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D Chen

Publications and source records attributed to D Chen.

At least 595 records · Page 33Linked to original sources
PubMed1996

The effects of N-methyl-D-aspartate agonists and antagonists on isolated bovine cerebral arteries.

This pharmacologic study examines the direct cerebrovascular effects of N-methyl-D-aspartate (NMDA) receptor agonists and antagonists to determine whether large cerebral arteries have NMDA receptors. Bovine middle cerebral arteries were cut into rings to measure isometric tension development in vitro. Two competitive agonists, L-glutamate and NMDA, each had negligible effects on ring tension in the absence of exogenous vasoconstrictors. L-glutamate (in high concentrations) produced direct relaxation of potassium (K+)-constricted arteries, but the relaxation was not selective for L-glutamate, D-glutamate, or mannitol. Relaxation with L-glutamate was abolished when it was isosmotically substituted in the K(+)-rich medium. NMDA (in the absence or presence of glycine) and two competitive antagonists, 2-amino-5-phosphopentanoic acid (AP5) and (+/-)-3-(s-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), each had little effect on the tone of arteries preconstricted with potassium or the stable thromboxane A2 analog U-46,619. Three noncompetitive antagonists (S(+)-ketamine, dizocilpine, and dextrorphan) and their steroeisomers (R(-)-ketamine, (-)MK-801, and levorphanol) each produced dose-dependent relaxation of K(+)- or U-46,619-constricted arteries; relaxation was not selective for the (+) or (-) stereoisomers. These results suggest that large cerebral arteries lack NMDA receptors mediating constriction or relaxation. All noncompetitive antagonists dilated cerebral arteries, but by mechanisms that were not stereospecific.

Animals↗
PubMed1996

Porcine gastroepiploic artery as an in vitro experimental model to study vasodilators in microsurgery.

Arterial vasospasm is a common problem in microsurgery. This pharmacological study compares seven vasodilators-lidocaine, papaverine, nicardipine, verapamil, diltiazem, sodium nitroprusside, and hydralazine-for their efficacy and potency in an experimental model of vasospasm. Porcine gastroepiploic arteries were cut into rings to measure isometric tension development in vitro. The arteries were preconstricted with endothelin-1, a stable thromboxane A2 analogue, norepinephrine, or potassium, and then exposed to increasing concentrations of each vasodilator. Every vasodilator except hydralazine and sodium nitroprusside was efficacious in producing near-maximal relaxation of arteries preconstricted with any vasospastic substance. The five efficacious vasodilators differed markedly in potency, as reflected in the concentrations producing half-maximal relaxation. The order of potency was nicardipine < or = verapamil or diltiazem < papaverine < lidocaine. This study suggests that nicardipine would be the most potent vasodilator for systemic or direct intra-arterial administration. Papaverine and lidocaine, in concentrations employed clinically, were both efficacious as topical vasodilators.

Animals↗
PubMed1996

Distal femoral fixation: a laboratory comparison of the 95 degrees plate, antegrade and retrograde inserted reamed intramedullary nails.

A biomechanical cadaver study was performed to compare the stability of three standard distal femoral fixation techniques. Eighteen mildly osteoporotic femurs were selected, based on a dual-energy x-ray absorption scanning bone density of 0.3-0.5 g/cm2 and a Singh index of III-IV. After initial mechanical characterization of these intact femurs, a distal femoral osteotomy was created, reduced, and stabilized under compression using random assignment to one of three methods of fixation: (a) six-hole 95 degrees supracondylar plate, (b) retrograde inserted statically locked supracondylar intramedullary nail, and (c) antegrade inserted statically locked Russell-Taylor nail. The instrumented femurs were mechanically tested, a 1-cm gap created, and the femurs retested. The specimens were finally loaded to failure in A-P three-point bending. The 95 degrees plate provided significantly stiffer fixation than the supracondylar intramedullary nail or Russell-Taylor nail in both a compressed transverse and gap distal femoral osteotomy model. The Russell-Taylor nail provided the least rigid fixation. The 95 degrees plate and Russell-Taylor nail had statistically significant greater loads to failure than the supracondylar intramedullary nail. These results support the use of a 95 degrees plate when maximum rigidity of fixation or maximum compression is desired.

Biomechanical Phenomena↗
PubMed1996

Assessing radiation and light field congruence with a video based electronic portal imaging device.

Projected light fields are used on treatment simulators and teletherapy treatment units to delineate the size and position of the radiation beam. Any discrepancy between these fields will lead to a systematic field placement error, with possibly serious implications with regard to the accuracy of the delivered dose distribution in the patient. Conventionally, film has been used for regular quality control tests of light and radiation field congruence, but this is a time consuming method and is not suitable for daily checks. A new method is described that uses a specially designed test phantom, a video-based electronic portal imaging device and a personal computer to test for radiation and light field congruence on treatment accelerators. This method consists of aligning the test phantom in the light field of a treatment linac and acquiring an electronic portal image. A computer program then automatically analyzes the image and determines the degree of congruence between the two fields. The final result of the test is a go, warning, or no go decision depending on the extent of misalignment between the light and radiation fields. Two algorithms were tested for reproducibility (<0.4 mm), sensitivity to noise (<0.2 mm), and positional accuracy (<0.4 mm) and are shown to give results comparable to the conventional film method. Daily testing of field congruence over a period of 84 days demonstrated differences in the results determined by the two algorithms of less than 0.1 +/- 0.2 mm (standard deviation) at 6 MV and 0.22 +/- 0.13 mm at 23 MV. Routine testing is possible as the effort and time required are minimal, and the test can be performed during daily routine start-up procedures.

Algorithms↗
PubMed1996

Evaluation of purified UspA from Moraxella catarrhalis as a vaccine in a murine model after active immunization.

Moraxella catarrhalis causes otitis media, laryngitis, and respiratory infections in humans. A high-molecular-weight outer membrane protein from this bacterium named ubiquitous surface protein A (UspA) is present on all isolates. A monoclonal antibody (MAb) to UspA that recognizes a conserved epitope of this protein has been shown to promote pulmonary clearance of bacteria in passively immunized mice. In the present study, M. catarrhalis heterologous isolates were screened by dot blot with a panel of four additional MAbs specific for surface-exposed epitopes of UspA from M. catarrhalis isolate 035E. Three of the MAbs were specific for 035E, and the fourth reacted with 17 (74%) of the 23 isolates tested. Thus, UspA contains highly conserved, semiconserved, and variable surface-exposed epitopes. The UspA was purified from the 035E isolate by ion-exchange and size-exclusion chromatography, formulated with the adjuvant QS-21, and used to immunize BALB/c mice. Upon pulmonary challenge with either 035E or the heterologous isolate TTA24, significantly fewer bacteria were recovered from the lungs of immunized mice 6 h postchallenge than from control mice. The immune sera from mice or guinea pigs contained high titers of antibodies to the homologous isolate and heterologous isolates in a whole-bacterial-cell enzyme-linked immunosorbent assay. Sera against UspA, whether prepared in mice or guinea pigs, had complement-dependent bactericidal activity toward homologous and 11 heterologous M. catarrhalis isolates. These results indicate that the conserved epitopes of the UspA are highly immunogenic and elicit broadly reactive and biologically functional antibodies. UspA may offer protection against M. catarrhalis infections and is being further evaluated as a vaccine candidate.

Animals↗
PubMed1996

Comparison between activation of ornithine decarboxylase and histidine decarboxylase in rat stomach.

We compared the responses of rat stomach ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) to food intake, oral treatment with antisecretagogues, NaHCO3, and hypertonic NaCl, antrectomy, intravenous infusion of gastrin-17, the selective cholecystokinin (CCK)-B/gastrin receptor antagonist L-365,260, and the somatostatin analogue RC-160. The serum gastrin concentration and oxyntic mucosal ODC and HDC activities were higher in freely fed rats than in fasted rats. Food intake in fasted rats raised the serum gastrin concentration and the ODC and HDC activities. Ranitidine, omeprazole, and NaHCO3 raised the serum gastrin concentration and activated ODC and HDC. Hypertonic NaCl raised the ODC activity 200-fold, whereas circulating gastrin and HDC activity were increased only moderately. Infusion of gastrin-17 activated HDC but not ODC. L-365,260 prevented the activation of HDC but not of ODC in response to food intake and treatment with omeprazole, NaHCO3, or hypertonic NaCl. Antrectomy prevented the food- and omeprazole-evoked rise in oxyntic mucosal HDC activity but not the rise in ODC activity. RC-160 suppressed HDC activity after food intake and treatment with omeprazole, NaHCO3, or NaCl. In contrast, RC-160 suppressed omeprazole- and NaHCO3-evoked ODC activation but not that evoked by food intake or NaCl. The results support the view that HDC in the oxyntic mucosa is activated by gastrin and suppressed by somatostatin. The induction of ODC is not mediated by gastrin; ODC activation appears to be related to acid inhibition per se or to mucosal maintenance and repair; somatostatin, or rather the lack of it, might contribute to the induction of ODC after acid blockade. The mechanism behind the activation of rat stomach ODC seems to differ depending on the type of stimulus.

Analgesics↗
PubMed1996

Impaired mobilization of intracellular calcium in neonatal platelets.

Abnormalities in platelet functions including aggregation and the release reaction have long been recognized to be present in neonatal platelets. Because calcium is an important mediator of many platelet functions, we have investigated the mobilization of calcium in neonatal platelets. All umbilical cord blood samples were obtained from healthy, full term gestations. Changes in cytoplasmic calcium levels were monitored using Fura-2 as a fluorescent probe. Fura-2-loaded washed platelets were stimulated with the agonists collagen (2 micrograms/mL) or thrombin (1.0 U/mL). When compared with adult controls, intracellular calcium release in the platelets of the neonate was significantly impaired in response to these agonists. Mean levels for calcium release in adults versus neonates in response to collagen were 168 +/- 120 nM (+/-SD, n = 10), and 61 +/- 69 nM (n = 7, p < 0.05). A decrease in response to thrombin was also observed [1296 +/- 503 nM (n = 8) in adults versus 603 +/- 482 nM (n = 7) in neonates, p < 0.025]. Results similar to those observed with unpaired neonatal and adult platelets were also obtained when neonatal platelets (n = 5) were compared with their paired maternal controls. In further studies, we have documented that the calcium content of the dense tubular system was normal in the neonatal platelet, indicating that the observed impairment in calcium mobilization in the neonate was not due to a decrease in calcium stores. The previously documented abnormalities in neonatal platelet function appear to be due to the impaired mobilization of this important intracellular mediator.

Adult↗
PubMed1996

Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.

BACKGROUND: Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. METHODS: In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. RESULTS: alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. CONCLUSION: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.

Animals↗
PubMed1996

Cholecystokinin-A and cholecystokinin-B/gastrin receptor mRNA expression in the gastrointestinal tract and pancreas of the rat and man. A polymerase chain reaction study.

BACKGROUND: Gastrin and cholecystokinin (CCK) are thought to exert trophic effects on the gastrointestinal tract and pancreas. Two types of receptors have been cloned, CCK-A and CCK-B/ gastrin. We have examined the occurrence of CCK-A and CCK-B receptor mRNA in the brain, digestive tract, pancreas, and kidney of the rat and man by Northern blot and reverse transcribed polymerase chain reaction (RT-PCR). METHODS: Total RNA was isolated from rat tissues and reverse transcribed into cDNA. cDNA from brain, kidney, and pancreas of the rat and man and from human whole stomach were commercially available. Northern blot and a PCR technique based on Taq polymerase-antibody interaction and using CCK-A and CCK-B receptor-specific primers, followed by Southern blot analysis, were the methods used. RESULTS: By means of Northern blots, CCK-A receptor mRNA was detected in rat fundus mucosa and pancreas but not in the remaining GI tract or brain. By means of RT-PCR, CCK-A receptor mRNA was demonstrated in the brain and the mucosa of the fundus, antrum, duodenum, and colon, kidney, pancreas and pancreatic islets. CCK-B receptor mRNA was detected by Northern blot analysis in the brain and the fundus mucosa but not in the rest of the digestive tract and not in the pancreas, pancreatic islets, or kidney. By RT-PCR, expression of CCK-B receptor mRNA could also be detected in antrum mucosa. In man, CCK-A receptor mRNA was detected in the brain, stomach, pancreas, and kidney, whereas CCK-B receptor mRNA was found in the brain, stomach, and pancreas but not in the kidney. Cloning and DNA-sequence analysis of the PCR-amplified rat and human CCK-A and CCK-B receptor DNA fragments, which cover the protein-encoding regions of the intracellular loop C3, showed complete sequence homology as compared with published rat and human sequences. CONCLUSIONS: It appears unlikely that CCK will have effects in the ileum, at least not effects mediated by CCK-A receptors. It also appears unlikely that physiologic concentrations of gastrin in the circulation will promote growth (or exert other effects) in the pancreas, duodenum, ileum, and colon, since CCK-B receptor mRNA is not expressed or is poorly expressed in these tissues.

Animals↗
PubMed1996

Gastrin does not stimulate growth of the rat pancreas.

BACKGROUND: Gastrin is thought to stimulate growth of the pancreas via gastrin/cholecystokinin (CCK)-B-type receptors. The aim of the present study was to examine the trophic response of the pancreas to exogenous gastrin or to hypergastrinemia of endogenous origin and to hypogastrinemia with or without concomitant hyperCCKemia. METHODS: Hypergastrinemia was induced in male Sprague-Dawley rats by continuous infusion of human Leu15-gastrin-17 (5 nmol/kg/h, subcutaneously), by removal of the acid-producing part of the stomach (fundectomy), or by treatment with omeprazole (400 mumol/ kg/day, orally). Hypogastrinemia was induced by antrectomy or by gastrectomy. HyperCCKemia was induced by pancreaticobiliary diversion (PBD). The rats were killed 10 days or 8 weeks after the operations or treatments. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The pancreatic weight and DNA content were determined. RESULTS: Gastrin infusion, omeprazole treatment, and fundectomy greatly increased the serum gastrin concentration. The resulting levels were very similar in the three groups and probably represent the maximum attainable physiologic serum gastrin concentration. Whereas gastrin infusion or omeprazole treatment (hypergastrinemia) and antrectomy (hypogastrinemia) were without effect on the weight and DNA content of the pancreas, gastrectomy (hypogastrinemia) and fundectomy (hypergastrinemia) increased the weight and DNA content. PBD (hyperCCKemia) greatly increased the weight and DNA content of the pancreas. PBD plus fundectomy, PBD plus gastrectomy, PBD plus antrectomy, and PBD plus omeprazole increased the weight and DNA content of the pancreas, as did PBD alone. CONCLUSION: CCK is a physiologically important trophic stimulus for the rat pancreas, but gastrin is not. The increase in pancreatic weight and DNA content after fundectomy and gastrectomy cannot be explained by means of either gastrin or CCK.

Animals↗
PubMed1996

Rat stomach enterochromaffin-like cells are not stimulated by pylorus ligation. A biochemical and ultrastructural study.

BACKGROUND: The enterochromaffin-like (ECL) cells in the rat oxyntic mucosa produce histamine and contain cytoplasmic granules, microvesicles, and secretory vesicles. The cells respond to gastrin by the release of histamine (associated with loss of secretory vesicles), which is thought to mediate the gastrin-induced stimulation of the parietal cells. Gastric acid secretion is stimulated also by vagal excitation, which can be induced, for instance, by pylorus ligation. The present study addresses the question whether the ECL cells are involved in the acid response to pylorus ligation. METHODS: Rats were subjected to pylorus ligation and killed 4 or 16 h later. Other rats were subjected to sham operation (laparotomy). Some of the rats received human Leu15-gastrin-17 (5 nmol/kg/h) by intravenous infusion for 30 or 60 min before being killed. The serum gastrin concentration, the oxyntic mucosal histidine decarboxylase (HDC) activity, HDC mRNA concentration, histamine concentration, and gastric acid output were measured. Specimens from the oxyntic mucosa were processed for transmission electron microscopy. Electron micrographs of ECL cells were analyzed planimetrically. RESULTS: The gastric acid output was high, but the serum gastrin concentration was not affected by the pylorus ligation. The HDC activity and the level of HDC mRNA in the oxyntic mucosa were reduced, but the histamine concentration was unchanged. The secretory vesicles and granules of the ECL cells were unaffected, whereas the number and volume density of the microvesicles were reduced. Gastrin administration to sham-operated and pylorus-ligated rats lowered the oxyntic mucosal histamine concentration and increased the HDC activity in both groups. CONCLUSIONS: ECL cells in the rat stomach do not mediate the gastric acid response to pylorus ligation, and ECL cells in the pylorus-ligated stomach retain their ability to respond to gastrin with activation.

Animals↗
PubMed1996

[Nosocomial bacterial infection in comprehensive intensive care unit].

OBJECTIVE: To establish the prevalence of nosocomial bacterial infection and changes in resistance in a comprehensive intensive care unit. METHODS: We retrospectively analyzed all the bacterial isolates of ICU, PUMC Hospital from 1989 to 1994, such as the species and resistance pattern. RESULTS: Among all bacterial isolates, the percentage of Gram-positive cocci steadily increased (16% in 1989, 33% in 1994), while that of Gram-negative bacilli decreased (84% in 1989, 67% in 1994). The most prevalent isolates of Gram-negative pathogens were Pseudomonas aeruginosa, Acinetobacter baumanii, inducible Enterobacteriaceae and Xanthomonas maltophilia, with imipenem and amikacin as the most susceptible antibiotics. Enterococci, oxacillin-resistant Staphylococcus epidermidis and oxacillin-resistant Staphylococcus aureus accounted for 44%, 21% and 10%, respectively. The resistant rate of these three Gram-positive bacteria to vancomycin were 19%, 0% and 0%. CONCLUSION: Understanding of the epidemiological data and changes of bacterial resistance profile is prerequisite to rational use of antibiotics, which is crucial to reducing the resistance of nosocomial infection pathogens.

Cross Infection↗
PubMed1996

Effect of captopril on intracellular free calcium ([Ca2+]i) of thymocytes in spontaneously hypertensive rats.

Hypertension is associated with dysfunction of the immune system. Intracellular free calcium ([Ca2+]i) was reportedly increased in immune cells, such as lymphocytes and thymocytes, both in hypertensive patients and in animals. To evaluate if captopril has an effect on the immune system, [Ca2+]i in thymocytes was monitored during the development of hypertension from 4-24 weeks, and after treatment with captopril for 4 and 12 weeks in spontaneously hypertensive rats (SHR). SHR (n = 24) were treated with captopril at a dose of 20 mg/kg/day at 12 weeks of age after establishment of hypertension. Untreated SHR (n = 17) and normotensive Wistar Kyoto (WKY n = 14) served as control. [Ca2+]i of thymocytes was measured using Fura-2. It was found that [Ca2+]i of thymocytes decreased both in SHR and WKY from 4-12 weeks of age. From 12-24 weeks, [Ca2+]i in thymocytes remained at a constant level in WKY. However, [Ca2+]i in thymocytes increased significantly in SHR after 12 weeks. Captopril (CAP) treatment significantly lowered [Ca2+]i in thymocytes derived from SHR at 24 weeks. This treatment was associated with a moderate reduction in systolic blood pressure. Established hypertension in SHR is associated with increased [Ca2+]i in thymocytes. This may be indicative of immunological dysfunction. Captopril inhibits the increase in [Ca2+]i of thymocytes in SHR.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Alterations in the progression of cells through the cell cycle after exposure to alpha particles or gamma rays.

A G1-phase delay after exposure to alpha particles has not been report ed previously, perhaps because immortalized cell lines or cell lines from tumor cells were used in past studies. Therefore, we compared the effects of alpha particles (0.19 or 0.57 Gy) and approximately equitoxic doses of gamma rays (2 or 4 Gy) on progression of cells through the cell cycle in normal human skin fibroblasts. Cell cycle analyses were performed using flow cytometry by measuring incorporation of bromodeoxyuridine (BrdUrd) in each phase of the cell cycle up to 44 h after irradiation. We observed an alpha-particle-induced G1-phase delay in human skin fibroblasts even at the lowest dose, 0.19 Gy. At equitoxic doses, more pronounced and persistent G1-phase delays and arrests were observed in gamma-irradiated cultures in that increased fractions of the G1-phase cells remained BrdUrd- over the course of the study after gamma-ray exposure compared to cells exposed to alpha particles. In addition, G1-phase cells that became BrdUrd+ after gamma irradiation re-arrested in G1 phase, whereas BrdUrd+ G1-phase cells in alpha-particle-irradiated cultures continued cycling. In contrast, comparable percentages of cells were delayed in G2 phase after either alpha-particle or gamma irradiation. Both gamma and alpha-particle irradiation caused increases in cellular p53 and p2lCip1 shortly after the exposures, which suggests that the G1-phase delay that occurs in response to alpha-particle irradiation is dependent on p53 like the initial G1-phase delay induced by gamma rays.

Alpha Particles↗
PubMed1996

Characterization of the nonmuscle myosin heavy chain IIB promoter: regulation by E2F.

To identify DNA sequences important for the transcriptional regulation of the nonmuscle myosin heavy chain IIB (NMMHC-IIB) gene we isolated and sequenced genomic clones that contain the promoter of the gene for both human and mouse. In addition to considerable homology in the first (untranslated) exon (91%) we found 80% sequence identity in the 700 base pairs immediately upstream of the major start of transcription (+1) as well as significant homologies as far as 1500 base pairs upstream. The promoter region was characterized using luciferase reporter constructs transiently transfected into NIH3T3 cells. Consensus binding sites for several known transcription factors are present that are completely conserved between the mouse and human genes, including CRE/ATF, Sp1, CAAT, and the cell-cycle transcription factor E2F. Gel shift assays indicated that E2F can bind to its putative binding site in vitro. To test whether this site is functional we cotransfected NMMHC-IIB promoter constructs driving luciferase with a vector expressing E2F-1. The E2F-1 vector stimulated luciferase activity from an intact promoter whereas mutation of the site eliminates binding and diminishes transactivation. These data provide strong evidence that E2F or an E2F-related transcription factor is involved in the regulation of nonmuscle myosin expression.

3T3 Cells↗
PubMed1996

[Studies on inhibition of activated oncogene expression by antisense RNA].

In this paper, the sense and antisense mammalian expression vectors of T24-ras activated oncogene were introduced into cultured NIH3T3 cells in sense-->antisense and antisense-->sense orders. The transfected cells were selected by drug selection. The morphology change, Southern hybridization, frequency of soft agar colonies and the detection of P21 amount were investigated. The results showed that the sense recombinant could cause the malignant transformation of NIH3T3 cells while the antisense recombinant could inhibit this kind of transformation. Furthermore, the inhibitory effect varied according to the different transfected orders.

3T3 Cells↗