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Y Aoyama

Publications and source records attributed to Y Aoyama.

At least 19 recordsLinked to original sources
PubMed2006

Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris, or just "witnesses of disease"?

Pemphigus vulgaris (PV) is fascinating to dermatologists, epithelial biologists and immunologists alike, as its pathogenesis has been clarified to a much greater extent than that of most other organ-specific autoimmune diseases, and as it has provided abundant novel insights into desmoglein biology and pathology along the way. Historically, the most influential PV pathogenesis concept is that of Stanley and Amagai. This concept holds that autoantibodies against desmogleins are both essential and sufficient for epidermal blister formation (acantholysis) by impeding the normal functioning of these major adhesion proteins. However, as with most good theories, this landmark concept has left a number of intriguing and important questions open (or at least has not managed to answer these to everyone's satisfaction). Moreover, selected dissenting voices in the literature have increasingly called attention to what may or may not be construed as inconsistencies in this dominant PV pathogenesis paradigm of the recent past. The present debate feature therefore bravely rises to the challenge of re-examining the entire currently available evidence, as rationally and as undogmatically as possible, by provocatively asking a carefully selected congregation of experts (who have never before jointly published on this controversial topic!) to discuss how essential anti-desmoglein autoantibodies really are in the immunopathogenesis of PV. Not surprisingly, some of our expert "witnesses" in this animated debate propose diametrically opposed answers to this question. While doing so, incisive additional questions are raised that relate to the central one posed, and our attention is called to facts that may deserve more careful consideration than they have received so far. Together with the intriguing (often still very speculative) complementary or alternative pathogenesis scenarios proposed in the following pages, this offers welcome "food for thought" as well as very specific suggestions for important future research directions--within and beyond the camp of PV aficionados. The editors trust that this attempt at a rational public debate of the full evidence that is currently at hand will constructively contribute to further dissecting the exciting--and clinically very relevant!--immunopathogenesis of PV in all its complexity.

Animals↗
PubMed2005

A steroidogenic cell line with differentiation potential from mouse granulosa cells, transfected with Ad4BP and SV40 large T antigen genes.

Several steroidogenic cell lines of granulosa cells (GC) have been used to elucidate differentiation mechanisms of GC during folliculogenesis. These cell lines, however, are of limited usefulness since they have lost some of their differentiation potential. The transcription factor adrenal-4 binding protein (Ad4BP), also known as steroidogenic factor-1 or NR5A1, is essential for the expression of all P-450 steroidogenic enzymes. By transfection with the Ad4BP gene together with SV40 DNA, we have generated several steroidogenic cell lines. One selective clone, named 4B2, retained its steroidogenic potential and was therefore analyzed in depth. This cell line responded to 8-Br-cAMP by displaying differentiation characteristics similar to those occurring in the differentiation process of primary cultured GC, including enhanced progesterone secretion, a cell shape change from a fibroblastic to epithelioid conformation, elongated mitochondria, increased gap junction formation and inhibition of cell proliferation. Prostaglandin E2 (PGE2), an intraovarian regulator of GC, stimulated cAMP production, and this eicosanoid, like 8-Br-cAMP, induced differentiation properties with the exception of cell conformation in 4B2 cells. These results suggest that expression of Ad4BP may provide the basis for a repertoire of cAMP-sensitive differentiation properties, including morphological alterations and growth inhibition. Thus, the 4B2 cell line may serve as a tool for elucidation of differentiation mechanisms that are under the control of Ad4BP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2003

Successful treatment with reduced-intensity stem cell transplantation in a case of relapsed refractory central nervous system lymphoma.

A 33-year-old male with refractory relapsed central nervous system lymphoma underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical sibling after reduced-intensity conditioning chemotherapy. The preparative regimen for allo-HSCT consisted of fludarabine and busulfan. Cyclosporine (CsA) and short-term methotrexate were used as prophylaxis for acute graft-versus-host disease (GVHD). Although CsA was quickly reduced to induce a graft-versus-lymphoma (GVL) effect, no symptoms of GVHD and GVL effect were evident. Donor lymphocyte infusion (DLI) was performed on day +40 following transplantation. The patient developed acute GVHD (grade III) after DLI, and lymphoma regression was observed after the occurrence of GVHD. Four months after transplantation, complete remission was achieved with extensive chronic GVHD, and the patient continues to be disease free at 15 months after transplantation.

Adult↗
PubMed2003

Block of the sacral segments in lumbar epidural anaesthesia.

BACKGROUND: Block of the first sacral segment is often delayed in lumbar epidural anaesthesia. The addition of either epinephrine or sodium bicarbonate to the local anaesthetic enhances the efficacy of epidural block. We assessed the block of lumbo-sacral segments in lumbar epidural anaesthesia adding epinephrine and/or bicarbonate to lidocaine. METHODS: Twenty-seven patients undergoing lumbar epidural anaesthesia with lidocaine 2%, 17 ml at L4-5 or L5-S1 were randomly divided into three groups. Plain lidocaine, lidocaine with 1:200,000 epinephrine or lidocaine-epinephrine-bicarbonate was administrated via an epidural catheter. The pain threshold after repeated electrical stimulation was used to assess the sensory block at the L2, S1, and S3 segments. Motor block was evaluated using the Bromage scale. RESULTS: Patient characteristics were comparable between the groups. The pH of lidocaine in the lidocaine-epinephrine-bicarbonate group was significantly higher than that in other groups. Pain thresholds at the S1 and S3 segments in the lidocaine-epinephrine-bicarbonate group were significantly higher than those in the lidocaine-epinephrine group. However, differences in the pain threshold at the L2 segment between groups were insignificant. The time to onset of sensory block at the S1 and S3 in the lidocaine-epinephrine-bicarbonate group was significantly shorter than that in the lidocaine group. Pain threshold by pinprick test was approximately within the 30-50 mA range. CONCLUSION: A combination of lidocaine, bicarbonate, and epinephrine increases the pain threshold over the sacral segments.

Adult↗
PubMed2002

Clinical significance of serum E-cadherin levels in patients with haematological malignancies.

E-cadherin is a transmembrane glycoprotein that mediates Ca2+-dependent intracellular adhesion in normal epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. However, the role of E-cadherin in haematopoietic cells is less clear. In this study, serum E-cadherin levels were therefore determined in patients with acute or chronic leukaemia, malignant lymphoma or myelodysplastic syndromes. Significant elevation of serum E-cadherin levels was detected in patients with haematological malignancies, and between types of acute leukaemias or subtypes of myelodysplastic syndromes, stages of malignant lymphoma, and phases of chronic leukaemia, respectively, compared with those in healthy adult volunteers. These findings suggest that E-cadherin might be expressed in malignant haematopoietic cells and might be useful as a diagnostic indicator in haematological malignancies.

Acute Disease↗
PubMed2002

E-cadherin expression in lymph nodes of three patients with non-Hodgkin's lymphoma.

The E-cadherins are a family of cell-cell adhesion molecules. These molecules exhibit Ca2+ dependent cell adhesion and are expressed on epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. We determined serum E-cadherin levels in 30 patients with non-Hodgkin's lymphoma (NHL) using an enzyme immunoassay and then investigated whether E-cadherin is expressed on lymphoma cells in lymph nodes of three cases selected to analyze from 15 cases of serum E-cadherin levels over mean + 2SD with monoclonal antibody immunohistochemistry. Results indicated that E-cadherin antigen is expressed on the lymphoma cells in these three patients with NHL, and that soluble E-cadherin might be released into blood from lymphoma cells. Expression of E-cadherin may contribute to the morphological appearance of some malignant lymphoma, although no conclusion can be drawn based on such small number of patients analyzed.

Adolescent↗
PubMed2001

Acute rhabdomyolysis following administration of high-dose cyclophosphamide: case report.

Rhabdomyolysis is an unusual complication of hematopoietic stem cell transplantation (HSCT). Cyclophosphamide has been one of the key drugs in the most common preparative regimen for HSCT. We present here a rare case of acute rhabdomyolysis following administration of high-dose cyclophosphamide. A 47-year-old woman with adult T-cell leukemia in remission was treated with high-dose cyclophosphamide as a preparative regimen for allogeneic bone marrow transplantation. Nineteen hours later, general convulsions and acidosis suddenly occurred. Levels of serum creatine kinase (skeletal muscle type), myoglobin, and aldolase were markedly elevated to 32870 IU/l, 640 ng/ml, and 240.3 IU/l, respectively. Rhabdomyolysis caused by high-dose cyclophosphamide was diagnosed, and the preparative chemotherapy was discontinued. Subsequently, her muscular signs and symptoms improved, and the results of laboratory examinations returned to normal after 2 weeks. She had previously been treated with conventional doses of cyclophosphamide, doxorubicin, vincristine, and prednisolone without evidence of rhabdomyolysis. Acute rhabdomyolysis may be an adverse effect specific to high-dose cyclophosphamide therapy.

Acute Disease↗
PubMed2001

Effect of solvation on induce-fit molecular recognition in supercritical fluid to organic crystals immobilized on a quartz crystal microbalance.

The inclusion behavior of guest molecules to a solid apohost of an orthogonal anthracene-bis(resorcinol)tetraol (1) was investigated in supercritical carbon dioxide (scCO(2)) by using a 9 MHz quartz-crystal microbalance (QCM). Compound 1 forms crystals composed of molecular-sheet bound together by an extensive hydrogen-bonded network. The selective binding of gaseous ethyl acetate to the apohost-immobilized QCM in scCO(2) was observed, and the inclusion amount of ethyl acetate showed a drastic increase above a threshold concentration, [Guest](th) = 0.08 M, and the apparent Gibbs' free energy for the binding was DeltaG(app) = -1.3 kcal mol(-1). Similar selective bindings of ethyl acetate or ethanol had been observed in the gas phase and in water: [Guest](th) = 0.002 M with DeltaG(app) = -3.5 kcal mol(-1) and [Guest](th) = 0.5 M with DeltaG(app) = -0.41 kcal mol(-1), respectively. These values obtained in scCO(2) were intermediate between those in the gas and water phases. Since various physical properties (viscosity, density, polarity, diffusion constant, and solvation) of supercritical fluid are known to be intermediate between gas and liquid, these values clearly reflect the solvation behavior of guest molecules. Thus, the lower solvation of guest molecules indicates the lower threshold concentration and the larger binding energy in the following order: in air > in scCO(2) > in water.

Journal Article↗
PubMed2001

Blastic NK-cell lymphoma/leukemia with T-cell receptor gamma rearrangement.

A 79-year-old Japanese man was admitted to our hospital with dyspnea in June 1999. Physical examination revealed general exanthema, hepatosplenomegaly, and lymphadenopathy. Increased numbers of abnormal cells were observed in peripheral blood; these cells were of lymphoblastic morphology with high nuclear/cytoplasm ratios and few azurophilic granules. Immunophenotypic analysis revealed positivity for CD2, CD4, CD56, and HLA-DR, and negativity for CD3, CD13, CD16, CD33, CD34, and T cell receptor (TCR). On genotypic analysis, TCRgamma chain was rearranged, but neither the TCRbeta chain nor TCRdelta chain. Despite an initial good response to chemotherapy the disease relapsed in the early stage, and the patient died 6 months after diagnosis.

Aged↗
PubMed2001

Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones.

The present work demonstrates that the 1,3-diazetidine-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and alpha-chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase.

Azetidines↗
PubMed2001

Total synthesis of human chymase inhibitor methyllinderone and structure--activity relationships of its derivatives.

Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of the active compound against human chymase using calculations.

Alkenes↗
PubMed2001

Virus-associated hemophagocytic syndrome due to rubella virus and varicella-zoster virus dual infection in patient with adult idiopathic thrombocytopenic purpura.

A 26-year-old woman with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital because of fever and rash. Blood tests revealed thrombocytopenia, liver dysfunction, coagulopathy, and hyperferritinemia. Bone marrow examination revealed many atypical lymphocytes and some histiocytes with hemophagocytosis. On admission she was diagnosed with rubella virus-associated hemophagocytic syndrome (VHAS), but on laboratory examination, she was seropositive for varicella-zoster virus (VZV)-IgM as well as rubella virus-IgM. She was therefore diagnosed with dual infection by rubella virus and VZV. Her simultaneous rubella virus and VZV infection may have been related to the VAHS pathogenesis. She was treated with prednisolone and gamma globulin therapy and recovered completely.

Adult↗
PubMed2001

Massive large bowel resection decreases bone strength and magnesium content but not calcium content of the femur in rats.

We examined the effects of massive large bowel resection (cecocolonectomy) on calcium and magnesium absorption and bone characteristics in rats. Male Sprague-Dawley rats were divided into two groups: sham-operated and cecocolonectomized rats. The rats were fed a sucrose-based diet containing casein at 250 g/kg diet for 10 d after a 9- to 10-d postoperative recovery period. Apparent magnesium absorption but not calcium absorption was lower in the resection group than in the sham group. There was a tendency of lower serum magnesium concentration (P = 0.070) but not calcium concentration (P = 0.418) in the resection group compared with the sham group. The maximum breaking force and magnesium content but not the calcium content of the femur were lower in the resection group than in the sham group. These results suggest that massive large bowel resection influences magnesium kinetics and decreases bone strength through reduction of the magnesium content of the femur in rats. Femoral breaking force was positively correlated (r = 0.617, P = 0.011) with only the magnesium content. We conclude that the changes in magnesium kinetics caused by cecocolonectomy could contribute to the fragility of bone.

Animals↗
PubMed2001

Non-essential amino acids play an important role in adaptation of the rat exocrine pancreas to high nitrogen feeding.

We have previously demonstrated that feeding a diet with a high amino acid (60% AA diet) content, as a mixture simulating casein, induced pancreatic growth and pancreatic protease production in rats. In the present study, we examined the effects of an increasing dietary content of essential amino acids (EAA, x1 - x3 in exp. 1 and x1 - x3.3 in exp. 2) and non-essential amino acids (NEAA, x1 - x3 in exp. 1 and x1 - x5.2 in exp. 2) on pancreatic growth, amylase and protease adaptation using casein-type amino acid mixtures (exp. 1, basal diet; 20% AA diet) and egg white-type amino acid mixtures (exp. 2, basal diet; 12% AA diet). Pancreatic growth and trypsin activity were induced as the dietary content of NEAA was increased in experiments 1 and 2. Amylase activity in the pancreas was also induced as the dietary content of NEAA was increased, even with the decrease in dietary carbohydrate in experiment 2. The values of all pancreatic variables decreased with the increase in dietary EAA (x2 and x3) without an increase in NEAA. The changes in the pancreas were coincident with increases in plasma arginine and lysine concentrations and a decrease in the plasma alanine concentration. In rats fed a 60% AA diet (EAA and NEAA x3), in the case of which the EAA content was balanced with the NEAA content, pancreatic growth and protease production increased and reached maximum levels as the plasma amino acid concentrations decreased, except for alanine. These results show that NEAA, not EAA, are associated with induction of pancreatic growth and protease production upon feeding a diet with a high AA content, and that some metabolites may be involved in the induction process. The suppression of pancreatic growth and protease production in rats fed the high EAA diets without balanced NEAA may be associated with impairment of amino acid metabolism rather than the increments in the concentration of one or more essential amino acids. Our results also suggest that there is an unknown mechanism or unknown factors involved in regulating pancreatic amylase.

Journal Article↗