Biomedical subjects
Publications and source records attributed to S Morimoto.
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A 65-year-old man had been followed by a family doctor for the treatment of hypertension and chronic hepatitis (type C) for about 20 years. Although he was pointed out to have impaired glucose tolerance and primary aldosteronism in 1995, he refused an adrenal tumor operation. He was admitted to our hospital on December, 1997 for further evaluation of general malaise, pitting edema of the legs, and positive urinary protein. A diagnosis of nephrotic syndrome was made on admission and a renal biopsy was performed. Histological findings indicated that he was at the early phase of diabetic nephropathy and hypertensive renal sclerosis. It is commonly believed that diabetic nephropathy develops after ten years of diabetic history and under poor control conditions. The diabetic history of this patient was only several years and the disease was under good control. In contrast to blood glucose, hypertension was not well-controlled with any antihypertensive drug, because he had a primary aldosteronism. Unfortunately, he could not take a spironolactone because of side effects. After removal of his adrenal tumor, his blood pressure was normalized gradually, and concomitantly his urinary protein was reduced and plasma protein and albumin were restored. Hypokalemia also disappeared. These findings suggest that uncontrolled hypertension may have accelerated the condition of diabetic nephropathy. The data indicates that the control of hypertension is important for inhibiting the progression of diabetic nephropathy.
The pathogenesis and clinical course of traumatic cerebral vasospasm (TCV) are not yet fully understood. We report a case of delayed symptomatic TCV exaggerated by hyponatremia in spite of minor subarachnoid hemorrhage. A 77-year-old woman was admitted to our hospital with multiple injury caused by a traffic accident. Glasgow coma scale on admission was 8, and CT scan revealed right temporal lobe contusion, thin sub-arachnoid hemorrhage in the right sylvian cistern and right temporal bone fracture. The patient's consciousness level and CT findings improved gradually, but on the 11th day, she suddenly fell into a comatose state. No apparent change was observed on the CT scan, but her serum sodium level was markedly low (113 mEq/L). Under the suspicion of hyponatremia induced consciousness disturbance, sodium replacement therapy was commenced. She showed transient neurological recovery, but on day 13, worsening of left hemiparesis and a new low density area on CT were observed. Vasospasms of the right M2 proximal portion were confirmed by cerebral angiogram, so we performed intraarterial papaverine infusion leading to good extension of spastic vessels, but regrettably, there was no neurological recovery. In general, subarachnoid blood plays an important role in the delayed development of cerebral vasospasm, following not only aneurysmal rupture but also head injury. TCV tends to pass subclinically, but secondary water and electrolyte imbalance may unexpectedly cause TCV to manifest itself clinically. We can confirm that with this patient management of electrolyte balance following head injury was the most important strategy to avoid symptomatic TCV.
Tibolone is a synthetic steroid with progestogenic, androgenic and estrogenic properties. In postmenopausal women it has been shown that improves climateric complaints and prevents osteoporosis, without impact on endometrial thickness and uterine fibroids volume. Tibolone administration decreases cholesterol and triglycerides. Although, the effects of hormonal replacement on insulin sensitivity and glucose metabolism has not been well established. The effect of tibolone 2.5 mg/day for 3 months was investigated in 10 healthy postmenopausal women. The results show that tibolone decreases tryglicerides and cholesterol levels along with an increase in fasting insulin levels. The oral glucose tolerance test was unaffected. This study suggests that tibolone reduces markers of cardiovascular disease.
Phosphorylation of the regulatory light chain (RLC) activates the actin-dependent ATPase activity of Dictyostelium myosin II. To elucidate this regulatory mechanism, we characterized two mutant myosins, MyDeltaC1225 and MyDeltaC1528, which are truncated at Ala-1224 and Ser-1527, respectively. These mutant myosins do not contain the C-terminal assembly domain and thus are unable to form filaments. Their activities were only weakly regulated by RLC phosphorylation, suggesting that, unlike smooth muscle myosin, efficient regulation of Dictyostelium myosin II requires filament assembly. Consistent with this hypothesis, wild-type myosin progressively lost the regulation as its concentration in the assay mixture was decreased. Dephosphorylated RLC did not inhibit the activity when the concentration of myosin in the reaction mixture was very low. Furthermore, 3xAsp myosin, which does not assemble efficiently due to point mutations in the tail, also was less well regulated than the wild-type. We conclude that the activity in the monomer state is exempt from inhibition by the dephosphorylated RLC and that the complete regulatory switch is formed only in the filament structure. Interestingly, a chimeric myosin composed of Dictyostelium heavy meromyosin fused to chicken skeletal light meromyosin was not well regulated by RLC phosphorylation. This suggests that, in addition to filament assembly, some specific feature of the filament structure is required for efficient regulation.
In the present study, clinical findings of 15 patients with cardiac sarcoidosis presenting as dilated cardiomyopathy were compared with those of 30 consecutive patients with idiopathic dilated cardiomyopathy. The sarcoidosis patients had different clinical features, including female predominance, a high incidence of grave conduction disturbance and abnormal wall thickness, uneven wall motion abnormalities, and perfusion defects preferentially affecting the anteroseptal and apical regions, and poor prognosis compared with those with idiopathic dilated cardiomyopathy.
The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 has been implicated in the establishment of cell-mediated immunity as well as humoral immune responses. To examine the role of CD40L in eliciting antitumor immunity, we introduced murine CD40L gene into P815 mastocytoma (CD40L-P815). CD40L-P815 cells underwent prompt rejection when inoculated s.c. into syngenic DBA/2 mice or athymic BALB/c nu/nu mice, which was mediated by NK cells and dependent on endogenous IL-12. The primary rejection of CD40L-P815 cells in DBA/2 mice elicited CD8+ T cell-mediated protective and systemic immunity against parental tumor cells, which was induced by CD4+ T cells and endogenous B7. These results indicated a potent antitumor effect of CD40L that is mediated by potentiation of host Ag-presenting cell functions, and introduction of CD40L will be useful as a new strategy of immuno-gene therapy against tumors.
We identified a rapid and novel system to effectively metabolize a large amount of H2O2 in the suspension cells of Scutellaria baicalensis Georgi. In response to an elicitor, the cells immediately initiate the hydrolysis of baicalein 7-O-beta-D-glucuronide by beta-glucuronidase, and the released baicalein is then quickly oxidized to 6,7-dehydrobaicalein by peroxidases. Hydrogen peroxide is effectively consumed during the peroxidase reaction. The beta-glucuronidase inhibitor, saccharic acid 1,4-lactone, significantly reduced the H2O2-metabolizing ability of the Scutellaria cells, indicating that beta-glucuronidase, which does not catalyze the H2O2 degradation, plays an important role in the H2O2 metabolism. As H2O2-metabolizing enzymes, we purified two peroxidases using ammonium sulfate precipitation followed by sequential chromatography on CM-cellulose and hydroxylapatite. Both peroxidases show high H2O2-metabolizing activity using baicalein, whereas other endogenous flavones are not substrates of the peroxidase reaction. Therefore, baicalein predominantly contributed to H2O2 metabolism. Because beta-glucuronidase, cell wall peroxidases, and baicalein pre-exist in Scutellaria cells, their constitutive presence enables the cells to rapidly induce the H2O2-metabolizing system.
Hydrogen peroxide (H2O2), an oxidant generated by inflammatory cells, is an important mediator of injury of endothelial cells (ECs). Here we show that H2O2 induces up-regulation of the expression of Fas, a death signal, in human ECs in culture. Flow cytometric analysis with a mAb against human Fas showed that incubation for 24 h with H2O2 induced a dose-dependent increase in the level of Fas in ECs. Coincubation with catalase, which rapidly degrades H2O2, inhibited H2O2-induced up-regulation of Fas. H2O2 also induced a dose-dependent increase in Fas mRNA level. A significant increase in Fas mRNA levels was observed from 6 h after stimulation with H2O2. Vanadate, a protein phosphatase inhibitor, significantly enhanced Fas mRNA and protein levels in H2O2-treated ECs. On the other hand, genistein, a tyrosine kinase inhibitor, inhibited H2O2-induced Fas mRNA expression. Furthermore, a flow cytometric method with propidium iodide staining and electron microscopic analysis showed that incubation with an agonistic Ab against Fas (anti-Fas IgM) induced apoptosis in H2O2-treated cells. These findings suggest that H2O2 induces up-regulation of Fas in ECs and that activation of protein tyrosine kinase may be involved in the mechanism of H2O2-induced Fas expression. Therefore, Fas-mediated apoptosis may have a pathologic role in H2O2-induced EC injury and thereby provide a new therapeutic target.
Hydroxyl radical-induced formation of a cross-link of thymine (Thy) and lysine (Lys) in the gamma-radiolysis of N2O-saturated aqueous solution was studied. A Thy-Lys cross-link (I) of the formal structure that OH radical and 4-carbon-centered Lys radical added respectively to C(5) and C(6) positions of Thy was isolated by a preparative HPLC and identified by a FAB-HRMS. The primary cross-link I was dehydrated by treatment with HCl at 120 degrees C to yield the secondary structure (II) possessing a C(5)-C(6) double bond in the Thy moiety: the latter structure II was reported previously (Dizdaroglu, M.; Gajewski, E. Cancer Res. 1989, 49, 3463-3467). A pulse radiolysis study with a redox titration method indicated that 4-carbon centered Lys radical intermediate was of neutral redox reactivity in contrast to reducing reactivity of 5-hydroxy-5,6-dihydrothymin-6-yl radical intermediate. The cross-link I could be formed by a conventional radical recombination mechanism, but not by an ionic recombination mechanism involving a redox reaction between the radical intermediates.
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Most accepted operations for childhood moyamoya disease have attempted to increase cerebral blood flow (CBF) in the ischaemic cortical areas around the central fissure. Developed ischaemic brain damage in the prefrontal area may lead to poor intellectual outcome and restrict patients' daily lives. Thus, extensive cerebral revascularization in both the ischaemic anterior and middle cerebral artery territories is mandatory. We describe the long-term follow-up results for intellectual outcome and performance status and make an evaluation of regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes performed as the initial management. In the past 10 years, 10 moyamoya patients less than 12 years of age consecutively underwent omental transplantation. The omental flap was spread over not only the symptomatic hemisphere but also the contralateral frontal lobe after a large craniotomy. Superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis was accomplished simultaneously. On the contralateral hemisphere, STA-MCA anastomosis combined with encephalomyosynangiosis was subsequently performed. The clinical observation period averaged 6.7 years (ranged 1.9 to 9.2 years). Apart from 2 patients in whom severe mental retardation had been disclosed pre-operatively, full-scale intelligence quotient scores have been maintained at over 90, that is, within the normal intellectual range. With respect to quality of life (QOL), these 8 patients have been leading normal daily lives since the operation. The focal decrease in CBF observed in the frontal lobe pre-operatively in 7 cases had disappeared after surgical treatment. In these patients, serial post-operative MR angiography revealed developed omental vessels and STAs. Deterioration of intellectual functions and QOL as well as cerebral ischaemic events in paediatric moyamoya patients can be prevented by extensive omental transplantation spread over both frontal lobes combined with STA-MCA anastomosis.
Changes in the circulating factors participating in involutional osteoporosis have been intensively investigated in women, but little is known about this in men. We investigated the possible participation of circulating factors including testosterone, vitamin D metabolites, and vitamins K1 and K2 in osteopenia in elderly men. In a group of 27 ambulatory men aged 74 +/- 10 years (mean +/- SD; range, 60 to 90), the bone mineral density (BMD) of the second to fourth lumbar vertebrae was measured by dual-energy x-ray absorptiometry (DXA) and expressed as a Z score, the age-adjusted BMD value for the Japanese population (mean +/- SD, 0 +/- 1). Although the plasma level of total testosterone significantly decreased with age in the group, it did not significantly correlate with the Z score. However, the plasma levels of 25-hydroxyvitamin D (25-OHD), phylloquinone, menaquinone-7 (MK-7), and albumin were significantly positively correlated with the Z score. Moreover, plasma 25-OHD and both phylloquinone and MK-7 were significantly positively correlated in the subjects. These observations suggest that depressed circulating levels of 25-OHD and vitamin K concomitantly and cooperatively participate in osteopenia in elderly men, which may reflect the etiology of the type II moiety of involutional osteoporosis.
Cannabichromenic acid synthase was purified to apparent homogeneity by sequential column chromatography including DEAE-cellulose, phenyl-Sepharose CL-4B, and hydroxylapatite. The enzyme catalysed the oxidocyclization of cannabigerolic acid and cannabinerolic acid to cannabichromenic acid. The K(m) values for both substrates were in the same order of magnitude although the Vmax value for the former was higher than that for the latter. These results suggested that cannabichromenic acid is predominantly formed from cannabigerolic acid rather than cannabinerolic acid. The enzyme required neither molecular oxygen nor hydrogen peroxide, indicating that the cannabichromenic acid synthase reaction proceeds through direct dehydrogenation without hydroxylation.
BACKGROUND: Three cases with intracranial facial neurinoma underwent tumor removal and facial nerve reconstruction with or without tympanoplasty. Surgical strategy for each case was tailored to: (1) the site of main tumor mass, (2) its extension along the facial nerve, and (3) involvement of the auditory organs. METHODS: Surgeries adopted in the three cases were: transpetrosal approach with intracranial-intratemporal facial nerve anastomosis, middle fossa and transmastoid approach with intratemporal facial nerve anstomosis and tympanoplasty, and middle fossa and transmastoid approach with intracranial-intratemporal facial nerve anastomosis and tympanoplasty. The greater auricular nerve was used as the nerve graft for all three cases. RESULTS: In the follow-up period of 8-13 months there was no tumor recurrence; facial function was scored 20/90 in modified May's scoring system in each case, but two are still in the process of functional recovery. One of the two cases who underwent tympanoplasty showed complete recovery of hearing within 1 month, and the other showed worsened hearing, which was not serviceable at 3 months postoperatively. CONCLUSION: Systematic surgical approach for tumor removal, facial nerve reconstruction, and auditory reconstruction should be considered in cases with intracranial facial neurinoma due to its varied clinical features.