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A Group 3 error-free facsimile terminal for use in an analog cellular network has been developed. This facsimile terminal is provided with the International Telecommunication Union (ITU-T, formerly CCITT) T.30 recommendation protocol and an adaptive error control scheme (AECS) for Group 3 communication and error-free communication. The AECS monitors the channel conditions and selects the optimum error correction code. The ITU-T V.27ter is used as the modulation method and the transmission rate is 4800 bps. This system is compatible with the modified Huffman (MH), modified READ (MR), and modified modified READ (MMR) image data compression codes. The average communication time of this facsimile terminal is 40 s per page while moving through the analog cellular network.

The effects of teprenone (6,10,14,18-tetramethyl-5,9,13, 17-nonadecatetraen-2-one) on changes in gastric mucosal blood flow, adenosine triphosphate (ATP) content, and incidence of histologic lesions were evaluated in rat gastric mucosa after hemorrhage and retransfusion.Teprenone (100 mg/kg) was administered orally once a day for 3 consecutive days. On the 3rd day hemorrhage was induced, withdrawn blood (retransfusion) was returned, and the above variables were determined.Teprenone significantly inhibited the decreases in blood flow and index of mucosal oxygen saturation (ISO2) during hemorrhage in the corpus and antral mucosa. However, no effect of teprenone was observed on systemic blood pressure and ATP levels after hemorrhage and retransfusion. Teprenone significantly (p0.05) decreased both the incidence of ischemic lesions and the increase in the severity of lesions after retransfusion in both mucosal regions.From these results, it is concluded that the protective effect of teprenone on blood flow was partly responsible for its inhibitory effect on the incidence of lesions in the rat stomach in this hypovolemic shock model, although the former effect might be not a direct effect on systemic vascular tone.

The relationship of gastric mucosal hemodynamics, energy metabolism, and acid to antral histological lesion incidence following hemorrhage and retransfusion was investigated in rats. Decrease of mucosal blood flow and of the index of mucosal oxygen saturation (ISO2) during hemorrhage were slightly greater in the corpus than in the antrum. ATP content and redox ratio in the corpus were decreased by shock; however, these hardly changed in the antrum. The index of tissue hemoglobin concentration (IHb) recovered to above the prehemorrhage value only in the antrum after retransfusion. Histological lesion incidence in the antral mucosa was more markedly increased by acid instillation and/or retransfusion than in the corpus. From these results, it was concluded that the decrease of blood flow is related as an underlying factor to induction of ischemic damage in the antral mucosa and that intraluminal acid and/or postischemic hyperemia play a causative role in the development of histologic lesions in the antral mucosa during shock and retransfusion in the rat stomach.

The application of antioncogene ribozyme in the gene therapy of breast cancer by means of recombinant adenoviral vector is dicussed in this chapter. We have shown that recombinant adenovirus encoding anti-cerbB2 ribozyme inhibited the breast cancer cell growth in vivo efficiently (1,2). We will talk about the detailed protocol here.

We have developed a new 40 GHz digital radio equipment which uses single Impatt diode oscillator functioning as transmitting local oscillator, transmitting frequency converter and receiving local oscillator simultaneously. This radio equipment is so designed compact that it ensures excellent cost-performance for local trunking.

Overexpression of NF-kappa B reportedly plays anti-apoptotic roles in the growth of AML cells. Control of AML cell growth was attempted using a replication-defective herpes simplex virus-1 vector, T0I kappa B alpha, overexpressing mutant I kappa B alpha to inhibit NF-kappa B in vitro. T0I kappa B alpha displays defective ICP4/ICP22/ICP27, isogenic thymidine kinase, and mutant I kappa B alpha. T0Z.1 expressing lacZ instead of I kappa B was used for controls. Infection of T0I kappa B alpha at 15 multiplicity of infection (MOI) with cells of AML lines, HL60, K562, and NB4 displaying90% infection efficiency and tumor killing in vitro. Use of 10 microM of Ara-C alone was clinically equivalent to high-dose Ara-C, displaying 11% tumor killing. Neither ganciclovir (GCV) nor Ara-C enhanced T0I kappa B- alpha mediated tumor killing. Attenuation of NF-kappa B by T0I kappa B alpha was confirmed by EMSA. T0I kappa B alpha induced caspase-3 activity, with subsequent apoptosis confirmed by colorimetric and TUNEL assays. Fresh AML cells from 8 patients were infected with T0I kappa B alpha at 3 MOI, with or without GCV or 10 microM of Ara-C in vitro. Infection efficiency was 10%. T0I kappa B alpha displayed 8-15% tumor killing, superior to Ara-C in 6 of the 8 patients. Administration of Ara-C enhanced tumor killing in 5 of these 6 cases. Our results suggest that T0I kappa B alpha-mediated gene therapy induces apoptosis of AML cells in vitro.

Requirements on instrumentation for automotive navigation systems are discussed, and liquid crystal display (LCD) equipment developed for this purpose is described. A direct multiplexed full-color LCD having 320*200 trio dots was developed and applied to a graphic display unit. Through the use of the newly developed COG (chip-on-glass) technology, a small and thin display module was realized. A route guidance indicator was developed using a segment-type LDC and a monochromatic dot-matrix LCD, and it was applied to an actual automotive navigation system. This indicator displays such information as the form and name of crossings as a car approaches it. Not only can it show the extracted principle information, but it can also be mounted at a place near the driver's regular eye position. For these reasons, this indicator is useful for improving the information cognitivity of navigation systems. >

A Group 3 error-free facsimile terminal developed for use in the cellular radio network is described. The terminal uses a CCITT V.27ter modem with eight-phase differential phase-shift keying (DPSK) modulation and an adaptive error control scheme developed for mobile telephone communication. An image data compression uses modified modified READ (MMR). The data transmission speed is 4800 b/s. The terminal can transmit a letter-size document (of the CCITT No. 1 chart) in 25 s. >

The commercial 4" GCT (gate commutated turn-off) thyristors, FGC4000BX-90DS, were typically destroyed just at the critical power density, J/sub A//spl middot/V/sub AK/=3/spl times/10/sup 5/ W/cm/sup 2/, in snubberless turn-off at V/sub D/=2250 V, 125/spl deg/C. We propose a primitive model which resembles the load-shorted operation of a p-n-p transistor. Our model explains that critical J/sub A//spl middot/V/sub AK/ value very well. Taking account of detailed experimental data, we consider that current 4" GCT thyristors operate uniformly and already realize the theoretical turn-off endurance limit. We also propose that an IGBT's limit (reverse bias SOA) would be compatible with 3/spl times/10/sup 5/ W/cm/sup 2/.

Excluding chronic myelomonocytic leukemia, a total of 92 consecutive patients with myelodysplastic syndrome showing less than 20% blasts in the bone marrow were analyzed. We evaluated the clinical significance of the WHO and MDS 2000 classifications by reviewing each MDS patient according to the classification. The WHO criteria classified the MDS patients into 36 with RA, 22 with RCMD and 33 with RAEB, whereas according to the MDS 2000 criteria there were 19 RAEB-I patients and 15 RAEB-II patients. Based on the WHO classification, the RCMD patients had higher platelet counts and percentages of blasts among BM cells than the RA patients (P = 0.0018, P = 0.0001). Twenty percent of the RA patients, 44.8% of the RCMD patients, and 70.8% of the RAEB patients had cytogenetic abnormalities. Among them, the poor karyotype was present in 6.7% of the RA patients, 21.0% of the RCMD patients and 41.6% of the RAEB patients. The rate of acute leukemia death was 14.3% in the RA patients, 67.7% in the RAEB patients and 50.0% in the RCMD patients. Analysis of survival times revealed significant differences between RA and RCMD patients (P = 0.0482). The clinical features of RCMD patients were intermediate between those of RAEB and RA patients. There was no difference between the clinical features of the RAEB-I and RAEB-II patients in the MDS 2000 classification.

A 41-year-old man visited his doctor in May 2000 because of a sore throat and high fever. His symptoms did not improve, despite administration of antibiotics and nonsteroidal anti-inflammatory drugs. Since a chest X-ray examination revealed an anterior mediastinal bulky tumor, he was referred and admitted to our hospital on June 21, 2000. The peripheral white blood cell count was 44,540/microliter with 74% myeloblasts. Bone marrow aspiration revealed a hypercellular marrow with 82% myeloblasts, which were negative for peroxidase and alpha-naphthyl butylate esterase staining. Blast cells were positive for CD7, CD13, CD33, CD34, and HLA-DR, and negative for CD56. A needle biopsy specimen of the mediastinal tumor consisted of myeloblasts. We diagnosed the patient as having CD7 (+) acute myeloid leukemia (AML) (M0) with a bulky mediastinal mass based on the surface marker analysis, although the clinical features resembled myeloid/NK precursor acute leukemia. The patient achieved a complete remission after two courses of induction therapy. We are planning an allogeneic stem cell transplantation during his first remission because of the high risk of relapse.

Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 103 subjects were evaluated, and the all over efficacy rate was 69.9%. Acute leukemia was found in the largest number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of myelodysplastic syndrome. By type of infection, patients having unknown origin were the largest in number, being 66, and the efficacy rate was 71.2%. The efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9% (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates by neutrophil counts before administration of CZOP and AMK and at 1 week after administration were both 53.3% in the group of less than 100/microliter, both 60% in the group of less than 500/microliter. The efficacy rate by neutrophil counts at 1 week after administration was 58.6% in the group of less than 100/microliter. The efficacy rate was 75.4% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of non-concomitant usage group. The efficacy rates by serum albumin levels before administration of CZOP and AMK and at 1 week after administration were both 92.9% in the group of over than 4 g/dl, both 50% in the group of less than 3 g/dl. Concomitant treatment with CZOP and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases.

We evaluated efficacy and safety of monotherapy with CZOP (1-2 g x 2/day) and combination therapy with CZOP (1-2 g x 2/day) and AMK (200 mg x 2/day) for infections in patients with hematological diseases. Efficacy was evaluated in 71 patients of monotherapy group and 70 patients of combination therapy group. Underlying diseases were mostly leukemia and lymphoma. Infections included sepsis, suspected sepsis, pneumonia and so on. Efficacy in CZOP monotherapy was excellent in 21 patients (31.3%), good in 23 patients (34.3%), fair in 5 patients (7.5%) and the efficacy rate was 65.7%. On the other hand, in combination therapy, each was 14 patients (21.2%), 23 patients (34.8%), 12 patients (18.2%) and the efficacy rate was 56.1%. Side effects such as eruption were noted in 2 patients. Abnormal laboratory findings were noted in 9 patients. All side effects as well as abnormal laboratory findings were minimal. It was concluded that CZOP monotherapy was effective in the treatment of various infections accompanying hematological diseases.

We identified a novel human long fatty acyl CoA synthetase 2 gene, ACS2, as a new ETV6 fusion partner gene in a recurrent t(5;12)(q31;p13) translocation in a patient with refractory anemia with excess blasts (RAEB) with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). ACS2 is expressed in the brain and bone marrow and is highly conserved in man and rats. The resulting ETV6/ACS2 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL case, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the AML case, and a short in-frame fusion of ETV6 exon 1 to the 3' untranslated region of ACS2 in the RAEB case. Reciprocal ACS2/ETV6 transcripts were identified in two of the cases. Fluorescence in situ hybridization (FISH) analysis with ETV6 cosmids on 12p13, and BACs and P1s on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5' portion of the ACS2 gene, and that the 5q31, breakpoint of the RAEB case involved the 3' portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the RAEB case led to a fusion protein. Disruption of the second ETV6 allele by t(12;19) was detected in the AML case by FISH analysis. These observations suggest that the disruption of ETV6 and/or ACS2 may lead to the pathogenesis of hematologic malignancies with t(5;12)(q31;p13).

The Wilms tumor gene (WT1) has been reported to be a prognostic factor and a marker for the detection of minimal residual disease (MRD) in acute leukemia. Using competitive polymerase chain reaction procedures, we examined the expression of the WT1 gene in acute leukemia patients with several tumor-specific DNA markers, including bcr/abl, PML/RAR alpha, and AML1/MTG8. A strong correlation was observed between the levels of WT1 and PML/RAR alpha expression. However, AML1/MTG8 transcripts were detected at all stages of the disease even when the expression level of WT1 gene was low. From these findings, we concluded that monitoring the WT1 expression level is a useful means of determining the effectiveness of chemotherapy, and that WT1 is an effective marker for the detection of MRD, especially in acute myeloid leukemia patients with AML1/MTG8.

A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical examination revealed marked hepatosplenomegaly. A peripheral blood examination disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb, and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal immunoglobulin of type lambda. Bone marrow specimens demonstrated marked granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP-16 with no improvement, and died of pneumonia and sepsis in June 1995. This case was considered to be consistent with atypical CML (aCML) according to the FAB classification because monocytosis was not observed. It seems likely and interesting that the coexistent monoclonal gammopathy and aCML might have arisen from common abnormal hematopoietic stem cells.

A 19-year-old male patient with virus associated hemophagocytic syndrome (VAHS) began receiving chemotherapy including etoposide (cumulative dose of 900 mg/m2 intravenously) and Ara-C (cumulative dose of 360 mg/m2 intravenously) in July 1994. He achieved complete remission, but developed acute myelomonocytic leukemia (AML, FAB M4) with t(9;11)(p22;q23) in March 1997 and a rearrangement of the MLL gene was also recognized. The MLL gene rearrangement is closely associated with secondary leukemia with an 11q23 translocation. It is highly likely that this case of AML was caused by the cytostatic treatment the patient received, including etoposide for VAHS.

A 77-year-old woman with complaints of fever and systemic lymphadenopathy was admitted to our hospital on February 16, 1995. Serum IgM was elevated to 2,097 mg/dl. Lymph node biopsy showed diffuse infiltration with lymphoplasmacytoid cells. Thus, she was diagnosed as having Waldenström's macroglobulinemia. Considering her age and congestive heart failure, she was treated with oral administration of low-dose etoposide (25 mg/day). Splenomegaly and superficial lymphadenopathy disappeared after one course of therapy. Until her death due to pneumonia, complete remission continued for one year without any symptoms and adverse effects except for mild diarrhea. Low-dose etoposide therapy was considered to be well tolerated and useful for elderly patients with Waldenström's macroglobulinemia.

Cefpirome (CPR) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 100 subjects were evaluated, and the allover efficacy rate was 72.0%. Acute leukemia was found in the largest number of patient, 55, followed by 12 cases of malignant lymphoma and 6 cases of chronic myelogenous leukemia. By type of infection, patients having suspected sepsis were the largest in number, being 50, and the efficacy rate was 68.0%. The efficacy rates for sepsis and pneumonia were 57.1% (7 cases) and 61.1% (18 cases), respectively. The efficacy rates by neutrophil counts before administration of CPR and AMK and at 7 days after administration were both 71.9% in the group of less than 500/microliter, both 60.0% in the group of less than 100/microliter. The efficacy rate was 75.0% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 70.0% in the non-concomitant usage group. Concomitant treatment with CPR and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases and high.

A 56-year-old man was admitted to our hospital in September, 1996. Chromosomal translocation (15; 17) and a PT-PCR study for PML-RAR alpha mRNA were positive in bone marrow aspirates, and acute promyelocytic leukemia was diagnosed. After CR was obtained with all-trans retinoic acid (ATRA) followed up with chemotherapy, the RT-PCR became negative. When he was readmitted in April, 1997, skin eruption on his chest and extremities were observed. Specimens taken for biopsy revealed leukemia cutis, and RT-PCR became positive in the same specimen. Bone marrow PT-PCR was also positive without abnormal promyelocytes. Although he was treated with oral ATRA 80 mg/day again, no significant improvement in leukemia cutis was noted. After combined therapy with Ara-C and acularubicin, skin eruption disappeared and bone marrow RT-PCR became negative. A second CR was then obtained. Although it is unknown whether the administration of ATRA is related to extramedullary relapse or not, we recommend combined chemotherapy for such cases.

We evaluated the effects of various hematopoietic growth factors (HGFs) on the prevention of apoptosis in blasts from 19 patients with acute myeloblastic leukemia (AML) by assessing DNA ladder formation. After incubation without HGF, apoptosis was noted in all but two patients. HGFs prevented, did not affect, or enhanced apoptosis in 39 (60%), 14 (22%), or 12 (18%) of 65 suspension cultures, respectively. HGFs that prevented apoptosis also stimulated and/or synergized blast colony formation in 35 of 39 corresponding methylcellulose cultures. HGFs that alone stimulated colony formation also prevented apoptosis in all but two of 28 corresponding suspension cultures. In contrast, HGFs that did not prevent apoptosis also failed to stimulate growth in 17 of 26 corresponding methylcellulose cultures. HGFs that enhanced apoptosis alone never stimulated colony formation. After incubation, we noted enhanced c-fos and cjun genes as well as induction of p21 protein. An appropriate dose of HGF elevated c-fos, reduced c-jun and p21, induced G1/S transition, and inhibited apoptosis. In two patients, apoptosis was not induced after incubation. Cells not treated with HGF expressed no c-fos, c-jun, or c-myc, and remained in G0/G1. Taken together, our results support the conclusion that not only c-fos, cjun, and c-myc, but also p53 and p21 are required for blast apoptosis. HGF differentially prevents apoptosis and induces mitosis, and both events seem to be integral to the self-renewal of AML clonogenic cells.

A 51-year-old man was admitted to our hospital in December 1993, because of fatigue. Peripheral blood tests showed a WBC of 49,400/microliter with 36% plasma cells and 35% monocytes, Hb 14.5 g/dl, and Plt 137,000/microliter. Bone marrow aspirate revealed hypercellularity with 48.7% plasma cells and 22.4% monocytes. Plasma cells in blood were positive for CD38 and PCA-1. Serum calcium, IgA and M-CSF levels were elevated to 14.1 mg/dl, 2,337 mg/dl and 2.7 ng/ml, respectively. Immunoelectrophoresis of serum and urine revealed IgA lambda type M protein and lambda type Bence Jones protein, respectively. Rearrangements of immunoglobulin heavy chain and light chain were demonstrated by Southern blotting analysis. Plasma cell leukemia (IgA lambda type) was diagnosed. He was treated with combination chemotherapy and IFN-alpha and achieved complete remission. However, he suffered a meningeal relapse in February 1995, and died in April 1996. It seems likely that the enhanced production of M-CSF by myeloma cells and/ or activated B cells stimulated monocyte production.

A multicenter randomized controlled study was undertaken in order to determine whether epoetin beta (EPO) ameliorates the anemia in aplastic anemia (AA) patients treated with granulocyte colony-stimulating factor (G-CSF). Enrolled patients were randomized into 3 groups: group C receiving G-CSF alone as the control; group L receiving G-CSF and 200 IU/kg of EPO; group H receiving G-CSF and 400 IU/kg of EPO. Throughout the study, the dose and the administration interval of G-CSF were adjusted to maintain neutrophil counts between 1000 and 5000 microliters EPO was administered subcutaneously for 12 wk as the first step in treatment and when favorable effects were observed over this period, treatment was continued for another 12 wk as the second step in treatment. Significant erythroid responses were defined as increases in untransfused hemoglobin values1.0 g/dl or50% decreases in RBC transfusion requirements over the treatment period. Of 131 patients enrolled, 88 patients allocated to groups L and H were evaluated for toxicity to EPO and 110 were evaluated for erythroid responses. Four of the 31 patients (12.9%) in group C, 6 of the 41 patients (14.6%) of group L, and 14 of the 38 patients (36.8%) of group H showed erythroid responses in the first step in treatment. The erythroid responses of group H were significantly higher than those of the other 2 groups (p0.05). The significant effects of EPO were due to erythroid responses in non-severe AA. Responding patients were significantly different from non-responders with regard to disease severity, hemoglobin concentration, reticulocyte count, serum endogenous erythropoietin levels and serum transferrin receptors; non-severe AA patients were more likely to respond to EPO, and responding patients had lower serum EPO and higher hemoglobin concentration, reticulocyte count and serum transferrin receptors than non-responders. The response rate increased in the second step in treatment, suggesting that long-term treatment improved the efficacy of EPO. No serious side-effects were observed. From these results, we conclude that EPO given in combination with G-CSF is a safe and effective alternative for the treatment of anemia of a subset of AA patients.

Cytokines regulate proliferation and differentiation of hematopoietic progenitor cells. Recently it has been clarified that physiological cell death, apoptosis plays important role of hematopoiesis. So we evaluated the effects of granulocyte-colony stimulating factor (G-CSF) on leukemic cells, especially focused on apoptosis. Intravenous inoculation of radiation-induced murine leukemia cell line, C2M-A5 into the parent C3H mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the daily subcutaneous injection of recombinant human (rh)G-CSF from the next day (Bessho M. et al., Leuk Res 1989:13:1001-1007). In the in vitro study using C2M-A5 cells, we found that apoptosis appears on the cells at 48 hours after addition of G-CSF in culture. The cells in this stage lost the leukemogenicity to C3H mice (Bessho M. et al., Leukemia 8:1185-1190:1994). To clarify the mechanism of the induction of apoptosis by G-CSF we studied cell cycle and molecular changes in C2M-A5 cells cultured in medium with or without rhG-CSF by means of using the flowcytometry and Northern and Western blot analyses. After addition of rh G-CSF to culture, C2M-A5 cells removed to S phase, next arrested at G0/G1 phase on and after 24 hours, and 48 hours later, apoptosis was observed. Overexpression of mRNAs for c-myc (3-24 hours later) and for p53 (6-24 hours later), were observed in the cell cultured in rhG-CSF administered medium with a concomitant down-expression of bcl-2 mRNA (from 6 hours later). Tyrosine-phosphorylated protein (17 kd) appeared at 48 hours after administration of rhG-CSF to cell culture. This protein was suggested for specific apoptosis induction by rhG-CSF. These results are summarized as follows. (1) rhG-CSF induced apoptosis to C2M-A5 and deprived its leukemogenicity to mice. (2) Induction of apoptosis was associated with cell cycle and correlated to the changes of the expression rates of c-myc,p53, and bcl-2. (3) Tyrosine kinase may play an important role in apoptosis induction to C2M-A5 by rhG-CSF.

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.

The breast cancer susceptibility gene (BRCA1) has been identified as a putative tumor suppressor on chromosome 17. We raised antibody against Ring-finger domain of BRCA1. The antibody recognizes a specific BRCA1 protein doublet of about 220 kD. The majority of BRCA1 protein is localized to the nuclear fraction of untreated MCF10A cells. Though BRCA1 is thought to be a growth suppressor gene, no change in BRCA1 protein level was found when MCF10A cells were arrested by growth factor deprivation or stimulation of cell proliferation by re-addition of growth factors. Furthermore the subcellular localization of the BRCA1 protein does not change throughout the cell cycle. These results suggest that BRCA1 may not be directly involved in the regulation of the cell cycle of breast cancer cell line.

A 33-year-old man was admitted to our hospital because of thrombocytopenia found on a periodic physical examination. Splenomegaly was recognized Peripheral blood showed WBC 4,510/microliters, Hb 12.5 g/dl, and Plt 40,000/microliters. Increased serum levels of acid phosphatase and angiotensin converting enzyme were observed on laboratory tests. Bone marrow aspirate revealed Gaucher cells. Decreased beta-glucosidase activity was demonstrated in blood leukocytes, cultured blood lymphocytes, and cultured bone marrow fubroblasts from the patient. His glucocerebrosidase genotype was T1448C/C1504T (L444P/R463C). Since neurological examination and skeletal X ray results were normal, Gaucher disease type 1 was diagnosed.

We studied 34 patients in remission of acute myeloid leukemia (AML) by performing clonal analysis of peripheral blood polymorphonuclear (PMN) cells and mononuclear (MN) cells, using X-linked DNA polymorphisms, in conjunction with the assessment of morphological myelodysplastic changes, performed by a scoring method. Nine patients demonstrated a non-random or skewed X-chromosome inactivation pattern in PMN cells. Three of these nine patients had an apparently random pattern in MN cells (group A), whereas the remaining six patients demonstrated no difference between the inactivation patterns of PMN and MN cells (group B). The PMN cells of the other 25 patients showed a random X-chromosome inactivation pattern, and the patterns of the PMN cells did not differ from those of the MN cells (group C). The scores for myelodysplasia were high (or = 4) in all three patients in group A, intermediate (2-3) in two patients and low (score2) in four patients in group B, and intermediate in five patients and low in 20 patients in group C. The duration of remission in patients with a myelodysplasia score ofor = 2 was significantly shorter than that of patients with a score of2 (P0.01). We conclude that clonal remission actually occurs with myelodysplastic features in some patients with AML (around 10%, group A). It is possible that this clonal analysis may not be sensitive enough to detect the preleukemic clone with myelodysplastic features when this clone constitutes only a minor population of remission hematopoiesis. To further elucidate the biology of such preleukemic clones it is essential to develop more sensitive molecular methods for the detection of genetic abnormalities specific to preleukemic hematopoiesis.

We evaluated the effects of transforming growth factor-beta 1 (TGF-beta 1) on the growth of hematopoietic progenitors in normal donors and in patients with hematologic malignancies now designed as clonal disorders of multipotential stem cells. TGF-beta 1 at 80 pM exhibited differential effects on the normal hematopoietic progenitors when cells were stimulated with different growth factors, such as G-CSF, GM-CSF, interleukin-3 (IL-3), or stem cell factor (SCF). The suppressive effect by TGF-beta 1 was increased for growth with GM-CSF, IL-3, and SCF, and growth with G-CSF was unaffected in hematologic malignancies, TGF-beta 1 suppression for growth with G-CSF was increased for essential thrombocythemia (ET) and polycythemia vera; chronic myelogenous leukemia (CML) in chronic phase; CML in accelerated phase; CML in myeloid crisis; myelodysplastic syndrome (MDS) in refractory anemia; MDS in refractory anemia with an excess of blasts; and acute myeloblastic leukemia (AML). In CML-myeloid crisis and AML, TGF-beta 1 almost completely abolished the growth, with some patient-to-patient variation. The mean ED50s for the growth of leukemic blast progenitors were 1.6, 1.2, 0.7, and 0.2 pM in the presence of G-CSF, GM-CSF, IL-3, and SCF, respectively, c-myc and c-myb antisense oligonucleotides significantly suppressed the growth of leukemic blast progenitors, but not that of clonogenic cells from normal donors and patients with ET. We also demonstrated that TGF-beta 1 inhibits mRNA expression by AML blasts for c-myc and/or c-myb. When the data are taken together, growth suppression by TGF-beta 1 appears to increase with the progression of clonal evolution in hematologic malignancies.

We studied the antileukemic effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by using a radiation-induced murine myeloid leukemia cell line C2M-A5. Intravenous inoculation of C2M-A5 cells into C3H/He mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the subcutaneous injections of rhG-CSF. In order to clarify the mechanism of the suppression, effects of rhG-CSF on C2M-A5 cells were studied in vitro. While C2M-A5 cells grew exponentially in the absence of rhG-CSF, the viability, the growth, and the self-renewal capacity of C2M-A5 cells were all suppressed in cultures in the presence of rhG-CSF. Preincubation with rhG-CSF for 48 h deprived C2M-A5 cells of the ability to induce leukemia in syngeneic mice. Morphological examination revealed the appearance of apoptotic changes of C2M-A5 cells in cultures containing rhG-CSF over the 2-day incubation period. In gel electrophoresis, the DNA from C2M-A5 cells incubated with rhG-CSF for 48 h showed a ladder of degradated DNA bands compatible with apoptosis. From these results, we concluded that the apoptosis of C2M-A5 cells played a key role in the antileukemic effect of rhG-CSF.

The M27 beta probe has been used to determine the clonality of human tumors, based upon X-chromosome inactivation. However, it occasionally gives rise to aberrant results. In this study, the M27 beta probe was used for clonal analysis in Japanese women with clonal stem cell disorders and in those with normal hematopoiesis. Restriction digestion with PstI indicated heterozygosity for the DXS255 locus in 41 out of 50 individuals (82%). Further digestion with HpaII in heterozygous women led to four distinct band patterns: I, both fragments were partially digested; II, either one of the two fragments was completely digested; III, a three-band pattern; and IV, neither fragment was digested. Of 21 hematologically normal females, 17 (81%) and four (19%) had patterns I and III, respectively. In some subjects with pattern I, imbalanced HpaII digestion in the two alleles was seen. Fifteen (65%) of the 23 patients with clonal stem cell disorders had pattern II, while the remainder (35%) had pattern IV. The normal tissues of three acute myeloid leukemia patients with pattern IV all revealed pattern I. It is possible that the aberrant band patterns could be caused by incomplete HpaII digestion in inactive X-chromosomes. In this study, we propose a hypothesis whereby, in normal tissues, aberrant cells, the DXS255 locus of which is not digested with HpaII despite their inactive status, would be mixed with cells demonstrating the usual methylation pattern. In normal tissues, complex of proportion of aberrant cells and skewed Lyonization could produce a variety of band patterns. If a cell with the usual methylation pattern proliferated monoclonally, pattern II would be seen: whereas if an aberrant cell proliferated, pattern IV would be demonstrated.

A 45-year-old male was hospitalized on September 2, 1989 with chief complaints of general fatigue and fever. Physical examination revealed hepatomegaly and massive splenomegaly. Laboratory tests on admission showed Hb of 7.5g/dl, PLT 4.8 x 10(4)/microliters and WBC 9,610/microliters with 81% hairy cells. Bone marrow aspirate demonstrated 55.1% hairy cells and moderate myelofibrosis. Cytochemically, hairy cells were positive for tartrate-resistant acid phosphatase (TRAP). Surface markers were SmIg G+ A+ kappa +, CD11b+, CD11c+, CD19+, CD20+, CD21-, CD25+, HC2+, HLA-DR+. From these findings, a diagnosis of hairy cell leukemia (HCL) was made. After administration of deoxycoformycin (DCF) at a dose of 5.0mg/m2 1-2 times monthly, splenomegaly disappeared, as did hairy cells from the peripheral blood. Hematological level returned to within normal range except for the presence of 1.2% hairy cells and mild myelofibrosis in bone marrow aspirates. DCF has so far been effective for this patient. While DCF has been reported to be effective in the treatment of HCL in the West, it has not been determined in Japanese patients with HCL, who have different hematologic features from those of HCL patients in the West.

Recent studies on the hematopoietic system have revealed that both constitutive and inducible hematopoiesis are regulated by complicated networks composed of various kinds of cytokines and that there are some general rules for hematopoietic cytokine biology. Further accumulation of knowledge about the regulation of proliferation and differentiation of hematopoietic cells by cytokines will serve to clarify the pathophysiology of hematological diseases, resulting in the development of therapeutic strategy for these diseases.

The therapeutic and hematological effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in combination with cyclophosphamide (CY) were investigated in a murine myeloid leukemia model. Ten daily administrations of rhG-CSF following CY prolonged the survival time of leukemic mice more than either agent alone. Hematological examination indicated that this effect was attributable to suppression with rhG-CSF of the leukemic repopulation after CY injection. In addition, rhG-CSF accelerated recovery from CY-induced neutropenia. Based on these hematological changes, a treatment regimen was established consisting of a single injection of CY on day 1 and daily injections of rhG-CSF on days 2-6; this combination treatment was given to the leukemic mice for up to four cycles, with a pause of one day between each cycle. The leukemic mice completed each cycle of treatment with few failures, and it resulted in a long survival time for the leukemic mice. The mean survival time of the mice receiving four cycles of treatment was 47 days, 30 days longer than that of the untreated mice. Hematological examination performed at the end of each cycle showed that the leukemic cell population was controlled at a level equal to or below the pre-treatment level, and peripheral blood neutrophils were maintained at a level equal to or above the normal level. These results indicate the possible effectiveness of combining rhG-CSF with chemotherapeutic drugs in controlling leukemic cell growth, and the effectiveness of rhG-CSF in enhancing neutrophil recovery after chemotherapy. However, it was found that the leukemic cells became resistant to treatment with rhG-CSF after four cycles of combination treatment, suggesting that great care should be taken in the clinical application of rhG-CSF, even when the growth of acute myelogenous leukemia cells is not apparently stimulated by it.

Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA.

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.

The blasts obtained from three freshly diagnosed acute myeloblastic leukemia (AML) patients were cultured in suspension to determine whether leukemic blast progenitors can indeed differentiate to form mature granulocytes. One patient was AML M2. The other two patients were bilineal and biphenotypic leukemia, respectively. Media conditioned by human bladder carcinoma line 5637 (5637-CM) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) was added to stimulate growth. In suspension, clonogenic cells grew for 1-3 weeks in two patients, while they did not increase in one patient. After repeated subculture, cells of blast morphology decreased in percentage and polymorphonuclear neutrophils, eosinophils, and monocyte-macrophages appeared. Lymphoid cell component of the patient 2, who was diagnosed as bilineal leukemia by dual-color immunofluorescence analysis, decreased in number after suspension culture and cells of myeloid phenotype became dominant. The findings show that clonogenic blast progenitors can renew themselves and can also undergo terminal differentiation to mature end cells.

New 40-GHs band digital radio equipment is described. In the equipment we adopted a new circuit configuration consisting of a single IMPATT diode oscillator which functions as both transmitter frequency converter and receiver load oscillator simultaneously. The principal system design factors, a unique IMPATT diode oscillator mount configuration and test results are described. The compact radio equipment is designed so that it ensures excellent cost performance for communication systems in local trunk service, even in short hop applications resulting from rainfall attenuation to the new band.

Autocrine growth factor activity was found in supernatants of AKR T-cell lymphoma lines cultured in serum-free medium. This factor was designated leukemia-derived growth factor (LDGF). Active supernatants stimulated the growth of the AKR murine T-cell lymphoma line SL 12, its cloned derivatives, and all other murine T-cell lymphoma lines tested. Growth factor activity in conditioned medium was found to be different from interleukin 2 (IL-2) and several other known growth factors. LDGF was able to stimulate growth of the human leukemia T-cells MOLT4f, and the LDGF from MOLT4f cells stimulated the mouse cells. Because mouse T-cell lymphoma lines produced and respond to this factor, it may support the continued proliferation of these cells and could be responsible for their malignant in vivo properties.