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Biomedical subjects

I Kodama

Publications and source records attributed to I Kodama.

At least 145 records · Page 8Linked to original sources

Cellularity and fibrin mesh properties as a basis for ultrasonic tissue characterization of blood clots and thrombi.

This in vitro study was designed to evaluate the ability of ultrasonic tissue characterization (UTC) based on power spectrum analysis of backscattered radio-frequency echo signals to distinguish two prominent variables of thrombi: cellularity (primarily red cell content) and fibrin-mesh density. Six types of clots simulating thrombus components were prepared by varying red-cell and platelet concentrations and shear forces during clotting. Data were acquired with a linear-array transducer, digitized, and analyzed in terms of slope and intercept parameters obtained from normalized power spectra of radio-frequency echo signals. Increased cellularity and fibrin-mesh density both produced lower slope and higher intercept values, which permitted statistically significant discrimination of cellularity and mesh density in the six types of clots analyzed. Shearing forces and (to a lesser degree) platelet concentrations increased fibrin-mesh density. This study suggests that UTC based upon the power spectrum of echo signals may be used to detect and follow compositional differences that have clinical relevance in the diagnosis and follow-up of thrombi.

Blood Coagulation↗

Effects of long-term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle.

1. The effects of long-term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2. ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg-1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14-0.18 micrograms ml-1 and 1.47-3.63 micrograms g-1 wet wt. respectively. 3. Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity (Vmax) was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E-4031, Cs+ and 4-aminopyridine, did not show marked reverse use-dependence. 4. APD and Vmax restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5. Acute application of amiodarone (10 microM) caused a significant decrease in APD and developed tension, as well as a marked use-dependent Vmax inhibition with fast recovery kinetics. 6. These findings suggest that a major and consistent electro-physiological effect of chronic amiodarone is repolarization delay (Class-III action) showing minimal frequency-dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class-I action would be added as an acute effect.

Action Potentials↗

Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea-pig ventricular cells.

1. The effects of diprafenone and propafenone on transmembrane action potential were examined and compared in papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, both diprafenone and propafenone > or = 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. 3. In the presence of either drug, trains of stimuli at rates > or = 0.1 Hz led to an exponential decline in Vmax. A time constant (tau R) for Vmax recovery from the use-dependent block was 15.5 s for diprafenone and 8.8 s for propafenone. 4. The use-dependent block of Vmax with diprafenone was enhanced when the resting potential was depolarized by high (8, 10 mM) [K+]o, whereas that with propafenone was virtually unchanged. tau R with diprafenone was shortened by the depolarization, while that with propafenone was rather prolonged. 5. In single myocytes perfused with diprafenone or propafenone, 10 ms conditioning clamp to 0 mV caused a significant decrease in Vmax of subsequent action potential. A prolongation of the clamp pulse duration resulted in a modest enhancement of the Vmax inhibition with diprafenone, while a large enhancement of the Vmax inhibition occurred with propafenone. 6. These findings suggest that diprafenone, like propafenone, may block the sodium channel during both the activated and inactivated states. The relative contribution of inactivation block is less important for diprafenone than for propafenone. The different voltage-dependence of use-dependent block with diprafenone from propafenone would contribute to its high antiarrhythmic potency.

Action Potentials↗

Desensitization to acetylcholine in single sinoatrial node cells isolated from rabbit hearts.

The negative chronotropic effect of acetylcholine (ACh) on the sinoatrial node fades in the continuous presence of ACh as a result of desensitization. We have investigated the mechanism underlying desensitization in single rabbit sinoatrial node cells using the whole cell patch clamp technique. The negative chronotropic effect resulting from the injection of a constant hyperpolarizing current faded. ACh activated an inwardly rectifying potassium current (iK,ACh), which faded in the continuous presence of ACh. ACh had no effect on "basal" L-type calcium current (iCa), but ACh decreased iCa, which had been potentiated by isoprenaline. This effect did not fade during a 2-min exposure to ACh. ACh decreased the hyperpolarization-activated current (i(f)). This effect again did not fade. These results suggest that desensitization of the negative chronotropic response to ACh is, in part, the result of the membrane hyperpolarization and, in part, the result of the fade of iK,ACh. These results also suggest that, whereas the activation of potassium current by ACh rapidly fades, the effects resulting from the inhibition of adenylate cyclase do not.

Acetylcholine↗

Protective action of iron-chelating agents (catechol, mimosine, deferoxamine, and kojic acid) against ischemia-reperfusion injury of isolated neonatal rabbit hearts.

Iron is suggested to play an important role in free radical generation during ischemia reperfusion. In the present study, the protective action of 4 iron-chelating agents, with different iron affinities, against reperfusion injury was examined in Langendorff-perfused hearts of neonatal rabbits. The chelators and their iron-binding constants (log Km) were as follows: catechol (43), mimosine (36), deferoxamine (31) and kojic acid (27). Following cardiac arrest, the hearts were subjected to global ischemia for 45 min at 37 degrees C, and then reperfused with modified Krebs-Henseleit solution for 30 min. In control, the left ventricular developed pressures (LVDP) after 30 min reperfusion recovered to 50.5 %/- 3.0% (mean +/- SEM; n = 5) of the preischemic level. In the hearts treated with catechol (30 microM), mimosine (30 microM) or deferoxamine (30 microM), the LVDP recovery was significantly improved up to 84.9 +/- 1.3, 88.2 +/- 2.9 or 87.4 +/- 1.5%, respectively (p < 0.01 vs. control). Creatine phosphokinase (CPK) leakage during the initial 5 min of reperfusion was significantly decreased to about half of control in the hearts treated with catechol, mimosine, or deferoxamine. However, the treatment with kojic acid (30 microM) showed no improvement in the LVDP recovery and CPK leakage. Free radical generation was measured with an electron spin resonance using a spin-trapping agent, 5,5-dimethyl-pyrroline-N-oxide (DMPO). The treatment with catechol, mimosine, or deferoxamine reduced the maximum intensity of DMPO-OH signal to about one third of control. However, the maximum intensity in the hearts treated with kojic acid showed a similar level to control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A model analysis for competitive binding of mexiletine and aprindine to the cardiac sodium channel.

A simulation model was developed to predict complex interaction between antiarrhythmic drugs and cardiac sodium channels. This model has four assumptions: (1) Vmax of the action potential is a linear indicator of available sodium channel conductance; (2) antiarrhythmic drugs block the channel by binding to a single common receptor site associated with the channel; (3) binding and dissociation rate constants differ for the three channel states: activated, inactivated and resting, and (4) both drug-free and drug-bound channels change states far more rapidly than binding and dissociation processes. Binding and dissociation rate constants for the three channel states were calculated from single cell experiments using guinea pig hearts. Vmax changes reflecting tonic and use-dependent sodium channel block in the presence of mexiletine and aprindine were simulated and compared with those obtained in the single cell experiments. The model predicted that 'tonic' Vmax inhibition would be enhanced, whereas 'use-dependent' ones would be attenuated after admixture of mexiletine with aprindine. The mechanisms would involve competitive interaction at the common receptor site. Single-cell experiments supported this prediction. We conclude that our simple two-drug binding model provides a useful tool to predict pharmacological interaction between class I antiarrhythmic drugs given in combination.

Action Potentials↗

A retrospective study of resected gastric cancers.

From 1976 to 1989, a total of 1303 patients with gastric cancers underwent gastrectomies in the First Department of Surgery, Kurume University Hospital. Of these, 358 (27.5%) were total gastrectomies, 84 (6.4%) were proximal gastrectomies and 825 (63.1%) were distal gastrectomies. The 5-year survival rate was 44.8% after the total gastrectomies, 38.9% after the proximal and 72.4% after the distal gastrectomies. The 5-year survival rate was 86.2% with the absolute curative resection, 36.3% with the relative curative resection, 29.3% with the relative non-curative resection and 9.4% with the absolute non-curative resection. Macroscopically, the 5-year survival rate was 95.1% for type 0 (early cancers), 61.3% for Borrmann type 1, 58.8% for Borrmann type 2, 37.5% for Borrmann type 3 and 16.5% for Borrmann type 4. According to the pathological cancer stage, the 5-year survival rate was 94.8% for stage I, 79.3% for stage II, 49.2% for stage III and only 11.3% for stage IV.

Gastrectomy↗

Retrospective studies of gastric subserosal (ss) cancer--in comparison to pm- and se-cancers.

The deepest gastric cancer invasion into the tela subserosa is expressed as the ss-cancer. Subserosal gastric cancers (ss) can be divided into 4 subtypes; ss alpha, ss beta, (ss gamma) and ss gamma, pathologically. These four subtypes were compared to cancerous invasion into the muscularis propria (pm-cancer) and cancerous invasion with serosal exposure (se-cancer). During the 10 years from 1979 to 1988, a total of 938 cases with gastric cancer were resected in the First Department of Surgery, Kurume University Hospital. Of these, 104 (11.1%) cases were ss-cancers, consisting of 28 (27%) cases of ss alpha, 33 (32%) cases of ss beta, 4 (3%) cases of (ss gamma) and 39 (38%) cases of ss gamma. Pm-cancers and ss-cancers were most frequently observed in Borrmann type 2, macroscopically, and in the differentiated type, histologically. On the other hand, se-cancers were frequently observed in Borrmann type 3 and in an undifferentiated type. Positive lymph node metastases were found in 49.1% of pm-cancers, in 50.0% of ss-cancers and in 79.9% of se-cancers (p < 0.01), with no statistical difference in the positive lymph node metastasis rates for the subdivisions of ss-cancer. In ss-cancer, however, there was a statistical difference in prognosis according to the tumor size, and according to the degree of subserosal infiltration. The 5-year survival rate was 82.3% for pm-cancer, 75.0% for ss-cancer and 34.7% for se-cancer (p < 0.01).

Female↗

Gastric cancer surgery in the elderly.

Although there is a decreasing number of gastric cancer patients in Japan, the number of patients over 80 years of age is increasing. Forty patients over 80 years of age (from 80 to 88 years) with gastric cancer (Group 1) during the 10 years from 1980 to 1989 were retrospectively investigated and compared with those 70-79 years of age (Group 2). The resectability rate was 80% in Group 1 and 89% in Group 2. Early gastric cancer was observed at a rate of only 25% in Group 1 and 39% in Group 2. Pathologically, the differentiated type occurred in 78% of those in Group 1 and 68% of Group 2. Total gastrectomy was performed in only 6% of the resected cases in Group 1 and in 25% of Group 2. A combined resection including such operations as pancreatico-splenectomy or splenectomy (PS) was employed in none of the total gastrectomy cases in Group 1 and in 30% of Group 2. R3 gastrectomy was performed in none of the patients in Group 1 and in 21% of those in Group 2. Postoperative complications occurred in 25% of Group 1 patients and in 12% of Group 2 patients. Anastomotic leakage occurred in 3% of those in Group 1 and in 4% of those in Group 2. The 5-year survival rate was 47% for all the resected cases in Group 1 and 68% for Group 2. The 5-year survival rate was 61% for those who underwent a curative (radical) gastrectomy in Group 1, and 84% for those in Group 2.

Aged↗

Operative color Doppler imaging for vascular surgery.

Operative color Doppler imaging (CDI) was performed during 57 vascular operations (24 carotid, 24 lower extremity, six renal artery, and three other operations), and its benefits were assessed in comparison to B-mode imaging. Pre-reconstruction operative CDI was used selectively in 18 operations, and post-reconstruction operative CDI was used routinely in all operations. In 16 operations (28.6%), post-reconstruction CDI diagnosed vascular defects such as intimal flaps (n = 4), anastomotic stenoses (n = 7), and in situ bypass arteriovenous fistulas (n = 4). Vascular defects at eight operations required immediate repair. Operative CDI had advantages over B-mode imaging in (1) detection of preoperatively unknown vascular abnormalities before reconstruction, (2) faster recognition of vascular defects after reconstruction, (3) unique ability to detect problems (i.e., arteriovenous fistulas) that were unidentifiable by B-mode imaging, and (4) provision of supplemental blood flow information.

Blood Flow Velocity↗

Remnant-stump gastric cancer following partial gastrectomy.

Between 1970 and 1990, a total of 2,189 patients with gastric cancer underwent resection in the First Department of Surgery, Kurume University Hospital. Of these, 54 patients had previously undergone a partial gastrectomy. The time interval between the initial partial gastrectomy and the resection of the remnant-stump gastric cancer was more than 10 years in 25 patients and less than 10 years in 29 patients. Those with a time interval of more than 10 years we have termed remnant-stump cancer. The original pathology was a gastric ulcer in 13, a duodenal ulcer in 5, a gastric polyp in 1, and a gastric cancer in 6 patients. Of the 19 patients that had undergone an initial operation for benign disease (Group 1), 15 (79%) patients had received initial reconstruction by B-II and 4 (21%) by B-I. On the other hand, of the 6 patients with an initial operation for gastric cancer (Group 2), 3 (50%) had undergone reconstruction by B-I and the other 3 (50%) had received a B-II procedure. Twenty-three of 25 (92%) remnant-stump gastric cancers underwent total gastrectomy, while the other 2 (8%) were early remnant-stump cancers in the stoma and underwent partial gastrectomy. In group 1, only 5 out of 19 (26.3%) patients are alive, while in group 2 all 6 patients are alive, including the 2 (33.3%) early-stage cancers that were found through periodical endoscopic follow-up examinations.

Adult↗

The value of operative ultrasonography in diagnosing tumor extension of carcinoma of the stomach.

Operative ultrasonography was performed during operations to improve the accuracy of diagnosing the extent of the spread of carcinoma of the stomach in the following areas: tumor invasion in the gastric wall (31 patients), para-aortic lymph node metastasis (30 patients) and hepatic metastasis (30 patients). The over-all diagnostic accuracy rates of operative ultrasonography were 81 per cent for determining the depth of tumor invasion, 80 per cent for carcinoma of the mucosa, 70 per cent for carcinoma of the submucosa, 83 per cent for carcinoma of the proper muscle, 80 per cent for carcinoma of the subserosa and 100 per cent for carcinoma of the extraserosa. The over-all accuracy of operative ultrasonography in diagnosing para-aortic lymph node metastasis was 93 per cent. In comparison with the results of preoperative studies, the accuracy (sensitivity) of operative ultrasonography was significantly superior in diagnosing metastasis to the lymph nodes. In three of 30 operations, preoperatively unrecognized and nonpalpable (occult) hepatic metastases were identified by operative ultrasonography. Operative ultrasonography provides more accurate information regarding the spread of carcinoma of the stomach, and thus may be helpful in deciding upon the type of surgical procedure or in avoiding unnecessary tissue dissection.

Carcinoma↗

Pharmacological characteristics of NP-252, a new dihydropyridine slow Ca2+ channel blocker, in isolated rabbit vascular smooth muscle and guinea pig myocardium: vascular selectivity.

NP-252, a new dihydropyridine derivative, and nifedipine non-competitively inhibited contractile responses to KCl and responses to Ca2+ in Ca(2+)-free medium containing KCl in rabbit aorta and renal, mesenteric, coronary and basilar arteries, mesenteric veins and vena cava. The effects of NP-252 in these smaller arteries and veins were much greater than those in aorta. However, a similar differential selectivity was not seen with nifedipine. In aorta, only NP-252 reduced total La3+ resistant 45Ca binding. However, the increases in bound 45Ca at La3+ resistant sites and 45Ca unidirectional influx due to KCl were inhibited by both NP-252 and nifedipine. The displacement of [3H]nitrendipine binding to rabbit aorta was monophasic for both NP-252 and nifedipine. In guinea-pig papillary muscles, NP-252 (greater than 10(-7) M) slightly decreased action potential duration, developed tension and slow action potentials. The cardiac effects of NP-252 were much less prominent than those of nifedipine. These results indicate that NP-252 inhibits voltage-operated Ca2+ channels in small arteries and veins much more effectively than those in aorta, and this tissue selectivity is more apparent for NP-252 than nifedipine.

Action Potentials↗

Effects of KT-362, a new antiarrhythmic agent with vasodilating action on intracellular calcium mobilization of atrial muscle.

Effects of KT-362 (5-[3[2-3, 4-dimethoxyphenyl) ethyl]amino]-1-oxopropyl]-2,3,4,5- tetrahydro-1,5-benzothiazepine fumarate; 3-100 microM) on the twitch contraction of isolated rabbit left atria were examined to elucidate the influence of this substance on the intracellular calcium mobilization of cardiac muscles. A 30-sec rest period interrupting the conditioning stimulation at rates greater than 0.5 Hz caused positive inotropy of the first postrest (B1) contraction (rest potentiation). The potentiated B1 contraction was much more resistant to the negative inotropic effect of nifedipine (1 and 3 microM) than the steady-state contraction. The nifedipine-resistant B1 contraction was abolished by ryanodine (30 nM) or caffeine (5 mM). Single treatment of the muscle with KT-362 much greater than or equal to 10 microM resulted in a concentration-dependent decrease in the steady state beat as well as in B1 contraction. In preparations pretreated with 1 microM nifedipine, KT-362 had greater inhibitory action against B1 contraction (IC50 = 7.8 microM). KT-362 (3 and 10 microM) reduced the late plateau amplitude of transmembrane action potential associated with the B1 contraction. Tetrodotoxin (1 and 3 microM) and quinidine (3 and 10 microM) caused a rightward shift of the force-frequency relationship for the B1 contraction but, unlike KT-362, they caused no or minimal reduction of the maximal B1 values. In the presence of 1 microM nifedipine, B1 contraction showed biphasic response to a prolongation of the preceding rest period, an initial rapid increase up to 30 sec was followed by a gradual decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The inhibitory action of okadaic acid on mechanical responses in guinea-pig vas deferens.

Okadaic acid and nifedipine inhibited contractions induced by noradrenaline (NA), KCl and ATP in guinea-pig vas deferens. NA, KCl and ATP induced initial spike-like changes followed by a sustained increase in cytosolic Ca2+ levels ([Ca2+]cyt) and tension. Okadaic acid inhibited the sustained increments in [Ca2+]cyt and muscle tension due to NA and ATP more than the initial spike-like changes, whereas nifedipine more strongly inhibited the initial spike changes. Okadaic acid also inhibited the KCl-induced contraction with only a small inhibition of the stimulated [Ca2+]cyt. By contrast, nifedipine (10(-7) M) inhibited the increments in both [Ca2+]cyt and muscle tension due to KCl. Okadaic acid markedly inhibited the maximal contractile response to Bay K 8644 but nifedipine only shifted the response curve to the right without affecting the maximum responses. In a Ca2(+)-free medium containing EGTA and nifedipine, okadaic acid did not inhibit the residual phasic contractile response to NA (10(-4) M) but the contractile response to a subsequent addition of Ca2+ (1.2 mM) was suppressed. These results suggest that, in guinea-pig vas deferens, okadaic acid has an inhibitory effect on smooth muscle contraction but not on the intracellular Ca2+ mobilization. The inhibitory effect may be due to the inhibition of Ca2+ influx and the possible interference of contractile elements.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Effects of combined use of class I antiarrhythmic agents on Vmax of guinea-pig ventricular muscles.

The effects of the combined use of class-I antiarrhythmic drugs on the resting potentials (RP), amplitude of action potential (AMP), and Vmax of the action potential were investigated in guinea-pig ventricular papillary muscles that were superfused with oxygenated Krebs-Ringer solution at 35 degrees C. Disopyramide (40 microM) reduced Vmax to 68.6 +/- 3.1% (mean +/- SE, n = 5) of the control with minimal changes in RP and AMP when preparations were stimulated at 1 Hz. The addition of mexiletine (20 microM) to the solution containing disopyramide (40 microM) caused a minimal reduction of Vmax (less than 5%) for the stimulation of 1 Hz, but a significant reduction of Vmax (13% p less than 0.05) when stimulation was increased to 2 Hz. This amount of the reduction is compatible with that obtained by mexiletine alone, suggesting a simple additive Na+ channel inhibition by this drug combination. This additive effect was also observed in the recovery process of Vmax from the use-dependent block induced by train stimuli at 1 Hz. Flecainide (5 microM) reduced Vmax to 58.6 +/- 13.3% (n = 5). The addition of mexiletine to the superfusate with flecainide produced a further depression of 14 +/- 2.6% of Vmax, even at 1 Hz. This depression was larger than that produced by mexiletine, suggesting a synergistic action of the two drugs on the Na+ channel. Such information about the interaction of the class I drug combinations with the Na+ channel may be clinically important.

Action Potentials↗

Technique of ultrasonic detection and mapping of abdominal wall adhesions.

A technique for noninvasive ultrasound examination to detect and map abdominal wall adhesions is described. The examination is based on the demonstration of movement of abdominal viscera during real-time imaging. This movement is called viscera slide and either occurs spontaneously as a result of respiratory movement or may be induced by manual compression. Abdominal wall adhesions produce a restriction of viscera slide. Ultrasonic demonstration of restricted viscera slide has been used for the precise localization and mapping of abdominal wall adhesions prior to abdominal surgery. The technique may be particularly useful in providing safe initial access in patients undergoing laparoscopy who are at increased risk for trocar injury of viscera due to abdominal wall adhesions resulting from previous surgery or peritonitis.

Abdominal Muscles↗

Induction of reinitiation of meiosis in amphibian Bufo and Xenopus oocytes by injection of M-phase extracts of ciliate Tetrahymena needs the recipient protein synthesis.

We show here that germinal vesicle breakdown of amphibian Bufo and Xenopus oocytes can be induced if ciliate Tetrahymena extracts are injected into them. The activity of meiosis-reinitiation-inducing factor (MRIF) appeared only a M-phase of a synchronously dividing culture, indicating that this MRIF has an important function for induction of M-phase in the mitotic cell cycle. MRIF of Tetrahymena differed from MPF (M-phase-promoting factor), because its action on the induction of GVBD was inhibited by cycloheximide and it could not induce GVBD in starfish oocytes by microinjection. MPF activity was not detected in extracts of vegetatively growing Tetrahymena. Preliminary experiments showed that MRIF was a heat-labile, Ca2(+)-sensitive, and trypsin-sensitive soluble protein.

Animals↗