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Biomedical subjects

M H Chen

Publications and source records attributed to M H Chen.

At least 109 records · Page 6Linked to original sources
PubMed1997

Predictive variable selection for the multivariate linear model.

We develop a predictive Bayesian approach to variable selection in the multivariate linear model. A criterion derived from the Bayesian predictive density is proposed and a calibration is provided for it. Reference and informative priors are discussed, and an automated method that focuses on the response variable is proposed for specifying informative priors for the regression parameters. Relationships between the proposed criterion and other several well-known criteria are examined. Illustrative examples involving real data are given to demonstrate the methodology.

Asbestos↗
PubMed1997

Streptococcus adjacens endocarditis in a patient with nephrotic syndrome.

Streptococcus adjacens has never previously been reported as an etiologic organism of infective endocarditis in Taiwan. We describe a case of severe native valve endocarditis caused by S. adjacens, involving the mitral valve, the aortic valve, and the left atrium, in a 29-year-old woman with nephrotic syndrome on steroid therapy. Blood cultures yielded gram-positive cocci that grew poorly on blood agar but strongly on chocolate agar. Despite aggressive antibiotic treatment, the patients continued to have high fever and progressive congestive heart failure, which necessitated surgical intervention. Symptoms were alleviated after surgery; teicoplanin was continued for 4 weeks and the patient remained symptom-free at the 6 month follow up. To our knowledge, this is the first reported case of bacterial endocarditis involving the left atrium without preexisting myxoma.

Adult↗
PubMed1996

Antibacterial agents that inhibit lipid A biosynthesis.

Lipid A constitutes the outer monolayer of the outer membrane of Gram-negative bacteria and is essential for bacterial growth. Synthetic antibacterials were identified that inhibit the second enzyme (a unique deacetylase) of lipid A biosynthesis. The inhibitors are chiral hydroxamic acids bearing certain hydrophobic aromatic moieties. They may bind to a metal in the active site of the deacetylase. The most potent analog (with an inhibition constant of about 50 nM) displayed a minimal inhibitory concentration of about 1 microgram per milliliter against Escherichia coli, caused three logs of bacterial killing in 4 hours, and cured mice infected with a lethal intraperitoneal dose of E. coli.

Amidohydrolases↗
PubMed1996

A genetic defect in phosphatidylcholine biosynthesis triggers apoptosis in Chinese hamster ovary cells.

We have investigated the cell death of a Chinese hamster ovary mutant (MT-58) with a thermo-sensitive CTP:phosphocholine cytidylyltransferase, the rate-limiting enzyme of the CDP-choline pathway for phosphatidylcholine biosynthesis (Esko, J. D., Wermuth, M. M., and Raetz, C. R. H. (1981) J. Biol. Chem. 256, 7388-7393). After MT-58 cells were shifted to the restrictive temperature of 40 degrees C, the cytidylyltransferase was inactivated immediately leading to a decrease in phosphatidylcholine biosynthesis and cell death. DNA content and number of cells in the S phase decreased significantly in the dying MT-58 cells according to flow cytometrical analyses. The fragmentation of genomic DNA was detected by DNA ladders in agarose gel and release of the prelabeled genomic DNA into cytosolic fractions 14 h after the temperature shift. The dying cells underwent a dramatic reduction of cellular volume while maintaining the membrane containment of cellular contents. These events indicated that the inactivation of cytidylyltransferase triggered apoptosis in Chinese hamster ovary cells. This is the first report that apoptosis was induced in cultured cells, not by an added agent, but by a mutation in phospholipid biosynthesis.

Animals↗
PubMed1996

Cytotoxic effects of gemcitabine-containing regimens against human non-small cell lung cancer cell lines which express different levels of p185neu.

A novel pyrimidine analogue, gemcitabine, has been found to inhibit DNA replication and repair. We speculated that gemcitabine in combination with DNA-damaging agents might be more active against high- than low-p185neu expressing non-small cell lung cancer (NSCLC) cells because the high-p185neu expressors were proposed to posses a more effective DNA repair ability. We therefore compared the combination effects of gemcitabine plus cisplatin, gemcitabine plus etoposide, and cisplatin plus etoposide in a panel of 12 NSCLC cell lines. We also investigated the correlations between the level of p185neu and the cytotoxicities of each single agent and the three combinations. We found that as single agents the cytotoxicities of cisplatin and etoposide but not gemcitabine were significantly correlated with the level of p185neu. In contrast to the tight cross-resistance between cisplatin and etoposide, gemcitabine demonstrated little cross-resistance to either etoposide or cisplatin. Both gemcitabine-containing combinations demonstrated equivalent or more active cytotoxicities compared to cisplatin plus etoposide, with gemcitabine plus cisplatin showing a greater synergistic activity which was effect (dose) dependent. The effect of cisplatin plus etoposide was not p185neu related, whereas gemcitabine-containing regimens, especially gemcitabine plus cisplatin, had a greater cytotoxicity against the high- than the low-p185neu expressors. Our findings indicate that gemcitabine in combination with cisplatin is active against NSCLC cells in vitro. The gemcitabine-cisplatin interaction is more active than the etoposide-cisplatin interaction in cells with high-p185neu expression.

Antimetabolites, Antineoplastic↗
PubMed1996

Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes.

In vitro studies in patients with hepatitis B virus (HBV) infection have suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is the most important effector pathway in eliminating infected cells. The recognition is implicated in the endogenously processed HBV antigens in the context of HLA class I molecules presented on the liver cell membrane. However, the naturally occurring HBV peptide antigens have not yet been demonstrated. We report here that a naturally processed peptide antigen P2 was isolated from HLA class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence that, in hepatitis B patients, antigenic peptides of HBV were processed by hepatocytes, presented with the class I MHC molecules, and recognized by CD8+ CTLs.

Adult↗
PubMed1996

Correlations between intrinsic chemoresistance and HER-2/neu gene expression, p53 gene mutations, and cell proliferation characteristics in non-small cell lung cancer cell lines.

Using a panel of 20 non-small cell lung cancer (NSCLC) cell lines established from previously untreated patients, we investigated the relationships between intrinsic chemoresistance (to four agents used commonly in the therapy of NSCLC) and HER-2/neu gene expression (which encodes glycoprotein p185neu), p53 gene mutations, and cell proliferation characteristics. Our results demonstrated that high p185neu expression was correlated with chemoresistance, low S-phase fractions, and long doubling times. By contrast, cell lines expressing relatively low levels of p185neu were relatively chemosensitive and had higher S-phase fractions and shorter doubling times. Although mutation of the p53 gene was a common event in this panel of cell lines (present in 18 of 20 lines), there was no relationship between mutations at any specific codon and chemoresistance or cell proliferation characteristics. Multivariate analysis revealed that the level of p185neu was the only independent predictor for chemoresistance to doxorubicin, etoposide, and probably cisplatin. Although intrinsic chemoresistance almost certainly is a multifactorial process, overexpression of p185neu may be an important factor in the chemoresistance of NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Laparoscopically assisted abdominal aortic aneurysm repair. A report of 10 cases.

BACKGROUND: Laparoscopic surgery decreases postoperative pain and length of hospital stay. Whether laparoscopically assisted abdominal aortic aneurysm (AAA) repair can be safely and reliably performed is unknown. This prospective study was designed to establish the feasibility of laparoscopically assisted AAA repair and its effects on intraoperative and postoperative variables. METHODS: With IRB approval, 10 patients with infrarenal AAA requiring a tube graft underwent laparoscopically assisted AAA repair. The procedure consisted of laparoscopic dissection of the aneurysm neck and iliac vessels. Then, through an 8-11-cm minilaparotomy, a standard endoaneurysmorrhaphy was performed. Data included laparoscopic and total operative times, blood loss, fluid requirements, duration of nasogastric suction (NGT), and lengths of intensive care unit (ICU) and postoperative hospital stays. RESULTS: Laparoscopically assisted AAA was completed in nine of 10 patients. The first patient was converted to a standard incision because the aneurysm neck could not be adequately dissected. Laparoscopic and total operative times were 1.8 +/- 0.4 and 4.5 +/- 0.7 h, respectively. Mean blood loss was 1 +/- 0.6 l. Intraoperative fluid requirement was 6.6 +/- 1.3 l. The duration of NGT suction was 1.8 +/- 1.0 days. The ICU stay was 2.1 +/- 0.8 days and hospital stay was 6.7 +/- 2.5 days. There were two minor complications and no deaths. CONCLUSIONS: Laparoscopically assisted AAA repair is technically feasible with acceptable blood loss, operative time, morbidity, and mortality. Potential advantages may be early removal of the NGT and shorter ICU and hospital stays. Prospective randomized trials are needed to determine if laparoscopically assisted AAA repair is advantageous.

Aged↗
PubMed1996

Intracardiac echocardiography: in vitro and in vivo validation for right ventricular volume and function.

To determine the feasibility and accuracy of intracardiac ultrasonography (ICUS) for the measurement of right ventricular (RV) volumes and function, a 10 MHz ICUS catheter was used in an in vitro and in vivo model. In the in vitro study, 16 sheep hearts were imaged. Sequential cross-sectional images from RV apex to base were recorded during a calibrated pullback. Volumes were calculated by applying Simpson's algorithm. ICUS-obtained volumes correlated well with actual volumes (standard error of estimate [SEE] = 2.3 ml, r = 0.98). For the in vivo study, a beating-heart canine model was used (31 hemodynamic stages in six dogs). Actual volumes were measured by an intracavitary balloon connected to an external column. Sequential cross-sectional images were recorded during the ICUS catheter pullback from apex to base of the RV, and volumes calculated by Simpson's algorithm. Good correlations were observed between ICUS and actual values for diastolic (SEE = 4.1 ml, r = 0.97), systolic (SEE = 3.4 ml, r = 0.96), and ejection fraction (SEE = 3.1%, r = 0.87) values. This new technique can accurately quantitate RV volumes, can function both in vitro and in vivo, and has the potential for increasing applications to questions of clinical and research interest.

Algorithms↗
PubMed1996

Effects of a program on symmetrical posture in patients with hemiplegia: A single-subject design.

OBJECTIVES: Asymmetrical posture during static stance has been identified as a common problem in persons with hemiplegia. This study examined the effect of an activity-based therapy regimen on symmetric weight bearing and midline position of center of gravity (COG) in three adult subjects with hemiplegia. METHOD: An ABAB single-subject design was used. The intervention program, including sanding in front of a standing table and play a bean bag game, was introduced for 30 min each day during each intervention phase. Quantitative measurements of the weight distribution and the midline position of COG were taken with the Balance Master System (version 2.20). RESULTS: Visual inspection and statistical analysis of the data revealed a significant improvement in symmetric weight distribution and midline position of COG. The study suggests that this program may be a promising alternative to a variety of postural rehabilitation programs for persons with hemiplegia. CONCLUSION: Insecurity caused by poor stabilization and abnormal reactions to body weight bearing in an antigravity position might contribute to asymmetric postures. Results of this study suggest that an activity-oriented program can be effective in helping the persons with hemiplegia achieve symmetric stances.

Aged↗
PubMed1996

Laparoscopic aortic replacement in the porcine model: a feasibility study in preparation for laparoscopically assisted abdominal aortic aneurysm repair in humans.

BACKGROUND: Current laparoscopic vascular techniques have centered around aortofemoral bypass for the treatment of patients with aortic occlusive disease. However, the majority of aortic surgeries are performed for the treatment of aortic aneurysmal disease. With this mind, we undertook this study to assess the feasibility of laparoscopic aortic replacement in the porcine model in preparation for laparoscopically assisted abdominal aortic aneurysm (AAA) repair in humans. STUDY DESIGN: Twenty-three female pigs weighing between 35 and 40 kg underwent laparoscopic aortic dissection by either a transabdominal or retroperitoneal approach. The infrarenal aorta was laparoscopically dissected, isolated, and cross clamped. Then a custom designed cuffed polytetrafluoroethylene graft was inserted. After reestablishing and confirming distal flow, the animals were sacrificed. RESULTS: Fifteen functioning aortic grafts were placed in 21 animals who had the transabdominal approach. One functioning graft was placed in the retroperitoneal group. Complications included bladder, ureteral, inferior vena cava, renal vein, and aortic injuries. By the end of the study, the operative time was reduced from six to less than two hours; blood loss was reduced from 1,000 to 150 mL; and cross-clamping time was reduced from 60 to 15 minutes. CONCLUSIONS: In the porcine model, laparoscopic abdominal aortic replacement is associated with a significant learning curve. However, this method of repair is technically feasible and warrants further investigation in the treatment of AAA in humans.

Animals↗
PubMed1996

Effect of retinoic acid on wound healing of laser burns to porcine retinal pigment epithelium.

OBJECTIVE: To determine the effect of retinoic acid on wound healing of laser burns to explants of porcine retinal pigment epithelium (RPE). DESIGN: With the help of a mirrored attachment to a Coherent argon laser, laser burns (spot size 100 mu, power 500 mW, duration 0.2 seconds) were performed in 12 explants. The explants were then cultured in the presence (six explants) or absence (six explants) of 1 microM retinoic acid. Two explants in either group were recovered 4, 8 and 12 days after treatment for histologic study and scanning electron microscopy. OUTCOME MEASURE: Mean burn area remaining after culture. RESULTS: The area of wound remaining unhealed in the presence of retinoic acid was significantly larger than the area of wound remaining unhealed in the absence of retinoic acid at each time point. CONCLUSIONS: Retinoic acid inhibited wound healing of laser burns to porcine RPE. This effect may illustrate a role for retinoic acid in the pharmacotherapy of proliferative disorders.

Animals↗
PubMed1996

CTP: phosphocholine cytidylyltransferase is both a nuclear and cytoplasmic protein in primary hepatocytes.

CTP:phosphocholine cytidylyltransferase (CT) has recently been reported to be a predominantly intranuclear enzyme in several cell lines (Wang et al., J. Biol. Chem. 268, 5899-5904 (1993)). This contrasts with previous reports that CT was a cytosolic protein that translocated to the endoplasmic reticulum upon activation. The aim of the present study was to compare the localization of CT in CHO cells and in primary rat hepatocytes. Indirect immunofluorescence of CHO cells revealed a largely nuclear localization of the CT. On the other hand, immunogold electron microscopy and biochemical studies showed a similar density of distribution of CT between the nucleus and cytoplasm. In primary rat hepatocytes immunofluorescence studies indicated that CT was largely cytoplasmic. Studies by immunogold electron microscopy of rat hepatocytes demonstrated that the enzyme was homogeneously distributed throughout all cytoplasmic regions and the nucleoplasm. This result was confirmed by biochemical studies using digitonin and streptolysin O, which permeabilizes the plasma membrane of cells. Enucleation studies indicated that in CHO cells 76% of the CT activity was in the nuclear fraction, whereas in hepatocytes only 32% was recovered in this fraction. The data indicate that CT is found both in nuclear and cytoplasmic fractions of primary hepatocytes and is not predominantly a nuclear enzyme.

Animals↗
PubMed1995

Structure of Saccharomyces cerevisiae alpha-agglutinin. Evidence for a yeast cell wall protein with multiple immunoglobulin-like domains with atypical disulfides.

alpha-Agglutinin of Saccharomyces cerevisiae is a cell wall-associated protein that mediates cell interaction in mating. Although the mature protein includes about 610 residues, the NH2-terminal half of the protein is sufficient for binding to its ligand a-agglutinin. alpha-Agglutinin20-351, a fully active fragment of the protein, has been purified and analyzed. Circular dichroism spectroscopy, together with sequence alignments, suggest that alpha-agglutinin20-351 consists of three immunoglobulin variable-like domains: domain I, residues 20-104; domain II, residues 105-199; and domain III, residues 200-326. Peptide sequencing data established the arrangement of the disulfide bonds in alpha-agglutinin20-351. Cys97 is disulfide-bonded to Cys114, forming an interdomain bond between domains I and II. Cys202 is bonded to Cys300, in an atypical intradomain disulfide bond between the A and F strands of domain III. Cys227 and Cys256 have free sulfhydryls. Sequencing also showed that at least two of three potential N-glycosylation sites with sequence Asn-Xaa-Thr are glycosylated. At least one of three Asn-Xaa-Ser sequences is not glycosylated. No residues NH2-terminal to Ser282 were O-glycosylated, whereas Ser282, and all hydroxy amino acid residues COOH-terminal to this position were modified. Therefore O-glycosylated Ser and Thr residues cluster in the COOH-terminal region of domain III, and the O-glycosylation continues into a Ser/Thr-rich sequence that extends from domain III to the COOH-terminal of the full-length protein.

Agglutinins↗
PubMed1995

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses.

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.

Animals↗
PubMed1995

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.

Administration, Oral↗
PubMed1995

Sex differences in perioperative and long-term cardiac event-free survival in vascular surgery patients. An analysis of clinical and scintigraphic variables.

BACKGROUND: Little information is available regarding the occurrence of perioperative and late cardiac events in women with vascular disease. The current study was performed to examine whether sex-specific differences exist in these outcomes in a large population of vascular surgery patients and to determine the value of clinical and dipyridamole thallium variables in predicting myocardial infarction and cardiac death. METHODS AND RESULTS: Preoperative dipyridamole thallium imaging was performed in 567 vascular surgery patients, including 380 men and 187 women. The incidence of nonfatal myocardial infarction and cardiac death was noted during the perioperative period and during a follow-up period of 50 +/- 5 months. Fixed and reversible thallium perfusion abnormalities were more common in men than in women (P < .001 and P = .004, respectively). Perioperative cardiac event rates were similar in men and women, 8.4% and 7.5%, respectively (P = .07). A transient thallium defect was associated with an increased risk of cardiac events by 3.9-fold in men (CI, 1.5 to 10.2) and 5.5-fold in women (CI, 1.4 to 22). Various clinical factors also were predictive of events but demonstrated substantial sex differences. For example, dipyridamole-induced ST-segment depression was strongly associated with perioperative events in men but not in women. There were 22 nonfatal myocardial infarctions and 29 cardiac deaths in men during the follow-up period, with comparable event rates noted for women. Cardiac event-free survival rates also were similar for men and women (P = .40). Multivariate analysis demonstrated that a history of heart failure was an important prognostic variable for both sexes, as was a fixed thallium defect. Significant sex differences in the predictive value of other clinical factors for late cardiac events was apparent. CONCLUSIONS: The present study demonstrates that (1) thallium perfusion defects are more common in men; (2) transient thallium defects are associated with perioperative myocardial infarction and cardiac death in both sexes; (3) long-term survival rates after vascular surgery are similar between men and women; (4) a fixed perfusion defect is predictive of late cardiac events in women, with a trend noted in men; and (5) sex-specific differences were noted with regard to the prognostic value of various clinical risk factors. Therefore, dipyridamole thallium plays a significant role in the assessment of perioperative and long-term prognosis for both male and female vascular surgery patients. On the basis of these observations, modifications in risk stratification based on sex may be appropriate for men and women with vascular disease.

Aged↗