubMed1989

Pharmacokinetics of busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation.

Busulfan is an alkylating agent that is widely used in preparative regimens for bone marrow transplantation (BMT). We developed a high-performance liquid chromatographic (HPLC) assay for the determination of plasma busulfan concentrations in 30 patients who received oral doses of 1 mg/kg. Concentrations were fit by a one-compartment pharmacokinetic model with first-order absorption. The pattern of absorption and elimination varied widely between patients, with peak concentrations ranging from 1.2 to 10.4 mumol/l (mean, 4.25 +/- 2.49). The elimination half-life ranged from 58 to 433 min (harmonic mean, 140 min). The AUC contributed by a single oral dose ranged from 606 to 5,144 mumol-min/l (mean, 2,012 +/- 1,223). Patients were evaluated for the development of veno-occlusive disease (VOD), a treatment complication that occurs in 20% of patients undergoing BMT and causes 10% of transplantation-related deaths. All six patients who developed VOD had an AUC greater than the mean, and five of them had an AUC that was greater than 1 SD above the mean. The occurrence of VOD was highly correlated with an increased AUC (greater than 1 SD above the mean) (X2 = 18; P less than 0.0001). Using multivariate logistic regression, no other statistically significant pharmacokinetic predictor of VOD was found. The tenfold variability in the busulfan AUC and the statistical association of increased AUC with the development of VOD suggest a possible role for therapeutic monitoring in this setting.

Absorption↗
PubMed1989

Neuroblastoma double minutes isolated by pulsed-field gel electrophoresis without prior strand-cleaving treatments.

In a human neuroblastoma line, minute chromosomes were separable from the bulk of interphase nuclear DNA by contour-clamped homogeneous electric field (CHEF) gel electrophoresis. The minute chromosomes showed a homogeneous size of approximately 3 Mbp and contained amplified N-myc genes. Fractionation was accomplished without prior strand-cleaving treatment of the DNA, indicating that at least a portion of the minute chromosomes exist as free entities in the interphase nuclei. Human alphoid satellite DNA sequences were also detected in the 3-Mbp band. It is possible that alphoid sequences are contained in the constricted central region that joins these double minutes.

DNA, Neoplasm↗
PubMed1989

1,25-Dihydroxyvitamin D3 interaction with dexamethasone and retinoic acid: effects on procollagen messenger ribonucleic acid levels in rat osteoblast-like cells.

We previously have reported that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], dexamethasone, and retinoic acid inhibit collagen synthesis in rat osteoblast-like cell primary cultures. We also have found that dexamethasone increases 1,25-(OH)2D3 receptor levels in these cells. Furthermore, this increase in 1,25-(OH)2D3 receptor level is paralleled by an enhanced inhibition of collagen synthesis when dexamethasone and 1,25-(OH)2D3 are used in combination. In contrast, retinoic acid at high doses decreases 1,25-(OH)2D3 receptor level in rat osteoblast-like cells and attenuates 1,25-(OH)2D3 inhibition of collagen synthesis. In the present study, we have used a [32P]cDNA probe for rat pro alpha 1 (I) to determine if these osteotropic agents act by modulating steady state procollagen mRNA levels. Hybridization with a [32P]cDNA probe for human actin was used as a control. We find that the steady state levels of procollagen mRNA are decreased in all cases, while there are negligible changes in actin mRNA levels. Dexamethasone, at the low dose of 13 nM, acts synergistically with 1,25-(OH)2D3 in decreasing procollagen mRNA levels. The effects of retinoic acid and 1,25-(OH)2D3 are additive at low doses (13 and 130 nM); however, at a high dose of retinoic acid (1.3 microM), combined treatment with 1,25-(OH)2D3 does not reduce procollagen mRNA levels beyond the decrease due to retinoic acid alone. The reduction in procollagen mRNA level after each of these treatments falls in the same range as inhibition of collagen synthesis measured at the protein level. These data suggest that the synthesis of collagen under these treatments is controlled primarily through modulation of steady state procollagen mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Modulation of transforming growth factor-beta actions in rat osteoblast-like cells: the effects of bFGF and EGF.

The present study examines how the mitogenic and differentiation functions of transforming growth factor-beta (TGF-beta) are modulated by basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in primary cultures of rat osteoblast-like (ROB) cells. TGF-beta, bFGF, and EGF individually stimulated [3H]thymidine incorporation and cell proliferation in a dose range of 0.01-10 ng/ml. When studied in combination, high doses of bFGF and EGF were additive to low doses of TGF-beta. The additive effects of bFGF and EGF on mitogenesis diminished with increasing doses of TGF-beta. These three factors also decreased alkaline phosphatase activity individually within the same dose range. When cells were treated with the combined factors, only high doses of bFGF and EGF were additive to the TGF-beta inhibition. We were unable to detect any change in collagen synthesis with each individual factor or in combined treatments. In addition, TGF-beta or bFGF alone or in combination did not affect fibronectin synthesis. Our studies showed that the biological functions of TGF-beta can be modulated by bFGF and EGF in ROB cells. The pattern of modulation is varied depending on the specific function examined.

Alkaline Phosphatase↗
PubMed1989

Evaluation of microleakage due to cuffs of endotracheal tubes during positive end-expiratory pressure ventilation.

Mallinkrodt tubes (internal diameter 8.0 mm) with high residual volume and low pressure cuffs were used to evaluate the influence of positive end-expiratory pressure (PEEP) on leakage from cuffed endotracheal tubes. A thin smooth epidural catheter (Portex) was placed immediately above the cuff to monitor visually whether methylene blue dye solution (2-3 ml) passed through the cuff and stained the trachea. One hundred male patients undergoing elective orthopedic surgical procedures were randomly divided into five groups: a control group and groups using 2.5, 5.0, 7.5, and 10 cm H2O of PEEP during nitrous oxide-oxygen-isoflurane anesthesia. The cuff pressure was set to 25 cm H2O in each group. The cuff pressure was recalibrated and evidence of staining below the cuff was sought with a fiberscope every twenty minutes for a total of three times. Leakage increased with PEEP level but the amount was not statistically significant and the difference between groups was not significant.

Humans↗
PubMed1989

Cardiac transplantation at National Taiwan University Hospital: a review from the anesthesiologist's standpoint.

We report our initial experience with three patients who underwent heart transplantations at National Taiwan University Hospital. Two had idiopathic dilated cardiomyopathy. One had ischemic heart disease. Anesthesia was induced with fentanyl, ketamine, etomidate and pancuronium. In addition to regular maintenance with fentanyl, diazepam and pancuronium, low doses of isoflurane were added for skin incision and sternotomy. The anesthetic courses were uneventful. Mild hypotension was noted in the first case after cardiopulmonary bypass, and was immediately corrected by increasing the preload and dosage of inotropes. Sinus tachycardia from the donor SA node was the predominant rhythm after cardiopulmonary bypass. Our experience agrees with other reports that anesthesia for cardiac transplantation is a relatively safe procedure under careful hemodynamic monitoring and pharmacological support. Aseptic techniques, adequate preload and hemostatic agents supply are the major concerns for anesthetists.

Adult↗