Allografting of peripheral blood stem cell mobilized from a donor developing herpes zoster virus infection.
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Acyclovir↗
Biomedical subjects
Mine Harada
Publications and source records attributed to Mine Harada.
Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations.
We herein report on two Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1). The brother, who expressed a characteristic phenotype of APS-1, had developed severe mucocutaneous candidiasis in early infancy and thereafter developed hypoparathyroidism and Addison's disease, along with a severe deterioration of his immunologic function. In contrast, the 44-year-old sister, who showed a noncharacteristic phenotype of APS-1, developed insulin-dependent diabetes with high anti-glutamic acid decarboxylase antibody, mild nail candidiasis, and autoimmune hepatitis with intact immunoreactivity. She had three susceptible human leukocyte antigen (HLA) loci for type 1 autoimmune diabetes. The expression of T cell receptor (TCR)V beta 5.1 increased in both patients, while the brother showed a widely suppressed expression of many TCRV beta families. Both individuals possessed compound heterozygous novel autoimmune regulator (AIRE) gene mutations (L29P and IVS9-1G > C). The same AIRE gene mutations can thus be associated with characteristic and noncharacteristic phenotypes of APS-1, and HLA may possibly influence the phenotype of APS-1.
Addison Disease↗
Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation.
A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. Eighteen days after transplantation, the patient developed grade II acute graft-versus-host disease (GVHD) and was treated with corticosteroids. On day 38, the patient complained of eye pain and lacrimation. A slitlamp examination revealed corneal ulcers and pseudomembranous formation in both eyes. Histologic and immunohistochemical examinations of the pseudomembrane disclosed an infiltrate dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence in situ hybridization identified a Y chromosome in the infiltrated mononuclear cells. Surveillance cultures from conjunctival swabs were negative. Thus, we diagnosed these ocular manifestations as an ocular involvement of acute GVHD.
Adult↗
Risk of neutropenic fever and early infectious complications after autologous peripheral blood stem cell transplantation for malignant diseases.
Autologous peripheral blood stem cell transplantation (auto-PBSCT) has facilitated high-dose chemotherapy for the treatment of various types of malignancy, but the factors affecting the treatment outcome have not been well defined. We evaluated patients who underwent auto-PBSCT (46 patients with hematological malignancies and 39 with solid tumors) to elucidate the risks of background factors, including age, in association with infectious complications. In contrast to former reports, faster engraftment did not influence the incidence of documented infection or neutropenic fever, whereas high age (age > or = 50 years old) and delayed platelet recovery (> or = 18 days) were demonstrated to be positively involved. The odds ratio (OR) for documented infection in elderly patients was 4.94 (95% confidence interval, 1.22-15.8). Another risk factor of infection was the HD-ICE regimen (ifosfamide, carboplatin, etoposide) given to patients with solid tumors (OR, 8.00; 95% confidence interval, 1.61-39.7). In conclusion, we found that elderly patients and patients on the HD-ICE regimen have a higher risk of infectious complications even after auto-PBSCT. Although the clinical indications for auto-PBSCT can be extended to elderly patients, thorough precautions should be taken against infectious complications during the pre-engraftment phase.
Adolescent↗
Successful treatment of progressive NK cell lymphoma with allogeneic peripheral stem cell transplantation followed by early cyclosporine tapering and donor leukocyte infusions.
We describe a patient with progressive natural killer (NK) cell lymphoma who was treated successfully with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) followed by early cyclosporine (CsA) tapering and donor leukocyte infusion (DLI). Because the disease showed early resistance to conventional chemoradiotherapy, we performed high-dose chemotherapy followed by allo-PBSCT. After achieving hematologic engraftment, the patient underwent early tapering of CsA and DLI in an attempt to induce a graft-versus-lymphoma effect. Although the disease was in a progressive state at the time of transplantation, complete remission was obtained after allo-PBSCT. As of this report, the patient has been well for more than 2 years.
Adult↗
Retrograde intrafamilial transmission of primary herpes simplex virus type 1 infection.
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Adolescent↗
Interleukin-12 augments cytolytic activity of peripheral blood mononuclear cells against autologous lung cancer cells in combination with IL-2.
The majority of patients with advanced lung cancer die within a few years. Accordingly, new therapeutic modalities need to be developed. Interleukin (IL)-12 was previously known as natural killer (NK) cell stimulatory factor or cytotoxic lymphocyte maturation factor. By virtue of its effects on T cells and NK cells, IL-12 seems to be one of the key cytokines that regulates cell-mediated anti tumor immune responses. Recently, there has been a substantial interest in the potential applications of IL-12 in the treatment of lung cancer. However, there have been no reports about the effect of IL-12 on peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients in an autologous setting. In this study, we examined the cytotoxicity of PBMC activated by IL-2, IL-12 or both against K562 or autologous lung cancer cells. In contrast to the effect of IL-2 on NK activity, IL-12 alone augmented NK activity against K562 cells, but not against autologous lung cancer cells. IL-12 augmented the IL-2 mediated cytotoxicity of PBMC against both K562 and autologous lung cancer cells. In the absence of IL-2, IL-12 alone cannot induce an autologous anti-tumor effect in vivo. In summary, our results clearly demonstrated that IL-12 can augment the cytolytic activity of PBMC against K562 and autologous lung cancer cells when combined with IL-2, although, IL-12 alone was unable to induce a marked increase in the cytotoxicity against autologous lung cancer cells. These results suggest that an administration of IL-12 in combination with IL-2 may be a useful therapeutic option for solid tumors.
Aged↗
Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy.
We established several in vitro drug-resistant cell lines after continuous, long-term exposure of each drug to elucidate mechanisms of drug resistance. Whether drug resistance in these in vitro resistant cell lines reflects clinical drug resistance still remains unanswered. In this study, a pair of lung cancer cell lines was established from one patient with squamous cell carcinoma of the lung, with one line being established before and one line after combination chemotherapy (cisplatin/ifosfamide/vindesine). Combination chemotherapy selected resistant EBC-2/R cells, which showed cross-resistance to 4-hydroxyifosfamide (3.2-fold), cisplatin (2.3-fold), and methotrexate (3.7-fold) and collateral sensitivity to vindesine (0.77-fold) compared with parent EBC-2 cells. EBC-2/R cells showed decrease in intracellular accumulation of cisplatin, increase in intracellular concentration of glutathione (GSH), and overexpression of multidrug resistance-associated protein (MRP) 3 when compared with EBC-2 cells. A single cycle of chemotherapy was not sufficient to select other mechanisms of drug resistance, such as multidrug resistance-1/P-glycoprotein, MRPs 1, 2, 4, and 5, lung resistance-related protein, metallothionein IIa, glutathione S-transferase pi, gamma-glutamylcysteine synthetase (light and heavy chain), and excision repair cross complementing 1. Sequentially we established two cell lines, which cell lines showed the differences of the cisplatin resistance, expression level of MRP3, intracellular GSH level and intracellular accumulation of cisplatin. A pair of cell lines will be useful to elucidate resistant mechanisms of cisplatin in heterogeneous lung cancer cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors.
UNLABELLED: In order to evaluate the activity and toxicity of a three-drug combination of vindesine, ifosfamide and cisplatin (VIP) for inoperable non-small-cell lung cancer (NSCLC), we conducted a randomized trial comparing VIP with a two-drug combination of cisplatin and vindesine (VP). Between September 1987 and March 1992, a total of 132 patients with stage III or IV NSCLC were randomly allocated to either VIP or VP. The VIP regimen consisted of vindesine (VDS 3 mg/m(2) on days 1 and 8), ifosfamide (IFX 1300 mg/m(2) on days 1-5), and cisplatin (CDDP 20 mg/m(2) on days 1-5). The VP regimen consisted of VDS and CDDP with the same dose and schedule as the VIP regimen. Both regimens were repeated every 4 weeks. Objective response rates were 49.3% (95% confidence interval: 95%CI, 43.1-55.4%) in the VIP arm and 44.6% (95%CI, 38.4-50.2%) in the VP arm; the difference was not significant (P=0.5390). Median response duration, median survival time, and two-year survival rates were 26.5 weeks, 49.6 weeks, and 14.9% in the VIP arm and 28.7 weeks, 37.1 weeks, and 12.3% in the VP arm, respectively. There were also no significant differences between these two treatment arms. In comparison with the VP regimen, however, a survival advantage of the VIP regimen could be confirmed when the data were evaluated with Cox's multivariate analysis (P=0.0131). In both arms, the principal toxicity was myelosuppression, which was significantly more frequent in the VIP arm, although generally well tolerated. CONCLUSION: This study suggested the survival advantage of the VIP regimen over the VP regimen for treatment of patients with advanced NSCLC.
Adult↗
Overexpression of novel short isoforms of Helios in a patient with T-cell acute lymphoblastic leukemia.
OBJECTIVE: In previous studies, we demonstrated overexpression of the dominant-negative isoform of the transcription factor Ikaros, Ik-6, in patients with blast crisis of chronic myelogenous leukemia and B-cell acute lymphoblastic leukemia. In the present study, we analyzed expression of the Ikaros family genes Ikaros, Aiolos, and Helios in a panel of human T-cell leukemia/lymphoma cell lines and bone marrow samples of patients with T-cell acute lymphoblastic leukemia. MATERIALS AND METHODS: We performed reverse transcriptase polymerase chain reaction, sequencing analysis, immunoblotting, and Southern blotting. RESULTS: We found overexpression of novel short isoforms of Helios (Hel-5 and Hel-6) in the HD-Mar cell line. Southern blot analysis suggested that there might be a small deletion in the Helios locus of HD-Mar. In addition, we observed decreased expression of more than one Ikaros family gene in 3 of 9 patients with T-cell acute lymphoblastic leukemia. Moreover, one of the patients overexpressed novel short isoforms of Helios (Hel-7 and Hel-8). CONCLUSION: This study provides the first evidence of an Ikaros family member (other than Ikaros) of which novel short isoforms become overexpressed in human leukemia.
Bone Marrow↗
A filter that prevents the spread of mail-attachment-type Trojan horse computer worms.
The malicious code "W32/Sircam" is spread via e-mail and potentially through the file space shared by local area networks. Such Trojan-horse-type computer worms easily penetrate Internet firewalls and propagate via the "backdoor" to other computers. Once a malicious code, such as "W32/Sircam," has been executed on a system, it may reveal or delete confidential data, such as clinical records. In order to protect against the leakage of clinical records, we devised a mail filter that successfully prevents the spread of mail containing this malicious code. It is significant that neither access control nor packet filtering is guaranteed to prevent the spread of this mail-attachment-type Trojan horse computer worm.
Computer Communication Networks↗
Identification of a novel WT1-derived peptide which induces human leucocyte antigen-A24-restricted anti-leukaemia cytotoxic T lymphocytes.
We previously reported the establishment of a Wilms' tumour (WT)1-derived peptide (CMTWNQMNL)-specific and human leucocyte antigen (HLA)-A24-restricted anti-leukaemia cytotoxic T lymphocyte (CTL) line, TAK-1. In this study, we have established a novel WT1-derived peptide (RWPSCQKKF)-specific CD8+ CTL line, designated NIM-1. NIM-1 lysed HLA-A24-positive leukaemia cells, but not HLA-A24-negative leukaemia cells or normal cells. The effects of TAK-1 and NIM-1 on cytotoxicity against leukaemia cells were not synergistic, suggesting that recognition of a single epitope on the tumour-specific antigen by CTLs is sufficient to exert maximal cytotoxic activity against tumour cells.
CD8-Positive T-Lymphocytes↗
Therapy-related chronic myelogenous leukaemia following autologous stem cell transplantation for Ewing's sarcoma.
A 17-year-old Japanese woman with Ewing's sarcoma was initially treated with conventional chemotherapy and local irradiation, and then with high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation. Four years later she was diagnosed with chronic myelogenous leukaemia (CML). The BCR/ABL fusion gene was detected in both peripheral blood and bone marrow cells by reverse transcription-polymerase chain reaction, but not in the harvest product of peripheral blood stem cells which were infused at the time of transplantation. This case adds to the accumulating evidence of therapy-related CML developing after high-dose chemotherapy and autologous stem cell transplantation.
Adolescent↗
Expression of cutaneous lymphocyte antigen is associated with a poor outcome of nasal-type natural killer-cell lymphoma.
Nasal and nasal-type natural killer (NK) lymphoma is a distinct clinicopathological entity mostly associated with Epstein-Barr virus. Cases that have widespread lesions are resistant to ordinary anti-cancer therapy and take a highly aggressive course. To date, there are no available data on the relationships between the localization, clinical outcome and expression of adhesion molecules in such cases. We examined the expression of cutaneous lymphocyte antigen (CLA) in 52 cases of NK-cell lymphoma. CLA was highly expressed in cutaneous cases. Also, the CLA+ group (n=29) had a much worse prognosis than the CLA- group (n=23), regardless of the primary site or clinical staging. Univariate analysis identified some significant prognostic factors, and multivariate analysis of these factors showed that the expression of CLA was an independent prognostic indicator. In conclusion, the present findings established that CLA is an independent and important prognostic factor in patients with NK-cell lymphomas.
Adolescent↗
Induction and characterization of cutaneous lymphocyte antigen on natural killer cells.
Cutaneous lymphocyte antigen (CLA) has been reported to be expressed mainly by memory/effector T lymphocytes infiltrating inflammatory skin lesions and cutaneous T-cell lymphoma. It has been suggested that CLA is a specific homing receptor, facilitating the T-cell migration into skin lesions, and also an indicator of the skin-homing T-cell subset. In the present study, we investigated the expression of CLA in natural killer (NK) cells defined phenotypically as surface CD3- and CD56+ cells in peripheral blood. CLA was definitely expressed on CD3-CD56+ cells at a level comparable to CD3+ cells in peripheral blood of normal Japanese volunteers. After in vitro stimulation of peripheral blood mononuclear cells with interleukin 2 (IL-2) and IL-12, there was a significant increase in the number and percentage of CLA+ NK cells but not CLA+ T cells (P < 0.01). To analyse the characteristics of CLA expressed by NK cells, we investigated a CLA+ NK-leukaemia cell line, NK-YS, established from a patient with NK leukaemia/lymphoma with skin infiltration. In the in vitro study, the CLA-expressing NK-leukaemic cell line bound to E-selectin-transfected cells and was inhibited by HECA 452 antibody or neuraminidase treatment of leukaemic cells. These findings suggest that CLA expressed by NK cells is a homing receptor for the E-selectin molecule and may explain skin infiltration by NK cells and NK lymphoma cells analogous to T cells. An NK-cell subset expressing CLA must play an important role in host defence against microorganisms and neoplasms in skin lesions.
Antigens, CD↗
Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells.
All-trans retinoic acid (ATRA) has been shown to induce differentiation of human acute promyelocytic leukaemia (APL) cells and eventual elimination of the malignant clone. Matrix metalloproteinase-9 (MMP-9) is produced by neutrophils and its expression appears to be linked with myeloid cell differentiation. We investigated effects of ATRA on MMP expression in two human myeloid leukaemia cell lines, PL-21 and NB4. Both cells could differentiate into neutrophils after exposure to ATRA. Both the activity and antigen levels of MMP-9 were much higher in NB4 cells than in PL-21 cells. Stimulation with ATRA significantly increased MMP-9 levels approximately three- to fivefold in both PL-21 and NB4-conditioned media. MMP-9 mRNA levels increased in ATRA-treated cells and was almost in parallel with the increase in MMP-9 activity, suggesting that ATRA induced MMP-9 by activating its gene expression. ATRA can induce interleukin 8 (IL-8) in APL cells. IL-8, chemokine for neutrophils and a potent inducer of MMP-9, was also induced by ATRA in PL-21 cells. However, recombinant IL-8 did not induce MMP-9 expression. In addition, a neutralizing antibody against IL-8 did not inhibit ATRA-induced MMP-9 expression in either cell type. These observations suggest that ATRA can induce both MMP-9 and IL-8, but IL-8 is not involved in ATRA-induced MMP-9 expression. As MMP-9 can truncate and activate IL-8, simultaneous induction of MMP-9 and IL-8 by ATRA could activate leucocytes excessively, causing the hyper-inflammatory events in retinoic acid syndrome.
Antineoplastic Agents↗
Multilineage involvement in hypereosinophilic syndrome terminating in granulocytic sarcoma and leukaemic transformation with trisomy 8.
We report a patient with hypereosinophilic syndrome (HES), which, 8 years later, transformed into granulocytic sarcoma in the brain and, subsequently, into acute myelocytic leukaemia. Repeated chromosome analyses showed a normal karyotype, until the time of leukaemic transformation when trisomy 8 was confirmed in cells from the bone marrow and cerebrospinal fluid. The combined techniques of May-Grunwald-Giemsa staining and fluorescence in situ hybridization identified trisomy 8 not only in blasts and eosinophils but also in neutrophils and erythroblasts. Our observation suggests that HES is a multilineage myeloproliferative disorder involving precursors of at least the eosinophil, neutrophil and erythroid lineages.
Acute Disease↗
Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization.
BACKGROUND: Enumeration of CD34+ cells in peripheral blood (PB) before apheresis predicts the number of CD34+ cells collected, although flow cytometric techniques used are complex and expensive. In an attempt to determine the optimal timing for peripheral blood progenitor cell (PBPC) collection, the usefulness of circulating immature cell (CIC) counts in PB was evaluated. STUDY DESIGN AND METHODS: CIC counts in PB and CD34+ cell counts in the apheresis product from 249 collections were assessed, and the relationship between these two parameters was evaluated by with the Pearson rank correlation analysis, the Fisher exact test, and the U-test. RESULTS: CIC counts were correlated significantly with the number of CD34+ cells per kg of patient's body weight in the apheresis product (Pearson rank correlation analysis: r = 0.635, p < 0.0001). When a level of 1 x 10(9) CICs per L was selected as a cutoff value, the sensitivity and specificity for collecting more than 1 x 10(6) CD34+ cells per kg of body weight were 75.7 and 85.5 percent, respectively. CONCLUSION: The present study strongly suggests that the number of CICs in PB may estimate the number of CD34+ cells collected. The data indicate that CIC counts above 1 x 10(9) per L can be used as a good predictor for PBPC collections containing more than 1 x 10(6) CD34+ cells per kg of body weight in a single apheresis procedure.
Adolescent↗