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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 307 records · Page 17Linked to original sources

Primary esophageal T cell lymphoma.

A 60 year-old woman with primary esophageal T-cell lymphoma in clinical stage I(E)B is presented. Immunohistologic examination showed tumor cells to be positive for anti-LCA, anti-UCHL-1, anti-MT-1, anti-CD3 antibodies, and negative for anti-L26 antibody. Disappearance of dysphagia and improvement in esophageal findings were noted after 65 Gy of irradiation, and biopsy specimens from the esophagus revealed no malignancy. Primary esophageal lymphoma is extremely rare, and this T-cell lymphoma is only the fourth case reported in the literature.

Antineoplastic Combined Chemotherapy Protocols↗

[Rapid recovery of hemopoiesis and alleviation of symptoms similar to peri-engraftment syndrome after donor leukocyte infusion].

A 28-year-old man who had received an allogeneic bone marrow transplant 7 years earlier experienced a relapse of chronic myelogenous leukemia in an accelerated phase. He was unsuccessfully treated with vincristine (VCR) and interferon-alpha (IFN-alpha), and subsequently received a donor leukocyte transfusion (CD3+ cells: 1.5 x 10(7)/kg). Rapid hematologic recovery was observed and a complete remission was obtained without graft-versus-host disease (GVHD) or bone marrow aplasia. It may be that the preceding regimen of chemotherapy (VCR + IFN-alpha) contributed to the patient's recovery by reducing the tumor burden.

Adult↗

Monitoring of human herpesviruses after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation.

Herpesviruses frequently cause serious complications after allogeneic bone marrow transplantation (allo-BMT). Recent studies have shown more rapid immune reconstitution after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) compared with allo-BMT. However, it has not been clarified whether the improved immune reconstitution after allo-PBSCT is associated with a lower incidence of herpesvirus infections. We monitored the emergence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and HHV-7 DNA by a nested-double polymerase chain reaction in peripheral blood leucocytes from 22 allo-BMT and 16 allo-PBSCT patients. Each virus had an unique temporal profile of detection. HHV-6 DNA was detected most frequently at 3 weeks after transplantation, whereas CMV and EBV DNA were detected later (2-3 months). Detection rates of HHV-6 DNA at 3 and 4 weeks after allo-BMT were significantly higher than those after allo-PBSCT (9/16 v 2/13 at 3 weeks, P < 0.01; 10/21 v 1/15 at 4 weeks, P < 0.01). Detection rates of the other three herpesviruses after the two types of allogeneic transplantation were not significantly different throughout observation period. Furthermore, detection of HHV-6 DNA within the first 4 weeks was associated with delayed platelet engraftment after both allo-BMT and allo-PBSCT (P < 0.01). These results suggest an advantage for allo-PBSCT over allo-BMT in terms of suppression of HHV-6 reactivation and prevention of subsequent complications.

Adolescent↗

Defective human T-lymphotrophic virus type I provirus in T-cell prolymphocytic leukaemia.

T-cell prolymphocytic leukaemia (T-PLL) is a rare form of post-thymic T-cell neoplasm, the aetiology of which remains unknown. We examined human T-lymphotropic virus (HTLV) provirus in five HTLV-I/II seronegative patients with T-PLL. Southern blotting did not show monoclonal integration of the HTLV-I genome in any of the DNA samples. However, two of the five DNA samples contained an HTLV-I tax sequence. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and LTR regions were all negative. HTLV-I tax gene expression and p40tax antibody were not detected in samples from cases with HTLV-I tax sequence. Our findings suggest that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis, in which HTLV-I genome insertion triggers T-PLL but the deletion of various regions of the integrated provirus subsequently prevents active replication and the expression of the virus.

Adult↗

Familial occurrence of chronic neutrophilic leukaemia.

A father and son who both developed chronic neutrophilic leukaemia (CNL) are reported. The father, aged 63, had been exposed to radioactive fallout after the atomic bomb attack on Hiroshima; he presented with hepatosplenomegaly and neutrophilic leucocytosis, and died of intracerebral haemorrhage 1 month after diagnosis. 4 years later his son, then aged 44, presented with neutrophilic leucocytosis. Leukaemic transformation to acute myelogenous leukaemia (AML-M1) occurred, and he died of refractory leukaemia 4 months after the diagnosis of CNL. This is the first report of this rare disease occurring in family members; genetic effect due to radioactive poisoning was suspected in the development of CNL in these two cases.

Adult↗

Ligation of CD40 induced tumor necrosis factor-alpha in rheumatoid arthritis: a novel mechanism of activation of synoviocytes.

OBJECTIVE: To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA). METHODS: The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG. RESULTS: Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells. CONCLUSION: These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13.

Arthritis, Rheumatoid↗

[Stentless aortic root bioprosthesis (freestyle) to patients of bicuspid aortic valve with abnormal positioning of the coronary ostia].

Stentless aortic root bioprosthesis (Freestyle) was implanted to two patients of bicuspid aortic valve stenosis with anatomically abnormal positioning of the coronary ostia. In a patient of LR type bicuspid valve, the left coronary artery was located at 180 degrees against the right coronary ostium. To match the Valsalva sinus of the patient with bioprosthesis, the left half of the native annulus, 23 mm in the diameter, was plicated corresponding to the one third of the Freestyle inflow, 21 mm in the diameter. In the other patient of AP type bicuspid valve, both coronary ostia were closely positioned at 90 degrees. To keep both ostia in the sinus of bioprosthesis, careful trimming and suturing were required in the narrow part of both ostia. Their postoperative courses were uneventful and no regurgitation has been observed in either case.

Aged↗

Direct expiratory gas analysis after hypothermic cardiopulmonary bypass.

We hypothesized that patients who have undergone hypothermic cardiopulmonary bypass may have abnormal oxygen metabolism after cardiac surgery because of oxygen debts that occurred during cardiopulmonary bypass. A prospective study was designed to determine oxygen consumption and carbon dioxide production using an indirect calorimeter in 45 adult patients who underwent hypothermic cardiopulmonary bypass. Inspiratory and expiratory gases were analyzed and the respiratory exchange ratio (carbon dioxide production/ oxygen consumption) was obtained every 6 hours up to 24 hours after surgery. The respiratory exchange ratio immediately following cardiopulmonary bypass was abnormally high then gradually decreased. The respiratory exchange ratio at 18 or 24 hours after surgery was significantly lower than the one on admission to the intensive care unit. Duration of cardiopulmonary bypass was the most significant parameter which correlated to the respiratory exchange ratio on admission to the intensive care unit (r = 0.82, p < 0.001). We conclude that the respiratory exchange ratio can be used to monitor systemic metabolism, especially during the recovery phase from metabolic abnormality following hypothermic cardiopulmonary bypass.

Adult↗

[Anesthetic management for implantation of implantable cardioverter-defibrillators].

Implantable cardioverter-defibrillators (ICDs) were implanted in 44 patients at the authors' institution. The anesthetic management was reviewed retrospectively. Ten of the 44 patients received the third generation ICD devices, while the rest received the fourth generation devices. For thirteen patients receiving the fourth generation devices, implantation was performed under local anesthesia with monitored care of anesthesiologists. Propofol was infused to achieve deep sedation during induced ventricular fibrillation and later cardioversion for testing the devices. Implantation was performed under general anesthesia with combination of fentanyl and volatile anesthetics for the remaining 31 patients. Patients who received ICDs under local anesthesia had significantly greater values of ejection fraction in preoperative examination than values in patients who received ICDs under general anesthesia. Operation time of the implantation under local anesthesia was significantly shorter than that under general anesthesia. Though infusion of propofol produced a moderate decrease of blood pressure in patients who received ICDs under local anesthesia, no patient showed major complication. Local anesthesia with sedation with propofol can be an option in anesthetic management for implantation of an ICD if an anesthesiologist cares the patient whose cardiac function is not compromised.

Adult↗

[Clinical results of surgical repair for thoracic aortic aneurysms: intraoperative blood loss and morbidity].

Clinical results of 64 patients who underwent surgical repair for thoracic aortic aneurysms were studied, focusing on the relationship between intraoperative blood loss and postoperative morbidity. Operative mortality was 22% in the urgent repair group and 9% in the elective repair group. Deep hypothermia, operative death, postoperative complication were the factors which significantly correlated to the amount of intraoperative blood loss. In patients who received deep hypothermia, larger blood loss and higher incidence of mortality and morbidity were observed. There was a significant relationship between the lowest core temperature during cardiopulmonary bypass and the lowest platelet count. Intraoperative blood loss revealed as a strong risk factor to directly influence postoperative clinical outcome of thoracic aortic operation.

Aortic Aneurysm, Thoracic↗

[A multicenter early phase II study of high-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of intermediate-grade non-Hodgkin's lymphoma. Japan Blood Cell Transplantation Study Group].

We conducted a multicenter early phase II study to evaluate the feasibility and therapeutic efficacy of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of intermediate grade non-Hodgkin's lymphoma (IG-NHL). High-dose etoposide or cyclophosphamide followed by G-CSF was used for PBSC mobilization, and a sufficient number of CD34+ cells (> 1 x 10(6)/kg) were collected. Out of 81 enrolled patients, 50 received high-dose chemotherapy with auto-PBSCT; Hematologic recovery after transplantation was rapid. The incidence of grade III/IV toxicity (Bearman) was about 6%; treatment-related mortality was 6% (3/50). The Disease-free survival rate for the patients in complete remission who received high-dose chemotherapy with auto-PBSCT was better than that for the patients who were treated with conventional chemotherapy (57% vs 35%). These preliminary results indicated that high-dose chemotherapy with auto-PBSCT is feasible and effective. A prospective randomized phase III clinical trial will be required to assess the efficacy of high-dose chemotherapy with auto-PBSCT as a post-remission therapy for IG-NHL.

Adolescent↗

[A case of microscopic polyangiitis with severe cardiac and respiratory muscle involvement].

A 66-year-old female was admitted to our hospital in January, 1998, complaining of low grade fever and muscle weakness of her legs. Physical examination revealed muscle weakness of her neck (4/5) and proximal skeletal muscles of her bilateral legs (3/5-4/5). She showed proteinuria and microhematuria. Her serum levels of ureanitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, creatinekinase, aldolase and myoglobin were all within the normal ranges. Antinuclear antibodies were negative, but her serum levels of pANCA (743 EU) and C reactive protein (18.0 mg/dl) were elevated. Neuroconduction velocity of her left common peroneal nerve was decreased to 40.8 m/sec and electric myograph showed neurogenic changes. Magnetic resonance images (MRI) of her bilateral thigh depicted high signal intensity in quadriceps by T 2 weighed images, but the signals were not enhanced by gadolinium injection. Muscle and renal biopsies revealed necrotizing vasculitis of the small arteries. Crescentic glomerulonephritis was also observed by renal biopsy. These findings supported the diagnosis of microscopic PN. On 16 th admission day, she developed acute cardiac and respiratory failures due to cardiac and respiratory muscle involvements with PN, and was assisted by mechanical ventilation. She was treated with methylprednisolone pulse therapy (500 mg/day, three consecutive days) on 18 th admission day, followed by 40 mg of oral prednisolone daily. However, her symptoms deteriorated, and herserum creatinine levels increased to 2.4 mg/dl. On 24 th admission day, intravenous cyclophosphamide pulse therapy (500 mg/day) was instituted. Her cardiac wall motion on echocardiography and serum creatinine levels gradually improved, but her skeletal and respiratory muscle weakness did not improve. On 38 th admission day, she was complicated with respiratory infection by methicillin resistant Staphylococcus aures. On 62 th admission day, she died of endotoxic shock. This is the first report describing respiratory muscle involvement with PN, and the second report describing MRI findings of muscle involvement by PN. Therefore, our case provides important clinical information for the diagnosis and treatment of the disease.

Aged↗

Analysis of circulating hematopoietic progenitor cells after peripheral blood stem cell transplantation.

We investigated the kinetics of posttransplant circulating progenitor cells (PTCPC) in the early phase after autologous (auto-) and allogeneic (allo-) peripheral blood stem cell transplantation (PBSCT). We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just prior to transplantation), 1 (12-15 hours after completion of first transplantation), 2, 3, 5, 7, 10, 14, 17, 21 and 28 (after auto-PBSCT), and also additionally on day 35 after allo-PBSCT. A standard methylcellulose colony assay was used for analysing the number of CFU-GGM and BFU-E on all of the days. In addition, high proliferative potential-colony forming cells (HPP-CFC) of the harvested PBSC from donors and day 1 PB from recipients were assayed in 5 allo-PBSCT patients. Furthermore, a proportion of CD38- cells among CD34+ cells in the harvested PBSC and day 1 PB was evaluated by two-color flow cytometric analysis in 5 allo-PBSCT patients. The number of CFU-GM on day 1 ranged from 7 to 119 per 10 ml PB after auto-PBSCT, and from 15 to 61 per 10 ml PB after allo-PBSCT. After these transient increases, PTCPC diminished rapidly. Then, PTCPC emerged again on day 7 after auto-PBSCT and on day 10 or 14 after allo-PBSCT along with neutrophil recovery. A proportion of HPP-CFC among myeloid colonies from day 1 PB of recipients was significantly higher than that from the harvested PBSC from donors (65.6 +/- 12.7% vs. 17.4 +/- 13.0%, respectively, n = 5, P = 0.0013). In addition, two-color flow cytometric analysis revealed that the proportion of CD34+CD38- cells was significantly higher in day 1 PB of recipients than in the harvested PBSC from donors (57.5 +/- 17.6% vs. 11.7 +/- 4.9%, n = 5, P = 0.005). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following PBSCT.

Adult↗

[Nation-wide survey for the treatment with cyclosporin A of interstitial pneumonia associated with collagen diseases].

OBJECTIVES: This study was performed to investigate the efficacy and safety of cyclosporin A (CsA) for the treatment of interstitial pneumonia (IP) associated with collagen diseases in Japan. METHODS: Questionnaires were sent to 36 hospitals specializing in collagen diseases. RESULTS: Fifty-eight patients (7 polymyositis (PM), 19 dermatomyositis (DM), 7 systemic sclerosis (SSc), 7 rheumatoid arthritis (RA), 2 mixed connective tissue disease (MCTD), 1 systemic lupus erythematosus (SLE) and 1 Sjögren's syndrome (SS), 1 RA + SSc, 2 PM + SSc, 1 DM + SLE, and 10 idiopathic interstitial pneumonia (IIP) with IP were treated with CsA at 14 hospitals. IP was classified into the acute or chronic type. In the PM/DM group (7 PM, 19 DM, 2 PM + SSC, 1 DM + SLE), 65.5% were the acute type. In the other collagen disease group (7 SSc, 7 RA, 2 MCTD, 1 SLE, 1 SS, and 1 RA + SSc) and IIP group, 36.8% and 50% were the acute type, respectively. Mean dosages of CsA were 3.7 +/- 1.3 mg/kg/day for the PM/DM group, 3.0 +/- 1.0 for the other collagen disease group, and 3.8 +/- 4.8 for the IIP group. Oral corticosteroids were administered in combination with CsA in 100, 73.7, and 70% of the patients with PM/DM, other collagen disease, and IIP groups, respectively. CsA was effective for 72.2, 33.3, and 25% of the acute IP cases in the PM/DM, other collagen disease, and IIP groups, respectively. CsA was effective for 50.0, 50.0, and 60.0% of chronic IP cases in the PM/DM, other collagen disease, and IIP groups, respectively. Twenty-three adverse effects were observed, but most of them ameliorated upon withdrawal or reduction of the CsA dose. CONCLUSION: CsA is effective for the treatment of acute type IP associated with collagen diseases, especially PM/DM. To perform a prospective multi-center trial, standards for the recruitment of patients, efficacy assessments, and trial course and treatment should be determined carefully.

Anti-Inflammatory Agents↗

Donor resting B cells induce indefinite prolongation of fully allogeneic cardiac grafts when delivered with anti-immunoglobulin-D monoclonal antibody: evidence for tolerogenicity of donor resting B cells in vivo.

BACKGROUND: Resting B (rB) cells have been shown to induce T-cell anergy in vitro and to prolong the survival of skin and cardiac grafts mismatched for minor histocompatibility antigens. However, rB cells were unable to modulate the rejection response when grafts mismatched for major histocompatibility complex antigens were transplanted. We reasoned that donor antigens, which presented via the indirect pathway by recipient antigen-presenting cells, in particular B cells, might influence the ability of rB cells to induce unresponsiveness. To explore this hypothesis, we used an anti-immunoglobulin (Ig)-D monoclonal antibody (mAb) specific for recipient B cells to deplete these cells, thereby decreasing the potential for indirect presentation in vivo. METHODS: CBA mice were pretreated with 1 x 10(7) donor rB or activated B (aB) cells 7 days before transplantation of a C57BL/10 cardiac graft in the absence or presence of anti-IgD mAb. RESULTS: Naive CBA mice rejected C57BL/10 grafts acutely (median survival time [MST]=8 days). Pretreatment with rB cells alone resulted in a modest prolongation of graft survival (MST=11.5 days). In marked contrast, when rB cells were delivered with anti-IgD mAb, indefinite graft prolongation (MST>100 days) was observed in all recipients. Interestingly, aB cells produced only a small prolongation of graft survival when delivered with anti-IgD mAb (MST=15 days). Recipients treated with anti-IgD mAb alone rejected C57BL/10 cardiac allografts acutely (MST=8 days). CONCLUSION: These data suggest that depletion of recipient B cells in vivo can augment the ability of donor rB cells to induce indefinite prolongation of fully allogeneic cardiac grafts. Thus, IgD+ B cells in the recipient may influence the development of unresponsiveness in vivo.

Animals↗