Enhanced anti-HIV-1 activity of CC-chemokine LD78β, a non-allelic variant of MIP-1α/LD78α

AbstractWe compared the anti-HIV-1 activity of CC-chemokine LD78β with that of MIP-1α, another CC-chemokine which shows 94% sequence homology with LD78β. Despite its close similarity to MIP-1α, the anti-HIV-1 activity of LD78β appeared to be nearly 10 times higher than that of MIP-1α. Mutagenesis of MIP-1α showed that the N-terminal additional tetrapeptide, which was present in LD78β and absent in MIP-1α, is responsible for enhanced anti-HIV-1 activity. The N-terminal structure-function relationship of LD78β described here will be of value in understanding the chemokine-receptor interactions and designing anti-HIV-1 compounds based on LD78β

A Case of Microscopic Polyangiitis Following Mycoplasma Infection in a Patient with MPO-ANCA Positive Pulmonary Fibrosis

ABSTRACTBackgroundMicroscopic polyangiitis is a vasculitic disease that may result in a pulmonary renal syndrome. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis is strongly associated with infection.Case SummaryWe describe a case of microscopic polyangiitis that developed in a patient with MPO-ANCA positive pulmonary fibrosis following infection with mycoplasma. A renal biopsy was undertaken following the detection of microscopic hematuria during follow-up but no abnormal findings were evident. The MPO-ANCA titer increased following infection with mycoplasma pneumonia and a second renal biopsy demonstrated crescentic glomerulonephritis. The degree of pulmonary fibrosis was unaffected.DiscussionThe present case suggests that the mycoplasma infection triggered the elevation of MPO-ANCA titer and provoked glomerulonephritis in a patient with MPO-ANCA positive IPF. This case indicates the importance of testing for MPO-ANCA at the time of initial diagnosis, performing urinalysis and examining the urine sediment during follow-up and being alert to the potential onset of vasculitis in cases of pulmonary fibrosis

24-hour intraocular pressure in glaucoma patients randomized to receive dorzolamide or brinzolamide in combination with latanoprost

Yoshimi Nakamura, Shusaku Ishikawa, Yuko Nakamura, Hiroshi Sakai, Ichiko Henzan, Shoichi SawaguchiDepartment of Ophthalmology, University of the Ryukyus Faculty of Medicine, Okinawa, JapanPurpose: To investigate the efficacy of dorzolamide 1% (bid or tid) or brinzolamide 1% bid on 24-hour intraocular pressure (IOP) control as well as patients’ preference for either drug when added in combination with latanoprost against glaucoma (IOP, ≥18 mmHg).Methods: In this randomized crossover study patients were assigned to receive latanoprost plus either dorzolamide or brinzolamide for four weeks. Thereafter, patients underwent 24-hour IOP monitoring while continuing to receive dorzolamide (for two successive days/nights: at first bid then tid) or brinzolamide bid (once overnight). They were then switched over to receive the other test medication for a further four weeks and subsequently reexamined for 24-hour IOP. A questionnaire survey on treatment satisfaction was performed.Results: In 20 patients dorzolamide bid or tid or brinzolamide bid exerted significant (p < 0.001) reductions of IOP from baseline at all time-points over 24 hours; no difference was detected among the treatment regimens. Significantly (p < 0.05) more patients preferred dorzolamide (n = 9) over brinzolamide (n = 2), whereas nine patients gave a neutral answer. Conclusion: Dorzolamide bid or tid and brinzolamide bid when combined with latanoprost therapy elicited significant IOP reduction for 24 hours. It is rational to consider patients’ preference of therapeutic regimen especially long-term users such as those with glaucoma.Keywords: glaucoma, brinzolamide, dorzolamide, latanoprost combination therapy, 24-hour intraocular pressure (IOP), questionnaire surve

PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy

Phosphoinositides regulate a wide range of cellular activities, including membrane trafficking and biogenesis, via interaction with various effector proteins that contain phosphoinositide binding motifs. We show that in the yeast Pichia pastoris, phosphatidylinositol 4′-monophosphate (PI4P) initiates de novo membrane synthesis that is required for peroxisome degradation by selective autophagy and that this PI4P signaling is modulated by an ergosterol-converting PpAtg26 (autophagy-related) protein harboring a novel PI4P binding GRAM (glucosyltransferase, Rab-like GTPase activators, and myotubularins) domain. A phosphatidylinositol-4-OH kinase, PpPik1, is the primary source of PI4P. PI4P concentrated in a protein–lipid nucleation complex recruits PpAtg26 through an interaction with the GRAM domain. Sterol conversion by PpAtg26 at the nucleation complex is necessary for elongation and maturation of the membrane structure. This study reveals the role of the PI4P-signaling pathway in selective autophagy, a process comprising multistep molecular events that lead to the de novo membrane formation

Selective Proliferation of Lactic Acid Bacteria and Accumulation of Lactic Acid during Open Fermentation of Kitchen Refuse with Intermittent pH Adjustment

When minced and autoclaved model kitchen refuse was inoculated with a small amount of non-autoclaved model kitchen refuse as seed culture, incubated at 37°C for 3-5 days and intermittently pH neutralized, 27-45 g/l of lactic acid was accumulated with a small amount of acetic acid and ethanol. The highest accumulation and highest productivity levels of lactic acid were observed at an initial and adjusted pH of 7.0 and a 6 h interval of pH adjustment. After several hours of lag, the lactic acid bacteria became the dominant cell type during the incubation, while the number of coliform bacteria and clostridia decreased. Such selective and stable accumulation of lactic acid was achieved in dozens of different experiments with various refuse preparations. In contrast, with continuous pH adjustment, Iactic acid once accumulated was labile and a small amount of butyric acid was produced, increasing the number of clostridia. The dominant bacteria isolated from the fermentation with intermittent pH adjustment were identified as Lactobacillus plantarnm and L. brevis

Prevalence and safety of robotic surgery for gastrointestinal malignant tumors in Japan

[Aim] The National Health Insurance system has reimbursed robotic gastrointestinal surgery since April 2018 in Japan. Additionally, strict facility and surgeon standards were established by the government and the academic society. This study aimed to evaluate the prevalence and safety of robotic surgery using a Japanese nationwide web-based database. [Methods] Patients who underwent the following robotic surgeries for malignant tumors in 2018 were included: esophagectomy (RE), total gastrectomy (RTG), distal gastrectomy (RDG), proximal gastrectomy (RPG), low anterior resection (RLAR), and rectal resections other than RLAR (RRR). The number of cases and surgical mortality rates each month were calculated to evaluate the prevalence and safety of robotic procedures. [Results] A total of 3281 patients underwent robotic gastrointestinal surgery. The monthly number of robotic surgeries nearly doubled in April 2018 when they were initially reimbursed by the National Health Insurance system. Operative mortality rates were 0.9%, 0.4%, 0.2%, and 2.8% for RE (n = 330), RTG (n = 239), RDG (n = 1167), and RPG (n = 109), respectively. No mortality was observed in RLAR (n = 1062) or RRR (n = 374). [Conclusion] Robotic surgery for gastrointestinal malignant tumors was safely introduced into daily clinical practice along with rigorous surgeon and facility standards in Japan

Laparoscopic Surgery for Acute Diffuse Peritonitis Due to Gastrointestinal Perforation: A Nationwide Epidemiologic Study Using the National Clinical Database

[Background] Elective laparoscopic surgery is now widely accepted in the treatment of abdominal diseases because of its minimal invasiveness and rapid postoperative recovery. It is also used in the emergency setting for the diagnosis and treatment of acute diffuse peritonitis regardless of the causative disease. However, the value of laparoscopy in acute diffuse peritonitis remains unclear. In this study we aimed to show trends in the use of laparoscopy over time and compare the real-world performance of laparoscopic surgery with that of open surgery for acute diffuse peritonitis due to gastrointestinal perforation. [Methods] We extracted data from the National Clinical Database, a nationwide surgery registration system in Japan, for patients with a diagnosis of acute diffuse peritonitis due to gastroduodenal or colorectal perforation between 2016 and 2019. Trends in the use of laparoscopy over time were identified. Patient characteristics, laboratory findings, surgical findings, and postoperative complications were compared between laparoscopic surgery and open surgery. [Results] Patients in poor condition and those with abnormal laboratory findings tended to undergo open surgery. Anesthesia time and operating time were longer for laparoscopic surgery in patients with gastroduodenal perforation but shorter in those with colorectal perforation. Fewer complications occurred in patients who underwent laparoscopic surgery. The number of institutions where laparoscopic surgery was performed and the proportion of the use of laparoscopy at each institution increased over time. [Conclusion] The use of laparoscopy is becoming common in surgery for acute diffuse peritonitis due to gastrointestinal perforation. This approach may be a useful option for acute diffuse peritonitis

The roles of "newcomer residents" and "populations who retain an interest in local villages (Kankei-Jinkou)" in depopulated countryside villages : A case study of students\u27 research activities in Kawakami village, Nara

This paper examines the interaction between local residents and newcomers in a forested village (Kawakami village) in Nara. The ageing of Japan\u27s countryside population, combined with a declining number of residents, has caused the government to establish policies which encourage city residents to move to the depopulated countryside. This village has welcomed several newcomers every year, so both the authors and undergraduate students, supervised by us, interviewed residents regarding their decisions to live in that village. Their life stories explained that there were differences and misunderstandings between local residents and newcomers, but also several places and occasions where both of them mixed and interacted together. This paper also explores ways in which students\u27 research could be used to produce connections with depopulated villages. The Cabinet Office and the Ministry of Internal Affairs and Communications have emphasized the importance of "Kankei-Jinkou," which means the population who retain an interest in the countryside villages they do not live in. As most of the students have been raised in cities, their experiences as fieldworkers made them interested in understanding the dynamics of the villages in spite of the limitation of a short-term research.人口減少が進む日本社会では、都市から地方への人口移動は国の政策課題の一つとなっている。本論文では、奈良県吉野郡川上村の事例から、都市からの移住と定住を促進する国の政策を地方自治体が施策としてどのように実践しているのかを考察する。またその制度の中で人々が実際に都市から移住し、長くその地域に住んできた住民と相互に関わっていくプロセスを記述する。本論文で行った調査は、大学の演習と関連付けて実施した。都市部に住む大学生が、親族や知人などを通じた個人的なつながりを持たない人口減少地域を調査によって理解し、関わりを持つような「関係人口」となりうるのかを考察する。調査結果から、川上村では新規移住者を村に取り込むさまざまな政策が一定の効果をもたらしている一方で、移住者と旧住民との間には依然として認識や文化の相違があることが分かった。他方で、移住者と旧住民が出会い、交流する場所の存在が、こうした相違を埋めていく場として機能し始めている。また今回の演習による大学生の調査は、「関係人口」というには短期間ではあるが、継続的に行う仕組みを作ることで、都市と地方を理解する人々を生み出す可能性を持っている