大腿骨頭靭帯の組織学的および分子学的特性に関する研究

The ligamentum capitis femoris (LCF) has increased in clinical significance through the development of hip arthroscopy. The histological pathologies and molecular composition of the femoral attachment of the LCF and the degeneration caused by LCF disruption were investigated in the human hip joint. Twenty-four LCFs were retrieved at surgery for femoral neck fracture (age range: 63–87 years). In the “intact” (i.e., intact throughout its length, n = 12) group, the attachment consisted of rich fibrocartilage. Fibrocartilage cells were present in the midsubstance. In contrast, the construction of the attachment in the “disrupted” (i.e., ligament no longer attached to the femoral head, n = 12) group had disappeared. The attachment in the disrupted group was not labeled for type II collagen or aggrecan, while that in the intact group was labeled for types I, II and III collagen, chondroitin 4-sulfate, chondroitin 6-sulfate, aggrecan, and versican. The percentage of single-stranded DNA-positive chondrocytes was significantly higher in the disrupted group than in the intact group. We conclude that the femoral attachment of the LCF has a characteristic fibrocartilaginous structure that is likely to adjust to the mechanical load, and suggest that its degeneration is advanced by disruption and should be regarded as a clinical pathology.博士（医学）・乙第1353号・平成27年3月16日© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Structure and Function of Myosin Isoforms in Adult Chicken Hindlimb Muscles

Although large accumulation of sequence data is published for a variety of myosin heavy chain (MHC) isoforms, the meaning of heterogeneity among the amino acid sequences remains unclear as to the key contractile and biochemical properties of muscle fibres. In the present study, we studied on MHC isoforms in three adult chicken hindlimb muscles: ilio-tibialis, gastrocnemius and femoritibialis) and pectoralis muscle, by means of in vitro motility assay and measurement of ATPase activity. The motility speed of myosins and ATPase activities of myofibrils extracted from the hindlimb muscles were significantly lower than those from the pectoralis muscle consisting of a homogeneous MHC (P-type). ATPase activity of femori-tibialis myofibril was remarkably lower than those of ilio-tibialis and gastrocnemius myofibrils. We found the differential expression of MHC isoforms in these muscles by northern blot analysis. Furthermore, we determined the amino acid sequences of the 23kDa, 50kDa and 20kDa fragments from a major MHC isoform (G-type) found in the three hindlimb muscles. There was approximately 4.3% amino acid difference between G-type and P-type, however the characteristically methylated amino acids were recognized in the G-type at the same residues as in the P-type. In the course of sequencing the 20kDa fragment from femori-tibialis muscle myosin, we found another MHC isoform (F-type). Contentratios of P-type, G-type and F-type were about 3 : 7 : 0 in ilio-tibialis, 2 : 7 : 0 in gastrocnemius, and 1 : 6 : 3 in femori-tibialis, respectively. All these data suggest that the motility speed of myosin and ATPase activity of myofibril correlate with the content-ratio of the MHC isoforms in each muscle

内反小趾変形のX線学的形態の特徴

Background: Bunionette deformity is characterized as head hypertrophy, lateral bowing, or splaying of the fifth metatarsal, or a combination of these deformities. Most previous studies have focused on the fourth and fifth metatarsals; few have analyzed the radiographic morphologic characteristics of the entire foot. The morphologic characteristics of the entire foot in cases of symptomatic bunionette deformity were analyzed with a radiographic image-mapping system. Methods: The system was used for the morphologic analysis of 112 feet with symptomatic deformity and 123 asymptomatic control feet. The mapping system includes 2-dimensional coordinates. We compared morphologies of both groups on the basis of simple models prepared from x and y coordinates of each reference point, calculated by using the mapping system and various angle measurements. We set cutoff values and categorized cases according to Fallat’s system. We evaluated the characteristics of each type and a new deformity type (type V) wherein no measurement exceeded the cutoff values. Results: The heads of the third, fourth, and fifth metatarsals were more laterally displaced, and the angles between the metatarsal axes were larger in the deformity group. Comparison of deformity types showed that the morphology of the fifth metatarsal might be only one cause of deformity. The intermetatarsal angles between the second and third metatarsals and between the third and fourth metatarsals were larger in deformity type II and type V feet than in control feet. Additionally, the intermetatarsal angles between the third and fourth metatarsals and between the fourth and fifth metatarsals were larger in deformity type III and type IV feet than in control feet. Conclusion: We believe it is necessary to not only focus on the fourth and fifth metatarsals, but also assess the morphologic characteristics of the entire foot in patients with a bunionette, including splaying of all the metatarsals and the forefoot width, when planning surgery. Level of Evidence: Level III, retrospective comparative study.博士（医学）・甲第651号・平成28年3月15日© The Author(s) 2015Copyright © 2016 by American Orthopaedic Foot & Ankle SocietyThe definitive version is available at " http://dx.doi.org/10.1177/1071100715614923

A case of a chronic expanding hematoma in a hemodialysis patient

A 70-year-old woman undergoing chronic maintenance hemodialysis had felt a mass in her left hip 4 years prior. As the mass gradually expanded, magnetic resonance imaging (MRI) was performed. The MRI findings showed mosaic patterns with various signal intensities inside the mass and a low-signal band at its periphery. Because of the slow expansion of the mass over a course of at least 4 years and its characteristic MRI findings, the patient was diagnosed with a chronic expanding hematoma (CEH), a comparatively rare type of hematoma. To our knowledge, this is the first report of a CEH occurring in a hemodialysis patient in the English literature

血液透析患者の栄養状態ならびに栄養摂取状況が生活の質(QOL)に及ぼす影響

血液透析患者において透析治療を長期に継続していく上で種々の透析合併症の予防のため適切な食事療法の実践が重要である｡厳格な食事療法は生活の質(QOL)や栄養状態の低下に繋がる可能性もある｡本研究では､外来血液透析患者70名を対象に栄養摂取状況と栄養状態及び QOL について評価､解析を行った｡その結果､約30%の患者が栄養状態にﾘｽｸありと判定された｡栄養状態と食事摂取量には相関は認められなかったが､栄養状態が低下した群では､豆類の摂取量が少なかった｡透析患者の栄養状態と QOL を詳細に解析すると女性は栄養状態が低下しても包括的尺度(SF-36)､腎疾患特異的尺度ともに比較的維持されていたが､男性は栄養状態の悪化により有意な低下が認められた｡SF-36 では身体的健康度だけでなく､精神的健康度も悪化していた｡男性患者にはより早期からの栄養面での管理と指導が重要であり､またきめ細やかなｹｱや周囲の人々からの精神的な支えや理解が大切である｡For patients undergoing long-term hemodialysis treatment, appropriate nutrition therapy is important to prevent complications. However, strict dietary regimens sometimes reduce the Quality of Life(QOL)and nutritional status. In this study, we examined and analyzed the nutrient intake, nutritional status, and QOL of 70 outpatients undergoing hemodialysis. As the results, approximately 30% of the subjects were judged to have nutritional problems. Although no association was observed between the nutritional status and amount of food intake, the consumption of bean products was lower in subjects with a reduced nutritional status. Analysis of the nutritional status and QOL of the dialysis patients showed that female subjects had favorable scores on the Short-Form 36(SF-36)Health Survey and Kidney Disease Quality of Life(KDQOL)despite a reduction in the nutritional status; however, a significant score reduction was observed in male subjects in association with the deterioration of their nutritional status. The results of SF-36 showed not only physical, but also mental health deteriorations. For male patients, early dietary interventions and guidance, as well as thoughtful care, emotional support, and understanding from people around them are essential

Epidemiology and Clinical Features of Pulmonary Nontuberculous Mycobacteriosis in Nagasaki, Japan

Background and Objectives: Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan. Methods: The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features. Results: A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up. Conclusions: The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region

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

In Vitro and In Vivo Activities of Novel Fluoroquinolones Alone and in Combination with Clarithromycin against Clinically Isolated Mycobacterium avium Complex Strains in Japan▿

The recommended treatments for Mycobacterium avium complex (MAC) infectious disease are combination regimens of clarithromycin (CLR) or azithromycin with ethambutol and rifamycin. However, these chemotherapy regimens are sometimes unsuccessful. Recently developed antimicrobial agents, such as newer fluoroquinolones (FQs) containing C-8 methoxy quinolone (moxifloxacin [MXF] and gatifloxacin [GAT]), are expected to be novel antimycobacterial agents. Here, we evaluated the in vitro and in vivo antimycobacterial activities of three FQs (MXF, GAT, and levofloxacin) and CLR against clinically isolated MAC strains. Subsequently, the in vitro and in vivo synergic activities of FQ-CLR combinations against MAC strains were investigated. CLR and the individual FQs alone showed promising activity against MAC strains in vitro, and the bacterial counts in organs (lungs, liver, and spleen) of MAC-infected mice treated with single agents were significantly reduced compared to control mice. CLR showed the best anti-MAC effect in vivo. When the three FQs were individually combined with CLR in vitro, mild antagonism was observed for 53 to 57% of the tested isolates. Moreover, mice were infected with MAC strains showing mild antagonism for FQ-CLR combinations in vitro, and the anti-MAC effects of the FQ-CLR combinations were evaluated by counting the viable bacteria in their organs and by histopathological examination after 28 days of treatment. Several FQ-CLR combinations exhibited bacterial counts in organs significantly higher than those in mice treated with CLR alone. Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required