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Biomedical subjects

T Kurihara

Publications and source records attributed to T Kurihara.

At least 253 records · Page 14Linked to original sources

Alternative splicing of mouse brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase mRNA.

A second cDNA for mouse brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase (cDNAII) encoding 420 amino acids was isolated. The only difference from the cDNA obtained previously (cDNAI), which encodes 400 amino acids, was the 5'-end 53 bp. Comparison of the sequence of the mouse gene with the sequence of cDNAII indicates alternative splicing within exon 1. The 5'-end sequence of cDNAII was found in a region of the gene upstream of exon 1 and a second transcription initiation site was identified.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

DARPP-32 development in the caudate nucleus is independent of afferent input from the substantia nigra.

DARPP-32, a dopamine- and adenosine 3':5'-monophosphate regulated neuronal phosphoprotein, Mr 32 kDa, is a phenotypic marker of the medium-size spiny neurons of the mammalian caudate-putamen. In the present study, we examined the ontogeny of DARPP-32 protein and mRNA, and compared it to the ontogeny of tyrosine hydroxylase and synapsin I, a synaptic-vesicle phosphoprotein. In vivo, the amount of DARPP-32 protein per mg total protein increased throughout the first three postnatal weeks, and then declined to plateau at adult levels. The mRNA level closely paralleled the protein, except that its rise preceded that of the protein. Tyrosine hydroxylase levels rose throughout the first 4 postnatal weeks, and synapsin I levels rose steadily during the same period. Primary reaggregate cultures containing cells from the caudate-putamen expressed DARPP-32 with a time course similar to that seen in vivo. The level of expression was not altered by coculturing with dopaminergic neurons from the rostral mesencephalic tegmentum. Thus, the postnatal increase in DARPP-32 levels in the caudate-putamen appears to be independent of transsynaptic or end-organ influences from the substantia nigra.

Animals↗

Purification and cDNA cloning of ARPP-16, a cAMP-regulated phosphoprotein enriched in basal ganglia, and of a related phosphoprotein, ARPP-19.

ARPP-16 (cAMP-regulated phosphoprotein of Mr = 16,000) is a substrate for cAMP-dependent protein kinase and is enriched in the basal ganglia. ARPP-16 has been purified to homogeneity from the soluble fraction of bovine caudate nuclei. An additional substrate for cAMP-dependent protein kinase of Mr = 19,000 (ARPP-19) was found to cross-react with rabbit anti-serum prepared against purified ARPP-16. Immunological analysis indicated that ARPP-16 was enriched in the basal ganglia while ARPP-19 was present in similar levels in all brain regions studied and was also present in non-neuronal tissues. ARPP-19 was also purified to homogeneity from bovine caudate nucleus cytosol. Using oligonucleotide probes based on the partial amino acid sequence of purified ARPP-16, cDNA clones for ARPP-16 and ARPP-19 were isolated from a bovine caudate nucleus cDNA library and sequenced. The predicted amino acid sequences of the two proteins were identical except that ARPP-19 had an additional 16 amino acids at the NH2-terminal. The two cDNA clones share an identical 3'-untranslated region of 756 nucleotides. The cDNA clone for ARPP-16 contained 806 additional nucleotides located 3' to this common sequence. The 5'-untranslated regions of the two clones were entirely different. The results suggest the possibility that ARPP-16 and ARPP-19 are produced by alternative transcription and splicing.

Amino Acid Sequence↗

Induction of myelin-associated glycoprotein mRNA in experimental remyelination.

Two forms of myelin-associated glycoprotein (MAG) mRNA are produced by alternative splicing of the exon 12 portion. Expression of the two forms of MAG mRNA was studied here in experimentally introduced demyelination and remyelination by Cuprizone intoxication. During the demyelinating stage, both forms of MAG mRNA decreased markedly. When feeding with Cuprizone was stopped, MAG mRNA began to increase. One form of MAG mRNA without the exon 12 portion, which appears in normal development at the period of active myelination, was characteristically induced during the remyelinating stage. The other form containing the exon 12 portion was also induced but recovered only to the level in normal development.

Animals↗

Rat DARPP-32: cloning, sequencing, and characterization of the cDNA.

DARPP-32, a substrate for cyclic AMP-dependent protein kinase, is highly enriched in the caudate nucleus. In the present study, the cDNA for rat DARPP-32 was isolated and characterized. When compared to the coding region of bovine DARPP-32 cDNA, there was 86% identity at the nucleotide level, and 84% identity at the amino acid level. The homology in the region previously noted to be similar to phosphatase inhibitor-1 remained intact. There were also 3'-untranslated regions that were highly conserved. The DARPP-32 mRNA, which appeared as a doublet, was widely distributed in the central nervous system and was highly enriched in the striatum. Southern blot analysis revealed a simple hybridization pattern, consistent with the presence of a single gene coding for rat DARPP-32. Unilateral destruction of the nigrostriatal dopaminergic pathway by injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra did not alter the striatal steady state levels of DARPP-32 mRNA.

Amino Acid Sequence↗

Electrical myotonia and cataract in X-linked muscular dystrophy (mdx) mouse.

An X chromosome-linked mouse mutant (mdx) has been investigated as an animal model of Duchenne's muscular dystrophy, and has been found to have the same defect of dystrophin in the muscle surface membrane. Intracellular recordings from the mdx mouse hemidiaphragm preparations revealed low resting membrane potentials and electrical myotonia which occurred at the time of microelectrode insertion and withdrawal. Electrical myotonia of the mdx mouse was observed in 30-50% of the impaled muscle fibers at low temperature, which decreased to only 7.8% at 37 degrees C. Electrical myotonia of mdx mice was not abolished by (+)-tubocurarine. Though there was no behavioral myotonia in mdx mice, repetitive bursts of action potentials in mdx mice were based on the abnormalities of the muscle membrane since neuromuscular blockade did not abolish the repetitive bursts. Also close observation of the lenses of mdx mice revealed cataracts from the newborn stage to the adult age. Slit lamp examination of the lenses of the mdx mice revealed nuclear cataracts followed by anterior subcapsular cataract as they grew. The cataract of mdx mice is different from that of myotonic dystrophy which is usually posterior subcapsular.

Animals↗

Distribution and cellular localization of DARPP-32 mRNA in rat brain.

In situ hybridization histochemistry has been used to determine the regional distribution and cellular localization of DARPP-32 mRNA in the rat brain. Results support the concept that DARPP-32 is present primarily in cells expressing the dopamine D1 subtype receptor, and that DARPP-32 is not synthesized in dopamine-containing cells. Strongly labelled neuronal cell bodies were found in the caudate nucleus, nucleus accumbens, olfactory tubercle, parts of the bed nucleus of the stria terminalis, and the amygdaloid complex. In addition large amounts of DARPP-32 mRNA were visualized in the medial habenula and around the third ventricle, in ependymal cells and tanycytes, and in the cerebellar Purkinje cells. A less pronounced activity was seen in layers II-III and VI throughout the cerebral cortex. The present studies together with previous biochemical and immunocytochemical studies demonstrate that DARPP-32 gene expression is greatest primarily in D1 dopaminoceptive cells, although there are exceptions. In situ hybridization may thus be used to quantitate regulation of DARPP-32 mRNA in discrete brain regions.

Animals↗

A case of bilateral ptosis associated with cerebral hemispheric lesions.

Ptosis occurs in a variety of disorders including myasthenia gravis, oculomotor palsy, Horner's syndrome and brain stem disorders. There are also supranuclear lesions causing blepharoptosis. The latter disorders are reflex blepharospasm, apraxia of eyelid opening and Meige's syndrome. Since the total number of bilateral ptosis associated with cerebral hemispheric lesions is very few, whether the responsible lesions are located in the nondominant hemisphere or bilateral hemispheres are still controversial. We report here a case of bilateral cerebral ptosis that occurred in association with cerebral infarction of the nondominant hemisphere.

Aged↗

The stabilizing effect of bestatin on the resting membrane potentials of X-linked muscular dystrophy mice.

The resting membrane potentials of X-linked muscular dystrophy (mdx) mice are about 10 mV lower than those of control (C57BL/10Sc) mice. Also repetitive action potentials which resemble insertion myotonia are frequently recorded intracellularly from the mdx mice of various ages. When the mdx mice are treated with bestatin intraperitoneally for 7 days, the RMP's improvement almost attained its normal levels. Repetitive action potential bursts (electrical myotonia) recorded at the time of microelectrode insertion had decreased or abolished after bestatin therapy. Another set of in vitro experiments to see direct action of bestatin to the hemidiaphragm preparations of the mdx mice reveal improvement in RMP's and a reduction in electrical myotonia within a 30-minute exposure to Tyrode's solution with bestatin. Bestatin has a favorable direct effect on the muscle fiber membrane to stabilize RMP's and suppress muscle membrane irritability.

Animals↗

The large isoform of myelin-associated glycoprotein is scarcely expressed in the quaking mouse brain.

Two polypeptide isoforms of myelin-associated glycoprotein (MAG) with molecular masses of 72 and 67 kDa are produced by alternative splicing of the exon 12 portion. Our previous work has demonstrated that in the quaking mouse brain this alternative splicing is lacking and that the mRNA coding the large MAG isoform (L-MAG) is scarcely expressed, whereas that of small MAG isoform (S-MAG) is overexpressed. In the present study, we prepared antisera specific to the S-MAG and L-MAG amino acid residues, respectively. Immunoblots showed that the L-MAG band was scarcely detectable in the quaking mouse brain, whereas the S-MAG band had an apparently higher molecular mass than in the normal control. Our immunohistochemical study also showed that L-MAG was scarcely stained in the quaking mouse brain. These results seemed to reflect a reduction in content of L-MAG mRNA and abnormal glycosylation in the quaking mouse brain.

Animals↗

Molecular conformations of aminophenylimidazoles exhibiting antiulcer activities.

To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational characteristics using X-ray diffraction and proton nuclear magnetic resonance (1H-NMR) methods, and for antiulcer activities on rats and H2-receptor antagonist activities in guinea pig. The ortho isomer 1, which preferentially formed an intramolecular N-H (amino)...N (imidazole) hydrogen bond, showed the highest antiulcer activity with half the efficacy of cimetidine. On the other hand, none of 1, 2 and 3 showed significant H2-receptor antagonist activity. Based on these results, the conformational characteristic for the exhibition of antiulcer activity has been discussed.

Aniline Compounds↗

[Left ventricular diastolic filling in elder patients with systemic hypertension].

To study the significance of left ventricular (LV) diastolic filling in elder patients with hypertension (HT), cardiac blood pool imagings with Tc-99m were obtained at rest in 17 normal subjects and 28 patients with systemic hypertension. The patients with hypertension did not show any evidence of coronary heart disease, renal insufficiency or other disease. Moreover, they showed normal LV ejection fraction (LVEF) and normal LV wall motion. They were divided into 4 groups: 1) normal-young (less than 60 years old, n = 10), 2) normal-old (greater than or equal to 65 years old, n = 7), 3) HT-young (less than 60 years old, n = 15), 4) HT-old (greater than or equal to 65 years old, n = 13). From the LV volume curve and its first differentiation curve, LVEF, mean first third ejection rate (ERm) and peak ejection rate (PER) were obtained as indices of the LV systolic function, and LV diastolic filling rate during the first third of diastole (FRm) and peak filling rate (PFR) were obtained as indices of LV diastolic function. All indices of LV systolic function were similar in all groups. In contrast, LV diastolic indices (FRm and PFR) of older groups were significantly lower than those of young groups both in HT and normal. Also, LV diastolic indices in HT groups decreased significantly in comparison with normal groups of the same age group. Among diastolic indices, FRm could distinguish patients with HT from normal subjects of the same age group more accurately than PFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Tachycardia-induced cardiomyopathy: a case report].

A 30-year-old man with chronic sustained ventricular tachycardia (VT) lasting more than seven years was treated with propranolol, 30 mg/day. This resulted in controlled cardiac rates of 90 to 130/min during sleep, and 100 to 195/min while awake. However, he experienced Adams-Stokes attacks twice, in September and December, 1986. During the second attack, ambulatory heart monitoring showed his VT rate of 212/min. An electrophysiological study revealed that the VT focal point was in the lower-mid region of the interventricular septum in the right ventricle. The VT was characterized by abnormal enhanced automaticity. This VT could not be interrupted either by single or multiple combinations of antiarrhythmic drugs. Cardiac catheterization revealed a diffusely enlarged hypokinetic left ventricle, even at the rate of 120/min VT (EF 27%, C.I. 2.3 l/min/m2). Because of his severe hemodynamic state, we performed electrical catheter ablation successfully. After the ablation, his left ventricular wall motion gradually improved. Nine months after the ablation, his left ventricular diastolic dimension decreased from 64 to 48 mm and the left ventricular systolic dimension decreased from 57 to 28 mm on M-mode echocardiography, while ejection fraction increased from 27 to 73% on the left ventriculography. Bi-ventricular myocardial biopsy specimens obtained prior to the ablation revealed only cellular hypertrophy of varying degrees, and vacuole degeneration consistent with non-specific cardiomyopathy. However, nine months after the ablation, these findings were no longer present. Thus, this case was considered tachycardia-induced cardiomyopathy initiated by VT, lasting many years.

Adult↗

[Effect of endothelin on gastric mucosal lesion in rats].

Gastric mucosal blood flow and gastric mucosal prostaglandin E2 (PGE2) and prostacyclin (PGI2) were investigated in male Wistar rats intraarterially injected with endothelin (ET), an endothelium-derived vasoconstrictor peptide. Immediately following ET (4 nmol/kg) administration, gastric mucosal blood flow decreased. Then 30 min later, the blood flow reached the minimum, but PGE2 and PGI2 showed the highest value. PGE2 showed a tendency to decrease 90 min later, while PGI2 continued to show high value. There were redness and hemorrhagic damage in the gastric mucosa. Endogenous PGs were presumed to be relate to the regulation of the development of the mucosal damage owing to decrease in the blood flow after ET administration.

Animals↗

[Eleven cases of spindle cell carcinoma of the breast, with special reference to cystic changes in the tumor].

The clinicopathological features of 11 cases of a spindle cell carcinoma handled by our department have been investigated and are presented, with two cases that demonstrated cystic changes. Out of a total of 1,524 breast carcinomas that were treated, 11 (0.72%) were spindle cell carcinomas. The size of the tumor was generally larger than in other more common types of breast carcinomas, but the degree of a lymph node metastasis was low and the prognosis was better. As for the ER status, 4 out of 5 cases were negative. As cystic changes in the tumor were found in 5 of the 11 cases, it would seem that spindle cell carcinomas of the breast tend to show cystic changes in their tumors.

Adult↗

[Infarctions in fibroadenomas of the breast during pregnancy--a case report and a review of the literature].

Described is a case of infarctions in fibroadenomas of the breast that occurred during pregnancy, with a review of the pertinent literature and a brief discussion on the difficulty of achieving a cytologic diagnosis. A 24-year-old female presented tender lumps that increased in size in her breast during the 7 months of her pregnancy. A subsequent cytologic examination revealed many typical cells with clustered nude nuclei. The cytologic diagnosis indicated a Group V, poorly differentiated adenocarcinoma. Following delivery of her infant, the lumps were excised. Microscopic examination revealed extensive infarcted fibroadenomas with lactational changes.

Adenocarcinoma↗