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Biomedical subjects

N Ohara

Publications and source records attributed to N Ohara.

At least 199 records · Page 11Linked to original sources

Tumor necrosis factor-induced lung injury is not mediated by platelet-activating factor.

Both tumor necrosis factor (TNF) and platelet-activating factor (PAF) have been incriminated as mediators of endotoxic shock. Since TNF stimulates PAF synthesis in vitro, we tested the hypothesis that PAF mediates TNF-induced lung injury in vivo using specific PAF receptor antagonists. Intravenous infusion of purified human recombinant TNF resulted in peripheral neutrophilia, lymphocytopenia, and hemoconcentration, caused hemorrhagic injury to the cecum, and increased lung tissue levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha. In addition, plasma glutathione disulfide (GSSG), an in vivo index of oxidative stress, was significantly increased. TNF (0.01-1 mg/kg) caused a dose-dependent increase in lung permeability-surface area product (PS) measured in isolated perfused lungs removed from rats 90 min after injection of TNF. [Lung PS in controls and after 0.01, 0.1, and 1.0 mg/kg of TNF were 0.022 +/- 0.001, 0.027 +/- 0.002, 0.033 +/- 0.001, and 0.036 +/- 0.005, respectively (P less than 0.05 from control for TNF 0.1 and 1 mg/kg).] Pretreatment of the rats with the PAF receptor antagonists WEB 2086 (10 mg/kg) and SRI 63-441 (10 mg/kg), at doses that previously protected against endotoxin-induced lung injury, did not significantly affect TNF-induced (0.1 mg/kg) changes in hematocrit, plasma GSSG, or lung PS. Moreover, WEB 2086 (10 mg/kg) did not inhibit TNF-induced (1 mg/kg) lymphocytopenia or the increases in lung tissue eicosanoid products. We conclude that TNF causes oxidative stress, eicosanoid activation, and acute lung injury in rats by a mechanism largely independent of PAF receptor activation.

Animals↗

Relationship between the number of sperms and the rate of implantation in bitches inseminated into unilateral uterine horn.

Studies were made on the number of sperms required for fertilization of ova ovulated from the bilateral ovaries in bitches. The experiment was carried out with 44 female beagles, which were divided into four groups of seven to eleven bitches each. The four groups were inseminated with 40 X 10(6) sperms/0.2 ml, 20 X 10(6) sperms/0.1 ml, 10 X 10(6) sperms/0.1 ml, and 3-5 X 10(6) sperms/0.1 ml, respectively. All the bitches were laparotomized at an optimum time for mating and inseminated at the tip of the horn of an unilateral uterus. In the four groups conception took place at a rate of 7/7, 8/8, 10/11, and 2/7, respectively. The number of puppies exceeded the number of ova ovulated on the inseminated side at a rate of 5/7, 6/8, 0/10, and 0/2 in the four groups, respectively. Therefore, it was clarified that when more than 20 X 10(6) sperms/0.1 ml were inseminated in the ipsilateral uterine horn, ova ovulated on the contralateral side were fertilized also. Then a unilateral ovary was ovariectomized in 11 bitches, which were inseminated with 10 X 10(6) sperms/0.1 ml in the ipsilateral uterine horn. As a result, only one bitch became conceptive and gave birth to only one puppy. From these results, it was considered that 10 X 10(6) sperms/0.1 ml may be most adequate for the ova on the side of insemination alone to be fertilized.

Animals↗

Hemodynamic evaluation and morphological changes of right ventricular out-flow tract and pulmonary valve after balloon pulmonary valvuloplasty.

Balloon pulmonary valvuloplasty (BPV) was attempted in 38 cases of congenital pulmonary valve stenosis. It was effective and was done without complication in 36 cases, however it was not effective in two cases of pulmonary valve dysplasia. The balloon used was 20-50% larger in diameter than the pulmonary valve annulus. In the seven cases in which the transvalvular pressure gradient was above 100 mmHg on cardiac catheterization, right ventriculography demonstrated that the functional obstruction of the right ventricular outflow tract increased immediately after BPV, however it subsequently improved at one year after the procedure. At between one and three months after BPV, two-dimensional echocardiography demonstrated that the morphological obstruction to the right ventricular outflow tract had diminished. In two cases, localized right ventricular septal hypertrophy with severe pulmonary valve stenosis was observed by two-dimensional echocardiography and right ventriculography, and persisted at one year. In all cases, two-dimensional echocardiography and angiography demonstrated doming pulmonary valves with valve stenosis, which was diminished by BPV. The pulmonary valve morphology was observed by two-dimensional echocardiography in three cases following BPV. In one case, partial relief of pulmonary valve obstruction was seen to be due to commissural splitting and in the other two, to tearing of cusp tissue. Inspection of the pulmonary valve at operation was made in one case who underwent elective surgery for repair of an atrial septal defect which was associated with pulmonary valve stenosis. It demonstrated partial relief of pulmonary valve stenosis by tearing of cusp tissue. In conclusion, BPV is as effective a treatment for congenital pulmonary valve stenosis as open valvulotomy. In our follow-up study, it has shown no apparent complications. The transient obstruction in the right ventricular outflow tract immediately after BPV improved within one month and improved further after three months and one year. However, in the more long-standing cases the localized right ventricular septal hypertrophy persisted and these cases will require, a long term follow-up.

Blood Pressure↗

Effects of l-carnitine on membrane potential derangements induced by palmitoylcarnitine and anoxia in isolated superfused guinea-pig papillary muscle.

We examined in isolated superfused guinea-pig papillary muscle whether palmitoylcarnitine caused electrophysiological derangements similar to those caused by anoxia, and whether l-carnitine was similarly effective in improving membrane potential characteristics in both cases. Superfusion with Krebs-Henseleit solution containing 3 x 10(-4) M palmitoylcarnitine for 30 min caused gradual reduction of resting membrane potential and amplitude of action potential, and marked shortenings of the duration of action potential and absolute refractory period. On the other hand, aeration with 95%N2-5%CO2 for 30 min caused the same electrophysiological changes as those caused by palmitoylcarnitine. In both deteriorated preparations with palmitoylcarnitine superfusion and with 95%N2-5%CO2 aeration, l-carnitine (3 x 10(-3) M) prevented the papillary muscle from these derangements and restored the membrane potential at 10(-2) and 3 x 10(-2) M. It is concluded from these results that acylcarnitines such as palmitoylcarnitine, the accumulation of which has been thought to inhibit oxidative phosphorylation in ischemic heart, induce electrophysiological derangements quite similar to those found under anoxia, and that the application of l-carnitine is an effective solution to improve the electrophysiological derangements.

Animals↗

[Valvular regurgitation in patients with Kawasaki disease and in healthy children: a pulsed Doppler echocardiographic study].

Valvular lesions in the acute stage of Kawasaki disease were observed using pulsed Doppler echocardiography. The subjects consisted of 65 patients with Kawasaki disease (2 months-6 2/12 years) who had been followed from the acute stage. The age-matched 113 controls were selected from 661 healthy children (2 months-14 years of age). In the acute stage of Kawasaki disease, tricuspid regurgitation (TR) was detected in 31 (48%), pulmonary regurgitation (PR) in 22 (34%) and mitral regurgitation (MR) in 17 (26%). There was no aortic regurgitation (AR). In the convalescent stage, TR was found in 26 (40%), PR in 20 (31%), and MR in 11 (17%), but no AR was detected. The incidence of each valvular regurgitation between the acute and convalescent stages in patients with Kawasaki disease did not differ significantly. Furthermore, there was no significant difference in the incidence of valvular regurgitation between patients with Kawasaki disease and the normal controls. In nine patients, however, valvular regurgitation in the acute stage had disappeared by the convalescent stage, and two patients had developed a new pansystolic murmur in the acute stage. We estimated the incidence of pathologic valvular involvement in Kawasaki disease to be 11/65 (17%). The incidence of valvular involvement in patients with coronary artery aneurysms was significantly higher than that of patients without coronary artery aneurysms (p less than 0.01). It was concluded that mild and transient valvular regurgitation, which cannot be detected by auscultation, may occur in some patients in the acute stage of Kawasaki disease. These may be caused by acute inflammation of the valve related to coronary artery lesions. In view of the Doppler echocardiographic findings in normal controls, these regurgitations should be distinguished from "physiological" ones.

Acute Disease↗

[A study on bone density in women during pregnancy and postpartum].

Although 25-30 grams of calcium is transported into the fetus during pregnancy, it is suggested that the maternal bone might be kept at the same density as in non-pregnant women by measuring serum or urinary calcium concentrations and calcium regulating hormones simultaneously (Ohara et al. Folia Endocrinol., 1986). In this study, the influence of pregnancy on the maternal bone was investigated by measuring the degree of bone density in the second metacarpal bone of pregnant or puerperal women in an X-ray picture using a microdensitometer and a computer (Microdensitometry method; MD method, Inoue et al., 1983). Among six indices provided by this method, d (bone marrow width) tended to increase, but MCI (Barnett's metacarpal index) tended to decrease toward late pregnancy. GSmin, GSmax and sigma GS/D were significantly lower in the third trimester of pregnancy than in the second trimester of pregnancy. The densitometric patterns were A in most of the pregnant and puerperal women, but one case with the pattern of AB and two cases with the pattern of B were found in the third trimester of pregnancy. The sum of the scores of the six indices, which were based on the severity of each index, was within 0-3 in pregnant or puerperal women though it tended to increase as pregnancy progressed. From these results, it was confirmed that maternal bone density was maintained within the normal limits throughout pregnancy and postpartum.

Absorptiometry, Photon↗

Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver.

Animals↗

Pharmacological studies of the new centrally acting muscle relaxant 4'-ethyl-2-methyl-3-pyrrolidinopropiophenone hydrochloride.

The pharmacological properties of 4'-ethyl-2-methyl-3-pyrrolidinopropiophenone hydrochloride (HSR-770), a new centrally acting muscle relaxant, were investigated in experimental animals. HSR-770, within a dose range of 1-10 mg/kg i.v., relaxed alpha- and gamma-rigidities in rats, the dose required to relax gamma-rigidity being lower than the dose required to relax alpha-rigidity. When HSR-770 was intraduodenally (i.d.) administered within a dose range of 25-50 mg/kg, the relaxant activity on alpha-rigidity was potent and long-lasting in comparison with eperisone or tolperisone. HSR-770 inhibited flexor reflex more strongly than patellar reflex in a dose-dependent manner within a dose range of 2.5-10 mg/kg i.v. or 25 and 50 mg/kg i.d. in anesthetized cats. In spinal cts, HSR-770 (5 and 10 mg/kg i.v.) inhibited flexor reflex but this potency was weaker than that in anesthetized cats. HSR-770 (12.5-50 mg/kg i.d.) inhibited he crossed extensor reflex in anesthetized rats. In spinal cats, HSR-770 inhibited mono- and polysynaptic reflex potentials to the same extent and also depressed dorsal root reflex potential at 5 and 10 mg/kg i.v. HSR-770 at a dose (50 mg/kg p.o.) which exerted muscle relaxant activity on both rigidity and flexor reflex, had little effect on spontaneous motor activity (mice), hexobarbital-induced sleeping time (mice) and conditioned avoidance response (rats). These results indicate that HSR-770 is a potent centrally acting muscle relaxant and that its central nervous system depressant activity is relatively weak.

Anemia↗

[Dynamics of calcium metabolism and calcium-regulating hormones in pregnancy-induced hypertension].

Serum concentrations of total calcium, ionized calcium and inorganic phosphorus in severe PIH were significantly lower than those in normal pregnancy during the 3rd trimester of pregnancy and continued to be low even at puerperium. On the other hand, serum concentrations of parathyroid hormone in severe PIH were significantly higher during the 3rd trimester of pregnancy and decreased at puerperium. Any remarkable differences in serum calcitonin levels were not found between severe PIH and normal pregnancy through the last trimester of pregnancy and puerperium. Serum concentrations of 1 alpha, 25-(OH)2 vitamin D3 increased significantly in the 3rd trimester of normal pregnancy, but in severe PIH, their increase was not observed, remaining at the normal levels of non-pregnant women. The kidney functions in the both groups were within the normal limits of non-pregnant women, but placental dysfunction was observed in severe PIH. These results suggest that the decrease in serum calcium and phosphorus levels might have occurred as a result of the decrease in the absorption of calcium and phosphorus from the intestine due to the decrease in serum 1 alpha, 25-(OH)2 vitamin D3 levels and that low serum 1 alpha, 25-(OH)2 vitamin D3 concentrations might be caused by the disturbance of the synthesis in the placenta rather than in the kidney.

Calcitonin↗

[Calcium metabolism and calcium-regulating hormones during normal pregnancy].

Dynamic changes in maternal and fetal calcium metabolism during pregnancy were investigated by simultaneously measuring serum or urinary concentrations of calcium and calcium regulating hormones. Serum concentrations of total calcium in maternal serum decreased significantly, but those of ionized calcium decreased slightly but not significantly late in pregnancy. Maternal serum levels of parathyroid hormone (PTH) were almost the same as non-pregnant values throughout pregnancy, but those of 1 alpha, 25-(OH)2 vitamin D3 increased as pregnancy progressed. Serum levels of calcitonin (CT) in maternal serum increased late in pregnancy but were statistically not significant. Calcium concentrations in maternal urine during pregnancy showed a slight decrease. It is suggested that calcium absorption in the maternal intestine might be increased by the action of increased serum 1 alpha, 25-(OH)2 vitamin D3, and the maternal bone during pregnancy might be kept at the same density as in non-pregnant women because increased CT protects the maternal skeleton by resisting the bone-resorbing activities of 1 alpha, 25-(OH)2 vitamin D3. The concentrations of ionized calcium and CT in umbilical cord blood were higher, but those of PTH and 1 alpha, 25-(OH)2 vitamin D3 were significantly lower than those of the maternal blood at term. It is considered that an active transport mechanism may be involved in the transplacental supply of calcium, and calcium transport from mother to fetus results in a decrease in the calcium concentrations of the maternal serum. Calcium transported into the fetus may be used as fetal body composition such as accumulation in the bone mainly by the action of serum CT.

Adult↗

Immunohistochemical study of gastroenteropancreatic endocrine cells of the herbivorous Japanese field vole, Microtus montebelli.

The gastroenteropancreatic (GEP) endocrine cells of the Japanese field vole were studied immunohistochemically. Somatostatin-, 5-hydroxytryptamine-, glicentin-, glucagon-, bovine pancreatic polypeptide-, gastrin-, gastric inhibitory polypeptide-, cholecystokinin-, substance P-, secretin-, neurotensin- and insulin-immunoreactive cells were revealed. The characteristic findings of the regional distribution and relative frequency of these immunoreactive cells in the GEP system of the vole were as follows. Somatostatin-immunoreactive cells were more numerous in the oxyntic glands than in the pyloric glands. Some somatostatin-immunoreactive cells were found in small clusters in the oxyntic glands. Gastrin-immunoreactive cells were detected not only in the pyloric glands and small intestine but also in the caecum and spiral colon. Gastric inhibitory polypeptide-immunoreactive cells were also detected in the pyloric glands and no motilin-immunoreactive cell was found in the gastroenteropancreatic system.

Animals↗

[Severity and extent of coronary artery disease and their relationship to left ventricular functional reserve in the chronic disease state].

Our previous observations showed that left ventricular wall motion abnormality (asynergy) induced by stress was observed in the phase response of radionuclide technique, and the severity and extent of coronary artery disease (CAD) assessed by the Pujadas score (PS) correlated well with the maximal phase delay response (delta MPD) but not with the ejection fraction response (delta EF) in patients with CAD without old myocardial infarction (MI). This study evaluated the usefulness of EF, MPD and the first-third filling fraction (FF, divided by the volume accrued throughout diastole) at rest and during stress, using ergometer and first-pass radionuclide angiocardiography (RNA), to determine the severity of CAD, and to evaluate any abnormalities in the systolic and diastolic coupling in left ventricular function during stress. Seventy-four patients with significant CAD, including 41 with previous transmural MI (MI group) and 33 without MI (angina group) were the subjects of this study. EF at rest and during stress inversely correlated, and MPD on stress linearly correlated with PS in angina group with PS greater than 10, while no such correlations were found in MI group. A normal EF response (delta EF greater than or equal to 5%) was accompanied by a greater-than-normal response in FF (delta FF) in both groups. A lower EF response was accompanied by a smaller delta FF in angina group, but by a larger delta FF in MI group. The difference was statistically significant (p less than 0.03), without significant differences by age, PS, peak heart rate, systolic blood pressure, and ischemia on ECG during stress. Resting EF and FF by the RNA method correlated with those by left ventriculography (LVG), respectively. It was suggested that RNA is an accurate method for determining EF and FF, while phase analysis may provide some additional information different from that provided by LVG. We concluded that EF and MPD during stress are as useful as delta MPD with the exception of a few cases in predicting the severity of CAD, and that scar tissue within the ventricular wall in MI may play an important role in determining the ventricular diastolic mechanical property during stress.

Angina Pectoris↗