Biomedical subjects

Yasuo Sugita

Publications and source records attributed to Yasuo Sugita.

At least 19 recordsLinked to original sources

PubMed2007

CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features.

CD10 and MUM1 are representative B cell differentiation markers. Follicular lymphoma (FL) is usually positive for CD10 and negative for MUM1. In this study, however, we compared 22 FLs with peculiar phenotype CD10-MUM1+ with 119 typical CD10+MUM1- FLs. All CD10-MUM1+ FL patients exhibited follicular structure with follicular dendritic meshwork, and a high rate of somatic hypermutation and ongoing mutation, similar to typical FL. However, CD10-MUM1+ FLs were encountered frequently in the elderly compared with CD10+MUM1- typical FLs (67.0 versus 58.7 years, P < .01), showed high grade (grade 3A or 3B) morphology (91% versus 17%, P < .001), diffuse proliferation (59% vs 19%, P < .001), and lacked BCL2/IGH translocation (5% versus 92.5%, P < .001), which is the most characteristic aberration in FL, and 88% showed BCL6 gene abnormalities (translocation or amplification). Our results indicate that CD10-MUM1+ FL is different from typical FL with respect to biologic and clinical features.

Aged↗

PubMed2006

Endoglin (CD 105) is expressed on endothelial cells in the primary central nervous system lymphomas and correlates with survival.

Endoglin (CD105) is predominantly expressed on the cellular lineages within the vascular system and it is overexpressed on proliferating endothelial cells that participate in neoangiogenesis, with a weak or negative expression in the vascular endothelium of normal tissues. To investigate the correlation between the CD105 expression and possible prognostic markers or progression in the primary central nervous system lymphomas (PCNSLs), the present study assessed 26 cases of PCNSL by immunostaining for CD105 and CD34. Intratumoral microvessel density (IMVD) was determined in the hotspots and interfaces at a magnification of x200. According to the mean value, the patients were classified into lower-IMVD and higher-IMVD groups. When CD34 was used as a marker of angiogenesis, the survival rates of these two groups demonstrated no significant difference. In contrast, when CD105 was used as a marker of angiogenesis, the survival rate of the lower-IMVD group was significantly higher than that for the higher-IMVD group (P < 0.01). In the group of CD34-immunostained vessels, no difference was observed in IMVD between the hotspots and interfaces (P = 0.31). In the group with CD105-immunostained vessels, a greater IMVD was observed in the hotspots than in the interfaces (P < 0.01). These results suggested that the growth of PCNSLs was dependent on angiogenesis, that IMVD as determined by anti-CD105 monoclonal antibody was a reliable prognostic marker in PCNSLs, and that PCNSLs may therefore not require sufficient neoangiogenesis at the start of PCNSLs, however, it may instead require a higher rate of neoangiogenesis as they infiltrate and destroy the brain parenchyma.

Aged↗

PubMed2006

D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells.

D2-40 antibody is raised against an oncofetal antigen, the M2A antigen. It has been used as a marker for lymphatic endothelium as well as mesothelioma and cerebellar hemangioblastoma. We demonstrate here that positive D2-40 immunoreactivity was found in the developing cerebrum, particularly in the germinal matrix layer, immature ependyma, choroid plexus and meninges. In the developing cerebellum, positive D2-40 immunoreactivity was found in the external granular layer particularly of the outer portion and the Purkinje cell layer as well as meninges. Some brain tumors such as anaplastic ependymoma, some medulloblastomas, glioblastoma, pineal germinoma, craniopharyngioma, choroid plexus papilloma, choroid plexus carcinoma, and meningioma showed positive immunoreactivity with D2-40. Therefore, D2-40 antibody is considered a useful marker for research on developing brain and diagnosis of brain tumors, differentiation between choroid plexus carcinoma and metastatic carcinoma. In addition, on cultured human neural cells, D2-40 immunoreactivity was found in nestin-positive neural stem/progenitor cells and neuronal lineage cells. As D2-40 antibody recognizes cell surface antigen M2A, it might be a candidate cell surface marker for isolation of human neural stem cells/neuronal lineage cells in the fluorescence-activated cell sorting technique.

Adult↗

PubMed2006

Olfactory neuroepithelioma: an immunohistochemical and ultrastructural study.

Three cases of olfactory neuroepithelioma are presented in this report. Histologically, these tumors were composed of small cells with round to oval, relatively hyperchromatic nuclei and scanty cytoplasm. The tumor cells were occasionally observed in tubular formations or rosette-like arrangements. Immunohistochemically, the tumor cells showed a positive reaction for cytokeratin AE1, cytokeratin CAM5.2, Ber-EP4, antisynaptophysin and anti-S100 protein in all cases. In two cases, LH-RH was detected in the tumor cells. Ultrastructurally, the tumor cells had the differentiation features of olfactory epithelium. Olfactory neuroepithelioma is a rare occurrence and it can be very difficult to distinguish olfactory neuroepithelioma from small cell carcinoma, neuroendocrine carcinoma and so-called "olfactory neuroblastoma" on the basis of hematoxylin and eosin stained sections alone. In controversial cases, a diagnosis of olfactory neuroepithelioma must be substantiated by ultrastructural and immunohistochemical findings, particularly regarding the detection of Ber-EP4 and LH-RH immunoreactivity.

Adolescent↗

PubMed2006

Organ-specific endoglin (CD105) expression in the angiogenesis of human cancers.

Some markers of angiogenic endothelial cells are emerging as targets for cancer therapy. The present study compared the expression of CD105 with that of other endothelial markers in cancers from various organs. Surgically resected cancer tissues from 188 patients comprising brain (n = 17), lung (n = 38), breast (n = 30), stomach (n = 30), colon (n = 31), liver (n = 32), and kidney (n = 10) cancers were immunohistochemically analyzed on tissue microarrays using a panel of eight endothelial markers. CD31 was expressed in vascular endothelial cells in cancer lesions as well as in non-cancerous areas (30-100%) in all core tissue samples. CD105 expression was intense and restricted to capillary endothelial cells in cancer lesions (>73%). In contrast, positive expression of CD105 was seen in <20% of non-cancerous areas in the same organs. However, no significant difference in CD105 expression in vascular endothelial cells between cancer lesions and non-cancerous areas from liver and renal cancer samples was found. Vascular endothelial growth factor (VEGF), Flt1, and Flk1 were also expressed, but only sporadically and in few samples (<30%), and transforming growth factor (TGF)-beta1 and TGF-betaRII were negative in vascular endothelial cells but generally positive in cancer cells. CD44 was strongly expressed in sinusoidal endothelial cells of the liver (90-100%). These results show that CD105 is expressed specifically in the tumor angiogenesis of brain, lung, breast, stomach, and colon cancers.

Adult↗

PubMed2005

Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers.

Some markers of angiogenic endothelial cells are emerging as targets of cancer therapy. The present study compares the expression of CD105 with that of other endothelial markers in all tissue layers during the development of colon cancer. We immunohistochemically analyzed the expression of the colon adenoma-carcinoma sequence by endothelial cells using a panel of eight endothelial markers. We examined sections from endoscopic mucosal resection and surgical resection of tubular adenoma (n=31), carcinoma in adenoma (n=11), and adenocarcinoma (n=34). Cylindrical cores were punched out from donor paraffin blocks of normal mucosa adjacent to tumors, from tumor lesions of mucosa, submucosa, muscularis propria, subserosa, and serosa, and from lymph node metastases. CD31 (PECAM-1) was universally expressed in the blood vessels of adenoma-carcinoma lesions as well as in normal mucosal vessels (80-95%), with no significant differences. In contrast, cancer-associated blood vessels (up to 80%) and cancer cells themselves expressed high levels of CD105. In normal mucosa, CD105 was weakly expressed in endothelial cells of capillaries (< or =21%), and significant differences in its expression in endothelial cells between the normal mucosa and adenoma, carcinoma in adenoma, and adenocarcinoma were found. Flt-1, Flk-1, transforming growth factor-beta1, transforming growth factor-beta receptor II, and CD44 were strongly expressed in the cancer cells but were not expressed in the blood vessels. Vascular endothelial growth factor was expressed at <30% in the blood vessels of adenoma, carcinoma in adenoma, and carcinoma. Moreover, this study provided evidence that CD105 was expressed exclusively in endothelial blood vessels by double immunostaining of CD105 and D2-40. The present study shows that de novo blood vessels of colon cancer specifically express CD105. These findings provide the basis for novel antiangiogenic cancer therapies.

Adult↗

PubMed2005

Expression of tubulin beta II in neuroepithelial tumors: reflection of architectural changes in the developing human brain.

Tubulin beta II (Tub-II) is widely distributed in the developing neuronal axons and dendrites. Recent studies have demonstrated that Tub-II is also important in the early development of the human brain, and Tub-II represents a marker for progenitor and neural stem cells. To elucidate the correlation between the developing brain and neuroepithelial tumors (NETs), the present study assessed Tub-II expression by NETs and normal brain tissue using immunohistochemical and immunoblot analyses. In the gliomas, decreased numbers and staining intensities of Tub-II-positive cells tended to be associated with increased differentiation. Conversely, neuronal neoplasms displayed high percentages and strong staining intensities among the Tub-II-positive cells, irrespective of differentiation. In neuronal neoplasms and neoplasms with neuronal differentiation, Tub-II staining was far more intense and more homogeneous than Tub-II staining in gliomas. These results indicate that the expression of Tub-II in NETs may reflect architectural changes in the developing brain and may support the hypothesis that neuroepithelial tumors originate from glioneuronal progenitor cells capable of generating astrocytic, and neuronal cell types.

Blotting, Western↗

PubMed2005

Probable chronic viral encephalitis with microglial nodules in the entire brain: a case report with necropsy.

BACKGROUND: Chronic encephalitis has rarely been seen, probably due to its viral origins, which may produce the disease in healthy or immunocompromised hosts. The etiology and pathophysiology of these types of encephalitis have not yet been clarified. CASE REPORT: A 63-year-old Japanese woman with underlying multiple myeloma developed chronic encephalitis with fever and progressive dementia, bilateral mild thalamic lesions on magnetic resonance imaging, and a prolonged pleocytosis, normal glucose value, and elevated interleukin-6 and interferon-gamma in the cerebrospinal fluid (CSF). The patient died of pneumonia 6 months after the onset of illness, and diffuse microglial nodules were found in the entire brain. No causative viral agents were identified by polymerase chain reaction and serological tests. CONCLUSIONS: The patient was presumed to have suffered from chronic viral encephalitis, based on clinical findings, including CSF and cytokine changes. Microglial nodules are observed in flavivirus group encephalitides, Rickettsia infections, and cytomegalovirus encephalitis in immunocompromised hosts. The possible pathogenesis of this rare encephalitis is discussed.

Autopsy↗

PubMed2005

Thrombus and encapsulated hematoma in cerebral cavernous malformations.

Thrombi, encapsulated hematomas, and granulation tissue are frequently seen in cerebral cavernous malformations (CCMs). We investigated the role that these histological changes play in repeated hemorrhages in CCMs as well as lesion growth, examining specimens of CCMs surgically harvested from 20 patients. The immunohistochemical study included thrombomodulin (TM) and endothelial cell protein C receptor (EPCR), which are important regulators of blood coagulation. Thick capsules, which contained blood degradation product, were seen in cases with encapsulated hematomas. Clusters of sinusoidal vessels were found outside of these thick capsules. Granulation tissue with inflammatory infiltrates and capillaries was seen in 4 cases with non-capsulated hematomas. Organizing thrombi were seen in sinusoidal vessels in 15 out of 20 cases. Factor VIII-related antigen staining demonstrated numerous capillaries in and around organizing thrombi and within the thickened vessel walls as well as in both the inner and outer sides of the hematoma capsule. TM and EPCR were positive in the endothelial cells of these capillaries, whereas they were negative in those of capillaries in the brain surrounding the lesions. Our study suggests that thrombosed sinusoidal blood vessels could gradually expand by repeated bleeding from numerous capillaries inside the wall and become encapsulated hematomas, and capillaries outside the thickened vessel wall could become sinusoidal blood vessels. Thrombosis within cerebral venules could be one of the causal factors of CCMs.

Actins↗

PubMed2005

[An autopsied case of limbic encephalitis associated with extremely high titers of anti-SS-A antibodies in serum and anti-neuronal antibodies in CSF].

A 76-year old man was referred to our department because of several episodes of generalized convulsion followed by a loss of consciousness and the right hemiparesis. The disturbed consciousness and hemiparesis disappeared soon but the personal change persisted thereafter. T2 and diffusion weighted images of MRI taken on the admission showed high intensity lesions in the left medial temporal lobe including the hippocampus. Antibodies (Abs) against herpes simplex virus were not elevated, however, serum titers of antinuclear and anti-SS-A/Ro Abs were extremely elevated. CSF IgG level and IgQ index were increased, and the CSF reacted with 78-kd bands on Western blots of rat brain homogenate. He died of bacterial pneumonia on the 28th day of illness and was autopsied. Malignant tumors were not found in any organs. In the left hippocampus, degeneration and loss of neurons, infiltration of macrophages, and microgliosis were observed. Vasculitis, however, was not found in the lesion. The immunohistochemical study showed that the CSF recognized the cytoplasm of neurons in the human hippocampus and also Purkinje cells. Those immunological and pathological findings thus suggest an antibody-mediated autoimmune limbic encephalitis in our case.

Aged↗

PubMed2004

SHP-1 expression in primary central nervous system B-cell lymphomas in immunocompetent patients reflects maturation stage of normal B cell counterparts.

SHP-1 is an important negative regulator involved in signaling through receptors for cytokine/growth factors, and differential patterns of SHP-1 expression in several types of B-cell lymphomas closely resemble the patterns seen in their normal B cell counterparts. In an effort to elucidate the origin of primary central nervous system lymphomas (PCNSL), the present study assessed 32 cases of PCNSL. Tumors were subclassified according to WHO classification and were evaluated by immunohistochemistry for expression of antigens associated with germinal center (GC) (CD10, Bcl-6) and non-GC stages (SHP-1, CD138). Twenty-nine cases showed diffuse large-cell centroblastic morphology, whereas three cases showed diffuse large-cell immunoblastic morphology. The immunophenotypes of PCNSL were as follows: SHP-1+/Bcl-6-/CD10-/CD138- (12 of 32 cases); SHP-1+/Bcl-6+/CD10-/CD138- (15 of 32 cases); SHP-1+/Bcl-6+/CD10+/CD138- (two of 32 cases); SHP-1+/Bcl-6-/CD10+/CD138- (one of 32 cases); and SHP-1-/Bcl-6-/CD10-/CD138- (two of 32 cases). These results indicate that PCNSL might be distinct lymphomas that originate from a late germinal center to an early postgerminal center.

Aged↗

PubMed2003

Epithelial differentiation in medulloblastoma: comparison with other embryonal tumors of neuroectodermal origin.

Three cases of medulloblastoma characterized by epithelial differentiation are described in patients 6-months-, 1-month- and 8-years-old. Histologically, tumors from the two infant patients showed a perivascular arrangement without apparent radiated cytoplasmic processes from the vessels. Tumor cells displayed round and/or pleomorphic vesicular nuclei and a more abundant eosinophilic cytoplasm than that found in classic medulloblastoma. Neither Homer-Wright rosettes nor ependymal or ependymoblastic rosettes were noted in these tumors. The tumor in the 8-year-old patient exhibited a classic medulloblastoma component intermingled with abundant eosinophilic cytoplasm forming a tubular structure. Immunohistochemically, tumor cells in all cases were positive for cytokeratin, synaptophysin, and vimentin. In the third case involving the 8-year-old patient, epithelial tumor cells were positive for cytokeratin, whereas classic medulloblastoma components were negative for cytokeratin. Positive staining for melanoma-specific antigen was seen only in the third case, where strong reactivity of tumor cells formed a tubulus. However, the classic medulloblastoma component was negative for melanoma-specific antigen. Ultrastructurally, basal laminae were observed around tumor cells in the 6-month-old patient. These morphological and immunohistochemical features suggest that medulloblastoma with epithelial differentiation is a rare but distinct variant of medulloblastoma, and that some of these tumors should show differentiation in ocular pigment epithelium.

Antigens, Neoplasm↗

PubMed2003

Fasciitis-like proliferation in the knee joint.

We describe the case of fasciitis-like proliferation in the knee joint in a 52-year-old man. The polypoid lesion developed from the synovial joint capsule around the quadriceps tendon and was impinging on the patellofemoral joint. Histologic and immunohistochemical studies revealed a myofibroblastic proliferation similar to nodular fasciitis. Until now, only 3 other cases have been reported in the English and Japanese language literature.

Arthroscopy↗

PubMed2002

Spinal extradural meningeal cyst: correct radiological and histopathological diagnosis.

OBJECT: Spinal extradural meningeal cysts are uncommon and rarely cause neural compression. The clinical, radiological, and histopathological characteristics of the lesions are discussed and previous reports reviewed. METHODS: The authors describe five cases of a spinal extradural meningeal cyst (three female and two male patients, with a mean age of 47 years (range 14-75 years). Four of the cysts were located at the thoracolumbar level, the fifth at the sacral level. Radiological and neuroimaging-based diagnosis was made using a combination of magnetic resonance imaging, myelography, and/or computerized tomography (CT) myelography. A connection between the spinal subarachnoid space and the cyst cavity was demonstrated on myelography and/or CT myelography in all cases, and dural defects were confirmed visually intraoperatively. In all cases histopathological examination confirmed that the cyst wall was formed by nonspecific fibrous connective tissue without a single-cell layer of inner arachnoid lining. CONCLUSIONS: A diagnosis of spinal extradural meningeal cyst is difficult to make based solely on histopathological examination. It is essential that the final characterization and diagnosis be based on intraoperative inspection combined with radiological and histopathological findings.

Adolescent↗

PubMed2002

Astroblastoma with unusual signet-ring-like cell components: a case report and literature review.

We report a case of astroblastoma with unusual signet-ring-like cell components. A 33-year-old-woman presented with occasional partial seizures of the face. Radiological studies revealed an enhanced frontal mass lesion. At surgery, a gray, soft, well-circumscribed mass was seen and shelled out. Histologically, the tumor showed a perivascular arrangement and papillary-like patterns with compact cellularity. The tumor cells radiating from the hyalinized vessels showed broader, shorter, less tapered processes. A part of each tumor cell displayed prominent islands of signet-ring-like cells. Glial fibrillary acidic protein reaction revealed strongly positive staining of tumor cells and signet-ring-like cells. Eight years after the operation the patient remains well with no tumor recurrence. It remains to be determined whether, in this astroblastoma, the unusual signet-ring-like cell components were related to benign biological characteristics or to the tumor's low-grade form with incidental signet-ring-like cell appearance.

Adult↗

PubMed2002

Primary intracerebral malignant fibrous histiocytoma in a child.

We report herein a rare case of pediatric intracerebral malignant fibrous histiocytoma (MFH). A 2-year-old boy gradually developed mild left hemiparesis and became somnolent. Magnetic resonance imaging upon admission revealed a well-enhanced mass lesion in the right frontotemporal operculum. Subtotal removal of the tumor was successfully performed using a right transsulcal and transcortical approach. The tumor developed as an extraaxial mass with brain adhesion to the arterial wall of the branch of the middle cerebral artery rather than to cerebral tissue. Pathological examination confirmed the presence of inflammatory-type MFH. Pediatric cases of intracerebral MFH are rare, and the possible origin of the tumor is discussed based on clinicopathological findings.

Brain Neoplasms↗

PubMed2002

Acute viral encephalitis: the recent progress.

In the new Japanese control law for infectious diseases, most varieties of acute viral encephalitis belong to Category IV requiring report of all cases at sentinel hospitals. Herpes simplex virus type 1 (HSV-1) encephalitis comprises the majority of cases. With the increased prevalence of diagnostic procedures such as polymerase chain reaction (PCR), several forms of HSV-1, and -2 central nervous system (CNS) infections, including acute disseminated encephalomyelitis, brainstem encephalitis, and myelitis, have been clarified. Since 1990 we have conducted a survey of HSV CNS infections in the Kyushu and Okinawa regions, and the data are reviewed here. Trends include an increase in a new subtype of non-herpetic acute limbic encephalitis. In contrast, the incidence of Japanese encephalitis (JE) in Japan has dramatically decreased to a few patients per year; however, JE remains a threat for those with decreased or absent immunity to the JE virus. Imported emerging and reemerging CNS infections such as Murray Valley and West Nile encephalitis can occur in Japan. Influenza-associated encephalitis/encephalopathy is also described as a threat for adults as well as young children.

Acute Disease↗

PubMedDate not supplied

Inhibition of endothelial cell proliferation, in vitro angiogenesis, and the down-regulation of cell adhesion-related genes by genistein. Combined with a cDNA microarray analysis.

Antiangiogenesis is presently one of the powerful strategies for treating cancer, and endothelial cells play a pivotal role in the process of angiogenesis. Genistein, a tyrosine kinase inhibitor, a major isoflavone plentiful in soybeans, is known to inhibit both tumor growth and angiogenesis. However, the precise molecular mechanism(s) by which genistein affects endothelial cells has yet to be elucidated. In the present study, a cDNA microarray was performed to investigate the targeted genes of human umbilical vein endothelial cells (HUVECs) affected by 10 microM genistein. As a result, a total of 256 genes showed an altered expression of more than twofold. Among them were the genes related to cell proliferation, adhesion, transcription, translation, metabolism, cytoskeleton, apoptosis, kinases, and functionally unknown. The down-regulation of mRNA or the protein expression of cell adhesion-related genes, including VE-cadherin, gap junction protein alpha 1 (connexin 43), integrin alpha V, and multimerin, were confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) or by immunofluorescence staining. The impaired cell-cell adhesion by genistein was also observed by electron microscopy. In addition, the antiangiogenesis role of genistein was confirmed on Matrigel using inverted microscopy and electron microscopy. In conclusion, genistein affects endothelial cells as a negative mediator of proliferation and angiogenesis in vitro, partially by down-regulating cell adhesion-related genes and impairing cell adhesions.

Angiogenesis Inhibitors↗