Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.     

Altered expression of dermokine in skin disorders

Background Although dermokine‐β, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl‐terminal domain shares a high pI value with many cytokines, suggesting similar functions. Objective To better understand the biology of dermokine, we here determined its localization under pathological conditions and examined factors that regulate its expression. Methods We generated an anti‐human dermokine‐β/γ monoclonal antibody cross‐reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine‐β/γ were performed with various tissue samples. Results Although human dermokine‐β/γ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti‐dermokine‐β/γ antibody in inflammatory skin disorders. Dermokine‐β/γ was expressed in keratoacanthoma and a part of well‐differentiated squamous cell carcinoma (SCC). However, dermokine‐β/γ was not detected in poorly differentiated SCC or tumours derived from non‐keratinocytes. In mice, dermokine‐β/γ‐expressed keratinocytes were increased in models of contact hypersensitivity, ultraviolet‐irradiated skin injury and wound healing. Consistent with expanded distribution in inflammatory skin diseases, proinflammatory cytokines such as interleukin‐1β, interleukin‐12, and tumour necrosis factor‐α augmented dermokine‐β/γ expression in cultured human keratinocytes. In contrast, growth factors including epidermal growth factor, insulin‐like growth factor‐I, keratinocyte growth factor and transforming growth factor‐α significantly reduced dermokine expression. Conclusion These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.     

Adenosine triphosphate maintenance by branched chain amino acids as a novel neuroprotective strategy for retinal neurodegenerative diseases

<正>Retinal neuronal cell death is caused in many incurable eye diseases such as retinitis pigmentosa(RP)and glaucoma,which are leading causes of adult blindness.In RP,progressive loss of photoreceptor cells leads to visual disturbance.No established treatments are available to date for this condition,although potential treatments,including regenerative medicine,gene therapy,and neurotropic factor therapy are being investigated.In glaucoma,retinal     

The age-specific normative values of standing whole-body sagittal alignment parameters in healthy adults: based on international multicenter data

European Spine Journal - To investigate the age-specific normative values of whole-body sagittal alignment (WBSA) including global balance parameters in healthy adults and to clarify the...     

Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference − 0.43, 95% confidence interval [CI] − 0.75 to – 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.

     

Induction of potent antitumor immunity by intradermal DNA injection using a novel needle-free pyro-drive jet injector

The current success of mRNA vaccines against COVID-19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle-free pyro-drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers. Intradermal injection of OVA-expression plasmid DNA into mice using the PJI, but not a needle syringe, rapidly and greatly augmented OVA-specific CD8⁺ T-cell expansion in lymph node cells. Increased mRNA expression of both interferon-γ and interleukin-4 and an enhanced proliferative response of OVA-specific CD8⁺ T cells, with fewer CD4⁺ T cells, were also observed. OVA-specific in vivo killing of the target cells and OVA-specific antibody production of both the IgG2a and IgG1 antibody subclasses were greatly augmented. Intradermal injection of OVA-expression plasmid DNA using the PJI showed stronger prophylactic and therapeutic effects against the progression of transplantable OVA-expressing E.G7-OVA tumor cells. Even compared with the most frequently used adjuvants, complete Freund's adjuvant and aluminum hydroxide with OVA protein, intradermal injection of OVA-expression plasmid DNA using the PJI showed a stronger CTL-dependent prophylactic effect. These results suggest that the novel needle-free PJI is a promising tool for DNA vaccination, inducing both a prophylactic and a therapeutic effect against cancers, because of prompt and strong generation of OVA-specific CTLs and subsequently enhanced production of both the IgG2a and IgG1 antibody subclasses.     

Application of superb micro-vascular imaging (SMI) in obstetrics

Superb Micro-vascular Imaging (SMI; Toshiba Medical Systems, Tokyo) is a new blood flow imaging technique that employs a unique algorithm to minimize motion artifacts by eliminating signals based on analysis of tissue movement. Compared to conventional blood flow imaging such as color and power Doppler imaging, SMI significantly reduces motion artifacts and can visualize low-velocity blood flow in small vessels. In the present report, the clinical value and future potential of SMI in obstetrics have been demonstrated for the first time. We believe this new blood flow imaging technique is acceptable for obstetricians for the purpose of perinatal clinical assessments.