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Biomedical subjects

K Yasui

Publications and source records attributed to K Yasui.

At least 127 records · Page 7Linked to original sources
PubMed1998

Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology.

Free cancer cells exfoliated from the cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in gastric carcinoma patients. This study was designed to evaluate the prognostic relevance of such free cells in peritoneal washes detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for carcinoembryonic antigen and conventional cytologic examination by Papanicolaou staining were performed on peritoneal washes, collected at laparotomy from 148 gastric carcinoma patients. Prognostic analyses were performed with 1) death due to cancer recurrence and 2) peritoneal dissemination as endpoints. RT-PCR was found to be more sensitive than cytologic examination for detection of free cancer cells in the peritoneal washes, with a higher detection rate for each of the T categories in the tumor-node-metastasis (TNM) classification. Five patients with synchronous or recurrent peritoneal dissemination were found among 17 patients with positive RT-PCR and negative cytologic results. Both positive cytologic results and positive RT-PCR results had significant influences over the survival of patients with advanced gastric carcinomas (n = 75, p < .002). Detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is promising as a predictor of peritoneal dissemination in patients with gastric carcinoma.

Carcinoembryonic Antigen↗
PubMed1998

Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.

The present study analyzed peripheral blood B cell populations separated by IgD and CD27 expression in six males with X-linked hyper-IgM syndrome (XHIM). Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from IgM to IgG and IgA with Staphylococcus aureus Cowan strain (SAC) plus IL-2 or anti-CD40 mAb (anti-CD40) plus IL-10. Measurable levels of IgE were secreted in some of the patients after stimulation with anti-CD40 plus IL-4. Costimulation with SAC plus IL-2 plus anti-CD40 plus IL-10 yielded secretion of significant levels of IgG in addition to IgM, but not IgA. The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells; IgD- CD27(+) memory B cells were greatly decreased. IgD+ CD27(+) B cells from an XHIM patient produced IgM predominantly. Our data indicate that the low response of IgG production in XHIM patients is due to reduced numbers of IgD- CD27(+) memory B cells. However, the IgG production can be induced by stimulation of immunoglobulin receptors and CD40 in cooperation with such cytokines as IL-2 and IL-10 in vitro.

Adolescent↗
PubMed1998

Sustained release dosage of thyrotropin-releasing hormone improves experimental Japanese encephalitis virus-induced parkinsonism in rats.

Thyrotropin-releasing hormone (TRH) has been reported to have some possibilities toward the treatment of affective CNS disorders. However, long term treatments with daily injections are often required. Effects of TRH-SR (sustained release microspheres of TRH) which is encapsulated in copoly (dl-lactic/glycolic acid) using an in-water drying method were investigated in experimental Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test and high performance liquid chromatography (HPLC) with an electrochemical detector (ECD). We have already reported that in adult Fischer rats killed 12 weeks after infection with JEV at the age of 13 days a marked decrease of tyrosine hydroxylase-positive neurons was found in the bilateral substantia nigra. TRH-SR (3 mg/kg per 2 weeks, 4 times injections, subcutaneous [s.c.]) improved bradykinesia observed in the JEV-induced parkinsonism rats. Dopamine (DA) concentrations in the JEV-infected rats were profoundly reduced in the striatum as compared with controls. TRH-SR (3 mg/kg, once, s.c.) increased DA in the striatum 7 days after the injection. Although the pathomechanism of post-encephalitic parkinsonism is different from that of Parkinson's disease and TRH possesses a variety of CNS effects as well, these results suggest that TRH-SR play a possible role in the treatment of Parkinson's disease in addition to post-encephalitic parkinsonism as a supportive drug of L-DOPA.

Animals↗
PubMed1998

Two large subunits of the fission yeast RNA polymerase II provide platforms for the assembly of small subunits.

The subunit-subunit contact network was analyzed for the Schizosaccharomyces pombe RNA polymerase II consisting of ten putative subunits. Previously we carried out far-Western blot analysis of bimolecular interaction with radio-labeled subunit 3 and 5 probes. Here we extended the analysis using another six small-sized subunits as probes. Taking the results together the subunit-subunit interaction was observed for a total 18 (or 19) combinations. All eight small-sized subunits exhibited binding activities to two large subunits, Rpb1 and Rpb2. In addition, bimolecular interaction was observed for the combinations of Rpb3-Rpb5, Rpb3-Rpb11 (and Rpb5-Rpb8/11). The subunit-subunit contact within the assembled RNA polymerase was then analyzed by protein-protein cross-linking using five species of bifunctional cross-linkers with different length and specificity. Cross-linking was observed for a total of 19 combinations, including five combinations between small subunits, Rpb3-Rpb10, Rpb3-Rpb11, Rpb5-Rpb6, Rpb6-Rpb7 and Rpb6-Rpb8. The results altogether indicate that two large subunits Rpb1 and Rpb2 provide the platform for assembly of small subunits and also small subunits interact with each other for limited combinations. Direct contact of the two large subunits, Rpb1 and Rpb2, was also demonstrated by cross-linking.

Cross-Linking Reagents↗
PubMed1998

Location of subunit-subunit contact sites on RNA polymerase II subunit 3 from the fission yeast Schizosaccharomyces pombe.

RNA polymerase II from the fission yeast Schizosaccharomyces pombe consists of 10 putative subunits. Subunit 3 (Rpb3) is a homologue of prokaryotic alpha subunit, which plays a key role in the assembly of core enzyme subunits. Previously we indicated that Rpb3 also plays an essential role in subunit assembly because it interacts with at least four subunits, two large subunits (Rpb1 and Rpb2) and two medium-sized subunits (Rpb3 and Rpb5) (1), and it constitutes a core subassembly consisting of Rpb2, Rpb3, and Rpb11 (2). Using a synthetic mixture of equimolar amounts of individual subunits, which were all purified from cDNA-expressed Escherichia coli, we found here that Rpb3 also interacts with Rpb11, another alpha homologue. By making a set of Rpb3 deletion derivatives, we carried out mapping of the Rpb5- and Rpb11-contact sites on Rpb3. By far-Western blot and GST pull-down assays, we found that the amino acid sequence between residues 105-263 of Rpb3 is involved in binding Rpb5, and the sequence between residues 105-297 is required for binding Rpb11. Although the Rpb5- and Rpb11-contact sites on Rpb3 overlap each other, both subunits are able to associate with Rpb3 simultaneously. The binding of Rpb5 stabilizes the Rpb3-Rpb11 heterodimer.

Binding Sites↗
PubMed1998

Early development of the peripheral nervous system in a lancelet species.

The developmental pattern of the lancelet (amphioxus) peripheral nervous system from embryos to larvae has been studied by using wholemount immunostaining and transmission electron microscopy. The peripheral nerves first appeared on the anterior dorsal surface of the medulla at the middle neurula stage, when the anterior nerve cord was just closing. A single axon with a large growth cone was the progenitor of each nerve. The nerve roots adopted an asymmetric arrangement soon after. The first nerve, likely a pair of pure sensory nerves, sprouted from the anterior tip of the nerve cord. This nerve may be comparable topographically to the preoptic nerve (the posterior branch of the terminal nerve) in lungfishes. However, the neuron that first extends its axon was located in the medulla, as in the other posterior nerves. One of the extramedullary primary sensory neurons, the corpuscles of de Quatrefages, appeared in larvae with the mouth and two anterior gill pores. Their axons were seemingly fasciculated with the efferent axon of the first nerve. The second nerve, the most complex one to appear during embryonic and early larval development, innervated the preoral pit and the buccal region. The third and fourth nerves on the left side also innervated the buccal region. The larval innervation patterns in the anterior region differed from the adult organization, suggesting a segmental rearrangement of the nerve supply during development. There was no evidence to dichotomize the peripheral nerves into cranial and spinal nerves, as exist in vertebrates. These characteristics of the peripheral nervous system in the lancelet indicate that this animal has a rather derived or primitive developmental system of peripheral nerves, making the analysis of homology with vertebrates difficult.

Animals↗
PubMed1998

Expression of a twist-related gene, Bbtwist, during the development of a lancelet species and its relation to cephalochordate anterior structures.

Mesoderm formation plays a crucial role in the establishment of the chordate body plan. In this regard, lancelet embryos develop structures such as the anteriorly extended notochord and the lateral divertecula in their anterior body. To elucidate the developmental basis of these structures, we examined the expression pattern of a lancelet twist-related gene, Bbtwist, from the late gastrula to larval stages. In late-gastrula embryos, the transcripts of Bbtwist were detected in the presumptive first pair of somites and the middorsal wall of the primitive gut. The expression of Bbtwist was then upregulated in the lateral wall of somites and the notochord. At the late-neurula stage, it was also expressed in the anterior wall of the primitive gut, as well as in the evaginating lateral diverticula. No signal was detected in the left lateral diverticulum when it was separated from the gut, while in the right one, the gene was expressed later during the formation of the head coelom in knife-shaped larvae, and in the anterior part of the notochord in the same larvae. In 36-h larvae, only faint expression was detected in the differentiating notochordal and paraxial mesoderm in the caudal region. These expression patterns suggest that Bbtwist is involved in early differentiation of mesodermal subsets as seen in Drosophila and vertebrates. The expression in the anterior notochord may be related to its anterior expansion. The expression in the anterior wall of the primitive gut and its derivative, the lateral diverticula, suggests that lancelets share the capability to produce a mesodermal population from the tip of the primitive gut with nonchordate deuterostome embryos.

Amino Acid Sequence↗
PubMed1998

Cervical spondylotic amyotrophy. Magnetic resonance imaging demonstration of intrinsic cord pathology.

STUDY DESIGN: Three case reports. OBJECTIVE: To elucidate the pathophysiology of cervical spondylotic amyotrophy. SUMMARY OF BACKGROUND DATA: Cervical spondylotic amyotrophy is the clinical syndrome in cervical spondylosis characterized by severe muscular atrophy in the upper extremities, with an absent or insignificant sensory deficit. Pathophysiology of this particular syndrome has not been well understood. METHODS: Three cases of cervical spondylotic amyotrophy are presented in which magnetic resonance imaging confirmed the intrinsic cord disease as the cause of the syndrome. RESULTS: The patients had segmental muscular atrophy of the proximal upper extremities, with an absent or insignificant sensory deficit. After initial disease progression, the symptoms stabilized for years. Sagittal T2-weighted magnetic resonance images showed multi-segmental linear high-signal intensity within the compressed spinal cord. These high-signal intensity lesions appeared to be located at the anterior horns on axial images. The spinal cord compression was less severe in the neck-neutral position, but spinal canal stenosis increased when the neck was extended. CONCLUSIONS: The results suggest that one pathophysiology of this syndrome may be multisegmental damage to the anterior horns caused by dynamic cord compression, possibly through circulatory insufficiency.

Aged↗
PubMed1998

Highly selective and orally active inhibitors of type IV collagenase (MMP-9 and MMP-2): N-sulfonylamino acid derivatives.

Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2. In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.

Administration, Oral↗
PubMed1998

Generation of plasma cells from peripheral blood memory B cells: synergistic effect of interleukin-10 and CD27/CD70 interaction.

B cells can differentiate into the antibody-secreting cells, plasma cells, whereas the crucial signals that positively control the entry into the pathway to plasma cells have been unclear. Triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). Differentiation into plasma cells by a combination of IL-10 and CD70 transfectants occurred in CD27+ B cells but not in CD27- B cells. Moreover, addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced differentiation into plasma cells. In the presence of only IL-2, IL-4, or IL-6, CD70 transfectants did not promote differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B-cell pool from peripheral blood B cells primarily activated by IL-2, IL-10, and anti-CD40 monoclonal antibody (MoAb). Finally, CD27 signaling also rescued B cells from IL-10-mediated apoptosis. These data demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10-mediated promotion of apoptosis and to direct the differentiation of CD27+ memory B cells toward plasma cells in cooperation with IL-10.

Adult↗
PubMed1998

Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM Classification? Tumor Node Metastasis.

BACKGROUND AND OBJECTIVES: The anatomical extent of nodal metastasis has been replaced by the number of metastatic nodes as a key indicator of prognosis (pN categories) in the fifth edition of Tumor Node Metastasis Classification for gastric carcinoma by the International Union Against Cancer. The rate of metastatic nodes among all the nodes harvested is also a good prognostic factor. The object of this study is to evaluate which of the three parameters for the assessment of nodal status is the most appropriate for use in the stage classification. METHODS: Retrospective survival analyses were performed in 656 consecutive patients with advanced gastric carcinoma who underwent D2 lymphadenectomy and for whom histopathologic data of more than 20 lymph nodes were available. RESULTS: Although all three systems served well to classify the patients into distinct groups in terms of survival curves, stratification by the number of metastatic nodes was vulnerable to stage migration because of differences in the number of lymph nodes harvested. Such stage migration was not evident for the other two parameters. CONCLUSIONS: Lymph node metastatic rate can be recommended as an internationally applicable parameter for lymph node involvement of gastric carcinoma.

Adult↗
PubMed1998

alpha1-adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+ channel expression differentially in cultured newborn rat ventricular cells.

Interest has arisen concerning the importance of alpha-adrenergic function and insulin-like growth factor-1 (IGF-1) in cardiac remodelling. The hypothesis that these two factors may underlie the regulation of voltage-gated K+ channel expression in hypertrophied cardiomyocytes was tested by performing Western blot analysis of the Kv1.5 K+ channel alpha-subunit in cultured newborn rat ventricular cells. Myocyte size was quantified by surface area and total cell protein concentration. Cell exposure to the alpha1-adrenoceptor agonist phenylephrine (PE, 20 microM) and IGF-1 (60 ng/ml) for 72 h both induced a significant increase of cell size indicating myocyte hypertrophy, which could be separately blocked by the protein kinase C inhibitor staurosporine (20 nM) and the tyrosine kinase inhibitor genistein (15 microM). Western blots of cell proteins prepared from myocyte cultures showed a single protein band at 75 kD recognized by the anti-Kv1.5 antibody, and demonstrated a 56% reduction in the Kv1. 5 immunoreactive protein level in the PE-treated cell preparations. This suppression was not affected by staurosporine, but was remarkably attenuated by W7 (20 microM), a selective calmodulin antagonist. In contrast to PE, a 48% enhancement of the protein expression of Kv1.5 channel was induced by IGF-1 and this stimulation was specifically blocked by genistein. Our findings suggest that the differential regulation of cardiac Kv1.5 K+ channel expression can be produced by alpha1-adrenoceptor activation and IGF-1 via distinctive signalling pathways. Calmodulin-dependent kinase and tyrosine kinase contribute importantly to the alpha1-adrenoceptor-mediated decrease and the IGF-1-mediated increase in cardiac Kv1.5 K+ channel expression, respectively.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1998

The number of metastatic lymph nodes: a promising prognostic determinant for gastric carcinoma in the latest edition of the TNM classification.

BACKGROUND: The number of metastatic regional lymph nodes determines the new pN categories in the 5th edition of the TNM classification. STUDY DESIGN: Our retrospective study was conducted to compare the new method of defining lymph node status with the conventional classification, consisting of the anatomic extent of lymph node metastases, a well-established prognostic factor. The study was based on clinical data for 493 patients with gastric carcinomas who underwent potentially curative operations and had histologically confirmed nodal metastases. These patients were stratified into 1) n categories according to the Japanese Classification of Gastric Carcinoma, 2) the new pN categories, and 3) the pN categories determined by the number of metastatic perigastric nodes resected by standard D1 gastrectomy. Survival data were analyzed for each group. RESULTS: The number of metastatic nodes after D2 lymphadenectomy reflected prognosis well and was shown by multivariate analysis to be a strong independent prognostic factor. When the classification was performed limited to the metastatic perigastric nodes, stage migration was evident, but the variable remained competent as a prognostic indicator. CONCLUSIONS: The number of metastatic nodes is a promising determinant in the new international stage classification.

Adult↗
PubMed1998

Characterization and localization of thromboxane A2 receptor in human and guinea-pig nasal mucosa using radiolabelled (+)-S-145.

1. TxA2 receptor (TP-receptor) antagonists such as S-1452 and Bay u 3405 have been shown to be effective in alleviating nasal blockage in patients with allergic rhinitis as well as guinea-pig allergic rhinitis models. The present study was conducted to examine the existence and localization of the TP-receptor in human and guinea-pig nasal mucosa by in vitro receptor binding autoradiography using radiolabelled (+)-S-145, which is a potent and specific TP-receptor antagonist with an extremely slow dissociation rate. 2. We ascertained the binding specificity of [3H]-(+ )-S-145 in human and guinea-pig platelet membranes by comparing the ability of four TP-receptor ligands of U-46619, (+)-S-145, I-(+)-S-145 and Bay u 3405 to displace the specific binding of [3H]-(+)-S-145 and [3H]-U-46619. The rank order of potency (Ki) for the displacement was correlated highly with that determined from [3H]-U-46619 binding to the same preparations. 3. Quantitative autoradiography using a radioluminographic imaging plate system, in which the radioactivity of [3H]-(+)-S-145 is expressed as photostimulated luminescence (PSL) per area (mm2), revealed that specific binding of [3H]-(+)-S-145 to human and guinea-pig nasal mucosa was saturable. Scatchard analysis showed about three fold higher affinity and two fold greater maximal binding to the nasal mucosa of humans than that of guinea-pigs: the KD and Bmax values in human mucosa were 2.82+/-0.35 nM and 6.47+/-0.33 PSL mm(-2) and those in guinea-pig mucosa were 8.23+/-1.93 nM and 3.37+/-0.66 PSL mm(-2), respectively. 4. Specific [3H]-(+)-S-145 binding to cryostat sections of human and guinea-pig nasal mucosa was displaced by another TP-receptor antagonist, Bay u 3405, and a TP-receptor agonist, U-46619. The order of potency (Ki value: nM) was (+)-S-145 (2.5) > Bay u 3405 (15.4) > > U-46619 (359.6) in human nasal mucosa and (+)-S-145 (22.8) > U-46619 (49.8) approximately Bay u 3405 (62.1) in guinea-pig nasal mucosa. These rank orders showed rather good correlation with those obtained for the respective platelet membranes. 5. Autoradiographs of human nasal mucosa demonstrated that specific [125I]-(+)-S-145 binding sites mainly exist on the smooth muscle layers of venous sinusoids and arterioles in the lamina propria, with few or no binding sites in the epithelium and nasal gland. 6. We concluded that radiolabelled (+)-S-145 can be used as a TP-receptor ligand for autoradiographic study, and that the TP-receptor is exclusively located on smooth muscle layers of venous sinusoids and arterioles in the nasal mucosa. The potent vasoconstrictive activity of TxA2 may cause reduction of local blood flow followed by mucosal oedema probably through mechanisms of vascular injury such as ischaemia-reperfusion.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Dynamics of hepatitis C viremia following interferon-alpha administration.

Knowledge of the dynamics of hepatitis C virus (HCV) in vivo is important for elucidation of its pathogenesis and the establishment of therapeutic guidelines. The aim of this study was to obtain kinetic information about virus load following interferon-alpha (IFN-alpha) administration. Serial serum HCV core protein and HCV RNA levels were measured. IFN-alpha exponentially reduced serum HCV levels. The mean (+/-SD) viral half-life was 7.0 +/- 2.6 h in HCV core protein assay and 7.2 +/- 3.1 h in HCV RNA assay on the first day of therapy. This initial rapid decrease was followed by a slower decrease in serum HCV levels thereafter. Thus, the biphasic reduction in virus load during IFN-alpha therapy was demonstrated.

Adult↗
PubMed1998

The role of radical gastrectomy with systematic lymphadenectomy for the diagnosis and treatment of primary gastric lymphoma.

OBJECTIVE: We evaluated the therapeutic efficacy of radical gastrectomy for primary B-cell lymphoma of the stomach and attempted to identify patients who could be adequately treated with surgery alone. SUMMARY BACKGROUND DATA: Several recent gastric lymphoma reports have discussed the therapeutic benefits of various treatment strategies for stage IE and IIE lymphoma. However, few studies have been based on patients accurately staged by systematic lymphadenectomy with subsequent pathologic examination. METHODS: A retrospective study was performed to evaluate the survival and biologic behavior of lesions in 60 patients with gastric lymphoma who were treated by radical gastrectomy alone. Tumors were classified according to the histopathologic concept of mucosa-associated lymphoid tissue (MALT)-derived lymphoma. RESULTS: A low histopathologic grade was associated with a significantly lower incidence of nodal metastasis (p = 0.07) and less extensive infiltration of the gastric wall (p < 0.005) despite larger tumor size. A 5-year survival rate of >95% was attained with surgery alone for MALT lymphoma and for true stage IE lymphoma diagnosed by pathologic examination of up to N2 lymph nodes routinely performed after radical gastrectomy. CONCLUSIONS: Surgery alone is adequate treatment for stage IE or pure MALT lymphoma, provided that the staging is performed after radical gastrectomy.

Adult↗
PubMed1998

The native form and maturation process of hepatitis C virus core protein.

The maturation and subcellular localization of hepatitis C virus (HCV) core protein were investigated with both a vaccinia virus expression system and CHO cell lines stably transformed with HCV cDNA. Two HCV core proteins, with molecular sizes of 21 kDa (p21) and 23 kDa (p23), were identified. The C-terminal end of p23 is amino acid 191 of the HCV polyprotein, and p21 is produced as a result of processing between amino acids 174 and 191. The subcellular localization of the HCV core protein was examined by confocal laser scanning microscopy. Although HCV core protein resided predominantly in the cytoplasm, it was also found in the nucleus and had the same molecular size as p21 in both locations, as determined by subcellular fractionation. The HCV core proteins had different immunoreactivities to a panel of monoclonal antibodies. Antibody 5E3 stained core protein in both the cytoplasm and the nucleus, C7-50 stained core protein only in the cytoplasm, and 499S stained core protein only in the nucleus. These results clearly indicate that the p23 form of HCV core protein is processed to p21 in the cytoplasm and that the core protein in the nucleus has a higher-order structure different from that of p21 in the cytoplasm. HCV core protein in sera of patients with HCV infection was analyzed in order to determine the molecular size of genuinely processed HCV core protein. HCV core protein in sera was found to have exactly the same molecular weight as the p21 protein. These results suggest that p21 core protein is a component of native viral particles.

Animals↗