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K Kitamura

Publications and source records attributed to K Kitamura.

At least 937 records · Page 52Linked to original sources
PubMed1989

An autopsy case of myelodysplastic syndrome (MDS): diagnostic problems between MDS and the other haematopoietic disorders including acute myelofibrosis.

We report an autopsy case of myelodysplastic syndrome (MDS) in a 35-year-old male, who presented with pancytopenia and bleedings. Bone marrow specimens disclosed myelofibrosis and hypercellular marrow with more than 60% atypical erythroblasts in the bone marrow cells. Type I or type II blasts were less than 10% of the peripheral blood and bone marrow cells during the clinical course. At autopsy, infiltration by myeloid and erythroid cells and megakaryocytes was noted in the liver, spleen and lymph nodes. According to the FAB classification, this case might be classified into refractory anemia with excess of blasts (RAEB) or RAEB in transformation. However, the remarkable neoplastic proliferation of three haematopoietic cell lines also indicates acute myeloproliferative disorder such as acute myelofibrosis or acute panmyelosis.

Acute Disease↗
PubMed1989

[An adult case of moyamoya disease associated with marked advance of occlusive lesion in the bilateral carotid system].

We reported an adult case with moyamoya disease in which unilateral obstructive process proceeded to the bilateral lesion during a period of 45 months. A 30-year-old female was admitted to our institute due to frequent ischemic episodes since she was 25 years old. At the time of admission, she was asymptomatic with slightly disturbed psychogenic reactions. At the time of the initial cerebral angiography when she was 25 years old, the right cerebral angiography demonstrated stenosis of the right ICA terminal portion with moyamoya vessels in the basal area and leptomeningeal anastomosis at the right parietal area. The left cerebral angiography revealed normal ICA system with a lightly narrowing Al portion, without Moyamoya vessels. The second cerebral angiography, taken 45 months after the initial angiography, demonstrated progression stenosis of the right ICA terminal portion, with decreasing moyamoya vessels at the basal area, obstruction of the left ICA terminal portion, stenosis at the Al portion with newly developed moyamoya vessels in the left basal area. We concluded at this time that this case was a definite case of moyamoya disease. The third cerebral angiography after right SDP (synangio-dural plasty), 49 months after the initial angiography, revealed, in the right angiography, newly formed anastomotic vessels perfusing the middle cerebral artery region via the extracerebral arteries and in the left cerebral angiography, and an increased obstruction of the ICA terminal portion, transdural anastomosis via the extracerebral arterial system, and a decrease of moyamoya vessels in the basal area. This rare case provided us a good picture of the pathogenic mechanism of moyamoya disease.

Adult↗
PubMed1989

Inhibitory actions of a novel benzothiazepine derivative, TA3090, on the electrical and mechanical responses of the rabbit mesenteric artery.

Actions of diltiazem and TA3090 [(+)-(2S, 3S)-3-acetoxy-8-chloro-5-[(2-dimethylamino)ethyl]-2,3-dihydro-2- (4-methoxy-phenyl)-1,5-benzothiazepine-4-(5H)-one maleate] on smooth muscle cells of the rabbit mesenteric artery were investigated using the microelectrode and tension recording methods. Diltiazem (greater than or equal to 10 microM) but not TA3090 (less than or equal to 100 microM) depolarized the membrane of the rabbit mesenteric artery. TA3090 (greater than or equal to 3 microM) inhibited the action potential and K-induced contraction (128 mM) more than diltiazem (IC50 for action potential, 6.7 microM for TA3090 and 11 microM for diltiazem in the presence of 5 mM tetraethylammonium; IC50 for phasic and tonic K-induced contractions, 3.1 and 0.1 microM, respectively, for TA3090 and 10 and 1 microM for diltiazem). When the membrane was depolarized previously by high concentrations of K in Ca-free solution, TA3090 more potently inhibited the K-induced contraction (128 mM). As a consequence, the concentration-response curve shifted to the left, suggesting that this agent produces voltage-dependent inhibition. Recovery of the amplitudes of action potential and contraction evoked by 128 mM K required a much longer period with TA3090 than diltiazem after removal of these agents and the recovery of the K-induced contraction was also voltage-dependent. Repetitive application of short stimulating pulses (50 musec, 30 Hz) produced an action potential on the excitatory junction potentials. TA3090 inhibited the action potential without change in the amplitude of excitatory junction potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Time- and voltage-dependent block of the delayed K+ current by quinidine in rabbit sinoatrial and atrioventricular nodes.

The modes in which quinidine blocks the delayed K+ current (IK) of rabbit sinoatrial and atrioventricular nodes were investigated by voltage clamp experiments using small preparations. Depolarizing pulses were applied from a holding potential of -50 mV and resultant IK current was evaluated. At a concentration of 2 x 10(-6) M, quinidine blocked 52 +/- 5% of IK with a 1000-msec test pulse of 0 mV, whereas it inhibited the slow inward current by only 5 to 10%. IK inhibition was enhanced with increasingly larger depolarizations. The activation curve obtained with the use of 1000-msec test pulses shifted toward hyperpolarization by 3.0 mV and its slope factor increased from 7.3 to 8.8, suggesting a voltage-dependent mechanism for IK blockage. Short and small depolarizing pulses from the holding potential of -50 mV hardly affected II. The activation of IK in the presence of quinidine did not show any delay. These results indicated a low affinity of quinidine to the closed (deactivated) channels. The deactivation time constant of IK was significantly prolonged from 120 to 145 msec at -50 mV. By applying the modulated receptor model to the K+ current, the tail current in the presence of quinidine was well reconstructed when the time constant of drug-channel interactions was 300 msec at -50 mV and 2000 msec at -30 mV. It is suggested that the unblocking of quinidine slows the decay of the IK tail current.

Animals↗
PubMed1988

Isozymes of fructose 6-phosphate,2-kinase:fructose-2,6-bisphosphatase in rat and bovine heart, liver, and skeletal muscle.

The distribution of Fructose 6-P,2-kinase:Fructose 2,6-bisphosphatase in rat and bovine heart, liver, and skeletal muscle tissues was examined. With DEAE-cellulose chromatography, two peaks (I and II) of Fru 6-P,2-kinase activity were detected in all tissue extracts. Peak I was the predominant form both in rat and bovine heart tissue, while peak II was the major form in liver and skeletal muscle. Antibodies to heart enzyme reacted specifically with peak I, and antibodies to liver enzyme reacted with peak II from both liver and skeletal muscle. All the isozymes were bifunctional. All the tissues examined contained other isozymes in minor amounts.

Animals↗
PubMed1988

Phosphorylation of myocardial fructose-6-phosphate,2-kinase: fructose-2,6-bisphosphatase by cAMP-dependent protein kinase and protein kinase C. Activation by phosphorylation and amino acid sequences of the phosphorylation sites.

Phosphorylation of pure fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase from bovine heart by cAMP-dependent protein kinase and protein kinase C was investigated. The major enzyme form (subunit Mr of 58,000) was rapidly phosphorylated by both cAMP-dependent protein kinase and protein kinase C, incorporating 0.8 and 1.0 mol/mol of subunit, respectively. The rate of phosphorylation of the heart enzyme by cAMP-dependent protein kinase was 10 times faster than that of the rat liver enzyme. The minor enzyme (subunit Mr of 54,000), however, was phosphorylated only by protein kinase C and was phosphorylated much more slowly with a phosphate incorporation of less than 0.1 mol/mol of subunit. Phosphorylation by either cAMP-dependent protein kinase or protein kinase C activated the enzyme, but each phosphorylation affected different kinetic parameters. Phosphorylation by cAMP-dependent protein kinase lowered the Km value for fructose 6-phosphate from 87 to 42 microM without affecting the Vmax, whereas the phosphorylation by protein kinase C increased the Vmax value from 55 to 85 milliunits/mg without altering the Km value. The phosphorylated peptides were isolated, and their amino acid sequences were determined. The phosphorylation sites for both cAMP-dependent protein kinase and protein kinase C were located in a single peptide whose sequence was Arg-Arg-Asn-Ser-(P)-Phe-Thr-Pro-Leu-Ser-Ser-Ser-Asn-Thr(P)-Ile-Arg-Arg-Pro. The seryl residue nearest the N terminus was the residue specifically phosphorylated by cAMP-dependent protein kinase, whereas the threonine residue nearest the C terminus was phosphorylated by protein kinase C.

Amino Acid Sequence↗
PubMed1988

Importance of folded monomer and extended antiparallel dimer structures as enkephalin active conformation. Molecular dynamics simulations of [Met5]enkephalin in water.

Simulations of the molecular dynamics of the [Met5]enkephalin monomer and dimer structures in water have been carried out. The dynamic trajectories have been analyzed in terms of the distances between intra- or intermolecular polar atoms. The time-correlated conformational transitions of an extended monomer structure have been converged into a stationary state among the beta-bend folded forms. However, the dynamics simulation of an extended antiparallel dimer structure has shown no noticeable conformation change. These results imply that both the beta-bend monomer and the extended dimer structures exist together as the fundamental conformation of enkephalins.

Calorimetry↗
PubMed1988

Molecular-dynamics simulations of [Met5]- and [D-Ala2,Met5]-enkephalins. Biological implication of monomeric folded and dimeric unfolded conformations.

To investigate the biologically active conformation of enkephalin, molecular-dynamics simulations were applied to [Met5]- and [D-Ala2,Met5]-enkephalins. The dynamic trajectory of monomeric extended [Met5]-enkephalin was analysed in terms of relative mobility between respective torsions of backbone chain. After 10 ps of the dynamics simulation, the conformational transition was converged into a stationary state among the beta-bend folded forms, where they are stabilized by several intramolecular hydrogen-bond formations. Similar conformational transition was also observed in the dynamics simulation of [D-Ala2,Met5]enkephalin, which is a more mu-receptor-specific peptide than [Met5]enkephalin. The geometrical correspondence between the monomeric enkephalin conformation in the stationary state and morphine molecule (a mu-specific rigid opiate) was surveyed by virtue of the triangular substructures generated by choosing three functional atoms in each molecule, and good resemblances were observed. On the other hand, the dynamics simulation of the antiparallel extended [Met5]enkephalin dimer showed a trajectory different from that of the monomeric one. Two intermolecular hydrogen bonds at Tyr1 (NH3+)...Met5(CO2-) end residues were held throughout the 100 ps simulation, the dimeric structure being consequently kept. The conformational transition of the backbone chains from the antiparallel extended form to the twisted one took place via an intermediate state. Many conformations revealed during the dynamics simulation showed that the relative orientations of each two Tyr1, Gly3, Phe4 and Met5 residues in the dimer are nearly related by a pseudo-C2-symmetry respectively, and both halves of the dimer structure could be further fitted to the monomeric folded enkephalin conformation. The monomeric and dimeric conformations of enkephalin at their stationary states are discussed in relation to the substrate-specificity for mu- and delta-opioid receptors.

Computer Simulation↗
PubMed1988

Purification and characterization of myocardial fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase.

Fructose-6-P,2-kinase:fructose-2,6-bisphosphatase has been purified to homogeneity from beef heart. The enzyme was bifunctional and the specific activities of the kinase and the phosphatase of the pure enzyme were 60 and 30 milliunits/mg, respectively. The molecular weight of the enzyme was 118,000, consisting of two subunits of 58,000. In some preparations of the enzyme a minor protein with a subunit Mr of 54,000 was present. This minor protein (54,000) was also bifunctional and showed the same immunoreactivity as the major protein. The specific activity of fructose-6-P,2-kinase of the minor component was three times higher than that of the major enzyme (58,000), but fructose-2,6-bisphosphatase activity was the same. These two forms have been separated by phosphocellulose chromatography. The tryptic peptide maps of these enzymes were very similar. The 58,000 enzyme was phosphorylated by cAMP-dependent protein kinase but the 54,000 enzyme was not. These results indicated that the minor 54,000 protein might be a proteolytically digested form of the 58,000 enzyme. The Km of the kinase for fructose-6-P and ATP was 70 microM and 260 microM, respectively for both the 58,000 and the 54,000 enzymes. Km for fructose-2,6-P2 and Ki for fructose-6-P of the phosphatase was approximately 40 and 11 microM, respectively. The enzyme was phosphorylated by fructose-2,6-P2 but the stoichiometry of the phosphate incorporation was 0.05 mol/mol subunit, while 0.4 mol/mol was incorporated in rat liver enzyme under the same conditions.

Animals↗
PubMed1988

Characterization of a monoclonal antibody reacting with a neutral glycolipid that is associated with human T-cell leukemia virus type I infection and freshly isolated adult T-cell leukemia.

During attempts to make antibodies cross-reactive with human lymphocytes, we established a monoclonal antibody (VJ-41) from the alloimmunization of mice, that is, B10.A(3R) anti-B10.A(5R). VJ-41 reacted with all cases of freshly isolated adult T-cell leukemia cells (36 cases) but not with cells from other hematological disorders (more than 50 cases). Human T-cell leukemia virus Type I healthy carriers also seemed to possess these VJ-41 antigen positive cells. However, in vitro established adult T-cell leukemia cell lines did not show the reactivity with VJ-41. Normal lymphocytes from humans or mice apparently did not carry this antigen, but mitogen activated lymphocytes or some in vitro maintained malignant cell lines of both human and mouse origins showed positive reaction. Having established solid phase radioimmunoassay to detect the VJ-41 antigen in plasma, it was found that healthy human T-cell leukemia virus Type I carriers, but not the majority of adult T-cell leukemia patients, predominantly possessed this antigen. Even though immunochemical characterizations of cellular materials were unsuccessful, a certain neutral glycolipid was detected from healthy human T-cell leukemia virus Type I carrier plasma by using thin-layer chromatography and immunostaining with the VJ-41 antibody.

Antibodies, Monoclonal↗
PubMed1988

Conformational characteristics of receptor-selective opioid peptides. 1H n.m.r. and c.d. spectroscopic studies of delta-kephalin and [Val4]morphiceptin.

An investigation on the conformations of highly receptor-selective opioid peptides was carried out to gain further understanding of the structure-activity relationship of endogenous enkephalins. The preferred conformations of a highly mu-selective [Val4]morphiceptin and a highly delta-selective delta-kephalin have been probed by 1H n.m.r. solvent-, concentration- and temperature-dependences of amide protons to take the folded conformations stabilized by an intramolecular hydrogen bond and the anti-parallely extended dimeric structures respectively. Their possible stereo-conformations were proposed, based on the analyses of the vicinal coupling constants (JHNC alpha H). The conformational difference between the mu- and delta-selective opioid peptides was further ascertained by the c.d. measurements. The c.d. spectra of the mu-selective peptides show negative bands in the range of 210-230 nm, while those of the delta-selective ones show the opposite positive bands. A correlation between c.d. spectra and receptor-selectivity was possible.

Circular Dichroism↗
PubMed1988

Clinical application of monoclonal antibody-drug conjugates for immunotargeting chemotherapy of colorectal carcinoma.

Monoclonal antibody-drug conjugates were applied as a clinical trial for patients who, based on the experimental study, had colorectal cancer. Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer, was used as a drug carrier for colon cancer. The anti-cancer drugs mitomycin C (MMC) and neocarzinostatin (NCS) were bound covalently to A7 to form the conjugates A7-MMC and A7-NCS. The in vitro cytotoxic effects of the conjugates on SW1116 cells were stronger than those on free MMC or NCS. The conjugate A7-NCS, when administered to nude mice, brought about the highest NCS tumor concentration, whereas normal immunoglobulin G (IgG)-NCS distributed evenly in all tissues. The conjugates showed a strong antitumor effect on colon cancer transplanted into nude mice. Forty-one patients with colorectal cancer, including ten patients with postoperative metastasis, were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens showed that NCS was localized specifically in cancer. Patients receiving the conjugate did not experience serious adverse effects. Of the eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on computed tomography (CT) scan and three claimed pain relief. The conjugate did not benefit patients with multiple lung metastasis or peritoneal metastasis.

Adult↗
PubMed1988

Isotype-specific immunoregulation. Systemic antigen induces splenic T contrasuppressor cells which support IgM and IgG subclass but not IgA responses.

In the present study, we have isolated and characterized the Lyt-1+, -2- T contrasuppressor (Tcs) cells from mice systemically primed with SRBC. Adoptive transfer of splenic Tcs cells from these mice abrogates oral tolerance and supports IgM and IgG anti-SRBC plaque-forming cell (PFC) responses; however, unlike the responses seen after transfer of Tcs cells derived from orally primed mice, low IgA responses were seen. Mice systemically primed with lower SRBC doses (0.01 to 1%) exhibited contrasuppression only within the L3T4- T cell subset, whereas mice primed with a high dose of SRBC (10%), harbored Lyt-1+, -2- Tcs cells in both the L3T4+ and L3T4- subsets. Both the L3T4- and L3T4+ Tcs cell subsets supported IgM and IgG responses when adoptively transferred to orally tolerized mice, and when added to tolerized spleen cell cultures. Splenic Tcs cells from systemically primed mice supported mainly IgG1 and IgG2b subclass anti-SRBC PFC responses, a pattern also seen with Tcs cells derived from orally primed mice. Both L3T4+ and L3T4- Tcs cells from systemically primed mice exhibited well established characteristics of contrasuppressor cells including binding to Vicia villosa lectin and expression of I-J. The splenic effector Tcs cells which support IgM, IgG1 and IgG2b anti-SRBC PFC responses are antigen-specific, since both L3T4- and L3T4+ Tcs cells from spleens of mice primed with 10% SRBC reverse tolerance to SRBC, but not to horse erythrocytes (HRBC). Further, both L3T4- and L3T4+ Tcs cells from HRBC-primed mice reverse tolerance to IgM and IgG anti-HRBC, but not to anti-SRBC responses. Isolation of T3-positive Lyt-1+, -2- and L3T4- Tcs cell subsets by flow cytometry followed by adoptive transfer, showed that effector Tcs cells express T3 and presumably contain an Ag-R (TCR-T3 complex). These studies show that systemic priming with heterologous RBC induces splenic Ag specific Tcs cells in a dose-dependent manner, which support IgM and IgG subclass responses, but not IgA responses.

Administration, Oral↗
PubMed1988

Alterations in local cerebral glucose utilization during electrical stimulation of the striatum and globus pallidus in rats.

Alterations in local cerebral glucose utilization (LCGU) in conscious rats during electrical stimulation of the striatum and the globus pallidus were investigated using the [14C]deoxyglucose method. Stimulation of the globus pallidus produced a marked contraversive circling behavior, while stimulation of the striatum led only to contraversive head turning. Unilateral stimulation of the striatum increased LCGU bilaterally in the globus pallidus and substantia nigra pars compacta, but only ipsilaterally in the entopeduncular nucleus, substantia nigra pars reticulata and subthalamic nucleus. Similar stimulation of the globus pallidus increased LGCU in the globus pallidus, substantia nigra pars reticulata and compacta, entopeduncular nucleus, subthalamic nucleus, lateral habenular nucleus, parafascicular nucleus of the thalamus, deep layers of the superior colliculus and pedunculopontine nucleus, exclusively on the ipsilateral side. These results indicate that the electrical stimulation induces LCGU changes in the respective structures having both monosynaptic and transsynaptic neuronal inputs. Some changes may also be mediated by antidromic activation. They also suggest that activation of a synaptic process whether excitatory or inhibitory results in increases in LCGU. The bilateral modulatory effects of striatal stimulation may cancel out the circling behavior seen during pallidal stimulation, and cause only head turning.

Animals↗
PubMed1988

Ischemic stroke in infancy, childhood, and adolescence.

The authors studied 34 patients with juvenile ischemic cerebrovascular disease over a 15-year period. Of the 34 patients, 23 had intracranial occlusions attributed to cerebral thrombosis or embolism and 11 had occlusions resulting from moyamoya disease. Clinicopathological features were evaluated in the 23 cases with ischemic stroke, but not those with moyamoya disease. The cause of the arterial occlusion remained undetermined in 11 patients and was found to be an embolism based on congenital heart disease in 8, on trauma in 3, and on infection in 1. Cerebral angiography was performed in 21 patients. Of these, 17 had stenoses or occlusions corresponding to their symptoms. CT scans were performed in 10 patients; the lesion in question showed no stenosis or occlusion with cerebral angiography. With regard to prognosis, patients with unknown etiology had good outcomes compared with those with congenital heart disease. With respect to "acute infantile hemiplegia", 10 patients had convulsive seizures and 4 had a history of an earlier infection. Angiography and CT scans in patients with congenital heart disease demonstrated arterial occlusive sites in the middle cerebral artery region. Three patients had abscesses after their ischemic lesions.

Adolescent↗
PubMed1988

The existence of a highly tetrodotoxin sensitive Na channel in freshly dispersed smooth muscle cells of the rabbit main pulmonary artery.

To characterize the inward current recorded from single smooth muscle cells of the rabbit main pulmonary artery, a voltage clamp procedure using patch pipettes filled with high Cs solution to inhibit K currents was employed. Under superfusion with normal physiological salt solution, application of a command potential to -10 mV from the holding potential of -80 mV elicited an inward current comprising fast and slow components. In Ca-free solution containing 2.5 mM Mn and 134 mM Na, the major part of the slow inwart current (Islow) ceased, but a transient fast inward current (Ifast) remained. A reduction in the Na concentration in the bath solution inhibited the amplitude of Ifast. Both nicardipine (30 nM) and diltiazem (1-10 microM) inhibited Islow but had no effect on Ifast. Application of tetrodotoxin (greater than 1 nM) in Ca free solution inhibited the amplitude of Ifast in a dose-dependent manner with a dissociation constant of 8.7 nM. Chloramine-T (0.3 mM) increased the peak amplitude and reduced the rate of decay of Ifast and completely inhibited Islow. These results suggest that the inward curent generated in the smooth muscle cells of the rabbit main pulmonary artery is associated with activation of a voltage-dependent Ca channel and a tetrodotoxin-sensitive Na channel.

Animals↗