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Biomedical subjects

T Sawada

Publications and source records attributed to T Sawada.

At least 397 records · Page 22Linked to original sources

Pivalate affects carnitine status but causes no severe metabolic changes in rat liver.

To investigate the carnitine deficiency induced by pivalate, rats had free access to drinking water with or without pivalate. Consumption of 20 mmol/L pivalate for 1 wk decreased the levels of both free and total carnitine in plasma to approximately 20% of levels before treatment. After 4 wk, the concentrations of free carnitine in the liver, heart and muscle of pivalate-treated rats were approximately 60-80% of the control, and in the kidney, 26% of the control. Fractional excretion of free carnitine (FEFC) in pivalate-treated rats was measured; however, the treatment for 3 or 8 d did not affect the values relative to those obtained before treatment. Treatment with pivalate for 4 wk did not affect plasma concentrations of glucose, ammonia and free fatty acids (FFA) in the rats; however, the concentration of 3-hydroxybutyrate (3-OHB) was higher, and the FFA/3-OHB ratio was lower than those of controls. In a liver perfusion study, ketogenesis from oleate and gluconeogenesis from lactate and pyruvate in rats treated with pivalate for 4 wk were not different from controls. These results suggest that administration of pivalate did not induce the excessive excretion of free carnitine in urine, and secondary carnitine deficiency induced by intake of 20 mmol/L pivalate for 4 wk did not cause severe metabolic changes in rat liver.

3-Hydroxybutyric Acid↗

A new model of transient cerebral ischemia in neonatal rats.

A new model of transient cerebral ischemia in 10-day- old rats is described. Under microscopic guidance, the right external and internal carotid arteries were electrically coagulated. A solid 0.47 mm diameter nylon thread was inserted into the right common carotid artery toward the ascending aorta up to 10-12 mm from the upper edge of the sternomastoid muscle (preischemic rats). A 60-min cerebral ischemia was induced by clamping the left external and internal carotid arteries (ischemic rats), followed by 3-h recirculation. 31P magnetic resonance (MRS) spectroscopic studies revealed that severe intracellular acidosis occurred and ATP disappeared completely for a least the last 20 min of ischemia. Cerebral blood flow (CBF), measured by the hydrogen clearance technique, decreased to approximately 11% of the preischemic level in the frontal cortex soon after the induction of ischemia. On resuscitation, ATP recovered completely and the preischemic intracellular pH level was restored within 180 min. CBF has recovered to approximately 30% of the preischemic level at 5 min after resuscitation. The CBF recovery was not compete even at 180 min after resuscitation. With this model, the effects of pure ischemia without hypoxia on the neonatal brain and the process of recovery from transient ischemia can be studied.

Adenosine Triphosphate↗

Radioimmunotherapy for pancreatic carcinoma using (131)I-labeled monoclonal antibody Nd2 in xenografted nude mice.

We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of (131)I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. (131)I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of (131)I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of (131)I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus (131)I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer.

Animals↗

Correlation of two argyrophilic nucleolar organizer region counting methods with the Ki-67 labeling index in uterine smooth muscle cell tumors.

The argyrophilic nucleolar organizer regions (AgNOR) are silver stained granules that are thought to correlate with cell proliferation activity. Two AgNOR counting methods: the mean AgNOR count (mAgNOR, the mean number of AgNOR granules in 100 cells) and the AgNOR proliferative index (pAgNOR, the percentage of cells exhibiting five or more AgNOR granules per nuclei) have been proposed. In this study, the two counting methods were applied to 58 cases of normal uterine corpus and uterine corpus tumors and were compared with the Ki-67 labeling index (Ki-67 LI) using MIB-1 monoclonal antibody and other histopathological criteria. Notable differences in the number of AgNOR and the Ki-67 LI were observed between benign and malignant smooth muscle tissue. Histopathologic features are well correlated to the proliferative activity of tumors. Although the most reliable method of predicting malignant potential cannot be determined, the methods outlined by this study are thought to be highly useful in assessing proliferative activities.

Cell Count↗

Early stage of human adenovirus type 12-inoculated retinal tissue of F344 newborn rat.

To elucidate the pathogenesis of adenovirus type 12 (Ad12)-induced rat retinal tumor, an experimental animal model of human retinoblastoma (RB), DNA analysis, in situ hybridization and immunohistochemistry were performed. The adenovirus oncogene E1A was detected in the host genome by Southern blot hybridization. Examined retinal tissues did not show any histological changes, but the number of retinal cells immunoreactive with an antibody to proliferating cell nuclear antigen (PCNA) increased with the course of study. In in situ hybridization, E1A gene expression was recognized at the inner granular layer of the retina at an early stage after virus inoculation, and subsequently, N-myc gene expression was recognized at the same region. No alteration was found in the retinoblastoma susceptibility gene (Rb gene) expression. The product of the virus oncogene integrated into the host genome could induce an increase in N-myc expression, without any abnormality of the Rb gene itself. Results from the present study could be useful in clarifying the tumorigenesis of this experimental model.

Adenoviridae↗

Motor nerve conduction studies on children with spinal muscular atrophy.

Median and posterior tibial motor nerve conduction studies were performed on 10 children with spinal muscular atrophy (SMA). Three patients with SMA type I, in whom rapid deterioration occurred, showed reduced motor nerve conduction velocity and a remarkably low M-wave amplitude in both nerves. In type II and III patients, the motor nerve conduction velocity was normal in the median nerve, although the M-wave amplitude was small in the tibial nerve. In four patients, a reduction of the M-wave amplitude was observed as clinical symptoms advanced. These findings may suggest that motor conduction studies in spinal muscular atrophy provide complementary information for understanding the pathogenesis and are also useful to clarify the heterogeneity of this disease.

Child↗

Role of insulin resistance associated with compensatory hyperinsulinemia in ischemic stroke.

BACKGROUND AND PURPOSE: Although insulin resistance and hyperinsulinemia play a crucial role in the pathogenesis of atherosclerosis, little is known about their roles in ischemic stroke. The purpose of this study was to clarify whether insulin resistance and hyperinsulinemia are causative factors in the pathogenesis of ischemic stroke. METHODS: Thirty-four consecutive patients with ischemic stroke, who were normotensive, nondiabetic, and not obese, were classified into three groups--atherothrombotic infarction (n = 16), lacunar infarction (n = 10), and cardioembolic infarction (n = 8)--based on clinical findings, brain imaging, and cerebral angiography. Both oral glucose tolerance tests and lipid analyses were performed. Insulin sensitivity was determined by the steady state plasma glucose method with the use of octreotide acetate. Data were compared with those of healthy control subjects (n = 15). RESULTS: Steady state plasma glucose levels were significantly higher in the atherothrombotic infarction group compared with control subjects and the other two stroke groups, indicating the presence of insulin resistance in patients with atherothrombotic infarction. In the atherothrombotic infarction group, the 2-hour insulin area (area under the plasma insulin concentration curve) during a 75-g oral glucose tolerance test was significantly increased and dyslipidemic changes (increased triglyceride and apolipoprotein B, decreased high-density lipoprotein) were observed, whereas these changes were not found in the lacunar infarction and cardioembolic stroke groups. CONCLUSIONS: Insulin resistance in association with compensatory hyperinsulinemia and dyslipidemia may be an important pathogenetic factor underlying the development of atherothrombotic infarction.

Aged↗

Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course.

BACKGROUND AND PURPOSE: Standard radiographic criteria for hematoma enlargement have not been established. We undertook this investigation to assess the incidence and time course of hematoma growth using objective cutoff values. METHODS: We reviewed the clinical records of 204 patients with spontaneous intracerebral hemorrhage treated nonsurgically who underwent initial computed tomography (CT) within 48 hours and repeat CT within 120 hours of the onset of symptoms. The consensus of five observers reading the CT films was considered the "gold standard" for hematoma enlargement. The discriminant values of the difference (V2-V1) or the ratio (V2/V1) of the hematoma volume on the initial (V1) and second (V2) CT scans were determined by use of receiver operating characteristic curves. We chose the cutpoint that had the highest sensitivity and specificity for identifying hematoma expansion. RESULTS: The cutpoint for hematoma enlargement was determined as V2-V1 = 12.5 cm3 or V2/V1 = 1.4 (sensitivity = 94.4%, specificity = 95.8%). Forty-one patients (20%) had changes that exceeded these criteria. Frequency of hematoma expansion was greatest among those who underwent the initial CT scan early (27 [36%] of 74 patients at < or = 3 hours) and progressively declined as the time to initial scan was prolonged (7 [16%] of 45 patients at 3 to 6 hours; 5 [15%] of 33 patients at 6 to 12 hours; 2 [6%] of 34 patients at 12 to 24 hours; and 0 [0%] of 18 patients at 24 to 48 hours). CONCLUSIONS: The enlargement of hematoma was defined radiographically as the increase of its volume by > or = 12.5 cm3 or by > or = 1.4 times. Although expansion of intracerebral hemorrhage on CT scan was common in the hyperacute stage, 17% of hematoma expansion occurred even after 6 hours of onset. Enlargement after 24 hours of onset seems extremely rare. Early CT scanning appears to increase the rate of detection of enlarging hematomas.

Aged↗

A rare case of arteriosclerosis obliterans without prominent risk factors complicated by idiopathic thrombocytopenic purpura. A case report.

An eighty-four-year-old man was admitted to the hospital because of pain at rest in the lower extremities. On physical examination, trophic changes of the skin and petechiae in the limbs were observed. Computed tomographic scan of the abdomen showed focal renal infarctions and calcification of the descending aorta. Moreover, radionuclide imaging of the arterial system revealed complete obstructions of the two right iliac arteries and the left external iliac artery, where collateral flows were observed. Laboratory examination showed a severe thrombocytopenia caused by immunoglobulin G (IgG)-type autoantibody against platelets. He was diagnosed as having arteriosclerosis obliterans complicated by idiopathic thrombocytopenic purpura, although no known risk factors promoting atherosclerosis other than age were evident. In such a case with hemorrhagic diathesis, a hemorheologic agent and the vasodilator prostaglandin could confer advantages in relieving and controlling the ischemic leg pain without hemorrhagic complications. Moreover, small doses of the initial prednisolone therapy for ITP might also be recommended to avoid thrombus formations in the atherosclerotic lesions.

Aged↗

Location of two photoaffinity-labeled sites on the ligand-binding domain of retinoic acid receptor alpha.

Retinoic acid receptors (RARs) consist of six domain structures. The C-terminal region (D/E/F-domains) is involved in ligand binding, dimerization, and ligand-dependent transactivation. Structural information about RARs is required for understanding its complex function. A photoreactive retinoid denoted as ADAM-3, which was designed as the result of comparison of two fluorescent retinoids (DAM-3 and DAM-15), was synthesized and used for photoaffinity labeling of recombinant protein MBP-RAR alpha/E. The photoaffinity-labeled site was determined by an endoprotease combination method which utilizes four endoproteinases in a two-phase digestion procedure. Two major labeled fragments were detected in each digestion, and the results of two-phase digestion allowed identification of the labeled residues as being located within residues 492-510 and 585-594, which correspond to 288-306 and 381-390 in human RAR alpha, respectively.

Affinity Labels↗

A possible involvement of monoaminergic and opioidergic systems in the analgesia induced by electro-acupuncture in rabbits.

To elucidate mechanisms involved in analgesia induced by effects of electro-acupuncture (EAP), effects of EAP on evoked potentials and release of substance P (SP) following tooth pulp stimulation (ST) in the superficial layers of the trigeminal nucleus caudalis (Vc-I-II) were studied in the rabbit. The potentials evoked by ST were composed of two main components with conduction velocity of ca. 30 m/sec (fast component) and ca. 12 m/sec (late component). The late component was significantly inhibited by morphine (10 mg/kg, i.v.) or CP-96,345 (5 mg/kg, i.v.), an SP antagonist. This inhibitory effect of morphine was antagonized by naloxone (1 mg/kg, i.v.) or methysergide (5 mg/kg, i.v.). In addition, the late component was significantly inhibited by EAP, which was observed in ca. 70% of the rabbits examined. This EAP-induced inhibitory effect was antagonized by naloxone (1 mg/kg, i.v.) or methysergide (5 mg/kg, i.v.), but not by prazosin (5 mg/kg, i.v.) and yohimbine (1 mg/kg, i.v.). The stimulus-evoked SP release was inhibited by EAP, which was significantly antagonized by pretreatment with naloxone (1 mg/kg, i.v.) or methysergide (5 mg/kg, i.v.). These results suggest that one of the mechanisms of analgesia induced by EAP is due to inhibition of the stimulus-evoked SP release in the Vc-I-II through activation of the descending serotonergic systems linking up with opioidergic systems.

Acupuncture Analgesia↗

Outbreaks of fowl cholera in Muscovy ducks (Cairina moschata) on a farm in Aomori Prefecture.

Outbreaks of a subacute disease characterized by lameness, corneal turbidity, dysstasia and depression occurred in Muscovy ducks (Cairina moschata) on a farm in Aomori Prefecture in February and May 1991. Nine strains of Pasteurella multocida were isolated from 5 to 6 dead ducks, and 4 of 8 ducks with clinical signs. Serotypes of the isolates were identified as Heddleston's serotype 1, 10 or 12 and Namioka's serotypes 5:A, 8:A, 9:A or 9:UT. These isolates were highly susceptible to 12 antibiotics, although, some of them were considerably resistant to chloramphenicol. Mouse LD50 values of the 9 isolates ranged from 10(1.0) to 10(5.3). The most virulent strain for the mouse killed 2 to 4 ducks when inoculated intramuscularly at a concentration of 10(3.3). This is the first report of outbreaks of fowl cholera in Muscovy ducks infected with various serotypes strains of P. multocida in Japan.

Animals↗

Serovars of Erysipelothrix strains isolated from pigs affected with erysipelas in Japan.

Serovars of 1,046 Erysipelothrix strains isolated from diseased pigs during a period from 1983 to 1993 in Japan were determined by an agar gel double-diffusion precipitation system using typing sera representing all the known serovars, 1 through 23 and type N, of 2 species of Erysipelothrix. A total of 943 strains could be serotyped within the serovars. The remaining 103 strains could not be determined for their serovars and were classified as untypable. Of the 938 (99.5%) strains serologically identified as Erysipelothrix rhusiopathiae, 423 (40.4%) belonged to serovar 1a, 359 (34.3%) to serovar 2, 65 (6.2%) to serovar 1b, 35 (3.3%) to serovar 6, 19 (1.8%) to serovar 5, 11 (1.1%) to serovar 21, and the remaining 26 to serovars 4, 8, 11, 12, 15, 17, or 19. Only 5 (0.5%) strains isolated from the cases of erysipelas belonged to Erysipelothrix tonsillarum and represented serovars 7 or 23.

Animals↗

Growth ability and immunological properties of Erysipelothrix rhusiopathiae serotype 2.

Five field strains of Erysipelothrix rhusiopathiae belonging to serotype 2 were compared for their growth ability, immunogenicity in mice, SDS-PAGE profile of cell surface proteins and their immunoblotting patterns. Strain Tama-96 showed the most stable growth in Feist medium and tryptose phosphate broth with Tween 80 (TPB), and its immunogenicity was highest in a mouse protection test using the inactivated vaccines prepared from 20-h TPB culture. The 50% mouse protective dose of the vaccine was only 12 microliter. SDS-PAGE and immunoblotting patterns of the proteins were similar among the strains in general and indicated that 66 to 64 kDa protein antigens were dominant.

Animals↗

[Suspension of ventilation during extracorporeal membrane oxygenation with veno-venous by pass in dogs].

We studied whether extracorporeal membrane oxygenation with a veno-venous bypass would allow withdrawal of mechanical ventilation. Three mongrel dogs were anesthetized with intravenous pentobarbital. A Swan-Ganz catheter was placed via the left jugular vein into the main pulmonary artery, and an extra-long total volume catheter was placed in the right femoral artery. The animals were placed in the lateral position, and cannulas (15 Fr.) were placed in the inferior vena cava and the superior vena cava via the right jugular vein and the right femoral vein. These cannulas were connected to a pump and a membrane oxygenator. When the pump flow was almost the same as the previous cardiac output, the partial pressure of oxygen in the pulmonary artery, was high enough to allow ventilation to be suspended. All dogs survived. This suggests that extracorporeal membrane oxygenation with a veno-venous bypass can allow mechanical ventilation to be suspended during tracheocarinal operations such as tracheocarcinal resection.

Animals↗