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Biomedical subjects

T Kamata

Publications and source records attributed to T Kamata.

At least 91 records · Page 5Linked to original sources
PubMed1996

Acute effect of epinephrine on muscle proteolysis in perfused rat hindquarters.

An acute and direct effect of epinephrine (Epi) on muscle proteolysis was investigated using a single-pass mode of rat hindquarter perfusion. The rate of tyrosine (Tyr) release at > 30 min with cycloheximide was regarded as the muscle proteolytic rate. Infusion of Epi (500 nM) to the hindquarters of fed rats led to a sharp decrease in the Tyr release to 50% within 5 min, accompanied by an increase in perfusion pressure and edema around the perfused tissues. To clarify the mechanism, alpha- and beta-antagonists were used together with Epi. A mixture of 10 microM prazosin and 10 microM yohimbine (alpha-adrenergic blockade) before or after Epi infusion completely prevented the edema development and resulted in a new steady state to 80% of the initial rate. On the contrary, 100 microM propranolol (a beta-antagonist) with Epi did not abolish the edema and caused fluctuation in Tyr release. Whether the above results are affected by changes in Tyr transport at the plasma membrane was tested by measuring Tyr efflux from the perfused muscle. Only a beta-adrenergic blockade significantly reduced the rate constant of Tyr efflux from the intracellular pool by 13%. These results suggested that the suppression of Tyr release by alpha-adrenergic activity was mainly due to the effect on Tyr efflux, whereas that by beta-adrenergic activity was not at the Tyr transport level but at the proteolysis level, demonstrating that Epi directly inhibits proteolysis of skeletal muscle via the beta-adrenoceptor.

Animals↗
PubMed1996

Late onset diabetes mellitus in patients with hereditary aceruloplasminemia.

Aceruloplasminemia is a systemic degenerative disorder characterized by mutations in the ceruloplasmin gene, the absence of serum ceruloplasmin, and iron accumulation in the brain, liver, and other tissues. Iron is an important catalyst of oxyradical-mediated cellular and tissue injury, and beta-cells in the pancreatic islets are susceptible to the cytotoxic effects of oxidative stress. We report three patients with aceruloplasminemia who have late-onset diabetes mellitus (DM) and impaired glucose tolerance (IGT) as well as neurologic symptoms. Their basal lipid peroxide levels, measured as thiobarbituric acid-reactive products, in plasma samples were three times the values for the controls. This increased susceptibility to lipid peroxidation in patients with aceruloplasminemia suggests that free-radical-mediated tissue injury plays a role in the occurrence of DM and IGT.

Brain↗
PubMed1996

A novel regulatory epitope defined by a murine monoclonal antibody to the platelet GPIIb-IIIa complex (alpha IIb beta 3 integrin).

We characterized a murine monoclonal antibody, PT25-2 (IgG1), raised against washed human platelets. The antibody and its Fab fragments were both capable of inducing platelet aggregation in a fibrinogen-dependent manner and induced 125I-fibrinogen binding to unstimulated platelets (120,000 molecules/platelet at a 100 nM IgG concentration). The antibody immunoprecipitated the alpha IIb beta 3 complex from lysates of iodinated platelets but did not react with the respective subunits when complex formation was disrupted by treatment with 5 mM EDTA at 37 degrees C for 30 min. However, simply removing the extracellular divalent cation with EDTA had no effect on antibody binding indicating that the antibody's epitope depends upon a conformational structure maintained by alpha beta subunit association. Antibody binding to unstimulated, washed platelets yielded binding parameters (Kd = 40 nM, Bmax = 100,000 molecules/platelet), which were found to be virtually unchanged when binding was performed using thrombin or RGDS-peptide-stimulated platelets. Thus, the PT25-2 antibody defines a novel regulatory epitope expressed by the alpha IIb beta 3 integrin on unstimulated, quiescent platelets.

Animals↗
PubMed1995

Critical amino acid residues for ligand binding are clustered in a predicted beta-turn of the third N-terminal repeat in the integrin alpha 4 and alpha 5 subunits.

Integrin alpha 4 beta 1 is a receptor for vascular cell adhesion molecule (VCAM)-1 and fibronectin (CS-1). The alpha 4 beta 1-ligand interaction is involved in the pathogenesis of diseases and is, therefore, a therapeutic target. Here, we identified critical residues of alpha 4 for ligand binding using alanine-scanning mutagenesis of the previously localized putative ligand binding sites (residues 108-268). Among 43 mutations tested, mutations of Tyr187, Trp188 and Gly190 significantly inhibited cell adhesion to both VCAM-1 and CS-1. This inhibition was not due to any gross structural changes of alpha 4 beta 1. These critical residues are clustered in a predicted beta-turn structure (residues 181-190) of the third N-terminal repeat in alpha 4. The repeat does not contain divalent cation binding motifs. Notably, the mutations within the corresponding region of alpha 5 significantly reduced fibronectin-alpha 5 beta 1 interaction. These findings suggest that the predicted beta-turn structure could be ubiquitously involved in ligand binding of non-I domain integrins.

Amino Acid Sequence↗
PubMed1995

Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor.

Macrophage-stimulating protein (MSP) is a chemotactic factor that activates the receptor tyrosine kinase RON. The involvement of Ras in MSP-induced signal transduction was investigated. Here we demonstrate that, in RON-transfected MDCK cells, an active GTP-bound form of Ras was rapidly accumulated by MSP treatment and the Ras-guanine nucleotide exchange activity in SOS immunoprecipitates was concomitantly increased. GAP activity was not changed under the same conditions used. Furthermore, the SH2 domain of adaptor protein GRB2, but not Shc, associated with the activated RON-beta chain, and GRB2-SOS complexes translocated from the cytosol to the membrane upon MSP treatment. These results strongly suggest that MSP activates Ras through RON, and that MSP-induced activation of Ras might be controlled by both the enhancement of catalytic exchange activity of SOS and its translocation to the membrane where its target Ras is localized.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Critical threonine and aspartic acid residues within the I domains of beta 2 integrins for interactions with intercellular adhesion molecule 1 (ICAM-1) and C3bi.

Integrins mediate signal transduction through interactions with multiple cellular or extracellular matrix ligands. Evidence is accumulating that the I (or A) domain, a approximately 200-residue inserted sequence in some integrin alpha subunits, mediates ligand binding. We have previously shown that Thr-221 of the putative ligand binding sites within alpha 2 I domain of alpha 2 beta 1 is critical for binding to collagen (Kamata, T., and Takada, Y. (1994) J. Biol. Chem. 269, 26006-26010). Here we report that the mutation of Thr-206 of alpha L blocks intercellular adhesion molecule 1 (ICAM-1) binding to alpha L beta 2 and mutation of Thr-209 of alpha M blocks ICAM-1 and C3bi binding to alpha M beta 2. The data indicate the Thr residues of alpha M and alpha L corresponding to Thr-221 of alpha 2 are critically involved in the ligand interaction with beta 2 integrins. The mutations of the Asp-137 and Asp-239 of alpha L also block ICAM-1 binding to alpha L beta 2, as do the corresponding Asp residues of alpha 2 or alpha M in collagen/alpha 2 beta 1 or C3bi/alpha M beta 2 interactions, respectively. These data suggest that these Thr and Asp residues, conserved among I domains, are critical for interaction with structurally distinct ligands (e.g. ICAMs, C3bi, and collagen).

Amino Acid Sequence↗
PubMed1995

Identification of putative ligand-binding sites of the integrin alpha 4 beta 1 (VLA-4, CD49d/CD29)

Integrin alpha 4 beta 1 recognizes both fibronectin (CS-1 sequence) and vascular cell adhesion molecule-1 (VCAM-1). To localize the ligand-binding sites of alpha 4, we located the epitopes for function-blocking anti-alpha 4 monoclonal antibodies (mAbs), including those that recognize previously described (but not yet physically localized) functional epitopes (A, B1, B2 and C) using interspecies alpha 4 chimeras expressed in mammalian cells. Epitopes B1 and B2 were associated with ligand binding, and epitopes A and B2 with homotypic cellular aggregation. mAbs P4C2 (epitope B2), 20E4 and PS/2 were mapped within residues 108-182; mAbs HP2/1 (epitope B1), SG/73 and R1-2 within residues 195-268; mAbs HP1/3 (epitope A) and P4G9 within residues 1-52; and B5G10 (epitope C) within residues 269-548. The data suggest that residues 108-268, which do not include bivalent-cation-binding motifs, are related to VCAM-1 and CS-1 binding, and more N-terminal portions of alpha 4 (residues 1 and 52 and 108-182) to homotypic aggregation. Since mAbs PS/2 and HP2/1 block alpha 4 beta 7 binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the MAdCAM-1-binding site is close to, or overlapping with, VCAM-1- and CS-1-binding sites. The role of Asp-130 of beta 1 in the binding to VCAM-1 and CS-1 peptide was examined. Chinese hamster ovary (CHO) cells expressing beta 1 (D130A) (Asp-130 to Ala mutant of beta 1) and alpha 4 showed much less binding to both ligands than CHO cells expressing wild-type beta 1 and alpha 4 [a dominant negative effects of beta 1 (D130A)], suggesting that Asp-130 of beta 1 is critical for binding to both ligands and that the two ligand share common binding mechanisms [corrected].

Animals↗
PubMed1995

Antiischemic effects of nicorandil during coronary angioplasty in humans.

The present study was undertaken on 10 patients with angina undergoing percutaneous transluminal coronary angioplasty. The angioplasty procedure consisted of two successive 30-second balloon inflations at 5 minute intervals. After the first inflation, nicorandil (0.1 mg/kg) was given intravenously over a 2-minute period. The second inflation was then performed 3 minutes after the completion of drug administration. Myocardial ischemia was measured as the magnitude of ST-segment elevation on the intracoronary electrocardiogram (intracoronary ECG) recorded from the guidewire. Nicorandil significantly reduced the magnitude of ST-segment elevation. Nicorandil did not change the heart rate-blood pressure product, nor the oxygen saturation of the blood sampled from the great cardiac vein, nor the velocity of coronary blood flow in those patients with no evidence of collaterals. These results favor the conclusion that nicorandil prolongs the intrinsic ability of cardiac myocyte to withstand oxygen deprivation. This salutary effect is possibly due to a direct cellular mechanism because nicorandil did not modify the peripheral and coronary hemodynamic parameters that govern myocardial oxygen consumption.

Aged↗
PubMed1995

[A case of vascular leiomyoma in the larynx].

We report a recently encountered case of vascular leiomyoma in the larynx. The patient was a 76-year-old man with a chief complaint of hoarseness. Laryngoscopy revealed a bean-sized, reddish tumor with a smooth surface, suspended from the right vocal cord toward the subglottis. Its border was clear on MR imaging. Tracheotomy was performed under local anesthesia, and laryngomicrosurgery was then carried out under general anesthesia. The tumor was encapsulated and could be completely resected. Histological study indicated smooth muscule cell proliferation, especially around capillaries, and the tumor was diagnosed as a vascular leiomyoma. Our extensive survey of the literature revealed 20 reports of benign myogenic tumor of the larynx (9 cases of simple leiomyoma, 10 of vascular leiomyoma, and 1 of leiomyoblastoma), many of which occurred in the middle and advanced years. The patients consisted of 15 men and 5 women, including 9 male vascular leiomyoma patients of middle or advanced age. The site of occurrence was supraglottic in 12, glottic in 4 and subglottic in 4; no relation was observed with the histological picture, however. Treatment was surgical, and some cases also required tracheotomy depending on the site of occurrence and morphology.

Aged↗
PubMed1995

Platelet unresponsiveness to collagen: involvement of glycoprotein Ia-IIa (alpha 2 beta 1 integrin) deficiency associated with a myeloproliferative disorder.

We studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,890 x 10(9)/l). There was no past history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen. Analysis of 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (alpha 2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient's platelets indicated that neither anti-GPIa nor anti-GPIIa (beta 1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient's platelets were totally deficient in surface expression of the GPIa-IIa complex (alpha 2 beta 1 integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex. The data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.

Acute Disease↗
PubMed1995

[A case report of variegate porphyria].

We reported a 30-year-old woman with variegate porphyria. Family history disclosed that her mother had the same skin lesions as the present case. She has had repeated vesicles and brownish pigmentation on her upper extremities since eighteen years of age. Recently she was suffering from common cold, and was treated with drugs. One week later, she started to develop weakness and dysesthesia in all limbs, hallucination, and urinary disturbance. Three weeks later, she was admitted to our hospital because she could not stand any more. On general examination, she had brownish pigmentations and crusts in hands and forearms. Neurologically she had moderate weakness, dysesthesia and hyperreflexia in all limbs. Urine was dark-red. Head and cervical MRI was normal. Nerve conduction studies and somatosensory evoked potentials were within normal limits. Excretion of porphyrins, especially protoporphyrin and X-porphyrin in the feces were markedly increased, and the diagnosis of variegate porphyria was made. Intravenous administration of glucose was effective and her symptoms began to improve in two weeks after her admission. However, recovery of weakness took two months and dysesthesia did not disappear in three months. We considered that her clinical manifestations were caused by involvement of the central and peripheral nervous systems.

Adult↗
PubMed1994

Direct binding of collagen to the I domain of integrin alpha 2 beta 1 (VLA-2, CD49b/CD29) in a divalent cation-independent manner.

Integrin alpha 2 beta 1 is a major divalent cation-dependent receptor for collagen. Here, we show that the recombinant inserted/interactive domain (I domain) of alpha 2 specifically interacts with collagen, indicating the I domain contains all the components necessary for collagen binding. Evidence was obtained that divalent cations are not required for collagen binding to the I domain fragment, indicating that divalent cations are not involved in the actual binding to collagen but probably in the regulation of the binding. We identified Thr-221 within the previously identified putative ligand binding region as a residue critical for collagen binding to both alpha 2 beta 1 and the I domain fragment. Thr-221 may be involved in the actual collagen binding and recognition.

Animals↗
PubMed1994

Nizofenone, a neuroprotective drug, suppresses glutamate release and lactate accumulation.

It was investigated whether nizofenone, 2'-chloro-2-(2-diethylaminomethyl-1- imidazolyl)-5-nitrobenzophenone fumarate, shows neuroprotective effect by inhibiting glutamate release and lactate accumulation in rats. Nizofenone (10 mg/kg i.p.) significantly inhibited neuronal cell death in the hippocampus CA1 pyramidal cells 7 days after 15 min of ischemia caused by 4-vessel occlusion. The extracellular level of glutamate and lactate increased in the hippocampus during ischemia. Upon reperfusion, the glutamate level decreased rapidly but, in contrast, the lactate level increased further and reached a maximum at 15 min following reperfusion. Nizofenone (10 mg/kg i.p.) completely inhibited the ischemic glutamate increase and post-ischemic lactate increase. These results suggest that the inhibition of ischemic release of glutamate and post-ischemic accumulation of lactate could contribute greatly to the neuroprotective effect of nizofenone.

Analysis of Variance↗
PubMed1994

Identification of putative ligand binding sites within I domain of integrin alpha 2 beta 1 (VLA-2, CD49b/CD29)

Integrin alpha 2 beta 1 is a cell surface adhesion receptor for collagen and echovirus 1. Here we localized the epitopes for anti-alpha 2 monoclonal antibodies using interspecies (human/bovine) alpha 2 chimeras with different lengths of human alpha 2 sequence on the amino-terminal side and site-directed mutagenesis. The antibodies that block the collagen and/or echovirus 1 binding to human alpha 2 beta 1 (6F1, RMAC11, 12F1, and AA10) recognizes a small region (residues 173-259) within the I domain. Asp-160 and Arg-242 are critical for binding of the two other function-inhibiting antibodies, P1H5 and 5E8, respectively. Notably, mutations of Asp-151 and Asp-254 block the binding of alpha 2 beta 1 to collagen. These data suggest that the I domain (residues 140-359) is critically involved in the ligand/receptor interactions, and collagen and echovirus 1 binding sites are adjacent or overlapping within the I domain. The sequence of the residues 173-259 of alpha 2 overlap with the peptide sequences (M11 and M20) that derive from von Willebrand factor A1 and A3 domains (homologous to the alpha 2 I domain) and block von Willebrand factor/collagen interaction, suggesting that the epitope region of alpha 2 (residues 173-259) may really be involved in ligand recognition.

Amino Acid Sequence↗
PubMed1994

Rapid improvement of coagulopathy by all-trans retinoic acid in acute promyelocytic leukemia.

Treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA) was associated with rapid improvement in hemostatic markers. We made serial analyses of various hemostatic parameters in seven newly diagnosed APL patients. In all patients at diagnosis, plasma fibrinogen/fibrin degradation product (fragment-E), cross-linked fibrin degradation product (D-dimer fragment), thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated, indicating the presence of disseminated intravascular coagulation (DIC). Antithrombin III (ATIII) levels were normal in all patients except for the patient with congenital ATIII deficiency. In four patients subsequently treated with ATRA without anticoagulant therapy, these hemostatic markers returned to near-normal levels by day 7 of treatment, indicating that DIC was essentially resolved. By contrast, in three patients who received conventional chemotherapy with a continuous low-dose heparin, improvement of coagulopathy was slower than in patients treated with ATRA. These results suggest that ATRA therapy exerts the rapid improvement in abnormal hemostatic markers in APL patients without any anticoagulant therapies, by inducing differentiation of leukemic cells and, in turns no massive release of procoagulant or fibrinolytic substances from these cells.

Adult↗