Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mechanisms and surface chemical prediction of imipramine-induced hemolysis suppressed by modified cyclodextrins.

The suppression of imipramine hydrochloride (IMP)- induced hemolysis by native cyclodextrins (alpha-, beta-, and gamma-CDs) and beta-CD derivatives is measured as a function of CD concentration and is quantitatively correlated with the surface tension of the solution determined at 37.0 degrees C. The modified beta-CDs are more or less adsorbed onto the air-water interface and occupy larger areas than the wider rim of beta-CD. The surface tension data at low CD concentrations in the presence of 3 mM IMP allow us to estimate the 1:1 binding constants of IMP with CDs. Both the capabilities of hemolysis suppression and surface tension elevation for 3 mM IMP are strong in the order carboxymethyl-beta-CD (CM) > beta-CD approximately equal to 6-O-glucosyl-beta-CD (G(1)) > gamma-CD > 2-hydroxypropyl-beta-CD (HP) > alpha-CD > or = 2,6-di-O-methyl-beta-CD (DM). The suppression of IMP-induced hemolysis is ascribed to the decrease in the concentration of free IMP molecules. This concentration can be quantitatively estimated from the surface tension data determined at 37 degrees C. Therefore, the suppression of IMP-induced hemolysis by most of the CDs can be quantitatively predicted from these surface tension data, regardless of the kind and concentration of CD. However, alpha-CD, HP, and DM are outliers of this prediction. This failure for alpha-CD and HP is ascribed to their weaker competitive binding to IMP than to membrane phospholipid. Because DM has a strong hemolytic activity, it does not almost suppress the IMP-induced hemolysis.

Antidepressive Agents, Tricyclic↗

PubMed2001

Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene transcript AML1c and its expression in early hematopoietic development.

Acute myeloid leukemia 1 (AML1: or runt-related transcription factor, RUNX1) encodes the DNA binding subunit of the heterodimering transcription factor complex PEBP2 (CBF), which plays an essential role for definitive hematopoiesis. Transcription of AML1 is controlled by two distinct promoter regions, which results in the generation of the respective AML1b and AML1c isoforms. Here we report the isolation of the mouse homologue of human AML1c, whose unique N-terminus is 100% identical at the amino acid level to its human counterpart and 63 and 37% identical to the respective family members AML2 and AML3. Semiquantitative RT-PCR assay on mouse embryonic stem cell clones during in vitro differentiation and Northern blot analysis of a mouse embryo revealed that AML1b is expressed in undifferentiated ES cells and upregulated in the early developmental stage, in contrast to the gradual upregulation and steady maintenance of AML1c expression during embryogenesis. In addition, maintenance of AML1c expression depended on the presence of active AML1 allele(s) while that of AML1b did not. Thus, these two AML1 isoforms driven by their respective promoters are differentially expressed and are likely to have distinct functions in early hematopoietic development.

Alternative Splicing↗

PubMed2001

Steroid sulfatase expression in ovarian clear cell adenocarcinoma: immunohistochemical study.

OBJECTIVE: Steroid sulfatase (STS) is an important enzyme that converts biological inactive steroid sulfate to active free steroid. As estrogen is thought to play an important role in cell proliferation in gynecological cancer, the existence of STS may have particular significance in the prognosis of ovarian cancer. In the present study, we determined the STS expression of ovarian clear cell adenocarcinoma (OCCA), which has the poorest prognosis among various ovarian cancers, immunohistochemically to clarify the biological nature of OCCA and also to determine whether STS expression is one of the prognostic factors in OCCA. METHODS: Forty-five archival, formalin-fixed, paraffin-embedded tissues from patients with OCCA and other epithelial ovarian cancers who were first operated on from 1987 to 1998 were subjected to analysis. Twenty-eight of forty-five (60.9%) OCCA cases coexisted with endometriosis. They were subclassified into papillary, solid, and tubulocystic types with respect to architectural pattern. Immunohistochemical staining of STS was performed using anti-human STS polyclonal rabbit antibody that had been immunized with purified STS from human placenta. RESULTS: STS was immunohistochemically stained positively in 70% (32/45) of OCCA, 33.3% of serous adenocarcinoma (6/18), and 50.0% of mucinous adenocarcinoma (4/8) specimens and was localized in the cytoplasm of neoplastic epithelial cells. No significant relationship was found between STS staining and FIGO staging. However, patients diagnosed as papillary type had a significantly lower survival rate and showed significantly more positive staining of STS (P < 0.05) than those with solid type. Stage, STS expression, and architectural type yielded a significant association with survival rate. CONCLUSION: It was proven that STS is present in the cytoplasm of patients with OCCA by an immunohistochemical method. OCCA patients with papillary tumor with positive STS expression are considered to have a poor prognosis.

Adenocarcinoma, Clear Cell↗

PubMed2001

A case of adenoid cystic carcinoma (ACC) of the breast and review of the utility of preoperative imaging diagnose.

A case of adenoid cystic carcinoma (ACC) of the breast in a 66-year-old woman is reported herein. ACC accounts for about 0.1% of all breast cancers. Our patient presented with a small, elastic and hard mass, measuring 2.0x2.0 cm, between both outer quadrants of the right breast. Although physical examination, ultrasonography and magnetic resonance (MR) mammography suggested a benign tumor, aspiration biopsy cytology (ABC) was performed twice, and the second ABC specimen was evaluated as suspicious for breast carcinoma. Breast conserving surgery with a level II lymph node dissection was subsequently performed. There was no lymph node metastases and estrogen receptor (ER) status was negative. Light microscopy revealed various growth patterns, with the cells showing biphasic cellularity. According to immunohistochemical analyses, CEA, actin and vimentin were positive, S-100 protein was negative, and the cytokeratin reaction was partially positive. Therefore, ACC of the breast was diagnosed. Although ACC of the breast is a rare neoplasm, it should be considered in the differential diagnosis even if various diagnostic imaging studies suggest a benign tumor of the breast. Awareness of this tumor will help prevent misdiagnosis.

Actins↗

PubMed2001

RUNX1/AML1: a central player in hematopoiesis.

It has been well established that a number of transcription factors play critical roles in regulating the fate of hematopoietic stem cell populations. One of them is the leukemia-associated transcription factor acute myeloid leukemia 1 (AML1; also known as runt-related transcription factor 1, or RUNX1). This gene was originally cloned from the breakpoint of the t(8;21) reciprocal chromosome translocation and was later recognized as one of the most frequent targets of leukemia-associated gene aberrations. Gene-targeting experiments revealed that transcriptionally active AML1 is essential for the establishment of definitive hematopoiesis. More specifically, this gene functions in the emergence of the hematopoietic progenitor cells from the hemogenic endothelium by budding in the aorta-gonad-mesonephros region, and its expression points to the sites with strong potential for the emergence of hematopoietic stem cells. This review discusses aspects of the biologic properties of AML1 in early hematopoietic development.

Animals↗

PubMed2001

Magnetic resonance imaging findings and postoperative neurologic dysfunction in elderly patients undergoing coronary artery bypass grafting.

BACKGROUND: Small cerebral infarctions are common in elderly patients, but the association between the magnetic resonance imaging finding and neurologic dysfunction after coronary artery bypass grafting has not been evaluated. METHODS: We determined, prospectively, whether varying degrees of abnormal findings on magnetic resonance images of the brain increased the incidence of preoperative cognitive decline, postoperative neuropsychological dysfunction, and stroke in 421 elderly patients (> or = 60 years) undergoing coronary artery bypass grafting. RESULTS: Control patients (almost normal or leukoaraiosis, n = 212) had rates of postoperative neuropsychological dysfunction (7%) and stroke (1.4%); the small infarctions group (some small infarctions, n = 126) had rates of 13% and 5.6%, respectively; whereas patients with multiple infarctions (multiple small infarctions or broad infarctions, n = 83) had rates of 20% and 8.4%, respectively (p = 0.004, p = 0.013). In the group with multiple infarctions, 49 patients (59%) were asymptomatic and 21 patients (25%) had cognitive decline. Stepwise logistic regression analysis demonstrated that the significant predictors of multiple small infarctions or large infarctions were history of cerebrovascular disease, renal insufficiency, cognitive decline, and cerebral arteriosclerosis. CONCLUSIONS: Multiple infarctions significantly increase the risk of neurologic dysfunction after coronary artery bypass grafting. Routine screening for preoperative cognitive decline should be performed to detect underlying ischemic cerebral disease in elderly patients.

Aged↗

PubMed2001

Polycyclic aromatic hydrocarbon (PAHs) and hopanes in stranded tar-balls on the coasts of Peninsular Malaysia: applications of biomarkers for identifying sources of oil pollution.

Malaysian coasts are subjected to various threats of petroleum pollution including routine and accidental oil spill from tankers, spillage of crude oils from inland and off-shore oil fields, and run-off from land-based human activities. Due to its strategic location, the Straits of Malacca serves as a major shipping lane. This paper expands the utility of biomarker compounds, hopanes, in identifying the source of tar-balls stranded on Malaysian coasts. 20 tar-ball samples collected from the east and west coast were analyzed for hopanes and polycyclic aromatic hydrocarbons (PAHs). Four of the 13 tar-ball samples collected from the west coast of Peninsular Malaysia were identified as the Middle East crude oil (MECO) based on their biomarker signatures, suggesting tanker-derived sources significantly contributing the petroleum pollution in the Straits of Malacca. The tar-balls found on the east coast seem to originate from the offshore oil platforms in the South China Sea. The presence of South East Asian crude oil (SEACO) tar-balls on the west coast carry several plausible explanations. Some of the tar-balls could have been transported via sea currents from the east coast. The tankers carrying SEACO to other countries could have accidentally spilt the oil as well. Furthermore, discharge of tank washings and ballast water from the tankers were suggested based on the abundance in higher molecular weight n-alkanes and the absence of unresolved complex mixture (UCM) in the tar-ball samples. The other possibilities are that the tar-balls may have been originated from the Sumatran oil fields and spillage of domestic oil from oil refineries in Port Dickson and Malacca. The results of PAHs analysis suggest that all the tar-ball samples have undergone various extent of weathering through evaporation, dissolution and photooxidation.

Biomarkers↗

PubMed2001

Isolation and characterization of coagulant extracted from Moringa oleifera seed by salt solution.

It is known that M. oleifera contains a natural coagulant in the seeds. In our previous research, the method using salt water to extract the active coagulation component from M. oleifera seeds was developed and compared with the conventional method using water. In this research, the active coagulation component was purified from a NaCl solution crude extract of Moringa oleifera seeds. The active component was isolated and purified from the crude extract through a sequence of steps that included salting-out by dialysis, removal of lipids and carbohydrates by homogenization with acetone, and anion exchange. Specific coagulation activity of the active material increased up to 34 times more than the crude extract after the ion exchange. The active component was not the same as that of water extract. The molecular weight was about 3000 Da. The Lowry method and the phenol-sulfuric acid method indicated that the active component was neither protein nor polysaccharide. The optimum pH of the purified active component for coagulation of turbidity was pH 8 and above. Different from the conventional water extracts, the active component can be used for waters with low turbidity without increase in the dissolved organic carbon concentration.

Chromatography, Ion Exchange↗

PubMed2001

Coagulation mechanism of salt solution-extracted active component in Moringa oleifera seeds.

This study focuses on the coagulation mechanism by the purified coagulant solution (MOC-SC-PC) with the coagulation active component extracted from M. oleifera seeds using salt solution. The addition of MOC-SC-PC tap water formed insoluble matters. This formation was responsible for kaolin coagulation. On the other hand, insoluble matters were not formed when the MOC-SC-PC was added into distilled water. The formation was affected by Ca2+ or other bivalent cations which may connect each molecule of the active coagulation component in MOC-SC-PC and form a net-like structure. The coagulation mechanism of MOC-SC-PC seemed to be an enmeshment of Kaolin by the insoluble matters with the net-like structure. In case of Ca2+ ion (bivalent cations), at least 0.2 mM was necessary for coagulation at 0.3 mgC l-1 dose of MOC-SC-PC. Other coagulation mechanisms like compression of double layer, interparticle bridging or charge neutralization were not responsible for the coagulation by MOC-SC-PC.

Cations, Divalent↗

PubMed2001

Distribution of the high-affinity choline transporter in the central nervous system of the rat.

In cholinergic nerve terminals, Na(+)- and Cl(-)-dependent, hemicholinium-3-sensitive, high-affinity choline uptake is thought to be the rate-limiting step in acetylcholine synthesis. The high-affinity choline transporter cDNA responsible for the activity was recently cloned. Here we report production of a highly specific antibody to the high-affinity choline transporter and distribution of the protein in the CNS of the rat. The antibody stained almost all known cholinergic neurons and their terminal fields. High-affinity choline transporter-immunoreactive cell bodies were demonstrated in the olfactory tubercle, basal forebrain complex, striatum, mesopontine complex, medial habenula, cranial nerve motor nuclei, and ventral horn and intermediate zone of the spinal cord. Noticeably, high densities of high-affinity choline transporter-positive axonal fibers and puncta were encountered in many brain regions such as cerebral cortex, hippocampus, amygdala, striatum, several thalamic nuclei, and brainstem. Transection of the hypoglossal nerve resulted in a loss of high-affinity choline transporter immunoreactivity in neurons within the ipsilateral hypoglossal motor nucleus, which paralleled a loss of immunoreactivity to choline acetyltransferase. The antibody also stained brain sections from human and mouse, suggesting cross-reactivity. These results confirm that the high-affinity choline transporter is uniquely expressed in cholinergic neurons and is efficiently transported to axon terminals. The antibody will be useful to investigate possible changes in cholinergic cell bodies and axon terminals in human and rodents under various pathological conditions.

Acetylcholine↗

PubMed2001

Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress.

Under conditions of endoplasmic reticulum (ER) stress, mammalian cells induce both translational repression and the unfolded protein response that transcriptionally activates genes encoding ER-resident molecular chaperones. To date, the only known pathway for translational repression in response to ER stress has been the phosphorylation of eIF-2alpha by the double-stranded RNA-activated protein kinase (PKR) or the transmembrane PKR-like ER kinase (PERK). Here we report another pathway in which the ER transmembrane kinase/ribonuclease IRE1beta induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. The evidence suggests that both pathways are important for efficient translational repression during the ER stress response.

Amino Acid Sequence↗

PubMed2001

The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells.

The chimeric transcription factor E2a-Pbx1 is expressed as a result of the 1;19 chromosomal translocation in some 5% of cases of pediatric acute lymphoblastic leukemia. We investigated the biological and transcriptional consequences of forced expression of E2a-Pbx1 in the interleukin-3 (IL-3) dependent, bone marrow-derived cell line Ba/F3. We show that forced expression of E2a-Pbx1 induces apoptosis in Ba/F3 cells without apparent effects on cell cycle progression. This pro-apoptotic effect is enhanced on cytokine deprivation. Furthermore, using cDNA representational difference analysis (RDA), we show that these cellular effects are associated with marked induction of the gene NDRG1, which was previously identified as a target of transcriptional repression by N-myc and induction by the tumor suppressor protein p53. We identify a portion of the NDRG1 promoter capable of mediating transcriptional induction by E2a-Pbx1 and show that NDRG1 is also induced on simple IL-3 deprivation of BaF3 cells. Although we show that E2a-Pbx1 induction of NDRG1 is not impaired as a result of targeting p53 using HPV E6, and therefore does not appear to be p53-dependent, our results overall are consistent with the notion that induction of NDRG1 by E2a-Pbx1 may represent part of an apoptotic or cytostatic cellular response to oncogene activation.

Apoptosis↗

PubMed2001

Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury.

BACKGROUND: Clusterin is a soluble complement regulatory protein that binds to C5b-7 and inhibits generation of membrane attack complex, C5b-9. Glomerular deposition of clusterin has been observed in human and experimental membranous nephropathy in association with C5b-9 and immune deposits. However, it is controversial as to whether clusterin observed in glomeruli is synthesized by the resident glomerular cells or is derived from the circulation. We examined whether clusterin is expressed by resident glomerular cells exposed to complement-mediated injury. METHODS: In vitro, cultured mesangial cells were exposed to antithymocyte serum immunoglobulin G and 5% normal rat serum as a complement source. In vivo, we induced anti-Thy1 nephritis in rats and examined the kidneys on days 8 and 29. RESULTS: We observed increased expression of clusterin in cultured rat glomerular mesangial cells stimulated by sublytic complement attack. We also demonstrated that in comparison with control rats, both a marked increase in clusterin mRNA in the glomeruli and marked deposition of clusterin protein in the mesangial area occurred in the OX-7-treated rats on day 8 in association with C5b-9 deposition and on day 29. CONCLUSION: Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This up-regulation of clusterin may play a critical role in protecting mesangial cells from complement attack.

Animals↗

PubMed2001

Noradrenaline receptor-mediated potentiation of caffeine-induced Ca( 2+)-activated K(+) currents in bovine ciliary muscle cells.

PURPOSE: Adrenoceptor-mediated modulation of a caffeine (CAF)-induced [Ca(2+)](i) elevation and resulting Ca(2+)-activated K(+) current (I(CAF)) in bovine ciliary muscle (CM) cells were investigated. METHODS: The nystatin-perforated patch clamp technique for the measurement of membrane currents and a microscope based fura-2 fluorescence imaging of [Ca(2+)](i) were applied to CM cells freshly dissociated with collagenase and identified with smooth muscle-specific alpha-isoactin. RESULTS: Under voltage-clamped conditions, noradrenaline (NA) potentiated I(CAF) in a NA concentration-dependent manner without producing current responses to NA when NA was applied alone. NA-induced potentiation of I(CAF) occurred within 20 sec after the application of NA, while the NA-potentiated I(CAF) gradually recovered to the control level within 30 min after removal of NA. Despite the little current response to NA applied alone, NA elicited a [Ca(2+)](i) elevation in a manner similar to that induced by CAF although the NA-induced [Ca(2+ )](i) elevation was smaller than the CAF-induced [Ca(2+ )](i) elevation. In contrast to the significant potentiation of I(CAF) with NA, NA produced little potentiation of the CAF-induced [Ca(2+)](i) elevation. The NA-induced potentiation of I( CAF) was antagonized by an alpha(1) adrenoceptor antagonist, prazosin. Neither clonidine nor isoproterenol had an effect on I(CAF), suggesting that alpha(2) and beta adrenoceptor are not involved in the response to NA. CONCLUSIONS: These results suggest that NA potentiates I( CAF) via alpha(1) adrenoceptor activation and that the NA-induced potentiation occurs at Ca(2+)-activated K(+) channels but not CAF-induced Ca(2+) releasing sites.

Adrenergic alpha-Antagonists↗

PubMed2001

Is elevation of carbon dioxide concentration beneficial to seedling photosynthesis in the understory of tropical rain forests?

Cuttings of the southeast Asian tropical rain forest tree species, Pongamia pinnata (L.) Pierre were raised in growth chambers providing a photosynthetic photon flux density (PPFD) of 60 micromol m(-2) s(-1) with either a low or a high red:far-red light ratio (LR and HR, repectively). The chambers were supplied with air containing CO(2) at a concentration of either 400 (LR4 and HR4, respectively) or 800 micromol mol(-1) (HR8 and LR8, respectively). After 4 months, leaf morphology and photosynthetic characteristics were determined. Relative to HR4, the LR4 treatment increased leaf area and total chlorophyll concentration (Chl) by 24 and 25%, respectively, but reduced leaf mass per unit area (LMA) by 19%. Elevated [CO(2)] significantly increased leaf area and LMA but did not affect Chl of LR or HR plants. Leaf nitrogen concentration was unaffected by the red:far-red light ratio but decreased significantly in seedlings in the elevated [CO(2)] treatment. Photosynthesis measured in situ under the growth conditions of ambient light and [CO(2)] (A(amb)) was 30% lower on an area basis and 14% lower on a mass basis in LR4 plants than in HR4 plants. Elevated [CO(2)] reduced the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase and thus decreased light-saturated photosynthetic rate in both HR and LR plants. Elevated [CO(2)] increased mean leaf area and decreased respiration rates in both LR and HR plants. The LR8 plants had significantly higher A(amb) than LR4 plants, but similar A(amb) to HR8 plants.

Carbon Dioxide↗

PubMed2001

Profile soft-seal cuff, a new endotracheal tube, effectively inhibits an increase in the cuff pressure through high compliance rather than low diffusion of nitrous oxide.

We assessed the nitrous oxide (N(2)O) gas-barrier properties of a new endotracheal tube cuff, the Profile Soft-Seal Cuff (PSSC) (Sims Portex, Kent, UK). The tracheas of randomly selected patients were intubated with the Trachelon (Terumo, Tokyo, Japan), Profile Cuff (PC) (Sims Portex), or PSSC (n = 15 for each) endotracheal tube. Cuffs were inflated with air, and intracuff pressure was measured during anesthesia with 67% N(2)O. The concentration of N(2)O in cuffs was measured at the end of anesthesia. Postoperative sore throat was assessed. The volume-pressure relationship and thickness of the cuff were also measured. Cuff pressure, which increased gradually during anesthesia, was significantly less in the PSSC and PC groups than in the Trachelon group. The PSSC had smaller pressure than the PC 120 min after the start of anesthesia (P < 0.05). There were no significant differences in the N(2)O concentration in cuffs among the groups, although the PSSC had the thinnest cuff with the highest compliance. The incidence of postoperative sore throat in the Trachelon group was significantly higher than in the other two groups. In summary, the PSSC effectively inhibits an increase in cuff pressure during anesthesia with N(2)O. The underlying mechanism is probably the higher compliance of the thinner cuff, rather than a reduction in N(2)O diffusion into the cuff.

Adult↗

PubMed2001

The occurrence of various collagen diseases in one family: a sister with ISSc, PBC, APS, and SS and a brother with systemic lupus erythematosus.

We encountered siblings who had collagen diseases and related symptoms. Case 1 was a 53-year-old woman who had limited cutaneous systemic sclerosis (ISSc) associated with primary biliary cirrhosis (PBC), antiphospholipid antibody syndrome (APS), and subclinical Sjögren's syndrome (SS). Case 2 was a 48-year-old man, her younger brother, with systemic lupus erythematosus (SLE) that developed at 32 years of age. Investigation of their family revealed that their mother had Raynaud's phenomenon, arthritis, and subclinical Sjögren's syndrome, and that another younger brother of Cases 1 and 2 had Raynaud's phenomenon and general fatigue. HLA analysis revealed that the sister and brother had some identical HLA antigens in common, including A2, A33 (19), B67, B44 (12), Cw7, DR2, DR6, DR52, and DQ1. The sister, brother and their mother had common HLA antigens including A2, B67, Cw7, DR2, and DQ1. Although Cases 1 and 2 shared the same HLA system, they presented different phenotypes of collagen disease.

Antiphospholipid Syndrome↗

PubMed2001

Selective isolation and distribution of the genus Planomonospora in soils.

For the screening of bioactive compounds and study of global distribution, a selective isolation method for Planomonospora strains by centrifugation from soil is examined. Planomonospora strains produced characteristic sporangia on the humic acid-trace salts gellan gum medium (pH 9.0) so that this genus was readily recognized on the isolation plate. High yields of motile spores were obtained by using a flooding solution containing 0.1% skim milk in 5 mM N-cyclohexyl-2-amino-ethanesulfonic acid (pH 9.0) followed by incubating the preparation at 32 degreesC for 90 min, centrifuging it at 1000 x g for 10 min, and further incubation at 32 degreesC for 60 min after centrifugation. By combining the techniques described above, we isolated 246 Planomonospora strains from 137 of the 1200 soil samples examined. Ninety-four percent of these strains were recovered from neutral to slightly alkaline soils (pH 7.0 to 9.0). Strains of P. venezuelensis group were obtained from 13 soil samples (1.1%), which were collected in Bolivia, Cyprus, Egypt, Greece, India, Japan, New Caledonia, and Turkey. Strains of this group appear widely distributed in the soil of tropical to temperate regions. To our knowledge, this is the first record that strains of this group have been isolated from a location other than Venezuela.

Actinomycetales↗