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Liquid crystal display (LCD) monitors show a homogenous quadratic pattern in the number of pixels, size, and dimensions. However, their modulation transfer function (MTF) has a non-isotropic effect in the vertical, horizontal, and diagonal directions on the screen from the shape and pattern of arrangement of pixels. Moreover, the MTF of the human eye differs in spatial frequency response directivity among individuals. In this study, the high-brightness LCD monitor detectability was physically simulated and visually examined throughout the system, including the imaging system. Furthermore, the influence of anisotropy of the LCD monitor was evaluated. The MTF of the LCD monitor was measured by acquiring a bar pattern using a digital camera with sufficiently small pixels in the vertical, horizontal, and diagonal directions and by performing interpolation processing through waveform reproduction and frequency analysis. The detectability of the LCD monitor was verified throughout the system, including the imaging system. Radiographs of the rectangular wave chart (0.5-10 LP/mm) were obtained in the vertical, horizontal, and diagonal (45°) directions to assess the perceivable limit of the human eye (LP/mm). The spatial resolution of the LCD monitor in the diagonal direction was higher than that in the vertical or horizontal direction, which was in good agreement with the results of the profile analysis and visual evaluation.

Purpose: To evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for renal angiomyolipoma (AML) using a micro-balloon catheter and a mixture of ethanol and lipiodol., Materials and Methods: Twelve consecutive patients with 15 AMLs, 9 females and 3 males, with a median age of 44 years (range, 11-81), underwent this procedure between 2011 and 2016. In all procedures, a micro-balloon catheter was advanced to the feeding artery of the AML and TAE was performed with a mixture of ethanol and lipiodol under balloon inflation. We reviewed medical records and images, and evaluated the technical success rate, clinical success rate, and complications. Technical success was defined as completion of TAE using the micro-balloon catheter and the mixture of ethanol and lipiodol. Clinical success was defined as reduction of tumor size on CT, which was performed before and after TAE., Results: In 14 of 15 AMLs, the micro-balloon catheter could be advanced to the feeding artery, and TAE was performed successfully. Thus, the technical success rate was 93%. Among these 14 AMLs of 11 patients, 13 AMLs of 10 patients could be followed and tumor shrinkage was confirmed in all. Thus, the clinical success rate was 100%. Four patients had mild symptoms after TAE; the minor complication rate was 33% (4/12), and the major complication rate was 0%., Conclusion: TAE for renal AML using the micro-balloon catheter and mixture of ethanol and lipiodol appears to be effective and safe.

Cyanobacteria are photosynthetic prokaryotes that perform oxygenic photosynthesis by extracting electrons from water, with the generation of oxygen as a byproduct. Cyanobacteria use oxygen not only for respiration to produce energy in the dark but also for biosynthesis of various metabolites, such as heme and chlorophyll. Oxygen levels dynamically fluctuate in the field environments, from hyperoxic at daytime to almost anaerobic at night. Thus, adaptation to anaerobiosis should be important for cyanobacteria to survive in low-oxygen and anaerobic environments. However, little is known about the molecular mechanisms of cyanobacterial anaerobiosis because cyanobacteria have been regarded as aerobic organisms. As a first step to elucidate cyanobacterial adaptation mechanisms to low-oxygen environments, we isolated five mutants, T-1-T-5, exhibiting growth defects under microoxic conditions. The mutants were obtained from a transposon-tagged mutant library of the cyanobacterium Synechocystis sp. PCC 6803, which was produced by in vitro transposon tagging of cyanobacterial genomic DNA. Southern blot analysis indicated that a kanamycin resistance gene was inserted in the genome as a single copy. We identified the chromosomal transposon-tagged locus in T-5. Two open reading frames (sll0577 and sll0578) were partially deleted by the insertion of the kanamycin resistance gene in T-5. A reverse transcription polymerase chain reaction suggested that these co-transcribed genes are constitutively expressed under both aerobic and microoxic conditions. Then, we isolated two mutants in which one of the two genes was individually disrupted. Only the mutants partially lacking an intact sll0578 gene showed growth defects under microoxic conditions, whereas it grew normally under aerobic conditions. sll0578 is annotated as purK encoding N 5 -carboxy-aminoimidazole ribonucleotide synthetase involved in purine metabolism. This result implies the unexpected physiological importance of PurK under low-oxygen environments.

Purpose: The aim of this study was to evaluate the technical and clinical efficacy and safety of CT-guided hookwire marking before video-assisted thoracoscopic surgery (VATS) for small pulmonary lesions., Materials and Methods: This procedure was performed on 161 lesions in 154 patients (75 men and 79 women; median age, 62 years; age range 23-89 years). Medical records and images were reviewed, and the technical success rate, surgical success rate and complications were evaluated. Technical success was defined as successful hookwire marking at the target site without marker dropping before VATS. Surgical success was defined as negative surgical margins on pathological examination after VATS., Results: There were 97 nodules and 64 ground-glass opacities, and their mean size was 9.8 mm (range 2-34). The technical success rate was 97.5% (157/161). In three of the four failed cases, another hookwire marker was placed, and in the remaining case, VATS was performed without a marker. The surgical success rate was 98.1% (158/161). In the three failed cases, the margin was positive, so lung lobectomy was performed in one case, and the other two cases were observed carefully. Complication rates were as follows: pneumothorax, 37.9% (61/161); focal intrapulmonary haemorrhage, 34.8% (58/139); haemoptysis, 0.6% (1/161); haemothorax, 0% (0/161); air embolism, 0.6% (1/161); dissemination, 0% (0/161); and death, 0% (0/161)., Conclusion: CT-guided hookwire marking appears to be useful for VATS, but the procedure may, although rarely, cause severe complications such as air embolism., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Acquiring new genetic traits by lateral gene transfer is a bacterial strategy for environment adaptation. We previously showed that Escherichia coli could laterally transmit non-conjugative plasmids in co-cultures containing strains with and without the plasmid. In this study, using the Keio collection, a comprehensive library of E. coli knock-out mutants for non-essential genes, we screened for genes responsible for repressing cell-to-cell plasmid transfer in recipient cells. By stepwise screening, we identified 55 'transfer-up' mutants that exhibited approximately 2- to 30-fold increased activities. We confirmed plasmid acquisition by these 'up' mutants and revealed that there were no significant changes in antibiotic resistance in the original Keio strains. The presumed functions of these gene products covered a wide range of activities, including metabolism and synthesis, transport, transcription or translation and others. Two competence-gene homologues (ybaV and yhiR) were identified from among these genes. The presumed localizations of these 55 gene products were estimated to be 34 cytoplasmic proteins, 20 in or around the cell surface and 1 unknown location. Our results suggest that these 55 genes may be involved in repressing plasmid uptake during cell-to-cell plasmid transfer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Acquisition of new genetic traits by horizontal gene transfer is a bacterial strategy for adaptation to the environment. We previously showed that Escherichia coli can transmit non-conjugative plasmids laterally in a co-culture containing strains with and without the plasmid. In this study, using the Keio collection, a comprehensive library of E. coli knock-out mutants for non-essential genes, we screened for genes responsible for the execution and promotion of cell-to-cell plasmid transfer in recipient cells. By stepwise screening of 'transfer-down' mutants, two essential genes and six promoting genes were obtained. One of the essential genes was priA, which is involved in DNA replication. This priA mutant was also unable to be transformed by artificial transformation methods, probably due to the deficiency of the plasmid maintenance function. The other essential gene was rodZ (yfgA), a gene involved in the regulation of rod-shaped structure of E. coli cells. This rodZ mutant was transformable by all three methods of artificial transformation tested, suggesting that this gene is essential for cell-to-cell plasmid transfer but not for artificial transformation. These are the first data that suggest that rodZ plays an essential role in DNA acquisition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recently, we discovered a novel phenomenon, "cell-to-cell transformation" by which non-conjugative plasmids are transmitted horizontally in co-cultures of Escherichia coli F(-) strains. In this study, we aimed to identify the DNA element responsible for the high cell-to-cell transformability of pHSG299. By transplanting pHSG299 DNA fragments into pHSG399, a plasmid showing low transformability, we discovered that a specific 88 bp fragment of pHSG299 significantly promoted pHSG399 transformability. Although several short motif-like repetitive sequences (6-10 bp) were present in the 88 bp sequence, no known DNA motifs were recognized, suggesting that this 88 bp sequence (cell-to-cell transformation promoting sequence, CTPS; Accession number: AB634455) is a novel DNA element., (Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Escherichia coli is not assumed to be naturally transformable. However, several recent reports have shown that E. coli can express modest genetic competence in certain conditions that may arise in its environment. We have shown previously that spontaneous lateral transfer of non-conjugative plasmids occurs in a colony biofilm of mixed E. coli strains (a set of a donor strain harbouring a plasmid and a plasmid-free recipient strain). In this study, with high-frequency combinations of strains and a plasmid, we constructed the same lateral plasmid transfer system in liquid culture. Using this system, we demonstrated that this lateral plasmid transfer was DNase-sensitive, indicating that it is a kind of transformation in which DNase-accessible extracellular naked DNA is essential. However, this transformation did not occur with purified plasmid DNA and required a direct supply of plasmid from co-existing donor cells. Based on this feature, we have termed this transformation type as 'cell-to-cell transformation'. Analyses using medium conditioned with the high-frequency strain revealed that this strain released a certain factor(s) that promoted cell-to-cell transformation and arrested growth of the other strains. This factor is heat-labile and protease-sensitive, and its roughly estimated molecular mass was between ∼9 kDa and ∼30 kDa, indicating that it is a polypeptide factor. Interestingly, this factor was effective even when the conditioned medium was diluted 10(-5)-10(-6), suggesting that it acts like a pheromone with high bioactivity. Based on these results, we propose that cell-to-cell transformation is a novel natural transformation mechanism in E. coli that requires cell-derived DNA and is promoted by a peptide pheromone. This is the first evidence that suggests the existence of a peptide pheromone-regulated transformation mechanism in E. coli and in Gram-negative bacteria.

Currently, the immunohistochemical evaluation of cytotoxic granule-associated proteins such as TIA-1 and granzyme B can be carried out on paraffin sections. This procedure has broadened our knowledge of cytotoxic lymphoid neoplasms. Their detection is now regarded as a useful adjunctive in some characterizations of cytotoxic T- or natural killer (NK)-cell lymphoma, mostly in lymphoma of extranodal origin. We report two cases of nodal cytotoxic large T-cell lymphoma with identical biologic properties. Both cases presented with systemic lymphadenopathy, lymphomatous bone marrow involvement, and thrombocytopenia. The clinical course was fulminant, and both patients died within 1 week of presentation. The cells had a characteristic immunophenotype of CD2+, CD3+, CD4-, CD5-, CD8+, CD30 -/+, CD56-, CD57-, TCR alpha/beta+, and TCR gamma/delta-. They also expressed the cytotoxic granule-associated proteins of TIA-1 and granzyme B, and exhibited clonal rearrangements of the T-cell receptor beta chain gene. Monoclonal integration of Epstein-Barr virus was also detected. The present cases exhibited clinicopathological features that were distinct from other types of malignant lymphoma expressing cytotoxic granule-associated proteins.

We report a case of early phase Takayasu arteritis that predominantly involved the pulmonary arteries and had, along with expected radiographic findings, the unusual pattern of diffuse pulmonary parenchymal lesions on CT. We suggest that this finding may be an additional feature in early phase Takayasu arteritis and need not require investigation for an additional diagnosis.

Clinical studies of bone marrow transplantation (BMT) suggest that the immune system contributes to the eradication of acute myeloid leukemia (AML). A recent study also showed that the Fas (CD95/APO1) mediates apoptotic signal from cytotoxic T lymphocytes. Sixty-four patients with AML were studied for the expression of Fas in the context of CD34 and CD38 coexpression. The clinical relevance of Fas expression and function on AML was also investigated. Fas was expressed on 2% to 98% of AML cells (2% to 20% in 11 patients, 20% to 50% in 20 patients, 50% to 80% in 24 patients, and 80% to 98% in nine patients). Only 44.4% of patients with AML M1 (French-American-British [FAB] classification) were Fas+ (>/=20% of leukemia cells expressed Fas), whereas 89.1% of patients with AML M2, M3, M4, M5 were Fas+ (P < .01). Among 43 CD34+ patients (>/=20% leukemia cells were CD34+), 34 were Fas+, and 19 of 21 CD34- patients were Fas+ (P = NS). Thirteen cases were studied for their expression of Fas in the context of CD34 and CD38 using three-color analysis. Fas is expressed at a high level in the gated CD34+CD38+/- and CD34+CD38+ population. In 10 AML samples, Fas was expressed at a higher level in CD34+/CD38+ population than in CD34+/CD38+/- or CD34- cell populations. Fas-induced apoptosis by anti-Fas monoclonal antibody (MoAb) was determined by morphologic features and colorimetric DNA fragmentation assay. Induction of apoptosis was found in 14 of 24 cases. However, no statistically significant correlation was observed between Fas expression and induction of apoptosis. Leukemia colony-forming unit assays suggested that in some cases, Fas-induced apoptosis occurred in the clonogenic cell populations. Parameters such as laboratory and clinical data at initial diagnosis were correlated with Fas expression and only response to initial induction chemotherapy showed significant correlation with Fas expression (P < .05). We conclude that the majority of AML cells exhibit variable expression of Fas, and apoptosis could be induced by anti-Fas MoAb in some cases. Our results suggest the Fas-mediated apoptosis may be clinically relevant, whereas the issue of clonogenic leukemia cells and Fas expression needs further studies.

We present a case of severe rhabdomyolysis developing after peripheral blood stem cell transplantation (PBSCT) in a 17-year-old woman with Ki-1 lymphoma. Severe muscle weakness, myoglobinemia and acute renal failure developed on day 23 following PBSCT associated with painful peripheral neuropathy. Cytomegalovirus infection may have been a contributory factor.

The Tokai Bone Marrow Bank was established in 1989 and coordinated 1,415 patients with 3,000 HLA-A, B-typed donors. Of the 1,415 patients, 757 patients had HLA-A, B-identical donors, 206 patients had HLA-DR-identical donors, and 80 patients had MLC-compatible donors. Finally, 55 unrelated donor bone marrow transplantations were done. The most frequent reason of interruption in coordination was disagreement of donor's family. We sent several questions by mail around 1 month after the donation to 55 donors to analyze the psychological reactions of unrelated bone marrow donors to donation. Donors were generally quite positive about the donation. 92% of the donors felt it was worthwhile and no one felt it was not at all worthwhile. 73% of the donors would be willing to donate again in the future. 79% of donors would like to know the clinical course of the patient after the bone marrow transplantation. We hope that these results may be helpful in the development of the Japan Marrow Donor Program.

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.

Seventeen patients with refractory or relapsed, intermediate or high grade non-Hodgkin's lymphoma (NHL) were treated with the combination of dexamethasone (40 mg/body x 3d, iv) (DeVIC) between January and December 1992. The treatments were repeated every three weeks for a minimum of two courses unless the patient had PD. G-CSF (2 micrograms/kg, sc) was given during leukopenia in most cases. Of 16 evaluable patients 6 (38%) achieved a complete remission (CR) and 4 showed a partial remission. With median follow up of 15 (7-26) months (mos.) all CR patients were alive in CR, except for 1 patient who died of secondary AML. The actuarial 50% survival duration after DeVIC was 15+ mos. One patient died of sepsis but myelosuppression was generally moderate and no other serious toxicity was observed. Although this is a preliminary study, DeVIC regimen seems to be an effective salvage therapy for patients with refractory or relapsed NHL with acceptable toxicity.

We performed cytogenetic studies in a patient with treatment-related acute leukemia (t-AL) to identify the associated chromosomal changes. Metaphase analysis revealed a t(3;21)(q26;q22) translocation. Acute promyelocytic leukemia (APL) had been diagnosed 4 years earlier and the patient had received intensive induction chemotherapy and sequential post-induction therapy that included agents that targeted DNA-topoisomerase II (topo II). This case suggests an association between previous therapy with topo II inhibitors and development of t-AL associated with a balanced aberration involving the 3q26 and 21q22 bands.

Alternating non-cross-resistant chemotherapy has been induced for the treatment of non-Hodgkin's lymphoma (NHL) with the aim of cure, even in advanced cases. We formulated a new high dose regimen, CAMBO-VIP, which was a weekly treatment. They were administered during alternate weeks for a total period of 12 weeks. We obtained high response rate and prolonged disease-free survival with this regimen. We noticed the elevation of serum LDH level in some patients at or shortly after the completion of CAMBO-VIP treatment. LDH elevation was not associated with liver function abnormality in terms of elevation of GOT or total bilirubin. All of these patients were in complete or partial response with no evidence of tumor progression. An LDH isozyme study which was done at the time of LDH elevation showed elevation of both LDH1 and LDH2. Interestingly serum haptoglobin was undetectable in all 6 patients measured at the time of LDH elevation. Reticulocytosis and leukoerythroblastosis in peripheral blood were also observed in all of these patients. These abnormalities including LDH elevation returned to normal within a rather short period, usually within 1 to 3 weeks. From these observations, it is most likely that these abnormalities were due to excessive blood cell destruction, which was observed in association with rapid recovery from myelosuppression.

Twenty-two patients with advanced diffuse large cell lymphoma (LSG classification) were treated with the combination chemotherapy of cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide and prednisolone (CAMBO-VIP) from Oct. 1987 to Sept. 1989. Eighteen (90%) of 20 evaluable patients achieved complete remission and 2 patients had partial remission. With a median follow-up of 52 mos, 3 patients relapsed (17%), and 2 patients died. The actuarial overall survival and relapse-free survival at 4 years were estimated to be 90% and 83%, respectively. Myelosuppression was severe, but transient. No serious infection was seen, and no platelet transfusion was required. Oral mucositis and liver damage (Grade 3 in WHO grading) was seen in one patient each, but no treatment-related fatalities were observed. CAMBO-VIP is a well tolerated, effective treatment regimen for advanced diffuse large cell lymphoma.

Thirty-nine patients with non-Hodgkin's lymphoma were treated with weekly alternating non-cross-resistant chemotherapy (CAMBO-VIP). We obtained a high response rate, and prolonged disease-free survival with side effects and complications of various severity were observed. Three patients were withdrawn from the study due to aggravation of liver cirrhosis, cerebral infarction, and poor tolerance. Thirty-six patients completed this 12-week intensive chemotherapy. The median treatment delay in all patients was 3 days (-4 to 29 days), and a delay of over 15 days was seen in 5 patients. The nadir of the neutrophil count was 0 to 2,100/microliters (median 140/microliters), and 15 patients were below 100/microliters. Two patients had pneumonia and 4 had herpes zoster infection. The platelet count nadir was 20,000 to 240,000/microliters (median 90,000/microliters). Ten patients were below 50,000/microliters, but none required platelet transfusion. Red cell transfusion was given in 6 patients. Elevation of transaminases was seen in 25 patients, but it was not serious except for a patient with liver cirrhosis. The elevation of serum LDH level and decrease of serum haptoglobin level seen shortly after completion of treatment seemed due to the increased blood cell destruction. Stomatitis was observed in 32 patients, 17 of whom showed more than grade 3 toxicity. Blister formation on palms and/or soles was noted in 6 patients. There was no treatment-related death observed.

Autologous BMT (auto-BMT) has been conducted for 17 high-risk common ALL antigen (CALLA)-positive non-T cell type ALL patients. Ex vivo purging of leukemia cells from infused BM cells was performed using complement and three kinds of mouse monoclonal antibodies reactive to CALLA-positive leukemia cells: NL-1 (IgG2a), NL-22 (IgM), and HL-47 (IgM). Minimal residual leukemia cells in BM were examined by PCR method in Philadelphia chromosome (Ph1)-positive ALL cases. BCR/ABL chimeric transcript, which was positive in BM samples before purging, was shown to be absent after ex vivo purging in all three cases tested. Among four Ph1-positive cases transplanted in first CR, three cases survived in CR remission 77, 29 and 26 months after BMT, and one case died without relapse 4 months after BMT. The other four Ph1-negative cases transplanted in the first CR also remained in CR except one who relapsed. The results of minimal residual leukemia cell studies and clinical data indicate the effectiveness of our ex vivo leukemia cell purging method and auto-BMT in the early stage of CR for patients with high risk ALL.

We analyzed immunoglobulin (Ig) gene rearrangements in 69 patients with B-cell malignancies by Southern hybridization. We used 5 probes which covered JH 5'S mu and S gamma 3 loci of the Ig heavy (IgH) chain gene, and C kappa and kappa de loci of the Ig light (IgL) chain kappa gene, respectively. DNA rearrangements were observed in 68 out of the 69 patients using the JH probe. In 97% (33/34) of patients with non-Hodgkin's lymphoma (NHL), 100% (5/5) of chronic lymphocytic leukemia (CLL), 42% (10/24) of non-T cell acute lymphoblastic leukemia (non-T ALL), and in 0% (0/4) of chronic myelogenous leukemia lymphoid crisis (CML-LBC), the rearrangements were detected by C kappa and/or kappa de probes. Furthermore, the genotype of the light chain was defined by rearrangement patterns of these 2 probes. The by using the 5'S mu-probe, class switch recombinations were detected in 76% (25/33) of NHL, 20% (1/5) of CLL, 17% (4/24) of non-T ALL, and in 0% (0/4) of CML-LBC. Among them, 1 case of IgM NHL and 3 cases of double bearer NHL had rearranged on both IgH alleles by the constant region. The results of this study indicate that genotypes correspond well to phenotypes of B-cell malignancies and that the determination of genotype will be useful for making an exact diagnosis of B-cell malignancies.

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.

A 40-year-old female was admitted in August 1989 with a diagnosis of acute promyelocytic leukemia (AML; M3). One course of modified-DCMP regimen induced complete remission in September, but she developed spiking fever at a nadir period of WBC after induction chemotherapy. CT revealed multiple hepato-splenic abscesses presumably due to candida infection. She was treated with intravenous administration of amphotericin B (AMPH-B) and other antifungal agents. Despite the hematological remission and prolonged use of these antifungal agents, high fever persisted. A catheter was inserted into the portal vein under ultrasonic-guidance. AMPH-B was administered through the catheter: the initial dose was 3 mg/day and was soon increased to 20 mg/day. Her fever subsided in 1 week, and the sizes of liver abscesses on CT reduced markedly. Chill and hypokalemia were observed during this therapy. The catheter was removed from the portal vein after 29 days. Partial portal vein thrombosis was noted around the catheter tip. This case suggests the usefulness of intraportal administration of AMPH-B in patients with hematological malignancy developing multiple liver abscesses.

We designed a post-induction therapy including intensive sequential therapy with non-cross-resistant drugs in an effort to prolong disease-free survival (DFS) for adults with acute myelogenous leukemia. Forty-five patients entered this study and 33 of 35 patients entering complete remission received the post-induction therapy. With a median follow-up for survivors of 3.5 years from complete remission, the actuarial 5-year DFS was 46% +/- 19% (95% confidence interval). The five-year DFS for patients over 45 years of age was comparable to that for patients under 45 years of age (50% +/- 26% vs 47% +/- 28%). Furthermore, the actuarial 5-year DFS for patients who required two courses of induction therapy was comparable to that for patients who required only one course of induction therapy (45% +/- 29% vs 50% +/- 25%). The toxicity of post-induction therapy was tolerable and no patients died during complete remission.

We analysed immunoglobulin (Ig) gene rearrangements in 28 patients with multiple myeloma by Southern hybridization method. We used 5 probes which cover C kappa and kappa de loci of Ig light chain kappa gene, and JH, 5'S mu and S gamma 3 loci of Ig heavy chain gene. In 11 out of 12 patients with kappa-producing myeloma, DNA rearrangements were observed using C kappa probe. Among them, kappa de region was rearranged in 7 patients and kept germline configuration in 4 patients. In all of 14 patients with lambda-producing myeloma, C kappa region was deleted and kappa de region was rearranged. 5'S mu-probe was very useful for detecting class switch recombination, and furthermore by using S gamma-probe together, S mu-S gamma joining could be detected. In all of 10 patients with gamma-producing myeloma, 5'S mu and S gamma-probes detected the rearranged band of the same size on at least 1 allele, which suggested the presence of S mu-S gamma joinings. In 8 of 10 patients with Bence-Jones myeloma, 5'S mu-probe detected rearranged bands and the presence of class switch recombinations were suggested as observed in other Ig secretory myelomas. In other 2 patients with Bence-Jones myeloma, non-functional class switch recombinations were detected. The results of this study indicated that genotypes corresponded well to phenotypes in multiple myeloma, and further analysis in other types of B cell malignancies will be interesting.

The mixed lymphocyte-autologous tumor cell reaction (MLTR) was performed in 15 patients with hematological malignancies. Lymphocyte proliferative response and generation of cytotoxic cells against autologous tumor cells were evaluated and as was the effect of interferon-beta (IFN-beta) (750 IU/ml). Lymphocytes from patients during complete remission had sufficient functions in mixed lymphocyte culture with normal lymphocytes. Tumor cells stimulated allogeneic lymphocytes, although to a generally lesser extent as compared with remission lymphocytes from the same patients. Increased [3H]TdR uptake was observed in 5 patients and was suppressed by the addition of IFN-beta. Autologous tumor cell kill activity was induced by MLTR in 3 patients; IFN-beta-enhanced killing activity was present in these patients as well as in 3 other patients. Tumor cells from the 3 patients with positive autologous tumor cell kill activity had almost the same stimulating capacity as lymphocytes. The expression of MHC class I antigen and IFN-beta-enhanced expression was observed in all tumor cells studied by indirect immunofluorescence. These data suggest that some factors on tumor cells, in addition to MHC class I antigen, participate in the generation of cytotoxic cells against autologous tumor cells and its enhancement by IFN-beta.

A 43-year-old patient with adult T cell leukemia (ATL) was treated with mega-dose cyclophosphamide and total body irradiation (TBI) followed by bone marrow transplantation (BMT) from his HLA-identical sibling who was not a carrier of ATL virus. After BMT, ATL cells rapidly decreased and disappeared, and the engraftment of marrow was confirmed on day 20. The patient showed normal hematologic recovery. However, he died on day 205 with interstitial pneumonitis caused by cytomegalovirus infection. Neither autopsy findings nor serologic and cytologic examinations showed any evidence of ATL relapse after BMT. This pilot study suggests that mega-dose chemotherapy and TBI followed by allogeneic BMT should be considered for such treatment of ATL.

Large granular lymphocytes (LGL) were obtained by Percoll density gradient centrifugation of peripheral mononuclear cells from 15 patients with hematological malignancies (10 acute leukemias and 5 non-Hodgkin's lymphomas). Five-hour 51Cr-release cytotoxic assay by LGL was performed against frozen autologous tumor cells in these patients. Mean percentage cytotoxicity by LGL was 5.6%, and this was enhanced to 15.0% by the addition of IFN-beta to the culture medium. A decrease of cytotoxicity was observed when LGL was treated with anti-Leu 11b antibody plus complement, or when LGL was pretreated with the unlabelled K562 as a competitive inhibition assay. The addition of monocytes also induced a decrease of cytotoxicity, suggesting that monocytes may act as a suppressive agent in autologous tumor cell killing by LGL.

IFN is known to enhance NK activity against cultured cell lines such as K562, but not against frozen autologous tumor cells. In order to obtain increased NK cytotoxicity using IFN-beta, various modifications were performed on autologous tumor cells. IFN-beta induced more enhanced NK cytotoxicity of normal lymphocytes when frozen tumor target cells were cultured for 4-5 days in the medium, or when these cells were treated with Vibrio cholerae neuraminidase (VCN). However, in an autologous setting, IFN-beta did not enhance NK cytotoxicity against either cultured autologous tumor cells or VCN-treated tumor cells. Also, IFN-beta did not enhance cytotoxic T cell activity against autologous tumor cells induced by mixed lymphocyte-tumor cell culture, although IFN-beta was able to induce enhancement of allospecific cytotoxic T cells mediated by mixed lymphocyte culture.