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Biomedical subjects

A Mikata

Publications and source records attributed to A Mikata.

At least 19 recordsLinked to original sources
PubMed1995

Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80-negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Adolescent↗
PubMed1995

Investigation of EB virus and cytomegalovirus in rapidly progressive interstitial pneumonitis in polymyositis/dermatomyositis by in situ hybridization and polymerase chain reaction.

In polymyositis/dermatomyositis (PM/DM), a rapidly progressive interstitial pneumonitis (RPIP) which is a fatal complication of unknown etiology has received increasing attention. We have encountered 9 RPIP cases among 150 PM/DM cases in the past 10 years. To investigate the pathogenic role of viruses in RPIP, we examined lung specimens from patients with RPIP in PM/DM for the presence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) using polymerase chain reaction (PCR) and in situ hybridization (ISH). We analyzed 21 specimens from RPIP in PM/DM (n = 9), collagen diseases (n = 6; 4 had interstitial lung disease), and controls (n = 6). EBV was frequently detected in RPIP (7/9 by PCR 3/9 by ISH), but was also detected in other collagen diseases of the lungs. In lung specimens from both patients with RPIP in PM/DM and those with collagen diseases, EBV was significantly detected (13/15 by PCR, 5/15 by ISH, P < 0.005) compared to controls (1/6 by PCR, 0/6 by ISH). CMV was detected by ISH in 2 RPIP patients but in none of he others, though by PCR CMV was detected equally in the three groups studied. These findings indicate that a direct involvement of EBV or CMV in RPIP of PM/DM is unlikely, although it is possible that an immune response to latent viruses or viral products in PM/DM may have a role in the pathogenesis of the RPIP.

Adult↗
PubMed1995

Restricted V beta gene usage of tumour-infiltrating T lymphocytes in primary gastric malignant B-cell lymphoma.

Ten cases of primary gastric malignant lymphoma (PGL) were investigated by immunohistochemical and molecular genetic analysis. These cases were diagnosed histopathologically as follicular small cleaved cell type (1 case), diffuse small cleaved cell type (3 cases) and diffuse large cell type (6 cases) based on the WF (Working Formulation) classification. Seven cases classified as small cleaved or diffuse large cell type belong to low (4 cases) or high (3 cases) grade MALT lymphoma according to Isaacson's classification. All PGL belonged to B lineage cells according to immunohistochemical study and immunoglobulin rearrangements. Rearrangements of TCR beta chain genes were observed in four of the ten cases. The possibility that the TCR beta rearrangements were caused by tumour-infiltrating T-cells (TILs) was supported by the following observations: the tumours did not show T- and B-cell biphenotype, TCR beta exhibited functional VDJ rearrangement and V beta usage pattern was not a neoplastic type. Analysis of the repertoire of the TCR beta chain in TILs revealed a common usage of V beta 2 in the above four cases, and furthermore, predominant usage of a particular beta chain composed of V beta 2-D beta 2.1-J beta 2.3 was observed in one of the four cases. These results indicate that the TILs of PGL have a restricted TCR repertoire.

Adult↗
PubMed1995

Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.

To study the effect of localised secretion of chemokines on tumour growth, the genes for human (hu) interleukin 8 (IL-8), hu-MCP-1 (MCAF), hu-MIP-1 alpha (LD78), murine (mu)-MCP-1 (JE), mu-MIP-1 alpha or mu-MIP-2 were introduced, via mammalian expression vectors, into Chinese hamster ovary (CHO) cells, and the ability of transfected cells to form tumours in vivo was evaluated. The production of hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha by transfected clones did not influence the growth rate in vitro, but drastically suppressed tumour growth when injected subcutaneously (s.c.) into nude mice. However, clones transfected with hu-MCP-1, mu-MCP-1 or mu-MIP-2 did not show any significant difference in growth rate in vivo compared with clones transfected with vector alone. Histological examination of the site of injection of CHO clones transfected with hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activity when released, even at low doses, at the tumour site, which may be mediated by recruitment and targeting of neutrophilic granulocytes to chemokine-releasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.

Amino Acid Sequence↗
PubMed1995

Immunoglobulin gene analysis of cutaneous pseudolymphoma by polymerase chain reaction.

Polymerase chain reaction (PCR) was used to amplify the V-D-J region of the immunoglobulin heavy chain gene from DNA extracted from the formalin fixed, paraffin embedded skin of 3 cases of pseudolymphoma. The products were electrophoresed and observed under ultraviolet light after ethidium bromide staining. Specimens of two cases showed smears of polyclonal amplified DNA. The specimen of one case (Case 3), however, showed a single band with a smear. The presence of monoclonality in B lymphocyte populations may suggest the possibility of low grade malignancy of pseudolymphoma or transformation to malignant lymphoma in the future.

Adult↗
PubMed1995

T cell-rich B cell lymphoma bearing Epstein-Barr virus in tumor cells: a case of IBL-T-like lesion following Lennert's lesion.

A case of T cell-rich B cell lymphoma (TCRBCL) with Epstein-Barr virus (EBV) infection in tumor cells is reported. A 50 year old male developed right cervical lymph node swelling in July 1988. Initial biopsy in April 1989 demonstrated many scattered Hodgkinoid atypical cells with Lennert's lesion. After partial remission following chemotherapy, the lymph nodes enlarged again, and a second biopsy in February 1991 showed an IBL-T-like lesion. Only a small number of Hodgkinoid atypical cells were still observed. After apparently, complete remission, the lesion soon recurred and the patient died in November 1992. Immunohistochemically the Hodgkinoid cells were positive for L26, but negative for LN2, LN3, UCHL-1, MT1, lysozyme, Ber-H2 and Leu-M1. Reactivity for immunoglobulins showed false-positive because of polyclonal staining. IgH monoclonality was detected by the polymerase chain reaction method in the first biopsied specimen, and by Southern blotting in the second biopsied snap-frozen specimen. Monoclonal TCR beta rearrangement was not detected. The Hodgkinoid atypical cells were positive for EBV-encoding RNA by in situ hybridization, and LMP-1 by immunostaining. Occasionally, EBV-bearing immunoblastic, medium sized, or small lymphocytic cells were also observed. This case indicates the possibility that EBV is related to the pathogenesis of TCRBCL.

Blotting, Southern↗
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↗
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

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↗
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↗
PubMed1991

Expression of functional molecules in non-Hodgkin's lymphoma. Correlation with bone marrow involvement and serum LDH value.

It is well known that non-Hodgkin's lymphoma (NHL) cells express various antigens which are normally involved in a variety of functions. In addition, NHL is diverse in its proliferative capacity. To investigate the relation between these factors and the clinical picture, 45 cases of NHL were studied by immunohistochemistry using snap-frozen materials obtained before therapy. Reactivities with 27 monoclonal antibodies were examined and the results were correlated with clinical findings. The expression of surface mu and ICAM-1 in B-NHLs and CD25 in T-NHLs were significantly associated with bone marrow involvement. B-NHLs without expression of CD21(B2) and T-NHLs with CD25 were seen more frequently in cases with a LDH value of over 500 units/ml. The positivity rate of Ki-67 on B-NHLs was correlated with serum LDH value, NHL histologic classification, and overall survival. These data indicate that immunophenotyping and determination of the proliferative capacity of NHL are of value not only for confirmation of the histopathologic classification of the tumor but also for assessment of clinical behavior.

Adult↗