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Biomedical subjects

M Sata

Publications and source records attributed to M Sata.

At least 253 records · Page 14Linked to original sources

MCI-154 increases Ca2+ sensitivity of reconstituted thin filament. A study using a novel in vitro motility assay technique.

MCI-154 (6-[4-(4'-pyridylamino)phenyl]-4,5-dihydro-3(2H)pyridazinone hydrochloride trihydrate) is a potent novel cardiotonic agent whose positive inotropism is shown to be mainly based on an increase in Ca2+ sensitivity of the contractile apparatus. To elucidate the exact mechanism through which this drug acts, we investigated the movement of the reconstituted thin filament on a myosin layer in vitro. Cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex purified from rat cardiac acetone powder separately. Double staining of the filament showed that tropomyosin-troponin complex was integrated along actin filament homogeneously. Thin filaments thus prepared were fluorescently labeled and made to slide on rat cardiac myosin fixed on a glass coverslip while varying the [Ca2+] of the medium (control, pH 7.2 at 25 degrees C). When [Ca2+] was low, the filaments showed only brownian motion. However, above a certain level of [Ca2+] (the threshold [Ca2+]), the filaments started to slide, and the velocity increased, reaching the maximum velocity within a very narrow range of [Ca2+]. The regulation was completely abolished by using simple actin filaments without tropomyosin-troponin complex, demonstrating that the regulatory proteins are responsible for this Ca2+ regulation of the movement of the reconstituted thin filament. Under the control condition, addition of MCI-154 shifted the threshold [Ca2+] to a lower level (sensitization) in a concentration-related manner. And 10(-4) mol/L of MCI-154 reversed the desensitization effect induced by either acidosis (pH 6.8), low temperature (15 degrees C), or the addition of inorganic phosphate (10 mmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

Relapsing polychondritis associated with subclinical Sjögren's syndrome and phlegmon of the neck.

A 25-year-old woman, diagnosed with Sjögren's syndrome at age 20, presented with painful edema of her left neck. Three days later, she additionally complained of bilateral auricular pain, and her nasal cartilage was tender to palpation. She was diagnosed as having phlegmon on the basis of her neck findings. Anti-human cartilage antibodies were demonstrated by indirect immunofluorescence, and the diagnosis of relapsing polychondritis was established. The patient was administered antibiotics and a non-steroidal anti-inflammatory drug, and her symptoms gradually improved. Relapsing polychondritis is one of the possible complications of autoimmune diseases, and infection might be a precipitating factor for this disease.

Adult↗

A case of acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg with remission of liver damage after long-term treatment with interferon.

The patient was a 47-year-old female with chronic hepatitis B having antibody to HBe antigen (HBeAg). She was admitted to our hospital in March, 1994, because of acute exacerbation of chronic hepatitis B. Laboratory data revealed the elevated serum transaminase and DNA-polymerase levels, and decreased prothrombin activity. The histological examination of the liver showed chronic active hepatitis with severe hepatic necrosis. Point mutation of the precore region of HBV-DNA (pre-C mutant) was observed in clones from this case by polymerase chain reaction method. The patient was treated with recombinant interferon alpha-2a 9 MU daily for 2 weeks and thereafter 3 times weekly for 6 months. After interferon therapy, the pre-C mutant disappeared with the improvement of transaminase levels and prothrombin activity. These findings suggest the possibility that long-term treatment with interferon therapy is effective for the acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg.

Chronic Disease↗

Thyroid dysfunction induced by interferon therapy for the treatment of hepatitis type C. A report of 4 cases.

We describe 4 patients with onset or aggravation of thyroid dysfunction induced by interferon (IFN) treatment of hepatitis type C. All 4 patients were females; 2 had hyperthyroidism and 2 had hypothyroidism during or after IFN therapy. The onset or aggravation of thyroid dysfunction occurred during administration of IFN in 1 patient and 4 weeks after the end of IFN therapy in the remaining 3 patients. The 2 patients who demonstrated hyperthyroidism were euthyroid and negative for thyroid autoantibodies before receiving IFN therapy. The remaining 2 patients who demonstrated hypothyroidism were positive for thyroid autoantibodies before IFN therapy. One of these patients had a slight decrease in thyroid function before IFN therapy. Anti-thyroid stimulating hormone (TSH) receptor antibodies became positive in all 4 patients. Since there may have been a causal relationship between IFN therapy and the onset or aggravation of thyroid dysfunction, IFN therapy should be administered with caution.

Adult↗

Clinical evaluation of intramuscular administration of natural interferon-gamma in the treatment of chronic hepatitis B.

Natural interferon-gamma at a dose of 0.5 x 10(6) or 1 x 10(6) IU daily was intramuscularly administered daily for 4 weeks to 15 patients with chronic hepatitis B. The efficacy and safety of the treatment were evaluated for 24 weeks following the completion of the 4-week treatment period. Persistent disappearance of HBeAg was observed in 5 of 15 patients. Serum hepatitis B virus (HBV)-related DNA polymerase disappeared in 5 of 13 patients at the end of interferon therapy. On the other hand, serum ALT and beta 2-microglobulin levels showed a significant increase during the interferon therapy period. The side effects were completely reversible. These findings suggest that interferon-gamma has an antiviral effect in patients with chronic hepatitis B and that the main mechanism of the therapeutic effect may be associated with the elimination of HBV-infected hepatocytes due to the immunopotentiating effect of the substance.

Adult↗

Role of cytoskeleton and acidification of endocytic compartment in asialoglycoprotein metabolism in isolated rat hepatocyte couplets.

The process of receptor-mediated endocytosis is common to a variety of species and cell types. One of the best characterized receptor-ligand systems is the hepatocyte receptor for asialoglycoproteins. We investigated the morphological features of the uptake and intracellular transport of gold-conjugated asialofetuin in isolated rat hepatocyte couplets. We assessed the effects of colchicine, lumicolchicine, cytochalasin B, and chloroquine on the uptake and intracellular transport of asialoglycoproteins. Isolated rat hepatocyte couplets were incubated with gold-conjugated asialofetuin, and transmission electron micrographs of these cells were analyzed to determine the density and distribution of gold particles in the peripheral and pericanalicular areas. Results were analyzed morphometrically. Colchicine significantly inhibited the uptake and intracellular transport of asialoglycoproteins, but did not affect membrane fusion of endocytic compartments in the peripheral area. Lumicolchicine and cytochalasin B had minimal effects on these processes. Chloroquine inhibited the uptake of asialoglycoproteins, but did not affect the intracellular transport of asialoglycoproteins. Results suggest that the microtubule is essential for intracellular movement of endocytosed asialoglycoproteins and receptor recycling, and that endocytic structures in the peripheral regions can fuse in the absence of intact microtubules. We also found that uptake and intracellular transport of asialoglycoproteins were independent of the microfilaments, and the pH gradient in endocytic compartments was important in receptor-mediated endocytosis of asialoglycoproteins.

Acids↗

Effects of extracellular matrices on tube formation of cultured rat hepatic sinusoidal endothelial cells.

To determine the effects of extracellular matrices on the function and morphology of hepatic sinusoidal endothelial cells, isolated rat hepatic sinusoidal endothelial cells were cultured in three-dimensional fashion on collagen gel containing various extracellular matrix components. Cells cultured on type I collagen gel with or without type IV collagen formed a cobblestone appearance on the surface of the gel. Cells cultured on laminin-containing type I collagen gel invaded the gel and exhibited three-dimensional tube formation with a decreased number of characteristic endothelial pores. Morphometrically, there was a significant relationship between the length of the tube formed and the concentration of laminin in the type I collagen gel. Cells cultured on Matrigel, which contains high concentrations of laminin, type IV collagen, fibroblast growth factor, tissue plasminogen activator, and other growth factors, formed a great number of tubes into a network on the surface of the gel, as is observed in the situ hepatic sinusoidal endothelial cells. Ultrastructurally, tube-forming endothelial cells cultured on Matrigel had many endothelial pores on the cell surface, with tubes (approximately 10 microns in diameter) formed by two or three hepatic sinusoidal endothelial cells. These results indicated that extracellular matrix components, especially laminin, induced the formation of tubes in cultured rat hepatic sinusoidal endothelial cells. Tube-forming sinusoidal endothelial cells cultured on Matrigel could provide more advantages than the two-dimensional culture model for investigating the function and morphology of these cells in vitro.

Animals↗