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Biomedical subjects

S Minoshima

Publications and source records attributed to S Minoshima.

At least 181 records · Page 10Linked to original sources

[A case of progressive systemic sclerosis with crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane antibody (anti-GBM Ab)].

A 42-year-old female with progressive systemic sclerosis (PSS) developed rapidly progressive renal insufficiency. Renal pathology revealed crescentic glomerulonephritis (CrGN) without mucoid intimal proliferation of the interlobular arteries and fibrinoid necrosis of the afferent arterioles. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Not only anti-glomerular basement membrane antibody (anti-GBM Ab), but also myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were simultaneously detected by an enzymelinked immunosorbent assay (ELISA). She did not develop pulmonary hemorrhage. These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of serum creatinine level (over 6.0mg/dl), a high titer of MPO-ANCA (660.7 ELISA unit/ml) and anti-GBM Ab (409 units). Therefore, she was started on methylprednisolone pulse therapy and temporary hemodialysis. After immunosuppressive therapy, both antibodies titers had fallen to within the normal range. However, end-stage renal failure did not improve and maintenance hemodialysis was introduced. Recently, six patients of PSS with MPO-ANCA were first reported in Japan. These autoantibodies detected in this case strongly suggested that there may be associations between anti-GBM Ab nephritis and ANCA-related vasculitis and PSS.

Adult↗

[Pulmonary involvement in patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody].

In order to examine the clinical features of pulmonary involvement in patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA), 46 MPO-ANCA positive patients with collagen-vascular disease and glomerulonephritis were investigated. Twenty eight patients (60.8%) had pulmonary involvement without tumor and infection, 20 (43.5%) of MPO-ANCA positive patients had interstitial pneumonitis, 11 (23.9%) had pulmonary hemorrhage, 3 had asthma (6.5%) and 7 had both interstitial pneumonitis and pulmonary hemorrhage. Patients with pulmonary involvement were older (mean age 61.1) and they had higher inflammatory acute phase reactants and higher mortality (42.9%) than patients without pulmonary involvement. Pulmonary hemorrhage revealed on both lung fields in 10 patients, 7 patients required artificial respirator and 6 died. Titer of MPO-ANCA increased paralleled with progression of pulmonary hemorrhage. Interstitial fibrosis revealed predominantly lower and lateral side of the lung. It is suggested that MPO-ANCA may be closely related to the pathogenesis of pulmonary hemorrhage and interstitial pneumonia. Careful management is needed in patients with pulmonary involvement, especially pulmonary hemorrhage in patients with MPO-ANCA.

Adult↗

A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET.

UNLABELLED: To improve the diagnostic performance of PET as an aid in evaluating patients suspected of having Alzheimer's disease, we developed a fully automated method which generates comprehensive image presentations and objective diagnostic indices. METHODS: Fluorine-18-fluorodeoxyglucose PET image sets were collected from 37 patients with probable Alzheimer's disease (including questionable and mild dementia), 22 normal subjects and 5 patients with cerebrovascular disease. Following stereotactic anatomic standardization, metabolic activity on an individual's PET image set was extracted to a set of predefined surface pixels (three-dimensional stereotactic surface projection, 3D-SSP), which was used in the subsequent analysis. A normal database was created by averaging extracted datasets of the normal subjects. Patients' datasets were compared individually with the normal database by calculating a Z-score on a pixel-by-pixel basis and were displayed in 3D-SSP views for visual inspections. Diagnostic indices were then generated based on averaged Z-scores for the association cortices. RESULTS: Patterns and severities of metabolic reduction in patients with probable Alzheimer's disease were seen in the standard 3D-SSP views of extracted raw data and statistical Z-scores. When discriminating patients with probable Alzheimer's disease from normal subjects, diagnostic indices of the parietal association cortex and unilaterally averaged parietal-temporal-frontal cortex showed sensitivities of 95% and 97%, respectively, with a specificity of 100%. Neither index yielded false-positive results for cerebrovascular disease. CONCLUSION: 3D-SSP enables quantitative data extraction and reliable localization of metabolic abnormalities by means of stereotactic coordinates. The proposed method is a promising approach for interpreting functional brain PET scans.

Aged↗

Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man.

Man is among the exceptional higher animals that are unable to synthesize L-ascorbic acid because of their deficiency in L-gulono-gamma-lactone oxidase, the enzyme catalyzing the terminal step in L-ascorbic acid biosynthesis. In the present study, we isolated a segment of the nonfunctional L-gulono-gamma-lactone oxidase gene from a human genomic library, and mapped it on chromosome 8p21.1 by spot blot hybridization using flow-sorted human chromosomes and fluorescence in situ hybridization. Sequencing analysis indicated that the isolated segment represented a 3'-part of the gene, where the regions corresponding to exons VII, IX, X, and XII of the rat L-gulono-gamma-lactone oxidase gene remain with probable deletion of the regions corresponding to exons VIII and XI. In the identified exon regions were found various anomalous nucleotide changes, such as deletion and insertion of nucleotide(s) and nonconformance to the GT/AG rule at intron/exon boundaries. When the conceptual amino acid sequences deduced from the four exon sequences were compared with the corresponding rat sequences, there were a large number of nonconservative substitutions and also two stop codons. These findings indicate that the human nonfunctional L-gulono-gamma-lactone oxidase gene has accumulated a large number of mutations without selective pressure since it ceased to function during evolution.

Amino Acid Sequence↗

[Fat suppression failure artifacts at the susceptibility interface on frequency selective fat suppression MR imaging in the head and neck].

Fat suppression MR imaging is a valuable technique mainly used for the orbit, head and neck, and spine, where the high signal from fat can often obscure adjacent pathology. Fat suppression failure artifact manifested as a high signal area without geographic distortion. The purpose of this study was to investigate the frequency and common location of these artifacts in clinical MR imaging and to caution against their misinterpretation. Fat suppression MR imaging of the head and neck was performed in 30 consecutive patients. The artifact was found in the orbital floor (57%), the skull base (10%), and subcutaneous fat (10%), where the air-fat interface is parallel to the static magnetic field direction. The fat signal in the air-fat interface perpendicular to the static magnetic field was well suppressed. This artifact was independent of the duration of TE, frequency/phase encoding direction, and the strength of gradient amplitude, and appeared to be related to the amount of surrounding air. This may simulate pathology if fat suppression is only performed following Gd-DTPA administration. The radiologist should be aware of the presence of artifact by considering the geographic relation to the static magnetic field.

Adipose Tissue↗

The human genes for desmogleins (DSG1 and DSG3) are located in a small region on chromosome 18q12.

Desmoglein is a transmembrane glycoprotein component of desmosomes in vertebrate epithelial cells. Two of the three currently known desmogleins are the autoantigens of autoimmune skin blistering diseases, pemphigus vulgaris and pemphigus foliaceus, in which autoantibodies cause the loss of cell adhesion of keratinocytes with resultant blister formation. In this study, the genes for two autoantigens (DSG1 for pemphigus foliaceus and DSG3 for pemphigus vulgaris) were mapped on band q12 of human chromosome 18 by fluorescence in situ hybridization. Furthermore, both genes were localized on a 320-kb genomic fragment separated by pulsed-field gel electrophoresis. These results suggest the possibility of a cluster for the desmoglein gene family on chromosome 18.

Animals↗

Changes in medial cortical blood flow with a stimulus-response compatibility task.

Previous work has suggested that human subjects engaged in tasks, like the Stroop task, that require response selection utilize the medial frontal cortex. We used positron emission tomography to measure blood flow changes in a stimulus-response compatibility task designed to maximize the demand on response selection processes. We report significant activation in the cingulate sulcus (Brodman's area 32) and a correlation of activity in this region with faster response time for an incongruent stimulus-response task.

Brain↗

Detection of epidermal growth factor receptor gene amplification in human squamous cell carcinomas using fluorescence in situ hybridization.

The gene for epidermal growth factor receptor (EGFR) is associated with development of certain human cancers. In this study, we employed the improved fluorescence in situ hybridization technique to detect EGFR gene amplification in cell lines and tissue sections from human squamous cell carcinomas. We detected multiple distinct signals as arrayed amplicons on metaphase chromosomes and interphase nuclei of tumor cells. Our results provide a basis for rapid and quantitative DNA diagnosis of the EGFR gene amplification in individual cells of tumor specimens.

Carcinoma, Squamous Cell↗

Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli.

1. To identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans, we performed H2 15O positron emission tomographic (PET) analyses of cerebral blood flow (CBF) on nine normal volunteers while they received repetitive noxious (50 degrees C) and innocuous (40 degrees C) 5 s heat pulses to the forearm (average resting temperature of 31.8 degrees C). Each subject rated the subjective intensity of each stimulation series according to a magnitude estimation procedure in which 0 = no heat sensation, 7 = barely painful, and 10 = barely tolerable. 2. Three scans were performed at each temperature. Mean CBF images were created for each experimental condition and oriented onto standardized stereotaxic coordinates. Subtraction images were created between conditions for each subject and averaged across subjects. Volumes of interest (VOI) were chosen, based on a priori hypotheses and the results of previously published PET studies. In addition, a separate statistical summation analysis of individual voxels was performed. Statistical thresholds were established with corrections for multiple comparisons. 3. Significant CBF increases to 50 degrees C stimuli were found in the contralateral thalamus, cingulate cortex, S2 and S1 cortex, and insula. The ipsilateral S2 cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis also showed significant CBF increases. All subjects rated the 50 degrees C stimuli as painful (average subjective rating = 8.9 +/- 0.9 SD) and the 40 degrees C stimuli as warm, but not painful (average subjective rating = 2.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Integrated and automated data analysis for neuronal activation studies using positron emission tomography: methodology and applications].

A data analysis method was developed for neuronal activation studies using [15O]water positron emission tomography (PET). The method consists of several procedures including intra-subject head motion correction (co-registration), detection of the mid-sagittal plane of the brain, detection of the intercommissural (AC-PC) line, linear scaling and non-linear warping for anatomical standardization, pixel-by-piexl statistical analysis, and data display. All steps are performed in three dimensions and are fully automated. Each step was validated using a brain phantom, computer simulations, and data from human subjects, demonstrating accuracy and reliability of the procedure. The method was applied to human neuronal activation studies using vibratory and visual stimulations. The method detected significant blood flow increases in the primary sensory cortices as well as in other regions such as the secondary sensory cortex and cerebellum. The proposed method should enhance application of PET neuronal activation studies to the investigation of higher-order human brain functions.

Adult↗

[Nontraumatic femoral head necrosis: classification of bone scintigraphic findings and diagnostic value of SPECT following planar imaging].

This study was conducted to determine bone scintigraphic findings in nontraumatic femoral head avascular necrosis and diagnostic value of SPECT imaging following a conventional planar imaging. Forty-three femoral heads in twenty-six cases with idiopathic femoral head necrosis (n = 2), systemic lupus erythematosus (n = 22), aplastic anemia (n = 1), and renal transplantation (n = 1) were studied. The diagnosis for femoral head necrosis was based on magnetic resonance imaging as well as other diagnostic studies in all cases. Scintigraphic findings of planar and SPECT images were classified into six categories: normal (N); cold or decrease (C); partial increase with cold or decrease (PH+C); ring-like increase with a cold center (RH+C); partial increase (PH); diffuse and/or irregular increase (DH). Avascular necrosis was confirmed in twenty-four femoral heads, in which planar and SPECT images showed scintigraphic findings of N (n = 3, 2), C (n = 1, 3), PH+C (n = 2, 8), RH+C (n = 2, 3), PH (n = 9, 2), and DH (n = 7, 6), respectively. Femoral heads without avascular necrosis demonstrated planar and SPECT findings of N (n = 16, 12), C (n = 0, 6), and DH (n = 3, 1), respectively. When considering C, PH+C, and RH+C as diagnostic findings for avascular necrosis, sensitivities of planar and SPECT images were 21% and 58%, and specificities were 100% and 68%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anatomic standardization: linear scaling and nonlinear warping of functional brain images.

UNLABELLED: An automated method was proposed for anatomic standardization of PET scans in three dimensions, which enabled objective intersubject and cross-group comparisons of functional brain images. METHODS: The method involved linear scaling to correct an individual brain size and nonlinear warping to minimize regional anatomic variations among subjects. In the linear-scaling step, the anteroposterior length and width of the brain were measured on the PET images, and the brain height was estimated by a contour-matching procedure using the midsagittal plane. In the nonlinear warping step, individual gray matter locations were matched with those of a standard brain by maximizing correlation coefficients of regional profile curves determined between predefined stretching centers (predominantly in white matter) and the gray matter landmarks. RESULTS: The accuracy of the brain height estimation was compared with skull x-ray estimations, showing comparable accuracy and better reproducibility. Linear-scaling and nonlinear warping methods were validated using [18F]fluorodeoxyglucose and [15O]water images. Regional anatomic variability on the glucose images was reduced markedly. The statistical significance of activation foci in paired water images was improved in both vibratory and visual activation paradigms. A group versus group comparison following the proposed anatomic standardization revealed highly significant glucose metabolic alterations in the brains of patients with Alzheimer's disease compared with those of a normal control group. CONCLUSION: These results suggested that the method is well suited to both research and clinical settings and can facilitate pixel-by-pixel comparisons of PET images.

Algorithms↗

[Surgical treatment for ossification of the posterior longitudinal ligament of the cervical spine].

The surgical results in 37 patients with cervical myelopathy due to ossification of the posterior longitudinal ligament of the cervical spine were described. This series consisted of 32 patients who underwent anterior decompression with anterior cervical fusion using bone grafts obtained from cervical vertebral bodies, and 5 patients who underwent expansive laminoplasty or laminectomy as a method of posterior decompression. 6 out of 32 patients with anterior cervical fusion were operated on at one level, 18 at two levels and 8 at three levels. The patients were out of bed within two days and treated using a soft collar for 3 months. In all patients, the symptoms improved postoperatively. Postoperative X-ray films showed solid bone fusion in all patients with anterior cervical fusion at a mean follow up time of one year and nine months (range 6 months to 3 years 6 months). Anterior angulation was found in one (3%) out of 32 patients who underwent anterior cervical fusion. Concerning the method of operation, the authors think that anterior decompression is to be recommended for cases with ossification within three consecutive vertebrae and posterior decompression should be applied to cases in which anterior decompression is very difficult. If necessary, a two-stage combined decompression is recommended.

Adult↗

In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM.

UNLABELLED: In the search for an in vivo marker of cholinergic neuronal integrity, we extended to human use the tracer (-)-5-[123I]iodobenzovesamicol (IBVM). METHODS: IBVM, an analog of vesamicol that binds to the acetylcholine transporter on presynaptic vesicles, was prepared with specific activity greater than 1.11 x 10(9) MBq mmole-1. After intravenous injection of [123I]IBVM, body distribution studies (n = 5) and brain SPECT studies (n = 5) were performed on normal human subjects (n = 10). SPECT images of the brain were collected sequentially over the first 4.5 hr following injection, and again 18 hr later. Data were realigned and transformed to stereotaxic coordinates, and localized activities were extracted for tracer kinetic analysis. The cerebral tracer input function was determined from metabolite-corrected radial arterial blood samples. The best data fit was obtained using a three-compartment model, including terms reflecting cerebral blood volume, exchange of free tracer between plasma and brain and specific binding. RESULTS: Dissociation of bound tracer was negligible for up to 4 hr. For the fitted parameters reflecting transport (K1) and binding site density index (k3), coefficients of variation were approximately 8% in cortical regions of interest. Relative distributions corresponded well with postmortem immunohistochemical values reported for the acetylcholine-synthesizing enzyme choline acetyltransferase, k3 (IBVM binding site density index), and tracer activity distribution at 22 hr, but not at 4 hr after injection. CONCLUSION: SPECT imaging of [123I]IBVM succeeds as an in vivo measure of cholinergic neuronal integrity and should be useful for the study of cerebral degenerative processes such as Alzheimer's disease.

Adult↗

Stereotactic PET atlas of the human brain: aid for visual interpretation of functional brain images.

UNLABELLED: In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. METHODS: The PET atlas was constructed from a high-resolution [18F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-old woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes by using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer's disease, and areas of functional alteration were localized visually by referring to the PET atlas. RESULTS: Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer's disease facilitated both indirect and direct localization of the cerebral structures. CONCLUSION: Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations.

Adult↗

Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene.

The primary structure of human xanthine dehydrogenase (hXDH) was determined by cloning and sequence analysis of the cDNAs encoding the enzyme. The nucleotide (nt) sequence has an open reading frame of 3999 nt encoding a protein of 1333 amino acids (aa) with a calculated M(r) of 146,604. The deduced aa sequence of hXDH is homologous to the previously reported rat XDH (rXDH) and Drosophila melanogaster XDH sequences with identities of 90.2 and 52.0%, respectively. The aa residues involved in both the reversible and the irreversible conversion from the dehydrogenase type to the oxidase type of rXDH are completely conserved between the rat and the human enzymes. This implies that the molecular mechanisms of the conversion of hXDH from dehydrogenase to oxidase are common to those of the well-characterized rXDH. Five sequence variations were detected in the isolated cDNA clones. Spot blot hybridization using flow-sorted human chromosome revealed that the hXDH-encoding gene (hXDH) was located on chromosome 2.

Amino Acid Sequence↗

Molecular cloning of cDNA encoding human drebrin E and chromosomal mapping of its gene.

Drebrins are novel actin-binding proteins in the brain which are developmentally regulated. Three isoforms: two embryonic types (E1 and E2) and an adult type (A) are generated by alternative RNA splicing from a single debrin gene in the chicken brain. A full length cDNA clone of human drebrin E has been isolated from a cDNA library of human fetus brain. The clone is 2596 base pairs in length and contains an open reading frame of 1947 nucleotides encoding a protein of 649 amino acids. The deduced amino acid sequence, except for the internal 138-nucleotide sequence (ins2), exhibits 88% homology with rat drebrin A. Spot blot hybridization using flow-sorted human chromosomes provides evidence that the gene encoding human drebrin protein locates on human chromosome 5.

Amino Acid Sequence↗