A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.     

Effects of intermanual transfer induced by repetitive precision grip on input–output properties of untrained contralateral limb muscles

Although there were many reports relating to intermanual transfer of behavioral motor tasks in humans, it is still not well-known whether the transfer phenomenon between the trained and untrained hand is accompanied by corresponding changes in motor system. In the present study we applied transcranial magnetic stimulation to investigate the practice effects of unilateral fingertip precision grip on corticospinal excitability, regarding both the trained and untrained hand muscles. The results showed that after practice fingertip grip force became steady and safety margin dramatically decreased not only in the trained hand, but also in the untrained hand. Regarding MEP and background EMG (B.EMG) activities, the regression slope of MEP/B.EMG ratio in the first dorsal interosseous (FDI) muscle became significantly steeper after practice in both hands, but in the thenar (TH) muscle there were no clear modulations. These results indicated that through practice qualitative or functional changes of corticospinal systems related to the reorganization for a fingertip precision grip prominently reflect only on FDI muscle which plays a dominant role in the task. More importantly, such effects were simultaneously seen in the untrained hand correspondent to the trained hand, i.e., changes of input–output property in M1 occur not only in the trained hand, but also in the untrained hand. Based on the present results, we suggest that training-induced neural adaptations of the central nervous system may include improvement of its predicting fingertip grip force for self-lifting of the object in the untrained hand.     

Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial manifestation of tumor progression

Myeloid sarcoma (MyS) is defined as an extramedullary tumor-forming neoplasm consisting of immature myeloid cells with/without maturation. We experienced a case involving a 68-year-old Japanese male patient who had been followed-up for four years with a diagnosis of chronic idiopathic myelofibrosis/primary myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic differentiation. As his complete blood count included a few myeloid blasts (1% of WBC) and a bone marrow biopsy detected fibrosis without evidence of acute myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation of PMF was made, which was confirmed later by V617F mutation in Janus kinase-2 in both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient died of pneumonia eight months after developing the axillary tumor. At autopsy, multiple MyS masses were detected in his soft tissue, but his bone marrow only contained fibrosis. Although MyS rarely develops before the leukemic transformation of PMF, no evidence of AML could be found in the patient's bone marrow at any point during the course of his disease. Thus, it is possible that the blasts in his peripheral blood were derived from the remaining MyS. Furthermore, the present case indicates that extramedullary blastic transformation, which is occasionally seen in CML, can also occur in PMF. Therefore, it is important to recognize that there is a wide variation in the pathogeneses of MyS and PMF.     

A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma

An evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.     

Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P?=?0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P?=?0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P?=?0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P?=?0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.     

Topical ocular dexamethasone decreases intraocular pressure and body weight in rats

Background

Recently, topical dexamethasone-induced ocular hypertension and a consequent loss of retinal ganglion cells (RGCs) have been described in mice. This has been proposed as a model of steroid-induced glaucoma. In this study, we set up and evaluated a similar model in rats.

Results

Ten-week old Sprague Dawley (SD) rats (N?=?12) were used to evaluate the effect of topical 0.1 % dexamethasone (50 μl) administered 3 times daily for 4 weeks. Sodium chloride (0.9 %) was used in another group of rats (N?=?12) that served as the controls. After 1 week, we observed a progressive decrease in body weight in the dexamethasone-treated rats compared both to the pre-treatment baseline and the vehicle-treated rats. In contrast to earlier work that showed elevated Intraocular pressure (IOP) following dexamethasone instillation in mice, IOP in the rats unexpectedly fell to 11.3?±?1.3 mmHg in the treated eyes, compared to 14.8?±?2.4 mmHg in the untreated eyes, after 3 weeks of topical dexamethasone (P?=?0.032). Blood tests performed after 4 weeks of treatment showed a 3.3-fold increase in both plasma cholesterol (P?<?0.001) and alanine transaminase (P?=?0.019) in the dexamethasone-treated rats compared to the control rats. Meanwhile, topical steroid did not induce changes in either plasma blood glucose or glycated hemoglobin (HbA1c). We also did not detect changes in the expression of RGC markers (with real-time PCR) following the treatment.

Conclusions

In contrast to mice, which previously showed increased IOP following the topical administration of dexamethasone, the rats displayed a paradoxical reduction in IOP following a similar treatment. This was accompanied by a loss of body weight without affecting the level of blood glucose.

     

Synthesis of a Multiblock Copolymer of cis‐1,4‐Polybutadiene and Poly(3‐buten‐1‐ol)

Synthesis of a multiblock copolymer composed of cis‐1,4‐polybutadiene (PBd) segments and poly(3‐buten‐1‐ol) segments is performed via successive hydroboration and oxidation of cis‐1,4/syn‐1,2‐multiblock PBd. The ratio of functionalization can be controlled by changing the amount of the borane reagent. The obtained polymer shows two distinctive glass‐transition temperatures, which correspond to the cis‐1,4‐PBd block and the poly(3‐buten‐1‐ol) block. These thermal properties clearly show that the functionalization of the PBd proceeds keeping the elastic property derived from cis‐1,4 segment.

     

Psychosocial factors associated with suicidal ideation in clinical patients with depression

Background

Depression is a major risk factor for suicide, but few studies have examined psychosocial risk factors for suicide in clinical patients with depression. The purpose of this study was to investigate psychosocial factors which could be associated with suicidal ideation in clinical patients with depression including: sick-leave, help-seeking behavior, and reluctance to admit mental health problems.

Methods

A multi-center cross-sectional survey using self-report questionnaire was conducted at 54 outpatient psychiatric clinics in Tokyo in 2012. Adult outpatients who were diagnosed by psychiatrists as mood disorders (F30–F39) in the International Classification of Diseases-10 (ICD-10) were included in the study. Those who met the criteria for current hypomanic or manic episode were excluded from the study.

Results

A total of 189 patients with depression participated in the survey. Multivariable logistic regression analysis showed that taking sick-leave and having sought help from family were associated with decreased odds of current suicidal ideation. Moderate or more severe depression was associated with increased odds of suicidal ideation, and reluctance to admit own mental health problem tended to increase odds of suicidal ideation.

Limitations

Living status and suicidal ideation before consultation with psychiatrist were not investigated. Severity of suicidal ideation and comorbid psychiatric disorders were not assessed.

Conclusions

Importance of treatment of more severe depression for suicide prevention was confirmed. Industrial health staffs should consider the possibility of positive effect of taking sick-leave when they see employees with depression. Promoting help-seeking for family and reducing stigma of mental illness may be effective for suicide prevention.     

Computerized detection of vertebral compression fractures on lateral chest radiographs: preliminary results with a tool for early detection of osteoporosis

Vertebral fracture (or vertebral deformity) is a very common outcome of osteoporosis, which is one of the major public health concerns in the world. Early detection of vertebral fractures is important because timely pharmacologic intervention can reduce the risk of subsequent additional fractures. Chest radiographs are used routinely for detection of lung and heart diseases, and vertebral fractures can be visible on lateral chest radiographs. However, investigators noted that about 50% of vertebral fractures visible on lateral chest radiographs were underdiagnosed or under-reported, even when the fractures were severe. Therefore, our goal was to develop a computerized method for detection of vertebral fractures on lateral chest radiographs in order to assist radiologists' image interpretation and thus allow the early diagnosis of osteoporosis. The cases used in this study were 20 patients with severe vertebral fractures and 118 patients without fractures, as confirmed by the consensus of two radiologists. Radiologists identified the locations of fractured vertebrae, and they provided morphometric data on the vertebral shape for evaluation of the accuracy of detecting vertebral end plates by computer. In our computerized method, a curved search area, which included a number of vertebral end plates, was first extracted automatically, and was straightened so that vertebral end plates became oriented horizontally. Edge candidates were enhanced by use of a horizontal line-enhancement filter in the straightened image, and a multiple thresholding technique, followed by feature analysis, was used for identification of the vertebral end plates. The height of each vertebra was determined from locations of identified vertebral end plates, and fractured vertebrae were detected by comparison of the measured vertebral height with the expected height. The sensitivity of our computerized method for detection of fracture cases was 95% (19/20), with 1.03 (139/135) false-positive fractures per image. The accuracy of identifying vertebral end plates, marked by radiologists in a morphometric study, was 76.6% (400/522) and 70.9% (420/592) for cases used for training and those for testing, respectively. We prepared 32 additional fracture cases for a validation test, and we examined the detection accuracy of our computerized method. The sensitivity for these cases was 75% (24/32) at 1.03 (33/32) false-positive fractures per image. Our preliminary results show that the automated computerized scheme for detecting vertebral fractures on lateral chest radiographs has the potential to assist radiologists in detecting vertebral fractures.