Thalidomide Prevents the Progression of Peritoneal Fibrosis in Mice

Thalidomide is clinically recognized as a therapeutic agent for multiple myeloma and has been known to exert anti-angiogenic actions. Recent studies have suggested the involvement of angiogenesis in the progression of peritoneal fibrosis. The present study investigated the effects of thalidomide on the development of peritoneal fibrosis induced by injection of chlorhexidine gluconate (CG) into the mouse peritoneal cavity every other day for 3 weeks. Thalidomide was given orally every day. Peritoneal tissues were dissected out 21 days after CG injection. Expression of CD31 (as a marker of endothelial cells), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), α-smooth muscle actin (as a marker of myofibroblasts), type III collagen and transforming growth factor (TGF)-β was examined using immunohistochemistry. CG group showed thickening of the submesothelial zone and increased numbers of vessels and myofibroblasts. Large numbers of VEGF-, PCNA-, and TGF-β-positive cells were observed in the submesothelial area. Thalidomide treatment significantly ameliorated submesothelial thickening and angiogenesis, and decreased numbers of PCNA- and VEGF-expressing cells, myofibroblasts, and TGF-β-positive cells. Moreover, thalidomide attenuated peritoneal permeability for creatinine, compared to the CG group. Our results indicate the potential utility of thalidomide for preventing peritoneal fibrosis

A pre-metazoan origin of the CRK gene family and co-opted signaling network.

CRK and CRKL adapter proteins play essential roles in development and cancer through their SRC homology 2 and 3 (SH2 and SH3) domains. To gain insight into the origin of their shared functions, we have investigated their evolutionary history. We propose a term, crk/crkl ancestral (crka), for orthologs in invertebrates before the divergence of CRK and CRKL in the vertebrate ancestor. We have isolated two orthologs expressed in the choanoflagellate Monosiga brevicollis, a unicellular relative to the metazoans. Consistent with its highly-conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can bind to the mammalian CRK/CRKL SH2 binding consensus phospho-YxxP, and to the SRC substrate/focal adhesion protein BCAR1 (p130(CAS)) in the presence of activated SRC. These results demonstrate an ancient origin of the CRK/CRKL SH2-target recognition specificity. Although BCAR1 orthologs exist only in metazoans as identified by an N-terminal SH3 domain, YxxP motifs, and a C-terminal FAT-like domain, some pre-metazoan transmembrane proteins include several YxxP repeats in their cytosolic region, suggesting that they are remotely related to the BCAR1 substrate domain. Since the tyrosine kinase SRC also has a pre-metazoan origin, co-option of BCAR1-related sequences may have rewired the crka-dependent network to mediate adhesion signals in the metazoan ancestor

Narratives on the Current Medical Situation in Japan According to Highly Specialized Foreign Professionals

In order to understand the difficulties faced by highly skilled foreign professionals when dealing with the Japanese healthcare system and to identify the support they require therein, university health center staff members of the Okinawa Institute of Science and Technology Graduate University conducted semi-structured interviews with faculty, staff, and students from the Institute. Data from the interviews were analyzed by subject matter analysis using a narrative-oriented approach. In total, 13 participants were interviewed, and five themes and 15 subthemes were generated from the 40 codes extracted. Although participants considered themselves to be accepting of other cultures and made little mention of the need for cultural and religious considerations that previous studies have identified as important, they reported that their experiences receiving healthcare in Japan were fraught with many difficulties. They felt that the capacity to communicate in Japanese was a prerequisite for receiving appropriate healthcare and that hospitals should assume the responsibility of providing language support. While they reported satisfaction with the easy and inexpensive access to advanced medical equipment and specialists in Japan, they also noted challenges in selecting medical institutions and departments, the flow and procedures in the hospital, and building open and direct relationships with doctors. In addition, based on the present study, people with chronic illnesses felt isolated from the community, worried about a lack of privacy, and wanted a primary care physician they could trust. In order to provide appropriate healthcare to foreigners, we require an accurate understanding of their needs, how to address these comprehensively and in a multifaceted manner, and how the communication responsibilities should be shared among the involved parties (i.e., foreign care recipients and Japanese medical professionals)

An Exploratory Quantitative Study of Factors Associated with Dissatisfaction with Japanese Healthcare among Highly Skilled Foreign Professionals Living in Japan

Background: To identify factors necessary for the proper inclusion of foreigners in Japanese healthcare, we conducted a survey to determine whether foreign residents, even those with high socioeconomic status, referred to as “Highly Skilled Foreign Professionals”, experience difficulties when visiting medical institutions in Japan, using satisfaction level as an indicator. Method: A five-point Likert-scale, anonymous, online questionnaire was administered to faculty and doctoral students enrolled at the Okinawa Institute of Science and Technology Graduate University (OIST). The respondents’ demographics and their opinions on what they found difficult or important during medical examinations, their impression of Japanese medical personnel, their requirements for language support and interpretation, and their opinions about local healthcare delivery systems were collected. The questionnaires were distributed and collected using Microsoft Forms. Results: Responses were obtained from 90 respondents (response rate: 20.7%). The percentage of respondents who were dissatisfied (bottom two of five Likert scales) with medical care in Japan was 23.4%. In univariate logistic regression analysis, 11 of 35 questions were significantly correlated with dissatisfaction with medical care (p < 0.1). Duration of stay, presence of family members living with the patient, satisfaction with life, and perceived usefulness of language support were negatively correlated with dissatisfaction with medical care, while communication problems with medical personnel, need for medical personnel to respect patients’ culture, religion, and privacy, and difficulty in getting to medical facilities were positively correlated with dissatisfaction with medical care. No significant correlations were found with age, gender, or Japanese language level. Multiple logistic regression analysis showed that the presence of family members living with the subject (AOR = 0.092, p = 0.010), the desire for multilingual documentation (AOR = 0.177, p = 0.046), the physician’s concern for the patient’s culture and religion (AOR = 8.347, p = 0.029), and difficulty in communication with healthcare providers (AOR = 6.54, p = 0.036) were significantly correlated with overall dissatisfaction with medical care. Discussion: On average, the targeted Highly Skilled Foreign Professionals did not have strong levels of dissatisfaction with Japanese healthcare, but when they did have dissatisfaction, it was related to language barriers, lack of cultural and religious considerations, and difficulty in communication with healthcare providers. We believe that the results indicate the focus points of support necessary for the inclusion of foreigners. We also believe that the finding that family cohabitation is associated with satisfaction with medical care is a useful insight into effective reciprocal support on the part of patients

Measuring the Broad-band X-Ray Spectrum from 400 eV to 40 keV in the Southwest Part of the Supernova Remnant RX J1713.7-3946

We report on results from Suzaku broadband X-ray observations of the southwest part of the Galactic supernova remnant (SNR) RX J1713.7-3946 with an energy coverage of 0.4-40 keV. The X-ray spectrum, presumably of synchrotron origin, is known to be completely lineless, making this SNR ideally suited for a detailed study of the X-ray spectral shape formed through efficient particle acceleration at high speed shocks. With a sensitive hard X-ray measurement from the HXD PIN on board Suzaku, we determine the hard X-ray spectrum in the 12--40 keV range to be described by a power law with photon index Gamma = 3.2+/- 0.2, significantly steeper than the soft X-ray index of Gamma = 2.4+/- 0.05 measured previously with ASCA and other missions. We find that a simple power law fails to describe the full spectral range of 0.4-40 keV and instead a power-law with an exponential cutoff with hard index Gamma = 1.50+/- 0.09 and high-energy cutoff epsilon_c = 1.2+/- 0.3 keV formally provides an excellent fit over the full bandpass. If we use the so-called SRCUT model, as an alternative model, it gives the best-fit rolloff energy of epsilon_{roll} = 0.95+/- 0.04 keV. Together with the TeV gamma-ray spectrum ranging from 0.3 to 100 TeV obtained recently by HESS observations, our Suzaku observations of RX J1713.7-3946 provide stringent constraints on the highest energy particles accelerated in a supernova shock.Comment: 11 pages, 11 figures, accepted for publication in Publications of the Astronomical Society of Japan (PASJ

Involvement of Leptin in the Progression of Experimentally Induced Peritoneal Fibrosis in Mice

013LeptinThe isJapana hormoneSociety mainlyof Histochemistryproduced byandwhite adipose cells, and regulates body fat and food intake by acting on hypothalamus. Leptin receptor is expressed not only in the hypothalamus but in a variety of peripheral tissues, suggesting that leptin has pleiotropic functions. In this study, we investigated the effect of leptin on the progression of peritoneal fibrosis induced by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 2 or 3 weeks in mice. This study was conducted in male C57BL/6 mice and leptin-deficient ob/ob mice. Peritoneal fluid, blood, and peritoneal tissues were collected 15 or 22 days after CG injection. CG injection increased the level of leptin in serum and peritoneal fluid with thickening of submesothelial compact zone in wild type mice, but CG-injected ob/ob mice attenuate peritoneal fibrosis, and markedly reduced the number of myofibroblasts, infiltrating macrophages, and blood vessels in the thickened submesothelial area. The 2-week leptin administration induced a more thickened peritoneum in the CG-injected C57BL/6 mice than in the PBS group. Our results indicate that an upregulation of leptin appears to play a role in fibrosis and inflammation during peritoneal injury, and reducing leptin may be a therapeutically potential for peritoneal fibrosis

In vitro expansion of CD34+CD38- cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia

advance online publication, August 8, 2014 [Epub ahead of print]ArticleLEUKEMIA. 29(3):606-614 (2015)journal articl

A case of a chronic expanding hematoma in a hemodialysis patient

A 70-year-old woman undergoing chronic maintenance hemodialysis had felt a mass in her left hip 4 years prior. As the mass gradually expanded, magnetic resonance imaging (MRI) was performed. The MRI findings showed mosaic patterns with various signal intensities inside the mass and a low-signal band at its periphery. Because of the slow expansion of the mass over a course of at least 4 years and its characteristic MRI findings, the patient was diagnosed with a chronic expanding hematoma (CEH), a comparatively rare type of hematoma. To our knowledge, this is the first report of a CEH occurring in a hemodialysis patient in the English literature