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Biomedical subjects

M Isono

Publications and source records attributed to M Isono.

At least 19 recordsLinked to original sources

Conduction pathways of motor evoked potentials following transcranial magnetic stimulation: a rodent study using a "figure-8" coil.

We have examined the conduction pathways of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation, and their correlation with locomotor function in rats. MEPs were concomitantly recorded from the spinal cord (sMEPs) and the limb muscles (mMEPs) before and after various spinal tract ablations. Motor function was also examined using an inclined plane test. sMEPs were composed of four negative peaks (N1-N4) and mMEPs of high-voltage, biphasic waves. Ventral funiculus transection reduced the N1-N3 peaks and abolished mMEPs. Contrarily, dorsal funiculus transection including the pyramidal tract did not alter these MEPs. Motor performance on an inclined plane was worse after ventral funiculus transection than after other transections. These findings indicate that, in rats, the N1-N3 peaks of magnetic sMEPs conduct ventral funiculus activity, and that magnetic mMEPs mainly reflect extrapyramidal activities and are correlated with locomotor function.

Animals

Atrial natriuretic peptide inhibits endothelin-1-induced activation of JNK in glomerular mesangial cells.

Atrial natriuretic peptide (ANP) has been shown to counteract various actions of endothelin-1 (ET-1) in mesangial cells. We have reported that both extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) are activated by ET-1 and ET-1-induced activation of ERK is inhibited by ANP. To further clarify the action of ANP, we examined the effect of ANP on ET-1-induced activation of JNK. ANP inhibited ET-1-induced activation of JNK in a dose-dependent manner. This inhibitory effect of ANP was reversed by HS-142-1, an antagonist for biological receptors of ANP, while C-ANP, an analog specific to clearance receptors of ANP, failed to inhibit ET-1-induced activation of JNK. 8-Bromo-cGMP and sodium nitroprusside were also able to inhibit ET-1-induced activation of JNK, suggesting cGMP-dependent action of ANP. In contrast, ANP failed to inhibit interleukin-1 beta (IL-1 beta)-induced activation of JNK. Since an increase in intracellular calcium ([Ca2+]i) was shown to be necessary for ET-1-induced activation of JNK in mesangial cells, we measured [Ca2+]i using fura-2. ANP attenuated the ET-1-induced increase in [Ca2+]i in concentrations enough to inhibit ET-1-induced activation of JNK. Finally, ANP was able to inhibit ET-1-, but not IL-1 beta-induced increase in DNA-binding activity of AP-1 by gel shift assay. These results indicate that ANP is able to inhibit ET-1-induced activation of AP-1 by inhibiting both ERK and JNK, suggesting that ANP might be able to counteract the expression of AP-1-dependent genes induced by ET-1.

Animals

Third ventricular neuroepithelial cyst originating from the massa intermedia--case report.

A 47-year-old female presented with a 3-year history of progressive emotional disturbance. Computed tomography and magnetic resonance imaging revealed a cyst in the third ventricle causing hydrocephalus. Endoscopic surgery found the cyst originated at the massa intermedia. Histological examination confirmed the diagnosis of neuroepithelial cyst. Neuroepithelial cyst originating from the massa intermedia may be due to persistence of neuroepithelial crest at this location.

Cerebral Ventricles

Minute findings of inner ear anomalies by three-dimensional CT scanning.

In actual clinical situations, inner ear anomalies must be diagnosed by image diagnosis such as high resolution CT-scanning of the temporal bone before three dimensional (3D) CT-scanning was introduced. In this paper, the usefulness of 3D-CT was investigated in some anomaly cases. It was found that 3D-CT was useful in observing the minute structure of the inner ear in that it could ascertain spatial relationships and minute constrictions and protrusions that could not be detected by 2D analysis. This CT was also capable of assessing the stage of embryological injuries and evaluating anomalies in cochlear turning that are the hidden factors of hearing impairment.

Adolescent

Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells.

Beraprost sodium, an analogue of prostacyclin, increases intracellular cyclic adenosine monophosphate (cAMP) in cultured glomerular mesangial cells. We examined the effect of beraprost on mesangial cell proliferation. Beraprost was able to inhibit fetal bovine serum-stimulated proliferation of mesangial cells in concentrations enough to increase cellular cAMP. By northern blot analysis, beraprost induced the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in a dose- and time-dependent manner, similarly to dibutyryl cAMP and adrenomedullin. These results indicate that beraprost inhibits the proliferation of mesangial cells and one of the mechanisms might be cAMP-dependent induction of MKP-1.

Animals

Microalbuminuria is not associated with cardiovascular death in Japanese NIDDM.

To evaluate whether the presence of microalbuminuria can predict cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus (NIDDM), we investigated 297 Japanese NIDDM patients with Albustix-negative urine. Patients were divided into two groups, normoalbuminuric (n = 201) and microalbuminuric (n = 96) and followed until death or the end of 1994 (the mean follow-up period was 6.4 years). During the follow-up period, 28 deaths (14 normoalbuminuric and 14 microalbuminuric patients) were confirmed and only 10 deaths were attributed to cardiovascular disease (6 normoalbuminuric and 4 microalbuminuric patients). Although the age- and sex-adjusted mortality rate from all-causes in the microalbuminuric group was significantly higher than that in the normoalbuminuric group (13.5 vs. 8.2 per 1000 person-years: P < 0.05), the mortality rate from cardiovascular disease was not significantly different between two groups (3.4 vs. 3.3 per 1000 person-years). On age-adjusted Cox proportional hazards analysis. HbA1c and triglyceride were independent risk factors in mortality from cardiovascular disease, while microalbuminuria was not associated with cardiovascular death. These results indicate that, unlike Caucasians, the presence of microalbuminuria can not predict cardiovascular death in Japanese subjects with NIDDM.

Aged

Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants.

Angiogenesis in rat sponge implants, as determined from the concentration of hemoglobin in the sponge granuloma tissues, was gradually increased over a 14-day experimental period. The inducible cyclooxygenase COX-2 was detected in the sponge granuloma tissues at day 4 by Western blot analysis using specific mouse COX-2 antibody. Angiogenesis in the sponge implants was enhanced by daily topical injections of human recombinant basic fibroblast growth factor (bFGF) or human recombinant epidermal growth factor (EGF) (100 or 1000 ng/sponge/day) for 4 days. These treatments clearly enhanced the expression of COX-2 in the sponge granuloma tissues. In immunohistochemical studies, COX-2-positive staining was mainly observed in the endothelial cells of the neovasculature and in the fibroblasts of the granuloma capsule. Administration of the selective COX-2 inhibitor NS-398 (p.o., 3 mg/kg, 3 times a day) for 14 days significantly inhibited the angiogenesis. The angiogenesis enhanced with bFGF or EGF (day 4) was inhibited by administration of indomethacin or NS-398, both in the above regimen, and fell to the level obtained without growth factor treatment. These results suggest that COX-2 induced in the sponge granuloma tissues may participate in neovascularization through prostaglandin formation.

Animals

Treatment of brain abscess associated with ventricular rupture--three case reports.

Three patients presented with brain abscess associated with ventricular rupture. The origins of infection were sepsis, congenital heart disease, and unknown, and the organisms were Gram-negative cocci in one and Streptococcus species in two. Ventricular rupture occurred before administration of antibiotics and caused consciousness disturbance in all three patients. Continuous ventricle drainage was begun and antibiotics were directly administered into the ventricles. Aspiration and drainage from the abscess was also performed in two patients. Ventricular irrigation resulted in an excellent effect in one patient. The outcomes were excellent in two patients and fair in one. Aggressive ventricular drainage in the very early stage and direct intraventricular administration of antibiotics are very important to obtain a favorable outcome in patients with brain abscess and ventricular rupture.

Adult

Mitogen-activated protein kinase cascade is activated in glomeruli of diabetic rats and glomerular mesangial cells cultured under high glucose conditions.

The activation of protein kinase C (PKC) found in diabetic glomeruli and glomerular mesangial cells cultured under high glucose conditions has been proposed to contribute to the development of diabetic nephropathy. However, the abnormalities distal to PKC have not been fully elucidated yet. Herein, we provide the evidence that mitogen-activated protein kinase (MAPK) cascade, an important kinase cascade downstream to PKC and an activator of cytosolic phospholipase A2 (cPLA2) by direct phosphorylation, is activated in glomeruli isolated from streptozotocin-induced diabetic rats. MAPK cascade was also activated in glomerular mesangial cells cultured under high glucose (27.8 mmol/l) conditions for 5 days, and the activation of MAPK cascade was inhibited by treating the cells with calphostin C, an inhibitor of PKC. Furthermore, the activities of cPLA2 also increased in cells cultured under the same conditions and this activation was inhibited by both calphostin C and PD 098059, an inhibitor of MEK (MAPK or extracellular signal-regulated kinase [ERK] kinase). These results indicate that MAPK cascade is activated in glomeruli and mesangial cells under the diabetic state possibly through the activation of PKC. Activated MAPK, in turn, may induce various functional changes of mesangial cells at least through the activation of cPLA2 and contribute to the development of diabetic nephropathy.

Animals

[Morphological characterization and classification of air cells in temporal bone by digital processing of CT images].

We determined the extent of pneumatization in the temporal bone and reconstructed three-dimensional structures of air cells by computer-assisted digital processing of high resolution CT images of the bone. We attempted morphological classification of temporal bone air cells by characterization of the three-dimensional structures obtained. A total of 52 ears in 33 normal subjects (18 males and 15 females; mean age 51 years) was examined. The volume of pneumatization in the temporal bone, as measured by CT, ranged from 2.08 to 20.05 ml (mean 6.40 +/- 4.09). The morphological characteristics of air cells in the three-dimensional images were examined with reference to the volume of air cells and the direct on of their growth. The three-dimensional structures were observed from four directions (lateral, supralateral, anterolateral and supramedial). Large air cells existed plentifully in all directions. Anteriorly, air cells were growing in two directions; laterally and toward the petrous apex. The growth in the latter direction was especially marked, and this contributed to the growth in the medial direction. Air cells that grew anteriorly had two directions of growth (lateral and toward the petrous apex). The directional difference in growth varied with the ear. On examining the suprainferior growth, air cells that grew large in the anterior direction were found to grow large in the suprainferior direction and those that did not grow large in the anterior direction were found contrarily to grow poorly in the suprainferior direction. With the above morphological characteristics taken into consideration, morphological classification of air cells into five types was attempted by the volume of air cells and the direction of their growth.

Adolescent

[CT-assisted measurement of total and regional volumes of pneumatization in the temporal bone].

The total volume of air cells in the temporal bone and the regional volumes (tympanic cavity, petrous apex and mastoid antrum) were measured by using a system which we developed for the measurement of air cells by computerized digital processing of high-resolution CT images. We examined a total of 41 normal ears in 25 subjects ranging in age from 12 to 82 years (mean age 46.2). The total volume of pneumatization was approximately 4.05 +/- 1.59 ml and the volume of air cells in the tympanic cavity was 0.45 +/- 0.07 ml. Alveolation of the petrous apex was detected in 15 (36.6%) of the 41 ears, and the volume of air cells in the petrous apex was approximately 0.24 +/- 0.26 ml. The volume of air cells in the mastoid antrum was approximately 0.53 +/- 0.20 ml. The ears were divided into two groups, one with petrous alveolation (15 ears) and the other without it (26 ears). The ratios of regional pneumatization to total pneumatization were studied in the two groups. Statistically significant differences were found in the total volume and the volume of air cells in the mastoid antrum between the groups with and without petrous pneumatization (p < 0.05). The total volume of air cells did not correlate to the volumes of air cells in the tympanic cavity, mastoid cavity and petrous apex.

Adolescent

[Neovascularization after encephalo-duro-arterio-synangiosis in elderly quasi-moyamoya disease: a case report].

A 65-year-old man who had a history of diabetes mellitus visited a hospital for recent memory disturbance. MR angiography showed stenoses of the main trunks of the intracranial arteries. He was admitted to our hospital, and angiography revealed occlusion of the left cervical internal carotid and right middle cerebral arteries, and stenoses of the right internal carotid, right anterior cerebral, left vertebral, and right posterior cerebral arteries. There was collateral circulation formed from the left external carotid and left posterior cerebral arteries. Basal moyamoya vessels were also observed. 123I-IMP SPECT showed low perfusion of the right cerebral hemisphere, and response to acetazolamide was poor. Based on the angiographical findings and the presence of diabetes mellitus, the patient was diagnosed as having quasi-moyamoya disease. Vascular reconstructive surgery was indicated. Since there was no recipient artery adequate for STA-MCA anastomosis, encephalo-duro-arterio-synangiosis was performed on the right side. Postoperatively, the patient's recent memory improved gradually, and angiography performed 7 months after the operation revealed neovascularization from the superficial and deep temporal arteries. Although indirect bypass surgery has been applied mainly to child moyamoya disease, its effectiveness for cerebral ischemia in adult patients has also been reported, particularly in cases with misery perfusion. Neovascularization with indirect bypass surgery can be expected if the patient is under misery perfusion, even in elderly patients.

Aged

Mechanism of the progression of diabetic nephropathy to renal failure.

Although the evolution of diabetic nephropathy is brought about mostly by persistent hyperglycemia, its progression may be influenced by various other factors such as hypertension and dietary protein intake. It has been recently suggested in the literature that the gene polymorphism of angiotensin converting enzyme (ACE) might be associated with the development of diabetic nephropathy, because the DD genotype of ACE gene is closely associated with the presence of nephropathy in diabetic subjects. However, in our present analysis the frequency of the DD genotype in patients with non-insulin dependent diabetes is not significantly related to the presence or absence of nephropathy. It remains to be clarified by multi-center analysis using large numbers of patients whether the gene polymorphism of ACE is related to the progression of diabetic nephropathy to renal failure. Furthermore, it has been postulated that the interstitial fibrosis evaluated in renal biopsy specimens is significantly correlated with the declining of renal function in diabetic patients. However, it is not possible to clinically quantitate the interstitial fibrosis without performing renal biopsy. We have recently found that the urinary excretion of type IV collagen is significantly increased in diabetic patients. Moreover, the increase in urinary type IV collagen is well correlated with the amount of urinary albumin. Since type IV collagen in the urine is probably derived from tubulointerstitial tissue, it is likely that the increased amount of type IV collagen in the urine may reflect the fibrotic change in diabetic kidneys. Whether the increase in urinary type IV collagen is able to predict for the progression of diabetic nephropathy in the future should be examined.

Collagen

Atrial natriuretic peptide induces the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in glomerular mesangial cells.

Atrial natriuretic peptide (ANP) has been shown to inhibit the proliferation of various types of cells including glomerular mesangial cells. The activation of mitogen-activated protein kinase (MAPK) is one of the main signal transduction systems leading to cell proliferation. MAPK is tightly regulated by the activating kinase, MEK, and specific phosphatase MKP-1. Constitutive expression of MKP-1 has been shown to inhibit cell proliferation by suppressing MAPK activity. In order to understand the mechanism of the anti-proliferative effect of ANP, we examined whether ANP could inhibit MAPK by inducing MKP-1 in cultured rat glomerular mesangial cells. ANP increased the expression of MKP-1 mRNA in a dose-dependent (10 nM maximum) and time-dependent, with a peak stimulation at 30 min, manner. Receptor for ANP is a transmembrane guanylyl cyclase. Activation of guanylyl cyclase of ANP receptor by ligand plays an essential role in ANP signal transduction. 8-Bromo-cGMP, a cell permeable analogue of cyclic GMP, and sodium nitroprusside, an activator of soluble guanylyl cyclase, could mimic the effects of ANP and were able to induce the expression of MKP-1 in a similar time course as ANP. The protein expression of MKP-1 was maximally stimulated by ANP at 120 min. Treatment of the cells with ANP for 120 min resulted in an inhibition of phorbol ester-induced activation of MAPK, while the activation of MEK was not affected by ANP. These results indicate that ANP might inhibit the proliferation of mesangial cells by inactivating MAPK through the induction of MKP-1.

Amino Acid Sequence

Bcl-2 expression is correlated with a low apoptotic index and associated with progesterone receptor immunoreactivity in endometrial carcinomas.

A total of 103 endometrial carcinomas (endometrioid type), as well as 15 samples of normal (atrophic or proliferative phase) and 26 of hyperplastic endometrium, were immunohistochemically investigated for expression of Bcl-2, and oestrogen and progesterone receptors (ER and PR), and the results compared with findings for apoptosis and cell proliferation. Carcinoma cases were subdivided into tubular and solid components on the basis of tumour growth patterns. Immunopositivity for Bcl-2, ER, and PR in tubular components was significantly higher than in the solid category, being negatively associated with histological grading. Immunoreactivity scores revealed that Bcl-2 in the tubular group was positively correlated with PR but not ER, while its expression in normal and hyperplastic endometrium was closely linked with both. Apoptotic and mitotic indices (AI and MI) were both significantly lower in tubular than in solid areas. In the tubular areas, AI, values were significantly lower in the subgroup with a high level of Bcl-2 expression than in either low-level or negative groups. These results indicate that Bcl-2 expression may play a central role in the inhibition of apoptosis in endometrial carcinoma, in particular those cases with tubular components, possibly being associated with PR rather than ER. Changes in the propensity for apoptosis may be related to alterations of tumour growth pattern and of features of differentiation.

Apoptosis

Corticospinal direct response to transcranial magnetic stimulation in humans.

The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5-72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recordings of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.

Aged