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Biomedical subjects

T Kawase

Publications and source records attributed to T Kawase.

At least 91 records · Page 5Linked to original sources

Effects of N(G)-monomethyl-L-arginine on Ca(2+) current and nitric-oxide synthase in rat ventricular myocytes.

The effects of N(G)-monomethyl-L-arginine (L-NMMA), a nitric-oxide synthase (NOS) inhibitor, on the L-type Ca(2+) current (ICa) and NO effects on NOS were determined in rat ventricular myocytes. L-NMMA (10 and 100 microM) had no significant effect on basal ICa, but in a cAMP-stimulated condition due to forskolin (1 microM) or milrinone (10 microM), a cGMP-inhibited cAMP-phosphodiesterase (PDE), L-NMMA (10 and 100 microM) concentration dependently augmented ICa. The enhancing effects of L-NMMA (10 and 100 microM) on ICa were not seen in the presence of either a nonselective inhibitor of PDE, 3-isobutyl-1-methylxanthine (20 microM), resulting in a stimulated ICa condition or a cGMP-dependent protein kinase activator, 8-bromo-cGMP (200 microM). 8-Bromo-cGMP (200 microM) inhibited 100 microM L-NMMA-induced ICa increase in the simultaneous application of forskolin (1 microM). Acetylcholine (ACh; 1 and 3 microM) inhibited 1 microM forskolin-stimulated ICa in a concentration-dependent manner, but this inhibitory action of ACh was significantly attenuated by the additional application of L-NMMA (100 microM). In the continuing presence of both L-NMMA (100 microM) and forskolin (1 microM), ACh (6 microM) had no inhibitory effect on ICa. In another series of experiments with isolated ventricular myocytes, we obtained both the positive staining of NADPH-diaphorase activity and the expression of the endothelial isoform of NOS. These data suggest that the effect of L-NMMA on ICa in a cAMP-stimulated condition with or without cholinergic inhibition is due to inhibition (acute effects) of a cGMP-stimulated cAMP-PDE via inhibition of the endothelial isoform of NOS.

1-Methyl-3-isobutylxanthine↗

[A case of aconitine poisoning saved with cardiopulmonary bypass].

"Torikabuto" is a kind of plant which contains deadly poison. Its ingredient is aconitine alkaloids. We report a case of aconitine poisoning with fatal arrhythmia and acute pulmonary edema who was saved with cardio pulmonary bypass. A 41-year-old male ate to mistake "Torikabuto" for wild plant. He developed symptoms of dysarthria and admitted to our hospital. He developed ventricular tachycardia and fibrillation soon after his admission. Then he developed cardiogenic shock. He was resuscitated and supported with a percutaneous cardio pulmonary bypass. Ventricular tachycardia disappeared 24 hours after admittion. About 1 week later, cardio pulmonary bypass was terminated and about 3 months later, he discharged from our hospital.

Aconitine↗

A 35-year-old man with cerebral hemorrhage and pheochromocytoma: the second brain-dead organ donor in Japan.

A 35-year-old man was brought into the emergency room of Keio University Hospital by ambulance because of a sudden onset of coma. His Glasgow Coma Scale was 3 and his blood pressure 150/100 mmHg. CT scanning revealed a subcortical hemorrhage 8 cm in diameter. His respiration deteriorated rapidly, and an emergency craniotomy was performed for hematoma removal and cerebral decompression. Postoperatively the patient remained in a deep coma (GCS = 3) requiring respiratory support. The family presented an organ donor card previously signed by the patient, and brain death was confirmed in accordance with Japan's transplant law. As a result of two tests conducted six hours apart brain death was confirmed on the 5th postoperative day. With the family's consent, the donor's heart, kidneys and skin were removed for organ transplantation to be performed in other institutions. An autopsy was performed after the removal of the organs and skin. An extensive subgaleal hemorrhage was found in the left cerebral hemisphere, and microscopic examination revealed extensive necrosis with karyolysis of neuronal cells, but no viable neuronal cells were found in the cerebrum. The brain stem was marked by edema, hemorrhage, infarction necrosis and neuronal cell loss. The cerebellum was swollen and congested and showed autolysis of the granular layer. These findings suggested brain death syndrome with respirator brain. Other autopsy findings included a huge pheochromocytoma in the right adrenal gland, bilateral bronchopneumonia, liver congestion and fatty metamorphosis with four cavernous hemangiomas, and mild chronic lymphocytic thyroiditis. This patient was the second brain-dead organ donor and the first brain-dead patient to undergo postmortem examination in Japan.

Adrenal Gland Neoplasms↗

Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness.

DFN3, an X chromosome-linked nonsyndromic mixed deafness, is caused by mutations in the BRN-4 gene, which encodes a POU transcription factor. Brn-4-deficient mice were created and found to exhibit profound deafness. No gross morphological changes were observed in the conductive ossicles or cochlea, although there was a dramatic reduction in endocochlear potential. Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. The findings suggest that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function.

Animals↗

Prospective study of interferon therapy for compensated cirrhotic patients with chronic hepatitis C by monitoring serum hepatitis C RNA.

Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status. A total of 157 cirrhotic patients were enrolled to receive 9 million units (MU) of interferon three times a week. The HCV RNA values were drawn 8 weeks apart and the patients were randomized to a further 16 or 32 weeks of treatment after two sequential findings of negativity for HCV RNA. A total of 73 out of 157 patients (46%) proceeded to randomization to different durations of treatment, 37 short-course and 36 long-course (duration: 38 +/- 8 and 49 +/- 13 weeks; total amount of interferon: 940 +/- 240 and 1130 +/- 390 MU, respectively). The remaining 84 patients without two sequential negative serum HCV RNA determinations received 44.8 +/- 27.4 weeks of interferon (IFN) therapy with total amount of 993 +/- 633 MU. Of these 157 patients, sustained virological and biochemical response was shown in 32 (20%) and 37 patients (24%), respectively. Sustained virological and biochemical response rate in the randomized patients was significantly higher than in nonrandomized patients (41% vs. 2%, and 38% vs. 11%; each P <.01). Of the 73 randomized patients, the rate of sustained virological response in patients with long-course treatment (50%) was significantly higher than that of patients with short-course treatment (32%) (P =.026: log-rank test), and in patients with early disappearance of HCV RNA especially within 8 weeks, in patients with low virus load (</=10(6.3) copies/mL) and with HCV 2a. Multivariate analysis revealed that HCV RNA level and subtypes were the most important factors contributing to sustained virological response. Interferon is effective even in cirrhotic patients with low viral load and HCV 2a, but requires a longer course of administration.

Adult↗

Possible regulation of epidermal growth factor-receptor tyrosine autophosphorylation by calcium and G proteins in chemically permeabilized rat UMR106 cells.

A model using chemically permeabilized cells was developed to examine mechanisms that regulate protein tyrosine phosphorylation in osteoblastic cells. Using either permeabilized UMR106 osteoblastic or A431 (reference) cells, epidermal growth factor (EGF)-induced cellular tyrosine phosphorylation, and whether there are previously unrecognized interactions between this transduction pathway and Ca2+- or G protein-dependent signalling pathways, were investigated. Both permeabilized cell types, when maintained in non-supplemented cytoplasmic substitution solution (basic CSS), responded to EGF (1-100 ng/ml) with dose-dependent increases in tyrosine phosphorylation. A complex and time-dependent pattern of phosphotyrosine-containing proteins resulted, but the profile of tyrosine phosphorylated proteins was appreciably less complex than in intact cells. Supplementation of basic CSS with MgATP restored the normal complexity of the profiles for EGF-induced tyrosine phosphorylation proteins in both permeabilized cell lines and produced a more sustained accumulation of phosphoprotein products in A431 cells. Adding Ca2+ (< or = 10(-6) M), with or without exogenous MgATP, dose-dependently attenuated EGF-induced tyrosine phosphorylation of EGF receptors (EGFR) and other substrates in UMR106 cells, but was less effective in A431 cells. In both cell types, genistein, an inhibitor of tyrosine kinases, was more effective in attenuating EGF-induced receptor tyrosine phosphorylation in permeabilized cells. Similarly, orthovanadate, an inhibitor of protein tyrosine phosphatases, stimulated the accumulation of phosphoprotein products more effectively in permeabilized cells. Thus, the permeabilization preserves many features of intact cells while facilitating manipulation of intracellular conditions. NaF reproducibly produced a significant vanadate-like action in permeabilized cells that was somewhat stronger than its effect on intact cells. In contrast, the well-known inhibition of tyrosine phosphorylation by phorbol 12-myristate 13-acetate (PMA) was less effective in permeabilized cells than in intact cells; these actions of PMA were Ca2+-dependent. In addition, guanylyl-imidodiphosphate (Gpp(NH)p) attenuated tyrosine phosphorylation in UMR106 cells, and this effect was specifically blocked by guanosine 5'-O-(2-thiodiphosphate) (GDPbetas). These results strongly suggest that there is crosstalk between EGFR-activated tyrosine phosphorylation/dephosphorylation pathways and both Ca2+- and G protein-mediated pathways in UMR106 cells, revealing a previously unrecognized modulation of EGF signalling in osteoblast-like cells that contrasts with the simpler regulatory mechanisms found in A431 cells.

Adenosine Triphosphate↗

Neuropsychological evaluation and cerebral blood flow study of 30 patients with unruptured cerebral aneurysms before and after surgery.

BACKGROUND: We have recently had many opportunities to operate on patients who presented with no neurologic deficits and were incidentally detected to have unruptured cerebral aneurysms. Therefore, it is very important to know how craniotomy affects the normal brain when making decisions regarding surgery for asymptomatic cerebral diseases. METHODS: Thirty patients with unruptured cerebral aneurysms were evaluated. Aneurysm sites were as follows: internal carotid artery (ICA) (eight cases), anterior communicating artery (ACoA) (seven), middle cerebral artery (MCA) (five), basilar artery-superior cerebellar artery (BA-SCA) (two), and multiple aneurysms (three) [bilateral MCA: (two), ICA + Basilar top: (one)]. These patients underwent neuropsychological examinations [the Mini-Mental State (MMS) test, the "Kana-hiroi" test, and the "Maze" test] and single photon emission computed tomography (SPECT) before and after surgery. RESULTS: The details of the 17 cases whose Kana-hiroi tests deteriorated 1 month after surgery are as follows: ACoA: seven, MCA: five, ICA: three, BA: two. SPECT showed a decrease in CBF in nine cases (ACoA: six, ICA: two, MCA: one). There was a statistically significant difference (p<0.05) between patients with ACoA aneurysms and ICA aneurysms. Three months after operation, all of the patients with neuropsychological deterioration and four of the six low CBF patients recovered to preoperative levels. CONCLUSIONS: These results indicated that the operation for unruptured cerebral aneurysms is moderately safe and meaningful; such a study should be required to determine when those patients could return to normal life.

Adult↗

Age-associated changes in the dopamine synthesis as determined by GTP cyclohydrolase I inhibitor in the brain of senescence-accelerated mouse-prone inbred strains (SAMP8).

Our objective in this study was to elucidate the mechanism underlying the decrease in dopamine (DA) levels in the brain with ageing We administered 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I to senescence-accelerated mouse-prones (SAMP8), to inhibit DA and serotonin syntheses, and following immunohistochemical staining, analyzed the immunoreactive intensities (IR-Is) for DA in the nigrostriatal dopaminergic neurons by microphotometry. The DA-IR-Is in the substantia nigra pars compacta and neostriatum of young mice (2 months old) reached a minimal value 3 h after DAHP administration and returned to the control value 12 h after the administration. However, in aged mice (10 months old), the minimal value was reached 6 h after the administration and the value remained at approximately 70 and 80% of the control value at 24 and 72 h, respectively, after DAHP administration. The results suggest that DA turnover is lower in aged mice than in young mice.

Aging↗

Prognosis of sudden deafness with special reference to risk factors of microvascular pathology.

OBJECTIVE: We attempted to elucidate the contribution of microvascular disorders as risk factors to the prognostic outcome in well-defined patients with sudden deafness. METHODS: One-hundred and thirty-two patients diagnosed as unilateral sudden deafness were retrospectively analyzed. Auditory function was determined by pure-tone audiometry. Diabetes, hyperlipidemia, and hypertension were considered as microvascular diseases. RESULTS: Concurrent microvascular diseases were recognized in 38 patients. Although the hearing disturbance at the first visit showed no difference from patients without concurrent diseases, a better outcome of hearing was obtained in patients without the concurrent diseases. CONCLUSION: The poor prognosis observed in patients with the concurrent diseases is likely to have been brought about by preexisting microvascular disease of the hearing organ, which is highly affected by aging.

Adult↗

Transcranial magnetic stimulation of the central and peripheral motor pathways to the lingual muscles in cats.

OBJECTIVE: We have assessed a technique to stimulate the intracranial hypoglossal nerve with ease and reproducibility by using magnetic coils (MCs) and to detect a reliable site of excitation in animal experiments in order to establish a method to evaluate the motor pathway to lingual muscles. METHODS: We recorded the motor responses from the lingual muscles of 5 adult cats under general anesthesia by magnetic and electrical stimulation of the intracranial hypoglossal nerves. Figure of 8 and round MCs were used to investigate the optimal position and direction to evoke the motor responses. RESULTS: The round MC was useful for cortical stimulation. The figure of 8 coil, positioned in the back of the head of the examined side, parallel to the cervical spine, was essential for stimulation of the intracranial hypoglossal nerve. Analysis of the latencies, and the observation that the motor responses disappeared after transection of the nerves at the exit of the hypoglossal canal, demonstrated that the site of the excitation is at the exit of the hypoglossal canal. CONCLUSION: Magnetic stimulation using a figure of 8 coil can elicit tongue motor responses with ease and reliable reproducibility, stimulating the hypoglossal nerve at the exit of the hypoglossal canal.

Animals↗

The excitation site of the accessory nerve to the magnetic stimulation--the relationship between the orientation of the magnetic field and the excitation site.

OBJECTIVE: The relationship between the accessory nerve excitation site and the magnetic field direction was investigated to prove whether the cranial nerve excitation site to the transcranial magnetic stimulation is constant or not. METHODS: Compound muscle action potentials (CMAPs) elicited by the transcranial magnetic stimulation were recorded from the trapezius muscles of 7 adult cats. The waveforms of CMAPs were detected before craniectomy, after craniectomy, and after cutting the accessory nerve at the C1, at the jugular tubercle, and at the jugular foramen. The optimal orientation was determined by rotating the coil clockwise in increments of 22.5 degrees from the rostral direction. RESULTS: The accessory nerve was stimulated by the magnetic stimulation at the C1, at the jugular tubercle or at the jubular foramen, and these excitation sites varied with coil orientation. The average angles of the optimal orientation of the magnetic coil were 77.1 degrees for C1, 122.1-263.6 degrees for the jugular tubercle, and 308.6-32.1 degrees for the jugular foramen. CONCLUSIONS: The accessory nerve excitation site varied with the orientation of the magnetic coil. This study suggested the possibility of a variety of the cranial nerve excitation sites to the transcranial magnetic stimulation.

Accessory Nerve↗

Morphological characterization and subtyping of silent somatotroph adenomas.

GH-producing adenomas clinically are endocrine-active tumors accompanied with acromegaly in most instances. However, GH-producing adenomas apparently unassociated with acromegaly, or so-called silent somatotroph adenomas (SSA), have recently been reported but rarely. The reported cases are characterized by normal or slightly elevated serum levels of GH but without acromegaly. Tumor cells contain moderate, trace or no GH immunoreactivity. We experienced 7 cases of SSA which were not always similar in morphology and pathogenetic mechanism. They could be further divided into the following 3 subtypes. Subtype 1 (N = 2): a moderate number of cells were immunopositive for GH, and GH mRNA was also expressed in moderate or numerous cells. Densely granulated cells were noted. It is assumed that inhibition of hormone release into circulation. Subtype 2 (N = 3): a small number of cells were immunopositive for GH, while GH mRNA was expressed in numerous tumor cells. They were sparsely granulated cells containing fibrous bodies. These findings suggest that posttranslational processing of the gene product may be defective. Subtype 3 (N = 2): Only a scattered number of cells were immunopositive for GH and GH mRNA was co-localized in immunopositive cells. They were sparsely granulated cells containing poorly developed organelles that did not resemble those of typical sparsely granulated GH cells. The findings indicate that adenoma cells are largely immature with minimal GH lineage differentiation.

Acromegaly↗

Suppression of glial tumor growth by expression of glial fibrillary acidic protein.

We examined the effect of expression of glial fibrillary acidic protein (GFAP) on the tumor growth of astrocytoma in vivo. When rat astrocytoma C6 cells were injected subcutaneously in athymic mice, the cells produced tumors that grew rapidly. The tumor growth of C6 cells transfected with GFAP cDNA was significantly reduced compared to that of control NeoC6 cells transfected only with the neomycin resistant gene. After implantation of C6 cells transfected with mutated GFAP cDNA at the phosphorylation sites, the tumor growth was suppressed similar to that of the wild GFAP transfectants. To determine whether the cell growth suppression by GFAP is specific for astroglial cells, we assessed the effect of GFAP on the cell growth of an L cell of fibroblast origin in vitro. By GFAP cDNA transfection, L cells showed morphological changes, but the cell growth was not reduced. These results suggest that GFAP is a critical regulator of the tumor growth of astrocytoma.

Amino Acid Sequence↗

Endoscopic variceal ligation is a sufficient procedure for the treatment of oesophageal varices in patients with hepatitis C liver cirrhosis: comparison with injection sclerotherapy.

AIMS: Endoscopic variceal ligation (EVL) is a recently developed alternative to endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal varices. Endoscopic variceal ligation and EIS were compared in an attempt to clarify the efficacy and safety of EVL for patients with cirrhosis due to hepatitis C. METHODS: Endoscopic variceal ligation was performed in 60 patients and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of 30) by EIS. RESULTS: There was no significant difference between EVL and EIS in relation to the incidence of bleeding and the 5 year survival rate after treatment. There were no severe complications except mild substernal pain after EVL, while pulmonary embolism occurred in one patient receiving EIS. CONCLUSIONS: Endoscopic variceal ligation is a safe and effective technique for eradicating oesophageal varices in patients with hepatitis C cirrhosis.

Esophageal and Gastric Varices↗

Anterior transpetrosal approach to the prepontine epidermoids.

We have operated on nine patients with a prepontine epidermoid extending to the bilateral cistern or the unilateral middle fossa using the anterior transpetrosal approach since 1986. The preoperative symptoms were unilateral trigeminal neuralgia, hearing disturbance, gait disturbance, double vision, facial hypesthesia, hemifacial spasm, and dysphagia. The most common neurological sign was unilateral trigeminal nerve disturbance. In two patients with useful hearing preoperatively lost, the labyrinth and mastoid air cells as well as the petrous apex were resected to extend the surgical field. Tumors were totally removed, except for capsules that were tightly adhered to the brain stem, cranial nerve, and vessels. The trigeminal neuralgia, hemifacial spasm, and dysphagia disappeared, but double vision improved only one out of three cases, and facial hypesthesia was unchanged in all cases. There were no postoperative deaths. New abducens palsy appeared in four cases and cerebrospinal fluid (CSF) leakage appeared in three cases postoperatively, but later these symptoms disappeared. In one case, postoperative chemical meningitis developed, and a ventricular shunt was required later to treat hydrocephalus. Postoperative follow-up, an average of 5,7 years, did not show any increases in any of the tumors. Based on our experience, we conclude that the anterior transpetrosal approach is more useful than the retromastoid suboccipital approach to resect the epidermoid located mainly in the prepontine cistern.

Journal Article↗

Glycerol attenuates the adherence of leukocytes in rat pial venules after transient middle cerebral artery occlusion.

Intravenous infusion of glycerol has been used in patients with a cerebral infarction, expecting improvement in brain edema and cerebral blood flow (CBF). However, the mechanism of the improvement of CBF has not been clearly demonstrated. The aim of this study in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO) is to examine the effects of glycerol on leukocyte-endothelium interaction, which plays a critical role in the pathogenesis of brain injury by ischemia/reperfusion and concerns induction of secondary brain damage. Rhodamine 6G-labeled leukocytes at the brain surface were visualized with intra-vital fluorescence videomicroscopy through a closed cranial window and an analysis was made of the number of adherent leukocytes and the centerline leukocyte velocity in the venule before MCAO, after reperfusion of MCAO and after infusion of glycerol (Group 1) or saline (Group 2). The number of adherent leukocytes decreased and the centerline leukocyte velocity increased statistically significantly immediately after the infusion of glycerol in Group 1, but there was no significant change in Group 2. The infusion of glycerol washes away the adherent leukocytes and prevents them from interfering with the blood cell and plasma flow. Furthermore, secondary brain damage may be relieved by decreasing the adherence of leukocytes. In conclusion, modulating the adherence of leukocytes is one of the important factors in the neuroprotective effect of glycerol.

Animals↗