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Abstract: ADP-glucose pyrophosphorylase (AGPase) catalyzes the first committed step of starch biosynthesis in higher plants. Previous studies have shown that two mutations in the large subunits of the potato and Arabidopsis AGPases resulted in the generation of enzymes with up-regulated allosteric properties, i.e. elevated sensitivity to 3-phosphoglycerate (3-PGA) and/or resistance towards inorganic phosphate (Pi) inhibition. To elucidate the effect of combining these mutations on the allosteric and kinetic properties, Ala33 to Lys and Gly96 to Asn substitutions were engineered into ApL1, the large subunit of the dominant Arabidopsis leaf AGPase expressed in leaves. When co-expressed with wild-type small subunit (wtApS1) in Escherichia coli, the resulting recombinant enzyme, designated Up3, showed allosteric regulatory properties distinct from Up1 and Up2 containing the single mutations. Up3 showed a 2.5-fold increase in 3-PGA affinity compared to wild-type and was more resistance to Pi than the other up-regulatory enzymes. Hence, the allosteric regulatory properties of Up3 are a non-additive product of the two mutations. To examine the effects of up-regulated ApL1 on transitory starch biosynthesis, the wild-type, Up1, Up2 and Up3 Apl1 genes were introduced into Arabidopsis ApL1 deficient TL46. Transgenic plants expressing the wild-type Apl1 gene restored starch levels to near normal levels, indicating that the introduced gene products complemented the genetic deficiency in TL46 plants. Transgenic plants expressing up-regulatory Apl1 genes showed greater AGPase activity and turnover of transitory starch than wild-type plants, the latter resulting in elevated carbon and energy to support heterotrophic growth during the night. [Copyright &y& Elsevier]

The author discusses protein Wnt5a as one of the molecules believed to be implicated in the pathogenesis of human psoriasis. The author states that the Wnt signalling pathways direct growth and morphogenesis during development and continues to regulate cell differentiation and proliferation in the whole adult life. Also discussed is the use of microarray analysis to compare the RNA expression profiles between the lesional and uninvolved skin of psoriasis.

Psoriasis is a chronic inflammatory skin disease that involves various systemic organs and tissues and is characterized by scaly erythematous skin. Among the different types of psoriasis, psoriatic arthritis (PsA) is frequently reported, and occasionally develops into severe arthritis leading to joint dysfunction. There are various tools, especially questionnaires, to identify the presence of PsA in European and American populations; however, little is known about the utility of these tools in the Asian population. In this study, we investigated the utility of a representative tool, the psoriasis epidemiology screening tool (PEST) questionnaire, to identify PsA among Japanese patients with psoriasis. A total of 143 patients with psoriasis were enrolled in this study. Among them, 29 patients were diagnosed with PsA. The frequency of PsA was significantly increased in patients with PEST scores > 3, with a sensitivity of 93.1% and a specificity of 78.9%. Among the questions in the PEST questionnaire, "Have you ever had a swollen joint?" showed the highest frequency to answer "Yes" among patients with PsA. Univariate and multivariate analyses revealed that high PEST scores (> 3) was an independent variable in PsA patients. Taken together, our study suggests that the PEST questionnaire is a useful tool to identify PsA among Japanese patients with psoriasis. [ABSTRACT FROM AUTHOR]

Telaprevir used as a protease inhibitor against hepatitis C virus is frequently associated with cutaneous adverse reactions. To explore a histological biomarker of cutaneous adverse events induced by telaprevir, we systematically searched for genes that were dysregulated by telaprevir in normal human epidermal keratinocytes (NHEKs). Microarray analysis and real-time polymerase chain reaction (PCR) revealed the significant increase in the expression of S100 calcium-binding protein A2 (S100A2) gene following treatment of NHEKs with telaprevir. Immunohistochemical analysis demonstrated that the expression of S100A2 was dominant in the spinous layer of the epidermis in patients with telaprevir-mediated severe-type drug eruptions and limited to the basal layer of the epidermis in healthy subjects. Furthermore, S100A2 expression increased after treatment with trichloroethylene and other medications, and the degree of S100A2 expression correlated with the severity of cutaneous adverse events. S100A2 expression also significantly increased in the skin of patients with atopic dermatitis and psoriasis. Taken together, S100A2 is highly expressed in the epidermis under inflammatory conditions and drug eruptions and may serve as a marker for keratinocyte damage in response to any inflammatory or toxic condition. [ABSTRACT FROM AUTHOR]

Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. [ABSTRACT FROM AUTHOR]

Long working hours have been associated with an increased risk of cardiovascular disease, but its relationship with hypertension remains unclear. The objective of this study is to examine the relationship between overtime and presence of hypertension using data from a large-scale multi-company study in Japan. Participants were 52 365 workers of four companies that provided both health-checkup data and self-reported data on overtime worked. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, and/or the use of antihypertensive drug. Logistic regression analysis was performed to determine the odds ratio for hypertension for each category of overtime work (<45, 45-79, 80-99 or ≥100 h/month) with adjustments for age, sex, company, smoking status and body mass index. The prevalence of hypertension tended to decrease with increasing overtime work: 17.5, 12.0, 11.1 and 9.1% for the shortest (<45 h/month) through the longest overtime category (≥100 h/month). The age-, sex- and company-adjusted odds ratios (95% confidence interval) were 1.00 (reference), 0.81 (0.75-0.86), 0.73 (0.62-0.86), 0.58 (0.44-0.76), respectively ( p for linear trend <0.001). In a sub-cohort, the inverse association remained statistically significant after an additional adjustment for other potential confounders. Results of the present large-scale study among Japanese workers suggest an inverse association between overtime work and presence of hypertension. [ABSTRACT FROM AUTHOR]

Aims Few studies have examined the prevalence of diabetes using glycated hemoglobin (HbA1c), a newly recommended diagnostic test. We examined the prevalence of diabetes and pre-diabetes using both HbA1c and fasting plasma glucose (FPG) and their associations with risk factors for type 2 diabetes in a large-scale Japanese working population. Methods Participants were 47,172 men and 8280 women aged 20–69 years who received periodic health checkup in nine companies which participated in the Japan Epidemiology Collaboration on Occupational Health study. Participants were categorized into diabetes (HbA1c ≥6.5% (≥48 mmol/mol), FPG ≥126 mg/dl (≥7.0 mmol/L), or medication for diabetes), pre-diabetes (HbA1c 6.0–6.4% (42–46 mmol/mol) or FPG 110–125 mg/dl (6.1–6.9 mmol/L) among those without diabetes), and normal glucose regulation. Results The prevalence of diabetes was 8.0% and 3.3% in men and women, respectively. Of individuals with diabetes, approximately 80% were defined by HbA1c ≥6.5% (≥48 mmol/mol) criterion. The prevalence of pre-diabetes was 14.1% in men and 9.2% in women. Prevalence of these glucose abnormalities increased with advancing age, especially during mid-40s and 50s. Higher body mass index and waist circumference, hypertension, dyslipidemia, and current smoking were each associated with higher prevalence of diabetes in both men and women. Conclusions Using HbA1c and FPG criteria or current medication, one in 13 men and one in 30 women had diabetes in the present Japanese working population. Interventions targeted for those in an early stage of impaired glucose metabolism would be required to prevent diabetes. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, have drastically changed treatments of advanced melanoma. However, ICI-related enterocolitis is often the most common adverse event, and represents the main reason for ICI discontinuation and mortalities. Here, we report the case of a metastatic melanoma treated with vedolizumab for ICI-induced colitis. A 67-year-old man treated with ipilimumab and nivolumab developed ICI-induced colitis and grade 3 diarrhea refractory to methylprednisolone and infliximab. After his third dose of vedolizumab, oral prednisolone ceased, and the colitis had completely resolved with no recurrence. This case report supports vedolizumab use in treating severe colitis which failed to resolve with first- and second-line immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Objective: Epidemiologic evidence on long working hour and diabetes has been conflicting. We examined the association between overtime work and prevalence of diabetes among Japanese workers. Methods: The subjects were 40,861 employees (35,170 men and 5,691 women), aged 16 to 83 years, of 4 companies in Japan. Hours of overtime were assessed using self-reported questionnaires. Diabetes was defined as a fasting plasma glucose ≥126 mg/dl (7.0 mmol/l), hemoglobin A1c ≥6.5% (48 mmol/mol), or current use of anti-diabetic drug. Multiple logistic regression analysis was used to calculate odds ratio of diabetes for each category of overtime. Results: After adjustment for age, sex, company, smoking, and BMI, there was a suggestion of U-shaped relationship between overtime work and prevalence of diabetes (P for quadratic trend = 0.07). Compared with those who worked <45 hours of overtime per month, the adjusted odds ratios (95% confidence interval) of diabetes were 0.86 (0.77–0.94), 0.69 (0.53–0.89), and 1.03 (0.72–1.46) for those who worked 45–79, 80–99, and ≥100 hours of overtime per month, respectively. In one company (n = 33,807), where other potential confounders including shift work, job position, type of department, alcohol consumption, sleep duration, leisure time physical activity, and family history of diabetes was additionally adjusted for, similar result was obtained (P for quadratic trend = 0.05). Conclusions: Long hours of overtime work may not be associated with increased prevalence of diabetes among Japanese workers. [ABSTRACT FROM AUTHOR]

Background: An anaphylactoid purpura affects small capillaries in the skin and other organs. Although two cases of anaphylactoid purpura exacerbated by cellulitis have been reported in Japanese literatures, its prognosis remains still unclear. Because cellulitis exacerbates various cutaneous inflammations, it has been speculated that cellulitis might also exacerbate cutaneous inflammation, such as vasculitis. Findings: In this article, we report that 78-year-old woman exhibited anaphylactoid purpura, following cellulitis. We also reviewed the literature concerning about this subject. Conclusions: This type of anaphylactoid purpura is thought to have a favorable prognosis dependent on the treatment for cellulitis. [ABSTRACT FROM AUTHOR]

Background: Calciphylaxis following acute renal failure is rare. Findings: We report A 57-year-old male with an acute renal failure associated with necrotizing fasciitis. We also review the cases of calciphylaxis due to acute renal disorder further. Conclusions: It should be kept in mind that calciphylaxis is observed in patient with not only chronic renal disease but also acute renal failure. [ABSTRACT FROM AUTHOR]

The article reports on the case of diagnosis of patient suffering from maculopapular type drug eruption caused by taking of pregabalin.

The article presents a case study of a 51-year-old male patient who suffered from benign prostatic hypertrophy for five years due to the consumption of silodosin for the treatment of urinary tract symptoms.

The article presents a case study of a 66-year-old female patient who suffered from tinea capitis due to Microsporum canis.

The article presents a case study of a 60-year-old female patient with Parkinson's disease who suffered from multiple and fixed drug eruption due to the consumption of ropinirole for the treatment of the said ailment.