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Biomedical subjects

Y Miwa

Publications and source records attributed to Y Miwa.

At least 109 records · Page 6Linked to original sources
PubMed1995

[A case of heterochronic bilateral renal infarction].

A 57-year-old man was admitted with aching pain in his left frank. Left renal infarction was revealed by CT scan and arteriogram. Intra-arterial thrombolytic therapy was performed, and resulted in a recanalization of the occluded artery and elimination of frank pain, but residual stenosis was recognized. At 27 hours after the onset of left renal infarction, in spite of the systemic anti-coagulant and thrombolytic therapy to prevent the recurrence of the thrombosis, right renal infarction occurred. Immediate intra-arterial thrombolytic therapy for right renal infarction was performed successfully. Subsequently the serum creatinine level increased from 0.8-0.9 to 1.2-1.3 mg/dl due to the functional loss of the left kidney, which was confirmed by follow-up renoscintigraphy. Conservative intra-arterial thrombolytic therapy seems to be the most effective treatment for renal infarction, but left renal salvage failed due to the prolonged time of occlusion and residual stenosis. Also, catheterization for diagnosis and therapy or thrombolytic therapy itself may induce an additional infarction.

Creatinine↗
PubMed1995

The rat homologue of the Wilson's disease gene was partially deleted at the 3' end of its protein-coding region in Long-Evans Cinnamon mutant rats.

LEC mutant rats exhibit an abnormal hepatic copper accumulation, due to the defection of the rat homologue of the Wilson's disease gene. In this study, we found a definitive evidence that the rat Wilson's disease gene of LEC rats was partially deleted at the 3' end of its protein-coding region, by performing Southern blot analysis. Furthermore, in Northern blot analysis, we confirmed that expression of the rat Wilson's disease gene was deficient in the liver of LEC rats. The partial deletion of the rat Wilson's disease gene should be responsible for the deficient expression of that gene in LEC rats.

Animals↗
PubMed1994

Clozapine injected into the nucleus accumbens potentiates apomorphine-induced jaw movements.

The effects of clozapine injected into the nucleus accumbens on apomorphine-induced jaw movements were studied. Jaw movements induced by apomorphine (0.5 mg/kg i.v.) were potentiated by clozapine (10 micrograms/0.2 microliters) injected into the nucleus accumbens 10 min before apomorphine. Enhancement of the apomorphine-induced jaw movements was also found with the muscarinic acetylcholine receptor antagonist, methylscopolamine (2.5 micrograms), whereas the acetylcholine receptor agonist, carbachol (2.5 micrograms), inhibited the effects of apomorphine. Injection of a smaller dose of carbachol (0.1 microgram) alone into the nucleus accumbens 10 min before failed to alter the effects of apomorphine but prevented the potentiation induced by clozapine. Both the 5-hydroxytryptamine(5-HT)2A receptor antagonist, 2-(2-dimethylaminoethylthio)-3-phenylquinoline hydrochloride (ICI 169,369, 0.1 and 0.2 microgram), and the alpha 1-adrenoceptor antagonist, prazosin (0.05 and 0.2 microgram), failed to affect the effects of apomorphine(0.5 mg/kg i.v.). In contrast, clozapine (1, 5 and 10 micrograms), ICI 169,369 (0.1 and 0.2 microgram) or prazosin (0.05 and 0.2 microgram) given into the ventral striatum inhibited the effects of apomorphine (0.5 mg/kg i.v.). It is suggested that the clozapine-induced potentiation in the nucleus accumbens might be due to its antimuscarinic properties.

Analysis of Variance↗
PubMed1994

Dorsal striatal mechanisms involved in the dopamine D2 receptor-mediated potentiation of apomorphine-induced jaw movements.

The role of dorsal striatal mechanisms in the regulation of apomorphine-induced jaw movements was studied. Jaw movements induced by apomorphine (0.2 mg/kg i.v.) were potentiated by quinpirole (10 micrograms/0.2 microliter) injected into the dorsal part of the striatum 10 min before apomorphine. Quinpirole injection into the ventral part of the striatum did not affect the effects of apomorphine. the quinpirole-induced potentiation in the dorsal striatum was prevented by l-sulpiride (25 ng), nemonapride (1 microgram), SCH23390 (1 microgram) or methylscopolamine (1 microgram), but not muscimol (50 ng), co-administered with quinpirole. Injection of these drugs alone 10 min before apomorphine failed to alter the effects of apomorphine. l-Sulpiride (25 ng) injected into the dorsal striatum 60 min before apomorphine increased the frequency of jaw movements induced by apomorphine (0.2 mg/kg). The l-sulpiride-induced potentiation was prevented by methylscopolamine (0.1 microgram) or l-sulpiride (25 ng) injected into the dorsal striatum 10 min before apomorphine; we had already found that this potentiation was also blocked by SCH23390. It is suggested that a synergistic dopamine D1/D2 receptor interaction underlies both the quick-onset potentiation by quinpirole and the delayed-onset potentiation by l-sulpiride.

Animals↗
PubMed1994

Possible function and some properties of the CcpA protein of Bacillus subtilis.

The ccpA mutations alsA1 (alsA1 is allelic to ccpA) and ccpA::Tn917 completely abolished catabolite repression of gluconate kinase and sorbitol dehydrogenase synthesis in Bacillus subtilis, whereas they only partially affected the catabolite repression of inositol dehydrogenase, histidase and xylose isomerase synthesis. The alsA1 mutation also partially affected catabolite repression of sporulation. Analysis of revertants from the alsA1 mutant by direct sequencing indicated that this mutation comprises a base substitution of guanine at nucleotide -14 to adenine within the Shine-Dalgarno sequence of the ccpA gene (ccpA translation starts at nucleotide +1). A 1.37 kb EcoRI fragment carrying the ccpA gene was cloned into Escherichia coli plasmid pUC19 and B. subtilis plasmid pUB110, resulting in plasmids pCCPA19 and pCCPA110, respectively. The ccpA gene carried in pCCPA110 complemented the alsA1 mutation. Western blotting revealed that the level of the CcpA protein in B. subtilis cells, which seemed to be constitutively synthesized, was approximately 10 times lower for the alsA1 mutant than for the wild-type. The CcpA protein synthesized by either E. coli cells bearing pCCPA19 or B. subtilis cells bearing pCCPA110 was purified to over 90% homogeneity; the latter cells were grown in the presence of glucose. The molecular mass of the protein purified from E. coli was 74 kDa, suggesting that this protein exists as a dimer because its subunit molecular mass was 38 kDa as determined by SDS-PAGE. Gel retardation analysis indicated that the purified CcpA protein in both cases did not bind to the cis sequence for catabolite repression of the gnt operon, but it bound non-specifically to DNA.

Bacillus subtilis↗
PubMed1994

Cloning and nucleotide sequencing of a 15 kb region of the Bacillus subtilis genome containing the iol operon.

Within the framework of an international project on the sequencing of the whole Bacillus subtilis genome, a 15 kb chromosome segment, which contains the iol operon involved in inositol utilization, has been cloned and sequenced. This region (14,974 bp) contains 12 complete open reading frames (ORFs; genes) and two partial ones; the seventh gene (E83G) is the idh gene encoding inositol dehydrogenase. All the genes identified are transcribed in the same direction as that of the movement of the replication fork. A homology search for their products deduced from the 12 complete ORFs revealed that eight of them exhibit significant homology to known proteins such as fructokinase, acetolactate synthase, fructose-1,6-bisphosphate aldolase (B. subtilis), and PhoB and FtsE proteins (Escherichia coli). It also implied that two genes (B65D and B65E) might encode a set of two-component regulatory proteins and that the B65F gene might encode a protein belonging to the ATP-binding cassette (ABC) family. Based on the features of the nucleotide sequence determined and the results of the homology search, the primary structure of the iol operon is predicted.

Amino Acid Sequence↗
PubMed1994

Augmented receptor-mediated Ca2+ mobilization causes supersensitivity of contractile response to serotonin in atherosclerotic arteries.

We have previously reported that atherosclerotic arteries obtained from Watanabe heritable hyperlipidemic (WHHL) rabbits exhibit a marked increase of contractile response to serotonin (5-hydroxytryptamine [5-HT]) and ergonovine and that these augmented contractile responses to specific agonists may play an important role in the pathogenesis of vasospasm. In the present study, we investigated whether supersensitivity to 5-HT in atherlosclerotic arteries was due to an increase in 5-HT receptor-mediated Ca2+ mobilization or to an increase in Ca2+ sensitivity of the contractile elements. We measured simultaneously both isometric tension and [Ca2+]i in fura 2-loaded aortic smooth muscle strips from control and WHHL rabbits. Muscle tension in the high K+ (72.7 mmol/L)-stimulated states and [Ca2+]i in both resting and high K(+)-stimulated states did not differ between control and WHHL rabbits. In atherosclerotic aortas from WHHL rabbits, the dose-response curves of both tension and [Ca2+]i for 5-HT were shifted to the left at lower threshold concentrations and one-half maximally effective dose. The maximum response of contraction produced by 5-HT in WHHL rabbits was augmented compared with that in control rabbits (123 +/- 17% versus 33 +/- 7% of the 72.7 mmol/L K(+)-induced contraction, P < .001). The maximum response of [Ca2+]i produced by 5-HT was also augmented in WHHL rabbits compared with control rabbits (29 +/- 4% versus 10 +/- 0.9% of the 72.7 mmol/L K(+)-induced [Ca2+]i, P < .001). In contrast, the responses of contraction and [Ca2+]i to phenylephrine were similar between control and WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Inter-laboratory validation study of the Skin2 Dermal Model ZK1100 and MTT cytotoxicity assay kits.

An inter-laboratory validation study was conducted to evaluate the potential of 4 chemicals to cause irritation with utilizing the Skin2 Dermal Model ZK1100 kit developed by Advanced Tissue Sciences, Inc. (formerly Marrow-Tech, Inc., La Jolla, California, USA). The chemicals tested were sodium dodecyl sulfate (SDS), 1-n-hexadecyl-pyridinium chloride monohydrate (CC), ethanol (EtOH), and dimethyl sulfoxide (DMSO). Eleven Japanese institutions participated in this validation research to evaluate the usefulness of the Skin2 Model ZK1100 kit in accordance with an identical protocol. None of the participating laboratories had previously used the Skin2 Model ZK1100 kit. The MTT-50 value obtained in the individual institutions was 42 to 91 micrograms/ml for SDS, 2.7 to 8.6 micrograms/ml for CC, 2.0 to 9.3% for EtOH, and 11.5 to 21.9% for DMSO. Reproducibility was reasonably good as noted when one test chemical was repetitively tested by the same investigator. MTT-50 values obtained with the present method correlated with DS20 values obtained with Draize's method (r = 0.9881) in one of the participant institutions. The irritation study using the Skin2 Model ZK1100 kit was easy to perform and generated quantitative data. When the test was repeated, reproducibility was demonstrated with a variation of less than 2 sigma. These data suggested that this newly developed in vitro method would be useful in toxicity screening studies in terms of both time and cost, and would serve as a useful alternative to the conventional methods of the eye irritation study.

Animals↗
PubMed1994

IgG subclass levels and southern analysis of DNA in primary immunodeficiency diseases including IgG subclass deficiency.

Serum IgG subclass levels are reported for twenty patients with primary immunodeficiency diseases, including four patients with IgG subclass deficiency, using an enzyme-linked immunosorbent assay with monoclonal antibodies. The disorder of each patient with IgG subclass deficiency seemed to be heterogeneous immunologically and clinically. One had complete IgG2-IgG4 deficiency, another had IgG2-IgG4-IgA deficiency and the other two had IgG2-IgA deficiencies. We did not find any structural-gene deletions in the constant region of the human immunoglobulin heavy-chain locus. Although the possibility of defects in genes controlling immunoglobulin expression, or small mutations, remains, these results suggest that IgG subclass deficiency is not always linked to particular structural-gene deletions.

Adolescent↗
PubMed1994

[Effect of intrathecal administration of opioid on minimum alveolar concentration and postoperative pain relief--a comparison of morphine and buprenorphine].

Intrathecal morphine (Mor) exerts potent analgesic effect and decreases anesthetic requirement. However, morphine was reported to have various uncomfortable side effects, and buprenorphine (BPN) is considered as an alternative opioid. The aim of this study was to investigate the effect of intrathecal BPN and Mor on the MAC of halothane and the relief of postoperative pain. The result shows that the MAC of halothane decreases dose dependently both in the BPN and Mor groups. The decrease in halothane MAC with 0.05 mg intrathecal BPN was equipotent with the intrathecal administration of 0.5 mg Mor. Adequate postoperative analgesia and severe pruritus were observed in the 0.5 mg Mor group. The intrathecal administration of 0.05 mg and 0.075 mg BPN has shown mild analgesic effect without any side effects.

Adult↗
PubMed1994

[Treatment of advanced prostate cancer].

The treatment against hormone relapsing prostate cancer was examined clinically, experimentally and by a review of the literature. Conventional systemic chemotherapy should be appreciated as one of the symptomatic treatment options; and suramin might be an effective chemotherapeutic agent, if severe and the wide spectrum of side effects were concurred. Intermittent administration of suramin is beneficial at present, with monitoring of its concentration in the blood. Some patients with wide spread bone metastases, especially if they are symptomatic, would be the candidates for hemiskeletal irradiation. Low dose of fractionated radiation was found to be more effective than high dose of single radiation. Bisphosphonate was found to protect bone resorption and destruction from the inoculated prostatic cancer cells in nude mice. In the clinic, the compound would be effective to the aggravation of bone metastasis, especially in combined use with irradiation.

Animals↗
PubMed1994

[Vertebral artery injury following mild neck trauma: report of two cases].

Two cases of vertebral artery injury following mild neck trauma are reported. A 52-year-old man was hospitalized with gait disturbance 7 days after mild traffic accident. Right vertebral angiogram revealed complete occlusion of the rt. vertebral artery (VA) and MR images revealed infarction in the rt. cerebellar hemisphere and rt. dorsolateral part of the medulla oblongata and revealed the thrombus in the rt. VA. He underwent anticoagulation and became asymptomatic. Angiogram 6 months later revealed the vessel to be normal. A 23-year-old man who has a habit of self-manipulation of his neck was hospitalized on the day when he experienced dysesthesia in the left part of his face and left upper and lower extremities and unsteady gait. MR images revealed multiple infarction in bilateral cerebellar hemispheres and thrombus in bilateral VAs. Bilateral vertebral angiogram revealed severe stenoses of bilateral VAs. He underwent anticoagulation and wore soft collar. Angiogram 20 days after onset revealed improvement of bilateral VA stenoses. He was discharged with no neurological deficit. It is said that vertebral artery injuries in association with head and neck trauma are relatively rare, but this condition is possible to be more common than realized, considering that the case of unilateral VA occlusion or the case with well developed collateral circulation is sometimes well tolerated for ischemia and that this condition can occur even after mild head and neck injury. The diagnosis must be established by vertebral angiogram, but MRI and MRA are very useful as ancillary methods. The therapeutic point is to prevent propagation of the thrombus and distal embolism, accordingly wearing a collar and anticoagulation are important.

Adult↗
PubMed1993

5-HT3 receptor antagonists. 3. Quinoline derivatives which may be effective in the therapy of irritable bowel syndrome.

A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT3 receptor antagonists due to deviation of a carbonyl moiety from the place of an aromatic ring in their minimum-energy conformations. These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats. Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID50 = 0.27, 0.12, and 0.0052 mg/kg, po, respectively). However, quinoline derivatives exhibited different activities depending on structural class. 4-Hydroxyquinoline-3-carboxylic acid derivatives 5 and 6a possess high affinity for the 5-HT3 receptor (Ki = 6.1 and 1.5 nM, respectively) and exhibit potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.0017 and 0.000 10 mg/kg, i.v., respectively), but they did not effectively inhibit the increase in fecal pellet output at the dose of 1 mg/kg, po. On the other hand, most of 1-substituted 2-oxoquinoline-4-carboxylates 10 showed less potent activity in the B-J reflex test than 1 or 2 but inhibited restraint stress-induced defecation more potently than 1 or 2. The ID50 value of endo-8-methyl-8- azabicyclo[3.2.1]oct-3-yl 1-isobutyl-2-oxo-1,2-dihydro-4- quinolinecarboxylate 10e was 0.013 mg/kg, po. With respect to the selected compounds 6a and 10e, effects of 5-HT- and thyrotropin-releasing hormone (TRH)-induced defecation, castor oil-induced diarrhea and wrap-restraint stress-induced colonic propulsion in rats were examined. These 5-HT3 receptor antagonists did not effectively inhibit castor oil-induced diarrhea, which has been reported not to be mediated via the 5-HT3 receptor. Although 10e showed 800-fold decreased potency compared with 4 in the B-J reflex test, 10e exhibited activity as potent as 4 in 5-HT- and TRH-induced defecation assays; 10e exhibited 7-fold increased potency compared with 4 in wrap-restraint stress-induced colonic propulsions. From these results, 10e appears to interact selectively with 5-HT3 receptors in the gastrointestinal system and might be effective in the therapy of irritable bowel syndrome (IBS).

Animals↗
PubMed1993

Further evidence for a functional dorsal-ventral division of the rat striatum: GABAergic involvement in oral movements.

Interactions between the gamma-aminobutyric acid (GABA)ergic system and the dopaminergic and cholinergic systems in the control of jaw movements, measured with a phototransducer system, were investigated in both dorsal and ventral regions of the rat striatum. Muscimol (25 and 50 ng/0.2 microliters) injected into the dorsal striatum did not affect jaw movements induced by apomorphine (0.2 mg/kg i.v.) or pilocarpine (4 mg/kg i.v.), but when injected into the ventral striatum it inhibited these jaw movements and those induced by carbachol (1 micrograms/0.2 microliters) injected into the ventral striatum. Picrotoxin (250 and 500 ng/0.2 microliters) injected into the dorsal striatum enhanced the effects of apomorphine (0.2 mg/kg) but not those of pilocarpine. When injected into the ventral striatum, picrotoxin did not affect apomorphine-induced oral movements but enhanced the effects of pilocarpine and carbachol. The benzodiazepine, flunitrazepam (100 ng/0.2 microliters), had no effect when injected in the dorsal striatum, and showed some inhibitory effects on dopaminergic and cholinergic oral movements when injected in the ventral striatum. The results suggest that the striatal GABAergic inhibitory effect on dopaminergic and cholinergic function is regionally specific, supporting a dorsal/ventral functional division of the rat striatum. The results also suggest that oral movements induced by dopaminergic and cholinergic drugs are distinct forms of repetitive oral behaviour.

Animals↗
PubMed1993

5-HT3 receptor antagonists. 2. 4-Hydroxy-3-quinolinecarboxylic acid derivatives.

A series of 4-hydroxy-3-quinolinecarboxylic acid derivatives (6) and 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid derivatives (7) were designed and synthesized as 5-HT3 receptor antagonists. Molecular modeling studies suggested that the 3-carbonyl moiety in 6 was almost coplanar to the plane of an aromatic ring, but in 7 there was a 30 degrees deviation. 4-Hydroxy substitution in quinoline derivatives enhanced affinity for the 5-HT3 receptors, and endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-4-hydroxy-3- quinolinecarboxamide (6f) exhibited the most potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.1 micrograms/kg, iv) among quinoline derivatives 6. Although 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives (7a) exhibited higher affinity (e.g., 7d: Ki = 0.48 nM) for the 5-HT3 receptors than ondansetron (Ki = 7.6 nM) or granisetron (Ki = 2.1 nM), these amides showed less potent activity in the B-J reflex test than the reference compounds. Interestingly, the ester derivatives 7c, 7f, and 7h eliminated affinity for the 5-HT3 receptors. These unusual structure-activity relationships and the deviation of the 3-carbonyl moiety from the plane of an aromatic ring suggest that the active conformation of 7a might be different from the proposed one for the preceding 5-HT3 antagonists. Thus, 6f was chosen for further studies. No receptor binding for a variety of ligands was significantly antagonized by 6f. Comparing the ratios of the ED50 value in the B-J reflex test (rat, iv) with the LD50 value in acute lethal toxicity (mouse, iv), 6f was proved to have a 600-fold wider margin of safety than ondansetron. Compound 6f dose-dependently attenuated both the incidence and frequency of emetic episodes induced by cisplatin in the dog (ED50 = 14 micrograms/kg, iv) more potently than ondansetron (ED50 = 210 micrograms/kg, iv). Compound 6f (KF-20170) is now under further investigation as a drug for treating gastrointestinal disorder.

Animals↗
PubMed1993

Crystal structures of Boc-D- and L-Iva-L-Pro-OBzl: unturned conformation of Aib-Pro sequence unaffected by replacement of Me with Et in Aib.

The crystal structures of the isovaline (Iva) containing dipeptides, Boc-D-Iva-L-Pro-OBzl and Boc-L-Iva-L-Pro-OBzl, were determined by x-ray diffraction. The diastereomeric peptides were shown to adopt unturned conformations closely similar to each other (phi Iva 52 degrees, psi Iva 46 degrees, phi Pro -65 degrees, and psi Pro 143 degrees for D-Iva-L-Pro sequence and phi Iva 52 degrees, psi Iva 44 degrees, phi Pro -63 degrees, and psi Pro 148 degrees for L-Iva-L-Pro sequence). The Pro ring of each peptide was in C gamma-endo conformation. The unusually large angle CIva-NPro-C delta Pro values (131 degrees in both peptides) were observed, that was due to steric repulsion between the delta-methylene of Pro and the alkyl side chain of Iva residue. These conformations were essentially the same as that of the corresponding alpha-aminoisobutyric acid (Aib)-containing peptide Boc-Aib-L-Pro-OBzl. The result has demonstrated that replacement of either one of the two methyl groups of the Aib residue in Boc-Aib-L-Pro-OBzl with an ethyl group does not cause any significant change in the unturned conformation of the dipeptide.

Aminoisobutyric Acids↗