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Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 181 records · Page 10Linked to original sources

Mechanism of phospholipase D activation induced by prostaglandin D2 in osteoblast-like cells: function of Ca2+/calmodulin.

Prostaglandin D2 (PGD2) stimulated the formation of choline in a dose-dependent manner in the range between 10 nM and 10 microM. The effect of PGD2 on the formation of inositol phosphates (EC50 was 20 nM) was more potent than that on the formation of choline (EC50 was 0.5 microM). The formation of choline stimulated by a combination of PGD2 and 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, was additive. Staurosporine, an inhibitor for protein kinases, enhanced the PGD2-induced formation of choline, but H-7, another inhibitor for protein kinases, had little effect. PGD2 stimulated Ca2+ influx from extracellular space dose-dependently. The depletion of extracellular Ca2+ by EGTA reduced the PGD2-induced formation of choline. W-7 and trifluoperazine dihydrochloride, antagonists of calmodulin, dose-dependently inhibited the PGD2-induced choline formation. These results strongly suggest that PGD2 activates phospholipase D in a Ca2+/calmodulin dependent manner in osteoblast-like cells, and that protein kinase C is not essential for the PGD2-induced activation of phospholipase D.

Animals↗

Evidence for a short form of alpha 1(IV) as a major polypeptide in bovine lens capsule.

The extracts from bovine lens capsule with acetic acid contained, after reduction, three major collagenous polypeptides with M(r) = 180k, 175k, and 160k, which were specifically immuno-stained with anti-type IV collagen polyclonal antibody. The biochemical properties of 180k and 160k polypeptides were akin and were distinct from that of 175k polypeptide [J. Biochem. (1993) 114,358-362]. In the present study, evidence that the 160k and 180k polypeptides from bovine lens capsule both originated from alpha 1(IV) was obtained on the basis of reactivity with a monoclonal antibody that recognizes alpha 1(IV) chain at the collagenous sequence contained in [KGEPGLPGRGFPGFP]. The epitope-bearing sequence was identified from the following three experiments. Pepsin-solubilized polypeptides from human placenta were purified by affinity chromatography on the antibody-coupled column and sequenced. The restriction map of the clones positively reactive with the monoclonal antibody from human placenta cDNA library was superimposed on that of human alpha 1(IV) cDNA at a specific region. Synthetic peptides corresponding to the sequence were assayed for inhibitory activity against the reaction between epitope-bearing pepsin fragments and the antibody. The 180k and 160k polypeptides showed similar intensities in protein staining as well as in immuno-staining with the monoclonal antibody. In contrast, the 175k polypeptide did not react with the monoclonal antibody, indicating that it is a genetically distinct type IV collagen chain, presumably alpha 2(IV) from its abundance. The 160k, a major type IV collagen polypeptide, is a short form of alpha 1(IV) present as a tissue form in bovine lens capsule.

Amino Acid Sequence↗

A case of subacute necrotizing fasciitis.

We report a 48-year-old woman who developed necrotizing groin fasciitis with insidious onset. Before she visited us, she had been unsuccessfully treated with several kinds of antibiotics by other doctors for one month, because of a small ulcer covered by blackish necrotic tissue. She was referred to us because of high fever, an ulcer on the left labium majus, and a cellulitis-like lesion with severe pain on the lower abdomen. Methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus intermedius, and Bacteroides uniformis were isolated from the wound. After aggressive debridement on the eighth day after admission of the whole indurated area and the fascia of the underlying muscle, healthy granulation tissue covered the defect, and the wound was finally closed with a skin graft Long-term administration of antibiotics along with insufficient and delayed surgical treatment were considered to have caused the full development of this disease.

Acute Disease↗

Mechanism of inhibition of carbonyl reductase from rabbit kidney by phenylbutazone.

Phenylbutazone showed significant inhibition against the metabolic reduction of acetohexamide catalyzed by carbonyl reductase purified from rabbit kidney. Thus, the inhibitory effect of phenylbutazone was kinetically examined. Phenylbutazone was a competitive inhibitor for the enzyme with respect to NADPH, whereas it noncompetitively inhibited the enzyme activity with respect to acetohexamide. A fluorescence study revealed that phenylbutazone decreases the binding of NADPH to the free enzyme (apoenzyme). These results suggest that phenylbutazone causes the inhibition of carbonyl reductase by competing with NADPH in its coenzyme-binding domain.

Alcohol Oxidoreductases↗

Asterixis and astatic seizures in association with bilateral insular lesions in a patient with viral encephalitis.

We report a 48-year-old man who suffered from viral encephalitis and developed involuntary movements of the hands and astatic seizures as sequelae. T2-weighted magnetic resonance imaging of the brain showed high intensity areas in the bilateral insulae. Electroencephalography (EEG) revealed spike and slow wave complexes and high-amplitude slow waves. The involuntary movements of the hands were diagnosed as asterixis by electromyography. Asterixis affected both hands. Administration of sodium valproate aggravated asterixis and EEG findings, but treatment with clonazepam markedly improved these findings and astatic seizures. The present case indicates that insular lesions might be also responsible for the development of asterixis.

Electroencephalography↗

Felbamate relieves several abnormal pain sensations in rats with an experimental peripheral neuropathy.

The antiepileptic drug, felbamate, was tested in a rat model of painful peripheral neuropathy (the chronic constriction injury model). Intraperitoneal doses of 150, 300 and 600 mg/kg were given to animals with established heat-hyperalgesia, mechanohyperalgesia, mechano-allodynia and signs of spontaneous pain (hindpaw guarding). Postinjection tests were conducted 2, 6, 12, 24 and 48 h later. The 150 mg/kg dose had little or no effect on any measure. Significant reductions in all measures of abnormal pain were seen after the 300 and 600 mg/kg doses; relief lasted 2 to 12 h. Side effects were trivial or absent by 2 h postinjection. Felbamate's actions were generally antihyperalgesic and antiallodynic, rather than analgesic, in that the responsiveness of the control (sham-operated) hindpaw was unaffected. We conclude that felbamate suppresses neuropathic pain sensations and that its effectiveness may be due to multiple mechanisms of action. The recently discovered severe side-effect liability of felbamate is likely to preclude its clinical application.

Analgesics↗

Mac-1 expression and superoxide generation of the peripheral polymorphonuclear leukocyte following gastrectomy and esophagectomy.

The aim of this study was to evaluate the characteristics of the polymorphonuclear leukocyte (PMN) function after surgical stress. We investigated Mac-1 expression and superoxide generation by peripheral PMNs and serum granulocyte-colony stimulating factor (G-CSF) concentrations in 15 patients who underwent either gastrectomy (n = 8) or esophagectomy (n = 7). The serum G-CSF rapidly increased within 24 hours after operation. The maximum levels of serum G-CSF in the cases of esophagectomy were about 5-8 fold those of gastrectomy, although the increases in PMN counts within 24 hours of esophagectomy were lower than those after gastrectomy. Mac-1 expression and superoxide generation by PMN counts and serum G-CSF. After esophagectomy, Mac-1 expression on peripheral PMNs remained elevated through the 7th day after operation, while superoxide generation by PMNs in response to PMA declined to below preoperative levels after the 3rd day. These results suggest that, after major surgery such as esophagectomy, there is a discrepancy between Mac-1 expression and superoxide generation by the peripheral PMN despite a high level of serum G-CSF.

Aged↗

[Clinical usefulness of polyamino acid particle agglutination test for detection of anti-HTLV-I antibody].

A new artificial carrier particle agglutination test using polyamino acid (polyamino PA) was developed for anti HTLV-I assay. We carried out the comparative study on anti-HTLV-I among polyamino PA, gelatin PA, EIA and WB methods. All of 76 ATL, 20 HAM/TSP, 53 patients with uveitis and 50 HTLV-I carriers were seropositive and 50 HTLV-I non carriers were seronegative with four methods. Eighteen of 503 patients include autoimmune diseases showed seropositive by polyamino PA and gelatin PA. One of 19 seropositives by EIA was false positive. All of 25 sera showed non-specific reaction by the gelatin PA were clearly negative by the polyamino PA. This is due to the fact that the polyamino acid particle has a greater specific gravity as carrier. The final judgement was got within 45 minutes. It was earlier more 30 minutes than the gelatin PA. The polyamino PA is a simple, rapid, sensitive and specific method. Therefore, it is useful for mass screening and clinical diagnosis.

Agglutination Tests↗

Role of melatonin deficiency in the development of scoliosis in pinealectomised chickens.

We studied the possible role of melatonin deficiency in experimentally-induced scoliosis. A total of 90 chickens underwent pinealectomy on the third day after hatching: 30 were treated with serotonin, 30 with melatonin and 30 received no therapy (control group). Scoliosis developed in all the control group, in 22 of the serotonin group, and in only 6 of the melatonin group. The six melatonin-treated chickens with scoliosis had less severe spinal deformities than those in the serotonin-treated group. There were lower blood melatonin concentrations in chickens with scoliosis than in those without. Our findings suggest that melatonin deficiency contributes to the aetiology of this experimental scoliosis, probably by interfering with the normally symmetrical growth of the proprioceptive system involving the paraspinal muscles and the spine.

Animals↗

Iron and copper deposition in chronic active hepatitis and liver cirrhosis; pathogenetic role in progressive liver cell damage.

Iron and copper deposition were examined in patients with chronic active viral hepatitis (CAH) and posthepatitic liver cirrhosis (LC) by Berlin blue, rhodanine, or Victoria blue staining and X-ray microanalysis. Considerable iron or copper deposition was demonstrated in the peripheral zones of hepatic lobules in both CAH (53% of specimens) and LC (63% of specimens). Frozen sections taken from the 2 CAH surgical sections with iron depositions were examined by photoncounting image analysis, and superoxide liberation from the metal granules were demonstrated. In areas of metal deposition, vacuolation of liver cell nuclei, accumulation of lipofuscin, and induction of metallothionein (69% of rhodanine- or Victoria blue-positive specimens) were often demonstrated, whereas induction of ferritin was found only in 14% of Berlin blue-positive specimens. The PCNA index was significantly lower in areas of metal deposition than in the adjacent areas without metal deposition, indicating lowered proliferative capability in the former. These results indicate that cell-mediated immune mechanisms causing the disturbance of bile secretion and heavy metal deposition in the peripheral zones of hepatic lobules may be involved in the progression of viral hepatitis from its acute phase to CAH and finally to LC phase, resulting in piecemeal necrosis. However, cholangitis could not be demonstrated in the present study.

Adult↗

Abnormal gene expression and regulation in the liver of jvs mice with systemic carnitine deficiency.

Carnitine-deficient jvs mice expressed reduced levels of a group of genes which are preferentially expressed in the liver, including urea cycle enzyme genes (Biochim. Biophys. Acta 1138, 167-171, 1992). The expression of alpha-fetoprotein and aldolase A was elevated, indicating that the liver of jvs mice is undifferentiated or dedifferentiated (FEBS Lett. 311, 63-66, 1992). Studies of the hormone signal transduction pathway showed that serum cortisol and plasma glucagon levels of jvs mice were 2 and 3 times higher, respectively, than those of normal mice, and that the hormone binding activity of glucocorticoid receptor (GR) in the cytosol of jvs liver was 50% of normal mice, which reflected the amount of receptor protein in the cytosol. On the other hand, GR protein accumulated in the nuclear fraction in jvs mice. Exogenously administrated dexamethasone induced carbamoyl phosphate synthetase (CPS) and tyrosine aminotransferase (TAT) mRNAs in jvs mice, indicating that CPS and TAT genes in jvs mice are responsive to induction by glucocorticoid and cAMP. Analysis of transacting factors by gel retardation assay revealed that HNF-1, COUP-TF and SP-1 were detected at almost the same level in the hepatic nuclear fraction of jvs mice as in normal littermates, and C/EBP and CREB were a little higher in jvs mice, suggesting that these factors are probably not targets of jvs mutation causing abnormal gene expression in the liver. On the other hand, AP-1 binding activity was much higher in jvs mice from an early age, preceding the abnormal expression of urea cycle enzyme, and carnitine administration normalized AP-1 binding activity. We suggest that elevated AP-1 binding induced by carnitine deficiency is closely connected with the abnormal gene expression in the liver.

Animals↗

Chemical modification of arginine and lysine residues in coenzyme-binding domain of carbonyl reductase from rabbit kidney: indomethacin affords a significant protection against inactivation of the enzyme by phenylglyoxal.

Carbonyl reductase from rabbit kidney was inactivated by phenylglyoxal (PGO) and 2,4,6-trinitrobenzenesulfonate sodium (TNBS). NADP+ protected the enzyme from the inactivations by PGO and TNBS, suggesting that essential arginine and lysine residues are located in coenzyme-binding domain of the enzyme. Judging from the effects of PGO-treated enzymes in the presence and in the absence of NADP+ on the fluorescence intensity of NADPH, one essential arginine residue in coenzyme-binding domain was found to have a role in the binding of NADPH to the enzyme. Indomethacin afforded a significant protection against inactivation of the enzyme by PGO, whereas it could not protect the enzyme from the inactivation by TNBS. It is reasonable to postulate that indomethacin interacts at least in part with or near one essential arginine residue in coenzyme-binding domain of carbonyl reductase from rabbit kidney.

Alcohol Oxidoreductases↗

Effects of long-term treatment with sustained-release nicardipine on left ventricular hypertrophy and function in patients with essential hypertension.

The effects of long-term treatment with sustained-release nicardipine (nicardipine SR) on left ventricular hypertrophy and function were studied. Ten uncomplicated essential hypertensive patients with left ventricular hypertrophy, aged 61 +/- 7.6 years old, were treated with nicardipine SR alone for an average of 20 months (range: 12-26 months). All patients underwent echocardiography for assessment of left ventricular diameters and function before and after the treatment. At the end of the treatment, systolic and diastolic blood pressures significantly decreased from 176.0 +/- 13.9 to 140.0 +/- 14.3 mm Hg and from 97.0 +/- 5.3 to 77.4 +/- 7.2 mm Hg, respectively (each P < 0.01), while heart rate did not change (73.8 +/- 14.6 vs. 69.9 +/- 13.5 beats/min). The left ventricular mass index significantly decreased from 132.1 +/- 14.4 to 114.4 +/- 15.7 g/m2 (P < 0.01) due to significant reductions in both interventricular septal thickness (P < 0.01) and left ventricular posterior wall thickness (P < 0.05). The ejection fraction (EF), fractional shortening (FS), peak shortening rate (PSR), and peak lengthening rate (PLR) were also improved significantly by the treatment (EF and FS, P < 0.05; PSR and PLR, P < 0.01). Significant inverse relationships existed between end-systolic wall stress and peak shortening or lengthening rate before the treatment (r = 0.80, P < 0.05; r = 0.86, P < 0.05, respectively). These relationships were unchanged after the treatment. Nicardipine SR reduced left ventricular hypertrophy and improved both left ventricular systolic and diastolic functions without causing any consistent augmentation of intrinsic left ventricular function in essential hypertensive patients with left ventricular hypertrophy.

Aged↗

Effects of a new calcium antagonist, CD-832, on coronary and systemic hemodynamics in conscious dogs.

The effects of a new calcium antagonist, CD-832, on coronary and systemic hemodynamics were compared with those of nifedipine in conscious dogs. A pair of 10-MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery (LCX) under sterile conditions to measure epicardial coronary artery diameter (CoD) and coronary blood flow (CBF), respectively. CD-832 (30, 100, and 300 micrograms/kg) and nifedipine (3, 10, and 30 micrograms/kg) produced dose-related increases in large epicardial CoD and in CBF. At doses of CD-832 (100 micrograms/kg) and nifedipine (30 micrograms/kg), producing the same increases in CoD and CBF, the duration of increases in CoD and in CBF was markedly longer after CD-832 than after nifedipine. CD-832 and nifedipine produced dose-related decreases in aortic blood pressure (AoP) and reflex increases in heart rate (HR). However, nifedipine produced significantly (p < 0.01) greater tachycardia than CD-832 in equieffective hypotensive doses. These results demonstrate that CD-832 produces sustained dilation of both large epicardial coronary arteries and small resistance vessels and that the degree of tachycardia after CD-832 is significantly less than that after nifedipine.

Animals↗

A case of superficial epithelioma with sebaceous differentiation.

Superficial epithelioma with sebaceous differentiation developed on the left cheek of a 58-year-old man over a three-year period. Biopsy of the lesion demonstrated plate-like lobules of basophilic basaloid cells with broad attachments to the overlying epidermis. Clusters of or solitary sebaceous cells were present within the lobules. Three tumor types were considered; a subtype of sebaceoma growing in the epidermis, an acanthotic seborrheic keratosis subtype with sebaceous differentiation, or a tumor of the follicular infundibulum with sebaceous differentiation.

Aged↗

Detection and typing of human rotavirus in reference to repeated acute gastroenteritis in infants.

Stool specimens from infants who visited a clinic because of acute gastroenteritis were tested for the presence of human rotavirus. Among the samples obtained were specimens taken from seven patients who had visited the clinic at two different times. In six of these seven children, human rotavirus (HRV) was detected in only one of the specimens taken (i.e. during only one of the two visits). One patient was shown to have excreted HRV twice; in both cases the HRV was serotyped to be type 1. The present results indicate that the symptomatic reinfection of HRV was not a widely occurring phenomenon in the group of infants tested.

Acute Disease↗

Glibenclamide prevents coronary vasodilation induced by beta 1-adrenoceptor stimulation in dogs.

This study aimed to determine whether a putative ATP-sensitive K(+)-channel blocker, glibenclamide (Glb), prevents metabolic coronary vasodilation associated with increased myocardial oxygen consumption (MVO2) caused by beta 1-adrenoceptor stimulation in anesthetized open-chest dogs. Isoproterenol (Iso) was infused selectively into the left circumflex coronary artery before and after Glb. Coronary blood flow (CBF) by an electromagnetic flowmeter, regional myocardial function by sonomicrometers, and left ventricular and arterial pressures were continuously measured. An intracoronary infusion of Iso (10 ng.kg-1 x min-1) resulted in the sustained increase in CBF as well as in the myocardial inotropic and chronotropic state. Glb (10, 30, and 100 micrograms/min ic) attenuated the Iso-induced increase in CBF in a dose-dependent manner, whereas inotropic and chronotropic responses to Iso were not affected by Glb. After beta 1-blockade with bisoprolol (0.3 mg/kg), which completely inhibited inotropic and chronotropic responses to Iso, the Iso-induced increase in CBF, presumably mediated by vascular beta 2-receptor stimulation, was not affected by Glb. Intracoronary denopamine (0.1 microgram.kg-1 x min-1), a beta 1-selective agonist, increased CBF, which was almost completely abolished by Glb. The increases in MVO2 induced by Iso or denopamine were similar before and after Glb, indicating that attenuation of the Iso- or denopamine-induced increase in CBF by Glb did not result from the decrease in MVO2. These results indicate that Glb prevented the increase in CBF associated with increased MVO2 caused by beta 1-adrenoceptor stimulation. It is suggested that ATP-sensitive K+ channels may play an important role in metabolic coronary vasodilation in dogs.

Adenosine Triphosphate↗