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Biomedical subjects

Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 19 recordsLinked to original sources

Establishment of a clonal cell line producing granulocyte colony-stimulating factor and parathyroid hormone-related protein from a lung cancer patient with leukocytosis and hypercalcemia.

Squamous cell lung carcinoma cells obtained from a patient who presented with leukocytosis and hypercalcemia were transplanted into nude mice and a serially transplantable cell line, OKa-N-1, was established. The nude mice transplanted with OKa-N-1 cells displayed leukocytosis and hypercalcemia. Serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) were both elevated in these mice. In vitro cultivation of this tumor cell line gave rise to a clonal cell line, OKa-C-1. Nude mice transplanted with the OKa-C-1 cell line also showed leukocytosis and hypercalcemia with high serum G-CSF and PTHrP levels. The culture supernatant of OKa-C-1 contained high levels of G-CSF and PTHrP. Immunohistochemical studies showed the expression of PTHrP in OKa-C-1 cells. Reverse transcription polymerase chain reaction revealed the presence of G-CSF and PTHrP mRNA in this cell line. Dexamethasone treatment inhibited the transcription of G-CSF and PTHrP genes. This new human squamous carcinoma cell line, OKa-C-1, would be useful for studying the mechanism of simultaneous production of G-CSF and PTHrP and their control in cancer patients with leukocytosis and hypercalcemia.

Animals

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

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

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

Myolipoma of the round ligament: report of a case with a review of the English literature.

Tumours consisting of a mixture of mature adipose and smooth muscle tissues, including those designated lipoleiomyomas, fibrolipoleiomyomas and myolipomas, are exceedingly rare, but most often occur in the uterine corpus. We describe here a case of such a tumour arising in the right round ligament of a 44-year-old woman. The tumour, which measured approximately 20x15x10 cm, was well encapsulated and did not involve the intrapelvic organs. Intricate mixtures of adult adipose tissue and bland smooth muscle exhibited no cellular atypia or nuclear mitotic figures, and there was little vascular proliferation. We diagnosed the lesion as a myolipoma of soft tissue with dual differentiation, and have found only 13 cases of this tumour including our own in the English literature. The present tumour is the first reported in the round ligament. Although this tumour is rare, its recognition is important for the avoidance of erroneous diagnoses.

Adult

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

Establishment of novel lymphoid cell lines dually infected with human T cell lymphotropic viruses types I and II.

With the goal of establishing an in vitro system of dual infection with human T cell lymphotropic viruses (HTLV) types I and II, rabbit lymphocytes were cocultured with a mixture of lethally irradiated HTLV-I-producing Ra-1 and HTLV-II-producing RII cell lines. This gave rise to a lymphoid cell line, RW-1, that was dually infected with HTLV-I and -II as detected by immunofluorescence staining, electron microscopy, and polymerase chain reaction using primers specific for the pol and env regions of each virus and by Southern blot hybridization. Two clonal cell lines derived from RW-1 were also coinfected with the viruses, indicating that dual infection had occurred at the single cell level. The coinfection could be readily propagated to fresh lymphocytes by coculture with RW-1. In contrast, attempts to superinfect HTLV-I-infected lymphoid cell lines with HTLV-II and vice versa were consistently unsuccessful, suggesting receptor interference between HTLV-I and -II.

Animals

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

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

Search for accumulation of p53 protein and detection of human papillomavirus genomes in sebaceous gland carcinoma of the eyelid.

Twenty-one Japanese patients with sebaceous carcinoma of the eyelid were investigated for tumour incorporation of human papillomavirus (HPV) types-6, 11, 16, 18, 31, and/or 33 DNA by in situ hybridization with fluorescein isothiocyanate-labelled DNA probes, and for p53 protein accumulation by immunohistochemical analysis with an antibody to p53 protein. Thirteen tumours (61.9%), including 9 cases of multiple infections, were positive for HPV DNA. Positive signal in the nucleus was observed not only in the cancer cells, but also in the cells of surrounding normal sebaceous glands and epidermis. Positive nuclear staining of cancer cells with the antibody to p53 protein was detected in 12 cases (57.1%). p53 protein accumulation was more frequently observed in the clinically advanced cases, occasionally in association with recurrence and/or metastasis. Among the 12 p53-positive cases, 7 were also positive for the presence of HPV DNA. HPV infections exist in a high percentage of sebaceous carcinomas of the eyelid in Japan; the overexpression of p53 protein may be important in both carcinogenesis and progression.

Aged

Periosteal osteosarcoma of the femur with bone marrow involvement: a case report.

Periosteal osteosarcoma is an exceedingly rare type of chondroblastic osteosarcoma, showing rather better prognosis, and secondary bone marrow involvement is unusual. A case of a 22 year old male with periosteal osteosarcoma of the right femur with an associated bone marrow lesion is presented. The juxtacortical tumor, 16 x 11 x 9 cm, was located on the bone cortex of the upper diaphysis and extended into the surrounding soft tissues. A minimal bone marrow lesion was present, although the bone cortex was quite intact. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. The bone marrow lesion, interestingly, contained both multiple nodules of well-differentiated chondrosarcomatous components and a few demarcated foci of atypical spindle cells producing a fine osteoid matrix. It was reasonable to conclude, therefore, that this tumor was a periosteal osteosarcoma with an unusual secondary bone marrow lesion rather than a conventional (central) chondroblastic osteosarcoma with soft tissue invasion. The patient's good prognosis with no tumor recurrence or metastasis during more than 7 years follow-up after surgery supports this conclusion.

Adult

Ileal lymphoma in swine.

Eleven cases of alimentary lymphoma affecting the ileum were observed among 26 cases of swine lymphoma detected by meat inspection in Kochi, Japan. The ileal lymphomas were located in the Peyer's patches, along with early involvement of regional lymph nodes, and showed a characteristic pattern of follicular invasion leading to diffuse growth. Following the National Cancer Institute Working Formulation, 10 neoplasms were classified as diffuse, large, noncleaved cell lymphomas and one neoplasm was a diffuse, mixed, small to large cell lymphoma. Both types of lymphoma featured numerous intermingled "starry sky" histiocytes. The lymphoma cells tended to infiltrate into the muscular layer of the ileum in an "Indian file" pattern. Two cases also showed transserosal metastasis into the abdomen and leukemic change. The lymphoma cells showed membrane positivity for alkaline phosphatase and diffuse cytoplasmic staining for acid phosphatase and non-specific esterase. Monoclonal intracytoplasmic immunoglobulins were demonstrated in nine neoplasms (IgM-lambda in seven, IgG-lambda in one, and IgG-kappa in one). In the areas of follicular invasion, an attenuated network of follicular dendritic cells was visualized via an antiserum against the beta subunit of S-100 protein. Ultrastructurally, strands of dilatated rough endoplasmic reticulum and scattered or clustered dense bodies were noted. When compared with feline and human alimentary lymphoma, including Burkitt's lymphoma, the present neoplasms possessed distinctive features, such as originating in Peyer's patches, transserosal metastasis, and predominantly large B cell type with IgM-lambda type immunoglobulin expression, although some features were similar.

Animals

Primary splenic lymphoma in a horse.

A well-demarcated solitary splenic mass (20 x 20 x 15 cm in size) containing hemorrhagic and necrotic foci was observed in a 4-year-old Thoroughbred stallion. Histologically, the mass consisted of lymphoma cells of the diffuse large non-cleaved type, with a high mitotic index and scattered macrophages that formed a starry sky pattern. The lymphoma cells revealed diffuse positivity for acid phosphatase and alpha naphthyl butyrate esterase, and were also positive for intracytoplasmic IgM on occasion, and mostly for proliferating cell nuclear antigen. Ultrastructural examination revealed moderately-developed rough endoplasmic reticulum sometimes with dilated cisternae. Thus, the diagnosis was a primary splenic lymphoma of B cell origin, but the exact reason for the absence of invasive growth or metastasis despite the high proliferative activity of this neoplasm was unclear.

Acid Phosphatase

Localized polyarteritis nodosa in the forearm and epididymis.

We report localized polyarteritis nodosa in a 31-year-old man who had painful nodules in the left forearm and scrotum. Histopathological findings of both tissues revealed distinct arteritis. However, he had no clinical evidence of any systemic disease. We finally diagnosed this case as a localized polyarteritis nodosa occurring in both the left forearm and epididymis. This form of polyarteritis nodosa has not been reported in the literature.

Adult

[A case of idiopathic pulmonary fibrosis associated with bilateral pulmonary arterial thrombosis found at autopsy].

A 73-year-old woman admitted to the hospital with dyspnea on exertion. Chest radiography revealed a diffuse interstitial shadow; PaO2 was 72 Torr, and PaCO2 was 41 Torr. Laboratory examination results were compatible with idiopathic pulmonary fibrosis (IPF). Prednisolone relieved the dyspnea, but tapering of the drug led to a recurrence of this symptom. Pulse therapy was started and azathioprine was added to the corticosteroid. Over the course of 6 months of treatment, the patient's respiratory function remained fairly stable. Then respiratory distress was induced by an attack of atrial fibrillation, with relief provided by anti-arrhythmic drugs and large doses of corticosteroids. The patient died suddenly 3 weeks later. An autopsy revealed large thrombi in both pulmonary arteries with 90% stenosis. Parts of the thrombi were organized, which suggests that 2-3 weeks had elapsed since initial thrombus formation. Histological examination of lung tissue showed usual interstitial pneumonia. Pulmonary thromboembolism should be considered in patients with IPF if respiratory distress suddenly and unexpectedly worsens.

Aged