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Biomedical subjects

T Matsusaka

Publications and source records attributed to T Matsusaka.

At least 55 records · Page 3Linked to original sources

A novel protein kinase gene ssp1+ is required for alteration of growth polarity and actin localization in fission yeast.

Temperature-sensitive suppressor mutants were isolated from two fission yeast mutants defective in cell shape control: ppe1, encoding a type 2A-like protein phosphatase, and sts5, one of 11 staurosporine-supersensitive mutants. Complementation tests showed that suppression was due to two chromosomal loci, ssp1 and ssp2. Cells of the ssp1 mutant grown at the restrictive temperature arrested uniformly with an elongated cell body and a 2C content of DNA. Interestingly, these mutant cells grew only in a monopolar manner. At a specific point in the G2 phase of the cell cycle, wild-type cells exhibit a drastic alteration in growth polarity, from mono- to bipolar. This change coincides with the distribution of cortical actin from one end of the cell to both ends. In the ssp1 mutant cells, cortical actin was localized only at one end, suggesting that the mutant fails to change growth polarity. Nucleotide sequence determination showed that ssp1+ encodes a novel protein kinase. Ectopic overexpression of ssp1+ resulted in an altered cell morphology and cortical actin was randomly dispersed within the cells. Immunocytological analysis revealed that the protein was primarily localized in the cytoplasm and that half of the protein existed in an insoluble fraction. These results show that the dynamics of actin-based growth polarity during the cell cycle are regulated, at least in part, by a novel set of protein kinases and phosphatases.

Actins↗

Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.

Acute-phase response factor (APRF) is a transcription factor that binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. We report here the purification and cloning of APRF. APRF exhibits a 52.5% overall homology at the amino acid level with p91, a component of the interferon (IFN)-stimulated gene factor 3 complexes. The cloned APRF protein is tyrosine phosphorylated and translocated into the nucleus in response to IL-6, but not in response to IFN-gamma. Tyrosine phosphorylation was also observed in response to other cytokines, such as leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor, whose receptors share the IL-6 receptor signal transducer gp130. In contrast, we observed that p91 is not tyrosine phosphorylated in response to IL-6. These results suggest that this novel p91-related protein may play a major role in the gp130-mediated signaling pathway and that selective activation of p91-related factors may explain the diversity of cellular responses to different cytokines.

Amino Acid Sequence↗

A point mutation at ATP-binding region of the ALD gene in a family with X-linked adrenoleukodystrophy.

A prenatal diagnosis was performed in a family with X-linked adrenoleukodystrophy (ALD). A fetus was at high risk of suffering the disease by segregation analysis and by very long chain fatty acid-CoA synthetase activity assay. A transition (G to A) at codon 617 of the candidate ALD gene was detected by reverse transcription PCR (RT-PCR) based sequencing of the fetal liver RNA. The mutation was located in highly conserved ATP-binding site in this gene and deduced amino acid transversion R617H was thought to be the cause of ALD in this family.

Adenosine Triphosphate↗

Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8.

Single binding sites for transcription factors NF-IL6 and NF-kappa B are present in the promoter of the interleukin (IL) 6 gene. Previous studies of internally deleted promoter mutants demonstrated that these two sites are important for the transcriptional regulation of this gene. In this report, we describe the synergistic activation of the IL-6 promoter by transcription factors NF-IL6 and NF-kappa B. Cotransfection of NF-IL6 with the NF-kappa B p65 subunit resulted in strong synergistic activation of an IL-6 promoter-reporter construct. Both the NF-IL6 and NF-kappa B binding sites in the IL-6 promoter were required for synergistic activation. Similar synergistic activation was observed in the IL-8 promoter, which also contains both NF-IL6 and NF-kappa B binding sites. Furthermore, we demonstrated that NF-IL6 and the NF-kappa B p65 subunit directly associated via the basic leucine-zipper domain of NF-IL6 and the Rel homology domain of p65. Since the promoters of many other genes involved in the inflammatory and acute-phase responses also contain binding sites for NF-IL6 and NF-kappa B, the cooperation between these two factors may have an important role in these responses. We also discuss the possible interplay between various viral gene products and these two factors in the process of viral infection and constitutive cytokine production.

Base Sequence↗

Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice.

The mechanisms through which pristane or mineral oil can induce plasmacytomas in BALB/c or NZB mice are not fully understood, but involvement of interleukin 6 (IL-6), a growth factor for plasmacytomas and myelomas, has been strongly suggested. To clarify the role of IL-6 in plasmacytomagenesis, a human IL-6 cDNA was introduced into mouse germ lines under the transcriptional control of the murine major histocompatibility complex class I (H-2Ld) promoter. IL-6 transgenic mice of C57BL/6 origin developed a massive plasmacytosis but not plasmacytomas. However, introduction of BALB/c genetic background into IL-6 transgenic mice could generate monoclonal transplantable plasmacytomas with the chromosomal translocation t(12;15). These results provide firm evidence of the critical role of IL-6 in the plasmacytoma development.

Animals↗

The role of interleukin 6 in plasmacytomagenesis.

Interleukin 6 (IL-6) is a polyfunctional cytokine which regulates the immune response, the acute-phase reaction and haemopoiesis. IL-6 plays a critical role in differentiation of B cells into plasma cells, and is a potent growth factor for plasmacytomas and myelomas. A relationship between IL-6 and polyclonal plasma cell abnormalities has been demonstrated. Abnormal production of IL-6 was first suggested to be related to hypergammaglobulinaemia with autoantibody production in patients with cardiac myxoma. A role of IL-6 in the generation of plasmacytoma has also been indicated. In support of these clinical and experimental observations, we demonstrated that transgenic C57BL/6 mice carrying the human IL-6 gene showed a massive polyclonal plasmacytosis with production of autoantibodies. However, the tumour was not transplantable to syngeneic animals. Susceptibility to pristane-induced plasmacytomagenesis is genetically determined--pristane can induce plasmacytomas in BALB/c but not in C57BL/6 mice. IL-6 transgenic C57BL/6 mice were backcrossed to BALB/c mice to elucidate the genetic influence on plasmacytomagenesis. Transplantable monoclonal plasmacytoma with a t(12;15) chromosomal translocation was generated in some of the backcrossed mice, indicating that IL-6 plays a key role in the multistep oncogenesis of plasma cell neoplasia.

Animals↗

Clinicopathologic evaluation of recurrence in early gastric cancer.

Five hundred ninety-two patients with early gastric cancer underwent surgical resection from 1970 to 1986 in our hospital, and 13 died from a recurrence of their disease. A careful analysis of these 13 patients suggests that carcinomas which invaded to the submucosa tend to recur more often than those confined to the mucosa. Well differentiated and papillary adenocarcinomas characterized by protruded or elevated lesions tend to recur earlier than poorly differentiated or signet-ring cell carcinomas characterized by depressed or excavated lesions. However, both types recurred from hematogenous metastases, with the liver being the most common site. Therefore, the macroscopic and histological features presently used to characterize early gastric cancer do not provide sufficient information to accurately predict which patients are at most risk for recurrence.

Adenocarcinoma↗

Enhancement of mucus accumulation in a human gastric scirrhous carcinoma cell line (KATO-III) by fibroblast-tumor cell interaction.

Human fibroblasts (WI-38 cells) were found to enhance mucus accumulation by human scirrhous carcinoma cells (KATO-III cells). Coculture of KATO-III with WI-38 cells resulted in enlargement of the KATO-III cells and increases in the proportions of PAS- and colloidal iron-positive KATO-III cells. These morphological alterations were reversed when the KATO-III cells were again cultured without WI-38 cells. Conditioned media from cultures of WI-38 cells or cocultures of KATO-III and WI-38 cells induced the same morphological alterations in KATO-III cells, suggesting that WI-38 cells produce a factor or factors that enhance mucus accumulation in KATO-III cells. This factor seemed to be a protein with a molecular weight of more than 10,000 daltons.

Adenocarcinoma, Scirrhous↗

Towards a generalized model of encystment (cryptobiosis) in ciliates: a review and a hypothesis.

In this work we propose a generalized model to explain encystment (cryptobiosis) in ciliates. The model is elaborated from both structural and physiological studies previously reported, and some hypothetical considerations. The main features of this model are the following: (a) starvation is considered as the most important inducer of ciliate encystment, and it constitutes the first trigger of this cell differentiation process; (b) the "switch on" of encystment genes involves the appearance of several new transcripts; (c) starvation involves cell autophagy and protein turnover, which provides material to synthesize the new cystic proteins; (d) cytoplasmic dehydration has an important role during the resting cyst formation; (e) a gradual loss of intracellular water can inactivate cell metabolism, leading to an ametabolic state (cryptobiosis); (f) as a late precystic event, the encysting cell forms a barrier (cyst wall), that isolates the cell from the hostile environment.

Animals↗

The lamina suprachoroidocapillaris of the guinea pig choroid confirmed by the rapid freezing and freeze-substitution method.

There is a compact layer (the lamina suprachoroidocapillaris) between the vascular and the choroidocapillaris layer of the guinea pig and rat choroids. The specimens were treated with the rapid freezing and freeze-substitution method. The choroidal melanocytes and their processes were exclusively built up of several layers, and the arterioles and venules passed through this layer. Numerous nerve terminals were seen throughout this layer, which contained small or large-size synaptic vesicles with dense or light core. These results may facilitate further understanding of the microcirculation in the choroidal architecture.

Animals↗

A clinicopathological study of synchronous multiple gastric cancer.

In a 7 1/2-year period (from 1 January 1980 to 30 June 1987), 997 patients with gastric cancer underwent gastric resection at the Department of Surgery, Matsuyama Red Cross Hospital, Japan. We studied clinicopathologically 83 patients (182 lesions) with synchronous multiple gastric cancer and compared them with patients who had solitary cancers only in the same period. We found that elderly men had a relatively high incidence of multiple gastric cancer, and that early cancer of the elevated well differentiated type was the most common. Of the 182 lesions, as many as 42 (23.1 per cent) were missed in the preoperative examination. Eighteen of these 42 lesions were found only with the aid of a microscope in sections almost incidentally excised. Small flat lesions tended to be missed. We should always be conscious that other gastric lesions may be present when treating patients with gastric cancer.

Female↗

[Relation of the serosal invasion mode to a recurrence in advanced gastric carcinomas].

Discussed are the attributable factors affecting the type of carcinomatous recurrence seen in 126 patients who had been operated on for their gastric carcinomas from 1979 to 1982 and who later showed a macroscopically positive serosal invasion (S0) and a histologically ss alpha approximately se invasion and required a curative resection. Forty-six percent of the patients with an ss beta approximately se invasion had a peritoneal recurrence, 21% a liver recurrence, and 33% a recurrence of some other type, whereas those with ss alpha had no such recurrence. Peritoneal recurrence tended to increase with the increase in the length of the serosal invasion and its rates were: one third in serosal invasions of less than 3 cm, one third in invasions of 3 approximately 6 cm and another third in invasions of over 6 cm. The smaller ratio of submucosal length to subserosal length, especially when less than 1.0, meant a greater frequency of peritoneal recurrence. The histologic characteristics of carcinomas that developed a peritoneal recurrence were poorly differentiated, contained INF alpha and had weaker cellular cohesion, whereas those that developed a liver metastasis were well differentiated carcinomas, contained INF beta and had a tighter cellular cohesion.

Adenocarcinoma, Mucinous↗

Morphological changes in a human scirrhous gastric carcinoma cell line (KATO-III) when cultured in collagen-coated dishes.

The morphological differences between cells of a human scirrhous gastric carcinoma cell line (KATO-III) cultured in plastic dishes and in collagen-coated dishes were examined by phase-contrast and electron microscopy. When KATO-III cells were inoculated into plastic dishes, a few cells became attached to the surface of the dishes and the rest remained in suspension. However, when they were inoculated into collagen-coated dishes, they all remained in suspension. In both types of dish, most of the cells in suspension were single although a few were in clusters. The cells in suspension in collagen-coated dishes differed in morphology from those in the plastic dishes. They had abundant cytoplasm, well-developed Golgi complexes, and many microvillus-like cell protrusions. Moreover, they had hemidesmosome-like and desmosome-like structures on their surface and an increased amount of intracytoplasmic desmosome-like structures. The cells in clusters in the collagen-coated dishes were closely connected by junctional complexes, such as tight junctions, desmosomes and interdigitations, whereas those in plastic dishes were linked only by desmosomes. These results suggest that collagen affects the morphology of human scirrhous carcinoma cells.

Adenocarcinoma, Scirrhous↗

Germanium-induced nephropathy: report of two cases and review of the literature.

We report two cases of renal failure following long-term ingestion of germanium dioxide (GeO2) and comment on eight other cases reported in Japan. Ge-induced nephropathy is characterized by insidious onset of renal failure without proteinuria or hematuria after oral intake of Ge-containing compounds for more than several months, and by degeneration of renal tubular cells with minor glomerular abnormality in histology. When patients ceased to ingest Ge compounds, renal function gradually recovered but never returned to the normal range. Serious extrarenal complication can contribute to an unfavorable prognosis.

Acute Kidney Injury↗