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Biomedical subjects

S Minoshima

Publications and source records attributed to S Minoshima.

At least 91 records · Page 5Linked to original sources
PubMed1999

Cerebral Responses to Warmth and Heat and Cold Pain Measured by Positron Emission Tomography.

Phasic heat and tonic cold stimuli that have different temporal patterns, afferent fiber activations, and perceived pain characteristics produce a shared pattern of cerebral activation in addition to modality specific activations. These patterns are different from the cerebral representation of innocuous temperature sensation. Functional brain imaging techniques provide an opportunity to study somatosensory organization in conscious humans under physiologic conditions, despite certain limitations of imaging modalities.

Journal Article↗
PubMed1999

Discordance between traditional pathologic and energy metabolic changes in very early Alzheimer's disease. Pathophysiological implications.

These results suggest that neither the loss of entorhinal efferents nor cholinergic deficit explains all the metabolic features seen in very early AD. Given recent immunohistological evidence of massive glutamatergic synaptic alteration in early AD cortex and insights into neuronal and glial mechanisms of glucose metabolism, very early metabolic changes in AD probably reflect a significant impairment of glycolytic activities in the cortico-cortical glutamatergic systems in a preclinical stage of the disease. However, the exact mechanisms of such impairment in these neurons are yet to be determined.

Acetylcholinesterase↗
PubMed1999

Head and neck cancer: detection of recurrence with three-dimensional principal components analysis at dynamic FDG PET.

Fully automated principal components analysis (PCA) was applied to dynamic 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomographic (PET) images obtained in 15 patients with previously treated head and neck cancer. PCA with time-activity curves incorporated kinetic information about FDG uptake, which improved tissue characterization on FDG PET images. The combination of standardized uptake value and PCA image sets likely will improve the reliability of tumor detection in head and neck cancers.

Adult↗
PubMed1999

Structure and chromosome mapping of the human SIX4 and murine Six4 genes.

Six4, a member of the homeobox gene subfamily (Six), is expressed in a developmentally regulated fashion, and supposed to be involved in embryogenesis. We cloned the human SIX4 and murine Six4 genomic DNAs and determined their structures. The structure, including the 5' upstream region of both genes, was well conserved suggesting the conserved function and regulation of these genes. Human SIX4 was mapped to chromosome 14q23.

Amino Acid Sequence↗
PubMed1999

Motor correlates of occipital glucose hypometabolism in Parkinson's disease without dementia.

OBJECTIVE: To determine whether occipital reduction in regional cerebral glucose metabolism in PD reflects retinal versus nigrostriatal dopaminergic degeneration. We hypothesized that occipital glucose metabolic reduction should be symmetric if parkinsonian retinopathy is responsible for the reduction. METHODS: PD patients without dementia (n = 29; age 63 +/- 10 years) and normal controls (n = 27; age 60 +/- 12 years) underwent [18F]fluorodeoxyglucose PET imaging. Regional cerebral glucose metabolic rates were assessed quantitatively. RESULTS: When compared with normal controls, PD patients showed most severe glucose metabolic reduction in the primary visual cortex (mean -15%, p < 0.001). Occipital glucose metabolic reduction was greater in the hemisphere contralateral to the side of the body affected initially or more severely in PD. There was an inverse correlation between side-to-side asymmetries in finger-tapping performance and occipital glucose metabolic reduction (r = -0.45, p < 0.05; n = 28). The correlation was strongest in patients with a relatively early stage of PD with more unilateral motor impairment (Hoehn and Yahr stage I, r = -0.74, p < 0.01; n = 10). CONCLUSION: The results indicate a pathophysiologic association between nigrostriatal dysfunction and occipital glucose metabolic reduction in PD.

Aged↗
PubMed1999

18F-FDG PET studies in patients with extratemporal and temporal epilepsy: evaluation of an observer-independent analysis.

UNLABELLED: The aim of this study was to evaluate an observer-independent analysis of 18F-fluorodeoxyglucose (FDG) PET studies in patients with temporal or extratemporal epilepsy. METHODS: Twenty-seven patients with temporal epilepsy and 22 patients with extratemporal epilepsy were included in the study. All patients with temporal epilepsy and 7 patients with extratemporal epilepsy underwent surgical treatment. In patients who showed significant postoperative improvement (temporal, n = 23; extratemporal, n = 6), the epileptogenic focus was assumed to be located in the area of surgical resection. In extratemporal epilepsy patients who did not undergo surgery, the focus localization was determined using a combination of semiology, ictal and interictal electroencephalography, [99mTc]ethyl cysteinate dimer SPECT, MRI and [11C]flumazenil PET. Visual analysis was performed by two experienced and two less experienced blinded observers using sagittal, axial and coronal images. In the automated analysis after anatomic standardization and generation of three-dimensional stereotactic surface projections (SSPs), a pixelwise comparison of 18F-FDG uptake with an age-matched reference database (n = 20) was performed, resulting in z score images. Pixels with the maximum deviation were detected, summarized and attached to one of 20 predefined surface regions of interest. For comparison with 18F-FDG PET and MR images, three-dimensional overlay images were generated. RESULTS: In patients with temporal epilepsy, the sensitivity was comparable for visual and observer-independent analysis (three-dimensional SSP 86%, experienced observers 86%-90%, less experienced observers 77%-86%). In patients with extratemporal epilepsy, three-dimensional SSP showed a significantly higher sensitivity in detecting the epileptogenic focus (67%) than did visual analysis (experienced 33%-38%, each less experienced 19%). In temporal lobe epilepsy, there was moderate to good agreement between the localization found with three-dimensional SSP and the different observers. In patients with extratemporal epilepsy, there was a high interobserver variability and only a weak agreement between the localization found with three-dimensional SSP and the different observers. Although three-dimensional SSP detected multiple lesions more often than visual analysis, the determination of the highest deviation from the reference database allowed the identification of the epileptogenic focus with a higher accuracy than subjective criteria, especially in extratemporal epilepsy. CONCLUSION: Three-dimensional SSP increases sensitivity and reduces observer variability of the analysis of 18F-FDG PET images in patients with extratemporal epilepsy and is, therefore, a useful tool in the evaluation of this patient group. The benefit of this analytical approach in patients with temporal epilepsy is less apparent.

Adolescent↗
PubMed1999

[Focal segmental glomerulosclerosis associated with type C virus hepatitis and decrement of proteinuria by interferon-alpha therapy].

Focal segmental glomerulosclerosis (FSGS) associated with type C virus (HCV) hepatitis has not been described in the literature to date. However, we experienced a 30-year-old man, who had had HCV hepatitis, developed nephrotic syndrome and was admitted to our hospital. The first renal biopsy showed FSGS which was diagnosed by light, immunofluorescent, and electron microscopic study. FSGS diagnosis was based upon the findings of focal segmental glomerular sclerosis associated with hyalinosis and foam cells, segmental deposition of IgM and C3 on glomeruli, and epithelial cell vacuolization in the Bowman's space. HCV hepatitis was treated with interferon-alpha (INF-alpha) over 6 months. The treatment brought the disappearance of not only HCV-RNA from the blood, but also the manifestation of nephrotic syndrome. Therefore, the second renal biopsy was performed, but did not reveal any great pathological improvement. Five months later after the remission, he again had an elevated HCV-RNA level and a relapse of nephrotic syndrome. He was retreated with the same therapy and achieved a second remission of nephrotic syndrome. FSGS associated with HCV hepatitis is described first and the implication of INF-therapy in the improvement of proteinuria is discussed.

Adult↗
PubMed1998

Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene--phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator.

The organization and structure of the gene coding for hepatocyte growth factor activator (HGFA) have been determined by isolation of unique clones from a human genomic library. These clones were characterized by restriction mapping, Southern blotting and DNA sequencing. The complete sequence of the gene was determined and found to span about 7.5 kilobases of DNA and consist of 14 exons separated by 13 introns. The coding region of HGFA consists of multiple putative domains that are homologous to those observed in blood coagulation factor XII (FXII). These regions were found as separate exons in the gene, and the exon/intron arrangement was similar to that of FXII, suggesting that the genes for HGFA and FXII have arisen through gene duplication events from a common ancestral gene. The major transcription initiation site is located 75 bp upstream of the translational start codon. The gene was mapped to chromosome 4p16, using spot-blot hybridization on sorted chromosomes and fluorescence in situ hybridization on metaphase chromosome spreads. The phylogenetic and functional relationships between HGFA and FXII as well as urokinase and tissue-type plasminogen activator are discussed.

Base Sequence↗
PubMed1998

Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain.

We have isolated cDNA clones for a novel human protein, TRPC7 (transient receptor potential-related channels), which consists of 1503 amino acid residues from the fetal brain and caudate nucleus cDNA libraries. Northern blot analysis indicated that the TRPC7 gene is highly expressed as a 6.5-kb transcript in brain. The TRPC7 protein has significant homology with Caenorhabditis elegans hypothetical proteins T01H8.5, C05C12.3, and F54D1.5 and with Drosophila and human transient receptor potential (trp) proteins. The TRPC7 protein has seven putative transmembrane domains that probably constitute a Ca2+ channel as in the above-mentioned proteins. Genomic sequencing revealed that the TRPC7 gene consists of 32 exons spanning approximately 90 kb. The TRPC7 gene was mapped between D21S400 and D21S171 on human chromosome 21q22.3, 14 kb distal to a NotI site in D21S400. This novel TRPC7 gene could be a candidate gene for genetic disorders such as bipolar affective disorder, nonsyndromic hereditary deafness, Knobloch syndrome, and holoprosencephaly, which were mapped to this region.

Amino Acid Sequence↗
PubMed1998

Identification of two novel 5' noncoding exons in human MNB/DYRK gene and alternatively spliced transcripts.

Previously, the comparison of human MNB/DYRK cDNA sequences with publicly available genomic DNA sequence made a conclusion that MNB/DYRK gene consists of 11 exons spanning 100 kb. Here we found a novel human MNB/DYRK cDNA clone that has the 5' end different from any of those reported MNB/DYRK cDNAs. The 5' end of this cDNA resides in a CpG island associated with the NotI linking clone LL390 that is located more than 50 kb upstream of the exon that contains an initiation codon ATG. Northern blot analysis indicated that almost all the MNB/DYRK transcripts start from the newly identified 5'-noncoding exon. PCR amplification of cDNAs from various human tissues indicated that some mRNAs contain an additional noncoding exon of 76 bp next to the 5'-end exon and there are at least three types of MNB/DYRK mRNAs containing alternatively spliced 5' exons including two novel exons. We now conclude that human MNB/DYRK gene consists of 13 exons (not 11 exons) spanning about 150 kb (not 100 kb).

Alternative Splicing↗
PubMed1998

Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene.

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral neurons. Recently, the parkin gene responsible for AR-JP has been identified. To date, we found two different deletional mutations including single and multiple exonic deletions. In the present study, we identified two types of point mutations (Thr240Arg and Gln311Stop) involving exons 6 and 8 in the parkin gene of the AR-JP patients from two Turkish families. This is the first report on point mutations for the parkin gene. Furthermore, the Thr240Arg mutation was located on a consensus sequence for the site of phosphorylation by casein kinase II. Identification of its mutation provides an important clue as to the role of the Parkin protein in degeneration of the substantia nigra in the brain of AR-JP patients.

Adolescent↗
PubMed1998

The gene for death agonist BID maps to the region of human 22q11.2 duplicated in cat eye syndrome chromosomes and to mouse chromosome 6.

Cat eye syndrome (CES) is associated with a duplication of a segment of human chromosome 22q11.2. Only one gene, ATP6E, has been previously mapped to this duplicated region. We now report the mapping of the human homologue of the apoptotic agonist Bid to human chromosome 22 near locus D22S57 in the CES region. Dosage analysis demonstrated that BID is located just distal to the CES region critical for the majority of malformations associated with the syndrome (CESCR), as previously defined by a single patient with an unusual supernumerary chromosome. However, BID remains a good candidate for involvement in CES-related mental impairment, and its overexpression may subtly add to the phenotype of CES patients. Our mapping of murine Bid confirms that the synteny of the CESCR and the 22q11 deletion syndrome critical region immediately telomeric on human chromosome 22 is not conserved in mice. Bid and adjacent gene Atp6e were found to map to mousechromosome 6, while the region homologous to the DGSCR is known to map to mouse chromosome 16.

Animals↗
PubMed1998

Novel nuclear localization signal between the two DNA-binding zinc fingers in the human vitamin D receptor.

The human vitamin D receptor (hVDR) possesses a unique array of five basic amino acids positioned between the two DNA-binding zinc fingers that is similar to well-characterized nuclear localization sequences in other proteins. When residues within this region are mutated to nonbasic amino acids, or when this domain is deleted, the receptor is still well expressed, but it no longer associates with the vitamin D-responsive element in DNA, in vitro, and hVDR-mediated transcriptional activation is abolished in transfected cells. Concomitantly, the mutated hVDRs exhibit a significant shift in hVDR cellular distribution favoring cytoplasmic over nuclear retention as assessed by subcellular fractionation and immunoblotting. Independent immunocytochemical studies employing a VDR-specific monoclonal antibody demonstrate that mutation or deletion of this basic domain dramatically attenuates hVDR nuclear localization in transfected COS-7 cells. Although wild-type hVDR is partitioned predominantly to the nucleus in the absence of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) hormone, treatment with ligand further enhances nuclear translocation, as it does to some degree in receptors with the basic region altered. The role of 1,25(OH)2D3 may be to facilitate hVDR heterodimerization with retinoid X receptors, stimulating subsequent DNA binding and ultimately enhancing nuclear retention. Taken together, these data reveal that the region of hVDR between Arg-49 and Lys-55 contains a novel constitutive nuclear localization signal, RRSMKRK.

Amino Acid Sequence↗
PubMed1998

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.

Parkinson's disease is a common neurodegenerative disease with complex clinical features. Autosomal recessive juvenile parkinsonism (AR-JP) maps to the long arm of chromosome 6 (6q25.2-q27) and is linked strongly to the markers D6S305 and D6S253; the former is deleted in one Japanese AR-JP patient. By positional cloning within this microdeletion, we have now isolated a complementary DNA done of 2,960 base pairs with a 1,395-base-pair open reading frame, encoding a protein of 465 amino acids with moderate similarity to ubiquitin at the amino terminus and a RING-finger motif at the carboxy terminus. The gene spans more than 500 kilobases and has 12 exons, five of which (exons 3-7) are deleted in the patient. Four other AR-JP patients from three unrelated families have a deletion affecting exon 4 alone. A 4.5-kilobase transcript that is expressed in many human tissues but is abundant in the brain, including the substantia nigra, is shorter in brain tissue from one of the groups of exon-4-deleted patients. Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'.

Adult↗
PubMed1998

Genomic organization of the human myocilin gene (MYOC) responsible for primary open angle glaucoma (GLC1A).

Myocilin is a newly found cytoskeletal protein involved in the morphogenesis of the basal body, a major microtubule organizing center, of the ciliated epithelium. It was recently realized that myocilin is virtually identical to the independently reported protein TIGR (trabecular meshwork-induced glucocorticoid response), which is responsible for the pathogenesis of chromosome 1q-linked primary open angle glaucoma (GLC1A). In this paper, we determined the genomic organization of the myocilin (MYOC/TIGR) gene by analyzing the nucleotide sequence of the BAC clones containing the MYOC/TIGR gene. The MYOC/TIGR gene consists of three exons. Each of the two splice donor and acceptor sites agrees well with the GT/AG rule. Primer sets to amplify each of the three exons are designed. The 5'-flanking region of MYOC gene contains the TGTTCT sequence overlapped with a palindromic sequence TTCTTTTTAAAAAGAA, which appears to be a glucocorticoid responsive element. There is also a unique sequence of dinucleotide repeat [(GT)2AA(GT)4AC(GT)13] which may also serve as a regulatory element. These results should aid in further detection of the MYOC/TIGR gene mutation and in depth understanding of the tissue-specific MYOC gene regulation.

Amino Acid Sequence↗
PubMed1998

The effect of emotional content on visual recognition memory: a PET activation study.

The emotional content of stimuli can enhance memory for those stimuli. This process may occur via an interaction with systems responsible for perception and memory or via the addition of distinct brain regions specialized for emotion which augment mnemonic processing. We performed an 15O PET study to identify neuroanatomical systems which encode visual stimuli with strong negative emotional valence compared to stimuli with neutral valence. Subjects also performed a recognition memory task for these same images, mixed with distracters of similar emotional valence. The experimental design permitted us to independently test effects of emotional content and recognition memory on regional activity. We found activity in the left amygdaloid complex associated with the encoding of emotional stimuli, although this activation appeared early in the scanning session and was not detectable during recognition memory. Visual recognition memory recruited the right middle frontal gyrus and the superior anterior cingulate cortex for both negative and neutral stimuli. An interaction occurred between emotional content and recognition in the lingual gyrus, where greater activation occurred during recognition of negative images compared to recognition of neutral images. Instead of distinct neuroanatomical systems for emotion augmenting memory, we found that emotionally salient stimuli appeared to enhance processing of early sensory input during visual recognition.

Adult↗
PubMed1998

Influence of ANOVA design and anatomical standardization on statistical mapping for PET activation.

We have created images of z value, error, and variation components for a PET activation study using various ANOVA designs and anatomical standardization methods. Data were acquired in four PET centers. In each center, CBF was measured on six normal male subjects under resting and covert verb generation, three times for each. The images were anatomically standardized with LINEAR transformation, SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was performed pixel by pixel to compute t (and z) for the task main effect (Verb vs Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two-way with interaction (2WI), (iii) subject considered a random factor (2WI-MX), and (iv) three-way (subject, task, and replication) (3W). A large area extending from the Broca to the left premotor cortex was activated. The localization of the highest peak depended both on the anatomical standardization and on the ANOVA design, the variation ranging 3-4 cm. Smoothing reduced the variation while erasing possible subfoci. The z images of 2W, 2WI, and 3W looked alike, whereas 2WI-MX presented lower peak z values. SPM tended to present higher z values than the other methods. The error was high in the gray and low in the white matter. The root mean square for the subject effect was high on the border of gray matter especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter distribution. The root mean square for the subject-by-task interaction effect revealed individual variation in activation.

Adult↗