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Biomedical subjects

M Morimoto

Publications and source records attributed to M Morimoto.

At least 163 records · Page 9Linked to original sources

[A longitudinal study of brain atrophy and its relation with background factors and common carotid hemodynamics].

This longitudinal study was performed to clarify the relation between brain atrophy and common carotid hemodynamics. A total of 147 patients, including 70 males and 77 females, who had neither neurologic deficits nor organic lesions on computed tomography of the brain, were enrolled in this study. The ages of the patients ranged from 47 to 76 years (mean: 62 years) at the first diagnosis of brain atrophy. The patients were divided into three groups: 66 controls without hypertension or diabetes mellitus (Group I), 60 with hypertension (Group II) and 21 with both hypertension and diabetes mellitus (Group III). Brain atrophy was diagnosed by caudate head index (CHI). Mean blood flow volume (BF) at the right common carotid artery was measured by an ultrasonic quantitative flow measurement system. Both CHI and BF were measured twice at a mean interval 6.5 years. Increment in CHI per year (delta CHI) and decrement in mean blood flow volume per year (delta BF) were calculated. delta CHI of Group I and Group II had a significant relation with aging. delta CHI of Group III showed a larger increase than that of both Group I and Group II in subjects in the sixties. delta CHI had a significant relation with delta BF in each group. These results indicate that complication of both HT and DM, or decrement in mean blood flow volume may cause brain atrophy to progress.

Aged↗

Fish oil, alcohol, and liver pathology: role of cytochrome P450 2E1.

Rats were fed ethanol in combination with fish oil or a corn diet in order to evaluate the effect of fish oil feeding on liver injury, microsomal ethanol oxidation, and NADPH-dependent lipid peroxidation. The rats were maintained on the dietary regimen for 72 days, and for comparison, pair-fed controls were studied. The liver pathology score progressively worsened in rats fed alcohol, both in combination with fish oil and corn oil, but the severity of inflammation and focal fibrosis was greater in the ethanol fish oil fed rats as compared with the ethanol corn oil group, whereas the fatty change was greater in the ethanol corn oil fed rats. The alcohol treatment caused a 2-fold increase of the liver microsomal P450 content, and about a similar increase in the rate of microsomal NADPH oxidation. The amount of ethanol-inducible CYP2E1 was about 10-fold higher in alcohol-fed rats as compared with pair-fed controls. The NADPH-dependent lipid peroxidation in liver microsomes was about 10-fold higher in microsomes from alcohol-treated rats fed corn oil as compared with controls, but only 2- to 3-fold higher in alcohol-fed rats receiving fish oil than in pair-fed controls. This was due to a higher rate of NADPH-dependent lipid peroxidation in the control rats receiving fish oil. There was a pronounced correlation between the amount of CYP2E1 and the microsomal NADPH peroxidation in variously treated rats, and between the 2E1 levels and the pathology score. The data suggest that fish oil diet, like corn oil, supports ethanol-induced liver injury which is related to CYP2E1 induction and the presence of polyunsaturated fatty acids in the diet (i.e., either n-6 or n-3).

Alanine Transaminase↗

Mitomycin derivatives having unique condensed-ring structures. Their synthesis and antitumor activity.

A series of mitomycin derivatives 1-3 having unique condensed-ring structures was synthesized and evaluated for their anticellular and antitumor activity. These compounds were synthesized by the Michael addition of 1.3-dicarbonyl compounds to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylenemitosanes (4-6, and 14) and the subsequent cyclization. For the preparation of 1. the allyloxycarbonyl (Aloc) group was employable for the protection of the aziridine (1a-N-H), since the deprotection proceeded without decomposition of the substrates under the mild conditions with Pd(0) and HCO2H-NEt3. Among these structurally unique derivatives, compounds 1a, 1b, 1d and 1e were quite potent against HeLa S3 human tumor cells and sarcoma 180 solid tumor in mice.

Animals↗

A third generation immunoassay for tumor necrosis factor alpha.

Tumor necrosis factor alpha (TNF alpha) is a polypeptide cytokine produced primarily by monocytes and macrophages. It is involved in a wide variety of immune reactions. Measurement of TNF alpha originally depended upon bioassays that are of varying reliability and reproducibility. Early immunoassays for TNF alpha required handling of radioisotopes and costly disposal of radioactive waste. Subsequent use of enzymes as reporter molecules in enzyme immunoassay (EIA) has eliminated the burden of radioisotope handling and its associated costs. However, EIA has presented new challenges. Use of thimerosal as a preservative in EIAs may require high disposal costs due to its mercury content. In addition, many EIAs lack the sensitivity achievable in radioimmunoassay (RIA). We have developed a simple microplate enzyme-linked immunosorbent assay (ELISA) for the detection of TNF alpha in serum, plasma and culture supernatants. Our high affinity capture antibody has enabled us to achieve a sensitivity of 1.5 pg/mL. The assay is calibrated to the World Health Organization (W.H.O.) first international standard for TNF alpha (87/650) and exhibits excellent precision and reproducibility. Tetramethylbenzidine is used to generate the colored end product of the reaction, and thimerosal has been removed from all components.

Enzyme-Linked Immunosorbent Assay↗

[Use of a disposable infusion device for continuous epidural block].

We analyzed 130 patients with intractable pain who were treated with continuous epidural block therapy using a disposable microinjector to evaluate its efficacy and utility. The mean treatment period was 4.3 +/- 0.4 weeks. After the treatment, the mean visual analog scale (VAS) improved to 3.3 +/- 0.2, from the pretreatment value of 6.5 +/- 0.1. Among the intractable pain conditions, postherpetic neuralgia (PHN) and pain in the neck, shoulder and upper limbs were relieved markedly, while cancer pain was difficult to reduce. These data show that continuous epidural block therapy using the disposable microinjector is particularly useful in PHN, in which sympathetic nerve block is the essential treatment. The pain in the neck, shoulder and upper limbs was relieved with continuous somatic nerve block.

Aged↗

MR of pulmonary hamartoma: pathologic correlation.

We describe the magnetic resonance (MR) appearance with pathologic correlation of six pulmonary hamartomas. All six tumors showed intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Four of the six tumors showed a lobulated appearance separated by septa on precontrast T1-weighted or T2-weighted images. Gadolinium-enhanced T1-weighted images showed marked enhancement of the septa that separated the tumors into less well enhanced lobules; this was seen in all six tumors. Comparison between MR images and pathologic specimens showed that the regions with less enhancement corresponded to core cartilaginous tissue and septa; areas of marked contrast enhancement corresponded to cleft-like branching mesenchymal connective tissue that dipped into the cartilaginous core. MR images correlated well with the surgically resected tumors.

Adult↗

[Two cases of craniopharyngioma associated with Rathke's cleft cyst].

Two rare cases of craniopharyngioma associated with Rathke's cleft cyst are reported. The patients were 74-year-old female and 12-year-old boy. The former complained bilateral impaired visual acuity and visual field disturbance with hypoprolactinemia, the latter complained diabetes insipidus and growth retardation. MR images of these cases demonstrated sellar resion tumors, which were composed with both cystic and solid component. Transsphenoidal tumor removal were performed to both cases, and their tumor tissues were studied by light and electron microscopy. The cyst wall were composed of three kinds of epithelial cells such as ciliated columnar cells, mucous cells and basal cells. The solid components were composed of stratified squamous cells. These two components shifted each other. For these facts, to consider that both Rathke's cleft cyst and craniopharyngioma originate in remnants of Rathke's pouch, it is concluded that Rathke's cleft cyst cells sometimes cause differentiation to craniopharyngioma on its growth process.

Aged↗

Ultrasonography of thymoma with pathologic correlation.

Preoperative ultrasonograms of 11 surgically proved thymomas and ex vivo ultrasonograms of 3 resected specimens were compared with pathologic findings of resected specimens. Among 11 thymomas 7 appeared solid, 3 were solid with several cystic regions, and the remaining one was unilocular cystic in appearance. Cystic regions on ultrasonograms corresponded to cystic changes on pathologic specimens. Six malignant thymomas showed a typical lacy appearance on ultrasonograms, which corresponded to the lobulated configuration separated by fibrous septa shown on the pathologic specimens.

Adult↗

Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit.

The white-spotting (Ws) locus of rats represents a 12-base deletion of the c-kit receptor tyrosine kinase. Homozygous Ws/Ws rats are deficient in melanocytes, mast cells, and erythrocytes. Although mice possessing two mutant alleles at the c-kit (W) locus, such as mice of W/Wv genotype, show severe anemia even in adult age, the anemia of Ws/Ws rats remarkably ameliorated with age. We investigated the mechanism of the age-dependent amelioration. Bone marrow cells of Ws/Ws rats did not form macroscopic colonies in the spleen of irradiated rats, and the concentration of burst-forming unit-erythroid in the marrow of Ws/Ws rats was comparable with that of +/+ rats. Therefore, the increase in morphologically identifiable erythroid precursors in the marrow of Ws/Ws rats was attributed to the increased concentration of colony-forming unit-erythroid (CFU-E). Furthermore, the increase in CFU-E appeared to result from the increased concentration of erythropoietin (EPO). Because injections of relatively low doses of EPO cured the slight anemia that remained in adult Ws/Ws rats, CFU-E and/or its immediate precursors of Ws/Ws rats appeared to be more sensitive to EPO than those of W/Wv mice, in which a huge dose of EPO was necessary to cure the anemia.

Age Factors↗

Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit.

All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50-fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T-cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production.

Animals↗

Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats.

Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c-kit gene and are deficient in both mucosal mast cells (MMC) and connective tissue-type mast cells (CTMC). The role of the c-kit receptor in the development of MMC and CTMC was investigated by infecting Ws/Ws and control +/+ rats with Nippostrongylus brasiliensis (NB), which induces T-cell-dependent mast cell proliferation. Although mast cells did not develop in the skin of Ws/Ws rats, a significant number of mast cells developed in the jejunum after NB infection. These mast cells had the MMC protease phenotype (rat mast cell protease [RMCP] I-/II+) and lacked heparin because they were not stained with berberine sulfate. Globule leukocytes were also detected in the mucosal epithelium of these rats. However, the number of MMC and the serum concentration of RMCP II in NB-infected Ws/Ws rats were only 13% and 7% of those of NB-infected +/+ rats, respectively. A small number of mast cells also developed in the lung, liver, and mesenteric lymph nodes of Ws/Ws rats after NB infection. Although mast cells in these tissues had the MMC phenotype throughout the observation period, the increased mast cells in the lung and liver of +/+ rats acquired a CTMC-like phenotype and were RMCP I+/II+, berberine sulfate+, and formalin resistant. These results indicate that the need for the stimulus through the c-kit receptor appears to be greater in the development of CTMC in the skin as well as for CTMC-like mast cells in the lung and liver than for the development of MMC.

Animals↗

Aberrant retrotracheal goiter: report of a case.

A case of intrathoracic retrotracheal goiter in a 40-year-old woman is herein described. A computed tomographic scan, magnetic resonance imaging and endoscopical ultrasonography all confirmed the existence of a retrotracheal encapsulated lesion, which was suspected to be aberrant mediastinal goiter. Radioiodine scintigraphy, however, demonstrated little uptake in the mass. A large (7 x 6 x 4 cm), encapsulated adenomatous goiter was then easily removed via a right thoracic approach.

Adult↗

Disposition and metabolism of KW-2149, a novel anticancer agent.

KW-2149 is a new derivative of mitomycin C (MMC). The plasma concentrations, distribution, metabolism, and excretion of [3H]-KW-2149 in normal and tumor-bearing mice after i.v. administration of 16.6 mg/kg were investigated. The plasma radioactivity decreased biexponentially after i.v. administration in normal mice. However, the unchanged drug disappeared rapidly, showing a half-life (t1/2) of 9.7 min, which was shorter than MMC's (18 min). The radioactivity was excreted in mouse urine (33%) and feces (58%) within 144 h. High radioactivity was distributed in the gallbladder, liver, kidney, pancreas, and lung at 1 h after i.v. administration to normal mice. The tumor concentration was lower than the plasma or blood concentration. The lowest radioactivity was observed in the brain. The metabolic rate of KW-2149 was very rapid. The methyl sulfide form (M-16), the symmetrical disulfide dimer (M-18), and the albumin conjugate were detected in plasma, which possessed anticellular activity. The specific anticellular activity of these compounds against uterine carcinoma (HeLa S3) was 1/100, 1, and 1/20 respectively, as compared with that of KW-2149.

Animals↗

Elevated serum thymidine kinase activity in patients with acute viral hepatitis.

To evaluate the clinical applications of serum thymidine kinase (TK) activity, we compared the results obtained with this parameter with those of other liver function tests in 27 patients with acute viral hepatitis and 16 normal controls. In those in the acute stage, the serum TK activity increased significantly to 55.5 +/- 66.5 U/L. There was no significant correlation between serum TK activity and findings for serum albumin, bilirubin, alkaline phosphatase or r-glutamyl transpeptidase. However, it did correlate significantly well with the serum activity of aspartate aminotransferase (AST) (r = 0.621, P < 0.01), alanine aminotransferase (ALT) (r = 0.551, P < 0.01), and lactate dehydrogenase (LDH) (r = 0.620, P < 0.01). Serum TK activity reached higher than 70 U/L in 8 of 11 patients with hepatitis A; however, no patients with the other types of hepatitis reached such a high level. During the recovery stage, the serum TK activity decreased significantly to 5.9 +/- 1.7 U/L (P < 0.01), and did not correlate with AST, ALT, LDH or other conventional liver function parameters. The data suggest that an elevation of serum TK in patients with acute viral hepatitis results from hepatocellular damage. A marked elevation of serum TK activity may thus provide a marker for acute hepatitis A infection.

Acute Disease↗

Improvement of cardiac function impaired by repeated ischemic arrests in isolated rat hearts.

We investigated the effects of coenzyme Q10 and verapamil, either alone or in combination, on cardiac function impaired by repeated ischemic arrests and reperfusion in the isolated rat heart. In the group with a single ischemic arrest, the aortic flow, cardiac output, stroke volume, coronary flow, and heart rate recovered well (72% to 100% of the prearrest values). In the repeated-arrest group, the recovery of aortic flow (24%), cardiac output (30%), stroke volume (40%), or coronary flow (63%) was much poorer than that in the single-arrest group. Pretreatment with coenzyme Q10 given intraperitoneally improved aortic flow, cardiac output, stroke volume, coronary flow, and heart rate. The addition of verapamil to the reperfusion solution also protected the cardiac function with a decrease in heart rate. However, combination therapy with coenzyme Q10 and verapamil further increased the recoveries of aortic flow, cardiac output, stroke volume, and coronary flow to 57%, 61%, 77%, and 84%, respectively, which were better than the values after treatment with coenzyme Q10 or verapamil alone. We, therefore, suggest that treatment with coenzyme Q10 or verapamil, alone or in combination, in addition to St. Thomas' Hospital solution effectively protects cardiac function impaired by repeated ischemic arrests and reperfusion.

Animals↗