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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 37 records · Page 2Linked to original sources
PubMed2005

Demonstration of reversed flow in segmental branches of the portal vein with hand-held color Doppler ultrasonography after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a severe complication of hematopoietic stem cell transplantation (SCT). When monitored with hand-held color Doppler ultrasonography during day -7 to +35 around SCT, reversed blood flow in the segmental branches of the portal vein was detected in nine of 56 patients who had undergone SCT. Three of nine patients had clinical evidence of VOD, but six patients did not fulfill the criteria for diagnosis of VOD initially. Two patients progressed to clinical VOD at a later date and the reversed portal flow disappeared with or without treatment for VOD in the other four patients. Monitoring for reversed portal flow with color Doppler ultrasonography may be a useful tool for the early diagnosis of VOD, and may improve prognosis by allowing early initiation of treatment.

Adolescent↗
PubMed2005

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT.

A growing body of evidence indicates that genetic factors are involved in an increased risk of infection. We investigated whether mannose-binding lectin (MBL) gene polymorphisms that cause low levels of MBL are associated with the occurrence of major infections in patients, mainly bearing hematological malignancies, after high-dose chemotherapy (HDT) rescued by autologous peripheral blood stem cell transplantation (auto-PBSCT). A retrospective evaluation of 113 patients treated with HDT and auto-PBSCT revealed that the low-producing genotypes, B/B and B/LXA, were associated with major bacterial infection (P=0.0016, OR 7.9). We next performed a nation-wide large-scale study to assess the allele frequency of the MBL coding mutation in a total of 2623 healthy individuals in Japan. The frequency of allele B was estimated to be approximately 0.2, almost the same in seven different areas of Japan. This common occurrence suggests that MBL deficiency may play an important role in the clinical settings of immunosuppression.

Alleles↗
PubMed2005

Efficient engraftment of primary adult T-cell leukemia cells in newborn NOD/SCID/beta2-microglobulin(null) mice.

Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells are intravenously transplanted into neonatal nonobese diabetic (NOD)/severe-combined immunodeficiency (SCID)/beta2-microglobulin(null) (NOD/SCID/beta2m(null)) mice. Acute-type ATL cells engrafted in the peripheral blood and in the lymph nodes of recipients at a high efficiency. Engrafted ATL cells were dually positive for human CD4 and CD25, and displayed patterns of HTLV-I integration identical to those of donors by Southern blot analysis. These cells infiltrated into recipients' liver, and formed nodular lesions, recapitulating the clinical feature of each patient. In contrast, in smoldering-type ATL cases, multiple clones of ATL cells engrafted efficiently in NOD/SCID/beta2m(null) mice. When smoldering-type ATL cells were retransplanted into secondary NOD/SCID/beta2m(null) recipients, single HTLV-I-infected clones became predominant, suggesting that clones with dominant proliferative activity can be competitively selected in this xenogeneic system. Taken together, the NOD/SCID/beta2m(null) newborn system is useful to understand kinetics, metastasis, and disease progression of ATL in vivo.

Anemia, Refractory, with Excess of Blasts↗
PubMed2005

Scratching behavior in spontaneous- or allergic contact-induced dermatitis in NC/Nga mice.

NC/Nga mice have pathological and behavioral features similar to those seen in human atopic dermatitis. There are two known dermatitis models in NC/Nga mice, one being spontaneous-induced dermatitis under conventional conditions and the other 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis. However, there are significant differences in time course on development of dermatitis. We studied the role of scratching behavior (sign of itch) on the development of dermatitis on spontaneous- and TNCB-induced dermatitis. We measured scratching counts, transepidermal water loss (TEWL), and skin inflammation score, under conventional conditions or by applying 5% TNCB once a week for 6 weeks in NC/Nga mice. In spontaneous-induced dermatitis, scratching counts increased with the passage of time. The scratching counts were significantly increased only 1 week after housing the mice under conventional conditions, but no changes were observed in cases of TNCB-induced dermatitis. In spontaneous-induced dermatitis, TEWL and skin-inflammation score were gradually increased, time-dependently. On the other hand, in TNCB-induced dermatitis, these dependent values rapidly increased and reached a maximum only after 24 h TNCB application. These data suggest that pathogenesis of spontaneous- and allergic contact-induced dermatitis was clearly different. It will be of major interest to identify the pruritic mediators causing profound scratching behavior and scratching-induced aggravation of inflammation in the spontaneous-induced dermatitis, as opposed to the inflammatory mediators that cause contact allergic dermatitis without major scratching.

Animals↗
PubMed2005

[Hemothorax associated with congenital pulmonary arteriovenous fistula; report of a case].

A 20-year-old man was admitted to our hospital with a sudden onset of dyspnea, caused by right pleural effusion. The patient was in a state of shock. Thoracentesis was revealed hemothorax. Right thoracotomy revealed pulmonary arteriovenous fistula projecting into the intrapleural space from the right upper lobe. Partial resection was performed. His postoperative course was uneventful. Intrapleural rupture of pulmonary arteriovenous fistula was reported rarely; therefore we described here our case.

Adult↗
PubMed2005

[Surgery for a pericardial diverticulum; report of a case].

We report a case with pericardial diverticulum in the mediastinum. A 64-year-old woman visited our hospital because of cough and dyspnea. Chest X-ray showed a smooth-bordered mass in the right superior mediastinum and computed tomography (CT) showed a homogeneous cystic mass in the paratracheal area. During right mini-thoracotomy, a thin-walled cystic lesion was found involving the trachea, the superior vena cava, and the azygos vein. The cyst extended a duct toward the pericardium. We performed total excision and pathological examination confirmed the diagnosis of a pericardial diverticulum. Mini-thoracotomy provides an effective and minimally invasive means of excising the mediastinal mass, relieving symptoms, and allowing pathological examination.

Diverticulum↗
PubMed2005

[Bentall operation for the annuloaortic ectasia which merged liver cirrhosis and pericarditis; report of a case].

We report a case of successful aortic root replacement using a stented bioprosthetic valved conduit and pericardiectomy in a patient with liver cirrhosis and constrictive pericarditis. A 72-year-old man treated for alcoholic liver cirrhosis was referred for the aortic regurgitation and dilatation of sinus of Valsalva. He underwent Bentall operation using a stented bioprosthetic valved conduit and pericardiectomy successfully. For patients whose anticoagulation is contraindicated, aortic root replacement using valved conduit with bioprosthesis is useful option. Concomitant pericardiectomy for constrictive pericarditis may provide better long-term results.

Aged↗
PubMed2004

Raised serum APRIL levels in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and correlate with autoantibody titres or disease activity, or both. METHODS: Serum samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked immunosorbent assay. Medical charts were retrospectively reviewed for autoantibody titres and immunoglobulin levels. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: The APRIL levels in the serum samples from patients with SLE were significantly higher than in those from healthy controls and those from patients with RA. Serum APRIL levels did not correlate with serum IgG and IgM levels, but had a tendency to correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL levels correlated significantly with musculoskeletal manifestations among patients with SLE when assessed by the BILAG index. CONCLUSION: APRIL may be an important factor in raised autoantibody titres and musculoskeletal disease in patients with SLE. Patients with raised serum APRIL levels may be ideal candidates for therapeutic targeting of APRIL.

Adult↗
PubMed2004

Identification of parathyroid hormone-related protein-derived peptides immunogenic in human histocompatibility leukocyte antigen-A24+ prostate cancer patients.

Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24(+) prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP(36-44) and PTHrP(102-111) peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8(+) T cells. Immunoglobulin G reactive to the PTHrP(102-111) or PTHrP(110-119) peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP(102-111) peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24(+) prostate cancer patients with metastases.

CD8-Positive T-Lymphocytes↗
PubMed2004

Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice.

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is up-regulated and recruits and activates inflammatory cells in human diffuse proliferative lupus nephritis (DPLN) and in nephritis of lupus model MRL/lpr mice. The aim of this study was to examine whether anti-MCP-1 gene therapy inhibits the progression of nephritis in MRL/lpr mice. METHOD: An NH(2)-terminal deletion mutant of the MCP-1 gene, 7ND, was injected into skeletal muscles of MRL/lpr mice with advanced stage nephritis to blockade MCP-1 and its receptor (CCR2) signalling pathway. RESULT: Histological findings of kidneys in treated mice, which received more than four injections of 7ND, showed that protection against renal injury resulted from reduced infiltration of leucocytes. Therefore, this therapy has been shown to prolong the life span of MRL/lpr mice. CONCLUSION: Anti-MCP-1 gene therapy is specifically effective in the localized inflammatory region. The data presented here indicate that this anti-MCP-1 gene therapy may be effective adjunct in the management of DPLN.

Animals↗
PubMed2004

A phase I trial of cytotoxic T-lymphocyte precursor-oriented peptide vaccines for colorectal carcinoma patients.

In most protocols of peptide-based vaccination, no consideration has been paid to whether or not peptide-specific cytotoxic T-lymphocyte (CTL) precursors are pre-existent in cancer patients. Initiation of immune boosting through vaccination is better than that of immune priming to induce prompt and strong immunity. In this study, 10 human histocompatibility leukocyte antigen-A24(+) patients with advanced colorectal carcinomas were treated with up to four peptides that had been positive for pre-vaccination measurement of peptide-specific CTL precursors in the circulation (CTL precursor-oriented peptide vaccine). No severe adverse effect was observed, although local pain and fever of grade I or II were observed. Post-vaccination peripheral blood mononuclear cells (PBMCs) from five patients demonstrated an increased peptide-specific immune response to the peptides. Increased CTL response to cancer cells was detected in post-vaccination PBMCs of five patients. Antipeptide immunoglobulin G became detectable in post-vaccination sera of seven patients. Three patients developed a positive delayed-type hypersensitivity response to at least one of the peptides administrated. One patient was found to have a partial response; another had a stable disease, sustained through 6 months. These results encourage further development of CTL precursor-oriented vaccine for colorectal cancer patients.

Adult↗
PubMed2004

Which infertile women should be indicated for sonohysterography?

OBJECTIVE: To evaluate the indications for transvaginal saline contrast sonohysterography (TV-SCSH) in endometrial screening by transvaginal sonography in infertile women. METHODS: The study involved 850 consecutive infertile women presenting to an outpatient clinic. Using transvaginal ultrasound endometrial images were evaluated in the proliferative phase. Abnormal images were classified as follows: rugged (R), hyperechoic (H), waved (W), or thick (T). Clinical symptoms such as hypermenorrhea, dysmenorrhea and abnormal uterine bleeding were also recorded. Abnormal endometrial images were further evaluated on TV-SCSH. Age-matched women with normal endometrial images underwent TV-SCSH as controls. RESULTS: The endometrial pattern was abnormal in 111 patients (13.1%). Lesions that had been identified by TV-SCSH including endometrial polyps (44 cases), submucosal myomata (29 cases), and intramural myomata with mucosal extension (24 cases) were largely associated with the R and/or the H pattern, the W or the T pattern, and the W pattern, respectively. Sensitivity and specificity of the abnormal endometrial image for any lesion were 100% and 91.5%, respectively. Sixty-four patients (59.3%) were asymptomatic despite an abnormal endometrial image. CONCLUSIONS: TV-SCSH should be performed on selected patients following assessment of endometrial images on transvaginal sonography in order to diagnose intra- and pericavitary lesions in infertile women.

Adult↗
PubMed2004

Allogeneic peripheral blood stem cell transplantation from two- or three-loci-mismatched related donors in adult Japanese patients with high-risk hematologic malignancies.

With the increasing frequency of haploidentical transplantation, it is becoming more important to establish the degree of HLA mismatch that can be accepted. We retrospectively analyzed clinical data of 50 adult Japanese patients with high-risk hematologic malignancies who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from two- or three-loci-mismatched related donors with HLA class I and II gene disparities in the graft-versus-host direction. They were treated at 20 transplant centers between 1996 and 2002. In all, 18 patients received unmanipulated PBSC, while 32 received purified CD34+ blood cells. Conventional (n=31) or reduced-intensity (n=19) conditioning regimens were used. Of the 39 patients (78%) who survived for > or =28 days after transplant, 37 (95%) achieved neutrophil engraftment, while graft failure and rejection occurred in two of 39 (5%) and three of 37 (8%) patients, respectively. Stepwise Cox regression analysis revealed a significantly lower incidence of grades II-IV acute GVHD in patients receiving purified CD34+ cells (hazard ratio 0.32; 95% CI 0.12-0.84; P=0.022). By 1 year post transplant, 28 patients (56%) had died of transplant-related problems, including infectious complications (30%). Although the number of patients is small, our data suggest that transplant-related problems, particularly infectious complications, are major obstacles to the success of this therapy.

Adolescent↗
PubMed2004

Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation.

To evaluate the clinical significance of a cytomegalovirus (CMV) antigenemia assay in the prediction and diagnosis of CMV gastrointestinal (CMV-GI) disease after hematopoietic stem cell transplantation (HSCT), 19 allogeneic HSCT recipients developing CMV-GI disease were retrospectively reviewed. All patients were monitored by a CMV antigenemia assay, at least once weekly after engraftment. The median onset of CMV-GI disease occurred 31 days post transplant (range: 19-62). Only four of 19 patients (21%) developed a positive CMV antigenemia test before developing CMV-GI diseases. Although all 19 patients subsequently developed positive CMV antigenemia tests during their clinical courses, the values remained at a low-level in nine (47%) patients. Among the 14 patients in whom results of real-time polymerase chain reaction (PCR) were available, seven (50%) yielded positive results of real-time PCR before developing CMV-GI disease. In contrast to the values of CMV antigenemia, all 14 patients exclusively yielded high viral loads (median: 2.8 x 10(4) copies/ml plasma). We conclude that CMV antigenemia testing has limited value in prediction or early diagnosis of CMV-GI disease, and that real-time PCR could have a more diagnostic significance.

Adult↗
PubMed2004

Clinical impact of graft-versus-host disease against leukemias not in remission at the time of allogeneic hematopoietic stem cell transplantation from related donors. The Japan Society for Hematopoietic Cell Transplantation Working Party.

Acute graft-versus-host disease (GVHD) increases post-transplant mortality and morbidity, but exerts a potent graft-versus-leukemia (GVL) effect. To clarify the impact of GVHD on outcome after transplant in aggressive diseases, patients with acute myeloid or lymphoblastic leukemia (AML, n = 366 or ALL, n = 255) in nonremission states, or chronic myelogenous leukemia (CML, n = 180) in accelerated phase (AP) or blastic crisis (BC), who received allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor between 1991 and 2000, were analyzed. Significant improvement in overall and disease-free survival (DFS) was detected with grade I acute GVHD in AML (P = 0.0002 for overall survival and 0.0009 for DFS, respectively) and in CML (P = 0.0256 and 0.0366, respectively), while the trend towards improved survival was observed in ALL. Relapse rate was lower in grade I acute GVHD than in grade II in all three diseases, suggesting that treatment for grade II GVHD may compromise the GVL effect associated with GVHD. Chronic GVHD was found to suppress relapse in CML and ALL, but not in AML, although no improvement in survival was observed in any disease category. Our results suggest that treatment for grade II acute GVHD may need to be attenuated in transplant for refractory leukemias.

Adolescent↗
PubMed2004

Cidofovir for treating adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients.

Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.

Adenoviridae↗