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Biomedical subjects

K Sano

Publications and source records attributed to K Sano.

At least 343 records · Page 19Linked to original sources

Modulation of AP-1 activity by nitric oxide (NO) in vitro: NO-mediated modulation of AP-1.

To understand the role of nitric oxide (NO) in controlling the specific DNA-binding activities of transcriptional factors, we investigated the in vitro effect of the NO-donor sodium nitroprusside (SNP) on the AP-1 activity of cultured mouse cerebellar granule cells. A gel-mobility assay showed that SNP inhibited AP-1 activity in the presence, but not the absence of dithiothreitol (DTT). This DTT-dependent inhibition of AP-1 activity by SNP corresponded with the activation of the chemical reactivity of SNP with DTT, which can be monitored by the production of nitrite (NO2-). In contrast, diamide, a typical sulfhydryl oxidizing agent, inhibited AP-1 activity in the absence of DTT and its inhibitory effect was reversed competitively by DTT. Studies using structurally or functionally related analogues of SNP demonstrated that S-nitrosylation of the AP-1 moiety mediated by some NO-carriers but not by free NO, which can be produced by the chemical reaction of SNP with DTT, was responsible for the inhibition of AP-1 activity, suggesting NO-mediated regulation of the AP-1 transcriptional factor.

3T3 Cells↗

Molecular cloning and characterization of two rab GDI species from rat brain: brain-specific and ubiquitous types.

Rab GDP dissociation inhibitor (GDI) is a regulatory protein for Rab proteins that controls not only the GDP/GTP exchange reaction of Rab proteins but also their translocation between the cytosol and cell membranes. Recently, rab GDI cDNAs have been isolated from human, bovine, rat, and Drosophila, and these Rab GDI proteins indicated an important role in the regulation of intracellular vesicle traffic. In this study, we have isolated two different rab GDI cDNAs, designated rat rab GDI alpha and beta, from a rat brain cDNA library using bovine rab GDI cDNA as a probe. Rat rab GDI alpha and beta show 99 and 86% amino acid identity with bovine rab GDI, respectively, indicating that rat rab GDI alpha is a rat counterpart of bovine rab GDI. Both rat Rab GDI alpha and beta proteins expressed in Escherichia coli showed a similar degree of activity of regulating the GDP/GTP exchange reaction to that of bovine Rab GDI using Rab3A and Rab11 as substrates. Northern blot analysis revealed that rab GDI alpha mRNA was expressed abundantly in brain but much less in other tissues, whereas rat rab GDI beta mRNA was ubiquitously expressed. Reverse transcription-polymerase chain reaction analysis revealed that astrocytes expressed rat rab GDI beta gene but not rat rab GDI alpha gene. These results indicate that Rab GDI alpha is involved in sorting of highly specialized vesicles in brain such as neurosecretory vesicles, whereas Rab GDI beta plays a general role in vesicular trafficking in diverse types of cells.

Amino Acid Sequence↗

Effect of YM737, a new glutathione analogue, on ischemic brain edema.

We investigated the effect of YM737, a monoester of glutathione (GSH), on brain edema and GSH content after occlusion of a middle cerebral artery (MCA) in the rat. The drug possesses stronger radical scavenging activity than GSH itself, and is more effectively transported into cells. Hemispheric water, sodium, and potassium contents were determined at 2.5 and 24 hours after MCA occlusion. The animals received either YM737 or GSH immediately after occlusion. Cerebral GSH content was measured by HPLC after 2.5 hours of ischemia. The increases in water and sodium contents at 2.5 and 24 hours after MCA occlusion were significantly suppressed by YM737. GSH content decreased by 53% in the caudate, and by 22% in the cortex after ischemia. YM737 significantly ameliorated the GSH decrease in the caudate, while administration of GSH showed little effects on the ischemia-induced changes in water, sodium, and GSH contents. The result suggests the role of free radicals in the pathogenesis of ischemic brain edema.

Animals↗

CT and MRI features of intracranial germ cell tumors.

The computed tomographic (CT) and magnetic resonance imaging (MRI) features of 73 histologically proven primary intracranial germ cell tumors were analysed. CT images were available for all 73 patients, and 22 of them were also examined by MRI. The tumors were classified as germinoma, mature teratoma, immature or malignant teratoma, yolk sac tumor, choriocarcinoma, embryonal carcinoma and mixed type. Germinoma was revealed as a high- or slightly high-density area on plain CT scan, and was enhanced homogeneously. MRI revealed iso- or slightly low signal intensity on T1-weighted images, and iso- or high intensity on T2-weighted images. Mature teratoma, which had a clear margin on neuroradiological images, was characterized by mixed density on CT scans, often showing large cysts and area of calcification. Immature or malignant teratoma had a similar pattern to that of mature teratoma, but the cystic components and area of calcification tended to be less and smaller respectively. The tumor margin was obscure in malignant teratoma, and perifocal edema was observed in some cases. The shape of yolk sac tumors was irregular. Plain CT scan revealed an iso- or low-density mass with good heterogeneous enhancement. Perifocal edema was observed in some cases. In mixed germ cell tumors, MRI imaging was useful for detecting teratomatous components, particularly fatty components. Although definite histological diagnosis cannot be achieved by CT and/or MRI alone, detailed analysis of neuroradiological images are useful for predicting the histological diagnosis.

Brain Neoplasms↗

The temporo-polar approach to basilar artery aneurysms with or without zygomatic arch translocation.

Since the publication of the temporo-polar approach to basilar artery aneurysms by Sano (1980 and 1987), various modifications of the approach were reported. The approach provides a better view and a wider operating field than the subtemporal or pterional ones. Usually the approach does not need temporary remove of the zygomatic arch. If however, a basilar tip aneurysm is located very high above the posterior clinoid, temporary removal of the zygomatic arch is necessary which is sutured back to its original position at the end of the operation.

Basilar Artery↗

Pleural lipoma: report of a case.

We report herein the unusual case of a 45-year-old Japanese man whose chest X-rays revealed an abnormal shadow, increasing in size. A chest wall tumor was suspected, based on the findings of computed tomography (CT) of the thorax, the CT number of which was -137, chest roentgenogram, and an echograph. An open biopsy was performed to establish the final diagnosis. The resected tumor was a pedunculated pleural mass, yellowish in color, the pathological diagnosis of which confirmed a lipoma. Intrathoracic lipomas are rare, but pleural lipomas are seen even less frequently. CT, echography, and percutaneous needle biopsy have been found useful for diagnosing intrathoracic lipomas, but these examinations are not always adequate for confirming the final diagnosis. Consequently, tumor resection is essential for obtaining a pathological diagnosis.

Humans↗

Biochemical and biophysical alterations of lipoprotein after liver transplantation from a living related donor. A biochemical and proton NMR study.

Changes in lipoprotein metabolism after liver transplantation from living related donors were investigated in nine pediatric patients by means of biochemical and proton nuclear magnetic resonance (NMR) analyses of lipoprotein. NMR offers rapid and nondestructive measurement of lipoprotein. The ratio of esterified cholesterol to total cholesterol, expected to be a prognostic indicator after liver transplantation, was low before the operation (0.44) and recovered to over 0.6 at 3 weeks. The half line width of the methylene peak of lipoprotein, as measured by proton NMR, was correlated with the ratio of esterified cholesterol to total cholesterol. It is suggested that proton NMR analysis can provide information about the biophysical changes in lipoprotein associated with liver transplantation.

Biochemical Phenomena↗

Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the superantigen staphylococcal enterotoxin B.

BACKGROUND/AIMS: Staphylococcal enterotoxin B (SEB) acts as a superantigen binding to class II major histocompatibility complex proteins, and this complex stimulates T cells. The aim of this study was to investigate the pathogenic effects of SEB on hepatic injury and lethal shock in mice. METHODS: SEB was administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver injury and levels of circulating cytokines were determined. In vitro cytokine production in response to SEB was also investigated. RESULTS: Intraperitoneal administration of SEB (50 micrograms) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GalN-sensitized mice, with no mortality on injection of up to 100 micrograms SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor alpha (TNF-alpha) levels reached a peak, followed by high levels of serum interferon-gamma (IFN-gamma) up to 10 hours after injection. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody (mAb) protected GalN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-gamma-neutralizing mAb. SEB induced the production of TNF-alpha and IFN-gamma in a dose-dependent manner from splenic mononuclear cells in vitro. CONCLUSIONS: The results show that SEB contributes to lethal shock associated with severe hepatic injury in GalN-sensitized mice and suggest that TNF-alpha and IFN-gamma produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.

Animals↗

Infectious complications in living related liver transplantation.

During the last 31 months, 50 children between 3 months and 15 years of age have undergone living related liver transplantation (LRLT) for end-stage liver diseases (39 biliary atresia, 2 Budd-Chiari syndrome, 2 progressive intrahepatic cholestasis, 3 liver cirrhosis, 1 Wilson disease, 1 protoporphyria, 1 tyrosinemia, and 1 fulminant hepatitis). Combined FK-506 and low-dose steroids were routinely used for immunosuppression. There were seven deaths, two of which were related to infection (Candida pneumonia and Epstein-Barr virus [EBV]-associated lymphoproliferative syndrome [LPS]). Five patients had a bacterial infection, all of which were associated with surgical complications. Three patients had Candida infection, all of which were malnourished, had biliary atresia, and had been managed with prolonged antibiotics against obstinate ascending cholangitis. There were 14 symptomatic viral infections (1 herpes simplex virus, 1 herpes zoster virus, 5 cytomegalovirus [CMV], 6 EBV, and 1 EBV-associated LPS). Three of the five CMV infections appeared in patients whose graft was ABO-incompatible, who were managed with prophylactic OKT-3. Most of the viral infections (except 1 EBV-associated LPS) were minor and were treated successfully. The low incidence and successful treatment of CMV infection are related to the high compatibility and low incidence of allograft rejection in LRLT. Bacterial and fungal infections can be decreased by greater refinement of surgical technique and more aggressive preoperative management. Treatment of EBV infection is still an unsolved problem.

Adolescent↗

Living related liver transplantation in children.

We reviewed 37 living related liver transplantations (LRLT) performed by our department during the last 27 months on children with end-stage liver disease. The patients were 15 boys and 22 girls aged 7 months to 15 years with biliary atresia (27), cryptogenic cirrhosis (3), Budd-Chiari syndrome (2), progressive intrahepatic cholestasis (2), protoporphyria (1), Wilson's disease (1), and fulminant hepatitis (1). The donors were 14 fathers and 23 mothers. Grafts were made from the left lateral segment (19), left lateral segment with partial S4 (11), left lobe (6), and right lobe (1). After graft harvesting all donors resumed normal liver function and normal life. The recipient underwent total hepatectomy with preservation of the inferior vena cava. FK506 and low-dose steroids were used for immunosuppression. The survival rate was 90% (27/30) in elective cases and 57% (4/7) in emergency cases. Six recipients had functioning grafts but died of extrahepatic complications. Hepatic vein stenosis occurred in 3 cases at 3 months after LRLT and was successfully treated by balloon dilatation. Portal vein stenosis occurred in 1 case at 8 months after LRLT and was also safely dilated. We incurred no hepatic artery thrombosis after introducing microsurgery techniques. Among 12 viral, 5 bacterial, and 3 fungal postoperative infections, 1 Candida pneumonia and 1 EBV-associated lymphoma were lethal. Three patients with ABO-blood group compatible grafts and one with an incompatible graft developed acute rejection, which was controlled in evey case by steroid bolus and/or increasing the dose of FK506. There were no definite episodes of rejection in ABO-identical cases. Children with moderate growth retardation (> or = -1.5 SD of normal growth) caught up in growth soon after LRLT, but those with severe retardation (<-1.5 SD) were slow to attain age-normal height. Appropriate timing, meticulous surgical procedures, and comprehensive management of complications are crucial for successful outcome with LRLT. LRLT is a promising option for alleviating the shortage of livers for pediatric transplantation and may be regarded as an independent modality to supplement cadaver donation.

Acute Disease↗

Sperm-egg fusion in the sea urchin is blocked in Mg(2+)-free seawater.

Magnesium ions as well as calcium ions are required for successful fertilisation in sea urchins. In the absence of Mg2+ spermatozoa attached to the egg plasma membrane, their acrosomal processes passing through the vitelline envelope, but could not enter the egg cytoplasm (Sano et al., Dev. Growth Differ. 22, 531-41, 1980). Such an individual spermatozoon was observed microscopically to resume entry into the egg immediately after the addition of a sufficient amount of Mg2+ to the surrounding medium. Neither any change in membrane potential nor an increase in intracellular Ca2+ concentration of the egg was observed after insemination in the absence of Mg2+, although both could be observed after the addition of Mg2+. The sperm heads did not show fluorescence when attached to the surface of an egg previously microinjected with mithramycin A in Mg-free seawater, indicating that there was no connection between the sperm and the egg. Therefore, occurrence of fertilisation potential must be a post-fusional event. These results suggest that Mg2+ are indispensable for fusion between the sperm acrosomal membrane and the egg plasma membrane.

Animals↗

Grading and timing of surgery for aneurysmal subarachnoid haemorrhage.

Among our series of 1519 cases of subarachnoid haemorrhage (SAH) due to aneurysmal rupture, 171 cases (11.3%) died of rebleeding while waiting for surgery mostly within one week after SAH. 1329 cases underwent surgery, 655 cases within one week and 674 cases later than one week after SAH. The mortality at 6 months following SAH was 14.5% in the former group of early surgery, and 3.9% in the latter group of delayed surgery. The latter, however, became 15-29%, if the above 11.3% were added to it. Scrutiny (chi 2-test and U-test) of the outcome at 6 months after SAH revealed the following: Cases of WFNS grade I (GCS: 15) just prior to surgery showed good results regardless of timing of surgery (good recovery: 87.1%, mortality: 2.9%), while WFNS grade IV (GCS: 12-7) and V (GCS: 6-3) cases showed rather poor results regardless of timing of surgery. For WNFS grades II and III cases (GCS: 14-13), surgery on Day 3-7 may better be avoided because of a higher mortality and morbidity due to vasospasm. For cases over 60 years of age, delayed surgery may be preferable especially in higher grade cases.

Aneurysm, Ruptured↗

Acute ischaemic and delayed ischaemic neurological deficits as the causes of bad grading in aneurysmal subarachnoid haemorrhage.

When subarachnoid haemorrhage (SAH) occurs, intracranial pressure (ICP) rises which heralds a series of symptoms termed acute ischaemic neurological deficits (AINDs). At the same time, free radicals are generated, and because of deficient scavenging mechanisms in the cerebrospinal fluid (CSF), these free radicals cause lipid peroxidation. Products of lipid peroxidation effect the cerebral arterial wall from the very early stage, probably infiltrating the wall through channels of the wall opening to the CSF space to exhibit inflammatory changes such as subintimal cell proliferation, myonecrosis etc. Lipid peroxidation also leads to degradation of membrane phospholipids, such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and to rise in the intracellular level of diacylglycerol (DAG), an intrinsic protein kinase C (PKC) activator. Subsequent release of free arachidonic acid from PC (and/or PE) stimulates the arachidonate cascade which generates various eicosanoids and free radicals contributing to inflammatory changes in the arterial wall. As the intracellular level of DAG is increased, the PKC system is more and more activated, resulting in the development of sustained smooth muscle contraction. This, together with inflammatory changes in the arterial wall, forms the full-fledged picture of delayed cerebral vasospasm, leading to delayed ischaemic neurological deficits (DINDs).

Animals↗

Disparity between sensory nerve activity and psychophysical responses for air-puff stimulation of the index finger and palm in man.

Air-puff stimuli were delivered to five successive sites over the index finger and palm to obtain psychophysical responses and to record sensory nerve action potentials (SNAPs) from the median nerve at the wrist for elucidating psychoneural correlations across different locations of the glabrous hand. Magnitude estimations at each location evoked uniform subjective magnitudes for all stimulus locations. The time-integral of all SNAP components was the largest at the finger tip and the smallest at the most proximal site over the palm in agreement with the reported receptor density gradient across the finger and palm. Thus, the constant magnitude estimations with different quantities of peripheral afferent inputs across areas imply that the central nervous system plays a major role in shaping subjective magnitude estimation across different locations.

Action Potentials↗

An improved non-radioisotopic reverse transcriptase assay and its evaluation.

We developed an improved, highly sensitive non-radioisotopic (non-RI) reverse transcriptase (RT) assay (RTA). While the original non-RI method previously reported made use of primer immobilization, our improved method was based on a primer-template immobilization procedure. We tested the template specificity, reproducibility and linearity of the new method in assays of human immunodeficiency virus type-1 (HIV-1) RT. The sensitivities of the method previously reported, the improved method and the sensitive radioisotopic (RI-) RTA were compared in assays of recombinant HIV-1 RT, partially purified HIV-1 particles, and the culture supernatant derived from HIV-1-infected cells. For each of these samples except the culture supernatant the improved method was the most sensitive. It appeared that the fetal bovine serum presented in the culture medium interfered with the assay reaction. The curve describing inhibition of the assay reaction by fetal bovine serum showed that the highest degree of sensitivity in the assay was obtained when the culture supernatant sample was diluted four times. With this degree of dilution, the sensitivity of the new method for assay of culture supernatant sample was still half that of the sensitive RI-RTA. Culture supernatants of five peripheral blood mononuclear cell samples obtained from HIV-1-seropositive carriers were assayed by both the improved method and the sensitive RI-RTA; and with each of the methods, however all virus-positive cultures could be detected. The improved non-RI RTA was considered especially useful for assay of culture supernatants for purposes of virus isolation because of its advantages of excellent sensitivity and lack of requirement for radioisotopes.

HIV Reverse Transcriptase↗

Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates by nonradioisotopic reverse transcriptase-typing assay.

We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay.

Antibodies, Viral↗

Dynorphin binds to neuropeptide Y and peptide YY receptors in human neuroblastoma cell lines.

The modulation of neuropeptide Y (NPY) and peptide YY (PYY) receptors by dynorphin, luteinizing hormone-releasing hormone (LHRH), corticotropin-releasing factor (CRF), and cholecystokinin octapeptide has been studied in human neuroblastoma cell lines SK-N-MC and SMS-MSN, which express Y1 and Y2 receptors for NPY/PYY. Dynorphin A and LHRH inhibited the binding of NPY/PYY to SK-N-MC cell membranes at concentrations ranging from 10(-7) to 10(-5) M, whereas dynorphin A and CRF were effective in SMS-MSN cells. The inhibitory effect of dynorphin A on NPY/PYY binding was observed in the presence of guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analogue, as well as H-7 and H-8, novel inhibitors of protein kinases C and A. However, U-50488, the most potent kappa-selective compound did not mimic the dynorphin action. Dynorphin A showed neither effect on the dissociation of NPY/PYY from their receptors nor inhibition on the basal as well as forskolin-stimulated adenosine 3',5'-cyclic monophosphate response. These results indicate that the interaction of dynorphin A with Y1 and Y2 receptors is not mediated by changes in receptor-G protein interaction, receptor phosphorylation, and allosteric binding to NPY/PYY receptors but that dynorphin A binds to NPY/PYY receptors at high concentrations, probably in an antagonistic manner.

Corticotropin-Releasing Hormone↗

Disturbance of retention of memory after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the behavioral changes, in particular retention of memory, after focal cerebral ischemia in rats. METHODS: Ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). For quantitative behavioral analysis, one-trial passive avoidance response and active avoidance response with the discrete lever-press avoidance procedure were observed. One group of animals was trained once to learn the passive avoidance task 1 day before surgery. The response latency was examined 4 and 14 days after surgery. The second group was trained to learn the active avoidance task for 2 weeks before surgery. The avoidance rate was examined 3 and 14 days after surgery. RESULTS: The MCA-occluded group showed significant failure of memory retention in both of these tasks (P < .01). The nonoperated group and sham-operated group showed no definite memory failure. CONCLUSIONS: Retention of memory in the passive avoidance response and the active avoidance response was disturbed after left MCA occlusion in the rat. These results strongly suggest that this model can be used to assess memory disturbance after focal cerebral ischemia.

Animals↗