Search PubMed⌕ Search

Biomedical subjects

M C Chen

Publications and source records attributed to M C Chen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Contribution of ductal cells to cytokine responses by human pancreatic islets.

In type 1 diabetes, autoimmune destruction of pancreatic beta-cells has been attributed to cytokines released from infiltrating immunocytes. Exposure of isolated islets to cytokines leads to nitric oxide (NO) production, which can damage beta-cells. Because ductal cells are closely associated with human beta-cells, we examined whether they can contribute to this process. Isolated human ductal cells were cultured for 48 h with various cytokines. The combination of interleukin-1beta (IL-1beta) plus interferon-gamma (IFN-gamma) increased nitric oxide production 12-fold while stimulating mRNA expression of inducible nitric oxide synthase (iNOS). In this condition, 10-20% of cells positive for the cytokeratin-19 duct marker also stained positive for iNOS protein, whereas no positive cells were found in control preparations. Comparison of the magnitude of iNOS mRNA expression and nitric oxide production in these cells with that in isolated human islets suggests that >50% of total islet nitric oxide production might originate from associated ductal cells. It is concluded that ductal cells are a potential source of nitric oxide production in human islets infiltrated by cytokine-releasing immunocytes.

Adolescent↗
PubMed1999

Serosurvey for selected virus infections of wild carnivores in Taiwan and Vietnam.

Serum samples from two leopard cats (Felis bengalensis) and four Formosan gem-faced civets (Paguma larvata taivana) in Taiwan, September 1995, and nine leopard cats in Vietnam, August and December 1997, were examined for the prevalence of antibodies against feline parvovirus, feline herpesvirus type 1, feline calicivirus and feline immunodeficiency virus. All civets and nine of 11 leopard cats were shown to have antibodies against feline parvovirus (FPV), and FPV's were isolated from mononuclear cells in the peripheral blood of the six leopard cats.

Animals↗
PubMed1999

The role of interferon regulatory factor-1 in cytokine-induced mRNA expression and cell death in murine pancreatic beta-cells.

Combinations of cytokines, including interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), induce nitric oxide (NO) production and cell death in pancreatic islet cells. We have previously shown that these events are preceded by increased expression of the transcription factor interferon regulatory factor-1 (IRF-1). We utilized an IRF-1 knockout mouse (IRF-1-/-) to investigate the role of IRF-1 in cytokine-induced islet- and beta-cell gene expression and cell death. For this purpose, pancreatic islets or FACS-purified beta-cells were isolated from wild type (wt) or IRF-1-/- mice. These cells were exposed for different time points to IL-1beta (50 U/mI), IFN-gamma (1,000 U/ml) and/or TNF-alpha (1,000 U/ml) before being harvested for determination of viability (by nuclear dyes) and mRNA expression (by RT-PCR with specific primers). Following a 24 hours exposure to IL-1beta or IL-1beta + IFN-gamma, pancreatic islets isolated from IRF-1-/- mice presented a 30-50% reduction in medium nitrite accumulation and inducible NO-synthase (iNOS) expression. Interestingly, both wt and IRF-1-/- purified beta-cells failed to produce NO in response to IL-1beta alone, but presented a similar increase in nitrite accumulation and iNOS expression following exposure to IL-1beta + IFN-gamma. The basal expression of MHC class I mRNA was lower in IRF-1-/- islet cells (30% reduction), but there was a similar 2-4 fold-increase in MHC expression in islet cells from both strains following cytokine exposure. IL-1beta induced serine protease inhibitor-3 (SPI-3; a putative cellular "defense" protein) mRNA expression in both wt and IRF-1-/- islets or beta-cells. IFN-gamma decreased the IL-1beta-induced SPI-3 expression in wt islets or beta-cells, but induced a 5-fold increase in the expression of this mRNA in IRF-1-/- islets cells, suggesting that IRF-1 mediates an inhibitory effect of IFN-gamma on SPI-3 expression. Treatment of whole islets for 3 days with IL-1beta + IFN-gamma induced significantly more islet cell death in wt than in IRF-1-/- mice (respectively 85 +/- 3% versus 31 +/- 4% dead cells). On the other hand, prolonged exposure (3-9 days) of FACS-purified beta-cells to the same cytokines, or a combination of 3 cytokines, led to a similar increase in cell death in both IRF-1-/- and wt islets. In conclusion, IRF-1 contributes to cytokine-induced islet iNOS expression and cell death. These effects are absent in purified beta-cells, suggesting that IRF-1 may mediate its effects on whole islets via activation of non-endocrine cells (e.g. macrophages and ductal cells) present in these preparations.

Animals↗
PubMed1999

Spontaneous bacterial peritonitis in adult patients with primary nephrotic syndrome.

BACKGROUND: Susceptibility to bacterial infection is a common problem in nephrotic patients. Spontaneous bacterial peritonitis, although characteristic of nephrotic children, is extremely rare in adults. METHODS: A retrospective review was performed on all adult patients with the discharge diagnoses of primary nephrotic syndrome and spontaneous bacterial peritonitis treated between 1986 and 1998 at Chang Gung Memorial Hospital in Kaohsiung, Taiwan. Ten patients were included in this study, 9 of them men and one woman. The average age was 30.5 years. RESULTS: All the patients had signs of active nephrosis and presented with diffuse abdominal pain, ascites, fever and/or chills. Thirty percent (3/10) of the causative pathogens were gram-positive bacteria and 60% (6/10) were gram-negative bacteria. One patient had sterile cultures. Seven patients recovered after antibiotic treatment for 1 to 2 weeks. Three patients died of septic shock. CONCLUSION: Therefore, to improve patient outcome, it is essential to establish a diagnosis early and to initiate broad-spectrum antimicrobial therapy even before culture results are available.

Adolescent↗
PubMed1999

Donor-site morbidity comparison between endoscopically assisted and traditional harvest of free latissimus dorsi muscle flap.

Endoscopically assisted harvest of free latissimus dorsi muscle flaps is being used more frequently in reconstructive microsurgery because it requires a smaller incision and leaves a more acceptable scar in the donor site. Donor-site morbidity was compared between groups of 22 latissimus dorsi muscles harvested using the endoscopically assisted technique and 26 using the traditional technique. The results revealed no statistically significant differences in the amount of intraoperative bleeding, the incidence of postoperative hematoma and seroma, and the incidence of donor-site wound infection as assessed by the surgeon. However, a patient questionnaire revealed that even though it did not reach a statistically significant difference, endoscopically assisted harvest of the latissimus dorsi muscle had less pain and allowed earlier and better movement of the upper extremity of the donor site. The patients' attitudes and feelings about the scar and overall satisfaction were also higher in the endoscopic group, which demonstrated a statistically significant difference.

Endoscopy↗
PubMed1998

Radiofrequency and cryoablation of atrial fibrillation in patients undergoing valvular operations.

BACKGROUND: Previous studies have shown that the maze operation can restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation. The purpose of this study was to test the feasibility of the application of radiofrequency and cryoablation as an alternative to the classic maze operation. METHODS: Twelve patients undergoing mitral valve procedures were included in this study. Radiofrequency and cryoablation were applied to create lesions in both atria to simulate the classic maze operation. RESULTS: There were two surgical deaths. At the mean follow-up of 10.25 months for the remaining 10 patients; 6 were in sinus rhythm, 2 in atrial rhythm, 1 in paroxysmal atrial tachycardia, and 1 in atrial fibrillation. Doppler echocardiography at 6-month follow-up showed emergence of biatrial transport function in 3 patients and right atrial contractility in 8. At 12-month follow-up of 5 patients, Doppler echocardiography showed biatrial transport function in 3 and right atrial contractility in 4. CONCLUSIONS: Our modified maze procedure during valvular operation is effective for achieving an acceptable success rate to restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation.

Adult↗
PubMed1998

Benzodiazepine binding site-interactive flavones from Scutellaria baicalensis root.

A benzodiazepine binding assay directed separation led to the identification of 3 flavones baicalein (1), oroxylin A (2), and skullcapflavone II (3) from the water extract of Scutellaria baicalensis root. Compounds 1, 2, and 3 interacted with the benzodiazepine binding site of GABAA receptors with a Ki value of 13.1, 14.6 and 0.36 micromol/L, respectively.

Animals↗
PubMed1998

Clinical diagnoses associated with histologic findings of fibrotic tissue and new bone in the inner ear.

Fibrotic tissue or new bone occurs following inner ear inflammation, fracture, or surgery. The prevalence is unknown and was investigated using the National Temporal Bone, Hearing and Balance Pathology Resource Registry database. A search yielded 264 temporal bones with diagnoses of otosclerosis, tumor, Meniere's disease, meningitis, labyrinthitis, chronic otitis media, autoimmune disease, temporal bone fracture, or sensorineural hearing loss. All autoimmune cases contained some new bone, whereas only 20% to 30% of the labyrinthitis/meningitis cases were reported to contain new bone. Otosclerosis, Meniere's disease, and otitis media had relatively few cases containing new bone. Although new bone may derive from surgical trauma, it is also likely to be a result of the disease process. It seems that all these disease processes may contain a common feature that acts as a stimulus to induce fibrosis or bone growth in the inner ear.

Autoimmune Diseases↗
PubMed1998

Immunohistochemical analysis of proliferating cells in a sterile labyrinthitis animal model.

Inflammatory reactions within the cochlea lead to the formation of fibrotic tissue and bone. To determine which cells are involved in the proliferation of the inflammatory response within the cochlea, sterile labyrinthitis was created by inoculating keyhole limpet hemocyanin (KLH) into the scala tympani of systemically sensitized animals. Cellular proliferation was assessed immunohistochemically using the monoclonal antibody Ki-67. Proliferating cells were identified among inflammatory cells and fibroblasts within the matrix, as well as in endosteal cells lining the scala tympani. Inflammatory and potential osteoprogenitor cells were labeled as late as 6 weeks after inoculation, suggesting the absence of a strong immunosuppressive mechanism. Endosteal cells may proliferate and secrete the extracellular matrix used by the inflammatory cells to move within the cochlear scalae. They may also participate in the ossification of the inflammatory matrix.

Animals↗
PubMed1998

Intercellular differences in interleukin 1beta-induced suppression of insulin synthesis and stimulation of noninsulin protein synthesis by rat pancreatic beta-cells.

The normal pancreatic beta-cell population exhibits intercellular differences in its responsiveness to glucose. This cellular heterogeneity allows glucose to regulate, in a dose-dependent manner, total rates of insulin synthesis and release. It may also predispose to intercellular differences in susceptibility to dysregulating agents. The present study examines whether this is the case for interleukin 1beta (IL-1beta), which is known to suppress glucose-induced insulin synthesis and release. The effects of the cytokine were compared on beta-cell subpopulations with, respectively, high and low sensitivity to glucose. These subpopulations were separated on the basis of differences in the cellular metabolic responsiveness to an intermediate glucose concentration (7.5 mmol/liter) and then cultured for 20 h at 5 or 20 mmol/liter with or without IL-1beta. The suppressive action of IL-1beta (0.1 ng/ml) occurred predominantly in glucose-activated beta cells, reducing their high rates of insulin synthesis and release by more than 80%. Glucose-unresponsive cells became subject to a similar inhibition after their activation during culture at 20 mmol/liter glucose. On the other hand, IL-1beta induced or enhanced the expression of several noninsulin proteins in both subpopulations. The IL-1beta-stimulated expression of inducible nitric oxide synthase (iNOS) and heat shock protein 70 was more marked in the glucose-responsive subpopulation; that of heme oxygenase and Mn superoxide dismutase was comparable in the two subpopulations. Exposure to IL-1beta resulted in 10-fold higher medium nitrite levels in both subpopulations; this effect was prevented by the iNOS blocker, N(G)-methyl-L-arginine, which also prevented the IL-1beta-induced suppression in the glucose-responsive subpopulation. This study demonstrates that the cellular heterogeneity in glucose responsiveness predisposes to intercellular differences in the IL-1-induced suppression of insulin synthesis and release. While the cytokine induces the expression of noninsulin proteins such as iNOS in both glucose responsive and unresponsive cells, the subsequent nitric oxide production appears to predominantly affect glucose-stimulated functions in the glucose-activated cells.

Animals↗
PubMed1998

Pharmacokinetic characteristics, efficacy, and safety of buccal testosterone in hypogonadal males: a pilot study.

Transbuccal administration of drugs provides an easy route of administration. To test the safety and efficacy of a novel testosterone (T) product, we performed a randomized, double blind, placebo-controlled study in a parallel design. Men with serum T levels below 250 ng/dL were administered either an active buccal tablet containing 10 mg T (n = 7) or a buccal placebo tablet (n = 6) containing 3 mg pseudoephedrine HCl for taste matching. Men were studied while taking a standard T enanthate dose, after 6 weeks of a wash-out period, and after 8 weeks of therapy. The men were matched for age (mean +/- SD, 41 +/- 16 vs. 47 +/- 16) and type of hypogonadism (three primary testicular failures in each group, with the remainder having a central etiology). Acute pharmacokinetic testing showed peak serum hormone levels at 30 min, with a mean serum T concentration of 2688 +/- 147 ng/dL (range, 1820-3770 ng/dL). Levels returned to baseline in 4-6 h, resulting in a total T area under the curve level of 3865 ng/hn.dL, less than that using other available forms of T administration. Similar pharmacokinetics were observed for the hormone's metabolites, bioavailable T, free T, and estradiol. After 8 weeks of treatment, the results of nocturnal penile tumescence studies evaluating rigidity and circumference were significantly different from those in the placebo group (P < 0.05) and comparable to those during T enanthate therapy. In conclusion, transbuccal T therapy was sufficient to maintain normal sexual function while minimizing the total time of exposure to elevated circulating serum T levels.

Administration, Buccal↗
PubMed1997

Immunopathology of the inner ear: an update.

We have reviewed the events of an inner-ear immune response. The perilymph contains antibody, presumably derived from the systemic circulation and CSF, which would allow for neutralization and help with opsonization and complement fixation. The endolymphatic sac contains immunocompetent cells capable of processing and presenting viral or bacterial antigen, potentiating the immune response, attacking the invaders directly or attacking infected cells, and developing immunoglobulin responses in situ. The early release of mediators such as IL-2 likely emanate from the endolymphatic sac and result in potentiation and regulation of the response and may assist in changes in the SMV, including expression of ICAM-1, which aid in the egress of immune cells from the systemic circulation. PMNs arrive first, followed by T cells and B cells, with secretion of specific antibody a relatively late event. Concomitant with the increase in cellular constituents is the formation of a dense extracellular matrix. The inner ear appears to have remarkable difficulty in clearing this matrix, ultimately resulting in ossification. The immune response is unfortunately deleterious to the inner ear, resulting in degeneration of the organ of Corti, stria vascularis, and spiral ganglion. Hearing loss is consistently seen following sterile and virally induced labyrinthitis. The inner ear also appears to be a target for autoimmune disease. While inner-ear damage has been described as part of non-organ-specific autoimmune disease, specific disease against the hearing apparatus is also likely. Experimental paradigms have allowed alterations of both the afferent and efferent limbs of this response; ultimately, with the hope that we can alter the course of the response and the subsequent damage in patients.

Animals↗
PubMed1997

Inhibition of protein synthesis by reduced K+ in cultured endothelial cells.

Total protein synthesis (as precipitable [3H] leucine incorporation) was determined under various experimental conditions to examine the relationship between cellular K+ and protein synthesis in human umbilical vein endothelial cells (HUVEC). We found that under normal external K+ concentration (5 mM), total protein synthesis was inhibited by cycloheximide and ouabain, with estimated values of IC50 of 0.41 microM and 0.60 mM, respectively. Cellular K+ concentrations were determined (102 +/- 4 mM for control cells) and found to be significantly increased (P < 0.01) by high external K+ (25 mM) and significantly decreased (P < 0.001) by low external K+ (0.5 mM) as well as by ouabain (2 mM). Under high external K+, total protein synthesis and the inhibitory responses of cycloheximide and ouabain were not altered. On the contrary, cellular K+ and protein synthesis were both further reduced by about half (P < 0.001) under low external K+. While ouabain further reduced cellular K+ by half (P < 0.001), protein synthesis was only slightly reduced (P < 0.05) under low external K+ and thus the relative reduction on protein synthesis was much less than that for cellular K+. These results indicate that while elevated intracellular K+ did not alter protein synthesis, reduced intracellular K+ correlated with a reduced cellular protein synthesis in HUVEC such that K+ may play a permissible role in the regulation of protein synthesis.

Cells, Cultured↗
PubMed1997

The effect of bedside case presentations on patients' perceptions of their medical care.

BACKGROUND: Concern that case presentations at the bedside may make patients uncomfortable has led many residency programs to move presentations to the conference room. We performed a randomized, controlled trial of the effect of these two approaches on patients' perceptions of their care. METHODS: The study patients were adults admitted to the general medical service of a teaching hospital. Four house-staff "firms" (each comprising teams of physicians) were randomly assigned to make their case presentations during morning rounds either at the patient's bedside or in a conference room for one week, to switch to the alternate site for a second week, and to return to the initial site for a third week. To assess patients' perceptions, a questionnaire was administered within 24 hours of admission. RESULTS: During the three weeks of the study, 95 patients had bedside presentations and 87 patients had conference-room presentations. When the former were compared with the latter, the patients with bedside presentations reported that their doctors spent more time with them on morning rounds (10 vs. 6 minutes, P<0.001). The patients with bedside presentations were also somewhat more likely to report favorable perceptions of their inpatient care (range of adjusted odds ratios, 1.12 to 2.17), although none of the associations were statistically significant. Better-educated patients were less likely to report that physicians used confusing terminology and explained tests and medications inadequately than were patients who had not completed high school. CONCLUSIONS: These data suggest that from the patient's perspective, bedside case presentations are at least as good as conference-room presentations, and perhaps preferable. When physicians make presentations at the bedside of less well educated patients, they should be especially careful to avoid medical jargon and to explain fully their plans for inpatient care.

Attitude to Health↗
PubMed1997

Single and multiple pyogenic liver abscesses: clinical course, etiology, and results of treatment.

A total of 483 patients with pyogenic liver abscess during the years 1986 to June 1995 were studied at Chang Gung Memorial Hospital in Kaohsiung: 343 were a single abscess and 140 were multiple abscesses. Males were predominantly affected by this disease. Abdominal pain was more frequent with the single abscess than with multiple abscesses, and jaundice was more frequent with multiple abscesses. Blood levels of alkaline phosphatase, bilirubin, and creatinine and the white blood cell count were significantly higher in patients with multiple abscesses than in those with a single abscess; and the hemoglobin level was higher with single abscesses. The single abscess was usually larger than 5 cm, and the multiple abscesses were usually smaller than 5 cm. The single abscess was always located on the right side (72%) and the multiple abscesses always on the right or both sides. Single abscesses mainly had a cryptogenic origin (58.9%) and multiple abscesses a biliary origin (45.0%). Liver aspirates revealed Klebsiella pneumoniae, Escherichia coli, Streptococcus, Bacteroides, Enterococcus, among others. K. pneumoniae was more often found in a single abscess and E. coli more often in multiple abscesses. Percutaneous catheter drainage and aspiration comprised the main treatment initially, and the failure rate with multiple abscesses was higher than that with single abscesses. Surgical intervention should be considered for multiple abscesses because of the underlying disease. The overall mortality with multiple abscesses (22.1%) was higher than that with a single abscess (12.8%). Partial hepatectomy produced a low mortality rate for both single and multiple abscesses and should be considered in the presence of severe hepatic destruction by an abscess or a stone.

Adult↗
PubMed1997

Effect of interferon-gamma and glucose on major histocompatibility complex class I and class II expression by pancreatic beta- and non-beta-cells.

Surface major histocompatibility complex (MHC) class I and class II expression by pancreatic islet cells is considered a local initiator or regulator of immune processes that can lead to diabetes. Locally released cytokines, in particular interferon-gamma, are known to stimulate MHC antigen expression by islet cells. The present study quantifies MHC expression in cultured pancreatic beta- and non-beta-cells from both rat and human organs. Interferon-gamma increased MHC class I expression in endocrine beta- and non-beta-cells as well as in pancreatic ductal cells. The cytokine induced a 6-fold increase in the MHC class I messenger ribonucleic acid levels in pancreatic beta-cells; this effect was 2-fold amplified in the presence of elevated glucose levels (20 mmol/L instead of 6 mmol/L). No MHC class II expression was observed in endocrine beta- or non-beta-cells; human, but not rat, ductal cells exhibited MHC class II expression that increased in the presence of interferon-gamma. These data indicate that the increase in beta-cell MHC class I expression described in the pancreata of diabetic patients may result from stimulated transcription after exposure to locally released interferon-gamma and/or to a hyperglycemic state. The association of human islets with ductal cells in which MHC class II expression is stimulated by interferon-gamma makes these cells potential participants in the autoimmune process in diabetes.

Adolescent↗