Biomedical subjects

T Nosaka

Publications and source records attributed to T Nosaka.

At least 37 records · Page 2Linked to original sources

PubMed1999

Biliary complications after orthotopic liver transplantation in rats.

We recently experienced a high frequency of biliary complications after orthotopic liver transplantation in rats (22 of 25 cases (88%): biloma, 20 cases; biliary peritonitis, 2 cases). These complications seemed to be rare in general, but some researchers reported such cases and addressed them mainly through rearterialization. The biliary complications we encountered were found to be associated with necrosis of the donor bile duct and an opportunistic infection of Enterobacteriaceae. After administering appropriate antibiotics, the complications significantly diminished (2 of 25 cases (8%), P = 0.0001). The nonarterialized bile duct, which becomes ischemic soon after liver transplantation, appears to be susceptible to infections. Such opportunistic infections may prevent the development of arterial collaterals, causing bile duct necrosis and the subsequent leakage of bile juice. When biliary complications frequently occur after nonarterialized liver transplantation in rats, the possibility of an opportunistic infection should thus be considered.

Animals↗

PubMed1998

Induction of synaptosomal-associated protein-23 kD (SNAP-23) by various cytokines.

Cytokines manifest their function through regulation of gene expression. We searched for immediate-early cytokine responsive genes by the mRNA differential display technique using interleukin-3 (IL-3)-dependent OTT-1 cells, and have isolated a novel cDNA which encodes 210 amino acids and shows 87% amino acid identity to human SNAP-23 (synaptosomal-associated protein of 23 kD). The message for this protein (mouse SNAP-23) was induced in OTT-1 cells by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5. The experiment using C-terminal deletion mutants of the common beta subunit (betac) of IL-3/GM-CSF/IL-5 receptors showed that expression of SNAP-23 was associated with the Ras-Raf-MAPK pathway, but not with the JAK-STAT pathway. Moreover, SNAP-23 was induced in response to a wide variety of cytokines, including IL-2, IL-3, IL-5, IL-10, stem cell factor, G-CSF, GM-CSF, leukemia inhibitory factor, and erythropoietin. Constitutive expression of SNAP-23 was seen in various tissues, including heart, lung, kidney, liver, spleen, and small intestine. Possible involvement of SNAP-23 in cytokine signal transduction is discussed.

Amino Acid Sequence↗

PubMed1998

Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis.

The tyrosine kinase Jak3 plays a key role in transducing signals from the IL-2, -4, -7, -9, and -15 receptors. Mice lacking Jak3 exhibit a profound, early block in both B and T cell development. To examine the mechanisms whereby Jak3 influences T cell function, we have reconstituted thymic development in Jak3-/- animals by introducing a Jak3 transgene in which expression was driven by the lck proximal promoter. Thymic reconstitution required Jak3 kinase activity, as catalytically inactive Jak3 did not restore early thymic development. Furthermore, the thymus-restricted expression pattern of the transgene allowed us to assess the requirement for Jak3 in peripheral T cells. In these mice, loss of Jak3 expression was associated with a failure to proliferate in response to antigen receptor crosslinking, the accumulation of T cells manifesting an activated cell surface phenotype, and an increased CD4/CD8 ratio among peripheral T cells, all of which are characteristics that were observed in Jak3-/- animals. Finally, we present data which suggest that peripheral T cells proliferate more rapidly in vivo and also undergo apoptosis more rapidly, upon loss of Jak3. Hence Jak3 exerts effects on mature peripheral T lymphocytes, as well as on thymocytes, resulting in the proper maintenance of circulating, quiescent cells.

Animals↗

PubMed1998

Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation.

STAT (signal transducers and activators of transcription) proteins are transcription factors which are activated by phosphorylation on tyrosine residues upon stimulation by cytokines. Seven members of the STAT family are known, including the closely related STAT5A and STAT5B, which are activated by various cytokines. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5 activation in various systems are not clear. We applied PCR-driven random mutagenesis and a retrovirus-mediated expression screening system to identify constitutively active forms of STAT5. By this strategy, we have identified a constitutively active STAT5 mutant which has two amino acid substitutions; one is located upstream of the putative DNA binding domain (H299R), and the other is located in the transactivation domain (S711F). The mutant STAT5 was constitutively phosphorylated on tyrosine residues, localized in the nucleus, and was transcriptionally active. Expression of the mutant STAT5 partially dispenses with interleukin 3 (IL-3) as a growth stimulant of IL-3-dependent cell lines. Further analyses of the mutant STAT5 have demonstrated that both of the mutations are required for nuclear localization, efficient transcriptional activation, and induction of IL-3-independent growth of an IL-3-dependent cell line, Ba/F3, and have indicated that a molecular basis for the constitutive activation is the stability of the phosphorylated form of the mutant STAT5.

Animals↗

PubMed1998

Cytokine receptors: structures and signal transduction.

The characteristic features of cytokines are functional pleiotropy and redundancy. Each cytokine is produced by a variety of cell types and acts on a wide range of target cells and tissues. Many cytokines have overlapping biological activities in the same cells. It was originally thought that each cytokine has a specific receptor and a unique signal transduction system. However, extensive studies on cytokines and their receptors revealed that many cytokines share receptor subunits and signal transduction system, and that biological functions of a single cytokine can vary depending on the status of the cells. Therefore, it is important to know the structure and function of cytokine receptors to understand the pleiotropy and redundancy as well as specificity of cytokines. Among signal transduction pathways, recently identified Jak/STAT pathway, which connects activation of the receptor complexes and transcription of various genes directly, would give us further insights in the mechanisms of cytokine action.

Animals↗

PubMed1997

Jaks and Stats in cytokine signaling.

Hematopoiesis is regulated through the binding of cytokines to receptors of the cytokine receptor superfamily. Although lacking catalytic domains, members of the cytokine receptor superfamily mediate ligand-dependent activation of protein tyrosine phosphorylation through their association and activation of members of the Janus kinase (Jak) family of protein tyrosine kinases. The activated Jaks phosphorylate the receptors which creates docking sites for SH2-containing signaling proteins which are tyrosine phosphorylated following their association with the complex. Among the substrates of tyrosine phosphorylation are members of the signal transducers and activators of the transcription family of proteins (Stats). Various cytokines induce the tyrosine phosphorylation and activation of one or more of the seven family members. The pattern of Stat activation provides a level of cytokine individuality that is not observed in the activation of other signaling pathways. The role of various Stats in the biological responses to cytokines has been assessed through the analysis of receptor mutations which disrupt Stat activation and more recently by disruption of the genes in mice. Our results have demonstrated that the activation of Stat5a and Stat5b by erythropoietin is critical for the activation of a number of immediate early genes but is not required for a mitogenic response. Mice in which the genes for Stat4 and Stat6 are disrupted are viable but lack functions that are mediated by interleukin 12 (IL-12) or IL-4, respectively, suggesting that these Stats perform very specific functions in immune responses.

Animals↗

PubMed1997

Suspension effect and dynamic evaluation of the total surface bearing (TSB) trans-tibial prosthesis: a comparison with the patellar tendon bearing (PTB) trans-tibial prosthesis.

X-ray and cineradiography measurements were used to compare the suspension effect and stability of a TSB trans-tibial prosthesis with an Icelandic Roll-On Silicone Socket (ICEROSS) system to that of a PTB trans-tibial prosthesis. The suspension effect was measured by the distance between the tibia and the socket in both suspension position and weight-bearing position in both type of prostheses. The suspension effect of the TSB prosthesis (2.53 +/- 0.90 cm) was superior to that of the PTB prosthesis (3.60 +/- 0.56 cm) (p < 0.05) by x-ray measurement. The suspension effect of the TSB prosthesis (0.1, 0.4, 0.72 cm) was superior to that of the PTB prosthesis (0.3, 0.48, 1.03 cm) (p < 0.01, p < 0.05) by cineradiographic measurement. The stability was measured as the angle between the axis of the tibia and the prosthesis at the time of heel contact and toe off. The angle change of the TSB prosthesis was statistically smaller than that of the PTB prosthesis.

Adult↗

PubMed1997

HIRF: a novel nuclear factor that binds to the human T-cell leukemia virus type I internal regulatory element (HIRE).

The transcription of human T-cell leukemia virus type I (HTLV-I) provirus starts from a promoter located in the 5' long terminal repeat (LTR). We have identified a second promoter at the 3' end of the pol gene. This internal promoter expresses the Tax transactivator protein, but does not require Tax for its activity. Furthermore, we have found the novel enhancer motif AGTTCTGCCC, which are located near the initiation site. We have named the sequence HIRE (HTLV-I internal regulatory element). The HIRE binding protein is a ubiquitous protein. We purified this protein from the HTLV-I producing cell line MT-2 cells by DNA affinity chromatography. SDS-PAGE analysis revealed four major bands (70, 85, 115 and more than 200 kDa) and some minor bands on the gel. We renatured each major protein and showed the 70 and 115 kDa proteins bind to DNA, although the 115 kDa protein seemed to bind nonspecifically. We have designated these components as HIRF (HTLV-I internal regulatory factor).

Base Sequence↗

PubMed1996

Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene.

Signal transducers and activators of transcription (Stats) are activated by tyrosine phosphorylation in response to cytokines, and are thought to mediate many of their functional responses. Stat6 is activated in response to interleukin (IL)-4 and may contribute to various functions including mitogenesis, T-helper cell differentiation and immunoglobulin isotype switching. To evaluate the role of Stat6, we generated Stat6-null mice (Stat6 -/-) by gene disruption in embryonic stem cells. The mice were viable, indicating the lack of a non-redundant function in normal development. Although naive lymphoid cell development was normal, Stat6 -/- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE. In contrast, IL-4-mediated proliferation was only partly affected.

Animals↗

PubMed1996

TmDOTP5-: a substance for NMR temperature measurements in vivo.

The chemical shifts of 31P and 1H in thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) (TmDOTP5-) are approximately two orders of magnitude more sensitive to temperature than are water proton and 19F shifts. In the physiologically relevant pH range, the 31P and 1H chemical shifts of TmDOTP5- are linear functions of temperature between 25 and 47 degrees C. The results indicate that using TmDOTP5- can provide measurements of temperature in vivo that are significantly more accurate than methods based on water and fluorocarbon chemical shifts.

Abdomen↗

PubMed1996

The post-transcriptional regulator Rev of HIV: implications for its interaction with the nucleolar protein B23.

Human T cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) belong to the complex retrovirus whose replication is controlled by trans-acting proteins. HIV-1 encodes several regulatory proteins, including two essential trans-activations for viral replication, Rev and Tat. Both Rev and Tat have a nucleolar targeting signal and are actually located predominantly in the nucleoli. Within the nucleoli, Rev is localized to the combined regions of the dense fibrillar (DFC) and the granular (GC) components. Tat does not colocalize precisely with any nucleolar component tested, but partly overlaps regions of the DFC and the GC. Regions of both Rev and Tat are overlapped by the distribution of the major nucleolar protein B23. Overexpression of Rev causes nucleolar ballooning and general structural deformity with aberrant accumulation of rRNAs, whereas Tat does not have that effect. B23 is markedly accumulated in those nucleoli deformed by Rev. Components of the nucleolar DFC, GC, and fibrillar center domains are not accumulated but dispersed in a few small spots or larger patches within the enlarged nucleoli. Cytophotometric DNA determinations revealed that transient expression of Rev results in accumulation of G2, prophase, and mitotic cells which have failed cytokinesis, suggesting that Rev is capable of preventing or slowing the progression through mitosis. Tat, in contrast, does not affect the cell cycle. We speculate, based on these results, that Rev represses cell growth inhibiting the transport of ribosomal proteins and preribosomal particles across the nuclear envelope and affecting the cell cycle, both of which may be related to the proposed functions of B23.

Animals↗

PubMed1996

Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response.

The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a membrane-distal region that is dispensable for mitogenesis but is required for the recruitment and tyrosine phosphorylation of a variety of signaling proteins. The membrane-proximal region of 96 amino acids is necessary and sufficient for mitogenesis as well as Jak2 activation, induction of c-fos, c-myc, cis, the T-cell receptor gamma locus (TCR-gamma), and c-pim-1. The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B. The membrane-proximal domain contains a single tyrosine, Y-343, which when mutated eliminates the ability of the receptor to couple Epo binding to the activation of Stat5. Furthermore, peptide competitions demonstrate that this site, when phosphorylated, can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor. Cells expressing the truncated, Y343F mutant (a mutant with a Y-to-F alteration at position 343) proliferate in response to Epo in a manner comparable to that of the controls. However, in these cells, Epo stimulation does not induce the appearance of transcripts for cis, TCR-gamma, or c-fos, suggesting a role for Stat5 in their regulation.

Amino Acid Sequence↗

PubMed1996

[Expression of major histocompatibility complex of advanced non-small cell lung cancer (NSCLC)].

Expression of major histocompatibility complex of lung cancer was examined to study the malignant potential of the tumor using immunochemical staining (anti-HLA class I monoclonal antibody; w6/32). Nuclear DNA contents and the labeling index of proliferating cell nuclear antigen (PCNA) were measured as well. Forty three advanced (p-stage IIIa) lung cancers resected by lobectomy (33 cases), pneumonectomy (9 cases), and segmentectomy (1 case) entered the study. Mediastinal lymph node dissection was performed in every case during the operation. Of the 43 cases, expression of HLA class I was positive in 17 and negative in 26. The patients with positive HLA expression showed significantly better prognosis than those with negative HLA expression in terms of 5 year survival (p < 0.01). The patients with aneuploid pattern and positive HLA class I expression had the best prognosis on the survival curve (p < 0.01). When the PCNA positive rate was high, the prognosis was poor. And the patients with negative PCNA and positive HLA class I expression had significantly better prognosis than the others (p < 0.01). These findings suggest that the expression of HLA class I on the tumor cells is an important prognostic factor in the patients with NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed1996

[Pulmonary aspergillosis: clinical findings and surgical treatment].

Between 1980 and 1995, 10 patients underwent thoracotomy for pulmonary aspergillosis. In six patients, hemoptysis and bloody sputum were the chief complaints. The other complaints were nonspecific. Six patients had a history of pulmonary tuberculosis, and two of those patients underwent upper lobectomy. Aspergillosis had developed in the residual space. A fungus ball was observed on the preoperative chest X-ray and CT scan films in seven patients. Lobectomy was done in three patients, segmentectomy in two, and partial pulmonary resection in four. The patients with lesions that had grown in the residual space underwent curettage with muscle plombage. Three patients underwent thoracoplasty. An additional operation was done in two patients because of poor residual lung expansion. No patient had recurrence. We conclude that surgical treatment should be based on symptoms and on pathological findings.

Adult↗

PubMed1996

[Repair of diaphragmatic hernia through the thoracoabdominal spiral incision].

Traumatic diaphragmatic hernia requires urgent surgical treatment. A 51-year-old female was injured in a speeding car. She had dyspnea, and resistance on the abdominal wall on physical examination. Intra-thoracic and abdominal visceral injury was suspected. A chest roentogenogram and CT scan revealed an obvious diaphragmatic herniation on the left which necessitated emergency operation. On the right semi-lateral position, left thoracoabdominal spiral incision was made through the 7th intercostal space. Good exposure of the chest and abdomen was easily obtained. Herniated organs and the abdominal cavity were thoroughly examined with ease. The diaphragm was repaired directly. She had an uneventful postoperative recovery, and was discharged in 17 days. Thoracoabdominal spiral incision offered an excellent operative exposure for the patient with a possible combined thoracic and abdominal visceral injury.

Female↗

PubMed1995

Defective lymphoid development in mice lacking Jak3.

The Janus tyrosine kinases (Jaks) play a central role in signaling through cytokine receptors. Although Jak1, Jak2, and Tyk2 are widely expressed, Jak3 is predominantly expressed in hematopoietic cells and is known to associate only with the common gamma (gamma c) chain of the interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors. Homozygous mutant mice in which the Jak3 gene had been disrupted were generated by gene targeting. Jak3-deficient mice had profound reductions in thymocytes and severe B cell and T cell lymphopenia similar to severe combined immunodeficiency disease (SCID), and the residual T cells and B cells were functionally deficient. Thus, Jak3 plays a critical role in gamma c signaling and lymphoid development.

Aging↗

PubMed1995

Nourishment of hepatocellular carcinoma cells through the portal blood flow with and without transcatheter arterial embolization.

BACKGROUND: Although transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) is very effective, local recurrence is not so rare. The reason is thought to be related to portal blood flow. The changes in the nourishing vessels in HCC after TAE were examined from the viewpoint of cell kinetics with direct reference to intracellular transportation of biochemical substrates, namely 5 bromo-2'-deoxyuridine (BrdU), an analogue of thymidine. METHODS: To examine the cell kinetics of carcinoma cells, BrdU was infused intraoperatively in 23 patients with HCC (12 without TAE and 11 post-TAE patients) directly into the portal branch feeding the region to be resected. Specimens were prepared for immunohistochemical staining using BrdU monoclonal antibodies and analyzed using the labeling index (LI). The distribution of the labeled S-phase cell was also examined. RESULTS: The LI in post-TAE patients was about six times higher than patients without TAE, with a significant difference at P < 0.001. Labeled cells were distributed not only peripherally but in the central part of the tumor, although the number was extremely small. CONCLUSIONS: Some HCC cells, although small in number, are nourished by the portal blood flow directly throughout the viable tumor mass, which may act as the main blood supplier during the period after TAE. For greater local control of HCC, complete resection of HCC and/or the use of chemotherapy via not only the hepatic artery but also the portal blood flow are beneficial.

Adult↗

PubMed1995

The cytotoxicity of human immunodeficiency virus type 1 Rev: implications for its interaction with the nucleolar protein B23.

Human immunodeficiency virus type 1 (HIV-1) encodes several regulatory proteins, including two essential trans-activators for viral replication, Rev and Tat. Both Rev and Tat have a nucleolar targeting signal and are actually located predominantly in the nucleoli. Within the nucleoli, Rev is localized to the combined regions of the dense fibrillar (DFC) and the granular (GC) components. Tat does not colocalize precisely with any nucleolar component tested, but partly overlaps regions of the DFC and the GC. Regions of both Rev and Tat are overlapped by the distribution of the major nucleolar protein B23. Overexpression of Rev causes nucleolar ballooning and general structural deformity with aberrant accumulation of rRNAs, whereas Tat does not have that effect. B23 is markedly accumulated in those nucleoli deformed by Rev. Components of the nucleolar DFC, GC, and fibrillar center domains are not accumulated but dispersed in few small spots or larger patches within the enlarged nucleoli. Cytophotometric DNA determinations revealed that transient expression of Rev results in accumulation of G2, prophase, and mitotic cells which have failed cytokinesis, suggesting that Rev is capable of preventing or slowing the progression through mitosis. Tat, in contrast, does not affect the cell cycle. We speculate, based on these results, that Rev represses cell growth by inhibiting the transport of ribosomal proteins and preribosomal particles across the nuclear envelope and affecting the cell cycle, both of which may be related to proposed functions of B23.

Animals↗