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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 307 records · Page 17Linked to original sources

A novel gene (drad-1) expressed in hematopoiesis-supporting stromal cell lines, ST2, PA6 and A54 preadipocytes: use of mRNA differential display.

We established a differentiation-inducible preadipocyte cell line, designated A54 preadipocytes, from C3H10T1/2 (10T1/2) mouse embryo fibroblasts. A54 preadipocytes had marked hematopoiesis-supporting ability in vitro but this ability was lost after terminal differentiation to adipocytes. In this study, to identify molecules that contribute to the hematopoiesis-supporting ability of A54 preadipocytes, we screened genes that were differentially expressed in A54 preadipocytes and isolated seven novel genes by reverse transcriptase polymerase chain reaction mRNA differential display. An RNase protection assay confirmed that one of these genes was expressed at high levels in parent 10T1/2 cells and A54 preadipocytes but to a much lesser extent in fully differentiated A54 adipocytes. This gene was defined as a gene that was downregulated during adipocyte differentiation-1 (drad-1). The size of drad-1 mRNA was 8.2 kb, and the gene was expressed in other mouse preadipocytes, namely, ST2 and PA6 cells, that have hematopoiesis-supporting ability. Moreover, drad-1 was also found to be expressed in bone marrow in vivo. The function of the protein encoded by drad-1 is unknown, but the expression of the gene may be useful as a molecular marker of adipocyte differentiation.

Adipocytes↗

Cortical laminar necrosis in brain infarcts: chronological changes on MRI.

We studied the MRI characteristics of cortical laminar necrosis in ischaemic stroke. We reviewed 13 patients with cortical laminar high signal on T1-weighted images to analyse the chronological changes in signal intensity and contrast enhancement. High-density cortical lesions began to appear on T1-weighted images about 2 weeks after the ictus. At 1-2 months they were prominent. They began to fade from 3 months but could be seen up to 11 months. These cortical lesions showed isointensity or high intensity on T2-weighted images and did not show low intensity at any stage. Contrast enhancement of the laminar lesions was prominent at 1-2 months and became less apparent from 3 months, but could be seen up to 8 months.

Aged↗

Shear stress-induced myosin association with cytoskeleton and phosphorylation in human platelets.

Upon platelet activation by a high shear stress (108 dyne/cm2), actin and actin-binding protein increased rapidly into the Triton-insoluble cytoskeleton, whereas the association of myosin increased gradually. The amounts of cytoskeleton-associated myosin depended on the extent of aggregation. Preceding the maximal aggregation and ATP secretion, the 20 kDa light chain of myosin (MLC) is rapidly phosphorylated to approx. 45% of 20 kDa MLC and is then dephosphorylated. Cytoskeletal association of myosin and phosphorylation of 20 kDa MLC was inhibited by OP-41483, a prostaglandin I2 analog, which inhibited the full aggregation response to shear stress. Exposure to high shear stress resulted in an increased association of myosin light chain kinase and protein phosphatase types 1 and 2A with the cytoskeleton, while the cytoskeletal association of protein kinase C was not evident. These results indicate that 20 kDa MLC phosphorylation is involved in shear stress-induced platelet activation, and that cytoskeletal association of protein phosphatases may regulate the phosphorylation level of cytoskeletal elements such as myosin together with myosin light chain kinase.

Blood Platelets↗

Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo.

Cilostazol(6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4- dihydro-2(1H)-quinolinone) selectively inhibits cGMP-inhibited phosphodiesterase (PDE3) and is a potent inhibitor of platelet aggregation induced by various agonists. Effect of cilostazol on shear stress-induced human platelet aggregation (SIPA) was examined in vitro and ex vivo. Cilostazol inhibited SIPA dose-dependently in vitro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2.6 microM (m +/- SE, n=5), which was very similar to that (12.5 +/- 2.1 microM) for inhibition of ADP-induced platelet aggregation. Cilostazol potentiates the inhibition of SIPA by PGE1 and enhances its ability to increase cAMP concentrations. A single oral adminstration of 100 mg cilostazol to healthy volunteers produced a significant inhibition of SIPA. This study demonstrates that cilostazol is an effective inhibitor of SIPA, which may be important for the prevention and the treatment of arterial occlusive diseases.

3',5'-Cyclic-AMP Phosphodiesterases↗

Vertebral artery occlusion after subarachnoid hemorrhage from a dissecting aneurysm of the vertebral artery: case report.

BACKGROUND: Generally speaking, occlusion of the vertebral artery is a finding of a dissecting aneurysm associated with completed stroke. We present a case of a vertebral dissecting aneurysm that produced subarachnoid hemorrhage (SAH). Angiography on the day of hemorrhage, however, demonstrated complete occlusion of the vertebral artery. CASE PRESENTATION: A 44-year-old hypertensive woman suffered a sudden onset of headache and vomiting followed by loss of consciousness due to SAH. Angiography on the day of hemorrhage revealed a complete occlusion of the right vertebral artery just distal to the dissecting aneurysm. This is the first report of such a case. The patient was still considered to be at significant risk of rerupture. Craniotomy and clip occlusion of the right vertebral artery and the origin of the right posterior inferior cerebellar artery were carried out to trap the thin-walled sac. At discharge, the patient had recovered completely except for some left limb ataxia, which subsequently disappeared. CONCLUSIONS: Two options are available for the treatment of such a case: surgical or medical treatment. We employed surgery. Which is the preferred approach, however, is a difficult judgment to make at this juncture.

Adult↗

Functional coupling of Gi subtype with GABAB receptor/adenylyl cyclase system: analysis using a reconstituted system with purified GTP-binding protein from bovine cerebral cortex.

A single molecular species of GTP-binding protein (G protein) has been purified from the bovine cerebral cortex. The immunoblot analysis indicated that the isolated G protein might be Gi1 or Gi2 but not Go, since it was reacted by specific antibodies, anti-Gi alpha 1-2 and anti-Gi alpha 1-1, but not anti-Go alpha. When the Gi protein was reconstituted into phospholipid vesicles with partially purified GABAB receptor and adenylyl cyclase, the stimulation of GABAB receptor by its agonists induced the inhibition of forskolin-stimulated cAMP accumulation. This GABA-induced inhibition was abolished by CGP 55845A, an antagonist of GABAB receptor. These results suggest that a Gi subtype, which was suggested to correspond to Gi1 or Gi2 may be functionally coupled with GABAB receptor/adenylyl cyclase system.

Adenylyl Cyclases↗

A case of early myoclonic encephalopathy with the congenital nephrotic syndrome.

We describe a male infant with early myoclonic encephalopathy (EME) associated with the congenital nephrotic syndrome, microcephaly, multiple minor anomalies, and cerebellar hypoplasia. He had erratic and massive myoclonus, and partial seizures from the neonatal period. Electroencephalography showed the so-called suppression-burst pattern. He died of disseminated intravascular coagulation caused by the congenital nephrotic syndrome at the age of two months. Our patients is the first reported case with EME associated with the congenital nephrotic syndrome.

Abnormalities, Multiple↗

Successful treatment of a patient with Graves' disease on hemodialysis complicated by antithyroid drug-induced granulocytopenia and angina pectoris.

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Agranulocytosis↗

Paracrine effect of human chorionic gonadotropin ectopically produced from papillary thyroid cancer cells on growth and function of FRTL-5 rat thyroid cells.

It is well known that human chorionic gonadotropin (hCG) is sometimes secreted from nontrophoblastic neoplasms. To elucidate the role of ectopic hCG, we investigated the effect of hCG produced from a papillary thyroid cancer cell line (B-CPAP cells) on stimulation and growth promotion of FRTL-5 rat thyroid cells. Ectopic hCG contained in the culture medium of B-CPAP cells was purified using gel filtration and bioassayed for thyrotropic activity in FRTL-5 cells. Addition of ectopic hCG (up to 5.2 x 10(4) IU/L) increased cyclic adenosine monophosphate (cAMP) accumulation and 3H-thymidine incorporation in FRTL-5 cells dose dependently. These effects were almost as potent as the stimulation induced by standard hCG CR-127. After the absorption of the ectopic hCG by anti-hCG-beta monoclonal antibody, the cAMP accumulation was significantly decreased. Analysis of ectopic hCG isoforms with different isoelectric points indicated the predominance of the acidic hCG isoform with isoelectric point (pI) 3.8-3.2 that is the major isoform of standard hCG. Basic isoforms (pI 5.7-5.3) with higher thyrotropic potency were also detected. These results indicate that the ectopic hCG secreted from papillary thyroid cancer cells possess intrinsic thyroid-stimulating and growth-promoting activity. The ectopic hCG may act as an autocrine-paracrine factor in nontrophoblastic neoplasms.

Animals↗

Simple analysis of diphenylmethane antihistaminics and their analogues in bodily fluids by headspace solid-phase microextraction-capillary gas chromatography.

Thirteen antihistaminic drugs and their analogues are tested for their extraction by headspace solid-phase microextraction from human whole blood and urine. Their determination is made by using capillary gas chromatography with flame ionization detection. Relatively high recoveries are obtained for terodiline, diphenhydramine, diphenylpyraline, and orphenadrine in urine; but the recoveries in blood extracts are 4-51 times lower than those in urine extracts for all drugs. Benactyzine and piperilate are not suited for the extraction method. The calibration curves are drawn for four drugs spiked to whole blood and for eleven drugs spiked to urine; excellent linearity is confirmed for the drugs. The detection limits for the drugs are 76-473 ng/mL in blood and 13-186 ng/mL in urine. Diphenhydramine is determined for whole blood obtained from a male subject who had received oral administration of 30 mg diphenhydramine-HCl 150 min before the sampling; the concentrations of the drug are 0.12 and 1.22 micrograms/mL for blood and urine, respectively.

Adult↗

Increased serum levels of thrombopoietin in patients with thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or disseminated intravascular coagulation.

The serum levels of thrombopoietin (TPO) were measured in 16 patients with thrombotic thrombocytopenic purpura (TTP), 12 with hemolytic uremic syndrome (HUS), 10 with aplastic anemia (AA), 10 with disseminated intravascular coagulation (DIC), and 71 with idiopathic thrombocytopenic purpura (ITP). The serum TPO levels were measured with a sensitive sandwich enzyme-linked immunosorbent assay. The serum TPO level in the ITP group (1.68 +/- 0.85 fmol/ml) were not significantly increased compared with those of the normal subjects. The TPO levels in the TTP (2.77 +/- 1.38 fmol/ml) and HUS groups (5.77 +/- 4.41 fmol/ml) were higher than those of the normal subjects. The patients with AA (12.7 +/- 8.0 fmol/ml) and those with DIC (13.3 +/- 5.7 mol/ml) had significantly higher serum TPO levels than did the normal subjects and ITP patients. The TPO levels were well correlated with the platelet counts in the TTP patients, and were negatively correlated with the platelet counts in the ITP patients. These results suggest that the serum TPO levels in some thrombocytopenic diseases are regulated not only by the platelet count and the megakaryocyte mass, but also by other factors.

Adult↗

Möbius-like syndrome associated with a 1;2 chromosome translocation.

We report here a rare case of Möbius-like syndrome associated with a 1;2 chromosome reciprocal translocation (46,XY,t(1;2)(p22.3;q21.1). The patient had facial diplegia, ptosis, anteverted nostrils, malformed and lowset ears, and slight developmental delay. Since a microdeletion could be present at the breakpoint in a reciprocal translocation, it is possible that the gene responsible for Möbius syndrome is located in this region of chromosome 1.

Chromosomes, Human, Pair 1↗

A case of lymphoid interstitial pneumonia in a 3-month-old boy not associated with HIV infection: immunohistochemistry of lung biopsy specimens and serum transforming growth factor-beta 1 assay.

The case of a 3-month-old boy with lymphoid interstitial pneumonia (LIP) is reported. He had cough and tachypnea, his weight gain was poor and a chest radiograph showed microgranular shadows in almost all lung areas. Histological investigations revealed severe cellular infiltration by a variety of lymphoid and plasma cells with lymphoid follicle formation in the alveolar walls and also around the bronchioles. Foamy macrophages, a few lymphocytes and exudate filled the alveolar spaces. Epithelial cells lining the air spaces expressed human leukocyte antigen (HLA)-DR. Lymphocytes and macrophages in the alveolar spaces expressed transforming growth factor (TGF)-beta strongly. Serum TGF-beta 1 concentrations were measured eight times during the course of his illness. They exceeded the upper end of the normal range in four samples and were within it in the others. These results suggested that dysfunction of the immune system, especially abnormal expression of HLA-DR in non-immune cells and exaggerated production of TGF-beta played important roles in the pathogenesis of LIP in this patient.

Antigens, CD↗

Large cell carcinoma of the lung metastatic to nuchal muscle.

Clinically apparent hematogenous skeletal muscle metastases from lung cancer are extremely rare. We present a 72-year-old man with a large cell lung carcinoma metastatic to nuchal muscle. Cervical computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a well-defined mass in the left splenius capitis muscle. A percutaneous needle biopsy was performed to establish a diagnosis. Localized skeletal muscle swelling may rarely prove to be metastases in patients with lung cancer, but should be investigated in the case of muscle swelling.

Aged↗

Platelet-associated IgM elevated in patients with chronic hepatitis C contains no anti-platelet autoantibodies.

We investigated whether thrombocytopenia in patients with chronic hepatitis C is due to anti-platelet autoantibodies. Platelet-associated IgG (PAIgG) and platelet-associated IgM (PAIgM) were measured by direct immunofluorescent flow cytometric analysis. Elevation of PAIgM level was detected in 70% of chronic hepatitis C patients, while only a mild elevation of PAIgG level was detected in 32% of the cases. The elevation of PAIgM values in these patients was comparable to that in patients with chronic immune thrombocytopenic purpura (ITP). However, elevated PAIgM was also found in both patients with and without thrombocytopenia, and no correlation was found between PAIgM and platelet count. Eluted PAIgM did not react with normal platelets in all cases with a positive PAIgM value, indicating that eluted PAIgM contained no detectable anti-platelet antibodies. During alpha-interferon therapy, the level of PAIgM increased in association with the decrease in platelet counts in 75% of the cases; however, eluted PAIgM at any day point never reacted with platelets from normal donors. PAIgM was elevated in patients with chronic hepatitis C, but contained no detectable anti-platelet autoantibodies. Thrombocytopenia in these patients is not due to anti-platelet autoantibodies.

Autoantibodies↗

Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats.

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

Animals↗