Heterogeneity of rabbit aortic endothelial cells, with special reference to phagocytosis.

Heterogeneity of aortic endothelial cells with regard to phagocytotic ability was examined by injecting India ink into normal rabbits. Light and electron microscopic analyses revealed that particles of India ink were phagocytosed in the endothelial cells, which in turn were localized at the distal side of the orifice of aortic branches, especially those of brachiocephalic, left clavicular, and dorsal intercostal arteries. No remarkable differences were found ultrastructurally between phagocytosing and nonphagocytosing endothelial cells. Ingested India ink particles were present within phagosomes of the endothelial cells for several hours after injection; the particles eventually accumulated in the subendothelial space twenty-four hours after injection. These results indicate that an active transport system of large molecules via the phagocytotic processes is present in endothelial cells located at the distal sides of the orifice of aortic branches. These regions are known to develop initial atherosclerotic lesions in hypercholesterolemic animals. Thus, a possible correlation between phagocytotic ability of endothelial cells and development of atherosclerosis is suggested.     

The review of seclusion and restraint in psychiatric practice]

In order to create the least restrictive setting in psychiatric practice, we investigated the effects of an assessment by a committee on seclusion and restraint. Using consistent procedures, the committees, which were established in 9 hospitals, reviewed seclusion and restraint maintained for periods of over 2 weeks during a 4-month period. Frequency and duration of seclusion and restraint, staff perceptions of and attitudes to the review system, and patient satisfaction were evaluated before and after the study period. As a result of this review process, the frequency of seclusion decreased slightly in 7 hospitals and 1 of the remaining 2 hospitals showed an increased frequency of seclusion days that were partially interrupted. Frequency of restraint decreased slightly in 5 hospitals, and of the remaining 3, 1 interrupted all periods of restraint, while the other 2 institutions showed an increase in interruption of restraint periods. As there were no common patients in 2 specialist psychiatric emergency hospitals between before and after the study periods, statistical analyses were performed. Only minor variables such as duration of partially interrupted periods of restraint, and duration of periods of restraint that were partially released showed a statistically significant increase. Although patient satisfaction showed a significant increase, staff attitudes to and perceptions of the review system became appreciably more negative. These findings suggest that although the review system had the potential to slightly reduce the use of seclusion and restraint, and to increase patient satisfaction, staff burnout was risked because staff effort was perceived to be disproportionately high in relation to the effect achieved. Furthermore, the possibility remains that the slight decrease of seclusion and restraint demonstrated did not necessarily reflect the appropriate use of these strategies, and were not necessarily lasting effects. However, as differences in opinion existed between the review system committee and treating clinicians regarding continuation of long term seclusion and restraint, the review system could have a role in monitoring the long term use of seclusion and restraint. Further investigation is needed into the long term effectiveness of procedures reviewing the use of seclusion and restraint in the psychiatric setting, taking into account both positive and negative outcomes.     

Increase in colony stimulating factor (CSF) in serum and augmentation of CSF responsiveness of lymphoid mononuclear cells by acute Trypanosoma cruzi infection in mice

Acute infection of Trypanosoma (T.) cruzi to C3H/HeN mice caused the induction of a higher level of serum colony stimulating factor (CSF) activity to support the proliferation of mouse bone marrow cells. The CSF activity reached a maximum 2 days after the infection and declined thereafter. Spleen cells of the T. cruzi-infected mice showed higher levels of responsiveness to CSF in L929-conditioned medium, mouse recombinant GM-CSF and infected mouse sera as compared with normal mouse spleen cells. The induction of CSF-responding cells became plateau 4 days after the infection and it decreased thereafter. In concomitant with the production of CSF activity in the infected mouse sera, large granular cells bearing high intensity of Mac-2 antigen increased in the infected mouse spleen. These cells were nylon nonadherent and displayed inhibitory effect on T cell response to Con A. These findings indicate that T. cruzi infection induces augmentation of in vivo CSF production, leading to the abnormal proliferation of CSF-responding cells and that augmented production of, and responsiveness to, CSF might be one of important mechanisms responsible for the induction of immune abnormalities in T. cruzi-infected mice.     

Role of nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia

Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization depends on not only angiogenesis but also vasculogenesis, which is mediated through mobilization of EPCs from BM and their recruitment to the ischemic sites. Reactive oxygen species (ROS) derived from Nox2-based NADPH oxidase play an important role in postnatal neovascularization; however, their role in BM and EPC function is unknown. Here we show that hindlimb ischemia of mice significantly increases Nox2 expression and ROS production in BM-mononuclear cells (BMCs), which is associated with an increase in circulating EPC-like cells. Mice lacking Nox2 show reduction of ischemia-induced flow recovery, ROS levels in BMCs, as well as EPC mobilization from BM. Transplantation of wild-type (WT)-BM into Nox2-deficient mice rescues the defective neovascularization, whereas WT mice transplanted with Nox2-deficient BM show reduced flow recovery and capillary density compared to WT-BM transplanted control. Intravenous infusion of WT- and Nox2-deficient BMCs into WT mice reveals that neovascularization and homing capacity are impaired in Nox2-deficient BMCs in vivo. In vitro, Nox2-deficient c-kit+Lin- BM stem/progenitor cells show impaired chemotaxis and invasion as well as polarization of actins in response to stromal derived factor (SDF), which is associated with blunted SDF-1-mediated phosphorylation of Akt. In conclusion, Nox2-derived ROS in BM play a critical role in mobilization, homing, and angiogenic capacity of EPCs and BM stem/progenitor cells, thereby promoting revascularization of ischemic tissue. Thus, NADPH oxidase in BM and EPCs is potential therapeutic targets for promoting neovascularization in ischemic cardiovascular diseases.     

Effect of transjugular intrahepatic portosystemic shunt formation on portal hypertensive gastropathy and gastric circulation

OBJECTIVES: The aim of this study was to investigate the effect of a transjugular intrahepatic portosystemic shunt (TIPS) on portal hypertensive gastropathy (PHG) and gastric hemodynamics. METHODS: A total of 16 patients with cirrhosis and portal hypertensive gastropathy were prospectively studied. Of these, 12 patients underwent TIPS for esophageal varices and four for refractory ascites. Gastric mucosal blood flow (GMBF) was assessed by laser Doppler flowmeter, and total blood flow (TBF) in submucosa and mucosa by near-infrared endoscopy. Portal venous pressure was obtained by a transducer during the TIPS procedure. The severity of portal hypertensive gastropathy was classified as none, mild, or severe. The examinations were performed before and 2 wk after the procedure. RESULTS: TIPS significantly reduced portal venous pressure. PHG improved in all four patients with severe PHG and in five of 12 patients with mild PHG after treatment. Gastric mucosal blood flow increased from 49.0 to 55.6 ml/min/100 g after TIPS. In contrast, TBF decreased from 0.35/s to 0.27/s after treatment. Liver function tests showed no significant changes before and after the procedure. CONCLUSIONS: It is considered that TIPS may have a beneficial effect on PHG at least for a short time. The mechanism by which PHG improves may be closely related to the improvement of the injured gastric perfusion in cirrhotic patients with PHG.     

ORMDL3/GSDMB genotype as a risk factor for early-onset adult asthma is linked to total serum IgE levels but not to allergic sensitization

BackgroundAn orosomucoid-like 3 (ORMDL3)/gasdermin B (GSDMB) gene locus on chromosome 17q is consistently associated with childhood-onset asthma, which is highly atopic. As some evidence suggests the relationship between asthma and allergic sensitization reflects asthma patient susceptibility to augmented IgE responses driven by common environmental allergens rather than an increased asthma risk after allergen exposure, we aimed to determine any relationships between this locus region and childhood-onset adult asthma with regard to serum total IgE levels or allergic sensitization.MethodsWe conducted a case–control association study using three independent Japanese populations (3869 total adults) and analyzed the ORs for association of rs7216389, an expression quantitative trait locus for ORMDL3/GSDMB, with adult asthma according to onset age. Additionally, associations between the rs7216389 genotype and total serum IgE levels or allergic sensitization was examined.ResultsRs7216389 was associated with both childhood-onset adult asthma (OR for asthmatic patients afflicted at the age of 10 years or younger = 1.61, p = 0.00021) and asthmatic patients with higher levels of total serum IgE (OR for asthmatic patients with IgE ≥1000IU/mL = 1.55, p = 0.0033). In both healthy controls and in the combined healthy and asthmatic individuals, rs7216389 was correlated with increased total serum IgE levels (p < 0.0005), but not allergic sensitization (p > 0.1).ConclusionsORMDL3/GSDMB is an important susceptibility gene for childhood-onset adult asthma in Japanese populations and this association is linked to elevated total serum IgE levels but not to allergic sensitization.     

Hyperlactemia during undiagnosed pheochromocytoma resection under laparoscopy

A 51-year-old man was scheduled to undergo adrenal tumor resection. Because his general physical findings and labolatory tests were not particular, and his serum concentrations of noradrenaline and adrenaline were within normal limit, the tumor was diagnosed as nonfunctional adrenal tumor. Anesthesia was induced with propofol, fentanyl and maintained with oxygen, air, propofol and remifentanil. When the surgeons started to work around the tumor, his blood pressure and heart rate increased suddenly. We decided to deal with the tumor as pheochromocytoma and started administering landiolol and prostaglandin E1. After the administration of the drugs, hemodynamic changes became stabilized; however, the increasing serum concentration of lactate continued until ligation of the adrenal vein. There were no clinical manifestations of circulatory failure and his liver function was within normal limits from his blood test. After the operation, we found his plasma concentration of adrenaline extremely high during the operation. Adrenaline increases blood lactate concentration due to metabolic effects. Hyperlactemia should be considered as one of the typical symptoms of pheochromocytoma.     

Asthma Phenotypes in Japanese Adults - Their Associations with the CCL5 ADRB2 Genotypes

BackgroundCluster analyses were previously performed to identify asthma phenotypes underlying asthma syndrome. Although a large number of patients with asthma develop the disease later in life, these previous cluster analyses focused mainly patients with younger-onset asthma.MethodsCluster analysis examined the existence of distinct phenotypes of late-onset asthma in Japanese patients with adult asthma. We then associated genotypes at the CCL5, TSLP, IL4, and ADRB2 genes with the clusters of asthma identified.ResultsUsing the 8 variables of age, sex, age at onset of the disease, smoking status, total serum IgE, %FEV1, FEV1/FVC, and specific IgE responsiveness to common inhaled allergens, two-step cluster analysis of 880 Japanese adult asthma patients identified 6 phenotypes: cluster A (n = 155): older age at onset, no airflow obstruction; cluster B (n = 170): childhood onset, normal-to-mild airflow obstruction; cluster C (n = 119): childhood onset, the longest disease duration, and moderate-to-severe airflow obstruction; cluster D (n = 108): older age at onset, severe airflow obstruction; cluster E (n = 130): middle-age at onset, no airflow obstruction; and cluster F (n = 198): older age at onset, mild-to-moderate airflow obstruction. The CCL5-28C>G genotype was significantly associated with clusters A, B and D (OR 1.65, p = 0.0021; 1.67, 0.018; and 1.74, 0.011, respectively). The ADRB2 Arg16Gly genotype was also associated with clusters B and D (OR 0.47, p = 0.0004; and 0.63, 0.034, respectively).ConclusionsThe current cluster analysis identified meaningful adult asthma phenotypes linked to the functional CCL5 and ADRB2 genotypes. Genetic and phenotypic data have the potential to elucidate the pheno- typic heterogeneity and pathophysiology of asthma.     

Layilin, a talin-binding hyaluronan receptor, is expressed in human articular chondrocytes and synoviocytes and is down-regulated by interleukin-1β

Objective

Layilin (LAYN), a 55-kDa transmembrane protein with homology to C-type lectins, has been identified as a receptor of hyaluronan (HA). Interestingly, LAYN does not share any sequence homology with CD44, a primary HA receptor. The primary aim of our study was to examine the expression and potential function of LAYN in human articular chondrocytes and synoviocytes.

Methods

Samples were obtained from patients undergoing joint arthroplasty. Cells were grown in vitro, then stimulated with interleukin (IL)-1β or tumor necrosis factor alpha (TNFα) for 24 h and the expression of LAYN was analyzed. To assess the function of LAYN, we transfected chondrocytes with siRNA against LAYN, treated them with HA and IL-1β, and then analyzed the production of matrix metalloproteinase (MMP)-1 and MMP-13 in the treated chrondrocytes.

Results

The results showed that LAYN was constitutively expressed in human articular chondrocytes and synoviocytes and that IL-1β significantly suppressed the expression of LAYN in these cells. HA repressed IL-1β-induced MMP-1 and MMP-13 production in chondrocytes, but this was significantly abrogated in chondrocytes transfected with siRNA against LAYN.

Conclusions

Our results show that human chondrocytes express LAYN, a novel HA receptor, and that LAYN may contribute to the regulation of HA functions in the arthritic condition. Further investigation of the HA receptor may lead to the development of novel therapeutics to regulate HA signaling in inflammatory arthritis.     

Identification of Factors Necessary for Enabling Technology-Based Dietary Record Surveys: A Qualitative Focus Group Interview with Japanese Dietitians

Weighed food records together with an in-person interview approach constitute the most basic methods used to estimate energy and nutrient intakes in dietary surveys. In the background of the coronavirus disease-2019 pandemic, the need for non-face-to-face dietary surveys using information and communication technology (ICT) is increasing. We aimed to evaluate ICT-based dietary record surveys and identify factors that may enable this survey method to become more widely used in the future. We conducted a non-face-to-face survey of dietary records of 44 Japanese individuals, maintained by dietitians using dietary photography and video conferencing services. We conducted a focus group interview with the six dietitians who conducted that survey. Their opinions on the factors necessary to popularize ICT-based dietary survey method were analyzed. In the focus group interview, dietitians highlighted fewer restrictions on time and place as positive aspects. Negative aspects included insufficient skills to operate computers, difficulty in hearing, and understanding facial expressions using ICT. We identified three main factors for enabling widespread use of ICT-based dietary record survey: individual skill, device and technology, and social environmental factors. This suggests that a comprehensive approach is necessary for popularizing the use of ICT in dietary surveys.