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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 271 records · Page 15Linked to original sources

[Effect of dilazep on experimental vasospasm--evaluation of angiographical vasospasm and cerebral blood flow].

The effects of dilazep dihydrochloride on angiographic vasospasm and regional cerebral blood flow after subarachnoid hemorrhage were evaluated in double hemorrhage canine model. Severe angiographic vasospasm of basilar artery (percent reduction of intra-luminal diameter; 52.4%) was shown in untreated dogs. Daily intra-venous administration of dilazep (0.3 mg/kg for one hour) significantly inhibited angiographic vasospasm (percent reduction of intra-luminal diameter; 33.2%, p less than 0.05). Dilazep had a marked vasodilatory effect even in severe vasospasm in untreated dogs, and had a tendency to increase cerebral blood flow of the cerebral cortex in spite of reduced blood pressure. From these characteristics of action, intra-venous administration of dilazep would be useful agent for the treatment of cerebral vasospasm after subarachnoid hemorrhage.

Animals↗

[An infected partially thrombosed giant aneurysm of the azygos anterior cerebral artery].

The authors report a case of partially thrombosed giant aneurysm which was secondarily infected with purulent meningitis. The relationship between the infection of the aneurysm, the rapid growth of the aneurysm and the development of severe cerebral edema was discussed. A 53 year-old man was admitted on September 1, 1986, with a diagnosis of bacterial meningitis. On his admission, his body temperature was 39 degrees C, and he showed mental confusion but no neurological deficits. Laboratory data revealed signs of infection in white blood cell count, CRP, and erythrocyte sedimentation rate. Computerized tomographic (CT) scan and magnetic resonance (MR) imaging showed a massive round mass with perifocal edema measuring 40mm in the maximum diameter in the left paramedian frontal region. T1 weighted MR image also showed the presence of pus accumulation in the left ventricle. Cerebral angiography demonstrated a giant aneurysm at the distal portion of the azygos anterior cerebral artery, and irregular narrowing of both the supraclinoid segment of the carotid artery and its main branches indicating arteritis due to purulent meningitis. The patient was treated with ventricular drainage and administration of antibiotics. Culture of the purulent CSF was negative. The patient's lab data, CSF finding and neurological status improved progressively. However, follow-up CT scan and angiogram a month later showed enlargement of the aneurysm, dilatation of the patent lumen and perifocal edema. On October 8, the patient suddenly became comatose with anisocoria. A CT scan showed massive edema with marked midline shift. Emergency bifrontal craniotomy was carried out, and clipping was completed after removal of the thrombosed portion of the aneurysm, and thromboendarterectomy of the aneurysmal neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm, Infected↗

Two distinct affinity binding sites for IL-1 on human cell lines.

We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated.

Adolescent↗

Subacute brain atrophy after radiation therapy for malignant brain tumor.

Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

Aged↗

Auger effects on bromo-deoxyuridine-monophosphate irradiated with monochromatic X-rays around bromine K-absorption edge.

In order to study the enhanced effect by Auger cascade, samples of bromo-deoxyuridine-monophosphate (Br-dUMP) in aqueous solutions were irradiated with monochromatic X-rays at 13.49 keV and 13.43 keV, just above and below the K-absorption edge of bromine, using synchrotron radiation as a source. Radiolytic products such as deoxyuridine-monophosphate (dUMP), uracil and bromo-uracil (Br-uracil) were isolated using high performance liquid chromatography. Their amounts were quantitatively analysed as a function of the absorbed dose in the solutions containing Br-dUMP for the energy of the X-rays. G values for these products were calculated on the basis of the absorbed energy. As the results, the ratios of G values of radiolytic products from Br-dUMP between X-rays of 13.49 keV and 13.43 keV were 2.2 for dUMP, 1.02 for Br-uracil and 1.23 for uracil, suggesting clearly the energy dependent enhancement. On the other hand, little significant difference between X-rays of 13.49 keV and 13.43 keV was observed for the G values of uracil released from dUMP irradiated in aqueous solutions. It seemed to confirm that the Auger electrons from K-shell of bromine atoms might play the main role for energy-dependent enhancement at induction of these radiolytic products.

Chromatography, High Pressure Liquid↗

Sequential changes of auditory brain stem responses in relation to intracranial and cerebral perfusion pressure and initiation of secondary brain stem damage.

The relationship of supratentorial intracranial pressure (ICP) and cerebral perfusion pressure (CCP) with serial changes in auditory evoked brain stem responses was investigated. Eighty-one patients without primary brain stem damage admitted to our emergency unit were studied. When ICP over 50 mm Hg persisted for 4 hours, the I-V interpeak latency was significantly prolonged. The threshold of this prolongation was 8 hours for the ICP over 45 mm Hg and 24 hours for that of over 40 mm Hg. The ICP of 35-40 mm Hg for 24 hours was the border zone. CCP did not show a significant relation with I-V interpeak latency changes. The loss of wave V was observed in a wide range of the ICP (30-147 mm Hg) and CPP (0-60 mm Hg). Wave III disappeared when the ICP exceeded 50 mm Hg. Wave I became undetectable with an ICP above 50 mm Hg or a CPP below 40 mm Hg. These results indicate that an increase of ICP over 40 mm Hg definitely initiates secondary brainstem dysfunction if it lasts for more than 24 hours and that the ICP should be reduced below this level, preferably below 35 mm Hg, to maintain brain function. The fact that both low CPP and high ICP were involved in the loss of wave I clearly shows that both ischaemia and displacement of the brain stem are the important pathophysiological factors for the disappearance of wave I.

Acoustic Stimulation↗

The role of free radicals and eicosanoids in the pathogenetic mechanism underlying ischemic brain edema.

Results of our consecutive study on the pathogenic mechanism underlying ischemic brain edema are summarized in this paper. Pertinent findings are as follows: (1) there is a close correlation between the influxes of water and sodium following ischemia; (2) the edema fluid can be regarded as the ultrafiltrate of serum; (3) there is a significant increase in the brain content of HETEs following ischemia; (4) the lipoxygenase activity of brain microvessels is increased following ischemia; (5) the lipoxygenase activity as well as the Na+, K+-ATPase activity of brain microvessels are enhanced by a hydroperoxide, 15-HPETE; (6) inhibition of Na+, K+-ATPase of brain microvessels by intraarterial infusion of ouabain resulted in a significant decrease in edema formation; and (7) not the cyclooxygenase, but the lipoxygenase pathway seems to be involved in the enhancement of microvessel Na+, K+-ATPase. Lipoxygenase(s) and Na+-K+-ATPase of brain microvessels, the activities of which are enhanced by an increased level of free radicals and/or hydroperoxides, may play a significant role in the occurrence of ischemic brain edema.

Animals↗

Modulation of porcine granulosa cell functions by interleukin-1.

Increasing evidence suggests that functions of the immune system and gonads are closely related with each other. In cultures of granulosa and luteal cells, macrophages have been shown to modulate steroidogenic functions. In this paper we present the modulatory effects of interleukin-1, a cytokine produced predominantly by activated macrophages, on gonadotropin-induced differentiation, as well as growth of cultured porcine granulosa cells.

Animals↗

The role of endothelin in the pathogenesis of vasospasm following subarachnoid haemorrhage.

The purpose of the present study was to evaluate the vasocontractile activity of endothelin, a newly isolated endothelium-derived constrictor peptide, in canine basilar arteries in vitro and in vivo. Endothelin at concentrations of 10(-12) M approximately 3 X 10(-8) M elicited dose-dependent contractions of canine basilar arteries in vitro. The maximum tension was larger than that induced by 40 mM KCl. The EC50 value was 1.9 +/- 0.6 X 10(-9) M (mean +/- SEM). The endothelin-induced contraction was reversed by 10(-8) M nicardipine or 10(-5) M approximately 10(-4) M papaverine. An intracisternal injection of 0.6 approximately 1.2 X 10(-12) mol/kg of endothelin caused biphasic contraction of the basilar artery lasting for more than 24 h. The initial phase of the contraction accompanied remarkable changes in vital signs such as an acute rise of blood pressure, bradycardia and respiratory arrest. An intracisternal injection of 2.0 X 10(-12) mol/kg of endothelin also induced acute contraction of the basilar artery. However, all of the dogs which received an intracisternal injection of 2.0 X 10(-12) mol/kg of endothelin died from sustained respiratory insufficiency. The present results demonstrate that endothelin induces strong and long-lasting contractions of cerebral arteries. Therefore, endothelin may play an important role in the pathogenesis of vasospasm.

Angiography↗

Endothelin-1 acts in cerebral arteries from the adventitial but not from the luminal side.

The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or cisternal injection of the peptide. In both cats and dogs, ET-1 (5-500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗

Beneficial effects of cervical spinal cord stimulation (cSCS) on patients with impaired consciousness: a preliminary report.

Electrical stimulation of the spinal cord can be used for treatment of intractable pain and spasticity. Based on our experimental findings cervical spinal cord stimulation (cSCS) was performed on eight patients with severe brain dysfunction due to traffic accidents, pronounced vasospasm caused by subarachnoid hemorrhage or surgery of huge cerebral tumors (chordoma). After a 1 to 2 month period of stimulation, two patients became conscious and began to speak. It remains unclear whether cSCS induced the restoration of consciousness and improved neurological deficits. Although the successful results might be due to chance, cSCS might have stimulated brain function. This preliminary report shows such excellent results that further studies are warranted.

Adult↗

Endothelin acts in feline and canine cerebral arteries from the adventitial side.

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗

Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.

Animals↗

Prostaglandin profiles in relation to local circulatory changes following focal cerebral ischemia in cats.

We explored the temporal and topographic relations between local cerebral blood flow and regional brain prostaglandin profile following prolonged or transient occlusion of the middle cerebral artery in cats. Each experimental group was subjected to a sham operation, prolonged ischemia, or recirculation. Local cerebral blood flow was measured by the hydrogen clearance method. Following in situ freezing, cortical samples were obtained from each gyrus for determination of prostaglandin (PG) F2 alpha, PGE2, 6-keto-PGF1 alpha, and thromboxane (TX) B2 concentrations by radioimmunoassay. During prolonged ischemia, the concentrations of PGF2 alpha and PGE2 within the middle cerebral artery territory were significantly increased. Immediately after recirculation, there was a prominent but transient increase in PGF2 alpha and PGE2 in gyri that had been exposed to moderate ischemia (perifocal area). By contrast, the increases in these prostaglandins were slow and less prominent in gyri that had been exposed to severe ischemia (the focal area). The concentration of 6-keto-PGF1 alpha did not change during prolonged ischemia but transiently increased following recirculation in both the focal and perifocal areas. The TXB2 concentration did not change in any experimental group. Our study revealed a homogeneous increase in the regional brain content of PGE2 or PGF2 alpha in spite of the heterogeneous reduction of local cerebral blood flow during prolonged ischemia. Following recirculation, the focal and perifocal areas exhibited different patterns of prostanoid content. No correlation was found between local cerebral blood flow and the regional concentration of any prostaglandin examined.

6-Ketoprostaglandin F1 alpha↗