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Biomedical subjects

M Takayasu

Publications and source records attributed to M Takayasu.

At least 91 records · Page 5Linked to original sources
PubMed1988

Effects of neuropeptide Y on canine cerebral circulation.

The effects of neuropeptide Y (NPY) on the vascular tone of isolated cerebral arteries and vertebral blood flow (VBF) were studied in dogs. NPY elicited a dose-dependent contraction of arteries derived from the brain with ED50 values of 2 nM for the middle cerebral and basilar arteries. Arteries from the neck did not respond to NPY. Intra-arterial administration of NPY as a bolus reduced the VBF dose dependently, with no significant alteration of mean arterial blood pressure and heart rate. The decrease in VBF developed slowly and had a long duration, which was consistent with the observations made in vitro. NPY suppressed the contractile effect of noradrenaline (NA) on isolated cerebral arteries and pretreatment with NPY suppressed the effect of NA on VBF, indicating that NPY contributes to the inhibitory modulation of postsynaptic adrenergic mechanisms. These findings suggest that NPY could have a role in the regulation of cerebral circulation.

Animals↗
PubMed1988

The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs.

The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20-30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Vasomotor responses of rat intracerebral arterioles to vasoactive intestinal peptide, substance P, neuropeptide Y, and bradykinin.

The effect of vasoactive peptides on vascular smooth muscle in the cerebral microcirculation was examined using an isolated intracerebral arteriole preparation. Extraluminally applied vasoactive intestinal peptide (VIP) dilated the spontaneous tone of intracerebral arterioles to 118.9 +/- 3.1% of control diameter at pH 7.30, with an EC50 of 7.27 X 10(-8) M. Similar degrees of dilation to VIP were seen in vessels preconstricted by changing bath solution to pH 7.60. Substance P had no effect on vessel diameter at pH 7.30. However, in vessels precontracted by pH 7.60, significant dose-dependent dilation was observed with an EC50 of 2.55 x 10(-10) M. Neuropeptide Y constricted intracerebral arterioles to 81.22 +/- 2.7% of control diameter, with an EC50 of 6.23 x 10(-10) M. Bradykinin dilated intracerebral arterioles at pH 7.30 and pH 7.60 to 130 +/- 3.0% of control diameter. VIP and bradykinin are potent vasodilators of intracerebral arterioles. Neuropeptide Y is a vasoconstrictor. The effect of substance P appeared to be either pH-dependent or dependent on some degree of precontraction by another agonist, but no effect on vessel diameter was seen at pH 7.30.

Animals↗
PubMed1988

Protein kinase activity in canine basilar arteries after subarachnoid hemorrhage.

To investigate the intracellular physiology of cerebral arterial vasospasm after subarachnoid hemorrhage (SAH), we measured the activity of three protein kinases related to vascular smooth muscle function. Myosin light chain kinase (MLCK), cyclic adenosine monophosphate (cAMP)-dependent protein kinase and cyclic guanosine monophosphate (cGMP)-dependent protein kinase activity was determined in canine basilar arteries using the SAH model created by two intracisternal injections of autologous blood. Moderate chronic cerebral vasospasm was confirmed angiographically 7 days after the first injection of blood, with a mean decrease in the diameter of the basilar artery to 61.2 +/- 2.3% (SE) of preinjection controls. Enzymatic analysis of basilar arteries excised from control dogs and from SAH model dogs 2 to 10 days after an intracisternal injection of blood demonstrated detectable MLCK and cyclic nucleotide-dependent protein kinase activity. The MLCK activity was approximately 3 times higher than the cyclic nucleotide-dependent protein kinase activity. There was no significant difference in basilar artery protein kinase activity between control animals and SAH model animals at any time for up to 10 days after the intracisternal injection of blood. As MLCK is involved with smooth muscle contraction and cAMP- and cGMP-dependent protein kinases are involved in smooth muscle relaxation, our results suggest that the metabolic machinery of vascular smooth muscle in the cerebral arterial wall is intact after SAH and that prolonged vasospasm represents an appropriate physiological response by the vascular smooth muscle to external stimuli. If this is correct, the successful pharmacological manipulation of vasospasm after SAH is more likely than if profound disruption had occurred, and further investigative efforts in this area should be encouraged.

Animals↗
PubMed1988

Effects of calcium antagonists on intracerebral penetrating arterioles in rats.

There is no direct information on the effect of calcium antagonists on intracerebral penetrating arterioles, which are responsible for a significant part of total cerebrovascular resistance. In a study on rats, the effects of four calcium antagonists (diltiazem, verapamil, nifedipine, and nimodipine) on isolated intracerebral penetrating arterioles with mean resting diameters (+/- standard error of the mean) of 52.3 +/- 3.0 micron were investigated. Vessel diameters were monitored in vitro by means of a video microscope dimensional analyzer under constant transmural pressure (60 mm Hg) after cannulation. Each calcium antagonist produced maximal dilation of about 50% (diltiazem 46.4% +/- 5.6%, verapamil 53.1% +/- 6.0%, nifedipine 46.9% +/- 6.1%, and nimodipine 47.1% +/- 5.4%) with varied sensitivity (median effective dose (ED50): diltiazem 1.52 X 10(-6) M, verapamil 1.08 X 10(-7) M, nifedipine 8.65 X 10(-9) M, and nimodipine 1.62 X 10(-9) M). Dilation effects persisted for a significantly longer time after washout with calcium antagonists such as diltiazem (15.5 +/- 1.8 minutes), nifedipine (19.0 +/- 3.9 minutes), and nimodipine (30.0 +/- 1.6 minutes) than after washout with adenosine (8.5 +/- 1.0 minutes). It appeared that the magnitude of vasodilation was greater and the duration of dilation after washout longer in intracerebral penetrating arterioles than that reported for pial arterioles, although sensitivity to each calcium antagonist was quite similar to that reported for larger cerebral arteries. These data provide a possible explanation for the apparent disparity between clinical efficacy and angiographically determined vessel diameter when patients with cerebral vasospasm are treated with calcium antagonists. These agents may have a greater effect on intracerebral penetrating arterioles than on angiographically visible larger arteries.

Animals↗
PubMed1987

Trigeminal sensory evoked potentials in patients with trigeminal neurinoma: report of two cases.

The trigeminal sensory evoked potentials (TEPs) in two patients with trigeminal neurinoma are reported. In contrast to the two cases previously reported by others, in which the preoperative TEPs were normal, the two cases reported herein showed significant changes on the affected side: the sensory thresholds were greater and the peak latencies of P19 and N28 were longer on the affected side than those on the normal side. Our results confirm that a TEP measurement is very useful in a preoperative examination of patients with trigeminal neurinoma, when the function of the trigeminal nerve should be evaluated objectively.

Cranial Nerve Neoplasms↗
PubMed1987

Mechanism of action of a novel antivasospasm drug, HA1077.

HA1077, but not the potent calcium entry blocker nicardipine reversed experimental chronic cerebral vasospasm induced in a two-hemorrhage canine model. The i.a. administration of HA1077 produced significant increases in vertebral blood flow in dogs. The effects of HA1077 on the vascular responses were studied in vitro. Spiral strips of rabbit aorta were mounted for isometric tension recording in physiological salt solution. HA1077 produced a competitive inhibition of the Ca++-induced contraction of the depolarized rabbit aorta. The pA2 of HA1077 for the Ca@-induced contraction was 6.71. The inhibitory effect of HA1077 on the KCl-induced contraction was not altered by atropine, propranolol, theophylline or indomethacin. HA1077 (10(-8) to 10(-4) M) inhibited contractile responses to KCl, phenylephrine (PHE) and prostaglandin (PG) F2 alpha similarly, whereas verapamil, diltiazem and nicardipine were much less effective in blocking the contractions induced by PHE or PG. Even in Ca++-free physiological salt solution, both PHE and PG were capable of contracting the aorta. These Ca++-free contractile responses to PHE and PG were antagonized effectively by HA1077. Verapamil failed to inhibit these contractions. We also investigated the effects of HA1077 on guinea pig heart contractility. In contrast to calcium entry blockers (which are known to have a direct negative inotropic effect), HA1077 did not change the developed tension in the left atrium at concentrations up to 3 X 10(-4) M. The present evidence demonstrates that the novel antivasospasm drug HA1077 is a class of calcium antagonists different from the calcium entry blockers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

The effects of HA compound calcium antagonists on delayed cerebral vasospasm in dogs.

The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquinolinesulfonamide) and HA 1077(1-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 X 10(-6) M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10(-5) M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10(-5) M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a "two-hemorrhage" canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% +/- 2% (mean +/- standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA 1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA 1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

[Immunohistochemical study of subependymal giant cell tumor associated with tuberous sclerosis].

Subependymal giant cell tumors from four patients associated with tuberous sclerosis were examined by peroxidase antiperoxidase (PAP) immunohistochemistry for neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S-100 protein. The tumor cells were grouped into three morphological types: ganglion-like pyramidal cells, swollen gemistocytic cells and fibrillated spindle cells. There was little difference in immunohistochemical property between these cell types in each case, suggesting that the tumor cells of different cell types have a same origin. The majority of the tumor cells was intensely stained for NSE in every case. On the other hand, for GFAP none of the tumor cells was stained in two cases, and the minority was weakly stained in the other two cases. The intensity of staining of the tumor cells for S-100 protein varied from case to case. Our findings together with those of others show the definite immunohistochemical characteristics of subependymal giant cell tumors with tuberous sclerosis, i.e., strong positivity for NSE in contrast to their negativity or weak positivity for GFAP. However, these findings do not necessarily suggest that the tumor is of neuronal origin, because in the case of neoplasms the significance of the presence of NSE as indicative of neuronal origin is open to question.

Adolescent↗
PubMed1985

Long-term follow-up of patients with optic glioma.

Patients with optic glioma were classified into two types: infant type and childhood. The infant type was usually immature astrocytomas that had an aggressive course and had a poor prognosis. On the other hand, the childhood type was usually mature astrocytomas with a rather benign, self-limiting course, even when the tumor had been left untreated. To make a long-term assessment, 11 patients with optic glioma were studied and 6 long-term survivors with chiasmal tumor invasion, in whom total removal of the tumor had not been feasible, were followed up for 8-12 years. Most of them had a stable course both clinically and radiologically.

Adolescent↗
PubMed1985

S-100 protein and calmodulin levels in cerebrospinal fluid after subarachnoid hemorrhage.

The levels of two calcium-binding proteins, S-100 protein and calmodulin, were measured serially in the cerebrospinal fluid (CSF) of patients after subarachnoid hemorrhage (SAH) and aneurysm surgery. These two proteins have a similar molecular structure and are highly concentrated in the central nervous system (CNS). The levels of S-100 protein found in the earliest postoperative CSF samples correlated with the preoperative SAH grades. High S-100 protein levels in the CSF were found in patients with poor SAH grades. Moreover, the prognosis of the patients correlated with the S-100 protein levels in the CSF samples taken during the immediate postoperative period and with the daily changes of the S-100 protein levels. Severe diffuse cerebral vasospasm was followed by a sharp S-100 protein increase. These results suggest that S-100 protein levels in the CSF provide a useful index of organic damage in the CNS, and furthermore that S-100 protein levels and their changes may have prognostic value for patients after SAH. On the other hand, there was a lack of correlation between the calmodulin levels and the preoperative grade or outcome. It would be inappropriate, however, to speculate from the results of this study that these calcium-binding proteins in the CSF play any causative role in pathological processes such as cerebral vasospasm or brain ischemia after SAH, since changes in the levels of these proteins followed the onset of clinical signs of deterioration.

Calcium-Binding Proteins↗