Biomedical subjects

Y Okada

Publications and source records attributed to Y Okada.

At least 523 records · Page 29Linked to original sources

PubMed1998

Effectiveness of superficial temporal artery-middle cerebral artery anastomosis in adult moyamoya disease: cerebral hemodynamics and clinical course in ischemic and hemorrhagic varieties.

BACKGROUND AND PURPOSE: The efficacy of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in adult moyamoya disease was evaluated by clinicopathophysiological studies. METHODS: Fifteen patients with cerebral ischemic attacks (ischemia group) and 15 patients with intracranial hemorrhages (hemorrhage group) were investigated. Clinicoangiographic features and regional cerebral blood flow (rCBF) of the MCA territory were preoperatively and postoperatively investigated, and cortical arterial pressure (CAP) and anastomotic blood flow (AF) were intraoperatively measured. RESULTS: In the ischemia group, the preoperative rCBF of 38.4 mL/100 g per minute was significantly increased to 42.1 mL/100 g per minute with a diminution of angiographic moyamoya vessels in 67% of patients after surgery. The mean CAP and AF were 25.6 mm Hg and 34.7 mL/min, respectively. Proximal and distal cerebral vascular resistance (PCVR = [Mean Systemic Arterial Blood Pressure-Mean CAP]/rCBF and DCVR = [Mean CAP/rCBF]) were 1.78 and 0.68, respectively. One patient died perioperatively as a result of intracerebral hemorrhage. During follow-up (mean, 67 months), 12 of 14 patients recovered without neurological deficits, 1 was moderately disabled because of the initial insult, and another patient experienced an intracerebral hemorrhage but recovered fully. In the hemorrhage group, the preoperative rCBF of 38.0 mL/100 g per minute was significantly increased to 42.7 mL/100 g per minute with a diminution of moyamoya vessels in 60% after surgery. The mean CAP and AF were 29.1 mm Hg and 24.1 mL/min, respectively. PCVR and DCVR were 1.72 and 0.77, respectively. One patient became hemiparetic because of perioperative intracerebral hemorrhage. During follow-up (mean, 94 months), 3 patients had fatal intracranial hemorrhages, 10 had good recoveries, and 2 had moderate disabilities. CONCLUSIONS: This study revealed a high PCVR and a very low DCVR in both the ischemia and hemorrhage groups of patients. STA-MCA anastomosis partially normalized cerebral circulation and decreased moyamoya vessels but did not completely prevent rebleeding.

Adult↗

PubMed1998

Effects of parathyroid hormone (PTH) and PTH-related peptide on expressions of matrix metalloproteinase-2, -3, and -9 in growth plate chondrocyte cultures.

The roles of PTH and PTH-related peptide (PTH-rp) in the expression of matrix metalloproteinases (MMPs) during endochondral bone formation were investigated, using various cartilages obtained from young rabbits and rabbit chondrocyte cultures. Immunohistochemical, immunoblotting, zymographical, and/or Northern blot analyses showed that MMP-2 and -9 levels were much higher in the growth plate than in permanent cartilage in vivo. In growth plate chondrocyte cultures, PTH, PTH-rp, and (Bu)2cAMP increased the amount of MMP-2 present in the culture medium, as revealed by zymograms and immunoblots, whereas the other tested growth factors or cytokines, including bone morphogenetic protein-2 and interleukin-1, did not increase the MMP-2 level. PTH also increased the MMP-2 messenger RNA level within 24 h. In addition, PTH increased MMP-3 and -9 levels in the growth plate chondrocyte cultures. However, in articular chondrocyte cultures, PTH had little effect on the levels of MMP-2, -3, and -9. In contrast to PTH, interleukin-1 induced MMP-3 and -9, but not MMP-2, in growth plate and articular chondrocytes. These findings suggest that in ossifying cartilage, PTH/PTH-rp plays a pivotal role in the induction of various MMPs, including MMP-2 (which is considered to be a constitutive enzyme), and that PTH/PTH-rp is involved in the control of cartilage-matrix degradation during endochondral bone formation.

Animals↗

PubMed1998

Purification method for human plasma kallikrein by a new affinity chromatography.

We synthesized a new affinity gel (PKSI-Toyopearl) using a selective synthetic inhibitor of plasma kallikrein (PKSI-527) as an affinity ligand, and employed it for the rapid purification of plasma kallikrein from human plasma. Human plasma activated with kaolin after acid treatment was applied to a PKSI-Toyopearl column. Adsorbed protein was eluted with 50 mM glycine-hydrochloric acid buffer (pH 3.0). Plasma kallikrein was purified 181-fold with a yield of 85% from the kaolin-activated plasma. Further purification was performed by chromatography on a DEAE-Toyopearl 650M column. Plasma kallikrein was finally purified 1720-fold with a 63% yield by these procedures. On sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, a band was observed at approximately 88 kDa. These findings indicate that PKSI-Toyopearl is a valuable tool for the purification of plasma kallikrein from human plasma.

Blood↗

PubMed1998

Characterization of ASK mice, a strain highly sensitive to anaphylactic shock.

A mouse strain named ASK that was originally isolated from El (epilepsy) mice has been shown to be highly sensitive to anaphylactic shock. Here, we characterized the bases of the sensitivity of ASK mice in comparison with the parental strain, El. More than 90% of ASK mice, but not El mice that had been sensitized either actively or passively, died within 1 h following an antigen challenge. The anaphylactic death was effectively blocked by diphenhydramine. Plasma histamine levels increased by 30-50 fold in ASK after the antigen challenge, but only a 2-3-fold increase was observed in El mice. All (El x ASK) F1 mice, either male or female, showed an ASK-like phenotype, suggesting that the impaired plasma histamine response in El mice is due to some recessive mutation(s). Consistent with the plasma histamine responses, cultured mast cells derived from El bone marrow showed impaired potency to degranulate in response to surface IgE engagement, in contrast to ASK mast cells which undergo normal degranulation. Another characteristic feature of ASK mice is their sensitivity to histamine, since 75% of the mice were killed by the subcutaneous administration of 100-200 mg/kg histamine, while C3H and BALB/c mice were resistant to even 600 mg/kg histamine. Taken together, the major bases of the susceptibility to anaphylactic shock in ASK mice are thought to be the enhanced sensitivity to histamine and the recovered degranulation machinery in mast cells that is impaired in El mice.

Anaphylaxis↗

PubMed1998

Amino acids and peptides. LII. Design and synthesis of opioid mimetics containing a pyrazinone ring and examination of their opioid receptor binding activity.

An amino group was introduced to the 3 or 6 position of a pyrazinone ring by cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the amino function, followed by removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-beta-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the mu-opioid receptor with a Ki value of 55.8 nM and to the delta-opioid receptor with a Ki value of 2165 nM and with a Ki mu/Ki delta value of 0.026.

Amino Acids↗

PubMed1998

Some properties and the inclusion behavior of three positional isomers of 6(1),6n-di-O-alpha-D-glucosyl-cyclomaltoheptaoses (beta-cyclodextrins).

Three positional isomers of 6(1),6n-di-O-alpha-D-glucosyl-cyclomaltoheptaose [1,n-(G)2-beta CDs; n = 2-4] which existed in the digests with glucoamylase of the products from cyclomaltoheptaose (beta-cyclodextrin, beta CD) and maltose with Klebsiella pneumoniae pullulanase, were purified by HPLC. The solubilities of two isomers of those doubly branched beta CDs, 1,2- and 1,3-(G)2-beta CDs, in water were much higher than those of parent non-branched beta CD and mono-branched beta CD, 6-O-alpha-D-glucosyl-beta CD (G-beta CD), while the solubility of another isomer, 1,4-(G)2-beta CD, was significantly lower than these two isomers, though it was higher than that of beta CD. On the other hand, the solubilities of 1,2- and 1,3-isomers in 10, 30, and 50% (v/v) aqueous methanol at 25 degrees C were independent of methanol concentrations and their solubilities were the same as those in water at 25 degrees C. However, that of 1,4-isomer increased with increasing methanol concentrations. The hemolytic activities of 1,n-(G)2-beta CDs on human erythrocytes in isotonic solution were lower than those of G-beta CD and beta CD, and became weaker in the order of 1,4- > 1,2- > 1,3-isomers. The complex-forming abilities of 1,n-(G)2-beta CDs for digitoxin, digoxin, fluorometholone, flurbiprofen, hydrocortisone acetate, and norfloxacin were about the same as those of beta CD and G-beta CD, whereas reserpine was more difficult to include within 1,n-(G)2-beta CDs than beta CD and G-beta CD. Nevertheless, the solubilities of those guest compounds were much more enhanced by 1,n-(G)2-beta CDs and G-beta CD than by beta CD.

Chemical Phenomena↗

PubMed1998

Design of plasma kallikrein inhibitors: functional and structural requirements of plasma kallikrein inhibitors.

The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.

Drug Design↗

PubMed1998

[Scavenging activity of furan derivatives against hydroxyl radical generated by Fenton system].

As the continuation of the work on the antioxidant properties of furan derivatives, we have studied hydroxyl radical (OH.) scavenging activity of dimethylfuran (DMF) and diphenylfuran (DPF), which are well-known as an effective scavenger of singlet oxygen, by an ESR spin trapping technique. The incubation mixture of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapping agent with FE2+ and H202 in 50% acetonitrile aqueous solution gave 1:2:2:1 line signals characteristic of DMPO-OH spin adduct. The additions of furan derivatives to the incubation mixture decreased the intensity of the DMPO-OH spin adduct signal in a dose-dependent manner. The activities of furan derivatives were in the order of DMF > DPF > furan. The decrease in the intensity of the signals was not due to the inhibition of OH. generating system itself and the destruction of the spin adduct by furan derivatives. By comparison with the common OH. scavengers, DMF and DPF were found to scavenge OH. more effectively than dimethylsulfoxide and mannitol. These results indicate that DMF and DPF can act as a OH. scavenger as well as a singlet oxygen scavenger.

Antioxidants↗

PubMed1998

Effects of KRN4884 (a novel K+ channel opener), levcromakalim, nilvadipine and propranolol on endothelin-1-induced heart disorders in anesthetized rats.

The effects of KRN4884 (5-amino-N-[2-(2-chrolophenyl)ethyl]-N'-cyano-3-pyridinecarboxa midine), a novel K+ channel opener, on the electrocardiogram changes caused by the intracoronary administration of endothelin-1 (ET-1) were studied in anesthetized rats and compared with the effects of levcromakalim, a K+ channel opener; nilvadipine, a Ca2+ antagonist; and propranolol, a beta-adrenoceptor antagonist. KRN4884 (50 microg/kg, i.v.) and levcromakalim (300 microg/kg, i.v.) inhibited the ST segment elevation and the development of arrhythmias induced by ET-1 (5 microg, i.c.) and decreased the incidence of death. Nilvadipine (300 microg/kg, i.v.) and propranolol (1000 and 3000 microg/kg, i.v.) each prevented the ST segment elevation, but the suppressions of the occurrence of arrhythmias produced by nilvadipine and propranolol were less than that shown by KRN4884. KRN4884 (30 and 50 microg/kg, i.v.), levcromakalim (100 and 300 microg/kg, i.v.) and nilvadipine (100 and 300 microg/kg, i.v.) significantly decreased the mean blood pressure in a dose-dependent manner, but propranolol did not. The heart rate was decreased by nilvadipine (100 and 300 microg/kg, i.v.) and propranolol (1000 and 3000 microg/kg, i.v.), but was not affected by KRN4884 (30 and 50 microg/kg, i.v.) or levcromakalim (100 and 300 microg/kg, i.v.). These results suggest that pretreatments with KRN4884 and levcromakalim are more effective on ET-1-induced electrocardiogram changes than those with nilvadipine and propranolol.

Anesthesia↗

PubMed1998

Treatment of osteomyelitis with antibiotic-soaked porous glass ceramic.

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good. Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results.

Adult↗

PubMed1998

Regulation of prostaglandin G/H synthase-2 expression by interleukin-1 in human osteoblast-like cells.

Interleukin-1 (IL-1) is an important factor in bone metabolism, and its actions may be mediated in part via prostaglandins. Prostaglandin G/H synthase (PGHS), a critical enzyme in the synthesis of prostaglandins, has two isoforms, PGHS-1, which is generally constitutively expressed, and PGHS-2, which is inducible. This study examines the effects of IL-1 on PGHS-2 mRNA expression in human osteosarcoma MG-63 cells, the human osteoblast-like initial transfectant (HOBIT) cell line, and primary human osteoblastic (HOB) cells. IL-1 induced PGHS-2 mRNA expression in MG-63 cells within 1 h, and expression was maintained for 24 h. There was a dose-related increase in PGHS-2 mRNA levels with 1-100 ng/ml of IL-1. Induction of PGHS-2 protein and media prostaglandin E2 (PGE2) paralleled induction of PGHS-2 mRNA levels. IL-1 similarly induced PGHS-2 mRNA expression and PGE2 production in HOBIT and HOB cells. Among other potential agonists, phorbol myristate acetate (PMA) was a potent inducer of PGHS-2 expression, while forskolin (FSK), serum, and prostaglandins had little effect. Cycloheximide enhanced effects of both IL-1 and PMA, suggesting that de novo protein synthesis is not required for induction of PGHS-2. Twenty-four hours of PMA pretreatment blocked the induction of PGHS-2 by PMA but not by IL-1, suggesting that IL-1 induction of PGHS-2 mRNA is not dependent on the protein kinase C pathway. Although FSK alone had little effect, it enhanced induction of PGHS-2 mRNA by IL-1. PGHS-1 was constitutively expressed and showed little change with treatment. In summary, we show that IL-1 is a potent inducer of PGHS-2 expression and PGE2 production in human osteosarcoma cells as well as in osteoblastic cells derived from normal human bone.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

The kallikrein-kinin system, but not vascular endothelial growth factor, plays a role in the increased vascular permeability associated with ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled stimulation treatment. Vascular endothelial growth factor (VEGF) has recently emerged as an important factor which may be responsible for the hyperpermeability seen in OHSS. The purpose of the present study was to investigate and compare the mechanisms by which ascites in patients with OHSS and ovarian carcinoma induce increases in vascular permeability in an in vitro assay and an in vivo animal experiment. We found 8-fold lower VEGF levels in ascites from patients with OHSS than in those from patients with ovarian carcinoma. Although VEGF is produced by the ovaries, it is not necessarily the factor responsible for hyperpermeability. We also demonstrated that the vascular hyperpermeability produced by OHSS ascites was not abolished by specific neutralizing anti-VEGF antibodies, and that not all of the VEGF found in the ascites fluid is biologically active. Moreover, our results strongly suggest that the vascular permeability produced by OHSS ascites may depend on activation of the kallikrein-kinin system. Possible evidence for this phenomenon was obtained by demonstrating that the hyperpermeability caused by the ascites could be blocked by Trasylol (known to inhibit bradykinin synthesis) and potentiated by captopril (a kininase II inhibitor). Taken together, the results suggest that, although VEGF is found in ascites fluid from patients with OHSS, it is unlikely that the cause of OHSS involves VEGF production by the ovaries. The kallikrein-kinin system may be more important in the hyperpermeability seen in OHSS.

Adult↗

PubMed1998

Different expression of Tn and sialyl-Tn antigens between normal and diseased human gastric epithelial cells.

Thomsen-Friedenreich antigen (T antigen) has been supposed to be a cancer-specific carbohydrate antigen. We have previously shown that one third of the Japanese population normally expressed T antigen in gastric surface epithelia and the other two thirds expressed fucosyl-T antigen. Their sialylation and blocked-synthesis were associated with diseased conditions. In the present study, we studied gastric surface epithelial expression of monosaccharide antigen Tn, i.e., a precursor of T antigen, and sialyl-Tn. Normal fundic and pyloric epithelia, respectively, expressed Tn supranucleally and cytoplasmically, but did not express sialyl-Tn. In the intestinal metaplasias and intestinal-type adenomas, goblet cells expressed sialyl-Tn in their vacuoles, and absorptive cells expressed Tn apically. In gastric-type adenomas, Tn, but not sialyl-Tn, was detected. Intestinal-type cancers expressed Tn and sialyl-Tn more often than the diffuse-type cancers. Five cancers did not express Tn, sialyl-Tn, or the T-related antigens. In these, four were diffuse-type cancers. We concluded that: a) normal gastric epithelial cells express Tn; b) metaplastic differentiation is associated with sialylation of Tn and c) expression of Tn and sialyl-Tn is depressed in the gastric cancers.

Adenoma↗

PubMed1998

Double infection with Giardia lamblia and Salmonella paratyphi A associated with acute renal failure.

While traveling in India, a previously healthy twenty-year-old man had febrile diarrhea. The patient was prescribed medical therapy, and all symptoms were resolved. Fourteen days later, however, similar symptoms recurred. The patient was admitted to a local hospital, but was transferred to our department because of oliguria. Salmonella paratyphi A was isolated from blood and stool specimens, and Giardia lamblia was identified in his stool. The patient's condition was complicated by acute renal failure. The patient received tosufloxacin and metronidazole. Renal function recovered completely without hemodialysis. Paratyphoid fever and giardiasis were resolved. It is suggested that giardiasis exacerbated the paratyphoid fever.

Acute Kidney Injury↗

PubMed1998

Tyrosine kinase-independent extracellular action of genistein on the CFTR Cl- channel in guinea pig ventricular myocytes and CFTR-transfected mouse fibroblasts.

The effects of genistein, a protein tyrosine kinase inhibitor, on the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel were studied in guinea pig ventricular myocytes and in NIH3T3 mouse fibroblasts stably transfected with CFTR cDNA by the whole-cell patch-clamp technique. Genistein did not activate whole-cell Cl- currents when applied to the intracellular (pipette) solution. In contrast, when applied to the extracellular solution, genistein alone promptly activated the Cl- current in a fully reversible manner. Also, extracellular genistein reversibly potentiated the forskolin-activated Cl- current. However, both basal and forskolin-activated Cl- currents were not affected by other protein tyrosine kinase inhibitors, including herbimycin A, lavendustin A, tyrphostin 21, tyrphostin 47, and tyrphostin 51. A nonspecific inhibitor of protein phosphatases, orthovanadate, had no effect on the genistein-induced activation of CFTR. Pretreatment with a protein kinase inhibitor, either H-89 or H-7, or with an adenylate cyclase inhibitor, SQ 22536, also had no effect on the genistein-induced response. Thus, it is concluded that genistein alone activates CFTR by a protein tyrosine kinase-independent and protein phosphatase-independent mechanism from the extracellular side, but not from the intracellular side.

3T3 Cells↗

PubMed1998

Magnetic resonance angiography visualization of four vessel (bilateral carotid and vertebral artery) occlusion--two case reports.

A 44-year-old female with transient vertigo and a 51-year-old female with headache and numbness of the hand presented with four vessel occlusion of the cerebral arteries (bilateral internal carotid arteries and bilateral vertebral arteries). This is an extremely rare entity, and the clinicoradiological features are not well documented. Magnetic resonance (MR) angiography visualized the cerebral arterial occlusion. Conventional angiography confirmed the diagnosis and demonstrated extensive collateral vessels. MR angiography is a useful method for screening patients with minimal or no symptoms for abnormalities in the cerebral circulation.

Adult↗

PubMed1998

Subarachnoid hemorrhage caused by Aspergillus aneurysm as a complication of transcranial biopsy of an orbital apex lesion--case report.

A 62-year-old male complaining of unilateral visual disturbance and pain in the involved eye had a small mass at the right orbital apex which was identified as an Aspergillus granuloma by transcranial biopsy. One month later, the patient became comatose because of fatal subarachnoid hemorrhage due to a newly developed aneurysm. Autopsy showed a ruptured aneurysm on the right internal carotid-posterior communicating artery. Histological examination demonstrated prominent Aspergillus invasion of the arterial wall. Aspergillus infection must be taken into consideration in patients with orbital apex syndrome, which may lead to serious cerebrovascular consequences. If sino-orbital lesions are detected by neuroimaging techniques, biopsy using an extradural approach should be performed to obtain a definitive diagnosis.

Aneurysm, Infected↗

PubMed1998

Permethrin emulsion ingestion: clinical manifestations and clearance of isomers.

BACKGROUND: Oral intoxication with permethrin, an insecticide which prolongs axonal sodium channel depolarization, has not been documented in humans. We treated a 59-year-old man who drank approximately 600 mL of 20% permethrin emulsion in a suicide attempt. METHODS: Sequential blood samples were obtained to determine permethrin isomer levels using high-performance liquid chromatography. RESULTS: Vomiting and diarrhea occurred after ingestion. On admission, loss of consciousness and metabolic acidosis were observed. On regaining consciousness, the patient complained of a burning sensation in the oral cavity. He received fluid therapy after gastric lavage and recovered without severe complications. Apart from initially impaired consciousness, no clinical neurotoxicity such as tremor, hyperexcitation, ataxia, convulsions, or paralysis occurred, though these have been reported in permethrin-intoxicated animals. Serum permethrin concentrations peaked 3-4 hours after ingestion at 868 ng/mL. Clearance of trans permethrin was more rapid than that of cis permethrin. CONCLUSION: The unequal clearance of permethrin isomers paralleled findings in animal experiments. Vomiting and diarrhea probably limited absorption in the present case, resulting in a peak serum concentration and a degree of neurotoxicity far less than those seen in animals.

Administration, Oral↗