Biomedical subjects
Publications and source records attributed to T L Chen.
We propose a new technique using trimmed plastic syringes as a "bridging skeleton" in delayed sternal closure for complex congenital heart surgery. The technique achieves at low cost good stability and the necessary compliance vital for ultimate survival.
A 14-year-old girl developed spontaneous vitreous hemorrhage from the free end of a partially regressed hyaloid artery. Fluorescein angiography confirmed the hemorrhage was from the retinal arterial rather than venous circulation. The vessel became a fibrosed, occluded, and semitransparent thread after 20 months of follow-up evaluation. It was postulated that the rapid eye movement (REM) phase during sleep may create a tractional force and leads to rupture of the freely floating hyaloid artery. A patent persistent hyaloid artery should be included in the list of the causes of vitreous hemorrhage, especially in healthy young people.
An immunophenotypic pattern characterized by increased proportions of CD10, CD19, and HLA-DR+ cells is observed in the bone marrow of some children with nonmalignant hematologic diagnoses. The purpose of this study was to ascertain the clinical and pathologic significance of this immunophenotype. The morphologic and immunophenotypic results of bone marrow specimens from 23 children with nonmalignant hematologic conditions are presented. In 11 children, an increased percentage of immature B-cell precursors was observed, suggesting the presence of B-lineage malignancy. None of the children have developed malignant lymphoproliferative disease in as long as 4 years of follow-up, despite the demonstration of a clonal lymphocyte proliferation in one patient. Although the biologic significance of the bone marrow immunophenotype is not yet understood, it is important to recognize that this lymphocyte pattern occurs commonly in children with nonmalignant hematologic conditions, and may reflect an increase in normally occurring lymphoid precursor cells.
Insulin-like growth factors (IGFs) stimulate growth and differentiation of osteoblasts in culture, and these biological functions can be modulated by their binding proteins (IGFBPs). Previous studies have shown that IGFBP-2 is the major IGFBP synthesized by fetal rat osteoblast-like (ROB) cells, which also secret a minor 24-kilodalton IGFBP, presumably IGFBP-4. In this study we examined the modulation of the abundance of IGFBPs by various growth factors. By immunoprecipitation and ligand blotting, we have proved that the 24 kilodalton protein, which appeared at 25 kilodalton in the present study, is IGFBP-4, whose level was strongly enhanced by basic fibroblast growth factor (bFGF) and platelet-derived growth factor BB homodimer. Induction of IGFBP-4 by these factors was detected at 1 nM (10- to 30-fold) and increased to 50- to 70-fold of control at 10 nM. The abundance of IGFBP-4 was also increased but to a lesser degree by transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF). As opposed to the actions of other growth factors, TGF-beta 1 substantially lowered the levels of IGFBP-2 and IGFBP-4. PTH and PTH-related peptide did not induce IGFBPs in ROB cells. This is in contrast to the findings from a malignant rat osteoblast-like cell line, UMR 106-01. Since the level of IGFBP-4 after bFGF treatment remained elevated in the presence of hydroxyurea, the induction was likely to be independent of the stimulatory effects of these factors on mitogenesis. To further examine the mechanisms by which IGFBPs were regulated, cultures were treated with actinomycin D and cycloheximide with and without bFGF. Although the synthesis of IGFBP-2 and IGFBP-4 were both inhibited by cycloheximide, actinomycin D blocked the synthesis of basal and bFGF-induced IGFBP-4 but not IGFBP-2. Total RNA extracted from ROB cells and hybridized with specific rat complementary DNAs for IGFBP-2 and IGFBP-4 showed single transcripts of 1.3 and 2.2 kilobases, respectively. Regardless of the changes at the protein level, the abundance of IGFBP-4 transcripts was not different from the vehicle-treated controls at 2, 8, and 24 h after bFGF treatment. Similarly, the levels of messenger RNA for IGFBP-2 and IGFBP-4 did not change during the same time course in the TGF-beta 1 treatment. These data demonstrate that in ROB cells, the abundance of IGFBPs is differentially regulated by various growth factors.(ABSTRACT TRUNCATED AT 400 WORDS)
The purpose of this investigation was to measure the changes of Prostacyclin(PG12) occuring in gingivitis and periodontitis.Fifteen cases of periodontitis,ten cases of gingivitis and ten cases of healthy participated in this study,Saliva was taken before treatment,Prostacyclin in saliva was measure by radioimmunoassay(RIA).The results showed that prostacyclin of human saliva is increased from healthy gingivitis to periodontitis.There is a statistical difference between groups,6-k-PGF1alpha in saliva of periodontitis is 3.6 folds of healthy.Gingivitis is 2.6 folds of healthy.There is also a significant difference between adult periodontitis our findings suggested that prostacyclin may play an important role in etiology of periodontal disease.Measured 6-k-PGF1alpha in saliva may indicate the severity of periodontal disease.
Though spinal reflexes have been described in experimental brain-death animals, no documentation has been previously provided for human. The hemodynamic responses to surgical stimuli have been investigated here in eight brain-death organ donors. Baseline systolic blood pressure, diastolic blood pressure, and heart rate in observed patients were 99 +/- 15 mmHg, 61 +/- 13 mmHg, and 105 +/- 22 beats/min respectively. After skin incision, these parameters elevated maximally to 130 +/- 23 mmHg, 74 +/- 17 mmHg, and 119 +/- 18 beats/min (p < 0.05). Either spinal reflex arcs or adrenal medullary stimulation, or both, have been speculated to possibly play the role in these hemodynamic responses. However, the existence of such responses should not invalidate the diagnosis of brain death.
Under different infusion rates in normal hearts and hearts with coronary ligation, the hemodynamic effects of propofol were measured in a coronary artery ligation model in twelve mongrel dogs. Propofol was given by 10 mg/kg intravenous bolus followed by 30 min infusion in succession with 20 mg/kg/hr, 40 mg/kg/hr and 80 mg/kg/hr in both normal hearts and hearts with coronary ligation. The range of blood concentrations in our study is 2.19 +/- 0.56 microgram/ml to 15.78 +/- 3.31 micrograms/ml. After ligation at 1 cm below first diagonal branch of left anterior descending artery (LAD) obvious cardiovascular changes were seen in a few seconds. However, non-significant hemodynamic changes were demonstrated between pre-ligated and 30 min after ligation. With increasing blood propofol concentrations, there was significant negative correlation (p < 0.01) in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) but central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) decreased non-significantly with increasing propofol concentrations in both non-ligated and ligated groups. Propofol infusion up to 80 mg/kg/hr did not decrease MAP, CO and systemic vascular resistance (SVR) further in hearts with coronary ligation than normal hearts in our study. SVR and pulmonary vascular resistance (PVR) changed non-significantly between each groups even in blood concentration as high as 15 micrograms/ml. We conclude that propofol depresses myocardial function associated with increasing blood propofol concentrations despite stable SVR and PVR. The hemodynamic effects of propofol were similar in the normal hearts and hearts with coronary ligation.(ABSTRACT TRUNCATED AT 250 WORDS)
A Dictyostelium mutant (7-11) that expresses less than 0.5% of wild-type levels of the myosin essential light chain (EMLC) has been created by overexpression of antisense RNA. Cells from 7-11 contain wild-type levels of the myosin heavy chain (MHC) and regulatory light chain (RMLC). Myosin isolated from 7-11 cells consists of the MHC with the RMLC associated in reduced stoichiometry, and binds to purified actin in an ATP-sensitive fashion. Purified 7-11 myosin displays calcium-activated ATPase activity with a Vmax about 15%-25% of that of wild type, and a Km for ATP of 27 +/- 5 microM versus 83 +/- 30 microM for wild type. At actin concentrations as high as 17 microM, 7-11 myosin displays greatly reduced actin-activated ATPase activity. Phenotypically, 7-11 cells resemble MHC mutants, growing poorly in suspension and becoming large and multinucleate. When starved for multicellular development, 7-11 cells take several hours longer than wild-type cells to aggregate. Although multicellular aggregates eventually form, they fail to develop further. The cells are also unable to cap receptors in response to Con A treatment. Since cells expressing the EMLC are phenotypically similar to MHC null mutants, the EMLC appears necessary for myosin function, at least in part because it is required for normal actin-activated ATPase activity.
Combination of low doses of de novo pyrimidine biosynthesis inhibitors with 5-fluorouracil (FU) has been proposed to increase the antitumor activity of FU. Brequinar is such an inhibitor that has little clinical anti-tumor effect when used alone. We determined the clonogenic survival of MGH-U1 cells treated with FU +/- leucovorin (LV) +/- brequinar and examined the effects of these treatments on thymidylate synthase (TS). After 24 h exposure, the concentrations resulting in 50% inhibition of cell growth (IC50) for brequinar, FU, and FU+LV (100 microM) were 0.4, 20, and 10 microM, respectively. Both 24 h pretreatment and 48 h continuous treatment with the IC10 (0.1 microM) of brequinar increased the cytotoxicity of FU but did not enhance that of FU+LV. Simultaneous 24 h exposure to 0.1 microM brequinar and FU +/- LV did not increase the cytotoxicity of FU +/- LV. Intracellular cytidine triphosphate (CTP) and uridine triphosphate (UTP) pools, free TS binding sites, and levels of free fluorodeoxyuridine monophosphate (FdUMP) and deoxyuridine monophosphate (dUMP) were measured in cells pretreated with 0.1 microM brequinar for 24 h alone or followed by a 2-h exposure to FU (25 microM) +/- LV (100 microM). In brequinar-treated cells, CTP and UTP pools amounted to 68% and 46% of control values, respectively. The free TS binding sites remaining amounted to 70% of control values in cells treated with FU and 9% of control levels in those treated with FU+brequinar. Free FdUMP levels increased 5-fold in cells pretreated with brequinar as compared with those treated with FU alone. The increased formation of FdUMP was inhibited by simultaneous exposure to 100 microM hypoxanthine and 25 microM FU. Intracellular dUMP levels were not affected by brequinar. We conclude that a low dose of brequinar increases the cytotoxicity of FU but does not enhance that of FU+LV when exposure to brequinar precedes FU treatment. This potentiation appears to be mediated by the increased formation of FdUMP as a consequence of an increase in the cosubstrate phosphoribosyl pyrophosphate (PRPP).
Explore the source record for details and available documents.
The effects of recombinant human transforming growth factor beta 1 (rhTGF-beta 1) on wound healing were examined in a rabbit ear ulcer model in which rhTGF-beta 1 was applied to full-thickness biopsy ulcers on the ears. The influence of perichondrium on healing was studied by comparing ulcers with and without perichondrium on 1) formation of total healing wound area (HWA, the newly formed connective and granulation tissues within the ulcer) over time and 2) the amount of collagen synthesized by the wound tissue at day 5. The HWA of ulcers with intact perichondrium increased sharply with time and reached a plateau at day 7, whereas a slower healing occurred in the perichondrium-free model where maximal HWA appeared at day 14. Topical application of 100 ng of rhTGF-beta 1 per wound accelerated healing by increasing HWA in both models. The enhancement of healing by rhTGF-beta 1 was associated with increased collagen synthesis. The percent collagen synthesis in the rhTGF-beta 1 was doubled in the perichondrium-intact ulcers and increased 40% in the perichondrium-free ulcers. DNA synthesis in the perichondrium-intact ulcers was not altered by rhTGF-beta 1 when measured at day 5 by in vitro labeling with [3H]thymidine ([3H]TdR). Autoradiography indicated that the primary cells labeled in the wound tissue were epithelial cells and rhTGF-beta 1 enhanced the migration of these cells from the wound margin towards the center. To evaluate the effects of rhTGF-beta 1 on fibroblasts derived from the granulation tissue of the wound, cells were treated with increasing concentrations of rhTGF-beta 1 and DNA and collagen synthesis were determined. rhTGF-beta 1 elicited a biphasic change in percent collagen synthesis with a maximal increase of 50% at 20 pM followed by a decline. A twofold increase in [3H]TdR incorporation that plateaued at 1 nM was also observed. Our results indicate that the cellular responses to rhTGF-beta 1 differ in vivo and in vitro. The perichondrium-intact ulcers contain more wound tissue and have larger responses to rhTGF-beta 1 stimulation, which allows better examination of biochemical and cellular events. The in vivo mechanisms are multi-factorial, which may involve cell migration and recruitment as results of numerous cell/cell and cell/matrix interactions.
This prospective and comparative study was designed to determine the role of cancer pain and attitudes towards morphine in attenuating the intensity and duration of physical dependence following chronic morphine treatment. Morphine was administered via a stepwise ladder approach in order of oral, spinal and intravenous routes depending on the adequacy of analgesia. On-demand titration of a dose, either upward or downward, was liberal and unlimited. Withdrawal strategy was evaluated and initiated either by patients (PI group) or their families (FI group). The manifestation of physical dependence on morphine was compared between patients who successfully withdrew (total withdrawal), and patients who failed to withdraw (episodic withdrawal), from morphine for a period of more than two weeks. Eighty-eight out of 627 patients (14.1%) were excluded from our protocol; 75% of these exclusions were due to objections toward morphine as the major form of analgesic. Drop-out due to poorly tolerated side effects was relatively rare (18.2%). Fifty-four (10.0%) achieved total withdrawal and 212 (39.3%) experienced episodic withdrawal. Non-pain-related abstinence symptoms were highly prevalent but were tolerable for both groups. Pain-related symptoms were more exaggerated during episodic withdrawal. Intolerable pain, rather than physical dependence, contributed to the failure to withdraw from morphine. Among a total of 539, addiction was found in only one patient (0.18%) who began drug use long before entering our protocol. Attitudes towards morphine affect the acceptance of treatment and hasten the withdrawal strategy. Families were more anxious about morphine than the patients themselves which led to more aggressive, but less tolerable, withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
The analgesic efficacy, side effects, and satisfaction of patient-controlled analgesia (PCA) with intravenous and epidural morphine for postoperative pain were evaluated in this study. Twenty patients undergoing major joint replacement surgery were randomly allocated to intravenous PCA (IPCA) group or epidural PCA (EPCA) group. All patients had a standardized balanced anesthesia, and an epidural catheter was introduced after the operation in EPCA group. Postoperative pain relief was evaluated with verbal pain scale. The result showed that pain intensity and pain relief were similar in either group without significant difference (p greater than 0.05). Morphine consumption in IPCA group was 1.72 +/- 0.30 mg/h in the postoperative 0 - 12 h and 1.14 +/- 0.44 mg/h in 12 - 24 h. In EPCA group, relatively low doses of morphine were used, i.e., 0.20 +/- 0.07 mg/h in the postoperative 0 - 12 h and 0.17 +/- 0.07 mg/h in 12 - 24 h. Both groups showed an "incomplete" but satisfactory analgesia with relatively low doses of morphine. The "equianalgesic dose ratio" of IPCA to EPCA with morphine was approximately 8.5:1. Sedation was minimal in both groups. No respiratory depression developed in all patients. Nausea and vomiting were the most prominent side effects which might limit the usefulness of PCA. The incidence was 5 out of 10 patients in IPCA group and 4 out of 10 patients in EPCA group, despite under the treatment of droperidol (15 micrograms/kg, iv, prn) for most of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
A single application of recombinant human transforming growth factor beta 1 (rhTGF-beta 1) adjacent to cartilage was found to induce bone formation in rabbit ear full-thickness skin wounds. At doses that optimally promote soft tissue healing, 25-100 ng rhTGF-beta 1 per wound caused osseous tissue formation starting 21 days after wounding to reach a peak incidence and area of bone formation at day 42. Bone formation was followed by active remodeling, resulting in lower incidence and area of bone formation at days 56 and 70. The early phase of bone formation was located overlying the cartilage and involved perichondrial cells that appeared to differentiate directly into osteoblasts forming bone matrix without a cartilage precursor. Cartilage was replaced with bone at later time points. rhTGF-beta 1 was able to increase the ratio of osteoblasts to osteoclasts lining the trabecular surface of bone and thus increase the net amount of bone formation. The present studies suggest a potential therapeutic role for rhTGF-beta 1 in hard tissue repair.
The biologic effects of recombinant human bone morphogenetic protein-2b (BMP-2b = BMP-4) were studied and compared with transforming growth factor-beta 1 (TGF-beta 1) in fetal rat osteoblast-like (ROB) cells. Similar to the effects of TGF-beta 1, BMP-2b stimulated DNA and collagen synthesis as well as protein accumulation. Unlike TGF-beta 1, which inhibited alkaline phosphatase activity, BMP-2b enhanced enzyme activity eight-to ninefold over the control level. The present study demonstrates direct actions of BMP-2b on bone-associated cells to stimulate osteogenic phenotypes in vitro and provides a cellular mechanism for the induction of bone formation by BMP-2b in vivo.
In the present study, we have shown that insulin-like growth factor-I (IGF-I) was released by primary cultures of rat osteoblast-like (ROB) cells into the conditioned medium (CM). Dexamethasone (DEX) caused a dose-dependent inhibition of the IGF-I. At 10(-8) M, DEX reduced IGF-I level to 70% of the control value (P less than 0.05); at 10(-7) M DEX, the IGF-I level was further reduced to 60% of the control (P less than 0.01). The active vitamin D metabolite 1,25-dihydroxycholecalciferol [1,25(OH)2D3] slightly increased the IGF-I level, but the increase was not statistically significant. However, in combined treatments of 10(-7) M DEX and 10(-8) M of 1,25(OH)2D3, the inhibition of DEX was partially antagonized by the presence of 1,25(OH)2D3. Studies with metabolically radiolabeled IGF-I by immunoprecipitation indicated the changes of IGF-I in the CM reflected synthesis of the protein by the cells. The alteration of IGF-I level may mediate some of the actions of these steroid hormones on bone cells.
In the prokaryote Synechococcus RF-1, circadian changes in the uptake of l-leucine and 2-amino isobutyric acid were observed. Uptake rates in the light period were higher than in the dark period for cultures entrained by 12/12 hour light/dark cycles. The periodic changes in l-leucine uptake persisted for at least 72 hours into continuous light (L/L). The rhythm had a free-running period of about 24 hours in L/L at 29 degrees C. A single dark treatment of 12 hours could initiate rhythmic leucine uptake in an L/L culture. The phase of rhythm could be shifted by a pulse of low temperature (0 degrees C). The free-running periodicity was "temperature-compensated" from 21 to 37 degrees C. A 24 hour depletion of extracellular Ca(2+) before the free-running L/L condition reduced the variation in uptake rate but had little effect on the periodicity of the rhythm. The periodicity was also not affected by the introduction of 25 mm NaNO(3). The uptake rates for 20 natural amino acids were studied at 12 hour intervals in cultures exposed to 12/12 hour light/dark cycles. For eight of these amino acids (l-Val, l-Leu, l-Ile, l-Pro, l-Phe, l-Trp, l-Met, and l-Tyr), the light/dark uptake rate ratios had values greater than 3 and the rhythm persisted in L/L.
Past studies have found that the laboratory rat placed in a temperature gradient prefers temperatures that are markedly below its lower critical ambient temperature (LCT), whereas other rodents (e.g., mouse, hamster, and guinea pig) generally select thermal environments associated with minimal metabolic expenditure. To further study the rat's thermoregulatory behavior, a temperature gradient was designed to monitor the selected ambient temperature (STa) and motor activity (MA) of food-deprived rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains over a 22-h period. All three rat strains selected relatively cool STas of 21-26 degrees C during the first 1-3 h in the temperature gradient. This was followed by a gradual increase in the STa that peaked at 4 (F344) to 6 h (SD and LE) after being placed in the gradient. The LE strain had a significantly lower STa during the initial period in the gradient. There were slight decreases in the STa during the nocturnal phase in the F344 and SD strains concomitant with marked increases in MA. These results indicate that the rat requires a relatively long adjustment period in a temperature gradient before it exhibits STas that are associated with minimal metabolic expenditure. Given adequate time for accommodation, behavioral thermoregulatory responses of the rat appear to be similar to those of other rodents.