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Biomedical subjects

M Mizuguchi

Publications and source records attributed to M Mizuguchi.

At least 73 records · Page 4Linked to original sources

Ultrastructural localization of CD38 immunoreactivity in rat brain.

The subcellular localization of CD38 in the rat cerebral and cerebellar cortices was studied using immunoelectron microscopy. In the cerebral cortex, immunoreactivity was present in a subset of pyramidal neurons, and was distributed predominantly in the perikarya and dendrites. It was found in association with rough endoplasmic reticulum, ribosomes, small vesicles, mitochondria and the plasma membrane including the postsynaptic densities. In the cerebellum, labeling was observed in several types of neuron such as granule, Golgi, basket and Purkinje cells. In contrast to the cerebrum, immunoreactivity was accentuated in the perikarya or axon terminals, and the synaptic vesicles represented another organelle that was immunopositive for CD38. In both of these CNS regions, the nuclear envelope, particularly the outer membrane, showed constant labeling. Diffuse immunoreactivity was also present in the astrocytes from the perikarya to the processes including the perivascular glia limitans. Oligodendrocytes and microglia were immunonegative for CD38. The pattern of distribution of CD38 in the CNS is suggestive of multiple roles for this molecule at various functional sites in both neurons and astrocytes.

ADP-ribosyl Cyclase↗

Spectroscopic evidence for the formation of four-stranded solution structure of oligodeoxycytidine phosphorothioate.

Oligodeoxycytidine phosphorothioate (PS-dCn, n = chain length), known to show virus inhibition ability by a mechanism other than the antisense one when n approximately 20, was explored for its solution structure by circular dichroism (CD) and ultraviolet (UV) absorption spectroscopy. For PS-dC4, when the strand concentration was higher than 10 microM, the respective 288-nm positive and 265-nm negative peaks appeared in the CD spectra at slightly acidic pHs and 0 degree C in the absence of salt, which is indicative of a four-stranded structure (namely, the i-motif). Strand concentration-dependent CD spectroscopy indicated that intermolecular association is responsible for this i-motif. The formation or i-motif was also characterized by UV absorption spectroscopy, in which the dissociation of this structure caused a sharp increase in the absorbance at 275 nm and a decrease at 305 nm. By plotting this change, the Tn values were estimated to be ca. 11 and 13 degrees C at 20 and 50 microM strand concentrations, respectively. Stability of the i-motif was compared between PS-dC, P-chiral diastereoisomers, and the Sp configuration produced a more stable structure than Rp. PS-dC20 was also investigated at physiological temperature, and the respective 288-nm positive and 265-nm negative peaks appeared at slightly acidic pH: it has been suggested that intermolecular folding was predominant above ca. 1 microM and that intramolecular folding dominated at low strand concentrations such as 0.05 microM. Gel-filtration chromatography and nondenaturing gel electrophoresis provided the supporting data for the four-stranded folding of PS-dC20.

Chromatography, Gel↗

Endoscopic ultrasonography for demonstrating loss of multiple-layer pattern of the thickened gallbladder wall in the preoperative diagnosis of gallbladder cancer.

The purpose of this study was to elucidate the roles of endoscopic ultrasonography (EUS), conventional US, CT, and MRI in differential diagnosis of gallbladder wall thickening. We scrutinized images for the presence of the multiple-layer patterns of the thickened gallbladder walls during preoperative images (EUS, n = 22; US, n = 23; CT, n = 20; MRI, n = 15) and retrospectively correlated them with surgical results in 25 patients. The pathological diagnoses included 7 gallbladder cancers, 9 cases of chronic cholecystitis, 5 cases of xanthogranulomatous cholecystitis, and 4 cases of adenomyomatosis. Multiple-layer patterns of gallbladder wall were observed in patients with inflammatory and benign diseases by US, EUS, CT, and MRI. This pattern was demonstrated by EUS more efficiently compared with other means of imaging. All subjects with loss of multiple layers were finally diagnosed by use of EUS as having gallbladder cancer at surgery. Loss of multiple-layer patterns of the gallbladder wall demonstrated by EUS was the most specific finding in diagnosing gallbladder cancer.

Adenomyoma↗

Tuberin immunohistochemistry in brain, kidneys and heart with or without tuberous sclerosis.

We have studied immunohistochemically the expression of tuberin, the protein product of the TSC2 gene, in cerebral, renal and cardiac tissues obtained from patients with tuberous sclerosis and from control patients. Tuberin immunoreactivity was moderate to strong in neurons and reactive astrocytes of control brains, but was reduced in brains with tuberous sclerosis. Staining intensity of abnormal giant cells varied from negative to moderate in cortical tubers, subependymal nodules and subependymal giant cell astrocytomas. In control kidneys, uriniferous and collecting tubules showed positive immunoreactivity, whereas a focal decrease in their staining intensity was noted in kidneys with tuberous sclerosis. Renal angiomyolipomas were negative for tuberin. In the heart, cardiac muscles in both control and tuberous sclerosis patients were strongly immunoreactive. Cardiac rhabdomyomas in the latter were stained less intensely. These results provide histological evidence for the loss of tuberin in tuberous sclerosis tissues, which is associated with the development of hamartomas in an organ-specific manner.

Adolescent↗

Developmental changes of glutamate receptors in the rat cerebral cortex and hippocampus.

We studied the immunohistochemical localization of the glutamate receptors (GluR-1, -2, and -3,) in the developing rat cerebral cortex and hippocampus using antibodies to GluR1 and to an epitope common to GluR2 and GluR3 (GluR2/3) subunits. In the cerebral cortex, GluR1 immunoreactivity appeared in the neurons from postnatal day (PND) 0, increased with maturation, was highest at PND 10, decreased until PND 30, and thereafter remained at the same level as on PND 0. GluR2/3 immunoreactivity appeared earlier in scattered neurons on embryonal day (ED) 18, increased with maturation and reached a peak between PND 10 and PND 15, after which the immunoreactivity gradually decreased and reached a plateau at PND 30. For both GluR1 and GluR2/3, some of the pyramidal neurons showed intense staining. In the pyramidal layers of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in all the pyramidal neurons of the CA1-4 area from ED 20. In the dentate gyrus of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in the neurons of the granule cells after PND 0. Immunoreactivity in the neurons of the subiculum was found after PND 5 and that of the polymorphic cell layers was found after PND 15-20. Our results indicate that the development of glutamate receptor subunits in the rat cerebral cortex and hippocampus is expressed in different spatial patterns and distinct temporal patterns throughout development and is scheduled during the early postnatal period, when synaptic plasticity or synaptic connection occurs in these regions.

Animals↗

Endoscopic submucosal tumorectomy for gastrointestinal submucosal tumors restricted to the submucosa: a new form of endoscopic minimal surgery.

BACKGROUND: Endoscopic minimally invasive therapy for submucosal tumors of the gastrointestinal tract by use of endoscopic ultrasound has not yet come into widespread use, and this technique has not been fully evaluated. We therefore investigated this method of treatment in patients with gastrointestinal submucosal tumors. METHODS: Forty-five patients with suspected gastrointestinal submucosal tumors (esophagus [5], stomach [1], duodenum [16], colon [23]) based on barium enema studies and endoscopy underwent endoscopic ultrasound by the water-filled or balloon method. The layer of origin and the internal echogenicity of the lesions were evaluated. After confirming that the tumors were submucosal, the lesions were resected using injection of physiological saline solution and electrocautery. RESULTS: Using a one-channel or two channel method, all tumors were completely resected without serious complications and the diagnosis was histologically confirmed. Ulceration at the site of resection healed within 2 to 4 weeks (mean 23 days) and there has been no local recurrence. CONCLUSIONS: Our technique of endoscopic submucosal tumorectomy appears to be a safe and useful diagnostic-cum-therapeutic procedure for gastrointestinal submucosal tumors.

Adult↗

Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan.

The clinical, radiological and pathological features of acute necrotizing encephalopathy of childhood, a disease entity established recently, are described. This disease predominantly affects infants and young children living in Japan and Taiwan, and manifests itself as acute encephalopathy following viral infections. The hallmark of this encephalopathy is multifocal, symmetric brain lesions affecting the bilateral thalamus, brainstem tegmentum, cerebral periventricular white matter and cerebellar medulla, which can be visualized by computed tomography and magnetic resonance imaging. Both the gray and white matter are involved, with neuropathological evidence of local breakdown of the blood-brain barrier (dysoria). The prognosis was poor in the 1980s, but has improved recently. A characteristic combination of focal neurologic signs is often recognized as the sequelae. Its distinction from clinically similar conditions, such as the Reye syndrome, and from pathologically related conditions, such as the Leigh and Wernicke encephalopathies, is also discussed.

Child↗

Developmental and aging changes in the expression of amyloid precursor protein in Down syndrome brains.

We studied immunohistochemically the expression of beta-amyloid precursor protein (APP) in the frontal lobes of 18 Down syndrome (DS) patients (20 gestation weeks (GW) to 50 years) and 15 controls (17 GW to 50 years) using six purified antibodies against the secretory forms (N-terminal, N-Amy and Amy540), the Kunitz-type protease inhibitor (KPI) domain, residues 1-28 of beta protein (Affi28), and the carboxyl-terminal fragment (Ac) of APP. In the cortex of fetuses, neonates and infants, immunoreactivity for N-Amy and Ac was observed in both neurons and glial cells, and that for Affi28 in glial cells in the subpial layer in both DS patients and controls suggesting the functioning role of APP was a growth factor. This immunoreactivity disappeared in childhood and reappeared in adulthood in only DS patients. The earlier reappearance of those in DS patients from a young adult age than in normal controls may result from a gene dosage effect, since APP is encoded on chromosome 21. The N-Amy, Amy540, Affi28 and Ac immunoreactivity in glial cells in the developing white matter in the both DS patients and controls may be associated with myelination glia. Immunoreactivity for KPI was noted on the tunica media of the arteries from the neonatal period to adulthood in only DS patients. In senile plaques in DS patients, N-terminal and Affi28 immunoreactivity became detectable at the age of 32 years. N-terminal immunoreactivity in the senile plaques was noted along the periphery of the senile plaques, while that for Affi28 was around the amyloid core. Thus, each fragment of APP exhibited a different localization and time course of immunohistochemical expression. The results indicated that APP plays a role in neuronal development and that its earlier reappearance in adult DS patients is associated with the regeneration process related to aging.

Adolescent↗

Differential development of the human cerebellar vermis: immunohistochemical and morphometrical evaluation.

Differential development of regions of the human cerebellar vermis was evaluated immunohistochemically and morphometrically between 18 weeks of gestation and 10 years of age. The density of Purkinje cells in the cerebellar vermis decreased rapidly until 38 weeks of gestation and slowly thereafter. At all stages of development, the density was higher in the posterior (lobules VI-IX) than the anterior vermis (lobules I-V). The area of cut sections of the anterior and posterior vermis in the mid-sagittal section increased rapidly before 40 weeks of gestation and gradually after birth, whereas growth was slower in the nodules. These developmental characteristics may be related to the selective susceptibility of cerebellar regions to environmental insults.

Cell Count↗

Expression of the LIS-1 gene product in brain anomalies with a migration disorder.

Miller-Dieker syndrome (MDS) is a prototype of brain malformations characterized by abnormal neuronal migration. To clarify the pathomechanisms underlying these anomalies, we performed immunohistochemical studies using specific antibodies against the protein product of LIS-1, the candidate gene responsible for the MDS phenotype. The LIS-1 protein was present abundantly and ubiquitously in normally developing brains. Loss of LIS-1 immunoreactivity was observed in brains with MDS, but not in brains with other malformations, such as isolated lissencephaly, holoprosencephaly, Fukuyama-type congenital muscular dystrophy, and Zellweger syndrome. These results suggest that the pathomechanism underlying abnormal neuronal migration in MDS may be specific to this particular type of malformation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Immunohistochemical expression of cell adhesion molecule L1 in hemimegalencephaly.

We demonstrated immunohistochemically an abnormal expression of the neural cell adhesion molecule L1 in 10 developing brains of children with hemimegalencephaly (HM) aged from 36 weeks gestation to 10 years of age, comparing them with 23 controls aged from 13 weeks of gestation to 14 years. There was dense L1 expression in focal regions of the molecular layer beneath leptomeningeal glioneuronal heterotopia, in areas of cerebral cortex with large neurons, and in the disorganized or neuronal heterotopic sites in the white matter in HM. L1 was also heterogeneously enhanced in the abnormal cortex after 1 year of age, suggesting that axonal growth was delayed. These changes persisted into the older age group in the abnormal areas of cortex in HM. The cell bodies of many enlarged neurons in HM were immunopositive for L1, whereas L1 was usually localized to the processes of normal neurons. The delayed L1 immunoreactivity and enlarged L1-immunopositive neurons may be closely related to the pathogenesis of unilateral megalencephaly with cortical dysplasia and heterotopia.

Adolescent↗

Predominant localization of the LIS family of gene products to Cajal-Retzius cells and ventricular neuroepithelium in the developing human cortex.

Mutations that perturb neuronal migration provide important biological clues that can lead to an understanding of the role of specific cells and molecules in the formation of the cortex. The human neuronal migration disorder, Miller-Dieker Lissencephaly, results from a hemideletion of LIS-1, which encodes a subunit of a brain platelet-activating factor acetylhydrolase. The cellular localization of the LIS-1 gene product in human fetal brain and its normal role in neuronal migration have yet to be determined. LIS-1 belongs to a family of genes that have identical coding sequences (LIS-1 [chromosome 17] and LIS-2 [chromosome 2]). In the brain, LIS-1 is the more abundant gene as determined by Northern blot analysis. Using antibodies raised against 2 epitopes of the LIS-1/LIS-2 protein sequence, we have localized the LIS family of gene products in the developing human brain to the Cajal-Retzius cells, some subplate neurons, thalamic neurons, the ventricular neuroepithelium, and at later gestational ages, to the ependyma. Therefore, LIS-1 bears some resemblance to reelin, the gene product involved in the cortical mouse mutant reeler, in that Cajal-Retzius cells demonstrate immunolocalization. However, unlike reelin, LIS proteins are expressed not only in the Cajal Retzius cells, but also in the ventricular neuroepithelium, suggesting a potential role for this structure in neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Gastrointestinal submucosal tumors: evaluation with endoscopic US.

PURPOSE: To describe the endoscopic ultrasound (US) features of benign versus malignant submucosal tumors throughout the gastrointestinal tract. MATERIALS AND METHODS: One hundred nine patients aged 24-81 years suspected to have submucosal tumors (11 esophageal, 41 stomach, 24 duodenal, and 33 colorectal tumors) at barium studies or endoscopy underwent endoscopic US. The layer of origin, internal echo pattern, and lesion margin were analyzed by means of consensus and independent interpretation by three radiologists. RESULTS: Endoscopic US findings revealed several distinct patterns among various submucosal tumors. Sixteen (94%) of the 17 homogeneous lesions with histopathologic findings of malignancy were hypoechoic, although 29 (43%) of the 68 homogeneous lesions with histopathologic findings of benignity were similarly hypoechoic. Homogeneous lesions that were anechoic, of intermediate echogenicity, or hyperechoic were almost exclusively benign (39 [98%] of 40). In contrast, 23 (96%) of the 24 malignant lesions were heterogeneous (n = 7) or homogeneously hypoechoic (n = 16). The sizes of benign and malignant lesions were significantly different (P < .05). There was no significant difference in the echo pattern (i.e., homogeneous versus heterogeneous), but there was a significant difference in the proportion of hypoechoic versus nonhypoechoic lesions (anechoic, hyperechoic, or of intermediate echogenicity; P < .001). CONCLUSION: The differential diagnosis of gastrointestinal submucosal tumors is assisted with endoscopic US.

Diagnosis, Differential↗

A guinea-pig model of ultrasonically nebulized distilled water-induced bronchoconstriction.

Ultrasonically nebulized distilled water-induced bronchoconstriction (UNDW-IB) is specific to asthma. The mechanisms underlying UNDW-IB are not fully understood, and no reproducible animal model has been reported. The purpose of this study was to develop a guinea-pig model of UNDW-IB. Ultrasonically nebulized distilled water (UNDW) was inhaled 20 min after an aerosolized antigen challenge in passively sensitized and artificially ventilated guinea-pigs. UNDW was also inhaled 5 and 20 min after 0.1 mg x mL(-1) methacholine inhalation in nonsensitized animals. In addition, 0.1 mg x kg(-1) S-1452, a thromboxane A2 antagonist, or saline was given intravenously 5 min before UNDW inhalation in sensitized animals. The inhalation of UNDW caused bronchoconstriction, when inhaled 20 min after an antigen challenge in sensitized guinea-pigs. UNDW inhalation did not produce bronchoconstriction after saline inhalation in nonsensitized or sensitized guinea-pigs, or after antigen inhalation in nonsensitized animals. Methacholine-induced bronchoconstriction did not evoke UNDW-IB. Neither did S-1452 reduce the UNDW-IB. In conclusion, the guinea-pig model of ultrasonically nebulized distilled water-induced bronchoconstriction developed in this study suggests that allergic reaction, but not bronchoconstriction, can induce bronchial hyperresponsiveness to ultrasonically nebulized distilled water, and that thromboxane A2 is not involved in ultrasonically nebulized distilled water-induced bronchoconstriction.

Administration, Inhalation↗

[Adenosquamous cell carcinoma of the lung with multiple cystic metastases in the liver].

A 70-year-old man was admitted to the hospital because of mild dyspnea, a cough, and hemoptysis. A chest X-ray film and a computed tomographic scan showed a mass in the S1.2 region of the left lung, and swollen mediastinal lymph noes. Cytologic examination of sputum sample resulted in the diagnosis of lung cancer. The tumor did not respond to chemotherapy, and the patient died after seven months. Autopsy disclosed a solid tumor of left lung and many cystic lesions in the liver. Histological examination of the lung lesion revealed adenosquamous cell carcinoma. Metastatic lesions in the liver consisted of adenosquamous cell carcinoma, with predominantly squamous cell carcinoma. Cases of lung cancer in which hepatic metastases have many cystic cavities are rare.

Aged↗

Inhibition of syncytium formation by antisense oligonucleotide phosphorothioates complementary to tax mRNA of human T-cell leukemia virus type 1 (HTLV-1).

HTLV-1 infection is known as the factor to cause adult T-cell leukemia (ATL). Antisense oligonucleotide phosphorothioates against tax gene and control oligonucleotide phosphorothioates were synthesized. Antisense oligonucleotide was complementary to the region of initiation codon of tax gene. Two control oligonucleotides were tax sense and random. HTLV-1-positive human T-cell line, C91/PL and HTLV-1 non-infected human glioma cell line, U251-MG were co-cultured in the presence of antisense or control oligonucleotides for 24 hours. Oligonucleotides used in this study were not toxic at 10 microM concentration. Antisense oligonucleotide against tax gene inhibited 59% the syncytium formation assay at 10 microM concentration.

Adult↗

[Successful use of fluconazole against semi-invasive--pulmonary aspergillosis].

A 53-year-old man was admitted to the hospital because of productive coughing general malaise, and right-sided chest pain. At 41 years of age he was given a diagnosis of gastric cancer, underwent a and gastrectomy, was treated with anti-cancer drugs. At 49 years of age he suffered from atypical mycobacteriosis and received anti-tuberculosis drugs for 1 year. A chest X-ray film showed infiltrative shadows with a cavity in the right upper lung field. Semi-invasive aspergillosis was diagnosed on the basis of the clinical and radiographic findings, positive sputum cultures, and positive serologic tests. After 8 months of therapy with intravenous and oral fluconazole, no pulmonary aspergillosis was evident. Treatment with fluconazole was effective in this case of semi-invasive aspergillosis.

Antifungal Agents↗

[Effects of a thromboxane-synthetase inhibitor in patients with chronic persistent coughing and no airwayhyperresponsiveness].

We studied the effects of the thromboxane-synthetase inhibitor ozagrel in 22 patients with chronic persistent coughing who did not have airwayhyperresponsiveness. Treatment with ozagrel (400 mg/day for 2 weeks) reduced coughing in 12 patients. Sputum from the patients in whom ozagrel was effective had a higher percentage of lymphocytes and a lower percentage of neutrophils than did sputum from those in whom ozagrel was not effective. Furthermore, in the former group the capsaicin cough threshold increased but in the latter it did not change consistently. These data indicate that thromboxane A2 may contribute to coughing associated with lymphocytic airway inflammation.

Adult↗