BACKGROUND: The effects of a newly synthesized potassium channel opener, KR-30816((-)(nitro-2-hydroxymethyl-2-methy-2H-1-benzopyran-4-y1)pyridine oxide) on the action potential of papillary muscles of guinea pigs and the ATP-sensitive potassium channel current(IKATP) of single ventricular muscle cells of rats were examined to make clear its action mechanism of the KATPchannel. METHODS: We used the conventional microelectrode and the excised inside-out patch configuration. RESULTS: KR-30816 caused a shortening of the action potential duration in dose-dependent manner, which was inhibited by glibenclamide(3microM). Before run-down of the K+channel, KR-30816 activated the cardiac ATP-sensitive K+ channel only in the presence of ATP and shifted the dose-response relation curve between [ATP]i and the channel activity to the right in parallel. After run-down of the KATP channel, KR-30816 did not after the channel opening either in the absence or in the presence of UDP. CONCLUSION: These results suggest that KR-30816 antagonizes the inhibitory effect of ATP on the KATPchannel in a competitive manner, thereby enhancing the channel openings.
Action Potentials ; Adenosine Triphosphate ; Animals ; Guinea Pigs ; Heart ; Microelectrodes ; Muscle Cells ; Papillary Muscles ; Potassium Channels* ; Potassium* ; Rats ; Uridine Diphosphate

To explore whether Cl- channel blockers interact with the ATP-sensitive K+ (KATP) channel, I have examined the effect of two common Cl- channel blockers on the KATP channel activity in isolated rat ventricular myocytes using patch clamp techniques. In inside-out patches, 4,4'-diisothio-cyanatostilbene-2,2'-disulfonic acid (DIDS) and niflumic acid applied to bath solution inhibited the KATP channel activity in a concentration-dependent manner with IC50 of 0.24 and 927 muM, respectively. The inhibitory action of DIDS was irreversible whereas that of niflumic acid was reversible. Furthermore, DIDS-induced block was not recovered despite exposure to ATP (1 mM). In cell-attached and inside-out patches, DIDS blocked the pinacidil- or 2,4-dinitrophenol (DNP)-induced KATP channel openings. In contrast, niflumic acid did not block the pinacidil-induced KATP channel openings in inside-out patches, but inhibited it in cell-attached patches. DIDS and niflumic acid produced additional block in the presence of ATP and did not affect current-voltage relationship and channel kinetics. All these results indicate that DIDS among Cl- channel blockers specifically blocks the cardiac KATP channel.
2,4-Dinitrophenol ; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ; Adenosine Triphosphate ; Animals ; Baths ; Inhibitory Concentration 50 ; Kinetics ; Muscle Cells ; Niflumic Acid ; Patch-Clamp Techniques ; Rats

BACKGROUND AND OBJECTIVES: Advanced or recurrent laryngeal cancers after chemoradiotherapy were mainly treated by total laryngectomy because of inadequate surgical margin, multifocal recurrent site, and delayed diagnosis. Recently, voice preservation through conservative laryngeal surgery in case of advanced or recurrent laryngeal cancer with strict application of surgical indication became possible. In this study, authors studied the usefulness of surpracricoid partial laryngectomy (SCPL) for advanced or recurrent laryngeal cancers is discussed. MATERIALS AND METHOD: Twenty-five laryngeal cancer cases of cricohyoido-epiglottopexy (CHEP) or cricohyoidopexy (CHP) from May 1996 through April 2001 were analysed retrospectively. In recurrent cases after radiotherapy, there were 8 cases with glottic T1, 6 with T2, 3 with T3, one with T4, one with supraglottic T2 and T3. In advanced cases without radiotherapy, there were 3 cases with glottic T3 and 2 with supraglottic T3. Evaluation of oncological and functional results were conducted. The mean follow-up period was 29.1 months. RESULTS: Local recurrence occurred in 1 patient (4.3%) and cricoid perichondritis in 5 patients (21.7%), laryngocutaneous fistula in 1 patient (4.3%) after the operation. Four patients (17.3%) had to be treated with completion laryngectomy. Voice function was preserved in 19 patients (82.7%). CONCLUSION: Our experience with supracricoid partial laryngectomy with CHEP or CHP suggests that this technique can be a valuable alternative to the total laryngectomy in the recurrent or advanced laryngeal cancer.
Chemoradiotherapy ; Delayed Diagnosis ; Fistula ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms* ; Laryngectomy* ; Radiotherapy ; Recurrence ; Retrospective Studies ; Voice

The influences of specific protein phosphatase and protein kinase inhibitors on the ATP-sensitive K+ (KATP) channel-opening effect of pinacidil were investigated in single rat ventricular myocytes using patch clamp technique. In cell-attached patches, pinacidil (100 muM) induced the opening of the KATP channel, which was blocked by the pretreatment with H-7 (100 muM) whereas enhanced by the pretreatment with genistein (30 muM) or tyrphostin A23 (10 muM). In inside-out patches, pinacidil (10 muM) activated the KATP channels in the presence of ATP (0.3 mM) or AMP-PNP (0.3 mM) and in a partial rundown state. The effect of pinacidil (10 muM) was not affected by the pretreatment with protein tyrosine phosphatase 1B (PTP1B, 10 mug ml-1), but blocked by the pretreatment of protein phosphatase 2A (PP2A, 1 U ml-1). In addition, pinacidil (10 muM) could not induce the opening of the reactivated KATP channels in the presence of H-7 (100 muM) but enhanced it in the presence of ATP(1 mM) and genistein (30 muM). These results indicate that the KATP channel-opening effect of pinacidil is not mediated via phosphorylation of KATP channel protein or associated protein, although it still requires the phosphorylation of serine/threonine residues as a prerequisite condition.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; Adenosine Triphosphate ; Adenylyl Imidodiphosphate ; Animals ; Genistein ; KATP Channels ; Muscle Cells* ; Phosphorylation* ; Pinacidil* ; Protein Kinase Inhibitors ; Protein Phosphatase 2 ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; Rats*

PURPOSE: Bone bruises of patients with acute traumatic knee injuries, that are not found on simple radiograph, can be found on magnetic resonance imaging (MRI). The purpose of this study is to evaluate the frequency and locations of bone bruises on MRI in acute traumatic anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) injury. MATERIALS AND METHODS: 25 and 19 MRls, in which acute traumatic ACL and PCL injury was pre sent and there was no abnormality in simple radiograph, were reviewed. MRI was taken within 51 days of injury. A bone bruise was determined as a geographic and nonlinear area of signal loss on T1 images and increased signal intensity on T2 images involving the subcortical bone. RESULTS: In 16 patients with bone bruises and acute ACL injury, bone bruises were found in the lateral compartment of the knee in 15 (93.8%) patients. The most common area was the lateral tibial plateau (11 cases, 68.8%) and the second was lateral femoral condyle (9 cases, 56.3%). In 5 patients with bone bruises and acute PCL injury, bone bruises were found in the lateral compartment of the knee in all 5 (100%) patients. The most common area was lateral tibial plateau (4 cases, 80%) and the second was lateral femoral condyle (2 cases, 40%). CONCLUSIONS: In patients with acute traumatic ACL or PCL injuries the bone bruises are often found on the lateral compartment of the knee, especially lateral tibial plateau and lateral femoral condyle on MRI.
Anterior Cruciate Ligament ; Contusions* ; Humans ; Knee ; Knee Injuries ; Magnetic Resonance Imaging* ; Posterior Cruciate Ligament

PURPOSE: Laparoscopic cholecystectomy has been used widely for effective management of acute cholecystitis. However, it has limitations. In this study, we compared laparoscopic approaches and an open method. The meaning of the open method was assessed again. METHODS: A retrospective review of 60 patients undergoing cholecystectomy for acute cholecystitis was done. Thirty patients were part of a laparoscopic cholecystectomy group; the other 30 patients were part of an open cholecystectomy group. Laparoscopic cholecystectomy was done using a 4-trochar method. We reviewed geographic characteristics, body mass index, white blood cell count, and clinical outcomes. RESULTS: Age, gallbladder wall thickness and white blood cell counts were significantly different between the 2 groups; operation time was not. The length of the postoperative hospital stay in the laparoscopic group was significantly shorter than that in the open group. There was one case of bile leakage in the laparoscopic group which was treated by endoscopic nasal bile drainage. CONCLUSION: Open cholecystectomy is still a valid choice for acute cholecystitis in the modern era of laparoscopic surgery. In severe cases, conversion is not a failure and should be done immediately if necessary.
Bile ; Body Mass Index ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Cholecystitis, Acute ; Drainage ; Gallbladder ; Humans ; Laparoscopy ; Length of Stay ; Leukocyte Count ; Retrospective Studies

Epilepsy affects more than 0.5% of the world population and is known to be associated with a large genetic component eliciting an electrical hyperexcitability in the central nervous system. However, its pathogenic mechanisms remain poorly understood. In order to gain greater molecular incite in the pathogenesis in epilepsy, we analyzed proteomes of human cerebral cortices. Quantitative proteome analysis was used to compare signals corresponding to individual proteins between epileptic cerebral cortices from patients with temporal lobe epilepsy and age-matched non-epileptic subjects. To minimize individual variations, gender and age of the patients were matched. Changes of several spots were consistent among 6 pairs of epileptic patients and nonepileptic subjects. One of the spots was identified as the mitochondrial type Mn-superoxide dismutase (Mn-SOD) confirmed by Western blot analysis with Mn-SOD antibody and enzyme activity assay. Such results were agreeable with chemical and physical parameters given by the 2-dimensional electrophoresis (2-DE) gel. Mn-SOD was consistently down-regulated in epileptic cerebral cortices compared with those of nonepileptic subjects. Our results demonstrate a clear link between pathogenesis of epilepsy and SOD. Additionally, we identified four proteins that were consistently over-expressed in all epileptic temporal neocortices specimens and the other four proteins that were found to be expressed less than non-epileptic control subjects. These proteomic data provide cellular markers in the understanding mechanism of the epilepsy pathogenesis.
Adult ; Biological Markers/analysis ; Brain Chemistry ; Case-Control Studies ; Cerebral Cortex/chemistry/*metabolism ; Down-Regulation ; Electrophoresis, Gel, Two-Dimensional ; Epilepsy/genetics/*metabolism ; Female ; Humans ; Male ; Middle Aged ; Mitochondria/chemistry/genetics/*metabolism ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Proteomics ; Research Support, Non-U.S. Gov't ; Superoxide Dismutase/analysis/genetics/*metabolism ; Up-Regulation

OBJECTIVE: The etiology and pathogenesis of moyamoya disease remain unclear. Furthermore, the definitive diagnostic protein-biomarkers for moyamoya disease are still unknown. The present study analyzed serum proteomes from normal controls and moyamoya patients to identify novel serological biomarkers for diagnosing moyamoya disease. METHODS: We compared the two-dimensional electrophoresis patterns of sera from moyamoya disease patients and normal controls and identified the differentially-expressed spots by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry and electrospray ionization quadruple time-of-flight mass spectrometry. RESULTS: We found and analyzed 22 differently-expressed proteomes. Two proteins were up-regulated. Twenty proteins were down-regulated. Complement C1 inhibitor protein and apolipoprotein C-III showed predominantly changed expressions (complement C1 inhibitor protein averaged a 7.23-fold expression in moyamoya patients as compared to controls, while apolipoprotein C-III averaged a 0.066-fold expression). CONCLUSION: Although our study had a small sample size, our proteomic data provide serologic clue proteins for understanding moyamoya disease.
Apolipoprotein C-III ; Biomarkers ; Complement C1 Inhibitor Protein ; Electrophoresis ; Humans ; Mass Spectrometry ; Moyamoya Disease ; Proteins ; Proteome ; Sample Size

Cyclic ADP-ribose (cADPR) releases Ca²⁺ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca²⁺ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca²⁺ ([Ca²⁺](i)) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca²⁺ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca²⁺ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.
Action Potentials ; Adenosine Diphosphate* ; Adenosine Triphosphatases ; Calcium ; Cyclic ADP-Ribose ; Cytochalasin B ; Endoplasmic Reticulum ; Homeostasis ; Muscle Cells* ; Myocytes, Cardiac ; Protein Tyrosine Phosphatase, Non-Receptor Type 1* ; Protein Tyrosine Phosphatases* ; Reticulum ; Ryanodine Receptor Calcium Release Channel ; Tyrosine

Carcinoma of the bladder is a worldwide disease with several histological patterns, 0.5 to 2.0% of which are caused by adenocarcinomas. The etiology of adenocarcinoma of the bladder is unknown Adenocarcinoma of the bladder may be classified as primary, urachal or metastatic based on the site or tumor origin. The primary site of metastatic adenocarcinoma include the rectum, stomach, endometrium, breast, prostate and ovary. Metastasis to the bladder from adenocarcinoma is a relatively rare phenomenon occurring in only 0.26% of cases. When urologic symptoms newly developed to the patients who had malignancy of digestive organs, metastatic malignancy of urinary tact should be considered. Herein, we report a case of metastatic bladder tumor from gastric cancer which occurred 15 months after subtotal gastrectomy.
Adenocarcinoma* ; Breast ; Endometrium ; Female ; Gastrectomy ; Humans ; Neoplasm Metastasis ; Ovary ; Prostate ; Rectum ; Stomach Neoplasms* ; Stomach* ; Urinary Bladder Neoplasms ; Urinary Bladder*