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Biomedical subjects

O Sakai

Publications and source records attributed to O Sakai.

At least 127 records · Page 7Linked to original sources

[Maximum-intensity-projection CT angiography for evaluating head and neck tumors: usefulness of helical CT and auto bone masking method].

Angiographic images of 10 adult patients with head and neck tumors were obtained by helical computed tomography (CT) using maximum intensity projection (MIP). In all cases, the vasculature of the head and neck region was clearly visualized, and hypervascular lesions were directly demonstrated. In the head and neck, bone masking is a more important problem than in other regions. We developed an effective automatic bone masking method (ABM) using 2D/3D connectivity. Helical CT angiography with MIP and ABM provided accurate anatomic depiction, and was considered to be helpful in preoperative evaluation of head and neck tumors.

Adult↗

Mitogenic effects of platelet-derived growth factor, fibroblast growth factor, transforming growth factor-beta, and heparin-binding serum factor for adult mouse Schwann cells.

Mitogenic effects of fetal calf serum (FCS), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), and forskolin to adult mouse Schwann cells were examined by bromodeoxyuridine (BrdU) incorporation and double immunofluorescence for S100 and BrdU. PDGF-BB, basic FGF, and TGF-beta 1 and beta 2 were all mitogenic for Schwann cells in media containing FCS. Forskolin suppressed the mitogenic activity of these factors. In serum-free media, PDGF-BB and bFGF were also mitogenic, but TGF-beta 1 and beta 2 were not. Heparin-binding fractions of FCS obtained by heparin-Sepharose chromatography synergized with TGF-beta 1 and beta 2 to produce a mitogenic response. Since PDGF-BB, acidic FGF, and basic FGF were not detected in these fractions by immunoabsorption and immunoblot assays, the presence of unidentified heparin-binding molecules in FCS bioactive for adult mouse Schwann cells is suggested.

Animals↗

Heparin selectively inhibits gene expression of matrix metalloproteinase transin in cultured mesangial cells.

The aim of this study is to examine the transcriptional regulation of matrix metalloproteinase transin in glomerular mesangial cells responding to inflammatory cytokines and heparin. Northern blot analysis revealed that IL-1 beta preferentially induced transin mRNA. The stimulatory effect was not specific to transin, and upregulation of procollagen alpha 1(IV), laminin B2 and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs was also observed. After IL-1 stimulation, expression of the transin transcript increased progressively for up to 48 hours, differing from the limited induction of procollagen alpha 1(IV) or TIMP-1. When mesangial cells were stimulated by IL-1 beta in the presence of heparin, transin expression was markedly suppressed in a dose-dependent manner. The inhibitory effect of heparin was specific to transin, and induction of procollagen alpha 1(IV), laminin B2 or TIMP-1 by IL-1 beta was not affected. These findings revealed the selective counter regulation by IL-1 beta and heparin of the transin expression in mesangial cells.

Animals↗

Cloning of a pH-sensitive K+ channel possessing two transmembrane segments.

The mammalian renal collecting ducts are responsible for secreting potassium ions into the urine and are a major regulatory site for potassium homeostasis, in which a voltage-independent pH-sensitive K+ channel in the apical membrane plays a central role. Here we describe a complementary DNA encoding a novel K+ channel from rabbit renal cortical collecting tubule cells (RACTK1). RACTK1 has the functional characteristics of the apical K(+)-permeable channel and consists of 284 amino acids, putatively with two transmembrane segments. The sequence of RACTK1, however, shows no homology to known voltage-dependent or -independent K+ channels, and has a different K(+)-driving path and regulatory sites. The study of this protein should provide insight into K+ homeostasis and diseases of K+ metabolism.

Amino Acid Sequence↗

Regulation by GTP of a Ca(2+)-activated K+ channel in the apical membrane of rabbit cortical collecting duct cells.

Ca(2+)-activated K+ channels play an important role in Ca2+ signal transduction and may be regulated by mechanisms other than a direct effect of Ca2+. Inside-out patches of the apical membrane of confluent transformed rabbit cortical collecting duct cells cultured on collagen were subjected to patch clamp analysis. Two types of K+ channel, of medium and high conductance, were observed. The latter channel was characterized by a K+/Na+ permeability ratio of 10, an inwardly rectified current, a conductance of 80 pS at 0 mV, and an open probability dependent on both voltage and Ca2+. Guanosine 5'-triphosphate (GTP) but not a guanosine 5'-diphosphate (GDP) analogue, adenosine 5'-triphosphate (ATP), cytidine 5'-triphosphate (CTP), or inosine 5'-triphosphate (ITP), inhibited the activity of this Ca(2+)-activated K+ channel. The inhibitory effect of GTP was dose dependent, with a 50% inhibitory concentration of 10(-5) M in the absence of Mg2+. In the presence of Mg2+ (1 mM), which is required for the binding of GTP to G proteins, the 50% inhibitory concentration decreased to 3 x 10(-12) M. Pertussis toxin or cholera toxin (each at 10 ng/ml) did not prevent the inhibitory effect of GTP. After removal of GTP from the medium bathing an inhibited channel, subsequent application of Ca2+ failed to activate the channel. Ca(2+)-activated K+ channels of smooth muscle cells and proximal tubule cells did not respond to GTP. Thus, the Ca(2+)-activated K+ channel in the apical membrane of collecting duct cells is inhibited by GTP, which appears to exert its effect via a G protein that is insensitive to both cholera and pertussis toxins.

Animals↗

Effect of pentoxifylline on CdCl2-induced nephrotoxicity in the rat.

We developed a rat model of cadmium (Cd)-induced nephrotoxicity and tried to prevent renal damage by treating the animals with pentoxifylline (PTX). Sprague-Dawley (SD) rats given CdCl2 3.0 mg/kg sc, daily for 2 wk showed evidences of renal proximal tubular damage, including significant increases in urine volume, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and fractional excretion of sodium (FENa), and a decrease in the percentage of tubular reabsorption of phosphate (%TRP). PTX significantly improved the urinary excretion of NAG and %TRP. Urine volume was increased threefold in the CdCl2-treated rats and fivefold in the Cd + PTX-treated rats, respectively, as compared with saline-treated control. Total protein, AAP, and creatinine clearance, showed no change after PTX administration. Concentration of Cd in the renal cortex was three times higher than that in the renal medulla, but there were no differences in concentration between the Cd-treated rats and the Cd + PTX-treated rats. Our animal model was useful in studying the renal tubular damage produced by cadmium. PTX appears useful for improving the nephrotoxicity of Cd.

Acetylglucosaminidase↗

Differential regulation of cation transport of vascular smooth muscle cells in a high glucose concentration milieu.

To gain new insights into the pathogenesis of diabetic angiopathy, the influence of high glucose concentration on cation transport of vascular smooth muscle cell (VSMC) membrane was investigated by measuring Na, K and Ca transport in serially passaged cultured VSMC. (1) Na-K pump activity, described as ouabain sensitive 86Rb uptake, and Na-K cotransport, described as bumetanide sensitive 86Rb washout of VSMC, grown in high glucose concentration medium (460 mg/dl), was lower than that grown in normal glucose concentration medium (100 mg/dl). A smaller 5-N,N-hexamethylene amiloride (HMA) sensitive 22Na uptake (Na-H antiport) in high glucose concentration medium. accounted for this difference. (2) 45Ca uptake was also smaller in VSMC cultured in high glucose concentration medium. However, the washout rate constant for 45Ca was comparable between high and normal glucose cultured VSMC. (3) Both intracellular concentration of Na and cytosolic free Ca concentration concentration ([Ca]i) of high glucose cultured VSMC were greater than normal glucose cultured VSMC. (4) Intracellular water volume based on the equilibrium distribution of 3-O-methyl-[14C]glucose was not different between normal and high glucose cultured VSMC. It is concluded that VSMC grown in high glucose concentration milieu manifests a decreased Na-K, and Ca transport in conjunction with an increase in intracellular concentration of Na and [Ca]i. These results suggest that high glucose, per se, may alter membrane permeability to cations, possibly leading to changes in VSMC contractility and/or proliferation. This abnormality seen in the diabetic state may closely link to the pathogenesis of diabetic angiopathy, thus as a result risking hypertension and vascular disease.

Amiloride↗

Crystalline inclusions in the glomerular podocytes in a patient with benign monoclonal gammopathy and focal segmental glomerulosclerosis.

We report a case of a 40-year-old woman with benign monoclonal gammopathy who developed focal segmental glomerulosclerosis associated with widespread deposition of large crystalline inclusions in the glomerular podocytes. Electron microscopy showed that the crystalline structures were electron dense and needle shaped or polygonal. At a higher magnification, they were seen to be surrounded by unit membranes and to feature a longitudinal filamentous substructure. These inclusions showed positive immunohistochemical staining for kappa light chain. Clinically, the patient had shown nephrotic syndrome on the first medical examination, and later revealed chronic renal failure and monoclonal gammopathy of the immunoglobulin G kappa type, but no evidence of multiple myeloma or other lymphoproliferative diseases. This patient seems to have had a rare form of glomerular involvement associated with benign monoclonal gammopathy.

Adult↗

The effect of selective growth hormone defect in the progression of glomerulosclerosis.

The role of endogenous growth hormone (GH) in the progression of glomerulosclerosis was examined in a new mutant strain of Sprague-Dawley (SD) rats with a selective GH gene defect. Fifteen spontaneous dwarf [GH(-)] rats and 10 SD rats underwent subtotal nephrectomy (Nx) or sham operation. Twelve weeks after Nx, the mean arterial pressure, glomerular filtration rate, urinary protein excretion rate, glomerular size, and frequency of glomerulosclerosis were examined. Marked elevation in mean arterial pressure was seen in both SD/Nx and GH(-)/Nx rats. In both strains, the glomerular filtration rate at 12 weeks after Nx was approximately 50% to 60% of that seen in the respective Sham-operated rat groups. The urinary protein excretion rate increased significantly only in the SD/Nx rats. The glomerular size, expressed as the ratio of glomerular volume to body weight, increased by 200% in the SD/Nx rats compared with the SD/Sham rats, in marked contrast to the 70% increase in the GH(-)/Nx rats compared with the GH(-) rats. The frequency of glomerulosclerosis in the GH(-)/Nx rats (1.0 +/- 0.5%) was significantly lower than that in the SD/Nx rats (16.7 +/- 2.8%). The frequency of glomerulosclerosis correlated with glomerular hypertrophy in both the SD and GH(-) rats (r = 0.88 and 0.67, respectively). These results show that the progression of glomerular sclerosis was markedly attenuated in the GH-defective rats. This attenuation of structural injury was correlated with a marked decrease in glomerular hypertrophy. These studies indicate that this specific growth regulatory peptide of endogenous origin plays an important determining role in the progression of glomerulosclerosis.

Analysis of Variance↗

Neonatal thymectomy diminishes renal IgA deposition in IgA nephropathy-prone ddY mice.

To understand the role of thymus-derived T cells in the development of IgA nephropathy (IgAN), we performed neonatal thymectomies on ddY mice, in which this disease occurs spontaneously. Although these thymectomized mice developed a renal lesion closely resembling that typical of IgAN, the extent of their mesangial IgA deposition was significantly milder than in control sham-operated mice. The immunological mechanisms responsible for curbing this mesangial deposition of IgA were then analyzed. The percentage of splenic T cells and the magnitude of mitogenic responses both decreased markedly in thymectomized compared with control mice. These results suggested the hypofunction of thymus-derived T cells. However, serum IgA levels were almost identical in both groups. Furthermore, sera from both groups contained similar amounts of macromolecular IgA, of the type formerly eluted from the affected glomeruli of patients with IgAN. These results strongly indicate that thymus-derived T cells or their products determine the amount of IgA deposited in the kidneys of ddY mice.

Animals↗

Cloned cells develop renal cortical collecting tubules.

We investigated the development and morphogenesis of stem cells cloned from cultured transformed collecting duct cells of the rabbit in the presence of hepatocyte growth factor/scatter factor (HGF), vitamin A, laminin and transforming growth factors, HGF and vitamin A induced peanut agglutinin (PNA) positivity in nonprincipal cells (PC) but not in PCs, only HGF induced tubule formation. Although HGF induced a tubule-like arrangement in both cell lines, tubules with PNA-positive cells were observed only in non-PC cells incubated with HGF. Vasopressin increased intracellular free calcium in PNA-negative cells but not in PNA-positive cells. Intracellular pH increased in PNA-positive cells but not in PNA-negative cells when gluconate was substituted for Cl in the buffer. Cloned non-PCs were stem cells that developed PC- and IC-like characteristics and formed collecting ducts when incubated with HGF.

Animals↗

Possible thyroidal involvement in a case of Fabry disease.

Endocrinological evaluations of a 48-year-old man with Fabry disease revealed low levels of serum thyroid hormones and high levels of serum thyrotropin (TSH), indicating that the patient had primary hypothyroidism. Also, an exaggerated growth hormone (GH) response to hypoglycemic stimuli was observed. Thin layer chromatography of the lipid extract of the thyroid gland obtained by biopsy demonstrated marked accumulation of ceramide trihexoside (CTH) and ceramide dihexoside (CDH). These findings strongly suggest that thyroid hypofunction and hypothalamic dysfunction could be involved in Fabry disease.

Fabry Disease↗

Myasthenia gravis associated with Addison's disease.

Idiopathic Addison's disease developed in a 52-year-old female with a 15-year history of myasthenia gravis. The association of myasthenia gravis with other autoimmune diseases is well known, however an association with Addison's disease is rare. It was speculated that the development of Addison's disease in this patient might have been due to common immunological abnormalities underlying these two diseases. We report this case and briefly discuss the pathogenetic mechanism of this association.

Addison Disease↗

Changes of blood volume distribution by postural changes in rats.

During a space flight the human body responds to many different gravities. The launching of the rocket, the weightlessness, the re-entry of the spacecraft, and other factors influence the astronaut's body. The fluid shifts and the effect on the cardiovascular system arising from these gravitational changes have been frequently studied in space medicine by using body tilting, lower body negative pressure (LBNP) and centrifugal accelerators. There exist, however, few reports about the changes in whole body blood volume distribution caused by body tilting. These changes can be measured using radioisotopes: scintigraphy using 99mTechnetium-labeled human serum albumin (99mTc-HSA), etc. In humans, however, because the visual field of the scintillation camera is so small, the simultaneous measurement of whole body blood volume distribution cannot be done during body tilting. We therefore used rats, whose whole bodies can be encompassed within the visual field of the camera, and we discussed the changes in blood volume distribution induced by body tilting. We also measured the blood concentrations in each organ by using whole body autoradiography in mice, and discussed the effect of postural changes on some abdominal organs.

Abdomen↗

The status of fluoride mouthrinse programmes in Japan: a national survey.

The purpose of this investigation was to determine the current status of fluoride mouthrinse programmes throughout Japan. Data collection and analysis took place in 1992. The focus of this study was on schools that were participating in the rinse programme at the time of the survey. Questionnaires were sent by mail to 49 dentist-members of the Association for the Promotion of Fluoride Use in Japan. These members gathered information from the schools and, when necessary, also from local government offices. Starting with a single prefecture in 1970, the rinse programme increased to 32 out of 47 prefectures by 1992. The total number of schools using fluoride mouthrinse was 1,183 (nursery schools and kindergartens 48 per cent, primary schools 46 per cent, and secondary schools 6 per cent). In nursery schools and kindergartens, 60 per cent of the participating schools adopted the daily method using 0.05 per cent NaF solution. In primary and secondary schools, 78 per cent adopted the weekly method using 0.2 per cent NaF solution. The costs for the rinse regimen were paid for by public funds of the prefectural and municipal governments in 71 per cent of the schools. Fifty-four per cent of the schools which first initiated the rinse programmes in their districts identified dentists and dental associations as the most influential in programme acceptance and implementation. Although the number of fluoride rinse programmes is increasing, it is still modest. These results suggest that cooperation between dental organisations, dental schools and prefectural governments can play very important roles in implementing school based rinse programmes.

Child↗

Characteristics of anemia in patients with nephrotic syndrome.

Primary nephrotic syndrome can, although infrequently, cause severe anemia. However, the mechanisms of the anemia remain unknown. We investigated the mechanism of anemia in nephrotic syndrome by measuring parameters of nephrotic syndrome and anemia in 44 nephrotic patients (male: female; 21:23, average age; 43.6 +/- 20.3 years). Nephrotic patients had significantly lower hematocrits than did healthy controls (43.3 +/- 3.7 vs. 46.8 +/- 3.4% in males, 37.4 +/- 3.5 vs. 40.8 +/- 2.8% in females). Serum erythropoietin (Epo) concentrations were correlated inversely with hemoglobin (Hb), hematocrit (Hct), and red blood cell corpuscle (RBC) counts. Furthermore, serum Epo correlated with the serum iron concentration, but not with the other parameters, such as reticulocytes, serum protein and proteinuria. However, the maximum Epo concentration was less than 100 mU/ml in spite of severe anemia, and this was thought to be inappropriate. On the contrary, urine Epo was not detected by the same method of serum Epo determination in spite of aggressive dialysis with distilled water. When four patients with severe anemia were subcutaneously administered recombinant Epo 6,000 unit two times a week, they showed marked improvement in Hb/Hct/RBC. The precise mechanism of anemia in NS was not elucidated by this investigation, but further study should clarify the causes of the inappropriately low concentration of serum Epo in patients with primary nephrotic syndrome.

Adult↗

Intermittent outpatient based ECUM. A case report.

Extracorporeal Ultrafiltration Method (ECUM) could be used in patients with refractory congestive heart failure (CHF). We have encountered a 56-year-old woman with refractory congestive heart failure (CHF) (NYHA II-III) due to coronary artery disease, complicated by moderately advanced diabetic nephropathy (Cr = 2.4 mg/dl). Due to the non-responsiveness to medical treatments, she has begun receiving the intermittent ECUM once or twice a week on an outpatient basis. ECUM effectively reduced cardiac preload and temporarily relieved her intractable respiratory distress. Based on our present clinical experience, we propose that one could consider an outpatient based intermittent ECUM as one of the useful therapeutic modalities to ameliorate refractory CHF.

Female↗