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Biomedical subjects

T Sawamura

Publications and source records attributed to T Sawamura.

At least 91 records · Page 5Linked to original sources
PubMed1997

Processing of proendothelin-1 at the C-terminus of big endothelin-1 is essential for proteolysis by endothelin-converting enzyme-1 in vivo.

Production of endothelin-1 is thought to be a three-step process consisting of an initial proteolytic cleavage of the proendothelin-1 precursor to big endothelin-1-Lys-Arg, C-terminal trimming by a carboxypeptidase and further processing of the big endothelin-1 peptide to endothelin-1 by endothelin-converting enzyme (ECE). To further clarify the mechanism of processing in the biosynthesis of endothelin-1, we introduced a point mutation into endothelin-1 cDNA to replace the Arg in the -4 position of the recognition motifs of furin-like convertase in human preproendothelin-1 (Arg49 or Arg89) by Gly. When mutant cDNAs were expressed in Chinese hamster ovary (CHO)-K1 cells, they failed to be processed at the mutated processing signal, suggesting that the Arg-Ser-Lys-Arg motifs of preproendothelin-1 are recognized by CHO-K1 furin-like convertase. Co-transfection with ECE-1 cDNA revealed that cleavage at Arg52 is not essential for cleavage by ECE-1, but that cleavage at Arg92 is critical. Although a high-molecular-mass form of endothelin-1 is produced by processing by ECE-1 without cleavage at Arg52, it did not evoke Ca2+ transient in endothelinA-receptor-expressing cells. In conclusion, prior cleavage at Arg92 by furin-like convertase is absolutely necessary for cleavage by ECE-1 at Trp73 to produce mature endothelin-1.

Amino Acid Sequence↗
PubMed1997

Physiological role of Ca2+-permeable nonselective cation channel in endothelin-1-induced contraction of rabbit aorta.

We previously showed a role for a nonselective cation channel (NSCC) in the ETA-dependent action of endothelin-1 in mouse fibroblast and rabbit aortic smooth-muscle cell. To clarify the physiological significance of NSCCs in endothelin-1 (ET-1)-induced vasocontraction, we examined the effects of NSCC blockers such as mefenamic acid and SK&F 96365 on the contractions of deendothelialized rabbit aortic rings induced by a low (10[-10] M) or high (10[-8] M) concentration of ET-1. Mefenamic acid (< or =10[-3] M) had little effect on the contraction induced by 45 x 10(-3) M K+ or 1 x 10(-6) M Bay K-8644 in combination with 15 x 10(-3) M K+, indicating that it does not affect voltage-operated calcium channels (VOCs) and contractile mechanisms. The contraction by a low concentration of ET-1 was abolished after removal of extracellular Ca2+, but it was reduced only to 50% by a maximally effective concentration (10[-5] M) of nifedipine, an inhibitor of L-type VOCs (L-VOC). Mefenamic acid and SK&F 96365 inhibited the ET-1-induced contraction with 50% inhibitory concentration (IC50) values of 10(-4) M and 2 x 10(-5) M, respectively, and abolished it at 10(-3) M and 10(-4) M. By contrast, nifedipine, mefenamic acid, or SK&F 96365 had little effect on the contraction by a high concentration of ET-1. The contraction induced by a low or high concentration of ET-1 was abolished by an ETA antagonist, BQ-123, but not by an ETB antagonist, BQ-788. These results demonstrate that the contraction induced by ET-1 is totally mediated exclusively by ETA, but that Ca2+ entry through NSCCs in addition to L-VOCs plays an important role in contractions induced by low concentrations of ET-1, whereas it plays only a minor role in contractions induced by high concentrations of ET-1.

Animals↗
PubMed1996

Chromosomal anomalies in cryptorchidism.

Chromosome analysis was performed in 160 patients with cryptorchidism. Chromosomal anomalies were found in 7 patients (4.4%). The incidence of chromosomal abnormalities was not significantly different between patients with bilateral or unilateral cryptorchidism. Of 7 patients, 1 had sex chromosomal aberration, 2 had marker chromosome and 4 had autosomal anomalies. Additional congenital anomalies were observed in 1 with sex chromosomal aberration, 2 with marker chromosome and 2 with autosomal anomaly. These facts indicate that we had better perform chromosome analysis in all patients with bilateral or unilateral cryptorchidism.

Adolescent↗
PubMed1996

Successful embolization of a renal artery aneurysm with preservation of renal blood flow.

A 76-year-old man with renal artery aneurysm was successfully treated by transcatheter embolization with complete preservation of renal blood flow. Embolization was performed with detachable platinum coils. Two months later, follow-up angiography showed completely packed aneurysm and preserved blood flow of the branch. It may be reasonable to consider that embolization of the aneurysm is the primary treatment modality for some of the patients with renal artery aneurysm.

Aged↗
PubMed1996

Derivative Y chromosome resulting from a t(Y;15) (q12;q11.2) in a boy with Prader-Willi syndrome.

Chromosome analysis of peripheral lymphocytes from a boy with Prader-Willi syndrome showed the presence of 45 chromosomes, including der(Y) resulting from a t(Y;15) (q12;q11.2). In situ hybridization using DYZ3 and D15S11 showed a positive signal and negative signal in derivative Y chromosome, respectively. The deficiency of 15pter q11.2 may not influence the clinical manifestation of Prader-Willi syndrome.

Child, Preschool↗
PubMed1996

Malacoplakia of the bladder: efficacy of enoxacine therapy.

Malacoplakia of the urinary bladder was seen in a 69-year-old woman with haematuria. We firstly treated her with distigmine bromide, ascorbic acid and trimethro-prim-sulfamethoxazole. Haematuria subsided but the lesion did not change after 6 weeks. Thereafter we tried enoxacine therapy. Eight weeks after the medication the tumorous lesion disappeared. Bladder biopsy performed 4 months after the initiation of the treatment revealed predominantly granulation tissue. We can find no previous case treated successfully with long-term enoxacine.

Aged↗
PubMed1996

Effective hyperbaric oxygenation with prostaglandin E1 for radiation cystitis and colitis after pelvic radiotherapy.

Gross haematuria and severe bleeding from the large intestine occurred after pelvic radiotherapy in an 84-year-old woman with cancer of the uterus. Hyperbaric oxygenation treatment at 2 atmospheric absolute pressures for 60 minutes daily over 30 days and infusion of prostaglandin E1 abolished completely haematuria and tarry stool, and reversed the endoscopic findings of radiation cystitis and colitis.

Aged↗
PubMed1996

Human endothelin converting enzyme gene (ECE1) mapped to chromosomal region 1p36.1.

The chromosomal localization of the human endothelin converting enzyme gene (ECE1) has been identified. Southern blot analysis of human genomic DNA from human x mouse somatic cell hybrids demonstrated that ECE1 maps to chromosome 1. Fluorescence in situ hybridization of a digoxigenin-labeled human ECE1 probe to normal human metaphase chromosomes showed that the gene is located within chromosome band 1p36.1.

Animals↗
PubMed1996

Role of dopamine in the striatum, renin-angiotensin system and renal sympathetic nerve on the development of two-kidney, one-clip Goldblatt hypertension.

PURPOSE: The possible role of the striatum and renin-angiotensin (R-A) system for the development of two kidney-one clip (2K-1C) Goldblatt hypertension is examined. MATERIALS AND METHODS: Monoamine contents of the striatum were determined by brain dialysis techniques, and plasma and kidney levels of the R-A system were measured by radioimmunoassay in sham-operated rats (experiment 1), 2K-1C hypertension (experiment 2), left renal denervation only (experiment 3), renal denervation of left clipped-kidney (experiment 4) and left renal artery clipping with renal denervation of right nonclipped kidney (experiment 5) in the acute phase. RESULTS: Plasma angiotensin I (ANG I) and plasma angiotensin II (ANG II) were initially increased between the first day and the first week, were suppressed at the second week, then increased again at the third week. Renal denervation of clipped or nonclipped kidneys did not influence the plasma R-A system in 2K-1C rats. The levels of striatum dopamine (DA), dihidroxyphenylacetic acid (Dopac) and homovanillic acid (HVA) in hypertensive 2K-1C rats were higher than those in normotensive sham-operated rats. There were significant positive relationships between these monoamines and systolic blood pressure. Renal levels of ANG I, II and angiotensin I converting enzyme activity (ACE) in the clipped-kidney were significantly higher than in sham-operated and nonclipped kidneys of 2K-1C rats. CONCLUSION: The enhanced R-A system in clipped-kidney and high levels of monoamines described above in the striatum appear to participate in the development of 2K-1C hypertensive rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Processing of proendothelin-1 by human furin convertase.

Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The peptide is initially synthesized as an inactive precursor (proET-1) which undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1. Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET-1 by furin, a mammalian convertase involved in precursor processing, produced bigET-1. Upon further processing, bigET-1 was converted to biologically active ET-1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-Val-Lys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.

Amino Acid Chloromethyl Ketones↗
PubMed1995

Serum concentration of iopamidol after retrograde urethrography in male patients with outlet obstructive symptoms.

Serum concentration of iopamidol was measured in 29 male patients with outlet obstructive symptoms after retrograde urethrography. Although no patient showed extravasation, serum iopamidol level was detectable in 4 (14%) patients. Since severe adverse effects are considerably reduced with iopamidol, we prefer to use this contrast medium for retrograde urethrography in male patients with outlet obstructive symptoms.

Aged↗
PubMed1995

Changes in serum levels of prostatic acid phosphatase and prostate specific antigen after luteinizing hormone-releasing hormone analogue administration in patients with metastatic prostatic cancer in relation to glandular differentiation.

Eighteen previously untreated patients with metastatic carcinoma of the prostate were treated with LHRH analogue. They were divided into 3 groups according to the degree of glandular differentiation. In all groups, a transient rise of PAP and PSA was observed after the LH and testosterone surge. However, relative values of LH, testosterone, PAP and PSA did not differ significantly among the 3 groups. These facts suggest that a transient rise of PAP and PSA is caused by testosterone surge independently from the degree of glandular differentiation after LHRH analogue administration in patients with advanced prostatic cancer.

Acid Phosphatase↗
PubMed1995

Ultrastructure of Leydig cells in Down's syndrome.

Hormonal and ultrastructural examinations of the testis were performed in a patient with Down's syndrome. Plasma testosterone was abnormally low, and circulating levels of LH and FSH were higher than the normal range. The administration of HCG resulted in a low response of plasma testosterone. Electron microscopy revealed proliferation of smooth endoplasmic reticulum, an increase in paracrystalline inclusions and the absence of Reinke's crystals in Leydig cells.

Adult↗
PubMed1995

Nuclear DNA ploidy pattern and tissue levels of dihydroxyphenylalanine and catecholamines in pheochromocytoma.

Flow-cytometric analysis of nuclear DNA and measurements of tissue levels of dihydroxyphenylalanine (dopa) and catecholamines were performed using fresh samples of tissue taken from 17 patients with pheochromocytoma. Nine (53%) tumors had a diploid pattern of DNA, and 8 (47%) had an aneuploid pattern. The tissue concentrations of dopa, dopamine, norepinephrine, and epinephrine did not differ significantly between pheochromocytomas with a diploid and those with an anoeuploid pattern. These results suggest that there is no correlation between nuclear DNA ploidy and tissue levels of dopa and catecholamines in pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1995

Cryptorchidism and marker chromosomes: identification of marker chromosomes by fluorescence in situ hybridization.

Identification of marker chromosomes by fluorescence in situ hybridization was performed in 2 cases of cryptorchidism. In case 1, the marker chromosome was derived from chromosome 22. In case 2, the origin of the marker was the centromere of chromosome 8. The extent of the congenital anomalies in these cases was milder than that in cases with complete trisomy of an autosome. These findings suggest that an incomplete extra autosome might influence clinical characteristics.

Adolescent↗
PubMed1994

cDNA cloning and expression of bovine endothelin converting enzyme.

We have cloned cDNA encoding bovine endothelin converting enzyme (ECE). The predicted amino acid sequence of bovine ECE consisted of 758 amino acid residues. Northern blot analysis revealed that ECE mRNA was abundantly expressed in lung. Co-expression of the cloned cDNA of bovine ECE with human preproET-1 cDNA in CHO-K1 cells resulted in the production of mature ET-1 and this production was inhibited by phosphoramidon.

Amino Acid Sequence↗
PubMed1994

Genetic transfer of endothelin converting enzyme activity to CHO-K1 cells: detection of positive cells by reverse hemolytic plaque assay.

We have established a novel method of molecular cloning of endothelin converting enzyme, a key enzyme in the production of a potent vasoconstrictor endothelin-1, by modification of the reverse hemolytic plaque assay. Also, we demonstrated that a cell line, CHO-K1, showed no detectable activity of endothelin converting enzyme. This cell line was transfected with a cDNA library of bovine endothelial cells. The modified reverse hemolytic plaque assay was shown to detect even a single CHO-K1 cell that was changed to produce mature ET-1 by transfection. Thus, this novel method is suggested to be useful for the molecular cloning of other secreted antigens and their processing enzyme.

Animals↗