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Biomedical subjects

M Kano

Publications and source records attributed to M Kano.

At least 199 records · Page 11Linked to original sources
PubMed1989

Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures.

Cerebral blood flow was measured and compared in 10 symmetrical brain regions following unilateral trigeminal ganglionectomy (n = 13), sham operation (n = 6), or trigeminal root section (rhizotomy) (n = 8) in cats. Multiple determinations were obtained in anesthetized and paralyzed animals using radiolabeled microspheres during (i) normocapnia-normotension, (ii) hypercapnia (5% CO2/95% room air), (iii) angiotensin-induced acute severe hypertension (190 greater than mean arterial blood pressure less than 210 mmHg), or (iv) bicuculline-induced seizures. Flow was symmetrical in all brain regions at rest and during increases induced by hypercapnia in the three groups. During severe hypertension or seizures, marked elevations developed bilaterally (approximately 93% and approximately 130%, respectively). In ganglionectomized animals, increases due to hypertension or seizures were attenuated by 28-32% on the denervated side within cortical gray matter regions corresponding to the anterior, middle, and posterior cerebral arteries. Flow was symmetrical within all brain regions in sham-operated animals and in the rhizotomy group, despite comparable increases in regional cerebral blood flow induced by angiotensin. Hence, the trigeminal nerve mediates blood flow adaptations during severe hypertension and seizures. Furthermore, since trigeminal cell bodies and peripheral axons are destroyed or degenerate following ganglionectomy but not following rhizotomy, local "axon reflex-like" mechanisms mediate these increases in cerebral blood flow.

Angiotensin II↗
PubMed1989

Postocclusive cerebral hyperemia is markedly attenuated by chronic trigeminal ganglionectomy.

Marked hyperemia may develop in brain following temporary cessation of blood flow and is associated with the morbidity following cardiac arrest, stroke, and head injury. Regional cerebral blood flow was measured using radiolabeled microspheres and compared in 10 symmetrical regions after chronic unilateral trigeminal ganglionectomy (n = 8), trigeminal rhizotomy (n = 4), or sham operation (n = 4) following 10 min of combined brachiocephalic-left subclavian occlusion and hypotension (mean arterial blood pressure less than 50 mmHg) in cats. Blood flow was symmetrical at rest in the three groups and was undetectable during the ischemic period. Within 30 min after re-establishing flow, values in cortical gray matter increased symmetrically to approximately 250 ml.100 g-1.min-1 in the rhizotomy and the sham groups. Increases of similar magnitude were measured on the intact side following trigeminal ganglionectomy but flow was attenuated by greater than 50% ipsilateral to the ganglionectomy. Marked hyperemia developed during reperfusion in thalamus, caudate, deep cortical white matter, midbrain, and pons, but no asymmetries were present in the three groups. These data suggest that cortical hyperemia is mediated by trigeminal neurogenic mechanisms via axonal reflexlike mechanisms and suggest the importance of therapeutic strategies based on blockade of this nerve or its constituent neuropeptides.

Animals↗
PubMed1989

Studies on antibacterial agents. I. Synthesis of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acids.

A series of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acids was synthesized and tested for antibacterial activities. Among them, 9-fluoro-6,7-dihydro-5-methyl-8-(4-methyl-1-piperazinyl)-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7241) exhibited potent antibacterial activity against gram-positive and -negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa, and 9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H, 5H-benzo[i,j]quinolizine-2-carboxylic acid (OPC-7251) showed potent activity characteristically against Propionibacterium acnes.

Anti-Bacterial Agents↗
PubMed1989

[Two cases of atypical HTLV-I associated myelopathy (HAM)].

We report two cases of HTLV-I associated myelopathy (HAM) who showed high HTLV-I antibody titers with clinically atypical neurological symptoms compared with typical HAM originally reported by Osame et al. Case 1 is a 59 year-old-woman who showed Shy-Drager syndrome-like symptoms such as a slowly progressive gait disturbance, pyramidal and extra-pyramidal symptoms, an orthostatic hypotension and a sweating disturbance. The anti HTLV-I antibody titer was highly positive in both her serum and cerebrospinal fluid (CSF), and there was also a high level of oligoclonal immunoglobulin in her CSF. These symptoms improved slightly with steroid therapy. Therefore, it was suspected that this neurological condition was associated with HTLV-I, which means that HTLV-I can be associated not only with myelopathy but also with various other neurological symptoms. The second case is a 52-year-old woman who had a myelopathy with a slowly progressive course. She had suffered from a transient optic neuritis 5 years before admission that had improved completely with steroid therapy. She had highly positive anti HTLV-I antibody in both her serum and CSF, and also showed a high level of oligoclonal immunoglobulin in her CSF. With administration of steroids, the sensory disturbances and abnormal findings in the CSF improved slightly. Koprowski et al reported that in some MS patients they found positive anti HTLV-I antibody and furthermore proved the presence of CSF cells which hybridized with a HTLV-I probe. They suggested the presence of an unknown HTLV-related agent which may be a pathogenic factor in some subtypes of MS. The transient optic neuritis responding to steroid therapy and the following transverse myelopathy, as seen in case 2, are highly characteristic of MS. Thus, some clinical features of HAM may be very similar to MS.

Female↗
PubMed1988

The glutamate receptor subtype mediating parallel fibre-Purkinje cell transmission in rabbit cerebellar cortex.

Responses of Purkinje cells to parallel fibre stimulation and to ionophoretically applied glutamate agonists, L-glutamate, L-aspartate, quisqualate, kainate and N-methyl-D-aspartate (NMDA), were extracellularly recorded in a superficial folium of the dorsal paraflocculus of high-decerebrate rabbits. NMDA caused an inhibition of simple spike discharge from Purkinje cells. 2-Amino-5-phosphonovalerate (APV), a selective NMDA receptor antagonist, effectively antagonized this inhibition. However, APV did not antagonize the excitation of Purkinje cells caused by quisqualate or parallel fibre stimulation. By contrast, both kynurenate and gamma-D-glutamylglycine (gamma-DGG) effectively antagonized the excitation of Purkinje cells by parallel fibre stimulation in a dose-dependent manner. Both kynurenate and gamma-DGG also antagonized the excitation of Purkinje cells caused by quisqualate, L-glutamate, L-aspartate or kainate. However, the antagonism was more prominent to L-aspartate and kainate than to quisqualate and L-glutamate. Quisqualate response was antagonized to an extent comparable with the response to parallel fibre stimulation. These results indicate that the receptor for the neurotransmitter at parallel fibre-Purkinje cell synapses is of quisqualate-specific type. The present data are consistent with the evidence that L-glutamate is the endogenous transmitter at these synapses.

2-Amino-5-phosphonovalerate↗
PubMed1988

Improved delivery through biological membranes. 26. Design, synthesis, and pharmacological activity of a novel chemical delivery system for beta-adrenergic blocking agents.

Novel ketoxime analogues of known beta-blockers (propranolol, timolol, carteolol) were synthesized and tested as potential site-specific chemical delivery systems. It was assumed that a hydrolysis-reduction sequence could produce the active beta-blockers in the iris-ciliary body. It was found that some of these bioprecursors are remarkably active in reducing intraocular pressure in rabbits. The ketoxime derivative of propranolol is more effective and much less irritant than its parent beta-blocker. While the ketoximes also displayed activity on isoprenaline-induced tachycardia after iv administration, they were void of activity when given orally. Propranolol was found for a prolonged time and in significant concentrations in the rabbit's eye following topical administration of its ketoxime precursor; however, the inactive ketoximes apparently were not converted to the corresponding beta-blockers in the eye. A correlation was found between the physicochemical properties of the ketoximes and their conversion to the amino alcohol and thus their subsequent activity. The results suggest that at least some of the ketoxime precursors could have a use as antiglaucoma agents without systemic side effects.

Adrenergic beta-Antagonists↗
PubMed1988

Soft drugs. 7. Soft beta-blockers for systemic and ophthalmic use.

The "inactive metabolite approach" was used to design a series of "soft" drugs derived from the acidic metabolite of metoprolol. Pharmacokinetic and pharmacodynamic properties of these novel "soft" beta-adrenoceptor antagonists were determined: half-lives in human blood ranged from 5 to 754 min. The rates of in vivo disappearance of representative slow, medium, and fast hydrolyzing esters were determined in rats. In each case rapid and quantitative conversion to the corresponding free acid was observed. This suggests a facile, one-step degradation to the predicted major metabolite. The compounds were tested for their ability to decrease intraocular pressure in a rabbit model. Five of the new compounds exerted an ocular hypotensive action comparable to or greater than that of the reference compound, timolol maleate, and with a prolonged duration of action in some cases. In contrast the new compounds showed reduced and shorter duration systemic activity. The adamantylethyl ester emerges as a potentially effective antiglaucoma agent with significantly improved site-specific activity.

Animals↗
PubMed1988

[3H]-nitrendipine binding in chick myotubes developing in culture.

Binding studies with the [3H]-nitrendipine were performed in homogenates of chick skeletal myotubes developing in culture. The specific binding data suggested two classes of binding sites with high and low affinities for nitrendipine. No significant changes in the dissociation constants of both high- and low-affinity sites could be detected over the development period studied. The estimated dissociation constant was 0.44 nM for the high-affinity binding site and 25.6 nM for the low-affinity binding site. Both binding sites appeared at an early myotubular stage of development (around 3 days in culture), and displayed rapid increases with age until peaks were reached around 6 days in culture, then began to decrease. These results were discussed taking into account voltage-dependent Ca channels.

Animals↗
PubMed1988

[A case report of primary liver cancer with cerebral metastasis after hepatic resection].

A 67-year-old male, who had a left hepatectomy for hepatocellular carcinoma, was readmitted to our hospital because of a left hemiparesis. A brain computed tomography scan and an r-carotid angiogram revealed a large mass involving the right parietal area, and thus a brain tumor removal was performed. A histological diagnosis of the removed brain tumor found it to be a metastatic, hepatocellular carcinoma. The patient died of pulmonary congestion due to lung metastasis, approximately 2 years and seven months after hepatectomy, and 1 year and three months after the removal of this metastatic brain tumor. In selected cases, the removal of a metastatic brain tumor seems to bring about improvements in the quality and duration of life.

Aged↗
PubMed1988

[Postnatal cell proliferation in the rat cerebrum: immunohistochemical study with bromodeoxyuridine (BrdU)].

The postnatal cell proliferation in the rat cerebrum was studied immunohistochemically using a monoclonal antibody to bromodeoxyuridine (BrdU). Since BrdU, a halogenated analogue of thymidine, is incorporated into nuclear DNA during duplication, S-phase cells can be detected by demonstrating intranuclear BrdU. 200 mg/kg of BrdU was administered to normal Wistar rats intraperitoneally on the day of birth or intravenously 1, 2, 3, 5, 8 or 24 weeks after birth. Thirty minutes later, the brain was fixed by perfusion with ethanol, and the paraffin-embedded sections were processed for the avidin biotin peroxidase-complex method. BrdU-positive nuclei were counted among 500 to 10,000 cells in several regions of the brain to obtain the BrdU-labeling index (the number of BrdU-positive cells per 100 cells scored, LI, %). The present study demonstrated that (1) proliferating cells in the gray matter (cerebral cortex and caudate-putamen) are only few at birth (LI = 0.54-0.78%), which further decrease during the following few weeks, and disappear by adulthood, (2) in the white matter (corpus callosum), cell proliferation is relatively active within 1 week after birth (LI = 5.6-6.3%), but becomes inactive thereafter, (3) the proliferative activity of the cells in the subependymal layer of the lateral ventricle is very high at birth (LI = 15.5%), which somewhat decreases during the following few weeks, but still remains high in adulthood (LI = 7.5%). This kind of continued cell proliferation in the brain after birth seems important in the postnatal development of the normal cerebral structure, and in several pathologic processes such as tissue repair and the development of brain neoplasm.

Age Factors↗
PubMed1988

Behavior of human apolipoprotein A-I: phospholipid and apoHDL:phospholipid complexes in vitro and after injection into rabbits.

Apolipoprotein A-I was purified from human high density lipoprotein and complexed with polyunsaturated phosphatidylcholine (PC) in deoxycholate (Lipostabil); the bile salt was removed subsequently by dialysis. The behavior of the resultant apoA-I/PC complexes was compared with that of Lipostabil in vitro and after injection into rabbits. In vivo apoA-I/PC complexes had the density of HDL throughout but had both alpha and pre beta electrophoretic mobility, the latter probably reflecting dissociation of apoA-I from PC. Lipostabil initially behaved like LDL but gradually acquired the density of HDL after incubation with plasma and in vivo. Both preparations increased plasma total phospholipids in normolipidemic rabbits to a similar extent, but, increments in HDL phospholipid were greater after apoA-I/PC complexes were injected. ApoHDL/PC complexes, prepared in a similar manner, appeared to promote efflux of cholesterol from perfused rabbit aortas in the presence of lecithin:cholesterol acyltransferase (LCAT) activity, consistent with a stimulatory effect on cholesterol mobilization. Injection of apoHDL/PC complexes into hyperlipidemic rabbits decreased plasma cholesterol but increased HDL cholesterol, whereas Lipostabil decreased both. These findings suggest that human apoA-I/PC complexes resemble HDL in their behavior more closely than does Lipostabil, and show that both types of liposome undergo modification upon interaction with plasma. It remains to be shown whether they possess any therapeutic potential.

Animals↗