サリチル酸誘発耳鳴に対する牛車腎気丸の抑制効果の行動学的および免疫組織化学的な根拠

Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models.博士（医学）・甲第851号・令和4年9月28日Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

Efficacy and Safety of Three-dimensional Conformal Radiotherapy for Macroscopic Vascular Invasion of Hepatocellular Carcinoma

Chemotherapy is insufficient to treat macroscopic vascular invasion (MVI) of hepatocellular carcinoma (HCC). We retrospectively investigated the treatment outcomes of patients who underwent three-dimensional conformal radiotherapy (3D-CRT) for HCC MVI and analyzed prognostic factors by multivariate analysis using a Cox proportional hazard model. Sixty-five patients were studied. MVI sites were the portal vein (n=48 patients), portal and hepatic veins (n=8), and hepatic vein (n=9). The median irradiation dose was 50 Gy. The median survival time (MST) was 7.5 months. Performance status 2 or 3, modified albumin-bilirubin grade 2b or 3, and massive/diffuse type were poor prognostic factors. Nineteen patients (29%) with a treatment effect of 3 or 4 (≥ 50% of tumor necrosis or regression) at the irradiation sites according to the Response Evaluation Criteria in Cancer of the Liver showed longer survival than those with an effect of 1 or 2 (MST 18.7 vs. 5.9 months, p<0.001). No treatment-related death occurred. The hepatic function reserve was preserved in more than 70% of patients. 3D-CRT controlled HCC MVI safely and was suggested to be a good treatment option

Reduced serum level of leukocyte cell-derived chemotaxin 2 is associated with the presence of diabetic retinopathy

AbstractBackgroundVascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR.MethodsThe study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR. Serum LECT2 levels were measured using an enzyme-linked immunosorbent assay. Data were evaluated using Spearman's rank correlation, univariate and multivariate logistic regression.ResultsSerum LECT2 levels were significantly lower in participants with DM having DR than in those not having DR (35.6±14.9ng/ml vs. 44.5±17.6ng/ml, P<0.001). Spearman's rank correlation analysis revealed a significant association between serum LECT2 levels and the presence of DR (P<0.001). Multiple regression analysis revealed that serum LECT2 levels were independently related to DR (P<0.001).ConclusionsThese findings indicated that serum LECT2 level is negatively associated with the presence of DR and suggest that low circulating LECT2 level is a risk factor for DR

Biological and Biochemical Studies on Melanogenesis and M elanoma Cells

For the previous ten years, we have been studying intracellular transport of melanosoma1 proteins and their biological and biochemical functions in melanoma cells. Melanosoma1 proteins,tyrosinase, tyrosinase-related protein 1 (TYRP1) and TYRP2/DOPAchrome tautomerase (DCT), gp100/Pme117 are transported from the trans-Golgi network (TGN) to earlystage melanosomes via endosoma1 compartments. We suggest that Rab7 is involved in the vesicular transport of tyrosinase and TYRP1 and in the melanogenesis through the regulation of gp100/Pme117 maturation. TYRP1 and TYRP 2/DCT were shown to play an essential role in suppressing TYR-mediated cytotoxicity in melanocytic cells, possibly through interaction with TYR in melanosomes. We also studied apoptotic cell death of melanoma cells and death mediators. Among p53 family members, p51A (p63) induced apoptosis in both wild-type and mutant p53-expressing melanoma cells more significantly than p53 and 73β. Interferon(IFN) exerts anti-tumor activities possibly by regulating IFN-stimulated genes. Caspase-2 activation was commonly associated with induction of apoptosis in IFN一β一sensitive melanoma cells. The diacylglycero1 kinase (DGK) , expressed in several human melanoma cell lines but not in melanocytes, was a novel positive regulator of NF-KB, which suppresses TNF一α一induced melanoma cell apoptosis

Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study

Background: Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. Methods: This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. Results: Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359–1.700, and adjusted HR 1.325, 95% CI 1.076–1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24–48 h, 198 (10.7%) at 48–72 h, 111 (6.0%) at 72–96 h, and 85 (4.6%) at 96–120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72–96 h (adjusted HR 1.528, 95% CI 1.062–2.197, and adjusted HR 1.334, 95% CI 0.756–2.352, respectively; referenced to reintubation within 24 h). Conclusions: Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation.Tanaka A., Shimomura Y., Uchiyama A., et al. Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study. Critical Care 27, 378 (2023); https://doi.org/10.1186/s13054-023-04668-3

Successful intrathecal chemotherapy combined with radiotherapy followed by pomalidomide and low-dose dexamethasone maintenance therapy for a primary plasma cell leukemia patient

Primary plasma cell leukemia (PPCL) is a rare aggressive variant of plasma cell disorder and frequently presents with extramedullary disease. Central nervous system (CNS) involvement with PPCL has an extremely poor prognosis. We describe a 46-year-old man with PPCL treated with a combination of lenalidomide, bortezomib, and dexamethasone as induction therapy following upfront allogeneic stem cell transplantation (allo-SCT). Despite achieving a very good partial response, the patient suffered from an isolated CNS relapse 12 months after allo-SCT. He was immediately started on concurrent intrathecal chemotherapy (IT) and cranial irradiation (RT). Subsequently, pomalidomide and low-dose dexamethasone (Pd) were given as maintenance therapy. He has been without CNS recurrence for more than 18 months. Our case suggests that concurrent IT and RT followed by Pd maintenance therapy may be an effective option to control CNS relapse of PPCL after allo-SCT