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Biomedical subjects

M Isono

Publications and source records attributed to M Isono.

At least 19 recordsLinked to original sources
PubMed2003

High frequency electrical stimulation attenuates progressive necrosis and cavitation following spinal cord injury.

This study evaluates the influence of preconditioning by following electrical stimulation on primary and secondary lesion formation following spinal cord injury in rats. The dorsal surface of the spinal cord was stimulated (500 Hz. 10 pulses/train, inter train interval of 10 sec. for 2 hrs) at the T7 level 24 hrs before a right side hemisection, carried out immediately after injury and maintained every 24 hrs for 7 days. Preconditioning by electrical stimulation of the spinal cord activates reactive astrocytes and significantly attenuates edema and progressive necrosis and cavitation, concerning especially the primary (1, 3 weeks post injury) and secondary (24 hrs, 1, 3 weeks post injury) lesion volume. The results suggest that pre-conditioning by electrical stimulation prevents spinal cord secondary lesion formation after injury, and that the beneficial effect is provided by astroglial cells with regard to their ability to attenuate trauma induced cellular cascades.

Animals↗
PubMed2003

Motor evoked potentials following transcranial magnetic stimulation after middle cerebral artery and/or basilar artery occlusions in rats.

To clarify the significance of motor evoked potentials following transcranial magnetic stimulation (MMEPs) in acute stage of cerebral ischemia, MMEPs were recorded in rats with the right middle cerebral artery (MCA) and/or the basilar (BA) artery occlusions. MMEPs from bilateral forelimb muscle and regional cerebral blood flow (rCBF) of the pons were recorded simultaneously. After MCA occlusion, the amplitudes of MMEPs from left forelimb were increased up to approximately 184-221% of the pre-ischemic value for 60 min, though the latencies were unchanged. On the other hand, in the rats of BA occlusion and both BA and MCA occlusion groups, MMEPs amplitudes were decreased to 8-25% of the pre-ischemic value for 60 min. Pontine rCBF was decreased to 28-44% in both groups. As a mechanism of the facilitation of MMEPs after MCA occlusion, the affection of the inhibitory mechanism between the cerebral cortex and the generator of MMEPs by MCA occlusion is speculated.

Animals↗
PubMed2001

Increased glomerular and tubular expression of transforming growth factor-beta1, its type II receptor, and activation of the Smad signaling pathway in the db/db mouse.

Activation of the renal transforming growth factor-beta (TGF-beta) system likely mediates the excess production of extracellular matrix in the diabetic kidney. To establish the role of the TGF-beta system in type 2 diabetic nephropathy, we examined the intrarenal localization and expression of the TGF-beta1 isoform, the TGF-beta type II receptor, and the Smad signaling pathway in the 16-week-old db/db mouse, a genetic model of type 2 diabetes that exhibits mesangial matrix expansion, glomerular basement membrane thickening, and renal insufficiency that closely resemble the human disease. Compared with its nondiabetic db/m littermate, the db/db mouse showed significantly increased TGF-beta1 mRNA expression by in situ hybridization in both glomerular and tubular compartments. Likewise, TGF-beta1 protein, by immunohistochemical staining, was increased in both renal compartments, but the fractional expression of TGF-beta1 protein was less than that of the mRNA in the glomerulus. In situ hybridization and immunohistochemical staining for the TGF-beta type II receptor revealed concordant and significant increases of both mRNA and protein in the glomerular and tubular compartments of diabetic animals. Finally, immunohistochemistry showed preferential accumulation of Smad3 in the nuclei of glomerular and tubular cells in diabetes. The complementary technique of Southwestern histochemistry using a labeled Smad-binding element demonstrated increased binding of nuclear proteins to Smad-binding element, indicating active signaling downstream of the TGF-beta stimulus. We therefore propose that the TGF-beta system is up-regulated at the ligand, receptor, and signaling levels throughout the renal cortex in this animal model of type 2 diabetes. Our findings suggest that the profibrotic effects of TGF-beta may underlie the progression to glomerulosclerosis and tubulointerstitial fibrosis that characterize diabetic nephropathy.

Animals↗
PubMed2001

Midaortic syndrome in childhood associated with a ruptured cerebral aneurysm: a case report.

BACKGROUND: We present a patient with a midaortic syndrome who presented with subarachnoid hemorrhage caused by rupture of an anterior communicating artery aneurysm. CASE DESCRIPTION: A 14-year-old boy with midaortic syndrome was admitted to our hospital because of subarachnoid hemorrhage due to rupture of an anterior communicating artery aneurysm. He also developed acute renal failure due to previously controlled hypotension. After blood dialysis, successful clipping of the aneurysm was performed. The postoperative course was complicated by malignant renovascular hypertension due to midaortic syndrome. Medical treatment failed to control his hypertension; left primary nephrectomy improved his condition. CONCLUSION: Although midaortic syndrome is rare, it may be significant as a cause of cerebral hemorrhage in childhood.

Adolescent↗
PubMed2001

Retro-odontoid soft tissue mass associated with atlantoaxial subluxation in an elderly patient: a case report.

BACKGROUND: We present the case of an elderly patient with a retro-odontoid soft tissue mass associated with atlanto-axial subluxation. CASE DESCRIPTION: A 74-year-old man was admitted to our hospital with progressive motor weakness in his right arm and neck pain. Radiological examinations revealed atlantoaxial subluxation and diffuse degenerative changes. Cervical MRI revealed a syrinx at the C1 level and a retro-odontoid soft tissue mass that severely compressed the spinal cord. The mass was of low signal intensity on both T1- and T2-weighted images. Conservative therapy could not stop the progression of his symptoms, so posterior decompression via a laminectomy of C1 and occipitocervical fixation was performed. These procedures resulted in an improvement of his neurological condition and in reduction of the mass and the compression of the spinal cord. CONCLUSION: The patient lacked any specific conditions that might have caused chronic atlantoaxial subluxation. The degenerative changes alone might have provoked chronic atlantoaxial subluxation and a subsequent retro-odontoid soft tissue mass. In patients with this condition, posterior fixation without direct removal of the mass should be the first choice for surgical intervention.

Aged↗
PubMed2001

Clinical features of symptomatic Rathke's cleft cyst.

To investigate the clinical features of Rathke's cleft cysts (RCCs), we retrospectively analyzed 15 cases with histologically confirmed RCCs. All patients underwent formal testing of visual field, endocrinological evaluation and magnetic resonance imagings. As overall presenting symptoms, endocrine disturbance was the most common symptoms, followed by visual disturbance and headache. Among the endocrine disturbances based on adenohypophysial dysfunction, hyperprolactinemia was most common. Considering the size of RCCs, RCCs could induce hyperprolactinemia only when the cysts became large enough to compress the infundibular system. Our series showed relative high incidence of pituitary dwarfism and diabetes insipidus (DI). These facts indicated that RCCs could evoke hyposecretion of growth hormone in young patients and DI in aged patients by direct compression of the pituitary gland in the early stage of progression. All cases who had headache had no other symptoms. We could not prove the evidence that RCCs could induce headaches in these cases. This might be suggested that headache could not be a sole symptom in cases of RCCs.

Adolescent↗
PubMed2001

Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-beta type II receptor expression.

BACKGROUND: Serum leptin levels correlate with fat cell mass and are elevated in patients with massive obesity and type 2 diabetes mellitus, which are strong risk factors for the development of glomerulosclerosis. We have previously shown in cultured glomerular endothelial cells that leptin stimulates cellular proliferation and expression of the prosclerotic cytokine transforming growth factor-beta1 (TGF-beta1). Although the effect of leptin on the hypothalamus to regulate energy homeostasis is well known, the effect of leptin on the kidney, and specifically on the glomerular mesangial cell, is unclear. METHODS: The obese, diabetic db/db mouse, which lacks the functional full-length Ob-Rb leptin receptor, is a suitable model to assess the effects of hyperleptinemia on peripheral tissues that express other receptor isoforms. The effects of leptin on glucose uptake, the TGF-beta system, and type I collagen production were evaluated in db/db mouse mesangial cells in culture. A phosphatidylinositol-3 kinase (PI-3K) inhibitor was used to assess the role of PI-3K in mediating the effects of leptin. RESULTS: A short form of the leptin receptor (Ob-Ra), but not Ob-Rb, was present by reverse transcription-polymerase chain reaction in the kidney and mesangial cells of both nondiabetic db/m and diabetic db/db mice. In db/db mesangial cells, leptin increased 2-deoxy-D-glucose (2DOG) uptake dose dependently and stimulated gene expression of TGF-beta type II receptor (TbetaRII) and alpha1(I) collagen, but not TGF-beta1. Protein production of type I collagen (enzyme-linked immunosorbent assay) was also increased by leptin. Both leptin-stimulated 2DOG uptake and type I collagen production were suppressed by a PI-3K inhibitor, LY294002. Mesangial cells pretreated with leptin exhibited increased responsiveness to exogenous TGF-beta1, as evidenced by a greater production of type I collagen protein in leptin-pretreated cells exposed to low-dose TGF-beta1 (0.5 ng/mL). The addition of both TGF-beta1 (2 ng/mL) and leptin (100 ng/mL) increased type I collagen production more than addition of either TGF-beta1 or leptin alone. CONCLUSIONS: Leptin increases glucose uptake and type I collagen in db/db mesangial cells through a PI-3K-dependent pathway. We postulate that increased leptin levels may transmit a signal through the short-form leptin receptor to up-regulate TbetaRII and activate the intraglomerular TGF-beta system, which may contribute to the glomerulosclerosis of obesity or type 2 diabetes.

Animals↗
PubMed2000

Adenovirus-mediated hepatocyte growth factor gene transfer prevents lethal liver failure in rats.

Hepatocyte growth factor (HGF) has a potent antiapoptotic effect on hepatocytes in D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-treated rats. Here, we report that adenovirus mediated HGF gene transfer into liver prevents liver failure and reduces mortality of rats treated with d-GalN/LPS. Fisher 344 rats, which were given intraperitoneal injections of pAxCAHGF 48 h before, were treated with D-GalN/LPS. Serum ALT in the HGF group at 6 and 12 h after D-GalN/LPS was decreased to 1/6 and 1/12 of the control group (P < 0.01, each). Concomitant reduction of apoptotic cells were also observed. The Kaplan-Meier analysis showed that a survival rate in the HGF group was improved, compared to that in the control group (P < 0.05). Caspase-3 activity in the HGF group decreased, compared to that in the control group, especially at 12 h (P < 0.05), although it maintained a high level in the control group. Expression of Bcl-xL and cyclooxygenase-2 (Cox-2) was induced in liver by HGF gene transfer. These data suggest that HGF exerts an antiapoptotic effect through dual induction of Bcl-xL and Cox-2, which suppresses caspase-3 activity.

Adenoviridae↗
PubMed2000

Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice.

Emerging evidence suggests that transforming growth factor-beta (TGF-beta) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-beta antibody (alphaT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-beta system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of alphaT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, a model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with alphaT or control IgG, 300 microgram three times per week for 8 wk. Treatment with alphaT, but not with IgG, significantly decreased the plasma TGF-beta1 concentration without decreasing the plasma glucose concentration. The IgG-treated db/db mice developed albuminuria, renal insufficiency, and glomerular mesangial matrix expansion associated with increased renal mRNAs encoding alpha1(IV) collagen and fibronectin. On the other hand, treatment with alphaT completely prevented the increase in plasma creatinine concentration, the decrease in urinary creatinine clearance, and the expansion of mesangial matrix in db/db mice. The increase in renal matrix mRNAs was substantially attenuated, but the excretion of urinary albumin factored for creatinine clearance was not significantly affected by alphaT treatment. We conclude that chronic inhibition of the biologic actions of TGF-beta with a neutralizing monoclonal antibody in db/db mice prevents the glomerulosclerosis and renal insufficiency resulting from type 2 diabetes.

Animals↗
PubMed2000

In vivo transfer of hepatocyte growth factor gene accelerates proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats.

To clarify the effect of hepatocyte growth factor (HGF) on proliferation of hepatic oval cells, we transferred HGF gene into liver of the Solt-Farber rat model. Male Fisher 344 rats were infected with a recombinant adenovirus carrying the cDNA for HGF (pAxCAHGF) from tail vein. HGF mRNA showed its peak at 4 days, and diminished thereafter. The total and proliferating cell nuclear antigen-positive hepatic oval cells were significantly elevated in HGF-transferred rats, in which stem cell factor and c-kit mRNA increased at each time point. Our results suggest that in vivo transfer of the HGF gene into liver accelerates proliferation of hepatic oval cells in the Solt-Farber model in rats.

2-Acetylaminofluorene↗
PubMed2000

Attempted gene therapy for intractable pain: dexamethasone-mediated exogenous control of beta-endorphin secretion in genetically modified cells and intrathecal transplantation.

For optimal neural transplantation using gene engineering, it might be important to control the expression of the transfected gene extrinsically as required. This strategy could be very useful for the treatment of intractable pain that responds to opioids. For this purpose, we established a genetically modified embryonal carcinoma cell line (P19) in which the expression of beta-endorphin (beta-EP) could be controlled by the addition of dexamethasone. To obtain extrinsic control, we transfected the cells with pMAMneo containing mouse MMTV-LTR as a promoter and cDNA of the artificial beta-EP. The upregulation of beta-EP, through the activation of MMTV by the administration of dexamethasone, was confirmed in vitro. Then we transplanted these cells into the subarachonoid space in rats and evaluated the analgesic potential of these cells in vivo by hot plate test and formalin test. In the rats that received beta-EP-producing cells, we observed prominent analgesic effects after the transplantation for a month. The administration of naloxone blocked these effects. Intraperitoneal injection of 100 mg/kg dexamethasone further enhanced these effects by up to two times. These data indicate obvious analgesic effects of the cells after the transplantation and the possible exogenous upregulation of transfected beta-EP gene expression in vivo. The application of this technique might provide a new therapeutic approach to various neurological diseases.

Animals↗
PubMed2000

Inner ear anomaly of three-dimensional computed tomography: computed tomographic attenuation and image changes.

With regard to image diagnosis of inner ear anomalies, three-dimensional computed tomography (3D-CT) is useful in obtaining very realistic images that are unmatched by 2D-CT. Unlike the step scanning in the existing 2D-CT, in helical 3D-CT, scanning is performed in a spiral motion by continuously rotating the scanner and moving the table along the body axis at a constant speed. As a result, data obtained by this CT are continuous and very smooth curves can be obtained. Among the data, the CT attenuation determines the quality of the final 3D images. In the present paper, the usefulness of 3D-CT was investigated in a case with Mondini-type inner ear malformation.

Adult↗
PubMed2000

Three-dimensional magnetic resonance imaging findings of inner ear anomaly.

Using three-dimensional magnetic resonance imaging (3D-MRI), the membranous labyrinth was examined in normal cases and in a case with bilateral Mondini-type inner ear malformations. Both ears were also examined by high-resolution computed tomography (CT) of the temporal bone. 3D-MRI provided more detail than findings obtained by conventional high-resolution CT and it enabled 3D observations to be made. Detailed examination of maximum intensity projection images along the cochlea axis revealed the cochlear turns in three dimensions.

Adolescent↗
PubMed2000

Stimulation of TGF-beta type II receptor by high glucose in mouse mesangial cells and in diabetic kidney.

Transforming growth factor-beta (TGF-beta) is important in the pathogenesis of diabetic nephropathy, but little is known about the regulation of the ligand-binding TGF-beta type II signaling receptor (TbetaIIR). There were significant increases in TbetaIIR protein and mRNA levels in kidney cortex after 1-6 wk of streptozotocin-induced diabetes. Mouse mesangial cells cultured in high glucose demonstrated significantly increased TbetaIIR protein and mRNA levels compared with normal glucose. This effect was independent of stimulation of TGF-beta bioactivity by high glucose. Consistent with transcriptional activation by high glucose, the half-life ( approximately 4 h) of TbetaIIR mRNA was not affected by glucose concentration. Moreover, mouse mesangial cells transiently transfected with reporter constructs containing the first 47- or 274-bp promoter fragments of TbetaIIR demonstrated significantly increased reporter activity in high glucose. Cells grown in high glucose demonstrated increased responsiveness to a relatively small dose of exogenous TGF-beta(1) (0.5 ng/ml): [(3)H]proline incorporation and alpha(1)(IV) collagen mRNA were significantly greater in cells cultured in high than in normal glucose. Hence, the expression of TbetaIIR is increased in the diabetic kidney and in mesangial cells cultured in high glucose, primarily because of stimulation of gene transcription. TbetaIIR upregulation by high ambient glucose may contribute to the increased sensitivity of mesangial cells to the profibrogenic action of TGF-beta(1).

Animals↗
PubMed2000

Dissecting aneurysm of the anterior cerebral artery requiring surgical treatment--case report.

A 45-year-old male presented with spontaneous dissecting aneurysm in the anterior cerebral artery manifesting as headache persisting for several days and speech disturbance. Neurological and laboratory examinations showed no abnormalities. Magnetic resonance imaging revealed infarction in the right cingulate gyrus. Angiography revealed occlusion of the right A2. Repeat angiography 8 months later showed a saccular aneurysm had developed. The interhemispheric approach exposed the aneurysm at the junction between the right frontopolar artery and the pericallosal artery. The aneurysm was fusiform due to the right A2 dissection. The aneurysm was trapped and resected. One month after the operation, the patient was discharged without neurological deficits. Cases of dissecting aneurysms in the anterior cerebral artery with ischemic onset are usually treated conservatively. Cases requiring surgery include those due to trauma, growing aneurysms, giant aneurysms, and uncontrolled hypertension. Some dissecting aneurysms of the distal anterior cerebral artery require only resection without bypass surgery.

Aortic Dissection↗
PubMed2000

Neurocutaneous vascular hamartomas mimicking Cobb syndrome. Case report.

The authors report the rare case of a patient with neurocutaneous vascular hamartomas mimicking Cobb syndrome. An 8-year-old boy was admitted to the authors' hospital with progressive urinary disturbance and upper back pain. Multiple skin nevi had been noted at the child's birth. Radiological examination revealed multiple cavernous angiomas in the spinal cord in the same metamere in which the skin nevi had been observed and also in the left cerebral hemisphere. His symptoms gradually improved without surgical intervention. Four years later he was readmitted because of a cerebral hemorrhage involving the left cerebral peduncle. Nonsurgical treatment was chosen because his symptoms promptly improved. To the best of the authors' knowledge, this is the first case of multiple cavernous angiomas in the brain and spinal cord associated with skin nevi. The authors discuss this clinical entity and the significance of the disease.

Back Pain↗
PubMed2000

[Reliability of electrogustatory threshold--electrogustometry using CNV].

CNV (contingent negative variation), an event-related potential, is induced when an oncoming imperative stimulus (S2) is anticipated after recognition of a warning stimulus (S1). With this in mind, we assessed the usefulness of electrogustometry using CNV as an objective gustatory test with an electric gustatory stimulus as a warning stimulus, S1. A gustatory test was performed on a total of 100 sides of the tongue in 50 subjects. Excluding no response cases on 5 sides in 5 subjects, the CNV threshold was successfully determined on 95 sides in 50 subjects. When the CNV threshold values obtained and the conventionally measured subjective threshold values were compared, a very high correlation was demonstrated between the two thresholds, with a correlation coefficient of 0.961. To assess the reliability of the CNV threshold, three additional measurements on 5 sides in 5 subjects with normal subjective threshold values were performed on different days, and the CNV threshold value variation among the three measurements in all 5 subjects never exceeded 13 microA. Separately, subjective threshold and CNV threshold values were compared in 4 patients with facial palsy (hence with gustatory abnormality) who consented to a follow-up examination. The difference between the subjective threshold and CNV threshold values in all 4 patients never exceeded 10 microA. These findings demonstrate that the reliability of the CNV threshold is satisfactory. Next, a gustatory imitation experiment was performed to assess the usefulness of electrogustometry using CNV as a means of detecting gustatory abnormality malingering. The experiment was performed on a total of 6 subjects: 3 physicians with knowledge of CNV (knowledge group) and 3 others with no knowledge of CNV (no-knowledge group). The differences between the imitated threshold and the subjective threshold values in all of these subjects never exceeded 10 microA, and the difference between imitated threshold and CNV threshold values never exceeded 13 microA. Comparison between the knowledge group and the no-knowledge groups showed that the imitated threshold values were very close to the subjective threshold and CNV threshold values. Based on the above results, it was concluded that gustometry using CNV is useful and can serve well as a method of objective evaluation of gustatory sensation. The results also suggested that it will be useful in diagnosing malingering.

Adolescent↗