This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, ...retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval CI, 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice ...between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.
A new type of meticillin-resistant Staphylococcus aureus (MRSA), designated community-acquired MRSA, is becoming increasingly noticeable in the community, some strains of which cause fatal infections ...in otherwise healthy individuals. By contrast with hospital-acquired MRSA, community-acquired MRSA is more susceptible to non β-lactam antibiotics. We investigated the high virulence potential of certain strains of this bacterium.
We ascertained the whole genome sequence of MW2, a strain of community-acquired MRSA, by shotgun cloning and sequencing. MW2 caused fatal septicaemia and septic arthritis in a 16-month-old girl in North Dakota, USA, in 1998. The genome of this strain was compared with those of hospital-acquired MRSA strains, including N315 and Mu50.
Meticillin resistance gene (mecA) in MW2 was carried by a novel allelic form (type IVa) of staphylococcal cassette chromosomemec (SCCmec), by contrast with type II in N315 and Mu50. Type IVa SCCmec did not carry any of the multiple antibiotic resistance genes reported in type II SCCmec. By contrast, 19 additional virulence genes were recorded in the MW2 genome. All but two of these virulence genes were noted in four of the seven genomic islands of MW2.
MW2 carried a range of virulence and resistance genes that was distinct from those displayed on the chromosomes of extant S aureus strains. Most genes were carried by specific allelic forms of genomic islands in the MW2 chromosome. The combination of allelic forms of genomic islands is the genetic basis that determines the pathogenicity of medically important phenotypes of S aureus, including those of community-acquired MRSA strains.
Notch is a transmembrane protein that plays a critical role in the determination of cellular differentiation pathways. Although its importance in the development of mesenchymal tissues has been ...suggested, its role in skeletal tissues has not been well investigated. Northern blot experiments showed the expression of Notch1 in MC3T3‐E1 osteoblastic cells at early differentiation stages. When a Notch1 cytoplasmic domain (Notch‐IC NIC) delivered by an adenovirus vector was expressed in osteoblastic MC3T3‐E1 cells, a significant increase in calcified nodule formation was observed in long‐term cultures. Activation of endogenous Notch in MC3T3‐E1 by coculturing them with Delta‐like‐1 (Dll1)‐expressing myeloma cells also resulted in a stimulation of calcified nodule formation. Not only affecting nodule formation, Notch activation also had effects on osteoblastic differentiation of multipotent mesenchymal cells. Osteoblastic differentiation of C3H10T1/2 cells induced by bone morphogenetic protein 2 (BMP‐2) was significantly stimulated, whereas adipogenic differentiation was suppressed strongly, resulting in a dominant differentiation of osteoblastic cells. NIC expression in primary human bone marrow mesenchymal stem cells (hMSCs) also induced both spontaneous and stimulated osteoblastic cell differentiation. These observations suggest that osteoblastic cell differentiation is regulated positively by Notch and that Notch could be a unique and interesting target molecule for the treatment of osteoporosis.
Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is ...responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type 1 diabetes caused by autoimmune attack against beta cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than beta cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of autoantibody against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathological change, the animals were resistant to the development of diabetes. The results suggest that Aire not only is critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus.
The transformation of xenobiotics in the soil was studied in a model experimental system using pentachlorophenol (PCP), an enzyme, and a potential humic precursor. It has been shown that potential ...humic precursors such as
p-coumaric acid greatly accelerated the peroxidase-catalyzed reaction of PCP (Morimoto K. and Tatsumi K, 1997. Effect of humic substances on the enzymatic formation of OCDD from PCP.
Chemosphere 34, 1277–1283). About 90% of the PCP reacted but almost no transformation products were detected by GC/MS analysis. Most of the transformed PCP was detected in the polymeric products by the determination of the adsorbable organic halide (AOX) in gel permeation chromatography (GPC) fractions. Pyrolysis gas chromatography/mass spectrometry (py-GC/MS) of the polymers showed that tetrachlorophenol (TeCP) was the major pyrolysis product. This accords with the ion chromatography observation that about 20% of the PCP chlorine was released as chloride ion. However, nitrobenzene oxidation produced only a small amount of PCP and no TeCP. Based on the selectivity of the two degradation methods, it is concluded that TeCP is bound to the polymer by a diphenylether linkage, and PCP by an ether linkage to the aliphatic side chain. Thus, it was concluded that the major part of the PCP was incorporated into the polymer from
p-coumaric acid by the release of a chlorine atom from the PCP molecule to form a diphenylether linkage with the
p-hydroxyl group of the
p-coumaric acid polymer.
AIRE functions as an E3 ubiquitin ligase Uchida, Daisuke; Hatakeyama, Shigetsugu; Matsushima, Akemi ...
The Journal of experimental medicine,
2004-Jan-19, 2004-01-19, 20040119, Letnik:
199, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Autoimmune regulator (AIRE) gene mutation is responsible for the development of autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy, an organ-specific autoimmune disease with monogenic ...autosomal recessive inheritance. AIRE is predominantly expressed in medullary epithelial cells of the thymus and is considered to play important roles in the establishment of self-tolerance. AIRE contains two plant homeodomain (PHD) domains, and the novel role of PHD as an E3 ubiquitin (Ub) ligase has just emerged. Here we show that the first PHD (PHD1) of AIRE mediates E3 ligase activity. The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity. These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved.
Transport and ESR measurements have been performed on organic semiconductors synthesized by the diffusion method. For (BEDT-TTF)Cu
2Br
4, a pressure of 1
GPa raises the conductivity by up to one ...order of magnitude, but does not alter the semiconducting nature. By the ESR measurements, we find no Cu
2+ signals, indicating that the BEDT-TTF molecules are divalent. The Hall carrier concentration increases exponentially with temperature, approaching the spin concentration evaluated by the low-temperature ESR from
π-electrons. Thermopower measurements also support the contribution of the thermally activated electronic carriers. For (BEDTTTF)
2Cu
3Br
7(H
2O), the conductivity increases twice by applying a pressure of 0.8
GPa.
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