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Simple Summary: The clinical course of classic Hodgkin lymphoma arising in immune deficiency/dysregulation (CHL-IDD) differs from that of CHL arising in immunocompetent cases and typically exhibits aggressive clinical behaviors. This study investigated the genetic aberration of 9p24.1 and protein expression of PD-L1 and also analyzed the clinicopathological association of these genetic lesions in CHL-IDD. Our findings showed that PD-L1 expression and 9p24.1 copy number alterations were observed in all patients analyzed in this study. Though it is recognized that an increase in 9p24.1 copy number alteration is associated with a more aggressive clinical course in immunocompetent CHL patients, we identified a subset of the 9p24.1 copy gain group, which had less 9p24.1 copy number alteration than the amplification group, exhibited more extensive extranodal lesions and had higher clinical stages in CHL-IDD cases. This finding speculates the presence of a genetically distinct subgroup within CHL-IDD patients, which may explain certain characteristic features. A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. [ABSTRACT FROM AUTHOR]

Background: tert-Butyl hydroperoxide (TBHP; CAS 75–91-2), a hydroperoxide, is mainly used as a polymerization initiator to produce polyethylene, polyvinyl chloride, and unsaturated polyester. It is a high-production chemical, widely used in industrial countries, including Japan. TBHP is also used as an additive for the manufacturing of food utensils, containers, and packaging (UCP). Therefore, there could be consumer exposure through oral intake of TBHP eluted from UCPs. TBHP was investigated in various in vitro and in vivo genotoxicity assays. In Ames tests, some positive results were reported with and/or without metabolic activation. As for the mouse lymphoma assay, the positive result was reported, regardless of the presence or absence of metabolic activation enzymes. The results of some chromosomal aberrations test and comet assay in vitro also demonstrated the genotoxic positive results. On the other hand, in in vivo tests, there are negative results in the bone marrow micronucleus test of TBHP-administered mice by single intravenous injection and the bone marrow chromosomal aberration test using rats exposed to TBHP for 5 days by inhalation. Also, about dominant lethal tests, the genotoxic positive results appeared. In contrast, there is little information about in vivo mutagenicity and no information about carcinogenicity by oral exposure. Results: We conducted in vivo gene mutation assay using MutaMice according to the OECD Guidelines for the Testing of Chemicals No. 488 to investigate in vivo mutagenicity of TBHP through oral exposure. After repeated dosing for 28 days, there were no significant differences in the mutant frequencies (MFs) of the liver and glandular stomach up to 300 mg/kg/day (close to the maximum tolerable dose (MTD)). The positive and negative controls produced the expected responses. Conclusions: These findings show that orally administrated TBHP is not mutagenic in the mouse liver and glandular stomach under these experimental conditions. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, cord blood is used for more than half of all unrelated stem cell transplantations. The public cord blood banks (CBBs) have been collecting information on cord blood transplantation‐related adverse events from physicians on a voluntary basis, without common definitions of the adverse reactions. The aims of this study were to compare two classification systems to improve the reporting system and to clarify the actual risk from cord blood infusion, which can then provide the impetus to take appropriate measures to reduce adverse events. Materials and Methods: We classified the reports according to existing criteria; one is the Proposed Standard Definitions for Surveillance of Non‐Infectious Adverse Transfusion Reactions by the International Society of Blood Transfusion (ISBT) Working Party on Haemovigilance, and the other is the Common Terminology Criteria for Adverse Events (CTCAE). There were 140 cases with adverse events reported from April 2014 through March 2019. Results: Twelve cases, such as donor‐derived leukaemia/myelodysplastic syndromes (MDS) and chromosomal aberrations reported after engraftment, were excluded from this analysis. Of the 128 cases with adverse events at cord blood infusion, the CTCAE and ISBT criteria could not classify 6 cases and 68 cases, respectively. Classifying by the CTCAE, the most common side effect was hypertension in 35 cases, followed by anaphylaxis, allergic reactions, nausea, urticaria, etc. Serious adverse events (grades 4 and 5) were mainly anaphylaxis, with a frequency of 0.23%. Conclusion: It is necessary not only to provide information on adverse events but also to standardize the reporting of adverse events to support measures to reduce them. [ABSTRACT FROM AUTHOR]

The article focuses on the use of gabapentin to treat apnea in infants with trisomy 13 and 18. The study presents a case series demonstrating the effectiveness of gabapentin in managing breath-holding spells associated with apnea in these infants, highlighting its potential as a therapeutic option. Topics discussed include the characteristics of apnea treated with gabapentin, the dosage recommendations, and the positive outcomes observed in the case series.

Research in the Department of Radiobiology at the Institute for Environmental Sciences (IES) has focused mainly on the biological effects of long-term low dose-rate radiation exposure on mice since its establishment 30 y ago. The IES has exposed thousands of mice of various strains, to gamma-rays, mostly chronically, at low dose-rates of 0.05, 1, 20 or 100 mGy/d, at medium dose-rates of 200 or 400 mGy/d or at acute high dose-rates of 0.7–0.9 Gy/min. The dose-rate 0.05 mGy/d is comparable with the dose limit for radiation workers of 100 mSv/5 y. The results will be presented based on the parameters examined at various endpoints such as life span, neoplasm (cancer incidence), chromosome aberrations frequencies, alterations in mRNA levels, tumour transplantability and developmental abnormalities after in utero exposures. The results from research collaborations with universities and institutions both domestic (within Japan) and international will be presented. Lastly, an outline of experiments (e.g. juvenile exposure, low dose tritium exposures) and projects (e.g. radiobiology archives) currently in progress and future research perspectives will be described. [ABSTRACT FROM AUTHOR]

We report a case of a neonatal diagnosis of Prader–Willi syndrome caused by uniparental disomy. A 34‐year‐old pregnant woman underwent noninvasive prenatal testing (NIPT) in a hospital that was not certified by the Japanese Association of Medical Sciences. The results of trisomy 13, 18, and 21 were negative; however, a possible abnormality in chromosome 15 was indicated by the Z‐score. Genetic counseling was not performed; thus, the woman did not understand the implication of this result. Therefore, she continued with the pregnancy and delivered a boy weighing 1892 g with hypogonadism at 38 weeks and 5 days. The infant was diagnosed with Prader–Willi syndrome caused by uniparental disomy derived from trisomy rescue. The NIPT results may have reflected placental mosaicism, emphasizing the importance of understanding the limitations of NIPT due to the presence of congenital chromosomal abnormalities that cannot be detected by NIPT platforms. [ABSTRACT FROM AUTHOR]

I will reflect on the role of genotoxicity in the regulation of chemical safety, summarizing the past and current situation, and giving personal views for the future. This includes how genotoxicity information has been, and is being, used in the evaluation of the safety of chemical substances including pharmaceuticals, pesticides, food additives and industrial chemicals before they are introduced into the market for sale. In Japan, the Industrial Safety and Health Act, enacted in 1972, assures workers' safety by including safety assessment of chemicals to which workers may be exposed in the workplace. The law firstly included the bacterial gene mutation assay with rat liver microsome fraction (Ames test) for the evaluation of chemical mutagenicity to predict carcinogenic potential, which was the forerunner of requiring a genotoxicity test by law. Since then, genotoxicity, especially the Ames test and the in vitro chromosomal aberration test using cultured mammalian cells (especially Chinese hamster cells) have been incorporated into several laws to assess the safety of various chemicals. Many test systems for different endpoints have been developed, improved, and used in practice. The battery strategy, combining several test systems to detect as many genotoxic chemicals as possible, was implemented because no one test system can detect all genotoxic agents with different mechanisms of genetic damage. In general, the standard battery consists of the Ames test, in vitro chromosomal aberration test and the in vivo rodent erythrocyte micronucleus test as a representative in vivo assay. Many other test systems have been used for supplementary testing as well as for research studies. Important keywords for regulatory science include 1) guidelines, 2) Good Laboratory Practice, 3) evaluation and interpretation of test results. Here, I discuss on these key points, and give personal opinions for the future. [ABSTRACT FROM AUTHOR]

Aims: Noninvasive prenatal testing (NIPT) of pregnant women has been performed worldwide since 2011, and it is currently performed in more than 90 countries. However, the rate of adoption in Japan remains at less than 2%. This review seeks to identify the ethical and practical issues surrounding noninvasive prenatal screening—including the purpose of the test, its pros and cons, issues surrounding fair treatment, and social factors—to better understand why the adoption rate remains low. Methods: This study examines the complex ethical issues surrounding noninvasive prenatal testing, including the purpose of the test, its pros and cons, issues related to fair treatment, and social factors. Results: Although cell‐free DNA analysis for common fetal trisomies using maternal blood is highly accurate, lack of access to such testing and discriminatory attitudes in society remain important barriers. Personal choices such as whether to undergo noninvasive prenatal screening and whether to continue a pregnancy are sometimes criticized by those who believe that it leads to the "selection of life" or discrimination against people with disabilities. Conclusions: Obstetrics has changed dramatically in recent years, and prenatal diagnosis technology has also advanced. To keep up with these advances, better information should be provided to ensure the public has a more nuanced understanding of the screening beyond the overused argument that it leads to "selection of life." [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with a rare chromosomal rearrangement known as Inverted-duplication-deletion of chromosome 10q (INV-DUP-DEL 10q). It is reported that the patient in this case was a female who exhibited developmental delay and distinctive facial features since early childhood. It is further reported that at the age of 13, the patient presented with symptoms suggestive of systemic lupus erythematosus (SLE).

Aim: This study is to investigate the role of amniocentesis for prenatal diagnosis before and after the beginning of noninvasive prenatal testing (NIPT) in Japan. Methods: We performed a retrospective analysis of genetic amniocentesis at mid‐trimester (15–20 gestational weeks) for fetal karyotype analysis at Nagoya City University between April 2006 and March 2020. The indications, test results, and the detection rate of fetal abnormal karyotype were compared before (phase 1, P1) and after (phase 2, P2) beginning of NIPT at April 2013. Results: A total of 2458 (P1: 1132, P2: 1326) amniocentesis were enrolled in this study. The most frequent indication was advanced maternal age in both phases (P1: 78.2% %, P2: 81.1%). In P2, 110 patients (8.3%) received amniocentesis after positive or nonreportable NIPT results. Other indications were fetal abnormal findings by ultrasounds (P1: 15.4%, P2: 17.7%), abnormal maternal serum screening results (P1: 8.0%, P2: 10%), previous child with fetal chromosome aberration (P1: 6.5%, P2: 3.5%), and translocation of either partner (P1:1.5%, P2: 2.1%). The detection rate for fetal chromosomal aberrations including all indications was significantly increased in P2 (15.9%, 95% CI 14.0–18.0) as compared to P1 (9.0%, 7.4–10.8). However, if the indication was only advanced maternal age, the positive detection rate kept low in both phases (P1: 5.2%, 3.7–7.1, P2: 4.2%, 2.9–5.9). Conclusion: Since the initiation of NIPT, the detection rate of fetal chromosomal abnormalities was higher in this study, suggesting that amniocentesis cannot be strongly recommended for advanced maternal age alone. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high‐risk pregnant women. Methods: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age‐specific PPV and NPV were estimated. Results: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78–99.96), 99.12% (95% CI: 96.83–99.76), and 100% (95% CI: 88.30–100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age‐specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high‐risk pregnant women, and maternal age‐specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is a common neoplasm in children, but less frequent in adults. Since information on clinical features and genetics of adult ALL in Japan is limited, we analyzed 215 subjects aged 16-65 years with untreated ALL enrolled in the Fukuoka Blood & Marrow Transplant Group studies ALL MRD 2002 and 2008. The prevalence of ALL was bimodal, with the larger group aged 56-65 years. Immunophenotypic characterization showed B-lineage is more frequent than T-lineage ALL (78.6 vs 13.0%), with age-related differences. The proportion with BCR-ABL1 rearrangement increased progressively with age, up to 55.7% among subjects aged over 56-65 years. Rearrangements involving the KMT2A gene, ETV6-RUNX1, and TCF3-PBX1 were rare in this study cohort. The overall incidence of hyperdiploidy was only 1.7%, and there were no cases with hypodiploidy. Overall survival varied by age and cytogenetics. Older subjects and those with BCR-ABL1 tended to have inferior outcomes. In this epidemiological study of Japanese adult ALL, the majority of subjects had B-lineage ALL, the T-cell phenotype was most frequent in those aged 16-25, and BCR-ABL1 rearrangement was very common, with prevalence increasing with age. These types of adult ALL are potentially manageable with targeted therapies. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to investigate the process mothers go through in coming to terms with raising a child with chromosomal structural abnormalities. Methods: Sixteen mothers living in Japan were interviewed and a modified grounded theory approach was used for the analysis. Results: A total of 35 concepts, nine subcategories, and six categories were extracted. The six categories were: (a) Concern about abnormalities; (b) A healthy child is considered as a standard; (c) Deepening attachment to the child; (d) Acceptance of the child as s/he is; (e) Changing attitude toward disabilities; (f) Creating a frontier for other mothers. The parenting journey meant that parents did not move in a straightforward way from the beginning of the process to the endpoint but instead moved between "Deepening attachment to the child" and "Acceptance of the child as s/he is" before they moved ahead. Conclusion: Having support and meeting peers of mothers with similar issues is essential for mothers to review their perspectives that healthy children are the standard against which to measure their child and to motivate them to raise their children, but it was extremely difficult to have such opportunities due to rarity of the disorder. It is crucial to accumulate more practical information so that mothers can access and use it. Mothers also need support to enhance their self‐worth while giving due consideration to the possibility that they may be conscious of being stigmatized. Nurses need to advocate for these children and families to get the appropriate help, understanding and support. [ABSTRACT FROM AUTHOR]

Background: Individuals with 22q11.2 deletion syndrome (22q11.2DS) exhibit various phenotypes. Objective: To compare the clinical and otorhinolaryngological features of Japanese patients with 22q11.2DS with those of patients reported in Western literature. Materials and methods: We retrospectively assessed the medical records of 17 Japanese patients with 22q11.2DS and compared our findings with previously reported findings in Western literature. Results: Hearing loss was the most frequent complaint (n = 8, 47%), followed by articulation disorders and/or nasopharyngeal closure failure (n = 4, 24%) and language development delay (n = 2, 12%). Ten patients (59%) had hearing loss regardless of the chief complaint (total 15 ears – mild, 9; moderate, 6). Four patients had bilateral hearing loss. One patient (6%) underwent tympanostomy tube placement for refractory exudative otitis media, another (6%) underwent myringoplasty, and three patients (18%) underwent tympanoplasties for chronic otitis media or middle ear malformation. Previous studies in Western countries reported similar results in terms of frequency of hearing loss, severity of hearing loss, and the percentage of middle ear malformations. Conclusions: The otorhinolaryngological characteristics of Japanese patients with 22q11.2DS were similar to those in Western countries. Hearing loss was primarily caused by disorders like otitis media and middle ear malformation. Significance: Our findings may aid treatment planning for Asian patients with 22q11.2DS. [ABSTRACT FROM AUTHOR]

Background: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children. Methods: We retrospectively collected clinical data on hypodiploid ALL cases from the registries of prospective multicenter trials conducted by the four independent clinical study groups in Japan between 1997 and 2012. Results: A total of 117 ALL patients with hypodiploidy were analyzed in this study. There were 101, eight, and eight patients with 45, 44, and fewer than 44 chromosomes, respectively. The 5 year overall survival rates differed significantly: 86.0%, 87.5%, and 62.5% for patients with 45, 44, and fewer than 44 chromosomes, respectively (P = 0.037). Of the eight patients with 44 chromosomes, seven were alive, including five patients who maintained complete remission without undergoing hematopoietic stem cell transplantation (HSCT). Of the eight patients with fewer than 44 chromosomes, six were good responders to prednisolone and none had induction failure, but the relapse rate was high (5/8). No patients had central nervous system relapse. Four patients underwent HSCT after relapse, but only one survived. Conclusions: Outcomes of Japanese ALL patients with fewer than 44 chromosomes were poor, as previously reported in other countries. Although the sample size was small, patients with 44 chromosomes had better prognoses than those previously reported. Further studies including international collaboration are needed to improve outcomes for pediatric ALL patients with fewer than 44 chromosomes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 3-year-old boy with trisomy 13, who was admitted to the hospital because of fever, and hypoxemia, 2-year-old girl with central hypoventilation syndrome, who presented with fever and convulsions due to hyponatremia, and 17-year-old girl admitted to hypoxemia of surgery for congenital heart disease. Topics include the none of these patients came in contact with COVID-19 patients, and the SARS-CoV-2 on rapid antigen test results to be positive for SARS-CoV-2.

An 11q23 abnormality presents in approximately 5% of adults with acute myeloid leukemia (AML) and is associated with adverse outcomes even after allogeneic hematopoietic cell transplantation (allo-HCT). To evaluate the outcomes and prognostic factors following allo-HCT for adult AML with 11q23 abnormality, we retrospectively analyzed the Japanese registration data of 322 adult AML patients with 11q23 abnormality who had received allo-HCT between 1990 and 2014. In total, the disease status at HCT was first complete remission (CR1) in 159 (49%) patients. The probability of overall survival and the cumulative incidence of relapse at 3 years were 44 and 44%, respectively. In the multivariate analysis, disease status beyond CR1 at the time of HCT was significantly associated with a higher overall mortality and relapse. The 11q23 fusion partner did not have a significant impact on survival. We also evaluated the prognostic value of minimal residual disease (MRD) status at HCT on transplant outcomes among hematological CR patients. MRD status at HCT was the significant prognostic indicator for hematological relapse and survival. These data suggested that allo-HCT offered a curative option for adult AML with 11q23 abnormality. Pretransplant MRD status was the significant prognostic indicator for relapse and survival in CR patients. [ABSTRACT FROM AUTHOR]

In this article the author talks about high prevalence of cholestasis at a tertiary neonatal intensive care unit. Topics discussed include unbound bilirubin is the unbound or "free" form of bilirubin, which is not bound to albumin and is known to be neurotoxic because it can cross the blood-brain barrier, and tertiary neonatal intensive care units (NICUs), preterm as well as surgical and cardiac infants who all have a high risk of developing hyperbilirubinemia are admitted for intensive care.

Myeloid sarcoma (MS) is a rare neoplastic condition that is often described in association with acute myeloid leukemia (AML). MS in childhood has received little attention, particularly in Japan. We carried out a nationwide retrospective analysis of Japanese children diagnosed with MS without bone marrow involvement. Inclusion criteria were diagnosis of MS at younger than 20 years of age between January 1, 2000 and December 31, 2013. There was a predominance of males (8:2), and the median age at MS diagnosis was 4 years. Sites of involvement varied and included skin (n = 3), head and/or neck (n = 2), and multiple sites (n = 2). Karyotypes were evaluated in seven patients, with one individual carrying t(8;21) and t(9;11). Four patients developed bone marrow involvement 2-55 months after diagnosis of MS. All patients received chemotherapy for de novo AML and two individuals received HSCT in first remission. Seven of ten patients survived for 50-152 months (median, 93 months) without disease after initial chemotherapy. This retrospective study confirmed that pediatric MS without bone marrow involvement in Japan is a very rare disease. MS patients responded favorably to therapies for de novo AML, and HSCT in first remission was not indicated for all patients. [ABSTRACT FROM AUTHOR]

The Japan Adult Leukemia Study Group (JALSG) Ph+ALL202 study reported a high complete remission (CR) rate for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients treated with imatinib-combined chemotherapy. However, the long-term treatment efficacy remains uncertain. Here, we report a final analysis of the JALSG Ph+ALL202 study. The outcomes were compared with those of the JALSG ALL93 and ALL97 studies, which were conducted in the pre-imatinib era. Ninety-nine newly diagnosed Ph+ALL patients were enrolled in Ph+ALL202 (median age, 45 years; median follow-up, 4.5 years). CR was achieved in 96/99 (97%) patients. Fifty-nine of these 96 patients (61%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in their first CR (CR1). The 5-year overall and disease-free survival (DFS) rates were 50 and 43%, respectively, which were significantly higher compared to those in the pre-imatinib era (15 and 19%, respectively). Multivariate analysis revealed that imatinib administration, allo-HSCT in CR1, and a white blood cell count < 30 × 109/L were favorable independent prognostic factors for long-term DFS. Improved odds of receiving allo-HSCT and a lower relapse rate leaded to good long-term outcomes. The 3-year DFS tended to be higher in PCR-negative than that in PCR-positive patients (29 vs. 14%) in the non-HSCT patients, and this tendency was also seen in the allo-HSCT patients (59 vs. 50%). The higher rate of CR upon imatinib use may have contributed to these improvements. [ABSTRACT FROM AUTHOR]

Objective: To investigate, how causes of intrauterine fetal death (IUFD) have changed in recent years with the advancement of prenatal diagnosis at a single perinatal center in Japan. Methods: Medical records were retrospectively reviewed for all cases of IUFDs that occurred between 2001 and 2014. The most commonly associated causes of fetal deaths were compared between 2001-2007 and 2008-2014. Results: The number of IUFD after 20 weeks' gestation/ all deliveries in our center was 38/6878 cases (0.53%) in 2001-2007 and 35/7326 (0.48%) in 2008-2014. The leading cause of IUFD in 2001-2007 was fetal abnormalities (43.2%), the prevalence of which was only 8.6% in 2008-2014 (P < 0.01). Meanwhile, the prevalence of umbilical cord abnormalities was relatively increased from 30.0% in 2001-2007 to 54.5% in 2008-2014 (P = 0.06). In 2001-2007, chromosomal abnormalities were frequently observed (56% of IUFDs due to fetal abnormalities). Hyper-coiled cord (HCC) and umbilical ring constrictions were the most frequent cause of IUFD in both periods. The relatively decreased prevalence of IUFD due to velamentous cord insertion and umbilical cord entanglement, HCC and umbilical cord constriction was increased. Conclusions: The prevalence of IUFD due to fetal abnormalities was reduced, but IUFD associated with umbilical cord abnormalities tended to increase relatively. [ABSTRACT FROM AUTHOR]

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan-Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols. [ABSTRACT FROM AUTHOR]

Objective: To investigate the rates of termination of pregnancy (TOP) for fetal chromosomal abnormalities and factors related to such parental decision in Japan.Methods: A multicenter retrospective cohort study of chromosomal abnormalities diagnosed before 22 weeks of gestation between April 2008 and March 2015. The pregnancy outcomes and parental decisions were investigated.Results: Among 931 fetuses with chromosome abnormalities, the total TOP rate was 75.1% (699/931). TOP rates were 89.3% (585/655) in autosomal aneuploidies and 40.8% (51/125) in sex chromosome aneuploidies. Trisomy 21 showed the highest TOP rate (93.8% [390/416]) followed by trisomy 18 (84.5% [163/193]) and trisomy 13 (71.9% [23/32]). Indications for karyotyping were related to a parental decision for TOP (p < 0.01): in cases of autosomal aneuploidy, with fetal abnormal ultrasound findings as the reference value, diagnoses made following positive results at non-invasive prenatal testing (adjusted odds ratio [OR]: 13.7, 95% confidence interval [CI] 4.07-45.9) and those because of advanced maternal age (adj. OR 2.91, 95% CI 1.15-7.35) were significantly more frequent.Conclusions: In Japan, pregnancies with fetal trisomy 21 are more likely to result in TOP when diagnosed in utero than any other chromosome anomaly. The indications for prenatal karyotyping strongly affect the decision to TOP. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses possible gene roles in pediatric high-hyperdiploid acute lymphoblastic leukemia. Topics covered include cAMP-response element binding protein-binding protein (CREBBP), and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation presence in diagnostic and relapse samples, respectively, and the deoxyribonucleic acid (DNA) mismatch repair deficiency via MutS homolog 2 (MSH2) deletion. Also noted is the better treatment of such conditions if identified early.

Objective. Chronic inflammation plays a key role in the development of atherosclerosis. Early progression of atherosclerosis has been reported in patients with RA. Cryopyrin-associated periodic syndromes (CAPS) are autosomal dominant autoinflammatory disorders caused by heterozygous NLRP3 gene mutations. Chronic infantile neurological cutaneous and articular (CINCA) syndrome is the most severe form of CAPS and patients display early onset of rash, fever, uveitis and joint manifestations. However, there has been no previous report on atherosclerosis in patients with CAPS. The objective of this study is to assess the development of atherosclerosis in patients with CINCA syndrome.Methods. Intima–media thickness (IMT) of the carotid arteries, stiffness parameter β, ankle brachial index (ABI) and pressure wave velocity (PWV) were evaluated by ultrasonography in 3 patients with CINCA syndrome [mean age 9.0 years (s.d. 5.3)] and 19 age-matched healthy controls [9.3 years (s.d. 4.3)].Results. The levels of carotid IMT, stiffness parameter β and PWV in CINCA syndrome patients were significantly higher than those in healthy controls [0.51 mm (s.d. 0.05) vs 0.44 (0.04), P = 0.0021; 6.1 (s.d. 1.7) vs 3.9 (1.0), P = 0.0018; 1203 cm/s (s.d. 328) vs 855 (114), P = 0.017, respectively].Conclusion. Patients with CINCA syndrome showed signs of atherosclerosis from their early childhood. The results of this study emphasize the importance of chronic inflammation in the development of atherosclerosis. Further analysis on atherosclerosis in young patients with CINCA syndrome may provide more insights into the pathogenesis of cardiovascular disease. [ABSTRACT FROM PUBLISHER]

Ailanthus altissima is a woody plant that has become invasively naturalized in many countries. Using nuclear SSR markers, we studied specimens of this species collected throughout Japan and found an individual (labeled Aa-1) that was not diploid. We examined pollen morphology and ploidy level of Aa-1 by optical microscopy and flow cytometry (FCM), respectively. Some pollen grains were morphologically abnormal and much larger than normal. FCM analysis demonstrated that Aa-1 was triploid. Formation of abnormal pollen indicates that Aa-1 may well have reduced fertility compared to normal diploids. If this were the case, vegetative progeny Aa-1 could be used as ornamentals without attendant risks of future naturalization. [ABSTRACT FROM AUTHOR]

Aim To establish reference values for the nuchal translucency ( NT) thickness in Japanese fetuses. Material and Methods Ultrasonographic measurements of the crown-rump length ( CRL) and NT were performed from 11 to 13 + 6 weeks of gestation in consecutive Japanese fetuses examined during prenatal visits between February 2011 and January 2012. The median, 5th and 95th percentiles of the NT thickness with 5 mm intervals of the CRL were confirmed. Results A total of 970 cases were enrolled in the study. The median NT thickness for a CRL between 45 and 80 mm ranged from 1.2 mm to 1.9 mm, and the 95th percentile of these values ranged from 2.1 mm to 3.2 mm, respectively. Conclusion The reference values for the NT thickness in Japanese fetuses were determined. These values should be useful for fetal biometry, morphological assessment and first trimester screening for chromosomal abnormalities in Japan. [ABSTRACT FROM AUTHOR]

Abstract: Dental technicians use various materials, particularly metal alloys and monomers and polymers based on methylmethacrylate. Environmental hygiene issues surrounding the work of dental technicians have been recognized. Despite the need for observance of occupational environmental controls and work management, compliance among dental laboratories appears to be low. We evaluated the relationship between genotoxic effects in dental technicians and occupational environmental controls and work management. We used cytokinesis-blocked micronuclei (CB-MN) frequencies in peripheral lymphocytes and metal levels in scalp hair. We also assessed nutritional factors related to anti-genotoxic effects using a self-administered brief diet history questionnaire. Study subjects were 54 male dental technicians and 38 male clerical workers. The parameters on the micronuclei (MN) frequency in dental technicians and clerical workers were analyzed by forward stepwise multiple regression analyses. Age (P <0.01, β =0.561), occupation as a dental technician (P <0.01, β =0.636) and aluminum levels in scalp hair (P <0.05, β =0.213) were risk factors that significantly increased MN frequency. The significant parameters on the MN frequency in dental technicians were observance of hand-washing as work management (P <0.01, β =−0.304), work period (P <0.01, β =0.509), germanium levels in scalp hair (P <0.01, β =−0.314) and workplace (P <0.05, β =0.235). To avoid genotoxic effects, observance of occupational environmental controls and work management is necessary for dental technicians. [Copyright &y& Elsevier]

Objective.We investigated the possible factors related to the birth weight (BW) using the Japanese perinatal database. Methods.The live infants born at 37 to 41 weeks of gestation were enrolled in this study.Caseswith diabetic pregnancy, preeclampsia, an anomalous fetus, and a fetus with chromosomal abnormalities were excluded. A multiple regression analysis for confounding factors and an analysis of covariance (ANCOVA) for comparing the BW in 2006 and 2010 were used for the statistical analysis. Results. The BW significantly decreased from 2950.8 g in 2006 (n = 27, 723) to 2937.5 g in 2010 (n = 38, 008) in the overall population, and this decrease was similar for male and female neonates. All confounding factors, except for the mode of delivery, affected the BW. Primiparity, smoking, and a female gender were related to the decrease in BW, whereas maternal age, maternal height, weight gain during pregnancy, BMI, the use of in vitro fertilization, induction of labor, and gestational duration were related to an increased BW. TheANCOVA showed that no significant change of the BWwas seen between 2006 and 2010 (the difference was 2.164 g, P = 0.414). Conclusion.The gestational duration is the most important factor affecting the BWin singleton term infants. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is primarily caused by deletions involving the paternally derived imprinted region at chromosome 15q11.2-q13 and maternal uniparental disomy 15 (upd(15)mat). The underlying mechanisms for upd(15)mat include trisomy rescue (TR), gamete complementation (GC), monosomy rescue and post-fertilization mitotic error, and TR/GC is mediated by non-disjunction at maternal meiosis 1 (M1) or meiosis 2 (M2). Of these factors involved in the development of upd(15)mat, M1 non-disjunction is a maternal age-dependent phenomenon. We studied 117 Japanese patients with PWS and identified deletions in 84 patients (Deletion group) and TR/GC type upd(15)mat through M1 non-disjunction in 15 patients (TR/GC (M1) group), together with other types of abnormalities. Maternal age was significantly higher in TR/GC (M1) group than in Deletion group (median (range), 37 (35-45) versus 30 (19-42); P=1.0 × 10−7). Furthermore, delayed childbearing age became obvious since the year 2003 in Japan, and relative frequency of TR/GC (M1) group was significantly larger in patients born since the year 2003 than in those born until the year 2002. The results imply that the advanced maternal age at childbirth is a predisposing factor for the development of upd(15)mat because of increased M1 errors. [ABSTRACT FROM AUTHOR]

We designed a treatment protocol for newly diagnosed adult acute lymphoblastic leukemia (ALL) in the pre-imatinib era, employing intensified consolidation therapy with a total of 330 mg/m² doxorubicin and adopting slightly modified induction and maintenance regimen of the CALGB 8811 study. Of 404 eligible patients (median age 38 years, range 15-64 years), 298 (74%) achieved complete remission (CR). The 5-year overall survival (OS) rate was 32%, and the 5-year disease-free survival (DFS) rate was 33%. Of 256 Philadelphia chromosome (Ph)-negative patients, 208 (81%) achieved CR and the 5-year OS rate was 39%, and 60 of them underwent allogeneic-hematopoietic stem cell transplantation (allo-HSCT) from related or unrelated donors during the first CR, resulting in 63% 5-year OS. Of 116 Ph-positive patients, 65 (56%) achieved CR and the 5-year OS rate was 15%, and 22 of them underwent allo-HSCT from related or unrelated donors during the first CR, resulting in 47% 5-year OS. In Ph-negative patients, multivariate analysis showed that older age, advanced performance status and unfavorable karyotypes were significant poor prognostic factors for OS and higher WBC counts for DFS. The present treatment regimen could not show a better outcome than that of our previous JALSG-ALL93 study for adult ALL. [ABSTRACT FROM AUTHOR]

A case study is presented of a 87-year-old man with bruise-like skin lesions on the trunk, thighs and upper arms. It informs that computed tomography images of the whole body showed splenomegaly and mild swelling of the mediastinal and inguinal lymph nodes. It further informs that the patient was diagnosed with leukemic phase blastic plasmacytoid dendritic cell neoplasm (BPDCN) with skin infiltration and concomitant autoimmune hemolytic anemia.

Abstract: This study evaluated the association of the polymorphisms in the Toll-like receptor (TLR)2 and TLR4 genes with acute pancreatitis (AP) in Japan. The numbers of guanine-thymine [(GT) n ] repeats in intron 2 of the TLR2 gene were counted in 202 unrelated patients with AP (80 with severe and 122 with mild disease) and in 286 healthy controls, using polymerase chain reaction and Genescan analysis. The alleles were divided into three subclasses: (GT)16 or less as the S allele; between (GT)17 and (GT)22 as the M allele; and (GT)23 or more as the L allele. Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene were examined by polymerase chain reaction–restriction fragment length polymorphism analysis. Patients with AP had more S alleles (p < 0.001; odds ratio = 2.37; 95% confidence interval = 1.78–3.17) and fewer M alleles (p < 0.001; odds ratio = 0.40; 95% confidence interval = 0.31–0.52) than did healthy controls. Genotypes SS and SL were more common, whereas MM and ML were less common in patients with AP. In subgroup analyses, the genotypes including S alleles were more common in patients with severe AP than in controls. No Asp299Gly and Thr399Ile polymorphisms were detected. In conclusion, microsatellite polymorphism in intron 2 of the TLR2 gene was associated with susceptibility to AP and its severity in Japan. [Copyright &y& Elsevier]

Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p < 0.05). The genome subgroup GG-P2s (partial chromosome gain/loss type with 1p/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p < 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP ≥ 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project. [ABSTRACT FROM AUTHOR]

Karyotypes of Tago’s brown frog Rana tagoi from the Chausu mountains in Minamishinshu of Nagano Prefecture were examined by conventional Giemsa staining, C-banding and late replication (LR)-banding. Chromosome number was 2n = 28 in all cases. The 28 chromosomes consisted of four pairs (1–4) of large biarmed chromosomes, two pairs (5–6) of telocentric chromosomes and eight pairs (7–14) of small biarmed chromosomes. Chromosome pair 11 had a secondary constriction on the long arm. In females, the C-band on the long arm of chromosome pair 6 was detected in both homologs, but was absent from the arms of the homologs of chromosome pairs 5 and 9. In males, C-bands were found in the long arms of both homologs of chromosome pairs 5 and 6, were present only in one homolog of chromosome pair 5 for certain male specimens and found in only one homolog of chromosome pair 9. Specimens of R. tagoi (2n = 28) should thus have two pairs of telocentric chromosomes to provide the same number of chromosome arms, these originating quite likely from chromosome pair 1 in the 26-chromosome specimens by centric fission. Heteromorphic sex chromosomes of the XX-XY type in R. tagoi (2n = 28) in the Chausu mountains were identified. Karyotypes of tail-tip cells from a hybrid tadpole between female R. tagoi (2n = 26) from the Hinohara village in Tokyo and male R. tagoi (2n = 28) from the Chausu mountain population were examined by squash preparation. Chromosome number was 2n = 27 in all tadpoles. The 27 chromosomes consisted of one chromosome set of R. tagoi (2n = 28) and one of R. tagoi (2n = 26). Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder, first described in a Japanese family, showing linkage to chromosome 19q13.4-qter. Recently, mutations have been identified in the PRKCG gene in families with SCA14. The PRKCG gene encodes the protein kinase Cγ (PKCγ), a member of a serine/threonine kinase family involved in signal transduction important for several cellular processes, including cell proliferation and synaptic transmission. To identify the disease-causing mutation in a large group of ataxia patients, we searched for mutations in the PRKCG gene. We ascertained 366 unrelated patients with spinocerebellar ataxia, either pure or with associated features such as epilepsy, mental retardation, seizures, paraplegia, and tremor. A C-to-G transversion in exon 4, resulting in a histidine-to-glutamine change at codon 101 of the PKCγ protein, was identified in patients from a family with slowly progressive pure cerebellar ataxia. Functional studies performed in HEK293 cells transfected with normal or mutant construct showed that this mutation affects PKCγ stability or solubility, verified by time-dependent decreased protein levels in cell culture. In conclusion, the H101Q mutation causes slowly progressive uncomplicated ataxia by interfering with PKCγ stability or solubility, which consequently may cause in either case a decrease in the overall PKCγ-dependent phosphorylation. [ABSTRACT FROM AUTHOR]

On the basis of transplantation data from the Japan Society for Hematopoietic Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at diagnosis on the outcome of transplantation in 628 patients with acute myeloid leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete remission. For autologous SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .017) and a significantly higher event-free survival (EFS) (P = .013) compared with those at intermediate risk. For allogeneic SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at poor risk. For unrelated SCT, there was no significant difference in relapse rate or EFS between patients at good risk and those at intermediate risk. Comparison of the 3 transplantation modalities revealed that autologous SCT patients had a significantly higher incidence of relapse compared with related or unrelated SCT patients in the intermediate-risk group but not in the good-risk group. However, there were no significant differences in EFS among the 3 transplant modalities in either of these 2 risk groups. In multivariate analysis, cytogenetics was found to be an independent predictor of relapse as well as of treatment failure. [ABSTRACT FROM AUTHOR]

Hemophilia A is genetically very heterogeneous because disease-causing mutations involving deletions, point mutations, insertions, and inversions are scattered throughout the factor VIII gene. Of these mutations, inversions, which are intrachromosomal recombinations between int22h-1 (intron 22 homologous region 1) and 1 of 2 other extragenic copies located 500 kilobases upstream, are the more frequently found defects, especially in patients with severe hemophilia A. Reportedly, approximately half of all severe hemophilia A patients have inversions in intron 22. A group of unrelated patients from the middle of Japan with severe hemophilia A were screened by Southern blot analysis for gene inversions. Forty-two of 100 severely affected patients presented factor VIII gene rearrangements. Of these patients, 36 exhibited the distal type of inversion, and 6 exhibited the proximal type. No other variant type of recombination was observed. In this study, neither the prevalence of inhibitor development against factor VIII nor the frequency of sporadic cases in the group presenting gene inversions was significantly different from that in the group without chromosomal inversions. Southern blot analysis successfully detected a carrier in a hemophilia family for which no patient was available. Genetic counseling of patients with severe hemophilia A and their families will be considerably improved, because the inversions occur in 42% of the Japanese patients with severe hemophilia. [ABSTRACT FROM AUTHOR]

Chromosome data pertaining to blood samples from 1,703 survivors of the Hiroshima and Nagasaki A-bombs, were utilized and different models for chromosome aberration dose response investigated. Models applied included those linear or linear-quadratic in equivalent dose. Models in which neutron and gamma doses were treated separately (LQ-L model) were also used, which included either the use of a low-dose limiting value for the relative biological effectiveness (RBE) of neutrons of R 0=70?10 or an RBE value of R 1=15?5 at 1 Gy. The use of R 1 incorporates the assumption that it is much better known than R 0, with much less associated uncertainty. In addition, error-reducing transformations were included which were found to result in a 50% reduction of the standard error associated with one of the model fit parameters which is associated with the proportion of cells with at least one aberration, at 1 Gy gamma dose. Several justifiable modifications to the DS86 doses according to recent nuclear retrospective dosimetry measurements were also investigated. Gamma-dose modifications were based on published thermoluminescence measurements of quartz samples from Hiroshima and on a tentative reduction for Nagasaki factory worker candidates by a factor of 0.6. Neutron doses in Hiroshima were modified to become consistent with recent fast neutron activation data based on copper samples. The applied dose modifications result in an increase in non-linearity of the dose-response curve for Hiroshima, and a corresponding decrease in that for Nagasaki, an effect found to be most pronounced for the LQ-L models investigated. As a result the difference in the dose-response curves observed for both cities based on DS86 doses, is somewhat reduced but cannot be entirely explained by the dose modifications applied. The extent to which the neutrons contribute to chromosome aberration induction in Hiroshima depends significantly on the model used. The LQ-L model including an R 1 value of 15 at 1 Gy which is recommended here, would predict between 10% and 20% of the observed chromosome aberrations to be due to neutrons, at all doses. Because of the good agreement between DS86 predictions and the results of retrospective gamma and neutron dosimetry, the modifications applied here to DS86 doses are relatively small. Consequently, the choices of model and RBE values were found to be the major factors dominating the interpretation of the chromosome data for Hiroshima and Nagasaki, with the dose modifications resulting in a smaller influence. [ABSTRACT FROM AUTHOR]

To clarify the clinical and genetic features of Burkitt lymphoma with or without leukemic presentation, we have conducted clinical, cytogenetic, and genetic studies. Of 40 Japanese patients with Burkitt lymphoma examined by cytogenetic and/or fluorescence in situ hybridization analysis or Southern blot analysis using MYC probes, 35 patients had t(8;14) translocations, and 5 had t(8;22). Breakpoints were located far upstream of MYC in 4 (12%) of 33 tumors with t(8;14), and Epstein-Barr virus infection was found in 3 (8%) of 40 tumors. These findings are similar to those reported for non-Japanese patients with the sporadic form of Burkitt lymphoma. Clinical and genetic characteristic were compared for 30 patients presenting with lymphoma and 10 presenting with leukemia. The overall survival was shorter in aggressively treated leukemia patients than in aggressively treated lymphoma patients (P = .003); however, the incidence rates of TP53 mutation, p16INK4a deletion, and p15INK4b deletion that were found in 6 (15%) of 40,3 (9%) of 35, and 2 (6%) of 35 tumors, respectively, were similar between the 2 subtypes. Thus, the present study has shown the different prognoses for the 2 subtypes of Burkitt lymphoma but has failed to clarify the genetic backgrounds that may explain the different outcomes. [ABSTRACT FROM AUTHOR]

Morphological alterations in the brains of schizophrenia patients suggest that neurodevelopmental dysfunction is involved in the etiology of the disease. Such dysfunction may be due to functional alterations of cell adhesion molecules, which play important roles in cell migration, axonal growth, fasciculation, synaptogenesis, and synaptic remodeling. We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense polymorphism (Leu17Phe) in the signal peptide region was identified. A case-control comparison revealed significantly higher frequencies of the Leu/Leu genotype (P=0.004) and the Leu allele (P=0.006) in 282 Japanese schizophrenic patients than in 229 Japanese control subjects. The estimated odds ratio for schizophrenia was 1.83 (95% CI, 1.28-2.26) for the Leu/Leu genotype compared with the other genotypes. An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Examines the prognostic factors in elderly patients with acute myelogenous leukemia in Japan. Use of anthracyclines for the induction therapy of the disease; Toxicity of intensive chemotherapies; Incidence of chromosomal abnormalities.

We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T-cell lymphoma. A 69-year-old man suffered from cutaneous adult T-cell lymphoma, which was treated with radiation to the skin and combination chemotherapy of CHOP-V-MMV and VEPA-B. After 14 months of these therapies, anemia and thrombocytopenia appeared, and bone marrow aspiration smears showed immature myeloblasts, dysplastic erythroblasts, and micromegakaryocytes. Therapy-related MDS of refractory anemia with an excess of blasts was diagnosed. Cytogenetic study of the bone marrow cells showed 5q- and additional abnormalities. Rearrangement of the MLL gene was observed in the bone marrow cells. Mutations of N-ras codons at 12,13, and 61, p53 tumor suppressor gene, and monoclonal integration of human T-lymphotrophic virus -1 provirus DNA were not observed in the bone marrow cells. The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell lymphoma. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed 336 patients with primary chronic myelofibrosis from 203 medical institutes in Japan. Notwithstanding their heterogeneous treatments, the median survival in 298 patients that could be evaluated was 10.0 years. Average age at onset was 60.7 years. Men were affected 1.4 times more frequently than women. The factors associated with shorter survival included anemia, leukocytosis/leukocytopenia, thrombocytopenia, and increased blasts in the peripheral blood, and sex (male), age (>60), and the presence of symptoms. A new scoring system based on the peripheral blood findings (hemoglobin [Hb] level, platelet count, and rate of blast formation) at initial diagnosis clearly correlated with survival rate. Accordingly, patients could be categorized into 3 groups by severity grading. Through stepwise multivariate survival analysis, the significant prognostic factors were identified as the severity grading based on the new scoring system (P = .0002), age (P = .0024), sex (P = .0153), and Hb (P = .0198). Chromosomal abnormalities were found in 58 of 154 patients (38%), although these did not influence survival. [ABSTRACT FROM AUTHOR]

We assessed a large number of adults (368 from Australia and 494 from Japan) with de novo acute myeloid leukemia (AML) to define the biological differences between the two populations. In this study, AML was classified using the French-American-British (FAB) criteria into seven groups (M1-M7). M2 was more common in Japan than in Australia, whereas M4 occurred more frequently in Australia than in Japan. Other FAB subtypes were evenly distributed. Cytogenetically, Japanese M2 displayed a higher frequency of t(8;21) than Australian (33.1% vs 15.3%, P < 0.05). The t(15;17), inv/del(16), 11q23 aberrations and 5/7/8 abnormalities were seen at similar frequencies. Immunophenotypically, Japanese M4/M5 more frequently displayed CD13 and CD14 than Australian, whereas the stem cell markers, CD34 and HLA-DR were observed at a relatively higher rate in Australian M3 than in Japanese M3. The B cell antigen, CD19 was more frequently seen in Japanese M2 than in Australian M2, but found more often in Australian M5 than in Japanese M5. In both populations, a close relationship was observed between the expression of CD19 and t(8;21). These findings suggest different biological characteristics of AML between the two populations, the main differences being generated by a higher frequency of t(8;21) chromosomal abnormality in Japanese AML. Leukemia(2000) 14, 163-168. [ABSTRACT FROM AUTHOR]

Describes the medical case of a Japanese man with acute minimally differentiated myeloid leukemia with an inversion in the long arm of chromosome 3, inv(3)(q21q26). Medical history and clinical presentation; Low platelet count with megakaryocytic dysplasia at diagnosis; Relationship between the karyotype abnormality and/or thrombopoiesis.

We conducted a collaborative validation study, under the auspices of the Japanese Ministry of Labour, on the in vitro micronucleus test to see if it could be used as an alternative to the in vitro chromosome aberration test for evaluation of chemical safety. We used the Chinese hamster lung cell line (CHL/IU), which is the most widely used system for the latter test in Japan, and evaluated 66 chemicals, including clastogens and polyploidy inducers. The cytochalasin B cytokinesis blocking method, which is commonly used in human lymphocyte culture, was applied to the established cell line, but did not improve the detection of chemically-induced micronuclei in continuously growing cells. The highest micronucleus frequencies were obtained at 48 or 72 h continuous treatments. In short treatments (6 h), a 42 h recovery time yielded the best responses. Concordance between the results of the micronucleus test and the chromosomal aberration test was satisfactorily high (88.7%), and we concluded that the in vitro micronucleus test could be used in place of the chromosomal aberration test as a simple and rapid method for detecting clastogens and aneugens in vitro. We also propose a protocol for the test. [ABSTRACT FROM PUBLISHER]

The incidence of non-familial multiple primary cancer in colorectal cancer patients has increased in recent years in Japan. To clarify the characteristic genetic aberrations in such multiple cancers, we examined structural chromosomal aberrations by fluorescence in situ hybridization, using chromosome 17-specific and p53 cosmid DNA probes. We established short-term cultures of 78 surgical specimens and were able to obtain observable metaphase spreads in 23 single colorectal cancer specimens and in 6 colorectal cancer specimens from patients with double primary cancers. The frequency of chromosome 17 and/or p53 locus translocation was significantly greater in tumors with double cancer than in single colorectal cancers (P < 0.05 and P < 0.01, respectively). These aberrations in double cancers frequently appeared even at an early Dukes' stage (A and B) of colorectal carcinoma. Our results suggest that translocation of chromosome 17 and the p53 locus may be specific genetic events probably associated with carcinogenesis of multiple primary cancers in colorectal cancer. [ABSTRACT FROM AUTHOR]

This article attempts to make clear the incidence of sex chromatin abnormalities for mentally retarded children in Japan. In many cases of sex chromosome abnormality the abnormal neuropsychiatric findings, especially mental retardation, have been well recognized. Thus, sex chromosome abnormalities are more frequent in mentally defective than in mentally normal populations. Sex chromatin screening tests were carried out on buccal mucosal cells and sex chromosome constitutions were confirmed by peripheral blood leucocyte cultures. Eighteen of 2,164 males and 12 of 1,519 females were found to have sex chromatin abnormalities.