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Noriko Kimura

Publications and source records attributed to Noriko Kimura.

At least 19 recordsLinked to original sources
PubMed2006

A novel G106D alteration of the SDHD gene in a pedigree with familial paraganglioma.

Head and neck paragangliomas are tumors derived from parasympathetic paraganglia. Familial cases account for 10% or more of these tumors, and mutations of the genes encoding subunits for the mitochondrial respiratory chain complex II, SDHD, SDHB, and SDHC, have been reported. We analyzed mutations in the all four SDH genes, SDHA through SDHD, in a Japanese family with cervical paraganglioma that include a father with bilateral tumors and his daughter with a malignant left carotid body tumor with nodal metastasis. This pedigree harbored a germline G106D alteration in exon 4 of the SDHD gene that has not previously been reported to date. The tumors of the father expressed biallelic SDHD, but the SDHD expression was highly suppressed by an unknown mechanism(s) in tumors of his daughter, and the wild-type allele was predominantly suppressed in the metastatic node. These results suggest that the missense dysfunction of SDHD prepares neoplastic condition and that expressional silencing, particularly of the wild-type allele, plays an important role in the malignant transformation of the paragangliomas. Our results may lead to a better understanding of this disease and to the development of methods for prevention of this disease.

Alleles↗
PubMed2006

Pathology of pheochromocytoma and extra-adrenal paraganglioma.

The 2004 WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. While arbitrary, this nomenclature serves to emphasize important distinctive properties of intra-adrenal tumors that must be taken into account in clinical practice and research. Those include an often adrenergic phenotype, a relatively low rate of malignancy, and a predilection to occur in particular hereditary syndromes. Current roles of pathology are limited to distinguishing primary or metastatic pheochromocytomas/paragangliomas from other endocrine or nonendocrine tumors, and flagging tumors that show features suggestive of malignant potential or syndromic disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy. Pathology practice currently rests mostly on interpretation of conventional histological sections stained with hematoxylin and eosin, with variable ancillary application of immunohistochemical staining. Malignancy is currently defined by the presence of metastases, not local invasion. Local invasion alone is a poor predictor of metastases, and the absence of apparent invasion does not preclude development of metastases. The two types of aggressive behavior might therefore have different biological underpinnings, and those will be resolved most effectively if consistent terminology is employed. In order to be optimally informative, pathology reports must employ consistent nomenclature and incorporate standard elements. Templates or checklists for minimal standard reporting are recommended by several pathology associations, but identification of some recommended and optional elements is currently subjective or inconsistent.

Adrenal Gland Neoplasms↗
PubMed2005

Granulocyte-colony stimulating factor- and interleukin 6-producing diffuse deciduoid peritoneal mesothelioma.

An autopsy case of granulocyte colony-stimulating factor (G-CSF)- and interleukin-6 (IL-6)-producing diffuse deciduoid peritoneal mesothelioma is reported. The patient was a 70-year-old man with abdominal distension and weight loss in the year prior to his death. Laboratory data suggested severe inflammation with marked leukocytosis, thrombocytosis and elevated serum levels of C-reactive protein, G-CSF and IL-6. Imaging studies showed an expansive mass occupying the entire abdomen and pelvic cavity. Histological diagnosis of tissue taken by needle biopsy was difficult due to the unusual sarcomatoid-appearance of the tumor. In addition, there was severe infiltration of numerous neutrophilic leukocytes. An autopsy revealed that the diffuse peritoneal tumor had a fresh fishmeat-like appearance with focal mucinous degeneration and entirely encased the abdominal organs. Histological examination showed a sheet-like proliferation of tumor cells with large ovoid or polygonal cytoplasm, large atypical nuclei and obvious nucleoli. The tumor cells showed abundant glycogen and hyaluronic acid, and were immunoreactive to cytokeratin, calretinin, epithelial membrane antigen (EMA), CA-125, and focally to vimentin. The tumor cells were immunoreactive to G-CSF and IL-6. Electron microscopy revealed long, slender microvilli on the tumor cell surface. This tumor was diagnosed as a G-CSF- and IL-6-producing, diffuse deciduoid mesothelioma. We report this case with special reference to the differential diagnosis of deciduoid peritoneal mesothelioma with paraneoplastic syndrome.

Aged↗
PubMed2005

Podoplanin as a marker for mesothelioma.

Podoplanin is a specific marker for lymph vessel endothelial cells. It was noted that podoplanin is expressed in reactive mesothelial cells. The utility of podoplanin for the histological diagnosis of tumors was then investigated, especially for mesothelioma. Immunohistochemical study of podoplanin was carried out in five malignant mesotheliomas and 118 other tumors including 93 adenocarcinomas, four squamous cell carcinomas, six gastrointestinal stromal tumors and five endocrine tumors. Immunoreactivity for podoplanin was demonstrated on the cell membrane of tumor cells for all mesotheliomas. All other tumors were negative for podoplanin. Among the many antibodies used for differential diagnosis of malignant mesothelioma, podoplanin has the potential to be an excellent tumor marker in both specificity and sensitivity. The utility of podoplanin as a marker for mesothelioma will be confirmed by further studies.

Adenocarcinoma↗
PubMed2005

Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colon.

Herein is presented a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron-dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors' knowledge, the present case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma.

Aged↗
PubMed2005

Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors.

Pheochromocytomas and extra-adrenal sympathetic paragangliomas show varied histological patterns, and it is difficult to diagnose malignancy or predict the clinical course using current histological criteria. In the present study, we reviewed 146 sympathetic paragangliomas including 116 adrenal (102 unilateral, 14 bilateral) and 30 extra-adrenal tumors including 38 metastatic tumors. We developed a scoring scale according to the following six factors: histological pattern, cellularity, coagulation necrosis, vascular/capsular invasion, Ki-67 immunoreactivity, and types of catecholamine produced. The tumors were classified as well (WD), moderately (MD), and poorly differentiated (PD) types according to their scores. The frequency of these tumor types were 113 WD (77%), 27 MD (19%), and 6 PD (4%). Metastasis was observed in 15 of 113 WD (13%), 17 of 27 MD (63%), and all 6 PD (100%). Five-year survivals of patients with metastases were 92% with WD, 69% with MD, 0% with PD. Respective 10-yr survivals were 83%, 38%, and 0%. Differences between groups were statistically significant. The data show that using this grading scoring system for sympathetic paragangliomas correlates with both metastatic potential and patient survival.

Adrenal Gland Neoplasms↗
PubMed2004

Spontaneous rupture of adrenal pheochromocytoma with capsular invasion.

A 67-year-old Japanese man developed a sudden onset of severe right-side upper abdominal pain, nausea and vomiting. On hospitalization, physical examination revealed sweating, tachycardia, hypertension and the appearance of peripheral vasoconstriction. An urgent computed tomography scan with contrast demonstrated a large hematoma in the right retroperitoneal space. A phentolamine test and an 131iodine metaiodobenzylguanidine scan suggested pheochromocytoma. An elective right adrenalectomy was successfully performed after pretreatment for sufficient volume replacement with continuous administration of alpha- and beta-adrenergic blocking agents. Pathological diagnosis was an adrenal pheochromocytoma 9.0 x 6.5 cm in diameter with evidence of capsular invasion, which could be associated with a tear in the capsule.

Abdomen, Acute↗
PubMed2003

Immunohistochemical localization of human pineal tissue antigens in normal retina and retinoblastomas.

The normal human retina and retinoblastomas were examined immunohistochemically to assess the localization of pineal antigens in the retina and the oncogenesis and differentiation of retinoblastoma. In the present study, 41 eyes excised from children (aged 4 months to 7 years, all unilateral occurrence) diagnosed to have retinoblastoma and 4 eyes with normal retinas, were used. Retinoblastomas were histopathologically classified into well-differentiated, moderately-differentiated, and poorly-differentiated types. The antibodies used were 9 monoclonal antibodies to human pineal antigens and 6 antibodies to neural tissues. In the normal retina, staining patterns characteristic of retinal cell layers were observed with PP1, PP3, PP5, PP6, PI1, and PI2 antibodies. In retinoblastomas, PP5 antibody, which reacts with horizontal cells and ganglion cells, and PP6 antibody, which reacts with part of the bipolar cells in the inner nuclear layer, showed intense staining in well-differentiated retinoblastomas, but the intensity of staining and the positivity decreased with the degree of dedifferentiation. Antigens recognized by PP3 and PP4 antibodies were positive in all retinoblanstomas. Reactions to GFAP antibody and antibodies that recognize Müller cells were negative. Retinoblanstomas may express markers of not only photoreceptor cells but also other retinal nuclear cells. These results suggest that the retinoblastoma might be developed from visual stem cells, which are common progenitor cells of photoreceptor cells, intermediate neurons, and ganglion cells.

Antibodies, Monoclonal↗
PubMed2003

Acute eosinophilic pneumonia associated with intravesical bacillus Calmette-Guérin therapy of carcinoma in situ of the bladder.

A 71-year-old man with a history of rheumatoid arthritis was treated with intravesical bacillus Calmette-Guérin (BCG) instillation of 80 mg once-a-week for carcinoma in situ. He developed low-grade fever followed by dyspnea and severe hypoxemia. Radiological and laboratory studies revealed bilateral diffuse reticulonodular infiltrates and hypereosinophilia. A lymphocyte stimulation test for BCG was strongly positive. From these findings, a pulmonary hypersensitivity reaction to immunotherapy was suspected, and therefore, methylprednisolone (500 mg per day) was started. After that, the fever and dyspnea disappeared, the hypereosinophilia was normalised and chest radiography results were clear. The present case is the first reported case of eosinophilic pneumonia following intravesical BCG therapy.

Acute Disease↗
PubMed2003

Synovial sarcoma with massive ossification--a case report.

Synovial sarcoma with extensive osteoid production is rare. We report a case of synovial sarcoma of monophasic type with massive ossification. The diagnosis was confirmed by reverse-transcripitase polymerase chain reaction (RT-PCR). The patient was an-81-year-old woman with recurrent synovial sarcoma in her right knee. The tumor was primarily excised in 1989. It recurred and was removed again in 1996. However, in 1999 a painful mass appeared in the same site. Preoperative plain radiography and computed tomography revealed a 5 x 5 cm soft tissue mass with extensive ossification in the medial side of the right knee joint. The tumor was widely excised in 2000. Soft X-ray examination revealed a trabecular pattern of ossification in the excised tumor. Microscopically the tumor was composed of hypercellular spindle cells with fascicular arrangement with prominent ossification but no epithelial component. The tumor cells were positive for vimentin and focally positive for cytokeratin. The tumor expressed a sequence of SYT-SSX1 fusion gene transcript demonstrated by RT-PCR. Twelve years long survival of the present case without metastasis in spite of repeated recurrence suggests a better prognosis of synovial sarcomas with ossification.

Aged↗
PubMed2002

Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth.

Myelin inhibitors of axonal regeneration, like Nogo and MAG, block regrowth after injury to the adult CNS. While a GPI-linked receptor for Nogo (NgR) has been identified, MAG's receptor is unknown. We show that MAG inhibits regeneration by interaction with NgR. Binding of and inhibition by MAG are lost if neuronal GPI-linked proteins are cleaved. Binding of MAG to NgR-expressing cells is GPI dependent and sialic acid independent. Conversely, NgR binds to MAG-expressing cells. MAG, but not a truncated MAG that binds neurons but does not inhibit regeneration, precipitates NgR from NgR-expressing cells, DRG, and cerebellar neurons. Importantly, NgR antibody, soluble NgR, or dominant-negative NgR each prevent inhibition of neurite outgrowth by MAG. Also, MAG and Nogo66 compete for binding to NgR. These results suggest redundancy in myelin inhibitors and indicate therapies for CNS injuries.

Animals↗
PubMed2002

Neurofibromin and NF1 gene analysis in composite pheochromocytoma and tumors associated with von Recklinghausen's disease.

Composite tumor of pheochromocytoma and neuroblastoma, or ganglioneuroma, or ganglioneuroblastoma (composite pheochromocytoma), also known as mixed neuroendocrine and neural tumor, are sometimes combined with neurofibromatosis type 1 (NF1). To better understand the relationship between NF1 and composite pheochromocytoma, an immunohistochemical study using anti-neuro-fibromin that is an NF1 gene product and DNA sequence of NF1 Exon 31 were carried out in five cases of composite pheochromocytoma and in various tumors from five patients with NF1. Neurofibromin was not expressed in Schwann cells and sustentacular cells of composite pheochromocytomas and was very weakly or negatively expressed in neurofibroma of NF1 patients. However, it was strongly expressed in ganglionic cells and pheochromocytoma cells of the composite pheochromocytomas and also in mucosal ganglioneuromas, a gangliocytic paraganglioma, and in pheochromocytomas from the patients with NF1. Although there was no mutation in NF1 Exon 31, it could not be ruled out that there were mutations in other sites of the NF1 gene. Neurofibromin insufficiency may induce abnormal proliferation of Schwann cells in composite pheochromocytomas as well as in neurofibromatosis.

Adrenal Gland Neoplasms↗
PubMed2002

Chromogranin A and chromogranin B in noninvasive and invasive breast carcinoma.

Recent progress in the study of chromogranins has revealed that there are many novel peptides derived from chromogranin with their multiple pathophysiologic roles. To learn the possible roles of chromogranin in breast carcinoma, we immunohistochemically investigated tissue localization of chromogranin A (CgA) and chromogranin B (CgB) in 10 normal breast tissues, 23 noninvasive ductal carcinomas (NIDCs), and 169 invasive ductal carcinomas (IDCs) and compared their expression with estrogen receptor (ER), progesterone receptor (PR), and Ki67. CgA and CgB were sporadically detected in normal cells of the ducts, acini, and luminal secretion. The expression of CgA and CgB was higher in NIDCs than in IDCs: CgA = 70% of NIDC vs 22% of IDC and CgB = 65% of NIDC vs 30% of IDC. There was a statistical correlation between the expression of CgA and PR (p < 0.05) and CgB and ER (p < 0.05) in IDCs without lymph node metastasis. On the other hand, there was a significant correlation between expression of CgB and PR and an inverse correlation between CgA and Ki67 in IDCs of overall cases. The data suggest that CgA and CgB may play some role in the early phase of neoplastic progression.

Biomarkers, Tumor↗
PubMed2001

Decreased sensitivity of distal nephron and collecting duct to parathyroid hormone in pseudohypoparathyroidism type I.

Parathyroid hormone (PTH) transiently increases urinary excretion of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase, which is distributed mainly in proximal tubules. The response is reduced in pseudohypoparathyroidism (PHP) type I, which is characterized by target-organ resistance to PTH. Evidenced by normal calcium resorption, distal tubule sensitivity to PTH has been believed to be normal in this disorder. This hypothesis was tested through a search for another marker of distal nephron sensitivity to PTH. In the human kidney, cathepsin D was expressed predominantly in distal segments of the nephron, cortical and medullary thick ascending limbs of Henle's loop, distal convoluted tubules, and connecting tubules and in cortical collecting ducts and medullary collecting ducts. PTH infusion transiently increased cathepsin D excretion in normal subjects. The cathepsin D response to PTH was reduced in the patients with PHP type I. The decrease in cathepsin D response in PHP type I indicates a resistance to PTH in the distal nephron (cortical thick ascending limbs of Henle's loop, distal convoluted tubules, and connecting tubules) and cortical collecting ducts. These observations suggest that the preservation of renal tubular sensitivity to PTH in this disorder may be confined to PTH-dependent calcium resorption in distal tubules.

Acetylglucosaminidase↗
PubMed1996

Tissue Localization of Nerve Growth Factor Receptors: trk A and Low-Affinity Nerve Growth Factor Receptor in Neuroblastoma, Pheochromocytoma, and Retinoblastoma.

The immunohistochemical localization of nerve growth factor receptor (NGFR)-high-affinity NGFR (trk A) and low-affinity NGFR (LNGFR)-was investigated in 23 neuroblastoma group tumors, 18 pheochromocytomas, 2 mixed neuroendocrine-neural tumors, and 16 retinoblastomas. trk A was expressed in the tumor cells of all neuroblastomas, pheochromocytomas, and retinoblastomas. Immunoreactive intensity was especially strong in the larger ganglionic tumor cells of ganglioneuroblastoma and ganglioneuroma. Messenger RNA (mRNA) of trk A was also strongly expressed in the ganglionic cells of ganglioneuroblastomas and chromaffin cells of pheochromocytomas by in situ hybridization method. LNGFR was negative in the tumor cells of neuroblastoma; however, it showed strong immunoreactivity in ganglionic tumor cells and Schwann cells of ganglioneuroblastoma/ganglioneuroma, and sustentacular cells of pheochromocytoma. Although normal retina expressed both trk A and LNG FR, tumor cells of retinoblastoma were positive for only trk A but negative for LNGFR. Such differences in the expression of trk A and LNGFR may reflect neuronglial interactions in the survival and maturation of the sympathetic nerves, retina, and tumors in these tissues.

Journal Article↗
PubMed1996

Deficiency of Phenylethanolamine N-Methyltransferase in Norepinephrine-Producing Pheochromocytoma.

Pheochromocytoma is a catecholamine (CA)-producing tumor that is classified into two types: the norepinephrine (NE) and the mixed NE and epinephrine type (E-type) from plasma CA levels. Phenylethanolamine N-methyltransferase (PNMT) is the terminal enzyme in CA synthesis; it catalyzes the synthesis of E from NE. It is not known whether the absence of immunoreactive PNMT is paralleled by a lack of PNMT mRNA. The mRNA of tyrosine hydroxylase (TI-I) and PNMT in seven pheochromocytomas, five NE-type and two E-type tumors, were examined by Northern blot analysis and in situ hybridization (ISH) technique. TH mRNA was detected in all tumors but PNMT mRNA was limited only to the E-type tumors. In addition to our previous immunohistochemical study of 70 pheochromocytomas and paragangliomas in which all pheochromocytomas had cells immunoreactive to TH, but PNMT was expressed only in E-type, we concluded that NE-type pheochromocytoma lacks PNMT both at the mRNA and protein levels, resulting in an inability to produce E. The essential difference between NE-type and E-type pheochromocytoma is that the NE-type lacks PNMT.

Journal Article↗