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Biomedical subjects

A Mikata

Publications and source records attributed to A Mikata.

At least 55 records · Page 3Linked to original sources
PubMed1995

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin.

To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we developed transgenic mice using a human IAPP cDNA connected to an insulin promoter. Ribonucleic acid blotting and immunohistochemistry revealed the expression of the transgene in the pancreatic beta cells. Immunogold electron microscopy showed that beta-secretory granules contained the human C-terminal flanking peptide of the IAPP precursor. Reverse-phase HPLC demonstrated human and mouse IAPP amide in the pancreas. Electron microscopy showed the accumulation of fibril-like material in a considerable number of beta-secretory granules. These results suggest that in transgenic mice, the human IAPP precursor is expressed in beta cells and becomes normally sorted into beta-secretory granules in which normal conversion to mature human IAPP takes place. The human IAPP molecules, because of their amyloidogenesis, aggregate into amyloid fibrils in secretory granules. Glucose tolerance was normal at 7 months old and islet amyloid was not observed. A longer time may be required for islet amyloid deposits and hyperglycemia to develop in mice. Our working hypothesis is that in human NIDDM, IAPP aggregates into amyloid fibrils in beta-secretory granules, and that the fibrils are released into the extracellular space and islet amyloid deposits become substantial with time.

Amyloid↗
PubMed1995

Establishment and characterization of a human malignant fibrous histiocytoma cell line.

Malignant fibrous histiocytoma is the most frequent soft tissue sarcoma. However, the pathogenesis still remains unclear, because there are very few human malignant fibrous histiocytoma cell lines available for precise cellular study. In this study, a human malignant fibrous histiocytoma cell line (MMF-1) was established from the pulmonary metastatic lesion of a 55-year-old man with malignant fibrous histiocytoma. Human cell line MMF-1 and its heterotransplanted tumor had almost the same characteristics as the original tumor morphologically and immunohistochemically. This cell line is expected to be a useful for studying the pathogenesis of malignant fibrous histiocytoma. The cloned cell lines (MMF-2 and MMF-3) also consisted of spindle-shaped, polygonal, and multinucleated giant cells, meaning that the fibroblast-like cells, histiocyte-like cells, and multinucleated giant cells seen in malignant fibrous histiocytoma were derived from a single tumor cell. Human cell line MMF-1 produced inflammatory cytokines, such as tumor necrosis factor-alpha, macrophage colony-stimulating factor, interleukin-8, and monocyte chemotactic and activating factor, that might be involved in the morphogenesis of malignant fibrous histiocytoma. Furthermore, the results of the analysis of human cell line MMF-1 suggested that malignant fibrous histiocytoma originated from a poorly differentiated fibroblast.

Cell Division↗
PubMed1995

[Molecular evidence for a single clonal origin in a patient with multiple myeloma and non-Hodgkin's lymphoma].

A 49-year old man was admitted in November 1989, because of anemia, abnormal shadowing on chest X ray and hyperproteinemia. Biclonal gammopathy (IgG kappa + IgA kappa) was shown in serum, and Bence Jones protein in urine. The bone marrow examination showed an increased number of abnormal plasma cells (15.7%) and no evidence of lymphoma, A diagnosis of multiple myeloma (MM) was made. In April 1990, while the patient was treated with the modified M2 regiman, swelling of the right cervical lymph node was observed. Lymph node biopsy revealed that he had non-Hodgkin's Lymphoma (:NHL, diffuse, mixed, B cell type). He was retreated with the CHOP regimen for both disease, but died of respiratory failure in October. 1991. To establish the clonal origin of this case of concominant MM and B-cell NHL, the immunoglobulin gene rearrangements in his lymph node and bone marrow were analyzed. Southern blot analysis with the JH probe and Ck probe showed one common band and one different band in the two samples. Our data suggest that two B-cell malignancies may have arisen from a single B-cell progenitor.

B-Lymphocytes↗
PubMed1995

VLA-4-dependent adhesion in follicular non-Hodgkin's lymphomas.

The cellular contact between B cells and follicular dendritic cells (FDCs) in the germinal center is thought to play a key role in B-cell maturation and proliferation. The adhesion pathway through the very late antigen 4 (VLA-4) on the B cells and the vascular cell adhesion molecule 1 (VCAM-1) on the FDCs support this binding process. The neoplastic follicular centers in follicular non-Hodgkin's lymphomas (FNHLs) have similar structures and cellular components to those of normal germinal centers, but their interaction between B cells and FDCs may be functionally disturbed. In view of this we analyzed the interaction between VLA-4 and VCAM-1 molecules in the germinal center microenvironment, both in neoplastic and normal follicles. The structural characterization of FNHLs and reactive lymph nodes was studied with indirect immunohistochemical stainings using monoclonal antibodies against VLA-4, VCAM-1, and fibronectin, with special reference to the reaction pattern in the normal and neoplastic follicles. In the reactive follicular centers most B cells did not show a positive reaction for VLA-4, except for moderate reaction products in the B cells of the light zone. In FNHLs, on the other hand, most follicular center B cells were positive for VLA-4. The reaction patterns of VCAM-1 and fibronectin in both normal and neoplastic follicular centers were not basically different. To investigate the interaction of VLA-4 with VCAM-1 in both neoplastic and normal follicular centers, we performed a frozen-section binding assay, which found decreased binding between VLA-4 and VCAM-1 in FNHLs. The results of this study indicated that the microenvironment in neoplastic follicular centers is different from that in their normal counterparts, in terms of the characteristic distribution pattern of the VLA-4-positive B cells, and the functional deterioration of the VCAM-1 on FDCs.

Cell Adhesion↗
PubMed1994

Islet amyloid polypeptide and its N-terminal and C-terminal flanking peptides' immunoreactivity in islet amyloid of diabetic patients.

We determined immunohistochemically whether the islet amyloid polypeptide (IAPP)/amylin precursor is one component of islet amyloid, using polyclonal antibodies specific for human IAPP8-17 and amino (N)-terminal and carboxy (C)-terminal flanking peptides. To enhance immunostaining of the amyloid, we pretreated the pancreatic tissue sections with 100% formic acid. In three non-diabetic subjects, pancreatic islet cells were immunoreactive to anti-IAPP8-17 and anti-N-terminal and C-terminal flanking peptide antibodies and the reactivity was enhanced with formic acid pretreatment. In six type 2 diabetic subjects and a subject with type A insulin resistance, islet amyloid deposits were reactive to anti-IAPP8-17 antibody, but not to anti-N-terminal and C-terminal flanking peptide antibodies. Formic acid pretreatment markedly enhanced the reactivity to anti-IAPP8-17 antibody; however, it failed to show the reactivity to anti-N-terminal and C-terminal flanking peptide antibodies. Formic acid pretreatment of pancreatic tissue sections prepared for immunostaining is useful for visualization of buried epitopes of mature IAPP and its precursor molecules, either in islet amyloid deposits or in the islet cells. We conclude that the IAPP precursor and N-terminal and C-terminal flanking peptides are not constituents of human islet amyloid.

Adult↗
PubMed1994

Molecular genetic, cytogenetic, and immunophenotypic analyses in Castleman's disease of the plasma cell type.

Systemic Castleman's disease shows characteristic morphologic features in the lymph node and laboratory findings, but patients with this disease have variable clinical courses. The disease may constitute a spectrum of benign to malignant diseases. Thus, the clonal nature of the proliferating lymphoid cells was determined to obtain further insight into the malignant process of the disease. Two cases of systemic Castleman's disease were evaluated immunophenotypically, immunogenotypically, and cytogenetically. Both patients had a chronic relapsing clinical course. One patient had a clonal rearrangement of the immunoglobulin (Ig) lambda chain gene, but no restriction of the light chain expression was detected. This patient showed germ-line configurations of the Ig heavy-chain and T-cell receptor (TCR) beta chain genes; no detectable abnormal metaphases in the lymph node were noted. Another patient had predominance of lambda chain-positive plasma cells in the lymph node with a clonal chromosome change, but had germ-line Ig and TCR beta chain genes. The authors identified clonal changes in two cases of systemic Castleman's disease; one had a clonal immunogenotypic change and the other had a clonal cytogenetic change with an Ig light chain deviation. In both cases, however, a discordance of immunogenotypic and immunophenotypic changes was evident. Thus, the alteration may represent a type of lymphoproliferative disorder that lies between benign and malignant diseases.

Castleman Disease↗
PubMed1994

T cell receptor V beta repertoires of angioimmunoblastic lymphadenopathy-like T cell lymphoma.

To elucidate the pathogenesis of angioimmunoblastic lymphadenopathy-like T cell lymphoma (AILD-T) we investigated the T cell receptor V beta gene repertoires of four AILD-Ts and compared them with those of other histological types of lymphomas and three cases with reactive disorders. All lymphoma patients had rearrangement bands detected by Southern blot analysis. Only 1 of the 4 cases of AILD-T showed a single predominant usage of V beta 20 gene by PCR with 20 different V beta specific primers and the others had repertoires somewhat restricted but similar to reactive lesions. Subsequent sequencing of this PCR product revealed that only 2 of 7 clones were identical. These results suggest the monoclonal malignant cells in AILD-T are scant and that the infiltrating T cells show a reactive pattern. In the only AILD-T case with a single dominant V beta usage, the relationships of this repertoire and lymphoma cells seems to be of some consequence.

Adolescent↗
PubMed1994

[Peripheral T cell lymphoma (immunoblastic type, HTLV-1 negative) associated with aganglionosis of the intestine].

A 56-year-old female was hospitalized in 1992, because of fever and lymphadenopathy. She had ileus due to aganglionosis of the intestine diagnosed in 1990. Blood tests disclosed anemia and thrombocytopenia. Peripheral blood smear demonstrated 69.5% abnormal cells and a T-cell origin was demonstrated on cell marker study by flow cytometry. Immunological examinations, including serum HTLV-1 antibody were negative. Lymph node biopsy revealed malignant lymphoma; diffuse large, immunoblastic. The clonality of the T-cell malignancy was shown by detecting rearrangement of T-cell receptor beta gene. A diagnosis of PTCL, high grade, immunoblastic, was made. The patient received various chemotherapeutic agents and achieved a short remission, then died 5 months after the diagnosis. The classification of T-cell lymphoma was established by Suchi and the Kiel classification. Many ATL/L cases have been reported in Japan before the above classification was affirmed, although there have been few reports of ATL/L-like diseases in which serum HTLV-1 antibodies were negative. The case reported here was HTLV-1 negative, although the patient was diagnosed as ATL/L-like disease, because the results of various laboratory examinations were similar to these of HTLV-1 positive cases. Characteristics of this case included a female patient and leukemic clinical features, because the gender preponderance of PTCL, high grade, immunoblastic is male and the clinical features of the disease are not usually leukemic. It was also characteristic that PTCL coexisted with aganglionosis of the intestine. Basic disturbances in the latter condition would be similar to aganglionic megacolon in which a possible aberrant immune mechanism was shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1993

Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma.

Epstein-Barr virus (EBV) has been detected in lymphoepithelioma of nasopharynx and lymphoepitheliomalike carcinomas in various organs. To clarify the association of EBV with gastric carcinoma with lymphoid stroma, which often resembles lymphoepithelioma, the authors examined 22 such cases by polymerase chain reaction and in situ hybridization techniques. In 18 informative cases, EBV DNA was detected by polymerase chain reaction in 14 (77.8%) cases, including lymph node metastases. EBV RNA was detected within the nuclei of carcinoma cells by in situ hybridization in all cases that were positive by polymerase chain reaction. Infiltrating lymphocytes and normal epithelia adjacent to carcinoma were EBV-negative. Southern blot analysis indicated clonal proliferation of tumor cells and episomal form of EBV. These findings suggest that EBV infection occurs before transformation and may be related to oncogenesis of EBV-associated gastric carcinoma.

Adult↗
PubMed1993

Establishment of a cell line from a human giant cell tumor of bone.

A cell line (CG-1) was established from a specimen of a 21-year-old woman with giant cell tumor of bone. Inverted-phase microscopic analysis showed that the cultured cells were spindle-shaped in appearance. Multinucleated giant cells and macrophagelike round cells characterizing the histology of giant cell tumor of bone were not found. It is believed that the spindle-shaped cells were the neoplastic element of this tumor, because they were cultured more than 40 passages over the course of one year and subsequent cytogenetic analysis with a G-band technique showed constant loss of chromosomes 14 and 19. The cell line was found to produce several cytokines: M-CSF, IFN-gamma and TNF-alpha, as demonstrated by Western blotting analysis. These cytokines are known to show chemotactic, differentiation-inducing, and activating effects on macrophages. Because it has been recently reported in the literature that there are many infiltrated macrophages in giant cell tumor of bone, and because multinucleated giant cells are formed by fusion of macrophages, the newly established cell line may prove a useful system in studying the nature of giant cell tumor of bone.

Adult↗
PubMed1992

Islet amyloid polypeptide-derived amyloid deposition increases along with the duration of type 2 diabetes mellitus.

To investigate the involvement of islet amyloid polypeptide (IAPP) and amyloid deposits in the pathophysiology of this disease, we studied the relationship between IAPP-derived amyloid deposition and the clinical features in type 2 diabetes mellitus. We examined pancreata obtained from 37 type 2 diabetic subjects and 12 non-diabetic ones by immunohistochemical techniques using two specific antibodies to IAPP. IAPP-derived deposits occurred in 1 of the 12 (8.3%) non-diabetic subjects and 28 of the 37 (75.7%) diabetics. When diabetic patients were divided into categories according to the presence of the deposits, the duration of the disease was significantly longer in patients with amyloid than that in the patients without it. The odds ratio of type 2 diabetes mellitus of at least 14-years-duration to the deposition was significantly high, and a body weight of at least 120% maximal ideal body weight was relatively high. In conclusion, IAPP-derived amyloid deposition increases along with the duration of type 2 diabetes mellitus and obesity may further enhance these deposits, hence hypersecretion of IAPP may be involved in the progression of this disease.

Aged↗
PubMed1992

Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with proliferative activity.

To evaluate the relationship between PET using 18F-fluorodeoxyglucose (FDG) and pathological findings and to compare indices obtained by FDG-PET, FDG-PET was performed in 23 patients with untreated malignant lymphoma. Three indices obtained by FDG-PET, tumor-to-normal contrast ratio (TCR), distribution absorption ratio (DAR), k1k2/(k2 + k3), correlated with proliferative activity which was pathologically estimated both by mitotic count and by proportion of cells in all phases of the cell cycle. The relationship did not significantly change according to which of the three indices was chosen. FDG-PET, which shows the proliferative activity of tumors, is considered to be a useful method for managing tumors.

Adult↗
PubMed1991

Prognostic factors for local control in nasopharyngeal cancer (NPC): analysis by multivariate proportional hazard models.

Despite the development of meticulous radiation therapy techniques, the local control of the nasopharyngeal cancer (NPC) remains unsatisfactory. We examined retrospectively the clinicopathologic factors which have impact upon local recurrence-free survival (LRFS) of the 67 patients with NPC who had been irradiated greater than or equal to 40 Gy with curative intent from 1975 through 1988. Three-year LRFS rate was 63%. T stage, histology, the presence of accompanying lymphocytic infiltration, and the properness of radiation therapy had influence upon LRFS with a statistical significance. Multivariate proportional hazard models showed that T stage and pathology retained significance. Radiation therapy properness emerged as a third factor when only the patients irradiated greater than or equal to 60 Gy were included in the analysis. From these results, three groups with low, moderate, and high risk of shortened LRFS could be separated. This risk classification could contribute to the stratification criteria of future study for the improvement of local control by new modalities.

Adult↗
PubMed1991

Non-Hodgkin's lymphoma confined to the nasal cavity: its relationship to the polymorphic reticulosis and results of radiation therapy.

From 1975 through 1988, nine patients with locally confined nasal non-Hodgkin's lymphoma (NHL) were treated with radiation therapy in the Department of Radiology, Chiba University Hospital. Immunohistochemical study disclosed that all NHL's have T-lineage. Additionally, unique histological pictures of polymorphism, angiodestruction, and necrosis were seen in most of cases. These three findings are the histological features of polymorphic reticulosis (PMR), which is the main cause of lethal midline granuloma and has recently been shown to belong to T-cell malignancy. Therefore, it is concluded that the nasal T-cell NHL and PMR are really a single disease entity. The predominance of the T-cell lymphoma in the nasal cavity as well as its histological distinctness clearly indicate that the head and neck extranodal NHL cannot be discussed together. Although the disorder was considered to be locally limited at presentation, only 3 of the 9 patients with nasal NHL could be induced into long-term remission with involved field radiotherapy. The distant extranodal spread was the primary cause of failure. Multimodality treatment using intensive chemotherapy might improve the prognosis of nasal NHL.

Female↗
PubMed1991

Multiple pulmonary hyalinizing granulomas associated with systemic idiopathic fibrosis.

A 41-year-old man with progressive nodular infiltration of the lung of about 2 years' duration died of cardiac and respiratory failure. Autopsy revealed bilateral multiple pulmonary hyalinizing granulomas (PHGs) diagnosed on the basis of the characteristic dense hyaline collagen bundles with nonspecific inflammatory infiltration. Constrictive pericarditis, retroperitoneal fibrosis, mediastinal fibrosis, fibrous thickening of the peritoneal and pleural surfaces, and fibrosis of soft tissue of the neck, flank, and hepatic hilar region were present, therefore, a diagnosis of systemic idiopathic fibrosis was made. The patient had anti-thyroglobulin and anti-thyroid microsomal antibodies and lymphocytic thyroiditis. The inflammatory process of PHG of the present case was active and the clinical course was progressive. PHG seems to be a lesion belonging to the systemic idiopathic fibrosis complex. Immunologic abnormalities may be related to PHG and systemic idiopathic fibrosis.

Adult↗
PubMed1991

Amyloid protein in somatostatinoma differs from human islet amyloid polypeptide.

Amyloid deposits in somatostatinomas are rare observations. To examine the characteristics of this amyloid, we compared amyloid deposits in a somatostatinoma to those found in pancreatic tissue in patients with Type II diabetes mellitus and in insulinomas, using immunohistochemical techniques and specific antibodies to islet amyloid polypeptide or other pancreatic hormones, as well as electron-microscopy. Antibodies to islet amyloid polypeptide regions 8-17 or 25-37 were confirmed to be specific. Amyloid deposits in patients with Type II diabetes mellitus and in insulinomas, but not those in the somatostatinoma strongly reacted with these antibodies, or to an antibody to amyloid P component. Amyloid deposits in the somatostatinoma were not reactive with antibodies to somatostatin or to other pancreatic hormones. Electron-microscopic examinations revealed that amyloid fibrils in the somatostatinoma were thinner and more randomly distributed than were those in islets from patients with Type II diabetes mellitus. As amyloid in somatostatinomas is unlike that consisting of islet amyloid polypeptide or other mature pancreatic hormones, it may be a novel type of local amyloid in pancreatic islets.

Adult↗