Two autopsied cases of Kallmann's syndrome with dysplasia of the hippocampus.
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Biomedical subjects
Publications and source records attributed to M Itoh.
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We previously found that the rate of [l8F]6-fluoro-L-dopa (FDOPA) uptake into the striatum (the Ki value) in Alzheimer's disease (AD) correlated with cognitive function. Patients with wandering behavior had an increased level of D2 dopamine receptors. Decreased cerebral glucose utilization (CMRglc) in the parietal and temporo-parieto-occipital region is a well-known PET finding in AD. We investigated the relationship between the Ki value and regional CMRglc (rCMRglc) with reference to cognitive impairment and wandering behavior. We studied 10 AD patients with moderately severe dementia. Using PET and the FDOPA and [18F]-fluoro-deoxyglucose techniques, the Ki value and rCMRglc in 10 regions in each hemisphere were measured. The Ki value was found to correlate with mean cortical rCMRglc. The rCMRglc of the anterior frontal, inferior frontal, and temporal lobes correlated with the Ki value; the patients with wandering behavior had lower values. Multiple regression analysis showed that the Mini-Mental State Examination score was significantly explained by the Ki value, the rCMRglc of the temporal lobe, and the rCMRglc of the parietal lobe. There is probably a functional neural network between the striatum and the frontal and temporal lobes in AD. We consider this network important, not only in cognitive impairment but also in abnormal wandering behavior.
Endothelial cells provide a crucial interface between blood and tissue environments. Free diffusion of substances across endothelia is prevented by the endothelial tight junction, the permeability of which varies enormously depending on tissue. Endothelial cells of the blood-brain barrier possess tight junctions of severely limited permeability, whereas those of non-neural tissue are considerably leakier, but the molecular basis for this difference is not clear. Occludin is a major transmembrane protein localizing at the tight junction. In this study, we show, by immunocytochemistry, that occludin is present at high levels and is distributed continuously at cell-cell contacts in brain endothelial cells. In contrast, endothelial cells of non-neural tissue have a much lower expression of occludin, which is distributed in a discontinuous fashion at cell-cell contacts. The apparent differences in occludin expression levels were directly confirmed by immunoblotting. The differences in occludin protein were reflected at the message level, suggesting transcriptional regulation of expression. We also show that occludin expression is developmentally regulated, being low in rat brain endothelial cells at postnatal day 8 but clearly detectable at post-natal day 70. Our data indicate that regulation of occludin expression may be a crucial determinant of the tight junction permeability properties of endothelial cells in different tissues.
This is a report on ten patients with cystic dilatation of the intrahepatic biliary system (CDIB) after hepatic portoenterostomy. They were five girls and five boys and the diagnosis of CDIB was made at ages 6 months to 11 years (mean age: 2.8 +/- 3.3 years). Follow-up ranged from one month to 15 years (mean: 5.5 +/- 4.9 years). In order to elucidate the factors which affect the clinical outcome of such patients, the types of CDIB (Type A: noncommunicating solitary cyst, Type B: communicating solitary cyst, Type C: multi-cystic dilatation), clinical symptoms at onset of CDIB and the method for the treatment were reviewed in relation to the outcome. For the purpose of understanding pathogenesis of CDIB, immunohistochemical study on hepatobiliary system was done with monoclonal antibody for cytokeratin. Outcome of the patients of Type C was poor, whereas the outcome of patients with type A and B was good. The outcome of preoperatively jaundiced patients was poor, but jaundice-free patients showed good outcome. Method of treatment was not related to the outcome. As epithelium of CDIB was positive for monoclonal antibody of cytokeratin, it was suspected that pathogenesis of CDIB might be related to peribiliary gland which originated from ductal plate.
Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injection into the facial nerve of the cat resulted in retrograde labeling in the geniculate and jugular ganglia ipsilaterally. Labeled fibers were found to enter into the brain stem through the intermediate and vagal nerves. These fibers ascended or descended into the dorsal portion of the spinal trigeminal tract and were distributed to the principal sensory nucleus of the trigeminal nerve, marginal layer of the interpolar part of the spinal trigeminal nucleus, nucleus of the solitary tract and ventrolateral portion of the cuneate nucleus. It was of particular interest in the present study that the intensive labeling was present in the medial portion of laminae I-IV of the upper cervical spinal cord. The immunohistochemical study revealed a lot of substance P-immunoreactive neurons in the geniculate and jugular ganglia, and heavy accumulation of immunoreactive fibers in laminae I-II of the upper cervical spinal cord.
Western blot analysis was carried out in order to evaluate new serodiagnostic markers, Em18 and Em16, for differentiation of alveolar echinococcosis (AE) from cystic echinococcosis (CE) using 36 serum samples from hydatid patients from Xinjiang, China, where AE and CE are both endemic and one double infection case has been reported. All AE cases except one (5/6) who exhibited a calcified lesion and a single case of double infection showed antibody responses against Em18 and Em16. Some of CE patient sera (6/22) showed antibody response against Em16 except one who showed that against Em18. Analyses of IgG subclass responses against Em18 and Em16 were carried out using all serum samples showing antibody responses against Em18 and/or Em16 (seven CE, five AE, and one AE + CE) and additional samples of three CE and 22 AE from Sichuan, China. IgG4 was the most predominant antibody subclass. Em18 and Em16 were recognized by both IgG4 and IgG1 (in most cases) or by either IgG4 or IgG1 (in minor cases) or by IgG3 (in very rare cases). Neither Em18 nor Em16 was recognized by IgG2 antibodies. The usefulness of Em18 and Em16 as potential new markers for serological differentiation of human AE and CE, respectively, is discussed.
Positron emission tomographic(PET) study using 18F-6-fluoro-L-dopa (18FDOPA) can provide efficient information on the pre-synaptic function of nigrostriatal dopaminergic neurons. In juvenile parkinsonism(JP), the accumulation of 18FDOPA is markedly decreased in the caudate nucleus and putamen on both hemispheres. This finding is different from those in dystonia syndromes such as dopa-responsive dystonia (DRD) and hereditary progressive dystonia with marked diurnal fluctuation(HPD), and it is rather similar to late onset of Parkinson's disease. Furthermore, we studied dopamine D2 receptor binding activity on the post-synaptic sites of the striatum using 11C-YM-09151-2(11C-YM), a highly selective dopamine D2 receptor antagonist. In JP, 11C-YM was highly accumulated in the striatum, and D2 receptor binding activity is not significantly different from that of age-matched young normal subjects, but much higher than that of aged subjects. This finding suggests that post-synaptic dopamine receptor function keeps still normal or hypersensitive in JP, and may be different from other degenerative disorders such as multiple system atrophy. Glucose metabolism using 18F-fluoro-2-deoxy-D-glucose(18FDG) was also within normal range in the cerebral cortex in JP, but was more increased in the striatum than in the cerebral cortex in some patients. These PET studies can provide efficient informations about the pathologic condition of JP.
6-[18F]-fluorodopa (FDOPA) was developed as an analogue of L-DOPA across the blood-brain-barrier and to carry into nigrostriatal dopaminergic neurons. PET study using FDOPA revealed presynaptic dopaminergic function in the striatum of nigrostriatal system of the human brain and many studies have performed to clarify the pathogenesis of Parkinson's disease. FDOPA is also an efficient tracer to analyze pharmacokinetics of L-DOPA by measuring radioactivities of its metabolites in the peripheral blood by HPLC and to evaluate pharmacological effects on dopamine metabolism by pretreatment of dopa decarboxylase inhibitor or COMT inhibitor. PET study using FDOPA is useful not only to diagnose Parkinson's disease but also to differentiate from parkinsonism in combination with other radioactive ligands and with other neuroimaging methods such as MRI.
In measurements of jaw movements employing an X-ray television, the orientation of the patient's head must be normalized relative to the measuring device. To avoid interferring with natural jaw movements caused by using a positioning jig, we have developed an automatic head positioning system consisting of a head position sensor and a robotized chair. The position and orientation of the head is monitored by detecting the three-dimensional positions of four non-coplanar LED markers mounted on the head, by means of a set of two photoelectronic cameras. If they are incorrect, the head is moved into the required position, using a 5-degree-of-freedom robotized chair. To accomplish this accurately, the positional relations of system components must be determined precisely. This paper proposes a least-square technique of calibrating the relationship between the position sensor and the chair. Consequently, accurate positioning is achieved. Accuracy verification studies revealed that overall positioning errors lay within 2.42 mm and 1.28 degrees with respect to the position and orientation, respectively, if the markers are secured to the head support of the chair.
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Occludin has been identified from chick liver as a novel integral membrane protein localizing at tight junctions, and the cDNA encoding its mammalian homologue was identified very recently (Ando-Akatsuka, Y., M. Saitou, T. Hirase, M. Kishi, A. Sakakibara, M. Itoh, S. Yonemura, M. Furuse, Sh. Tsukita, J. Cell Biol. 133, 43-47 (1996)). Here we describe the basic properties of mammalian occludin in epithelial cells at the DNA, RNA, and protein levels. The human occludin gene was mapped to chromosome band 5q13.1 by fluorescent in situ hybridization. Northern blotting identified several occludin mRNA bands, suggesting the possible expression of several alternatively spliced products. Occludin mRNA was detected in cultured epithelial cells, but not in cultured fibroblasts. The mRNA level was high in the testis, kidney, liver, lung, and brain, which reportedly bear well-developed tight junctions. We then produced monoclonal and polyclonal antibodies using recombinant mouse occludin as the antigen, which reacted not only with mouse, but also human, dog and pig occludin. These antibodies recognized several bands around 60 kDa in epithelial cells but not in fibroblasts. Immunofluorescence microscopy of various tissues revealed that the staining intensity of occludin correlated well with the number of tight junction strands in epithelial cells. By contrast, the staining of ZO-1, a well-characterized tight junction-associated protein, was not specific for tight junctions. Furthermore, the exclusive concentration of occludin at tight junctions in epithelial cells was confirmed by immunoreplica electron microscopy.
Current positron emission tomography is capable for three dimensional data acquisition and reconstruction (3D PET). The main advantage of 3D PET is its detectability for lower tracer concentrations. The images by a 3D PET have better signal to noise ratios compared to those by conventional 2D PET. This point is especially important for the studies of distributions of ligands for neuroreceptors such as F-18 FDOPA and C-11 YM-01951, since these ligands show low accumulation in brain. Reduction of scanning time is useful as well for patients are permitting extended scanning periods
Status marmoratus (ST) of the basal ganglia and thalamus has been observed in cases of perinatal hypoxic ischemic encephalopathy and rarely of postnatal encephalopathy. In occasional cases, the cerebral cortex is also involved. Here, we reported a 22-year-old male with a sequela of postnatal anoxic encephalopathy. He had been bedridden with severe mental retardation since he suffered anoxic encephalopathy at 3 months of age. ST was found in the cerebral cortex as well as basal ganglia and thalamus. In addition to ST, the cerebral cortex and white matter were remarkably devastated. We also performed a preliminary immunohistochemical study to investigate the process of ST formation, using antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and synaptophysin. MBP-positive abnormal myelinated fibers were identified in the ST areas, which were not colocalized with GFAP-immunopositivity. Synaptophysin was positive in the areas of ST, which were not stained with Holzer method. These results suggest that the myelination in the early infancy damage of basal ganglia and cerebral cortex could be implicated in the formation of ST.
The M1 protein of influenza virus regulates the bi-directional transport of ribonucleoprotein (RNP) into and out of the nucleus. At the beginning of infection, the incoming RNP is transported into the nucleus only after detachment from M1, where RNP is involved in transcription/replication of the viral genome. In the late stage of infection, M1 inhibits viral RNA polymerase activity by binding to RNP, which may be a signal for RNP-transport from the nucleus to the cell surface. Finally, M1 mediates the association of RNP with viral envelope glycoproteins on the inner surface of the cytoplasmic membrane, which then promotes the virion formation and budding. Thus, M1 is a multi-functional protein that plays important roles in various steps of virus replication.
UNLABELLED: In the steady state method, 15O-labeled gases (C15O2, 15O2 and C15O) are administered to the body by continuous inhalation in various clinical PET studies. During inhalation, the nasal cavity and major airway may obtain a substantial amount of dose, being the source organs as well as the target organs. The internal absorbed dose to those organs and their contribution to the other target organs have not been calculated by the MIRD method. To calculate the internal dose in the MIRD method, the S values, the absorbed doses per unit of cumulated activities from nasal cavity and major airway to the other organs and vice versa, are needed, and these values are not available. METHODS: In this study, we introduced a mathematical model of the nasal cavity and major airway to calculate their S values to 23 target organs and from 11 source organs to them. Individual experiments were performed to measure the total uptake percentage and body surface doses of 15O-labeled gases from continuous inhalation. RESULTS: Using the body surface doses measured by thermoluminescent dosimeters, the cumulated activities of 11 source organs were estimated with the mathematical transformation method, and then the internal absorbed doses in 23 target organs were calculated by the MIRD method. Our experimental results were compared with the other results, and good agreements were observed. CONCLUSION: Among the target organs, the critical organ is the airway, and the absorbed dose is 2.57 x 10(-2) mGy.MBq-1.
We examined the clinical picture of eight patients with severe intellectual and motor disabilities, who had experienced prolonged and severe neonatal jaundice, and showed localized lesions in the globus pallidus, subthalamic nuclei and hippocampus on MRI. All patients had athetoid tetraplegia, and five patients showed disturbed ocular movements and seven showed dysphagia. Five patients could communicate with others or utter words, and all showed mental retardation. Auditory brainstem responses were abnormal in seven, and the percentage of REM sleep on all-night polysomnography was reduced in three. Neither CT nor T1-weighted MR images could detect any changes in the pallidum or subthalamic nuclei, while T2-weighted MR images disclosed bilateral high signals in the pallidum, especially in the internal segment, in all patients. Five of the 7 patients, in whom coronal T2-weighted MR imagings were obtained, showed high signals in the subthalamic nuclei. The hippocampus showed atrophy and/or T2-prolongation in seven patients. In one autopsy case, these MRI changes were concordant with pathological lesions. In patients with athetoid cerebral palsy, brainstem dysfunctions, and abnormal ABR, localization of MRI lesions to the pallidum and subthalamic nuclei is evidence for neonatal bilirubin encephalopathy.