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Biomedical subjects

M Takano

Publications and source records attributed to M Takano.

At least 73 records · Page 4Linked to original sources
PubMed2000

The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A.

Functional ATP-sensitive K (KATP) channels have an octameric subunit structure with four pore-forming subunits (Kir6.x) and four sulfonylurea receptors (SURx). In the present study, the properties of the heteromeric KATP channel whose pore subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous expression system. In COS7 cells co-transfected with Kir6.1, Kir6.2 and SUR2A at a ratio of 1:1:2, KATP channels showed various unitary conductances between those of Kir6.1/SUR2A (33.6+/-4.2 pS) and Kir6.2/ SUR2A (67.1+/-1.6 pS). Kir6.1-6.2 tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus of Kir6.2 with a ten glutamine linker sequence, also formed a channel with an intermediate conductance (58.9+/-1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar sensitivity to ATP4-: half-maximal inhibition (IC50) was obtained at 14.1+/-12.8 microM and 17.6+/-9.6 microM, respectively. In the presence of Mg2+, Kir6. 1-6.2 was significantly less sensitive than Kir6.2 to MgATP (IC50=95.5+/-49.6 microM versus 18.9+/-5.0 microM). These results suggest that Kir6.1 and Kir6.2 are endowed with the potential to form a heteromeric KATP channel, which has a low sensitivity to MgATP.

Adenosine Triphosphate↗
PubMed2000

Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes.

Sarcolemmal adenosine 5'-triphosphate-sensitive K+ channels (K(ATP)) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5-bisphosphate (PIP2). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the K(ATP) channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 microM) inhibited KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC50) fell from 62.0+/-2.7 to 30.3+/-5.5 microM]. In contrast, PIP2 attenuated the ATP sensitivity (IC50 343.6+/-54.4 microM) and restored Ca2+-induced inactivation of KATP channels (94.1+/-13.7% of the control current immediately before the Ca2+-induced inactivation). Pretreatment of the patch membrane with 1 microM L-PC, however, reduced the magnitude of the PIP2-induced recovery to 22.7+/-6.3% of the control (P<0.01 vs. 94.1+/-13.7% in the absence of L-PC). Conversely, after the PIP2-induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP2-mediated decrease in the ATP sensitivity (IC50 fell from 310+/-19.2 to 93.1+/-9.8 microM). Thus, interaction between L-PC and PIP2 in the plasma membrane appears to regulate K(ATP) channels.

Adenosine Triphosphate↗
PubMed2000

Effect of cisplatin on H+ transport by H+ -ATPase and Na+/H+ exchanger in rat renal brush-border membrane.

The effect of the potent anticancer drug cisplatin, cis-diamminedichloroplatinum (II) (CDDP), on H+ -ATPase and Na+/H+ exchanger in rat renal brush-border membrane was examined. To measure H+ transport by vacuolar H+ -ATPase in renal brush-border membrane vesicles, we employed a detergent-dilution procedure, which can reorientate the catalytic domain of H+ -ATPase from an inward-facing configuration to outward-facing one. ATP-driven H+ pump activity decreased markedly in brush-border membrane prepared from rats two days after CDDP administration (5 mg/kg, i.p.). In addition, N-ethylmaleimide and bafilomycin A1 (inhibitors of vacuolar H+ -ATPase)-sensitive ATPase activity also decreased in these rats. The decrease in ATP-driven H+ pump activity was observed even at day 7 after the administration of CDDP. Suppression of ATP-driven H+ pump activity was also observed when brush-border membrane vesicles prepared from normal rats were pretreated with CDDP in vitro. In contrast with H+ -ATPase, the activity of Na+/H+ exchanger, which was determined by measuring acridine orange fluorescence quenching, was not affected by the administration of CDDP. These results provide new insights into CDDP-induced renal tubular dysfunctions, especially such as proximal tubular acidosis and proteinuria.

Adenosine Triphosphate↗
PubMed2000

The effects of caffeine on ATP-sensitive K(+) channels in smooth muscle cells from pig urethra.

The effects of caffeine on both levcromakalim-induced macroscopic and unitary currents in pig proximal urethra were investigated by the use of patch-clamp techniques (conventional whole-cell configuration and cell-attached configuration). The effects of caffeine were also examined on currents in inside-out patches of COS7 cells expressing carboxy terminus truncated inwardly rectifying K(+) channel (Kir6.2) subunits (i.e. Kir6.2DeltaC36) which form ATP-sensitive K(+) channels (K(ATP) channels). In conventional whole-cell configuration, the levcromakalim (100 microM)-induced inward current (symmetrical 140 mM K(+) conditions) was inhibited by caffeine (> or =1 mM) at a holding potential of -50 mV. In contrast, ryanodine (10 microM) caused no significant inhibitory effect on the gradual decay of the levcromakalim-induced current at -50 mV. The amplitude of the 30 microM levcromakalim-induced current was enhanced by 3-isobutyl-1-methylxanthine (IBMX, 100 microM). In cell-attached configuration, the levcromakalim-induced K(+) channel openings were inhibited by subsequent application of 10 mM caffeine, decreasing the channel open probability at -50 mV. Reverse transcriptase-polymerase chain reaction (RT - PCR) analysis revealed the presence of Kir6.2 transcript in pig urethra. Caffeine (> or =3 mM) inhibited the channel activity of Kir6.2DeltaC36 expressed in COS7 cells (3 mM caffeine, 65+/-6%, n=4; 10 mM caffeine, 29+/-2%, n=4). These results suggest that caffeine can inhibit the activity of K(ATP) channels through a direct blocking effect on the pore-forming Kir subunit.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Dural arteriovenous malformations associated with cerebral aneurysms.

Only limited information is available concerning dural arteriovenous malformations (AVMs) found in association with cerebral aneurysms. The present report focuses on six such cases, concentrating attention on clinical characteristics and significance. Of a total of 46 dural AVMs encountered over a given period, six (13%) were linked with cerebral aneurysms. Particularly strong associations were noted for dural AVMs in the anterior cranial fossa (three of four cases) and convexity (all of three cases). With dural AVMs in the anterior cranial fossa, subarachnoid haemorrhage is common, so that where this is encountered the possibility of a complicating aneurysm should be considered in order to select an appropriate treatment.

Adolescent↗
PubMed2000

Rice NPH1 homologues, OsNPH1a and OsNPH1b, are differently photoregulated.

The members of nonphototropic hypocotyl 1 (NPH1) family of genes in plants are considered to be the blue-light photoreceptors for phototropism. We isolated and characterized two NPH1 homologues from rice named as OsNPH1a and OsNPH1b. The predicted proteins of both OsNPH1 genes include LOV (LOV1 and LOV2) and protein kinase domains which are typically conserved regions in all the members of NPH1 family. Comparison of OsNPH1 apoproteins with those from other plant species revealed a close homology of OsNPHla with Arabidopsis, maize and oat NPH1, while the OsNPH1b appeared to be more closer to the recently found Arabidopsis NPL1. These structural homologies indicate that NPH1 homologues can be grouped into two classes namely "NPH1 type" and "NPL1 type". Northern blot analysis showed that OsNPH1a was strongly expressed in coleoptiles, whereas OsNPH1b was highly expressed in leaves of dark-grown rice seedlings. When the dark-grown seedlings were transferred to the continuous white light, the abundance of the OsNPH1a transcript in coleoptiles rapidly declined to the minimum levels, whereas the OsNPH1b transcript level in leaves gradually increased. These results lead us to conclude that expression of OsNPH1a and OsNPH1b is differently photoregulated in different tissues of rice seedlings.

Amino Acid Sequence↗
PubMed2000

Interaction of platelet activating factor, reactive oxygen species generated by xanthine oxidase, and leukocytes in the generation of hepatic injury after shock/resuscitation.

OBJECTIVE: To evaluate the putative relation of platelet activating factor (PAF), xanthine oxidase, reactive oxidants, and leukocytes in the pathogenesis of hepatic injury after shock/resuscitation (S/R) in vivo. BACKGROUND: Reactive oxygen metabolites generated by xanthine oxidase at reperfusion have been found to trigger postischemic injury in many organs, including the liver. However, the precise linear sequence of the mechanism of consequent hepatic injury after S/R remains to be characterized. METHODS: Unheparinized male rats were bled to a mean blood pressure of 45 +/- 3 mmHg. After 2 hours of shock, they were resuscitated by reinfusion of shed blood (anticoagulated with citrate-phosphate-dextrose) and crystalloid and observed for the next 6 or 24 hours. RESULTS: S/R caused the oxidation of hepatic glutathione and generated centrolobular leukocyte accumulation at 6 hours, followed by predominantly centrolobular hepatocellular injury at 24 hours. Each of these components was attenuated by PAF inhibition with WEB 2170, xanthine oxidase inhibition with allopurinol, antioxidant treatment with N-acetylcysteine, or severe leukopenia induced by vinblastine. In each case, the degree of leukocyte accumulation at 6 hours correlated with the hepatocellular injury seen at 24 hours. However, xanthine oxidase inhibition with allopurinol failed to attenuate further the small level of residual hepatocellular injury seen in leukopenic rats. CONCLUSION: These findings suggest that reactive oxidants generated by xanthine oxidase at reperfusion, stimulated by PAF, mediate hepatocellular injury by triggering leukocyte accumulation, primarily within the centrolobular sinusoids.

Animals↗
PubMed2000

Modification of autolysis by synthetic peptides derived from the presumptive binding domain of Staphylococcus aureus autolysin.

The autolytic cell wall hydrolase of Staphylococcus aureus, Atl, contains three highly cationic repeats in the central region of the amino acid sequence, and the repeats are presumed to have the role of binding the enzyme to some components on the cell surface. To explain the possible function of the repeats, we synthesized a number of 10- to 30-mer oligopeptides based on the Atl amino acid sequence (Thr432-Lys610) containing repeat 1, and examined their effects on the autolysis of S. aureus cells. When the peptides were added to a cell suspension of S. aureus under low ionic strength conditions, five peptides, A10, A11, A14, A16 and B9, showed immediate increases in optical density (OD) of the cell suspension accompanied by decreases in viable cell counts. After the immediate increases, the ODs for A10 and A14 changed little in the first 2 hr. In contrast, the ODs for A11 and A16 decreased rapidly. When peptide A10 was added to suspensions of heat-killed whole cells, crude cell walls and a crude peptidoglycan preparation, their ODs were increased approximately 2-fold. In contrast, the OD was not increased when the peptide was added to a suspension of pure peptidoglycan from which anionic polymers had been removed. Light microscopic and transmission electron microscopic study showed that A10 and A14 inhibited autolysis and that A11 and A16 induced autolysis earlier than the control. These results suggest strongly that the peptides adsorb to and precipitate on the anionic cell surface polymers such as teichoic acid and lipoteichoic acid via ionic interaction. The effects of peptides on the autolysis may be the results of the modification of S. aureus autolysin activities. These peptides, especially the 10-mer peptide B9 (PGTKLYTVPW) that represents the C-terminal half of A10 and N-terminal half of A11, may be important segments for Atl to bind to the cell surface.

Amino Acid Sequence↗
PubMed2000

Anti-Candida activity of a new platinum derivative.

A new platinum derivative of the form H[Pt(IV)(Hdigly)Cl(2)(OH)(2)] (Hdigly==glycylglycine) damaged the Candida albicans cell membrane and inhibited the growth of the cells. The cytotoxic activity of H[Pt(IV)(Hdigly)Cl(2)(OH)(2)] on mammalian cells was 10-fold lower than that of cis-diammine-dichloroplatinum (cisplatin). Substitution of platinum for peptides is effective for enhancement of antifungal activity and reduction of the toxicity to mammalian cells.

Antifungal Agents↗
PubMed2000

Tissue-Specific expression of rat kininogen mRNAs.

To characterize the local kallikrein-kinin system, tissue distribution of mRNAs for kininogens, precursor proteins of kinins, such as high-molecular-weight (H-), low-molecular-weight (L-) and T-kininogens, were studied in the rat by means of reverse-transcription polymerase chain reaction (RT-PCR) using a fluorophore Cy5-labeled 5'-primer. High levels of these three kininogen mRNAs were present in the liver. Relatively high levels of H-kininogen mRNA were also detected in the skin, lung, kidney, and testis in a descending order, whereas L-kininogen mRNA was detectable in the lung and brain, but not in the kidney, skin, testis, heart, adrenal gland, or skeletal muscle. T-Kininogen mRNA was present in these tissues, except for skeletal muscle. These findings suggest that the expression of each kininogen mRNA is regulated by the tissue-dependent mechanisms which is closely associated with functions of the kallikrein-kinin system in the tissue.

Animals↗
PubMed2000

Preparation of novel synthons, uniquely functionalized tetrahydrofuran and tetrahydropyran derivatives.

The dianion of the acetoacetic ester reacts with epibromohydrin derivatives to afford a mixture of (Z)-2-alkoxycarbonylmethylidenetetrahydrofuran derivative and (E)-2-alkoxycarbonylmethylidenetetrahydropyran derivative. The selective formation of the tetrahydrofuran derivative is achieved by the use of LiClO4 as the additive. The preparation of the optically active tetrahydrofuran derivatives and tetrahydropyran derivatives is also examined, and the optical purity and absolute configuration of the products is elucidated.

Furans↗
PubMed2000

Takayasu's arteritis in a 69 year-old woman.

Takayasu's arteritis and temporal arteritis share many clinical and pathological features. The most discriminatory feature between the two diseases is the age at onset; the mean age at onset of the disease was reported as being 26 years for Takayasu's arteritis and 69 years for temporal arteritis. Here we report a 69-year-old woman who presented with a weak right radial artery pulse. The ethnic background and the presence of vascular insufficiency of the right upper extremity and the absence of clinical signs such as shoulder stiffness and tender scalp indicate that her diagnosis is Takayasu's arteritis. It must be emphasized that the two conditions could be differentiated based on the clinical findings even in a patient as old as 69 years old.

Age of Onset↗
PubMed2000

Gravimorphogenesis of Cucurbitaceae plants: development of peg cells and graviperception mechanism in cucumber seedlings.

We examined the effect of microgravity on the peg formation of cucumber seedlings for clarifying the mechanism of gravimorphogenesis in cucurbitaceous plants. The spaceflight experiments verified that gravity controls the formation of peg, hypocotyl hook and growth orientation of cucumber seedlings. Space-grown cucumber developed a peg on each side of the transition zone of the hypocotyl and root, indicating that on the ground peg formation is regulated negatively by gravity (Takahashi et al. 2000). It was found that the auxin-regulated gene, CS-IAA1, was strongly expressed in the transition zone where peg develops (Fujii et al. 2000). In the seedlings grown horizontally on the ground, CS-IAA1 transcripts were much abundant on the lower side of the transition zone, but no such differential expression of CS-IAA1 was observed in the space-grown cucumber (Kamada et al. 2000). These results imply that gravity plays a role in peg formation through auxin redistribution. By the negative control, peg formation on the upper side of the transition zone in the horizontally growing seedlings might be suppressed due to a reduction in auxin concentration. The threshold theory of auxin concentration accounted for the new concept, negative control of morphogenesis by gravity (Kamada et al. 2000). Anatomical studies have shown that there exists the target cells destined to be a peg and distinguishable at the early stage of the growth. Ultra-structural analysis suggested that endoplasmic reticulum develops well in the cells of the future peg. Furthermore, it was found that reorganization of cortical microtubules is required for the change in cell growth polarity in the process of peg formation. The spaceflight experiment with cucumber seedlings also suggested that in microgravity positive hydrotropic response of roots occurred without interference by gravitropic response (Takahashi et al. 1999b). Thus, this spaceflight experiment together with the ground-based studies has shown that cucumber seedling is an ideal for the study of gravimorphogenesis, hydrotropism and their interaction. Although peg formation is seen specifically in cucurbitaceous seedlings, it involves graviperception, auxin transport and redistribution and cytoskeletal modification for controlling cell growth polarity. This system could be a useful model for studying important current issues in plant biology.

Cucumis sativus↗
PubMed2000

[Day surgery for anal disease].

Historically, patients with anal diseases treated on a day surgery basis had inadequate cure rates and a high complication rate. After World War II, modern treatment methods were learned from the UK and USA and improved in Japan. However, the improved radical methods were so complex that approximately 2 weeks' hospitalization was needed. Recently, day surgery for various diseases including hemorrhoids has been recommended by the Japanese ministry of Health and Welfare. However, the characteristics of anal anatomy and physiology make the smooth healing of wounds difficult and tend to cause postoperative pain, bleeding, infection, prolonged healing time, etc. To prevent such difficulties, care must be well planned following the critical path of informed consent, careful surgery, postoperative observation, and management at home. However, hospital staff in charge of such surgery are under so much stress that only patients with less severe anal disease without local or systemic complications should be selected for day surgery.

Ambulatory Surgical Procedures↗
PubMed2000

[Comparative genomic hybridization for analysis of chromosomal changes in cisplatin-resistant ovarian cancer].

In our attempt to find characteristic genetic changes in resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers, using the comparative genomic hybridization (CGH) method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy in comparison with 14 tumors from patients who completely responded to the chemotherapy. We found gains in chromosomal region 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators and regulators of the apoptotic pathway are found to be located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance for cisplatin-based chemotherapy in ovarian cancer patients based on the CGH analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients prior to cisplatin-based chemotherapy.

Antineoplastic Agents↗
PubMed2000

[Midbrain infarction presenting isolated inferior rectus nuclear palsy].

We presented a patient of isolated inferior rectus muscle palsy from midbrain lacunar infarction involving the oculomotor nucleus. The patient noticed sudden onset diplopia gazing to the right side, especially to the right-lower direction. He did not have any other symptom, and neurological examination revealed no other findings. Brain MRI documented the focal hyperintense lesion on T2-weighted images in the right-median midbrain ventral to the aqueduct at the level of the superior colliculus. This lesion involved the right oculomotor nucleus, especially the dorso-lateral subnucleus extend to the inferior rectus muscle. The oculomotor nuclear complex consists of one unpaired subnucleus and four paired subnuclei. Among them, the inferior rectus subnucleus lies dorso-laterally. So nucleus lesion may cause isolated weakness of one of muscles innervated by the oculomotor nerve. Among them the isolated inferior rectus muscle palsy can occur relatively.

Aged↗