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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 1,081 records · Page 60Linked to original sources

An autopsy case of Kawasaki disease with reference to occurrence of acute coronary thrombosis in the convalescent stage.

A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease.

Acute Disease↗

Prolonged QT interval in alcoholic autonomic nervous dysfunction.

QT prolongation on electrocardiography is related to sudden cardiac death and is frequently found in alcoholics. We studied QT prolongation in relation to the function of cardiac autonomic nerves assessed by the coefficient of variation of the R-R interval (CVRR) in three age-matched groups of men: 32 alcoholics with autonomic nervous dysfunction (AN), 32 alcoholics without AN, and 32 healthy controls. The QTc interval and CVRR were measured at rest on the 30th day of abstinence, when electrolyte imbalance had disappeared. Subjects with arrhythmia, conduction abnormality, cardiomegaly, ischemic heart disease or diabetes mellitus were excluded. A CVRR of less than 80% of standard predicted value was judged to represent AN. In alcoholics, QTc correlated negatively with the ratio of CVRR to its standard value (r = -0.49, p < 0.0001). The incidence of QTc prolongation was higher in alcoholics with AN (46.9%) than in alcoholics without AN (21.9%, p < 0.05). QTc prolongation was not observed in healthy controls. The QTc interval was significantly (p < 0.01) longer in alcoholics with AN (444 +/- 20 msec) than in alcoholics without AN (426 +/- 17) and in healthy controls (398 +/- 18). These results suggest that alcoholism causes dysfunction of the autonomic nerves as well as worsening QT prolongation, and this may predispose such patients to sudden cardiac death.

Adult↗

Effect of intraduodenal HCl and soybean extract on pancreatic juice secretion during atropinization and cold vagal blockade in calves.

In order to elucidate the mechanisms by which intraduodenal hydrochloric acid (HCl) and soybean extract influence exocrine pancreatic secretion in the young ruminant, we conducted experiments repeatedly on six conscious calves with and without blockade of the extrinsic and intrinsic neural pathways. In the absence of blockade, each of the two stimuli increased the juice volume, the HCl effect being far stronger than that of soybean extract. Intrinsic cholinergic blockade by atropinization blocked the stimulatory work of soybean extract on pancreatic secretion and on HCl-stimulated protein but had a weak effect on the amount of juice evoked by HCl. Temporary vagal blockade by chilling virtually abolished the excitatory effects of both soybean extract and HCl. With or without blockade, duodenal HCl resulted in a noteworthy increase in plasmal secretin and a slight increase in cholecystokinin (CCK). With alimentary proteins, acidification of the duodenum was responsible for both the composition and secretion of pancreatic juice in young calves, generally via neural pathways. Atropine-sensitive nerves of the pancreas totally regulate the intestinal phase of pancreatic juice secretion allied with intraduodenal protein, whereas HCl-dependent excitation of the exocrine pancreas takes place partly via atropine-resistant nerves. However, as hardly any pancreatic juice was secreted independently of the vagi, the vagi are deemed to govern all the postprandial regulatory mechanisms of the exocrine pancreas in the young calf.

Animals↗

Quantitative Southern blot analysis in the dystrophin gene of Japanese patients with Duchenne or Becker muscular dystrophy: a high frequency of duplications.

Eighty-four unrelated patients with Duchenne or Becker muscular dystrophy in Japan were studied by quantitative Southern blot analysis with dystrophin cDNA probes. We found partial deletions and duplications in 47 (56%) and 12 (14%) cases respectively by HindIII digestion. The duplications were confirmed by BglII digestion and densitometric scanning. The frequency of duplications in this study is significantly higher than those previously reported. This may be because of the small sample number, the racial difference, or our quantitative methods. Our results suggest that attempts to detect duplications are important for a precise diagnosis. Both deletions and duplications clustered at the two hot spots as reported previously. Six cases were exceptions to the 'reading frame hypothesis'. We detected three types of HindIII RFLP. Based on the results of one duplication case, we propose a revised sequential order of exons in the cDNA10 region of the dystrophin gene.

Adolescent↗

Monoclonal antibodies recognising pol and env proteins of mammalian retroviruses.

Mouse monoclonal antibodies were generated for three 20- to 23-mer synthetic peptides whose amino acid sequences were highly conserved in the pol or env regions of 14 mammalian and two avian retroviruses. By Western-blot analysis, these antibodies recognised the epitopes in major and minor pol or env proteins of six mammalian type-C and -D retroviruses. One of the anti-env monoclonal antibodies was found to recognise all the env transmembrane proteins of six mammalian retroviruses examined.

Amino Acid Sequence↗

Acute transverse myelitis in a 15-month-old girl: report of a case with MRI findings.

A 15-month-old girl demonstrated progressive weakness in all limbs. Magnetic resonance imaging (MRI) on admission revealed (1) diffuse and symmetric cervical cord swelling, (2) diffuse decrease and increase in signal intensity within the affected cord on T1- and T2-weighted images, respectively, (3) preserved anatomic structure of gray and white matter of the cord, and (4) lack of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancing effect. She showed rapid clinical improvement in response to steroid therapy, and repeat MRI showed marked reduction in the degree of cord swelling and abnormal signal intensity. Based on the above clinical and MRI findings, the diagnosis of acute transverse myelitis was made. Although various pathologic conditions also could produce similar cord swelling and abnormal signal intensity on MRI, the third and fourth findings mentioned above suggested that the lesion was inflammatory rather than neoplastic. Our case indicates that MRI may be informative in differentiating acute transverse myelitis from other intramedullary disorders.

Acute Disease↗

Comparative effects of chloroflavone congeners as inducers of hepatic microsomal monooxygenases in rats.

The inductive effects of pretreatment with 10 synthetic chloroflavone isomers and congeners (80 mg/kg/d for 3 d, i.p.) on hepatic microsomal monooxygenases were examined with male Wistar rats. All chloroflavone congeners, except 3'-chloroflavone (CF), significantly increased (1.2- to 2-fold) the content of total cytochrome P-450 (P-450s) in microsomes. The effects of these congeners were evaluated based on the activities of microsomal aminopyrine N-demethylase, aniline hydroxylase and scoparone (6,7-dimethoxycoumarin) O-demethylase, and the CO difference spectrum and sodium dodecyl sulfate-gel electrophoretogram of cytochrome P-450s. The results were compared with those of phenobarbital (PB), 3-methylcholanthrene (MC) and PB plus MC. Based mainly on effects on the CO difference spectrum and ratio of the two O-demethylase activities of scoparone, 2'-CF and 2',4'-dichloroflavone (DCF) were categorized as the PB-type, 4'-CF and 6,8-DCF as the MC-type, 3',6-DCF and 3',5',6-trichloroflavone as weak MC-type, and 6-CF and 2',6-DCF as mixed (PB plus MC)-type inducers. A comparison of chloroflavone isomers and congeners indicated that (1) the presence of the 2'-chloro substituent of the flavone system is a minimal requirement for exhibiting the PB-type effect, (2) the absence of the 2'-chloro substituent is possibly that for exhibiting the MC-type effect and (3) the induction potencies by individual chloroflavone congeners may not be related to the degrees of chlorination.

Aminopyrine N-Demethylase↗

Novel benzamides as selective and potent gastrokinetic agents. IV. Synthesis and structure-activity relationships of 2-substituted 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chlorobenzamides.

A new series of 2-substituted 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chlorobenzamides (4-39) including a few 4-fluorobenzyl analogues were prepared and evaluated for their gastrokinetic activity by determining their effects on the gastric emptying activity of phenol red semisolid meal in rats. The C-2 substituent comprises alkoxy and variously substituted alkoxy groups. Among the derivatives, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-2-(n-butoxy)-5-chlorobenza mide (5), its 4-fluorobenzyl (6), and 3-methyl-2-butenyloxy analogues (22) were superior to cisapride and essentially equipotent to the 2-ethoxy analogue (1b, AS-4370 as its citrate) in gastrokinetic activity. These compounds, like AS-4370, had no dopamine D2 receptor antagonistic activity.

Animals↗

Novel benzamides as selective and potent gastrokinetic agents. III. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]-benzamides.

A series of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]benzamides (11-64) were prepared and evaluated for gastrokinetic activity by determining their effects on the gastric emptying of phenol red semisolid meal in rats. The N-4 substituent includes alkyl, phenoxyalkyl, (4-fluorobenzoyl)alkyl, and heteroarylmethyl groups. The benzamide derivatives, having an isopropyl, isoamyl, neopentyl, 3-(4-chlorophenoxy)-propyl, or pyridylmethyl group at N-4, showed potent in vivo gastric emptying activity. In particular, 4-amino-5-chloro-2-ethoxy-N-[[4-(3-pyridylmethyl)-2- morpholinyl]methyl]benzamide (57b) was equipotent to the 4-fluorobenzyl analogue 1b (AS-4370 as its citrate) in the gastrokinetic activity on phenol red semisolid meal in rats and mice, and on resin pellet solid meal in rats. Moreover, compound 57b was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests. Structure-activity relationships of compounds with various substituents at N-4 are also discussed.

Animals↗

Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with roxatidine.

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.

Acetamides↗

Progressive systemic sclerosis complicated with immune thrombocytopenia during D-penicillamine therapy.

Immune thrombocytopenia is a rare complication of progressive systemic sclerosis (PSS). A 47-year-old female with PSS treated with D-penicillamine developed immune thrombocytopenia, which promptly responded to prednisolone and withdrawal of D-penicillamine. Platelet-associated IgG was elevated and the bone marrow megakaryocyte count was normal. There was an inverse relationship between the level of platelet-associated IgG and the platelet count. A lymphocyte stimulation test sensitized by D-penicillamine was positive. The present case suggests that immune thrombocytopenia may be regarded as one of the D-penicillamine-related immune abnormalities. To our knowledge, its association with PSS has never been reported.

Blood Platelets↗

Role of cytosolic Ca2+ in impaired sensitivity to glucose of rat pancreatic islets exposed to high glucose in vitro.

Sustained exposure to high concentrations of glucose selectively impairs the ability of pancreatic islets to secrete insulin in acute glucose stimulation. In order to evaluate the interrelationship between impaired insulin secretion and the dynamics of the cytosolic free Ca2+ level ([Ca2+]i), we have investigated the effect of high glucose exposure on both [Ca2+]i dynamics in single rat beta-cells and insulin release from rat pancreatic islets. Islets cultured at a high glucose concentration (16.7 mM) for 24 h showed significant reductions of the 16.7 mM GSIR compared with islets cultured at a normal glucose concentration (5.5 mM) (3.38 +/- 0.24 vs. 4.26 +/- 0.34%, respectively, P < 0.05). The capacity of glucose to raise the [Ca2+]i level also was significantly reduced in the beta-cells maintained for 24 h at 16.7 mM glucose (P < 0.001). An additional culture in the medium with 5.5 mM glucose for 16 h restored both the GSIR and the [Ca2+]i response of islets cultured at high glucose. On the other hand, insulin release and [Ca2+]i rise in response to 20 mM L-Arg were well preserved. These observations confirm that exposure of pancreatic beta-cells to high glucose concentrations induces a selective reduction of the GSIR and, further, shows that this impaired response is reversibly restored by an additional culture with normal glucose. We also suggest that the inability of glucose to provoke a [Ca2+]i rise, which is observed in the beta-cells exposed to high glucose, may be responsible for the selective impairment of the GSIR.

Animals↗

A supernumerary muscle between the adductors brevis and minimus in humans.

In order to elucidate the nerve supply of a supernumerary muscle observed between the adductors brevis and minimus in humans and to investigate its true nature and mechanism of formation, 100 body halves from 50 adult Japanese cadavers were subjected to gross anatomical examination. A supernumerary muscle was noted in 33 (33.0%) out of the 100 thighs. In each of these thighs, it arose from the upper part of the inferior ramus of the pubis and ran obliquely downwards and laterally. It was inserted into the anterior surface of the insertion aponeurosis of the adductor minimus (17/33 thighs, 51.5%), the upper part of the pectineal line (9/33 thighs, 27.3%), or the posterior side of the base of the lesser trochanter (7/33 thighs, 21.2%). It was supplied, from its posterior aspect, by a filament from the twig originating from the posterior branch of the obturator nerve and being distributed to the superficial fasciculus of the obturator externus (18/33 thighs, 54.5%) or by a twig directly originating from the posterior branch (15/33 thighs, 45.5%). The obturator nerve received fibers from L1234 (4/33 thighs), L234 (25/33 thighs), L2345 (2/33 thighs) or L34 (2/33 thighs) and, moreover, its posterior branch ran through (25/33 thighs, 75.8%) or over (8/33 thighs, 24.3%) the obturator externus to emerge into the thigh. Based on the topographical-anatomical relationships of this muscle to its nerve supply, it seems probable that it is formed by separation from the superficial layer of the obturator externus and changes into an independent structure during the process of ontogeny. Furthermore, from a statistical standpoint, the segmental composition or course of the obturator nerve is not related to either the formation or incidence of this muscle.

Cadaver↗

[Frequency of the development of RNA-rich reticulocytes in allogeneic bone marrow transplant recipients].

We measured appearance rates of RNA-rich reticulocytes in 8 patients undergoing allogeneic bone marrow transplantation, using a Sysmex R-1000 reticulocyte counter which utilizes laser flow cytometry. The changes in proportion of RNA-rich reticulocytes (high fluorescence ratio: HFR) and maturation index (MI: HFR + middle fluorescence ratio/low fluorescence ratio) were compared with those of WBC, neutrophil or reticulocyte counts. Engraftment was defined as an HFR of greater than or equal to 5% or a MI of greater than or equal to 15%. Engraftment was confirmed significantly earlier by HFR (13.5 +/- 2.4 days) and MI (13.1 +/- 2.9 days) than by neutrophils (17.1 +/- 3.2 days) or reticulocytes (20.4 +/- 6.2 days). The maturation of reticulocytes would be a useful indicator for engraftment or recovery from marrow aplasia in cases of bone marrow transplantation.

Adolescent↗

Efficient cDNA cloning method using solid phase DNA probe.

We are now developing a novel and efficient method using solid phase DNA probe to isolate a particular recombinant cDNA from single stranded cDNA library. Target clone coding metapyrocatechase (MPC) and cDNA library constructed from mRNA of U-937 (human lymphoma cell line) were converted to single stranded form by superinfection of helper phage (M13KO7). Probe DNA (25 mer) composed of a portion of the target cDNA was synthesized, attached to an HPLC gel and used as a solid phase DNA probe. Hybridization between probe DNA and target clone was performed in an Eppendorf tube within a few hours. Competent cell (JM109) was transformed with about one-twentieth of hybridized and eluted fraction by Hanahan's method. From the mixture of 1 ng of MPC vector and 5 micrograms of cDNA library, we obtained 50 colonies containing MPC gene out of 63 transformed colonies.

Catechol 2,3-Dioxygenase↗

Genomic changes in the WT-gene (WT1) in Wilms' tumors and their correlation with histology.

The authors studied genomic changes in unilateral Wilms' tumors by using WT33, a candidate cDNA for the tumor, and their correlation with histology. By Southern blot analysis, three cases of genomic deletions of both alleles were found in 25 tumors. The three tumors that showed genomic deletions were histologically classified as triphasic nephroblastic Wilms' tumor and one of them was associated with intralobar nephroblastomatosis and a rhabdomyomatous component. In one case, the WT1 gene was totally deleted, in another case, the 3' region of the gene was partially deleted, and in the last one, the deletion of DNA was intragenic. This is the first report of a comparison of genomic alteration with histopathology. These findings show new aspects of the role of the WT1 gene in the development of Wilms' tumor.

Blotting, Southern↗

Endothelin-specific antibodies decrease blood pressure and increase glomerular filtration rate and renal plasma flow in spontaneously hypertensive rats.

OBJECTIVE: Studies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGN: The technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the contribution of endothelin to the in vivo control of blood pressure and renal hemodynamics. METHODS: Endothelin-specific antibodies were administered intravenously into anesthetized SHR and Wistar-Kyoto (WKY) rats, and the effects upon blood pressure and renal function (renal plasma flow and glomerular filtration rate) assessed. Using the same antibodies, baseline plasma levels of endothelin in both strains of rats were determined by radioimmunoassay. RESULTS: Infusion of endothelin-specific antibodies into SHR decreased mean arterial pressure by approximately 10% and renal vascular resistance and renal vascular resistance by approximately 35%. Glomerular filtration rate and renal plasma flow both increased by approximately 50% over control. In contrast, infusion of normal rabbit serum into SHR or of endothelin-specific antibodies into WKY rats did not result in any significant change in renal hemodynamics or arterial blood pressure. Baseline plasma levels of immunoreactive endothelin in SHR were significantly lower than those in WKY rats. CONCLUSION: These results suggest that endothelin plays an important role in the modulation of systemic blood pressure and renal function in SHR.

Animals↗