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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 415 records · Page 23Linked to original sources

Structure-activity relationships of phenylethylamine analogs in their serotonergic depressant effects on the spinal monosynaptic reflex in rats.

The effects of 2-phenylethylamine (PEA) and related compounds on the spinal monosynaptic reflex (MSR) were examined using C1-spinalized rats. At low doses, PEA, S(+)-amphetamine, S(+)-methamphetamine and phentermine increased the amplitude of the MSR, whereas high doses of these drugs reduced it. p-Substituted PEA analogs (p-C1-PEA, p-methoxy-PEA and (+/-)-p-C1-amphetamine) only reduced the MSR. Low doses of PEA-related rigid compounds, R(+)-2-aminotetralin, (+/-)-N-methyl-2-aminotetralin and (+/-)-N,N-dimethyl-2-aminotetralin only reduced the MSR. S(-)-2-Aminotetralin did not affect the MSR. Depressions of MSR produced by PEA, S(+)-methamphetamine and R(+)-2-aminotetralin were antagonized by ketanserin and haloperidol which have 5-hydroxytryptamine (5-HT) antagonistic activity, and the MSR depression caused by S(+)-methamphetamine but not PEA and R(+)-2-aminotetralin was abolished by intracisternal 5,6-dihydroxytryptamine treatment or chronic spinal transection. These results suggest that PEA-related compounds cause MSR depression by direct and indirect 5-HT agonistic mechanisms, and support the proposal that the PEA moiety which exists in R(+)-2-aminotetralin is important for the direct 5-HT agonistic activity of some hallucinogens.

Animals↗

The effect of left ventricular wall motion during isovolumetric relaxation period in coronary artery disease.

The effect of the left ventricular (LV) regional wall motion during isovolumetric relaxation period (IRP) were studied in 9 patients with old anteroseptal myocardial infarction (OMI) and 8 normal subjects (NOR). There were no significant differences in heart rate, peak LV systolic pressure and peak (+) dP/dt between the groups. LV cavity was divided into the anterior and inferior sides by a long axis, which was equally divided with 3 perpendicular lines, creating 4 areas in each side. The sums of the 2 middle areas in each side were defined as Aa and Ab, respectively. During IRP the pattern of (-) dP/dt at the upstroke phase was convex-downward in OMI, but convex-upward in NOR. Time constant (T) was significantly prolonged in OMI compared with NOR (50 +/- 9 vs 37 +/- 6 msec; p less than 0.01). On NOR, Aa increased significantly after 33.4 msec from peak (-) dP/dt, while Ab remained unchanged. In OMI, Ab increased after 50.1 msec from peak (-) dP/dt, associated with decrease in Aa, suggesting the passive shortening of the anterior wall by the active expansion of the inferior. Such asynchronous LV wall motions during IRP might impair LV relaxation and influence the upstroke pattern of (-) dP/dt.

Adult↗

Effect of D-galactosamine on blood clearance of 99mTc-phytate in dogs.

The effect of D-galactosamine (GalN) on the blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and the blood clearance test of 99mTc-P was compared with the cases of the serum transaminase and bilirubin test. Serum transaminase and bilirubin levels in dogs increased dose-dependently after GalN administration, and the degree of increase in these parameters was much higher than the cases in rats. The disappearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of GalN and with the passage of time after the GalN administration. Changes of the blood clearance of 99mTc-P after GalN treatment in dogs may be influenced by the disorder in the hepatocytes. The blood clearance test of 99mTc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by GalN equally to the serum transaminase and bilirubin test.

Alanine Transaminase↗

Effect of alpha-naphthylisothiocyanate on blood clearance of 99mTc-phytate in dogs.

The effect of alpha-naphthylisothiocyanate (ANIT) on blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and blood clearance test of 99mTc-P was compared with the cases of serum transaminase test or serum bilirubin test. Serum transaminase and bilirubin levels in dogs increased after ANIT administration, however, the degree of increase in these parameters was much lower than the cases in rats. The disappearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of ANIT and with the passage of time after the ANIT administration. Changes of the blood clearance of 99mTc-P after ANIT treatment in dogs may be influenced by the disorder in the hepatocytes rather than in the bile ductule cells. The blood clearance test of 99mTc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by ANIT equally to the serum transaminase test or the serum bilirubin test.

1-Naphthylisothiocyanate↗

Relation between blood clearance and hepatic uptake of 99mTc-phytate in rats with hepatic injury.

The relation among the blood clearance of 99mTc-phytate (99mTc-P), the hepatic uptake of 99mTc-P and the severity of hepatic injury was investigated by using the rats with carbon tetrachloride (CCl4), D-galactosamine (Gal N), alpha-naphthylisothiocyanate (ANIT) or DL-ethionine (EthN) induced hepatic injury. After the administration of CCl4, GalN or ANIT, serum GPT activity increased significantly with the increase of dose level, and the degree of this increase was in the order: GalN greater than CCl4 greater than ANIT. However, the mild increase in serum GPT activity was observed after EthN administration. The blood clearance rate of 99mTc-P and the hepatic uptake ratio of 99mTc-P decreased with the increase of dose level after CCl4, GalN or ANIT administration, but significant changes were not found after EthN administration. The degree of decrease in the blood clearance rate of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT, and the degree of decrease in the hepatic uptake ratio of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT. These results suggest that the disorder in the hepatocytes may be one of causes for inducing the decrease in the hepatic uptake of 99mTc-P, and the consequence of this decrease may induce the decrease in the blood clearance of 99mTc-P.

1-Naphthylisothiocyanate↗

Metabolic fate of the new anti-ulcer drug enprostil in animals. 3rd communication: tissue accumulation after consecutive oral administration of [3H]-enprostil in rats.

Accumulation characteristics of radioactivity in organs and tissues were investigated after oral administration of [3H]-enprostil ((+/-)-11a,15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorp r osta-4,5,13(t)- trienoic acid methyl ester, TA-84135) to male rats once a day (20 micrograms/kg/d) for 1, 7 or 14 days. [3H]-Enprostil was found to be partially metabolized in vivo to volatile tritium (3H2O). The ratios of volatile tritium to total radioactivity in plasma increased with repeated administration of [3H]-enprostil and the levels of volatile tritium were almost equilibrated within 7 days of drug administration. The formation rate of volatile tritium was estimated to be 1-2% of the single dose. The blood levels of non-volatile radioactivity at 1 h after each daily dosing were nearly constant. The levels at 24 h, however, increased with repeated dosing. The levels of non-volatile radioactivity in most tissues at 1 h after the multiple administration (7 and 14 times) were higher than those after the single dose. At 24 h, levels were noticeable after multiple dosing even in the tissues in which levels below the detection limit were found after the single dose. From the comparison of the multiple-dose groups, the levels in most tissues attained steady state within 7 times dosing. The daily excretions of radioactivity in the urine, feces and expired air were constant throughout the period of consecutive administration. The total recovery of administered dose was 92%, which was similar to that achieved in the single-dosing group. As described above, the retention of non-volatile radioactivity was observed in most tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Metabolic fate of the new anti-ulcer drug enprostil in animals. 4th communication: effect on hepatic drug metabolizing enzyme system in rats.

Effects of multiple oral administration of enprostil ((+/-)-11 alpha,15 alpha-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorprosta- 4,5,13(t)-trienoic acid methyl ester, TA 84135) (20 micrograms/kg/d) and its solvent propylene carbonate (PC, 100 microliters/kg/d) on body weight gain, liver weight, hepatic drug metabolizing enzyme system and hexobarbital sleeping time were investigated in male rats during a 14-day period. Cytochrome P-450 content (as compared to the untreated control) and cytochrome b5 content (as compared to PC treated group) were slightly, but significantly, reduced in the group given a single oral dose of enprostil. However, these slight reductions were not augmented significantly by repeated administrations of enprostil. Slight but significant increase in microsomal protein content was observed in the group given 14 oral doses of enprostil and PC. Enprostil did not affect the other indicators used to evaluate the status of the hepatic drug metabolizing enzyme system. Additionally, single or multiple oral doses of enprostil or PC showed no effect on the hexobarbital-induced sleeping time. It therefore may be safely concluded that multiple oral administration, both of enprostil and of PC, has very little effect on drug metabolizing enzyme inducing or inhibiting activity in rats.

Animals↗

[Pulsatile assistance for profoundly hypothermic circulatory arrest, low-flow perfusion, and moderate-flow perfusion: comparative study of brain tissue pH, PO2, and PCO2].

The pH, oxygen tension, and carbon dioxide tension of canine brain tissue were experimentally examined during profoundly hypothermic cardiopulmonary bypass with and without pulsatile assistance. After core cooling, a 60-minute of circulatory arrest was performed in group 1 (n = 16), a 120-minute of low-flow perfusion (25 ml/kg/min) in group 2 (n = 16), and 120 minute of moderate-flow perfusion (50 ml/kg/min) in group 3 (n = 16). The core rewarming was done to the temperature above 32 degrees C. Each group was divided into two subgroups with and without pulsatile assistance (subgroup-p; n = 8, subgroup-c; n = 8). In group 1, progressive brain tissue acidosis and hypercapnea were recovered by use of pulsatile assistance. In group 2, brain tissue acidosis and hypercapnea were recovered completely with pulsatile assistance, but incompletely without it. In group 3, mild acidosis and hypercapnea were eliminated with pulsatile assistance. Brain tissue hypoxia was severe in group 1, slight in group 2, but not found in group 3. We conclude that a pulsatile assistance provides brain protection at any flow-ratio, and that the less flow-ratio and the longer perfusion period will make the pulsatile assistance the more necessary.

Animals↗

[Exercise induced hypoxemia and exercise tolerance in patients with COPD and the benefits of oxygen supplementation].

In order to evaluate the benefits of O2 supplementation during exercise, slowly incremental treadmill exercise tests were performed twice with 30 minutes interval rest in fourteen patients with severe COPD. The patients breathed room air. 31/min of compressed air by nasal prongs, and 31/min of supplemental oxygen in single blind fashion at random. The patients who developed arterial desaturation below 88% on exercise, group D, showed slight but significant increase in walked distance (397 m vs 424 m) and significant decrease in breathlessness (22.9 vs 16.9) on oxygen as compared to on air. On the other hand in patients without significant arterial desaturation, group S, there was no improvement in those parameters. The increase in walked distance on oxygen was closely related with the decrease in mean inspiratory flow (VT/Ti), blood lactate level, and CO2 production at identical work load. Plasma human atrial natriuretic peptide (h-ANP) levels in group D increased with exercise from a resting value of 27.6 +/- 6.9 to 44.0 +/- 9.0 on compressed air whereas the increase was significantly suppressed to 35.4 +/- 9.0 on oxygen. In group S there was no difference in the increase of plasma h-ANP levels between air and oxygen breathing during exercise (33.1 +/- 5.1 vs 31.9 +/- 9.6). A close correlation (r = 0.908) was found between mean pulmonary artery pressures and plasma h-ANP levels at rest and during exercise performed in four patients breathing air and oxygen. Those findings suggested that arterial plasma h-ANP levels reflected the right ventricular afterload and that they could be used to evaluate the effectiveness of O2-supplementation during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Kaposi's sarcoma developing during corticosteroid therapy in idiopathic thrombocytopenic purpura].

A case of Kaposi's sarcoma developing during corticosteroid therapy for idiopathic thrombocytopenic purpura is reported. The patient is a 58-year-old female who was admitted to Sapporo City General Hospital for bleeding tendency in March 1987. She had been treated before admission with prednisolone (over 40 mg/day) for idiopathic thrombocytopenic purpura since October 1986, but her platelet count was below 40,000/microliters. In April 1987, several dark red or blue nodules appeared on the tip of her nose, left forearm, right shoulder, trunk and tongue. These nodules rapidly grew. Biopsy specimens from the nodule of the left forearm showed the histologic changes of Kaposi's sarcoma. She was treated with irradiation. Splenectomy was done in May 1987 and prednisolone was decreased to 5 mg/day. Her platelet count was continually kept 50,000/microliters or more. Her Kaposi's sarcoma completely regressed in January 1988. The relationship of immunosuppressive therapy to Kaposi's sarcoma is discussed.

Female↗

Multi-organ damage (MOD) induced by cancer cachexia and its pathogenesis.

The intraperitoneal implantation of the ascitic hepatoma cells, AH-130 to rats induced marked atrophy of the systemic organs within 2 weeks, resulting in the animal death. By the method of Feulgen hydrolysis curve analysis, the amount of single-stranded DNA and the degree of DNA instability were shown to be increased in these atrophic organs. In keeping pace with the progression of the cachectic multi-organ damage (MOD), the amount of lipidperoxide and the activity of superoxide dismutase (SOD) as measured by electron spin resonance (ESR) were increased in the ascites toward the end stage of chachexia. The increased lipidperoxide and SOD induction reflect the increased production of active oxygens, especially superoxide. The marked systemic organ damage induced in cancer cachexia seems to be due to DNA damage by active oxygens.

Animals↗

[Brachiocephalic arterial aplasia of the right aortic arch with subclavian steal syndrome].

A 44-year-old man was admitted to our hospital with complaint of weakness in his left upper extremity, vertigo, and diplopia. After aortic root injection of contrast medium, a right aortic arch was visualized. The left brachiocephalic artery was not found, however. An operation was performed through a midline sternotomy. The first branch of the aortic arch was the right common carotid artery, and the second branch was the right subclavian artery. The left brachiocephalic arterial aplasia was recognized. An E-PTFE graft was anastomosed proximally to the ascending aorta and distally to the junction of the left common carotid and left subclavian arteries. After the operation, some of the symptoms were improved and the others were removed.

Adult↗

[A case of tracheal agenesis].

A case of neonate boy with tracheal agenesis and other anomalies, which is very rare, is reported. This case belongs to VATER association. No radiolucent area of trachea could be seen and esophagography demonstrated tracheoesophageal fistula and defects of trachea.

Abnormalities, Multiple↗

[Effect of myocardial preservation and preoperative left ventricular end-diastolic pressure upon the early postsurgical cardiac function after prosthetic cardiac valve replacement].

We investigated the effect of myocardial preservation and preoperative stroke work index (SWI) and left ventricular end-diastolic pressure (LVEDP) upon the early postsurgical kinetics of left ventricular function in thirty-four patients after prosthetic cardiac valve replacement. They received both-sided cardiac catheterization and measurement of cardiac output by dye dilution method in a standard fashion. Myocardial temperature was measured simultaneously and consecutively during aortic cross-clamping period (greater than 70 min) on open heart surgery. Thereafter, each postsurgical left ventricular function was estimated at three, six, twenty-four and forty-eight hours after weaning from cadiopulmonary bypass (CPB) by using Swan-Ganz catheter. SWI0 X 1000/AnI was used as an improved index of postsurgical cardiac function, because it was incorporated with the preoperative left ventricular stroke work index (SWI0) and anoxic index (AnI), which was the integral of myocardial temperature during aortic cross-clamping period. Otherwise, we regarded LVEDP as an estimate of preoperative cardiac function. So we compared them with the early postsurgical left ventricular SWI, respectively. As a result, the relation between SWI0 and the postsurgical SWI (SWI24 and SWI48) showed positive correlations with correlation coefficients 0.52 and 0.70, and the relation between AnI and the early postsurgical SWI (SWI3 and SWI6) showed negative correlations with correlation coefficients -0.56 and -0.52. While the relation between SWI0 X 1000/AnI and postsurgical SWI (from SWI0 to SWI48) showed positive correlations with correlation coefficients decreasing from 0.76 to 0.57. LVEDP showed negative correlations to SWI0 and SWI48 with correlation coefficients -0.48 and -0.45.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Comparison of cold blood cardioplegia and cold crystalloid cardioplegia with or without magnesium].

Blood cardioplegia has recently been advocated as a superior method of myocardial protection, but its temperature is important, and it has not been compared to a magnesium containing crystalloid cardioplegia. This study was undertaken to compare the protective effect of cold blood cardioplegia (BCP) and cold crystalloid cardioplegia with or without magnesium (MgKCP and KCP). Fourty-five patients were undertaken prosthetic cardiac valve replacement with left ventricular volume overload from valvular regurgitation. They were divided into three groups for the difference of the cardioplegic solution. Intraoperatively, myocardial temperature and the tissue PCO2 was monitored, and the content of calcium and magnesium of right atrium was measured before and after aortic cross clamping. Postoperatively, left ventricular stroke work index and serum CPK-MB isozyme activity were measured at 3, 6, 24 and 48 hours after weaning from cardiopulmonary bypass. The increase of the tissue PCO2 during aortic cross clamping and its recovery at ten minutes after reperfusion were significantly suppressed in BCP. The retension of the tissue calcium after reperfusion and calcium to magnesium ratio were significantly low in MgKCP. The recovery of cardiac pump function and decrease of CPK-MB were superior in MgKCP.

Cardioplegic Solutions↗

[Effect of magnesium containing cardioplegic solution on the cases of extended aortic cross clamping].

We have investigated about the preservation of myocardium using magnesium containing cardioplegic solution. In this study we have concluded that magnesium containing cardioplegic solution is effective especially in the cases of extended Aortic cross clamping. 91 cases were availed for studying the post-operative cardiac function, and 32 cases of which were availed for seeking the content of calcium and magnesium of the myocardium. GK-Mg solution was superior in the post-operative cardiac function, and in the total CPK-MB. The retention of calcium in the myocardium after Ao declamping was higher in the cases of using GK solution. And Ca.Mg ratio was also higher in GK solution. Especially in the cases of extended Ao cross clamping, increase of calcium in the myocardium and Ca.Mg ratio was suppressed by using the GK.Mg solution. Although magnesium have several effects on the myocardium, but we think that suppressing the influx of calcium into the myocardium is one of the most important factor of the magnesium for the preservation of myocardium.

Aorta↗