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Biomedical subjects

Masahiro Abe

Publications and source records attributed to Masahiro Abe.

At least 37 records · Page 2Linked to original sources

High-dose chemotherapy and autologous peripheral blood stem cell transplantation in high-risk multiple myeloma.

We compared the effect of high-dose therapy together with autologous peripheral blood stem cell transplantation (autoPBSCT) in 60 patients with multiple myeloma (MM) with 90 patients who underwent conventional chemotherapy. We scored the prognostic factors according to our reported classification system that includes measurements of serum albumin, serum beta-2-microglobulin, and morphology of myeloma cells selected by multivariate analysis. We separated the patients into three risk groups at stratification level I (low, intermediate and high) and into two risk groups at stratification level II (low and high). AutoPBSCT tended to be as effective for high, as for low-risk patients in level I, and was obviously as helpful for high, as for low-risk patients in stratification II. In conclusion, high-risk patients with MM should be treated with high-dose therapy accompanied with autoPBSCT like low-risk patients.

Adult↗

Primary adult T-cell leukemia/lymphoma of bone.

A 77-year-old man developed primary adult T-cell leukemia/lymphoma (ATL) of the bone with osteolytic lesions. A biopsy of the lesion revealed proliferation of atypical, large lymphoid cells with a local increase of osteoclasts. The clonal integration of human T-lymphotropic virus type I proviral DNA revealed the tumor cells to be ATL. They produced macrophage inflammatory protein 1alpha (MIP-1alpha) but not parathyroid hormone-related protein or other osteoclast-activating factors. Because MIP-1 produced by tumor cells enhances the expression of receptor activator of nuclear factor kappaB ligand (RANKL) of local osteoblasts and stromal cells, even of tumor cells, the increase of osteoclasts in the close vicinity of ATL cells was considered to result in local bone destruction.

Aged↗

Clarithromycin-induced eosinophilic pneumonia.

Clarithromycin (CAM) has been widely used for the treatment of respiratory infection. Macrolides are generally well tolerated and their adverse reactions are rare. An 80-year-old woman with nontuberculous mycobacterium infection was treated with combined chemotherapy, including isoniazid, rifampicin, and ethambutol. She developed a fever and peripheral blood eosinophilia, and new subpleural consolidations were observed on chest radiography three days after add-on therapy with CAM. The symptoms and clinical findings improved with the withdrawal of CAM. Histopathologic examinations confirmed the diagnosis of eosinophilic pneumonia. This is the first report of CAM-induced eosinophilic pneumonia.

Aged↗

[A case of quadruple cancer arising in the stomach, lung, liver and prostate].

A 75-year-old man was admitted to our hospital because of severe dyspnea and pollakiuria in October 2001. We diagnosed his illness as carcinomatous pericarditis caused by the recurrence of primary lung cancer and prostatic hypertrophy. He had undergone surgery for gastric cancer in 1986, and for lung cancer in 1996. Furthermore, he had been treated for hepatocellular carcinoma in 1997. He finally died in February 2002 of respiratory failure due to the carcinomatous lymphangitis that followed the lung cancer. After autopsy, a microscopic view of the prostate revealed that he had prostatic carcinoma. Such a case is rare.

Adenocarcinoma↗

[Biochemical markers in bone metastasis].

Certain types of cancers have a strong propensity to metastasize to bone, which requires combination of multiple factors responsible for the different steps of metastasis. Bone metabolic markers are now widely used in clinical practice and give useful information on the ongoing bone metabolism, reflecting the activity of bone-resorbing osteoclasts and bone-forming osteoblasts. Bone markers have a potential as diagnostic tools for bone metastasis, and are useful in monitoring the response to anticancer as well as antiresorptive therapies. Since bone metabolic markers alone are insufficient for the diagnosis and assessment of bone metastasis, it is important to combine bone markers with tumor-related markers and imaging studies such as scintigraphy and MRI. More recently, soluble receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) have been implicated as markers for osteoclastogenic activity. Serum levels of these factors and/or their ratios may provide additional information on the severity of bone disease and the prognosis.

Biomarkers, Tumor↗

Incomplete Brown-Séquard syndrome caused by cervical kyphosis secondary to neurofibromatosis: report of a case.

The case of a 17-year-old boy who suffered from incomplete Brown-SEquard syndrome caused by dystrophic cervical kyphosis secondary to neurofibromatosis is presented. He became aware of weakness of his left upper and lower extremities and was unable to walk within 1 month of his first feeling numbness in the right upper and lower extremities. Thereafter his condition deteriorated rapidly. On radiological investigation the entire dural sac was shifted anteriorly and the spinal cord was flattened anteroposteriorly and asymmetrically at the angular kyphosis level, as in Hirayama's disease. Despite morphological similarities to Hirayama's disease, this patient presented with quite different clinical features: incomplete Brown-SEquard syndrome and rapidly progressive symptoms. It is suspected that the myelopathy in this case can be attributed to compression of the spinal cord between the vertebral body and the posterior dural wall on only one side. He was successfully treated with posterior interspinous wiring combined with anterior decompression and fusion. The neurological deficit fully disappeared, and complete bony union was obtained 1 year after the operation.

Adolescent↗

Stem cell activity of porcine c-kit+ hematopoietic cells.

OBJECTIVE: A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS: The HSC activity of porcine c-kit+ BMCs was evaluated both in vitro using colony-forming unit (CFU) and cobblestone area-forming cell (CAFC) assays and in vivo in nonobese diabetic/severe combined immunodeficiency transgenic (NOD/SCID-Tg) mice carrying porcine cytokine transgenes. RESULTS: Purified c-kit+ BMCs were substantially enriched for both CFUs and CAFCs in vitro and their transplantation led to long-term porcine hematopoiesis in vivo in mice. Although porcine chimerism was detectable in the peripheral blood of NOD/SCID-Tg mice receiving porcine c-kit- BMCs at early time points after transplantation, the levels were markedly lower than those in mice receiving purified c-kit+ BMCs (0.2%+/-0.14% vs 7.7%+/-1.6% and 0.17%+/-0.17% vs 5.6%+/-2.1% at weeks 3 and 6, respectively). Importantly, all mouse recipients of porcine c-kit+ BMCs showed durable multilineage chimerism (>19 weeks), whereas no recipients of porcine c-kit- BMCs sustained long-term engraftment. Moreover, porcine HSCs that had engrafted for 19 weeks in the recipients of porcine c-kit+ BMCs gave rise to clonogenic progenitors in vitro and reconstituted porcine hematopoiesis in secondary recipients. CONCLUSION: The present study demonstrates that c-kit is an essential marker of both long-term-repopulating HSCs and progenitor cells with early engraftment capacity.

Animals↗

C4d deposition in peritubular capillary and alloantibody in the allografted kidney suffering severe acute rejection.

BACKGROUND: Alloantibodies and C4d deposition in peritubular capillaries (PTCs) are thought to be related to antibody-mediated acute rejection. The purpose of this study was to evaluate the relationship between C4d deposition in PTCs and alloantibodies at various days after allograft dysfunction due to severe acute rejection. METHOD: There were 620 renal transplantations (Tx) performed. Forty patients diagnosed with acute humoral and/or vascular rejection showed graft dysfunction with anuria or dysuria. The patients were divided into four groups by ABO compatibility and clinical course after graft dysfunction: compatible recipients with graft loss (c-GL; n = 6); compatible recipients with recovery from graft dysfunction (c-RE; n = 10); incompatible recipients with graft loss (i-GL; n = 9); and incompatible recipients with recovery from graft dysfunction (i-RE; n = 15). RESULTS: C4d depositions in 4/6 c-GL recipients increased, and those in 8/10 c-RE recipients decreased after graft dysfunction. These changes in C4d deposition between the c-GL and the c-RE groups were significantly different (P < 0.01). These titres of anti-A/B IgG antibody in 7/9 i-GL recipients increased and those in 8/15 i-RE recipients decreased after graft dysfunction. These changes in titre between the i-GL and the i-RE groups were significantly different (P < 0.01). All c-GL recipients and 4/10 c-RE recipients had anti-HLA antibody at the last biopsy. There was a significant difference in the number of recipients who had anti-HLA antibody between the c-GL and the c-RE groups (P < 0.05). CONCLUSIONS: These results indicate that changes in C4d deposition in PTCs in the c-ABO group and titre of anti-A/B IgG antibody in the ABO-incompatible groups exert a strong impact on graft survival after dysfunction in the early period after Tx.

ABO Blood-Group System↗

[A case of small-cell lung cancer during treatment for active pulmonary tuberculosis after surgery for non-small-cell lung cancer].

A 76-year-old man taking anti-tuberculous drugs for active pulmonary tuberculosis was admitted to our hospital requiring further examination of a pulmonary mass in the left upper lobe. He had had right lower lobectomy and partial middle lobectomy for non-small-cell lung cancer two years before admission. Retrospectively, the left upper lobe mass had been gradually growing for about 2 months. We performed a transbronchial lung biopsy of the pulmonary mass, and diagnosed small-cell lung cancer. This report describes a rare case of small-cell lung cancer appearing during treatment for active pulmonary tuberculosis after non-small-cell lung cancer surgery.

Aged↗

[Assessment of therapeutic effect in acute myocardial infarction using early/delayed images of 123I-BMIPP myocardial scintigraphy].

This study was aimed at analyzing the discordance between the initial and late scintigraphic images in patients with acute myocardial infarction (AMI), and utilizing the data obtained for the treatment of AMI patients. Ninety-one patients with a history of the first episode of AMI were enrolled as subjects for this study. Emergency coronary angiography was performed in all the patients and left ventriculography (LVG) was carried out subsequently. 123I-BMIPP myocardial scintigraphy was performed to obtain initial images (BMi) and delayed images at 4 hours (BMd). Scintigraphy was performed a mean of 6 days after the onset of AMI in the patients. The subjects were classified into three groups according to the scintigraphic data. Quantitative gated single photon emission computed tomography (SPECT) with 99mTc-sestamibi (MIBI) was also conducted one month and 6 months later in all the patients. Discordance was observed in 51% of the patients. Left ventricular volume based on the quantitative gated SPECT (QGS) data at one month and 6 months after myocardial scintigraphy was significantly smaller in the washout group than in the other two groups. There was no significant change in LV volume measured at 6 months as compared to that measured at one month in the washout group. Significant increases in LVEDVI and LVESVI were observed over time in the no discordance group. In the fill-in group, the LV volume at one month was significantly higher than that in the washout group, but no significant change with time was observed. During the subacute stage of myocardial infarction, discordance is often seen between initial and late BMIPP-myocardial-scintigraphic images. The presence of such discordance, and analysis of its pattern, may be useful in predicting the cardiac function in these patients during the chronic phase of this disease.

Fatty Acids↗

Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma.

Multiple myeloma (MM) cells cause devastating bone destruction by activating osteoclasts in the bone marrow milieu. However, the mechanism of enhanced bone resorption in patients with myeloma is poorly understood. In the present study, we investigated a role of C-C chemokines, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, in MM cell-induced osteolysis. These chemokines were produced and secreted by a majority of MM cell lines as well as primary MM cells from patients. Secretion of MIP-1alpha and MIP-1beta correlated well with the ability of myeloma cells to enhance osteoclastic bone resorption both in vitro and in vivo as well as in MM patients. In osteoclastogenic cultures of rabbit bone cells, cocultures with myeloma cells as well as addition of myeloma cell-conditioned media enhanced both formation of osteoclastlike cells and resorption pits to an extent comparable to the effect of recombinant MIP-1alpha and MIP-1beta. Importantly, these effects were mostly reversed by neutralizing antibodies against MIP-1alpha and MIP-1beta, or their cognate receptor, CCR5, suggesting critical roles of these chemokines. We also demonstrated that stromal cells express CCR5 and that recombinant MIP-1alpha and MIP-1beta induce expression of receptor activator of nuclear factor-kappaB (RANK) ligand by stromal cells, thereby stimulating osteoclast differentiation of preosteoclastic cells. These results suggest that MIP-1alpha and MIP-1beta may be major osteoclast-activating factors produced by MM cells.

Animals↗

Changes in expression of voltage-dependent ion channel subunits in dorsal root ganglia of rats with radicular injury and pain.

STUDY DESIGN: Changes in expression of voltage-dependent ion channel subunits were examined in the radicular pain state. Furthermore, antinociceptive effects of gabapentin on radicular pain were compared with effects on peripheral neuropathic pain. OBJECTIVES: To clarify molecular substrates involved in the development of radicular pain, and to investigate the responsiveness of radicular pain to gabapentin. SUMMARY OF BACKGROUND DATA: Peripheral nerve injuries are known to induce dynamic changes of voltage-dependent Na+ and Ca2+ channel subunits expression in dorsal root ganglion neurons. However, the expression profiles of Na+ and Ca2+ channel subunits in the radicular pain state have not been examined. METHODS: Two radicular pain models and one peripheral neuropathic pain model were prepared. By using semiquantitative reverse transcriptase-polymerase chain reaction, the expression levels of several Na+ and Ca2+ channel subunits in the dorsal root ganglions of these pain model rats were investigated. The antinociceptive effects of gabapentin were examined in a behavioral study using the aforementioned pain models. RESULTS: All three neuropathic pain operations induced comparable mechanical allodynia and thermal hyperalgesia. The upregulation of the Na(v)1.3 Na+ channel and Ca(v)alpha2delta Ca2+ channel subunits was observed only in the peripheral nerve injury model. A downregulation of the Na(v)1.9 channel was observed in all three pain model rats. A lower dose of gabapentin was significantly more effective in alleviating the mechanical allodynia of rats with radicular pain. CONCLUSIONS: The reduction of Na(v)1.9 found in all three models may link to the neuropathic pain state, including radicular pain. The lower sensitivity to gabapentin in rats with peripheral neuropathic pain might be partly explained by the marked upregulation of Ca(v)alpha2delta in the dorsal root ganglions, suggesting that gabapentin may be more effective in radicular pain treatment.

Acetates↗

Mixed chimerism induces donor-specific T-cell tolerance across a highly disparate xenogeneic barrier.

Induction of tolerance is likely to be essential for successful xenotransplantation because immune responses across xenogeneic barriers are vigorous. Although mixed hematopoietic chimerism leads to stable donor-specific tolerance in allogeneic and closely related xenogeneic (eg, rat-to-mouse) combinations, the ability of this approach to induce tolerance across a highly disparate xenogeneic barrier has not yet been demonstrated. In this study, we investigated the immune responses of murine T cells that developed in mice with pre-established porcine hematopoietic chimerism. Our results show for the first time that induction of porcine hematopoietic chimerism can eliminate the development of antiporcine donor responses in a highly disparate xenogeneic species. Porcine hematopoietic chimeras showed donor-specific nonresponsiveness in the mixed lymphocyte reaction, lack of antidonor IgG antibody production, and acceptance of donor skin grafts. Thus, mixed chimerism is capable of inducing tolerance in a highly disparate xenogeneic combination and may have clinical potential to prevent xenograft rejection. (Blood. 2002;99:3823-3829)

Animals↗

Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases.

KL-6, surfactant protein (SP)-A, SP-D, and monocyte chemoattractant protein-1 (MCP-1) are reported to be sensitive markers for interstitial lung diseases (ILD). However, each marker has been studied independently. The aim of this study was a comparative analysis of the diagnostic values of these markers. Subjects consisted of 33 patients with ILD (21 cases of idiopathic pulmonary fibrosis and 12 associated with collagen vascular diseases) and 82 control subjects (12 cases of bacterial pneumonia and 70 healthy volunteers). Receiver operating characteristic curves revealed that KL-6 was superior to the other markers. The cut-off levels for these markers that resulted in the highest diagnostic accuracy were determined to be 465 U/ml for KL-6, 48.2 ng/ml for SP-A, 116 ng/ml for SP-D, and 1080 pg/ml for MCP-1. The sensitivity, specificity, and diagnostic accuracy were 93.9%, 96.3%, and 95.7% for KL-6; 81.8%, 86.6%, and 85.2% for SP-A; 69.7%, 95.1%, and 87.8% for SP-D; and 51.5%, 92.7%, and 80.9% for MCP-1; respectively. The serum levels of SP-A and SP-D, but not of KL-6, were significantly higher in patients with bacterial pneumonia than in healthy volunteers. These results suggest that of the markers studied, KL-6 is the best serum marker for ILD.

Antigens↗

Elimination of porcine hemopoietic cells by macrophages in mice.

The difficulty in achieving donor hemopoietic engraftment across highly disparate xenogeneic species barriers poses a major obstacle to exploring xenograft tolerance induction by mixed chimerism. In this study, we observed that macrophages mediate strong rejection of porcine hemopoietic cells in mice. Depletion of macrophages with medronate-encapsulated liposomes (M-liposomes) markedly improved porcine chimerism, and early chimerism in particular, in sublethally irradiated immunodeficient and lethally irradiated immunocompetent mice. Although porcine chimerism in the peripheral blood and spleen of M-liposome-treated mice rapidly declined after macrophages had recovered and became indistinguishable from controls by wk 5 post-transplant, the levels of chimerism in the marrow of these mice remained higher than those in control recipients at 8 wks after transplant. These results suggest that macrophages that developed in the presence of porcine chimerism were not adapted to the porcine donor and that marrow-resident macrophages did not phagocytose porcine cells. Moreover, M-liposome treatment had no effect on the survival of porcine PBMC injected into the recipient peritoneal cavity, but was essential for the migration and relocation of these cells into other tissues/organs, such as spleen, bone marrow, and peripheral blood. Together, our results suggest that murine reticuloendothelial macrophages, but not those in the bone marrow and peritoneal cavity, play a significant role in the clearance of porcine hemopoietic cells in vivo. Because injection of M-liposomes i.v. mainly depletes splenic macrophages and liver Kupffer cells, the spleen and/or liver are likely the primary sites of porcine cell clearance in vivo.

Animals↗

Potent induction of activin A secretion from monocytes and bone marrow stromal fibroblasts by cognate interaction with activated T cells.

Activin A is a multifunctional cytokine essential for cell differentiation and apoptosis including erythroid cell differentiation in the bone marrow. In addition, activin A is induced by inflammation and exerts anti-inflammatory effects. However, the mechanism of activin A induction is still unclear, especially by inflammatory processes. Here we show that activin A secretion from monocytes and bone marrow stromal fibroblasts, its major sources in the bone marrow, is markedly enhanced by cognate interaction with activated T cells. This process is mediated by CD40/CD40 ligand interaction as well as concomitantly secreted T cell-derived cytokines, granulocyte macrophage-colony stimulating factor, and interferon-gamma. Furthermore, stromal fibroblasts as well as monocytes provide a costimulatory signal to anti-CD3-treated T cells via CD80 and CD86 to maintain the enhanced activin A production. These findings suggest that activin A is potently induced in the bone marrow and may play a role in the suppression of inflammatory or immune processes.

Activins↗