Biomedical subjects

M Fukayama

Publications and source records attributed to M Fukayama.

At least 73 records · Page 4Linked to original sources

PubMed1998

Establishment and characterization of a human Epstein-Barr virus-associated gastric carcinoma in SCID mice.

A transplantable human Epstein-Barr virus-associated gastric carcinoma (EBVaGC), designated KT, was propagated in severe combined immunodeficiency (SCID) mice for 12 passages. Mucin and cytokeratin expression and the Alu sequence in tumor DNA confirmed that the KT tumor was derived from human epithelial tissue. The identity of clonal EBV in the original and KT tumors was demonstrated by terminal repeat analysis of EBV DNA. The pattern of latency gene expression of EBV was the same in both tumors. EBER1 was presented similarly in tumor cell nuclei by in situ hybridization. Reverse transcription-PCR analysis also demonstrated Q-promoter-driven EBNA1 expression but not BZLF1, EBNA2, or LMP1 expression. Thus, the transplantable human EBVaGC KT retains the original EBV with the same latency gene expression and can serve as a model for this unique type of gastric carcinoma.

Adenocarcinoma↗

PubMed1998

Immunohistochemical localisation of advanced glycation end products in pulmonary fibrosis.

AIM: To investigate the presence and distribution of advanced glycation end products (AGE) in pulmonary fibrosis. METHODS: Lung tissue samples obtained from seven necropsy cases with idiopathic pulmonary fibrosis and seven with normal pulmonary parenchyma were examined immunohistochemically with a monoclonal antibody specific for AGE: 6D12. We also tested three cases with diffuse alveolar damage. RESULTS: All the specimens from cases with pulmonary fibrosis and diffuse alveolar damage showed strong AGE expression on macrophages. Lung specimens from normal parenchyma showed positive AGE immunoreactivity on macrophages from only two of seven cases. CONCLUSIONS: These findings suggest that AGE modified proteins accumulate in alveolar macrophages in patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.

Aged↗

PubMed1997

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus.

The significance of CD44 variants in gastric carcinoma has not been fully investigated in terms of the pathological features of the carcinoma, including its association with Epstein-Barr virus (EBV). In this study, a total of 104 primary gastric carcinoma tissues (EBV-associated gastric carcinomas, EBVaGC, and EBV-negative carcinomas) were evaluated by immunohistochemistry. When the immunoreactivity of formalin-fixed, paraffin-embedded sections was graded on a scale of 0-3, the frequencies of grades 0-1, 2 and 3 were, respectively, 77%, 16% and 7% using monoclonal antibody (MAb) 3G5, which recognizes V3-5, and 70%, 14% and 15% with MAb 2F10, which recognizes V6. The expression of CD44 variants is independently correlated with lymph node metastasis and EBV-association in gastric carcinoma. Significant correlations were observed between V3-5 expression and lymph vessel invasion or lymph node metastasis, and between V6 expression and lymph node metastasis. The expression of both variants was significantly correlated with EBV-association. EBV-association and lymph node metastasis contributed independently to CD44 variant expression by multivariate analysis. Thus, the mechanism and significance of CD44 variant-expression are different in gastric carcinomas with or without EBV. EBVaGC is a distinct type of gastric carcinoma which should be considered separately from EBV-negative carcinoma.

Adolescent↗

PubMed1997

Primary gastric T-cell lymphoma with and without human T-lymphotropic virus type 1.

BACKGROUND: Gastric T-cell lymphomas are rare, and their incidence and viral status have not yet been fully clarified. METHODS: Sixty-seven cases of surgically resected gastric lymphomas from city hospitals in Tokyo were evaluated. The surface phenotype was determined by immunohistochemistry, gene rearrangement by Southern blot hybridization, association with Epstein-Barr virus (EBV) by EBV-encoded small RNAs in situ hybridization, and the presence of human T-cell lymphotropic virus type 1 (HTLV-1) by serology, Southern blot hybridization, and polymerase chain reaction analysis. RESULTS: Five of the 67 cases were T-cell lymphoma (7%): 3 cases were HTLV-1 negative (-) and 2 were HTLV-1 positive (+). Systemic eosinophilia was observed in the three HTLV-1(-) gastric lymphomas. Neoplastic cells were morphologically similar in both groups, but a granulomatous reaction with marked eosinophilia was observed only in the two cases of HTLV-1(-) lymphoma. They also had characteristics of natural killer (NK) cell-like T-cell lymphoma, expressing NK markers and TCRgamma gene rearrangement. Positivity with HML-1 (specific for intestinal epithelial T-cells lymphoma was observed in one HTLV-1(+) lymphoma. The EBV gene was detected in only one case of B-cell lymphoma but not in any case of T-cell lymphoma. CONCLUSIONS: Gastric T-cell lymphoma occurs in 7% of gastric lymphomas in Japan and is comprised of HTLV-1-related lymphomas and lymphomas unrelated to HTLV-1, including NK cell-like lymphomas with eosinophilia.

Adult↗

PubMed1997

Gastric neuroendocrine carcinoma associated with chronic atrophic gastritis type A.

We report a case of gastric neuroendocrine (NE) carcinoma associated with chronic atrophic gastritis type A (CAG/A) or reversed atrophic type gastritis. A 9 x 6 cm tumor was resected from the stomach to control pain in a 55-year-old Japanese woman with peritoneal dissemination and metastatic tumors of the liver and ovary. Histologically, the tumor was NE carcinoma which showed an organoid structure, but consisted of NE cells with overt cytological atypia and frequent mitotic activity. Multiple microcarcinoids and NE cell micronests (NECMs) were also observed in the atrophic non-neoplastic mucosa of the gastric body. CEA immunoreactivity and a high Ki-67 labeling index were characteristic features of the neoplastic NE cells of the carcinoma. Although most NE tumors arising from CAG/A are typical carcinoid tumors, the present case illustrates that a high-grade NE carcinoma can develop from diverse NE cell proliferation in association with CAG/A.

Biomarkers, Tumor↗

PubMed1997

A case of inflammatory pseudotumour of the common bile duct.

Inflammatory pseudotumour of the common bile duct (CBD) is extremely rare. A 58-year-old Japanese female without choledocolithiasis underwent pancreatico-duodenectomy for constriction of the middle lower region of the CBD. A submucosal tumour protruding into the CBD, was histologically inflammatory consisting of fibroblastic cells, collagen fibres and myxoid stroma with chronic inflammatory cells. This lesion was surrounded by an irregular fibrosclerosing lesion with obliterative phlebitis which involved the neighbouring pancreas and lymph nodes. Clonal analysis of the tumour by polymerase chain reaction analysis of X chromosome inactivation patterns, confirmed the polyclonal nature of the lesion. Immunohistochemically, the fibroblastic cells in both lesions had the same phenotype [vimentin (+), desmin (-), muscle-specific actin (-) and CD34 (+)] suggesting that these lesions with different histological features represent zonation of the same inflammatory process. The outer lesion extended irregularly into adjacent pancreatic tissue and lymph nodes. This fact made it difficult to differentiate this from a malignant lesion, even if frozen sections contained no atypical cells.

Antigens, CD34↗

PubMed1997

Clonality in nevocellular nevus and melanoma: an expression-based clonality analysis at the X-linked genes by polymerase chain reaction.

The true nature of nevocellular nevus is still unknown and it has been ambiguously classified as a neoplasm or a hamartoma. We studied the clonality of nevocellular nevus and melanoma (malignant melanoma), using an expression-based clonality analysis at the X-linked genes by means of polymerase chain reaction. DNA was extracted from cryostat sections of 20 nevocellular nevi (10 compound and 10 intradermal type) and five melanomas from female patients. A polymorphic portion of the inactivated X-linked gene was amplified after selective digestion of the active X-chromosome with a methylation-sensitive restriction enzyme, Hpa II. Paternal- and maternal-derived fragments were resolved with electrophoresis using the polymorphic restriction endonuclease (BstX I) site for the phosphoglycerate kinase assay, and using the difference of CAG repeats for the human androgen-receptor gene assay. Both assays revealed that all informative nevocellular nevi were polyclonal in origin and all melanomas were monoclonal. Results of the clonality were independent of either the histologic type of nevocellular nevus or whether the nevocellular nevus was of congenital or acquired origin. Thus, nevocellular nevus, congenital or acquired, may be a hamartomatous rather than a neoplastic lesion. The analysis of clonality could be applied to the differential diagnosis of benign melanocytic disease and melanomas.

Adolescent↗

PubMed1997

Cystic pulmonary metastases of endometrial stromal sarcoma of the uterus, mimicking lymphangiomyomatosis: a case report with immunohistochemistry of HMB45.

A case of endometrial stromal sarcoma (ESS) showed cystic pulmonary metastases mimicking lymphangiomyomatosis (LAM). A 58-year-old female, who had undergone total hysterectomy for low-grade ESS 16 years previously, had repeated bouts of pneumothorax. Multiple thin-walled cysts in the peripheral lung were revealed by radiological examinations. In an open-lung biopsy specimen, cystic lesions were surrounded by layers of spindle-shaped cells of varying thickness that resembled LAM. However, in addition to subtle histologic differences from LAM, HMB45 (antimelanoma antibody) showed positive in LAM (n = 3), but was negative in ESS (n = 2) and the cystic lesions of this case. Using myogenic markers (desmin and alpha-smooth muscle actin), metastatic ESS could be immunohistochemically differentiated from mesenchymal cystic hamartoma (n = 1). HMB45 immunohistochemistry is useful in the differential diagnosis of cystic pulmonary lesions.

Actins↗

PubMed1997

A case of Epstein-Barr virus infection with exophthalmos and ocular muscle swelling.

A 14-year-old girl with Epstein-Barr virus (EBV) infection developed exophthalmos and ocular muscle swelling. The EBV genome was detected in T lymphocytes taken from the submandibular gland, temporal muscle and cervical lymph nodes. A surface marker analysis of her peripheral blood demonstrated that CD45RO-positive T lymphocytes were strongly activated. Immunosuppressive treatment, including steroid and cyclophosphamide, was effective in improving the symptoms. Immunosuppressive therapy may be included as the choice of treatment for EBV infection.

Adolescent↗

PubMed1997

[Clinical study on penicillin insusceptible/resistant Streptococcus pneumoniae in the elderly patients].

Clinical features of respiratory infection in the elderly with penicillin insusceptible (31 cases) and resistant (7 cases) Streptococcus pneumonia (PSSP/PRSP) are compared to those with penicillin sensitive S. pneumoniae (PSSP) (29 cases). Incidence of bacteremia and pneumonia was higher in the PSSP group. PISP/PRSP tend to be isolated from patients with bronchitis underlaid with chronic pulmonary disease without statistic significance. Efficacy of the penicillins and 1st and 2nd generation cephem was satisfactory except in only one case of pneumonia with PISP which needed an alternative choice to the 3rd generation cephem. Now a day the degree of resistance is not so high and the available antibiotics are sufficient for the treatment of pneumococcal infection in the elderly patients. However, the wide use of oral cephems and certain new quinolones which do not have enough activity against Streptococcus pneumoniae may increase resistance. In which case, continuous surveillance and clinical caution against this resistant strain is necessary.

Aged↗

PubMed1997

[State of art: Epstein Barr virus-associated gastric carcinoma].

Epstein Barr virus(EBV)-associated gastric carcinoma (EBVaGC), comprising 10% of gastric carcinoma, is the most frequent EBV-associated neoplasm in Japan. EBVaGC is a distinct type of gastric carcinoma, which is marked by the monoclonal EBV, and its morphogenesis seems to be different from that of other gastric carcinomas. Future studies are necessary to disclose precise timing of EBV infection to the epithelial cells of the stomach, status and mechanism of EBV-infection in the non-neoplastic gastric mucosa, molecular mechanism of the development of EBVaGC, and role of EBV in the maintenance of EBVaGC. Development of new therapeutic approach specific to EBVaGC will also facilitate the recognition of this entity in clinical medicine.

Herpesviridae Infections↗

PubMed1997

[Epstein-Barr virus associated gastric carcinoma: the genetic alteration and the expression of CD44 variant].

Epstein-Barr virus (EBV), a ubiquitous human herpes virus, was recently identified in 2-16% of gastric carcinomas. EBV-encoded small RNA was found in nearly all of the carcinoma cells even at the intramucosal stage. EBV in EBV associated gastric carcinoma (EBVaGC) is monoclonal based on Southern blot hybridization using probes adjacent to the unique terminal repeat of EBV-DNA. Furthermore, the genetic pathway of this carcinogenesis is different of EBVaGC: deletion of 5q and/or 17p and microsatellite instability are extremely rare in EBVaGC, in contrast to their high frequency in EBV-negative carcinomas. We also examined the relationship between the expression of CD44 variants and EBVaGC, and found the expression of CD44 variants was significantly correlated with EBV-etiology.

CD40 Antigens↗

PubMed1997

[The in vitro antifungal activities of fluconazole against pathogenic yeasts recently isolated from clinical specimens].

The emergence of Candida albicans resistance to azole antifungal agents have been reported in the U. S. and Europe. We examined the in vitro antifungal activities of fluconazole against clinical isolates collected by seven investigators in three years to examine if a tendency existed toward the development of azole-resistance among fungal isolates in Japan. The following results were obtained: 1. Sensitivities to fluconazole (FLCZ) were determined for yeast-like fungi, including 113 strains isolated in 1993, 149 strains isolated in 1994 and 205 strains isolated in 1995. No significant differences in sensitivities in the three years were detected. 2. Minimum inhibitory concentrations of FLCZ were 0.1-0.78 microgram/ml for C. albicans and 3.13-25 micrograms/ml for C. glabrata. Strains with 25 micrograms/ml of FLCZ's MIC were detected; two strains of C. krusei and one strain each of C. krusei, Trichospron beigelii and Hansenula anomala. No strains with higher than 50 micrograms/ml MIC of FLCZ were detected. 3. In vitro activities of FLCZ were compared between clinical strains isolated between 1993 and 1995 and clinical strains isolated before the marketing of FLCZ (up to December 1987) or clinical yeasts isolated between 1991 and 1992. No significant differences were observed, suggesting that no tendency existed toward azole resistance among fungal strains examined.

Antifungal Agents↗

PubMed1997

Microsatellite instability and loss of heterozygosity in gastric lymphoma.

To evaluate the significance of microsatellite instability (MI) and loss of heterozygosity (LOH) in the development of gastric lymphoma, we examined 33 tissue-samples of 20 primary gastric B-cell lymphomas (6 low-grade lymphomas of mucosa-associated lymphoid tissue [MALT; 10 samples] and 14 diffuse large B-cell lymphomas [23 samples]). MI and LOH were evaluated at 13 microsatellite loci. In MALT lymphoma, four of six cases showed MI at one to two microsatellite loci (average 1.0 per case, 0.8 per sample), whereas in diffuse B-cell lymphoma, all samples showed MI at one to five microsatellite loci (average 2.4 per case, 2.7 per sample) (p < 0.05 and p = 0.0001). MI at the c-myc gene locus was most frequent in both types of gastric lymphomas (3 of 6 and 11 of 14 cases, respectively). Regional heterogeneity of the MI pattern was observed in two of four cases of MALT lymphoma and in four of five cases of diffuse B-cell lymphoma. On the other hand, LOH was observed only in one MALT lymphoma and in three diffuse B-cell lymphomas. Genetic instability may be an important mechanism for the development and progression of gastric lymphoma. Frequent MI at the c-myc locus might reflect an activated state and the importance of this gene in mucosal lymphocytes of chronic gastritis.

Adult↗

PubMed1996

Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas.

We report a case of pancreatic acinar cell carcinoma which contained a large number of pleomorphic inclusions with fibrillary internal structures and mature zymogen granules. To clarify the significance of fibrillary inclusions in the differentiation of acinar cells of the pancreas, we further investigated fetal pancreases (gestational weeks 16, 17, 19, 20 and 28). We found two types of inclusions: type A, corresponding to fibrillary inclusion of neoplastic acinar cells, was observed only in a 19-week fetus; type B showed a homogeneous density similar to that of zymogen granules. Type B was observed in all the fetuses after the 17th gestational week. Although the type A inclusion might be generated through a different mechanism than the type B inclusion, the appearance of a large number of fibrillary inclusions in neoplastic acinar cells may represent a transient form of zymogen granule.

Carcinoma, Acinar Cell↗

PubMed1996

Crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma mimicking Weber-Christian disease: immunohistochemical, ultrastructural, and gene-rearrangement studies.

A case of crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma is presented. Unlike previous cases, this patient presented with signs and symptoms suggestive of Weber-Christian disease. Biopsy of subcutaneous nodules showed numerous deposits of crystal-storing histiocytes with lymphoplasmacytic cells, the latter exhibiting light chain restriction (lambda-chain) with a predominance of immunoglobulin (Ig)G heavy chain. Polymerase chain reaction (PCR) analysis of CDR-II* region of the immunoglobulin heavy chain locus confirmed monoclonality of the lymphoplasmacytic cells in the nodule. Electron microscopy showed polygonal-shaped amorphous crystals, characteristic of immunoglobulin in the histiocytic cells. Crystal-storing histiocytosis should be examined by immunohistochemical and DNA analysis to confirm or exclude the possibility of lymphoplasmacytic lymphoma.

Adult↗

PubMed1996

Neuroendocrine differentiation in pancreatic duct carcinoma special emphasis on duct-endocrine cell carcinoma of the pancreas.

To evaluate the significance of neuroendocrine differentiation in duct carcinoma of the pancreas, we investigated 79 pancreatic carcinomas, applying histochemistry and immunohistochemistry (chromogranin A, Leu-7, synaptophysin and neuron-specific enolase (NSE), and correlated the morphologic differentiation pattern with clinicopathological characteristics. There were two types of neuroendocrine differentiation: scattered (n = 23) and diffuse (n = 3). The scattered type of pancreatic duct carcinoma contained scattered endocrine cells amounting to less than 10% of the neoplastic cells and was seen more frequently in well-differentiated carcinomas. There was no characteristic clinical feature found in the scattered type when compared with the tumors devoid of endocrine cells (n = 53). In contrast, the diffuse type showed diffuse immunostaining with NSE and synaptophysin in tumor cells and dense core granules ultrastructurally. These tumors showed a greater hypervascularity in angiography (p < 0.01) and the patients had relatively longer survival (33.3 months, p < 0.05) than unresectable cases of other histological types of pancreatic cancer. Two types of neuroendocrine differentiation (scattered and diffuse) existed in pancreatic ductal carcinoma. The diffuse type (Duct-Endocrine Cell Carcinoma of the Pancreas) showed synchronous duct and endocrine differentiation and particular clinical features.

Adenocarcinoma↗

PubMed1996

Nosocomial diarrhoea in the elderly due to enterotoxigenic Clostridium perfringens.

To diagnose sporadic diarrhoea due to Clostridium perfringens infection, faecal specimens from elderly patients were examined directly for C.perfringens enterotoxin using reverse passive latex agglutination assay, and then cultured for this organism. C.perfringens isolates from those samples were grouped by slide agglutination and by pulsed-field gel electrophoresis (PFGE). Fifty of the 60 isolates agglutinated with newly raised antiserum WX2 and 38 shared the same genomic PFGE pattern. Characteristics of the epidemics and experimental data suggest that the diarrhoea was caused by a nosocomial spread of C.perfringens, and not by a food-borne outbreak.

Aged↗