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Biomedical subjects

A Hattori

Publications and source records attributed to A Hattori.

At least 19 recordsLinked to original sources
PubMed1992

Mitogen-induced tyrosine phosphorylation of 41 kDa and 43 kDa proteins. Potential role in integrating multiple mitogenic signalling pathways.

We have examined the possible involvement of pertussis toxin (PT)-sensitive GTP-binding protein and protein kinase C (PKC) in mitogen-induced tyrosine phosphorylation of the 41 kDa and 43 kDa cytosol proteins using PT-pretreated (inactivation of PT-sensitive GTP-binding protein) or phorbol 12-myristate 13-acetate (PMA)-pretreated (depletion of PKC) mouse fibroblasts. The effects of the inactivation of PT-sensitive GTP-binding protein and the depletion of PKC on mitogen-stimulated tyrosine phosphorylation of the proteins were similar and varied significantly and systematically in response to growth factors. The important finding was that such inhibitory effects of PT-sensitive GTP-binding protein inactivation and PKC depletion on protein tyrosine phosphorylation induced by each mitogen always correlated well with their inhibitory effects on each mitogen-stimulated DNA synthesis. Although the extent of platelet-derived-growth-factor-induced phosphorylation of the proteins was decreased to approx. 50% in PT- and PMA-pretreated cells compared with native cells, protein phosphorylation itself was not affected and occurred at identical sites on each protein in native, PT- and PMA-pretreated cells. These results suggest that: (1) 41 kDa and 43 kDa proteins are located downstream of PT-sensitive GTP-binding protein and PKC in the mitogenic signalling pathways of growth factors, (2) protein phosphorylation occurs via a cascade of events which includes the activation of the receptor tyrosine kinases, PKC and other unidentified kinase(s) which directly participate(s) in the phosphorylation of the 41 kDa and 43 kDa proteins, and (3) their phosphorylation may play an important role in integrating multiple mitogenic signalling pathways.

3T3 Cells↗
PubMed1992

Hepatocyte growth factor rapidly induces the tyrosine phosphorylation of 41-kDa and 43-kDa proteins in mouse keratinocytes.

We have examined the hepatocyte growth factor (HGF)-mediated changes in protein-tyrosine phosphorylation in mouse keratinocytes (PAM-212) and canine kidney epithelial cells (MDCK). In PAM-212 cells HGF and epidermal growth factor, both of which stimulated the DNA synthesis, rapidly induced the tyrosine phosphorylation of two 41-kDa and two 43-kDa proteins: increased tyrosine phosphorylation of those proteins has been commonly observed when quiescent fibroblasts are stimulated with a variety of mitogenic agents. In contrast, HGF did not stimulate the DNA synthesis but induced cell dissociation in MDCK cells; under this condition, increased tyrosine phosphorylation of the 41-kDa and 43-kDa protein was not observed. A possible role of the increased tyrosine phosphorylation of 41-kDa and 43-kDa protein in the signaling pathway of HGF is discussed.

Amino Acids↗
PubMed1992

Mitogen-induced tyrosine-phosphorylated 41- and 43-kDa proteins are family members of extracellular signal-regulated kinases/microtubule-associated protein 2 kinases.

Two antipeptide antibodies, one against the peptide corresponding to residues 307-327 (alpha Y91) and one against the peptide corresponding to the C-terminal portion (alpha C92) of the deduced amino acid sequence of the extracellular signal-regulated kinase 1 (ERK1), precipitated two 41-kDa and/or two 43-kDa phospho-proteins from mitogen-stimulated Swiss 3T3 cells. Electrophoretic mobilities on two-dimensional gels of the immunoprecipitated 41- and 43-kDa phosphoproteins were similar to those of the 41- and 43-kDa cytosol proteins, whose increased tyrosine phosphorylation we and others had originally identified in various mitogen-stimulated cells (Cooper, J. A., Sefton, B. M., and Hunter, T. (1984) Mol. Cell. Biol. 4, 30-37; Kohno, M. (1985) J. Biol. Chem. 260, 1771-1779); phosphopeptide map analysis revealed that they were respectively identical molecules. All those phosphoproteins contained phosphotyrosine, and the more acidic forms contained additional phosphothreonine. Immunoprecipitated 41- and 43-kDa phosphoproteins had serine/threonine kinase activity toward myelin basic protein (MBP) and microtuble-associated protein 2 (MAP2). With the combination of two-dimensional gel electrophoresis and the kinase assay in MBP-containing polyacrylamide gels of the alpha Y91 immunoprecipitates, with or without phosphatase 2A treatment, we showed that only their acidic forms were active. These results clearly indicate that 41- and 43-kDa proteins, the increased tyrosine phosphorylation of which is rapidly and commonly induced by mitogen stimulation of fibroblasts, are family members of ERKs/MAP2 kinases and that phosphorylation both on tyrosine and threonine residues is necessary for their activation.

3T3 Cells↗
PubMed1992

Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase).

The cDNA for prostaglandin endoperoxide synthase (cyclooxygenase) was cloned from human platelets by the polymerase chain reaction amplification method, and the primary structure of the enzyme was deduced from the nucleotide sequence. The enzyme was composed of 599 amino acids including 23-amino acid signal sequence, and the calculated molecular weight of the mature protein was 65,995. The enzyme was immunoaffinity-purified from human platelets. The N-terminal amino acid sequence determined by Edman degradation was Ala-Asp-Pro-Gly-Ala-Pro-Thr-Pro-, and the result confirmed the primary structure of the enzyme, which was deduced from the cDNA sequence.

Acetylation↗
PubMed1992

Calcium-induced splitting of connectin filaments into beta-connectin and a 1,200-kDa subfragment.

When rabbit skeletal muscle myofibrils were treated with a solution containing 0.1 mM Ca2+ and 30 micrograms of leupeptin/ml, alpha-connectin, which forms very thin filaments in myofibrils, was split into beta-connectin and a 1,200-kDa subfragment. A part of beta-connectin located near the junction between beta-connectin and the subfragment seems to have an affinity for calcium ions and to be susceptible to the binding of large amounts of calcium ions. The calcium-binding site on beta-connectin is localized near the N2 line in the I band, and the subfragment is localized adjacent to the Z disk. It is possible that connectin filaments change their elasticity during the contraction-relaxation cycle of skeletal muscle at the physiological concentration of calcium ions. Because postmortem skeletal muscles lose their elasticity and become plastic in association with the calcium-specific splitting of connectin filaments, the splitting is considered to be a factor in meat tenderization during postrigor ageing.

Animals↗
PubMed1992

Purification and characterization of nebulin subfragments produced by 0.1 mM CaCl2.

Nebulin, which forms a long inextensible filament in sarcomeres, was fragmented into 200-, 180-, 40-, 33-, and 23-kDa subfragments on treatment with 0.1 mM CaCl2. The subfragments released from myofibrils were successfully purified by immunoaffinity column chromatography. The 200-, 40-, 33-, and 23-kDa subfragments were released from myofibrils and occupied 80% of the nebulin filaments. The remainder comprised the 180-kDa subfragment bound to the myofibrils. There is a possibility that an entire nebulin filament is constructed from the 200-, 180-, 40-, 33-, and 23-kDa subfragments. We have developed a new "fluorescence-method" to detect the binding of calcium ions to a protein using quin2, and clarified that nebulin is a calcium-binding protein, and that calcium ions bind to the 200-, 40-, and 23-kDa subfragments. Nebulin filaments are probably fragmented on the binding of large amounts of calcium ions to the 200-, 40-, and 23-kDa subfragments.

Amino Acids↗
PubMed1992

Increase in ubiquitin-immunoreactive nuclei in rat pituitary luteinizing hormone cells after castration.

Immunocytochemical detection of ubiquitin in the nucleus of rat LH cells and the effects of castration and testosterone replacement on the occurrence of immunoreactive ubiquitin in the nucleus were investigated. Immunoreactive ubiquitin occurred in certain nuclei, mostly belonging to identified LH cells. The concentration of testosterone in blood was altered by castration and implantation of testosterone into castrated rats, and the occurrence of ubiquitin was examined weekly for the following 4 weeks. In castrated rats, the proportion of LH cells with ubiquitin-immunoreactive nuclei was high throughout the experiment. In castrated rats implanted with testosterone, on the contrary, the proportion remained significantly lower. Ubiquitin may be involved in the cellular activity of LH cells in the rat pituitary.

Animals↗
PubMed1992

Accuracy and reliability of quantitative measurement of coronary arterial stenosis by videodensitometry on coronary angiogram.

This study was undertaken to investigate the accuracy and reliability of videodensitometry (VDM) in measuring the magnitude of coronary arterial stenosis on coronary angiogram (CAG). CAG taken after administration of sublingual nitroglycerin was analyzed with VDM (XR-70 Coronary Analyzer, Vanguard). The magnitude of stenosis in coronary segments with four different classes of stenosis was consecutively measured 10 times by the same observer, and the values were 89.0 +/- 1.4, 70.9 +/- 2.1, 59.5 +/- 2.5, and 22.8 +/- 3.4%. The coefficients of variation (CVs), indicating intraobserver variability, were low for severe to moderate lesions (1.6, 2.9, and 4.3%, respectively), but was higher for low-grade lesions (14.8%). When the same lesions were measured by 2 observers, the measurements were highly correlated (r = 0.971, p < 0.01). The results of VDM were consistent with those of conventional gross examination for moderate to severe lesions, and the discrepancy was mainly found in low-grade lesions. The magnitude of stenosis of the same lesion was measured from the right and the left anterior oblique views, and the cineangle was found not to affect the results of VDM. Moreover, cardiac cycle did not affect the videodensitometric measurements of % area stenosis. In order to further investigate the accuracy of VDM, the magnitude of stenosis was measured in nine phantom arteries, and the value measured by VDM significantly correlated with the actual stenosis (r = 0.969, p < 0.001). These results indicate that the values of coronary arterial stenosis on CAG measured by VDM are accurate and clinically acceptable, even though variability is somewhat high for low grade lesions. VDM may be useful for evaluation of the outcome of PTCA and the anti-atherogenic action of some agents.

Absorptiometry, Photon↗
PubMed1992

Stress platelets in normal individuals and patients with idiopathic thrombocytopenic purpura.

To test the hypothesis that stress platelets (SPs) described by Tong et al. in rats may be a parameter of young platelets in humans, we examined and characterized SPs in normal individuals and in patients with idiopathic thrombocytopenic purpura (ITP). Our results indicated that SPs comprise about 1.2% of the circulating platelets in normal individuals and 2.6% in ITP patients. The configuration of SPs as well as of various irregular forms of circulating platelets was found to be supported by synergism of both the platelet microfilaments and microtubules. SPs showed some segmentation, the degree of which was similar in normal individuals and ITP patients, and they underwent further segmentation during in vitro incubation, mainly promoted by microtubules, so that they sometimes appeared like discoid platelets in a chain. These observations suggest a new mode of production of discoid platelets in the circulation. Thus, identification and enumeration of SPs may be useful for evaluating thrombocytopoiesis in humans.

Adult↗
PubMed1992

[Analysis of platelet shape change, inositol metabolism, and Ca mobilization in patients with platelet dysfunction].

Agonists-induced platelet shape change, inositol metabolism, and Ca mobilization were investigated in patients with various platelet dysfunctions. The platelet shape change determined by our method revealed that arachidonate-induced platelet shape change was completely defective in patients with cyclo-oxygenase (CO) deficiency (A). STA2-induced platelet shape change was also defective in one of five patients with impaired aggregation to STA2 (B). Thrombin-induced platelet shape change was weak in patients with Bernard-Soulier syndrome. In patient with Hermansky-Pudlak syndrome, the platelets did not respond normally to STA2, arachidonate or PMA. These findings suggested that the determinations of platelet shape change by our method was useful in diagnosing platelet dysfunctions. Inositol metabolism and Ca mobilization in response to thrombin, STA2, or NaF were also investigated in patient A,B, and impaired aggregation to A23187 in patient C. The responses were normal in patient A, suggested that CO activity did not affect them. Inositol metabolism was also normal in patient C, although Ca mobilization in response to A23187 was delayed, and that in response to thrombin was defective in the absence of extracellular Ca2+. This suggests that the patient's platelets have a defective IP3-induced Ca mobilization pathway. STA2 selectively failed to induce IP3 formation and Ca mobilization in patient B, although 3H-labelled thromboxane ligand (3H-U46619) bound to the patient's platelets, normally. These findings suggested that the patient's platelets have a defect in postreceptor signal transduction, especially thromboxane receptor-mediated phospholipase C activation pathway.

Blood Platelet Disorders↗
PubMed1992

[PI metabolism and Ca mobilization in patients with platelet dysfunction].

The effect of STA2, thrombin and NaF on PI metabolism and Ca mobilization was investigated in patients with three kinds of platelet dysfunction, one each with platelet cyclo-oxygenase deficiency (A), defective aggregation to A23187 (B) and defective aggregation to STA2 (C). These responses were normal in patient (A), suggesting cyclooxygenase activity did not affect PI metabolism and Ca mobilization. PI metabolism was also normal in (B), although Ca mobilization in response to A23187 was delayed and that in response to thrombin was defective in the presence of extracellular Ca2+. This suggests that the patient's platelets have a defective IP3-induced Ca mobilization pathway. STA2 selectively failed to induce IP3 formation and Ca mobilization in (C), although 3H-labelled thromboxane ligand (3H-U46619) bound to the patient's platelets normally. It was suggested that the patient's platelets have a defect in postreceptor signal transduction, especially thromboxane receptor-mediated PLC activation pathway.

Blood Coagulation Disorders↗
PubMed1992

[Hemostatic control in platelet dysfunction and abnormality by DDAVP].

DDAVP infusion shortens the bleeding time in patients with some types of platelet dysfunction and may be useful for hemostatic control. In order to clarify the mechanism of DDAVP to correct or bypass the release defect, we examined the effect in 17 patients with prolonged bleeding time, i.e., 11 with various kinds of platelet dysfunction, 4 with idiopathic thrombocytopenic purpura (ITP), 1 with chronic myelocytic leukemia (CML), and in an aspirin-ingested volunteer. DDAVP shortened the bleeding time in 9 patients with platelet dysfunctions, one with ITP, and the one aspirin ingested volunteer. No improvement was found in the aggregability and the retention rates, and no signs of activation occurred in the platelet shape. The RCof was elevated in all of the patients after the infusion. Our data suggests that DDAVP improves the hemostasis through primary aggregation and release of dense bodies, and not directly through an increase of RCof.

Bleeding Time↗
PubMed1992

[Strategies for antiplatelet therapy-drug-fixed method and suppression-fixed method].

The strategies for antiplatelet therapy and recent trends in the research field are reviewed. In addition to the approach to finding new drugs, basic research on the function of the platelet which should be suppressed and on how drugs should be used, is required for the improvement of the efficacy of antiplatelet therapy. Our approach to suppression-fixed antiplatelet therapy which is in contrast with the previous drug-fixed method and is based on a principle that aggregation and release are strongly suppressed by the use of aspirin plus ticlopidine close to the limit, found observations on primary platelet dysfunction is described. Preliminary results of this on the prevention of stroke indicate that recurrence was 0.88% per year in contrast with the 4.3% in a group with normal platelet function and 5-15% in groups without antithrombotic therapy in Japan.

Aspirin↗
PubMed1992

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia with elevated level of serum interleukin-6].

A 38-year-old male was admitted in January 1984 due to lymphadenopathies with hyperimmunoglobulinemia with a serum IgG level of 2,872 mg/dl. Following this, he was observed as an outpatient in regard to lymphadenopathies of unknown origin. In 1989, after the fourth lymph node biopsy he was diagnosed as having idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. At that time his serum IgG level was 8,090 mg/dl. The elevated serum interleukin-6 (IL-6) level, up to 21.1 pg/ml, was particularly interesting, because IL-6 is involved in the oncogenesis of plasmacytoma/myeloma. The patient also had thrombocytosis, hematuria, and a serum increased level of C reactive protein which seemed to be related to the effects of IL-6 i.e. thrombopoiesis, induction of the proliferation of mesenchymal cells, and induction of the production of acute phase proteins by hepatocytes, respectively. Even though he displayed no outward symptoms before and after treatment with prednisolone and melphalan, elevated immunoglobulin levels were still present.

Humans↗
PubMed1991

[Evaluation of the measurement of plasma fructosamine concentration in aged subjects].

Recently, plasma fructosamine concentration has been used as an indication of mean plasma glucose level preceding at last 1 to 2 weeks. In the present study, to characterize the clinical significance and problems of plasma fructosamine concentration in aged subjects (greater than or equal to 65 yrs), we determined plasma fructosamine concentration as well as serum albumin, total protein, HbA1, AbA1c and fasting plasma glucose concentrations in 81 (less than 65 yrs) non-diabetic subjects (group A), 161 aged (greater than or equal to 65 yrs) non-diabetic subjects and 26 aged diabetics (group D). Aged non-diabetic subjects were further classified into 75 subjects with good ADL (group B) and 86 with poor ADL (group C). The normal limit of plasma fructosamine concentration (mean +/- 2SD) in group A was 24% higher (3.1 mmol/l) than that in group B (2.5 mmol/l) but the plasma fructosamine/serum albumin ratio (F/ALB) was similar in these two groups. Plasma fructosamine correlated negatively (p less than 0.01) with age. This aging effect was explained by the reduced serum albumin in aged subjects. However, in group C, reduced plasma albumin was not associated with reduced plasma fructosamine. Plasma fructosamine corrected by albumin (F/ALB) is a useful parameter of blood glucose control in aged subjects. In aged subjects with poor ADL, HbA1, HbA1c and plasma glucose should be determined with fructosamine.

Aged↗
PubMed1991

[Intermittent administration of natural interferon-alpha for over 5 years induced complete suppression of Philadelphia chromosome in a patient with myelogenous leukemia].

A 60-year-old woman was admitted to our hospital because of gastric ulcer, anemia, and leukocytosis in November 1984. Blood cell counts on admission were as follows: RBC 407 x 10(4)/microliters, Hb 9.8 g/dl, WBC 33,000/microliters (baso 8%, eo 7%, myelo 11%, meta 2%, stab 4%, seg 54%), Plt 93.7 x 10(4)/microliters. Bone marrow showed hypercellular and myeloid hyperplasia. She was diagnosed as Ph1-chromosome positive chronic myelogenous leukemia. She received natural interferon-alpha at the dosage of 600 x 10(4) IU daily for 22 days from January 14, 1985. After March 1985, she has been given intermittent administration of interferon once in 10 to 20 days, and maintained normal blood cell counts. Cytogenetic improvement was seen on 35 months after the start of IFN and complete suppression of Ph1 chromosome was observed at July 1990 (66 months after).

Drug Administration Schedule↗
PubMed1991

[Follow-up study in a case of traumatic epilepsy with increased accumulation of 123I-N-isopropyl-p-iodoamphetamine].

Recent studies suggested the potential use of 123I-N-isopropyl-p-iodoamphetamine (IMP) for the assessment of pathophysiology of epilepsy. We studied a case of epilepsy with increased accumulation of IMP. Brain SPECT scan of IMP was performed in a case of 31-year-old male with traumatic epilepsy. Increased accumulation of IMP was observed in the left temporal area on both early (20 min after injection) and delayed (3 hr) images of studied 6 weeks after the head trauma. X-CT did not show any abnormalities. The accumulation of IMP decreased as the symptom of the patient improved. The SPECT study performed 3 months after the accident showed slightly decreased uptake in the left temporal area on the early image with homogeneous uptake in the delayed image. These findings suggested the altered retention mechanism of IMP in this case.

Adult↗