Biomedical subjects
Publications and source records attributed to S Kato.
We have developed a novel method for synthesizing a full-length cDNA based on the addition of DNA-RNA chimeric linker to the CAP site of mRNA. The DNA-capped mRNA was used as a template for cDNA synthesis with a dT-tailed vector primer. The model experiment using rabbit globin mRNA showed that more than 80% of the clones encoding alpha- and beta-globin contains a full-length cDNAs starting from the CAP site.
The pharmacological effects of the metabolites M1 and M2 of mosapride citrate ((+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholi nyl] methyl]benzamide citrate, AS-4370, CAS 112885-42-4), a gastroprokinetic agent with serotonin 5-HT4 receptor agonist property, were compared with those of mosapride. In isolated guinea-pig ileum treated with phenoxybenzamine, the metabolites M1 and M2 enhanced electrically-evoked contractions with EC50 values of 1.2 x 10(-7) mol/l and 1.0 x 10(-6) mol/l, respectively. The metabolite M1 was twice less potent than that of mosapride. When administered intravenously, the metabolite M1 enhanced gastric emptying of a semisolid meal in mice and rats; the potency was 3 times less than that of mosapride in mice and almost equal to that of mosapride in rats. When administered orally, the metabolite M1 enhanced gastric emptying of a semisolid meal in mice and rats, and also enhanced gastric emptying of a resin pellet meal in rats. The potency of metabolite M1 was 10 times less than that of mosapride in rats, although it was equal to that of mosapride in mice. In these experiments, the metabolite M2 was far less active. In addition to these gastroprokinetic properties, the metabolite M1 possessed a potent 5-HT3 receptor antagonist property. The metabolite M1 antagonized the 2-methyl-5-HT-induced bradycardia in anesthetized rats with an ED50 value of 10.5 micrograms/kg, i.v., and inhibited the cisplatin-induced emesis in ferrets with a potency approximately 25 times that of mosapride. These results suggest that the metabolites M1 and M2 of mosapride do not play a crucial role in the gastroprokinetic effect of mosapride.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical characteristics of late deterioration in adult cerebral palsy were reported with detailed neurological evaluations and analyses. 10 adult cases, 9 male and 1 female, with cerebral palsy (CP) were included aged from 24 to 58 years on admission. Without marked mental retardation all had been ambulant and completely independent of ADL with residual spasticity and/or dyskinesia of minimal degree until the second or third decade. Late deterioration of functional abilities starting with numbness or pain in upper extremities at age 24-45 (mean: 36.2 y), associated with profound atrophy of the shoulder girdle and hand muscles. Dyskinesia and spasticity markedly aggravated with urinary and respiratory dysfunctions, resulting in tetraplegia in a couple of years. Mentality is generally unaffected, however, severe dementia occurred in one case. Intensive clinical examinations revealed no particular abnormalities except for mild segmental neurogenic changes by needle EMG. Neuroradiological surveys revealed a marked narrowing of upper to middle cervical spinal canal with deformity and shrinkage of the corresponding cord in most cases. Cranial CT scans and MRI were unremarkable except for diffuse cortical atrophy and ventricular dilation. These studies showed that in adult CP an unexpectedly severe deterioration of sensory, motor and/or mental functions may appear even in previously well achieved cases. These dramatic changes of the clinical features of CP after middle age might be suggestive of the degenerating process and precocious aging of the CNS.
Bone marrow transplantation (BMT) has been increasingly applied to a variety of potentially fatal diseases in childhood. However, trends of indication of BMT are changing because chemotherapy in leukemia and immunosuppressive therapy with/without colony stimulating factor in aplastic anemia are improving. Several progresses have been noted in matched unrelated BMT and peripheral blood stem cell transplantation as well as in sibling BMT or autologous BMT. Many efforts are being made to decrease rejection rate or leukemia relapse and to improve quality of life by new conditioning regimens. Attempts to induce GVL effects or syngeneic GVHD are currently under progress. The quality of life in long term surviving children are generally good and acceptable, although delay in growth, infertility, cataract and obstructive lung disease are seen in a few patients.
The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
The present paper concerns the clinicopathological study of two patients with sporadic amyotrophic lateral sclerosis (ALS) with 21 or 22 years' clinical course without respirators. The two cases developed marked upper motor neuron signs and continually progressive paralysis. Involvement of the facial and bulbar muscles remained fairly mild. At autopsy, the anterior horns showed marked loss of motor neurons associated with numerous reactive astrocytes. On the other hand, the motor cortex and the pyramidal tract showed diminution of Betz cells and large myelinated fibers but no positive materials by fat stain. In addition, the anterolateral funiculi of the spinal cords revealed widespread myelin pallor. One of the case showed intracytoplasmic eosinophilic inclusions in some neurons of the medullary reticular formation. Recent articles have reported several rapidly progressive ALS patients who developed ophthalmoplegia, while on respirators, and widespread degeneration in the CNS. By contrast, our extremely slowly progressive ALS patients developed alterations confined to upper and lower motor neurons. There may exist some diversities in ALS.
A case in which P. carinii was observed in bronchoalveolar lavage fluid during steroid therapy for interstitial pneumonia in a 63-year-old man is reported, he had received steroid therapy for interstitial pneumonia of unknown origin. Three weeks later, he developed acute pneumonia with Streptococcus pneumoniae, and simultaneously P. carinii was detected in the bronchoalveolar lavage fluid. Both the pneumonic shadows and P. carinii disappeared following intravenous infusion of penicillin and rapid reduction of steroid. Electron microscopic analysis of P. carinii demonstrated numerous tubular expansions and endogenies of P. carinii, suggesting that P. carinii was growing in the intra-alveolar spaces. Phospholipid analysis demonstrated a transient increase in total phospholipid content during P. carinii pneumonia, suggesting that P. carinii can affect surfactant metabolism.
A 55-year-old man was admitted to our hospital with chief complaints of exertional dyspnea and chest x-ray abnormalities. On physical examinations, clubbing and systolic murmur were detected. The patient's hemoglobin rose to a level of 19.0 g/dl, with a rise in hematocrit to 58.8%. While the patient was breathing room air, the PaO2 was 52.8 mmHg, the PaCO2 33.3 mmHg and the pH 7.43. In chest x-ray film, oval well-margined 38 x 30 mm density with enlarged afferent and efferent vessels in the left upper lobe (lts4) and 15 x 13 mm "coin lesion" in the right lower lobe (rts7) were observed. Pulmonary angiography demonstrated that these lesions were arteriovenous fistulas. In cardiac catheterization, an estimated right to left shunt of 31.1% was calculated. Because of the exertional dyspnea and the large shunt, a segmentectomy of the lingula and a wedge resection of the rts7 were simultaneously performed. After the treatment, exertional dyspnea, hypoxia and polycythemia disappeared. As far as we know, this patient is one of the most elderly patients in Japan to be successfully treated surgically for bilateral pulmonary arteriovenous fistulas.
The influence of endogenous nitric oxide, which is generated by stimulation with lipopolysaccharide, on the mitochondrial energization of rat hepatocytes was investigated in vitro and ex vivo. Using a fluorescence microscope equipped with a silicon intensifier target camera, we visualized fluorescence of rhodamine-123, a mitochondrial energization-sensitive fluorescence probe, in individual hepatocytes and measured the fluorescence intensity with a digital imaging processor. Although addition of Kupffer cells or lipopolysaccharide in a range of 0.1 to 1.0 microgram/ml caused no significant alteration in the fluorescence in hepatocytes, Kupffer cells plus 1.0 microgram/ml lipopolysaccharide reduced fluorescence intensity in the cocultured hepatocytes. The alteration of rhodamine-123 fluorescence in the hepatocytes induced by lipopolysaccharide-activated Kupffer cells was significantly inhibited by the addition of NG-monomethyl-L-arginine, a selective inhibitor of nitric oxide synthesis. The transportal infusion of lipopolysaccharide also decreased rhodamine-123 fluorescence in perfused rat liver. The decrease was significantly enhanced in the pericentral regions. Autofluorescence of NADH was elicited by continuous infusion of lipopolysaccharide; this reaction was also enhanced in the pericentral regions. We showed the main site of uptake of infused lipopolysaccharide in the hepatic lobule to be in the periportal regions with fluorescein isothiocyanate-labeled lipopolysaccharide. Our results indicate that the inhibition of mitochondrial energization occurs mainly in pericentral regions, which are distant from the lipopolysaccharide uptake site. The continuous administration of NG-monomethyl-L-arginine significantly attenuated the lipopolysaccharide-induced decrease in rhodamine-123 fluorescence and increase of the NADH contents of the hepatic lobule.(ABSTRACT TRUNCATED AT 250 WORDS)
Postspinal headache (PSH) is the most frequent complication of spinal anesthesia. The factors responsible for the development of PSH include needle size, shape of the needle tip, patient's age, sex, infusion volume and period of resting. The purpose of this study is to compare the incidence of PSH between two different types of needle, Sprotte needle and Quincke needle. The Sprotte needle is characterized by a round profiled tip equipped with a lateral orifice. Our investigation by questionnaires revealed that the incidences of PSH after using either 22G Sprotte needle or 21-25G Quincke needle were 0% and 38.8%, respectively. We conclude that the Sprotte needle decrease the incidence of PSH.
The mean platelet volume (MPV) was measured in 14 patients with acute leukemia during the course of chemotherapy for remission induction and 21 patients undergoing bone marrow transplantation, in order to assess its usefulness as an indicator for megakaryothrombopoiesis at bone marrow suppression and recovery. In patients with acute leukemia, the MPV fell from 9.7 +/- 0.8 fl to 9.2 +/- 0.4 fl during the myelosuppression, and then it rose transiently to 10.2 +/- 0.5 fl and fell to 9.3 +/- 0.5 fl during recovery of platelet count. Similarly, in patients undergoing bone marrow transplantation, the MPV elevation was followed by the recovery of platelet count. Thus, when engraftment was defined as this MPV elevation, engraftment was confirmed significantly earlier by MPV (19.9 +/- 5.8 days) than by platelet count (24.8 +/- 6.7 days). MPV should be a useful indicator for engraftment or recovery from marrow aplasia in cases of acute leukemia and those of bone marrow transplantation.
From March 1988, 19 vesicoureteral reflux (VUR) patients were treated by endoscopic injection of Teflon paste. Of these patients 17 cases 27 ureters were followed for more than one year. After injection of Teflon paste, reflux was eliminated in 63%, decreased in 30%, and unchanged in 7%. Then 7 ureters were injected twice and 1 ureter three times. Finally, reflux was eliminated in 93% of all cases, and decreased in 7%. Early complications were fever up in 4 cases, flank pain 3, acute cystitis 1. In the follow up period, acute cystitis occurred in 1 patient, ureter stone in 1, and renal failure in 1. However, the ureter stone and renal failure were probably not caused by this procedure.
The effects of halothane, isoflurane and epidural anesthesia combined with isoflurane on hemodynamic and metabolic changes caused by hepatic ischemia and reperfusion were studied in 16 pigs. Hepatic arterial and portal venous blood flows were measured electromagnetically. Lactate pyruvate ratio (L/P) and arterial ketone body ratio (AKBR) were calculated as markers of hepatic aerobic metabolism. Total hepatic blood flow (THBF), cardiac output (CO) and THBF/CO showed no significant differences among three anesthetic methods in ischemic and reperfusion period. In the group with epidural anesthesia combined with isoflurane, L/P was significantly lower and AKBR was significantly higher compared with the data obtained in ischemic period. However, hepatic metabolism was severely disturbed after the reperfusion of the liver in all three groups. Especially, halothane group showed the most remarkable decrease in AKBR. In summary, epidural anesthesia will be useful for aerobic hepatic metabolism because of inhibition of the release of endogenous cathecolamines, but hepatic metabolism will not be maintained following hepatic ischemia and reperfusion.
The prevalence of diabetic ocular complications and the correlation between diabetic retinopathy and systemic factors were examined in 2,300 cases (4,600 eyes) with non-insulin-dependent diabetes mellitus. The prevalence of cataract was 66.7%, of retinopathy 37.0%, of refractive and accommodative change 6.2%, of glaucoma 1.9% (rubeotic glaucoma was 1.0%), of rubeosis iridis 1.5%, of iridocyclitis 0.8%, of extraocular muscle palsy 0.2%, and of ischemic optic neuropathy 0.1%. Duration of diabetes mellitus, HbA1C value, methods of diabetic control, age, diabetic nephropathy, diabetic neuropathy, hypertension, systolic blood pressure, diastolic blood pressure, and arteriosclerosis obliterans were related with diabetic retinopathy. We suggest that the management of diabetic patients needs sufficient attention in the cases with oral administration of medication, insulin therapy, and diabetic nephropathy.
The antioxidant activities of various natural and synthetic carbazoles were studied in the oxidations of methyl linoleate in homogeneous solution and soybean phosphatidylcholine (PC) liposomes in aqueous dispersion induced by free radicals. Carazostatin, 1-heptyl-3-hydroxy-2-methyl carbazole, which was isolated from a culture of Streptomyces chromofuscus, was found to be a strong antioxidant in both oxidation systems. Carbazomycin B, 4-hydroxy-3-methoxy-1,2-dimethylcarbazole, showed a moderate antioxidant activity. Other derivatives from these carbazoles without a free hydroxy group did not suppress the oxidation appreciably. The antioxidant activity of carazostatin in the oxidation of soybean PC liposome was stronger than that of alpha-tocopherol, although the latter exhibited stronger antioxidant activity than carazostatin in the oxidation in homogeneous solution. Vitamin C acted as a synergist in combination with carazostatin in the oxidation of soybean PC liposomes.
We produced hepatitis in guinea pigs by immunization with acetaldehyde adducts and ethanol treatment. Human hemoglobin-acetaldehyde adducts were prepared without any reducing agents and affinity purified with polyclonal antibodies against acetaldehyde adducts. Female guinea pigs were immunized with the adducts and were simultaneously given ethanol for 40 days. These treatments induced hepatic necrosis with infiltration of mononuclear cells in the hepatic lobules. The formation of the lymphoid follicle was also observed in severe cases. These changes were accompanied by the elevation of serum AST and lactic dehydrogenase activities and titers of circulating antibodies against acetaldehyde adducts. By contrast, the combination of ethanol and immunization with unmodified hemoglobin produced only fatty change of the liver, and animals immunized with the adducts alone had minimal inflammatory changes of the liver. Peripheral blood lymphocytes obtained from the animals with hepatitis were shown to be stimulated by acetaldehyde adducts to a significantly greater degree than those from control animals who received nothing, ethanol alone or ethanol and unmodified hemoglobin. These results suggest that the immune response to acetaldehyde adducts may be involved, at least partly, in the pathogenesis of inflammation observed in alcoholic liver disease.
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We produced an experimental adult respiratory distress syndrome model by intravenous administration of oleic acid (OA) in 30 dogs (Group I: 10 normal dogs; Group II: 10 dogs with 0.02 ml/kg of OA; Group III: 10 dogs with 0.04 ml/kg of OA; Group IV: 10 dogs with 0.08 ml/kg of OA). Changes in albumin (AL) and fibronectin (FN) in serum and BALF of these dogs were examined. The following results were obtained: 1) Serum values of AL and FN were significantly decreased after OA injection as compared with the baseline values. These changes were not correlated with the severity of pulmonary edema. 2) BALF values of AL and FN were significantly increased after OA injection as compared with the baseline values. Significant linear correlations were found between the BALF value of AL and ELWV, and between BALF value of AL and delta ELWV, [r = -0.682, 0.573 (p < 0.01)]. Significant linear correlations were also found between the BALF value of FN and ELWV, and the BALF value of FN and delta ELWV, [r = 0.722, 0.650 (p < 0.01)]. BALF value of AL increased significantly even with the low OA dose (0.02 ml/kg). Thus in comparison with BALF value of AL after OA injection, BALF value of FN was significantly higher than that in the normal group even when pulmonary edema were severe (Groups III and IV). We concluded that we could estimate the severity of pulmonary edema by measuring BALF value of AL and FN simultaneously.