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Biomedical subjects

A Tamura

Publications and source records attributed to A Tamura.

At least 109 records · Page 6Linked to original sources
PubMed1999

Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase.

We have mapped large (cybL) and small (cybS) subunits of cytochrome b in the succinate-ubiquinone oxidoreductase (complex II) of human mitochondria to chromosome 1q21 and 11q23, respectively (H. Hirawake et al., Cytogenet. Cell Genet. 79 (1997) 132-138). In the present study, the human SDHD gene encoding cybS was cloned and characterized. The gene comprises four exons and three introns extending over 19 kb. Sequence analysis of the 5' promoter region showed several motifs for the binding of transcription factors including nuclear respiratory factors NRF-1 and NRF-2 at positions -137 and -104, respectively. In addition to this gene, six pseudogenes of cybS were isolated and mapped on the chromosome.

Amino Acid Sequence↗
PubMed1999

Relation between negative U waves in precordial leads on the admission electrocardiogram and time course of left ventricular wall motion in anterior wall acute myocardial infarction.

This study indicates that patients with anterior wall acute myocardial infarction showing negative U waves in the precordial leads on the admission electrocardiogram have greater improvement in left ventricular wall motion in the infarct region between 1 and 6 months after acute myocardial infarction. This suggests that these patients have a larger amount of stunned myocardium in the infarct region.

Aged↗
PubMed1999

Relation of QT dispersion to infarct size and left ventricular wall motion in anterior wall acute myocardial infarction.

Previous studies have shown that QT dispersion increases during acute myocardial infarction (AMI). However, the relation of QT dispersion to infarct size and left ventricular (LV) function in AMI has not yet been fully clarified. Accordingly, this study was conducted to elucidate this relation at 1 month after anterior wall AMI. We examined 94 patients with first anterior wall AMI (< or = 6 hours) who underwent coronary arteriography at admission, 1 month, and 6 months after AMI, and left ventriculography at 1 and 6 months after AMI. Mean QT dispersion on the chronic phase (about 1 month after AMI) electrocardiogram was 79 +/- 33 ms. There were no significant correlations between QT dispersion and peak creatine phosphokinase levels, LV ejection fraction, and regional wall motion in the infarct region at 1 month after AMI (r = 0.06, p = 0.57; r = 0.11, p = 0.29; r = -0.05, p = 0.63, respectively). In conclusion, the findings of this study suggest that QT dispersion on the resting electrocardiogram at 1 month after anterior wall AMI is unrelated to infarct size estimated by the peak creatine phosphokinase level and the degree of LV dysfunction.

Aged↗
PubMed1999

Multistep denaturation of Borrelia burgdorferi OspA, a protein containing a single-layer beta-sheet.

Outer surface protein A (OspA) from the Lyme disease spirochete, Borrelia burgdorferi, is a dumbbell-shaped protein in which two globular domains are connected by a three-stranded beta-sheet segment that is solvent-exposed on both faces. Previous studies showed that the whole protein, including the single-layer beta-sheet, is highly rigid. To elucidate the folding mechanism and the role of the central beta-sheet in the formation of the rigid molecule, we investigated the equilibrium thermal denaturation reaction of OspA. We applied differential scanning calorimetry, heteronuclear NMR spectroscopy, and solution small-angle X-ray scattering (SAXS) to characterize the reaction in detail. All three techniques revealed that OspA denatures in two separable cooperative transitions. NMR measurements on OspA specifically 15N-labeled at Lys residues identified the locations of the two folding units and revealed that the C-terminal segment is less stable than the remaining N-terminal segment. The boundary between the two folding units is located within the central beta-sheet. The interconversion among the three folding states (fully folded, C-terminus unfolded, and fully denatured) is slow relative to chemical shift differences (<24 Hz), indicating that there are significant kinetic barriers in the denaturation reactions. SAXS measurements determined the radius of gyration of the native protein to be 25.0 +/- 0.3 A, which increases to 34.4 +/- 1.0 A in the first transition, and then to 56.1 +/- 1.6 A in the second transition. Thus, the intermediate state, in which the C-terminal folding unit is already denatured, is still compact. These results provide a basis for elucidating the folding mechanism of OspA.

Antigens, Surface↗
PubMed1999

Nitrosyl hemoglobin detected by near-infrared spectroscopy in rat liver allografts.

Near-infrared spectroscopy (NIRS) is a noninvasive biomeasurement system with rays in the near-infrared region that possess high permeability to biological tissues. NIRS was applied to liver allografts undergoing rejection in rats treated with deoxyspergualin (DSG) or tacrolimus (FK506). The nitrosyl hemoglobin (Hb) levels detected in the liver grafts increased 3 days and 5 days after grafting in both allogeneic and syngeneic transplantation. The levels on day 8 remained high in the allogeneic graft, but markedly decreased in the syngeneic graft. Although the serum levels of nitrite and nitrate were extremely low 8 days after grafting in allografted recipients treated with DSG or FK506, the nitrosyl-Hb level in DSG-treated graft was much higher than that in FK506-treated graft. There was no significant difference in survival time between DSG-treated and FK506-treated recipients. In conclusion, DSG and FK506 have a different effect on NO production in allografted liver with ongoing rejection, and circulating nitrite and /nitrate levels do not reflect the local levels of NO in the graft.

Animals↗
PubMed1999

A group of schwannomas with interstitial deletions on 22q located outside the NF2 locus shows no detectable mutations in the NF2 gene.

Schwannomas are tumors arising mainly at cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type2 (NF2). The NF2 gene has been cloned and comprehensive analysis of its mutations in schwannomas shows that up to 60% of tumors carry inactivating mutations. Thus, the genetic mechanism behind the development of more than 40% of schwannomas without NF2 mutations is unknown. We have therefore studied tumor tissue from 50 human schwannomas by allelotyping and have found chromosome 22 deletions in over 80% of the cases. We detected 14 cases (27%) that revealed partial deletions of one copy of chromosome 22, i.e., terminal and/or interstitial deletions. We sequenced the NF2 gene in seven of these tumors and detected only one case with mutations. The deletion mapping of chromosome 22 in tumors with partial deletions indicates that several regions, in addition to the NF2 locus, harbor genes involved in schwannoma tumorigenesis. Our findings suggest that heterogeneity in the mechanisms leading to the development of schwannomas probably exists. These findings are in agreement with the recent analysis of schwannomas from familial and sporadic cases of schwannomatosis and point to a possible role of an additional gene, which, in cooperation with the NF2 tumor suppressor, causes schwannomas.

Adolescent↗
PubMed1999

Immunohistochemical study of tyrosine phosphorylation signaling in Hassall's corpuscles of the human thymus.

Tyrosine phosphorylation signaling has been reported to play a key role in thymocyte development. However, the physiological role of signaling in thymus stroma is poorly understood, and there is lack of information on the in situ localization of elements of the signaling pathway in thymus stroma. In the present study, we have found by immunohistochemical analysis that tyrosine-phosphorylated proteins are present in high amounts in Hassall's corpuscles of the thymus medulla. Hassall's corpuscles represent end stages of maturation of thymic medullary epithelium. We have also investigated the localization of the src family that is involved in tyrosine phosphorylation signaling in Hassall's corpuscles. A member of the src family protein tyrosine kinases, p59fyn, was shown to be abundantly expressed in the outer layer of Hassall's corpuscles. Another member of the family, p60c-src, was highly expressed in the entire Hassall's corpuscles. Furthermore, p50csk and p130cas, both of which are involved in the pathway, were shown to be preferably expressed in the outer layer of Hassall's corpuscles. These findings suggest that tyrosine phosphorylation signaling may play a role in thymic medullary epithelial maturation and that the src family is involved in the process.

Child, Preschool↗
PubMed1999

Possible involvement of calcineurin, protein kinase C, and Src-family kinases in angiotensin II-induced tyrosine phosphorylation of p130cas in rat cardiac muscle.

Anigiotensin II (AII) has been documented to induce cardiac hypertrophy and rapid tyrosine phosphorylation of multiple intracellular substrates including 120 kD and 70 kD protein in cardiac cells. We have found that the 120 kD protein is a Crk-associated Src substrate, p130(cas). Specific inhibition of Src-family tyrosine kinases attenuated the AII-induced p130(cas) tyrosine phosphorylation. Either chelation of intracellular Ca(2+) or inhibition of protein kinase C resulted in the decrease of the phosphorylation. Further, we have investigated the relationship between the AII-induced p130(cas) tyrosine phosphorylation and a Ca(2+) and calmodulin dependent protein phosphatase calcineurin which is known to be involved in the signaling pathway of cardiac hypertrophy. Pretreatment with an immunosuppressant cyclosporin A, a specific inhibitor of calcineurin, resulted in the decrease of the phosphorylation. These findings strongly suggest that the AII-induced p130(cas) tyrosine phosphorylation might be associated with the signaling pathways of Src-family tyrosine kinases, protein kinase C and calcineurin in rat cardiac muscle.

Journal Article↗
PubMed1999

Haplotype analysis of a de novo allele at a vWF STR locus using flanking STR loci.

We have detected an unusual allele at the vWF-Kimpton (vWF-K) loci in the DNA of a child (genotype: 1415) in a paternity trio case. One allele of the child's DNA was found to derive neither from the mother (1214) nor from the putative father (1314), whose paternity was established not only by conventional polymorphic markers (probability 0.99999) but also by the other 10 STRs and the D1S80 and HLA DQ alpha loci. Two STRs flanking vWF-K comprise vWF haplotypes, which allow the parental origin of the unusual allele to be determined. Sequencing of clones encompassing the three STRs showed that the unusual allele segregated with the paternal haplotype. The de novo allele of the child thus seemed to be generated from the longer allele (14) by gaining a single unit (TCTA) through slippage replication.

Journal Article↗
PubMed1999

An improved method for the purification of stellate cells from rat liver with dichloromethylene diphosphate (CL2MDP).

Hepatic perisinusoidal cell population consists of hepatic stellate cells, Kupffer cells, endothelial cells, and Pit cells. These cells are isolated by enzymic digestion and purified by density gradient centrifugation. With isolation of stellate cells, conventional method is unable to eliminate the contamination of Kupffer cells because the densities of these two cells are similar. We report here an improved method for isolation of highly purified hepatic stellate cells, using dichloromethylene diphosphate (CL2MDP), which has selective cytotoxicity of Kupffer cells. Three days after the single intravenous administration of liposome-encapsulated CL2MDP, the Kupffer cells disappeared almost completely from the liver. Following Percoll density gradient centrifugation, the purity of the hepatic stellate cells exceeded 98% without any contamination of the Kupffer cells. Kupffer cells are reported to affect the physiological functions of stellate cells. The availability of highly purified stellate cells will facilitate the investigation of their functions in primary culture.

Animals↗
PubMed1999

Cutaneous papules and nodules in the diagnosis of the antiphospholipid syndrome.

Of 11 patients with primary or secondary antiphospholipid syndrome (APS), four exhibited papules or nodules on the finger, sole or leg as the initial cutaneous manifestation. Histological examination demonstrated thrombosed vessels or vessels containing organized thrombi in the dermis or in the subcutaneous fat tissue. Cutaneous papules and nodules should be recognized as skin manifestations of APS. Screening tests for antiphospholipid antibodies and lupus anticoagulant are required in patients with cutaneous papules or nodules of unknown aetiology. In cases of positive antiphospholipid antibodies and/or lupus anticoagulant, histological examination is critical in the establishment of the diagnosis of APS.

Adolescent↗
PubMed1999

Lung cancer in patients who had received thoracoplasty for pulmonary tuberculosis.

BACKGROUND: In Japan in the 1950s, thoracoplasty was a powerful therapy for pulmonary tuberculosis. Now there are many aged people who have tuberculosis sequelae caused by thoracoplasty. We have encountered some cases of lung cancer among these people. METHODS: To elucidate the features of lung cancer occurring after thoracoplasty for pulmonary tuberculosis, we reviewed for analysis 20 such cases. RESULTS: There were 17 men and three women, aged 55 to 78 years (mean 65 years). All had respiratory dysfunction and most were cigarette smokers. Lung cancers were located in the upper lobes in nine cases, in the middle lobe in one and in the lower lobes in 10. Ten lung cancers were in the thoracoplastied lung and the remaining 10 in the opposite lung. Histologically, squamous cell carcinoma was predominant (11 cases). Eight lung cancers were detected in stages I and II and 12 in stages III and IV. Most cancer lesions were separate from tuberculosis lesions. Surgical resection was selected in only three of 11 stages I-IIIA cases in consideration of respiratory dysfunction and/or ventilatory impairment due to thoracoplasty. Chemotherapy and/or radiotherapy were performed in nine and supportive care alone was performed in eight. Fourteen patients died of lung cancer and four died of cor pulmonale due to tuberculosis sequelae. Five-year survival was achieved in only one surgical case. Eight of the nine patients who received chemotherapy or radiotherapy died within 1 year, and, further, seven of eight patients who received supportive care died within 6 months. CONCLUSION: Lung cancer in the patients who had received thoracoplasty occurred in each lung and every lobe, independent of thoracoplasty. In addition, delay of detection was such that stage III-IV cases were in the majority, there were some limitations in therapeutic benefits related to thoracoplasty and the prognosis was very poor. Physicians should avoid delay in the detection of lung cancer through careful follow-up of such patients.

Aged↗
PubMed1999

Secondary structures and structural fluctuation in a dimeric protein, Streptomyces subtilisin inhibitor.

Based on the nuclear magnetic resonance assignments of a dimeric protein, Streptomyces subtilisin inhibitor (SSI), microscopic details of secondary structures in solution have been elucidated. The chemical shift index of C(alpha) signals, together with information on the hydrogen exchange rates of the backbone amide protons, were used to identify secondary structures. The locations of these secondary structures were found to be different in some critical points from those determined earlier by X-ray crystallography of the crystal. Notably, the beta3 strand is completely missing and the alpha2 helix is extended toward the C-terminus. Furthermore, hydrogen exchange experiments of individual peptide NH protons under strongly folding conditions revealed mechanisms of global and local structural fluctuation within the dimeric structure. It has been suggested that the global fluctuation of the monomeric unit occurs without affecting the accompanying monomer, in contrast to the equilibrium thermal unfolding, which is cooperative. Higher protection against hydrogen exchange for residues in part of the beta4 strand implies that this region might serve as a folding core.

Amino Acid Sequence↗
PubMed1999

The gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible: its role in cerebral ischemia.

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor-alpha (TGF-alpha) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the likelihood that HB-EGF is a neuroprotective factor in cerebral ischemia.

Animals↗