Search PubMed⌕ Search

Biomedical subjects

M Kunimoto

Publications and source records attributed to M Kunimoto.

At least 37 records · Page 2Linked to original sources

Schwann cell proliferation as the cause of peripheral neuropathy in neurofibromatosis-2.

We report a 18-year-old man who developed slowly progressing right drop foot. Bilateral acoustic neurinoma was found and he was diagnosed as neurofibromatosis-2. Right sural nerve biopsy showed multiple small onion-bulb-like structures in the nerve fascicle. Electronmicroscopic and immunohistochemical studies on this structure confirmed cytological characteristics of Schwann cells, while previous reports suggest that this structure originates from perineural cells. The present report is the first to show both ultrastructurally and immunohistochemically that the onion-bulb-like structure is derived from Schwann cell.

Adolescent↗

Autocrine regulation of interleukin-8 by interleukin-1alpha in respiratory syncytial virus-infected pulmonary epithelial cells in vitro.

Respiratory epithelial cells infected with respiratory syncytial virus (RSV) produce interleukin-8 (IL-8); however, the mechanisms of RSV-induced regulation of IL-8 are poorly understood. In the present study, the regulation of IL-8 by RSV was evaluated using pulmonary type II-like epithelials (A549). Live purified RSV (pRSV) induced a significant increase in IL-8 after 8 hr of exposure, while conditioned supernatants from pRSV-infected A549 cells (cRSV) induced IL-8 production in fresh A549 cultures within 4 hr of infection. Furthermore, cRSV that had been rendered non-infectious by ultraviolet-irradiation (UV-cRSV) or ribavirin treatment also induced an increased production of IL-8 in fresh A549 cells, suggesting that RSV induced the synthesis of a soluble mediator(s) which in turn enhanced the synthesis of IL-8. We have previously shown that RSV-infected A549 cells produce IL-1alpha, IL-1-beta and tumour necrosis factor-alpha (TNF-alpha), which by themselves are known to induce the synthesis of IL-8. Preincubation of UV-cRSV or simultaneous incubation of pRSV with recombinant IL-1 receptor antagonist almost completely blocked (95-98%) the production of IL-8 by A549 cells. Furthermore, incubation with neutralizing antibodies against IL-1alpha, IL-1beta and TNF-alpha showed that IL-1alpha was the predominant soluble mediator that enhanced the mRNA expression and synthesis of IL-8. IL-1beta and TNF-alpha induced the synthesis of IL-8 at 24 hr, but partially inhibited the synthesis at 48 hr. In summary, these experiments provide direct evidence for an autocrine mechanism of enhanced IL-8 production in RSV-infected epithelial cells that is primarily mediated by IL-1alpha. In clinical settings, inhibitors of IL-1alpha may be useful in suppressing inflammation due to IL-1alpha as well as IL-8.

Antibodies, Monoclonal↗

Expression and localization of brain ankyrin isoforms and related proteins during early developmental stages of rat nervous system.

Expression and localization of two isoforms of brain ankyrin, 440- and 220-kDa ankyrinB, were studied in the developing nervous system of the rat fetus. The 440-kDa ankyrinB appeared on as early as embryonic day 13, and its level increased progressively toward the day of birth, which was similar to the expression pattern of growth-associated protein (GAP)-43, a well-established axonal protein. On the other hand, 220-kDa ankyrinB was expressed at a low level but constitutively throughout the latter prenatal period and was a major isoform even before embryonic day 14. Whereas the localization of 440-kDa ankyrinB was essentially confined to the axons, judging from the similarity with that of GAP-43, 220-kDa ankyrinB showed a rather general distribution in neural tissue. The localization of L1, known as an ankyrinB-binding protein, was similar to that of 440-kDa ankyrinB in the brain tissue, whereas it was similar to that of 220-kDa ankyrinB in cultured neurons, suggesting that the interaction of L1 with brain ankyrins in neurons is affected by their environment.

Animals↗

Antibody against ganglioside GD1c containing NeuGcalpha2-8NeuGc cooperates with CD3 and CD4 in rat T cell activation.

Gangliosides have long been implicated in T cell activation. GD1c with two N-glycolylneuraminic acids [GD1c(NeuGc,NeuGc)] is the predominant ganglioside in rat T cells. In the present study, the anti-GD1c(NeuGc,NeuGc) mAb, AC1, which binds to the NeuGcalpha2-8NeuGcalpha2- sequence, was found to enhance Con A-activated cellular proliferation at a concentration at which AC1 alone did not activate the cells. The potentiation by AC1 was observed more consistently and effectively in the cellular activation elicited by cross-linking of anti-CD3 and anti-CD4, rather than in the cell growth induced by immobilized anti-CD3 alone. Moreover, the combination of immobilized anti-CD4 and soluble AC1 had a remarkable mitogenic effect. In addition, we have demonstrated the existence of a 100 kDa protein in rat T cell lysates which reacts with AC1 on Western blots, and this interaction is abolished by sialidase-treatment of the membrane. Pronase treatment of the T cells, which rendered the 100 kDa protein undetectable on Western-blotting, reduced the number of AC1-positive cells by 40-50% on flow cytometry. On the other hand, all cells became AC1-negative after sialidase treatment. These findings indicated that AC1 reacts with both GD1c(NeuGc,NeuGc) and the 100 kDa glycoprotein on rat T cells. Taken together, these results predict the presence of a novel regulatory mechanism of T cell activation involving CD4 and the NeuGcalpha2-8NeuGcalpha2- sequence.

Animals↗

Production of eicosanoids and angiotensin II in resistance vessels in spontaneously hypertensive rats.

1. Angiotensin II (AngII) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and beta-adrenoceptor stimulation on the production of vascular AngII and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5, 17 and 30 weeks, and age-matched Wistar-Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail-cuff method. Mesenteric arteries were isolated and perfused with Krebs'-Henseleit solution. The outflows of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and AngII were measured by specific radioimmunoassays. 3. The SBP was higher in SHR than in WKY rats in the 17- and 30-week-old groups and increased with age. Basal levels of PGE2 were significantly lower in SHR than in WKY rats. The ratios of 6-keto-PGF1 alpha to TxB2 and PGE2 to TxB2 were significantly lower in 17-week-old SHR compared with age-matched WKY rats. Basal AngII release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of AngII; the magnitude of the increment was greater in WKY rats than in age-matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed. 4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR. Our findings suggest that vascular AngII plays a role in the ageing process and that beta-adrenoceptor-stimulated release of vascular AngII is impaired in SHR.

6-Ketoprostaglandin F1 alpha↗

Autocrine regulation and experimental modulation of interleukin-6 expression by human pulmonary epithelial cells infected with respiratory syncytial virus.

The mechanisms of regulation of interleukin-6 (IL-6) production in respiratory syncytial virus (RSV)-infected respiratory epithelial cells were evaluated in A549 cell cultures. Incubation with purified RSV resulted in significant production of IL-1alpha, IL-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Addition of saturating concentrations of neutralizing antibodies against IL-1alpha, IL-1beta, or TNF-alpha into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1alpha antibody had the most predominant effect (80% inhibition). Anti-IL-1alpha antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 microM) or ribavirin (90 microg/ml), an antiviral agent, also significantly inhibited the synthesis of IL-6. Hence, in clinical settings, pharmacological agents such as the specific antagonists of IL-6-inducing cytokines, as well as dexamethasone and ribavirin, could be used to modulate IL-6 production.

Antiviral Agents↗

[Pain caused by ephaptic transmission occurring in the recovery phase of diabetic vascular mononeuropathy was effectively suppressed with L-threo-3,4-dihydroxyphenyl-serine].

A 59-year-old man with an 8-years history of diabetes mellitus had an acute onset of sharp pain in the anterior part of right lower leg. One month later, the pain changed to deep dull nature in the deeper site of the peroneal region. The pain increased, when he stood up, walked, and stayed in the cold room and decreased by rest. It was more painful in the evening than in the morning. The first sharp pain was thought to be caused by ischemia due to diabetic vascular neuropathy. The next dull pain was considered to be originated from ephaptic transmission between sympathetic efferent fibers to group IV and afferent ones from the skeletal muscle. The latter dull pain was selectively suppressed by nerve block when it became effective to the branch of deep peroneal nerve to extensor digitorum longus muscle. The hypothesis of ephaptic transmission was supported by meaningful decrease of muscle sympathetic activity detected by microneurography before and after the dosage of L-DOPS, which effectively suppressed the pain as well as other alpha-stimulant, midodrine hydrochloride. We concluded that the ephaptic pain caused by muscle sympathetic activity could be suppressed by the vasoconstrictive drugs through the mechanism of baroreflex control.

Adrenergic alpha-Agonists↗

Migration of granule neurons in cerebellar organotypic cultures is impaired by methylmercury.

To examine whether abnormal migration of granule cells in the external granular layer during cerebellar development is in part of the etiology of fetal Minamata disease, organotypic culture of rat cerebellar slice was established. Migration of external granule cells pulse-labeled with bromodeoxyuridine (BrdU) toward the internal granular layer was inhibited by the presence of methylmercury (0-10 microM) in a dose-dependent manner. Nuclear condensation and DNA fragmentation visualized by the indirect immunofluorescence method with anti-BrdU antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method indicated that a large fraction of cells in the external granular layer underwent apoptotic death in the slices treated with 10 microM methylmercury. Thus, methylmercury inhibits the migration of cerebellar granule cells in a model system for neural development. The impaired migration was a possible cause of the apoptotic death of external granule cells.

Animals↗

Effect of dibutyryl cyclic AMP on plasma renin activity in normal men and patients with primary aldosteronism.

Dibutyryl cyclic AMP (DBcAMP) directly stimulates the release of renin from the juxtaglomerular (JG) cells in vitro. We investigated the effect of DBcAMP on plasma renin activity (PRA) in 6 normal men and in 8 patients with primary aldosteronism (PA). A 20-min infusion of 0.33 mg/kg/min of DBcAMP significantly increased PRA in normal men, but had little effect on PRA in patients with PA. Infusion of DBcAMP significantly reduced the blood pressure and the levels of serum sodium and potassium in normal men and the patients with PA. Infusion of DBcAMP significantly increased urine volume in normal men, but not in patients with PA. Urinary excretion of sodium increased in both groups after the infusion of DBcAMP. Thus, DBcAMP did not stimulate renin release in patients with PA, suggesting that the chronic excess production of aldosterone suppresses the release of renin from JG cells.

Adult↗

Distribution of ankyrin isoforms and their proteolysis after ischemia and reperfusion in rat brain.

The distribution of brain-type ankyrin (ankyrinB, 212 kDa) and erythrocyte-type ankyrin (ankyrinR, 239 kDa) was investigated in the subcellular fractions of rat forebrain (P1, 1,000 g pellet; P2, 15,000 g pellet; P3, 100,000 g pellet; S, 100,000 g supernatant) by immunoblotting using specific antibodies. The P2 fraction contained approximately 40% of the 212- and 163-kDa isoforms of ankyrinB and the 239-kDa isoform of ankyrinR. Further subfractionation of the P2 by Percoll gradient centrifugation followed by separation of myelin showed association of the three ankyrin isoforms with the synaptosome-rich fraction but not with the myelin-rich fraction. The plasma membrane-rich P3 fraction contained a concentration of ankyrin isoforms similar to that in the P2 fraction. In vitro proteolysis of ankyrin in the P2 fraction with calpain showed that the 212-kDa ankyrinB was more susceptible to calpain than was ankyrinR. In the two-vessel occlusion model, ischemia for 30 min generated the 160-kDa fragment of ankyrinR, and reperfusion for 60 min after 30 min of ischemia remarkably increased the 160-kDa fragment. The reperfusion also significantly decreased the 212-kDa isoform of ankyrinB. Both ischemia-reperfusion and in vitro proteolysis with calpain generated the 160-kDa fragment of ankyrinR, suggesting the involvement of calpain.

Animals↗

Glial cyst in the thalamus with intracystic hemorrhage--case report.

A 19-year-old female presented with an unusual glial cyst of the thalamus that caused development of acute hydrocephalus due to hemorrhage and manifested as headache and fainting attacks. Computed tomography showed a large cystic mass lesion in the left thalamus with intracystic hemorrhage. The cyst was subtotally removed. Microscopic examination revealed mild gliosis with marked hemosiderin deposits. The inner surface of the cystic wall lacked an epithelial lining. The diagnosis was glial cyst. Magnetic resonance (MR) imaging 2 months after surgery showed a residual cyst in the left thalamus. However, after 12 months she was asymptomatic, neurologically intact, and MR imaging showed no regrowth of the cyst. Treatment of glial cyst must provide sufficient communication between the cyst and the cerebral ventricles rather than attempt total removal of the cyst, which may present a considerable challenge.

Adult↗

Hypervascularity in Lhermitte-Duclos disease--case report.

A 61-year-old male presented with a hypervascular variant of dysplastic gangliocytoma (Lhermitte-Duclos disease) manifesting as gait disorder. Computed tomography and magnetic resonance imaging both showed enhancement of the tumor after injection of contrast medium. Angiography demonstrated a tumor stain. Histological examination showed a double-layered structure comprising an outer layer of myelinated axons and an inner layer of dysplastic granular cells, and numerous dilated thin-walled blood vessels. Partial resection of the tumor resulted in resolution of the neurological deficit.

Cerebellar Neoplasms↗

[Image-guided surgery for epilepsy].

Availability of a neuronavigation system for epilepsy surgery was reported, and its practical use was discussed. Four of nine patients with intractable epilepsy underwent surgical procedures using a neuronavigation system, Viewing wand, from November 1995 to August 1996, in our hospital. The ages of patients were between 9 to 46 years old. Three of them had temporal lobe epilepsy and one had generalized tonic seizures. One of the temporal lobe epilepsy cases had focal cortical dysplasia in the left posterior temporal lobe, and the other one showed that left hippocampal atrophy on MR images. The remaining two patient had no abnormality on MR images. All patients underwent video-EEG monitoring and habitual seizures were recorded at least three times. Ictal and/or interictal SPECT and neuropsychological testing were also performed. Electrocorticograms were recorded intraoperatively in all patients. Surgical procedures using the neuronavigation system were anterior temporal lobectomy, corpus callosotomy and lesionectomy of focal cortical dysplasia. A patient with temporal lobe epilepsy underwent implantation of depth electrodes under the neuronavigation. In temporal lobectomy, image-guided surgery helped to make a decision concerning the safely-resectable size of the lateral temporal cortex and hippocampus. The hippocampus was resected with minimum surgical damage and it made possible a complete histopathological examination. In corpus callosotomy, although it was not easy to confirm the length of the callosal section, the neuronavigation system enabled this to be done quickly. The real-time navigation showed the accurate operating position on three-dimensional images. The location of focal cortical dysplasia was often difficult to identify macroscopically. However, the location of the lesion can be projected to the skin surface under the neuronavigation system. The width of skin incision and craniotomy was able to be made smaller, and the surgery was able to be performed less invasively. The Viewing Wand system was accurate, reliable and easy to operate in these procedures. The navigating error was 2-5 mm. Using CT image data of 5 mm thickness the error was greater, although use of MR image data of 2 mm thickness resulted in relatively small error up to 2-3 mm. The first major factor of the error was the fiducial registration of the patient's head. While the registration was made more strictly with multiple fiducial points, the error was smaller. The second factor was movement of patient's head and/or the navigation arm. The arm and the head should be fixed tightly to the operating table, and it is better if they are fixed together with a supporting arm. The third factor was intraoperative brain shift caused by flow out of the cerebrospinal fluid or removal of mass lesions. This type of error is common in all navigation systems. However, it may be avoided making some real-time feedback system. With the Viewing Wand system, repetition of the intraoperative registration using intracranial anatomical structures reduces this type of error. On the other hand, there were some difficulties on stereotaxic procedures, such as implantation of depth electrodes, using the Viewing Wand. The error was larger than that recorded in other frame-based stereotaxic apparatus. This problem may be improved by a supporting system to fix the probe position. As a neuronavigation system can be widely applied to neurosurgical procedures, we consider that epilepsy and skull-base surgery are the best targets for it because of the minimum possible brain shift. We hope that accurate and less-invasive surgery using a neuronavigation system will contribute to a better outcome for epilepsy patients.

Adolescent↗

[Hippocampal hemosiderin deposit due to large pituitary adenoma presenting temporal lobe epilepsy--a case report].

There have been reports of epilepsy associated with pituitary adenoma, but the epileptogenic zone and its histopathology have never been sufficiently described. We report a case of pituitary adenoma complicated by temporal lobe epilepsy, in which the epileptogenic focus was identified, resected, and examined histopathologically. The patient was a 38-year-old man on bromocriptine therapy for a huge pituitary adenoma (prolactin-producing) since 1985. He also had a history of temporal lobe epilepsy since 1989. CT images in 1985 revealed the tumor extending to the supra- and left para-sellar region. MR images in 1995 showed a significant decrease in the size of the tumor and a signal void area that was interpreted as a hemosiderin deposit in the left mesial temporal lobe. Ictal EEG demonstrated that seizure discharges were elicited at the left sphenoidal electrode and propagated to the both temporal lobes. Interictal SPECT revealed a local area of hypoperfusion in the left fronto-parietal lobe. An epileptogenic focus in the left mesial temporal lobe was diagnosed on the basis of the above examinations. The patient was treated by left anterior temporal lobectomy with partial hippocampectomy. Hemosiderin deposition in the hippocampus was suspected during surgery. Histopathological examination showed pyramidal cell loss and gliosis in the left hippocampus and confirmed the presence of hemosiderin in the CA1 region. The hemosiderin deposition in the hippocampus was inferred to have resulted from intratumoral hemorrhage due to bromocriptine therapy, and it may have caused the temporal lobe epilepsy in this patient. The outcome of surgery was freedom from seizures for eight months. Intra-tumoral hemorrhage in mesial temporal structures must be borne in mind as one of the epileptogenic mechanisms in pituitary adenoma, especially in cases in which hemosiderin is detected on MR images.

Adenoma↗

[Experimental bilateral focus model of complex partial seizure: clinical, electrophysiological and pathological studies].

Stereotactic surgery was performed in Wistar rats and stainless steel injection chemitrode were inserted in bilateral amygdala (AM). Stainless steel screws were placed on the dura over bilateral motor cortex (Cx). One week after the surgery, rats were placed in the recording chamber. Kainic acid (KA) injection was performed into the left AM and focal AM seizure status was induced. Seizures evolved into limbic seizure status during 3 days. Seven days after the first KA injection, KA was injected into the right AM. The limbic seizure status was elicited again, however, these seizures subsided within 3 days. About 3 week after the first KA injection, spontaneous limbic seizures developed. Three ictal EEG patterns were seen (1) Bilateral independent seizures, (2) Synchronous ictal discharge over the bilateral AM, and (3) Switch of lateralized ictal activity from one to the other AM. The histological study demonstrated bilateral hippocampal cell loss and hippocampal atrophy. These changes are very similar to those observed in human intractable complex partial seizures with bilateral mesial temporal focus. The result suggests that this model will be a good tool in order to resolve intractability of complex partial seizure in patients with bilateral temporal focus.

Animals↗

Intraoperative electrocorticography in children with medically intractable epilepsy.

Intraoperative electrocorticography (ECoG) was performed to localize epileptic foci in 20 children undergoing temporal and extratemporal surgery for intractable epilepsy under modified neuroleptanalgesia. Nitrous oxide gas was discontinued at least 15 minutes before and during preresection ECoG recording, which lasted for 30 minutes. Seventeen patients showed epileptiform discharges on preresection ECoG. Hyperventilation loading, monitored by electroencephalography or ECoG in all patients, induced enhanced or induced epileptiform activities in 17 patients and provoked electroencephalographic seizures in 10 patients. All foci in non-eloquent areas were resected. Fifteen patients have been seizure-free with reduced medication, and two patients have achieved worthwhile improvement. Habitual seizures have remained in three patients. Two of these patients had foci in eloquent areas which could not be resected. Intraoperative ECoG can improve the outcome of surgery for intractable epilepsy by localizing epileptic foci for resection.

Adolescent↗

[Therapeutic trials with topical capsaicin cream and iontophoretically applied lidocaine for diabetic painful truncal neuropathy].

We report a 63-year-old man with a history of diabetes mellitus for 23 years. Painful dysesthesia developed in his toes and trunk with weight loss of 2kg in two months, after the therapy for diabetes mellitus. Truncal painful dysesthesia was symmetrically distributed in the bilateral posterior and anterior T8-11 dermatomes, sparing the bilateral lateral tholacic areas. Electromyography showed denervation potentials in bilateral abdominal rectus muscles at the levels of Th8-10. Histopathological study of the biopsied right sural nerve revealed small fiber neuropathy. We suspected the truncal painful dysesthesia of this patient resulted from diabetic small fiber polyneuropathy, which was resistant to ordinary medical treatments such as non-steroidal anti-inflammatory drugs. Capsaicin cream containing 0.075% capsaicin, and lidocaine delivered by iontophoresis were both effective for his painful dysesthesia.

Capsaicin↗

[A case of cervical liquorrhea with headache in and around the area of the great occipital nerve].

We report a 44-year-old man who had sudden-onset severe pain with ardor at the left occipital and nuchal region without trauma in July, 1992. Severe pain disappeared soon after, but dull pain continued intermittently. Four months later, he was referred to our hospital. Neurological examination showed no abnormalities. Cervical CT scan and myelography disclosed liquorrhea. Digital subtraction myelography confirmed cerebrospinal fluid leakage from the level of C1/2 disc. He underwent laminectomy of C1 and C2, and dural plasty on April 6, 1993 with subsequent disappearance of headache. We suppose that this headache was due to rupture of the root sleeve and compression to the root and dorsal root ganglia by outflowed liquor.

Adult↗