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Biomedical subjects

Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 127 records · Page 7Linked to original sources
PubMed1998

Adult T cell leukemia/lymphoma with massive involvement of cardiac muscle and valves.

An autopsy case of a 58-year-old woman with massive cardiac involvement of adult T cell leukemia/lymphoma (ATLL) is reported. She developed cardiac failure due to aortic and mitral regurgitation with cardiac infiltration of ATLL cells, and underwent replacement of both aortic and mitral valves. Studies of the cut-surfaces revealed diffuse thickening of the subendocardial wall of the left chamber with widespread whitish-brown tumor infiltrates. In the regions surrounding the replaced aortic and mitral valves there was also massive tumor cell infiltration. The tumor cells infiltrating the cardiac muscle wall were T cell in origin and exhibited Leu-3a (CD4)-positive immunoreaction. Ultrastructurally, tumor cells contained markedly indented nuclei and some were attached directly to the muscle cells. These findings suggest that this was an unusual form of ATLL with widespread involvement of the heart.

Biomarkers, Tumor↗
PubMed1998

Marked elevation of CA19-9 in a patient with idiopathic pulmonary fibrosis: CA19-9 as a bad prognostic factor.

A 53-year-old Japanese female, who had been suffering from idiopathic pulmonary fibrosis (IPF) for 3 years, was admitted with dyspnoea. The important laboratory finding on admission was a serum CA19-9 level of 649 U/mL. Despite steroid treatment for IPF, her respiratory condition gradually deteriorated with the increase of serum CA19-9 level up to 3020 U/mL and she died of respiratory failure. Immunohistochemistry showed the positive stain of CA19-9 in bronchoepithelial cells. We also reviewed the Index Medics and picked up the cases who had elevation of CA19-9 more than 1000 U/mL, and six patients were listed. Five of these six patients died within 6 months, therefore the marked elevation of CA19-9 seemed to be a bad prognostic factor in patients with pulmonary fibrosis.

CA-19-9 Antigen↗
PubMed1998

Detection of anti-cytokeratin 8 antibody in the serum of patients with cryptogenic fibrosing alveolitis and pulmonary fibrosis associated with collagen vascular disorders.

BACKGROUND: It has been suggested that the humoral immune system plays a role in the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating autoantibodies to lung protein(s) have been suggested, none of the lung proteins have been characterised. The purpose of this study was to determine the antigen to which the serum from patients with pulmonary fibrosis reacted. METHODS: The anti-A549 cell antibody was characterised in a patient with CFA using Western immunoblotting and immunohistochemical staining of A549 cells. As we identified that one of the antibodies against A549 cells was anti-cytokeratin 8, the expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we attempted to establish an enzyme linked immunosorbent assay to measure the levels of anti-cytokeratin 8 antibody in the serum of patients with CFA and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). RESULTS: Initially two anti-A549 cell antibodies were detected in the serum of patients with pulmonary fibrosis, one of which was characterised as anticytokeratin 8 antibody by Western immunoblotting. We were able to establish an ELISA to measure anti-cytokeratin 8 antibody and found significantly higher levels in patients with CFA and PF-CVD than in normal volunteers, patients with sarcoidosis, pneumonia, and pulmonary emphysema. CONCLUSIONS: One of the anti-A549 cell antibodies in the serum of patients with CFA was against cytokeratin 8. The serum levels of anti-cytokeratin 8 antibody were increased in patients with CFA and PF-CVD. These results suggest that anticytokeratin 8 antibody may be involved in the process of lung injury in pulmonary fibrosis.

Adult↗
PubMed1998

T-cell-rich B-cell lymphoma in a pig.

A case of multicentric lymphoma with a mixed cell population of large to small round cells with the same nuclear features in a pig was studied immunohistochemically. Neoplastic tissues were composed of 20-50% B-cell lymphoma cells with lambda-type light chain restriction, and 50-80% cluster of differentiation (CD)3+ T-cells. These findings were similar to those of human T-cell-rich B-cell lymphoma (TCRBCL). In addition, both immunoglobulin IgM and IgG were detected in the cytoplasm of the identical lymphoma cell. This pattern of heavy chain expression appeared to be due to maturational arrest in cellular development at the point of heavy chain class switching, as occurs in biclonal gammopathy in human lymphoid malignancy. This case as TCRBCL containing two types of heavy chains with light chain restriction (IgM-lambda and IgG-lambda) appears to be the first of its kind reported in the English literature for either pigs or domestic animals.

Animals↗
PubMed1998

Neutrophil elastase: alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis.

It was hypothesized that neutrophil elastase released from activated neutrophils may play an important role in the pathogenesis of pulmonary fibrosis. In the present study, we measured the neutrophil elastase:alpha-1-proteinase inhibitor complex (E-PI) in serum and bronchoalveolar lavage fluid (BALF) in 26 patients with pulmonary fibrosis and evaluated the correlation between E-PI levels and several parameters. E-PI levels in serum of patients with pulmonary fibrosis (635.8+/-112.0 ng.mL(-1)) were significantly elevated compared to normal nonsmokers (122.0+/-4.0 ng.mL(-1)) as well as normal smokers (132.8+/-8.4 ng.mL(-1)) (p<0.01). E-PI levels in serum significantly correlated with hepatocyte growth factor (HGF) levels in serum, C-reactive protein (CRP), and negatively correlated with arterial oxygen tension (Pa,O2), and arterial carbon dioxide tension (Pa,CO2). E-PI/albumin levels in BALF significantly correlated with HGF/albumin levels in BALF, lactate dehydrogenase (LDH)/albumin in BALF, total number of inflammatory cells (alveolar macrophages and neutrophils) in BALF, and several markers derived from epithelial cells in BALF. Our data demonstrated: 1) neutrophil elastase:alpha-1-proteinase inhibitor complex in serum increased in patients with pulmonary fibrosis; and 2) neutrophil elastase:alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid correlated with clinical parameters in pulmonary fibrosis. These results suggest that neutrophil elastase may play a significant role in the process of lung injury in pulmonary fibrosis.

Adult↗
PubMed1998

Heterogeneous point mutations of the p53 gene in pulmonary fibrosis.

Lung cancer is a frequent complication in pulmonary fibrosis. Overexpression of p53 proteins has been demonstrated by immunostaining in bronchoepithelial cells in patients with idiopathic pulmonary fibrosis. However, it is still unclear whether this overexpressed p53 protein is wild-type or mutant. It was hypothesized that pulmonary fibrosis may be a precancerous lesion with deoxyribonucleic acid point mutations in bronchoepithelial cells. Mutations of the p53 gene were tested for by fluorescence-based single-strand conformation polymorphism (FSSCP), cloning-sequencing and immunostaining techniques. Out of 10 tissue samples that demonstrated overexpression of p53 protein by immunostaining, nine (90%) exhibited point mutations and eight (80%) exhibited heterogeneous point mutations of the p53 gene. The mutations found in pulmonary fibrosis were scattered throughout the central part of the p53 gene, and both guanine (G):cytosine (C) to adenine (A):thymine (T) and A:T to G:C transitions were frequently observed. In conclusion, frequent heterogeneous point mutations of the p53 gene were detected in pulmonary fibrosis. These mutations may have resulted from several types of deoxyribonucleic acid damage that occurred in bronchoepithelial cells and this may explain previous findings of a very high incidence of lung cancer complicating pulmonary fibrosis.

Adult↗
PubMed1998

Eosinophilic proliferative pylephlebitis in the liver of Japanese beef cattle with fascioliasis.

Intrahepatic pylephlebitis was detected in 17 Japanese beef cattle. Grossly, the intrahepatic vessels in the caudate lobe and/or in the periphery of the other hepatic lobes were thickened and protruded above the lobar surface. The vessel lumina were packed with white to red, waste thread-like contents. A few immature flukes were found in the bile ducts in 3 of the 7 cases with biliary thickening. Foci of hepatic necrosis and hemorrhage were scattered around the thickened vessels in 8 cases. Histologically, the interlobular veins were thickened due to severe intimal hyperplasia with endothelial proliferation and eosinophilic accumulation and medial hypertrophy, accompanied by fibrosis and eosinophilic infiltration in the portal areas. Hepatic tissues with necrosis and hemorrhage were surrounded by eosinophils and histiocytes including a granulomatous reaction. One immature fluke was detected in one of these regions of necrosis. Immunoperoxidase staining revealed that the small fluke, Kupffer cells, and histiocytes in the liver of all cases were positively stained with anti-Japanese Fasciola sp. antiserum. Enzyme-linked immunosorbent assay of the sera of 15 cases revealed that all were positive for the anti-Fasciola antibody. On the basis of these findings, the present cases were regarded as an atypical form of fascioliasis, characterized by eosinophilic proliferative pylephlebitis of the liver.

Animals↗
PubMed1998

Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma.

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.

Adenocarcinoma↗
PubMed1998

Determination of p53 protein and high-risk human papillomavirus DNA in carcinomas of the renal pelvis and ureter.

The presence and distribution of high-risk human papillomavirus (HPV) DNA type-16 and -18 or overexpression of the p53 protein were determined in 31 patients with renal pelvic and ureteral carcinoma in Saga prefecture of Japan, consisting of 28 transitional cell carcinomas (TCCs) and 3 squamous cell carcinomas (SCCs). In situ hybridization with DNA probes for HPV-16 and -18 was performed as well as immunohistochemical techniques using antibody to p53 protein. Fresh tumor tissues from 8 patients were also studied for p53 mutations in exons 5 through 8 by direct sequencing. Of 28 TCC patients at Saga prefecture in Japan, 10 tested were positive for HPV DNA, 5 for HPV type-16, 4 for HPV type-18 and one doubly-positive case. Of the remaining 18 tumors, seven showed positive nuclear staining in cancer cells with p53 antibody. One of the 3 patients with SCCs also revealed the nuclear positivity of the cancer cells with p53 antibody but not with HPV infection. p53 point mutation was detected in 2 cases also showing p53 immunopositivity. Overexpressed p53 protein was statistically more common in invasive and non-papillary (p<0.05) and in high-grade TCCs (p<0.05). These findings suggest that HPV infection, and expression (mutation) of p53 protein may be intimately related to the pathogenesis of urothelial tumor cell growth and progression.

Aged↗
PubMed1998

[Behçet's disease with acute inflammatory foci and localized secondary organizing pneumonia].

A 68-year-old man with incomplete-type Behçet's disease was admitted to our hospital with a one-month history of a high fever and a persistent pulmonary infiltration shadow in the left lower lobe. Chest CT films showed localized round air-space consolidation in the left lower lobe. The fever did not responded to antibiotics, but did resolve with administration of prednisolone 15 mg/day. Left lower lobectomy was done to avoid life-threatening hemoptysis. Histological examination of the main pulmonary lesions revealed old vascular changes such as irregular intimal thickening and perivascular fibrosis. Disoriented elastic fibers of arteries was seen in some areas as were acute inflammatory foci with neutrophilic infiltration, and secondary organizing pneumonia with Masson bodies. From these findings Beçet's disease related pulmonary involvement could not be excluded. Localized secondary organizing pneumonia associated with acute inflammatory foci, as found in this case, is a very rare pulmonary manifestation of Behçet's disease.

Aged↗
PubMed1997

Molecular cloning and expression of a novel human cDNA containing CAG repeats.

A novel human cDNA containing CAG repeats, designated B120, was cloned by PCR amplification. An approximately 300-bp 3' untranslated region in this cDNA was followed by a 3426-bp coding region containing the CAG repeats. A computer search failed to find any significant homology between this cDNA and previously reported genes. The number of CAG trinucleotide repeats appeared to vary from seven to 12 in analyses of genomic DNA from healthy volunteers. An approximately 8-kb band was detected in brain, skeletal muscle and thymus by Northern blot analysis. The deduced amino-acid sequence had a polyglutamine chain encoded by CAG repeats as well as glutamine- and tyrosine-rich repeats, which has also been reported for several RNA binding proteins. We immunized mice with recombinant gene product and established a monoclonal antibody to it. On Western immunoblotting, this antibody detected an approximately 120-kDa protein in human brain tissue. In addition, immunohistochemical staining showed that the cytoplasm of neural cells was stained with this antibody. These findings indicated that B120 is a novel cDNA with a CAG repeat length polymorphism and that its gene product is a cytoplasmic protein with a molecular mass of 120 kDa.

Amino Acid Sequence↗
PubMed1997

Human herpesvirus 6 (HHV-6)-positive Burkitt's lymphoma: establishment of a novel cell line infected with HHV-6.

Human herpesvirus 6 (HHV-6) DNA has been detected in several human lymphoproliferative disorders. We report a case of HHV-6-infected Burkitt's lymphoma, from which a cell line, designated Katata, has been established. Katata cells had an immature B-cell phenotype with an L3 morphology and carried a t(8;14)(q24;q32) chromosomal abnormality. The HHV-6 DNA sequences were detected in both the patient's tumor cells and Katata cell line by polymerase chain reaction using three sets of primers that target different regions of HHV-6 DNA. The presence of HHV-6 DNA in Katata cells was also shown by Southern blot hybridization with the BamHI fragment of HHV-6. It is likely that the virus is in a latent state, since (1) virion-associated protein was not expressed in Katata cells, (2) transcriptional level of the immediate-early gene was very low, and (3) no viral particles were observed by electron microscopy. Katata cells were highly tumorigenic in nude mice and the tumor cells also contained HHV-6 DNA. We have successfully obtained several clonal lines by allowing the cells to form colonies in soft agarose and by the limiting dilution method. HHV-6 DNA was detectable in all 13 clones analyzed, suggesting that virtually all Katata cells are infected with HHV-6. This is the first report of a case of HHV-6+ Burkitt's lymphoma in the absence of Epstein-Barr virus. Furthermore, there has been no report of lymphoma cell lines that are persistently and nonproductively infected with HHV-6. The Katata Burkitt's lymphoma cell line, therefore, would provide a useful tool for studies of the mechanisms of HHV-6 latency and reactivation.

Animals↗
PubMed1997

Transgenic expression of a novel thymic epithelial cell antigen stimulates abberant development of thymocytes.

We previously reported a novel thymic stromal cell Ag, HS9, as a potent molecule participating in intrathymic T cell development. HS9 Ag is expressed on thymic stromal cells especially in the cortex but not on thymocytes. In the present study, we isolated and characterized a novel cDNA, N14, encoding HS9 Ag. Sequencing analysis of N14 cDNA has revealed it to be a novel one without any significant homology to previously reported functional molecules. COS7 cells transfected with expression vectors harboring N14 cDNA became reactive with HS9-specific mAb. Northern blot analysis and in situ hybridization revealed that several tissues that are positive for HS9 mAb expressed N14 mRNA. To examine the role of this molecule in T cell development, transgenic mice were generated. In situ hybridization and immunohistochemical study showed that the transgene was significantly overexpressed on both cortical and medullar thymic stromal cells but not on thymocytes. Flow cytometric analyses showed that the percentages of mature CD4- CD8+ or CD4+ CD8- thymocytes in transgenic mice were approximately twice and triple, respectively, those in control littermates. Moreover, substantial CD4+ CD8+ thymocytes appeared to have high levels of TCR compared with peripheral T cells. Histologic examination revealed that transgenic mice had thin cortex and relatively developed medulla. These data indicate the critical role of the N14 gene in T cell development.

Amino Acid Sequence↗
PubMed1997

Ameloblastoma of the mandible metastasizing to the orbit with malignant transformation. A histopathological and immunohistochemical study.

We report here a case of ameloblastoma of the mandible with multiple local recurrences and metastasis to the orbit. The patient was a 63-year-old Japanese woman with visual disturbance of her right eye. Diagnostic imaging revealed a mass occupying the right orbital apex with partial intracranial involvement. She had been surgically treated for mandibular ameloblastoma 27 years previously, and the tumour had recurred three times in the past 5 years. The orbital tumour and recurrent ameloblastomas were investigated histopathologically and immunohistochemically. The tumour changed in morphology as it recurred, from follicular ameloblastoma without atypia to apparent malignant tumours disclosing undifferentiated or squamoid features. On immunohistochemical analysis, staining for cytokeratin was positive in the squamoid cells but not in the undifferentiated cells. Both histopathologically and immunohistochemically, the orbital tumour was almost identical to the undifferentiated recurrent tumour. The orbital tumour was distinct from the primary site or sites of recurrence of ameloblastoma, and we concluded that the mandibular ameloblastoma underwent malignant transformation with multiple recurrences and finally metastasized to the orbit.

Ameloblastoma↗
PubMed1997

Epithelioid sarcoma producing granulocyte colony-stimulating factor.

An epithelioid sarcoma of the perineum of a 60-year-old man with widespread metastases produced leukocytosis, myeloid hyperplasia of the bone marrow, and splenomegaly. High titers of granulocyte colony-stimulating factor (G-CSF) were found in the patient's serum and primary culture medium of the tumor tissue. The tumor tissue extract contained m-RNA for G-CSF in large quantities, proving that the tumor was the source of this cytokine.

Granulocyte Colony-Stimulating Factor↗
PubMed1997

An HTLV-I carrier with Graves' disease followed by uveitis: isolation of HTLV-I from thyroid tissue.

We report a long-term (14-year) follow-up of a human T-lymphotropic virus type I (HTLV-I)-infected male who was successively afflicted with Graves' disease followed by uveitis. HTLV-I proviral DNA was detected by polymerase chain reaction in the thyroid tissue and HTLV-I was isolated from thyroid tissue by coculture with peripheral blood lymphocytes from an HTLV-I-uninfected healthy female. This case study supports a close relationship between Graves' disease and uveitis in an HTLV-I carrier.

Adult↗
PubMed1997

High serum levels of CA125 and interleukin-6 in a patient with Ki-1 lymphoma.

We report a 53-year-old-man with an aggressive Ki-1 lymphoma who had high serum CA125, a marker protein of the epithelial ovarian cancer, and interleukin-6 (IL-6) concentrations. Both CA125 and IL-6 levels decreased after chemotherapy and elevated with disease progression. The patient's lymphoma cells obtained before chemotherapy grew continuously in vitro, were IL-6 dependent and were found to secrete CA125 in culture medium. These results indicate that CA125 can be secreted by Ki-1 lymphoma cells and IL-6 may promote the growth of Ki-1 lymphoma cells.

Aged↗