A case of idiopathic musical hallucination with increasing repertoire.
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Biomedical subjects
Publications and source records attributed to M Satoh.
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OBJECTIVES: To study the efficacy and safety of monthly intravenous pulse cyclophosphamide (IVCYC) therapy for progressive interstitial pneumonia in polymyositis/dermatomyositis (PM/DM). METHODS: Seventeen patients with PM/DM/amyopathic DM (mean age 51.4 +/- 10.4, mean follow-up 32 months) who received IVCYC for progressive interstitial pneumonia between August 1993 and October 2002 were studied. Nine patients had failed to respond to previous treatment with high-dose steroid and/or immunosuppressant. Cyclophosphamide (300-800 mg/m2) was given at least six times every 4 weeks. Oral prednisolone (0.5-1 mg/kg/day) was administered for the first 2 weeks and was gradually tapered. Response to treatment was evaluated based on the degree of exertional dyspnea, pulmonary function test and high-resolution computed tomography (HRCT). RESULTS: Eleven of 17 patients showed improvement in their dyspnea; six out of seven patients who had required oxygen treatment before IVCYC no longer did so after IVCYC. Eight of 17 patients had >or=10% improvement of vital capacity (VC)% and 9/17 had >or=10 point reduction in their HRCT score. Twelve patients had exhibited at least one result. Two patients with anti-Jo-1 antibodies showed a flare-up of interstitial pneumonia or myositis. After the IVCYC therapy, mean VC% improved by 15% (from 68 to 83%, P = 0.0034). The extent of abnormal lesions in HRCT was reduced from 24 to 13% (P = 0.0055). There was neither death nor severe toxicities observed. CONCLUSIONS: In this open-label study, IVCYC improved symptoms, pulmonary function tests and HRCT findings in patients with PM/DM. Longitudinal controlled studies are required to further confirm the efficacy of IVCYC.
Leukotriene B4 is a potent lipid mediator, which has been identified as a potent proinflammatory and immunomodulatory compound. Although there has been robust evidence indicating that leukotriene B4 is synthesized in the normal brain, detailed distribution and its functions in the nervous system have been unclear. To obtain insight into the possible neural function of leukotriene B4, we examined the immunohistochemical distribution of leukotriene A4 hydrolase, an enzyme catalyzing the final and committed step in leukotriene B4 biosynthesis, in the mouse nervous system. Immunoreactivity for leukotriene A4 hydrolase showed widespread distribution with preference to the sensory-associated structures; i.e. neurons in the olfactory epithelium and vomeronasal organ, olfactory glomeruli, possibly amacrine cells, neurons in the ganglion cell layer and three bands in the inner plexiform layer of the retina, axons in the optic nerve and tract up to the superior colliculus, inner and outer hair cells and the spiral ganglion cells in the cochlea, vestibulocochlear nerve bundle, spinal trigeminal tract, and lamina II of the spinal cord. Double immunofluorescence staining demonstrated that most of the leukotriene A4-hydrolase-immunopositive neurons coexpressed calretinin, a calcium-binding protein in neurons. The ubiquitous distribution of leukotriene A4 hydrolase was in sharp contrast with the distribution of leukotriene C4 synthase [Shimada A, Satoh M, Chiba Y, Saitoh Y, Kawamura N, Keino H, Hosokawa M, Shimizu T (2005) Highly selective localization of leukotriene C4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain. Neuroscience 131:683-689] which was confined to the hypothalamic and extrahypothalamic vasopressinergic neurons. These results suggest that leukotriene B4 may exert some neuromodulatory function mainly in the sensory nervous system, in concert with calretinin.
AIMS: To investigate the expression of p62 in various prostatic tissues, and to demonstrate different immunohistochemical patterns of p62 expression in distinct pathological entities of the prostate. The p62 sequestosome 1 (SQSTM1) gene product is a multifunctional protein with ubiquitous expression in normal adult tissue. METHODS AND RESULTS: Overexpression of p62 was detected in prostate cancer cell lines and tissues by reverse transcriptase-polymerase chain reaction. Immunohistochemical staining for p62 was performed on 73 cases of paraffin-embedded prostatic tissue. p62 was negative or weakly positive only in the nucleus (pattern N) of prostatic gland epithelium in nine normal and hyperplastic prostate specimens, whilst most cancerous tissue showed intense, uniform staining for p62 in the cytoplasm (pattern C). Of the prostate cancer specimens, 91% showed positive pattern C immunoreactivity. Of the cases with high-grade prostatic intraepithelial neoplasia (PIN) around cancer, 77% showed pattern C. However, in specimens from the patients without prostate cancer PIN displayed pattern C in only 32% of cases. Western blot analysis showed that all cancer cell lines expressed p62 in the cytoplasm but there was little nuclear expression. CONCLUSION: Cytosolic overexpression of p62 is a novel immunohistochemical characteristic in prostatic adenocarcinoma and high-grade PIN, suggesting that p62 might be a novel marker for prostatic malignancy.
The SAMP10 mouse is a model of accelerated ageing in which senescence is characterized by age-related atrophy of the cerebral cortex and limbic structures, poor learning and memory task performance with depressive behaviour and cholinergic and dopaminergic alterations. Here we studied age-related changes in the dendritic arbors and spine density of pyramidal cells in the medial prefrontal cortex of SAMP10 mice using a quantitative Golgi method. Dendrites of prefrontal neurones gradually retracted with ageing towards the soma with the relative preservation of overall complexity. Apical dendrites were much more severely affected than basal dendrites. The combined length of the apical dendrites and spine density were decreased by 45% and 55%, respectively, in mice at 12 months, compared with mice at 3 months of age. Immunohistochemical and immunoblot analyses indicated that expression of microtubule-associated protein (MAP) 2, a marker of dendrites, decreased in an age-related manner not only in the anterior cortex but also in the posterior cortex and olfactory structures in SAMP10 mice. Decreased expression of MAP2 mRNA caused the decrease in MAP2 protein expression. These results suggest that retraction of apical, but not of basal dendrites, with a loss of spines in prefrontal neurones, appears to be responsible for poor learning and memory performance in aged SAMP10 mice. It is also suggested that age-related dendritic retraction occurs in a wide area including the entire cerebral cortex and olfactory structures.
BACKGROUND AND OBJECTIVE: The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. MATERIAL AND METHODS: Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. RESULTS: In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell-cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. CONCLUSION: These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.
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Light and electron microscopic features and immunohistochemical features of Cryptosporidium andersoni (C. andersoni) and host reaction in the mucosa were studied. Although the affected cattle demonstrated no apparent clinical signs, a severe infection of C. andersoni was observed in the abomasum. C. andersoni were round in shape, measured 6-8 microm in size and were mainly observed to be freely located in the gastric pits, being attached in occasional cases to the surface of the abomasum epithelium. Frequent inflammatory cells had infiltrated the lamina propria of the affected mucosa, and frequent mitotic figures were observed in epithelial cells at the dilated isthmus. To access the cell kinetics, the number of epithelial cells infected with C. andersoni were counted and compared with noninfected cattle. The number of gastric pit cells in infected cattle was significantly higher than that in the controls. The number of proliferative cells determined by the Ki-67 antigen in C. andersoni infected cattle was also significantly higher than that in the controls. Transmission electron microscopy and scanning electron microscopy revealed that the morphology of the C. andersoni organism was common to those of other Cryptosporidium spp. Immunohistochemically, several commercial antibodies against Cryptosporidium spp. showed positive reactions at the wall of these oocysts or parasitophorous vacuoles. This report is possibly the first to discuss the prominent hyperplasia of the abomasum mucosa, as well as morphologic features of C. andersoni in cattle.
BACKGROUND AND PURPOSE: We can easily recognize familiar music by listening to only one or 2 of its opening bars, but the brain regions that participate in this cognitive processing remain undetermined. We used positron-emission tomography (PET) to study changes in regional cerebral blood flow (rCBF) that occur during listening to familiar music. METHODS: We used a PET subtraction technique to elucidate the brain regions associated with the recognition of familiar melodies such as well-known nursery tunes. Nonmusicians performed 2 kinds of musical tasks: judging the familiarity of musical pieces (familiarity task) and detecting deliberately altered notes in the pieces (alteration-detecting task). RESULTS: During the familiarity task, bilateral anterior portions of bilateral temporal lobes, superior temporal regions, and parahippocampal gyri were activated. The alteration-detecting task bilaterally activated regions in the precunei, superior/inferior parietal lobules, and lateral surface of frontal lobes, which seemed to show a correlation with the analysis of music. CONCLUSION: We hypothesize that during the familiarity task, activated brain regions participate in retrieval from long-term memory and verbal and emotional processing of familiar melodies. Our results reinforced the hypothesis reported in the literature as a result of group and case studies, that temporal lobe regions participate in the recognition of familiar melodies.
We have investigated the localization and physiological roles of metallothioneins (MTs) in the olfactory pathway after exposure to mercury (Hg0) vapor. Male MT-null and wild-type mice were examined for the distribution of mercury, MT immunoreactivity and MT-III mRNA expression. There were no signs of histological changes in MT-null or wild-type mice. Light and electron microscopy of the samples stained with autometallography demonstrated chronological transfer of exposed mercury granules to the olfactory bulb by way of the olfactory tract. Basal expression of MT-I and -II immunoreactivity was observed in supporting cells, basal cells and acinar cells of the Bowman's gland of the olfactory mucosa in wild-type mice even without mercury exposure. In situ hybridization showed that signals for MT-III mRNA dominated in the olfactory cells of the olfactory mucosa, neurons in the olfactory bulb and those of brain in MT-null and wild-type mice. No difference in these findings was observed between samples taken at any interval after mercury exposure.
BACKGROUND: Collagen lattice contraction has been reported as another aspect of the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH). Recently, some authors have suggested that matrix metalloproteinase-1 (MMP-1) plays an important role in collagen lattice contraction. Therefore, this study aimed to clarify a role of MMP-1 during cerebral vasospasm in a rat SAH model. METHOD: We used a single-SAH model in rats and assessed the basilar arteries (BAs) at 30 minutes and on 2 days after SAH by cross-sectional area measurement and other histological parameters. Immunohistochemistry and Western blot analysis were used to quantify MMP-1 expression and activation. RESULTS: BAs in rats significantly exhibited severe cerebral vasospasm at 30 minutes after SAH and moderate vasospasm on Day 2. The immunohistochemistry and Western blotting performed in BAs of rats demonstrated that both expression and activation in MMP-1 peaked at 30 minutes after SAH and then declined to the control level. CONCLUSIONS: MMP-1 is expressed and activated in a parallel time course to the development of cerebral vasospasm in an experimental model of SAH.
While leukotriene C4 (LTC4) was originally identified as a potent bronchoconstrictor, the compound has versatile biological activities besides inflammatory reactions. Although the high content of LTC4 has been reported in the hypothalamus and median eminence, the precise localization of the compound remained obscure. To elucidate its possible functions in the neuroendocrine systems, we determined immunohistochemical localization of LTC4 synthase, a key enzyme to produce LTC4 using mouse brains. Light microscopy and confocal laser scanning microscopy showed that LTC4 synthase was selectively localized in the vasopressinergic magnocellular neurons of the hypothalamic paraventricular, supraoptic and suprachiasmatic nuclei and in the retrochiasmatic area, as well as in axons that emanated from these neurons to the pars nervosa of the pituitary gland. At subcellular level, however, LTC4 synthase and arginine vasopressin appeared to localize differently within individual neurons. LTC4 synthase immunoreactivity was also observed in the axons of the extrahypothalamic system including the bed nucleus of the stria terminalis, lateral habenular nucleus, midbrain central gray, medial amygdaloid nucleus and ventral septal area, although this immunoreactivity was relatively minor. The other brain regions did not contain LTC4 synthase immunoreactivity. The distribution of LTC4 synthase did not overlap with that of either oxytocin or luteinizing hormone releasing hormone. Therefore, LTC4 is considered to be involved in neural functions of the brain magnocellular vasopressinergic system such as water retention. LTC4 may also be involved in extrahypothalamic vasopressinergic neural functions including the regulation of learning and memory, social recognition memory, sexual and aggressive behavior, etc.
The central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST) are key structures of the extended amygdala, which is suggested to be involved in drug addiction and reward. We have previously reported that the Ce plays a crucial role in the negative affective component of morphine withdrawal. In the present study, we examined the involvement of the neural pathway between the Ce and the BST in the negative affective component of morphine withdrawal in rats. Rats were rendered morphine dependent by s.c. implantation of a 75-mg morphine pellet for 3 days, and morphine withdrawal was precipitated by an i.p. injection of naloxone (0.3 mg/kg). In the place-conditioning paradigm, discrete bilateral excitotoxic lesions of the Ce or the BST significantly reduced naloxone-precipitated morphine withdrawal-induced conditioned place aversion. On the other hand, they had little effect on morphine withdrawal-induced somatic signs. In an immunohistochemical study for c-Fos protein, naloxone-precipitated morphine withdrawal dramatically induced c-Fos-immunoreactive neurons in the capsular part of the Ce, and the lateral and medial divisions of the BST. Bilateral excitotoxic lesion of the Ce reduced the number of morphine withdrawal-induced c-Fos-immunoreactive neurons in the lateral and medial BST, with significant decreases in the posterior, ventral and juxtacapsular parts of lateral division, and anterior part of the medial division, but not in the ventral part of the medial division of the BST. On the other hand, bilateral excitotoxic lesion of the BST had no effect on such c-Fos induction within the capsular part, nor the ventral and medial divisions of the Ce. These results suggest that activation of the BST mediated through the neural pathway from the Ce contributes to the negative affective component of morphine withdrawal.
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The complete nucleotide sequence (501,020 bp) of the mitochondrial genome from cytoplasmic male-sterile (CMS) sugar beet was determined. This enabled us to compare the sequence with that previously published for the mitochondrial genome of normal, male-fertile sugar beet. The comparison revealed that the two genomes have the same complement of genes of known function. The rRNA and tRNA genes encoded in the CMS mitochondrial genome share 100% sequence identity with their respective counterparts in the normal genome. We found a total of 24 single nucleotide substitutions in 11 protein genes encoded by the CMS mitochondrial genome. However, none of these seems to be responsible for male sterility. In addition, several other ORFs were found to be actively transcribed in sugar beet mitochondria. Among these, Norf246 was observed to be present in the normal mitochondrial genome but absent from the CMS genome. However, it seems unlikely that the loss of Norf246 is causally related to the expression of CMS, because previous studies on mitochondrial translation products failed to detect the product of this ORF. Conversely, the CMS genome contains four transcribed ORFs (Satp6presequence, Scox2-2 , Sorf324 and Sorf119) which are missing from the normal genome. These ORFs, which are potential candidates for CMS genes, were shown to be generated by mitochondrial genome rearrangements.
Previously we found that exposure to mercury vapor effectively induced metallothionein (MT) biosynthesis in rat brain. Although the induction of not only MT-I/II but also MT-III was evident, the induction rate of the latter was much lower than that of the former. The brain of an MT-null mouse lacks MT-I/II, but has MT-III. Here we examined the effects of sub-chronic pulse exposure to mercury vapor on the brain MT in MT-null mice and their wild type controls. MT-null and wild type mice were preliminarily exposed to mercury vapor for 2 weeks at 0.1 mg Hg/m(3) for 1 h/day for 3 days a week, and then exposed for 11 weeks at 4.1 mg Hg/m(3) for 30 min/day for 3 days a week. This exposure caused no toxic signs such as abnormal behavior or loss of body weight gain in the mice of either strain throughout the experimental period. Twenty-four hours after the termination of the exposure, mice were sacrificed and brain samples were subjected to mercury analysis, MT assay, and pathological examination. The MT-null mice showed lower accumulation of mercury in the brain than the wild type mice. Mercury exposure resulted in a 70% increase of brain MT in the wild type mice, which was mostly accounted for by the increase in MT-I/II. On the other hand, the brain MT in the MT-null mice increased by 19%, suggesting less reactivity of the MT-III gene to mercury vapor. Although histochemical examination revealed silver-mercury grains in the cytoplasm of nerve cells and glial cells throughout the brains of both strains, no significant difference was observed between the two strains.
The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.