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Biomedical subjects

N Katayama

Publications and source records attributed to N Katayama.

At least 109 records · Page 6Linked to original sources

Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigen-expressing leukemia.

We describe very uncommon phenotypic and cytogenetic findings in a 40-year-old female with blast phase of Philadelphia chromosome (Ph)-positive CML. In addition to the t(9;22)(q34;q11) that was detected in all metaphases, a t(11;17)(q23;q21) was identified in 15 of 20 metaphases. Reverse transcription-polymerase chain reaction showed the major and minor bcr/abl fusion transcripts in the cells from a bone marrow (BM) sample. Fluorescence in situ hybridization (FISH) analysis also showed that fusion signals of the bcr and abl probes were found in 95% of blastic cells and in 64% of neutrophils. MLL gene rearrangement was also detected in some blastic cells but not in neutrophils by FISH analysis. Phenotypically, blastic cells expressed mixed lineage antigens such as CD34, CD33, CD13, CD19, CD7, and CD41. Immunogenotypically, some population of BM cells showed monoclonal rearrangements of immunoglobulin heavy chain and T-cell receptor gamma chain genes by Southern blot analysis. Clinical course was aggressive, and therapy was poorly tolerated. Such findings seem to support an association between Ph and an abnormality of 11q23 with poor prognosis, and suggest that the expression of both abnormal genes may be related to this mixed lineage antigen-expressing leukemia.

Adult↗

Measurement of the CP violation parameter sin2 phi(1) in B(0)(d) meson decays.

We present a measurement of the standard model CP violation parameter sin2 phi(1) (also known as sin2beta) based on a 10.5 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) collider. One neutral B meson is reconstructed in the J/psiK(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psiK(L), or J/psipi(0) CP-eigenstate decay channel and the flavor of the accompanying B meson is identified from its charged particle decay products. From the asymmetry in the distribution of the time interval between the two B-meson decay points, we determine sin2 phi(1) = 0.58(+0.32)(-0.34)(stat)+0.09-0.10(syst).

Journal Article↗

Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine released from T-cells and macrophages. Although a detailed understanding of the biological functions of MIF has not yet been clarified, it is known that MIF catalyzes the tautomerization of a nonphysiological molecule, D-dopachrome. Using a structure-based computer-assisted search of two databases of commercially available compounds, we have found 14 novel tautomerase inhibitors of MIF whose K(i) values are in the range of 0.038-7.4 microM. We also have determined the crystal structure of MIF complexed with the hit compound 1. It showed that the hit compound is located in the active site of MIF containing the N-terminal proline which plays an important role in the tautomerase reaction and forms several hydrogen bonds and undergoes hydrophobic interactions. A crystallographic study also revealed that there is a hydrophobic surface which consists of Pro-33, Tyr-36, Trp-108, and Phe-113 at the rim of the active site of MIF, and molecular modeling studies indicated that several more potent hit compounds have the aromatic rings which can interact with this hydrophobic surface. To our knowledge, our compounds are the most potent tautomerase inhibitors of MIF. One of these small, drug-like molecules has been cocrystallized with MIF and binds to the active site for tautomerase activity. Molecular modeling also suggests that the other hit compounds can bind in a similar fashion.

Binding Sites↗

Efficient ex vivo generation of human dendritic cells from mobilized CD34+ peripheral blood progenitors.

We tried to efficiently generate human dendritic cells (DCs) from CD34+ peripheral blood hematopoietic progenitor cells mobilized by high-dose chemotherapy and subsequent administration of granulocyte colony-stimulating factor, using a liquid suspension culture system. Among various combinations, the combination of c-kit ligand, flt-3 ligand, c-mpl ligand (TPO), and interleukin (IL)-4 most potently generated the number of CD1a+CD14- DCs in cultures containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The delayed addition of IL-4 on day 6 of culture gave rise to an additional increase in the yield of CD1a+CD14-DCs that were characterized by the expression of HLA-ABC, HLA-DR, CD80, CD86, and CD83. The majority of the sorted CD1a-CD14+ cells derived from 6-day culture of CD34+ cells gave rise to CD1a+CD14- DCs and CD1a-CD14+ macrophages on day 12 of culture in the presence and absence of IL-4, respectively. These findings suggest that IL-4 promotes the differentiation of CD1a- CD14+ cells derived from mobilized CD34+ peripheral blood hematopoietic progenitors to CD1a+ CD14- DCs. The majority of these DCs expressed CD68 but not the Langerhans-associated granule antigen, a finding that suggests they emerge through the monocyte differentiation pathway. The addition of TPO and IL-4 to cultures did not affect the potential of DCs to stimulate the primary allogeneic T-cell response. These findings demonstrated that the combination of c-kit ligand plus flt-3 ligand plus TPO with GM-CSF plus TNF-alpha, followed by IL-4, is useful for ex vivo generation of human DCs from mobilized CD34+ peripheral blood progenitors.

Antigens, CD1↗

Directional asymmetry of nystagmus elicitation in humans during step and sinusoidal modes of lateral linear acceleration.

We investigated nystagmus elicitation in 50 normal subjects who were exposed interaurally to linear acceleration with step (rectangular) and sinusoidal modes of oscillation using a linear accelerator. Relatively strong G-loads of 0.3-0.5 G at a 10 m stroke were applied to subjects who looked at a memorized target in darkness, with the head and trunk tightly restrained in the upright sitting position. Horizontal and vertical eye movements were recorded by electrooculography (EOG). Various levels of G-directional preponderance (DP), including completely one-sided, were observed similarly in either stimulus mode, strongly suggesting that directional asymmetry in nystagmus elicitation may be a functional characteristic in the otolith-ocular response, in contrast to the canal-ocular response. The effects of G-load increase were less congruent between the two stimulus modes. In the step-mode oscillation, the desaccaded slow eye position which corresponds to the vestibuloocular reflex (VOR) was saw-toothed in shape as was the stimulus velocity curve, but the baseline often drifted slowly and DP-dependently in the direction opposite to the fast phase of nystagmus. When the slow phase velocity (SPV), a slope of the saw-tooth, was adjusted mathematically for such slow drift, it revealed that the adjusted SPVs were almost symmetrical between rightward and leftward G-directions. These results suggest that DP generation is separate from VOR generation which is primarily symmetrical.

Acceleration↗

Successful treatment with low-dose splenic irradiation for massive splenomegaly in an elderly patient with hairy-cell leukemia.

The therapeutic approach to hairy-cell leukemia (HCL) is in some instances still debated. Although management with alpha-interferon and purine analogues is well established, there is an alternative role for therapeutic splenectomy in patients with massive splenomegaly who have failed to respond to systemic therapy. Most patients with HCL will not be suitable for treatment with splenectomy as their ages at diagnosis are high. Here, we report an elderly Japanese HCL patient whose refractory massive splenomegaly responded well to low-dose splenic irradiation.

Aged↗

Successful autologous peripheral blood stem cell transplantation for relapsed intravascular lymphomatosis.

We describe a case of relapsed intravascular lymphomatosis (IVL) successfully treated with autologous PBSCT. A 59-year-old Japanese female patient with IVL who had achieved CR after six courses of biweekly CHOP therapy developed lymphoma. She achieved a second CR after six courses of modified biweekly CHOP therapy, followed by autologous PBSCH and high-dose chemotherapy (CBDCA, VP-16, MCNU, CY) with PBSCT. There has not been any evidence of recurrence 48 months after PBSCT. Our case suggests that PBSC is acceptable as a source for stem cell rescue in IVL.

Antigens, CD34↗

Aggressive neoplastic plasma cell growth with MLL gene rearrangement after high-dose therapy with autologous stem cell support for multiple myeloma.

We report a case of a patient with IgA kappa multiple myeloma (MM) mobilized with etoposide and subsequently receiving high-dose melphalan (HDM) with stem cell support. She relapsed rapidly post transplantation. Southern blot and fluorescent in situ hybridization analysis showed MLL gene rearrangement in the myeloma cells, which was not detected in the sample at diagnosis or in the PBSC harvested with etoposide plus G-CSF. These observations suggest that clonal rearrangement of the MLL gene is caused by etoposide. Patients with MM undergoing HDM with stem cell rescue may be at an increased risk of not only secondary leukemia, but also secondary genetic abnormalities in myeloma cells, especially those receiving priming with etoposide for peripheral blood stem cell collection.

Antineoplastic Agents, Phytogenic↗

Efficient ex vivo generation of dendritic cells from CD14+ blood monocytes in the presence of human serum albumin for use in clinical vaccine trials.

Dendritic cells (DC) with the potential to induce anti-tumour immunity represent one of the promising candidates for cancer vaccines. Efficiency of ex vivo DC generation depends on culture conditions, especially protein components in the plasma or serum used. Using human serum albumin (HSA), we devised a constant and reproducible culture method for DC generation from peripheral blood CD14+ cells. The number of DC obtained with 2% HSA-supplemented cultures containing granulocyte-macrophage colony-stimulating factor and interleukin 4 were consistently higher than in cultures with various concentrations of autologous plasma or serum. The concentrations and time points tested for plasma or serum considerably affected the number of DC recovered. DC prepared with HSA acquired the ability to uptake dextran, and expressed high levels of major histocompatibility (MHC) and co-stimulatory molecules similar to DC cultured with autologous plasma or serum. Although DC cultured with autologous plasma or serum consisted of CD1a+ and CD1a- populations, DC differentiated in the presence of HSA expressed CD1a. DC obtained with HSA primed and induced immunogenic peptide-specific cytotoxic T lymphocytes against a tumour rejection antigen, HER2. These findings suggest that our method for preparation of DC with HSA should prove valuable in DC generation for immunotherapy.

Cancer Vaccines↗

Sensory neuropeptides are not involved in acetaldehyde-induced bronchoconstriction in guinea-pigs.

1. Alcohol-induced asthma is characterized by worsening of asthmatic symptoms after alcohol ingestion. Acetaldehyde, a metabolite of ethanol, is thought to be a main factor of alcohol-induced asthma. Although airway sensory nerves are known to be activated in asthma, there have been no studies investigating the role of tachykinins in the airway response to acetaldehyde. The purpose of the present study was to evaluate the involvement of tachykinins on acetaldehyde-induced bronchoconstriction in guinea-pigs. 2. After capsaicin desensitization or intravenous administration of 10 mg kg(-1) FK224, a NK1 and NK2 dual antagonist, airway responses to ascending doses (2.5-20 mg ml(-1)) of inhaled acetaldehyde was examined using a modified Konzett-Rössler method in guinea-pigs. 3. Inhalation of acetaldehyde induced bronchoconstriction in a dose-dependent manner. The FK224 failed to reduce the acetaldehyde-induced bronchoconstriction. Pretreatment with capsaicin did not alter the bronchoconstriction induced by acetaldehyde at a dose of 2.5-10 mg ml(-1). Pretreatment with capsaicin slightly, but significantly, inhibited bronchoconstriction induced by 20 mg ml(-1) of acetaldehyde. 4. The present results suggest that tachykinins are not involved in acetaldehyde-induced bronchoconstriction in guinea-pigs.

Acetaldehyde↗

Synchronization between hippocampal theta waves and PGO waves during REM sleep.

We investigated the temporal relationship between hippocampal theta waves (referred to as 'theta waves') and ponto-geniculo-occipital (PGO) waves in cats. We measured the time intervals between an occurrence of a PGO wave and the prior and posterior adjacent positive peaks of the theta wave. The unimodal distributions of these intervals suggested a close temporal relationship between PGO and theta waves (i.e. synchronization). In addition, the period of a theta wave during which a PGO wave occurred was not statistically different from that without a PGO wave. This result suggests that the synchronization found here is characterized by phase-locking rather than phase-resetting. Common mechanisms are suggested to underlie the generation of PGO and theta waves.

Animals↗

A circadian system model with feedback of cross-correlation between sleep-wake rhythm and oscillator.

Recent findings suggest that social entrainment factors work on an oscillator other than the temperature and melatonin rhythms. This indicates that there is a feedback loop affected on oscillators. In the present study, a circadian system model, including mutually coupled two oscillators and sleep-wake rhythm, is constructed, where cross-correlation between a sleep-wake rhythm and an oscillator is set to modify the coupling from one oscillator to the other. Based on the model simulation, a mechanism underlying delayed sleep phase syndrome is elucidated by the reduction in the cross-correlation resulting from dissociation between the delayed sleep phase and the oscillator.

Body Temperature↗

Effect of a cysteinyl leukotriene antagonist, pranlukast hydrate, on acetaldehyde-induced bronchoconstriction in asthmatic patients.

Acetaldehyde is a main factor of alcohol-induced asthma. We previously reported that the cysteinyl leukotriene (cys-LT) receptor antagonist, pranlukast hydrate, inhibits acetaldehyde-induced airway hyperresponsiveness in guinea pigs. The purpose of this study was to evaluate the involvement of cys-LT on bronchial responsiveness to acetaldehyde in asthmatic patients. We investigated the bronchial response to inhalation of acetaldehyde in 10 asthmatic patients, who were treated with placebo or pranlukast hydrate (225.5 mg), a cys-LT receptor antagonist, twice a day for 1 wk using a double-blind, randomized, placebo-controlled, cross-over design. Although a remarkable improvement of acetaldehyde bronchoconstriction was observed in 3 out of 10 subjects, PC(20)-AcCHO values were identical between placebo [12.0 (GSEM, 1.192) mg/ml] and pranlukast [14.7 (GSEM, 1.245) mg/ml] groups. The changes in bronchial responsiveness to acetaldehyde were similar in the six patients who had never experienced alcohol-induced asthma and the four who had. In conclusion, cys-LTs are not involved in acetaldehyde-induced bronchoconstriction.

Acetaldehyde↗

Muscle sympathetic outflow during horizontal linear acceleration in humans.

To elucidate the effects of linear acceleration on muscle sympathetic nerve activity (MSNA) in humans, 16 healthy men were tested in a linear accelerator. Measurements of MSNA, electrocardiogram, blood pressure, and thoracic impedance were undertaken during linear acceleration. Sinusoidal linear acceleration with peak values at +/-0.10, +/-0.15, and +/-0.20 G was applied in anteroposterior (+/-G(x), n = 10) or lateral (+/-G(y), n = 6) directions. The total activity and burst rate of MSNA decreased significantly during forward, backward, left, or right linear accelerations. The total activity of MSNA decreased to 50.5 +/- 6.9, 52.5 +/- 4.4, 71.2 +/- 9.6, and 67.6 +/- 8.2% from the baselines (100%) during linear accelerations with peak values at +/-0.20 G in the four directions, respectively. These results suggest that dynamic stimulation of otolith organs in horizontal directions in humans might inhibit MSNA directly in order to quickly redistribute blood to muscles during postural reflexes induced by passive movement, which supports the concept that the vestibular system contributes to sympathetic regulation in humans.

Acceleration↗

[Two cases of alimentary tract perforation owing to ingested foreign bodies: diagnosis by CT].

We report the CT diagnosis of two cases of alimentary tract perforation caused by the ingestion of foreign bodies. The first case was a common fish bone perforation of the ileum with postoperative scar. The second case was a rare perforation caused by the impact of an uncooked rice cake on sigmoid colon diverticula. Helical CT scan clearly revealed the fish bone as a linear high-density area in the soft tissue between the right abdominal oblique muscles and ileum, and demonstrated the rice cake as high-density material in the bowel.

Colon, Sigmoid↗

Effects of carbocysteine on antigen-induced increases in cough sensitivity and bronchial responsiveness in guinea pigs.

Carbocysteine is a mucoactive drug and is being used for both acute and chronic infectious airway diseases. Although carbocysteine can repair the damage of epithelial cells caused by exposure to various agents, the effects of this agent on allergic airway diseases such as asthma and eosinophilic bronchitis with an isolated chronic cough, in both of which epithelial damage may be characteristic, is not clear. We investigated the effects of carbocysteine on antigen-induced cough hypersensitivity to inhaled capsaicin at 48 h and bronchial hyperresponsiveness to inhaled methacholine at 72 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. After measuring bronchial responsiveness, we examined neutral endopeptidase (NEP) activity in the tracheal tissue. Carbocysteine (10, 30, or 100 mg/kg) was given intraperitoneally every 12 h for 3 days after antigen challenge. The number of coughs elicited by an aerosol of capsaicin (10(-4) M) was significantly (p < 0.01) decreased in carbocysteine groups (6.13 +/- 0.59 at 10 mg/kg, 4.88 +/- 0.67 at 30 mg/kg, and 4.50 +/- 0.33 at 100 mg/kg during 3 min measurement) compared with the control group (9.75 +/- 0.53). Furthermore, carbocysteine dose dependently repaired the antigen-induced decrease of NEP activity in the tracheal tissue, but it did not influence the bronchial hyperresponsiveness or bronchoalveolar lavage cell component. These findings suggest that carbocysteine promotes the repair of damaged epithelium by allergic reaction and may be useful in allergic airway diseases accompanied by isolated chronic coughing, especially eosinophilic bronchitis without asthma and tracheobronchitis with cough hypersensitivity.

Administration, Inhalation↗

Stability in velocity of otolith-ocular reflex with different stimulus frequencies during step-mode linear acceleration.

Velocity changes in the otolith-ocular reflex (OOR) during a step mode of lateral linear acceleration were examined by electrooculography (EOG) in 4 normal subjects. They were oscillated in darkness at a constant stimulus frequency of 0.175 Hz with 4 different G-levels between 0.2-0.4 G and at a constant G-level of 0.3 G with 4 different stimulus frequencies between 0.115-0.215 Hz. The OOR velocity was increased linearly by elevation of the G-level, though the increase varied considerably among subjects. On the other hand, changes in the stimulus frequency had minimal effect on the OOR velocity. The results indicate that the OOR response property is frequency-independent at a low stimulus-frequency range, even when the head was oscillated rectangularly instead of sinusoidally.

Acceleration↗