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Biomedical subjects

J Kato

Publications and source records attributed to J Kato.

At least 109 records · Page 6Linked to original sources
PubMed2000

Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.

The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.

Albuminuria↗
PubMed2000

Dose-dependent effects of mandibular advancement on pharyngeal mechanics and nocturnal oxygenation in patients with sleep-disordered breathing.

STUDY OBJECTIVES: To examine dose-dependent effects of mandibular advancement on collapsibility of the passive pharynx and sleep-disordered breathing (SDB). DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: Thirty-seven adult patients with SDB. INTERVENTIONS: Oral appliances with 2-, 4-, and 6-mm advancement of the mandible. MEASUREMENTS AND RESULTS: Overnight oximetry was performed with and without oral appliances. Each 2-mm mandibular advancement coincided with approximately 20% improvement in number and severity of nocturnal desaturations. Percentages of patients producing a > 50% improvement rate of the number of desaturations were 25%, 48%, and 65% with use of oral appliances with 2-, 4-, and 6-mm mandibular advancement, respectively. Static pharyngeal mechanics were evaluated in six completely paralyzed patients with SDB under general anesthesia with and without the oral appliances. Advancement of mandibular position was found to produce dose-dependent closing pressure reduction of all pharyngeal segments. Normalization of nocturnal oxygenation was associated with negative closing pressure, especially at the velopharynx. CONCLUSIONS: We conclude that improvement of both nocturnal oxygenation and pharyngeal collapsibility significantly depends on the mandibular position.

Adult↗
PubMed2000

Differentiation-associated expression and intracellular localization of cyclin-dependent kinase inhibitor p27KIP1 and c-Jun co-activator JAB1 in neuroblastoma.

Neuroblastoma is a unique pediatric cancer, which spontaneously regress in some infants and undergo maturation in older children. The cyclin-dependent kinase inhibitor p27KIP1 negatively control cell cycle progression and its expression is reported to be associated with differentiation and prognosis of some human cancers. To examine whether p27KIP1 is involved in differentiation of neuroblastomas, expression and localization of p27KIP1 in 30 cases of neuroblastic tumors were determined with immunohistochemistry. p27KIP1 was expressed in all cases, but staining intensity and intracellular localization varied in association with tumor differentiation. Primitive small round neuroblasts showed negative or only weak nuclear staining, while differentiating tumor cells displayed a novel, intense cytoplasmic positivity besides the nuclear staining, and mature ganglion cells showed intense positive reaction confined to the nucleus. A neuroblastoma cell line TGW was also immunostained positively for p27KIP1 in the cytoplasm after differentiation induction, and western blot analysis revealed an increase of p27KIP1 in these cells, corroborating the in vivo observations. JAB1, which is thought to bind p27KIP1 and transport it from the nucleus to the cytoplasm for proteasome/ubiquitin-mediated degradation, was found to be localized both in the cytoplasm and the nucleus in undifferentiated and differentiating tumors whereas located predominantly in the nucleus of differentiated tumor cells. These data indicate that the cytoplasmic localization of p27KIP1 in the process of differentiation is due to upregulation of p27KIP1 synthesis and subsequent degradation and suggest a role of p27KIP1 in differentiation of neuroblastoma.

Blotting, Western↗
PubMed2000

[Acute eosinophilic pneumonia induced by cigarette smoking].

The subject was a 24-year-old man who presented with acute fever, dry cough, and dyspnea. Chest X-ray films revealed diffuse infiltrates in both lungs. Bronchoalveolar lavage fluid specimens contained an increased number of eosinophils. Transbronchial lung biopsy specimens demonstrated the infiltration of eosinophils into alveolar walls and air spaces. These findings were consistent with acute eosinophilic pneumonia. The patient recovered without medical treatment. Eight days prior to admission, he had resumed smoking after 3 years of abstention. It was suggested that the cause of acute eosinophilic pneumonia in this case was associated with the resumption of smoking. To confirm that association, a smoking challenge test is usually necessary. However, similar symptoms also developed later, after the patient was passively exposed to cigarette smoke. Therefore, we concluded that smoking was probably the etiologic agent of his illness.

Acute Disease↗
PubMed2000

[Multi-vasospastic angina refractory to medical therapy caused by hyperthyroid stage of chronic thyroiditis and hypereosinophilia: a case report].

A 49-year-old woman with bronchial asthma was followed up at our hospital. After 3 years, she experienced an attack of chest pain with ST elevation in the precordal leads of electrocardiography. After admission, the chest pain and ST elevation disappeared, but the chest pain recurred after 6 days. Coronary angiography revealed no significant stenosis in the coronary arteries. After discharge, she had the chest pain repeatedly. ST elevation in the II, III, aVF leads was recorded. The diagnosis was coronary multispasm. The chest pain was refractory to medical therapy. Hypereosinophilia developed and bronchial asthma worsened. After steroid administration, the angina and bronchial asthma ceased. She has lost about 15 kg during 1 year. Laboratory data revealed low thyroid-stimulating hormone, high thyroid hormone, positive thyroglobulin antibody, and negative thyroid-stimulating hormone receptor antibody. The diagnosis was chronic thyroiditis. The multi-vasospastic angina refractory to medical therapy was caused by the hyperthyroid stage of chronic thyroiditis and hypereosinophilia.

Angina Pectoris↗
PubMed2000

[Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE].

A 48-year-old woman, who had been suffering from systemic lupus erythematosus (SLE), developed normochromic normocytic anemia after receiving clomipramine hydrochloride. Her reticulocyte count was low, and a bone marrow aspirate revealed erythroid hypoplasia without involvement of other cell lines. Thus a diagnosis of pure red cell aplasia (PRCA) was made. The anemia gradually resolved following withdrawal of the drug. Although several drugs are known to cause PRCA, this is the first time that clomipramine hydrochloride has been reported to have such an effect. The underlying SLE in this case suggested the possible immunological pathogenesis of drug-induced PRCA.

Antidepressive Agents, Tricyclic↗
PubMed2000

[Identification of environmental estrogens with a three-dimensional quantitative structure-activity relationship(3D-QSAR) analysis].

The quantitative structure-activity relationship(QSAR) technique has been used by computing the structural data from many chemical compounds. In order to predict the estrogenic actions of chemical compounds, various steric(van der Waals) and electrostatic(Coulombic) interaction energy from those compounds are calculated at the standard with a comparative molecular field analysis(CoMFA) and the comparison of these results with template estradiol is drawn as a three-dimensional image. The three-dimensional structural features of various chemical compounds are compared with those of estradiol. The binding affinities of various chemical compounds with estrogen receptor could be predicted. Steric bulk of a chemical compound molecule and electric potential of substituents bound to the molecule can be also drawn on the basis of the three-dimensional data obtained. The results from CoMFA/QSAR analysis correlates well with ones from the presently widely-used bioassay, indicating compatibility of two methods. The 3D-QSAR technique with CoMFA/QSAR analysis seems to be useful for selection of the target disruptors prior to the time-consuming and tedious bioassays.

Animals↗
PubMed2000

[Retardation of platelet recovery after autologous stem cell transplantation in a patient with acute lymphoblastic leukemia: possible role of decreased thrombopoietin production by bone marrow stromal cells].

A 16-year-old boy was diagnosed as having acute lymphoblastic leukemia and underwent autologous stem cell transplantation at the time of his second complete remission. Retardation of platelet recovery was evident at day 90 (< 5 x 10(4)/microliter), and at day 660 after transplantation the platelet count was 8.5 x 10(4)/microliter. Neutrophils and RBCs showed only slightly retarded recovery. Bone marrow stromal cells, which are thought to play an integral role in megakaryopoiesis, were examined. Although TPO mRNA expression per cell was normal, CFU-F was significantly decreased, resulting in a decrease of total TPO mRNA expression. In contrast, expression of G-CSF mRNA per cell was increased. It was thought that chemotherapy before bone marrow transplantation may have reduced the number of stromal cells, leading to retardation of platelet recovery because of low TPO expression.

Adolescent↗
PubMed1999

Inorganic polyphosphate kinase is required to stimulate protein degradation and for adaptation to amino acid starvation in Escherichia coli.

Inorganic polyphosphate (polyP) kinase was studied for its roles in physiological responses to nutritional deprivation in Escherichia coli. A mutant lacking polyP kinase exhibited an extended lag phase of growth, when shifted from a rich to a minimal medium (nutritional downshift). Supplementation of amino acids to the minimal medium abolished the extended growth lag of the mutant. Levels of the stringent response factor, guanosine 5'-diphosphate 3'-diphosphate, increased in response to the nutritional downshift, but, unlike in the wild type, the levels were sustained in the mutant. These results suggested that the mutant was impaired in the induction of amino acid biosynthetic enzymes. The expression of an amino acid biosynthetic gene, hisG, was examined by using a transcriptional lacZ fusion. Although the mutant did not express the fusion in response to the nutritional downshift, Northern blot analysis revealed a significant increase of hisG-lacZ mRNA. Amino acids generated by intracellular protein degradation are very important for the synthesis of enzymes at the onset of starvation. In the wild type, the rate of protein degradation increased in response to the nutritional downshift whereas it did not in the mutant. Supplementation of amino acids at low concentrations to the minimal medium enabled the mutant to express the hisG-lacZ fusion. Thus, the impaired regulation of protein degradation results in the adaptation defect, suggesting that polyP kinase is required to stimulate protein degradation.

Adaptation, Physiological↗
PubMed1999

Induction of S phase by G1 regulatory factors.

The first gap phase (G1) in the mammalian cell cycle plays a pivotal role in determining whether or not cells are to initiate DNA replication. Progression through G1 phase and transition into S phase are positively and negatively regulated by a series of factors, collectively termed G1 regulators. Among them, D-type G1 cyclins and a Cdk inhibitor, p27Kip1, function as the target of growth factors to integrate extracellular signals into cell cycle regulators. Another G1 cyclin, cyclin E, and a transcription factor E2F are situated the furthest downstream of known G1 regulators and seem to be directly involved in the initiation of chromosomal DNA replication. Alterations in G1 regulator genes are often present in human tumors, indicating that G1 regulators participate in tumor suppressive mechanisms as well as in cell proliferation.

Animals↗
PubMed1999

Transforming growth factor-beta1 (TGF-beta1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-beta receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-beta itself with high specificity.

The present study was designed to test the concept that platelets release a humoral factor that plays a regulatory role in megakaryopoiesis. The results showed that, among various hematoregulatory cytokines examined, transforming growth factor-beta1 (TGF-beta1) was by far the most potent enhancer of mRNA expression of bone marrow stromal thrombopoietin (TPO), a commitment of lineage specificity. The TPO, in turn, induced TGF-beta receptors I and II on megakaryoblasts at the midmegakaryopoietic stage; at this stage, TGF-beta1 was able to arrest the maturation of megakaryocyte colony-forming units (CFU-Meg). This effect was relatively specific when compared with its effect on burst-forming unit-erythroid (BFU-E) or colony-forming unit-granulocyte-macrophage (CFU-GM). In patients with idiopathic thrombocytopenic purpura (ITP), the levels of both TGF-beta1 and stromal TPO mRNA were correlatively increased and an arrest of megakaryocyte maturation was observed. These in vivo findings are in accord with the aforementioned in vitro results. Thus, the results of the present investigation suggest that TGF-beta1 is one of the pathophysiological feedback regulators of megakaryopoiesis.

Bone Marrow↗
PubMed1999

Conformational multiplicity of the antibody combining site of a monoclonal antibody specific for a (6-4) photoproduct.

The antigen binding site of monoclonal antibody 64M5, which possesses a high degree of affinity for DNA containing pyrimidine (6-4) pyrimidone photoproducts, were investigated by use of stable-isotope-assisted NMR spectroscopy. A variety of 64M5 Fab fragments specifically labeled with 13C and 15N at backbone amide groups were prepared. Extensive assignments of amide resonances originating from the variable region of 64M5 were made by using 2D-HN(CO) measurements along with recombination of the heavy and light chains of 64M5. On the basis of chemical shift changes of the amide resonances caused upon addition of d(T[6-4]T) and d(GTAT[6-4]TATG), the binding sites of 64M5 Fab for the (6-4) photodimer and for the oligodeoxynucleotides flanking it were identified. It was revealed that the L1 and L3 segments, which are responsible for the binding to (6-4) photodimer, exhibit conformational multiplicities in the absence of antigens, and take different conformations between the d(T[6-4]T) and d(GTAT[6-4]TATG)-bound forms. On the basis of spectral comparison with another Fab fragment with a similarity in the amino acid sequence of the VL domain of 64M5, we suggest that the conformational multiplicities observed in the present study is caused by a substitution of an amino acid residue at the position of a key residue in L3 canonical structure, which leads to a preferable effect on the antigen binding, and by a specific combination of L1 and L3 canonical structures.

Amino Acid Sequence↗
PubMed1999

Apoptosis induced by the myelodysplastic syndrome-associated NPM-MLF1 chimeric protein.

The NPM-MLF1 chimeric protein is produced by the t(3;5)(q25.1;q34) chromosomal translocation, which is associated with myelodysplastic syndrome (MDS) prior to progression into acute myeloid leukemia (AML). Here we report that K562 human leukemia cells ectopically expressing NPM-MLF1, but not those with wild-type MLF1, were gradually eliminated from the culture by undergoing apoptosis. NIH3T3 mouse fibroblasts engineered to overexpress NPM-MLF1 grew normally but serum deprivation triggered apoptotic cell death with slower kinetics than did other well-known apoptotic inducers such as c-Myc or E2F-1. Quantitative analysis of apoptotic induction confirmed that, neither NPM nor MLF1, but the NPM-MLF1 fusion protein was able to induce apoptosis. Analyses using a variety of deletion mutants of NPM-MLF1 revealed that induction of apoptosis required the N-terminal domain of MLF1 and the NPM domain containing nuclear localization signal and that removal of the NPM dimerization domain markedly impaired the ability to induce apoptosis. Co-expression of Bcl-2 rescued NIH3T3 fibroblasts from NPM-MLF1-mediated cell death without affecting the expression level or the subcellular localization of NPM-MLF1 and enabled cells to progress into S phase in low serum. These findings provide an NPM-MLF1-mediated novel mechanism of apoptotic induction and imply that NPM-MLFI in collaboration with anti-apoptotic oncoproteins may play an important role in multi-step progression from MDS to AML.

3T3 Cells↗
PubMed1999

Mechanism of DNA gyrase-mediated illegitimate recombination: characterization of Escherichia coli gyrA mutations that confer hyper-recombination phenotype.

To study the mechanism of DNA gyrase-mediated illegitimate recombination in Escherichia coli, we isolated temperature-sensitive gyrA mutants that confer spontaneous illegitimate recombination and spontaneous induction of lambda prophage at higher frequencies than that in the wild-type. After reconstruction of single mutations by targeted mutagenesis, we confirmed that two single mutations, gyrAL492P and gyrAL488P, and a double mutation, gyrAI203V+gyrAI205V, show the same properties as those described above. With respect to the phenotypes of hyper-recombination and higher induction of lambda prophage, these mutations were dominant over the wild-type. Analysis of recombination junctions of lambdabio transducing phages formed spontaneously in these mutants showed that the parental E. coli bio and lambda recombination sites have a homologous sequence of only 0. 7 base-pair on average, indicating that homology is not required for this illegitimate recombination. Analysis of nucleotide sequences of mutant gyrA genes revealed that the gyrAL492P and gyrAL488P mutations contain amino acid substitutions of Leu492-->Pro and Leu488-->Pro, respectively, which correspond to the alpha18 helix in the breakage-reunion domain of DNA gyrase A subunit. The gyrAI203V and gyrAI205V mutations contain Ile203-->Val and Ile205-->Val, respectively, which correspond to the alpha10' helix, also in the breakage-reunion domain of DNA gyrase A subunit. Biochemical analysis indicated that the GyrA63 protein that contains the L492P mutation has an apparently normal supercoiling activity, but it also produces a small amount of linear DNA in the absence of DNA gyrase inhibitor during the supercoiling reaction, suggesting that the mutant DNA gyrase may have a defect at the step of religation or a defect in the subunit interaction. These results suggest that the recombination is induced by defects of religation and/or dimer formation in the mutant DNA gyrases, implying that two alpha helices, alpha10' and alpha18, of DNA gyrase A subunit have crucial roles in subunit interaction and/or resealing of DNA.

Alleles↗
PubMed1999

p19ARF prevents G1 cyclin-dependent kinase activation by interacting with MDM2 and activating p53 in mouse fibroblasts.

p19ARF encoded by the INK4a tumor suppressor gene locus functions upstream of p53 to induce cell cycle arrest. p19ARF can interact with MDM2 and p53 in cells ectopically overexpressing these three components, but the biochemical cascades from p19ARF to cell cycle arrest has not been fully elucidated. In this study, we generated stably transfected NIH3T3 cells that express exogenous p19ARF under the control of a heavy metal-inducible metalothionine promoter. Cells arrested in G1 by ectopically expressed p19ARF contained considerably reduced G1 cyclin dependent kinase (cdk2 and cdk4) activities. The expression of cyclin A (a regulatory subunit of cdk2) markedly decreased, while cyclin D1, the major cdk4 partner in fibroblasts, expressed at a slightly higher level and formed complexes with cdk2 and cdk6 in addition to cdk4. Induction of p19ARF activated p53 by increasing its stability, and allowed the expression of p21Cip1, which bound to all of the cyclin D1-cdk complexes (cyclin D1-cdk2, -cdk4, and -cdk6) thereby inhibiting their kinase activities. p19ARF formed complexes with several cellular proteins including mouse MDM2. The majority of MDM2 was found in the complex with p19ARF, while no p53 was detected in association with p19ARF. Thus, we propose that p19ARF neutralizes MDM2 by sequestration from p53, which results in activation of p53, inhibition of G1 cyclin-cdk activities, and G1 arrest.

3T3 Cells↗