Biomedical subjects

M Fukayama

Publications and source records attributed to M Fukayama.

At least 37 records · Page 2Linked to original sources

PubMed2001

Pulmonary gangliocytic paraganglioma: case report and comparative immunohistochemical study of related neuroendocrine neoplasms.

The authors report a case of gangliocytic paraganglioma of the lung, which has not yet been described in a pulmonary neoplasm. A 75-year-old man underwent right middle and lower lobe lobectomy. A slightly yellowish mass was located at the bifurcation between the lower and middle lobe bronchus, protruding into the truncus intermedius. The neoplastic cells were composed of three cellular elements: uniform endocrine cells in a Zellballen arrangement, large ganglion-like cells within the nests of endocrine cells, and spindle-shaped cells arranged in streams to surround the nests. Each component exhibited the characteristic immunohistochemical properties, which were similar to those of the corresponding neuroendocrine neoplasms: Endocrine cells were positive for CAM 5.2, chromogranin A, and synaptophysin, like carcinoid tumor; ganglion-like cells were positive only for neurofilament, like ganglioneuroma; and spindle-shaped cells were positive for neurofilament and S-100 protein, like paraganglioma. These results agreed with those in gangliocytic paraganglioma of the duodenum. Pulmonary gangliocytic paraganglioma is similar to that in the duodenum, and is a hamartomatous proliferation of epithelial endocrine and neuronal cells of the bronchus.

Aged↗

PubMed2001

Detection of t(I 1; 18) in MALT-type lymphoma with dual-color fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction analysis.

t(11:8) is a recurrent chromosomal abnormality observed in mucosa-associated lymphoid tissue (MALT)-type lymphoma. API2 and MLT genes have been implicated. The authors devised a dual-color interphase fluorescence in situ hybridization (FISH) system to detect splitting of 11q22 and its fusion with 18q21. Subjects were 44 cases of extranodal lymphoma and cases of primary macroglobulinemia. Whenever RNA was available, reverse transcriptase-polymerase chain reaction followed by sequence analysis was performed. Positive cases by dual-color FISH analysis were restricted to MALT-type lymphoma and one case of primary macroglobulinemia. Among 24 cases of MALT-type lymphoma, 14 (58%) (4 gastric, 5 pulmonary, 3 orbital, 1 salivary, and 1 thyroid lymphomas) had splitting of the 11q22 region probes and fusion of signals suggesting the translocation of chromosome 11 and 18. Reverse transcriptase-polymerase chain reaction analysis showed the API2/MLT gene fusion in 9 of 10 cases. Sequence analyses showed three different modes of involvement of the MLT gene, whereas the breakpoint at API2 was the same. Monoclonal component of serum immunoglobulin M was observed in 3 of 14 positive cases for the translocation. Direct visualization using dual-color FISH on samples serves as a molecular tool for management of MALT-type lymphoma with API2/MLT gene fusion.

Adult↗

PubMed2001

Mutations in c-kit gene exons 9 and 13 in gastrointestinal stromal tumors among Japanese.

Gain-of-function mutation in c-kit proto-oncogene exon 11 has been described in about 20 -- 50% of gastrointestinal stroma tumor (GIST). Recently, additional mutational hot-spots in exon 9 and exon 13 of the c-kit gene have been reported in GISTs without mutations of exon 11, but a subsequent report in a Western population indicated that only a small portion of GISTs (eight of 200 GISTs, 4%) showed mutations in these regions. In this study, we evaluated mutations in exon 9 and exon 13 of the c-kit gene by both polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing in 48 GISTs in a Japanese population, for which the clinicopathological and immunohistochemical features and mutations in exon 11 had previously been reported. C-kit gene mutation in exon 9, representing insertion of GCC TAT, was identified in only 4 of 48 GISTs (8%), and none of the GISTs had mutations in exon 13. All four GISTs with mutation in exon 9 were high-risk, and the patients died of multiple tumor metastasis. Mutations in exon 9 and exon 13 of the c-kit gene were also rare events in Japanese GISTs and were related to a poor prognosis. These results in Japanese are consistent with those in Western populations, although a preferential occurrence of GISTs with exon 9 mutation in the small intestine, which was suggested in a previous report, was not observed.

Actins↗

PubMed2001

Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes.

PPARgamma is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARgamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARgamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.

3T3 Cells↗

PubMed2001

[A case of primary lung adenocarcinoma with diffuse calcification in the tumor by psamoma bodies].

A 78-year-old asymptomatic woman was referred to our department for the treatment of a right lung tumor. The patient had been suffering from rheumatoid arthritis and followed up in outpatient clinic. On March 6, 1995, abnormal shadow in the right upper lobe was pointed out by routine chest X-ray. Chest CT revealed calcification in the shadow, and benign lesion, such as old pulmonary tuberculosis, was suspected. During follow-up, the size of the shadow and calcification area in the shadow gradually increased. Malignancy was suspected based on the increasing size of the tumor. On July 12, 2000, video-assisted right upper lobectomy with hilar and mediastinal lymph node sampling was performed. Pathological examination revealed that the tumor was primary lung adenocarcinoma containing psamoma bodies in the tumor.

Adenocarcinoma↗

PubMed2000

Epstein-Barr virus-encoded poly(A)(-) RNA supports Burkitt's lymphoma growth through interleukin-10 induction.

Akata and Mutu cell lines are derived from Burkitt's lymphoma (BL) and retain the in vivo phenotype of Epstein-Barr virus (EBV) expression that is characterized by expression of EBV-determined nuclear antigen 1 (EBNA1), EBV-encoded RNAs (EBERs) and transcripts from the BAM:HI A region (BARF0). We found that EBV-positive Akata and Mutu cell clones expressed higher levels of interleukin (IL)-10 than their EBV-negative subclones at the transcriptional level. Transfection of an individual EBV latent gene into EBV-negative Akata cells revealed that EBERs were responsible for IL-10 induction. Recombinant IL-10 enabled EBV-negative Akata cells to grow in low (0.1%) serum conditions. On the other hand, growth of EBV-positive Akata cells was blocked by treatment either with an anti-IL-10 antibody or antisense oligonucleotide against IL-10. EBV-positive BL biopsies consistently expressed IL-10, but EBV-negative BL biopsies did not. These results suggest that IL-10 induced by EBERs acts as an autocrine growth factor for BL. EBERs, EBER1 and EBER2, are non-polyadenylated RNAs and are 166 and 172 nucleotides long, respectively. The present findings indicate that RNA molecules could regulate cell growth.

Burkitt Lymphoma↗

PubMed2000

Neuronal expression of the fukutin gene.

Fukuyama-type congenital muscular dystrophy (FCMD), a relatively common autosomal recessive disorder in Japan, is characterized by severe congenital muscular dystrophy in combination with cortical dysgenesis (polymicrogyria). The gene responsible for FCMD encodes a novel protein, fukutin, which is likely to be an extracellular protein. Pathological study of brain tissue from FCMD fetuses revealed frequent breaks in the glia limitans and basement membrane complex. Disruption of the basal lamina in FCMD muscle was also seen. Thus, structural alteration of the basal lamina appears to play a key role in the pathophysiology of FCMD. To investigate the role of fukutin in brain anomalies, we examined fukutin mRNA expression in the human brain. Northern blot and RT-PCR analysis revealed that the fukutin gene is expressed at similar levels in fetal and adult brain, whereas its expression is much reduced in FCMD brains. Tissue in situ hybridization analysis revealed fukutin mRNA expression in the migrating neurons, including Cajar-Retzius cells and adult cortical neurons, as well as in hippocampal pyramidal cells and cerebellar Purkinje cells. However, we observed no expression in the glia limitans, the subpial astrocytes (which contribute to basement membrane formation) or other glial cells. In the FCMD brain, neurons in regions with no dysplasia showed fair expression, whereas transcripts were nearly undetectable in the overmigrated dysplastic region. These observations suggest that fukutin function may influence neuronal migration itself rather than formation of the basement membrane. Furthermore, differences in mRNA levels among neurons in early developmental stages may partially differentiate normal and abnormal regions.

Adult↗

PubMed2000

Constitutive tyrosine phosphorylation of ErbB-2 via Jak2 by autocrine secretion of prolactin in human breast cancer.

Overexpression of the oncogene for ErbB-2 is an unfavorable prognostic marker in human breast cancer. Its oncogenic potential appears to depend on the state of tyrosine phosphorylation. However, the mechanisms by which ErbB-2 is constitutively tyrosine-phosphorylated in human breast cancer are poorly understood. We now show that human breast carcinoma samples with ErbB-2 overexpression have higher proliferative and metastatic activity in the presence of autocrine secretion of prolactin (PRL). By using a neutralizing antibody or dominant negative (DN) strategies or specific inhibitors, we also show that activation of Janus kinase Jak2 by autocrine secretion of PRL is one of the significant components of constitutive tyrosine phosphorylation of ErbB-2, its association with Grb2 and activation of mitogen-activated protein (MAP) kinase in human breast cancer cell lines that overexpress ErbB-2. Furthermore, the neutralizing anti-PRL antibody or erbB-2 antisense oligonucleotide or DN Jak2 or Jak2 inhibitor or DNRas or MAP kinase kinase inhibitor inhibits the proliferation of both untreated and PRL-treated cells. Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation. The identification of this novel cross-talk between ErbB-2 and the autocrine growth stimulatory loop for PRL may provide new targets for therapeutic and preventive intervention of human breast cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Aspiration and imprint cytopathology of thyroid carcinoma associated with familial adenomatous polyposis.

Thyroid carcinomas occur in association with familial adenomatous polyposis (FAP), and some are the first symptom of FAP. Although several histological features have been reported, the cytopathology of FAP-associated thyroid carcinoma has not yet been described. We report on two cases of FAP-associated thyroid carcinomas diagnosed by fine-needle aspiration biopsy and one case imprinted after resection. All 3 patients belonged to the same family, and thyroid carcinoma was the first symptom of the proband. Cytological features include fascicular or whorl formation of spindle cells with papillary, follicular, and/or solid architectures, in addition to the typical features of papillary carcinoma. The cytological features of FAP-associated thyroid carcinomas are characteristic and may suggest FAP.

Adenomatous Polyposis Coli↗

PubMed2000

Apoptosis and its regulation in flat-type early colorectal carcinoma: comparison with that in polypoid-type early colorectal carcinoma.

PURPOSE: The aim of this study was to investigate the relationship among apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins (p53, p21 (WAF1/CIP1), and bax) in flat-type early colorectal carcinoma and to compare these factors with those in polypoid-type early colorectal carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissues of 11 flat-type early colorectal carcinomas and 17 polypoid-type early carcinomas were studied. The histologic diagnosis was either well-differentiated adenocarcinoma or carcinoma in adenoma, and the depth of invasion was limited to mucosa or submucosa. Apoptotic cells were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method, and proliferative activity was determined by Ki-67 immunohistochemistry using monoclonal antibody MIB-1. Apoptosis-regulating proteins were determined by immunohistochemistry using antibody DO-7 (p53), Cip1 (p21 (WAF1/CIP1)), and Bax (bax). RESULTS: There was no significant difference in terminal deoxynucleotide transferase-mediated deoxy-uridine triphosphate-biotin nick end-labeling index between flat-type early colorectal carcinoma and polypoid-type early carcinoma, at 1.9 vs. 1.1, respectively. In flat-type carcinoma terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index in the p53 protein overexpression group was significantly smaller than that in the p53 protein-negative group (P < 0.05). The Ki-67 labeling index/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio in the p53 protein overexpression group was significantly higher than that in the p53 protein-negative group (P < 0.05). In polypoid-type carcinoma, the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index and Ki67/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio showed no significant difference between the p53 protein overexpression group and p53 protein-negative group. CONCLUSION: p53-dependent apoptosis may contribute to the development of flat-type early colorectal carcinoma. Apoptosis and its regulation in flat-type early colorectal carcinoma may differ from those in polypoid-type carcinoma.

Apoptosis↗

PubMed2000

An autopsy case of Alzheimer's disease with a progressive supranuclear palsy overlap.

A 74-year-old man developed abnormal forgetfulness, soon followed by unstable speech content and marked disorientation. At 77 years of age, the patient started to occasionally fall, an aspect of progressive supranuclear palsy. He then became bedridden. The patient eventually died of pneumonia at 79 years of age. Neuropathological examination revealed profiles of both progressive supranuclear palsy and Alzheimer's disease. Although the two conditions both belong to tauopathy, their pathologically proven combination was rare. Furthermore, the case had the possibility of being a subgroup of tauopathy.

Aged↗

PubMed2000

Expression of cytokeratin 1, 5, 14, 19 and transforming growth factors-beta1, beta2, beta3 in osteofibrous dysplasia and adamantinoma: A possible association of transforming growth factor-beta with basal cell phenotype promotion.

To elucidate the precise origin and characteristics of the epithelial components of osteofibrous dysplasia (OF) and adamantinoma (AD), the expression of transforming growth factor (TGF)-beta1, beta2 and beta3 and cytokeratin (CK) subtypes were studied in five cases of AD and 18 cases of OF by immunohistochemistry. CK1 was expressed in 10 out of 18 OF cases; CK5 was expressed in one OF case; CK14 was positively stained in 10 cases of OF; CK19 was positively stained in 16 OF cases; CK1 was expressed in three out of five AD cases; CK5 was expressed in one case of AD; CK14 was positively stained in four AD cases; and CK19 was positively stained in five AD cases. In OF, TGF-beta1, beta2 and beta3 were expressed in both fibroblasts and osteoblasts. In AD, TGF-beta1, beta2 and beta3 were expressed in both epithelial and fibrous components. These results suggest that epithelial components of AD and OF share epidermal characteristics, CK1, express basal cell phenotype and cytokeratins 5, 14 and 19. In addition to these epithelial characteristics, strong immunoreactivity for TGF-beta poses the possibility of TGF-beta promotion of basal cell phenotype expression for the epithelial components in OF and AD.

Adolescent↗

PubMed2000

CD70 expression in thymic carcinoma.

CD70, a type II transmembrane glycoprotein, is a member of the tumor necrosis factor (TNF) family that mediates the interaction between B- and T-lymphocytes. CD70 has been shown to be expressed by malignant lymphoma, especially Hodgkin's disease, and by nasopharyngeal carcinoma, both of which are frequently associated with Epstein-Barr virus (EBV). In this study, we investigated the expression of CD70 in epithelial cells of various types of thymic epithelial tumors and its association with EBV. Immunohistochemical expression of CD70 was studied on frozen tissue. In a series of 27 thymic epithelial tumors, including thymic carcinomas (n = 8), atypical thymomas (n = 5), thymomas (n = 13), and thymic carcinoid (n = 1), 7 (88%) thymic carcinomas and 1 (20%) atypical thymoma showed positive immunoreactivity for CD70, whereas CD70 was not detected in other tumors. Twenty-four intrathoracic malignant epithelial tumors of nonthymic origin, including lung (n = 17), esophagus (n = 5), and mesothelium (n = 2), showed no immunoreactivity for CD70. Northern blot analysis also revealed that CD70 messenger RNA was expressed in 2 of 2 thymic carcinomas, 0 of 2 atypical thymomas. and 0 of 2 thymomas. All of the 27 thymic epithelial tumors were EBV-negative as assessed by EBV-encoded small RNA in situ hybridization. The expression of CD70 is closely related to the pathogenesis of thymic carcinoma but unrelated to EBV infection in the thymus.

Antigens, CD↗

PubMed2000

Nuclear localization of immunoreactive beta-catenin is specific to familial adenomatous polyposis in papillary thyroid carcinoma.

Thyroid carcinoma is the first symptom in some patients with familial adenomatous polyposis (FAP). We evaluated the cellular localization of beta-catenin in thyroid carcinomas associated (n = 4) or not associated (n = 173) with FAP, since loss of functional protein of the adenomatous polyposis coli (APC) gene leads to nuclear accumulation of beta-catenin in adenomas and carcinomas of the FAP colon. Immunoreactive beta-catenin was demonstrated at the cell membrane of glandular cells of the non-neoplastic thyroid and non-FAP carcinomas. On the other hand, cytoplasmic and nuclear accumulation of beta-catenin is specific to FAP-associated papillary carcinomas. The abnormality in the APC / beta-catenin pathway is thus also important in FAP-associated thyroid carcinoma, and beta-catenin immunohistochemistry is a feasible screening method to identify occult FAP in young patients with thyroid tumors.

Adenomatous Polyposis Coli↗

PubMed2000

Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Since c-kit mutation occurs only in one-third of GIST, there might be other molecular mechanisms. Loss of heterozygosity (LOH), microsatellite instability (MSI) and NF2 gene mutation were investigated in 22 GISTs (9 low-risk and 13 high-risk tumors). LOH and MSI were evaluated using 41 markers on 21 chromosomal arms, and NF2 gene mutation was examined by PCR-SSCP. High frequency of LOH was observed on 14q (9 / 19, 47%), and 22q (17 / 22, 77%). The frequencies were similar in low-risk and high-risk tumors, and were unrelated with gastric or intestinal origin. Two other abnormalities, additional LOH on other chromosomes and MSI at more than two loci, were characteristic of the high-risk tumors (P < 0.05). NF2 gene mutation was identified in two cases showing 22q-LOH (8 bp deletion on the splice donor site of exon 7, and 1 bp insertion at position 432 of exon 4, which resulted in nonsense mutation). There was no significant correlation between these results and c-kit gene mutation, which was observed in 8 of 22 tumors. Suppressor genes on 14q and 22q may be involved, independently of c-kit gene mutation, in the development of GIST. NF2 contributes as a tumor suppressor in a small subset of GIST. These abnormalities are presumably followed by increased genetic instability.

Adult↗

PubMed2000

High incidence of acute myositis with type A influenza virus infection in the elderly.

We describe six elderly cases of acute myositis with type A influenza virus infection (Sydney) during the 1998-1999 outbreak. All six cases suffered from myalgia or muscle weakness especially in the lower extremities and the serum creatine kinase (CK) values were elevated above 1,000 IU/l without MB isoenzymes or electrocardiogram abnormalities. There have been a few case reports of acute myositis associated with influenza virus infection in the elderly. However, we noticed a high incidence of acute myositis among elderly patients with type A influenza virus infection. This complication may occur more commonly in elderly patients than has previously been thought.

Acute Disease↗

PubMed2000

[Effect of the level of basic activities of daily living on home caregiver burnout].

To relieve the stress of caregivers, it is critical to identify and classify the burden factors in the elderly patients. In order to determine the factors that exhaust caregivers, a cross sectional survey was done. The study employed a self-recording questionnaire form which included the Pines' burnout scale and the level of patient's basic activities of daily living (BADL). Seventy-three caregivers filled in the questionnaire. They reported the difficulty of care for an elderly patient in the home, and the degree of the difficulty correlated well with the burnout score (r = -0.517; p < 0.001). The caregivers' burnout score did not correlate so well with the level of their patient's BADL (r = -307; p = 0.014). Among the factors in BADL, aid for toilet use, feeding, sitting, and transferring raised the burnout scale. On the other hand, assistance for bathing and dressing did not correlate with the burnout score. On multiple regression analysis using the background factors for the burnout score as explanatory variables, aid for feeding and sitting were significant independent contributing factors. Since it became clear that the caregivers in the home were almost burnt out owing to the aid they need to give for the elderly person's BADL, attempts should be done to reduce their burden as soon as possible.

Activities of Daily Living↗

PubMed2000

Integration of proviral sequences, but not at the common integration sites of the FGF8 locus, in an androgen-dependent mouse mammary Shionogi carcinoma.

A retroviral insertional mutation, especially by mouse mammary tumor virus (MMTV), is a major cause of murine mammary tumorigenesis. Prompted by our previous finding that FGF8, an insertionally activated cellular oncogene, is highly expressed in androgen-dependent mouse mammary Shionogi carcinoma cells, we here investigated retroviral integration adjacent to the fgf8 locus in Shionogi carcinoma. In the genomic Southern blots for fgf8 and its 5'-upstream gene npm3, the hybridized fragments were identical to the host DD/Sio mice, the original Shionogi carcinoma 115 tumor, and a pair of cultured Shionogi carcinoma cell lines of SC-3 and SC-4, suggesting that no retroviral integration occurred around either loci. The genomic cloning for the fgf8 locus from SC-3 cells also confirmed no MMTV integration. In addition, npm3, which is usually coactivated with fgf8 by MMTV insertion,was not up-regulated by androgens in SC-3 cells. All these findings led us to conclude that no retroviral insertion was present at the common integration sites adjacent to the fgf8 locus in Shionogi carcinoma although we demonstrated in this study that multiple proviral sequences of MMTV, Moloney murine sarcoma virus and FBJ-murine sarcoma virus are integrated into SC-3 cells in association with their distinct promoter activity in SC-3 cells.

Animals↗