低蛋白血症で発見された骨髄腫関連疾患の一症例

広義の骨髄腫関連疾患には,古典的なmyelomaを始めとして,plasmacytic leukemia,plasmacytomaさらにmacroglobulinemia,lymphoplasmacytic lymphomaなどが含まれる.一般的には特徴的検査所見の一つに,血清総蛋白の高値がある.ところが,今回我々は血清総蛋白がむしろ低値であった骨髄腫関連疾患を経験した.症例は85歳女性.貧血軽度,黄疸(-),肝脾腫(-),リンパ節腫大(-),骨病変は軽微であった.検査所見:末梢血WBC4370/μl,RBC242万/μl,Hgb8.1g/dl,Hct25.6%,PLT6.2万/μl,Neut70.7%,Lym23.6%,Mono5.0%,Eos0.2%,Bas0.5%.生化学:TP5.3g/dl,Alb2.0g/dl,Glob3.3g/dlそのうちIgG532mg/dl,IgA79mg/dl,IgM2,035mg/dlで,免疫電気泳動にて明らかなM-bowを認め,IgM-_K型と判明した.骨髄:採取した標本では低形成で,Mgk10/μl,赤芽球15.6%,顆粒球系60.3%,リンパ球系23.8%,そのうち形質細胞1.9%であった.形態学的には,マクログロブリン血症の際にみられるリンパ・形質細胞様の所見であった.細胞表面マーカーの検索では,リンパ球全体ではCD7 33.5%,CD138 0.7%,CD19 7.0%,CD20 32.8%,形質細胞ではCD7 21.8%,CD138 57.7%,CD19 21.1%,CD20 39.7%であった.病理検査では,N/C比が高く異型性のある核を持つ細胞のシート状の集簇が認められた.腫瘍細胞の透過型電顕所見では,核は偏在し,大型のゴルジ野を有し,粗面小胞体はよく発達し,蛋白合成の盛んなことが推測された.細胞によっては,分化度が低く核クロマチンは繊細で明らかに芽球様の細胞も認められた.染色体分析:46,XX.末梢血生化学所見では総蛋白量の明らかな減少が認められたが,その病因は腫瘍細胞によるIgMの過剰産生にあり,その腫瘍性性質のため正常免疫グロブリン特にIgGおよびIgAの著しい産生抑制を生じたものと考えられる.細胞学的にはマクログロブリン血症と多発性骨髄腫とにまたがる境界領域に位置付けられるBリンパ球系悪性疾患と推定される.It is known that myeloma-related disorders include classical myeloma, plasmacytic leukemia, plasmacytoma, macroglobulinemia, lymphoplasmacytic lymphoma and others. Increased serum protein is one of the characteristic features in these disorders. We have recently experienced a case of myeloma-related disorder with hypoproteinemia. The patient (a 85 year-old female) demonstrated hypoproteinemia (total protein 5.3g/dl, Alb2.0g/dl, Glob3.3g/dl) with increased IgM 2,035mg/dl contrary to decreased IgG(532mg/dl) and IgA(79mg/dl). The presence of IgM-_K monoclonality was detected by immunoelectrophoresis. Peripheral blood showed slight anemia(RBC 2.42×10^6/μl) and thrombocytopenia(62×10^3/μl). Peripheral lymphocytes were 23.6% with lymphoplasmacytic appearance. Bone marrow examination revealed that lymphocytes were 23.8% with 1.9% of plasma cells: CD79a(+), CD138(+/-), CD20(+/-), CD5(-), cyclin D1(-), IgM(+), IgA(-), IgG(+-), and IgM_K -monoclonality(+) by immune staining method. Surface makers of all lymphoid cells indicated CD138 57.7%, CD19 21.1%, and CD20 39.7%. Clusters of malignant lymphoid cells were present in bone marrow specimen. Transmission electron microscopy (TEM) on the lymphoid cells indicated the dislocated nucleus and profound rough-surfaced ribosomes with large Golgi apparatus suggesting the markedly enhanced protein production. In some cells, the blastic appearance with fine nuclear chromatin structure was observed. The pathogenesis of hypoproteinemia appears to be due to suppression of IgG and IgA by increased IgM monoclonality, in addition to decreased level of serum albumin. The disorder is considered to be localized at the border area between classical myeloma and macroglobulinemia

Identification of a GTPase-activating protein homolog in Schizosaccharomyces pombe.

Loss of function of the Schizosaccharomyces pombe gap1 gene results in the same phenotypes as those caused by an activated ras1 mutation, i.e., hypersensitivity to the mating factor and inability to perform efficient mating. Sequence analysis of gap1 indicates that it encodes a homolog of the mammalian Ras GTPase-activating protein (GAP). The predicted gap1 gene product has 766 amino acids with relatively short N- and C-terminal regions flanking the conserved core sequence of GAP. Genetic analysis suggests that S. pombe Gap1 functions primarily as a negative regulator of Ras1, like S. cerevisiae GAP homologs encoded by IRA1 and IRA2, but is unlikely to be a downstream effector of the Ras protein, a role proposed for mammalian GAP. Thus, Gap1 and Ste6, a putative GDP-GTP-exchanging protein for Ras1 previously identified, appear to play antagonistic roles in the Ras-GTPase cycle in S. pombe. Furthermore, we suggest that this Ras-GTPase cycle involves the ra12 gene product, another positive regulator of Ras1 whose homologs have not been identified in other organisms, which could function either as a second GDP-GTP-exchanging protein or as a factor that negatively regulates Gap1 activity

Caregivers' mental distress and child health during the COVID-19 outbreak in Japan.

To clarify the physical and mental conditions of children during the coronavirus disease 2019 pandemic and consequent social distancing in relation to the mental condition of their caregivers. This internet-based nationwide cross-sectional study was conducted between April 30 and May 13, 2020. The participants were 1,200 caregivers of children aged 3-14 years. Child health issues were categorized into "at least one" or "none" according to caregivers' perception. Caregivers' mental status was assessed using the Japanese version of the Kessler Psychological Distress Scale-6. The association between caregivers' mental status and child health issues was analyzed using logistic regression models. Among the participants, 289 (24.1%) had moderate and 352 (29.3%) had severe mental distress and 69.8% of children in their care had health issues. The number of caregivers with mental distress was more than double that reported during the 2016 national survey. After adjusting for covariates, child health issues increased among caregivers with moderate mental distress (odds ratio 2.24, 95% confidence interval 1.59-3.16) and severe mental distress (odds ratio 3.05, 95% confidence interval 2.17-4.29) compared with caregivers with no mental distress. The results highlight parents' psychological stress during the pandemic, suggesting the need for adequate parenting support. However, our study did not consider risk factors of caregivers' mental distress such as socioeconomic background. There is an urgent need for further research to identify vulnerable populations and children's needs to develop sustainable social support programs for those affected by the outbreak

Effect of birth season on allergic rhinitis and cedar pollinosis considering allergen and vitamin D exposure: The Japan Environment and Children's study (JECS)

Background: The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account. Methods: This study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders. Results: Participants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13–3.82 for spring; aOR: 1.89, 95% CI: 1.03–3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10–2.15; Der f 1, aOR: 1.44, 95% CI: 1.03–2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively. Conclusions: Spring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required

Obesity as a potential risk factor for stillbirth: The Japan Environment and Children’s Study

The relationship between high body mass index (BMI) >25 kg/m2 and risk for stillbirth in the Japanese population remains unclear. This study aimed to estimate the impact of maternal obesity on the risk of stillbirth in a Japanese population. This prospective cohort study used data from the Japan Environment and Children’s Study, which recruited pregnant individuals between 2011 and 2014. A total of 93,772 fetuses were considered eligible for inclusion in this study. Stillbirth (fetal death before or during labor at ≥22 completed weeks of gestation) rates were compared among four pre-pregnancy BMI groups: underweight (<18.5 kg/m2), reference (18.5 to <25.0 kg/m2), overweight (25.0 to <30.0 kg/m2), and obese (≥30.0 kg/m2). The association between pre-pregnancy BMI and the risk of stillbirth was estimated using multiple logistic regression analyses. The overall stillbirth incidence was 0.33% (305/93,722). Compared with the reference group, the risk of stillbirth was significantly higher in the overweight group (adjusted odds ratio [aOR]: 1.55; 95% confidence interval [CI]: 1.08–2.23) and the obese group (aOR: 2.60; 95% CI: 1.59–4.24). The overall incidence of early stillbirth (i.e., <28 weeks) was 0.17% (155/93,722). Similarly, after adjusting for potential confounding factors, the risk of early stillbirth was significantly higher in the obese group (aOR: 4.33; 95% CI: 2.44–7.70). Increased maternal BMI was associated with an increased risk of stillbirth in the Japanese population. Therefore, counselling women planning for pregnancy on the importance of an appropriate pre-pregnancy BMI to minimize the risk of stillbirth is important

Mutation in Sodium-Glucose Cotransporter 2 Results in Down-Regulation of Amyloid Beta (A4) Precursor-Like Protein 1 in Young Age, Which May Lead to Poor Memory Retention in Old Age

Senescence-accelerated mouse prone 10 (SAMP10) exhibits cerebral atrophy and depression-like behavior. A line of SAMP10 with spontaneous mutation in the Slc5a2 gene encoding the sodium-glucose cotransporter (SGLT) 2 was named SAMP10/TaSlc-Slc5a2slc (SAMP10-&Delta;Sglt2) and was identified as a renal diabetes model. In contrast, a line of SAMP10 with no mutation in SGLT2 (SAMP10/TaIdrSlc, SAMP10(+)) was recently established under a specific pathogen-free condition. Here, we examined the mutation effect in SGLT2 on brain function and longevity. No differences were found in the survival curve, depression-like behavior, and age-related brain atrophy between SAMP10-&Delta;Sglt2 and SAMP10(+). However, memory retention was lower in SAMP10-&Delta;Sglt2 mice than SAMP10(+). Amyloid beta (A4) precursor-like protein 1 (Aplp1) expression was significantly lower in the hippocampus of SAMP10-&Delta;SGLT2 than in SAMP10(+) at 2 months of age, but was similar at 12 months of age. CaM kinase-like vesicle association (Camkv) expression was remarkably lower in SAMP10(+). These genes have been reported to be involved in dendrite function. Amyloid precursor proteins have been reported to involve in maintaining homeostasis of glucose and insulin. These results suggest that mutation in SGLT2 results in down-regulation of Aplp1 in young age, which can lead to poor memory retention in old age

Exposure to House Dust Mite Allergen and Endotoxin in Early Life and Sensitization and Allergic Rhinitis: The JECS

The association between endotoxin and allergic rhinitis (AR) is not conclusive. The aim of this study was to determine the association between endotoxin and house dust mite (HDM) allergens in dust, and HDM sensitization and AR among Japanese infants. This study included 4188 participants in the Sub-Cohort Study of the Japan Environment and Children&rsquo;s Study. Dust was collected from children&rsquo;s mattresses at age 18 months and endotoxin and HDM allergen levels were measured. A logistic regression model was used to analyze the association between endotoxin or HDM allergen and the sensitization to HDM (specific-IgE) at age 2 and AR at age 3. The median (interquartile range) endotoxin level was 375.1(186.9&ndash;826.5) EU/m2 and the Der 1 (Der p 1 + Der f 1) level was 51.2 (14.8&ndash;168.6) ng/m2. There were significant positive associations between endotoxin and HDM sensitization (Der f 1, adjusted odds ratio [aOR] quartile [Q] 4 vs. Q1, 1.44, 95% CI, 1.04&ndash;2.00; Der p 1, aOR Q4 vs. Q1, 1.56, 95% CI, 1.12&ndash;2.16). There were also significant positive associations between Der 1 exposure and HDM sensitization (Der f 1, aOR Q3 vs. Q1, 1.75, 95% CI, 1.26&ndash;2.44; aOR Q4 vs. Q1, 2.98, 95% CI, 2.15&ndash;4.13; Der p 1, aOR Q3 vs. Q1, 1.91, 95% CI, 1.37&ndash;2.66; aOR Q4 vs. Q1, 2.91, 95% CI, 2.09&ndash;4.05). There were, however, no associations between endotoxin or Der 1 and AR. In the population residing mostly in non-farming settings, both endotoxin and HDM allergens in dust were associated with an increased risk of HDM allergen sensitization, but not with AR

Appropriate procedures to increase the adherence of children to blood collection: A cross‐sectional study

Abstract Background and Aim Venipuncture for blood collection elicits fear and pain in children. We investigated factors that affect satisfaction with health checkups that included blood collection in healthy 7–8‐year‐old children who underwent blood collection with topical anesthesia. Method Two studies, one questionnaire survey, and the other structured interviews were conducted to gather insights and understand the emotions of 492 and 20 children, respectively. Results We found that the following six points can be applied to encourage children to assess their experience of blood collection positively: (1) prior information using a pamphlet; (2) telling the children that the volume of blood drawn will be small; (3) carefully explaining the risk and benefit of topical anesthesia; (4) conducting the blood collection process swiftly; (5) praising and thanking the children's effort and cooperation; and (6) explaining the results of the research to the children if their blood is going to be used for research. Conclusion The findings indicate that with appropriate measures to reduce pain and fear, children's initial negative feelings toward blood collection can be replaced by positive feelings after the procedure