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Biomedical subjects

H Osada

Publications and source records attributed to H Osada.

At least 217 records · Page 12Linked to original sources

A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Phenotypic and genotypic findings were correlated and compared for 35 specimens taken from 34 patients with three specific types of low-grade peripheral T-cell lymphoma: lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphoma. Frozen sections were stained by the double immunoenzymatic method using a combination of the monoclonal antibody Ki-67 for proliferating nuclei and those against lymphocyte surface antigens. Data were correlated by observing clonal rearrangements in the genes of the T-cell receptor beta chain (TCR beta). Of the 35 specimens studied, 32 (91%) were of predominantly CD4+ helper cell proliferation, and 21 (60%) showed the TCR beta gene rearrangement. There were 15 cases of AILD and TzL with predominantly helper cell proliferation, which contained a minimum of 21% CD4+Ki-67+ cells based on the total number of cells present in the specimen. Of these, 13 (87%) showed TCR beta rearrangement. In eight cases, containing a maximum of 20% CD4+Ki-67+ cells, only one (13%) showed any rearrangement. In addition, TCR beta rearrangement was observed in five of the nine cases of LeL, including two cases with only 12% CD4+Ki-67+ cells. For each of the three types, the proportion of CD4+ cells among the Ki-67+ population showed a relatively good correlation with the clonal TCR beta gene rearrangement. Moreover, there was a significant difference (P less than 0.05) in survival curves between groups with and without TCR beta rearrangement, although no obvious plateau was seen. These results suggest that the paucity of tumor cells in these lesions may account for the absence of a detectable band of rearrangements in some patients with one of these three specific types of low-grade peripheral T-cell lymphoma.

Antigens, CD↗

Phenotypic and genotypic lineage switch of a lymphoma with shared chromosome translocation and T-cell receptor gamma gene rearrangement.

A case of non-Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T-cell type, pleomorphic small cell lymphoma developed, followed by B-cell type, diffuse centroblastic/centrocytic lymphoma, and finally T-zone lymphoma without follicles again developed, from which AST-1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B-cell tumor, the second relapsed T-cell tumor and AST-1 cell line. Furthermore, T-cell receptor (TCR) gamma gene rearrangement bands of the same size were observed in the first relapsed B-cell tumor and the second relapsed T-cell tumor as well as AST-1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR delta/alpha gene complex, was observed in the second relapsed tumor and AST-1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR delta/alpha gene complex was studied. The result showed that two rearrangements of TCR alpha gene detected with J alpha probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST-1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.

Amino Acid Sequence↗

Epiderstatin induces the flat reversion of NRK cells transformed by temperature-sensitive Rous sarcoma virus.

Epiderstatin is a unique glutarimide antibiotic which was found by screening for inhibitors of the signal transduction of epidermal growth factor (EGF). The antibiotic (0.01 microM) was found to reverse the morphology of NRK cells that were infected with a temperature-sensitive mutant of Rous sarcoma virus (srcts-NRK) from the transformed phenotype to the normal phenotype at the permissive temperature (32 degrees C). Epiderstatin did not inhibit the protein kinase activity of p60v-src. The cell cycle progression of src(ts)-NRK cells was blocked at G0/G1 phase, which was caused by the inhibition of biosynthesis of p60v-src but not the transcription of v-src mRNA.

Animals↗

A case of right atrial mobile thrombus complicating multiple pulmonary emboli.

Right atrial thrombi are usually immobile. However, a mobile type mimicking a cardiac tumor, especially myxoma, has been described on rare occasions. We report here a case of atrial thrombus which was mobile in the cardiac chambers. A 29-year-old male was admitted because of exertional dyspnea. On admission, his echocardiogram showed an abnormal mass in the right atrium with a stalk attached to the interatrial septum. It decreased in size on the next day. On the fourth day of admission, it moved to the right ventricle. Multiple pulmonary emboli were revealed by the lung perfusion scintigram. Two days after the administration of intravenous urokinase, the abnormal mass in the cardiac chambers was no longer seen on the echocardiogram. This was a rare case of mobile atrial thrombus associated with multiple pulmonary emboli. Thrombolytic therapy appeared to be effective in this case.

Adult↗

Reveromycins, new inhibitors of eukaryotic cell growth. II. Biological activities.

Reveromycins A, B, C and D showed inhibitory activity against EGF-stimulated mitogen response in Balb/MK cells. Furthermore reveromycins A, C and D exhibited morphological reversion of srcts-NRK cells, antiproliferative activity against human tumor cell lines and antifungal activity. The effects of reveromycins A, C and D on eukaryotic cells were closely similar to each other, but those of reveromycin B were very weak. In vitro studies revealed that reveromycin A is a selective inhibitor of protein synthesis in eukaryotic cells.

Animals↗

Reveromycins, new inhibitors of eukaryotic cell growth. III. Structures of reveromycins A, B, C and D.

Reveromycins A, B, C and D are new group inhibitors of the mitogenic activity of epidermal growth factor (EGF), produced by Streptomyces sp. Reveromycins are novel polyketide type antibiotics which have two terminal carboxylic groups, a spiroketal, a succinate and a varied side chain in the molecule. Determination of their structures by chemical and spectroscopic methods, in particular NMR studies, is described.

Acetylation↗

A new inhibitor of protein kinase C, RK-1409B (4'-demethylamino-4'-hydroxy-3'-epistaurosporine).

RK-1409B, a new inhibitor of protein kinase C, was isolated from the culture broth of Streptomyces platensis subsp. malvinus RK-1409. The structure was elucidated on the basis of spectroscopic analyses. RK-1409B inhibited protein kinase C in vitro and the morphological change of a human chronic leukemia cell line, K-562, induced by phorbol 12,13-dibutyrate with IC50 value of 0.4 microM.

Carbazoles↗

A new inhibitor of protein kinase C, RK-1409 (7-oxostaurosporine). I. Taxonomy and biological activity.

A novel inhibitor of protein kinase C was found in the fermentation of a soil actinomycete, strain RK-1409. According to the taxonomic studies, the producing strain was designated as Streptomyces platensis subsp. malvinus RK-1409. The protein kinase C inhibitor, RK-1409 (7-oxostaurosporine) inhibited the morphological change of a human chronic erythroleukemia cell, K-562, induced by phorbol 12,13-dibutyrate (PDBu) at the concentration of 10 ng/ml. The concentration of 3 ng/ml inhibited the activity of protein kinase C in vitro. RK-1409 inhibited the cell cycle progression at G2 phase of K-562 cells.

Alkaloids↗

[A study of intraoperative rapid frozen section diagnosis focusing on accuracy and quality assessment].

Accuracy of frozen section (FS) diagnoses was investigated in a consecutive series of 1129 intraoperative consultations. In our series, the correct diagnosis including clinically not serious minor errors was made in 96.9% of the cases. Whereas the accuracy ratio of FS diagnosis for unknown pathologic process decreased to 92.2%. Among all the types of tissues, central nervous system was shown to be the most frequently handled for FS, followed by lung/bronchus, breast, liver/biliary tract, lymph node and so forth. The requesting ratio of FS, on the other hand, tended to be high in the following specialties; neurosurgery (46.5%), thoracic surgery (19.0%), general surgery, (10.0%). Deferred diagnosis with a provisional diagnosis and misinterpretations in histology typing without serious clinical problem accounted for 2.7% and 3.1% respectively. Causes of erroneous diagnoses seemed to be multifactorial, such as inappropriate sampling, diagnosis on poor quality histology sections, lack of clinical information, lack of enough experience in FS practice of pathologists, or a combination of more than two of them, though inevitable cases showing minimal cytological and structural atypia were included. Intraoperative consultation by FS diagnosis is now essential to serve a good quality medication to patients. It is thus necessary that to establish a tight peer review system and also to provide an education program with regard to practice in FS diagnosis particularly for young pathologists.

Frozen Sections↗

Clinicopathologic study of large cell anaplastic lymphoma (Ki-1-positive large cell lymphoma) among the Japanese.

The clinical, prognostic, phenotypic, and genotypic findings of 30 patients with large cell anaplastic lymphoma (Ki-1-positive large cell lymphoma) were analyzed. There were 13 male and 17 female patients (male-female ratio, 0.8) whose ages ranged from 3 to 81 years of age (mean, 28 years of age; 67% of the patients younger than 30 years of age). The 5-year survival rate was 52%; this was better than that of other types of high-grade peripheral T-cell lymphoma. Histologic examination showed distinctive morphologic features such as tumor cell pleomorphism, sinus infiltration, fibrosis, partial lymph node involvement, sparing of B-cell regions, and occasional plasma cell infiltrates. Eighty percent of the cases were of T-cell phenotype, and others expressed neither B-cell nor T-cell markers. The tumors were frequently positive for a histocompatibility antigen (HLA-DR), CD25 (the interleukin-2 receptor), and epithelial membrane antigen. Rearrangements of the T-cell receptor beta gene were observed in nine of 13 cases (69%). These findings indicated that many of the tumors had the phenotype and genotype of activated T-cells. This study also showed that large cell anaplastic lymphoma has a survival figure intermediate between Hodgkin's disease and low-grade peripheral T-cell lymphoma.

Adolescent↗

An assay system for the modulators of plasminogen activation on the cell surface.

Plasminogen activation on the cell surface is regulated by a variety of modulators which balance surface-bound plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs). In this study, we developed as assay system to assess modulation of cell-associated plasminogen activation. Plasmin generation by endogenous plasminogen activators was measured with a combination of exogenously added plasminogen and a chromogenic substrate, S-2251, in the presence of living cells. A cell surface PA activity was quantitated by adopting a rate of plasmin generation. We used HT-1080, a human fibrosarcoma cell line, as representative of cells which have both PAs and PAIs on their cell surface. A basal level of cell surface PA activity was specifically reduced by anti-urokinase-type PA IgG and enhanced by anti-PAI-1 IgG, suggesting that the basal level is determined by a balance between uPA and PAI-1 on the cell surface. We examined effects of dexamethasone and thrombin on cell surface PA activity in the assay system. Dexamethasone appeared to suppress the cell surface PA activity by enhancing de novo synthesis of PAI-1, whereas thrombin suppressed it by inactivating single-chain urokinase-type plasminogen activators. These results indicate that our assay system can be adapted for the screening of various types of PA modulators.

Cell Membrane↗

Dumbbell neurogenic tumor of the mediastinum: a report of three cases undergoing single-staged complete removal without thoracotomy.

Of a total thirteen patients who underwent surgery for a neurogenic tumor in the posterior mediastinum 4 (30.8 per cent) presented with dumbbell type development of the tumor. Along with a comparatively greater incidence in the number of cases of dumbbell neurogenic tumors in the posterior mediastinum, resection has also recently become more popular, necessitating the establishment of a standard operative approach for this type of tumor. We successfully removed dumbbell neurogenic tumor from the posterior mediastinum in our 3 most recent cases via a dorsal approach by virtue of a laminectomy and resection of a small portion of the neighbouring rib root without opening the parietal pleura at all. These three patients were a 14 year old female, a 54 year old male and a 68 year old female, respectively, and the largest diameter in cm and level of origin of the tumors were 5.5 at Th 1 in case 1, 3.0 at Th 2 in case 2 and 3.7 at Th 11 in case 3. The operative approach described herein was easy to perform, felt secure and was less invasive and better tolerated by the patients than the thoracotomy approach. Avoiding a thoracotomy in such cases has many advantages to enumerate, but does not seem to have been clearly aimed at by others to date. We therefore propose our technique as a standard approach for dumbbell neurogenic tumors in the posterior mediastinum.

Adolescent↗

Genetic identification of pregnancies responsible for choriocarcinomas after multiple pregnancies by restriction fragment length polymorphism analysis.

The pregnancies responsible for two cases of choriocarcinomas were determined by the restriction fragment length polymorphism of human leukocyte antigen-DQ genes in the tumors and leukocytes from the patients, their husbands, and their children. The first case was preceded by three normal pregnancies, and the second case was preceded by two normal pregnancies and a complete hydatidiform mole. Comparison of the restriction fragment length polymorphism patterns revealed that the first case of choriocarcinoma carried the parental genome and originated from the third normal pregnancy, whereas the second case was of androgenetic origin from the complete mole. By choosing an appropriate probe (or probes), restriction fragment length polymorphism analysis is shown to be a useful method for identification of the pregnancy responsible for choriocarcinoma.

Adult↗

Uncoupled cell cycle without mitosis induced by a protein kinase inhibitor, K-252a.

The staurosporine analogues, K-252a and RK-286C, were found to cause DNA re-replication in rat diploid fibroblasts (3Y1) without an intervening mitosis, producing tetraploid cells. Analysis of cells synchronized in early S phase in the presence of K-252a revealed that initiation of the second S phase required a lag period of 8 h after completion of the previous S phase. Reinitiation of DNA synthesis was inhibited by cycloheximide, actinomycin D, and serum deprivation, but not by Colcemid, suggesting that a functional G1 phase dependent on de novo synthesis of protein and RNA is essential for entry into the next S phase. In a src-transformed 3Y1 cell line, as well as other cell lines, giant cells containing polyploid nuclei with DNA contents of 16C to 32C were produced by continuous treatment with K-252a, indicating that the agent induced several rounds of the incomplete cell cycle without mitosis. Although the effective concentration of K-252a did not cause significant inhibition of affinity-purified p34cdc2 protein kinase activity in vitro, in vivo the full activation of p34cdc2 kinase during the G2/M was blocked by K-252a. On the other hand, the cyclic fluctuation of partially activated p34cdc2 kinase activity peaking in S phase still continued. These results suggest that a putative protein kinase(s) sensitive to K-252a plays an important role in the mechanism for preventing over-replication after completion of previous DNA synthesis. They also suggest that a periodic activation of p34cdc2 is required for S phases in the cell cycle without mitosis.

Animals↗