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T Okada

Publications and source records attributed to T Okada.

At least 19 recordsLinked to original sources

An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin-1(11-21)

In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21), IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ETA receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is therefore, considered to be the first antagonist selective to the ETB receptor.

Amino Acid Sequence

A reversible radioligand specific for the ETB receptor: [125I]Tyr13-Suc-[Glu9,Ala11,15]-endothelin-1(8- 21), [125I]IRL 1620.

Suc-[Glu9,Ala11,15]-endothelin(ET)-1(8-21), IRL 1620, is a linear ET-analog specific for the ET-isopeptide-nonselective ETB receptor. The radio-iodinated analog, [125I]IRL 1620, showed a single class of saturable binding to the ETB receptors in porcine lung membranes with a Kd of 18 pM and a Bmax of 930 fmol/mg protein, which are almost comparable to the values obtained with [125I]ET-3 (6 pM and 900 fmol/mg protein). In competitive binding assays with [125I]IRL 1620, unlabeled ET-1, ET-3, IRL 1620 and [monoiodo-Tyr13]-IRL 1620 showed almost identical displacement curves with Ki of 8 to 16 pM. However, [125I]IRL 1620 was dissociated from the binding sites by addition of an excess amount (100 nM) of any of these unlabeled peptides, each with the same t1/2 of 100 min. This was in marked contrast to [125I]ET-3 which was hardly dissociated from the binding sites.

Animals

A rare case of serous cystadenocarcinoma of the pancreas.

Serous cystadenocarcinoma of the pancreas, a rare disease, developed in a 63-year-old Japanese woman. Pathologic examinations of the pancreatic tumor at the subtotal pancreatectomy showed it to be serous cystadenoma with focal atypical lesions. Three years after the operation, however, metastatic liver nodules were found, and the histologic characteristics of these lesions were quite similar to those of the pancreatic neoplasm. Both primary and metastatic tumors were composed of multiple cysts separated by fibrous septa. The epithelium of cysts was cuboidal and had clear cytoplasm, which had positive results for periodic acid-Schiff (PAS) and negative results for PAS with diastase, Alcian blue, and mucicarmine. To the knowledge of the authors, serous cystic neoplasms of the pancreas have been uniformly benign in biologic behavior. Recently, however, serous cystadenocarcinoma of the pancreas has been reported as a new entity. The current case is the second reported case and might support the existence of serous cystadenocarcinoma of the pancreas.

Cystadenocarcinoma

Genetic regulation of CD5+ B cells in autoimmune disease and in chronic lymphocytic leukemia.

CD5+ B cells have attracted much attention, because of their involvement in both autoimmunity and B cell-type chronic lymphocytic leukemia (B-CLL). B-CLL is a type of leukemia most often occurring among close relatives and is partly associated with the major histocompatibility complex (MHC), a finding relevant to autoimmune disease. We established MHC (H-2)-congenic NZB x NZW (NZB/W) F1 mice (H-2d/z, H-2z/z, and H-2d/d), in that only H-2d/z heterozygotes developed severe SLE, associated with IgG anti-DNA antibodies, as the animals aged. Such age-associated changes occurred in parallel with the decrease in the splenic, but not peritoneal, CD5+ B cells. By contrast, H-2z/z homozygotes did not develop SLE but, in turn, a marked clonal proliferation of CD5+ B cells resembling B-CLL did occur. H-2d/d homozygotes also did not develop the typical SLE, and a moderate CD5+ B frequency persisted. Despite the finding that all the three H-2-congenic NZB/W F1 strains produced IgM anti-DNA antibodies, only the H-2d/z heterozygotes produced IgG antibodies. Whereas the surface phenotype of major IgM producers was CD5+ sIgM+, that of IgG producers was CD5-sIgM-. Genetic and cellular analyses supported our thesis that in the heterozygotes IgM to IgG isotype switching probably emerges in CD5+ B cells and that this event is associated with the loss of CD5 molecules. Because of the lack of genetic elements required for differentiation, only signals for proliferation would be functioning in CD5+ B cells in the H-2z/z homozygotes. These observations infer that certain different, but related, MHC haplotypes may predispose either to B-CLL or to autoimmune disease in close relatives.

Animals

[Cystic falx meningioma: report of a case with difficulty in radiologic diagnosis].

A case of cystic falx meningioma in the frontal region in which preoperative neuroradiologic diagnosis was difficult is reported. This 33-year-old man had suffered from epileptic seizures three times in one month. Physical and neurological examinations on admission were normal. A cystic mass with a small nodule was found on CT in the frontal region. Thin wall was enhanced smoothly and the nodule attached to the falx was enhanced heterogeneously. The mass was considered to be an extra-axial lesion on MRI. The right anterior falcine artery seemed to feed the mass. Bifrontal craniotomy was performed. Cyst was evacuated, and a soft reddish mass was subtotally removed. Cyst fluid was yellowish and protein content was 3.5 g/dl. Histopathological diagnosis was a meningotheliomatous meningioma and tumor cells were present also in the thin cyst wall. At the second operation the mass was completely removed, cyst wall inclusive. When we encounter a cystic mass in the sites of predilection of meningiomas, we have to consider the possibility of a cystic meningioma. If the mass has meningeal vascularization, a correct diagnosis is not difficult. Taking the location of the mass into consideration, an accurate interpretation of CT and MRI findings indicating extra-axial nature of the mass is indispensable.

Adult

A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor.

A series of C-terminal linear peptides of endothelin (ET)-1 and their N alpha-succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ETA and ETB, in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu9,Ala11,15]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ETB receptor (KiETA/KiETB approximately equal to 120,000) as judged by the Ki values for ETA (1.9 microM) and ETB (16 pM) receptors. IRL 1620 was 60 times more selective for the ETB receptor than ET-3 (KiETA/KiETB approximately equal to 1,900). IRL 1620 (10(-9)-10(-7) M) induced contractions of the guinea pig trachea with a comparable potency to those of ET-1 or ET-3, suggesting that IRL 1620 is a potent ETB receptor agonist.

Amino Acid Sequence

Endothelin stimulates both cAMP formation and phosphatidylinositol hydrolysis in cultured embryonic bovine tracheal cells.

Embryonic bovine tracheal (EBTr) cells were found to possess receptors for endothelin (ET) of ET-1-selective (ETA) subtype with a Kd for ET-1 of 114 pM and a Bmax of 12.9 fmol/10(5) cells. Stimulation of EBTr cells with 100 pM to 100 nM ET-1 increased the contents of both inositol phosphates and cAMP in a concentration-dependent manner, indicating that the receptors are coupled to both phosphatidylinositol hydrolysis and cAMP formation in EBTr cells.

Animals

Autocrine receptors for endothelins in the primary culture of endothelial cells of human umbilical vein.

Human umbilical vein endothelial cells (HUVECs) in primary culture produced and secreted endothelin 1 (ET-1) actively. Specific binding of [125I]ET-1 to these cells was not detectable because of the saturation of ET receptors with endogenously produced ET-1. However, addition of phosphoramidon, an inhibitor of ET-converting enzyme, to the medium reduced the production of ET-1 and thus the receptors on HUVECs were made available for exogenously added [125I]ET-1. Binding studies using phosphoramidon-treated HUVECs indicated the existence of a non-isopeptide-selective type (ETB) of ET receptor with a Kd of 17 pM. This receptor is thought to be involved in ET-induced vasodilation in an autocrine manner in vivo.

Binding Sites

In vitro and in vivo digestion of collagen covalently immobilized onto the silicone surface.

In order to study the in vivo digestion of immobilized collagen and gelatin, these proteins labeled with 125I or fluorescein isothiocyanate (FITC) were covalently immobilized onto silicone surfaces, which were grafted with acrylic acid to introduce carboxyl groups, and implanted subcutaneously in rats and mice. When the proteins were labeled with FITC, the amount of proteins immobilized decreased with the increase of the number of FITC molecules conjugated with the protein molecule. In the wet state, FITC conjugated with the proteins was less stable than 125I. Approximately half of the amount of the immobilized proteins was digested in vivo within the first week and until 5 weeks after implantation the proteins were gradually digested. At that time, the amount of the proteins remaining on the silicone surface ranged from 0.6 to 1.0 microgram/cm2, which was several times larger than the amount of an assumed monolayer adsorption of proteins. Even after 15 weeks, the amount of proteins remaining on the silicone was almost the same as after 5 weeks. No significant difference in digestion was observed between collagen and gelatin, regardless of the labeling agent. Because of less stability and easier handling of FITC and higher stability and more difficult handling of 125I, FITC seems more suitable for short-term and 125I for long-term studies.

Animals

Esophageal clearance scintigraphy, in diabetic patients--a preliminary study.

The aim of this preliminary study was to evaluate the predictive value of esophageal clearance scintigraphy (ECS) in the diagnosis of esophageal autonomic neuropathy in diabetic patients without any esophageal symptoms. A single swallow ECS was performed in 12 diabetic patients and 15 normal volunteers, and esophageal transit time (ETT) and esophageal (Es) T 1/2 values were calculated. ETT and Es T 1/2 were found to be significantly prolonged in the diabetic group (p less than 0.01 and p less than 0.05, respectively). In this preliminary study, our results strongly suggest that ECS may be an important noninvasive diagnostic tool in the evaluation of diabetic patients with asymptomatic esophageal autonomic neuropathy.

Adult

Degradation of collagen suture in vitro and in vivo.

In vitro and in vivo degradation of collagen suture was investigated focussing on the change in the mechanical properties and weight. The in vitro hydrolysis was carried out for catguts using collagenase (pH 7.4) and pepsin (pH 1.6), simulating the in vivo environments. The kinetic study on the weight loss of the fibre at the collagenase hydrolysis suggested that the degradation proceeded gradually from the surface of the fibre into the core. The enzymatic hydrolysis was different from the non-enzymatic acidic hydrolysis which resulted in almost homogeneous degradation throughout the cross-section of the fibre from the beginning of the hydrolysis reaction. The rate of weight loss with enzymatic hydrolysis was in good agreement with that predicted under the assumption of continuous erosion from the surface. When the collagen sutures were implanted in the subdermal tissue of rabbits, severe infiltration of macrophages and neutrophils was observed at 4 wk post-implantation, probably because of the degradation products from the implanted sutures. Comparison of the tensile strength decrease with the weight loss observed at the in vivo degradation revealed that enzymatic and non-enzymatic hydrolysis occurred concurrently in the subcutaneous tissue.

Animals

Daily activity and persistent sleep-wake schedule disorders.

1. Patients with disorders of entrainment to external time cues such as delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (HNS) were treated with non-pharmacological interventions and/or pharmacological agents. 2. Resetting the circadian clock with chronotherapy was easy in all DSPS patients, but it was not as easy to maintain the reset rhythm without additional therapy. Triazolam was effective in treating the phase delay that reappeared after chronotherapy. 3. Vitamin B12 (methylcobalamin) was strikingly effective in some patients with DSPS or HNS. 4. All the adolescent patients who complained of inability to attend school finally returned to their classes after treatment. Maintaining the reset rhythm in adolescent patients was easier than in adults.

Adolescent

Mother-to-infant transmission of hepatitis C virus.

Prospective studies of an infant of a mother infected with hepatitis C virus indicated that an HCV infection developed in the infant in early life. Perinatal transmission appeared to be the most likely explanation.

Female