Biomedical subjects

A Kida

Publications and source records attributed to A Kida.

At least 19 recordsLinked to original sources

PubMed2006

Rottlerin synergistically enhances imatinib-induced apoptosis of BCR/ABL-expressing cells through its mitochondrial uncoupling effect independent of protein kinase C-delta.

Although the BCR/ABL tyrosine kinase inhibitor imatinib is highly effective for treatment of chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (ALL), relapse with emerging imatinib-resistance mutations in the BCR/ABL kinase domain poses a significant problem. Here, we demonstrate that rottlerin, a putative protein kinase C-delta (PKCdelta)-specific inhibitor, acts synergistically with imatinib to induce apoptosis of BCR/ABL-expressing K562 and Ton.B210 cells. However, rottlerin inhibited neither PKCdelta nor BCR/ABL in these cells. On the other hand, rottlerin, previously characterized also as a mitochondrial uncoupler, transiently but significantly reduced mitochondrial membrane potential and gradually induced mitochondrial membrane permeabilization. Moreover, two other mitochondrial uncouplers, FCCP and DNP, very similarly induced apoptosis of BCR/ABL-expressing cells in a synergistic manner with imatinib. Imatinib synergistically enhanced mitochondrial membrane permeabilization induced by mitochondrial uncouplers, which led to release of cytochrome c into the cytoplasm and activation of caspases-3 and -9. Rottlerin also enhanced the cytotoxic effect of imatinib in leukemic cells from patients with CML blast crisis and Ph-positive ALL or a cell line expressing the imatinib-resistant E255K BCR/ABL mutant. The present study indicates that rottlerin synergistically enhances imatinib-induced apoptosis through its mitochondrial uncoupling effect independent of PKCdelta and may contribute to the development of new treatment strategy to overcome the imatinib resistance and to cure the BCR/ABL expressing leukemias.

Acetophenones↗

PubMed2006

Calcium carbonate deposition in a cell wall sac formed in mulberry idioblasts.

Although calcium carbonate is known to be a common biomineral in plants, very little attention has been given to the biological control of calcium carbonate deposition. In mulberry leaves, a subcellular structure is involved in mineral deposition and is described here by a variety of cytological techniques. Calcium carbonate was deposited in large, rounded idioblast cells located in the upper epidermal layer of mulberry leaves. Next to the outmost region ("cap") of young idioblasts, we found that the inner cell wall layer expanded to form a peculiar outgrowth, named cell wall sac in this report. This sac grew and eventually occupied the entire apoplastic space of the idioblast. Inside the mature cell wall sac, various cellulosic membranes developed and became the major site of Ca carbonate deposition. Concentrated Ca2+ was pooled in the peripheral zone, where small Ca carbonate globules were present in large numbers. Large globules were tightly packed among multiple membranes in the central zone, especially in compartments formed by cellulosic membranes and in their neighboring membranes. The maximum Ca sink capacity of a single cell wall sac was quantified using enzymatically isolated idioblasts as approximately 48 ng. The newly formed outgrowth in idioblasts is not a pure calcareous body but a complex cell wall structure filled with substantial amounts of Ca carbonate crystals.

Calcium↗

PubMed2005

Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer.

The purpose of this study was to determine the feasible adjuvant therapy administration schedule of S-1 for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients receiving definitive treatments were randomly assigned to either arm A (51 cases) receiving oral S-1 of 2-week administration followed by 1-week rest for 6 months, or arm B receiving S-1 of 4-week administration followed by 2-week rest for 6 months. Planned treatment was given in 40% of patients in arm A and 29% in arm B. The cumulative rates of the relative total administration dose of S-1 at 100% were 54.9% (95% CI: 40.1-69.7%) in arm A and 34.3% (95% CI: 21.1-47.4%) in arm B, respectively (P=0.054). Adverse events were recorded in 41 patients (82.0%) in arm A and 48 patients (94.1%) in arm B (P=0.060). The incidences of diarrhoea (10 vs 28%; P<0.05) and skin toxicities (18 vs 37%; P<0.05) were significantly higher in arm B. One-year disease-free survival was similar in both arms: arm A 81.2% (95% CI: 70.0-92.4%); arm B 77.0% (95% CI: 65.0-89.0%). The schedule of 2-week administration followed by 1-week rest seems to be more feasible for oral 6-month administration of S-1 in adjuvant chemotherapy of locoregionally advanced SCCHN.

Administration, Oral↗

PubMed2001

Use of digital subtraction fluoroscopy to diagnose radiolucent aspirated foreign bodies in infants and children.

OBJECTIVES: Most tracheobronchial foreign bodies in children are radiolucent, and accurate diagnosis of such foreign bodies is not always easy. This can result in delay of diagnosis or misdiagnosis of foreign body aspiration. We report the usefulness and pitfalls of use of digital subtraction fluoroscopy (DSF) to diagnose radiolucent aspirated foreign bodies in infants. METHODS: From 1991 through 1999, DSF was conducted for a total of 19 patients (ranged from 11 months to 4 years and 7 months in age (mean 1.8+/-0.9 years)) who were suspected to have radiolucent aspirated foreign bodies. Since DSF revealed abnormal findings in a trachea or main bronchus in 18 cases, inspection was performed for foreign body bronchofiberscopically. In the one remaining case, no abnormality was recognized on DSF, but since the symptoms at the time of onset strongly suggested aspirated foreign body, bronchofiberscopy was also performed. RESULTS: Foreign body was verified bronchoscopically in 13 of 19 cases, and all 13 (100%) had abnormal findings on DSF, including obstruction of the trachea in two, obstruction of the bronchial lumen in nine, and indistinct visualization of the bronchial lumen in two. Bronchial stenosis was verified bronchoscopically in five of the remaining six cases, including mucus plug in three, granuloma in one and mucosal edema in one case. All five patients (100%) had abnormal findings on DSF, including obstruction of the bronchial lumen in four and indistinct visualization of the bronchial lumen in one. In the one remaining patient with normal findings of DSF, no foreign body or pathological bronchial changes were noted. CONCLUSIONS: DSF was very sensitive in the diagnosis of foreign body aspiration and stenotic changes in the bronchial lumen. However, its diagnostic specificity for aspirated foreign body itself was not high (17%). Therefore, when abnormalities are found on DSF, we recommend to perform flexible bronchofiberscopy initially under general anesthesia via a tracheal tube. When a foreign body is verified, rigid ventilation bronchoscopy is successively performed to retrieve the foreign body.

Bronchi↗

PubMed2001

Blepharismins, produced by the protozoan, Blepharisma japonicum, form ion-permeable channels in planar lipid bilayer membranes.

Blepharismins are polycyclic quinones found in the pigment granules of the ciliated protozoan, Blepharisma. Exposure to purified blepharismins results in lethal damage to several other ciliates. We here report that, at cytotoxic concentrations, blepharismins formed cation-selective channels in planar phospholipid bilayer membranes. The channels formed in a diphytanoylphosphatidylcholine bilayer had a K(+)/Cl(-) permeability ratio of 6.6:1. Single channel recordings revealed the conductance to be quite heterogeneous, ranging from 0.2 to 2.8 nS in solutions containing 0.1 M KCl, possibly reflecting different states of aggregation of blepharismin. Our observations suggest that channel formation is a cytotoxic mechanism of blepharismin's action against predatory protozoa.

Animals↗

PubMed2001

CD7+ near-tetraploid acute myeloblastic leukemia M2 with double t(8;21)(q22;q22) translocations and Aml1/ETO rearrangements detected by fluorescence in situ hybridization analysis.

Near-tetraploidy is a rare cytogenetic abnormality observed in acute myeloblastic leukemia (AML). It was recently suggested that near-tetraploid AML may be associated specifically with t(8;21)(q22;q22). We report here a new case of near-tetraploid AML with double t(8;21)(q22;q22) translocations. A 61-year-old woman was admitted to our hospital because of high fever and pancytopenia. Her bone marrow was markedly hypercellular, with 72% giant and bizarre myeloblasts. These myeloblasts were positive for CD7, CD13, CD19, CD33, CD34, and HLA-DR but negative for CD2 and CD56. The patient's disease was diagnosed as the M2 subtype of AML (by French-American-British classification). Chromosome analysis revealed a karyotype of 45,X,-X, t(8;21) (q22;q22)[1]/90,XXX,-X,t(8;21)(q22;q22)x2,-9[7]/46,XX[12]. Fluorescence in situ hybridization (FISH) analysis with an AML1/ ETO probe detected 4 fusion signals on 2 der(8)t(8;21) and 2 der(21)t(8;21) in near-tetraploid cells. Reverse transcription-polymerase chain reaction analysis revealed the presence of the AML1/ETO fusion transcript. These findings suggested that near-tetraploidy may be a secondary genetic change originating from a diploid clone with t(8;21) and that 2 AML1/ETO fusion genes are generated on the der(8)t(8;21) in near-tetraploid clones. Consideration of the other reported cases suggests that the immunophenotypes of near-tetraploid AML with double t(8;21) are heterogenous, but it is possible that t(8;21)-AML with expression of CD2 or CD7 may be associated with a secondary clonal evolution to near-tetraploidy.

Antigens, CD7↗

PubMed2001

Deletion of 16q11 is a recurrent cytogenetic aberration in acute myeloblastic leukemia during disease progression.

Abnormalities of chromosome 16 other than inv(16)(p13q22), t(16;16)(p13;q22), and del(16)(q22) have not been fully characterized in acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS). We report here the first case of AML with del(16)(q11) as a sole abnormality. A 53-year-old woman was initially diagnosed as MDS, refractory anemia with excess of blasts in transformation with normal karyotype. After sixteen months, the disease progressed to overt AML-M1. Myeloblasts were positive for CD13, CD33, and CD34, but negative for HLA-DR. Chromosome analyses of the bone marrow cells showed 46,XX,del(16)(q11) in all metaphase spreads. Multicolor spectral karyotyping also confirmed that del(16)(q11) was not derived from a cryptic translocation, but a simple deletion. Our results, together with three previously reported cases, suggest that del(16)(q11) may be one of the recurrent aberrations in AML and that it could be associated with clonal evolution or disease progression.

Adolescent↗

PubMed2001

A morphological study of age changes in adult human auricular cartilage with special emphasis on elastic fibers.

OBJECTIVE: It is well known that the size of the human auricle increases after it has finished development. The reason why the size of the human auricle continues to enlarge until advanced age after reaching adulthood was investigated by observation of the ultrastructure of elastic fibers in human auricular cartilage. METHODS: A total of 1958 subjects (966 males and 992 females) were classified into 18 age groups from 0 to 5 years up to 85 years and above by 5-year intervals. Ear length, ear width, and length of ear attachment were measured with calipers. Human auricular cartilage was obtained from 26 subjects (16 males and 10 females) aged 14 to 79 years, stained by orcein, and examined by light and electron microscopy. RESULTS: Each item of measurement of human auricular size increased significantly with age in both males and females. On morphological examination by light and electron microscopy after orcein staining, elastic fibers in the cartilage were almost homogeneous in diameter and surrounded the cartilage lacuna in bundle-like fashion in young persons, whereas those in elderly persons were heterogeneous in thickness and had many fragments surrounding the territorial matrix. In elderly persons, collagen-like fibers and small vesicles with heterogeneous electron density were frequently observed near elastic bundles around the territorial matrix. CONCLUSION: Structural changes of auricular cartilage associated with morphological age changes of elastic fibers may be one of the causes of expansion of the auricle after reaching adulthood.

Adolescent↗

PubMed2001

[Anthropometric study on normal human auricle in Japan].

OBJECTIVE: Japanese people are physically larger and live longer than in the past. In light of these changes, we studied anthropometric auricular morphology in Japanese people in all age groups. METHODS: Subjects were 1,958 healthy Japanese people with no ear disease, 966 males aged 0-94 years and 992 females aged 0-99 years. They were classified at 5-year intervals into 18 age groups, and each group consisted of 50-72 persons. Bilateral size of auricles (ear length, ear width, length of ear attachment, auricular cartilage length, and auricular lobe length) were measured in the usual manner. All measurements were made with calipers by a single observer. RESULTS: Larger values were obtained in males than in females in almost all age groups. Rapid growth was observed until late teenage, and significant growth continued thereafter until advanced age. Auricular size was found to be greater than that in Japanese people in the past. CONCLUSIONS: In addition to changes in auricular size believed attributable to growth until late teenage, age-associated changes appear to continue during adulthood.

Adolescent↗

PubMed2001

Primary stages in photosignal transduction leading to step-up photophobic response in the unicellular eukaryote Blepharisma japonicum.

In order to elucidate the primary stage in the blepharismin phototransduction pathway, changes in the molecular structure of light-exposed blepharismins and oxyblepharismins, were examined. When exposed to light, blepharismins (pink form) were converted into oxyblepharismins (blue form) or dissociated into stentorins/p-hydroxybenzaldehyde with an O2-requiring process, whereas light-exposed oxyblepharismins were not dissociated into stentorins/p-hydroxybenzaldehyde. Since both blepharismins and oxyblepharismins can activate the phototransduction chain leading to the step-up photophobic response presumably through the same pathway, dissociation of p-hydroxybenzaldehyde may not be involved in signal transduction. The fact that the step-up photophobic response requires O2, and both blepharismins and oxyblepharismins produce hydroxyl (OH) radicals probably derived from O2 implies that OH radicals may activate the photosignalling pathway. The step-up photophobic response was not suppressed by a spin trapping reagent for hydroxyl radicals. Other possible primary responses leading to the step-up photophobic response are discussed.

Animals↗

PubMed2001

[Late phase II study of S-1 in patients with advanced head and neck cancer].

A late phase II clinical study of S-1, a novel oral antitumor agent of fluorinated pyrimidines, in patients with advanced/recurrent head and neck cancer was conducted in 25 institutions across Japan as a multi-institutional cooperative study from August 1995 to March 1998. Out of 59 eligible patients, the objective responses were 4 complete responses (CR) and 13 partial responses (PR). The response rate was 28.8% (17/59, 95% CI: 17.8-42.1%). The response rate in previously treated patients was 28.3% (15/53), whereas that in treatment naive patients was 33.3% (2/6). The response rate in patients with prior chemotherapy was 26.7% (12/45). Major adverse reactions of grade 2 or more were anemia (25.4%, 15/59), leucopenia (22.0%, 13/59), neutropenia (25.4%, 15/59), thrombocytopenia (3.4%, 2/59), anorexia (6.8%, 4/59), nausea/vomiting (1.7%, 1/59), stomatitis (1.7%, 1/59), skin symptoms including eruptions or desquamation (5.1%, 3/59), and malaise (1.7%, 1/59). Grade 4 anemia was observed in one case; however, this returned to the normal level after the termination of drug administration and the blood transfusion. Therefore, this event was confirmed to be reversible. Based on these results, we conclude that S-1 is an active agent for the treatment of advanced/recurrent head and neck cancer.

Administration, Oral↗

PubMed2000

Immunochemical analysis of a photoreceptor protein using anti-IP3 receptor antibody in the unicellular organism, Blepharisma.

The blepharismin-200 kD protein complex of the ciliated protozoan Blepharisma is a novel type of photosensor responsible for the step-up photophobic response of the cell. In immunoblotting assays, the 200 kD protein is weakly cross-reacted with anti-inositol triphosphate receptor antibody (anti-IP3 R antibody). Indirect immunofluorescence assays show that the pigment granules in which the blepharismin-200 kD protein complex is localized are labelled by anti-IP3 R antibody. When the anti-IP3 R antibody or antisense oligonucleotide for IP3 receptor is introduced into the living cells of Blepharisma, both the photosensitivity of the cells and content of blepharismin-200 kD protein are reduced. The results suggest that the photoreceptor 200 kD protein is possibly an IP3 receptor-like protein.

Amino Acid Sequence↗

PubMed1999

The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro.

UNLABELLED: The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. IMPLICATIONS: The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.

Adrenergic alpha-Agonists↗

PubMed1999

[Acute otitis media associated with bone conduction hearing loss].

Eleven patients (12 ears) with acute otitis media associated with raised bone conduction were studied. The patients were from 19 to 70 years old and came to our hospital between November 1996 through May 1997. Pure tone audiometry revealed mixed hearing loss, but there was no bullous myringitis in all cases. They were treated by oral or intravenous antibiotics, steroids, and myringotomy. Bacteriological examination was done in seven cases, and revealed penicillin resistant Streptococcus pnumoniae in three cases. Complete recovery of hearing loss was obtained in 10 of 12 ears, but sensorineural hearing loss remained in 2 patients. Bacteriological examination and pure tone audiometry in acute otitis media are important for detecting the severity of the disease, determining the administration of steroids, and for the selection of antibiotics.

Acute Disease↗

PubMed1999

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Adenocarcinoma↗

PubMed1998

Synthesis of (+/-)-cassumunins A and B, new curcuminoid antioxidants having protective activity of the living cell against oxidative damage.

A chemical synthesis of cassumunins A (1) and B (2), natural curcuminoid antioxidants, was developed. The synthesis was started from o-vanillin and after nine reaction steps resulted in 20% and 26% overall yields of 1 and 2, respectively. The synthetic cassumunins showed stronger protective activity than curcumin against oxidative cell death induced by hydrogen peroxide in a rat thymocyte system.

Animals↗

PubMed1998

Evaluation of expiratory effort on dysphonic patients on increasing vocal intensity.

It is conceivable that the subjects who have phonatory disorders, in comparison with normal individuals, exert a greater expiratory effort when phonating loudly. Furthermore, we presume that the extent and pattern of the changes in the expiratory effort for increasing vocal intensity may vary according to the types of laryngeal lesions. To prove these hypotheses, we investigated the changes in expiratory effort for increments of the vocal intensity by measuring the expiratory lung pressure. The subjects included 10 each of normal controls, patients with Reinke's edema, and those with recurrent laryngeal nerve paralysis. For the normal controls, the increase in vocal intensity was achieved by slightly increasing the expiratory lung pressure. The patients with Reinke's edema showed a greater increase in expiratory lung pressure, as compared with the normal group. The patients with recurrent laryngeal nerve paralysis exhibited greater expiratory effort with extreme increases in airflow than normal group for louder phonation. It was concluded that the subjects who have phonatory disorders, in comparison with normal individuals, require a greater expiratory effort. This phonatory function test with an increase in voice intensity made the aerodynamic pathologic condition clearer.

Adult↗

PubMed1998

[Early phase II study of S-1 in patients with advanced head and neck cancer. S-1 Cooperative Study Group (Head and Neck Working Group)].

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.

Administration, Oral↗