Biomedical subjects

S Nagao

Publications and source records attributed to S Nagao.

At least 127 records · Page 7Linked to original sources

PubMed1997

Embryonic transplantation and ischemic memory deficit.

Transient forebrain ischemia is associated with selective neuronal vulnerability and persistent memory deficit. This study compares functional outcome and morphological changes in rats subjected to post-ischemic CA1 or hilus/dentate gyrus region hippocampal fetal transplantation. Ischemia was produced by bilateral common carotid artery occlusion with hypotension. Fetal hippocampal neurons were transplanted into both sides of the CA1 or hilus/dentate gyrus region of the dorsal hippocampus, 1 week post-ischemia. Four weeks post transplantation, the rats underwent behavioral testing for 5 consecutive days using the water maze trial. All animals were perfusion fixed for morphological studies. Transplants in the CA1 region of the dorsal hippocampus were associated with memory and morphological recovery, while grafts placed into the hilus/dentate gyrus region of the dorsal hippocampus were not. Similarly, neurons transplanted in the CA1 region of the dorsal hippocampus were morphologically similar to CA1 pyramidal cell neurons and stained positive with calbindin D(28k). In contrast the grafts transplanted into the hilus/dentate gyrus region of the dorsal hippocampus were morphologically heterogeneous and staining with calbindin D(28k) was not as robust. Post-ischemic transplantation in the CA1 region of the dorsal hippocampus is effective in improving memory and morphological function.

Animals↗

PubMed1997

Location of efferent terminals of the primate flocculus and ventral paraflocculus revealed by anterograde axonal transport methods.

Efferents of the flocculus (FL) and ventral paraflocculus (VP) were examined in seven anesthetized Macaca fuscata by anterograde axonal transport method using wheat germ agglutinin-conjugated horseradish peroxidase or phaseolus vulgaris leucoagglutinin. Several major foci of axon terminals were found in the vestibular nuclear complex and cerebellar nuclei. A difference was seen in the location of efferent terminals between the FL and VP. When the tracer covered the FL, labeled axon terminals were located within the medial and ventrolateral parts of the medial vestibular nucleus, superior vestibular nucleus and y-group. When the tracer covered the VP, labeled axon terminals were located within the caudo-ventral part of posterior interpositus and dentate nuclei, in addition to the medial and ventrolateral parts of the medial vestibular nucleus, superior vestibular nucleus and y-group. Labeled terminals were virtually absent in the basal interstitial nucleus of the cerebellum. On the points of neo- or paleo-cerebellar cortex fiber connections, these results correspond to our previous anatomical observations that the FL received mossy fiber afferents mainly from the vestibular system and nucleus reticularis tegmenti pontis and very little from the pontine nuclei, whereas the VP received mossy afferents mainly from the nucleus reticularis tegmenti pontis and pontine nuclei and very little from the vestibular system. These anatomical observations are consistent with a hypothesis in our previous anatomical and physiological study that the primate FL and VP mediate rather different functional roles in the oculomotor control.

Animals↗

PubMed1997

The effect of paclitaxel on the progression of polycystic kidney disease in rodents.

Woo et al (Nature 368:750-753) reported that parenteral administration of paclitaxel arrested the striking renal enlargement and prolonged life in C57BL/6J-cpk/cpk mice with a rapidly progressive form of polycystic kidney disease (PKD). In the current study, we sought to determine whether paclitaxel could alter the progression of other forms of hereditary PKD in rodents. Paclitaxel was administered by intraperitoneal injection to C57BL/6J-cpk/cpk mice and Han:SPRD-Cy/Cy rats with rapidly progressive PKD and to DBA/2FG-pcy/pcy mice and Han:SPRD-Cy/+ rats with slowly progressive PKD. Paclitaxel (150 micrograms/wk) prolonged the survival of cpk/cpk mice from 24.5 days to more than 65 days and decreased kidney weight relative to body weight from 16.5% at 21 days of age to 8.2% at more than 65 days of age. Mortality attributable to paclitaxel was 12%. By contrast, the administration of paclitaxel (0.1 to 15 mg/kg/wk) to 7- to 10-day-old Han:SPRD-Cy/Cy rats with rapidly progressive PKD had no effect on the course of the disease; moreover, paclitaxel caused severe side effects and premature death in all the Cy/Cy animals. Heterozygous male Cy/+ rats develop slowly progressive renal enlargement and azotemia. Paclitaxel, administered at 7, 15, or 27 mg/kg/wk to male Cy/+ rats from 4 until 10 weeks of age, reduced body weight gain, had an inconsistent effect on kidney weight relative to body weight, and had no effect on the serum urea nitrogen concentration. Mortality associated with the 7, 15, and 27 mg/kg/wk doses of paclitaxel was 0%, 15.4%, and 28.5%, respectively. DBA/2FG-pcy/pcy mice of either sex developed slowly progressive renal enlargement and azotemia. The administration of paclitaxel (100 to 150 micrograms/wk) from 2 to 10 weeks of age to DBA/2FG-pcy/pcy mice with cystic disease had no effect on the increase in kidney weight or on the level of serum urea nitrogen in comparison to untreated cystic animals. Mortality associated with 100- and 150-micrograms/wk doses of paclitaxel was 0% and 20%, respectively. We conclude that paclitaxel diminished the rate of renal enlargement and increased the life span of cpk/cpk mice but not Cy/Cy rats with rapidly progressive forms of PKD. Paclitaxel had no apparent benefit in Cy/+ rats nor pcy/pcy mice with slowly progressive PKD. On the basis of these studies in rodents, it appears that paclitaxel has limited potential usefulness as a therapeutic agent in the treatment of PKD.

Animals↗

PubMed1997

Renal accumulation and excretion of cyclic adenosine monophosphate in a murine model of slowly progressive polycystic kidney disease.

Evidence from in vitro studies indicates that increased proliferation of epithelial cells and secretion of fluid by these cells may be important factors in the progressive enlargement of renal cysts. The rate of cellular proliferation and fluid secretion by cyst epithelium in vitro can be strikingly accelerated by cyclic adenosine 3'5' monophosphate (cAMP) and agonists that lead to the production of this nucleotide. The extent to which renal cAMP content is increased in polycystic kidneys is unknown. In the current study, we determined the amount of this nucleotide in intact kidneys, cyst fluid, plasma, and urine in nonazotemic mice (DBA/2FG-pcy/pcy) with a slowly progressive form of inherited polycystic kidney disease (PKD). In 45 pcy/pcy mice studied 20, 45, or 70 days after birth, the total kidney cAMP content was 0.22 +/- 0.01, 0.46 +/- 0.02, and 0.90 +/- 0.05 pmol/mg tissue, respectively. By contrast, in 37 control DBA/2J mice the levels of cAMP at identical times remained relatively constant at 0.22 +/- 0.01, 0.21 +/- 0.01, and 0.29 +/- 0.01 pmol/mg tissue, respectively. In 70-day-old nonazotemic pcy/pcy mice with normal serum levels of parathyroid hormone, cAMP generated by the kidneys (nephrogenous cAMP) was 22.9 +/- 2.8 nmol/100 mL creatinine clearance, compared with 6.5 +/- 1.3 in normal animals of the same age (P < 0.001). The cyst fluids of 70-day-old pcy/pcy mice contained a lipid that increased transepithelial secretion of fluid by MDCK monolayers from a baseline of 0.012 +/- 0.002 to 0.136 +/- 0.008 microL/cm2/hr (P < 0.05). This lipid also stimulated cellular proliferation by monolayers of cultured MDCK and LLC-PK1 cells 2.5- and 7.9-fold (P < .05), respectively, and stimulated cAMP accumulation by these cells 1.6- and 2.0-fold (P < .05), respectively. These studies illustrate that renal cAMP production and excretion increase in concert with the cystic enlargement of the kidneys in DBA/2FG-pcy/pcy mice and identify a lipid cAMP agonist in murine renal cystic kidney disease.

Aging↗

PubMed1997

EAAT4, a glutamate transporter with properties of a chloride channel, is predominantly localized in Purkinje cell dendrites, and forms parasagittal compartments in rat cerebellum.

Glutamate transporters play a pivotal role in terminating glutamatergic transmission by eliminating glutamate from the synaptic cleft. Four different glutamate transporter cDNAs have been isolated thus far, and their tissue distribution has been investigated using northern blot and immunohistochemical analysis. We raised site-directed antisera against a synthetic oligopeptide corresponding to the C-terminal of EAAT4, a recently cloned human glutamate transporter, and investigated the distribution of EAAT4 in rat cerebellum. Western blot analysis demonstrated that the affinity-purified antiserum SAE4 recognized specifically a single band (about 62 kDa) in the rat cerebellum, cerebrum and spinal cord. The SAE4-immunoreactivity was localized predominantly in the dendritic spines and distal dendrites of Purkinje cells. The intensity of the immunoreactivity was uneven among Purkinje cells, forming parasagittal compartments. Since EAAT4 also has the properties of a glutamate-gated chloride channel, it should be able to modulate the transmission at the parallel fiber-Purkinje cell synapses.

Amino Acid Transport System X-AG↗

PubMed1997

Centrally administered calcium increases the maximum vagal activation of baroreceptor reflex control of heart rate in spontaneously hypertensive rats.

Baroreceptor reflex control of heart rate (HR) was examined before and 15 min after intracerebroventricular infusion (i.c.v.) of 10 microliters of high-Ca2+ solution (Ca2+, 16.3 mM) in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). The slope of the individual regression line of the relation between reflex HR changes (delta HR) and changes in mean arterial pressure (delta MAP) produced by bolus injections of phenylephrine or sodium nitroprusside (delta HR/delta MAP; beats/min/ mm Hg) for bradycardia was significantly less in SHR (-0.60 +/- 0.30; n = 10) than in WKY (-1.78 +/- 0.27; n = 10; p < 0.01) at baseline. The slope increased in SHR during administration of high Ca2+ to -1.39 +/- 0.17 (p < 0.01) but not in WKY: In contrast, no significant changes were observed for the reflex tachycardia both in SHR (n = 7) and WKY (n = 10). Further, we analyzed sigmoidal MAP-HR reflex curves in SHR with i.c.v. of either high Ca2+ (n = 6) or artificial cerebrospinal fluid (aCSF; n = 5). Administration of high Ca2+ reduced the bradycardic plateau and increased HR range without changes in average gain. Our results suggest a modulatory role for central Ca2+ in the baroreceptor reflex control of HR in SHR.

Animals↗

PubMed1997

Enhanced depressor effect of centrally administered high-calcium solution in salt-loaded experimental hypertension.

The depressor effect by oral calcium supplementation is known to be more pronounced in salt-dependent than in renin-dependent hypertension. This study was conducted to investigate the role of central calcium on two different pathophysiologic subtypes of experimental hypertension; (a) salt-dependent, deoxycorticosterone acetate-salt hypertensive rats (DOCA), and (b) renin-dependent, 2-kidney, 1 clip (2-K, 1C) hypertensive rats. In DOCA (n = 10), high-calcium solution (Ca+2, 65.2 mM, 10 microl) given centrally (i.c.v.) elicited a marked decrease in mean blood pressure (MBP; 170 +/- 4 to 138 +/- 5 mm Hg, p < 0.01) with a decrease in heart rate (HR; 390 +/- 18 to 344 +/- 17 beats/min, p < 0.05) lasting for 40 min. In 2-K, 1C (n = 10), high-Ca2+ i.c.v. showed a lesser decrease in MBP (178 +/- 4 to 171 +/- 5 mm Hg) and HR (419 +/- 10 to 395 +/- 12 beats/min) with shorter duration (for 20 min) than in DOCA. This significant depressor and bradycardic response to Ca2+ i.c.v. observed in DOCA was dose dependent at Ca2+ concentrations between 65.2 and 130.4 mM. In DOCA, high Ca2+ i.c.v. reduced the plasma noradrenaline (Nad) concentration significantly (479 +/- 81 to 319 +/- 62 pg/ml, p < 0.05). These results suggest that central Ca2+ plays a more important role in regulating sympathetic nerve activity and BP in salt-dependent than in renin-dependent experimental hypertension.

Animals↗

PubMed1997

Ultrasonic bruits in the circle of Willis due to a large nonfunctioning pituitary adenoma.

In a man with a histologically verified non-functioning pituitary adenoma with suprasellar extension, Doppler signals resembled those associated with bruits (ultrasonic bruits). These signals were detected in the anterior circulation of Willis both preoperatively and intraoperatively. The large tumor was resected subtotally via a right orbitozygomatic approach. The use of microvascular sonography for intraoperative monitoring can provide information on the potential cerebrovascular complications of surgery. No previous studies on the presence of ultrasonic bruits associated with pituitary adenomas have been reported. The clinical implications for the surgical treatment of pituitary adenomas are discussed.

Adenoma, Chromophobe↗

PubMed1997

Detection of subependymal veins using high-resolution magnetic resonance venography.

High-resolution magnetic resonance venography (HR-MRV) of intracranial subependymal veins using a two-dimensional Fourier-transform time-of-flight technique was performed on normal volunteers and clinical cases of cerebral disease. For the pulse sequence, fast-field-echo sequence was used with the following parameters: TR/TE/flip angle = 34 ms/12 ms/50 deg., 256 x 256 matrix, 1 mm effective slice thickness, 150 mm field of view, and one signal acquisition. Sequential vertical coronal sections were taken against the skull base. The anterior septal vein, the medial atrial vein, the anterior caudate vein and thalamostriate vein were detected in all subjects. In all clinical cases, HR-MRV was equal in diagnostic capability to conventional cerebral angiography.

Adult↗

PubMed1997

Intraarterial infusion of papaverine in experimental cerebral vasospasm.

PURPOSE: To determine the effectiveness of intraarterial infusion of papaverine hydrochloride (PPV) in an experimental model of cerebral vasospasm and to measure the mean blood flow velocity of the middle cerebral artery (MCA). METHODS: Seven Japanese monkeys were divided into three groups: those studied 3 days-after surgery (the third-day group, n = 3); those studied 7 days after surgery (the seventh-day group, n = 3); and a control group (n = 1). Vasospasm was induced in the experimental groups by placing a blood clot in the subarachnoid space around the top of the internal carotid siphon. PPV (5 mg/kg) was infused (over 60 minutes) into the internal carotid artery (ICA). The vascular diameters of the ICA and MCA were measured on angiograms before and after infusion. The mean blood flow velocity in the MCA was measured on transcranial Doppler sonograms before and 24 hours after infusion. After fixation, the MCA was dissected out, stained, and examined microscopically. RESULTS: After vasospasm induction, both arteries were narrowed more than 30% in the third-day group and more than 50% in the seventh-day group. After PPV infusion in both groups, vascular dilatation of about 20% was seen. The mean increase in blood flow velocity in the third-day group (30%) was smaller than in the seventh-day group (70%). The mean blood flow velocity in the MCA decreased by about 30% in both groups, but increased again after 24 hours nearly to the level before PPV infusion. The intimal layer was more corrugated in the seventh-day group, and hypertrophy in the smooth muscle layer was also seen. Clinical examination showed no neurologic deficit in the third-day group 24 hours after PPV infusion; neurologic deficits were observed in the seventh-day group. CONCLUSION: PPV infusion may be more effective in early stages of vasospasm when vascular walls have fewer histologic changes.

Animals↗

PubMed1997

Benign osteoblastoma of the temporal bone.

We report a case of benign osteoblastoma arising in the temporal bone of a 28-year-old woman. Plain radiography showed a mass with an amorphous calcified matrix and a thin radiolucent marginal zone. CT and MR imaging were useful in delineating the extent of the tumor, and angiography showed its hypervascularity. Preoperative transarterial embolization was effective in reducing bleeding during surgery.

Adult↗

PubMed1997

[Effectiveness of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for symptomatic vasospasm after subarachnoid hemorrhage].

PURPOSE: To evaluate the clinical effectiveness of PTA and/ or intra-arterial infusion of papaverine (PPV) for the treatment of symptomatic vasospasm after subarachnoid hemorrhage. MATERIALS AND METHODS: From September 1989 to March 1996, twenty patients with symptomatic vasospasm were treated by PTA and/or intra-arterial infusion of PPV. Nine of the patients were treated by only PTA, eight by only PPV infusion, and three by both PTA and PPV infusion. Early clinical results were evaluated within 48 hours after treatment. Changes in the mean flow velocity (MFV) of the M1 segment as determined by TCD before and after treatment were also evaluated. RESULTS: Six of the nine patients (66.7%) treated only by PTA, six of the eight patients (75%) treated only by PPV, and all three patients (100%) treated by both PTA and PPV infusion showed improvement of neurological deficits within 48 hours after treatments. CONCLUSION: PTA was effective for main trunk vasospasm, while PPV infusion was more effective for peripheral severe vasospasm in recovery from neurological deterioration after subarachnoid hemorrhage. Use of both treatments further increased the effectiveness.

Adult↗

PubMed1997

Synergistic antitumor effects of human interferon-beta and interferon-gamma on human gastric adenocarcinoma cells.

The combined effects of different classes of interferon (IFN) on human gastric adenocarcinoma cell line HPE-GAC-2 (GAC-2) were investigated in vitro. Synergistic effects of IFN-beta and -gamma, causing cell death, were observed in a dose-dependent manner. IFN-gamma modulated the sensitivity of GAC-2 cells to the cytocidal effect of IFN-gamma. The modulatory effect was independent of the cytostatic or cytocidal activity of IFN-beta since brief contact with IFN-beta did not influence the growth kinetics of the cells and was effective in modulate the cellular sensitivity to IFN-gamma. A brief pretreatment of the cells with IFN-alpha or-beta resulted in a variable level of modulation, whereas coculture of the cells with IFN-beta or -alpha and IFN-gamma had a similar cytotoxic effect indicating a different level of activity induced by IFN-alpha and -beta with the common type I receptor. These results suggest that IFN-beta-induced modulation was receptor-mediated. Phase contrast microscopy showed evidence of apoptotic cell death induced by one or more IFN agents. The morphological changes included chromatin condensation and nuclear fragmentation which were apparent at as early as 6 hr of culture with a high concentration of IFN(s). Our results indicate that IFN-beta and IFN-alpha enhance the in vitro apoptotic effects of IFN-gamma against GAC-2 tumor cells.

Adenocarcinoma↗

PubMed1997

[Expression of ATP binding cassette superfamily (multidrug resistance-1, multidrug resistance-associated protein, human canalicular multispecific organ anion transporter) mRNA in etoposide and m-AMSA resistant cell lines].

The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase (topo) II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to etoposide or m-AMSA. Subsequently, a population of cells from each sublines was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. Quantitative aspects of MRP and C-MOAT were studied by Northern blotting in 66 resistant cell lines. Increased MRP mRNA was observed in 48.5% of resistant cell lines (64.7% of etoposide resistant cells and 31.3% of m-AMSA resistant cell lines). Increased C-MOAT mRNA was also observed in 39.4% of resistant cell lines (41.2% in etoposide resistant cell lines and 37.5% in m-AMSA resistant cell lines). To characterize the function of C-MOAT, cellular accumulation assay for 3H-etoposide was performed in three resistant cell lines which overexpress C-MOAT but do not express MRP. Accumulation of etoposide was reduced in the cell lines. Our findings suggest that increased MRP and O-MOAT mRNA seems to be an important mechanism of resistance to topo II inhibitors.

ATP-Binding Cassette Transporters↗

PubMed1997

[Expression of DNA topoisomerases (I, II alpha, II beta) mRNA in etoposide- and mAMSA-resistant cell lines].

The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase (topo) II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to etoposide or m-AMSA. Subsequently, a population of cells from each subline was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. Quantitative aspects of topo I, II alpha, and II beta were studied by Northern blotting in 66 resistant cell lines. Reduced topo II alpha mRNA was observed in 95.5% of resistant cell lines, and median topo II alpha mRNA was lower (38.0 +/- 28.1%) in resistant cell lines in comparison to parental cell lines, while increased topo I and II beta were observed (145.5 +/- 89.3%, and 165 +/- 105.9% of that of parental cell lines). But the expression of the topo I and II beta gene were not correlated to that of topo II alpha. Our findings suggest that reduced topo II alpha mRNA seems to be the most important mechanism of resistance to topo II inhibitors.

Amsacrine↗

PubMed1996

Nitric oxide released from zwitterionic polyamine/NO adducts inhibits Cu2+-induced low density lipoprotein oxidation.

The effects of nitric oxide (NO) released from zwitterionic polyamine/NO adducts on Cu2+-induced low density lipoprotein (LDL) oxidation were studied. When each of the two kinds of NO releasing zwitterionic polyamine/NO adducts (NOC5 and NOC7) was incubated at 5 microM with isolated human LDL (0.25 mg/ml) and Cu2+, the formation of thiobarbituric acid reactive substances (TBARS) was inhibited. The duration of inhibition by NOC7 (20 min) and NOC5 (100 min) corresponded to the NO generation lives of respective zwitterionic polyamine/NO adducts. The duration of inhibition was dependent on the amount of NOC5 added (2.5-20 microM). Repeated additions of 5 microM NOC5 at 100 min intervals worked as inhibitor in the same manner. NOC5 broke to inhibit at any process of the Cu2+-induced LDL oxidation reaction. Fragmentation of apolipoprotein B derived from Cu2+-induced LDL oxidation was also prevented by the addition of NOC5. These results clearly indicate that NO inhibits the oxidative modification of LDL induced by Cu2+. NO releasing zwitterionic polyamine/NO adducts are good reagents for NO studies.

Antioxidants↗

PubMed1996

Protective effect of vagus nerve stimulation on forebrain ischaemia in gerbil hippocampus.

The left vagus nerve was stimulated during transient forebrain ischaemia in gerbils. The animals were exposed to 3 min of forebrain ischaemic insult at 37.5 degrees C. On day 5 post-ischaemia, the animals were perfusion-fixed for qualitative and quantitative histopathological analyses. High current stimulation of the vagus nerve inhibited ischaemic neuronal damage in the hippocampal CA1 sector (p < 0.01), but low current stimulation did not (p < 0.01). These effects might have been due to inhibition of the effects of excitatory amino acids during ischaemia. These results indicate that vagus nerve stimulation might be protective to neurones subjected to ischaemic insult.

Animals↗

PubMed1996

Effect of tris-(hydroxymethyl)-aminomethane on experimental focal cerebral ischemia.

Systemic and focal cerebral acidosis is considered deleterious to cell metabolism and neuronal recovery. We investigated the immediate effect of tris-(hydroxymethyl)-aminomethane (THAM), an alkalizing agent, on focal cerebral ischemia produced by occlusion of the left middle cerebral artery (MCA) in cats with systemic acidosis. Occlusion of MCA resulted in prompt decreases in local cerebral blood flow of the ipsilateral marginal and ectosylvian gyri from 47.7 ml/100 g per minute in control to 32.3 ml/100 g per minute and 8.3 ml/100 g per minute, respectively. In the control group, physiological saline was infused continuously and the treated group received 0.3 M THAM to normalize systemic and focal cerebral acidosis. There were no significant changes in the systemic arterial pressure, arterial PO2 and PCO2 throughout the experiments in the two groups. Arterial pH decreased from 7.42 to 7.30 in the control, while it remained normal during THAM treatment. Extracellular pH of the marginal gyrus (peri-infarct zone) decreased from 7.39 to 6.87 with 6 h ischemia in the control group. In THAM infusion, extracellular pH was kept between 7.26 and 7.29, which was significantly higher than the control group. THAM significantly decreased infarct volume and lactate and water contents of the gray matter in the marginal gyrus at 6 h after occlusion. It is concluded that THAM infusion immediately after ischemia onset is considered effective in improving acidosis at the site of ischemic penumbra and consequently reduces lactate production, brain edema, and infarct volume.

Acid-Base Equilibrium↗