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Biomedical subjects

Toshiaki Hanafusa

Publications and source records attributed to Toshiaki Hanafusa.

At least 55 records · Page 3Linked to original sources
PubMed2005

[A case of systemic lupus erythematosus associated with hypertrophic cardiomyopathy].

The patient was a 37-year-old female, who was diagnosed as having systemic lupus erythematosus (SLE) with nephrotic syndrome in 1991. SLE has been well controlled with a combination therapy of prednisolone, cyclophosphamide and mizoribine. She was admitted to our hospital for chest pain on exertion in June 2002. A grade of 2 systolic murmur was heard along left sternal border and edema in the both lower legs was present. Laboratory findings showed proteinuria and anemia. Serological tests did not show decrease in complements and was negative for autoantibodies including anti-ds-DNA antibody. The serum level of brain natriuretic peptide was 651 pg/ml. On chest X-ray films, there were no remarkable findings. An electrocardiogram showed a pattern of left ventricular hypertrophy with inverted T wave. The heart ultrasonic test recognized asymmetric hypertrophy of the septum, being more prominent in the apex, but there was no obstruction of the left ventricular outflow tract. Examination of an endomyocardial biopsy specimen showed disarray and mild hypertrophy of myocardial cells, which were compatible with hypertrophic cardiomyopathy (HCM), but there were no pathological findings specific for SLE. Additional treatment with beta-blocker under a diagnosis of HCM resulted in a favorable response. Although 7 SLE patients with HCM have been reported, endomyocardial biopsy was not performed. There appears to have been a chance association between SLE and HCM, considering the clinical courses in reported cases and the pathological findings in our case.

Adrenergic beta-Antagonists↗
PubMed2005

[Graft-versus-ATLL effect induced by abrupt discontinuation of immunosuppression following allogeneic bone marrow transplantation].

A 46-year-old man was admitted to our hospital with swelling of a neck lymph node in June, 2002, and was diagnosed with adult T-cell leukemia/lymphoma (ATLL). As ATLL cells were detected in the peripheral blood after two courses of multi-agent chemotherapy (LSG 15), the treatment was changed to biweekly CHOP therapy. After two courses, hematological remission was achieved. Allogeneic bone marrow transplant (allo-BMT) from HTLV- negative and HLA-matched sibling donor was performed (conditioned with cyclophosphamide 60 mg/kg x 2 and total body irradiation 12 Gy). Cyclosporine A (CsA) and short-term methotrexate (MTX) were used for graft-versus-host disease prevention. Though the HTLV- provirus DNA (Southern blot) disappeared, HTLV-I provirus DNA (real-time PCR) T-cell receptor ygammachain gene rearrangement DNA (Southern blot) were detected in bone marrow after allo-BMT. MRD disappeared after the withdrawal of CsA. After the allo-BMT transplant, a graft-versus-ATLL (GVATLL) effect may be induced by abrupt discontinuation of immunosuppression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

[Intestinal bleeding during the treatment of chronic myeloid leukemia with imatinib mesylate].

A 35-year-old woman attended our hospital with chronic myeloid leukemia and was prescribed imatinib mesylate. She was admitted with lower abdominal pain, stomatitis, and hyposthenia after an increase in her dose of imatinib mesylate. When the treatment was changed to interferon-alpha and Ara-C, the lower abdominal pain, stomatitis, and hyposthenia improved, but bone marrow aspiration showed 36.4% blasts. After the treatment was changed back to an increased dose of imatinib mesylate (800 mg), the stomatitis deteriorated and intestinal bleeding reoccurred. Endoscopy demonstrated the presence of multiple ulcers in the ascending colon and 99mTc RBC scintigraphy demonstrated lesions of the large and small intestine. The patient declined any treatment except for transfusion and died suddenly after ten days. The present case suggests that we should carefully consider the possibility of intestinal bleeding when prescribing imatinib mesylate.

Adult↗
PubMed2005

[Successful treatment of refractory mantle cell lymphoma with irinotecan].

A 59-year-old man presented in January 2003 with generalized lymphadenopathy. An inguinal lymph node biopsy showed mantle cell lymphoma (MCL). After four courses of Rituximab-CHOP therapy were administered, complete response (CR) was achieved. However, in August 2003, he presented with neck lymphadenopathy and was found to have relapsed. Several salvage therapies (ESHAP, Hyper-CVAD/MTX-ara-C) were administered, but CR was not achieved. After two courses of single-agent chemotherapy with CPT-11 (40 mg/m2) were administered on days 1, 2, 3, 8, 9, and 10, CR was achieved. Several studies reveal that the long-term prognosis for MCL with conventional therapy is poor. This report describes CPT-11 therapy for MCL and provides evidence that CPT-11 is another therapeutic option in refractory cases of MCL.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Expression of TH1/TH2-related chemokine receptors on peripheral T cells and correlation with clinical disease activity in patients with multiple sclerosis.

Th1 cells play an important role in the pathogenesis of multiple sclerosis (MS), a disease likely linked to an autoimmune process. We measured the levels of chemokines in serum or cerebrospinal fluid (CSF) samples by ELISA, and also studied the expression of Th1-related CXCR3/CCR5 chemokine receptors and Th2-related CCR4/CCR3 chemokine receptors on blood cells from MS patients using three-color flow cytometry. The Bonferroni correction was used for the statistical analysis. The levels of CXCL10, CCL3, and CCL5 in the CSF samples for the MS groups were significantly higher than those for the control group. However, the levels of CCL2 in both the CSF and serum samples for the remission group were significantly higher than those for the active group. The percentage of CXCR3-expressing CD4+ T cells in patients with MS was significantly elevated compared with the healthy controls. Moreover, MS patients in an active phase showed a more increased CD4+CXCR3+/CD4+CCR4+ ratio than patients in a remission phase. The increased percentage of CD4+CXCR3+ cells in the blood was associated with relapses in MS. This study suggested that the CD4+CXCR3+/CD4+CCR4+ ratio could be a sensitive maker of immune dysfunction in MS.

Adult↗
PubMed2004

Decreased CD14+CCR2+ monocytes in active multiple sclerosis.

The expression of CCR2, a receptor to MCP-1, on blood monocytes was measured in 15 patients with active multiple sclerosis (MS). We determined the ratio of CD4+CXCR3+cells (Th1), CD4+CCR4+cells (Th2), and CD14+CCR2+ cells using 3-color flow cytometry. The CD4+CXCR3+/CD4+CCR4+ ratio, which represents the Th1/Th2 balance, was significantly elevated in the active MS patients compared to the healthy controls. The expression of CCR2 and CD14 on the monocytes in the MS patients was markedly decreased. There was a significant negative correlation between the Th1/Th2 ratio and the CCR2 and CD14 expression on monocytes. In the pathogenesis of MS, the CD14+CCR2+ blood monocytes may play an important role in the shift from active MS to a state in which the disease is in remission.

Adult↗
PubMed2004

CCL2, a product of mice early after systemic inflammatory response syndrome (SIRS), induces alternatively activated macrophages capable of impairing antibacterial resistance of SIRS mice.

Infection associated with systemic inflammatory response syndrome (SIRS) is a major cause of morbidity and mortality in patients with major surgery, polytrauma, and severe burn injury. In previous studies, mice with severe pancreatitis (a mouse model of SIRS, SIRS mice) have been shown to be greatly susceptible to various infections. In the present study, a mechanism involved in the impaired resistance of SIRS mice to infectious complications was investigated. Sera from SIRS mice impaired the resistance of normal mice to infectious complications induced by cecal ligation and puncture (CLP). CC chemokine ligand 2 (CCL2) was detected in sera of SIRS mice. Resident macrophages (RMphi) cultured with SIRS mouse sera converted to alternatively activated macrophages (AAMphi), which were also demonstrated in mice treated with recombinant murine CCL2. However, AAMphi were not demonstrated in mice injected with SIRS mouse sera and anti-CCL2 monoclonal antibody (mAb) in combination. Furthermore, normal mice that received SIRS mouse sera and anti-CCL2 mAb resisted CLP-induced infectious complications. These results indicate that the resistance of SIRS mice to infectious complications is impaired by AAMphi generated from RMphi in response to SIRS-associated CCL2 production.

Animals↗
PubMed2004

Delayed shrinkage triggered by the Na+-K+ pump in terbutaline-stimulated rat alveolar type II cells.

Terbutaline (10 microm) induced a triphasic volume change in alveolar type II (AT-II) cells: an initial shrinkage (initial phase) followed by cell swelling (second phase) and a gradual shrinkage (third phase). The present study demonstrated that the initial and the third phases are evoked by the activation of K+ and Cl- channels and the second phase is evoked by the activation of Na+ and Cl- channels. Ouabain blocked the third phase, although it did not block the initial and second phases. This suggests that the third phase is triggered by the Na+-K+ pump. Tetraethylammonium (TEA, a K+ channel blocker) decreased the volume of AT-II cells and enhanced the terbutaline-stimulated third phase, although quinidine, another K+ channel blocker, increased the volume of AT-II cells. The TEA-induced cell shrinkage was inhibited by ouabain, suggesting that TEA increases Na+-K+ pump activity. Ba2+, 2,3-diaminopyridine and a high [K+]o (30 mm) similarly decreased the volume of AT-II cells. These findings suggest that depolarization induced by TEA increases Na+-K+ pump activity, which increases [K+]i. This [K+]i increase, in turn, hyperpolarizes membrane potential. Valinomycin (a K+ ionophore), which induces hyperpolarization, decreased the volume of AT-II cells and enhanced the third phase in these cells. In conclusion, in terbutaline-stimulated AT-II cells, an increase in Na+-K+ pump activity hyperpolarizes the membrane potential and triggers the third phase by switching net ion transport from NaCl entry to KCl release.

Amiloride↗
PubMed2004

Axillo-axillary bypass for in-stent restenosis in Takayasu arteritis.

We report a patient with Takayasu arteritis (TA) who initially received stent placement (SP) following percutaneous transluminal balloon angioplasty for stenotic lesion of the left subclavian artery and subsequently had recurrent in-stent restenosis three times. Every time restenosis occurred, percutaneous transluminal rotational arterectomy (RA) was performed. After all, the patient underwent axillo-axillary bypass and has remained asymptomatic for 10 months after the surgery. We suggest that surgical treatment is beneficial for in-stent restenosis in patient with Takayasu arteritis.

Axillary Artery↗
PubMed2004

Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus.

Neutrophils (PMN) have been described as critical effector cells in the host's antibacterial innate immunities. However, the classification of murine PMNs remains unclear. Here, we show that in addition to normal PMN (PMN-N), there are at least two distinct subsets of PMNs (PMN-I and PMN-II) distinguished as follows: (1) cytokine and chemokine production (PMN-I, IL-12/CCL3; PMN-II, IL-10/CCL2; PMN-N, no cytokine/chemokine production), (2) macrophage activation (PMN-I, classically activated macrophages; PMN-II, alternatively activated macrophages; PMN-N, no effect on macrophage activation), (3) Toll-like receptor (TLR) expression (PMN-I, TLR2/TLR4/TLR5/TLR8; PMN-II, TLR2/TLR4/TLR7/TLR9; PMN-N, TLR2/TLR4/TLR9), and (4) surface antigen expression (PMN-I, CD49d(+)CD11b-; PMN-II, CD49d(-)CD11b+; PMN-N, CD49d(-)CD11b-). PMN-I was obtained from MRSA (methicillin-resistant Staphylococcus aureus)-resistant hosts, while MRSA-sensitive hosts were a source of PMN-II. PMN-N was obtained from naive mice. Anti-MRSA innate immunities might be influenced differently by these biochemically and physically distinguished PMNs. PMN-N may convert to PMN-I or PMN-II in response to host circumstance.

Animals↗
PubMed2004

High diagnostic value of a radioiodine uptake test with and without iodine restriction in Graves' disease and silent thyroiditis.

The necessity of iodine restriction before radioiodine uptake (RAIU) testing for differentiation of thyrotoxicosis is controversial. The present study was undertaken to investigate the effects of iodine restriction on the RAIU value, and the necessity of iodine restriction in differentiating between Graves' disease (GD) and silent thyroiditis (ST). We investigated 415 patients, 277 of whom were patients with GD who had undergone iodine restriction before RAIU [GD(+)], 66 were patients with GD who did not undergo iodine restriction [GD(-)], 61 were patients with ST who had undergone iodine restriction [ST(+)], and the remaining 11 were patients with ST who did not undergo iodine restriction [ST(-)]. The RAIU value of the GD(+) group, 47.6% +/-14.4% (mean +/-standard deviation [SD]), was significantly higher than that of the GD(-) group, 42.4% +/- 17.6% (p = 0.03). However, the areas under the curves from the receiver operator characteristics analyses for the comparison between groups GD(+)/ST(+), GD(+)/ST(-), GD(-)/ST(+) and GD(-)/ST(-) were 0.99967, 0.99967, 0.98436, and 0.98485, and very high, respectively. High diagnostic value of the RAIU test was confirmed, but not affected by the presence of iodine restriction in the differentiation between GD and ST, therefore, iodine restriction before the RAIU test was unnecessary.

Adult↗
PubMed2004

Serum concentrations of granulocyte colony-stimulating factor (G-CSF) in antithyroid drug-induced agranulocytosis.

Granulocyte colony-stimulating factor (G-CSF) levels in serum were determined by a highly-sensitive chemiluminescent enzyme immunoassay (limit of detection, 0.5 pg/ml) in 54 patients with Graves' disease including 6 patients complicated with methimazole-induced agranulocytosis. Serum G-CSF levels in patients with Graves' disease were not different from normal subjects and did not correlate with serum FT4 level or circulating neutrophil counts. Before the onset of agranulocytosis, there was no difference in serum G-CSF level between the patients complicated with agranulocytosis and the uncomplicated patients. When circulating neutrophil counts decreased to less than 0.5 x 10(9)/L, serum G-CSF level elevated with the mean of 106.8 +/- 82.2 (SD) pg/ml, but the level did not correlate with the duration of agranulocytosis. Interestingly, maximum serum G-CSF level during the treatment with recombinant human G-CSF (100 microg/day) was related to bone marrow finding at the onset of agranulocytosis and correlated with the duration of agranulocytosis (r = 0.824, p < 0.05). In conclusion, measuring serum G-CSF levels with a highly-sensitive chemiluminescent enzyme immunoassay revealed that 1) thyrotoxicosis does not affect serum G-CSF level, 2) serum G-CSF level during antithyroid drug treatment does not play an important role in development of agranulocytosis, 3) the maximum serum G-CSF level in the course of agranulocytosis is related to the responsiveness of bone marrow to G-CSF and the recovery time from agranulocytosis.

Adult↗
PubMed2004

[Multiple organ relapse in primary de novo CD5+ diffuse large B cell lymphoma of the bone after a complete response].

A 57-year-old woman was admitted with swelling of the femur. MRI showed that an intramedullary lesion had expanded from the trunk to the distal portion where it had formed an extramedullary tumor mass. An open biopsy showed diffuse proliferation of abnormal lymphoid cells. Immunohistochemical staining and flow cytometry demonstrated LCA+, CD3-, CD23-, CD79a+, CD5+, IgM+, IgD- and kappa + and cyclin D1-. FISH analysis did not detect t(11;14)(q13;q32). The final diagnosis was de novo CD5+ diffuse large B-cell lymphoma (DLBL) of the bone at clinical stage IEA. The patient suffered a pathological fracture in the femur after two courses of CHOP. The therapy was changed to ESHAP and irradiation. The result was assessed as a complete remission (CR). One month later, the patient presented with epigastric pain. MRI showed the tumor at the spleen and kidney and hydronephrosis due to pelvic lymphadenopathy, but did not show a tumor in the femur. An open biopsy of the pelvic lymph node showed relapse. The tumor and hydronephrosis disappeared and necrosis in the kidney was observed on MRI after ESHAP. De novo CD5+ DLBL appears to constitute a unique subset of DLBL with an aggressive clinical course and requires established therapeutic strategies.

Bone Neoplasms↗
PubMed2003

Beta 2-adrenergic regulation of ciliary beat frequency in rat bronchiolar epithelium: potentiation by isosmotic cell shrinkage.

Single bronchiolar ciliary cells were isolated from rat lungs. The beta(2)-adrenergic regulation of ciliary beat frequency (CBF) was studied using video-optical microscopy. Terbutaline (a beta(2)-adrenergic agonist) increased CBF in a dose-dependent manner, and it also decreased the volume of the ciliary cells. These terbutaline actions were inhibited by a PKA inhibitor (H-89) and mimicked by forskolin, IBMX and DBcAMP. Ion transport inhibitors were used to isosmotically manipulate the volume of the terbutaline-stimulated bronchiolar ciliary cells. Amiloride (1 microM) and bumetanide (20 microM) potentiated cell shrinkage and the CBF increase, and they shifted the terbutaline dose-response curve to the lower-concentration side. Quinidine (500 microM), in contrast, increased cell volume and suppressed the CBF increase. Moreover, a KCl solution containing amiloride (1 microM) and strophanthidin (100 microM) increased cell volume and suppressed the CBF increase, and then the subsequent removal of either amiloride or strophanthidin decreased cell volume and further increased CBF. NPPB (10 microM) or glybenclamide (200 microM) had no effect on the action of terbutaline. Thus, in terbutaline-stimulated ciliary cells, cell shrinkage enhances the CBF increase; in contrast, cell swelling suppresses it. However, the results of direct manupulation of cell volume by applying osmotic stresses (hyperosmotic shrinkage or hyposmotic swelling) were the opposite of the findings of the isosmotic experiments: hyposmotic cell swelling enhanced the CBF increase, while isosmotic swelling suppressed it. These results suggest that isosmotic and non-isosmotic volume changes in terbutaline-stimulated bronchiolar ciliary cells may trigger different signalling pathways. In conclusion, terbutaline increases CBF and decreases the volume of rat bronchiolar ciliary cells via cAMP accumulation under isosmotic conditions, and the isosmotic cell shrinkage enhances the CBF increase by increasing cAMP sensitivity.

Adrenergic beta-2 Receptor Agonists↗