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Biomedical subjects

A Nakamura

Publications and source records attributed to A Nakamura.

At least 73 records · Page 4Linked to original sources

Neural substrates for recognition of familiar voices: a PET study.

Identification of familiar people is essential in our social life. We can identify familiar people by hearing their voices as well as by viewing their faces. By measuring regional cerebral blood flow (rCBF) by positron emission tomography (PET), we identified neural substrates for the recognition of familiar voices. The brain activity during discrimination of voices of the subjects' associates and friends from those of unfamiliar people was compared with that during an analogous discrimination of their own voice from unfamiliar voices as well as during vowel discrimination. The left frontal pole, right temporal pole, right entorhinal cortex, and left precuneus were activated to a greater extent during discrimination of familiar voice than during control discriminations, suggesting that these brain regions are involved in the recognition of familiar voices. Furthermore, the adjusted values of rCBF in the left frontal pole and right temporal pole correlated with the number of subjects' correct identification of familiar voices. The present results suggest that these two regions are coactively associated with matching the currently heard voice to familiar voices in one's memory.

Adult↗

Normal ventilation and ventilatory responses to chemical stimuli in juvenile mutant mice deficient in endothelin-3.

Congenital central hypoventilation syndrome (CCHS) and Hirschsprung's disease (HSCR) are often classified as neurocristopathies and are thought to share a common molecular pathogenesis related to the genes that control the development of neural crest cells. We examined whether endothelin-3 (ET-3), one of the developmental regulators of neural crest cells and of which null mutation results in aganglionic megacolon in mice, fulfills the requirements for such a common molecule. To investigate the possible involvement of ET-3 in central ventilatory control, we measured ventilation in mutant mice deficient in ET-3 by whole body plethysmography. Tidal volume and breathing frequency were measured during breathing of room air, hypoxic, hyperoxic, or hypercapnic gas mixtures in awake and anesthetized mice. There were no significant differences in resting ventilation as well as ventilatory responses to hypoxia and hypercapnia between ET-3-knockout mice and wild-type mice. Our results indicate that ET-3 can not be considered as a common pathogenic mechanism for CCHS and HSCR at least in mice.

Anesthesia↗

Different neural systems for recognizing plants, animals, and artifacts.

The purpose of this study was to investigate functional organization in the human brain involved in the representation of knowledge regarding plants. We measured the brain activity of eight male volunteers during the recognition of visual stimuli representing plants, animals and artifacts, using positron emission tomography. The participants were presented with and were required to name silently two different images each of 15 entities belonging to three ontological categories, and 30 series of four to six digits. Marked increases in regional cerebral blood flow were found in the hippocampus and the parahippocampal areas bilaterally and the right lateral occipital cortex during the silent naming of all three categories, compared with that during the silent reading of digits. The right lateral occipital cortex was specifically activated in association with the naming of plants, and the right fusiform cortex was specifically activated in association with the naming of animals. In addition, the right temporo-occipital cortex was activated only during animals and plants, not artifacts. Our results indicate that there were a few characteristic activations for the different categories, and that entities belonging to the different categories are not necessarily represented in different locations of the brain.

Cerebral Cortex↗

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

Acetylcholine↗

Activation of calcineurin and stress activated protein kinase/p38-mitogen activated protein kinase in hearts of utrophin-dystrophin knockout mice.

Dilated cardiomyopathy is a common complication of Duchenne and Becker muscular dystrophies, which are caused by mutations in the dystrophin gene. The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD) and shows mildly dystrophic changes in the heart. By contrast, the utrophin-dystrophin knockout (dko) mouse shows severe dystrophic changes in cardiac muscle, that more closely resembles DMD cardiomyopathy than mdx mouse. However the pathogenesis of development has not been fully understood. Recently many reports have revealed that calcineurin and stress activated protein kinase (SAPK)/p38-mitogen activated protein kinase (MAPK) hypertrophic signalling pathways are associated with the development of some forms of hypertrophic and dilated cardiomyopathies. These signalling pathways may have some roles in the development of dystrophin-deficient cardiomyopathy. Here we report that calcineurin and SAPK/p38-MAPK signalling pathways were constantly activated in dko hearts, but the activation varied in mdx hearts. The pathogenesis of the development of dystrophin-deficient cardiomyopathy may be associated with the activation of these signalling pathways.

Age Factors↗

Orally active cephalosporins. Part 3: synthesis, structure-activity relationships and oral absorption of novel C-3 heteroarylmethylthio cephalosporins.

A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-(heteroarytmethylthio)cephalosporins was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity was markedly influenced by the structure of the heteroaromatic ring moiety. Oral absorption was influenced by the heteroaromatic ring moiety as well as by the arrangement of heteroatoms. Among these compounds, FK041 (2o), having a 4-pyrazolylmethylthio moiety, showed potent antibacterial activity against both gram-positive and gram-negative bacteria including Haemophilus influenzae. Further, it showed higher oral absorption than CFDN.

Administration, Oral↗

Effect of salt and heating on a mesoscopic structure composed of ovalbumin globules in aqueous solution.

Mesoscopic structural changes of an ovalbumin solution by heating and adding NaCl have been investigated with a small-angle neutron scattering method. In the natural solution, a broad peak at q = 0.057 A(-1), which disappeared by adding NaCl, indicates the existence of an electrostatic long-range interaction between the ovalbumin globules. Along with the broad peak, a prominent intensity increase in a very small q region was observed on heating except for the initial and final stages, indicating the coexistence of a disordered structure of the denatured ovalbumin and a regular-interspacing structure of the natural ovalbumin globules. Though the macroscopic feature in the final stage, whether the solution forms a gel (10 wt %) or not (5 wt %), strongly depended on the concentration of the ovalbumin, the scattering profiles showed a common characteristic feature: the appearance of a new peak around q = 0.023 A(-1), which indicates the emergence of another regular structure.

Animals↗

Transmission of mouse senile amyloidosis.

SUMMARY: In mouse senile amyloidosis, apolipoprotein A-II polymerizes into amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of AApoAII fibrils into young mice induces systemic amyloidosis (Higuchi et al, 1998). We isolated AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2(c) mice and injected them with feeding needles into the stomachs of young R1.P1-Apoa2(c) mice for 5 consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart, and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid deposition was induced in young mice reared in the same cage for 3 months with old mice who had severe amyloidosis. Detection of AApoAII in feces of old mice and induction of amyloidosis by the injection of an amyloid fraction of feces suggested the propagation of amyloidosis by eating feces. Here, we substantiate the transmissibility of AApoAII amyloidosis and present a possible pathogenesis of amyloidosis, ie, oral transmission of amyloid fibril conformation, where we assert that exogenous amyloid fibrils act as templates and change the conformation of endogenous amyloid protein to polymerize into amyloid fibrils.

Amyloid↗

Cytokines in pleural liquid for diagnosis of tuberculous pleurisy.

An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNFalpha and IFNgamma levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0.770, 0.875, 0.892 and 0.987, respectively for IL-8, TNFalpha, ADA and IFNgamma. No false-positives were encountered with IFNgamma and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFNgamma is a very reliable marker of tuberculous pleurisy.

Adenosine Deaminase↗

Nonsteroidal anti-inflammatory drug-associated colitis with a histology of collagenous colitis.

Here we report a case of nonsteroidal anti-inflammatory drug (NSAID)-associated colitis with a histology of collagenous colitis in a 77-year-old woman. The patient had taken aspirin since 1993 after being diagnosed at another hospital, as having multiple cerebral infarctions. She began to suffer from intermittent diarrhea in April 1999. Serological examination showed hypoproteinemia, which indicated that she had protein-losing enteropathy. By July 1999, she had undergone colonoscopic examination four times. Biopsy specimens taken during the fourth colonoscopy revealed collagenous colitis. As the patient had been taking aspirin for 6 years, she was diagnosed as having NSAID-associated colitis with a histology of collagenous colitis. When she stopped taking aspirin, the diarrhea ceased. Three months later, the patient underwent a fifth colonoscopy. A histological examination of the biopsy specimen revealed that the collagen band had vanished. NSAID-associated colitis sometimes shows collagenous colitis histologically and is cured by withdrawing the drug. It is important to differentiate NSAID-associated colitis, even if it shows a histology of collagenous colitis, from collagenous colitis as the two diseases differ in etiology and therapy.

Aged↗

Tumoral calcinosis in both index fingers: a case report.

Tumoral calcinosis is an uncommon disease of unknown aetiology that usually involves the periarticular tissues of large joints. We report a rare case in which it presented in both index fingers in a 5-year-old boy. The tumours were resected and he made an uncomplicated recovery except for mild tapering deformity on the left. There has been no sign of recurrence a year later.

Calcinosis↗

Myosin light chain kinase as a multifunctional regulatory protein of smooth muscle contraction.

Myosin light chain kinase (MLCK) is a regulatory protein for smooth muscle contraction, which acts by phosphorylating 20-kDa myosin light chain (MLC20) to activate the myosin ATPase activity. Although this mode of action is well-established, there are numerous reports of smooth muscle contraction that is not associated with MLC20 phosphorylation. The kinase activity for the phosphorylation is localized at the central part of MLCK, which is also furnished with actin-binding activity at its N terminal and myosin-binding activity at its C terminal. This article overviews as to how such multifunctional properties of MLCK modify the actin-myosin interaction and presents our observations that the phosphorylation is not obligatory in induction of smooth muscle contraction.

Actins↗

Regulatory mechanism for the stability of the meta II intermediate of pinopsin.

Pinopsin is a chicken pineal photoreceptive molecule with a possible role in photoentrainment of the circadian clock. Sequence comparison among members of the rhodopsin family has suggested that pinopsin might have properties more similar to cone visual pigments than to rhodopsin, but the lifetime of the physiologically active intermediate (meta II) of pinopsin is rather similar to that of metarhodopsin II, which is far more stable than meta II intermediates of cone visual pigments [Nakamura, A. et al., (1999) Biochemistry 38, 14738-14745]. In the present study, we investigated the amino acid residue(s) contributing to this unique property of pinopsin by using site-directed mutagenesis to pinopsin-specific structural features, (i) Ser171, (ii) Asn184, and (iii) the second extracellular loop two-amino acids shorter than that of cone visual pigments. The meta II stability of the 171/184 double mutant of pinopsin (S171R/N184D) is almost the same as that of wild-type pinopsin. In contrast, the meta II lifetime is markedly shortened (one third) by introduction of the third mutation (replacement of a six-amino acid stretch, 188-193, by the corresponding eight residues of chicken green-sensitive cone pigment) to the 171/184 double mutant of pinopsin. Consistently, meta II of the green-sensitive pigment mutant, in which the eight-amino acid stretch is inversely replaced by the corresponding six residues of pinopsin, is more stable than meta II of the wild-type pigment. These results strongly suggest that the specific sequence and/or the number of residues at amino acids 188-193 in pinopsin play an important role in the stabilization of the meta II intermediate.

Amino Acid Substitution↗

Pattern visual evoked potentials in malingering.

OBJECTIVES: We previously developed a new method for estimating objective visual acuity by means of pattern visual evoked potentials (PVEP). In this study, this method was applied to the diagnosis of malingering. MATERIALS AND METHODS: Six patients ranging in age from 40 to 54 years (mean 47 years) with suspected malingering were evaluated by means of the visual evoked potential test, optokinetic nystagmus (OKN) inhibition test, and the visual field test. In the PVEP study, the stimulus consisted of black and white checkerboards (39', 26', 15', and 9') with a visual angle of 8 degrees, contrast level of 15%, and a frequency of 0.7 Hz. One hundred PVEP responses were averaged per session. RESULTS: Routine ophthalmic examinations were normal in all patients. Five patients had a tubularly constricted visual field, and the remaining patient had a normal visual field. The objective visual acuities of the six patients estimated from PVEP were better than their subjective visual acuities estimated with Landolt rings. CONCLUSIONS: Among a variety of psychophysical and electrophysiologic ancillary tests, we consider our PVEP method a useful method for objectively determining visual acuity in a patient with signs of ocular malingering.

Adult↗

No leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y in Japanese population or Japanese with alcoholism.

We have screened 200 Japanese workers and 105 Japanese patients with alcoholism for the mutation in the signal peptide of pre-pro-neuropeptide Y resulting in a substitution of proline for leucine at position 7. This polymorphism was reported in the Finnish and Dutch populations recently. None of our subjects displayed the mutation at this site. Therefore, this allele does not play any role in the development of alcoholism in the Japanese population.

Alcoholism↗

Sentinel lymph nodes study in 30 cases of melanoma.

In 30 cases of melanoma, we attempted to detect sentinel lymph nodes using 1-2% patent blue dye and were able to detect them in 27 cases (90%): 19 cases out of 21 cases in the groin area (90%), 5 out of 5 cases in the axilla area (100%), and 3 out of 4 cases in the neck area (75%). The numbers of sentinel lymph nodes were one in 16 cases, two in 7 cases, three in 2 cases, and four in 2 cases. The cases with three and four nodes were all in the groin area. In 22 cases, tumor metastasis was negative in sentinel lymph nodes. Sentinel lymph nodes were detected in 36 out of 174 samples, and tumor metastasis was negative except in these sentinel lymph nodes (false negative 0%). In the groin area, sentinel lymph nodes were located around the femoral and great saphenous vein junction. In the axilla area, sentinel lymph nodes were located in the central, lateral and subscapular lymph nodes. In the head and neck area, sentinel lymph nodes were found in the submandibular and occipital lymph nodes. The positions of sentinel lymph nodes differed a little with tumor location. By accumulating cases, it should become possible to predict the positions of sentinel lymph nodes before operations. Sentinel lymph node biopsy is easy and requires only a small incision.

Adult↗

Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers.

hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key component of the mitotic checkpoint system. Recently, mutations and decreased expression of mitotic checkpoint genes including hsMAD2 have been reported in cancer cell lines with defective mitotic checkpoint. However, the genetic alterations in the genomic hsMAD2 gene have not been determined in gastric cancers. Moreover, the biological implications of the overexpressed hsMAD2 in primary cancers are unknown. In this study, we analyzed 32 primary gastric cancers with polymerase chain reaction (PCR) amplification of all exons, including flanking intronic sequences, of the genomic hsMAD2 gene followed by direct DNA sequencing. We also measured the hsMAD2 protein levels in cancer and normal tissues by semi-quantitative immunoblotting. No mutations were found in the coding sequences, although three single nucleotide polymorphisms (SNPs) were identified in the noncoding sequences in 13 of 32 patients. These SNPs were not associated with either hsMAD2 expression or disease progression. The semi-quantitative western blot analysis showed hsMAD2 was significantly overexpressed in gastric cancer tissues compared with corresponding normal tissues (P < 0.001). The calculated ratio of the hsMAD2 protein in cancer tissue (C) to that in corresponding normal tissue (N) (C / N ratio) was significantly higher in patients with well differentiated adenocarcinoma (P = 0.0274) or with synchronous liver metastasis (P = 0.0025). A C / N ratio greater than 3 was observed more frequently in patients with synchronous liver metastasis. Therefore, C / N ratio > 3 may be clinically important as a predictive indicator for metachronous liver metastasis of gastric cancers.

Adenocarcinoma↗