Ultrastructural Evidence for Temperature-Dependent Ca2+ Release from Fish Sarcoplasmic Reticulum During Rigor Mortis

The release or leakage of ca2+ from the sarcoplasmic reticulum (SR) during rigor mortis of fish muscle was investigated by transmission electron microscopy using pyroantimonate and related biochemical changes. Ca2+ -pyroantimonate deposits were observed in the SR immediately after spiking the fish. At the onset of rigor for fish stored at 0°C, no deposits were found in the SR; however, fish stored for the same period at woe which were still in the pre-rigor state, clearly showed Ca2+ deposits in the SR. In association with the Ca2+ translocation, ATP degraded faster at 0 c than at 10 °C, probably due to enhancement of myofibrillar ATPase activity by the increasing Ca2 + concentrations. Therefore, rapid Ca2+ release from the SR at 0°C seemed to trigger the acceleration of fish rigor mort is at this temperature, analogous to the phenomenon called cold shortening

Optical conductivity from local anharmonic phonons

Recently there has been paid much attention to phenomena caused by local anharmonic vibrations of the guest ions encapsulated in polyhedral cages of materials such as pyrochlore oxides, filled skutterdites and clathrates. We theoretically investigate the optical conductivity solely due to these so-called rattling phonons in a one-dimensional anharmonic potential model. The dipole interaction of the guest ions with electric fields induces excitations expressed as transitions among vibrational states with non-equally spaced energies, resulting in a natural line broadening and a shift of the peak frequency as anharmonic effects. In the case of a single well potential, a softening of the peak frequency and an asymmetric narrowing of the line width with decreasing temperature are understood as a shift of the spectral weight to lower level transitions. On the other hand, the case of a double minima potential leads to a multi-splitting of a spectral peak in the conductivity spectrum with decreasing temperature.Comment: 8 pages, 11 figures, accepted for publication in Phys. Rev.

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Japanese perspective

Striking advances in systemic therapy for unresectable advanced hepatocellular carcinoma (HCC) have improved the average prognosis of patients with HCC. As a result, the guidelines for the treatment of HCC have changed significantly. However, various issues have emerged in clinical practice. First, there is no established biomarker that can predict response to systemic therapy. Second, there is no established treatment regimen after primary systemic therapy, including combined immunotherapy. Third, there is no established treatment regimen for intermediate-stage HCC. These points make the current guidelines ambiguous. In this review, we present the Japanese guidelines for the diagnosis and treatment of HCC based on the latest evidence; introduce various efforts mainly in Japanese real-life practice to update these guidelines; and present our perspectives on future guidelines

FDG-PET/CT findings of soft tissue lesoions

Objective : To evaluate the correlations between F-18 FDG uptake imaged with PET/CT and pathological findings in soft tissue lesions. Methods : Fifty-four soft tissue lesions in 47 patients were evaluated. The correlations between the degree of FDG uptake, pathological type and grade, and MRI signal intensity and/or enhancement pattern were evaluated. Tumor FDG uptake was quantified by the maximum standardized uptake value (SUVmax). Results : Thirty-one lesions were malignant and twenty-three lesions were benign. The difference between SUVmax in the malignant and benign groups was statistically significant (p<0.001). Malignant myxoid lesions and well differentiated liposarcoma showed low FDG uptake. Benign neurogenic lesions showed low FDG uptake while malignant neurogenic tumors showed high FDG uptake, and the difference between SUVmax in the benign and malignant lesions was statistically significant (p<0.001). In a neurofibromatosis type-1 patient who had multiple neurogenic tumors, FDG-PET/CT could distinguish malignant peripheral nerve sheath tumors from other benign lesions with similar MRI findings. Conclusions : FDG-PET/CT is useful for differentiating malignant from benign soft tissue lesions, but malignant soft tissue lesions may show various patterns on FDG-PET, and MRI may be helpful for a differential diagnosis

22q11欠失症候群モデルマウスの神経発達障害には、マイクロRNAが介在するCxcr4/Cxcl12シグナリングの欠損が寄与する

22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions, some of which are classified as schizophrenia and bipolar disorder in the current diagnostic categorization. However, it remains elusive how the chromosomal microdeletion leads to the mental manifestation at the mechanistic level. Here we show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human 22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and hippocampal dentate precursor cells. Furthermore, Df1/+ mice show functional defects in Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which reportedly underlie interneuron migration. Notably, the defects in interneuron progenitors are rescued by ectopic expression of Dgcr8, one of the genes in 22q11 microdeletion. Furthermore, heterozygous knockout mice for Dgcr8 show similar neurodevelopmental abnormalities as Df1/+ mice. Thus, Dgcr8-mediated regulation of microRNA is likely to underlie Cxcr4/Cxcl12 signaling and associated neurodevelopmental defects. Finally, we observe that expression of CXCL12 is decreased in olfactory neurons from sporadic cases with schizophrenia compared with normal controls. Given the increased risk of 22q11DS in schizophrenia that frequently shows interneuron abnormalities, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia and related mental conditions.博士（医学）・乙1331号・平成26年3月17

Validation of radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas: Japanese Orthopaedic Association Committee on Musculoskeletal Tumors Cooperative Study

AbstractBackgroundThe radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated.MethodsWe conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients’ overall survival using the Kaplan-Meier method and the log-rank test.ResultsThe JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing’s sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid.ConclusionsThe JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas

Thallium-201 chloride scintigraphy in soft tissue tumors

Objective We report the findings of Thallium-201 chloride (201TlCl) scintigraphy and consider how to use this technique to evaluate the character of soft tissue lesions. Patients and Methods We enrolled 91 consecutive patients (45 males and 46 females, age range 8-91-years-old). Nineteen patients were malignant and 72 were benign. Patients were scanned 15 minutes (early phase) and 3 hours (delayed phase) after 201TlCl injection. More intense uptake in the lesion compared to the normal side was considered as ‘high’, the same degree of uptake was considered ‘iso’, and decreased uptake was ‘low’. The retention index (RI) was calculated in 9 patients in the malignant group and in 16 patients in the benign group. Results In malignant tumors, 15 of 19 patients showed high uptake in both the early and delayed phases. One malignant fibrous histiocytoma patient was high only in the delayed phase and 1 liposarcoma patient was high only in the early phase. Two liposarcoma patients showed an iso uptake in both phases. One of these patients was pathologically diagnosed as a myxoid type. In benign lesions, no lipoma showed increased uptake. All neurogenic tumors except for 2 demonstrated high uptake. All 3 ganglions of the lower extremities showed iso uptake. Most inflammatory diseases showed increased uptake. Clinically-considered benign patients consisted of tumorous lesions or inflammatory disease. Only 2 patients were considered ‘low’, and these were diagnosed as intramuscular hematoma and cyst. RI was variable in both malignant and benign lesions and no statistically significant difference was seen between malignant and benign lesions by t-test (p=0.72). Conclusions A high 201TlCl uptake lesion is more frequently seen in malignant tumors, but regardless of whether the tumor is benign or malignant, according to the histopathological variety, the 201TlCl uptake pattern can not be the only indicator to differentiate malignant from benign tumors. We ultimately need to evaluate the nature of tumors by a combination of several imaging techniques

The physiological uptake pattern of 18F-FDG in the left ventricular myocardium of patients without heart disease

Purpose : The purpose of this study was to evaluate the physiological uptake pattern of 18F-FDG in the left ventricular myocardium of patients under preparation for tumor FDG-PET. Patients and Methods : We enrolled 188 patients without cardiac disease. The accumulation patterns were classified as either ‘none’, ‘diffuse’, ‘focal’ or ‘focal on diffuse’. When a focal uptake was only observed on the basal wall, then the patterns were classified as having either a ‘ring’, ‘over half’ or ‘spot’ uptake. Results : The frequencies of the myocardial FDG uptake patterns were as follows : none, n=52 (27.7%) ; diffuse, n= 63 (33.5%) ; focal on diffuse, n=40 (21.3%) and focal, n=33 (17.6%). The age, blood glucose level, weight and dose of FDG did not differ significantly for each pattern. The focal and focal on diffuse patterns were seen in 73 patients, and 65 patients had a focal uptake only on the basal wall ; ring uptake in 29 patients, over half in 20 and spot uptake in 16 patients. Conclusions : The physiological myocardial uptake showed several patterns. Focal uptake was often seen in patients with cardiac disease, but it did not always indicate an abnormal finding when the accumulation was only on the basal wall

Cryosurgical Hemorrhoidectomy: Technique and Method

The key to gain successful results with cryosurgical hemorrhoidectomy is based on the prevention of prolapse of the edematous tissue after freezing. To prevent the edema, it is important to pull out the hemorrhoid as much as possible during freezing, to freeze only on the rectal side of the anal verge, to avoid freezing the anal verge, and to freeze the hemorrhoids in two or three separate stages when they are large such as the fourth-degree. The anal discomfort and discharge in these patients are related to prolapse of frozen tissue. Cryosurgery is an effective method of treatment for hemorrhoids if care is taken to use the proper techniques

Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication in SLE. Although the mechanism of NPSLE remains unclear, cytokines and chemokines are considered to be involved in their pathogenesis. Here we used Bio-Plex Pro assays to examine 27 types of cytokines and chemokines in the cerebrospinal fluid (CSF) of 32 NPSLE patients. We used the CSF of 20 patients with multiple sclerosis (MS) and 22 patients with neuromyelitis optica (NMO) as a disease control group. Fourteen of 27 cytokines/chemokines were significantly higher in the NPSLE patients compared to the MS/NMO patients. We could identify six "minimum predictive markers" by using a weighted-voting algorithm that could distinguish NPSLE from MS and NMO: interleukin (IL)-17, IL-2, interferon (IFN)-γ, IL-5, basic fibroblast growth factor (FGF)-basic and IL-15. The determination of various types of CSF cytokine profiles may contribute to the diagnosis of NPSLE and may help elucidate the mechanisms underlying this disease