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Biomedical subjects

Y Minami

Publications and source records attributed to Y Minami.

At least 127 records · Page 7Linked to original sources
PubMed1996

Trends in the incidence of female breast and cervical cancers in Miyagi Prefecture, Japan, 1959-1987.

Trends in the incidence of female breast and cervical cancers were examined, using the cancer registry data in Miyagi Prefecture, Japan, during 1959-1987. The age-standardized incidence rate of breast cancer has been increasing, while that of cervical cancer has been decreasing. Age-period-cohort models were applied to clarify the trends in incidence. For breast cancer incidence, the age-period model adequately represented the data, and demonstrated that the risk of developing breast cancer has been increasing in recent time periods. The effect of cohort on breast cancer incidence was insignificant and the full model containing age, period and cohort showed irregularities in the cohort effect. For cervical cancer incidence, the effect of period was significant, while the effect of cohort was marginal. The full model containing age, period and cohort showed that cervical cancer risk has been decreasing in recent time periods and younger birth cohorts. Using published reports, we investigated the trends in the prevalence of various risk factors and compared them with the trends in the incidence at both sites. It is suggested that the effects of period and cohort might be related to the changes in the prevalence of these risk factors as well as to improvements of the diagnostic procedures.

Adult↗
PubMed1996

Macromolecule-macromolecule interaction in drug distribution. V. Effects of plasma proteins on uptake of fractionated [3H]heparin in isolated rat Kupffer cells.

Effects of plasma proteins such as alpha-globulin on the uptake of high molecular weight (HMWFH: 23000 Da) and low molecular weight fractionated [3H]heparin (LMWFH: 10000 Da) were examined in isolated rat Kupffer cells. alpha-Globulin (8 mg/ml) affected neither surface binding nor internalization of LMWFH by Kupffer cells, while it reduced both surface binding and internalization of HMWFH without affecting the fraction internalized, which was a ratio of internalized amount to the total association. The total associations of HMWFH were about four times larger than that predicted assuming only the unbound fraction is available for uptake, suggesting the participation of protein-mediated transport in the uptake of HMWFH in Kupffer cells. Based on the same assumption, the saturable initial uptake of HMWFH versus concentration profile in the presence of alpha-globulin (8 mg/ml) was also analyzed to further examine the suggested protein-mediated transport. The estimated dissociation constant of 487 nM was three times larger than that in in vitro binding experiments (168 nM) and the binding capacity of 0.155 was one third of the value in vitro (0.5), suggesting apparent reductions in both binding affinity and capacity. Thus, we demonstrated the involvement of protein-mediated transport in the uptake of fractionated heparin in Kupffer cells and kinetically characterized it as the apparent enhancement of dissociation.

Alpha-Globulins↗
PubMed1996

[Early and late results of pericardiectomy for constrictive pericarditis].

Seven patients (4 males and 3 females: age 1 to 71 years old) who underwent operations for constrictive pericarditis from 1980 were reviewed. The median sternotomy approach was used without cardiopulmonary bypass. The pericardial flap was excised just anterior to both phrenic nerves. The postoperative hemodynamic improvement was good, especially in cardiac index (from 2.30 to 3.30 l/min/m2). Two patients were operative death. One was metastasis to pericardium from gastric cancer and another was multiple organ failure due to sepsis. Long-term survival was 3 to 13 years. One patient was dead at nine years after operation. Others were in New York Heart Association Class 1 or 2 in the long-term period after surgery. We conclude that our method can lead to good cardiac functional results and long-term good results. Our report wishes to emphasize early diagnosis and operation.

Adult↗
PubMed1996

[Significance of systemic inflammatory response syndrome at cardiopulmonary bypass].

Systemic Inflammatory Response Syndrome (SIRS) is a new concept of entry criteria for sepsis. This concept, when applied to area of Multiple Organ Failure (MOF), is considered to be a preparatory state for MOF. To study the significance of SIRS state at cardiac surgery, we measured the body temperature, white blood cell count, respiratory rate and heart rate of 18 patients who underwent elective cardiac surgery, from the 1st post-operative day to the 7th post-operative day. We also measured Interleukin-6 and 8 (IL-6 and IL-8) to understand the relationship between the SIRS state and inflammatory cytokines just after cardiopulmonary bypass (CPB), at the 1st, 3rd and 6th postoperative day. The result was as follows: Patients with CPB more than 120 minutes have more frequency and longer duration of SIRS than patients with CPB less than 120 minutes. Serum levels of IL-8 at SIRS state were revealed statistically higher than at non-SIRS case. Duration of SIRS state was related to CPB time and serum levels of IL-6 and IL-8 just after CPB. We concluded that SIRS state is an indication for anti-cytokine therapy to prevent MOF, and it is important to shorten CPB time in order to decrease the duration of SIRS.

Cardiopulmonary Bypass↗
PubMed1996

[Reconstruction of right ventricular outflow tract-pulmonary artery utilizing autologous tissue in extreme tetralogy of Fallot after coil embolization for major aortopulmonary collateral artery: report of a case].

We report a successful surgical treatment for tetralogy of Fallot with pulmonary atresia. A 18-year-old girl was admitted because of increasing exertional dyspnea and cyanosis. She had undergone bilateral classical Blalock-Taussing shunt. Prior to the correction, two major aortopulmonary collateral arteries were embolized using steel coils. Under cardiopulmonary bypass, posterior wall of the pulmonary artery was anastomosed directly to the cranial margin of the ventriculotomy for a floor made of autologous tissue. The roof was reconstructed using a patch with a monocusp. The patient is in a good postoperative condition. A coil embolization is useful and this reconstruction utilizing autologous tissue could prevent a late stenosis of the reconstructed pulmonary artery tract.

Adolescent↗
PubMed1995

Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).

Thymic shared antigen-1 (TSA-1) is a glycosyl-phosphatidylinositol (GPI)-anchored differentiation Ag expressed on murine lymphocytes, and is identical to stem cell Ag-2 (Sca-2). Using newly established mAb against TSA-1/Sca-2, we have previously shown that surface TSA-1 expression is induced upon activation in T cells, and that anti-TSA-1 inhibits IL-2 production induced by anti-CD3 stimulation in T cell hybridomas. In the present study, we have analyzed the functional role of TSA-1 during T cell activation using normal T cells, T cell hybridomas, and transfected Jurkat cell lines that expressed either GPI-anchored or transmembrane form of TSA-1. Anti-TSA-1 inhibited IL-2 production from normal T cells stimulated with soluble anti-CD3 plus accessory cells. Anti-TSA-1 exhibited the inhibitory effect on T cells, but not on accessory cells, because anti-TSA-1 inhibited IL-2 production in Jurkat cells transfected with TSA-1 cDNA, but not in control transfectant. A transmembrane form of TSA-1 was expressed in Jurkat cells by fusing the extracellular portion of TSA-1 to the transmembrane and cytoplasmic regions of the class 1 Db. The analysis using this transfectant revealed that anti-TSA-1-mediated inhibition of IL-2 production did not require the GPI anchor of TSA-1. Finally, in addition to the inhibition of IL-2 production, tyrosine phosphorylation of CD3 zeta-chains observed following TCR stimulation, one of the important early activation events, was markedly reduced by anti-TSA-1. These results imply that TSA-1/Sca-2 plays an important regulatory role in the TCR signaling pathway of activated T cells in addition to its role in T cell differentiation.

Animals↗
PubMed1995

Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle.

The Hsc70-interacting protein Hip, a tetratricopeptide repeat protein, participates in the regulation of the eukaryotic 70 kDa heat shock cognate Hsc70. One Hip oligomer binds the ATPase domains of at least two Hsc70 molecules dependent on activation of the Hsc70 ATPase by Hsp40. While hydrolysis remains the rate-limiting step in the ATPase cycle, Hip stabilizes the ADP state of Hsc70 that has a high affinity for substrate protein. Through its own chaperone activity, Hip may contribute to the interaction of Hsc70 with various target proteins. We propose a mechanism for the regulation of eukaryotic Hsc70 that is distinct from that of bacterial Hsp70. The Hsc70/Hsp40/Hip system is apparently independent of a GrpE-like nucleotide exchange factor.

Acute-Phase Proteins↗
PubMed1995

Preliminary X-ray diffraction study of a new crystal form of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 from Streptomyces globisporus.

A new crystal form of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 isolated from Streptomyces globisporus was obtained by the vapor-diffusion procedure using lithium sulfate as a precipitant. In the present crystallization, it is noteworthy that large-sized single crystals successfully grew from very small droplets (less than 1.01 micro l). The present crystals belong to the trigonal system, space group P3(1)21 or P3(2)21 with cell dimensions of a = b = 62.6 and c = 54.2 A. Assuming that the asymmetric unit contains one molecule, the V(m) value is calculated as 2.9 A(3) Da(-1). A total of 3654 independent reflections from two native crystals was obtained up to 2.5 A resolution with synchrotron radiation, the merging R factor being 0.097.

Journal Article↗
PubMed1995

IL-2-induced gene expression of protein-tyrosine phosphatase LC-PTP requires acidic and serine-rich regions within IL-2 receptor beta chain.

A protein-tyrosine phosphatase LC-PTP is preferentially expressed in hematopoietic cells and is an early response gene in lymphokine stimulated cells. Here, we found the LC-PTP mRNA induction by IL-2 was markedly inhibited by several tyrosine kinase inhibitors. The induction required both the acidic and serine-rich regions of the IL-2 receptor beta chain (IL-2R beta) in mouse IL-3-dependent pro-B BAF-B03 transfectants. This is strikingly different from the induction of c-myc gene expression, which requires the serine-rich region alone. In addition, overexpression of activated-Lck or -Raf kinases resulted in augmented LC-PTP mRNA expression in myeloid cell line 32D transfectants. Considering the previous findings that the acidic region of the IL-2R beta is responsible for association with Lck and activation of Raf kinase, IL-2-induced expression of LC-PTP mRNA may be primarily transduced through a Lck-Raf mediated signaling pathway.

Animals↗
PubMed1995

Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.

The interleukin 2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta c, and IL-2R gamma c chains. Two Janus family protein tyrosine kinases (PTKs), Jak1 and Jak3, were shown to associate with IL-2R beta c and IL-2R gamma c, respectively, and their PTK activities are increased after IL-2 stimulation. A Jak3 mutant with truncation of the C-terminal PTK domain lacks its intrinsic kinase activity but can still associate with IL-2R gamma c. In a hematopoietic cell line, F7, that responds to either IL-2 or IL-3, overexpression of this Jak3 mutant results in selective inhibition of the IL-2-induced activation of Jak1/Jak3 PTKs and of cell proliferation. Of the three target nuclear protooncogenes of the IL-2 signaling, c-fos and c-myc genes, but not the bcl-2 gene, were found to be impaired. On the other hand, overexpression of the dominant negative form of the IL-2R gamma c chain, which lacks most of its cytoplasmic domain, in F7 cells resulted in the inhibition of all three protooncogenes. These results provide a further molecular basis for the critical role of Jak3 in IL-2 signaling and also suggest a Jak PTK-independent signaling pathway(s) for the bcl-2 gene induction by IL-2R.

Animals↗
PubMed1995

IL-2 signaling involves recruitment and activation of multiple protein tyrosine kinases by the IL-2 receptor.

The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains, the last of which is also used in the receptors for IL-4, IL-7, IL-9, IL-13, and IL-15. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2R beta and IL-2R gamma, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here we summarize our current understanding of the mechanisms by which IL-2R transmit signals by using multiple protein kinases. In fact, at least four protein tyrosine kinases (PTKs) are physically associated with IL-2R: p56lck (and its members), Syk PTK, and the Janus kinases, Jak1 and Jak3. cDNA expression studies revealed that the activation of these PTKs is critical for IL-2-induced proliferative signal transmission. Our findings indicate that a unique property of the IL-2R cytoplasmic domains is to recruit a variety of signaling molecules, which may suggest a mechanism by which these PTKs and other signaling molecules function in concert.

Animals↗
PubMed1995

Cyclic AMP-elevating agents negatively regulate the activation of p72syk in N-formyl-methionyl-leucyl-phenylalanine receptor signaling.

Here we investigated the involvement of the non-receptor protein-tyrosine kinase p72syk in formyl methionyl-leucyl-phenylalanine (fMLP) receptor signaling. The activity of p72syk began to rise from 15 s and reached to maximum within 2-5 min after 5 microM fMLP stimulation in porcine polymorphonuclear neutrophils (PMNs). Cyclic AMP (cAMP)-elevating agents, prostaglandin E2 (PGE2) and forskolin, or dibutyryl cAMP partially suppressed p72syk activities stimulated by fMLP in PMNs. Pretreatment with an inhibitor of cAMP-dependent protein kinase abolished the suppression of the fMLP-induced p72syk activation by these cAMP-elevating agents. It was also observed that cAMP-dependent protein kinase phosphorylates p72syk on serine residues in vitro. These results indicate a possibility that cAMP-dependent protein kinase negatively regulates the activation of p72syk in fMLP-receptor signaling.

Amino Acid Sequence↗
PubMed1995

Activation of Stat5 by interleukin 2 requires a carboxyl-terminal region of the interleukin 2 receptor beta chain but is not essential for the proliferative signal transmission.

The high-affinity interleukin 2 (IL-2) receptor (IL-2R) consists of three subunits: the IL-2R alpha, IL-2R beta c, and IL-2R gamma c chains. Two members of the Janus kinase family, Jak1 and Jak3, are associated with IL-2R beta c and IL-2R gamma c, respectively, and they are activated upon IL-2 stimulation. The cytokine-mediated Jak kinase activation usually results in the activation of a family of latent transcription factors termed Stat (signal transducer and activator of transcription) proteins. Recently, the IL-2-induced Stat protein was purified from human lymphocytes and found to be the homologue of sheep Stat5/mammary gland factor. We demonstrate that the human Stat5 is activated by IL-2 and that Jak3 is required for the efficient activation. The cytoplasmic region of the IL-2R beta c chain required for activation of Stat5 is mapped within the carboxyl-terminal 147 amino acids. On the other hand, this region is not essential for IL-2-induced cell proliferation.

3T3 Cells↗
PubMed1995

Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation.

Two interleukin-2 receptor-dependent signaling pathways have thus far been identified: the c-fos/c-jun induction pathway mediated by src family protein-tyrosine kinases and the c-myc induction pathway. Here, we provide evidence for the existence of a third, rapamycin-sensitive pathway, which results in the induction of another proto-oncogene, bcl-2. In the hematopoietic cell line BAF-B03, the expression of any two of lckF505 (an active form of p56lck), Bcl-2, or c-Myc is sufficient to promote transit of the cell cycle, regardless of the activation state of the third pathway. We also provide evidence that epidermal growth factor receptor signaling may act through the same pathway that involves p56lck. These studies demonstrate a novel approach to dissecting signaling pathways regulating cellular proliferation.

Animals↗
PubMed1995

Expression of bovine heart fructose 6-phosphate,2-kinase:fructose 2,6-bisphosphatase and determination of the role of the carboxyl terminus by mutagenesis.

Bovine heart fructose 6-P,2-kinase:fructose 2,6-bisphosphatase was expressed in Escherichia coli. In order to determine the role of the carboxyl-terminal peptide, 49 and 78 amino acids from the C-terminus were deleted using oligonucleotide-directed mutagenesis. The expressed wild-type and mutant enzymes were purified to homogeneity, and the steady-state kinetics of the mutant enzymes were compared to those of the wild-type enzyme. Deletion of 49 residues (Del 49) resulted in a 35% decrease in KmFru6P, a 36% increase in Vmax, and a 2-fold increase in Kcat/Km of the kinase. There was no change in the kinetic properties of the phosphatase activity. Deletion of 78 residues (Del 78) resulted in a 4.5-fold decrease in KmFru6P, a 2.5-fold increase in Vmax, a 12-fold increase in kcat/Km of the kinase, and a 3-fold increase in kcat/Km of the phosphatase. Phosphorylation of the wild-type and Del 49 enzymes resulted in decreased KmFru6P and activation of the kinase without affecting the phosphatase activity. Thermal inactivation rates of the wild-type and Del 49 enzymes were similar, but the rate of Del 78 was more rapid. The phosphorylated wild-type and Del 49 enzymes were more sensitive to thermal inactivation than the dephospho forms. Urea inactivation of the kinase and phosphatase of wild-type and Del 49 were similar, but Del 78 was more sensitive to urea. All phosphorylated enzymes were more susceptible to urea inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Stimulation of NK-like YT cells via leukocyte function-associated antigen (LFA)-1. Possible involvement of LFA-1-associated tyrosine kinase in signal transduction after recognition of NK target cells.

The YTA-1 anti-LFA-1 alpha mAb activates protein tyrosine kinase (PTK), augments NK cytotoxicity, and induces proliferation of fresh CD3- large granular lymphocytes. We demonstrate here that LFA-1 is physically associated in the YT human NK-like cell line cells with a PTK(s) that is distinct from Src family PTKs such as Lck, Fyn, or Lyn. In vitro kinase assays revealed similar association of protein kinase activity with LFA-1 in normal CD3- large granular lymphocytes. Tyrosine phosphorylation of the proteins associated with LFA-1 drastically increased in YT cells after stimulation with NK-sensitive K562 cells but not with NK-resistant P815 cells. Furthermore, pretreatment of YT cells with TS1/22 anti-LFA-1 alpha and TS1/18 anti-LFA-1 beta mAbs abrogated not only the cytotoxicity against K562 cells but also an increase in tyrosine phosphorylation of LFA-1-associated molecules induced by K562 stimulation. These results provide biochemical evidence that the PTK(s) associated with LFA-1 is involved in the signal transduction that follows the recognition of NK target cells.

Antibodies, Monoclonal↗