ペルーの人工変形頭蓋正中矢状面輪郭における若干の顔面角について

ペルー人男性の前頭後頭型人工変形頭蓋における頭蓋型と，正中矢状面輪郭上の歯槽性突顎に関連する若干の角について調べた．変形頭蓋は非常に大きな頭蓋示数を有するが，頭蓋モズルスは非変形頭蓋との間に有意差がなかった．Basion （Ba）-Nasion （Na）-Prosthion （Pr）角とBa-Na-Subspinale （Ss）角における両頭蓋間の差は有意であった．これに対し，Na-Pr線，Na-Ss線とフランクフルト面（FHP）のなす角度の差は有意でなかった．また，Na-Ba線とFHPとのなす角に有意差が認められた．これらの結果から人工変形はNa-Ba線の位置変化をもたらすが，歯槽性突顎の形態には影響を与えないことが示唆される．Three principal cranial dimensions and six angles on sagittal cranial profile related with facial prognathism, between artificially front-occipital deformed and undeformed Peruvian skulls were examined. The deformed skull group was characterized by a shorter and wider neurocranial vault. Angular analyses suggested that the skull deformation caused displacement of the basion-nasion line. However, the significant difference in the facial prognathism between the deformed and undeformed skulls could not be confirmed in this craniogeometric study

解剖実習体の膝関節にみられた円板状外側半月の一例について-特に関節内靱帯との関係-

65歳男性遺体の右膝に見いだされた円板状外側半月を観察し，特に関節内付属靱帯との関係を記載した．円板状外側半月は比較的幅広く，脛骨の外側顆上関節面をほぼ完全に被い，肉眼的観察およびX線撮影ではその損傷や石灰化などの異常は見られなかった．本例では，全体的に半月の固定に関係する靱帯の発達が良好であった．すなわち，半月の前角と後角は靱帯を介して強固に脛骨に付着し，さらに，強い半月横靱帯が内・外側半月の前部を連結していた．後方では外側半月後角から起こる太い後半月大腿靱帯が認められた．加えて，内側・外側半月の前角から起こり前十字靱帯に合流する靱帯小束が認められたが，これらは半月の前部固定に関与すると考えられた．The right knee, from a male cadaver aged 65, with discoid lateral meniscus was carefully dissected. The meniscus and its anatomical relationships with some associated ligaments of the knee are described. The discoid meniscus was a wide structure covering nearly the articular surface of the tibia and was almost intact macroscopically. Neither meniscal calcification nor ossification was demonstrated by radiography. There were strong transverse ligament, solid attachments from both anterior and posterior horns to the tibia, distinct posterior menisco-femoral ligament, and ligamentous slips from both anterior horns of the medial and lateral menisci to the anterior cruciate ligament. The knee anatomy was characterized by the well-development attachment system of the menisci. The medial meniscus was anatomically normal

Periarticular Osteophytes as an Appendicular Joint Stress Marker (JSM): Analysis in a Contemporary Japanese Skeletal Collection

Objective: The aim of this study was to investigate the possibility that periarticular osteophytes plays a role as a appendicular joint stress marker (JSM) which reflects the biomechanical stresses on individuals and populations. Methods: A total of 366 contemporary Japanese skeletons (231 males, 135 females) were examined closely to evaluate the periarticular osteophytes of six major joints, the shoulder, elbow, wrist, hip, knee, and ankle and osteophyte scores (OS) were determined using an original grading system. These scores were aggregated and analyzed statistically from some viewpoints. Results: All of the OS for the respective joints were correlated logarithmically with the age-at-death of the individuals. For 70 individuals, in whom both sides of all six joints were evaluated without missing values, the age-standardized OS were calculated. A right side dominancy was recognized in the joints of the upper extremities, shoulder and wrist joints, and the bilateral correlations were large in the three joints on the lower extremity. For the shoulder joint and the hip joint, it was inferred by some distinctions that systemic factors were relatively large. All of these six joints could be assorted by the extent of systemic and local factors on osteophytes formation. Moreover, when the age-standardized OS of all the joints was summed up, some individuals had significantly high total scores, and others had significantly low total scores; namely, all of the individuals varied greatly in their systemic predisposition for osteophytes formation. Conclusions: This study demonstrated the significance of periarticular osteophytes; the evaluating system for OS could be used to detect differences among joints and individuals. Periarticular osteophytes could be applied as an appendicular joint stress marker (JSM); by applying OS evaluating system for skeletal populations, intra-skeletal and inter-skeletal variations in biomechanical stresses throughout the lives could be clarified

Characterization of Individuals with Sacroiliac Joint Bridging in a Skeletal Population: Analysis of Degenerative Changes in Spinal Vertebrae

Theaimof this study was to characterize the individualswith sacroiliac joint bridging (SIB) by analyzing the degenerative changes intheirwhole vertebral column and comparing themwith the controls.Atotal of 291modern Japanesemale skeletons,with an averageage at death of 60.8 years, were examined macroscopically. They were divided into two groups: individuals with SIB and thosewithout bridging (Non-SIB).The degenerative changes in their whole vertebral column were evaluated, and marginal osteophytescores (MOS) of the vertebral bodies and degenerative joint scores in zygapophyseal jointswere calculated. SIBwas recognized in 30individuals froma total of 291 males (10.3%).The average of age at death in SIB group was significantly higher than that in Non-SIBgroup. The values ofMOS in the thoracic spines, particularly in the anterior part of the vertebral bodies, were consecutively higherin SIB group than in Non-SIB group. Incidence of fused vertebral bodies intervertebral levels was obviously higher in SIB groupthan in Non-SIB group. SIB and marginal osteophyte formation in vertebral bodies could coexist in a skeletal population of men.Some systemic factors might act on these degenerative changes simultaneously both in sacroiliac joint and in vertebral column

Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Chlorella extract （CE） has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin （OVA）-induced airway hyperresponsiveness （AHR） and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups: a control group （no OVA exposure, not given CE）, a CE group （no OVA exposure, given CE）, an asthma group （sensitized/challenged with OVA, not given CE） and a CE＋asthma group （sensitized/challenged with OVA, given CE）. In the asthma and CE＋asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE＋asthma groups, the mice were given feed containing 2％ CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage fluid （BALF）, serum, lung tissue and spleen cells. Administration of CE was associated with significantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines （IL-4, IL-5 and IL-13） in BALF. In addition, administration of CE significantly decreased the numbers of periodic acid-Schiff （PAS）-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma

Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis

Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility

Preterm toddlers have low nighttime sleep quality and high daytime activity.

A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers’ waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development

上腸間膜動脈限局性の高安動脈炎の一例

腹痛を呈した上腸間膜動脈（superior mesenteric artery: SMA）に限局した高安動脈炎の一例を経験したので，文献的考察を加えて報告する．症例は17歳，男性．心窩部痛・右背部痛を認め，近医を受診し，その際施行した体外式腹部超音波検査（ultrasound: US）でSMA の壁肥厚が疑われ，当院総合診療科を紹介受診した．身体診察では上腹部正中に軽度圧痛を認め，血液生化学検査では血沈（60min）35mm, CRP 3.92mg/dL と軽度上昇を認めた．US では，腹痛を訴える部位に一致してSMA 起始部にびまん性の壁肥厚を認め，血管炎が疑われた．胸部造影・上腹骨盤部単純造影CT 検査（computed tomography: CT）ではSMA 周囲に造影効果を認める軟部影を認め，18F-FDGPET（18F-fluorodeoxyglucose positron emission tomography: PET）/CT 検査ではSMA 起始部付近に腫大と軽度のFDG 集積を認め，動脈炎による集積で矛盾しない所見であった．以上のことから，SMA に限局した高安動脈炎と診断した．ステロイド治療を開始し腹痛は速やかに消褪すると共に，US 所見にも改善がみられた．We report the case of a 17-year-old male who visited a hospital complaining of epigastric and right back pain. Thickening of the wall of the superior mesenteric artery （SMA) was suspected by ultrasound （US), and he was referred to our hospital. Physical examination revealed median upper abdominal tenderness. Laboratory tests showed an erythrocyte sedimentation rate （60 min) of 35 mm and C-reactive protein of 3.92mg/dL. US examination in our hospital showed diffuse wall thickening at the origin of the SMA. Because the location of the pain and the affected area identified by US were the same, we suspected angiitis. An enhanced area around the SMA was revealed by computed tomography. 18F-fluorodeoxyglucose positron emission tomography/computed tomography showed swelling at the origin of the SMA and mild accumulation of fluorodeoxyglucose. He was diagnosed with Takayasu arteritis involving the SMA. Steroid therapy was started, and his abdominal pain and US findings improved

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target