[Diffuse alveolar damage].
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Biomedical subjects
Publications and source records attributed to S Irino.
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A new human small cell lung carcinoma (SCLC) cell line, designated MT-428, was derived from a patient who showed neurological paraneoplastic syndrome (combined with subacute cerebellar degeneration and peripheral sensory neuropathy) and was established in tissue culture. This cell line exhibited small cell (variant type) morphology as observed by phase contrast and electron microscopy. The MT-428 cells had a doubling time of 72 hours. Chromosomal analysis showed complicated rearrangements at short and long chromosomes with a modal number of 68. Several tumor markers, NSE, TPA and CPK-BB, were detected in culture medium. This cell line had a cloning efficiency of 1.3% in 0.8% methylcellulose. Finally, it should be noticed that autoantibody against MT-428 cell was demonstrated in serum of the patient. We concluded that the MT-428 cell line may provide a suitable model for studies of neurological paraneoplastic syndrome.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) not only enhanced the growth of HL-60 cells, but also significantly increased NBT-reducing ability and alkaline phosphatase (ALP) activity of the cells, which were enhanced by the treatment with retinoic acid (RA). Protein kinase C inhibitors (H-7 and staurosporine) significantly suppressed this induction of ALP. The pretreatment with RA followed by rhG-CSF treatment showed almost the same degree of ALP activity as that induced by the simultaneous treatment with RA and rhG-CSF. This study suggests that RA and rhG-CSF are the potent inducers of ALP activity of HL-60 cells and protein kinase C is supposed to have a role in this induction of ALP.
HL-60 cells have been shown to differentiate into monocyte-like cells as a consequence of the interaction of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) with a specific intracellular receptor (VDR). Of c-myc it has been reported that it plays a role in cell proliferation and differentiation. We have investigated the expression of VDR and c-myc mRNA of three subclones of HL-60 cells (N, R and MR) after exposure to 1,25(OH)2D3. The N cell is a normal clone in which 1,25(OH)2D3 inhibited cell proliferation and also induced cell differentiation. The R cell is a resistant clone whose proliferation and differentiation are not affected by 1,25(OH)2D3. The MR cell is a mixed response type clone whose proliferation was not inhibited by 1,25(OH)2D3, while its differentiation was actually induced by 1,25(OH)2D3. The VDR mRNA expression of the N and MR cells reached a peak at 2 h (2.3- and 2.6-fold induction, respectively) and returned to the control level after 24 h treatment of 1,25(OH)2D3. The c-myc mRNA expression was significantly inhibited in the 1,25(OH)2D3-induced N cells, but not in the MR cells. In contrast, 1,25(OH)2D3 did not induce any changes of the VDR and c-myc mRNA levels in the R cells. In separate experiments, the level of the VDR in the three clones was determined via Scatchard analysis; the VDR of the N, MR and R cells were found to be 4500/cell, 3570/cell and less than 600/cell, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Five cDNA clones for TAXREB proteins that bind to the tax-responsive enhancer element of human T-cell leukemia virus type I (HTLV-I) were isolated from a Jurkat cell cDNA library. The beta-galactosidase fusion proteins of three of these clones specifically recognized the domain C within the enhancer. One of the three cDNAs, encoding TAXREB107, contained an open reading frame with 288 amino acid residues. RNA blot analysis showed that the level of mRNA for TAXREB107 increased transiently in Jurkat cells on treatment with TPA. Immunoblot analysis showed that polyclonal antibody against TAXREB107 specifically recognized a 34-kD protein in Jurkat cells. TAXREB107 may participate in tax-mediated trans-activation of transcription.
The frequency of streptococcal infections has been reported to be increasing. To determine the significance of such infections complicating treatment of leukemia, we studied the incidence and clinical features of Streptococcus mitis septicemia among 51 leukemia patients in our department. During 166 consecutive treatment courses for leukemia, eight episodes of Streptococcus mitis septicemia were observed in 35 septicemic patients. In seven out of eight episodes (88%), severe mucositis developed after aggressive chemotherapy, suggesting that oral mucosa might be the site of entry for Streptococcus mitis. The isolates were sensitive to imipenam/cilastatin and cefuzonam, and were relatively resistant to amikacin. Although none of the patients died of Streptococcus mitis septicemia, life-threatening adult respiratory distress syndrome (ARDS) developed in two independent treatment courses. We should thus be aware of the risk of ARDS in patients with Streptococcus mitis septicemia.
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Serum electrolytes were measured in 14 patients with myotonic dystrophy and 25 healthy controls. The serum level of sodium was 144.8 +/- 3.2 (mean +/- SD) mEq/l in myotonic dystrophy and 142.0 +/- 1.9 mEq/l in the controls, and the level of potassium was 4.6 +/- 0.4 mEq/l and 4.0 +/- 0.3 mEq/l, respectively. Both electrolyte levels were significantly higher in the disease (p < 0.01, p < 0.001). Blood samples obtained from 5 patients and 5 controls were allowed to stand at room temperature, and serum electrolyte levels were repeatedly measured at 5, 30, 60, 120 minutes after blood collection. The measurement of serum potassium in myotonic dystrophy was elevated in the parallel with standing-time. The serum potassium was significantly higher in the patients than in the controls at 60 and 120 minutes standing. These results suggest that myotonic dystrophy has red blood cell membrane abnormality which allows potassium to leak.
A 57-year-old female, who had a 14-year history of rheumatoid arthritis, developed aplastic anemia. Treatment with anti-lymphocyte globulin (ALG) and methylprednisolone pulse therapy achieved complete remission. However, twenty months after ALG treatment she developed acute monocytic leukemia. In spite of the chemotherapy, consisting of cytosine arabinoside and etoposide, she died of pneumonia. Recently, reports from Western countries have claimed that patients with aplastic anemia frequently develop clonal disorders following ALG treatment. To our knowledge, this is the first report in Japan of a case developing acute leukemia following ALG treatment.
Chromosome translocation t(15;17) specifically found in acute promyelocytic leukemia (APL) results in cleavage in the introns of PML gene on chromosome 15 and in the intron of the retinoic acid receptor alpha (RAR alpha) gene on chromosome 17, creation and expression of PML-RAR alpha and RAR alpha-PML fusion genes. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to detect the PML-RAR alpha fusion transcripts rapidly in APL patients. The fusion transcripts could be detected in all of the 10 APL patients studied. Of the two breakpoints in the PML gene so far reported, seven APL patients had the fusion transcript compatible with the downstream (3') breakpoint, and the other three APL patients were considered to have the upstream (5') breakpoint. RT-PCR could detect the fusion transcripts from as little as 50 pg bone marrow RNA, and from as little as 0.5 pg bone marrow RNA with the nested PCR. This method was applied to detect minimal residual leukemia cells in an APL patient who had undergone allogeneic bone marrow transplantation, in whom the RT-PCR could not detect the PML-RAR alpha fusion transcripts at several post-transplant time points. This system could be useful to detect minimal residual leukemia cells and accordingly modify the treatment strategy, as well as to make a quick diagnosis with a small amount of clinical sample.
A cell line (TI-1) has been established from the peripheral blood of a patient with acute myeloid leukemia (M2). A typical TI-1 cell displayed many abnormalities of its chromosomes, but not the Philadelphia (Ph1) chromosome. Light and electron microscopic examination and histochemical analysis indicated that the TI-1 cells were undifferentiated blast cells, but immunologic marker studies suggested that these cells had myeloid characteristics. The proliferation of TI-1 cells was dependent on the concentration of fetal bovine serum (FBS). Their doubling time was 13.8 hours when they were cultured in a medium containing 10% FBS. Phorbol-12 myristate 13-acetate (PMA) induced the TI-1 cells to differentiate into monocyte-like cells, as judged by their morphologic similarity to monocytes, their adhesion to the culture dish, and their increase of both nitroblue tetrazolium (NBT)-reducing ability and nonspecific esterase (NSE)-activity. PMA significantly inhibited the proliferation and DNA synthesis of TI-1 cells in a dose-dependent manner. The PMA-induced differentiation was significantly inhibited by the protein kinase C inhibitors (H-7, staurosporine). Hemin induced the TI-1 cells to differentiate into erythroid cells. The number of hemoglobin-producing cells and hemoglobin production was increased by hemin treatment. Hemin also inhibited the proliferation of the TI-1 cells. Thus, the TI-1 cell represents a bipotent, granulo-monocytoid, and erythroid cell line. The TI-1 cell line will be a useful model for monocytoid and erythroid differentiation.
Grönbland-Strandberg syndrome is an inherited connective tissue disorder with cutaneous, ophthalmologic, and systemic manifestations. Here we report a case of AML with thrombocytosis arising in a patient with this syndrome. Karyotypic analysis of bone marrow cells revealed the inversion 3 (q21.3;q26.2). To our knowledge, this is the first report of the association of AML with thrombocytosis and Grönbland-Strandberg syndrome. This might be a coincidental association, but it suggests some interesting speculations regarding the pathogenesis of these diseases.
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Human neutrophil elastase plays an important role in the development of several inflammatory lung diseases; however, there have been relatively few investigations using plasma samples. In this report, we describe alterations in the plasma elastase:alpha 1-PI complex in patients with chronic obstructive pulmonary disease (COPD) (15 cases), COPD with infection (8), diffuse panbronchiolitis (DPB) (8), bronchiectasis (9), pneumonia (10), and the adult respiratory distress syndrome (ARDS) (14), and in 15 normal volunteers. The elastase:alpha 1-PI complex concentration was determined by an enzyme-linked immunosorbent assay. Western immunoblot analysis of the elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex levels in patients with COPD with infection (504 micrograms/L +/- 93 micrograms/L) were significantly higher, as compared with those with COPD but without infection (118 micrograms/L +/- 9 micrograms/L) and normal volunteers (122 micrograms/L +/- 4 micrograms/L). Increased complex concentrations were also found in patients with DPB and bronchiectasis (643 micrograms/L +/- 222 micrograms/L and 558 micrograms/L +/- 198 micrograms/L, respectively) as compared with normal volunteers. Increased complex concentrations were also found in patients with pneumonia and ARDS (450 micrograms/L +/- 101 micrograms/L and 1,400 micrograms/L +/- 438 micrograms/L, respectively). Western immunoblot analysis using anti-alpha 1-PI antibody and antineutrophil elastase antibody showed two types of elastase:alpha 1-PI complexes, one with a molecular weight of 60,000 daltons (60 kilodaltons [KD]) and the other at 50,000 daltons (50 KD). Although the native 80-KD elastase:alpha 1-PI complex was detected in bronchoalveolar lavage fluid, it was not found in plasma. In summary, these results demonstrated that levels of the truncated complex were increased in patients with various inflammatory lung diseases. This truncated form may play an important role in the pathophysiology of inflammatory processes.
This report describes pneumococcal meningitis in two splenectomized patients with lymphoid malignancy. Early diagnosis and emergency treatment of pneumococcal infection in splenectomized patients is proven to be of significant value. Prophylactic antibiotics targeted against pneumococcus should be considered for the clinical management of such conditions in splenectomized patients, particularly during cytotoxic chemotherapy.