YKL-40 is structurally similar to chitotriosidase (CHIT1), an active chitinase, but it lacks chitin-degrading activity while retaining chitin-binding capability. Elevated YKL-40 levels are associated with inflammatory diseases and cancers, making it a valuable biomarker. We previously reported that the W69T substitution in YKL-40 significantly reduces its chitin-binding affinity, identifying W69 as a crucial binding site.
View Article and Find Full Text PDFThe only cure of HIV has been achieved in a small number of people who received a hematopoietic stem cell transplant (HSCT) comprising allogeneic cells carrying a rare, naturally occurring, homozygous deletion in the CCR5 gene. The rarity of the mutation and the significant morbidity and mortality of such allogeneic transplants precludes widespread adoption of this HIV cure. Here, we show the application of CRISPR/Cas9 to achieve >90% CCR5 editing in human, mobilized hematopoietic stem progenitor cells (HSPC), resulting in a transplant that undergoes normal hematopoiesis, produces CCR5 null T cells, and renders xenograft mice refractory to HIV infection.
View Article and Find Full Text PDFAccumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity.
View Article and Find Full Text PDFBackground: Atrial tachyarrhythmias (ATAs) are the primary cause of inappropriate implantable cardioverter-defibrillator (ICD) therapy in patients with idiopathic ventricular fibrillation (IVF) and are associated with decreased quality of life and increased mortality. Nonetheless, the incidence of ATAs in IVF cases has not been clarified.
Objective: The study sought to determine the incidence and clinical significance of ATAs in patients with IVF compared with those with Brugada syndrome (BrS).
Malignant lymphoma is a relatively rare complication in patients with ulcerative colitis (UC) and its etiology is unclear. We present a hard-to-diagnose case of Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly patient with UC who was treated with the immunomodulator tacrolimus and herbal medicine including indigo naturalis. Because malignant lymphomas can mimic other inflammatory diseases macroscopically, diagnosis in such cases can be challenging.
View Article and Find Full Text PDFEur Heart J Case Rep
November 2024
Background: Myocarditis is associated with an increased risk of conduction disturbances during the acute phase, which recovers in most cases but rarely recurs during the chronic phase.
Case Summary: A 50-year-old man who developed fulminant myocarditis after COVID-19 mRNA vaccination was discharged 24 days after admission. He was readmitted for heart failure associated with two P waves: one P wave (P1) had a normal amplitude and was dissociated from the QRS, and the other (P2) had a very low amplitude and was associated with the QRS.
APOHIDE Lotion 20% is a topical agent for treating primary palmar hyperhidrosis that contains the active ingredient oxybutynin hydrochloride. Oxybutynin hydrochloride has anticholinergic effects and inhibits sweating by binding to the M receptor, a subtype of the muscarinic acetylcholine receptor, in eccrine sweat glands. The clinical response to oxybutynin hydrochloride treatment also involves N-desethyloxybutynin, an active metabolite of oxybutynin.
View Article and Find Full Text PDFGeriatr Gerontol Int
November 2024
Objective: Understanding the characteristics of falls among older adults is necessary to prevent them. These characteristics include questions such as when (month and time), where (places), who (age), what (injury), why (trigger), and how (direction) the falls occur. The objective of this study was to identify the characteristics of falls in individuals aged 65-74 years (young-old), 75-84 years (old-old), and ≥85 years (oldest-old).
View Article and Find Full Text PDFJ Med Ultrason (2001)
October 2024
Background: A sinus of Valsalva aneurysm involving a single cusp is a rare condition, and coronary computed tomography angiography with fractional flow reserve-computed tomography helps evaluate not only the anatomical aspects of the aneurysm and coronary artery but also the physiological details of coronary artery disease.
Case Summary: A 71-year-old woman presented with exertional chest pain and dyspnoea. Enhanced computed tomography revealed an aneurysmal change in the right sinus of Valsalva, and coronary computed tomography angiography revealed diffuse narrowing of the proximal segment of right coronary artery due to mechanical stretching by the large Valsalva aneurysm.
RNAs undergo more than 300 modifications after transcription. Aberrations in RNA modifications can lead to diseases; their involvement in fetal development has been suggested. This study explored the RNA modifications related to fetal development in mice.
View Article and Find Full Text PDFPurpose: To evaluate retinal circulation in eyes with central retinal artery occlusion.
Methods: The best-corrected visual acuity (BCVA), fluorescein angiography, and laser speckle flowgraphy values were measured at the first visit in 42 patients with central retinal artery occlusion (42 eyes; mean age, 66.0 ± 14.
YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity.
View Article and Find Full Text PDFTransfer RNA (tRNA) modification is essential for proper protein translation, as these modifications play important roles in several biological functions and disease pathophysiologies. AlkB homolog 8 (ALKBH8) is one of the nine mammalian ALKBH family molecules known to regulate selenoprotein translation through the modification of the wobble uridine (U34) in tRNA; however, its specific biological roles remain unclear. In this study, we investigated the role of ALKBH8 using -knockout () mice, which were observed to have reduced 5-methoxycarbonylmethyluridine (mcm5U) and (S)-5-methoxycarbonylhydroxymethyluridine levels; notably, the mcm5U level was partially compensated only in the brain.
View Article and Find Full Text PDFBackground: Endothelial dysfunction (ED), a well-established risk marker of cardiovascular events, is associated with heart failure (HF) and atrial fibrillation (AF). Its relationship with cardiovascular events in patients with HF undergoing AF ablation remains unclear. We aimed to elucidate the association between ED and the outcomes after AF ablation in patients with HF.
View Article and Find Full Text PDFA 73-year-old female was diagnosed with gallbladder cancer, but the future liver remnant volume was deemed insufficient for curative resection. Consequently, transileocolic portal vein embolization was performed. During laparotomy, multiple nodules were palpable on the peritoneal surface of the pelvic floor.
View Article and Find Full Text PDFPurpose: To compared the vessel density (VD) around the optic nerve head (ONH) in eyes with cone-rod dystrophy (CORD) and healthy control eyes in a sector-wise manner and to investigate the relationship between VD around the ONH and visual function in CORD eyes.
Methods: Twenty-six eyes in 14 CORD patients and 25 eyes in 25 healthy control subjects were examined. Using OCT angiography images, the VDs in the superficial and deep capillary plexus at the macula (sVDm and dVDm) and those around the ONH in the superior, temporal, inferior and nasal region (VDnh_s, VDnh_t, VDnh_i, and VDnh_n, respectively) were measured for each eye.
Background: We aimed to investigate risk factors predicting oxygen demand in COVID-19 patients.
Methods: Patients admitted to Shizuoka General Hospital with COVID-19 from August 2020 to August 2021 were included. First, we divided patients into groups with and without oxygen demand.
Aims: Direct oral anticoagulants (DOACs) have become the first-line antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF). During this period, the incidence of thromboembolisms and major bleeding events has decreased. However, no studies have shown a correlation between them, and even fewer data are available on older patients.
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