Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal formation in the balloon-injured rat carotid arteries in vivo.
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Adenoviridae↗
Biomedical subjects
S Nishio
Publications and source records attributed to S Nishio.
Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac.
Bacterially expressed glutathione S-transferase fusion proteins containing Rac1 were used to identify binding proteins of this Rho family GTPase present in a bovine brain extract. Five proteins of 85, 110, 125, 140 and 170 kDa were detected, all of which were associated exclusively with guanosine 5'-[gamma-thio]triphosphate-bound Rac1, not with GDP-bound Rac1. The 85 and 110 kDa proteins were identified as the regulatory and catalytic subunits respectively of phosphatidylinositol 3-kinase. Several lines of evidence suggested that the 125 kDa protein is identical with Nck-associated protein 1 (Nap1). The mobilities of the 125 kDa protein and Nap1 on SDS/PAGE were indistinguishable, and the 125 kDa protein was depleted from brain extract by preincubation with the Src homology 3 domain of Nck to which Nap1 binds. Furthermore, antibodies to Nap1 reacted with the 125 kDa protein. Nap1 was co-immunoprecipitated with a constitutively active form of Rac expressed in Chinese hamster ovary cells. The observation that complex formation between activated Rac and PAK, but not that between Rac and Nap1, could be reproduced in vitro with recombinant proteins indicates that the interaction of Nap1 with Rac is indirect. The 140 kDa Rac-binding protein is a potential candidate for a link that connects Nap1 to Rac. The multimolecular complex comprising Rac, Nap1 and probably the 140 kDa protein might mediate some of the biological effects transmitted by the multipotent GTPase.
Animals↗
Detection of lipid peroxidation and hydroxyl radicals in brain contusion of rats.
To examine the relationship between the free radicals and brain tissue damage, we investigated the intensity of brain hydroxyl (OH) radical generation and lipid peroxidation in the rat contusion injury model. A unilateral contusion was induced by a weight-drop method. All rats were decapitated six hours after the injury, and brain samples were taken from three portions (core, peripheral, and distal) to examine the specific gravity as an indicator of brain edema, generation of OH using an electron paramagnetic resonance spectrometer (EPR), and malondialdehyde (MDA) and 4-hydroxyalkenals production. Analysis of the specific gravity revealed cerebral edema on the ipsilateral side in the injured group. The signal intensity of EPR in the core and peripheral portions in the contusion group was significantly higher than that in the distal portion of the contusion group and that of all portions in the control animals. No significant difference was observed between the core and peripheral portions of the contusion group. The MDA and 4-hydroxyalkenals production was significantly higher in the core and peripheral portions than in the distal portion of the contusion group and that of all portions of the control group. The degree of posttraumatic brain edema was closely correlated with the increase of DMPO-OH adduct, MDA, and 4-hydroxyalkenals. These results support the current concept that free radical production following traumatic brain injury may induce lipid peroxidation and may be the direct cause of edema formation.
Animals↗
Effects of lecithinized SOD on contusion injury in rats.
To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic injury, the expression of Cu,Zn-SOD mRNA was examined after contusion in rat using Northern blotting. As determined by specific gravity, lecithinized SOD decreased brain edema. The expression of Cu,Zn-SOD mRNA increased at the core, peripheral and contralateral hemisphere of injury. These increases were then suppressed by lecithinized SOD. Our results support the hypothesis that superoxide may play an important role in edema formation after contusion, and that lecithinized SOD appears to prevent brain edema through a protective effect against superoxide injury.
Animals↗
Medulloblastoma: survival and late recurrence after the Collins' risk period.
Sixty-three patients with cerebellar medulloblastoma were treated between 1963 and 1992 at our institution. Among them, 10 patients have survived beyond the Collins' risk period. These included 6 males and 4 females who ranged in age from 6 months to 12 years at the time of diagnosis. A total removal of the tumor was achieved in 4 patients, while there was a subtotal removal in 3, and a partial removal in 3. Histologically, 6 tumors were classified as a classical type of medulloblastoma, and 4 were diagnosed as being a desmoplastic type. Postoperatively, 9 patients received craniospinal radiation therapy, and one received local radiation to the primary site. During the follow-up period of 3.9-25.4 years, 5 patients have been in continuous remission for from 14.2 to 25.4 years and are leading normal lives, 2 have survived for 18.1 and 18.5 years with mild to moderate neurological deficits, while the remaining 3 died after the Collins' risk period. Two out of these last 3 patients were under the age of one year at the time of onset, while the remaining one died after a second recurrence. We conclude that careful follow-up is needed for all long-term survivors even after the Collins' risk period, especially for those who were under the age of 1 year at onset and who failed in the initial treatments.
Adolescent↗
Traumatic aneurysm of the superficial temporal artery in an elderly patient.
An elderly patient suffering from the posttraumatic development of a superficial temporal artery (STA) aneurysm is described. Because the patient had renal dysfunction, angiography was performed through a direct puncture of the anterior branch of the STA in order to reduce the required dosage of contrast medium. With the patient under local anesthesia, the STA was ligated proximal and distal to the aneurysm, and thereafter removed. The diagnosis and treatment of traumatic STA aneurysms in the elderly are discussed.
Aged↗
Flow cytometric evaluation of transferrin receptor in transitional cell carcinoma.
We evaluated flow cytometric (FCM) analysis of transferrin receptor (TFR) expression as a marker for the malignant potential in transitional cell carcinoma (TCC). TCCs from 55 patients were analyzed by FCM using an anti-TFR monoclonal antibody (CD71) and a TCC-specific monoclonal antibody (EH14), which recognizes most TCC cells irrespective of the grade. The cells were divided into subpopulations according to DNA ploidy determined simultaneously. TFR expression correlated well with the grade and the stage of the tumors. TFR expression of the aneuploid tumors was significantly higher than that of the euploid tumors in all subpopulations. EH14 expression did not correlate with the grade or the stage of the tumors. EH14 expression of the aneuploid tumors was significantly higher than that of the euploid tumors in the whole cell population but not in the subpopulations. In moderately differentiated tumors or in T1 tumors, TFR expression was higher in multiple or recurrent tumors than in simple tumors. The cell size or shape were not the primary reasons for the enhanced expression of TFR in the high-grade or the high-stage tumors; instead, overproduction of TFR may take place in these tumors. Clinically, many of the TCC tumors are grouped into G2 or T1 tumors, some of which will be invasive cancers. Quantitative analysis of TFR expression using FCM may be useful to predict the prognosis of these tumors.
Aged↗
Thalamic gliomas: a clinicopathologic analysis of 20 cases with reference to patient age.
Twenty patients (M 11, F9; ranging from 1-77 years old) with histologically proven glial tumours in the thalamic region, treated from 1979 until 1994 at Kyushu University Hospital were retrospectively reviewed and analysed in order to elucidate their clinical and neuropathological characteristics. The initial common clinical manifestations were those of increased intracranial pressure or motor weakness. The histological diagnosis of the tumour was pilocytic astrocytoma in 2 patients, fibrillary astrocytoma in 7, anaplastic astrocytoma in 7, and glioblastoma multiforme in 4. The initial treatment was surgery alone in 4 patients, surgery followed by radiation therapy in 5, surgery followed by radiation therapy and chemotherapy in 9, and conventional radiation therapy alone in 2 patients. The 3-year overall actuarial survival rate for all patients was 20% but was related to both the histological type and the age of the patients: As a result, the rate was 44% for patients with low-grade astrocytoma compared to 0% for those with high-grade astrocytoma. While 5 out of 11 patients under the age of 25 years at their initial presentation have survived for from 2-16 years after the diagnosis, all patients presenting after the age of 25 years died within 3 years after treatment. Thalamic glial tumours are not a homogeneous group of tumours in terms of clinical behaviour and histopathological features, and the poor overall results, especially in adult tumours, thus emphasise the need for continued research in the treatment of these tumours.
Adolescent↗
Two new isomers of domoic acid from a red alga, Chondria armata.
Isodomoic acids G and H, two new isomers of the neurotoxin domoic acid, along with isodomoic acids A, B, E and F, were isolated from a red alga, Chondria armata, collected at the southern tip of Kyushu Island. The structures of two of these were deduced to be (E, E) and (Z, E) isomers of 2-carboxy-4-(5-carboxy-l-methyl-2-hexenylidene)-3-pyrro- lidineacetic acid, based on electrospray ionization mass and [1H]nuclear magnetic resonance spectral analyses including [1H-1H]correlation spectroscopy and nuclear Overhauser effect correlation spectroscopy.
Chromatography, High Pressure Liquid↗
Anti-inflammatory effects of beraprost sodium, a stable analogue of PGI2, and its mechanisms.
We examined whether beraprost sodium (beraprost), a stable analogue of PGI2, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 micrograms/head) plus epinephrine (0.6 microgram/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 +/- 1.64 micrograms/lung, beraprost 10 micrograms/kg; 7.49 +/- 1.36 micrograms/lung, 30 micrograms/kg; 5.33 +/- 0.71 micrograms/lung, 100 micrograms/kg; 5.52 +/- 0.79 micrograms/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE1 (170 micrograms/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 +/- 0.01, control; 3.96 +/- 0.04) and right ventricular hypertrophy (normal; 28.2 +/- 0.9%, control; 32.3 +/- 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 micrograms/kg/day of beraprost, the effects were statistically significant (beraprost 30 micrograms/kg/day; 3.85 +/- 0.02 and 27.8 +/- 1.4%, 100 micrograms/kg/day; 3.85 +/- 0.02 and 27.3 +/- 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, beraprost 10(-13) mol/paw; 91.19 +/- 2.22%, 10(-12) mol/paw; 85.79 +/- 4.85%, 10(-11) mol/paw; 78.49 +/- 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (-)-isoproterenol (10(-12) mol/paw), but PGE1 (10(-11) mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo.
Alprostadil↗
Effects of lecithinized superoxide dismutase on traumatic brain injury in rats.
Only small amounts of superoxide dismutase (SOD) are present in the extracellular space to scavenge excess amounts of superoxide anions (02-) released after traumatic brain injury (TBI). Experiments were performed in rats with cerebral contusion produced by weight-drop technique. We investigated the effects of exogenous lecithinized SOD (PC-SOD) on accumulation of 02- produced in our model, by measuring the level of SOD activity (using the NBT-reducing method) and the expression of copper, zinc-SOD (Cu, Zn-SOD) mRNA (by Northern blot analysis). As determined by tissue-specific gravity, administration of PC-SOD reduced brain edema in the periphery of the lesion 6 h after contusion. SOD activity increased in the peripheral region at 30 min after contusion, but returned to normal levels at 6 h after TBI. Administration of PC-SOD increased SOD activity up to 6 h after TBI. The expression of Cu, Zn-SOD mRNA increased in the core region, peripheral portion, and contralateral hemisphere up to 6 h after TBI, then was suppressed in all three regions by PC-SOD. Our results confirm the important role of 02- in the development of brain edema after TBI and indicate that PC-SOD diminishes brain edema through a protective effect against 02-.
Animals↗
Cholesteatoma of the ureter: a case report.
A 72-year-old man complained of general fatigue and had low grade fever. Ultrasonography, excretory urography, retrograde urography, and computed tomography revealed left hydronephrosis due to a middle ureteral tumor. A nephroureterectomy was performed. The histological diagnosis was hyperkeratosis with a cholesteatoma.
Aged↗
Phosphoinositide 3-kinase is required for insulin-induced but not for growth hormone- or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes.
The(1) regulatory mechanism of glucose uptake in 3T3-L1 adipocytes was investigated with the use of recombinant adenovirus vectors encoding various dominant negative proteins. Infection with a virus encoding a mutant regulatory subunit of phosphoinositide (PI) 3-kinase that does not bind the 110-kDa catalytic subunit (delta p85) inhibited the insulin-induced increase in PI 3-kinase activity co-precipitated by antibodies to phosphotyrosine and glucose uptake in a virus dose-dependent manner. Overexpression of a dominant negative RAS mutant in which Asp57 is replaced with tyrosine (RAS57Y) or of a dominant negative SOS mutant that lacks guanine nucleotide exchange activity (delta SOS) abolished the insulin-induced increase in mitogen-activated protein kinase activity, but had no effect on PI 3-kinase activity or glucose uptake. Although GH and hyperosmolarity attributable to 300 mM sorbitol each promoted glucose uptake and translocation of glucose transporter (GLUT)4 to an extent comparable to that of insulin, these stimuli triggered little or no association of PI 3-kinase activity with tyrosine-phosphorylated proteins. Overexpression of delta p85 or treatment of cells with wortmannin, an inhibitor of PI 3-kinase activity, had no effect on glucose uptake or translocation of GLUT4 stimulated by GH or hyperosmolarity. Moreover, overexpression of delta SOS or RAC17N also did not affect the increase in glucose uptake induced by these stimuli. A serine/threonine kinase Akt, a constitutively active mutant of which was previously shown to stimulate glucose uptake, is activated by insulin, GH, and hyperosmolarity to approximately 4-fold, approximately 2.1-fold, and approximately 2.3-fold over basal level, respectively. These results suggest that insulin-induced but neither GH- or hyperosmolarity-induced glucose uptake is PI 3-kinase-dependent, and neither RAS nor RAC is required for glucose uptake induced by these stimuli in 3T3-L1 adipocytes.
3T3 Cells↗
[Research and development of beraprost sodium, a new stable PGI2 analogue].
A novel prostaglandin I2 (PGI2) analogue, beraprost sodium, is the first launched drug as an orally active PGI2. PGI2 was discovered in 1976, and has attracted much attention as a medicine for cardiovascular diseases such as strokes and heart attacks because of its potent antiplatelet and vasodilating effect. However, PGI2 is extremely unstable for the use as practical medicines. Thus, stable PGI2 analogues have been explored by a large number of researchers in the world. Just after the discovery of PGI2, we started a research on chemically and metabolically stable PGI2 derivatives with longer duration of action and less adverse reaction. We invented a novel class of stable PGI2, 5,6,7-trinor-4,8-inter-m-phenylenePGI2 analogues that have the phenol moiety instead of the enolether moiety of PGI2. Further efforts were devoted to enhance the efficacy of the PGI2 analogues and to eliminate their side effects, and an orally active analogue, beraprost sodium, was obtained. In order to establish the synthetic route of beraprost sodium, various novel processes were invented, including ortho-selective metalation of bromoanisoles by means of Grignard reagents, copper-catalyzed SN2' cyclization to prepare cyclopenta[b]benzofuran, and stereo-selective elongation of the omega-side chain by Prins reaction. Beraprost sodium inhibit platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen and arachidonic acid. It was shown that the drug has a potent antiplatelet effect both in vitro and ex vivo in human and several animal species. In clinical studies, beraprost sodium exerted a marked effect to improve arteriosclerosis obliterans. No serious adverse effects related with the drug have been reported. It was highly evaluated as an orally active PGI2 by pharmaceutical companies overseas as well, and now clinical trials are under way in U.S.A. and Europe.
Animals↗
Movable oil in the brain: intracranial ruptured dermoid tumors. Case illustration.
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Adult↗
[Surgical management of intractable epilepsy in patients with ganglioglioma].
Long-standing intractable seizures are common manifestation of cerebral gangliogliomas. There is much controversy regarding the most appropriate surgical treatment (lesionectomy vs resection of the epileptogenic cortex with the lesion) for patients with intractable epilepsy associated with gangliogliomas. We reported 2 cases, in which the favorable seizure outcome was obtained following lesionectomy alone. (Case 1) Nine-year-old female developed attack of abnormal sensation in her left upper limb followed by motor seizure in her left limbs since 5 years old. MRI revealed hyperintense tumor in the right medial frontal lobe. Chronic invasive subdural recording showed that ictal onset zone was located in the hand motor area. Following lesionectomy alone, she became free from seizures. (Case 2) Eight-year-old girl had intractable generalized seizure since 6 years old. MRI revealed a cystic tumor in the right parietal lobe. She had multiple spike foci on electroencephalography and magnetoencephalography, and intraoperative electrocorticography failed to reveal the paroxysm. Following lesionectomy, she had good relief with less than one minor seizure per 1-3 months. Thus, lesionectomy, even without resection of the epileptogenic cortex, may improve seizure outcome in patients with ganglioglioma-associated epilepsy.
Brain Neoplasms↗
[An operated case of intractable occipital lobe epilepsy associated with calcification in the occipital lobe].
We reported a 20-year-old female of intractable occipital lobe epilepsy associated with calcification in the left occipital lobe. She developed seizures since 2 years old and electroencephalography showed paroxysmal activities on the left occipital area. At 8 years old, partial resection of the lesion and interictal spike focus under intraoperative corticography guidance was performed, but the favorable seizure outcome was not obtained. At the age of 20 years old, the frequency of her seizures has increased and admitted to our department. Preoperative evaluation with chronic invasive subdural recording showed that the ictal zone was located in the inferior (tentorial) surface and convexity of the left occipital lobe. Functional mapping involving cortical stimulation and cortical recording of pattern-reversal visual evoked potentials demonstrated that the ictal onset zone was not in the visual area. Following cortical resection of the ictal onset zone and multiple subpial transection on the surrounding cortex, she had good relief with less than one minor seizure per 1-3 months. Histological findings of the resected specimen were consistent with those of Sturge-Weber syndrome. Thus chronic invasive subdural recording may improve seizure outcome in patients whose epileptogenic area was located near the visual field.
Adult↗
[Low flow anesthesia using a fresh gas flow of 600 ml.min-1 for 5 hours].
Low flow anesthesia (LFA) using a fresh gas flow (FGF) of 600 ml.min-1 with oxygen and nitrous oxide flow each set at 300 ml.min-1, and dial setting of sevoflurane 3% was administered to 30 patients for a duration of 5 hours. There were no problems such as unsuitable concentrations of nitrous oxide and sevoflurane in inspired and expired gases or low FIO2 below 0.3 during anesthesia in 15 patients of group A. Their body weight was 53 +/- 5 kg. FIO2 decreased below 0.29 at about 4 hours in 7 patients of group B weighing 62 +/- 6 kg, and at about 1 h in 8 patients of group C weighing 71 +/- 7 kg. In group A and B, the sum of concentrations of oxygen, nitrous oxide and sevoflurane in inspired gas decreased for a moment and recovered as anesthesia progressed, but in group C, it kept decreasing without recovery. The body weight was significantly different among the 3 groups (P < 0.05). It was suggested that in group A the FGF per body weight was suitable; in group B though oxygen flow was larger than oxygen consumption, hypoxia occurred due to saturation of nitrous oxide in the body; and in group C the FGF was insufficient. The compound A was detected in the breathing circuit, and the concentration was around 20 ppm and it did not depend on the duration of LFA. It was concluded in this study that LFA using the FGF of 600 ml.min-1 with setting of 3% sevoflurane, 50% oxygen and nitrous oxide, could be performed safely without risks such as hypoxia and severe delay of induction for patients weighing 53 +/- 5 kg for a duration of 5 hours.
Adult↗