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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 217 records · Page 12Linked to original sources

The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism.

In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (ICGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model, 14C-Iodo-antipyrine and 14C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0-10% of the control level in the ischaemic core and to 12-40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.

Animals↗

Expression of multidrug resistance-related P-glycoprotein shows good prognosis in neuroblastoma.

Expression of P-glycoprotein was studied in formalin-fixed tissue sections from 75 materials with an immunoperoxidase (ABC) method using the monoclonal antibody MRK-16. Specimens examined were from three monkey fetuses, eight autopsy cases, and 64 neuroblastoma patients, 25 of whom were underwent mass screening for diagnosis. P-glycoprotein test results were positive in fetal lung alveolar tissue and in the adrenal medulla of three of seven adult autopsy cases. Expression of P-glycoprotein was demonstrated in 22 of 35 cases (63%) in a group of neuroblastoma patients younger than 12 months of age, as compared with 9 of 20 (31%) who were older than 12 months of age at diagnosis. P-glycoprotein positivity was higher in patients who were alive (25 of 40, 63%) than in those who had died (6 of 24, 25%). Previous studies on P-glycoprotein expression in neuroblastoma were carried out using specimens mainly from older children, and the results were not analyzed with reference to the findings in normal tissues. The present study has clearly shown that positive P-glycoprotein expression in neuroblastoma patients should be evaluated carefully in infant cases because it stains frequently in normal adrenal glands.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Single-step synthesis of [18F]haloperidol from the chloro-precursor and its applications in PET imaging of a cat's brain.

We have established a convenient synthesis process for the synthesis of[18F]haloperidol using a single-step 18F-for-Cl exchange reaction and a new elution system for the preparative high performance liquid chromatography (HPLC) using C18 bonded vinylalcohol copolymer gel (ODP) and a basic eluent. We successfully applied the product to cat-PET study and got clear images of the striatum, showing the usefulness of this synthesis.

Animals↗

Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

Acromegaly↗

Alopecia universalis with remission during pregnancy and prednisolone therapy.

In a 32-year-old woman, alopecia universalis went into unequivocal remission during pregnancy and prednisolone therapy. A skin biopsy specimen showed intense infiltration of the lymphocyte around the hair follicle without immunoglobulin and complement deposition. Autoantibody test results were negative except for the antithyroid and anti-nuclear antibodies. Human leukocyte antigen haplotypes common in Japanese patients with insulin-dependent diabetes were found in this patient. However, thyroid function and glucose tolerance were normal, and other clinical evidence of collagen vascular disorders was not found. In this patient, alopecia was considered to have been caused by autoimmune abnormalities. This is the first documentation of remission of autoimmune alopecia universalis during pregnancy.

Adult↗

Xenon contrast CT-CBF measurements in high-intensity foci on T2-weighted MR images in centrum semiovale of asymptomatic individuals.

BACKGROUND AND PURPOSE: White matter lesions (WMLs) on T2-weighted MR images occurring in the centrum semiovale of normal individuals are a subject of great clinical interest. We therefore investigated regional cerebral blood flow (rCBF) of the centrum semiovale among neurologically normal individuals. METHODS: One hundred thirty-five neurologically normal subjects were divided into four grades of WML on the basis of their MR images. rCBF values in the centrum semiovale were measured by xenon contrast CT methods. RESULTS: Advanced age and associated hypertension were significant risk factors for higher grade WMLs. Centrum semiovale rCBF values on the left side were 24.27 +/- 2.60 mL.100 g-1.min-1 in grade 0, 23.52 +/- 2.78 in grade I, 19.35 +/- 2.81 in grade II, 15.82 +/- 2.05 in grade III, and 11.31 +/- 2.56 in grade IV. Differences were significant between grades (P < .005 between grade 0 and grades II, III, and IV; between grade II and grades III and IV; and between grades III and IV). Patients with hypertension had lower rCBF values than those without in grades 0, I, II, and III, with significant difference in grade I (P < .005). Age-matched studies between patients 61 to 70 years old confirmed a significant difference between WML grades. CONCLUSIONS: WMLs in centrum semiovale are associated with greater age, hypertension, and reduced rCBF values.

Adult↗

Two signaling pathways, from the upper glycolytic flux and from the mitochondria, converge to potentiate insulin release.

In the rat pancreatic beta cell, low concentrations of glucose potentiate D-glyceraldehyde (GA)-induced insulin release without any potentiation of the triose-induced elevation of cytosolic free Ca2+ concentration. Namely, 2-3 mM glucose strongly potentiates 5 mM GA-induced insulin release, and the combination of stimulatory concentration of glucose (10 mM) and 5 mM GA elicits far more than additive insulin release: this glucose action is independent of ATP-sensitive K+ channel closure because it can be seen in the presence of diazoxide, an opener of the K+ channel. The triose-induced elevation of cytosolic free Ca2+ concentration was not potentiated by the presence of 3 mM glucose, and oxidation of labeled GA by the islet cells was not enhanced by the presence of glucose. The glucose action can be mimicked by mannose, but not by galactose, and was suppressed by inhibition of glucose phosphorylation with mannoheptulose or 2-deoxyglucose. Glucose also potentiates 2-ketoisocaproate-induced insulin release. In contrast, a combination of GA and 2-ketoisocaproate elicits only additive insulin release. Strikingly, 3 mM glucose does not potentiate insulin release in response to a depolarizing concentration of K+. Therefore, at least two signal pathways, one from upper glycolytic flux and one from mitochondrial metabolism, must converge to provide the potentiation of insulin release. We conclude that the upper glycolytic flux, acting at a site unrelated to the elevation of cytosolic free Ca2+, potentiates insulin release triggered by triose and mitochondrial fuels.

Animals↗

3,5,3'-Triiodo-L-thyronine potentiates all-trans-retinoic acid-induced apoptosis during differentiation of the promyeloleukemic cell HL-60.

Although the programmed cell death mediated by thyroid hormone is not well evaluated in mammalian cells, thyroid hormone plays a crucial role in differentiation of the cells during the metamorphosis of Xenopus, suggesting that thyroid hormone has the potential ability to induce the apoptosis. To investigate the thyroid hormone-inducible apoptosis, we cultured HL-60 cells with various amounts of all-transretinoic acid (RA) and L-T3. T3 alone did not induce the apoptosis of the cells. T3, however, suppressed the proliferation of cells in the presence of RA. DNA ladder and microscopical examination showed that the reduction of cell number was due to the apoptosis induced by RA. These findings suggested that T3 affects the apoptotic process during the differentiation of HL-60 cells by RA. T3-inducible apoptosis may require the factors augmented by RA in HL-60 cells.

Apoptosis↗

An early insulin intervention accelerates pancreatic beta-cell dysfunction in young Goto-Kakizaki rats, a model of naturally occurring noninsulin-dependent diabetes.

This study was designed to delineate the nature of beta-cell dysfunction in a model of genetically determined nonobese diabetes, the Goto-Kakizaki (GK) rat. Pancreatic beta-cell function was analyzed immediately after weaning and 5 weeks thereafter, comparing animals with or without insulin treatment during the interval. In 3.5-week-old GK rats, fasting plasma glucose was mildly elevated with normoinsulinemia, and the islet insulin content was reduced by 33%. When incubated with 3-30 mM glucose in vitro, the GK rat islets showed reduced glucose sensitivity, i.e. the EC50 values were 19.5 and 15.9 mM, and the Hill constants for the positive cooperativity 2.1 and 4.2 in the islets of GK and the control rats, respectively. On the other hand, the maximum response to glucose was not attenuated when reduced islet insulin content was considered. In 8.5-week-old GK rats hyperglycemia worsened and glucose-stimulated insulin release by the islets more severely impaired. A daily insulin injection from the 3.5-8.5 weeks of age significantly lowered plasma glucose in the GK rat, accompanied by a marked suppression of both basal (with 3 mM glucose) and glucose (6-30 mM)-stimulated insulin release by the islets. In the GK rat, beta-cell dysfunction develops by the age of 3.5 weeks, and insulin treatment during the subsequent 5 weeks accelerates its progression.

Animals↗

Insulinoma in a patient with non-insulin-dependent diabetes mellitus.

Insulinoma in a patient with pre-existing diabetes is exceedingly rare. Only a small number of well-documented cases have been reported in the world during the last 40 years. We describe a case with non-insulin-dependent diabetes mellitus who after seven years of sulfonylurea treatment experienced recurrent episodes of hypoglycemia. Endogenous hyperinsulinism was found and radiographical examination and transhepatic venous sampling confirmed an insulin secreting pancreatic tumor. After surgical excision of the tumor, patient was relieved from hypoglycemic attacks but required to initiate insulin injection for the treatment of hyperglycemia.

Aged↗

Multiple endocrine neoplasia type 1 is not rare in Japan.

Multiple endocrine neoplasia type 1 (MEN 1) is rarely reported in Japanese and other oriental populations. To examine if there is a racial difference in the prevalence of MEN 1, we initiated extensive work on patients with endocrine tumors for additional lesions, and annual screening of family members of affected patients. In a four-year study, eleven asymptomatic patients were found by family screening, and the number of patients with MEN 1 in our clinics increased from 16 to 38. Estimated prevalence of MEN 1 was no less than 0.018/1000. MEN 1 may not be as rare as had been thought in Japanese, and the prevalence of MEN 1 in Japanese would not be significantly different from that of Caucasians. Systemic surveillance and extensive screening of family members are required for early detection and management of patients.

Adolescent↗

Secretory meningioma with severe perifocal edema--case report.

An 82-year-old male presented with a small parasagittal meningioma associated with disproportionately severe perifocal edema. Histological examination including immunohistochemical staining and electron microscopy resulted in a diagnosis of secretory meningioma. In addition to tumor size, the edema could not be explained by location, growth rate, vascular involvement, or other factors. We conclude that secretory meningiomas may possess an innate ability to cause brain edema.

Aged↗

[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↗

[A case of acute cervical epidural abscess].

Epidural abscess is very uncommon in the cervical region, and it is difficult to diagnose because of the diversity of its clinical course. The resulting neurological deficits remain unacceptably severe because of delays in diagnosis and treatment. We present a rare case of acute cervical epidural abscess. A 57-year-old man was admitted to our hospital because of esophageal carcinoma. During an overnight stay outside the hospital, he experienced sudden lumbago while removing snow at his home. The next day he developed back pain and high fever. He was drowsy but complained of neck pain. Lumbar puncture was dry. Two hours after the procedure, he developed respiratory arrest and became comatose. Consciousness and motor function recovered in response to artificial ventilation, but tetraplegia developed three days later. Cervical enhanced-CT suggested an epidural abscess. Emergency decompression laminectomy and drainage of the abscess combined with systemic antibiotics was performed. Postoperatively, the patient was afebrile, and his respiration and motor function gradually recovered. The histopathological diagnosis was abscess, but its origin was undetermined.

Abscess↗

[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↗

Hyperthyroidism.

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Antithyroid Agents↗

[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↗