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Biomedical subjects

M Inagaki

Publications and source records attributed to M Inagaki.

At least 181 records · Page 10Linked to original sources

[Developmental dyslexia and dysgraphia--a case report].

We reported a 7-year-old, right-handed boy whose reading and writing of kana and kanji were impaired. He also showed a severe deficit in visuo-spatial perception skills. Nevertheless, his ability to read and write kana characters was facilitated by means of the Japanese Syllabaries. It is generally considered that the Syllabary involve two kinds of language modalities: auditory-verbal and visuo-verbal language systems. In spite of his intact auditory-verbal language system, his visuo-verbal language skills involved in writing kanji were severely impaired. It was suggested that a severe deficit of visuo-spatial perception skills influenced performance of visuo-verbal language systems. Accordingly, we inferred that the patient recalled a kana character by use of the Japanese Syllabaries based on his good auditory-verbal language system, and supposed that his reading and writing disorders were similar to alexia with agraphia in adult patients with angular lesions.

Agraphia↗

[A semantic-pragmatic learning disabled child who showed a discrepancy between the abilities of verbal and non-verbal comprehension].

A learning disabled (LD) child with disorder of verbal semantic comprehension was reported. This case showed normal ability of non-verbal semantic comprehension. He was not able to understand the meaning of what he read aloud and/or repeated, which he did well. The focus of his brain dysfunction in the left temporal lobe was revealed by SPECT in spite of MRI findings of no particular lesions. Neuropsychological and cognitive-psychological findings were similar to those reported of adult sensory aphasias with localized lesions.

Child↗

[A child showing memory disorders].

We report a girl with memory disorders. Her memory remained disturbed regardless of input or output modalities. She could recognize items and recall them randomly, but she could not recall them in the correct order. She showed memory impairment with regard to temporal context. We could clearly demonstrate this by cognitive psychological and neuropsychological tests and by analyzing the results of ordinary intelligence tests by input and output modalities. These results suggest that subjects who show memory disorders should undergo further resting to clarify the qualitative aspects of these disorders and the possibility that learning disabilities caused by memory disorders should be considered a specific type of learning disability.

Child↗

Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas.

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are ideal neoplasms to study clonal progression and genetic diversity because of their large size and prominent intraductal component. We microdissected 55 histologically defined areas from 13 IPMNs, extracted the DNA from each, and performed polymerase chain reaction (PCR)-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 3p, 6q, 8p, 9p, 17p, 18q, and 22q. LOH was identified at 1p in two cases, at 3p in four cases, at 6q in seven cases, at 8p in four cases, at 9p in eight cases, at 17p in five cases, at 18q in five cases, and at 22q in one of the IPMNs examined. In one of the IPMNs, the allelic losses were uniform throughout multiple microdissected areas, and in four of the IPMNs, there was evidence of clonal progression. In contrast, in three of the IPMNs, substantial allelic heterogeneity was seen. This remarkable heterogeneity may, in part, be due to the slow growth rate of these neoplasms.

Adenocarcinoma, Mucinous↗

[Mismatch negativity of patients with hydranencephaly].

We examined auditory evoked potentials and passive event-related potentials in two patients with hydranencephaly. In the middle latency response, a Na component was observed in both cases. Mismatch negativity was elicited in response to tone bursts and three patterns of vowel sounds in Patient 1, and three patterns of vowel stimuli in Patient 2. These results implicate the subcortical components of the auditory system in the generation of mismatch negativity.

Adolescent↗

Depressed mechanoenergetics and compensatory responses in idiopathic dilated cardiomyopathy.

The aim of this study was to clarify that the depressed mechanoenergetics in patients with idiopathic dilated cardiomyopathy (DCM) resulted from compensation for the decreased contractility. The study population consisted of eight control subjects, with normal left ventricular size and ejection fraction and 31 patients with DCM. Left ventricular end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and the pressure-volume area (PVA) were measured, using a dual-field volume conductance catheter equipped with a micromanometer-tipped catheter. Ea/Ees was evaluated as ventriculoarterial coupling. Normal hearts worked at almost optimal condition (defined as Ea/Ees = 1/2), while ventriculoarterial coupling was far from the optimum (Ea > Ees) in patients with DCM. Ees in patients with DCM was less than that in control subjects; however, Ea was similar in the two groups. The mismatch of Ea/Ees observed in DCM leads to depressed mechanoenergetics as a result of the compensatory response to maintain adequate blood pressure. Volume enlargement plays an important role in maintaining adequate blood pressure and cardiac output in the course of chronic deterioration of contractility.

Blood Pressure↗

Keratin 8 phosphorylation in vitro by cAMP-dependent protein kinase occurs within the amino- and carboxyl-terminal end domains.

We reported earlier that phosphorylation in vitro of keratin filaments reconstituted from rat type I keratin 18 and type II keratin 8 by cAPM-dependent protein kinase induces disassembly of the keratin filament structure. Keratin 8 rather than keratin 18 was the major target of the kinase. We have now identified the sites on rat keratin 8 for cAMP-dependent protein kinase. Sequential analysis of the purified phosphoropeptides, together with the known primary sequence, revealed that four major sites, Ser-12, Ser-23, Ser-36, and Ser-50, and three minor sites, Ser-8, Ser-33, Ser-42, are located in the amino-terminal head domain, while three minor sites, Ser-416, Ser-423 and Ser-425 locate in the carboxyl-terminal tail domain.

Amino Acid Sequence↗

Primary structure of light and heavy chain variable regions of antibodies recognizing phosphorylated vimentins.

We determined the primary structure of three types of monoclonal antibodies against phosphorylated vimentin, 4A4, YT33, and MO82, which recognize phosphorylated Ser55, Ser33, and Ser82 on vimentin, respectively. The amino acid sequences between these antibodies and the anti-phosphotyrosine antibodies previously reported, (Asn/Gln)-X-(Gln/Tyr)-Ser-Tyr in the complimentarity determining region (CDR) 3 of the light chain of 4A4 and YT33, Asn-Pro-Asn-(Asn/Ser)-Gly-X-(Ser/Thr)-(Ser/Thr)-Tyr-Asn-Gln-(Arg/Lys)-Ph e-Lys in the heavy chain CDR2 of MO82, and Lys-X-Ser-(Ser/Asn) in the heavy chain CDR3 of YT33 and MO82, were highly conserved. These motifs may play a role in recognizing phosphate groups of phosphoserine and phosphotyrosine.

Amino Acid Sequence↗

Microinjection of intact MAP-4 and fragments induces changes of the cytoskeleton in PtK2 cells.

The molecular cloning and sequencing of microtubule-associated protein (MAP)-4 identified microtubule-binding repeats near the C-terminus and a projection domain near the N-terminus. Although it is well known that MAP-4 stimulates the assembly of and stabilizes microtubules (MT) in vitro, the function of MAP-4 in vivo is still unclear. In this study, we examined the function of MAP-4 in the cytoskeleton both in vitro and in vivo. Intact MAP-4 was prepared from bovine adrenal cortex, and the truncated fragments of the N- and the C-terminal halves (named NR and PA4 fragments, respectively) were expressed in Escherichia coli and isolated. In vitro studies demonstrated that in a solution containing a physiological concentration of NaCl, intact MAP-4 and the PA4 fragment were bound to MT, but not to F-actin. The NR fragment was not bound to MT or to F-actin. We also examined the MT changes in PtK2 cells after they had been microinjected with intact MAP-4 and the truncated fragments of PA4 and NR. The injection of intact MAP-4 or PA4 into the cells induced an increase in the number of cytoplasmic MT, as well as MT bundling. The NR fragment did not affect the MT array. Injected MAP-4 and PA4 were associated with the increased MT. In addition, injection with MAP-4 and PA4 stabilized MT in relation to treatment with the MT-disrupting drug, nocodazole. These results indicated that intact MAP-4 and the PA4 fragment promoted MT assembly and stabilized MT, by binding to MT, in vivo as well as in vitro. Further, the injection of the PA4 fragment induced an increase in stress fibers. However, these proteins did not show any association with the stress fibers. Our results suggest that there is an indirect effect of MAP-4 on stress fibers rather than a direct interaction between MAP-4 and stress fibers.

Actins↗

Visualization of protein kinase activities in single cells by antibodies against phosphorylated vimentin and GFAP.

Vimentin and glial fibrillary acidic protein (GFAP) are intermediate filament proteins expressed in the cytoplasm of various types of cells. The head domains of these proteins are phosphorylated by various protein kinases. Site- and phosphorylation-specific antibodies which recognize a phosphorylated serine/threonine residue in the head domains and its flanking sequence provide a useful tool to monitor and visualize protein kinase activities in single cells.

Amino Acid Sequence↗

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease.

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.

Adult↗

Detection of protein kinase activity specifically activated at metaphase-anaphase transition.

We have previously reported that Ser13 and Ser34 on glial fibrillary acidic protein (GFAP) in the cleavage furrow of glioma cells are phosphorylated during late mitotic phase (Matsuoka, Y., K. Nishizawa, T. Yano, M. Shibata, S. Ando, T. Takahashi, and M. Inagaki. 1992, EMBO (Eur. Mol. Biol. Organ.) J. 11:2895-2902). This observation implies a possibility that there is a protein kinase specifically activated at metaphase-anaphase transition. To further analyze the cell cycle-dependent GFAP phosphorylation, we prepared monoclonal antibodies KT13 and KT34 which recognize the phosphorylation of GFAP at Ser13 and Ser34, respectively. Immunocytochemical studies with KT13 and KT34 revealed that the GFAP phosphorylation in the cleavage furrow during late mitotic phase occurred not only in glioma cells but also in human SW-13 and mouse Ltk- cells in which GFAP was ectopically expressed, thus the phosphorylation can be monitored in a wide range of cell types. Furthermore, we detected kinase activity which phosphorylates GFAP at Ser13 and Ser34 in the lysates of late mitotic cells but not in those of interphase cells or early mitotic cells. These results suggest that there exists a protein kinase which is specifically activated at the transition of metaphase to anaphase not only in GFAP-expressing cells but also in cells without GFAP.

Anaphase↗

Mitosis-specific phosphorylation of vimentin by protein kinase C coupled with reorganization of intracellular membranes.

Using two types of anti-phosphopeptide antibodies which specifically recognize vimentin phosphorylated by protein kinase C (PKC) at two distinct PKC sites, we found that PKC acted as a mitotic vimentin kinase. Temporal change of vimentin phosphorylation by PKC differed form changes by cdc2 kinase. The mitosis-specific vimentin phosphorylation by PKC was dramatically enhanced by treatment with a PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), while no phosphorylation of vimentin by PKC was observed in interphase cells treated with TPA. By contrast, the disruption of subcellular compartmentalization of interphase cells led to vimentin phosphorylation by PKC. Cytoplasmic and nuclear membranes are fragmented and dispersed in the cytoplasm and some bind to vimentin during mitosis. Thus, targeting of activated PKC, coupled with the reorganization of intracellular membranes which contain phospholipids essential for activation, leads to the mitosis-specific phosphorylation of vimentin. We propose that during mitosis, PKC may phosphorylate an additional subset of proteins not phosphorylated in interphase.

Amino Acid Sequence↗

Subfoveal choroidal neovascularization in uveitis.

Only rarely can the development of subretinal foveal or parafoveal neovascularization be observed in patients with chronic uveitis. We report herein the clinical characteristics pertaining to neovascular membranes and the treatment thereof in 3 patients afflicted with either sarcoidosis (2 patients) or Behçet syndrome (1 patient). Peroral steroids contributed to a reduction of neovascular membranes in 1 patient with sarcoidosis. The management of uveitis is mandatory for the prevention of subretinal foveal neovascular membranes.

Anti-Inflammatory Agents↗

Blink reflex in cerebral palsy: evaluation of late components in patients with normal auditory brainstem responses.

The electrically elicited blink reflex was examined and evaluated quantitatively in 60 controls and seven patients with cerebral palsy due to perinatal asphyxia who exhibited normal auditory brainstem responses. In the controls, the early component (R1) latency changed slightly from infancy to adulthood, and the late component (R2 and R2') latencies decreased to adult values by 4 to 6 years of age. The electromyographic activity of R2 and R2' increased later and became mature in the young adolescent period. Prolonged R2 latency and decreased R2 amplitude were observed more frequently than R1 abnormalities in the patients. The electromyographic activity of R2 in the patients was lower than that in control subjects more than 13 years old. Almost all patients showed bilateral cerebral atrophy and dilated lateral ventricles, but only one patient exhibited distinct pontine atrophy on cranial computed tomographic scan. These electrophysiologic abnormalities suggest that decreased excitability of interneurons of the reflex arc was present in the patients, particularly in older ones. The blink reflex test seems to be more sensitive than the auditory brainstem response for detecting brainstem dysfunction in patients with cerebral palsy due to neonatal asphyxia.

Adolescent↗

Effects of ganglioside GD1a on the fluidity and phase transition of phosphatidylcholine model membrane immobilized on porous cellulose acetate filter.

The thermotropic effect of ganglioside GD1a on the phosphatidylcholine membrane immobilized on the porous cellulose acetate filter was investigated by ESR spin-labeling and DSC. The spin-labeled GD1a having 12-DOXYL-stearic acid instead of the long acyl chain of the ceramide portion (GD1a*) was incorporated into the model membrane. An ESR examination of the membrane showed that GD1a* undergoes an anisotropic rotation in the wide range of temperature -30-70 degrees C. By monitoring the overall splitting (2T parallel) of spin-labeled phosphatidylcholine (PC*), the model membranes were found to show decreased fluidity in accordance with the GD1a content. The phase transition temperature (Tm) of distealoylphosphatidylcholine (DSPC) model membranes could be estimated by the measurement of ESR and DSC. The effects of GD1a were found to be more significant in broadening the phase transition rather than in elevating the Tm of DSPC model membranes.

Animals↗

[A specific disorder in Kanji writing in a learning disabled child with a visual cognition disorder--a cognitive-neuropsychological and electrophysiological analysis].

We reported a learning disabled child with a specific disorder involving Kanji writing. The patient was a 13-year-old boy. Although he manifested generally normal intellectual ability and his performance on WISC-R indicated that VIQ was 101 and PIQ 84, he could only write approximately 20% of Kanji, which he learned at age 6 to 7. On cognitive-psychological tests, he showed a visual cognition disorder that was different from that in a previously reported case during information processing. Electrophysiologically, he showed a disorder in visual task-relevant potentials. The mechanism underlying this patient appears to be a retrieval disorder for complex graphic forms in addition to a visual cognition disorder because of two reasons. One is that he could distinguish Kanji from similar graphic forms. The other is that he could read Kanji aloud.

Adolescent↗