Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment

<p>Abstract</p> <p>Background</p> <p>It has been accepted that HIV buds from the cell surface in T lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent studies, on the other hand, suggest that HIV preferentially buds from the cell surface even in monocytic cells. However, most studies are based on observations in acutely infected cells and little is known about HIV budding concomitant with reactivation from latency. Such studies would provide a better understanding of a reservoir for HIV.</p> <p>Results</p> <p>We observed HIV budding in latently infected T lymphocytic and monocytic cell lines following TNF-α stimulation and examined the upregulation of host factors that may be involved in particle production. Electron microscopy analysis revealed that reactivation of latently infected J1.1 cells (latently infected Jurkat cells with HIV-1) and U1 cells (latently infected U937 cells with HIV-1) displayed HIV particle budding predominantly at the plasma membrane, a morphology that is similar to particle budding in acutely infected Jurkat and U937 cells. When mRNA expression levels were quantified by qRT-PCR, we found that particle production from reactivated J1.1 and U1 cells was accompanied by CD44 upregulation. This upregulation was similarly observed when Jurkat and U937 cells were acutely infected with HIV-1 but not when just stimulated with TNF-α, suggesting that CD44 upregulation was linked with HIV production but not with cell stimulation. The molecules in endocytic pathways such as CD63 and HRS were also upregulated when U1 cells were reactivated and U937 cells were acutely infected with HIV-1. Confocal microscopy revealed that these upregulated host molecules were recruited to and accumulated at the sites where mature particles were formed at the plasma membrane.</p> <p>Conclusion</p> <p>Our study indicates that HIV particles are budded at the plasma membrane upon reactivation from latency, a morphology that is similar to particle budding in acute infection. Our data also suggest that HIV expression may lead to the upregulation of certain host cell molecules that are recruited to sites of particle assembly, possibly coordinating particle production.</p

Culturally-adapted resilience-building curriculum for medical students: a comprehensive approach at Showa University School of Medicine, Japan

The growing prevalence of psychological morbidity, depersonalization, and low personal accomplishment among medical students underscores the need for resilience-enhancing programs tailored to their specific needs. Incorporating cultural perspectives and societal context into these interventions is crucial to ensure their effectiveness and relevance. In response, Showa University School of Medicine in Japan has pioneered a culturally-adapted, resilience-based curriculum for medical students from their first through sixth years since 2020. This presentation will outline the comprehensive framework of the resilience-focused curriculum, including course objectives, content, learning resources, timetables, and pedagogical approaches. Key components of the curriculum encompass self-assessment and reflection, stress management strategies, effective communication and conflict resolution skills, and fostering a growth mindset. Additionally, interdisciplinary collaborations with psychology and social work departments provide individual supports and resources for students. Emphasizing the distinct challenges faced by medical students, such as academic stressors, relationships with senior clinical educators, patient and family interactions, and managing errors and burnout, the presentation will highlight the classes on the curriculum, support systems and mentorship programs in promoting mental well-being and resilience. The experiences and outcomes of the 2020-2022 cohorts will be shared, offering valuable insights into the effectiveness of the resilience-building curriculum in the Japanese context. Lessons learned from the implementation process, including challenges faced and strategies employed, will provide practical examples for other medical schools seeking to develop similar programs

A study of x-rays protection in a hip-joint radiography examination

幼小児を含めた若年者の股関節X線撮影検査においては鉛板などで生殖腺を防護して行うのが通常である。男性の場合は生殖腺は体外に露出しているので，それを鉛板で包むようにすればある程度目的は達成される。しかし，女性の場合，生殖腺は骨盤腔内に存在するため，卵巣及び子宮を防護でき診断目的領域にかからないように鉛板を成形し，腹壁上に置いて撮影する。X斬写真上ではグリッドで散乱線を除去しているため，鉛板の陰影がくっきりと撮影され，生殖腺は完全に防護されているように見える。しかし，体内では散乱線によるかなりの被曝があるものと考えられる。そこで今回，鉛板下の散乱線量を鉛板幅及び電圧を変化させ，ファントム内各深さの散乱線量を測定した。その結果，鉛板下の散乱線量が相当量認められ，その量は深さ3～4cmでピークを形成した。鉛板幅による変化は幅が狭いほど線量は大きくなり，電圧による変化は60kVと80kVを比べると80kVの方が多くなった。これを鉛板なしの場合と比較すると，ファントム内意さが増すにしたがい増大した。したがって，臨床において鉛板がずれて再撮影をすることのないよう細心の注意が必要であると考えられた。Usually in a hip-joint radiographic examination for the youth including children, the gonads should be well protected with an appropriate lead shield etc. Since the male gonads are in the outside of the body, if covered with a lead shield, the shield can protect them. However, in the case of the female, since the gonads of exist in a pelvic cavity, the lead shield is cut to a specific pattern so that it can protect the ovaries and the womb, and it is set on the abdomen during the radiographic exposure. Since the scattered radiation on an X-ray film can be removed with the grid, the image of a lead shield is obtained clearly, and the gonads seem to be protected completely. The shield can not protect the gonads of the female from the scattered radiation, though it protects them almost completely from the primary X-rays beam. Therefore, the gonads have radioactive contamination from scattered radiation. Then, in order to estimate the amount of scattered radiation under the lead shield, the dose under the shield was measured by using a phantom in this research, changing lead shield width, the tube-voltage, and the monitoring depth of a phantom. As a results, the dose under the lead shield was observed considerably and showed the peak at the depth of 3 or 4cm. Therefore, it was thought that a careful caution was required for obviating lead shield in clinical

Application of artificial sunlight for the elderly as a possible environmental nursing practice

Aging and aged societies have arrived in many countries where significant development of medicine and the economy has been achieved. Japan is a highly aged society with a shortage of carers both at home and in long-term care settings. In fact, more persons of advanced age who do not need intensive care in hospitals strongly desire health care to be delivered in their own home with their family. Environmental nursing practice, which means that nurses improve the environment of patients or the elderly properly in accordance with healthcare considerations, is currently playing a more important role, not only to prevent the elderly from contracting various diseases, but also to provide a facility for supporting an aged person to live a fulfilling life, preferably one that includes independence. This approach will lead to a reduction in medical expenditure by increasing the number of aged people with healthy longevity without the need for hospitalization or intensive care. This short communication focuses on healthy lighting for the elderly based on our research and experience regarding the beneficial effects of artificial sunlight on nonalcoholic steatohepatitis (NASH), asthma and food allergy, and ulcerative colitis in experimental animal models and clinical settings. Then, we review other studies and discuss how artificial sunlight would be useful for the elderly as one of the environmental nursing practices

Differentiation of murine B cells induced by chondroitin sulfate B

A two-step culture system was used to investigate the role of chondroitin sulfate (CS) B, which is mitogenic to B cells, in differentiation of B cells. Mouse spleen B cells were incubated for 3 days with CSB in the presence of interleukin (IL)-4 and IL-5. After washing, the cells were replated at 10(5) viable cells/well and recultured without CSB in the presence of IL-4 and IL-5. CSB dose-dependently increased IgM production, the greatest enhancement being 450%. Dextran sulfate had a similar effect, whereas other glycosaminoglycans, CSA, CSC, heparin and hyaluronic acid, were marginally effective. Treatment of B cells with CSB resulted in increases in the number of IgM-secreting cells and numbers of CD138-positive cells and CD45R/B220-negative cells. CSB-induced IgM production was inhibited by the protein kinase C (PKC) inhibitor GF109203X but not by the phosphatidylinositol 3-kinase (P13K) inhibitor wortmannin. These results demonstrated that CSB promoted differentiation of B cells in the presence of IL-4 and IL-5 and suggested that PKC but not P13K is crucial for CSB-induced IgM production.</p

Prophylactic clip closure for mucosal defects is associated with reduced adverse events after colorectal endoscopic submucosal dissection: a propensity-score matching analysis

博士（医学）乙日本医科大学202

Neuropeptides and ATP signaling in the trigeminal ganglion

Peripheral nociceptive stimuli from orofacial structures are largely transmitted by the trigeminal nerve. According to the peripheral noxious stimuli, neurons in the trigeminal ganglion (TG) produce neuropeptides such as substance P, and calcitonin-gene-related peptide, etc. Beside the production of neuropeptides, there exists unique non-synaptic interaction system between maxillary and mandibular neurons in the TG. Neurons in the TG are surrounded by satellite glial cells (SGCs), which initially receive the signal from TG neurons. These activated SGCs secrete a transmitter to activate adjacent SGCs or TG neurons, thereby amplifying the signal, for example, from mandibular neurons to maxillary neurons in the TG. Similar to the dorsal root ganglion, in the TG, microglia/macrophage-like cells (MLCs) are activated by uptake of a transmitter from TG neurons or SGCs. This communication between neurons, SGCs, and MLCs results in responses such as ectopic pain, hyperesthesia, or allodynia. The focus of this review is the cooperative interaction of the maxillary and mandibular nerves in the TG by neuropeptides, and adenosine 3′-phosphate (ATP) signaling from neurons to SGCs and MLCs. Stimulated neurons either secrete ATP by means of vesicular nucleotide transporters, or secrete neuropeptides from the neuronal cell body to mediate signal transmission