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Biomedical subjects

Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 19 recordsLinked to original sources
PubMed1995

p53 and human papillomavirus DNA in renal pelvic and ureteral carcinoma including dysplastic lesions.

Ninety-eight cases of transitional-cell carcinoma (TCC) of the renal pelvis and ureter, including dysplastic lesions, were studied for tumor incorporation of human papillomavirus (HPV) type-16 and type-18 DNA by in situ hybridization (ISH) with DNA probes for each HPV viral type. Immunohistochemical analysis of p53 expression was also performed. Fresh tumor tissues from 26 patients were also studied for p53 mutations in exons 4 through 9 by direct sequencing and for HPV infection by polymerase chain reaction (PCR). Thirty-two tumors were positive for HPV DNAs, including 6 double-positive cases. Among these tumors, adjacent dysplastic lesions in 21 cases (66%) also revealed identical reactivity. Overexpressed p53 was detected in 26 cases. Expression of p53 was also detected in dysplastic lesions in 19 out of these 26 cases (73%). Three cases were positive for both HPV DNA and p53 antibody. p53 point mutation was detected in 7 of 26 cases, 6 of which were also positive for p53. HPV type-16 DNA was detected in 6 cases by PCR, 4 of which were also ISH-positive. Overexpressed p53 was frequently detected in invasive and non-papillary tumors (p < 0.01) and in high-grade tumors (p < 0.05). HPV infection was more common in non-invasive and papillary tumors (p < 0.05). These findings suggest that HPV infection or overexpression (mutation) of p53 may be an early event and be related to phenotypes of tumor-cell growth patterns and progression.

Adult↗
PubMed1995

Inactivation of the DCC tumor suppressor gene in a B-cell lymphoma cell line with the alteration of chromosome 18.

A B-cell lymphoma cell line, designated KML-1, was established from pleural effusion of a patient with non-Hodgkin's lymphoma of large-cell type. The lymphoma arose in the pelvis and ran an aggressive clinical course. Chromosome analysis of the cell line exhibited a complex karyotype including the loss of chromosome 18. To evaluate the molecular events in the cell line that may be associated with the development of the lymphoma, we investigated the expression and/or alterations of several classes of human genes, including oncogenes, tumor suppressor genes, and cytokine genes. The expression of the DCC (deleted in colorectal cancer) gene, located on the chromosome 18q21, was extremely reduced in KML-1 cell line, as compared with that in a normal spleen tissue and other 4 lymphoma cell lines by the reverse transcription-polymerase-chain-reaction (RT-PCR) method. This finding suggests that inactivation of the DCC gene might play a role in the pathogenesis of the case of lymphoma.

Adult↗
PubMed1995

The pathogenesis of so-called cardiac rhabdomyoma in swine: a histological, immunohistochemical and ultrastructural study.

To determine whether cardiac rhabdomyoma (CR) is a hamartoma of fetal cardiac myocyte, we investigated five cases of CRs that spontaneously developed in five 6-month-old hybrid swine with histological, immunohistochemical, and ultrastructural techniques. The cases were four multiple and one solitary neoplasms, which appeared as intraventricular nodules of various sizes without any congenital malformations. Histologically, the large ovoid CR cells with an occasional spiderweb appearance showed a transition from normal-looking cardiac myocytes or rarely from Purkinje cells, but no mitotic figures. Besides large amounts of glycogen, the CR cells contained many PAS-negative, large cytoplasmic vacuoles filled with eosinophilic or fibrillar substance. Immunohistochemically, the CR cells showed intense positivity for desmin and variable positivities for vimentin, alpha-atrial naturiuretic peptide, and proliferating cell nuclear antigen. These positivities were not seen in adjacent cardiac myocytes. Cytokeratin was negative in the CR cells but was positive in fetal cardiac myocytes of early gestation. Rod-like or granular positivity for alpha-actinin in the CR cells was similar to that in nemaline myopathy. Ultrastructurally, the CR cells contained myofibrils that frequently showed myofibrillar degeneration and produced large intracytoplasmic vacuoles. These myofibrils often mingled with nemaline bodies and leptofibrils that continued to the Z bands. T-systems, sarcoplasmic reticulum, and intercalated discs, which are specific features of postnatal cardiac myocytes, were sometimes observed in the CR cells. Increase of glycogen and mitochondria and appearance of atrial-specific granules associated with the Golgi apparatus were other features noted. The present findings have not been reported, even in human CR. From these new observations with the recent report on the occurrence of CR in neonatal piglets, swine CR does not belong to the entity of hamartoma but may be a congenital dysplasia of the perinatal cardiac tissues with myofibrillar degeneration, affecting mainly cardiac myocytes and rarely Purkinje cells. The various immunophenotypic changes including proliferating cell nuclear antigen and the increase and appearance of cytoplasmic elements compared with mature cardiac myocytes can be interpreted as reactive or regenerative changes due to myofibrillar degeneration.

Animals↗
PubMed1995

Clinicopathological study on two types of cryptogenic organizing pneumonitis.

Clinical and pathological studies on cryptogenic organizing pneumonitis (COP) were performed in 19 cases diagnosed with transbronchial lung biopsy (TBLB). All patients suffered from fever and several respiratory symptoms. Laboratory data showed increases in erythrocyte sedimentation rate, positivity for C-reactive protein, negative tuberculin reactions and increases in complement level. Pathological findings demonstrated that there were two kinds of organizing processes. Fourteen of the 19 cases were treated with prednisolone, and two cases were observed without administration. The remaining three cases could not be followed up after therapy. In 11 of the 16 cases, abnormal shadows in chest X-ray disappeared, but remained present in five cases. As for the relationship between pathological findings and shadows in chest X-ray, Masson bodies without fibrin were observed in the 11 cases which were without shadows on X-ray, but Masson bodies containing or related to fibrin were observed in the five cases in which abnormal shadows remained. These results suggest that there are two types of organizing process in COP. Type I is an unexplained organizing process in which fibrin is not present or involved. It responds well to steroids and the prognosis is favourable. Type II is an organizing process which involves fibrin, and the character of the fibroblast-like cells is very similar to that of myofibroblasts. Type II organizing process responds poorly to steroids. Both processes can be notified relatively easily, even by TBLB tissues.

Adult↗
PubMed1995

Direct transplantation of chronic myelogenous leukemia cells into nude mice and establishment of a leukemic stem cell (Ph1+, CD34+) line dependent on mouse bone marrow stromal cells in vitro.

Peripheral blood cells from a female patient with Ph1-positive chronic myelogenous leukemia (CML) in blast crisis were serially transplanted in BALB/c nude mice for 16 passages. This in vivo cell line, designated CML-N-1, had Ph1 chromosome abnormality and BCR gene rearrangement. The cells expressed CD11b, CD13, CD33, CD34, CD38, and HLA-DR antigens until the 11th passage and subcutaneous tumors produced by these passages were composed of admixtures of immature and maturing cells that differentiated to basophils when cultured in vitro. From the 12th passage on, the tumors became composed mainly of immature cells expressing CD13, CD34, and HLA-DR, and no longer differentiated to basophils even upon in vitro culture. In contrast to the vigorous proliferation in vivo, CML-N-1 cells from any passage failed to proliferate in vitro under standard liquid culture conditions with or without growth factors, such as granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte colony-stimulating factor, interleukin 3, interleukin 6 and stem cell factor. However, a continuously growing cell line, designated CML-C-1, was established by culturing CML-N-1 cells on feeder layers of mouse bone marrow stromal cells. This mouse bone marrow stromal cell-dependent cell line showed immature cell morphology and expressed early myeloid phenotype positive for CD13, CD34, and HLA-DR. These results indicate that mouse bone marrow stromal cells provide a certain growth factor(s) active on human leukemia cells.

Adult↗
PubMed1995

Mucinous cholangiocarcinoma featuring a unique microcystic appearance.

An autopsy case is presented of a peculiar type of intrahepatic mucinous adenocarcinoma with microcyst formation arising in a 78 year old Japanese man who died of hepatic coma and renal failure 4 months after onset. Macroscopically, the cut surface of the lesion revealed a characteristic honeycomb-like appearance, consisting purely of microcysts, 0.2-0.4 cm in diameter, lined by prolific mucin-producing adenocarcinoma cells. The lesion did not have large cystic space, fibrous capsule, or benign cystadenomatous component other than neoplastic microcyst formation. The carcinoma cells showed various proliferating patterns, such as irregularly shaped nest-like, trabecular, papillary and tubular ones, directly invaded the hepatic parenchyma and portal tract with loose or thick fibrosis, and infiltrated extensively into both intrahepatic and extrahepatic stroma along the vascular structures. From these clinicopathological findings, we consider the present tumor to be a variant of mucinous cholangiocarcinoma with characteristic microcyst formation rather than a type of cystadenocarcinoma.

Aged↗
PubMed1993

Morphological characterization of a new human epithelioid sarcoma cell line, ES020488, in vitro and in vivo.

A new human epithelioid sarcoma cell line (ES020488) was established from a cutaneous metastasis in 26-year-old man, and was morphologically characterized in vitro and in vivo by comparison with the original tumor. The ES020488 cells showed a male karyotype ranging from 39 to 83 chromosomes, with various abnormalities but no specific pattern. The cells were round, polygonal or spindle-shaped with abundant cytoplasm and round nuclei containing prominent nucleoli; they proliferated in a sheet-like pattern. Tumors transplanted into nude mice revealed essentially the same features as the original tumor. Both in vitro and in vivo, the cells immunohistochemically expressed vimentin, cytokeratin, and EMA, but not desmin and S-100 protein. Ultrastructural study revealed irregular or round nuclei containing abundant euchromatin and prominent nucleoli, many intermediate filaments running irregularly or around the nucleus, and a number of filopodia-like processes. ES020488 cells were thus proven to retain and exhibit the unique morphological characteristics of an epithelioid sarcoma both in vitro and in vivo. These cells are possibly derived from synovioblastic mesenchyme.

Adult↗
PubMed1993

Cutaneous plexiform schwannoma in a pig.

A plexiform schwannoma (PFS) observed as a solitary mass in the dermis of a 6-month-old pig consisted of schwannoma cells of Antoni A type and B type. Neoplastic cells in Antoni A type areas sometimes showed cord-like outgrowths or a neurofibromatous pattern. Neoplastic cells in Antoni B type areas showed erythrophagocytosis, some encircling the microvasculature. Immunohistochemically, neoplastic cells were strongly positive for S-100 protein and vimentin. Peripheral parts of the nodules were cytokeratin (clone AE1/AE3)-positive, as in normal swine perineurial cells. Double immunostaining clearly demonstrated neoplastic cells doubly positive for both S-100 protein and cytokeratin, suggesting that S-100-positive Schwann cells and cytokeratin-positive perineurial cells are functional variants of the same cell type. Ultrastructurally, neoplastic cells in Antoni A type areas possessed characteristics of Schwann cells, such as cytoplasmic interdigitation, external laminae and intercellular junctions. At the periphery of the nodules, features of perineurial cells were detected. Neoplastic cells in Antoni B type areas seemed to be undergoing degenerative processes similar to those in Antoni A type regions and they contained many lysosomes. The neoplasm was generally similar in both location and histology to that seen in man, but there were some histological, immunohistochemical and ultrastructural differences. This is the first reported case of PFS in domestic animals.

Animals↗
PubMed1992

Inhibitory effects of human interferons on the immortalization of human, but not rabbit, T lymphocytes by human T-lymphotropic virus type-I (HTLV-I).

The effects of human interferon (IFN)-alpha, -beta, and -gamma on the immortalization of human and rabbit lymphocytes by human T-lymphotropic virus type-I (HTLV-I) have been investigated. The immortalization of human peripheral-blood lymphocytes co-cultured with lethally X-ray-irradiated HTLV-I-producer cells, MT-2, was blocked in the presence of more than 40 u/ml human recombinant IFN-alpha or more than 200 u/ml human natural type IFN-beta. However, rhIFN-gamma did not block immortalization by HTLV-I even at higher doses. On the other hand, the presence of high doses of hIFN-alpha, -beta, or -gamma did not exhibit any biological effect on the immortalization of rabbit peripheral-blood lymphocytes co-cultured with lethally X-ray-irradiated MT-2 cells. Integration of the full length of HTLV-I genome was detected in every transformant by Southern blot analysis. All cell lines established were CD4+/CD8 divided by T-lymphocytes, except for one cell line of CD4+/CD8+. Morphologically intact HTLV-I production was observed by electron microscopy in these cells. Our results indicate that HTLV-I released under the strongly suppressed condition in the presence of IFNs remains active and able to immortalize T lymphocytes. It is also suggested that immortalization of human T lymphocytes by HTLV-I can be inhibited by the antiviral state induced by the treatment with low doses of hIFN-alpha and -beta, whereas immortalization of rabbit T lymphocytes is not inhibited because of the species specificity of hIFNs.

Animals↗
PubMed1992

Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin.

A new Hodgkin's cell line, designated HD-70, was established from the peripheral blood of a 69-year-old man with Hodgkin's disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relatively abundant cytoplasm that is positive for acid phosphatase, alpha-naphthyl butyrate esterase, and periodic acid-Schiff stains. HD-70 cells are positive for CD30 (Ki-1/Ber-H2), CD15 (Leu-M1), and CD71 (OKT9) antigens and contain cytoplasmic immunoglobulin (Ig) (A, kappa). Southern blot analysis showed that the cells have Ig heavy and kappa light chain gene rearrangement and lack T-cell receptor gene rearrangement. Chromosome analysis disclosed that the cells have a human karyotype with complicated abnormalities, including a 14q+. Heterotransplantation of the HD-70 cell line into newborn hamsters treated with antilymphocyte serum produced massive tumors with remarkable fibrosis and collagen band formation. These tumors displayed histologic features similar to those of the nodular sclerosing type tumor of the patient. Such fibrosis production and collagen band formation in heterotransplanted tumors suggest that a certain cytokine that induces fibrosis might be produced by HD-70 cells. This cell line may be useful for understanding the biology and pathogenesis of Hodgkin's disease.

Aged↗
PubMed1992

Establishment and characterization of a thymic carcinoma cell line (Ty-82) carrying t(15;19)(q15;p13) chromosome abnormality.

A new human cell line, designated Ty-82, was established from the pleural effusion of a 22-year-old woman with undifferentiated thymic carcinoma. This cell line consisted of primitive cells that were positive for alpha-naphthyl butyrate esterase and acid phosphatase. The cells were shown to express epithelial membrane antigen, but were completely negative for cytokeratin, carcinoembryonic antigen, glial fibrillary acidic protein, desmin, S-100 protein, lysozyme, Leu-7, HLA-DR (Ia), leukocyte common antigen, Ki-I antigen, T-cell antigens, B-cell antigens, myelomonocyte antigens, and Epstein-Barr-virus nuclear antigen. Electron microscopy showed that the cells were highly anaplastic, with no sign of cellular differentiation to any lineages. The Ty-82 cell line was found to have a karyotype of 46,XX,t(15;19)(q15;p13), being identical to that of the patient's tumor cells. Four of 5 nude mice inoculated sub-cutaneously with Ty-82 cells developed tumors which displayed a histological picture similar to the original tumor. Thymic carcinoma is a recently recognized entity, and its cellular and clinical behavior are poorly understood. The newly established thymic carcinoma cell line would provide a useful tool for the better understanding of this rare disease.

Adenocarcinoma↗
PubMed1992

IgD myeloma presenting as a testicular tumor: establishment and characterization of an IgD-secreting myeloma cell line.

A 72-year-old man presented with a left testicular tumor and underwent orchiectomy. The tumor was massively infiltrated with myeloma cells bearing monoclonal cytoplasmic IgD lambda. Three months after orchiectomy, he developed huge abdominal masses and subsequently ascites containing numerous myeloma cells. An IgD-secreting myeloma cell line, designated delta-47, was established from the ascites. This cell line expressed CD4 and CD38, but lacked Fc and complement receptors, surface immunoglobulin, CD19, HLA-DR, and PCA-1. CD30 was detected on the cultured cells but not on the ascites tumor cells. Delta-47 cells secreted the same immunoglobulin (IgD lambda) as was found in the patient's serum. The light chain had a molecular weight of 35 kD which was larger than that of the normal light chain. Chromosome analysis of delta-47 revealed an aneuploid karyotype with complex abnormalities including 1q+, 2p+, and 14q+. To our knowledge, this is the only IgD-secreting myeloma cell line and would provide a useful tool for the study of IgD production and IgD myeloma.

ADP-ribosyl Cyclase↗
PubMed1992

Immunohistochemical and ultrastructural studies of intraluminal crystalloids in human prostatic carcinomas.

Intraluminal crystalloids (ICr) observed in 19 cases of incidental or invasive human prostatic carcinoma (PCa) and in a case of benign prostatic hyperplasia were examined extensively by immunohistochemistry and electron microscopy. They were brilliantly eosinophilic with haematoxylin and eosin, manifesting needle-like, triangular, rectangular, hexagonal and irregular lump-like in shape. They were strongly positive, dark blue, with phosphotungstic acid -haematoxylin (PTAH) stain in all cases examined. Among the human antibodies tested, epithelial membrane antigen (EMA) gave specifically positive immunostainability with ICr in all cases. Annual ring-like lamellar or concentric structures were detected by electron microscopy. Positive staining of ICr with PTAH and anti-EMA antibody is very useful as a diagnostic marker for PCa in human prostatic tissues.

Aged↗
PubMed1992

HLA-DR antigen- and S-100 protein-positive dendritic cells in esophageal squamous cell carcinoma--their distribution in relation to prognosis.

The distribution of immunohistochemically labeled HLA-DR antigen- and S-100 protein-positive dendritic cell (DR+DC and S100+DC) was investigated in 59 human esophageal squamous cell carcinomas (SCCs). A dense infiltration of both DR+DC and S100+DC was detected in 11, only DR+DC in two, and only S100+DC in one. In the remaining 45 tumors infiltrating DC were sparse. By means of double immunostaining or the mirror section method, three different types of DC, namely S-100-negative and HLA-DR-positive DC(S100-DR+DC), S-100-positive and HLA-DR-negative DC(S100+DR-DC) and double-positive DC(S100+DR+DC) were clearly identified. With regard to postoperative survival, these patients with tumors in which there was a dense infiltration of DR+DCs and/or S100+DCs showed a significantly better survival rate than those in which DC were sparse (DR+DCs - P less than 0.001; S100+DCs - P less than 0.01). These results indicate that DC infiltration may be a prognostic factor in esophageal SCCs.

Adult↗
PubMed1992

Similarity, in molecular structure and function, between the plant toxin purothionin and the mammalian pore-forming proteins.

Many proteins containing domains of a cysteine-rich repeated motif, such as epidermal growth factor (EGF), have been reported. Here we report strong similarity between the amino acid sequence of a plant toxin--i.e., purothionin and its homologues--and with those of a domain found in mammalian pore-forming cytoplasmic proteins: components of complement and perforin of cytotoxic T-lymphocytes or natural killer-like cytotoxic cells. These similar sequences were found to be identical to the so-called EGF-like cysteine-rich repeated motif itself. Electron-microscopic observations indicated that, like complement and perforin, purothionin forms pores in the cytoplasmic membrane of target cells, resulting in their death within a few hours. On the basis of these sequence comparisons and physiological functions, we propose a scheme for the evolution of proteins containing modules of the cysteine-rich repeat motif.

3T3 Cells↗
PubMed1992

Human helper T cell lines established by coculture of normal human cord leukocytes with an HTLV-II-infected rabbit leukocyte cell line (Ra-IIA).

Three helper T cell lines, designated CR-IIA (CR-IIA-1, CR-IIA-2, and CR-IIA-3), were established by coculturing normal human cord leukocytes with a lethally irradiated HTLV-II (human T-lymphotropic virus type II)-infected rabbit leukocyte cell line (Ra-IIA). CR-IIA had a normal human karyotype and expressed the surface markers CD3(+), CD4(+), CD8(-), CD19(-), CD25(+) and HLA-DR(+), confirming their helper T cell nature. CR-IIA cells were all free of Epstein-Barr virus nuclear antigen and were immunoreactive with serum samples from HTLV-I- or HTLV-II-infected patients and with anti-HTLV-I, p19 or p24 antibody. The provirus genome of HTLV-II was detected in these cell lines by the polymerase chain reaction combined with a digoxigenin-enzyme-linked immunosorbent assay. Electron microscopy of CR-IIA-1 cells revealed a few immature type C virus particles. These results suggest that HTLV-II was transmitted from the infected rabbit leukocyte cell line to human cord helper T lymphocytes with the development of immortalized HTLV-II-producing T cell lines.

Animals↗