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Biomedical subjects

A Sakamoto

Publications and source records attributed to A Sakamoto.

At least 19 recordsLinked to original sources

Endothelin receptors in human parathyroid gland.

We studied whether specific receptors for endothelins (ETs) exist in human parathyroid tissues and whether ETs may have any effect on secretion of PTH from parathyroid cells. Binding studies using [125I]ET-1 to the parathyroid membranes obtained from patients with hyperparathyroidism (2 adenomas, 2 hyperplasias) revealed that ET-1 competitively inhibited the binding of [125I]ET-1 to the membranes (the apparent Kd: 62 +/- 18 pM), whereas ET-3 showed biphasic and less steep inhibition curve than ET-1 in all tissue membranes examined. Northern blot analysis of poly(A)+ RNA from the parathyroid adenoma clearly demonstrated gene expression of both ETA and ETB receptors as well as preproET-1. ET-1 inhibited basal PTH secretion from dispersed adenoma cells more potently than ET-3. The present study clearly demonstrates the presence of both ETA and ETB receptor subtypes in human parathyroid tissues through which ETs may modulate PTH secretion in an autocrine and/or paracrine manner.

Adenoma

Genomic structure of the gene for copper/zinc-superoxide dismutase in rice.

We have isolated and determined the nucleotide sequence of the structural gene (sodB) coding for one of the copper/zinc-superoxide dismutase (Cu/Zn-SOD) isozymes from rice plants (Oryza sativa L.). The sodB gene is split into 8 exons spread about 2 kb of the chromosomal DNA, with the coding sequence beginning in the 2nd and ending in the 8th. Although none of sodB introns are inserted into similar positions in Cu/Zn-SOD genes from other sources, four of six introns in the protein-coding region are located at discriminating positions within structural domains of the protein. Genomic Southern analysis indicated that cytosolic Cu/Zn-SOD is coded for by 2-3 genes in the rice genome.

Amino Acid Sequence

Highly conserved hexamer, octamer and nonamer motifs are positive cis-regulatory elements of the wheat histone H3 gene.

Base substitution mutations were introduced into the promoter region of the wheat histone H3 gene, and promoter activity was assayed in stably transformed sunflower calli or in wheat protoplasts transfected transiently. At least four positive regulatory elements, a hexamer motif (ACGTCA), two octamer(-like) motifs of a direct (CcCGGATC) and a reverse (aATCCGCG) form, and a nonamer motif (CATCCAACG) were identified within the -185 region of the H3 promoter. Analyses of the type I element (CCACGTCACCaATCCGCG) consisting of the hexamer and reverse-oriented octamer motifs, and which is conserved in other plant histone genes as well, predicted the presence of an octamer-binding protein(s).

Base Sequence

Concomitant expression of receptor subtype and isopeptide of endothelin by human adrenal gland.

We studied whether specific receptors for endothelin (ET) isopeptide exist in human aldosterone-producing adenoma and normal adrenal cortex, and whether ET isopeptides are produced by human adrenal gland. Competitive binding studies using [125I]ET-1 as a radioligand revealed the presence of a single class of high-affinity binding sites for ET-1 with the apparent KD of 70 +/- 31 pM and Bmax of 226 +/- 139 fmol/mg protein in adenoma membranes almost comparable to those in adjacent normal cortex. The apparent Ki for ET-2 and ET-3 were 89 +/- 33 pM and 82 +/- 16 pM, respectively. Northern blot analysis of poly(A)+ RNA of adenoma and adjacent normal cortex using cDNAs for ET receptor subtype (ETA, ETB) and ET isopeptide (ET-1, ET-3) as probes revealed that ETA and ETB receptors as well as ET isopeptides (preproET-1, preproET-3) are concomitantly expressed in both tissues. Our data demonstrate for the first time that ET receptor subtype (ETA and ETB) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by human adrenal cortex, suggesting the potential role of ETs as a local mediator in human adrenal gland.

Adenoma

T cell receptor V beta repertoire of double-negative alpha/beta T cells in patients with systemic sclerosis.

OBJECTIVE: To analyze the T cell receptor V beta gene on double-negative (DN) alpha/beta T cells, which are increased in number, on peripheral blood lymphocytes (PBL) from patients with systemic sclerosis (SSc). METHODS: The DN alpha/beta T cells were sorted by flow cytometry from PBL obtained from 3 patients with SSc. The V beta repertoire was analyzed by polymerase chain reaction. RESULTS: Only 1 or 2 V beta genes (V beta 5/7, 5, or 17) were predominantly expressed on DN alpha/beta T cells from these 3 patients. CONCLUSION: The V beta repertoire on DN alpha/beta T cells in PBL from patients with SSc is rather restricted.

Base Sequence

Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells.

The present study was undertaken to clarify the relationship between c-fos and c-jun protooncogene expression and the differentiation and/or proliferation of osteoblasts, using osteoblast-like MC3T3-E1 (E1) cells. c-fos mRNA was barely detectable, whereas c-jun mRNA was constitutively expressed in E1 cells after serum deprivation for 24-72 h. When serum was added, a rapid and transient induction of c-fos and c-jun mRNAs was observed. The c-fos and c-jun mRNAs reached peak levels at 30 minutes, with a rapid disappearance of c-fos mRNA within 3 h and a much slower decrease in c-jun mRNA. The addition of serum together with cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both c-fos and c-jun mRNAs. Among various growth factors, PDGF, EGF, and bFGF mimicked the serum effect, whereas IGF-I and TGF-beta failed to induce c-fos and c-jun mRNA. The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism. Nuclear runoff experiments showed that the transcription rate of c-fos and c-jun protooncogenes was increased by serum and growth factors. The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Inhibition of lipid peroxidation by prostaglandin oligomeric derivatives.

The inhibition of lipid peroxidation by oligomeric derivatives synthesized from prostaglandin E1 (PGE1) and PGB2 was studied using two rat models. In an in vitro model, the brain was exposed to decapitation-ischemia, the cortex was removed and homogenized, and the formation of thiobarbituric acid reactive substances (TBAR) was measured after exposing the homogenate to in vitro reoxygenation either in the presence or absence of oligomers. It was found that these oligomers could inhibit lipid peroxidation, and that their activities were higher than that of superoxide dismutase (SOD). In an in vivo administration model, either the oligomer or the vehicle was injected i.p. 30 min before decapitation. The brain was exposed to decapitation-ischemia, the cortex was homogenized and exposed to 'in vitro' reoxygenation, after which TBAR value was determined. Ester-type compounds had a greater activity than free-acid type compounds in inhibiting lipid peroxidation. A possible mechanism of the protective effect of these oligomers in ischemia/reperfusion injury may be to scavenge oxygen free radicals.

Alprostadil

Predominant expansion of V gamma 9/V delta 2 T cells in a tularemia patient.

We describe a 58-year-old man with tularemia and expanding gamma delta T cells in his peripheral blood lymphocytes (PBL) (32.7% of total PBL). In the present work, we analyzed the T-cell receptor V gamma/V delta repertoire of these cells by making use of the polymerase chain reaction and flow cytometry and found that they were mostly CD4- CD8- CD3+ V gamma 9/V delta 2+. The sequence analysis of 16 cDNA clones encoding the V gamma 9-J region revealed that the V gamma 9-Jp combination was strikingly overrepresented but that the junctional (N) region was heterogeneous. This suggested that the gamma delta T cells in PBL from a patient with tularemia were polyclonally expanded.

Base Sequence

Lobenzarit disodium (CCA) inhibits in vitro immunoglobulin production via direct interaction with B lymphocytes.

The regulatory effects of lobenzarit disodium (CCA), a therapeutic agent for treating rheumatoid arthritis (RA), on polyclonal immunoglobulin production by human lymphocytes were investigated in vitro. CCA inhibited the production of immunoglobulin in all the classes examined at a clinically relevant concentration. Moreover, it inhibited the immunoglobulin production as well as lymphocyte proliferation even when purified B lymphocytes preactivated by Staphylococcus aureus COWAN I were cultured with recombinant lymphokines such as IL2 and IL6. These results suggest that CCA acts directly on B lymphocytes. The analysis at each of two different stages of B lymphocyte activation lineage, i.e., the primary activation stage and a stage of proliferation and differentiation to antibody secreting cells, has indicated that CCA inhibits the proliferation-differentiation stage of B lymphocytes. CCA does not inhibit B lymphocytes at the primary activation stage; actually, it augments them, resulting in the subsequent enhancement of immunoglobulin production.

Adult

A rare case of extramedullary plasmacytoma in the mediastinum.

A rare case of extramedullary plasmacytoma in the mediastinum is reported. An 80-year-old man was admitted for further examination of a mediastinal tumor. Chest computed tomography (CT) revealed a large mediastinal mass and right interlobar pleural effusion. Needle biopsy under CT guidance established a diagnosis of plasmacytoma. Immunohistochemical staining revealed that the tumor cells were producing monoclonal IgA kappa. Serum immunoelectrophoresis revealed an IgA kappa monoclonal component with a serum concentration of 5,040 mg/ml. The bone marrow aspiration was normal. Bone roentgenogram and bone scintigram showed osteoporosis but no neoplastic lesion.

Aged

[ESR study of free radical formation during ischemia-reperfusion injury in the rat brain and the protective effect of a new antioxidant].

By using the spin-trapping technique and electron spin resonance spectroscopy (ESR), we detected directly oxygen-derived free radicals in the brain exposed to ischemia and reperfusion. Forebrain ischemia was produced in the rat by bilateral occlusion of the common carotid arteries combined with hemorrhagic hypotension. The whole cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-alpha-phenylnitrone, followed by a Folch extract. Spin-adducts were detected using ESR. As the index of tissue injury, the lipid peroxidation was estimated from both the amount of thiobarbituric acid reactive substance and the formation of conjugated diene. After 10 or 20 min of ischemia, reperfusion induced a burst of spin adduct formation which peaked at 5 min reperfusion time. The peak value increased with the ischemia time. The degree of lipid peroxidation, which was measured after 20 min of reperfusion, also increased with the ischemia time. When the oligomeric derivative was administered (9 mg . kg-1, i.p.) 30 min before ischemic insult, both spin adduct formation and lipid peroxidation were reduced. The results support the current view that free radicals produced upon reperfusion may be the direct cause of the subsequent lipid peroxidation.

Animals

[Selection of graft materials in case of emergency coronary bypass surgery following failed angioplasty].

The clinical characteristics of selection of graft materials were analysed for patients undergoing emergency coronary artery bypass surgery (CABG) following failed coronary angioplasty (PTCA). Ten emergency CABGs were performed from January 1983 to December 1991. Perioperative variables and follow-up were compared to 18 patients undergoing elective CABG after PTCA. The emergency group had shorter operative time (p less than 0.01) and shorter bypass time (p less than 0.05). Moreover the emergency group had decreased use of the internal thoracic artery (ITA) (40% vs 94.4%, p less than 0.01). There was no use of bilateral ITAs in the emergency group. There was not significant difference in hospital mortality and medium term follow-up between two groups. In conclusion, emergency CABG carries a significantly less use of ITA graft than elective CABG although ITAs are superior to SVGs about long term patency rate. So it is desirable that arterial graft should be used under an appropriate selection at emergency operation.

Aged

[A 14-year-old with pulmonary hamartomatous lymphangiomyomatosis associated with bilateral pneumothoraces].

A 14-year-old girl was admitted because of cough, chest pain and hemosputum. Chest roentgenogram on admission showed a pneumothorax and a cavitary lesion with niveau formation in the right lung and cystic lesions in the bilateral lung fields. After bed rest and intravenous administration of antibiotics for two weeks, the right lung inflated well and the niveau formation disappeared, and the patient was discharged. One week later, she was readmitted with sudden-onset severe dyspnea, caused by bilateral pneumothoraces. Emergency tube thoracostomy and wedge resection of the bullous lesion was performed. Macroscopically, multiple small cystic changes were seen on the surface of the right lung. Histological examination revealed nodular proliferations of smooth muscle cells in the interstitium and vessel walls in the lung, which contained slit-like lymphatic channels. The diagnosis of pulmonary lymphangiomyomatosis was made. In this case, we could not measure receptors for estrogen and progesterone. Recently, hormonal therapy and oophorectomy have been reported as being useful. Tamoxifen (Norvadex) was therefore initiated, and the patient has remained well with slight dyspnea on exertion. There has been no recurrence of pneumothorax. Lymphangiomyomatosis is a rare disease of unknown etiology which occurs exclusively in women, mostly in those of reproductive age. We report a 14-year-old female patient with lymphangiomyomatosis associated with repeated pneumothorax, who had been under treatment for epilepsy. We believe this case to be of importance because of the long discussed relation between pulmonary lymphangiomyomatosis and tuberous sclerosis.

Adolescent

[A case of pulmonary fibrosis in which inhibition of pulmonary vasoconstriction was detected using DSA pulmonary wedge angiography].

A 65-year-old man was admitted to our hospital complaining of productive cough and dyspnea on exertion. X-ray films and CT scan of the chest disclosed diffuse reticular shadows, especially in the bilateral lower lung fields. Blood gas analysis showed severe hypoxemia. Pulmonary function test disclosed severe restrictive pattern. From these findings, the patient was thought to have pulmonary fibrosis. Right heart catheterization showed pulmonary hypertension. To evaluate the pulmonary vascular bed, we performed DSA pulmonary wedge angiography. The pulmonary capillary phase stained homogeneously in normal subjects. However, in the present case, filling of the right pulmonary A9 was incomplete and capillary bed staining was decreased under room air condition. After breathing 5 L/min oxygen for 20 min., the A9 was filled well and capillary bed staining was increased. We consider that this change was induced by inhibition of hypoxic pulmonary vasoconstriction (HPV) by oxygen. DSA pulmonary wedge angiography was useful for visual evaluation of HPV.

Aged

[A case of pulmonary adenocarcinoma in a young man with multiple metastasis to the nasopharynx and paranasal sinuses].

A 36-year-old man who complained of bloody sputum showed a mass-like shadow in the right upper lung field on chest X-ray, which was diagnosed as adenocarcinoma by sputum cytology in August, 1990. Since his clinical stage was too advanced for curative operation, chemotherapy was started on October 1, 1990. On October 26, he brought up a polyp-like mass, and was found to have polypoid tumors on the bilateral tonsils and nasopharynx, which were biopsied and diagnosed as poorly-differentiated adenocarcinoma. On November 21, CT of the face showed soft tissue density tumors in the bilateral paranasal sinuses. According to the clinical course, all tumors were thought to be metastatic lesions. Since he had suffered from epistaxis and nasal obstruction due to the enlargement of metastatic tumors, nebulization chemotherapy and palliative resection were performed. In February 1991, he developed severe headache due to brain metastasis. Despite irradiation therapy, he died from cerebral intra-tumorous hemorrhage on February 22. We reported a rare incurable case of lung cancer with metastasis to the nasopharynx and paranasal sinuses.

Adenocarcinoma

Abnormalities of the autonomic nervous system of the duodenum in streptozotocin-induced diabetic rats.

The changes in sensitivity of the rat duodenum to ATP were examined in preparations from control rats and from rats with streptozotocin (STZ)-induced diabetes. ATP was able to relax the duodenum of control animals in a concentration-dependent manner and this relaxation was significantly increased in STZ-diabetic rats. In preparations from diabetic rats, relaxation responses to ATP were greater than those of age-matched control groups. These results suggest that functional changes or degeneration of non-adrenergic, non-cholinergic nerves in the myenteric plexus may occur in STZ-diabetic rats, and that these alterations may result in the increased sensitivity of the relaxation of the duodenum to ATP.

Adenosine Triphosphate

Cloning and functional expression of human cDNA for the ETB endothelin receptor.

We report the cloning of human cDNA encoding an ETB (non-isopeptide-selective) subtype of the endothelin receptor. The predicted amino acid sequence of the human ETB endothelin receptor was 87.8% and 62.9% identical with the previously cloned rat ETB and ETA receptors, respectively. COS cells transiently transfected with the cloned cDNA expressed specific, high-affinity binding sites for endothelin isopeptides and responded to the peptides with a transient increase of [Ca2+]i; endothelin-1 and endothelin-3 exhibited approximately equal potencies both in displacing 125I-labeled endothelin-1 binding and in eliciting [Ca2+]i transients. The ETB receptor mRNAs were expressed in various human tissues and also in the intact porcine aortic intimal cells ex vivo.

Amino Acid Sequence