Biomedical subjects

Hirofumi Hirano

Publications and source records attributed to Hirofumi Hirano.

16 recordsLinked to original sources

PubMed2005

High incidence of microbleeds in hemodialysis patients detected by T2*-weighted gradient-echo magnetic resonance imaging.

The incidence and characteristics of microbleeds in hemodialysis (HD) patients were investigated to elucidate the clinical significance with T(2)(*)-weighted gradient-echo magnetic resonance (MR) imaging. The 57 patients with chronic renal failure maintained by HD had no previous history of stroke. The control group consisted of 53 patients without previous history of stroke or chronic renal failure. The incidence and the number of microbleeds were assessed in the HD and control groups. The findings of microbleeds with T(2)(*)-weighted gradient-echo MR imaging were compared with those of T(1)- and T(2)-weighted MR imaging in HD patients. The incidence of microbleeds was significantly greater in the HD patients compared with the control patients. T(2)(*)-weighted gradient-echo imaging revealed a total of 44 microbleeds in 11 HD patients. T(2)-weighted imaging demonstrated 13 of 44 microbleeds as hyperintensity, whereas T(1)-weighted imaging demonstrated 12 lesions as hypointensity. T(2)- and T(1)-weighted imagings did not demonstrate any findings in 31 and 32 lesions, respectively. T(2)(*)-weighted gradient-echo MR imaging is effective to detect microbleeds which may be a predictor of intracerebral hemorrhage in HD patients and should be included in the protocol for the study of cerebrovascular disease, because T(2)- and T(1)-weighted MR imaging recognizes microbleeds as lacunar infarction.

Aged↗

PubMed2005

The environment of increased concentration of docosahexaenoic acid in glioblastoma may suppress the anti-tumor effect of macrophages.

Regarding glioblastoma, there has been controversy over whether a large number of infiltrating macrophages act as anti-tumor effectors or not. It has been exhibited that intratumoral lipid environments have a possible influence on anti-tumor immunity. Necrosis of glioblastoma and non-necrotic tissues of astrocytic tumors were analyzed to compare the amount of free docosahexaenoic acid (DHA) content. The apoptosis inducible effects of DHA on macrophages derived from peripheral blood monocytes and cultured glioma cells were evaluated by flow cytometry. The influence of DHA on the anti-tumor effects of macrophages was assessed at 0, 30, 60, and 90 mM of DHA by (51)Cr releasing assay and MTT assay. The mean concentration of free DHA in necrotic tissues (757.6 mmol/kg) was 5 times higher than that in non-necrotic tissues (147.2 mmol/kg). The DHA concentration of 30 mM induced apoptosis in macrophages, however, glioma cells were not affected even at a DHA concentration of 60 mM. Macrophages pre-exposed to DHA for 24 h decreased the cytotoxicity to U251MG cells as shown by (51)Cr releasing assay. Total viability of co-cultured macrophages and U251MG cells showed an increase at high concentrations of DHA (60 and 90 mM) according to 24 h MTT assay, although each separate culture did not. The DHA concentration in necrosis of glioblastoma was sufficient for macrophages to cause apoptosis and suppress their anti-tumor effects. The results suggest that liberated DHA in necrosis can induce apoptosis in macrophages and inhibit their functions.

Apoptosis↗

PubMed2004

Expression and distribution of c-kit receptor and its ligand in human CNS germ cell tumors: a useful histological marker for the diagnosis of germinoma.

We previously reported the expression of protooncogene c-kit in CNS germ cell tumors and suggested that the soluble form of c-kit (s-kit) may represent a specific clinical marker for germinoma-containing tumors. Here we investigated the expression of stem cell factor (SCF), a specific ligand of c-kit, in CNS germ cell tumor samples from 16 patients, using immunohistochemical methods to assay the expression of c-kit and SCF protein. The immunostaining patterns of c-kit and SCF were almost identical. In all germinoma-containing tumors, c-kit and SCF were diffusely expressed on the surface of germinoma cells; lymphocytes and interstitial cells were negatively stained. In immature teratomas, only some mature components, e.g., cartilage and gland, were immunoreactive for c-kit and SCF. Syncytiotrophoblastic giant cells (STGCs) were negative for both SCF and c-kit, suggesting that germinoma cells primarily coexpress SCF and c-kit. The coexpression of c-kit and SCF may be an important immunohistochemical marker for the diagnosis of CNS germinoma, and the SCF/c-kit pathway may be an alternative molecular target for the treatment of human CNS germinomas.

Biomarkers, Tumor↗

PubMed2004

Thyrotropin-producing pituitary adenoma associated with Graves' disease.

OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.

Adenoma↗

PubMed2004

Intractable hiccups as a presenting symptom of cerebellar hemangioblastoma. Case report.

The authors report on a 52-year-old woman with a cerebellar hemangioblastoma who presented with a 2-year history of intractable hiccups. Computerized tomography scans and magnetic resonance images revealed a cerebellar hemangioblastoma with compression of the brainstem at the level of the medulla oblongata. The patient has been free of hiccups and has been neurologically intact since the day after total removal of the tumor. A review of the literature on medullary lesions presenting with intractable hiccups is provided.

Brain Stem↗

PubMed2003

Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.

Adolescent↗

PubMed2003

Postoperative regression of desmoplastic infantile gangliogliomas: report of two cases.

OBJECTIVE AND IMPORTANCE: Desmoplastic infantile gangliogliomas (DIGs) are extremely rare tumors that respond well to treatment. However, their biological behavior remains to be clarified. We describe two patients whose DIGs spontaneously regressed after surgery, without adjuvant therapy. CLINICAL PRESENTATION: A 9-month-old girl presented with left hemiparesis, and a 6-month-old boy presented with increasing head circumference. For both patients, neuroimaging demonstrated a huge cystic tumor that included a solid portion and was widely attached to the dura. Gadolinium-diethylenetriamine penta-acetic acid produced strong enhancement. INTERVENTION: One patient underwent partial and the other subtotal tumor removal. Histologically, both tumors were diagnosed as DIGs. Postoperatively, the residual tumors were monitored without adjuvant therapy, and both regressed in several months. CONCLUSION: Our experience suggests that DIGs may include a subgroup of tumors with a tendency for spontaneous regression, possibly attributable to the induction of apoptosis.

Apoptosis↗

PubMed2003

Pathodynamics of nitric oxide production within implanted glioma studied with an in vivo microdialysis technique and immunohistochemistry.

Nitric oxide (NO) is thought to be a mediator in many of the processes of malignant brain tumor progression. We examined NO production in the brain of normal conscious, freely moving rats with or without implanted C6 glioma. Both nitrite (NO(2)(-)) and nitrate (NO(3)(-)) in the dialysates of the two groups were measured using an in vivo microdialysis technique. The mean concentration of NO(2)(-) in the glioma group was two-times higher than that in the control group (P<0.01). Concentrations of both NO(2)(-) and NO(3)(-) in the glioma and control groups decreased following intraperitoneal injection of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of NO synthase (NOS). NO production was also significantly suppressed in the glioma group, but not the control group, by intraperitoneal injection of 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a selective inhibitor of inducible NOS (iNOS). On immunohistochemical examination, diffuse iNOS-positive cells were located within glioma tissue. ED1-positive cells (microglia/macrophages) were intermingled between glioma cells on double immunostaining. These results indicate that the basal level of NO production in the glioma group is higher than that in the control group and that the increased NO production was continuously induced by iNOS-expressing cells in glioma.

Animals↗

PubMed2003

Germinoma with syncytiotrophoblastic giant cells recurring 13 years after radiotherapy for a pineal germinoma--case report.

A 28-year-old man presented with progressive mental deterioration. Thirteen years earlier he had undergone radiation therapy for a pineal germinoma. Neuroimaging showed a homogeneously enhanced mass lesion along the ventricular wall. The cerebrospinal fluid (CSF) level of human chorionic gonadotropin (HCG) was high. Endoscopic biopsy revealed that the tumor was a two-cell pattern germinoma. The diagnosis was germinoma with syncytiotrophoblastic giant cells (STGC). He first received three cycles of chemotherapy with carboplatin and etoposide and then two cycles with ifosfamide, cisplatin, and etoposide. Subsequently, the tumor size decreased markedly and the CSF level of HCG returned to normal. However, he died 22 months after the recurrence. Histological verification and measurement of tumor markers are necessary for the optimum treatment of germ cell tumors. Adequate initial chemotherapy and long-term follow up are essential for patients with germinoma with STGC.

Adult↗

PubMed2003

Optic nerve glioma manifesting as intratumoral hemorrhage in a pregnant woman--case report.

A 33-year-old pregnant woman presented with intratumoral hemorrhage in an astrocytoma of the left optic nerve and chiasm manifesting as poor vision in her left eye. Visual examination found no light perception in the left eye and deteriorated acuity with temporal hemianopsia in the right eye. Computed tomography demonstrated a round high-density mass in the suprasellar region. T2-weighted magnetic resonance (MR) imaging showed the center of the mass as mildly hypointense and T2-weighted MR imaging as hypointense. Both T1- and T2-weighted MR imaging showed the rim of the mass as hyperintense. She delivered a healthy baby by cesarean section. A left frontotemporal craniotomy was then performed. Incision of the lateral surface of the left optic nerve revealed clotted blood from the left optic nerve and the left side of the chiasm. No vascular malformation was noted in the hematoma cavity. Histological examination revealed a neoplasm composed of well-differentiated astrocytic cells. No Rosenthal fibers were identified. The patient made an uneventful postoperative recovery. Her right visual acuity returned to normal, but the temporal hemianopsia in the right eye and the blindness in the left eye persisted. Gliomas of the anterior visual pathways are rare, especially in adults. The hemorrhage may have been caused by the hypercoagulable state associated with pregnancy. Optic nerve astrocytic glioma with intratumoral hemorrhage should be considered in the differential diagnosis of suprasellar hematoma.

Adult↗

PubMed2003

Tumefactive myelinoclastic diffuse sclerosis--case report.

A 6-year-old boy presented with mental disturbance and progressive left hemiparesis. Magnetic resonance imaging demonstrated large intracranial mass lesions with ring-like enhancement. His neurological condition deteriorated rapidly. Open biopsy via craniotomy was performed under the suspicion of tumor. Histological examination showed massive demyelination and axon preservation, but no tumor cells. The diagnosis was myelinoclastic diffuse sclerosis (MDS). He was treated with high-dose methylprednisolone and improved dramatically. MDS is a rare demyelinating disorder of the central nervous system that affects mainly children and may mimic a brain tumor. MDS must be included in the differential diagnosis in young patients with a brain tumor with atypical radiological appearance.

Brain Neoplasms↗

PubMed2002

Age-related changes in the immunoreactivity of the monocyte/macrophage system in rat molar pulp after cavity preparation.

OBJECTIVE: Our objective was to compare the response of the monocyte/macrophage system of dental pulp to cavity preparation in aged rats (12 and 18 months old) with that seen in young adult rats (3 and 6 months old). STUDY DESIGN: Cavities were prepared on the upper first molars, and the lower first molars served as intact controls. Specimens were collected at 1 day after cavity preparation, and cryostat sections were made. RESULTS: Accumulation of OX6+ antigen-presenting cells along the pulp-dentin border and a marked increase in cell size ED2+ resident macrophages were noted in both young adult and aged rats after cavity preparation. In both cases, the number of ED1+ cells increased significantly after cavity preparation because of infiltrating monocytes. CONCLUSION: These findings suggest that the pulpal defense reaction of the monocyte/macrophage system to cavity preparation in aged rats does not differ markedly from that in young adult rats.

Age Factors↗

PubMed2002

Brain surface ependymoma with repeated episodes of intratumoral hemorrhage--case report.

A 70-year-old woman presented with a rare brain surface ependymoma with repeated intratumoral hemorrhage. She was admitted with progressive dementia. Two years earlier, a diagnosis of subcortical hematoma in the right frontal lobe had been made following a fall. On admission, magnetic resonance imaging showed a huge right frontal mass lesion with multiple hemorrhagic cysts. She underwent gross total resection. The tumor was located on the surface of the frontal lobe, and was sharply demarcated from the surrounding brain tissue with no attachment to the ventricular wall. The histological features were consistent with an ependymoma forming perivascular pseudorosettes. Immunohistochemistry showed positive staining for glial fibrillary acidic protein. Electron microscopy showed microvilli and zonula adherens. This case demonstrates the natural course of malignant progression of ectopic ependymomas. Ependymoma should be included in the differential diagnosis of tumors associated with repeated subcortical hematomas, even if located on the brain surface and distant from ventricles.

Aged↗

PubMed2002

Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors.

OBJECT: Overexpression of the protooncogene c-kit has been suggested in a gonadal germ cell tumor (GCT). Recently, the soluble isoform of c-kit (s-kit) has been expressed in a variety of cell types. The goal of this study was to investigate the expression of c-kit and the clinical significance of s-kit in patients with GCTs. METHODS: The authors first conducted an immunohistochemical investigation of the expression of the c-kit protein in 27 surgical specimens. In all 18 specimens that contained germinomas, c-kit was diffusely expressed on the cell surface of the germinoma cells, but was not found on lymphocytes or interstitial cells. In seven of eight immature teratomas, only some mature components, such as cartilage and glands, were immunoreactive for c-kit. Syncytiotrophoblastic giant cells (STGCs) demonstrated negative findings as well, suggesting that primarily germinoma cells express c-kit. Next, 47 cerebrospinal fluid (CSF) samples collected from 32 patients with GCTs (15 samples from patients with pure germinomas, 16 from patients with STGC germinomas, 14 from patients with teratomas, and two from a patient with a choriocarcinoma) were analyzed using a sandwich enzyme-linked immunosorbent assay. The level of s-kit was significantly higher in CSF collected from patients with germinomas and STGC germinomas than in CSF collected from patients with teratomas or non-germ cell brain tumors, or in CSF collected from controls. The concentration of s-kit in CSF was correlated with the patient's clinical course: it was significantly higher in pretreatment samples obtained before and in samples obtained at the time of tumor recurrence than in samples collected from patients in whom the tumor was in remission. The level of s-kit was remarkably high in CSF collected from patients with subarachnoid tumor dissemination. CONCLUSIONS: These results indicate that the concentration of s-kit in CSF may be a useful clinical marker for germinomas, especially for detecting recurrence or subarachnoid dissemination of these lesions.

Biomarkers, Tumor↗

PubMed1998

Pituitary Adenoma with Cholesterol Clefts.

Histologically, cholesterol clefts are often observed in craniopharyngioma, Rathke's cleft cyst, and various granulomas. However, pituitary adenomas with cholesterol clefts are rare. A 46-year-old woman developed visual field disturbance. She had no history of severe headache that would suggest pituitary apoplexy. She presented with homonymous bitemporal hemianopsia and galactorrhea. Blood prolactin level was 63.1 ng/mL Other hypophysial hormone levels were within normal range. Magnetic resonance imaging revealed a pituitary tumor with intratumoral cyst. The cyst showed high intensity on T1- and T2-weighted images. The tumor was demonstrated with iso intensity on T1-weighted image and with high intensity on 12-weighted image. She underwent trans-sphenoidal surgery. The tumor was soft, with yellowish, oily fluid, probably the cyst content. By light microscopy with hematoxylin and eosin staining, a typical chromophobic adenoma of the pituitary was identified. Immunostaining revealed immunoreactivity for ACTH in several cells. Many cholesterol clefts and several hemosiderin pigment containing macrophages were observed. Electron microscopy demonstrated a pituitary adenoma with sparse and small secretory granules and numerous lysosomes. The cyst was most likely caused by focal hemorrhagic infarction, followed by the formation of cholesterol crystals, the appearance of hemosiderin containing macrophages, foreign body product cells, and accumulation of lysosomes.

Journal Article↗

PubMedDate not supplied

The expression of tissue factor correlates with proliferative ability in meningioma.

Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the extrinsic pathway of coagulation; this is inhibited by tissue factor pathway inhibitor (TFPI). As TF reportedly regulates tumor growth and angiogenesis, we investigated the role of TF in meningioma. Using immunohistochemical methods, we studied the expression of TF, TFPI, MIB-1 labeling index in 44 meningiomas to determine whether those factors reflect histological grade and proliferative ability. CD31 and CD68 immunostaining was used to assess vascular density and macrophage infiltration, respectively. Additionally we assessed the influence of TF on meningioma cell proliferation by MTT assay. TF was expressed in 1 of 34 (2.9%) benign, 1 of 5 (20%) atypical, and all of 5 anaplastic meningiomas. TFPI was detected in 2 benign (5.9%), 1 atypical (20%), and 3 (60%) anaplastic meningiomas. Both TF and TFPI expression was significantly correlated with the MIB-1 labeling index (LI). However, neither TF nor TFPI showed a correlation with vascular density. The density of tumor-associated macrophages was not correlated with TF or TFPI immunoreactivity. MTT assay revealed that TF increased the proliferation of meningioma cells. Although some macrophages expressed TF, a great number of the TF immunopositive parenchymal cells in the meningiomas were tumor cells. The present study suggest that the TF system reflects the proliferative ability and malignancy of meningiomas.

Antigens, CD↗