Biomedical subjects

K Kitano

Publications and source records attributed to K Kitano.

At least 55 records · Page 3Linked to original sources

PubMed1999

Acute myelogenous leukemia with a t(2;17;4)(p13;q21;p16) aberration: effective treatment with all-trans retinoic acid and granulocyte colony-stimulating factor.

The efficacy of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL) has been well documented. However, ATRA is not as effective against other types of acute myelogenous leukemia (AML) or myelodysplastic syndromes. We present a patient with AML (FAB: M2) associated with a t(2;17;4)(p13;q21;p16) chromosomal defect in which the 17q21 breakpoint was not within the retinoic acid receptor alpha locus which is typically rearranged in APL. This patient was successfully treated with ATRA and granulocyte colony-stimulating factor and improvement of hematological parameters lasted for 19 months without the use of cytotoxic agents.

Antineoplastic Agents↗

PubMed1999

Fibrinogen Matsumoto III: a variant with gamma275 Arg-->Cys (CGC-->TGC)--comparison of fibrin polymerization properties with those of Matsumoto I (gamma364 Asp-->His) and Matsumoto II (gamma308 Asn-->Lys).

Fibrinogen Matsumoto III (M-III) is a dysfibrinogen identified in a 66-year-old woman with rectal cancer. The fibrinogen level determined by the thrombin-time method was markedly decreased in preoperative coagulation tests of her plasma. Three fibrinogen polypeptide-chain gene fragments from the proposita were amplified by the polymerase chain reaction method, then sequenced. The triplet CGC encoding the amino acid residue gamma275 was replaced by TGC, resulting in the substitution of Arg->Cys. There have been previous reports of nine families with the same alteration, nine families with an Arg->His variant and one family with an Arg->Ser variant in this residue, which has been shown to be one of the most important amino acids in the 'D:D' interaction site. In addition, there are three silent mutations in the Aalpha-chain gene and two mutations in the intron of the Bbeta-chain and the gamma-chain gene. However, none of these mutations is thought to be the cause of the dysfunctional fibrinogen. The thrombin-catalyzed fibrin polymerization in the presence of 1 mM Ca ions was markedly delayed in purified M-III. Its lag period was longer than those of Matsumoto II (M-II; gamma308Asn->Lys) and Matsumoto I (M-I; gamma364Asp-His). gamma364Asp is one of the most important residues in the polymerization pocket of the 'D:E' interaction site and gamma308Asn is located in the vicinity of a high affinity Ca2+ binding site in the D-domain, gamma311-336. The maximum slope of the polymerization curve for M-III was about 4-fold steeper than that for M-1 but less steep than that for M-II. These results may suggest that the tertiary structure of the polymerization pocket plays a more important role in the lateral aggregation of protofibrils than that of the 'D:D' interaction site.

Aged↗

PubMed1999

Polymorphisms of platelet membrane glycoprotein Ib alpha and plasma von Willebrand factor antigen in coronary artery disease.

To examine the relationships of two polymorphisms of platelet glycoprotein (GP) Ib alpha and coronary artery diseases (CAD) in Japanese patients, we conducted a case-control study with 158 Japanese patients and 169 control subjects. The frequencies of HPA-2 polymorphism and the variable number of tandem repeat (VNTR) polymorphisms in the macroglycopeptide region did not significantly differ between CAD patients and control subjects. The polymorphisms of GPIb alpha were not associated with the number of affected vessels in CAD patients. When patients with acute coronary syndrome only were analyzed, the frequencies of the two polymorphisms of GPIb alpha showed no significant difference. Although plasma von Willebrand antigen (vWF:Ag) levels in patients were significantly higher than in controls, no association between vWF concentration and GPIb genotypes was observed. In patient groups with higher or lower vWF:Ag concentrations, no increase in the frequencies of Met145 or larger VNTR polymorphisms was seen in either group. Our findings indicate that no association exists between the frequencies of the two polymorphisms of GPIb alpha and CAD.

Aged↗

PubMed1999

Liver cirrhosis with marked thrombocytopenia and highly elevated serum thrombopoietin levels.

Three patients with liver cirrhosis (LC) and a bleeding tendency due to marked thrombocytopenia of less than 20 x 10(9)/l were admitted to our hospital for further examination. Bone marrow examination revealed megakaryocytic hypoplasia in all three patients. All patients exhibited amegakaryocytic thrombocytopenic purpura, myelodysplastic syndrome, or bone marrow hypoplasia. 111In-labeled platelet kinetic studies revealed decreased platelet production in all patients. Although serum thrombopoietin (sTPO) levels are usually within the normal level in patients with LC, the sTPO levels of our patients were about 10 times higher than the levels of normal subjects (1.22 +/- 0.37 fmol/ml): 13.34, 16.79, and 10.46 fmol/ml, respectively. These sTPO data supported our findings of decreased megakaryopoiesis. Our findings suggest that examination of sTPO levels is useful in determining the etiology of marked thrombocytopenia in LC patients.

Blood Platelets↗

PubMed1999

Low prevalence of a polymorphism of platelet membrane glycoprotein Ib beta associated with neonatal alloimmune thrombocytopenic purpura in Asian populations.

Iy alloantigen system is the first polymorphism of platelet glycoprotein Ib beta reported to cause neonatal alloimmune thrombocytopenic purpura. We investigated the allelic frequency of Iy alloantigen among Japanese and Korean populations by polymerase chain reaction-restriction fragment length method to determine the possibility of alloimmunization against Iy. Two hundred and nine Japanese and 97 Korean subjects were examined. All 306 individuals were homozygous for glycine at amino acid position 15 and negative for Iy. The allelic frequency of Iy in these populations was calculated to be less than 0.0016. Alloimmunization associated with Iy antigen in Asian populations seems unlikely from these results.

Amino Acid Substitution↗

PubMed1998

Retrieval dynamics in oscillator neural networks.

We present an analytical approach that allows us to treat the long-time behavior of the recalling process in an oscillator neural network. It is well known that in coupled oscillatory neuronal systems, under suitable conditions, the original dynamics can be reduced to a simpler phase dynamics. In this description, the phases of the oscillators can be regarded as the timings of the neuronal spikes. To attempt an analytical treatment of the recalling dynamics of such a system, we study a simplified model in which we discretize time and assume a synchronous updating rule. The theoretical results show that the retrieval dynamics is described by recursion equations for some macroscopic parameters, such as an overlap with the retrieval pattern. We then treat the noise components in the local field, which arise from the learning of the unretrieved patterns, as gaussian variables. However, we take account of the temporal correlation between these noise components at different times. In particular, we find that this correlation is essential for correctly predicting the behavior of the retrieval process in the case of autoassociative memory. From the derived equations, the maximal storage capacity and the basin of attraction are calculated and graphically displayed. We also consider the more general case that the network retrieves an ordered sequence of phase patterns. In both cases, the basin of attraction remains sufficiently wide to recall the memorized pattern from a noisy one, even near saturation. The validity of these theoretical results is supported by numerical simulations. We believe that this model serves as a convenient starting point for the theoretical study of retrieval dynamics in general oscillatory systems.

Artifacts↗

PubMed1998

Anti-herpesvirus activity profile of 4'-thioarabinofuranosyl purine and uracil nucleosides and activity of 1-beta-D-2'-fluoro-4'-thioarabinofuranosyl guanine and 2,6-diaminopurine against clinical isolates of human cytomegalovirus.

Newly synthesized 4'-thio- and 2'-fluoro-4'-thioarabinofuranosyl purine and pyrimidine nucleosides were compared with the corresponding 4'-oxo type arabinosyl nucleosides for anti-herpesvirus and anti-cell proliferative potencies. 4'-Thioarabinosyl- and 2'-fluoro-4'-thioarabinofuranosyl 5-substituted uracils had selective antiviral activities, but were not superior to 4'-oxo nucleosides, except for the activity of 5-ethyl-uracil 4'-thio nucleosides against herpes simplex virus. Furthermore, 4'-thio substituted derivatives of sorivudine (BV-araU) and related compounds, and 2'-fluoro-5-methyl-arabinosyluracil exhibited reduced activity against varicella-zoster virus compared with the parent compounds. The 4'-thioarabinosyluracils, except for 5-methyluracil derivatives, were inactive against human cytomegalovirus (HCMV). 4'-Thioarabinofuranosyl guanine and diaminopurine had the most potent anti-HCMV and anti-proliferative activities, whereas arabinosyl guanine and diaminopurine had only marginal antiviral activity. 2'-Fluoro-4'-thioarabinofuranosyl derivatives of guanine (4'-thio-FaraG) and 2,6-diaminopurine (4'-thio-FaraDAP), however, had particularly high activity against all herpesviruses tested with anti-proliferative activity equipotent to that of arabinosyl guanine and diaminopurine. 4'-Thio- and 2'-fluoro-4'-thioarabinofuranosyladenines exhibited biological activities similar to that of arabinosyladenine. Both 4'-thio-FaraG and 4'-thio-FaraDAP had a 6-fold lower ED50 than ganciclovir against clinical isolates of HCMV. A ganciclovir-resistant isolate, obtained from a patient who had received long-term ganciclovir-treatment, was susceptible to 4'-thio-FaraG and 4'-thio-FaraDAP.

Antiviral Agents↗

PubMed1998

Cold agglutinin disease by autoanti-i blood type antibody associated with B cell chronic lymphocytic leukemia.

Cold agglutinin (CA) disease is a rare complication of B cell chronic lymphocytic leukemia (CLL). We report a case of CA disease by autoanti-i blood type antibody associated with CD5-negative CLL. The specificity of cold agglutinin in the sera and eluates from red blood cells were analyzed by reactivity against panels of red blood cells and also hemagglutinin inhibition assay using lactonorhexaosylceramide, and were determined to be an anti-i blood group antibody of the monoclonal IgM kappa isotype. PCR analysis of immunoglobulin heavy-chain genes from bone marrow-derived genomic DNA showed CLL cells utilizing DP-54 as a VH gene, differing from the reported VH genes used for cold agglutinin with anti-I/i specificity. The anti-i antibody in this patient might be secondarily produced by residual B cells due to an immunodysregulatory state, and not from CLL cells.

Adult↗

PubMed1998

A case of pathophysiologic study in Kimura's disease: measurement of cytokines and surface analysis of eosinophils.

BACKGROUND: Kimura's disease is a rare but distinctive eosinophilic inflammatory disorder of unknown etiology; few reported case studies have focused on the immunopathologic background of this unique disease. OBJECTIVE: To define better the immunopathogenetic features of Kimura's disease, we attempted to quantitatively analyze values of cytokines and soluble interleukin-2 receptor (sIL-2R) in peripheral blood (PB), as well as perform surface immunophenotypic analysis of eosinophils from a Japanese patient with chronic relapsing Kimura's disease. RESULTS: Granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and sIL-2R were elevated, and newly expressed antigens on eosinophils CD4, CD25, and HLA-DR were found to be involved in the pathophysiology of this disorder. CONCLUSIONS: Kimura's disease may be a disease in which activated lymphocytes release cytokines, and these released cytokines, such as GM-CSF and TNF-alpha cause eosinophil activation. These processes may be related to the pathogenesis of this disorder.

Aged↗

PubMed1998

Purification of a novel muscle cell growth factor S-myotrophin from porcine skeletal muscle.

A comparison of muscle weight between denerved and control rabbit hind legs revealed that a water-soluble 12 kDa substance was reduced in atrophied muscles after denervation. We hypothesised that a water-soluble growth factor exists which mediates a signal from motor nerves to muscles. To isolate this factor we modified the purification procedures of Sen et al. [S. Sen, G. Kundu, N. Mekhail, J. Castel, K. Misono, B. Healy, Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth, J. Biol. Chem. 265 (1990) 16635-16643.], who originally purified a water-soluble growth factor from cardiac muscles. Four additional purification steps were added to the method. Using this technique, a novel muscle cell growth factor, named s-myotrophin, was purified from porcine skeletal muscle (M. longissimus thoracis). Purified s-myotrophin appeared as a single band (12 kDa) on SDS-PAGE and had a strong growth promoting activity (increase of protein synthesis) of cultured primary skeletal muscle cells. Almost no loss of growth promoting activity was observed after trypsin and chymotrypsin digestion. No fragmentation of s-myotrophin was observed after exposure to lysylendopeptidase, thermolysin, trypsin and chymotrypsin. Crude preparation of this molecule could be detected by periodic acid/Schiff (PAS) staining. Deglycosylation of s-myotrophin produced a smaller molecule having an approximately 7 kDa mass. These data indicate a novel 12 kDa protein has been isolated which has growth promoting properties on skeletal muscle cells.

Animals↗

PubMed1998

Fas and mutant estrogen receptor chimeric gene: a novel suicide vector for tamoxifen-inducible apoptosis.

Several cancer gene therapy strategies involve suicide genes to kill the neoplasm, or to regulate effector cells such as lymphocytes. We have developed an inducible apoptosis system with a Fas-estrogen receptor fusion protein (MfasER) for rapid elimination of transduced cells. In the present study, we further improved this molecular switch for estrogen-inducible apoptosis to overcome concerns with the wild-type estrogen receptor and its natural ligand, 17beta-estradiol (E2). The ligand-binding domain of MfasER was replaced with that of a mutant estrogen receptor which is unable to bind estrogen yet retains affinity for a synthetic ligand, 4-hydroxytamoxifen (Tm). The resultant fusion protein (MfasTmR) and MfasER were expressed in L929 cells for examination of their ligand specificities. Tm induced apoptosis in MfasTmR-expressing cells (L929MfasTmR) at 10(-8) M or higher concentrations, but induced no apoptosis in MfasER-expressing cells (L929MfasER) at up to 10(-6) M. On the other hand, E2 induced apoptosis in L929MfasER at concentrations as low as 10(-10)-10(-9) M, while it did so partially in L929MfasTmR at concentrations greater than 10(-7) M. Thus, L929MfasTmR cells were highly susceptible to Tm, but refractory to E2, with 100-1,000 times more tolerance than L929MfasER. These results suggest that the MfasTmR/Tm system would induce apoptosis in the target cells more safely in vivo, working independently of endogenous estrogen.

Animals↗

PubMed1998

Changes in serum thrombopoietin levels after splenectomy.

To clarify the role of thrombopoietin (c-Mpl ligand, TPO) in 'hypersplenic' thrombocytopenia, we used an enzyme-linked immunosorbent assay to examine changes in serum TPO levels accompanied with splenectomy in 6 patients with liver cirrhosis, 4 patients with gastric cancer, and 2 patients with lymphoid malignancies. We also measured serum levels of other thrombopoietic cytokines such as interleukin-6 (IL-6) and erythropoietin. Platelet counts reached a maximum at day 14 after splenectomy in all subjects. In patients with liver cirrhosis, a lower elevation of platelet counts was observed compared with that in patients with gastric cancer. Serum TPO levels gradually elevated after splenectomy and reached a maximum 3.5 days after splenectomy in noncirrhotic patients, whereas peak serum TPO levels were delayed until day 7 in the cirrhosis group. IL-6 and erythropoietin showed similar kinetics between cirrhotic and noncirrhotic patients. These findings suggest that transient thrombocytosis after splenectomy may be associated with an alteration in the site of TPO catabolism by platelets from spleen to the blood and that deterioration of TPO production may play a role in thrombocytopenia in liver cirrhosis.

Adult↗

PubMed1998

Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group.

PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

Adolescent↗

PubMed1998

Transluminal percutaneous septal myocardial ablation in a patient with hypertrophic obstructive cardiomyopathy.

Reduction of septal mass by inducing septal infarction using catheter techniques is a new therapy for hypertrophic obstructive cardiomyopathy (HOCM). We report a case of severe HOCM that was dramatically improved by this non-surgical treatment. A 60-year-old woman with HOCM had suffered dyspnea (NYHA class III) with syncopal attack despite medical treatment. Left heart catheterization showed a resting pressure gradient across the left ventricular outflow tract of 156 mmHg. Two proximal septal branches of the anterior descending coronary artery were catheterized with a balloon catheter by the usual percutaneous coronary angioplasty techniques and were completely blocked by injection of absolute alcohol. The pressure gradient decreased to 26 mmHg after the procedure. Symptoms were markedly improved (NYHA class I) without any medical treatment. The reduced pressure gradient was maintained at the 3-month follow-up catheterization (36 mmHg). Further long-term follow-up is needed, but this treatment would seem to to be a promising technique for reducing pressure gradient in symptomatic patients with HOCM.

Cardiomyopathy, Hypertrophic↗

PubMed1997

Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins.

Crm1 of Schizosaccharomyces pombe, a nuclear protein essential for proliferation and chromosome region maintenance, is a possible target of leptomycin B, an antifungal and antitumor antibiotic with cell cycle-arresting activity. cDNA encoding a human homolog of Crm1 was cloned. Human CRM1 (hCRM1) consisted of 1071 amino acids, of which the sequence showed 52% homology with S. pombe Crm1. hCRM1 weakly complemented the cold-sensitive mutation of S. pombe crm1-809, as did S. pombe crm1+. Overproduction of hCRM1 under the control of a series of nmt1 promoters suppressed cell proliferation in wild-type S. pombe in an expression level-dependent manner. A similar inhibitory effect was also observed for crm1+. Cells overproducing either hCRM1 or S. pombe Crm1 were distinctly larger than uninduced cells and contained compacted and fragmented nuclei. Furthermore, calcofluor staining demonstrated that most of these cells formed two septa per cell and accumulated a large amount of chitin or its related polysaccharides around the septa. Closely similar phenotypes between hCRM1- and S. pombe Crm1-induced cells indicate that the cloned cDNA encodes a functional homolog of S. pombe crm1+. Northern blot analyses with RNAs isolated from synchronized mammalian cells showed that the expression of mammalian CRM1 was initiated in late G1 and reached a peak at G2/M, although its protein level unchanged during the cell cycle. Transient expression of hCRM1 fused to the green fluorescent protein (GFP) in NIH3T3 cells showed that hCRM1 was localized preferentially in the nuclear envelope and was also detectable in the nucleoplasm and the cytoplasm. A crm1 mutation of S. pombe caused nuclear import of a GFP fusion protein containing a nuclear export signal but no change in the distribution of a GFP fusion protein containing a nuclear localization signal. All of these data suggest that CRM1 is a novel cell-cycle regulated gene that is essential for the nuclear export signal-dependent nuclear export of proteins.

3T3 Cells↗

PubMed1997

Sealing effects of (-)-epigallocatechin gallate on protein kinase C and protein phosphatase 2A.

(-)-Epigallocatechin gallate (EGCG) was reported to inhibit protein kinase C (PKC) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA), and inhibit interaction of tumor promoter with its receptors, named 'a sealing effect'. In order to clarify the sealing effect of EGCG, we prepared liposomes and examined inhibition of PKC activation by various concentrations of EGCG dispersed in the liposome. EGCG added to a liposome dispersion existed either in a buffer solution as aggregates or in phospholipid bilayer membranes, and EGCG disturbed membrane structure. The potency of inhibitory effect of EGCG on PKC activation was dependent on the nature of liposomes, indicating that interaction of EGCG with phospholipid bilayer membrane affects PKC activation. Moreover, EGCG prevented the binding of adenosine 5'-triphosphate and TPA to PKC, resulting in inhibition of PKC activation. On the other hand, the activity of protein phosphatase 2A (PP2A) was suppressed in the presence of liposomes, but was not influenced by EGCG. Moreover, EGCG recovered phosphatase activity of PP2A in a buffer solution, the activity of which was inhibited by okadaic acid. All the results indicated that EGCG possesses sealing effects in terms of PKC and PP2A, by inhibiting interaction of various ligands with proteins.

Catechin↗

PubMed1997

Identification and characterization of a novel human cortistatin-like peptide.

Expressed sequence tags (ESTs) that showed significant homology to rat cortistatin (CST) were found in a human fetal brain cDNA library. A protein coded by the cDNA showed 55% identity to rat preprocortistatin in amino acid. Similarly in the generation of mature peptides from rat preprocortistatin, it was expected that cleavage at dibasic amino acids in the C-terminal portion of the coded protein might produce at least two different sizes of mature peptides with 29 and 17 amino acid residues, respectively. We chemically synthesized the predicted mature peptide with 17 amino acid residues (hCS-17) and examined its biological activities. It bound to all human somatostatin receptor (SSTR) subtypes in almost the same manner as rat CST-14. It also inhibited cAMP production induced by forskolin through SSTRs. Administration of hCS-17 to the cerebral ventricle showed flattening of cortical and hippocampal electroencephalograms in rats. These results indicate that a bioactive peptide encoded by the cDNA is a human counterpart corresponding to rat CST.

Amino Acid Sequence↗

PubMed1997

Free radical-mediated tissue injury in acute lung allograft rejection and the effect of superoxide dismutase.

BACKGROUND: The role of monocytes and neutrophils is crucial during acute allograft rejection. They have the capacity to generate toxic reactive oxygen intermediates in response to specific agonists that may act as tissue destructive molecules. We examined the possibility of reactive intermediate-mediated tissue injury in acute lung allograft rejection, as well as the effect of superoxide dismutase. METHODS: Allogenic (Brown Norway to F344) or syngenic (F344 to F344) rat left-lung transplantation was performed. Generation of reactive oxygen intermediates in peripheral blood was evaluated by the method of luminol-dependent chemiluminescence. Cell membrane phospholipid peroxidation in the graft was measured as malondialdehyde concentration. The third group of animals having allografts received bovine erythrocyte superoxide dismutase (5,000 U/kg intravenously every 12 hours after transplantation). RESULTS: Relative chemiluminescence response in the allograft recipient to normal F344 was elevated on postoperative day 1 (257%), then decreased slightly on day 3 (156%) and was elevated again on day 7 (560%) as the process of rejection progressed. Allograft tissue malondialdehyde levels (248.37 +/- 112.35 nM/whole lung, n = 6; p < 0.05 by Student's t test) were higher than isograft levels (139.29 +/- 35.93 nM/whole lung, n = 6) on day 7. Superoxide dismutase treatment significantly ameliorated the histologic degree of rejection on day 7. CONCLUSIONS: These results demonstrate the tissue destructive activity of reactive oxygen intermediates during lung allograft rejection. To scavenge free radicals may be a useful therapeutic modality in the management of acute lung allograft rejection.

Acute Disease↗