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Biomedical subjects

S Uchida

Publications and source records attributed to S Uchida.

At least 289 records · Page 16Linked to original sources

Vogt-Koyanagi-Harada disease in identical twins.

BACKGROUND: Certain aspects in the development of Vogt-Koyanagi-Harada (VKH) disease are documented, and immunogenetic studies have revealed a high relevance of some HLA types. Roles of possible environmental factors in disease onset are not fully understood, however. METHODS: Two cases involving monozygotic twin sisters who were diagnosed as having VKH disease and followed for more than 2 years are presented. RESULTS: Both patients showed the diffuse panuveitis that is characteristic of VKH disease and shared the same HLA typings. However, there was a 16-year time lag between onset of disease in the two patients, and many differences in their lifestyles before disease onset were noted. CONCLUSION: Although certain endogenous factors play an important role in the development of VKH disease, some exogenous factors may also affect the onset of the disease.

Adult↗

Induction of multinucleated giant cells from rheumatoid arthritis (RA) synovial adherent cells by anti-DR antibody.

To determine the effects of signalling through the DR molecule on synoviocytes from RA patients, the synovial adherent cells were incubated with anti-DR antibodies. After 24 h incubation, we found the formation of multinucleated giant cells in that culture. These multinucleated giant cells showed characteristics of monocyte-macrophage lineage cells and precursor of osteoclasts. Cyclohexamide inhibited the formation of multinucleated giant cells, but not the aggregation of synovial cells, suggesting that newly synthesized proteins are associated with the cell fusion. These results revealed a new mechanism in multinucleated giant cell formation.

Antibodies, Monoclonal↗

Role of endothelium-derived nitric oxide and adenosine in functional myocardial hyperemia.

To investigate the role of endothelium-derived nitric oxide (EDNO) and adenosine in functional myocardial hyperemia, we examined the effect of NG-nitro-L-arginine (L-NNA) and 8-p-sulfophenyltheophylline (8-SPT) on coronary vasodilation in response to increased myocardial oxygen consumption in pentobarbital sodium-anesthetized dogs. L-NNA significantly attenuated the increase in coronary conductance from 28 +/- 6 to 16 +/- 2% with atrial pacing, from 69 +/- 5 to 36 +/- 6% with isoproterenol, and from 25 +/- 6 to 9 +/- 4% with constriction of the aorta. 8-SPT given alone attenuated the increase in coronary conductance to the same extent as L-NNA. The combined administration of L-NNA and 8-SPT did not further change coronary conductance. These findings suggest that EDNO and adenosine play an important role in functional hyperemia. EDNO-induced functional hyperemia appears to be dependent on adenosine receptor activation.

Adenosine↗

Glomerular endothelial cells in culture express and secrete vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a specific growth factor for endothelial cells, and its abundant expression has been reported in kidney glomeruli. In this study, we focused on glomerular endothelial cells (GEN) as a possible source of VEGF secretion and sought to uncover a potential autocrine role of VEGF for GEN. Ribonuclease protection assay demonstrated VEGF mRNA expression in cultured GEN, and 46-kDa VEGF protein was detected in the conditioned medium by immunoblot analysis using polyclonal antibody raised against the NH2-terminal portion of VEGF. Removal of fetal bovine serum (FBS) from the culture medium for 2 h decreased VEGF mRNA abundance, which was restored by the readdition of FBS (10%) within 2 h. The effect of FBS was completely abolished by protein kinase inhibitor H-7 (10 microM), suggesting that FBS-stimulated VEGF mRNA induction involves activation of protein kinases. The treatment of GEN with 10(-7) M 12-O-tetradecanoylphorbol-13-acetate (TPA) increased the VEGF mRNA abundance fivefold, supporting the idea that VEGF expression is regulated by protein kinase C. [3H]thymidine incorporation into GEN treated with TPA (10(-7) M) was inhibited by neutralizing antibody for VEGF. Thus VEGF was identified as an autocrine growth factor for GEN in vitro. Its physiological role might be the regulation of GEN proliferation, and the induction of VEGF expression by FBS and TPA suggests its involvement in the response of glomerular capillary endothelial cells to injury in certain pathophysiological states.

Animals↗

Functional characterization and cell immunolocalization of AQP-CD water channel in kidney collecting duct.

Vasopressin-regulated water permeability of the kidney collecting duct is a key component of the urine concentration machinery. Recently, a cDNA for AQP-CD, the vasopressin-regulated water channel, initially reported as WCH-CD, has been isolated (K. Fushimi, S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. Nature Lond. 361: 549-552, 1993). AQP-CD was expressed in oocyte membrane using a Xenopus expression vector, and functional characteristics of AQP-CD were examined. Osmotic water permeability (Pf) of oocytes expressing AQP-CD was 138 +/- 19 microns/s (mean +/- SE), 12 times greater than the control (11 +/- 3 microns/s), 90% inhibited by 0.3 mM HgCl2, and weakly temperature dependent (energy of activation for Pf was 4.0 kcal/mol). Urea influx measured from 15-min [14C]urea uptake by oocytes injected with AQP-CD/expression vector 1 cRNA was 86 +/- 17% of the control. Two-electrode voltage-clamp experiments revealed insignificant ion conductance of AQP-CD. Immunoblots of membranes from rat kidney medulla and oocytes expressing AQP-CD using anti-AQP-CD COOH-terminal antibody showed a 29-kDa protein and 35- to 50-kDa high-molecular-mass forms. Immunohistochemistry showed apical and subapical localization of AQP-CD in the collecting duct principal cells. Our results indicated that AQP-CD is a 29-kDa protein, a selective water channel, distinct from a urea channel, and localized to the membranes of vasopressin-sensitive components in kidney collecting duct principal cells.

Amino Acid Sequence↗

A rise in antineutrophil cytoplasmic antibody in a patient with systemic vasculitis in remission.

We report a 42-year-old man who showed alveolar hemorrhage and glomerulonephritis as well as episcleritis and skin rash. He had an extremely high titer of cytoplasm-staining antineutrophil cytoplasmic antibody (C-ANCA) and was diagnosed as having systemic vasculitis based on histological findings of kidney and skin biopsies. After immunosuppressive therapy clinical manifestations resolved within several weeks and C-ANCA titers commensurably declined. C-ANCA titers, however, increased again and remained high despite clinical remission. In general, there is a close relationship between ANCA titers and clinical activities in ANCA-associated diseases, but they displayed a large discrepancy in this patient. Indeed, the serum of the patient in remission contained the antibody against 29-kD neutrophil extracts which was detected by immunoblot analysis. These findings suggest that C-ANCA may not necessarily be, by itself, pathogenetic for the development of the vasculitis.

Adult↗

Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

We recently cloned a cDNA of the collecting duct apical membrane water channel of rat kidney, which is important for the formation of concentrated urine (Fushima, K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Nature [Lond.]. 361:549-552). Since urine concentrating ability varies among mammalian species, we examined whether an homologous protein is present in human kidney. By screening a human kidney cDNA library, we isolated a cDNA clone, designated human aquaporin of collecting duct (hAQP-CD), that encodes a 271-amino acid protein with 91% identity to rat AQP-CD. mRNA expression of hAQP-CD was predominant in the kidney medulla compared with the cortex, immunohistochemical staining of hAQP-CD was observed only in the collecting duct cells, and the staining was dominant in the apical domain. Functional expression study in Xenopus oocytes confirmed that hAQP-CD worked as a water channel. Western blot analysis of human kidney medulla indicated that the molecular mass of hAQP-CD is 29 kD, which is the same mass expected from the amino acid sequence. Chromosomal mapping of the hAQP-CD gene assigned its location to chromosome 12q13. These results could be important for future studies of the pathophysiology of human urinary concentration mechanisms in normal and abnormal states.

Amino Acid Sequence↗

Effects of nipradilol on venous hemodynamics: evaluation with a Doppler blood flow method.

Nipradilol is a newly synthesized beta-blocker which has a propranolol-like structure and contains a nitrate moiety. To examine the effect of nipradilol on venous blood flow, a single oral dose of nipradilol (6 mg) and propranolol (20 mg) was administered in the same 15 normal volunteers on separate days. Peak flow velocities, flow velocity integrals, and the diameter of the right brachiocephalic vein were measured before and 2 h after drug administration using Doppler echocardiography. These two beta-blockers significantly decreased systolic blood pressure to the same extent as they did heart rate. Nipradilol dilated the venous diameter by 8% and decreased peak flow velocity by 8% during systole and 9% during diastole. The flow velocity integral in one cardiac cycle also decreased significantly by 14%. Propranolol, however, failed to modify these parameters. These results suggest that nipradilol decreased venous return through its nitroglycerin-like direct vasodilating action.

Adult↗

Pharmacokinetics of amlodipine and its occupancy of calcium antagonist receptors.

We characterized the occupancy of dihydropyridine (DHP) calcium antagonist receptors by amlodipine in spontaneously hypertensive rats (SHR) in relation to its pharmacokinetics. Oral administration of amlodipine (10 mg/kg) in SHR produced a significant (20-70%) decrease in the number of specific (+)[3H]PN 200-110 binding sites in cardiac tissues 0.5-18 h later, and the effect was greatest 3 h later. In these rats, there was little change in cerebral cortical (+)[3H]PN 200-110 binding. Occupancy of cardiac calcium antagonist receptors after oral administration of amlodipine correlated well with its plasma concentration. In vitro blockade of cardiac (+)[3H]PN 200-110 binding sites induced by amlodipine also persisted after the tissues were washed by centrifugation and suspension, whereas that induced by nifedipine was reversible under these conditions. Thus, our results suggest that the gradual onset and long-lasting pharmacologic effect of amlodipine are due to its slow binding kinetics (association and dissociation) of cardiovascular receptor sites in addition to its slow pharmacokinetics.

Amlodipine↗

Suppressive effect of cyclophosphamide on the progression of lethal graft-versus-host disease in mice--a therapeutic model of fatal post-transfusion GVHD.

In this paper, we examine in a murine system whether cyclophosphamide (CY) could prevent the development of fatal GVHD and furthermore whether it could be used to treat on-going GVHD. (C57BL/6xDBA/2)F1 (BDF1) mice were injected with spleen cells from B6 donors and their thoraces were opened to mimic cardiac operation. These mice lost body weight gradually and most of them died during 2-4 weeks post-transfusion. They showed splenomegaly, thymic atrophy and marked bone-marrow aplasia. When CY was administered at 100 mg kg-1 on days 0, 2, 7 and 9, all mice were relieved of GVHD and their organs were almost free of signs of GVHD. CY (100 mg kg-1) administered on days 7 and 9 also save mice from lethal GVHD. Moreover, CY administered at a dose of 20 mg kg-1 on days 9 and 11 when GVHD became apparent was also effective. These data suggest that CY might be used as a therapeutic agent for lethal post-transfusion GVHD.

Animals↗

ClC family in the kidney.

PCR cloning strategy was used to isolate cDNAs of ClC family members in the kidney. Three new members, named ClC-K1, ClC-K2, ClC-3, have been isolated. Functional expression studies in the Xenopus oocytes confirmed that these are chloride channel proteins. Northern blot and immunohistochemistry showed that ClC-K1 and ClC-K2 are selectively expressed in the kidney, while ClC-3 distributes in a variety of organs such as brain, lung, and kidney. Identification and characterization of new ClC channel proteins will contribute to a better understanding of chloride transport in the kidney.

Animals↗

Cloning and expression of a PKC-regulated chloride channel.

The cDNA of a protein kinase C-regulated chloride channel (CIC-3) was cloned. CIC-3 encodes 760 amino acids, which has significant amino acid identity with the previously cloned CIC chloride channels. CIC-3 cRNA elicited the chloride currents in Xenopus oocytes, which was completely blocked by activation of protein kinase C by 12-O-tetradecanoylphorbol 13-acetate (TPA). The most abundant expression of CIC-3 mRNA was observed in rat brain, and the moderate level of CIC-3 expression was also observed in various rat tissues including adrenal gland, kidney, and lung. These findings suggest that CIC-3 may have important roles in various types of cells with regulation by protein kinase C.

Animals↗

Glibenclamide reduces the coronary vasoactivity of adenosine receptor agonists.

Experiments in guinea pig heart Langendorff preparations assessed the effect of KATP channel blockade on the coronary vasoactivity of adenosine and 17 analogs chosen to represent a variety of purine and ribose modifications. Although glibenclamide is a functional antagonist that acts at the level of an effector rather than at a receptor, it caused parallel rightward shifts of agonist dose-response curves. The size of the shift of EC50 differed according to the kind of analog: the ranking was, generally, N6-phenethyladenosines > 2-aryl-aminoadenosines = 2-(1-alkyn-1-yl)adenosines > N6-cycloalkyladenosines = adenosine-5' -uronamides. The coronary vasoactivity ranking of agonists in the presence of supramaximal concentrations of glibenclamide was 2-(1-alkyn-1-yl)adenosines = 2-aralkoxyadenosines > 2-aralkylaminoadenosines > 2-arylaminoadenosines > N6-substituted adenosines. Glibenclamide did not affect the vasoactivity of adenosine itself, perhaps because avid uptake by endothelial cells prevented penetration of the agonist to receptors deeper in the vascular wall. The results exclude a model consisting of one kind of receptor acting exclusively through a KATP channel, argue against one kind of receptor coupled to a KATP channel as well as to an additional effector but is consistent with two kinds of vasodilatory adenosine receptors, one of which activates a KATP channel. The identity of the adenosine receptor coupled to the KATP channel is uncertain; the other receptor has the pharmacological profile of an A2a-adenosine receptor.

Adenosine↗

[Relation between surgical outcome and preoperative end-systolic volume of the left ventricle in patients with regurgitant valvular heart disease].

The relation between the end-systolic volume index of the left ventricle (ESVI (ml/m2)) and the early and late results after valve replacement were reviewed in 249 patients with pure aortic regurgitation (AR) and 189 patients with pure mitral regurgitation (MR). The patients with AR were classified into 4 groups (A1-A4) and those with MR were classified into 3 groups (M1-M3) according to the ESVI. The ESVI, the number of patients (No of P), early mortality rate (EM) and the actuarial survival rate at 12 years after valve replacement (AS at 12 yr) in each group are shown in the following Table. [table: see text] The actuarial survival rate at 12 years after operation in A1 and A2 were significantly lower than that in A3 and A4. In 57% of the late deaths in A1 and A2 patients, the cause of the death was thought to be rhythm disturbance. In contrast, there were no differences in late survival among the three groups with MR (M1, M2 and M3). The minor axis of the left ventricle at end-diastole and at end-systole (Dd and Ds) and shortening fraction of the left minor axis (FS), evaluated by echocardiography, were normalized early after the operation in A1 patients only. The Dd, Ds and FS in A2 and A3 returned to normal late after the operation. However, in A4, these parameters still remained abnormal. Thus, patients with a deteriorated left ventricle can survive the operation. However, the long-term results in patients with AR with ESVI more than 150 ml/m2 were unsatisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗

[A study of diagnostic scale in borderline personality disorder that was synthesis of symptomatic and personality structural element].

The diagnostic criteria for BPD such as the DSM-III(-R) and DCR, based on polythetic format for prototypal categories, has not always been able to result in accurate clinical diagnosis of BPD. Reasons posited for this were that DSM-III(-R) criteria consist of symptom items based on descriptive phenomenology, even for Axis II personality diagnosis, and that descriptions of the criteria were vague because of the standardization of vocabulary which aimed at improved inter-rater reliability. With the polythetic "yes/no" format, diagnosis was influenced by the determination of only one item; furthermore, different combinations of items yielding a heterogeneous membership might lead to the same diagnosis. It was, therefore, considered difficult to perform an accurate diagnosis of BPD in clinical practices using the existing general diagnostic criteria, and it was realized that the development of new diagnostic criteria for BPD was necessary. For those reasons, we generated a Clinical BPD Scale (CBS) as diagnostic evaluation scale of BPD with considering advantages for clinical use. This reconstituted some features of BPD which have been reported by many researchers, synthesizing symptomatic elements and personality structural elements. CBS is composed of four clusters, Two of these four clusters are evaluated by four grade anchor points which are provided for the rating of the severity of symptoms, and that are illustrated on the radarchart for comprehensive evaluation of the severity of the disorder. CBS was confirmed to have a high degree of validity, and achieved a satisfactory degree of inter-rater reliability by ANOVA ICC, and it has been found in application of CBS to several cases in the clinical practice that the degree of severity of each symptom could be clarified and differential diagnosis was possible with this diagnostic scale. Furthermore, the outcome of treatment could be confirmed at any time during the clinical follow up. In addition, through the dimensions, it is possible to grasp the severity, and further, through spectrum and hierarchy. We considered diagnostic area of BPD and its position by CBS correlating the other closely related disorders.

Borderline Personality Disorder↗

Diagnosis of post-transfusion graft-versus-host disease after formalin-fixation.

A 72-year-old woman with multiple recurrence of gallbladder cancer was treated by intrahepatic-arterial infusion of doxorubicin using an extracorporeal system of direct hemoperfusion with venovenous bypass. During this treatment, the patient received 600 ml of fresh whole blood and 30 units of platelet concentrate from five unrelated donors. Thereafter, high fever, skin rash over the whole body, and watery diarrhea developed, followed by leukopenia progressing to a fatal sepsis. Post-transfusion graft-versus-host disease (PT-GVHD) was suspected by the clinical manifestations and postmortem pathologic findings. To establish the diagnosis of PT-GVHD, polymerase chain reaction (PCR) amplification of DNA polymorphism associated with length variation in dinucleotide or trinucleotide microsatellite repeats at the loci of D6S89, int-2 protooncogene, and human growth factor with each of the different primer sets was performed using DNA from blood drawn from the patient with clinically established PT-GVHD of a donor origin and formalin-fixed pancreas of recipient origin. Genetic analysis revealed the changes in the patient's lymphocytes from that of the patient to that of donor origin. The present finding that formalin-fixed tissues can be used as a material of patient origin may contribute to accurate diagnosis of PT-GVHD after autopsy.

Aged↗