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Biomedical subjects

H Morimoto

Publications and source records attributed to H Morimoto.

At least 163 records · Page 9Linked to original sources
PubMed1989

[Synthesis and biochemical actions of idebenone and related compounds. Ubiquinone and related compounds, XL].

Syntheses of some metabolites of ubiquinone and of related compounds are described. Idebenone (QSA-10), a methyl-dimethoxy-benzoquinone bearing an omega-hydroxydecyl side chain in 3-position, restored the oxidation of succinate and of NADH in ubiquinone-depleted mitochondrial preparations and showed a stabilizing effect on lysosomal membranes and an inhibitory effect on cAMP-phosphodiesterase. It inhibited lipid peroxidation in canine brain mitochondria and in microsomes from canine brain and rat liver. Administered orally to rats, it increased the respiratory control index for glutamate and succinate oxidation but had no effect on the ADP/O2 ratio. Pharmacological effects of idebenon are also briefly discussed.

Animals↗
PubMed1989

Functional and geometrical interference and interdependency between the right and left ventricle in cor pulmonale: an experimental study on simultaneous measurement of biventricular geometry of acute right ventricular pressure overload.

To clarify the effects of right ventricular (RV) pressure overload on functional and geometrical interference and interdependency between the right and left ventricle, both ventricular internal diameters were measured by the microcrystal technique during lycopodium induced pulmonary embolization in the dog. By repeated embolization, RV systolic pressure was increased progressively until it reached a peak value of about 60-70 mmHg, then it began to fall. At the same time, the hemodynamics deteriorated progressively resulting in death. During the experiment, gradual leftward displacement of the interventricular septum (IVS) without any change in left ventricular (LV) free wall geometry was observed. In pulmonary embolic shock, which showed a fall in LV pressure to about 60 mmHg and cardiac output to about 40% of control, the leftward displacement of IVS became marked, and the cooperative movement of IVS to LV contraction disappeared. The IVS position during acute RV pressure overload was able to account for the transseptal pressure gradient. The importance of IVS position and motion in cardiac function during acute RV pressure overload was stressed. Furthermore, to establish the theoretical treatment in acute cardiopulmonary resuscitation, ligation of the descending aorta (AoL) or norepinephrine ("N") or isoproterenol ("I") administration were examined in a canine pulmonary embolic shock model. AoL or "N" improved the deteriorated hemodynamics with restoration of biventricular geometry. However, "I" did not restore the biventricular geometry despite the transiently improved hemodynamics, and the experimental animals were unable to survive. These results suggest the importance of the maintainance of systemic pressure for the restoration of failed RV function. Further integrated studies are required to understand biventricular interference and interdependency.

Animals↗
PubMed1989

Plasma extravasation by chemical mediators in rat skin and trachea: a role of neurogenic agents on tracheal edema formation.

The plasma extravasation inducing activities of several chemical mediators (allergic agents: histamine, leukotriene C4 (LTC4) and platelet activating factor (PAF); neurogenic agents: substance P, capsaicin and carbachol) have been investigated and characterized in rat skin and trachea. Substance P, histamine, LTC4 and PAF induced dose-dependent plasma extravasation in rat skin. The activities of these mediators in inducing tracheal plasma extravasation were very different from those in the skin reactions. When these mediators were injected intravenously, substance P induced severe plasma extravasation, and the activities of histamine and PAF were weaker than that of substance P. When injected intratracheally, only substance P and capsaicin induced tracheal plasma extravasation, while none of the allergic mediators tested caused any plasma extravasation in the trachea. Carbachol did not induce any plasma extravasation in either skin or trachea. These results indicate that the stimulation of afferent substance P-containing nerve fibers has a more important role in the induction of tracheal plasma extravasation than that of allergic chemical mediators.

Animals↗
PubMed1989

[The effect of cimetidine to suppress the reduction of gastric mucosal blood flow caused by immobilization in water--its relationship to noradrenaline].

Reduction of gastric mucosal blood flow has been regarded as being the most important event for the gastric defensive mechanisms. In male Wistar rats immobilized in water, the authors recently studied the effect of cimetidine on the gastric mucosal blood flow and the mechanism for that action of cimetidine. In vivo, animals were divided into four groups (PGE2-treated, PGI2-treated and cimetidine-treated groups and an untreated control group), and mucosal blood flow before and 4 hours after the start of immobilization was determined with the electrolytic hydrogen gas clearance technique. In vitro involving perfusion of the isolated gastric blood vessels, the effect of treatment with PGE2, PGI1 or cimetidine in the presence of stimulation with noradrenaline was assessed. The stress-caused blood flow reduction was significantly suppressed in the PGE2-treated group (26.9% reduction in blood flow), the PGI2-treated group (15.7%) and also in the cimetidine-treated group (39.2%) as compared to the controls in which blood flow was reduced by 58.0% following immobilization. In vitro, cimetidine treatment resulted in a reduction of gastric perfusion pressure by 36.6% at maximum although the reduction was more marked following treatment with PGE2 (44.9% reduction) or PGI2 (49.4%). This result suggests that cimetidine also has a vasodilative action.

Animals↗
PubMed1989

[An in vitro drug screening assay, scintillation assay, and its clinical application].

We have developed an in vitro drug screening test by scintillation assay with which we can assess the chemosensitivity of solid human tumors during the 5 days following tumor resection. We are able to evaluate 62% (271/439) of the human tumors' chemosensitivity results. Seventy-seven of these cases were examined for in vitro-in vivo correlations. In 14 of 33 in vitro sensitivity cases (42%) we found clinical responses. And, in 41 of 44 in vitro resistance cases (95%) we found progressive disease. These in vitro-in vivo correlations with the scintillation assay were similar to those in other reports with different types of chemosensitivity assay. The true-positive accuracy of these tests averaged 50%, while the true-negative accuracy averaged 90%. We think that tumor cell heterogeneity is one of the main reasons for low true positive accuracy in the drug screening assays. In some studies we implanted human tumors into nude mice. The resulting xenografts demonstrated that fresh human tumors are composed of heterogeneous subpopulations of cells with varying chemosensitivities and varying DNA indexes. This heterogeneic nature of human tumor cells means that a single biopsy specimen may not comprehensively define the chemosensitivity of a patient disease.

Drug Screening Assays, Antitumor↗
PubMed1988

Alpha-fetoprotein-producing renal cell carcinoma.

A case of alpha-fetoprotein (AFP)-producing renal cell carcinoma with multiple bone and lung metastases, but without liver involvement is reported. The stain specific to AFP (avidin-biotin complex) proved the presence of the AFP in the cytoplasms of some cells of the renal tumors. In addition, three other cases of AFF-producing renal cancer recently published in the literature in Japan are reviewed. These four cases indicate that mesoderm-originating malignant tumors such as renal cell carcinomas can produce AFP in some situations. So, AFP is probably more universal than believed, although it is generally a popular and useful tumor marker for hepatocellular carcinomas and yolk sac tumors. The knowledge of the presence of AFP-producing renal cell carcinomas will make a new contribution to the study of the oncogenesis of AFP-producing tumors.

Carcinoma, Renal Cell↗
PubMed1988

[Obstructive sleep apnea syndrome with reversible interventricular septal displacement during sleep: a case report].

A case of the obstructive sleep apnea syndrome revealed reversible leftward displacement of the interventricular septum by echocardiography during sleep. A 46-year-old housewife with congenital micrognathia was admitted to our hospital complaining of severe dyspnea and general edema. On admission, she had severe hypoxemia (PaO2 = 35.2 mmHg), pulmonary hypertension (mean pulmonary artery pressure = 70 mmHg) and right heart failure. Her echocardiograms revealed enlargement of the right ventricle with a flattened left ventricle. A sleep study performed after partial resolution of her right heart failure disclosed that severe hypoxemia and pulmonary hypertension (mean pulmonary artery pressure = 70 mmHg) occurred after relatively long periods of apnea. With vigorous inspiratory efforts during sleep apnea, transient enlargement of the right ventricle and leftward displacement of the septum causing the flattened left ventricle were observed echocardiographically. A concomitant decrease in left ventricular inflow velocities was also observed by the pulsed Doppler method. However, these findings immediately returned to normal with the resumption of ventilation. We concluded that these repetitive apneic events due to obstruction of the airway during sleep might accelerate complete eventual pulmonary hypertension and right heart failure.

Echocardiography↗
PubMed1987

Proton nuclear magnetic resonance and spectrophotometric studies of nickel(II)-iron(II) hybrid hemoglobins.

Ni(II)-Fe(II) hybrid hemoglobins, alpha(Fe)2 beta(Ni)2 and alpha(Ni)2 beta(Fe)2 have been characterized by proton nuclear magnetic resonance with Ni(II) protoporphyrin IX (Ni-PP) incorporated in apoprotein, which serves as a permanent deoxyheme. alpha(Fe)2 beta(Ni)2, alpha(Ni)2 beta(Fe)2, and NiHb commonly show exchangeable proton resonances at 11 and 14 ppm, due to hydrogen-bonded protons in a deoxy-like structure. Upon binding of carbon monoxide (CO) to alpha(Fe)2 beta(Ni)2, these resonances disappear at pH 6.5 to pH 8.5. On the other hand, the complementary hybrid alpha(Ni)2 beta(Fe-CO)2 showed the 11 and 14 ppm resonances at low pH. Upon raising pH, the intensities of both resonances are reduced, although these changes are not synchronized. Electronic absorption spectra and hyperfine-shifted proton resonances indicate that the ligation of CO in the beta(Fe) subunits induced changes in the coordination and spin states of Ni-PP in the alpha subunits. In a deoxy-like structure, the coordination of Ni-PP in the alpha subunits is predominantly in a low-spin (S = 0) four-coordination state, whereas in an oxy-like structure the contribution of a high-spin (S = 1) five-coordination state markedly increased. Ni-PP in the beta subunits always takes a high-spin five-coordination state regardless of solution conditions and the state of ligation in the partner alpha(Fe) subunits. In the beta(Ni) subunits, a significant downfield shift of the proximal histidyl N delta H resonance and a change in the absorption spectrum of Ni-PP were detected, upon changing the quaternary structure of the hybrid.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1987

Tumor imaging with anti-CEA antibody labeled 19F emulsion.

The possibility of using 19F MRI for detection of tumors using a 2-T NMR system was examined in animals. Anticarcino-embryonic antigen (CEA) antibody conjugated with perfluorochemical (perfluorotributylamine, FTBA) was administered to nude mouse inoculated with LOVO, a CEA-producing human cancer cell line. Tumor imaging based on the 19F NMR was examined after excision of the tumors from nude mice (ex vivo). The imaging pattern of the tumor coincided with the antibody distribution determined immunohistologically.

Animals↗