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Biomedical subjects

S Minoshima

Publications and source records attributed to S Minoshima.

At least 127 records · Page 7Linked to original sources
PubMed1997

Isolation of specific interference processing in the Stroop task: PET activation studies.

The Stroop task, in which subjects must name the color of letters that spell color words different than the color-to-be-named, provides an important experimental paradigm for the study of selective attention. Cerebral blood flow activation studies have not always demonstrated consistent activation patterns; inconsistent results may reflect nonspecific responses, such as arousal or anticipation, rather than cerebral networks specific to Stroop interference processing. In order to identify regions consistently implicated in Stroop interference processing, we undertook two experiments with a Stroop interference paradigm and contrasting lexical and nonlexical control conditions. In our first experiment, standard Stroop stimuli, e.g., the word "RED" displayed in a green font, were contrasted with color naming of the font of noncolor words and color naming of a false font. In our second experiment, we compared Stroop stimuli with colored symbols and a control condition designed to elicit nonspecific interference-taboo words displayed in color fonts. Only two brain regions showed a consistent CBF change in both experiments. Activation in the left inferior frontal gyrus reflected processing more specific to the Stroop task, while deactivation in the right superior temporal gyrus occurred for the Stroop and the taboo conditions, consistent with more nonspecific processing. Activation in the anterior cingulate cortex occurred in only one comparison in one experiment and may not reflect functions central to overcoming Stroop interference.

Adult↗
PubMed1997

Positional cloning of the APECED gene.

Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C-->T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A-->G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.

Amino Acid Sequence↗
PubMed1997

Central motor processing in Huntington's disease. A PET study.

Repeated PET cerebral blood flow measurements using H2(15)O were performed in 13 patients with confirmed Huntington's disease and nine age-matched controls. The activation paradigm consisted of an externally triggered finger opposition task (1.5 Hz) with the dominant hand, the control condition being the auditory input. In the patients with Huntington's disease, impaired activity of the striatum and its frontal motor projection areas (rostral supplementary motor area, anterior cingulate and premotor cortex) could be demonstrated along with enhanced activity mainly in parietal areas during movement. The results suggest that the pathology of Huntington's disease causes impairment of the output part of the basal ganglia-thalamo-cortical motor circuit and may induce a compensatory recruitment of additional accessory motor pathways involving the parietal cortex.

Adult↗
PubMed1997

Isolation and characterization of the plasma hyaluronan-binding protein (PHBP) gene (HABP2).

PHBP is a novel human plasma hyaluronan-binding protein that shows significant homology in amino acid sequence to hepatocyte growth factor activator. Two overlapping clones that encode the human plasma hyaluronan-binding protein (PHBP) gene (HABP2) were isolated and characterized. The PHBP gene spans 35 kb and is composed of 13 exons from 37 to 1,394 bp in size with consensus splice sites. The gene's regulatory sequences contain putative promoter elements, but no typical TATA box. Some exons of this gene showed significant similarities to those of coagulation factor XII, tissue-type plasminogen activator, and urokinase genes in nucleotide length and in intron phasing. We also report the chromosome mapping of this gene by fluorescence in situ hybridization (FISH) using a genomic DNA fragment as a probe. The PHBP gene (HABP2) was located on chromosome 10q25-q26.

Base Sequence↗
PubMed1997

Anterior decompression and fusion using bone grafts obtained from cervical vertebral bodies for ossification of the posterior longitudinal ligament of the cervical spine: technical note.

OBJECTIVE: To describe a surgical technique of anterior decompression and fusion using bone grafts obtained from cervical vertebral bodies with ossification of the posterior longitudinal ligament of the cervical spine. This technique seeks to avoid complications associated with an anterior approach of decompression and bone fusion, which widely uses autogenous bone from the iliac crest. METHODS: Forty patients with cervical myelopathy were studied. The ossified ligament was localized to one, two, three, four, five, six, and seven vertebral bodies in 10, 18, 5, 4, 1, 1, and 1 patients, respectively. The ossified area of all posterior longitudinal ligament was completely removed using microsurgical techniques, and 11 patients were operated on at one level, 21 at two levels, and 8 at three levels. RESULTS: The symptoms of all patients improved after the operation. Postoperative x-ray films showed solid bone fusion in all patients at a mean follow-up time of 3 years (range, 1-5.25 yr). Anterior angulation was found in one of eight patients (13%) who underwent three-level fusion. CONCLUSION: Two major advantages were as follows: 1) no complications related to the iliac donor site occurred, and 2) early mobilization of patients was possible with a soft cervical collar. Anterior decompression and fusion should be used for cases with ossification of up to three consecutive vertebrae needing either one- or two-level fusions.

Adult↗
PubMed1997

One-megabase sequence analysis of the human immunoglobulin lambda gene locus.

A total of 1,025,415 bases of nucleotide sequence, including the entire human immunoglobulin lambda gene locus has been determined. This is the largest contiguous human DNA sequence ever published. The sequence data revealed the organization of 36 potentially active V lambda gene segments, 33 pseudogene segments, and seven J lambda-C lambda gene segments. Among these 69 functional or nonfunctional V lambda gene segments, 32 were newly discovered. These V lambda gene segments are located within five gene-rich clusters and are divided into five clans based on sequence identity. Five potentially active nonimmunoglobulin genes were also detected within the lambda gene locus, and two other genes were observed in the upstream region. Sequence organization suggests that large DNA duplications diversified the germ-line repertoire of the V lambda gene segments.

Alleles↗
PubMed1997

Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region.

As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis. These exons were used to clone and characterize two human homologs of the Drosophila sim gene, SIM1 and SIM2, which map to chromosomes 6q16.3-q21 and 21q22.2, respectively; SIM2 maps within the so-called Down syndrome chromosomal region. Recently, two mouse homologs, Sim1 and Sim2, also have been identified. There is a high level of homology among human, mouse, and Drosophila sim genes in their amino-terminal half where the conserved bHLH, PAS1, PAS2, and HST domains are present. In contrast, the carboxy-terminal parts are only homologous between SIM1 and Sim1 and SIM2 and Sim2. Two isoforms (SIM2 and SIM2s) of human SIM2 have been detected that differ in their 3' ends. Northern blot analysis revealed one mRNA SIM1 species of approximately 9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney. The function of both human SIM1 and SIM2 is unknown. However, three copies of SIM2 may contribute to some specific Down syndrome phenotypes because of (1) mapping position, (2) potential function as transcriptional repressor, (3) likely dimerization with other transcription factors, (4) the temporal and spatial expression pattern of mouse Sim2, and (5) the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis.

Amino Acid Sequence↗
PubMed1997

Cerebral processing of acute skin and muscle pain in humans.

The human cerebral processing of noxious input from skin and muscle was compared with the use of positron emission tomography with intravenous H2(15)O to detect changes in regional cerebral blood flow (rCBF) as an indicator of neuronal activity. During each of eight scans, 11 normal subjects rated the intensity of stimuli delivered to the nondominant (left) forearm on a scale ranging from 0 to 100 with 70 as pain threshold. Cutaneous pain was produced with a high-energy CO2 laser stimulator. Muscle pain was elicited with high-intensity intramuscular electrical stimulation. The mean ratings of perceived intensity for innocuous and noxious stimulation were 32.6 +/- 4.5 (SE) and 78.4 +/- 1.7 for cutaneous stimulation and 15.4 +/- 4.2 and 73.5 +/- 1.4 for intramuscular stimulation. The pain intensity ratings and the differences between noxious and innocuous ratings were similar for cutaneous and intramuscular stimuli (P > 0.05). After stereotactic registration, statistical pixel-by-pixel summation (Z score) and volumes-of-interest (VOI) analyses of subtraction images were performed. Significant increases in rCBF to both noxious cutaneous and intramuscular stimulation were found in the contralateral secondary somatosensory cortex (SII) and inferior parietal lobule [Brodmann area (BA) 40]. Comparable levels of rCBF increase were found in the contralateral anterior insular cortex, thalamus, and ipsilateral cerebellum. Noxious cutaneous stimulation caused significant activation in the contralateral lateral prefrontal cortex (BA 10/46) and ipsilateral premotor cortex (BA 4/6). Noxious intramuscular stimulation evoked rCBF increases in the contralateral anterior cingulate cortex (BA 24) and subsignificant responses in the contralateral primary sensorimotor cortex (MI/SI) and lenticular nucleus. These activated cerebral structures may represent those recruited early in nociceptive processing because both forms of stimuli were near pain threshold. Correlation analyses showed a negative relationship between changes in rCBF for thalamus and MI/SI for cutaneous stimulation, and positive relationships between thalamus and anterior insula for both stimulus modalities. Direct statistical comparisons between innocuous cutaneous and intramuscular stimulation with the use of Z scores and VOI analyses showed no reliable differences between these two forms of noxious stimulation, indicating a substantial overlap in brain activation pattern. The comparison of noxious cutaneous and intramuscular stimulation indicated more activation in the premotor cortex, SII, and prefrontal cortex with cutaneous stimulation, but these differences did not reach statistical significance. The similar cerebral activation patterns suggest that the perceived differences between acute skin and muscle pain are mediated by differences in the intensity and temporospatial pattern of neuronal activity within similar sets of forebrain structures.

Acute Disease↗
PubMed1997

Probable diffuse Lewy body disease presenting as REM sleep behavior disorder.

Rapid eye movement sleep behavior disorder may herald several neurodegenerative disorders associated with parkinsonism, including Parkinson's disease. A 72-year-old man with a 17-year history of rapid eye movement sleep behavior disorder confirmed by polysomnography developed a progressive dementia that met operational clinical criteria for diffuse Lewy body disease. The differential diagnosis of progressive neurodegenerative disorders heralding as rapid eye movement sleep behavior disorder should now include diffuse Lewy body disease.

Aged↗
PubMed1997

[Computer softwares for DNA diagnosis: GeneViewPLUS and Mutation View].

We have developed two computer softwares GeneViewPLUS and Mutation View. GeneViewPLUS is designed to quickly display chromosomal mapping information on human genes and diseases whereas Mutation View is designed to display mutations of disease-causing genes. Both softwares are operated on UNIX workstation with X-window.

Chromosome Mapping↗
PubMed1997

Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity.

UNLABELLED: Despite controversial clinicopathological distinctions between Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD), similar patterns of metabolic reduction in the posterior brain were reported previously using PET with [18F]fluorodeoxyglucose. The current study was designed to examine more specific regional differences in cerebral glucose metabolism between PDD and AD using accurate and objective brain mapping techniques. METHODS: This study included nine normal subjects, nine PDD patients and nine AD patients. PDD and AD groups were matched carefully for age, sex and general dementia severity as measured by Mini-Mental State Examination and Clinical Dementia Rating scales. Each subject underwent [18F]fluorodeoxyglucose-PET and neuropsychological testing. After anatomic standardization of PET image sets and stereotactic data extraction, absolute and normalized cerebral metabolic rates were assessed by region of interest and pixel-by-pixel analyses. RESULTS: PDD and AD showed global glucose metabolic reduction with similar regional accentuation involving the lateral parietal, lateral temporal and lateral frontal association cortices and posterior cingulate cortex in comparison to normal controls. When comparing between PDD and AD, however, PDD showed greater metabolic reduction in the visual cortex and relatively preserved metabolism in the medial temporal cortex. CONCLUSION: Although a common feature of metabolic abnormalities in the posterior brain exists in PDD and AD, the presence of regional metabolic differences suggests different degrees and combinations of disease specific underlying pathological and neurochemical processes.

Aged↗
PubMed1997

Quantitative assessment of cerebral blood flow in patients with Alzheimer's disease by SPECT.

UNLABELLED: This study evaluated an automated analysis of SPECT brain imaging in patients with Alzheimer's disease (AD). METHODS: Patients [n = 81; mean age, 69.9 +/- 10.6 yr (mean +/- s.d.)] with a clinical diagnosis of probable AD (NINCDS-Alzheimer's Disease and Related Disorders Association criteria) underwent 99mTc-ethyl cysteine dimer SPECT imaging. After imaging registration and data extraction using three-dimensional stereotactic surface projections, a pixel-wise comparison of ethyl cysteine dimer uptake was performed using a reference database of 10 cognitive intact controls of comparable age. RESULTS: When individual cases were compared to the normal database, temporo-parietal regional cerebral blood flow (rCBF) abnormalities across different levels of dementia severity were clearly depicted on pixel-wise Z-score images. The rCBF reduction in cortical association areas showed a significant correlation with an overall level of cognitive decline, as assessed by the Mini Mental State Examination and by the cognitive section of the Cambridge Mental Disorders of the Elderly Examination. In addition, there were significant region-specific correlations between left temporo perfusion deficit and language performance and between right parietal rCBF reduction and praxis. CONCLUSION: These results indicate that this observer-independent analysis of SPECT data enables objective and semiquantitative assessment of the magnitude and extent of cortical perfusion abnormalities in patients with AD.

Alzheimer Disease↗
PubMed1997

Assessment of local brain activation. A simultaneous PET and near-infrared spectroscopy study.

In five healthy human subjects, near-infrared spectroscopy (NIRS) and positron emission tomography (PET) examinations were performed simultaneously. Changes in [oxy-Hb], [deoxy-Hb] and [total-Hb] as measured by NIRS over the left forehead were compared to measurements of cerebral blood flow by PET during rest and during performance of a calculation task and a Stroop task. When a penetration depth of near-infrared light 0.9 cm into the brain cortex was assumed, a statistically significant correlation between changes in CBF and changes in [total-Hb] was found. These data confirm the validity of NIRS measurements in human adults.

Aged↗
PubMed1997

[MPO-ANCA related vasculitis with pulmonary hemorrhage during propylthiouracil (PTU) therapy].

We described a case of pulmonary hemorrhage associated with myeloperoxidase-antineurophil cytoplasmic antibodies (MPO-ANCA) without renal involvement during propylthiouracil (PTU) treatment. A 36-years old female was admitted to our hospital because of progressive dyspnea with hemosputum after flu-like symptom and episcleritis. She had been receiving PTU for three years to Graves' disease. On admission her chest Xp showed bilateral massive infiltrative shadow and bronchofiberscopy demonstrated pulmonary hemorrhage. MPO-ANCA and anti-thyroperoxidase antibodies were positive, but she had normal urinalysis and normal renal function. After withdraw of PTU, pulmonary hemorrhage disappeared. But 15 days later pulmonary hemorrhage recurred associated with high MPO-ANCA titer. Corticosteroid bolus therapy and oral cyclophasphamide administration improved pulmonary hemorrhage, and MPO-ANCA titer also decreased. It is suggested that MPO-ANCA and PTU might be closely related to the pathogenesis of pulmonary hemorrhage in this case.

Adult↗