Monocytes and Dendritic Cells in Sjögren’s Syndrome

Sjögren’s Syndrome is an autoimmune disorder with an estimated prevalence of around 3-4% in women. The disease is characterized by lymphocytic infiltration in the salivary and lachrymal glands, leading to decreased

Repurposing Miltefosine for the Treatment of Immune-Mediated Disease?

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

The influence of different floor-surf ace on starting to move a wheelchair

高齢者用車いすが在宅床面素材によってどのような影響を受けるのかを調べるため、特性の異なる車いす7台を用い、6種の床面で始動力を測定した。その結果、床面の種類、車いすの種類に有意な差を認めたため、さらに各床面で最も軽く、または重くなる車いすの構成要因を分析した。フローリンクとパイルカーペットでは、主輪空気圧を高めたものが軽く(p<0.01)なった。畳ではエアーキャスター付き車いすが軽く(p<0.01)、ソリットキャスターと主輪の空気圧を高めたものが最も重く(p<0.01)なった。畳にカーベットを敷いた床面では、ソリットキャスターと主輪の空気圧を高めたものが最も重く(p<0.01)なった。敷居や戸当段差では、81～252Nと他の床面に比べて全ての車いすが重く(p<0.01)なったが、その中でもエアーキャスターを装備する車いすは軽く(p<0.01)なった。このことから、床面の違いによって車いすの始動力は大きく影響を受け、硬い床面で軽く、柔らかな床面で始動力は重くなり、病院や施設で軽く動く車いすが在宅では同じ特性とならないことが明確となった。使用環境により車いすの構造や部品選択基準が異なることが示唆された。今回の研究により、住環境の床面条件に合わせた車いす構成要素の選択が重要であると考えられた。 / This study was conducted in order to examine the influence of different floor-surfaces on starting to move a wheelchair. The measurement performed in this study was the force required to move a wheelchair under six conditions of floor-surface, using seven types of wheelchair. Analysis of variance (ANOVA) was done among the different conditions and different types of wheelchair. As a result, significant differences were found depending on the conditions of floor-surfaces and the types of wheelchair. Therefore, we analyzed the composition factor of the wheelchair for which the force to move is the lowest, or the highest, on each floor-surface. ANOVA revealed, on flooring and pile carpet, the force to move a wheelchair with high pressure in its main tires was the lowest (p<0.01). On a tatami mat, that of the wheelchair with air casters was the lowest (p<0.01), while that of the wheelchair with solid casters and the one with high-pressure main tires was the highest (p<0.0l). On a carpeted tatami mat, that of the wheelchair with solid casters and the one with high-pressure main tires was also the highest (p<0.0l). At threshold and doorsill, the force was high (81-252N) compared with the other floor-surfaces and all wheelchairs, although that of the wheelchair with air casters was lower than others (p<0. 01). The differences of floor-surface have a great influence on the force required to move a wheelchair; it is higher on soft floor-surfaces and lower on hard floor-surfaces. It became obvious that wheelchairs which move easily at hospitals and facilities did not show the same characteristic at the home. The results of this study suggest that the structure and choice of parts for a wheelchair should be considered in relation to the environment where it will be used, with particular attention to floor-surface materials

Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression

Objective To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called "IFN type I signature", in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). Methods Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. Results An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren'

Miltefosine Suppresses Inflammation in a Mouse Model of Inflammatory Bowel Disease

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Kinome-wide analysis of the effect of statins in colorectal cancer

Background Epidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome. Methods CRC cells with or without Lovastatin treatment were used for kinome analysis. Findings on kinome arrays were further confirmed by immunoblotting with activity-specific antibodies. Experiments in different CRC cell lines using immunoblotting, siRNA-mediated knockdown and treatment with specific BMP inhibitor Noggin were performed. The relevance of in vitro findings was confirmed in xenografts and in CRC patients treated with Simvastatin. Results Kinome analysis can distinguish between non-specific, toxic effects caused by 10 mu M of Lovastatin and specific effects on cell signalling caused by 2 mu M Lovastatin. Statins induce upregulation of PTEN activity leading to downregulation of the PI3K/Akt/mTOR signalling. Treatment of cells with the specific BMP inhibitor Noggin as well as PTEN knockdown and transfection of cells with a constitutively active form of AKT abolishes the effect of Lovastatin on mTOR phosphorylation. Experiments in xenografts and in patients treated with Simvastatin confirm statin-mediated BMP pathway activation, activation of PTEN and downregulation of mTOR signalling. Conclusions Statins induce BMP-specific activation of PTEN and inhibition of PI3K/Akt/mTOR signalling in CRC.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Kinome-wide analysis of the effect of statins in colorectal cancer (Mar, 10.1038/s41416-021-01318-9, 2021)

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Microtubule-Driven Multimerization Recruits ase1p onto Overlapping Microtubules

Microtubule (MT) crosslinking proteins of the ase1p/PRC1/Map65 family play a major role in the construction of MT networks such as the mitotic spindle. Most homologs in this family have been shown to localize with a remarkable specificity to sets of MTs that overlap with an antiparallel relative orientation []. Regulatory proteins bind to ase1p/PRC1/Map65 and appear to use the localization to set up precise spatial signals []. Here, we present evidence for a mechanism of localized protein multimerization underlying the specific targeting of ase1p, the fision yeast homolog. In controlled in vitro experiments, dimers of ase1-GFP diffused along the surface of single MTs and, at concentrations above a certain threshold, assembled into static multimeric structures. We observed that this threshold was significantly lower on overlapping MTs. We also observed diffusion and multimerization of ase1-GFP on MTs inside living cells, suggesting that a multimerization-driven localization mechanism is relevant in vivo. The domains responsible for MT binding and multimerization were identified via a series of ase1p truncations. Our findings show that cells use a finely tuned cooperative localization mechanism that exploits differences in the geometry and concentration of ase1p binding sites along single and overlapping MT

Quilting prevents seroma formation following breast cancer surgery: closing the dead space by quilting prevents seroma following axillary lymph node dissection and mastectomy

Item does not contain fulltextBACKGROUND: Seroma is a frequent problem after mastectomy (ME) and axillary lymph node dissection (ALND). Seroma is associated with pain, discomfort, impaired mobilisation and repeated aspirations, often resulting in a surgical site infection (SSI). It has already been demonstrated that minimizing dead space through fixation of the skin flaps to the underlying muscles (quilting) lowers the incidence of seroma. The aim of this study was to evaluate the effect of quilting on the incidence of seroma, and SSI. METHODS: Two consecutive groups with a total of 176 patients following ME and/or ALND were retrospectively compared. Endpoints were the incidence of seroma, and number and volume of aspirations and SSIs. Analysed risk factors were age, ME, lymph node dissection, neoadjuvant therapy, body mass index (BMI) and hypertension. RESULTS: The quilted group (n = 89) scored significantly better on all endpoints compared with the conventional group (n = 87). The incidence of seroma decreased from 80.5 % to 22.5 % (p < 0.01), the mean number of aspirations from 4.86 to 2.40 (p = 0.015), the volume of aspirations from 1660 ml to 611 ml (p = 0.05) and the SSIs from 31.0 % to 11.2 % (p < 0.01). Increasing age and lymph node dissection were found to be risk factors for seroma; quilting was a protective factor. CONCLUSION: Quilting is an effective method for preventing seroma and its complications