[Clinical characteristics of perimenopausal female patients with rheumatoid arthritis].

Objective: To explore the menopause status of patients with rheumatoid arthritis (RA) and clinical characteristics of perimenopausal RA patients. Methods: A cross-sectional study. Female RA patients were recruited retrospectively in the Sun Yat-Sen Memorial Hospital from August 2015 to August 2023. Clinical data were collected, including onset age, disease duration, RA disease activity indicators, functional assessment, and radiographic scores. According to menopausal status, the patients were categorized as pre-menopausal, perimenopausal and post-menopausal groups to explore their menopausal and clinical characteristics. Results: A total of 1 151 female patients were enrolled, with a mean age of (50.2±13.0) years. At enrollment, there were 470 (40.8%), 140 (12.2%) and 541 (47.0%) patients in pre-menopause, perimenopause and post-menopause status, respectively. The mean age of menopause was (49.0±4.2) years. Compared with pre-menopausal group, perimenopausal RA patients had higher disease activity indicators [clinical disease activity index (CDAI) 17 (6, 26) vs 10 (3, 19) ], higher levels of inflammation [erythrocyte sedimentation rate (ESR) 35 (21, 65) vs 26 (14, 44) mm/1h, C-reactive protein (CRP) 6.2 (3.2, 16.8) vs 3.3 (3.2, 13.6) mg/L], and a higher proportion of functional limitation [25.0%(35/140) vs 10.4%(49/470)] (all P<0.016 7); while there was no significant differences in disease activity[M(Q1, Q3)] [CDAI 17 (6, 26) vs 14 (6, 25)], levels of inflammation [ESR 35(21, 65) vs 42 (23, 72) mm/1h, CRP 6.2 (3.2, 16.8) vs 6.2 (3.3, 23.9) mg/L] and functional limitation [25.0%(35/140) vs 28.8%(156/541)] when compared with those in post-menopausal group (all P>0.016 7). In RA patients during the perimenopausal period, 49 cases (35.0%) developed RA during this period. Compared with patients with RA onset during reproductive age, patients with RA onset during the perimenopausal period had higher numbers of 28-joint tender joints [7 (2, 10) vs 4 (0, 8)], higher CDAI [20 (12, 29) vs 14 (4, 24)], and higher ESR [45 (25, 72) vs 32 (18, 56) mm/1h] (all P<0.05). Conclusion: Perimenopausal patients with RA have severe disease activity and functional limitation.

[The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis].

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

[Predictive value of anti-mutated citrullinated vimentin antibody on one-year radiographic progression in patients with rheumatoid arthritis].

Objective: To investigate the value of baseline anti-mutated citrullinated vimentin (MCV) antibody for predicting one-year radiographic progression in patients with rheumatoid arthritis (RA). Methods: Consecutive RA patients were recruited from November 2014 to July 2018 at Department of Rheumatology, Sun Yat-sen Memorial Hospital, Clinical data were collected including disease activity score in 28 joints with four variables including C-reactive protein (CRP).Serum anti-MCV antibody at baseline was detected by enzyme-linked immunosorbent assay. X ray assessment of both hands/wrists was performed and assessed according to the Sharp/van der Heijde modified score (mTSS) at baseline and the 12th month. Univariate and multivariate logistic regression analyses were used to identify the risk factors for one-year radiographic progression. Results: Among 220 RA patients recruited, the positive rate of anti-MCV antibody at baseline was 77.7%. Compared with those with negative anti-MCV antibody, RA patients with positive anti-MCV antibody had higher disease activity score in 28 joints with four variables induding CRP [3.8 (2.4, 5.0) vs. 3.1 (2.1, 4.0), P=0.007], more physical dysfunction (21.6% vs. 8.2%, P=0.033) and higher radiographic indicators including mTSS [11 (2, 27) vs. 4 (1, 10), P=0.003], joint space narrowing [JSN, 4 (0, 14) vs. 2 (0, 6), P=0.024] and joint erosion[JE, 5 (1, 18)vs. 3 (0, 5), P=0.003]. After one-year follow-up, sixty-six RA patients (30.0%) developed radiographic progression, the percentage of whom was significantly higher in positive anti-MCV group than that in negative anti-MCV group (33.9% vs.16.3%, P=0.018). Multivariate logistic regression analysis suggested that positive anti-MCV antibody at baseline was an independent risk factor for one-year radiographic progression (OR=2.341, 95%CI 1.002-5.469). Conclusion: Positive anti-MCV antibody at baseline predicts one-year radiographic progression in RA patients. In the future, anti-MCV antibody can be used not only as a supplementary laboratory marker, but also in disease activity assessment and prognosis prediction for RA.

Liver Macrophages Stimulate the Expression of Hepatocyte Nuclear Factor-6 and Promote Hepatocyte Proliferation at the Early Stage of Liver Regeneration.

Hepatocyte nuclear factor (HNF-6) is a liver-specific protein and a key component in the differentiation process during the development of mature liver. The immunohistochemical staining and RT-PCR techniques were employed to examine the expression of HNF-6 and proliferation of Ki-67+ cells during the early regeneration of the liver on postsurgery in 3, 6, 12, and 24 h in original model of partial hepatectomy in rats. The earliest proliferating (Ki-67+) cells were observed in 3 h after surgery in liver sinusoids (liver macrophages) and then in liver parenchyma. Expression of HNF-6 in hepatocytes and epithelial cells of the bile ducts attained maximum in 6 h after surgery. At later terms, this parameter somewhat decreased, but still surpassed the control level.

[Predictive value of 3 different risk stratification models for patients after congenital heart surgeries].

Objective: To evaluate the predictive value of 3 different risk stratification models including the risk adjustment in congenital heart surgery-1 (RACHS-1), Aristotle basic complexity (ABC), and Society of Thoracic Surgeons-European Association for cardiothoracic surgery congenital heart surgery mortality score (STAT) risk scoring system for death and major complications in patients after congenital heart surgeries. Methods: A total of 3 578 patients (age<18 years old) received surgery for congenital heart diseases from January to December 2015 in Fuwai hospital were enrolled, and the clinical data were retrospectively analyzed. The congenital heart disease patients were 1.7 (0.8, 4.5) years old, and the male accounted for 54.3% (1 943 cases).Death after surgery and major complications including use of extracorporeal membrane oxygenation, bedside thoracotomy, peritoneal dialysis for renal failure, bedside hemofiltration for renal failure, tracheotomy, reoperation for mediastinum infection, reoperation for heart in hospital were observed. The area under the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive value for mortality after surgery and major complications with RACHS-1, ABC, and STAT risk scoring systems. Results: The mortality after surgery was 0.4% (14/3 578) , and the rate of major complications was 3.2% (113/3 578) . For mortality after surgery, areas under the ROC curve were 0.682 (95%CI 0.570-0.795, P=0.002), 0.722 (95%CI 0.612-0.832, P<0.001), and 0.753 (95%CI 0.659-0.847, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. For major complications, areas under the ROC curve were 0.709 (95%CI 0.667-0.751, P<0.001), 0.743 (95%CI 0.702-0.784, P<0.001), and 0.731 (95%CI 0.693-0.770, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. Conclusion: STAT risk scoring system is superior to RACHS-1 and ABC risk scoring systems on predicting death after surgery, and ABC risk scoring system is superior to RACHS-1 and STAT risk scoring systems on predicting major complications in Chinese patients with congenital heart disease in the single center.

Serum hCG-ß levels of postovulatory day 12 and 14 with the sequential application of hCG-ß fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PURPOSE: To investigate hCG-ß level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. METHODS: A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-ß levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-ß levels and the degree of hCG-ß increase from POD 12 to 14 were determined for each pregnancy outcome. RESULTS: POD 12 and 14 hCG-ß levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-ß levels of POD 12 and 14 and the fold increase of hCG-ß levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-ß had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-ß levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-ß levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-ß for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-ß and fold increase of hCG-ß improved predictability of pregnancy outcome as compared with that of POD 12 hCG-ß alone. The cutoff values of POD 12 and 14 serum hCG-ß levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-ß level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-ß level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-ß was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-ß level and fold increase of hCG-ß significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. CONCLUSIONS: Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

α-secretase cleaved amyloid precursor protein (APP) accumulates in cholinergic dystrophic neurites in normal, aged hippocampus.

AIMS: Dystrophic neurites are associated with ß-amyloid (Aß) plaques in the brains of Alzheimer's disease (AD) patients and are also found in some specific areas of normal, aged brains. This study assessed the molecular characteristics of dystrophic neurites in normal ageing and its difference from AD. METHODS: We compared the dystrophic neurites in normal aged human brains (age 20-70 years) and AD brains (Braak stage 4-6) by immunostaining against ChAT, synaptophysin, γ-tubulin, cathepsin-D, Aß1-16, Aß17-24, amyloid precursor protein (APP)-CT695 and APP-NT. We then tested the reproducibility in C57BL/6 mice neurone cultures. RESULTS: In normal, aged mice and humans, we found an increase in clustered dystrophic neurites of cholinergic neurones in CA1 regions of the hippocampus and layer II and III regions of the entorhinal cortex, which are the major and earliest affected areas in AD. These dystrophic neurites showed accumulation of sAPPα peptides cleaved from the amyloid precursor protein by α-secretase rather than Aß or C-terminal fragments. In contrast, Aß and APP-CTFs accumulated in the dystrophic neurites in and around Aß plaques of AD patients. Several experiments suggested that the accumulation of sAPPα resulted from ageing-related proteasomal dysfunction. CONCLUSIONS: Ageing-associated impairment of the proteasomal system and accumulation of sAPPα at cholinergic neurites in specific areas of brain regions associated with memory could be associated with the normal decline of memory in aged individuals. In addition, these age-related changes might be the most vulnerable targets of pathological insults that result in pathological accumulation of Aß and/or APP-CTFs and lead to neurodegenerative conditions such as AD.

A crystal plasticity model for metal matrix composites considering thermal mismatch stress induced dislocations and twins.

Originated at heterogeneous interfaces with distinct coefficient of thermal expansion (CTE), thermal mismatch stress is one of the critical influential factors to mechanical properties of metal matrix composites (MMCs). This stress is normally accommodated plastically by various defects, for example, high-density dislocations and twins in Al near heterogeneous interfaces in SiC/Al composites. Basic knowledge on the influence of defect characteristics is important but difficult to extrapolate from experimental results. However, existed theoretical models more focus on the influence of dislocation density, but less focus on defects variety, volume and distribution. In this paper, we propose a physics-based crystal plasticity model that has the capability of dealing with thermal mismatch stress induced dislocations and twins (denoted as TMDT model). The proposed TMDT model that is implemented in the Visco-Plastic Self-Consistent (VPSC) method considers defect heterogeneous distribution (gradient range), defect type (dislocations vs. twins) and defect volume fraction (twin spacing vs. twin volume). We demonstrate the validity and the capability of the VPSC-TMDT model in SiC/Al composites with thermal mismatch induced dislocations or twins. Furthermore, this model predicts the ultra-high strength of Graphene/Copper composites with high-density nanoscale twins, which is in turn the future aim for such nanocomposites.

Differential expression of intestinal ion transporters and water channel aquaporins in young piglets challenged with enterotoxigenic Escherichia coli K88.

The study was to determine whether the expression of genes involved in intestinal water and ion transport would be affected by enterotoxigenic (ETEC) K88 both in vitro and in vivo. First, 36 male piglets (4 d old) were randomly allotted to either the control or the ETEC K88 group. Each group had 6 replicates with 3 piglets per replicate. All piglets were fed with the same diets for 17 d. On d 15, piglets in the ETEC K88 group were challenged with ETEC K88 (serotype O149:K91:K88ac) at 1 × 10 cfu per pig, whereas those in the control group received the same volume of sterile PBS. After being challenged with ETEC K88 for 72 h (d 18), 1 piglet from each replicate was selected for slaughter to collect samples from the jejunum, ileum, and colon. The mRNA expression and protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in the ileum and colon were increased compared with that in the control group ( < 0.05). Furthermore, the mRNA expression of () in the ileum and colon was increased by ETEC K88 challenge ( < 0.05), whereas in the jejunum, both its mRNA and protein expression were increased by ETEC K88 treatment ( < 0.05). Additionally, an established porcine intestinal epithelial cell line (IPEC-J2) was used to investigate the effect and possible mechanism of ETEC K88 on expression of water channel aquaporins (AQP) and ion transporters. Cells (1.17 × 10 per well) were grown in 6-well plates and treated with ETEC K88 at a multiplicity of infection of 50:1 for 3 h. The mRNA expression of , , and () in IPEC-J2 cells was reduced after ETEC K88 treatment ( < 0.05). Further analyses using western blotting also demonstrated that ETEC K88 decreased the protein expression of AQP3, AQP9, and AQP11 in IPEC-J2 cells ( < 0.05). Moreover, the phosphorylation levels of protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) were decreased by ETEC K88 challenge ( < 0.05). The results indicate that ETEC K88 challenge induced differential expression of intestinal ion transporters and AQP in young piglets, probably by regulation of the cAMP-PKA signaling pathway. This study might provide new insights about the importance of fluid homeostasis in control of ETEC-induced diarrhea in young piglets.

Cytoplasmic DRAK1 overexpressed in head and neck cancers inhibits TGF-ß1 tumor suppressor activity by binding to Smad3 to interrupt its complex formation with Smad4.

Head and neck squamous cell carcinoma (HNSCC) is an extremely aggressive cancer with a poor prognosis and low patient survival. Because chemotherapy for advanced HNSCC is often ineffective, discovering new therapeutic targets that are important for HNSCC development and progression and elucidating their molecular mechanisms are required. In the present study, we describe the role of DRAK1 (death-associated protein kinase-related apoptosis-inducing kinase 1) as a novel negative regulator of the transforming growth factor-ß (TGF-ß) tumor suppressor signaling pathway for the first time in human HNSCC cells. DRAK1 was significantly overexpressed in primary human HNSCCs and in HNSCC cell lines. Through gain- and loss-of-function experiments, we demonstrated that the DRAK1 expression level regulated TGF-ß1-induced transcriptional activity and expression of the tumor suppressor gene p21(Waf1/Cip1). DRAK1 depletion enhanced TGF-ß1-induced growth inhibition in vitro and suppressed tumorigenicity in xenograft models in vivo. Mechanistically, DRAK1 was predominantly localized in the cytoplasm and bound to Smad3, thereby interrupting Smad3/Smad4 complex formation, which is the core process for the induction of tumor suppressor genes by TGF-ß1. Thus, our findings suggest that cytoplasmic DRAK1 increases tumorigenic potential through inhibition of TGF-ß1-mediated tumor suppressor activity in HNSCC cells and may be a potential therapeutic target for HNSCCs.

Microencapsulated iron for milk fortification.

This study was designed to develop a microencapsulated iron that could be used to fortify milk and to determine the sensory properties of milk fortified with microencapsulated iron. Coating material was polyglycerol monostearate (PGMS), and selected core material was ferric ammonium sulfate. The highest efficiency of microencapsulation was 75% with 5:1:30 ratio (w/w/v) as coating to core materials to distilled water. Iron release was 12% when stored at 4 degrees C for 3 days. The TBA value was the lowest when 100 ppm of capsulated iron was added into milk and was significantly lower in capsulated groups compared with that in uncapsulated groups. In an in vitro study, only 3-5% of iron was released in simulated gastric fluid (pH 3, 4, 5, and 6). Comparatively, iron release increased dramatically from 12.3% (pH 5) to 95.7% (pH 8) for 60 min of incubation in simulated intestinal fluid. In a sensory analysis, most aspects except for metallic taste and color were not significantly different between control and capsulated iron fortified milk at 3 days of storage. However, between capsulated and uncapsulated groups, astringency, metallic, color, and overall scores were significantly different. The present study indicated that the use of microencapsulated iron with PGMS is effective for fortifying milk.

Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is known to receive its blood supply principally from the hepatic arteries. Recent studies have reported differences in the vascular supply, especially arterial supply among low- and high-grade dysplastic nodules (DNs) (also referred to as adenomatous hyperplasia and macroregenerative nodules) and HCCs. Increased expression of vascular endothelial growth factor (VEGF) has been reported in HCC. In addition, VEGF may play an important role in the early phases of hepatocarcinogenesis. METHODS: We immunohistochemically stained 7 low-grade DNs, 8 high-grade DNs, 11 early HCCs, 17 small HCCs, and 21 advanced HCCs with antibodies against VEGF, alpha-smooth muscle actin (to identify unpaired arteries, ie, arteries not accompanied by bile ducts, indicative of angiogenesis), CD34 (as a marker of sinusoidal capillarization), and proliferation cell nuclear antigen. RESULTS: Expression of VEGF was found in the hepatocytes and HCC cells. The degree of VEGF expression increased gradually according to the stepwise development of hepatocarcinogenesis. It was higher in high-grade DNs and early HCCs than in low-grade DNs. The hepatocytes and HCC cells adjacent to peliosis and fibrous septa showed stronger VEGF expression. Angiogenesis, unpaired arteries, and sinusoidal capillarization developed from low-grade DNs and gradually increased. It was highest in HCCs. The proliferation cell nuclear antigen labeling indexes of hepatocytes and HCC cells also increased gradually as hepatocarcinogenesis progressed. Small HCCs showed a higher status of neoangiogenesis and cell proliferation activity than advanced HCCs. The degree of VEGF expression was correlated with angiogenesis and cell proliferation activity. CONCLUSION: We conclude that VEGF plays a significant role in angiogenesis, growth, and development of HCC.

E-cadherin expression in thymomas.

For the purpose of investigating the pattern of E-cadherin (E-CD) expression in thymomas, 72 cases were immunostained using monoclonal antibody (HECD-1) and microwave-enhanced immunohistochemical method on formalin-fixed, paraffin-embedded tissue sections. The thymomas were classified according to modified Müller-Hermelink classification. The spindle-shaped, medullary type tumor epithelial cells in medullary (3 cases) and composite type (20 cases) thymomas rarely expressed E-CD except in focal areas showing microcystic change observed in 8 cases. Meanwhile, the cohesive epithelioid tumor cells in every case of well-differentiated thymic carcinomas (WDTC) (29 cases) expressed E-CD. The epithelial cells in cortical type (13 cases) expressed stronger E-CD compared with those of organoid type (7 cases). In cases of WDTC admixed with cortical type, we observed increasing expression of E-CD as the tumor epithelium forms cohesive sheets. We could not find any loss of E-CD expression in invasive foci of the 11 cases of high-staged WDTC examined. Since the results of our study show a strong correlation between E-CD expression and epithelioid morphology of the tumor, E-CD seems to play a major role as a morpho-regulatory factor rather than as a suppressor of invasion in organotypic thymomas.

Pulmonary asbestosis: radiologic-pathologic brief report.

Pulmonary asbestosis is defined as bilateral diffuse interstitial fibrosis of the lungs caused by exposure to asbestos. Many occupations are at risk for asbestos exposure, particularly in the mining, milling, manufacturing, construction, shipbuilding, and automotive industries. Therefore, the prevalence of asbestosis should be fairly widespread. The diagnosis of asbestosis can be made on either clinical or pathological grounds. We recently encountered one case of asbestosis which was confirmed histologically. On HRCT, there was ground-glass opacity with irregular linear shadows, subpleural curvilinear lines and parenchymal bands. Neither plaque nor calcification were noted. The histologic findings observed on open-lung biopsy specimen were well in accord with those in HRCT. Many asbestos-coated bodies were present along with black dust.

Brazilin augments cellular immunity in multiple low dose streptozotocin (MLD-STZ) induced type I diabetic mice.

Brazilin, an active principle of Caesalprenia sappan, was examined for its immunopotentiating effects in multiple low dose streptozotocin (MLD-STZ) induced type diabetic mice. Brazilin was intraperitoneally administered for 5 consecutive days to MLD-STZ induced type I diabetic mice. Delayed type hypersensitivity, Con A-induced proliferation of splenocytes and mixed lymphocyte reaction, which had been decreased in diabetic mice, were significantly recovered by the administration of brazilin. Brazilin increased IL-2 production without affecting suppressor cell activity. Con A-induced and IL-2-induced expression of high affinity IL-2 receptors were also enhanced by brazilin. These results indicate that brazilin augments cellular immune responses, which are suppressed in the MLD-STZ induced type I diabetic mice, by increasing IL-2 production and responsiveness of immune cells to IL-2.

Effects of Brazilin on induction of immunological tolerance by sheep red blood cells in C57BL/6 female mice.

Brazilin was examined for its effects on the induction of immunological tolerance. Brazilin was administered to C57BL/6 female mice for 2 consecutive days before the immunization with high dose SRBC (10(9) cells) which can produce immunological tolerance. Delayed type hypersensitivity, IgM plaque forming cells, ConA induced IL-2 production and mitogen- or antigen-induced proliferation of lymphocytes were measured as evaluation parameters. Administration of brazilin prior to immunization could keep the DTH and IL-2 production almost optimally immunized levels. Brazilin also inhibited the elevation of non-specific suppressor cell activity. ConA induced proliferation of splenocytes in high dose SRBC immunized mice was significantly decreased by pretreatment of brazilin. And this might be one of the reason for augmentation of DTH by brazilin. However, IgM plaque forming cells were not affected by the treatment of brazilin. These results indicate that brazilin prevents the induction of immunological tolerance caused by high dose SRBC by suppressing the elevation of suppressor cell activity and by inhibiting the decrease in IL-2 production in C57BL/6 female mice.

Effect of Lactobacillus plantarum on diarrhea and intestinal barrier function of young piglets challenged with enterotoxigenic Escherichia coli K88.

The present study was performed to investigate the preventative effect of Lactobacillus plantarum on diarrhea in relation to intestinal barrier function in young piglets challenged with enterotoxigenic Escherichia coli (ETEC) K88. Seventy-two male piglets (4 d old) were assigned to 2 diets (antibiotic-free basal diet with or without L. plantarum, 5 × 10(10) cfu/kg diet) and subsequently challenged or not with ETEC K88 (1 × 10(8) cfu per pig) on d 15 in a 2 × 2 factorial arrangement of treatments. Feed intake and BW were measured on d 15 and 18 (3 d after challenge) for determination of growth performance. On d 18, 1 piglet from each pen was slaughtered to evaluate small intestinal morphology and expression of tight junction proteins at the mRNA and protein levels while another piglet was used for the intestinal permeability test. Before and after ETEC K88 challenge, piglets fed L. plantarum had greater BW, ADG, and ADFI (P < 0.05) and marginally greater G:F (P < 0.10) compared to piglets fed the unsupplemented diet. After ETEC K88 challenge, the challenged piglets did not show an impaired growth performance but had greater incidence of diarrhea compared to the nonchallenged piglets. There was an interaction between dietary L. plantarum and ETEC K88 challenge (P < 0.05) as L. plantarum prevented the ETEC K88-induced diarrhea. Piglets challenged with ETEC K88 also had greater urinary lactulose:mannitol and plasma concentration of endotoxin, shorter villi, deeper crypt depth, and reduced villous height:crypt depth in the duodenum and jejunum and decreased zonula occludens-1 mRNA and occludin mRNA and protein expression in the jejunum (P < 0.05). These deleterious effects caused by ETEC K88 were inhibited by feeding L. plantarum (P < 0.05). There were no effects of either treatment on the morphology and expression of tight junction proteins in ileum. In conclusion, L. plantarum, given to piglets in early life, improved performance and effectively prevented the diarrhea in young piglets induced by ETEC K88 challenge by improving function of the intestinal barrier by protecting intestinal morphology and intestinal permeability and the expression of genes for tight junction proteins (zonula occludens-1 and occludin).

Activation of de novo GSH synthesis pathway in mouse spleen after long term low-dose γ-ray irradiation.

Glutathione (GSH) is an important cellular antioxidant and has a critical role in maintaining the balance of cellular redox. In this study, we investigated the GSH biosynthesis genes involved in the elevation of endogenous GSH levels using an irradiation system with an irradiation dose rate of 1.78 mGy/h, which was about 40,000 times less than the dose rates used in other studies. The results showed that GSH levels were significantly increased in the low-dose (0.02 and 0.2 Gy) irradiated group compared to those in the non-irradiated group, but enzymatic antioxidants such as superoxide dismutase and catalase were not induced at any doses tested. The elevation in GSH was accompanied by elevated expression of glutamate-cysteine ligase modifier subunit, but no changes were observed in the expression of glutamate-cysteine ligase catalytic subunit and thioredoxin in de novo GSH synthesis. In the case of genes involved in the GSH regeneration cycle, the expression of glutathione reductase was not changed after irradiation, whereas glutathione peroxidase was only increased in the 0.2 Gy irradiated group. Collectively, our results suggest that the de novo pathway, rather than the regeneration cycle, may be mainly switched on in response to stimulation with long-term low-dose radiation in the spleen.

Atomistic view of the recombinative desorption of H2 from H/Si(100).

Scanning tunneling microscopy is employed to investigate the recombinative desorption of H2 from hydrogenated Si(100) surfaces consisting of dihydride (SiH2) and monohydride (SiH) surface species organized in (1 x 1), (3 x 1), and (2 x 1) configurations. The results show that desorption from dihydrides involves a pair of neighboring dihydrides linked along the tetrahedral bond direction. Dihydrides in (3 x 1) domains are separated in the same direction by monohydrides, and desorption from a pair is geometrically impossible. The same desorption mechanism nevertheless applies via first a position switching of dihydrides with neighboring monohydrides.