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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 397 records · Page 22Linked to original sources

Delayed onset of intraventricular hemorrhage following removal of acute subdural hematoma--case report.

A 68-year-old male presented with neurological deterioration after a lucid interval following head trauma. Computed tomographic (CT) scans on admission demonstrated a subdural hematoma in the right frontotemporal region accompanied by subarachnoid hemorrhage in the right Sylvian and interhemispheric fissures. The subdural hematoma was removed via a right frontotemporoparietal craniectomy. However, immediate postoperative CT scans revealed hemorrhage in the third and both lateral ventricles, apparently separate from the primary hemorrhages. Decompressive rupture of damaged subependymal veins is suggested as the cause of the delayed traumatic intraventricular hemorrhage.

Acute Disease↗

[Expression of major histocompatibility complex antigens and intercellular adhesion molecule-1 (ICAM-1) on renal cell cancer. De novo expression and modulation by cytokines on renal cell cancer cell lines].

Major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1) play important roles in immune response. In order to investigate the association between renal cell cancer (RCC) and host's immune system, expression of MHC antigens and ICAM-1 was examined on RCC. Immunohistochemical analysis revealed a positive correlation between the expression of MHC antigens and ICAM-1. In general, tumor with higher degree of mononuclear cell infiltration expressed MHC antigens and ICAM-1 more frequently and intensely. Among cytokines which were reported to be potent inducers of ICAM-1 on malignant melanoma cell lines, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha augmented the expression of ICAM-1 on ACHN cells whereas ICAM-1 and class I antigens on KRC/Y cells. IFN-alpha enhanced MHC class I antigens but not ICAM-1. Class II antigen expression of both cell lines was augmented by only IFN-gamma. These results suggest that cytokines which could be produced by tumor-infiltrating mononuclear cells, especially IFN-gamma and TNF-alpha, might modulate expression of MHC antigens and ICAM-1, and influence host immune response against RCC.

Adult↗

Identity of brain-associated small cell lung cancer antigen and the CD56 (NKH-1/Leu-19) leukocyte differentiation antigen and the neural cell adhesion molecule.

Previous studies have demonstrated the monoclonal antibody, TFS-4, to recognize a cell surface antigen, 124,000 Daltons, of molecular weight expressed selectively on small cell lung cancer but not on non-small cell lung cancer, and to cross-react with the human brain, cardiac muscle and some smooth muscle cells. The cross-reactivity of TFS-4 with peripheral blood lymphocytes was examined by two color immunofluorescence analysis, using monoclonal antibodies to leukocyte differentiation antigens. Flow cytometric analysis revealed an identical subset of cells to express both BASCA and CD56(NKH-1 antigen). The immunofluorescence profiles for both TFS-4 and NKH-1 were, furthermore, identical to those of the background controls, identicating identical quantities of the antigens to be present on each cell within the population. Since CD56 has been show to be identical to the neural cell adhesion molecule (N-CAM), we determined the amino-terminal amino acid sequence of BASCA purified from the human brain. The amino-terminal amino acid sequence of BASCA was identical to that of N-CAM.

Amino Acid Sequence↗

[Effect of L-carnitine in patients with ischemic heart disease].

To assess the protective effects of L-carnitine (LC) infusion on ischemic heart disease, 30 patients who had angina and ischemic ECG changes during exercise were evaluated by bicycle ergometry. They were categorized in LC and non-treatment (NT) groups. There were no significant differences in age and sex between the 2 groups. Before exercise, 15 patients (9 males and 6 females) received 60 mg/kg LC and the results including hemodynamics, coronary circulation, and cardiac metabolism at rest and during exercise were compared with those of the NT group studied in the same protocol (50 watts x to cycle, 15 min). At the end of 30 min LC drip infusion, the arterial carnitine content (LC (a)) reached 1,980 +/- 257.3 microM and then was maintained at 1,212.7 +/- 136.2 microM during exercise. There was no correlation of LC (a) with the coronary arterio-venous difference nor with myocardial uptake of LC. Although there was no significant difference in coronary blood flow (CBF: mliters/100 g/min) between the LC and NT groups at rest (LC: 92.1 +/- 29.0 vs NT: 88.0 +/- 26.5), CBF during exercise increased significantly in the LC group compared with the NT group (LC: 230.4 +/- 113.8 vs NT: 139.1 +/- 52.7; p < 0.05). In the NT group, there was no significant change in coronary arterio-venous oxygen difference ((a-cs) O2: vol %) during exercise, but in the LC group (a-cs) O2 increased significantly from 10.2 +/- 1.3 to 11.5 +/- 1.9 (p < 0.01). Furthermore, although there was no significant difference in myocardial oxygen consumption (MVO2: mliters/100 g/min) at rest between the 2 groups (LC: 9.30 +/- 2.96 vs NT: 9.71 +/- 3.09), it increased significantly in the LC group compared with the NT group during exercise (LC: 25.11 +/- 9.98 vs NT: 15.55 +/- 6.09). MVO2/LVWI (LVWI = left ventricular work index) and MVO2MT (MT = myocardial tension) did not significantly differ at rest between the 2 groups. However, these 2 indices decreased significantly during exercise (p < 0.05) in the NT group, and remained unchanged in the LC group, showing a significant difference between the 2 groups (both p < 0.05). In myocardial energy substrates, the myocardial uptake ((a-cs) x CBF) of free fatty acid (FFA: muEq/100 g/min) increased significantly in the LC group compared with that of the NT group (LC: 10.16 +/- 13.26-->31.88 +/- 27.58* vs NT: 16.02 +/- 27.92-->18.11 +/- 31.00;* = p < 0.05, LC vs NT).

Adult↗

Analysis of ion behavior and potentials in a Na+ ion-selective membrane containing methyl monensin.

Ion-selective electrodes (ISEs) are widely used in clinical examinations. The mechanisms of ISEs have been studied to develop a disposable ISE for "dry chemistry" analyses. The behavior of Na+ and Ag+ in an ion-selective polymer liquid membrane (ISM) containing methyl monensin (MMO), which is selective for Na+, has been clarified by x-ray microanalysis and measurement of electrical potential. The results indicate that Na+ is not transported across the membrane because of a stability of the Na(+)-MMO complex, whereas Ag+ (from the Ag/AgCl electrode) is transported with Cl- across the membrane by diffusion. The difference in potential, which follows a Nernst gradient, is generated by the formation of a double layer of electrons at the interface between the ISM and the electrolyte solution. These results are explainable by the stability of the trap in the polymer liquid membrane. MMO acts as a stable trap of Na+ and as a metastable site of Ag+ for movement.

Cations↗

Endothelium-independent and endothelium-dependent contractions mediated by P2X- and P2Y-purinoceptors in canine basilar arteries.

Both alpha, beta-methylene ATP and beta, gamma-methylene ATP (P2X selective agonists) were shown to induce transient contraction in intact and endothelium-removed preparations of canine basilar arteries. 2-Methylthio ATP (a P2Y selective agonist) caused transient contraction of intact arteries and this response was nearly abolished by removal of the endothelium. In the presence of alpha, beta-methylene ATP (10(-6) M), the endothelium-independent contractions induced by alpha, beta-methylene ATP itself (10(-6) M) and by beta, gamma-methylene ATP (10(-5) M) were both abolished. The endothelium-dependent contraction induced by 2-methylthio ATP (10(-7) M) was not attenuated by alpha, beta-methylene ATP. The contraction induced by 2-methylthio ATP (10(-7) M) was attenuated markedly by reactive blue 2 (a P2Y antagonist) (3 x 10(-6) M), aspirin (5 x 10(-5) M), OKY-046 (thromboxane A2 synthetase inhibitor) (10(-5) M) and ONO-3708 (thromboxane A2 antagonist) (10(-8) M). However, these agents did not affect the endothelium-independent contraction induced by alpha, beta-methylene ATP (10(-6) M). Neither TMK-777 (a 5-lipoxygenase inhibitor) (10(-7) M) nor superoxide dismutase (100 U/ml) plus catalase (1,000 U/ml) affected either contraction. The present experiments demonstrate that P2X-purinoceptors mediate endothelium-dependent contraction in the canine basilar artery, and that the endothelium-derived contracting factor in this system is probably thromboxane A2.

Adenosine Triphosphate↗

[Expression of transferrin receptor on transitional cell cancer].

We examined the expression of transferrin receptor (TR) in transitional cell cancer (TCC) immunohistologically, to clarify its implication in tumor malignancy. Forty eight out of 51 tumors expressed TR while TR was not detected on the normal transitional epithelium of renal pelvis, ureter and urinary bladder. In general, a higher grade and more invasive TCC expressed TR more frequently and more intensely. Furthermore, recurrent tumors treated with transurethral resection significantly more frequently expressed TR than the initial tumor. These results indicate that the detection of TR on the tumor cells is useful for estimating the degree of their malignancy.

Carcinoma, Transitional Cell↗

[A case report of long-term post-thoracotomy pain management with intrapleural bupivacaine].

A 50-year old woman with right post-thoracotomy pain was referred to us for assistance with pain control. She required pentazocine 60-150 mg per day before our treatment. First, we treated her with intercostal nerve block or oral morphine sulfate. But the result was not satisfactory after five months. Then we tried intrapleural bupivacaine. An epidural catheter was inserted into the pleural space from eight intercostal space at the anterior axillary line and 10 ml of 0.5% bupivacaine was instilled. The treatment was effective for about 4-5 hours. We continued this method for 42 days with 10 ml of 0.25% or 0.5% bupivacaine once or twice a day. She felt so good from the intrapleural analgesia and could be discharged. There was no hypotension, respiratory depression, urinary retention except burning thoracic sensation. We think it is possible to use this intrapleural bupivacaine to treat a certain kind of unilateral chronic pain.

Bupivacaine↗

Expression of intercellular adhesion molecule-1 (ICAM-1) on renal-cell cancer: possible significance in host immune responses.

In this study we examined the expression of intercellular adhesion molecule-1 (ICAM-1) in 28 cases of renal-cell cancer (RCC). We also examined ICAM-1 expression on RCC cell lines in response to cytokines. Immunohistochemistry revealed frequent expression (23 positive cases among the 28 RCCs) of ICAM-1 in RCC. The molecule was not detected on renal tubular cells as far as could be determined. Furthermore, the number of ICAM-1-positive cells in RCC was significantly correlated with the degree of mononuclear cell infiltration, involving mainly T lymphocytes and a smaller number of macrophages bearing the LFA-1 molecule. Expression of ICAM-1 on RCC cell lines was augmented by in vitro treatment with interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1)beta. These results suggest that the expression of ICAM-1 on RCC might be modified by cytokines produced by tumor-infiltrating mononuclear cells, and that ICAM-1 expression on RCC might augment the host immune reaction.

Adult↗

Physicochemical and biological characterization of asialoerythropoietin. Suppressive effects of sialic acid in the expression of biological activity of human erythropoietin in vitro.

Various partially or fully desialylated human erythropoietins were obtained by neuraminidase digestion of the hormone, without non-specific proteolysis and degradation of carbohydrates. Asialoerythropoietin showed a specific activity of 220-IU/mg protein in vivo, although that of the intact erythropoietin was 2.2 x 10(5) IU/mg. A linear relationship was found between the logarithm of the specific activity in vivo and the number of sialic acids. The asialoerythropoietin showed a four-times-higher specific activity in vitro compared with intact erythropoietin using mouse bone marrow cells. It also showed an approximately six-times-higher specific activity in a colony-forming assay for the erythroid colony-forming unit and the erythroid burst-forming unit. Partially or fully de-N-glycosylated erythropoietin derivatives also showed lower in vivo activity but higher in vitro activity than the intact erythropoietin, dependent on the number of sialic acids. To clarify the reason for the enhanced biological activity of asialoerythropoietin in vitro, the binding of intact 125I-erythropoietin or 125I-asialoerythropoietin to cells containing specific receptors for the hormone was analyzed. 125I-asialoerythropoietin bound to spleen cells from anemic mice approximately five times faster than did intact 125I-erythropoietin. The amount of 125I-asialoerythropoietin internalized by target cells, measured in the absence of NaN3, was four times higher than that of intact erythropoietin. These results demonstrate that asialoerythropoietin binds to its receptor faster than the intact form. This may be the main reason for the increased activity of asialoerythropoietin in vitro.

Animals↗

Depletion of CD8+ cells exacerbates organ-specific autoimmune diseases induced by CD4+ T cells in semiallogeneic hosts with MHC class II disparity.

Autoimmune diseases are known to be induced in some donor-recipient combinations of mice undergoing the graft-vs-host reaction (GVHR). In this paper, we report on the development of primary biliary cirrhosis (PBC)-like hepatic lesions and also on pancreatic insulitis in (B6 x bm12)F1 mice injected with B6 CD4+ T cells. At the sites of these lesions, cellular infiltration around ductal structure was observed. Immunohistochemical studies revealed that both CD4+ and CD8+ T cells were present in the lesions of the liver and pancreas. To clarify the role of the CD8+ T cells, which were probably of host origin, we used a mAb against the Lyt-2 molecule. Both the PBC-like hepatic lesions and pancreatic insulitis were exacerbated by eliminating CD8+ T cells from mice with MHC class II GVHR. Also, autoantibodies against the pyruvate dehydrogenase-E2 component, which has been recently found to contain an immunodominant site (autoepitope) for B cell reactivity in patients with PBC, were detected in the sera of these mice by ELISA and their presence was confirmed by immunoblotting procedures. Our findings suggest that similar mechanisms as in GVHR caused by MHC class II disparity are active in the development of PBC. It should also be noted that, in addition to the hepatic lesions, insulitis closely resembling that seen in the nonobese diabetic mouse was induced in our experimental system. The results suggest that our model provides a unique opportunity to study organ-specific autoimmune diseases. Because the effector in our experimental system was defined to be CD4+ T cells responding to Iabm12 Ag, our findings support the hypothesis that an excessive immune response directed against Ia Ag can produce autoimmune disease.

Animals↗

A potent antibacterial protein in royal jelly. Purification and determination of the primary structure of royalisin.

A new potent antibacterial protein, for which we propose the name royalisin, was found in royal jelly of the honeybee Apis mellifera L. and purified to homogeneity for the first time by acid extraction, gel filtration, and reverse-phase high pressure liquid chromatography. The primary structure of royalisin was determined to consist of 51 residues, with three intramolecular disulfide linkages, having a calculated molecular mass of 5523 Da. Royalisin is an amphipathic protein, with the C-terminal half of the molecule being rich in charged amino acids; and it showed extensive sequence homology to two other antibacterial proteins, sapecin from embryonic Sarcophaga peregrina cells and phormicins from Phormia terranovae larvae. Royalisin was found to have potent antibacterial activity against Gram-positive bacteria at low concentrations, but not against Gram-negative bacteria. Royalisin may be involved in a defense system active against bacterial invasion of the honeybee.

Amino Acid Sequence↗

ADP-ribosylation of the rho/rac proteins induces growth inhibition, neurite outgrowth and acetylcholine esterase in cultured PC-12 cells.

Botulinum ADP-ribosyltransferase C3 (C3 exoenzyme) was purified to homogeneity and added to cultured rat pheochromocytoma PC-12 cells. Incubation with this exoenzyme caused inhibition of cell growth and induced neurites as well as acetylcholine esterase in these cells. These changes were dependent on the amount of the enzyme added to the culture, which correlated with the in situ ADP-ribosylation of the rho/rac proteins in the cells. Preincubation with a specific anti-C3 exoenzyme monoclonal antibody inhibited both the ADP-ribosyltransferase activity and the neurite-inducing activity of the enzyme preparation. These results suggest that C3 exoenzyme affected the cellular function of the rho/rac proteins by ADP-ribosylation to induce these changes in the cells.

Acetylcholinesterase↗

Analysis of the T cell repertoire for myelin basic protein in thymus-grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease inducible in rodents by immunization of brain-specific antigens such as myelin basic protein (MBP). It is also well known that various strains of rats differ in their susceptibility to EAE upon active immunization. To elucidate the immune mechanisms of susceptibility and resistance to EAE, we first examined the T cell repertoire for MBP using thymectomized chimeras that possessed thymuses from EAE-susceptible (LEW) or EAE-resistant (BM) strains. It was revealed that T cell specificity of these chimeras was skewed toward that of the grafted thymus. Very interestingly, the chimeras bearing thymuses from the resistant strain developed severe EAE, keeping a hole in the encephalitogenic 68-88 sequence of MBP. These findings suggest that the strain-specific T cell repertoire itself is not involved in the regulation of EAE susceptibility. Furthermore, the analysis of the chimeras reconstituted with F1 T cells and marrow cells from various strains indicates that the major histocompatibility complex (MHC) molecules expressed on accessory cells primarily determine susceptibility or resistance to EAE. We finally showed, using various inbred and congenic rats carrying RT1l or RT1n, that susceptibility to EAE of rats carrying RT1l is heavily influenced by the background genes, whereas resistance to EAE of rats carrying RT1n is primarily regulated by the MHC molecules expressed on accessory cells without influence of the background genes.

Animals↗

Reduction of major histocompatibility complex class I antigens on invasive and high-grade transitional cell carcinoma.

We examined immunohistologically the expression of major histocompatibility complex (MHC) class I and II antigens, which play important roles in immune reactions, on transitional cell carcinoma (TCC). When stained with monoclonal antibody W6/32 against class I antigens, reduced staining was observed in 34 of 46 TCCs and was virtually absent in 15 of these. The cases showing reduced staining were much more frequent (29 of 34) in high- to moderate-grade than in low-grade TCC. Furthermore, class I antigens were reduced in 18 of 19 invasive TCCs, but in 16 of 27 superficial TCCs. Thus, the reduction of class I antigens was correlated significantly with a decreased degree of tumour cell differentiation and the presence of invasion. Class II antigens on TCC showed variable expression and were not related to tumour grade or stage.

Adult↗