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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 577 records · Page 32Linked to original sources
PubMed1994

Alterations in CD45 glycosylation pattern accompanying different cell proliferation states.

CD45 is a leukocyte-specific transmembrane glycoprotein whose intracellular domain exhibits protein tyrosine phosphatase activity and plays a critical role in signal transduction. CD45 derived from stationary lymphocytes migrated faster in SDS-PAGE than that derived from exponentially growing cells. A change in N-linked saccharide structure other than the neuraminidase-sensitive terminal sialic acid portion was found to be responsible for the molecular size change in CD45. The differential glycosylation appeared to occur during late-stage posttranslational processing of CD45. We speculate that the N-glycosylation difference affects the interaction between CD45 and other factors involved in signal transduction leading to modulation of leukocyte proliferation.

Amidohydrolases↗
PubMed1994

Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells.

A newly identified human peptide, adrenomedullin (AM) increased cAMP levels with dose and time dependencies in a manner similar to that of human calcitonin gene-related peptide (CGRP) in rat vascular smooth muscle cells (VSMC). The EC50 value of human AM is 2 x 10(-8) M which is slightly higher than that of CGRP (8.5 x 10(-9) M). In a receptor binding assay for AM in rat VSMC, the binding of [125I] AM was competitively inhibited by human AM, but not by human CGRP. Thus, AM is thought to increase intracellular cAMP in rat VSMC via its specific receptor to evoke vasodilation.

Adrenomedullin↗
PubMed1994

Immunoreactive adrenomedullin in human plasma.

A specific and sensitive radioimmunoassay for adrenomedullin has been developed. Half-maximal inhibition of binding of radioiodinated adrenomedullin was observed at 4 fmol/tube. The radioimmunoassay recognized the entire adrenomedullin molecule and has little crossreactivity with adrenomedullin fragment peptides. Adrenomedullin-like immunoreactivity was found to circulate in human plasma at considerable concentration (3.3 +/- 0.39 fmol/ml). The immunoreactivity of adrenomedullin was eluted at almost the same position as synthetic adrenomedullin on gel-filtration chromatography and reverse-phase high-performance liquid chromatography, suggesting that circulating adrenomedullin recognized by the present radioimmunoassay is identical or very similar to authentic adrenomedullin. Plasma immunoreactive adrenomedullin significantly increased in patients with hypertension, with a progressive rise proportionate to disease severity.

Adrenomedullin↗
PubMed1994

Complete amino acid sequence of porcine adrenomedullin and cloning of cDNA encoding its precursor.

Porcine adrenomedullin was isolated from adrenal medulla extract and its amino acid sequence was determined. The peptide is identical to human adrenomedullin with a single replacement of Gly for Asn at position 40. The cDNA clone encoding the porcine adrenomedullin precursor was isolated and sequenced. The precursor for adrenomedullin (preproadrenomedullin) is 188 amino acids in length, including the adrenomedullin sequence, followed by a glycine (the amide donor). In addition to adrenomedullin, proadrenomedullin (proAM) contains a candidate for a unique 20-residue peptide, proAM-N20, whose carboxy-terminus may be amidated. By RNA blot analysis, porcine adrenomedullin mRNA was found to be highly expressed in several porcine tissues including lung and kidney as well as adrenal medulla.

Adrenal Medulla↗
PubMed1994

Molecular cloning of the CD45-associated 30-kDa protein.

CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, mediates signal transduction pathways critical for immune responses. However, the mechanism of CD45-mediated signal transduction and the identity of CD45-associated proteins have remained unclear. A CD45-associated 30-kDA phosphorylated protein (CD45-AP) was purified by virtue of its specific association with CD45, and its mouse cDNA was cloned by using the internal amino acid sequence information. In vitro translated CD45-AP bound specifically to CD45. CD45-AP appears to be leukocyte-specific and shares no significant homology with presently known sequences. The predicted sequence contains no consensus tyrosine phosphorylation sites or conserved sequences of GTP-binding proteins. CD45-AP may act as an adapter molecule for CD45-mediated signal transduction.

Amino Acid Sequence↗
PubMed1994

Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma.

A specific and sensitive radioimmunoassay for human adrenomedullin has been developed and distribution and characterization of immunoreactive adrenomedullin in human tissue were investigated. The radioimmunoassay specifically recognizes its carboxyterminal region and half maximal inhibition of binding of radioiodinated adrenomedullin(40-52)NH2 was observed at 11 fmol/tube. Immunoreactive adrenomedullin was abundant in adrenal medulla (47.7 +/- 26.1 fmol/mg, mean +/- S.D.) and was ubiquitously found in all tissue examined. The mean plasma concentration of adrenomedullin in three normal individuals was 17.2 +/- 6.4 pg/ml (mean +/- S.D.). By analysis with reverse-phase high-performance liquid chromatography coupled with the radioimmunoassay, most immunoreactive adrenomedullin in the adrenal medulla, atrium and lung was found to be adrenomedullin(1-52)NH2.

Adrenal Glands↗
PubMed1994

GM3 directly inhibits tyrosine phosphorylation and de-N-acetyl-GM3 directly enhances serine phosphorylation of epidermal growth factor receptor, independently of receptor-receptor interaction.

GM3 ganglioside (II3NeuAcLacCer) inhibits epidermal growth factor (EGF)-dependent receptor autophosphorylation and cell growth (Bremer, E.G., Schlessinger, J., and Hakomori, S. (1986) J. Biol. Chem. 261, 2434-2440), whereas de-N-acetyl-GM3 (deNAcGM3; II3NeuNH2Lac-Cer) promotes these processes (Hanai, N., Dohi, T., Nores, G. A., and Hakomori, S. (1988) J. Biol. Chem. 263, 6296-6301). Receptor-receptor interaction has been proposed as an essential initial mechanism for EGF-dependent activation of EGF receptor kinase (EGF-RK) (Schlessinger, J. (1988) Trends Biochem. Sci. 13, 443-447). We studied the effects of GM3 and deNAcGM3 on EGF-RK function and EGF-R dimerization, and observed that (i) EGF-dependent in vitro and in vivo (in situ) phosphorylation of A431 cells at both monomeric and dimeric forms of EGF-R was inhibited in a dose-dependent manner by GM3, but unaffected by GM1. (ii) Quantities of both forms of EGF-R remained constant regardless of addition of various quantities of GM3 or GM1, as revealed by blotting with antibodies directed to the C-terminal region of EGF-R, or by cell surface 125I-labeling followed by immunoprecipitation. (iii) DeNacGM3 in the absence as well as in the presence of a minimal quantity of detergent significantly enhanced EGF-R phosphorylation, particularly Ser phosphorylation. (iv) DeNAcGM3 was detected in a large variety of actively growing tumor cells. Findings i and ii above indicate that GM3 directly inhibits EGF-dependent Tyr phosphorylation but does not affect receptor-receptor interaction. Findings iii and iv suggest that deNAcGM3 strongly promotes serine phosphorylation (in addition to Tyr phosphorylation) of EGF-R and may function as a second messenger in the process of cell growth stimulation.

Animals↗
PubMed1994

Antitumor effect of neocarzinostatin conjugated to human/mouse chimeric Fab fragments of the monoclonal antibody A7 on human pancreatic carcinoma.

The anticancer agent neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of the monoclonal antibody A7 to form the conjugate chA7Fab-NCS. The antitumor effect of chA7Fab-NCS was tested by measuring the inhibition of 3H-thymidine incorporation into human pancreatic carcinoma cells. The chA7Fab-NCS was approximately 2.3 times as effective as free NCS against human pancreatic carcinoma cells which reacted with the monoclonal antibody A7. The antitumor activity of chA7Fab-NCS was inhibited by excess chA7Fab. ChA7Fab-NCS had an antitumor effect equivalent to free NCS on human pancreatic carcinoma cells which did not react with the monoclonal antibody A7. ChA7Fab-NCS appears to be a potentially useful conjugate for immunotargeting chemotherapy against pancreatic carcinoma.

Animals↗
PubMed1994

X-ray crystal structure and molecular dynamics simulation of bovine pancreas phospholipase A2-n-dodecylphosphorylcholine complex.

The crystal structure of n-dodecylphosphorylcholine (n-C12PC)-bovine pancreas phospholipase A2 (PLA2) complex provided the following structural characteristics: (1) the dodecyl chain of n-C12PC was located at the PLA2 N-terminal helical region by hydrophobic interactions, which corresponds to the binding pocket of 2-acyl fatty acid chain (beta-chain) of the substrate phospholipid, (2) the region from Lys-53 to Lys-56 creates a choline-receiving pocket of n-C12PC and (3) the N-terminal group of Ala-1 shifts significantly toward the Tyr-52 OH group by the binding of the n-C12PC inhibitor. Since the accuracy of the X-ray analysis (R = 0.275 at 2.3 A resolution) was insufficient to establish these important X-ray insights, the complex structure was further investigated through the molecular dynamics (MD) simulation, assuming a system in aqueous solution at 310K. The MD simulation covering 176 ps showed that the structural characteristics observed by X-ray analysis are intrinsic and also stable in the dynamic state. Furthermore, the MD simulation made clear that the PLA2 binding pocket is large enough to permit the conformational fluctuation of the n-C12PC hydrocarbon chain.

Animals↗
PubMed1994

A special-purpose computer for molecular dynamics: GRAPE-2A.

Molecular dynamics simulations have been extensively used in research of proteins. Since these simulations are quite computer intensive, their acceleration is of main interest of the research. In molecular dynamics simulations, almost all computing time is consumed in calculating the forces between particles, e.g., Coulomb and van der Waals forces. We have designed and built GRAPE-2A (GRAvity PipE 2A), a special-purpose computer for use in simulations of classical many-body systems. GRAPE-2A calculates forces exerted on a particle from the other particles. GRAPE-2A can calculate force of an arbitrary functional form of a central force. The host computer, which is connected to GRAPE-2A through the VME bus, performs other calculations such as time integration. The peak speed of GRAPE-2A is 180 Mflops. We can also stimulate systems with periodic boundary conditions by the Ewald method, using GRAPE-2A and another special-purpose computer, WINE (Wave space INtegrator for the Ewald method).

Computer Simulation↗
PubMed1994

Dipyridamole inhibits early wound healing in rat skin incisions.

In an effort to investigate the significance of platelet aggregation on early wound healing, the inhibitory effects of an antiplatelet drug (dipyridamole) on tensile wound strength was assessed. The breaking strength of the dorsal incisional wounds in Donryu rats both with and without the administration of dipyridamole was measured. In experiment I, the intraperitoneal administration of dipyridamole (100 mg/kg/day, Group A; 50 mg/kg/day, Group B) and saline (3 ml/day; Group C) was performed during the periods between the day of incision and the excision of the healing wound specimen in a 2.0-cm width on the third and seventh postoperative days (POD). The wound breaking strength was 229 +/- 44, 256 +/- 39, and 352 +/- 38 g/cm2 on POD 3 and 477 +/- 67, 578 +/- 60, and 764 +/- 31.9 g/cm2 on POD 7, in Groups A, B, and C, respectively. In experiment II, we performed the intraperitoneal administration of either dipyridamole (100 mg/kg) or 3 ml of saline as a control just before incision (Group a) as well as at 4 hr (Group b), and 12 hr (Group c) after incision, and the percentages of tensile strength compared with the control were 72 +/- 8, 89 +/- 13, and 103 +/- 23% in Groups a, b, and c, respectively. The administration of dipyridamole significantly inhibited the wound healing and, therefore, platelet aggregation would appear to play an important role in the early phase of wound healing.

Animals↗
PubMed1994

Partial deuteration and blood-brain barrier (BBB) permeability.

Boron neutron capture therapy (BNCT) is one method of radio-surgery used for malignant brain tumor. The theory of this method is based on the nuclear reaction that occurs when boron-10 is radiated with and absorbs neutrons. When treating deep-seated brain tumor, partial deuteration of body water is used to improve the penetration of neurons into the tissue. In order to investigate the change in the BBB function under partial deuteration, we measured brain water content and the permeability of protein. Wistar rats were given 99% heavy water (approx. 10% of body weight/day) as drinking water. On the day of the experiment, all animals received 125-I labeled albumin as a tracer of protein. Light water in the control group or heavy water (D2O) in the experimental group was given by drip infusion for 60 min. Heavy water was measured by infrared spectroscopic analysis. Water content was measured by the freeze-dry method. The radioactivity of 125-I was determined with a gamma scintillation counter. Mean values of D2O concentration in the tissue were 17.9-36.5%. Water content increased in the cortex in all animals. The ratio of 125-I in the brain tissue to blood showed significant differences between the control group and animals deuterated to more than 30% of body water. Brain tissue deuterated over 10% showed a mild leakage of water, indicating the early stage of brain edema. Deuteration higher than 30% caused a leakage of protein, which might indicate the leakage of boron compound from the vessels into the normal brain tissue.

Animals↗
PubMed1994

Properties of inactivation of calcium channel currents in smooth muscle cells of rabbit portal vein.

With 10 mM Ba2+ as the charge carrier, inactivation of Ca2+ channel currents could be subdivided into at least two exponentials in smooth muscle cells dispersed from the rabbit portal vein by use of the whole-cell configuration of the patch-clamp technique: fast and slow inactivation. All characteristics of inactivation were independent of the size of the currents. Step changes in the holding potential unveiled an extremely slow recovery and an onset of inactivation of the order of several minutes. Steady-state inactivation critically depended on the duration of the pre-steps. Inactivation curves obtained under steady-state conditions showed as shift by approximately 25 mV towards negative potentials by comparison with curves obtained using 1-s pre-pulses. This shift greatly reduced the window current. Recovery from inactivation studied with double-pulse protocols could be classified into at least two exponentials. The contribution of the slow recovery was accentuated at negative holding potentials. Recovery from inactivation critically depended on the duration of the conditioning voltage step, and was also dependent on the duration of the pre-step: its voltage dependence disappeared when pre-pulses longer than 2 s were applied. Onset of inactivation was composed of at least two exponentials: the fast component was accelerated at less negative pre-step potentials. We propose that several inactivated states are involved in Ca2+ channel inactivation. Transitions between these states are voltage dependent and voltage independent.

Animals↗
PubMed1994

Pre-operative estimation of complete resection for patients with oesophageal carcinoma.

Three hundred and seventy-nine patients were studied retrospectively regarding the possibility of a complete resection of the oesophageal carcinoma based on the combined findings of pre-operative oesophagogoraphy and computed tomography (CT). One hundred and four out of 129 patients (96.1%) having lesions which did not demonstrate all three of the aforementioned factors (a lesion shorter than 8 cm, a normal oesophageal axis, and normal contact of the lesion with neighboring organs in CT) underwent a complete resection of the oesophageal lesion. Fifty-three percent of the patients (52/97) with a lesion showing only one of these factors had a complete resection. Whereas, on the other hand, a complete removal of the malignancy was only possible in 22% of the patients with two or all three of the findings. Moreover, as a result of further analysis limited for resected cases, the number of positive factors in these pre-operative findings correlated with the advancement of the surgical stage, which reflected a curability in surgery and a rate of postoperative complications. In order to make adequate plans for the treatment of patients with advanced oesophageal cancer, the finding of (i) the length of lesion, (ii) a deep ulceration and deformity of the oesophageal axis and (iii) any abnormal contact in CT, are considered to be very useful.

Adult↗
PubMed1994

Plasma concentration of human brain natriuretic peptide in patients on hemodialysis.

The plasma concentration of immunoreactive human brain natriuretic peptide (ir-BNP) was measured in 40 patients on hemodialysis (HD) and in 12 healthy subjects. Immunoreactive human atrial natriuretic peptide (ir-ANP) was also measured. The mean (+/- SE) plasma ir-BNP concentration in the patients before HD (18.4 +/- 3.4 fmol/mL) was markedly higher than that in the control group (0.39 +/- 0.08 fmol/mL). The plasma ir-BNP level was significantly decreased by HD from 18.4 +/- 3.4 fmol/mL to 10.5 +/- 2.2 fmol/mL (P < 0.001), but the latter value was still higher than the upper limit of the normal range for our laboratory. There were significant correlations between the plasma ir-ANP level and the mean blood pressure before HD (P < 0.05) and between the HD-induced changes in plasma ir-ANP level and mean blood pressure (P < 0.001). These correlations were not observed between the plasma ir-BNP level and mean blood pressure. The plasma ir-BNP level correlated with the cardiothoracic ratio and this correlation was closer to that between the plasma ir-ANP level and cardiothoracic ratio. Ultrasound echocardiographic studies in 13 patients revealed that the pre-HD state of high cardiac output was correlated by HD in association with decreases in plasma ir-BNP and ir-ANP levels. Correlations were observed between the pre-HD ir-ANP level and the interventricular septal thickness index (r = 0.68, P < 0.05) and between the change in ir-BNP level and that in left atrial diameter (r = 0.806, P < 0.001). In conclusion, BNP levels were high in HD patients compared with the control subjects and were decreased during HD. In addition, BNP and ANP levels correlated with several parameters of volume change and cardiac status.

Atrial Natriuretic Factor↗
PubMed1994

Congenital abnormal eye movement without gaze nystagmus.

Ten cases with congenital abnormal eye movements were reported. Eye movement abnormalities were confined to horizontal pursuit, OKN, and visual suppression. Horizontal saccade and VOR, and vertical eye movements were normal in most cases. Gaze nystagmus was not observed in any case. No serious lesion in the CNS concerning eye movements was detected. Although the cause of abnormal eye movements was not clear, congenital origin was postulated. Similar cases reported in the literature were discussed. These cases may be called "congenital nystagmus without gaze nystagmus."

Audiometry↗