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Biomedical subjects

N Yanagihara

Publications and source records attributed to N Yanagihara.

At least 127 records · Page 7Linked to original sources
PubMed1994

Occurrence and activation of Ca2+/calmodulin-dependent protein kinase II and its endogenous substrates in bovine adrenal medullary cells.

We investigated the presence of and the endogenous substrates for Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in cultured bovine adrenal medullary cells. By a series of chromatographic steps using DEAE-cellulose, calmodulin affinity, and Sephacryl S-300 columns, we partially purified two CaM kinases (peaks I and III) and one calmodulin-binding protein (peak II). Both of the kinases (peaks I and III) showed broad substrate specificities. Peak I, but not peak III, was immunoprecipitated with an antibody against rat brain CaM kinase II, suggesting that peak I is CaM kinase II or a closely associated CaM kinase. Although the anticaldesmon antibody recognized a 77-kDa protein (low molecular mass caldesmon) in crude preparations from the cells, the protein in peak II was not immunoblotted with the antibody. The peak II protein was phosphorylated by the CaM kinase in peak I but not by the CaM kinase in peak III. Peak I kinase also phosphorylated purified tyrosine hydroxylase and several proteins from chromaffin granule membranes. Stimulation of cultured bovine adrenal medullary cells with 56 mM K+ evoked rapid increases in 45Ca2+ influx and autonomous CaM kinase II activity, both of which were attenuated by the addition of 20 mM MgSO4, an inhibitor of voltage-dependent Ca2+ channels. These results suggest that an isozyme of CaM kinase II exists in adrenal medullary cells and is activated by cell depolarization. Furthermore, the peak II protein is apparently a novel endogenous substrate for CaM kinase II.

Adrenal Medulla↗
PubMed1993

Receptors for C-type natriuretic peptide in cultured rat glial cells.

To characterize sites of action of C-type natriuretic peptide (CNP) in the glial cells, the effect of CNP on cGMP accumulation and the binding of [125I]CNP in rat astrocyte RCR-1 cells were studied. CNP stimulated cGMP accumulation in the cells from 10(-9) M in a dose-dependent manner, but ANP (atrial natriuretic peptide) had a negligible effect on cGMP accumulation in the cells. [125I]CNP was bound to the cells and its Kd value was 2 orders of magnitude lower than that of the ED50 value for stimulation of cGMP accumulation in the cells. Not only CNP but also ANP displaced [125I]CNP binding to the cells. These results suggest that RCR-1 cells have a B-receptor which contains a guanylate cyclase domain and is preferentially activated by CNP, and that they also have a C-receptor which does not contain a guanylate cyclase domain that reacts with both ANP and CNP.

Animals↗
PubMed1993

Sudden hearing loss induced by acoustic neuroma: significance of small tumors.

In our series of 111 patients operated on for acoustic neuroma from 1972 to 1990, 21 (18.9%) had sudden hearing loss. The 21 tumors involved were comprised of 9 small, 5 medium, and 7 large tumors. Emphasis is placed on the fact that even a small tumor has the potential to produce sudden hearing loss (SHL) and that the possibility of seeing patients with SHL is increasing thanks to advances in imaging diagnosis. Recognition of SHL as an initial symptom of acoustic tumor is considered essential to detect small acoustic neuroma.

Adolescent↗
PubMed1993

Experimental vestibular neuritis induced by herpes simplex virus.

An animal model of vestibular neuritis was developed by inoculating herpes simplex virus type 1 (HSV-1) in the auricle of a mouse. Deviation of the body was observed in 4 of 30 mice 6 days after inoculation. These animals were sacrificed 6 to 10 days after inoculation and the vestibular nerve was examined histopathologically and immunohistochemically. The HSV-1 antigens were recognized exclusively in Scarpa's ganglion of the vestibular nerve in 2 of 4 mice in which signs of vestibular involvement were manifested.

Animals↗
PubMed1993

Prevention of recurrence of cholesteatoma in intact canal wall tympanoplasty.

In the treatment of cholesteatoma employing intact canal wall tympanoplasty, staging the operation and re-establishment of aeration of the tympanic cavity are required to eradicate possible causes of recurrence, cholesteatoma residue, and retraction pocket. The planned staged tympanoplasty with preventive measures for recurrence has evolved. At the second-stage operation, one of the following three types of operations was performed according to the grade of aeration and healing of tympanic cavity: type S1, only ossiculoplasty; type S2, ossiculoplasty and scutumplasty; and type S3, ossiculoplasty, scutumplasty, and mastoid obliteration. The surgical concept, indication, and technique are described in detail. The recurrence rate in the 134 patients without previous surgery, 95 adults and 39 children, operated on between 1987 and 1991 was 2.2 percent (7.6% in the children and 0% in the adult). Although the rate of the recidivism was significantly reduced, deep retraction pocket developed in 15 percent of adults and in 23 percent of children. The incidence of deep retraction pocket formation was lowest in the adults with type S1 operation and highest in the children with type S3 operation.

Adolescent↗
PubMed1992

Inhibition of nicotinic acetylcholine receptor-mediated secretion and synthesis of catecholamines by sea urchin toxin in cultured bovine adrenal medullary cells.

We previously reported the partial purification and characterization of a toxic substance (sea urchin toxin) isolated from the pedicellariae of the sea urchin Toxopneustes pileolus (Nakagawa and Kimura, Jpn J Pharmacol 32: 966-968, 1982). In the present study, we examined the effect of sea urchin toxin on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Sea urchin toxin inhibited the secretion of catecholamines stimulated by carbachol and nicotine but not by veratridine or a high concentration of K+. The toxin inhibited the carbachol-evoked influx of 22Na+ and 45Ca2+ at concentrations similar to those for catecholamine secretion. The inhibition of catecholamine secretion by sea urchin toxin was not overcome by increasing the concentration of carbachol. Preincubation of cells with the toxin caused a time-dependent inhibition in the secretion stimulated by carbachol even when the toxin was removed from the incubation medium. The toxin suppressed catecholamine synthesis and tyrosine hydroxylase activity in carbachol-stimulated cells. In addition, sea urchin toxin inhibited [3H]phencyclidine binding to adrenal medullary cells whereas it did not alter cyclic GMP accumulation caused by muscarine. Further purified fractions from sea urchin toxin by concanavalin A affinity column chromatography also inhibited carbachol-evoked secretion of catecholamines. These results suggest that sea urchin toxin inhibits carbachol-enhanced secretion and synthesis of catecholamines by suppression of nicotinic acetylcholine receptor-mediated Na+ influx and subsequent Ca2+ influx in cultured adrenal medullary cells.

Adrenal Medulla↗
PubMed1992

Lithium chloride stimulates catecholamine synthesis and secretion in cultured bovine adrenal medullary cells.

We examined the effects of lithium treatment on the synthesis and secretion of catecholamines in cultured bovine adrenal medullary cells. The treatment of cells with lithium (0.5-4 mmol/L) for 7 days caused an increase in basal and carbachol-stimulated synthesis of 14C-catecholamines from [14C]-tyrosine but not from [14C]-DOPA. Lithium treatment (4 mmol/L, 7 days) increased the activity of tyrosine hydroxylase in the cells. Lithium treatment (2-4 mmol/L, 7 days) also enhanced the secretion of catecholamines caused by carbachol, although the carbachol-induced influx of 45Ca2+ was reduced. Lithium (4 mmol/L, 7 days) potentiated the secretion of catecholamines evoked by the Ca2+ (1 mumol/L) from cells that were permeabilized by digitonin. The activity of protein kinase C in a soluble fraction was increased in lithium-treated cells (4 mmol/L, 7 days). These results demonstrate that lithium treatment increases the synthesis and secretion of catecholamines and the activity of protein kinase C in cultured adrenal medullary cells.

Adrenal Medulla↗
PubMed1992

Veratridine causes the Ca(2+)-dependent increase in diacylglycerol formation and translocation of protein kinase C to membranes in cultured bovine adrenal medullary cells.

Our previous studies suggested that protein kinase C is involved in the veratridine (an activator of voltage-dependent Na+ channels)-induced phosphorylation and activation of tyrosine hydroxylase as well as the synthesis of catecholamines in adrenal medulla (Uezono et al. 1989). In the present study, we investigated whether treatment of cultured bovine adrenal medullary cells with veratridine causes the accumulation of diacylglycerol, a physiological activator of protein kinase C and the translocation of protein kinase C from cytosol to membrane, a process required for protein kinase C activation. Veratridine (100 mumol/l) increased diacylglycerol level about 2.2 fold in a monophasic manner, with peaking at 5 min and declining toward the basal level within 20 min. Veratridine also increased membrane protein kinase C from 15.6% to 26.9% of total protein kinase C in a time-course similar to that of diacylglycerol accumulation. Both stimulatory effects of veratridine were inhibited by tetrodotoxin and not observed in Ca(2+)-free, EGTA-containing medium. Amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchange, did not alter veratridine-induced events. These results suggest that veratridine-induced Ca2+ influx contributes to the accumulation of diacylglycerol and the activation of protein kinase C in adrenal medullary cells.

Adrenal Medulla↗
PubMed1992

Overproduction of voltage-dependent Na+ channels in the developing brain of genetically seizure-susceptible E1 mice.

We used E1 mice, a ddY mouse-derived, autosomal mutant strain and a model of hereditary sensory-precipitated epilepsy, to test the hypothesis that epileptic susceptibility may be associated with the activity of voltage-dependent ion channels. We examined the saxitoxin binding capacity of the receptor site 1 of the Na+ channel alpha-subunit, the expression activity of the Na+ channel mRNA, the veratridine-induced 22Na+ influx in the brain synaptosomes, and the regional distribution of Na+ channels in the brain. Compared with control ddY mice, in E1 mice which have not experienced seizures, the number of Na+ channels in the brain synaptosomes increased by approximately 20% starting at the fourth postnatal week through the adult stage as determined by [3H]saxitoxin binding assay. Northern blot hybridization analysis showed excess expression of Na+ channel mRNA (by 30-40%) coincidentally with Na+ channel increases. Regional analysis using the saxitoxin binding assay demonstrated approximately 1.3-fold denser distribution of Na+ channels in the cortex and cerebellum but not the hippocampus and midbrain including thalamus of E1 mice compared to ddY mice. Scatchard plot analysis for saxitoxin binding in the cortex of E1 mouse brains revealed higher maximum binding capacity (Bmax) values (ddY, 4.43 +/- 0.28 pmol/mg protein; E1, 5.43 +/- 0.25 pmol/mg protein) without a change in Kd (ddY, 1.05 +/- 0.03 nM; E1, 1.03 +/- 0.01 nM). Lastly, veratridine-evoked 22Na+ influx, sensitive to tetrodotoxin, was increased approximately 45% in the cortical synaptosomes in six-week-old E1 mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Incidence of attic retraction after staged intact canal wall tympanoplasty for middle ear cholesteatoma.

Incidence of retraction pocket and recurrent cholesteatoma in the attic after surgery for middle ear cholesteatoma using the staged intact canal wall technique were investigated in 95 ears of 91 patients, all of which had various degrees of bone defect in the tympanic scutum. Surgical procedures employed in the second stage for prevention of attic retraction were classified into three types: Type I, no scutumplasty; Type II, scutumplasty; Type III, scutumplasty plus mastoid obliteration. In 83 ears followed up for more than 1 year after the second stage, such retraction troubles occurred in 2 of 13 ears (15%) in Type I, 8 of 20 ears (40%) in Type II, and 24 of 50 ears (48%) in Type III. Incidence of retraction troubles was higher in Types II and III, probably because these procedures were indicated in ears with large scutum defects. Dislocation and atrophy of the graft materials, together with bone resorption around the bone defect were the main reasons for failure in scutumplasty. Dysfunction of the eustachian tube and traction of the eardrum by the scar tissue behind it may have also contributed to attic retraction. Mastoid obliteration with small blocks of hydroxyapatite was more effective in prevention of retraction troubles than that with pedicled temporalis muscle flap.

Adolescent↗
PubMed1992

Surgical management of petrous apex cholesteatoma: a therapeutic scheme.

From 1969 to 1990, 16 patients were treated for petrous apex cholesteatoma invading or extending beyond the internal auditory canal. This type of cholesteatoma poses various specific surgical problems and various surgical procedures are necessary for treatment. To attain maximal therapeutic effect and ensure postoperatively a satisfactory quality of life, the preoperative therapeutic scheme for each individual patient is very important, as is demonstrated by the case study presented here. The therapeutic scheme includes the following: (1) surgical approach; (2) management of a cavity following removal of the cholesteatoma; (3) handling of problems such as involvement of the dura and internal carotid artery; and (4) management of the facial nerve.

Journal Article↗
PubMed1992

Transmandibular transpterygoid approach to the nasopharynx, parapharyngeal space, and skull base.

The nasopharynx, upper part of the parapharyngeal space, and skull base are relatively inaccessible to the surgeon without major postoperative complications. Operative fields reached by conventional approaches through the palate and maxillary sinus are too limited and narrow to remove extensive tumors. The authors applied a transmandibular transpterygoid approach for the removal of five residual nasopharyngeal carcinomas (NPCs) after full doses of irradiation, one pleomorphic adenoma of the nasopharynx, and one large parapharyngeal schwannoma extending into the jugular foramen. This approach offers a wide operative field so that large blood vessels and cranial nerves can be managed easily. All tumors were successfully resected. Two patients with benign neoplasma had uneventful recoveries after treatment. Of five patients with NPC, two are alive with no evidence of disease for 68 months and 50 months, respectively, while two died of metastases to the liver and bones. The other patient is alive with metastases in the lungs. No tumor recurred in the local primary site, however. Since the number of NPC cases is small, the usefulness of surgical removal of the postirradiation residual NPC is not clear. Our experience proved that the transmandibular transpterygoid approach is a practical method in the treatment of neoplastic lesions in the nasopharynx, parapharyngeal space, and skull base.

Adenoma↗
PubMed1992

Cooperative modulation of voltage-dependent sodium channels by brevetoxin and classical neurotoxins in cultured bovine adrenal medullary cells.

The effects of Ptychodiscus brevis toxin (PbTx-3) on 22Na influx, 45Ca influx and catecholamine secretion were examined in cultured bovine adrenal medullary cells and compared with the effects of classical neurotoxins. PbTx-3 alone had no effects, but greatly enhanced veratridine (30 microM)-induced Na influx, Ca influx and secretion, with a EC50 of 30, 25 and 23 nM, respectively. PbTx-3 (1 microM) reduced EC50 values of veratridine approximately 3-fold and increased the maximal responses caused by saturating concentration (300 microM) of veratridine approximately 1.3 fold. alpha- and beta-Scorpion venom shifted the concentration-response curves of veratridine to the left without altering maximal responses. PbTx-3 in combination with either alpha- or beta-scorpion venom showed only additive effects on Na influx, but augmented veratridine (30 microM)-induced Na influx to a greater extent than PbTx-3, alpha- or beta-scorpion venom alone. Na influx due to these toxins was abolished by 1 microM saxitoxin. Our results suggest that Na channels in adrenal medullary cells have neurotoxin receptors for brevetoxin that allosterically stimulate Na influx initiated by veratridine, leading to increased Ca influx and catecholamine secretion. Allosteric interactions do not exist between brevetoxin and alpha-scorpion venom, or between brevetoxin and beta-scorpion venom, but once Na channels are gated by veratridine, these toxins cooperatively augment Na influx.

Adrenal Medulla↗
PubMed1992

Transmission of change in the atmospheric pressure of the external ear to the perilymph.

In experiments using guinea pigs, the middle ear and perilymphatic pressures were simultaneously registered in response to pressure change in the external ear canal. In the first experiment, pressure was slowly loaded in the ear canal in the range of 200 mm H2O to -200 mm H2O. Pressure transmission to the perilymph was smaller when the bulla was open to the outside than when it was closed. It was significantly impaired by disruption of the ossicular chain and especially by closure of the round window. The data indicate that air volume in the middle ear cavity plays an important role in transmission of slowly changing atmospheric pressures. In the second experiment, the eustachian tube was closed and the pressure was changed in the range of 1000 mm H2O to -1000 mm H2O. The middle ear and perilymphatic pressures increased or decreased corresponding to the loading pressure in the range of 400 mm H2O and -200 mm H2O. Beyond these levels, response rate of the middle ear pressure decreased and perilymphatic pressure declined in spite of further increase in loading pressure. The increase in pressure difference between the middle ear and the inner ear might cause disruption of the round and/or oval windows.

Animals↗
PubMed1991

Inhibitory effect of okadaic acid on carbachol-evoked secretion of catecholamines in cultured bovine adrenal medullary cells.

We examined the effect of okadaic acid on catecholamine secretion caused by carbachol in cultured bovine adrenal medullary cells. Treatment of cells with 100 nM okadaic acid for 3-24 hr produced an inhibition of catecholamine secretion stimulated by carbachol. The half-maximal and maximal inhibition of secretion was observed at 40 nM and 300 nM okadaic acid for 24 hr, respectively. Okadaic acid also inhibited veratridine- and high K(+)-induced secretion but not ionomycin-induced secretion. Okadaic acid strongly suppressed 45Ca2+ influx and slightly inhibited 22Na+ influx in carbachol-stimulated cells. These results suggest that okadaic acid inhibits carbachol-evoked secretion of catecholamines mainly by suppression of Ca2+ influx in adrenal medullary cells.

Adrenal Medulla↗
PubMed1991

Stimulatory effects of brain natriuretic peptide on cyclic GMP accumulation and tyrosine hydroxylase activity in cultured bovine adrenal medullary cells.

We studied the effect of brain natriuretic peptide (BNP) on the accumulation of cyclic GMP and the phosphorylation and activity of tyrosine hydroxylase, compared with that of atrial natriuretic peptide (ANP), in cultured bovine adrenal medullary cells. 1. BNP as well as ANP increased cellular cyclic GMP accumulation in a concentration-dependent manner (10-1000 nmol/l). BNP (1 mumol/l) and ANP (1 mumol/l) produced a 60-fold and 30-fold increase in cyclic GMP accumulation, respectively. 2. The stimulatory effects of BNP and ANP on cyclic GMP accumulation were observed even when Ca2+ or Na+ was removed from the incubation medium. 3. 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, inhibited the stimulatory effect of BNP on cyclic GMP accumulation in a concentration-dependent manner (1-100 nmol/l). Furthermore, the BNP-induced accumulation of cyclic GMP was attenuated by forskolin (1 mumol/l), an activator of adenylate cyclase. 4. BNP (1 mumol/l) and ANP (1 mumol/l) caused a significant increase in phosphorylation and activity of tyrosine hydroxylase in the cells. 5. In digitonin-permeabilized cells, cyclic GMP (1-100 mumol/l) activated tyrosine hydroxylase in the presence of ATP and Mg2+. These results suggest that BNP stimulates the accumulation of cyclic GMP in a manner similar to that of ANP. The increased accumulation of cyclic GMP by these peptides may be negatively modulated by protein kinase C and cyclic AMP and may cause the phosphorylation and activation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.

Adrenal Medulla↗
PubMed1991

Staurosporine: an effective inhibitor for Ca2+/calmodulin-dependent protein kinase II.

We investigated the effect of staurosporine on Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) purified from rat brain. (a) Staurosporine (10-100 nM) inhibited the activity of CaM kinase II. The half-maximal and maximal inhibitory concentrations were 20 and 100 nM, respectively. (b) The inhibition with staurosporine was of the noncompetitive type with respect to ATP, calmodulin, and phosphate acceptor (beta-casein). (c) Staurosporine suppressed the auto-phosphorylation of alpha- and beta-subunits of CaM kinase II at concentrations similar to those at which the enzyme activity was inhibited. (d) Staurosporine also attenuated the Ca2+/calmodulin-independent activity of the autophosphorylated CaM kinase II. These results suggest that staurosporine inhibits CaM kinase II by interacting with the catalytic domain, distinct from the ATP-binding site or substrate-binding site, of the enzyme and that staurosporine is an effective inhibitor for CaM kinase II in the cell system.

Adenosine Triphosphate↗