Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.     

GIANT CELL CARCINOMA OF THE PANCREAS

A case of giant cell carcinom of the pancreas is reported herein. The patient is a 67-year-old Japanese woman complaining of ascites, general fatigue, loss of weight, abdominal distention, nausea, and vomiting. Cytological diagnosis of ascites revealed adenocarcinoma. At autopsy, a whitish tumor measuring around 5 cm in diameter was found at the head of the pancreas. Metastasis was seen only in the liver. Histological examination displayed bizarre multinucleated giant cells occasionally phagocytosing the tumor cells and neutrophils.     

Nondestructive evaluation of blood flow in a dialyzer using X-ray computed tomography

It is very important to observe the concentrations and flow patterns of blood through a dialyzer to evaluate its function and to obtain the most appropriate design. We established a visualization method for the blood flow pattern in a dialyzer using X-ray computed tomography, and investigated the so-called internal filtration phenomenon. The results obtained were as follows: (1) The influence of 5% BaSO₄, which was added to the blood as a contrast medium, on the filtration rate of the dialyzer was minimal. (2) The relationship between the concentration of BaSO₄ and the Hounsfield unit value was expressed by linear regression. (3) Hounsfield unit values increased massively just after blood entered the dialyzer and peak values increased with dialysate perfusion under the following conditions: the dialyzer (BS-1.6UL, polysulfone hollow fibers) was used, and bovine blood with 5% BaSO₄ added was used at a blood flow rate of 200ml/min. The dialysate flow rate was 500ml/min and the slice thickness of X-ray computed tomography was 1–10mm. (4) It was observed that blood flowed slightly faster in the center than the peripheral portion of the dialyzer, when the flow pattern was followed after pulse injection of blood containing 20% BaSO₄ into the dialyzer. It was concluded that this method could possibly be utilized not only qualitatively but also quantitatively for observation of the real state of blood flow and in designing dialyzers.     

Cloning and nucleotide sequence of the gene encoding arginine deiminase of Mycoplasma arginini.

The existence of a mycoplasmal arginine deiminase which catalyzes the conversion of L-arginine to L-citrulline has been postulated. Here we show the partial amino acid sequence of arginine deiminase of Mycoplasma arginini and the complete nucleotide sequence of the arginine deiminase gene of M. arginini. The open reading frame deduced from this sequence consists of 1,230 bp encoding 410 amino acids. The mature form of this enzyme contains 409 amino acids after the deletion of the first methionine. In this open reading frame, TGA nonsense codons are used as tryptophan codons; this usage was verified by determination of the amino acid sequence. The molecular weight of the enzyme calculated from the deduced amino acid sequence is 46,372. Recently, the nucleotide sequence of the arginine deiminase gene of M. arginini was reported by Kondo et al. (K. Kondo, H. Sone, H. Yoshida, T. Toida, K. Kanatani, Y.-M. Hong N. Nishino, and J. Tanaka, Mol. Gen. Genet. 221:81-86, 1990). However, their sequence differed from ours in several places and especially at the C terminus.     

Polymorphism in genes for the enzyme arginine deiminase among Mycoplasma species.

The extent of restriction fragment length polymorphism in genes for the arginine deiminase enzyme among 28 species of mycoplasmas was assessed by Southern blot analysis of DNA digested with EcoRI or TaqI nuclease probed with a 725-bp internal fragment of the arginine deiminase gene from Mycoplasma arginini. The results indicated unexpected heterogeneity among species of a single genus.     

Polymorphism of the ABO blood group genes in Han, Kazak and Uygur populations in the Silk Route of northwestern China

Genetic polymorphism in the ABO blood group gene of Han, Kazak and Uygur populations inhabiting the most northwestern part of China was investigated using polymerase chain reaction-based techniques. The present study enrolled 43 healthy unrelated Han, 37 Kazak and 59 Uygur volunteers. The allele in A1 blood group is distinguished A0101 and A0102 in difference of nucleotide position 467. The A0101 allele is more frequent in Caucasian and the A0102 allele is characteristic in Mongoloid. It must be notable that A0201 in the A2 group (with a single base deletion at nucleotides 1059 to 1061) which was characteristic of Caucasian was observed in Kazak and Uygur populations but not in Han. Further, 00201 (with no nucleotide deletion at 261 and three nucleotide differences), which is frequent in different races including Caucasian except for Mongoloid, was detected also in Kazak and Uygur populations. The frequencies of B0101 in Kazak, Uygur and Han were comparable to those of other Asian populations but higher than those of Caucasian populations. Collectively, these results reveal that the allele frequencies of Kazak and Uygur at the ABO blood group locus are an intermediate between those of Mongoloid and Caucasian, suggesting the admixed feature of Kazak and Uygur with Mongoloid and Caucasian.     

Abscess-forming granulomatous lymphadenitis: Histological typing of suppurative granulomas and clinicopathological findings with special reference to cat scratch disease

In order to clarify the histological and immunohistochemical characteristics of suppurative granuloma in abscess-forming granulomatous lymphadenitis (AGL), and the relation between AGL and cat scratch disease (CSD), 36 cases of AGL were studied. The combined results showed that there were two types of suppurative granulomas. The suppurative granulomas histologically revealed small lymphocytes of predominantly T cell phenotype distributed among the epithelioid histiocytes bordering central necrotic areas in the suppurative granulomas. These suppurative granulomas could be further subdivided into two groups, mainly those with and without the intermingling of large transformed cells of B-cell phenotypes: Type B granuloma with large transformed B cells and Type A without large transformed B cells. Both types of granulomas were observed in a varying degree in most cases. According to the predominant type of granulomas, 36 patients with AGL were further classified into two groups: Group I of Type A dominance and Group II of Type B dominance. Warthin-Starry (WS) silver stain positive bacteria, which are said to be a causative agent of CSD, were present in about 50% of both groups. No Brown-Hopps' Gram-positive bacteria, fungus, toxoplasma, Chlamydia or Bacillus Calmette-Guerin antigen were found in any case. Clinically, there was no significant difference between these two groups. On the other hand, the detection of WS-positive bacteria seemed to have some relationship with the duration of disease and the history of exposure to cats, and 70% of AGL cases occurred in autumn without a single concurrent epidemic.     

Sensitive and rapid detection of herpes simplex virus and varicella-zoster virus DNA by loop-mediated isothermal amplification

Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method in which reagents react rapidly and efficiently, with a high specificity, under isothermal conditions. We used a LAMP assay for the detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV). The virus specificities of primers were confirmed by using 50 HSV-1, 50 HSV-2, and 8 VZV strains. The assay was performed for 45 min at 65 degrees C. The LAMP assay had a 10-fold higher sensitivity than a PCR assay. An analysis of nucleotide sequence variations in the target and primer regions used for the LAMP assay indicated that 3 of 50 HSV-1 strains had single nucleotide polymorphisms. No HSV-2 or VZV strains had nucleotide polymorphisms. Regardless of the sequence variation, there were no differences in sensitivity with the HSV-1-specific LAMP assay. To evaluate the application of the LAMP assay for clinical diagnosis, we tested clinical samples from 40 genital herpes patients and 20 ocular herpes patients. With the LAMP assay, 41 samples with DNA extraction and 26 direct samples without DNA extraction were identified as positive for HSV-1 or HSV-2, although 37 samples with DNA extraction and just one without DNA extraction were positive by a PCR assay. Thus, the LAMP assay was less influenced than the PCR assay by the presence of inhibitory substances in clinical samples. These observations indicate that the LAMP assay is very useful for the diagnosis of HSV-1, HSV-2, and VZV infections.     

Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells

To evaluate the potential role of NK1.1 (CD161c) cells in autoimmune uveoretinitis, we treated experimental autoimmune uveoretinitis (EAU)-susceptible mice with anti-CD161c antibodies (PK136) to deplete natural killer (NK) cells. Injection of anti-CD161c antibodies deleted NK cells from the peripheral blood of EAU-susceptible mice. The T cell proliferative response against the ocular autoantigen K2 was not suppressed in mice treated with anti-CD161c antibody when compared with T cells from control mice. Although mice treated with anti-CD161c developed EAU, the clinical severity on days 17 and 19 after induction of EAU was significantly mild in anti-CD161c-treated mice compared with control mice. In addition, the histopathological severity of EAU was significantly milder in mice treated with anti-CD161c antibodies than controls 21 days after induction of EAU. Our results indicate that the severity of EAU is augmented by NK1.1(+) NK cells.