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Biomedical subjects

J Iwata

Publications and source records attributed to J Iwata.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

Phenotypic progression of a rat lymphoid cell line immortalized by human T-lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats.

Rat lymphoid cells, TARS-1, immortalized by coculture with adult T-cell leukemia cells, were intraperitoneally injected into 65 newborn, inbred WKAH/Hkm rats. In most of the rats, tumor nodules were discernible 7 to 15 days after transplantation but were completely rejected within 5 to 6 weeks. Two rats with no tumor nodules exhibited gait disturbances and paralysis of the hind legs 3 to 4 weeks after transplantation. Histological and hematological examinations revealed that a lymphoma/leukemia-like disease had developed in one of the two rats, and the T-lymphoid cell line WLeuk-1 was established from peripheral blood mononuclear cells from this rat. When the WLeuk-1 cells were transplanted into newborn WKAH/Hkm rats, the animals died of a lymphoma/leukemia-like disease within several weeks after transplantation, in contrast to their rejection of the TARS-1 cells. Southern blot and karyotype analyses revealed that WLeuk-1 cells had retained the marker chromosomes and human T-lymphotropic virus type I (HTLV-I) integration patterns of the parent cell line, TARS-1. The additional specific chromosome abnormalities 3p+,t (12;13), and Xq+ were found in the WLeuk-1 cells. Moreover, the expression of HTLV-I structural proteins was slightly depressed in WLeuk-1 cells, while that of the transacting factors p40tax and p21x, but not that of p27rex, was enhanced about fivefold compared with that in TARS-1. The transactivating function of p40tax was intact in WLeuk-1, as evidenced by enhanced interleukin-2 receptor alpha chain expression. These results suggest that aberrant expression of HTLV-I regulatory genes and alteration of cellular genes were associated with the phenotypic progression of the WLeuk-1 cell line.

Animals↗

Establishment and characterization of a new human synovial sarcoma cell line, HS-SY-II.

BACKGROUND: The line of differentiation in synovial sarcoma still remains controversial. Thus far, only a few human synovial sarcoma cell lines have been described. However, their morphologic characteristics have not been fully established. EXPERIMENTAL DESIGN: We established a new synovial sarcoma cell line (HS-SY-II) from pleural effusion with lung metastasis in a typical example of the monophasic spindle cell type. The HS-SY-II cells, in vitro and in vivo, were examined by light microscopy, immunohistochemistry, electron microscopy, and cytogenetics. RESULTS: The HS-SY-II cells showed a hypertriploid karyotype with complex chromosome abnormalities including pathognomonic t(X;18)(p11;q11), and have been stably maintained for more than 40 months in vitro, showing rather small spindle or polygonal shape without conspicuous pleomorphism. Histologic features of initially and serially transplanted tumors in nude mice were essentially the same as those of the original sarcoma, corresponding to the monophasic spindle cell variant with a prominent palisading pattern and calcified foci in parts. The HS-SY-II cells in vitro and in vivo similarly expressed vimentin and cytokeratin by immunohistochemistry, and also exhibit the same ultrastructural features such as irregularly shaped nuclei with prominent nucleoli, many paranuclearly running intermediate filaments, and filopodia-like processes. CONCLUSIONS: This HS-SY-II cell line retaining the distinct morphological characteristics as the monophasic spindle cell type of synovial sarcoma therefore will be extremely useful for various pathomorphologic investigations on synovial sarcoma.

Cytological Techniques↗

Novel t(15;19)(q15;p13) chromosome abnormality in a thymic carcinoma.

A 22-year-old female with a thymic carcinoma is reported. The tumor was refractory to both chemotherapy and irradiation. The patient died with an aggressive clinical course. Cytogenetic study showed that the tumor cells had a chromosome translocation, t(15;19)(q15;p13), which was not identified previously in human cancer.

Adult↗

Characterization of two human lymphoid cell lines producing human T-lymphotropic virus type I (HTLV-I) isolated from patients with HTLV-I-associated myelopathy or encephalopathy.

Two cell lines, CNS-5 and CNS-6, were established by cocultivation of sedimented cells in cerebrospinal fluid (CSF) from two anti-human T-lymphotropic virus type I (HTLV-I) antibody-positive male patients with encephalopathy and HTLV-I-associated myelopathy, respectively, with peripheral blood mononuclear cells from a healthy seronegative female. These cell lines, possessing a normal female karyotype, revealed similar characteristics as follows; they expressed HTLV-I-related antigens, they produced C-type retrovirus particles, HTLV-I provirus genomes were integrated into their DNAs, and they had CD4+ activated T-cell markers. In addition, immunocytochemical and immunoelectron microscopic studies showed peculiar immunoreactivity of these cell lines with anti-alpha/beta T-cell antigen receptor (TCR) antibodies; beta Fl, defining beta chain epitope, was only positive in the perinuclear spaces and rough endoplasmic reticulum in some cells, and WT31, recognizing alpha/beta framework, was mostly negative, while CD3 was expressed in the majority of the cells. These facts indicate that HTLV-I-infected cells were present in CSF of these two patients, and suggest that neurological disorders associated with HTLV-I may not be restricted to myelopathy and may include brain abnormalities.

Aged↗

Morphological characterization of a newly established human osteosarcoma cell line, HS-Os-1, revealing its distinct osteoblastic nature.

A newly established human osteosarcoma cell line, HS-Os-1, from an osteoblastic tumor arising in the left humerus of an 11-year-old girl was morphologically characterized in vitro and in vivo. HS-Os-1 cells in a monolayer have been maintained for more than 2 years since the initial cultivation, and were round or polygonal in shape with marked pleomorphism. Their cytoplasm was strongly positive for specific markers of osteoblasts, such as alkaline phosphatase and osteocalcin. Tumors induced in nude mice by HS-Os-1 cell inoculation at passage 12 or 23 revealed typical histological features of osteoblastic osteosarcoma, similar to those observed in the original tumor, producing prominent osteoid matrix with calcification. Ultrastructurally, HS-Os-1 cells in vitro and tumor cells in vivo showed similar well-developed, markedly dilated rough endoplasmic reticulum, polysomes and microfilaments in their cytoplasm. Additionally, many collagen fibers associated with deposition of electron-dense material were detected in the stroma featuring osteoid matrix. Thus, the HS-Os-1 cell line was shown to exhibit its osteoblastic nature in vitro and in vivo, and therefore might become an extremely useful tool for various pathomorphological investigations on human osteosarcomas.

Animals↗

Exercise-loaded blood pressure and Li-Na countertransport system in the erythrocyte membrane as predictors of mild essential hypertension prognosis.

1. The blood pressure response to exercise loading, Na concentration in the erythrocyte and Li-Na countertransport (Li-Na CT) system in the erythrocyte membrane in 40 male volunteers and 98 patients with mild essential hypertension were investigated. Subjects were divided into a juvenile group (less than 36 years) and a middle-aged (greater than 36 years and less than 65 years) group. Exercise-loaded blood pressure in patients with mild essential hypertension was followed up for more than 5 years. 2. Systolic blood pressure (SBP) at 6 min during exercise loading was significantly higher in the mild hypertension group compared with the control group. 3. Patients with high SBP at exercise loading in the mild hypertension group transferred more often to the moderate hypertension group within 5 years. 4. No difference in the haemodynamic parameter at rest was noted in the transferred group for moderate hypertension and the non-transferred group. 5. A higher blood pressure response to noradrenaline was noted in the transferred group compared with the non-transferred group of the juvenile group. 6. High Na concentration in the erythrocyte and acceleration of the Li-Na CT system in the erythrocyte membrane were noted in the mild hypertension group compared with the volunteer group. 7. A correlation between SBP at exercise loading and Li-Na CT system in the erythrocyte membrane was noted. This correlation was strongly noted in subjects less than 50 years old. 8. From these results it was concluded that SBP at exercise loading and Li-Na CT system in the erythrocyte membrane are useful as indicators for the prognosis of mild essential hypertension.

Adult↗

Single cilium in human leukemic cells heterotransplanted into hamsters.

Single cilium formation was studied in two human hematopoietic cell lines, KCL-22 and MT-2, KCL-22, established from a patient with chronic myelogenous leukemia in blastic crisis, and MT-2, a human cord T cell line carrying human T-lymphotropic virus type I, were transplanted into hamsters. Ciliogenesis was observed in both cell lines, only after transplantation into hamsters.

Animals↗

Pre-elastofibroma-like colonic polyp: another cause of colonic polyp.

We present a case of pre-elastofibroma-like lesion, a kind of elastic-producing fibrous tumor. The small colonic polyp, which was found in a 49-year-old asymptomatic man in association with a large colonic adenoma, showed submucosal nodular deposits of fine granular or fibrillar eosinophilic materials with interspersed fibroblastic cells. Elastic stain revealed these deposits to consist mainly of dark gray granular or partially fibrillar dense elastinophilic materials, most of which were digested with elastase. This stromal lesion somewhat resembled a pre-elastofibroma. Therefore, pre-elastofibroma-like lesions should be kept in mind as a possible origin of colonic polyp.

Colonic Polyps↗

Ribosome-lamella complexes observed in an Epstein-Barr virus-producing B-cell line, infected with human T-lymphotropic virus type I.

Co-cultivation of peripheral blood mononuclear cells, from a 4-year-old boy with infectious mononucleosis, with a human T lymphotrophic virus type I (HTLV-I)-producing T-cell line resulted in the establishment of an HTLV-I infected Epstein-Barr virus (EBV)-producing B-cell line. Ultrastructural examination revealed the presence of ribosome-lamella complexes (RLCs), in a small proportion of long-term cultured cells. Evidence is presented of continuity between RLC and the rough endoplasmic reticulum, and in some instances there was also an intimate relationship with tubuloreticular structures. The findings support the view that RLC is derived from the rough endoplasmic reticulum and also provide further evidence of the non-specific nature of RLC in relation to cell type.

B-Lymphocytes↗

[Establishment and characterization of a cell line, HS-Os-1 derived from an osteoblastic type of human osteosarcoma].

A new human cell line, HS-Os-1, derived from a case of osteoblastic osteosarcoma arising in the humerus of an 11-year-old girl was established. Light microscopically, HS-Os-1 cells growing in a monolayer (in vitro) were pleomorphic, intermingled with a few multinucleated giant ones, and positive with alkaline phosphatase reaction. In the transplanted tumors in athymic nude mice (in vivo), atypical spindle or polygonal cells densely proliferated with prominent osteoid formation and even calcification. HS-Os-1 cells, both in vitro and in vivo, were mostly positive for vimentin and a few for S-100 protein. Ultrastructurally, HS-Os-1 cells in vitro and in vivo also revealed essentially the same features as the eccentrically located, euchromatin-rich nuclei with prominent nucleoli, a lot of well-developed, irregularly-dilated rough endoplasmic reticula, polysomes and microfilaments in the cytoplasm. Namely, HS-Os-1 cells fully expressed and possessed morphological characteristics as osteoblastic nature during the cultivation and heterotransplantation. This cell line, therefore, proved to be extremely useful to search for human osteosarcomas.

Animals↗

[Establishment and characterization of a human cell line, HS-MM, derived from a case of clear cell sarcoma].

The characteristics of a new human clear cell sarcoma (CCSa) cell line, HS-MM, established from the pleural effusion in a 39-year-old man with lung metastasis, have been morphologically studied in vitro and in vivo. HS-MM cells growing on a cover-slip were round or spindle in shape with round nuclei containing extremely prominent nucleoli. Heterotransplantation of the cells into nude mice was easily succeeded following tumor development. Light microscopically, HS-MM cells, both in vitro and in vivo, were positive for anti-S-100 protein and anti-melanoma specific antibodies with immunostain, but no melanin pigment was detected in them. Ultrastructurally, the cells had round euchromatin-rich nuclei with large nucleoli revealing conspicuous nucleolonema, and contained a few mitochondria, rough endoplasmic reticulum and lysosomal dense bodies, besides a large amount of glycogen, but no melanosome in their cytoplasm. HS-MM cells retained and fully expressed morphologically unique characteristics as a CCSa, compatible with amelanotic type of malignant melanoma also. This cell line, HS-MM, therefore, proves to be extremely useful for clinicopathological studies on a CCSa.

Adult↗

[A case of surgical excision of intracerebral cavernous angioma in a patient with thrombasthenia].

A case of thrombasthenia (Glanzmann) associated with an intracerebral cavernous angioma in a 32-year-old woman is reported. Since her childhood, the patient had experienced a tendency to develop purpura following minor trauma. But she had not had major bleeding even during pregnancy and delivery. On April 4, 1987, she presented generalized convulsion. A high density mass in the right temporal lobe was demonstrated with CT scan. Carotid angiogram was normal except that the right anterior choroidal artery was stretched. Inhomogeneous signal intensities in T1- and T2-weighted MRI images were seen in the tumor locus. The clinical diagnosis was cavernous angioma which was complicated with intracerebral hemorrhage. The patient had a disorder of platelet function without thrombocytopenia. Her bleeding time was markedly prolonged. Because of this, we did not try surgical excision at first. During the 13-month observation period, however, intracerebral bleeding occurred 5 times. We decided to operate on the patient using fresh blood and platelet transfusion. The postoperative course was uneventful and pathological diagnosis confirmed cavernous angioma. We would like to emphasize possible pitfalls in treating cases of intracerebral angioma with thrombasthenia.

Adult↗