Search PubMed⌕ Search

Biomedical subjects

S Minoshima

Publications and source records attributed to S Minoshima.

At least 163 records · Page 9Linked to original sources

[A case of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis associated with Cogan's syndrome].

We report here a case of Cogan's syndrome associated with systemic vasculitis as well as myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis. A 71-year-old woman with the diagnosis of aortitis syndrome and pulmonary fibrosis for 7 years, complained of vertigo and hearing impairment. A diagnosis of serous otitis media was made. Although steroid therapy was effective, the symptoms relapsed several times. Seven months after the first manifestation of aural symptoms, she developed painful red eyes bilaterally and proteinuria. On admission, perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MOP-ANCA was detected by enzyme linked immunosorbent assay using the 363 ELISA Unit. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. A diagnosis of atypical Cogan's syndrome with systemic vasculitis and pulmonary fibrosis was made from the clinical and histological findings. As nephrotic syndrome progressed after admission, she was started on high-dose corticosteroid administration. Urinary protein and other symptoms, except for hearing acuity, improved in parallel with a decrease in the MPO-ANCA titer to normal values. While tapering the dose of corticosteroid, the MPO-ANCA titer increased again and dyspnea occurred. Although pulse methylpredonisolone therapy was performed, the patient died of respiratory failure complicated with sepsis. Postmortem lung biopsy showed pulmonary fibrosis and massive alveolar hemorrhage. The findings of this case study suggest that MPO-ANCA may be closely related to the pathogenesis of Cogan's syndrome.

Aged↗

Determination of regional rate constants from dynamic FDG-PET studies in Parkinson's disease.

UNLABELLED: Dynamic [18F]fluorodeoxyglucose (FDG) PET was used in Parkinson's disease patients and normal controls to determine kinetic rate constants for FDG. The goal was to assess whether the metabolic decreases observed in Parkinson's disease are associated with transport or phosphorylation processes or both. METHODS: Fluorine-18-FDG was administered to 18 Parkinson's disease and 15 normal control subjects. Dynamic PET scanning was performed for 1 h and rate constants were obtained by nonlinear, least-squares analysis. Regional glucose metabolic rate was calculated from the individually fitted rate constants and by two standard static scan analyses. RESULTS: Global CMRglu was decreased in Parkinson's disease (mean reduction 22%), reaching statistical significance in all regions investigated. K1 was significantly reduced in parietal cortex, temporal cortex and striatum while k3 was significantly reduced only in parietal cortex. The rate constant k2 was unchanged. CONCLUSION: K1, k3 and CMRglu all demonstrated greater deficits across the brain with progression of disease and development of dementia, particularly in the parietal an occipital cortex. This suggested that the metabolic disturbance may be a global dysfunction throughout the brain. Because altered rate constants are specifically taken into account, dynamic measurements has shown to provide higher sensitivity for detecting diminished glucose utilization in Parkinson's disease than static approaches.

Adult↗

Structural organization and chromosomal localization of the human nuclear gene (NDUFV2) for the 24-kDa iron-sulfur subunit of complex I in mitochondrial respiratory chain.

The structural organization of the entire human nuclear encoded gene for the 24-kDa iron-sulfur subunit of mitochondrial NADH-ubiquinone oxidoreductase (Complex I) and its chromosomal localization were determined. The gene contains 8 exons spanning 31.5 kb. The 5' flanking region sequenced lacks typical CAAT and TATA boxes but contains three putative GC boxes and there is one GC box at the beginning of the first intron. The sequences matching completely with the NRF-1 binding site and Mt elements were not identified in the flanking region. This gene was assigned to human chromosome 18 at region p11.3, by fluorescent in situ hybridization.

Base Composition↗

Human ribosomal RNA gene cluster: identification of the proximal end containing a novel tandem repeat sequence.

Human ribosomal RNA genes (rDNA) are arranged as tandem repeat clusters on the short arms of five pairs of acrocentric chromosomes. We have demonstrated that a majority of the rDNA clusters are detected as 3-Mb DNA fragments when released from human genomic DNA by EcoRV digestion. This indicated the absence of the EcoRV restriction site within the rDNA clusters. We then screened for rDNA-positive cosmid clones using a chromosome 22-specific cosmid library that was constructed from MboI partial digests of the flow-sorted chromosomes. Three hundred twenty rDNA-positive clones negative for the previously reported distal flanking sequence (pACR1) were chosen and subjected to EcoRV digestion. Seven clones susceptible to EcoRV were further characterized as candidate clones that might have been derived from the junctions of the 3-Mb rDNA cluster. We identified one clone containing part of the rDNA unit sequence and a novel flanking sequence. Detailed analysis of this unique clone revealed that the coding region of the last rRNA gene located at the proximal end of the cluster is interrupted with a novel sequence of approximately 147 bp that is tandemly repeated and is connected with an intervening 68-bp unique sequence. This junction sequence was readily amplified from chromosomes 21 and 15 as well as 22 using the polymerase chain reaction. Fluorescence in situ hybridization further indicated that the approximately 147-bp sequence repeat is commonly distributed among all the acrocentric short arms.

Animals↗

Cot-1 banding of human chromosomes using fluorescence in situ hybridization with Cy3 labeling.

We developed a new chromosome banding method by in situ hybridization of human Cot-1 DNA as a probe. Clear banding was produced on metaphase chromosomes of lymphoblastoid cells after probe detection with a fluorescent dye Cy3. Comparison with the known banding patterns revealed a similarity to the R-banding with some significant differences: some centromeric heterochromatin regions show Cot-1 positive bands. This suggests that some repetitive sequences from the heterochromatin regions constitute a major component of Cot-1 DNA. This unique chromosome banding method, Cot-1 banding, may be used as a supplement to the conventional karyotype analysis. Scanning analysis of the fluorescence intensities of Cot-1 banding and Q-banding are useful for objectively analyzing the banding pattern including a detection of chromosome aberrations. The Cot-1 banding with Cy3 is particularly powerful when applied for the gene mapping by fluorescence in situ hybridization (FISH) because red fluorescence of Cy3 for chromosome staining can be readily distinguished from green fluorescence of fluorescein isothiocyanate (FITC) for probe labeling. Using this novel method, we mapped a 4 kb-DNA fragment from myelin protein zero (MPZ) gene on the chromosome 1q22 to q23.

Carbocyanines↗

A potential use of a 123I-labelled benzodiazepine receptor antagonist as a predictor of neuronal cell viability: comparisons with 14C-labelled 2-deoxyglucose autoradiography and histopathological examination.

In the treatment and therapy of patients suffering a stroke, it is very important to predict whether viable neurones, even those of poor function, remain intact in the lesions of the brain. To determine whether viable neurones of low functional activity are represented in in vivo neuroreceptor imaging, we undertook experiments in gerbils with cerebral infarction, in which we examined histological changes and the results of dual-tracer in vivo autoradiography of glucose utilization with 14C-labelled deoxyglucose and benzodiazepine receptor binding with 123I-labelled Ro 16-0154. The unrelated findings of cerebral glucose metabolism and benzodiazepine receptor binding were observed in the primary infarct lesion and in remote areas, including the ipsilateral striatum and thalamus. Our experiments showed that when viable neurones with low functional activity remain intact, normal in vivo binding to benzodiazepine receptors is demonstrated as hypometabolism of glucose utilization. This functional, contrast-enhanced technique with 123I-labelled Ro 16-0154 may have an important role to play in the prediction of neuronal cell viability after recent brain infarction in experimental animals and humans using single photon emission tomography (SPET).

Animals↗

The organization of the human immunoglobulin lambda gene locus.

To elucidate the complex structure of the human immunoglobulin lambda gene locus, a 1020-kb contig was constructed using 184 cosmid clones and one bacterial artificial chromosome (BAC) clone. A high-resolution physical map of this contig revealed that the entire lambda gene locus is 911 kb in length. It contains seven constant region (C lambda) gene segments and 69 unique EcoRI-HindIII segments that hybridize to variable region gene (V lambda) probes. The VpreB gene, BCRL4, and gamma-glutamyl transpeptidase gene (GGT)-like sequences are also located within the lambda gene locus. Hybridization analysis suggested that the lambda gene locus has undergone extensive amplification events in evolution.

Base Sequence↗

Mapping of human inter-alpha-trypsin inhibitor family heavy chain-related protein gene (ITIHL1) to human chromosome 3p21-->p14.

Inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) is a novel glycoprotein isolated from human plasma. The cDNA encoding IHRP has recently been cloned from human liver cDNA libraries. We report the mapping of this gene (ITIHL1) by fluorescence in situ hybridization using a 2.5-kb cDNA fragment as a probe. ITIHL1 was localized to chromosome region 3p21-->p14 where the genes of heavy chain 1 and 3 of inter-alpha-trypsin inhibitor are located. This result, together with significant homology between the nucleotide sequences of ITIHL1 and the heavy chain genes, supports ITIHL1 as being a member of an evolutionary related gene family of ITI heavy chains. Northern blot analysis indicated that IHRP was predominantly synthesized in liver. From Southern blot analysis, it was tentatively concluded that ITIHL1 is a single copy gene.

Blood Proteins↗

[Studies on functions of neutrophils in MPO-ANCA related glomerulonephiritis and plasma effect on MPO release from neutrophils].

In order to examine the role of myeloperoxidase (MPO) and neutrophil activation in the pathogenesis of MPO-ANCA related necrotizing crescentic glomerulonephritis (GN), we investigated MPO release and superoxide anion (O-2) production from the neutrophils in MPO ANCA related GN. Plasma effect on MPO release from neutrophils was also studied in MPO-ANCA related GN. Neutrophils and plasma were obtained from 10 patients with MPO-ANCA-related GN (A), 10 patients with MPO-ANCA non related GN (B) and 10 healthy controls (C). MPO release and O-2 production were assayed by using chemotactic factor, N-formyl-methionyl-leucyl-phenyalanine (FMLP) and cytochalasin B (CB). In MPO-ANCA related GN, MPO release and O-2 production were significantly higher than in the other groups. [MPO release (%) A: 43.02 +/- 18.33, B: 33.26 +/- 11.58, C: 19.73 +/- 8.38, sensitivity to FMLP (%) A: 894.56 +/- 381.96, B: 512.86 +/- 314.91, C: 301.12 +/- 139.8, O-2 production (nmoles/min/10(6) cells) A: 13.06 +/- 5.28, B: 3.57 +/- 2.02, C: 2.83 +/- 1.16] Furthermore, MPO release, sensitivity to FMLP and O-2 production were shown to increase in parallel with clinical disease activity. Plasma from MPO-ANCA related GN increased sensitivity to FMLP in neutrophils obtained from healthy controls [plasma concentration 1%, A: 311.5 +/- 110.3, B: 227.2 +/- 101.4, C: 215.5 +/- 93.7], and plasma from MPO-ANCA related GN suppressed %MPO release from neutrophils with MPO-ANCA related GN [plasma concentration 0.1%, A: 11.56 +/- 6.17, C: 15.51 +/- 8.01]. It was concluded that in patients with MPO-ANCA related GN, large amounts of MPO can be easily released from activated neutrophils and this might be influenced by some stimulating and suppressing factors contained in the plasma.

Adult↗

[Evaluation of hilar 67Ga-citrate uptake in bronchogenic carcinoma].

We evaluated hilar uptake on 67Ga-citrate scintigraphy and correlated with hilar lymph node metastases in one-hundred seventeen cases (two-hundred thirty four hila) of bronchogenic carcinoma. Hilar uptake was classified into three grades independently on anterior and posterior chest views: no uptake (grade 0), uptake equal to that in the thoracic vertebrae (grade 1), uptake higher than that in the thoracic vertebrae (grade 2). If a summed grade of anterior and posterior view was larger than 3, hilar uptake was considered as positive. In forty-four cases (forty-nine hila) with hilar lymph node metastases, positive hilar uptake was found in ten cases (eleven hila), resulting in sensitivity of 22% based on cases and 23% based on hila. In seventy-three cases (one-hundred forty-six hila) without hilar lymph node metastases, positive hilar uptake was found in six cases (ten hila), resulting in specificity of 91% based on cases and 93% based on hila. In comparison to scintigraphic findings of unilaterally positive hilar uptake, findings of bilaterally positive hilar uptake showed significantly lower accuracy in determining presence of hilar lymph node metastases. No definite correlation between hilar uptake and histopathology or 67Ga-citrate uptake in a primary tumor was observed. The results indicate that usefulness of 67Ga-citrate scintigraphy is limited when evaluating hilar lymph node metastases in bronchogenic carcinoma.

Adult↗

[A case of multiple organ failure induced by postoperative radiation therapy probably evoking oxidative stress].

In recent years, several laboratories have suggested that serum levels of antioxidant activity and redox balance are reduced in patients with chronic renal failure. Some clinical reports have also proposed that defective serum antioxidative enzymes may contribute to a certain uremic toxicity through peroxidative cell damage. A 48-year-old woman was referred to us from the surgical department of our hospital because of consciousness disturbance, pancytopenia and acute acceleration of chronic azotemia after postoperative radiation therapy. We diagnosed acute acceleration of chronic renal failure with severe acidemia and started hemodialysis therapy immediately. Two days after admission to our department, she developed upper abdominal sharp pain and bradyarrhythmia. Serum amylase activity was elevated markedly and the ECG finding showed myocardial ischemia. On the 24th hospital day these complications were treated successfully with conservative therapy and hemodialysis. We considered that radiation therapy in this patient with chronic renal failure evoked marked oxidative stress and that deficiency of transferrin played an important role in peroxidative cell damage.

Female↗