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Biomedical subjects

M C Chen

Publications and source records attributed to M C Chen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of primary angioplasty on total or subtotal left main occlusion: analysis of incidence, clinical features, outcomes, and prognostic determinants.

BACKGROUND: Although acute left main coronary artery (LMCA) occlusion is a rare clinical entity, it carries a very high mortality rate. The purposes of this study were to evaluate the effect of primary angioplasty for a severely obstructed or totally occluded LMCA, and to determine the incidence, clinical features, outcome, and prognostic determinants in this clinical setting. MATERIALS AND METHODS: Between May 1993 and July 2000, a total of 740 patients with acute myocardial infarction underwent primary angioplasty in our hospital. Eighteen of 740 patients (2.4%) with a severely obstructed or totally occluded LMCA constituted the population of this study. RESULTS: Seventeen of 18 patients (94.4%) experienced pulmonary edema (including 14 patients in cardiogenic shock). Six patients (33.3%) sustained sudden death due to malignant ventricular tachyarrhythmias. Coronary angiography showed that there were variable grade flow of intercoronary collaterals in 12 patients (66.7%), a totally occluded LMCA in 8 patients (44.4%), an incompletely occluded LMCA in 10 patients (55.6%), and a dominant right coronary artery (RCA) in 16 patients (88.9%). Primary angioplasty of the LMCA was performed with a 72.2% procedural success rate. Four patients (22.2%) received coronary artery bypass surgery after angioplasty. Six patients (33.3%) died in the hospital. Two patients died after discharge. Ten of 18 patients (55.6%) survived in long-term follow-up (mean +/- SD, 44 +/- 14 months). Those patients who survived to be discharged had significantly higher combined coexisting incidence of intercoronary collaterals, dominant RCA, and incompletely occluded LMCA (100% vs 0.0%, p = 0.0006) than those patients who died in the hospital. CONCLUSIONS: Acute obstructive LMCA disease generally presented as pulmonary edema, cardiogenic shock, or sudden death. Only those who had combined coexistence of intercoronary collaterals, a dominant RCA, and an incompletely occluded LMCA could survive to be discharged. Our experience suggests that primary LMCA angioplasty is a feasible and effective procedure, and it may save lives in this clinical setting.

Adult↗
PubMed2001

Underutilization of anticoagulation therapy in chronic atrial fibrillation.

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.

Aged↗
PubMed2001

Reproducibility of hippocampal single-Voxel proton MR spectroscopy and chemical shift imaging.

OBJECTIVE: We investigated between- and within-acquisition reproducibility of hippocampal metabolite ratios obtained using automated proton MR spectroscopy. SUBJECTS AND METHODS: We examined 30 healthy adults with a 1.5-T scanner four times on 3 days using single-voxel spectroscopy over the left hippocampus, chemical shift imaging over the left hippocampus, and chemical shift imaging over the bilateral hippocampi. Metabolite ratios were derived from the integral values of three major peaks: N:-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr). The random-effects model of one-way analysis of variance was used to evaluate the reproducibility in terms of coefficient of variation; the mixed-effects model was used to compare the results of different hippocampal regions and spectroscopic techniques. RESULTS: Most coefficients of variation for the NAA/(Cho+Cr) ratio were less than 20%. All the coefficients of variation for the posterior hippocampus (15-25%) were less than those for the anterior hippocampus (20-44%). The posterior hippocampal NAA/(Cho+Cr) ratio of unilateral chemical shift imaging had the lowest coefficient of variation (<16%). Single-voxel spectroscopy and unilateral chemical shift imaging had similar coefficients of variation for the anterior hippocampal NAA/(Cho+Cr) ratios (17-20%). There was a significant difference in metabolite ratios measured in different hippocampal regions (p<0.01) and in those acquired with different spectroscopic techniques (p<0.001). CONCLUSION: The NAA/(Cho+Cr) ratio is the most reproducible parameter for hippocampal MR spectroscopy on a 1.5-T scanner. Regional variation and technical differences in metabolite ratios must be considered when interpreting proton spectra of the hippocampus.

Adolescent↗
PubMed2001

Randomized comparison of local versus epidural anesthesia for tension-free vaginal tape operation.

PURPOSE: We determine the difference between local anesthesia and epidural blockade for the tension-free vaginal tape operation. MATERIALS AND METHODS: Between November 1995 and November 1997, 73 women who had genuine stress incontinence in the absence of pelvic prolapse underwent a prospective randomized study. The study was conducted using a standardized protocol for different types of anesthesia for the tension-free vaginal tape procedure. A formal pain scale was used to determine the pain score for the patients during the operation. Additionally an anxiety scale was used to measure the anxiety level of the subjects immediately after admission to the ward and before discharge from the hospital. RESULTS: One woman was excluded from study due to loss at followup. The comparisons of pain score, duration of procedure and anxiety level of the 2 different types of anesthesia were not significantly different in the 72 study subjects. There was no significant difference in the amount of blood loss, while initial spontaneous voiding occurred significantly earlier (3.5 +/- 2.3 versus 5.8 +/- 0.1 hours, p <0.01), the number of patients in whom initial spontaneous voiding occurred more than 6 hours postoperatively was fewer (2 versus 10, p =0.01), amount of post-void residual during hospitalization was significantly less (98 +/- 63 versus 155 +/- 56 ml., p <0.01) and length of hospital stay was significantly shorter (3.4 +/- 1.4 versus 5.5 +/- 1.6 days, p <0.01) in the local anesthesia compared to epidural group. Subjective and objective success rates were not significantly different in these 2 groups. CONCLUSIONS: Both anesthetic methods can be equally effectively used for the tension-free vaginal tape operation. Local may be better than epidural anesthesia but its clinical significance needs to be proved by further study.

Adult↗
PubMed2001

Primary angioplasty in acute inferior myocardial infarction with anomalous-origin right coronary arteries as infarct-related arteries: focus on anatomic and clinical features, outcomes, selection of guiding catheters and management.

BACKGROUND: Inferior wall myocardial infarction caused by obstruction of an anomalous-origin right coronary artery (RCA) is a rare angiographic finding; primary angioplasty to an anomalous-origin RCA has never been reported. METHODS: In 185 patients with acute inferior wall myocardial infarction resulting from RCA occlusion who underwent primary angioplasty, eight patients (4.3%) had anomalous-origin RCAs. RESULTS: Coronary angiography showed that all 8 patients had a dominant RCA. Six patients (75%) had an anomalous-origin RCA arising from the anterior aspect of the ascending aorta above the sinotubular line and the other 2 patients (25%) had an anomalous-origin RCA arising from the left sinus of Valsalva with a separate ostium from the left main coronary artery. The standard Judkins right guiding catheter did not offer adequate support in these patients. In the group of 6 patients, an Amplatz guiding catheter offered good support, while a standard Judkins left guiding catheter was adequate in the other 2 patients. Obstruction of the proximal RCA occurred in 6 patients (75%). Successful reperfusion was achieved in 6 patients (75%), resulting in an uneventful clinical course and long-term survival (mean follow-up, 24.9 +/- 16.5 months). Two patients (25%) had unsuccessful reperfusion and died from cardiogenic shock. CONCLUSIONS: In this small series, anomalous-origin RCAs were the dominant artery and predisposed to atherosclerosis at the proximal portions. We suggest that appropriate guide catheter selection and careful manipulation are essential for the success of revascularization. Complete reperfusion results in an excellent clinical and long-term outcome in patients with anomalous-origin RCAs.

Angioplasty, Balloon, Coronary↗
PubMed2001

Computed tomography and angiography in hepatic tuberculosis mimicking liver tumor.

Tuberculosis is one of the most common and well-documented infectious diseases, with a vast variety of clinical manifestations. A case of isolated hepatic tuberculosis mimicking liver tumor is presented. The patient was a 44-year-old man who had suffered from intermittent epigastralgia for about 2 years. Abdominal computed tomography demonstrated a low density mass with internal calcification over the left lobe of the liver. Celiac angiography showed encasement of the hepatic propia and occlusion of the left hepatic artery. Abnormal tortuous vascular structures were found at the hepatic hilar region. The patient underwent surgical intervention under the impression of left liver tumor. Microscopically, the resected liver tissue specimen revealed tuberculosis.

Adult↗
PubMed2001

Reversible infra-Hisian atrioventricular block in acute myocarditis.

Symptomatic second- or third-degree atrioventricular (AV) block at any anatomical level is a class I indication for permanent pacemaker implantation. We describe a 44-year-old male with acute viral myocarditis who suffered from syncope followed by a seizure attack associated with AV conduction disturbance. His initial electrocardiogram in our emergency room revealed sinus tachycardia with 2:1 AV conduction and a right bundle branch block QRS morphology with a ventricular rate of 60 beats/min. Because of episodic slowing of the heart rate below 40 beats/min, he received 1 mg atropine intravenously which increased the atrial rate but further worsened the AV conduction, resulting in ventricular asystole for more than 30 seconds associated with loss of consciousness and seizure-like activity. He was immediately paced transcutaneously and transferred to the catheterization laboratory to receive temporary transvenous cardiac pacing. The cardiac catheterization study showed a normal coronary angiogram and very mild diffuse hypokinesis. Electrophysiological studies revealed advanced infra-Hisian AV block. The infra-Hisian AV block, however, resolved rapidly in 2 days. The patient did not receive a permanent pacemaker and remained asymptomatic with normal electrocardiogram over 1 year of follow-up. We suggest that symptomatic infra-Hisian AV block due to viral myocarditis can be reversible, and implantation of a permanent pacemaker may not be necessary.

Acute Disease↗
PubMed2001

Implications of sonographic identification of duplex kidney in adults.

BACKGROUND: Duplication of the renal pelvis and ureter constitutes the most common anomalies of the upper urinary tract. Most patients are asymptomatic and don't need treatment. However, the associated anomaly and acquired renal disease may cause morbidity and mortality. The aim of this study was to investigate the prevalence of duplex kidney in sonographic examinations and the predictive capability of this method. An analysis of patients with urography-confirmed duplication anomaly was also performed. METHODS: During a period of 9 year (from 1988 to 1996), sonographic examination records of 19,287 patients were reviewed. Patients with a diagnosis of duplex kidney were enrolled. Their clinical characteristics and radiological images were recorded and evaluated. RESULTS: One hundred and sixty-three patients were found by sonography to have duplex kidney, for an prevalence of 0.85%. Urography studies were done on 64 (39.2%) patients, and 42 patients were proven to have duplex kidney. The positive predictive rate of sonography was 65.6%. Eighty percent of patients with duplex kidney had associated ureteral duplication. No associated anomalies were found. Four patients had urolithiasis, and 3 patients had recurrent urinary tract infection. One patient had coexisting uroepithelial malignancy, and 1 patient had refractory gross hematuria. CONCLUSIONS: Duplex kidney is an uncommon finding during adult sonographic examinations. The sensitivity and specificity of sonography in identifying this anomaly are controversial. An experienced hand with good knowledge of the anomaly and its sonographic signs is helpful in more accurately diagnosing this anomaly.

Adolescent↗
PubMed2000

Cloning and characterization of a novel nuclear Bcl-2 family protein, zfMcl-1a, in zebrafish embryo.

The importance of the Bcl-2 family proteins in normal vertebrate embryogenesis is being recognized; however, their regulatory mechanism is poorly understood. To elucidate the embryonic roles of Bcl-2 family proteins, we cloned and characterized the first zebrafish Bcl-2 family protein, zfMcl-1a. Zebrafish Mcl-1a shows the highest homology to rat Mcl-1 and contains several conserved BH domains of the Bcl-2 family proteins. It also contains a nuclear localization signal (NLS). Using EGFP reporter analysis, we verified the nuclear localization of zfMcl-1a. Deletion of the NLS resulted in distribution of the fusion protein in the cytoplasm. Northern blot analysis indicated that zfMcl-1a mRNA is 1.5 kb and was expressed in oocytes and throughout embryonic development. Notably, the expression of zfMcl-1a transcript was significantly downregulated during gastrulation. These results suggest that zfMcl-1a is a novel nuclear Bcl-2 family protein and is likely to play an important role in zebrafish oogenesis and embryogenesis.

3T3 Cells↗
PubMed2000

Overexpression of bcl-2 enhances LIGHT- and interferon-gamma -mediated apoptosis in Hep3BT2 cells.

LIGHT is a member of the tumor necrosis factor superfamily and is the ligand for LT-betaR, HVEM, and decoy receptor 3. LIGHT has a cytotoxic effect, which is further enhanced by the presence of interferon-gamma (IFN-gamma). Although LIGHT/IFN-gamma can activate caspase activity, neither benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone nor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone can completely inhibit LIGHT/IFN-gamma-mediated apoptosis. Moreover, overexpression of Bcl-2 further enhances LIGHT/IFN-gamma-mediated apoptosis. It appears that LIGHT and IFN-gamma act synergistically to activate caspase-3, with the resultant cleavage of Bcl-2, removal of the BH4 domain, leading to conversion of Bcl-2 from an antiapoptotic to a proapoptotic form in p53-deficient hepatocellular carcinoma Hep3BT2 cells. Thus, LIGHT seems to be able to override the protective effect of Bcl-2 and induce cell death. Although benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone can prevent the cleavage of Bcl-2 by LIGHT/IFN-gamma, they only partially inhibit apoptosis in Hep3BT2 cells that are overexpressing Bcl-2. In contrast, both LIGHT/IFN-gamma-mediated apoptosis and Bcl-2 cleavage are inhibited by free radical scavengers, indicating that free radicals may play an essential role in LIGHT/IFN-gamma-mediated apoptosis at a step upstream of caspase-3 activation. These results suggest that LIGHT signaling may diverge into multiple, separate processes.

Amino Acid Sequence↗
PubMed2000

Actions of Ginkgo Biloba related to potential utility for the treatment of conditions involving cerebral hypoxia.

Neuronal hypoxia results from a variety of cerebrovascular accidents or 'normal' age-associated anatomic changes. The consequences vary from mild deficits in neurologic function to massive neuropathology. Present pharmacotherapeutic therapy is not ideal. Two apparently disparate approaches to the search for better treatment or prevention-one involving reassessment of herbal remedies as 'alternative' medicine and the other one involving the desirability of increased structural diversity in HTS (high-throughput screening) libraries and as combinatorial chemistry templates-have converged in a rekindling of interest and a reevaluation of the pharmacologic properties of substances such as extract from the leaves of Ginkgo biloba Linne (form. Salisburia adiantifolia Sm.). There are reports of positive results from a small number of controlled clinical trials (albeit with small numbers of patients) sufficient to suggest that 'Ginkgo' might have therapeutic benefit in some situations or subset of patients. The pharmacologic mechanism by which Ginkgo might be able to provide the observed effect is not clear. However, it is believed that the flavonoid and terpenoid components of Ginkgo extract might produce beneficial therapeutic effects through mechanisms acting separately or in concert, such as the antagonism of PAF (platelet activating factor), antioxidant and metabolic actions, and effects on neurotransmitters. These mechanisms are reviewed in this article.

Ginkgo biloba↗
PubMed2000

Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness.

Mounting evidence suggests that obsessive compulsive disorder (OCD) results from functional aberrations of the fronto-striatal circuitry. However, empirical studies of the behavioral manifestations of OCD have been relatively lacking. The present study employs a behavioral task that allows a quantitative measure of how alternative percepts are formed from one moment to another, a process mimicking the brain state in which different thoughts and imageries compete for access to awareness. Eighteen patients with OCD, 12 with generalized anxiety disorder, and 18 normal subjects participated in the experiment, in which they viewed one of the three Schröder staircases and responded by pressing a key to each perceptual reversal. The results demonstrate that the patients with OCD have a higher perceptual alternation rate than the normal controls. Moreover, the frequency of perceptual alternation is significantly correlated with the Yale-Brown obsessive compulsive and the Hamilton anxiety scores. The increase in the frequency of perceptual reversals cannot easily be accounted for by learning or by different patterns of eye fixations on the task. These results provide further evidence that an impairment of the inhibitory function of the cortico-striatal circuitry might underlie the etiology of OCD. The implications of the results for a general role of the cortico-striatal circuitry in mediating awareness are discussed.

Adult↗
PubMed2000

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population.

OBJECTIVE: Vitamin D and its receptor have been suggested to play a role in the pathogenesis of type 1 diabetes mellitus. We have therefore studied the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes, and rates of glutamic acid decarboxylase (GAD65) autoantibody and islet cell autoantibody (ICA512) positivity. SUBJECTS: AND MEASUREMENTS One hundred and fifty-seven type 1 diabetic patients and 248 unrelated normal controls were recruited for this study. Genomic DNA was extracted from peripheral blood leucocytes. All type 1 diabetic patients and controls were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), for three restriction sites in the VDR gene, BsmI, ApaI and TaqI. The chi2 test was used to compare the frequency of the VDR gene polymorphisms in patients and normal controls. The association of VDR gene polymorphisms in type 1 diabetes with the presence of GAD65 and ICA512 autoantibodies were also examined using the chi2 test. RESULTS: The allele frequency of the BsmI and ApaI polymorphisms, but not TaqI polymorphism, differed between patients and controls (BsmI P = 0.015; ApaI P = 0.018; TaqI P = 0.266). However, after correction for the three different polymorphisms tested, only the BsmI was significant (pc = 0.045). CONCLUSIONS: Vitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.

Adolescent↗
PubMed2000

Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese.

The peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) has been studied extensively because of its putative role in adipocyte differentiation and insulin sensitivity. The association of the Pro12Ala and Pro115Gln PPARgamma2 gene variants with type 2 diabetes mellitus, the body mass index (BMI), and other diabetes-related phenotypes was examined in the Taiwanese population. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Allele frequencies were compared between 280 subjects with type 2 diabetes mellitus and 310 subjects without diabetes using the chi-square test. Continuous phenotype analysis was performed by multiple logistic regression adjusting for age and BMI where appropriate. There was no significant association between the Pro12Ala gene variant and type 2 diabetes; the frequency of the Ala12 allele was 0.03 in type 2 diabetics and 0.04 in nondiabetics (P = .40). The Gln115 allele was not detected in any of the cases or controls. In multiple linear regression analysis of all cases and controls combined adjusted for age, sex, and diabetic status, carriers of the Ala12 allele had a mean BMI of 25.9+/-0.5 kg/m2 (mean +/- SE), compared with 24.2+/-0.1 kg/m2 in Pro12 homozygotes (P < .001). In addition, carriers of the Ala12 allele have a 2.9 times (95% confidence interval [CI], 1.5 to 5.5) higher odds of having a BMI of at least 25 kg/m2. These results suggest that in the Taiwanese, the Pro12Ala PPARgamma2 gene variant may contribute to fat accumulation and a higher BMI independent of type 2 diabetes. These results need to be confirmed in future studies, as a linkage disequilibrium of this variant with other mutations cannot be ruled out.

Adult↗
PubMed2000

Unexpected loss of bipolar pacing with implanted dual chamber pacemakers.

Bipolar leads are most commonly used in the current practice of pacemaker therapy. In our study of 124 patients implanted with Guidant/Cardiac Pacemakers (CPI) Vigor dual chamber pacemakers, 5 patients had unexpectedly abrupt increases in bipolar lead impedance and pacing threshold 2 weeks to 18 months postimplantation without changes in sensing function. With the lead configuration reprogrammed to unipolar, the lead impedance and pacing threshold were restored to appropriate ranges. The changes in bipolar lead parameters can be caused by the CPI's "Quick Connect" (QC1) header lead system incorporated in these pacemakers.

Aged↗
PubMed2000

Increased expression and immunogenicity of sequence-modified human immunodeficiency virus type 1 gag gene.

A major challenge for the next generation of human immunodeficiency virus (HIV) vaccines is the induction of potent, broad, and durable cellular immune responses. The structural protein Gag is highly conserved among the HIV type 1 (HIV-1) gene products and is believed to be an important target for the host cell-mediated immune control of the virus during natural infection. Expression of Gag proteins for vaccines has been hampered by the fact that its expression is dependent on the HIV Rev protein and the Rev-responsive element, the latter located on the env transcript. Moreover, the HIV genome employs suboptimal codon usage, which further contributes to the low expression efficiency of viral proteins. In order to achieve high-level Rev-independent expression of the Gag protein, the sequences encoding HIV-1(SF2) p55(Gag) were modified extensively. First, the viral codons were changed to conform to the codon usage of highly expressed human genes, and second, the residual inhibitory sequences were removed. The resulting modified gag gene showed increases in p55(Gag) protein expression to levels that ranged from 322- to 966-fold greater than that for the native gene after transient expression of 293 cells. Additional constructs that contained the modified gag in combination with modified protease coding sequences were made, and these showed high-level Rev-independent expression of p55(Gag) and its cleavage products. Density gradient analysis and electron microscopy further demonstrated that the modified gag and gag protease genes efficiently expressed particles with the density and morphology expected for HIV virus-like particles. Mice immunized with DNA plasmids containing the modified gag showed Gag-specific antibody and CD8(+) cytotoxic T-lymphocyte (CTL) responses that were inducible at doses of input DNA 100-fold lower than those associated with plasmids containing the native gag gene. Most importantly, four of four rhesus monkeys that received two or three immunizations with modified gag plasmid DNA demonstrated substantial Gag-specific CTL responses. These results highlight the useful application of modified gag expression cassettes for increasing the potency of DNA and other gene delivery vaccine approaches against HIV.

AIDS Vaccines↗
PubMed2000

Interleukin-1beta regulates phospholipase D-1 expression in rat pancreatic beta-cells.

The cytokine interleukin (IL)-1beta induces a biphasic effect in rat pancreatic islets, with an early and transitory stimulation of insulin release followed by progressive functional suppression. To clarify the mechanisms involved in these effects, we have recently performed a differential display of messenger RNA (mRNA) by RT-PCR (DDRT-PCR) on rat beta-cells exposed for 6 or 24 h to IL-1beta. Among the different IL-1beta-induced genes, there was an early and transient increase in phospholipase D-1 (PLD1) expression. PLD1 can induce phosphatidic acid formation and subsequent activation of protein kinase C, a process which stimulates insulin release. In the present study, we characterized the regulation of PLD isoforms by IL-1beta in pancreatic beta-cells. By using different combinations of primers and RT-PCR, we observed that IL-1beta induces an early increase (2 and 6 h) in the expression of both alternatively spliced isoforms of PLD1 (PLD1alpha and 1b). Prolonged exposure to IL-1beta (12 and 24 h) caused a decrease of PLD1a mRNA expression compared with control beta-cells, and lead to a return of PLD1b mRNA to basal level. NG-methyl-L-arginine (LMA), a blocker of the inducible form of nitric oxide synthase (iNOS), prevented this late inhibitory effect of IL-1beta, suggesting that IL-1beta-induced decrease in PLD1a expression is NO-mediated. IL-1beta induced an early (2-6 h) and sustained (16-24 h) increase in PLD1a mRNA expression in insulin-producing RINm5F cells. This was paralleled by a cytokine-induced increase in PLD1 protein expression and enzyme activity. RINm5F cells, but not primary beta-cells, expressed PLD2, and the expression of this gene was not affected by IL-1beta. In conclusion, we have shown that the cytokine IL-1beta regulates PLD1 expression in primary and clonal beta-cells. The early induction of PLD1 probably contributes to the early stimulatory effects of IL-1beta on islet insulin release.

Alternative Splicing↗