Microscopic polyangiitis associated with marked systemic bleeding tendency caused by disseminated intravascular coagulation

A 57-year-old woman was admitted to our hospital because of severe dyspnea due to pulmonary hemorrhage and rapidly progressive renal failure. The patient was positive for perinuclear pattern anti-neutrophil cytoplasmic antibody (p-ANCA) and was manifested with gastrointestinal bleeding and brain hemorrhage. Thus, she was diagnosed as having microscopic polyangiitis (MPA). Laboratory examination demonstrated severe thrombocytopenia, increased prothrombin time and a high concentration of fibrin degradation products. In addition, the elevated plasma levels of D-dimer, thrombin-antithrombin complex and plasmin-plasmin inhibitor complex led us to make a diagnosis of disseminated intravascular coagulation (DIC). Complication of DIC was considered to have caused further deterioration in bleeding tendency due to MPA in the present case. The patient was treated with plasma exchange, hemodialysis, administration of corticosteroid including pulse therapy and cyclophosphamide. Continuous infusion of gabexate mesilate proved effective for improvement of systemic bleeding tendency. However, she finally died of severe infectious diseases. In conclusion, it is suggested that ANCA-associated vasculitis could be accompanied by DIC and gabexate mesilate may be a useful therapeutic agent for these disorders.     

A case of planned pregnancy with an interruption in infliximab administration in a 27-year-old female patient with rheumatoid-factor-positive polyarthritis juvenile idiopathic arthritis which improved after restarting infliximab and methotrexate

We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy. These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients.     

Normocytic normochromic anemia due to automatic neuropathy in type 2 diabetic patients without severe nephropathy: a possible role of microangiopathy

We describe here four male patients with long-term and poorly controlled type 2 diabetes mellitus. They shared many common characteristic complications, such as severe autonomic neuropathy, proliferative retinopathy and normocytic normochromic anemia without progressive renal failure and macroangiopathy. They also showed normal levels of erythropoietin and reticulocyte, which was considered relatively low. The coefficient of variation of R–R, a useful method to estimate autonomic failure, showed markedly advanced autonomic neuropathy in all four patients. Coronary angiography did not reveal stenosis, anomaly or collateral vessels, but left ventriclography showed diffuse or partial hypokinesis. Massive proteinuria, high urinary levels of N-acetyl-β-d-glucosamidase (NAG) and β₂-microglobulin (β₂M) were detected, though creatinine clearance (Ccr) was not so deteriorated. Treatment with recombinant erythropoietin increased their hemoglobin and hematocrit levels. These common points have a possibility to be brought about by tubulointerstitial damage and microangiopathy may be involved in it.     

Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism

Background

In a genome-wide association study of autism, zinc finger protein 804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally associated in verbally deficient individuals with autism. Zinc finger protein 804A copy number variations (CNVs) have also been observed in individuals with autism. In addition, ZNF804A is known to be involved in theory of mind (ToM) tasks, and ToM deficits are deemed responsible for the communication and social challenges faced by individuals with autism. We hypothesized that ZNF804A could be a risk gene for autism.

Methods

We examined the genetic association and CNVs of ZNF804A in 841 families in which 1 or more members had autism. We compared the expression of ZNF804A in the postmortem brains of individuals with autism (n = 8) and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing on the expression of several genes known to be involved in verbal efficiency and social cognition.

Results

We found that rs7603001 was nominally associated with autism (p = 0.018). The association was stronger (p = 0.008) in the families of individuals with autism who were verbally deficient (n = 761 families). We observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A knockdown cells, the expression of synaptosomal-associated protein, 25kDa (SNAP25) was reduced compared with controls (p = 0.009). The expression of ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate gyrus (ACG) of individuals with autism. There was a strong positive correlation between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001).

Limitations

Study limitations include our small sample size of postmortem brains.

Conclusion

Our results suggest that ZNF804A could be a potential candidate gene mediating the intermediate phenotypes associated with verbal traits in individuals with autism.     

Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors

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Lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 pandemic in Japan

Aims/IntroductionThis study aimed to reveal lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 (COVID‐19) pandemic in Japan.Materials and MethodsWe retrospectively analyzed 1,402 outpatients with diabetes at a clinic in Osaka, Japan, who responded to an interview sheet regarding lifestyle changes during the COVID‐19 pandemic between 28 March and 30 May 2020. The association of lifestyle changes with hemoglobin A1c (HbA1c) and weight changes from February to May 2020 was investigated using the linear regression model. We also investigated the association with clinically important change of HbA1c (by ≥0.3%) and bodyweight (by ≥3%), using the cumulative link model.ResultsLeisure time and other outside physical activities were decreased in one‐quarter of patients during the COVID‐19 pandemic, whereas the amount of meals and snacks was decreased and increased in approximately 10%, respectively. The change in leisure time physical activities was inversely associated with HbA1c and weight changes, whereas the quantitative change of meals with the decline in eating out and that of snacks were positively associated with HbA1c and weight changes (all P < 0.05). The quantitative change of meals without the decline in eating out was also positively associated with weight change (P = 0.012). The cumulative link model for clinically important HbA1c and weight change showed broadly similar associations, except for that between snacks and bodyweight (P = 0.15).ConclusionsA considerable number of outpatients with diabetes experienced lifestyle changes during the COVID‐19 pandemic. The lifestyle changes were associated with HbA1c and weight changes.     

Plaque variants of Sindbis virus

Summary Large plaque (G) and small plaque (8) variants were cloned from stock culture of Sindbis virus. Addition of protamine to agar overlay was shown to have little or no effect on the size of plaques produced by G variant, whereas S virus plaque size was significantly increased. This finding suggests that the S variant is more susceptible than the G variant to the inhibitory action of agar factor. The G and S variants differed markedly in their sensitivity to the antiviral action of interferon. Evidence was obtained that the S variant is more susceptible to the action of interferon. The difference of G and S variants in susceptibility to the action of interferon and agar factor may account for the difference of their plaque size. Growth and cytopathic effect of the S variant in a HVJ carrier HeLa cell culture (HeLa_HVJ) was greatly enhanced in contrast to those in normal HeLa cells. Enhancement of growth of wild-type virus in HeLa_HVJ cells was not so significant as in the case of the S variant. These observations were discussed in relations to the properties of the S variant and the cells of HeLa_HVJ.Dedicated to ProfessorJohn F. Enders on the occasion of his 70th birthday.     

Potential function of TGF-β isoforms in maturation-stage ameloblasts

Objectives

To investigate potential functions of transforming growth factor-beta (TGF-β) isoforms in maturation-stage ameloblasts during amelogenesis.