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Biomedical subjects

M Fukayama

Publications and source records attributed to M Fukayama.

At least 91 records · Page 5Linked to original sources

Detection of human T lymphotropic virus type I proviral DNA in patients with diffuse panbronchiolitis.

In Japan a number of reported cases of diffuse panbronchiolitis (DPB) have been associated with human T lymphotropic virus type I (HTLV-I) infection. In this study the hypothesis that HTLV-I proviral DNA may be prevalent in DPB was examined using polymerase chain reaction (PCR) for the region of env or the two-step PCR for the pX region of this virus. The presence of HTLV-I proviral DNA was studied in the peripheral blood mononuclear cells (PBMC) obtained from 10 patients with DPB. The presence of proviral DNA in PBMC in 12 patients with chronic obstructive pulmonary disease (COPD), eight patients with idiopathic interstitial pneumonia (IIP), four patients disease were also studied as relevant controls. The lung tissue obtained from 11 patients with DPB, 12 patients with diffuse aspiration bronchiolitis (DAB) at autopsy, and the surgical lung samples obtained from 12 patients with bronchogenic cancer were also studied. Peripheral blood mononuclear cells obtained from one DPB patient and one bronchogenic carcinoma patient were positive for the HTLV-I pX region. The presence of the pX region was also found in the lung tissue of three DPB patients (27.3%) and one DAB patient (8.3%). None of other subjects were positive for HTLV-I proviral DNA, In conclusion, HTLV-I is not the causative virus in the pathogenesis of COPD, IIP, bronchiectasis and bronchogenic carcinoma. There is a likelihood that HTLV-I infection is associated with some cases of DPB; however this association needs further verification.

Blotting, Southern↗

Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis.

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.

Activins↗

Relapsing oral and colonic ulcers with monoclonal T-cell infiltration. A low grade mucosal T-lymphoproliferative disease of the digestive tract.

BACKGROUND: Some cutaneous T-cell lymphoproliferative diseases (LPD), such as lymphomatoid papulosis and pityriasis lichenoides et varioliformis acuta, are characterized by an indolent or waning and waxing clinical course. However, such T-cell LPD are rarely documented in other organs. METHODS: A patient with T-cell LPD of the digestive tract characterized by repetitive episodes of self-healing ulcers in the oral and intestinal mucosa over the course of 17 years is reported. Biopsy specimens from oral and intestinal mucosa were studied by conventional pathology, immunocytochemistry, and Southern blot analysis of T-cell receptor (TCR)-beta and -gamma gene rearrangement. RESULTS: Immunocytochemically, the infiltrating lymphocytes were lamina propria T cells with a dominant phenotype CD3+, CD4+/-, CD8-, and HML-1-. DNA study revealed the same rearranged configuration of TCR-beta and -gamma genes in specimens from both oral and colonic lesions. CONCLUSIONS: The present case may represent a novel T-cell lymphoproliferative disease (i.e., a digestive-tract mucosal counterpart of cutaneous dysplastic LPD).

Colonic Diseases↗

Annular pancreas associated with carcinoma in the dorsal part of pancreas divisum.

A carcinoma in the dorsal part of the pancreas divisum with an annular pancreas in the anterior part is reported. A 79-yr-old female was admitted in our hospital complaining of epigastralgia. Computed tomography (CT) and ultrasound (US) showed an irregular mass in the pancreatic body. A pancreatogram obtained through the major duodenal papilla demonstrated only the ventral pancreatic duct that encircled the duodenum. Contrast medium injected from the minor duodenal papilla showed Santorini's duct obstruction at the neck portion of the pancreas without communication with the ventral pancreatic duct. The patient died with liver metastases. Autopsy confirmed annular pancreas and a 6-cm tumor in the pancreatic body extending to the pancreatic head and pancreas divisum. Pancreatic carcinoma; histologically a moderately differentiated adenocarcinoma; originated from the dorsal part of pancreas divisum. To our knowledge this is the first report of pancreatic carcinoma associated with annular pancreas coexistent with pancreas divisum.

Adenocarcinoma↗

Pyothorax-associated lymphoma: development of Epstein-Barr virus-associated lymphoma within the inflammatory cavity.

Pyothorax-associated lymphoma (PAL) is a B cell lymphoma that develops in Japanese patients with tuberculosis-associated chronic pyothorax (TaCP). Epstein-Barr virus (EBV) has been shown to be causally related to PAL. To clarify the developmental process of PAL, the systemic and local presence of EBV, and serum profile of anti-EBV antibodies was investigated in TaCP. EBV genome was found in peripheral blood mononuclear cells by PCR in a 10(-4)-10(-5) amount of Raji cell-DNA in three of four patients with TaCP, but was also identified in patients with pyothorax caused by other diseases (2/2) or without pulmonary diseases (2/6). EBER1 in situ hybridization and EBNA2 immunocytochemistry revealed clusters of EBV-carrying cells in the cavity content (3/18) but not at the pyothorax wall; EBV(+) histological lymphoma cells were found in two cases and EBV(+) mononuclear cells were found in one case. A simultaneous increase in serum titers of anti-EBV viral capsid antigen IgG and IgA antibodies was observed in TaCP (4/16). These results suggest that a local factor, an inflammatory cavity, has a pivotal role in the development of PAL, which might be reflected in the serum titers of anti-EBV antibodies in patients with TaCP.

Antibodies, Viral↗

Mesothelial cyst of the adrenal gland.

A case of mesothelium-lined cyst of the adrenal gland is reported. Although more than 300 adrenal cysts have been reported in the literature, epithelial cell-lined cysts are rare and comprise only 9% of the cases. An adrenal cyst was found, the lining cells of which had features consistent with mesothelial cells. The inner surface of the cyst was lined by a single layer of cuboidal cells, which showed alcian blue positive cellular outline. Immunohistochemically, the lining cells were positively stained for keratin, epithelial membrane antigen and CA-125. Electron microscopic examination revealed many long complex microvilli and desmosomes in the lining cells. There was a basal lamina beneath the cell layer. These morphological and immunohistochemical findings indicated that the lining cell is derived from mesothelium.

Adrenal Gland Diseases↗

Intracranial meningioma masquerading as a primary pleuropulmonary tumor.

Extracranial metastasis was found in an intracranial meningioma with low proliferative potential before the detection of the primary tumor. Pleuropulmonary tumors were incidentally detected on chest X-ray in an asymptomatic 25 year old female. Excised tumors of the right pleura and lung showed histological features similar to meningotheliomatous meningioma, which led to the discovery and excision of the intracranial tumor. Both tumors showed the same histologic pattern: meningotheliomatous meningioma with low mitotic activity. The proliferative component, determined by the monoclonal antibody Ki-67, was further evaluated in the primary tumor and the metastases of the present case, as well as in 12 other intracranial meningiomas. Ki-67 positive ratios at the primary and metastatic sites of the present cases were 1.2 and 1.1%, respectively, which is as low as other benign meningiomas, and this suggests that factors other than the proliferative potential is responsible for extracranial metastasis of meningioma.

Adult↗

Microsatellite instability in the progression of gastric carcinoma.

Seventy-six gastric carcinomas were analyzed with regard to whether or how microsatellite instability was associated with the development of the carcinoma. Microsatellite instability occurred as a late genetic alteration, with an incidence significantly higher in the advanced stage (17 of 51) than in the early stage (3 of 25; P < 0.05). Chromosomal losses on 5q and 17p, detected by polymerase chain reaction-restriction fragment length polymorphism, more frequently accompanied microsatellite instability (9 of 15 and 8 of 11, respectively), compared with carcinomas which lacked instability (5 of 28 and 9 of 30, respectively; P < 0.01 and P < 0.05, respectively). Epstein-Barr virus was observed in only 8 of 76 carcinomas, none of which was associated with microsatellite instability. No significant correlation was found between instability and the familial tendency to develop gastric carcinomas. Our results suggest that microsatellite instability might play a role in the progression of gastric carcinomas but not in Epstein-Barr virus-associated gastric carcinomas.

Adult↗

Inhibition of growth of human small cell lung cancer by bromocriptine.

Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.

Animals↗

Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors.

Mutation of the adenomatous polyposis coli (APC) gene was analyzed in 500 colorectal tumors from 70 familial adenomatous polyposis (FAP) and 102 non-FAP patients and in normal tissues from 119 FAP patients, using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing methods. These tumors were histopathologically diagnosed. Sixty-eight germ line mutations (62% deletion, 9% insertion, and 29% single-base substitution) and 241 somatic mutations (56% deletion, 12% insertion, and 32% single-base substitution) were detected. All mutations formed stop codons resulting in truncated APC proteins, except for one germ line mutation. Differences were found between somatic and germ line mutations, including 3 new hot spots of mutation at codons 1378, 1450, and 1487-1490, which frequently occurred in somatic mutations but not in germ lines. The frequency of mutation in each histopathological type of FAP tumor was 53% in moderate adenoma, 64% in severe adenoma, 52% in intramucosal carcinoma, and 33% in invasive carcinoma, whereas the loss of heterozygosity including the APC gene increased with development to each histopathological type. A similar tendency was observed in non-FAP tumors. Additionally, we found 10 FAP tumors that had both somatic mutation and loss of heterozygosity. These tumors were assumed to have developed from moderate adenomas with germ line and somatic mutations, followed by deletion of the allele with germ line mutation. These results suggest that inactivation of the APC gene by two mutations is involved in the development of moderate adenoma, and loss of heterozygosity of the APC gene is associated with further development to carcinoma. It was also observed that the distribution of 75 somatic mutations from one FAP patient on the APC sequence was similar to the distribution of 159 somatic mutations from 83 patients with FAP and non-FAP, which suggests that the position of somatic mutation is mostly due to the APC sequence itself.

Adenoma↗

Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential.

BACKGROUND: The molecular genetic changes associated with colorectal carcinoma are among the best understood of any common human cancer. The genetic changes during the late stages of colorectal carcinomas may be useful in clinical management for determining the metastatic potential of the carcinoma. METHODS: Tumor tissues were evaluated by restriction fragment length polymorphism (RFLP) analysis of chromosomes 5q, 17p, 18q, and 22q (n = 98), by reverse transcription-polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of the DCC gene (deleted in colorectal carcinoma) (n = 27) and by immunohistochemical analysis of p53 protein expression (n = 44). RESULTS: Loss of heterozygosity (LOH) on chromosomes 17p, 18q, and 22q, but not on 5q, was much more frequently detected in advanced carcinomas than in intramucosal carcinomas (P < 0.01). 17p LOH was significantly correlated with vascular invasion (P < 0.001), whereas 18q LOH was correlated with lymphatic invasion and hepatic metastasis (P < 0.01), and 22q LOH was correlated with lymph node metastasis (P < 0.05). LOH on 5q did not show a significant correlation with any factors of tumor invasion or metastasis. DCC expression was not observed in any of five hepatic metastasis or in five of seven advanced carcinomas that were accompanied by hepatic metastasis (10 of 12). However, a similar lack of expression was observed in only 5 of 15 carcinomas without hepatic metastasis (P < 0.05). p53 Expression was found to vary in both primary and metastatic carcinomas by immunohistochemistry. CONCLUSIONS: The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22q and RT-PCR analysis of DCC expression into messenger RNA) can be used to determine the metastatic potential of colorectal carcinomas.

Adult↗

Pyothorax-associated pleural lymphoma. A case evolving from T-cell-rich lymphoid infiltration to overt B-cell lymphoma in association with Epstein-Barr virus.

BACKGROUND: Pyothorax-associated pleural lymphomas (PAPL) occur in patients with long-standing pyothorax. Epstein-Barr virus (EBV) plays an important role in its development. METHODS: An atypical case of PAPL is reported and its clinical features are compared with those of five cases of ordinary PAPL. RESULTS: The histology of the lymphoma changed from prominent T-cell infiltration to an overt B-cell lymphoma of diffuse, large cell-type. DNA studies of the lymphoma at the first presentation demonstrated dual rearrangement in the T-cell receptor beta (TCR beta) and immunoglobulin heavy chain J region (IgJH) genes. EBV genome analysis demonstrated monoclonal expansion of EBV-infected cells. EBV gene products were present only in large lymphocytes with B-cell phenotype. The same rearranged band of the IgJH gene, but not clonal rearrangement of the TCR beta gene, was observed in the overt B-cell lymphoma at the relapse. The same EBV-infected clone was observed throughout the course of the disease. The tumor was localized at the pyothorax wall, and cell-mediated immunity, reflected by a positive tuberculin reaction, was preserved only in the current case. CONCLUSIONS: T-cell-rich lymphoid infiltration in the current case is a variant of EBV-associated PAPL, which is infiltrated by reactive T-cells with clonal accentuation. This is the first documented case of EBV-associated PAPL evolving from T-cell-rich lymphoid infiltration.

Aged↗

CD5 expression in thymic carcinoma.

To determine the differences between the cellular characteristics of thymic carcinoma and thymoma, immunohistochemical analysis with lymphocyte markers (CD1a, 3, 4, 5, 8, 10, 20, 21, 25, 30, 57, and 72) was performed on 23 thymic epithelial tumors other than lymphocytic thymoma: overt thymic carcinoma (OC, n = 7), atypical thymoma (n = 5), and typical thymoma (epithelial or mixed thymoma, n = 11). Among the surface antigens examined, CD5, a type of receptor molecule that signals cell growth in T cells, was expressed in neoplastic epithelial cells of the thymus, in OC (seven of seven) and atypical thymoma (two of five), but not in typical thymoma. Double labeling immunofluorescence demonstrated expression of CD5 in cytokeratin-positive cells. The CD5 molecule extracted from an OC tumor showed the same molecular size as that in the spleen, but CD72, a ligand of CD5 on the surface of B cells, was not found in the epithelial cells of OC or atypical thymoma. Expression of CD5 was not observed in carcinomas of other organs, such as lung (n = 15), breast (n = 4), esophagus (n = 6), stomach (n = 6), colon (n = 9), and uterine cervix (n = 3). CD5 is closely related to morphological changes in thymic epithelial tumors and may play a role in the evolution of OC through receptor-ligand interaction.

Antigens, CD↗

Epstein-Barr virus-associated gastric carcinoma and Epstein-Barr virus infection of the stomach.

BACKGROUND: Epstein-Barr virus (EBV) has been found to be associated with a type of gastric carcinoma (EBVaGC). However, many questions remain unanswered, such as epidemiology, and pathologic features of EBVaGC and the significance of EBV in the genesis of EBVaGC. EXPERIMENTAL DESIGN: Gastric carcinoma and non-neoplastic mucosa were evaluated to reveal the following issues: the incidence of EBVaGC in Japanese population, pathologic features and EBV genotype, clonality, and gene-expression in EBVaGC, localization of EBV in non-neoplastic stomach, and serum titer of anti-EBV antibodies in EBVaGC-carrying patients. RESULTS: Using PCR and EBER1 in situ hybridization, EBVaGC (definitely amplifiable EBV-DNA and positive EBER1-signal in the nuclei of carcinoma cells) was found in 8 of 72 gastric carcinomas (11%). The dominant genotype of EBV was type A (7/8), with type C (6/8), and F (8/8) restriction enzyme polymorphism, which are the predominant type of EBV found in throat washing of the general population in Japan. EBVaGC was found in the cardia (4/8) or body (4/8) of the stomach, and consisted of 7 advanced and 1 intramucosal carcinoma. By Southern blot analysis of EBVaGC hybridized with right- and left-side probe adjacent to the terminal repeats, EBV was present in a monoclonal episomal form in all of the EBVaGC. EBVaGC lacked expression of EBNA2 (0/8) and LMP1 (0/8) by immunocytochemistry. In non-neoplastic mucosa, EBER1 signal was identified in the infiltrating lymphocytes and shedding epithelial cells predominantly in fundic gland mucosa of patients with EBVaGC (8/8). Patients with EBVaGC showed high titers of anti-VCA IgG (8/8), anti-VCA IgA (2/8) and anti-EA IgG (7/8) antibodies just before surgery. CONCLUSIONS: EBV may infect the surface epithelium of the stomach through the reactivated EBV-carrying lymphocytes. EBV may be a factor initiating EBVaGC. Anti-EBV antibodies or EBER1 in situ hybridization may help to identify patients at high risk for EBVaGC.

Antibodies, Viral↗

[Cardiac infection].

Cardiac infection usually refers to infective endocarditis (IE) and purulent pericarditis. Though, IE was initially observed in patients with congenital or rheumatic heart disease, currently, persons with prosthetic cardiac valves and with degenerative heart disease account for the majority of the cases and there has been a significant trend toward an increase in the age of patients. Echocardiography, especially, transesophageal echocardiography, has provided valuable information for diagnosis. Since cure requires eradication of all the organisms, bactericidal agents must be used sufficient period to sterilize the vegetation. Overall mortality from recent reports is 10%. Purulent pericarditis almost always occurs in the setting of other serious disease and it's specific signs are often absent, so the disease still carries a high mortality.

Aged↗