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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 199 records · Page 11Linked to original sources

Thrombotic thrombocytopenic purpura accompanied by transient pure red cell aplasia and thymoma.

We describe a 64-year-old man with thrombotic thrombocytopenic purpura (TTP), transient pure red cell aplasia (PRCA) and thymoma. TTP in this case was thought to be idiopathic and was accompanied by microangiopathic hemolytic anemia. The patient, therefore, had an aplastic crisis due to PRCA. He was treated with peritoneal dialysis, plasma exchange with plasma infusion, red blood cell transfusion, methylprednisolone pulse therapy followed by maintenance dosing with intravenous prednisolone, gamma-globulin, vincristine, and dipyridamol. As a result, the patient's mental disorder, acute renal failure, anemia and thrombocytopenia improved; however, the haptoglobin level remained low. The pathogenesis of PRCA and thymoma indicates that these are immunological disorders often associated with each other. To our knowledge, there are no reports of TTP with transient PRCA and thymoma. Although such a combination is considered relatively rare, this case suggests that there is an immunological contribution to the pathogenesis of the association of these disorders.

Humans↗

[A case of thymoma with pleural dissemination which was treated by pleurectomy with patient survival without recurrence for more than five years].

A 46-year-old woman was admitted to our hospital with chest pain. Chest X-ray and CT revealed an anterior mediastinal mass as well as several small masses attached to the left chest wall. Thymoma was diagnosed by percutaneous biopsy. The serum level of anti-acetylcholine receptor antibody was 30.3 pmol/ml. At operation, the thymoma was found left in the anterior mediastinum, extending to the upper lobe of the lung. There were also numerous tumors of various size in the left parietal pleura. Thymectomy, partial resection of the upper lobe of the lung and pleurectomy were performed. One month later, she developed myasthenia gravis. After a complete remission of myasthenia gravis brought about by anti-choline esterase therapy, the patient was treated with irradiation. She has been well for more than five years after the operation but her serum anti-acetylcholine receptor antibody level is still higher than normal.

Combined Modality Therapy↗

[Construction of illegal drug images and mass media in Japan].

This study attempts to clarify the drug problem of Japan in terms of images of illegal drugs (stimulants, marijuana, and volatile solvents) by comparing (1) different types of drugs and (2) differences between generations. Another objective of this research was to examine influence by the mass media reports with regard to drug incidents which influence upon image formation of illegal drugs among people. In this study 488 males from the city of Osaka were chosen by a random sampling method and a door to door survey was undertaken utilizing a self-administered questionnaire with a partial interview method. It was revealed that as a whole negative images such as "dangerous" and "terrible" were still widely prevailing and positive image such as "fashionable" was much less prevailing. Specially, stimulants were regarded more dangerous compared to marijuana and volatile solvents. In contrary, marijuana was regarded more fashionable compared to stimulants and volatile solvents. Volatile solvents were considered more "intimate" compared to other drugs. With regard to generation differences, it was the youth who possessed more positive images towards marijuana and more intimate feelings about volatile solvents than other generations. Findings show that with regard to news about illegal drug incidents, respondents' appraisal of the news of mass media primarily make significant influence, as compare to mere cognition, on images of illegal drugs. Furthermore, it was revealed that there was likely to result in positive images of illegal drugs due to lack of adequate information. From the aspects of education, it was suggested that dissemination of information at a vast range and maintenance of negative images might become a crucial task.

Adult↗

[Significant correlation of telomerase activity in lung adenocarcinomas with cell differentiation and chromosome aberration].

Of a total of 21 surgically resected lung adenocarcinomas (15 men and 6 women with an average age of 59.6 yr) well, moderately and poorly differentiated types were 6, 7 and 8 cases, respectively. Telomerase activity determined by the TRAP assay was classified into four types as follows; negative = Score 0, weakly positive = 1, moderately positive = 2, strongly positive = 3. Chromosome aberrations were also classified into four groups: Score 0, 1, 2, 3 according to the number of marker chromosomes, 0, 1-5 6-15 and over 16 respectively. CT-Indices (chromosome aberration x telomerase activity) of well, moderately, and poorly differentiated types were 1, 4.3, 5.1 respectively. Thus, CT-Indices were correlated with cell differentiation in the lung adenocarcinomas (p < 0.01).

Adenocarcinoma↗

[The coexistence of pulmonary tuberculosis and thymoma a case report].

A 33-year-old male was admitted with complaints of cough, dysphagia, and swelling of face and upper extremities. Chest X-ray and CT scan revealed a large mediastinal mass and infiltrates in the right upper lobe. Percutaneous biopsy proved the mediastinal tumor as thymoma with cellular atypia. After irradiation, the tumor was surgically removed. Caseous epitheloid granulomas were found in the dissected mediastinal lymph nodes. AFB (Acid fast bacillus) stain of the patient's gastric fluid was positive for Mycobacterium. The coexistence of these two diseases was incidental, however, this case suggested that clinicians should perform careful evaluation of lung parenchyma as well as mediastinum on chest X-ray to identify occult diseases including pulmonary tuberculosis in patients with mediastinal mass lesion.

Adult↗

L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol stimulates ganglioside biosynthesis, neurite outgrowth and synapse formation in cultured cortical neurons, and ameliorates memory deficits in ischemic rats.

To address the role of brain gangliosides in synaptic plasticity, the synthetic ceramide analog, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) was used to manipulate the biosynthesis of gangliosides in cultured cortical neurons. Spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons, which represents synapse formation, was suppressed by the depletion of endogenous gangliosides by D-threo-PDMP, an inhibitor of glucosylceramide synthase. The decreased functional synapse formation was normalized by supplementation of GQ1b but not by the other gangliosides, suggesting that de novo synthesis of ganglioside GQ1b is essential for the synaptic activity (Mizutani A. et al., Biochem. Biophys. Res. Commun. 222, 494-498, 1996). On the other hand, the enantiomer of the inhibitor, L-threo-PDMP, could elevate cellular levels of glycosphingolipids including gangliosides. This paper presents our recent findings on the neurotrophic actions of L-threo-PDMP in vitro and in vivo. We found that L-PDMP could up-regulate neurite outgrowth, functional synapse formation and ganglioside biosynthesis through activating GM3, GD3 and GQ1b synthases. Simultaneously, the activity of p42 mitogen-activated protein kinase was also facilitated by L-PDMP. To evaluate the efficacy of this drug on long term memory, rats were trained for 2 weeks using an 8-arm radial maze task, and then forebrain ischemia was induced by 4-vessel occlusion (for 10 min x 2 with a 60 min interval). Repeated treatment of L-threo-PDMP (40 mg/kg, i.p. for 6 days, twice a day) starting 24 h after the ischemia, improved the deficit of the well-learned spatial memory, demonstrating the potential therapeutic use of the ceramide analog for treatment of neurodegenerative disorders.

Animals↗

Scalp localization using a simple algorithm.

We have developed a simple algorithm for scalp localization for craniotomy. Using a series of CT/MRI data, the point on the scalp closest to the center of the lesion (T) is determined by our program. A plane (plane R) is defined by three points: bilateral auditory meati and T. Point S is the intersection of three planes: the plane R, the scalp surface and the midsagittal plane. The distance from either S or the ipsilateral external auditory meatus to T is measured along the scalp surface on the plane R. The distance from the nasion to S along the scalp surface on the midsagittal plane is also measured. To determine the craniotomy site, these distances are measured directly on a patient's scalp in the operating room. This simple and accurate method for scalp localization could be used by installing our program in conventional CT/MR scanners.

Aged↗

Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells.

In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin-/- (beta 2m-/-) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK-T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55. EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, beta 2m-/-, and recombination activation gene 2 (RAG-2)-/- mice, indicating that the regulation by NK cells can be independent of T, B, or NK-T cells. We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.

Amino Acid Sequence↗

Type II alveolar epithelial cells in lung express receptor for advanced glycation end products (RAGE) gene.

Messenger RNA of receptor for advanced glycation end products (RAGE) is abundantly expressed in the lung. However, cell types expressing RAGE mRNA in the lung have not been identified. In order to elucidate the function of RAGE in pulmonary tissue, we have identified a cell type expressing RAGE mRNA by in situ hybridization and compared its expression level of RAGE mRNA by RNA blot analysis of isolated cells. In situ hybridization revealed that RAGE mRNA was intensely and specifically visualized in alveolar epithelial type II (AT-II) cells, and weakly in alveolar macrophages. The expression of RAGE mRNA in the primary culture of AT-II cells was at a high level, but that in alveolar macrophages isolated from alveolar lavage was under the level of detection by RNA blot analysis. These results showed that RAGE mRNA is specifically expressed in AT-II cells, and suggested that RAGE makes a substantial contribution to the function of AT-II cells in the lung.

Animals↗

Novel hepatitis C virus protease inhibitors: thiazolidine derivatives.

This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A.

Enzyme Inhibitors↗

Up-regulation of ganglioside biosynthesis, functional synapse formation, and memory retention by a synthetic ceramide analog (L-PDMP).

To address the role of brain gangliosides in synaptic activity, the ceramide analogs, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) and its enantiomer, L-PDMP, were used to inhibit and stimulate ganglioside biosynthesis in cultured cortical neurons. Prolonged treatment with both PDMP isomers exhibited opposite effects on functional synapse formation measured by spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons: suppression by D-PDMP and facilitation by L-PDMP. Up-regulation of synaptic activity by L-PDMP could be correlated with the slow but robust stimulation of ganglioside biosynthesis through activating GM3, GD3 and GQ1b synthases. In a similar time course, the activity of p42 mitogen-activated protein kinase was also enhanced by L-PDMP. To evaluate the efficacy of this drug in long-term memory, rats were trained for 2 weeks using an 8-arm radial maze task, and then forebrain ischemia was induced by 4-vessel occlusion. Treatment with L-PDMP starting 24 hours after the transient ischemia ameliorated the deficit of a well-learned spatial memory, demonstrating the potential therapeutic intervention of the ceramide analog for neurodegenerative disorders.

Animals↗

A novel fungal gene encoding chitin synthase with a myosin motor-like domain.

A csmA gene that encodes chitin synthase with a myosin motor-like domain was isolated from the filamentous fungus Aspergillus nidulans. Initially, we obtained the csmA as a homolog of the Aspergillus fumigatus chsE-partial fragment. A large open reading frame encoding a polypeptide of 1,852 a.a. was identified by determining the cDNA sequences. The chitin synthase conserved region was situated at the C-terminus and classified into class V as reported previously. On the other hand, the N-terminal region showed significant similarity to myosin motors and could not be classified into any types of myosins identified so far. Thus, it is suggested that this is the first report of unconventional myosin fused to a metabolic enzyme. The finding of this new type of chitin synthase gene suggests that localization of chitin synthesis may be guided by association with cytoskeletal structures.

Amino Acid Sequence↗

Two forms of avian(chicken) TATA-binding protein mRNA generated by alternative polyadenylation.

We have isolated and sequenced the cDNA encoding avian(chicken) TATA-binding protein (cTBP). The cTBP protein shows a significant homology to those of the other species, and especially its C-terminal region (180 amino acid residues) is identical to those of the vertebrates. By Northern blot analysis, we found that two transcripts with about 2.1 kb (cTBP0) and 2.7 kb (cTBP1) were expressed in various chicken tissues, though only one type of the TBP transcript was reported in vertebrates. A primer extension study demonstrated a single transcription start site. The analysis of the genomic structure of cTBP with the sequences of the two types of cTBP cDNAs(cTBP0 and cTBP1) revealed that the alternative polyadenylation generates two transcripts with different 3'untranslated regions (3'UTRs), indicating a putative role of the different 3'UTRs on the stability of cTBP mRNAs.

Amino Acid Sequence↗

The Aspergillus nidulans genes chsA and chsD encode chitin synthases which have redundant functions in conidia formation [corrected and republished article originally appeared in Mol Gen Genet 1996 Jun; 251(4):442-50].

We previously isolated three chitin synthase genes (chsA, chsB, and chsC) from Aspergillus nidulans. In the present work, we describe the isolation and characterization of another chitin synthase gene, named chsD, from A. nidulans. Its deduced amino acid sequence shows 56.7% and 55.9% amino acid identity, respectively, with Cal1 of Saccharomyces cerevisiae and Chs3 of Candida albicans. Disruption of chsD caused no defect in cell growth or morphology during the asexual cycle and caused no decrease in chitin content in hyphae. However, double disruption of chsA and chsD caused a remarkable decrease in the efficiency of conidia formation, while double disruption of chsC and chsD caused no defect. Thus it appears that chsA and chsD serve redundant functions in conidia formation.

Amino Acid Sequence↗

Characterization of pH-Dependent Poly(acrylic Acid) Complexation with Phospholipid Vesicles

The pH-dependent complexation of poly(acrylic acid) (PAA) with phospholipid (phosphatidylcholine) vesicles was characterized by fluorescence polarization, differential scanning calorimetry (DSC), and surface pressure measurements of phospholipid monolayers. The complexation was pronounced below pH 4, when the polymer carboxyl groups are protonated, as shown by the binding of PAA to vesicles and the decrease in polymer mobility. The complexation was strong at low polymer concentrations and was weaker at higher polymer concentrations. PAA complexation increased the gel to liquid crystalline (LC) phase transition temperature (Tm) and enthalpy (DeltaH) of the vesicles accompanied by a decrease in the transition cooperativity. This is most likely due to perturbations in the phospholipid headgroup upon PAA interaction. The effect of polymer adsorption on the phospholipid surface was investigated at the phospholipid/water interface. The ability of PAA to penetrate between the phospholipid molecules as a function of pH was determined by the lateral expansion of the monolayer at a constant surface pressure. The ability of the polymer to penetrate into the monolayer increased with decreasing pH. These results suggest that PAA complexation leads to expansion of the phospholipid packing of the vesicles by altering the phospholipid headgroup conformation.

Journal Article↗

Expressions of a calcium-binding protein (spot35/calbindin-D28K) in mouse olfactory cells: possible relationship to neuronal differentiation.

We used immunohistochemistry to investigate the expression of spot35/calbindin-D28k (calbindin) in mouse olfactory epithelium during development. Cell stages of immunopositive olfactory cells were determined by comparing the levels of proliferating cell nuclear antigen (PCNA). Calbindin-positive cells were abundant in the middle layer of the epithelium of animals before 2 weeks of age and gradually diminished during development. Only low levels were detectable near the basement membrane in the adult. Changes of calbindin-positive cells in terms of number and distribution were apparently compatible with localization changes of premature olfactory cells. PCNA overlapped calbindin in the nasal mucosa at lower magnifications on stained serial sections and immunohistochemical double staining revealed that calbindin-immunoreactive cells were located mainly just above PCNA-immunoreactive cells in the basal layer of the epithelium. This indicated that calbindin is expressed postmitotically in immature olfactory cells and is lost by mature cells. These findings suggest that calbindin might support the maturation of the olfactory cells, such as the projection of the neuronal processes, by stabilizing intracellular calcium ions in immature cells.

Aging↗

The production of a new water-soluble polysaccharide by Acetobacter xylinum NCI 1005 and its structural analysis by NMR spectroscopy.

A new water-soluble polysaccharide (WSP) was isolated from a culture of Acetobacter xylinum NCI 1005 grown on sucrose. The structure of the WSP was analysed by nuclear magnetic resonance spectroscopy and determined to be a beta-(2-->6)-linked polyfructan, which is structurally different from the polymer synthesized from glucose instead of sucrose by the same strain. The discovery of this new polysaccharide has revealed that the bacterium is able to synthesize two different kinds of water-soluble polysaccharides.

Carbohydrate Sequence↗

Induction of autoimmune-like hepatic and ductal lesions by administration of lipopolysaccharide in mice undergoing graft-versus-host reaction across MHC class I difference.

In this paper, we examined the induction of autoimmune-like histologic changes in the liver and other organs of mice undergoing graft-versus-host reaction (GVHR) with MHC class I disparity by the administration of bacterial lipopolysaccharide (LPS), on the assumption that stimulation with LPS could be an exacerbating factor. Spleen cells of C57BL/6 (B6) mice were injected twice into (B6 x bml) F1 recipient mice at an interval of 7 days to induce MHC class I GVHR and then challenged with 1 microg of LPS intravenously on the next day of the cell transfer. The hepatic lesions of the group of MHC class I GVHR mice challenged with LPS showed marked cellular infiltration at the portal area and focal necrosis was observed in the hepatic lobule. The major infiltrating cells were CD8+, and others including CD4+ cells being of minor populations. In addition, ductal lesions in extrahepatic organs, including the pancreas and salivary glands also showed marked cellular infiltration. Thus, we have demonstrated that LPS induced ductal lesions in mice with MHC class I disparity. CD8+ cells were detected at the destructive hepatic lesions, which might be effector cells. These findings indicate that LPS might be one of the potential factors which augment autoimmune-like lesions.

Alanine Transaminase↗