tbuckley/cabot-search huggingface dataset:
TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells
Authors: Julien C. Marie, John J. Letterio, Marc Gavin, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2005)

Transforming growth factor (TGF)-β1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-β1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4+CD25+ regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8–10-d-old TGF-β1–deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-β–mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-β1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.
Abstract LB-26: Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors
Authors: Yun Qiu, Feng Sun, Xi Yang
Journal: Cancer Research (2014)

Abstract Deregulation of androgen receptor (AR) splice variants have been implicated to play a role in prostate cancer development and progression. To understand their functions in prostate, we established a transgenic mouse model (AR3Tg) with targeted expression of the constitutively active and androgen-independent AR splice variant AR3 (a.k.a. AR-V7) in prostate epithelium. We found that over-expression of AR3 modulates expression of a number of tumor-promoting autocrine/ paracrine growth factors (including Tgfβ2 and Igf1) and expands prostatic progenitor cell population, leading to development of prostatic intraepithelial neoplasia. In addition, we showed that some epithelial-mesenchymal-transition (EMT) associated genes are upregulated in AR3Tg prostates, suggesting that AR3 may antagonize AR activity and halt differentiation process driven by AR and androgen. This notion is supported by our observations that the number of ck5+/ck8+ intermediate cells is increased in AR3Tg prostates after castration, and expression of AR3 transgene in these intermediate cells compromises prostate epithelium regeneration upon androgen replacement. Our results demonstrate that AR3 is a driver of prostate cancer, at least in part, through modulating multiple tumor-promoting autocrine/paracrine factors. Citation Format: Yun Qiu, Feng Sun, Xi Yang. Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-26. doi:10.1158/1538-7445.AM2014-LB-26
Mutations in exons 2 and 3 of the cationic trypsinogen gene in Japanese families with hereditary pancreatitis
Authors: I Nishimori, M Kamakura, K Fujikawa-Adachi, M Morita, S Onishi, K Yokoyama, I Makino, H Ishida, M Yamamoto, S Watanabe, M Ogawa
Journal: Gut (1999)

Background/Aims Single-point mutations in the cationic trypsinogen gene have been reported in hereditary pancreatitis kindreds in the white population. The aim of the present study was to investigate whether similar gene mutations are present in Japanese hereditary pancreatitis kindreds. Methods All five exons of the cationic trypsinogen gene were amplified by polymerase chain reaction and sequenced in six Japanese families with hereditary pancreatitis. Results Two types of single-point mutation in the cationic trypsinogen gene, which were identical with those reported in white families with hereditary pancreatitis, were observed in separate Japanese families with hereditary pancreatitis: 21 Asn (AAC) to Ile (ATC) (N21I) in exon 2 and 117 Arg (CGC) to His (CAC) (R117H) in exon 3. Pancreatitis occurred at more advanced ages in patients with the N21I mutation than in those with the R117H mutation. Besides normal polymorphisms in exons 4 and 5, no mutation was found in patients in the remaining four families with hereditary pancreatitis, 21 patients with sporadic chronic pancreatitis, or five normal subjects. Conclusions These results show heterogeneity, but no racial specificity, in the cationic trypsinogen gene mutations in hereditary pancreatitis kindreds. A distinctive clinical feature for each of the mutation types is suggested: adult onset for the N21I mutation and childhood onset for the R117H mutation.
Oral treatment with probiotic Lactobacillus johnsonii NCC533 (La1) for a specific part of the weaning period prevents the development of atopic dermatitis induced after maturation in model mice, NC/Nga
Authors: R. Inoue, A. Nishio, Y. Fukushima, K. Ushida
Journal: British Journal of Dermatology (2007)

The inhibitory effect of probiotic bacteria on atopic dermatitis has been shown in human infants, but the mechanism is still unclear.This study aimed to show the effects of the administration of a probiotic during the weaning period in mouse models on production of the intestinal secretory IgA (sIgA) and on the development of atopic dermatitis (AD) in later life.The effects of the administration of Lactobacillus johnsonii NCC533 (La1) during weaning were evaluated using a mouse model (Balb/c). The weaning period of mice was divided into three phases according to the evolution of faecal IgA. La1 was administered in each phase and the evolution of the faecal IgA was estimated. In the next experiment, the effect of the administration of La1 in phase 2 on host immunity after maturation was further assessed by using the model NC/Nga mouse for human AD.Administration of La1 in each phase showed a distinct effect on the production of sIgA. But sIgA production was only positively stimulated when La1 was administrated in phase 2. The development of AD induced by mite antigen from 6 weeks old was significantly prevented by the primary administration of La1 in phase 2. AD-like lesions were significantly milder than those of the control mice, and histological observations showed an almost normal appearance of the epidermis and upper dermis of the mice treated with La1.This study suggested that the primary administration of La1 in a specific part of the weaning period is effective in preventing or inhibiting the development of AD after maturation by modulating or accelerating the gut immune response.
Frozen chips: an unusual cause of severe frostbite injury: Figure 1
Authors: Colin A Graham, James Stevenson
Journal: British Journal of Sports Medicine (2000)

A case of severe frostbite injury to the right foot is presented. This was caused by the inappropriate application of a bag of frozen chips to the foot in an attempt to ease non-specific pain. No specific acute traumatic injury was identified. As the patient was a teacher of physical education, the pain had initially been assumed to originate from a minor musculoskeletal injury. Full recovery ensued after surgical excision of necrotic tissue and split skin grafting. The danger of inappropriate overenthusiastic use of ice packs or other frozen material to treat soft tissue injuries is emphasised. The need for education to prevent similar future injuries is discussed.
Optimization of folic acid, vitamin B<sub>12</sub>, and vitamin B<sub>6</sub> supplements in pediatric patients with sickle cell disease
Authors: Fey P.L. van der Dijs, M. Rebecca Fokkema, D.A. Janneke Dijck‐Brouwer, Bram Niessink, Thaliet I.C. van der Wal, John‐John B. Schnog, Ashley J. Duits, Fred D. Muskiet, Frits A.J. Muskiet
Journal: American Journal of Hematology (2002)

Abstract Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B 12 , and vitamin B 6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7–16 years). Daily supplements of folic acid (400, 700, or 1,000 μg), vitamin B 12 (1, 3, or 5 U.S. 1989 RDA), and vitamin B 6 (1 or 3 U.S. 1989 RDA) were gradually increased in an 82‐week dose‐escalation study. Blood was taken at 9 occasions for measurements of erythrocyte (RBC) and serum folate, plasma vitamin B 12 , whole‐blood vitamin B 6 , and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 μg and vitamin B 12 from 3 to 5 RDA did not further decrease homocysteine. Percentages of patients exhibiting significant individual homocysteine decreases amounted to 43% (folic acid from 0 to 400 μg, vitamins B 12 and B 6 from 0 to 1 RDA), 14% (folic acid from 400 to 700 μg), 24% (vitamin B 12 from 1 to 3 RDA), and 18% (vitamin B 6 from 1 to 3 RDA ). The lowest plasma homocysteine at 82 weeks was 5.9 ± 2.2 μmol/L. Patients with HbSS had higher RBC folate than HbSC. The entire group exhibited an inverse relation between RBC folate and hemoglobin. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. Optimal dosages are as follows: 700 μg folic acid (3.5–7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B 12 (4.2–6.0 μg), and 3 U.S. 1989 RDA vitamin B 6 (4.2–6.0 mg). A practical daily combination is 1 mg folic acid (4.3–8.5 U.S. 1998 RDA when taken with meals), 6 μg vitamin B 12 (2.5–5 U.S. 1998 RDA), and 6 mg vitamin B 6 (4.6–10 U.S. 1998 RDA). This combination may by simple and relatively inexpensive means reduce these patients' inherently high risk of endothelial damage. Am. J. Hematol. 69:239–246, 2002. © 2002 Wiley‐Liss, Inc.
Resident macrophages (ramified microglia) of the adult brown Norway rat central nervous system are constitutively major histocompatibility complex class II positive.
Authors: J D Sedgwick, S Schwender, R Gregersen, R Dörries, V ter Meulen
Journal: The Journal of Experimental Medicine (1993)

A flow cytometric phenotype for isolated adult central nervous system (CNS) ramified microglia was previously defined (CD45low CD11b/c+) in the Lewis strain rat, that clearly distinguished these cells from all blood-derived leucocytes, the latter being CD45high. Consistent with the reported lack of major histocompatibility complex (MHC) expression in the CNS, isolated microglia were mostly MHC class II-. Employing these phenotypic criteria, we now show that a proportion of microglia in Brown Norway (BN) strain rats are constitutively MHC class II+. In spinal cord, up to 25% of microglia are distinctly positive and most have some level of expression. In situ staining of MHC class II+ microglial cells in BN rats indicates that positive cells are typical of ramified microglia on the grounds of both morphological appearance and anatomical location. In Lewis (LEW) rats, the few MHC class II-expressing cells isolated from the normal CNS are CD45high blood-derived cells and not resident microglia. After infection of both LEW and BN rats with a neurotropic murine hepatitis virus (MHV-JHM), MHC class II was rapidly upregulated on microglia in the BN but not in the LEW strain. In the latter, inflammatory cells were the predominant MHC class II-expressing population. Nevertheless, most microglia in the LEW strain could, after some delay, be induced to express MHC class II after transfer of an experimental autoimmune encephalomyelitis (EAE)-inducing encephalitogenic T cell line. Paradoxically, strains resistant to EAE (exemplified by the BN) contained more constitutive MHC class II-expressing microglia than susceptible ones, when a variety of strains were examined. The results clearly establish that the normal CNS may contain MHC class II-expressing cells that are a resident rather than a transient blood-derived population. It is significant that this expression is strain related, but there is no evidence that microglial cell constitutive MHC class II expression predisposes to EAE susceptibility.
Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease
Authors: Jeffrey T-J Huang, Rekha Chaudhuri, Osama Albarbarawi, Alun Barton, Christal Grierson, Petra Rauchhaus, Christopher J Weir, Martina Messow, Nicola Stevens, Charles McSharry, Giora Feuerstein, Somnath Mukhopadhyay, Jeffrey Brady, Colin N A Palmer, Douglas Miller, Neil C Thomson
Journal: Thorax (2012)

<h3>Background</h3> Although an increased concentration of degraded elastin products in patients with chronic obstructive pulmonary disease (COPD) has been reported for many years, its clinical validity and utility remain uncertain due to technical difficulties, small study groups and the unknown relationship between exacerbation and elastin degradation. The objectives of this study were to determine the validity of urinary and blood total desmosine/isodesmosine in patients with COPD and asthma and to evaluate their relationship to exacerbation status and lung function. <h3>Methods</h3> Urinary and blood desmosine levels were measured using validated isotopic dilution liquid chromatography–tandem mass spectrometry methods. <h3>Results</h3> 390 study participants were recruited from the following groups: healthy volunteers, stable asthma, stable and ‘during an exacerbation’ COPD. Compared with healthy non-smokers, we found increased urinary or blood desmosine levels in patients with COPD, but no differences in patients with asthma or healthy smokers. The elevation of urinary desmosine levels was associated with the exacerbation status in patients with COPD. Approximately 40% of patients with stable and ‘during an exacerbation’ COPD showed elevated blood desmosine levels. Blood desmosine levels were strongly associated with age and were negatively correlated with lung diffusing capacity for carbon monoxide. <h3>Conclusion</h3> The results suggest that urinary desmosine levels are raised by exacerbations of COPD whereas blood desmosine levels are elevated in a subgroup of patients with stable COPD and reduced lung diffusing capacity. The authors speculate that a raised blood desmosine level may identify patients with increased elastin degradation suitable for targeted therapy. Future prospective studies are required to investigate this hypothesis.
mTOR inhibition rescues osteopenia in mice with systemic sclerosis
Authors: Chider Chen, Kentaro Akiyama, Dandan Wang, Xingtian Xu, Bei Li, Alireza Moshaverinia, Frank Brombacher, Lingyun Sun, Songtao Shi
Journal: The Journal of Experimental Medicine (2014)

Fibrillin-1 (FBN1) deficiency-induced systemic sclerosis is attributed to elevation of interleukin-4 (IL4) and TGF-β, but the mechanism underlying FBN1 deficiency–associated osteopenia is not fully understood. We show that bone marrow mesenchymal stem cells (BMMSCs) from FBN1-deficient (Fbn1+/−) mice exhibit decreased osteogenic differentiation and increased adipogenic differentiation. Mechanistically, this lineage alteration is regulated by IL4/IL4Rα-mediated activation of mTOR signaling to down-regulate RUNX2 and up-regulate PPARγ2, respectively, via P70 ribosomal S6 protein kinase (P70S6K). Additionally, we reveal that activation of TGF-β/SMAD3/SP1 signaling results in enhancement of SP1 binding to the IL4Rα promoter to synergistically activate mTOR pathway in Fbn1+/− BMMSCs. Blockage of mTOR signaling by osteoblastic-specific knockout or rapamycin treatment rescues osteopenia phenotype in Fbn1+/− mice by improving osteogenic differentiation of BMMSCs. Collectively, this study identifies a previously unrecognized role of the FBN1/TGF-β/IL4Rα/mTOR cascade in BMMSC lineage selection and provides experimental evidence that rapamycin treatment may provide an anabolic therapy for osteopenia in Fbn1+/− mice.
Comparison of the Effects of Vitamins and/or Mineral Supplementation on Glomerular and Tubular Dysfunction in Type 2 Diabetes
Authors: Maryam Sadat Farvid, Mahmoud Jalali, Fereydoun Siassi, Mostafa Hosseini
Journal: Diabetes Care (2005)

The present study was designed to assess the effect of magnesium plus zinc, vitamins C plus E, and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients.In a randomized, double-blind, placebo-controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months: group M (n = 16), 200 mg Mg and 30 mg Zn; group V (n = 18), 200 mg vitamin C and 100 IU vitamin E; group MV (n = 17), minerals plus vitamins; and group P (n = 18), placebo. Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity (NAG) in urine were determined at the beginning and at the end of the trial. Treatment effects were analyzed by general linear modeling.Results indicate that after 3 months of supplementation, levels of urinary albumin excretion decreased in the V and MV groups (P = 0.034 and P = 0.005, respectively). Urinary NAG activity did not significantly change in any treatment groups. Levels of systolic, diastolic, and mean blood pressure significantly decreased in the MV group (P = 0.008, P = 0.017, and P = 0.009, respectively). Also, combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose (P = 0.035) and malondialdehyde concentrations (P = 0.004) and in increasing HDL cholesterol and apolipoprotein A1 levels (P = 0.019). There was no significant change in the levels of these parameters in the other three groups.In conclusion, the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium, zinc, and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients.
Extracellular hemin crisis triggers acute chest syndrome in sickle mice
Authors: Samit Ghosh, Olufolake Adetoro Adisa, Prasanthi Chappa, Fang Tan, Kesmic Ann Jackson, David Robert Archer, Solomon Fiifi Ofori-Acquah
Journal: Journal of Clinical Investigation (2013)

The prevention and treatment of acute chest syndrome (ACS) is a major clinical concern in sickle cell disease (SCD). However, the mechanism underlying the pathogenesis of ACS remains elusive. We tested the hypothesis that the hemolysis byproduct hemin elicits events that induce ACS. Infusion of a low dose of hemin caused acute intravascular hemolysis and autoamplification of extracellular hemin in transgenic sickle mice, but not in sickle-trait littermates. The sickle mice developed multiple symptoms typical of ACS and succumbed rapidly. Pharmacologic inhibition of TLR4 and hemopexin replacement therapy prior to hemin infusion protected sickle mice from developing ACS. Replication of the ACS-like phenotype in nonsickle mice revealed that the mechanism of lung injury due to extracellular hemin is independent of SCD. Using genetic and bone marrow chimeric tools, we confirmed that TLR4 expressed in nonhematopoietic vascular tissues mediated this lethal type of acute lung injury. Respiratory failure was averted after the onset of ACS-like symptoms in sickle mice by treating them with recombinant hemopexin. Our results reveal a mechanism that helps to explain the pathogenesis of ACS, and we provide proof of principle for therapeutic strategies to prevent and treat this condition in mice.
Ascorbic acid deficiency in liver disease.
Authors: A D Beattie, S Sherlock
Journal: Gut (1976)

Leucocyte ascorbic acid (LAA) levels were measured in 138 patients with liver disease. Significantly reduced levels were found in 37 patients with alcoholic liver disease (P less than 0-01) and 25 patients with primary biliary cirrhosis (P less than 0-05). In the primary biliary cirrhosis patients, cholestyramine therapy was associated with significantly lower levels of the vitamin (P less than 0-05). Liver ascorbic acid measured in Menghini needle biopsies in 20 patients was significantly correlated with LAA (r=0-807, P less than 0-001). No significant correlation was found between LAA and haematological indices, conventional liver function tests, or cholesterol levels in any group of patients. Patients with LAA levels below 100 nM/10(8) WBC had significantly higher antipyrine half-lives (mean=28-3 h) than patients with LAA levels above this level (mean=18-6 h) (P less than 0-05). Delayed drug metabolism related to low LAA should be considered when drugs metabolised by the liver are prescribed for patients with alcoholic liver disease or primary biliary cirrhosis.
Nonthermal Plasma Sterilization of Living and Nonliving Surfaces
Authors: N. De Geyter, R. Morent
Journal: Annual Review of Biomedical Engineering (2012)

The recent tremendous progress in understanding physical plasma phenomena, together with the development of new plasma sources, has put a growing focus on the application of nonthermal plasmas in the biomedical domain. Among several novel applications, the inactivation of bacteria by nonthermal plasmas (so-called plasma sterilization) is particularly interesting. This introductory review provides a summary of the current status of this emerging research field. In addition to the inactivation of bacteria on nonliving surfaces, this review also focuses on the sterilization of living surfaces, such as animal and human tissues. Clearly, nonthermal plasmas have undoubtedly great potential as a novel method for low-temperature sterilization.
Bilateral Renal Vein Thrombosis
Authors: R A M KENGEN, E H DE GROOT, J G ZIJLSTRA, D A PIERS
Journal: Clinical Nuclear Medicine (1990)

Unilateral or even bilateral renal vein thrombosis is a frequent complication in patients with a nephrotic syndrome. The patient presented developed bilateral thrombosis: the left side was clinically symptomatic and showed clear renographic changes, which resolved without therapy. The thrombosis at the right side was asymptomatic and showed no renographic changes because of synchronous formation of a collateral network. The following is therefore concluded: 1) normalization of the renographic study in renal vein thrombosis is not necessarily due to treatment: it can occur after spontaneous formation of collaterals; 2) renal vein thrombosis can be unremarkable not only clinically but also on the renogram.
Are Health Care Professionals Advising Patients With Diabetes or At Risk for Developing Diabetes to Exercise More?
Authors: Elaine H. Morrato, James O. Hill, Holly R. Wyatt, Vahram Ghushchyan, Patrick W. Sullivan
Journal: Diabetes Care (2006)

OBJECTIVE—With increased focus on the obesity and diabetes epidemics, and the clear benefit of exercise in disease prevention and management, this study determined the lifetime prevalence of health professional advice to exercise among individuals with or at risk for diabetes. RESEARCH DESIGN AND METHODS—The Medical Expenditure Panel Survey is a nationally representative survey of the U.S. population. In the 2002 survey, 26,878 adults responded when asked about ever receiving health professional advice to exercise more. Information on sociodemographic characteristics and health conditions were self-reported. Type 2 diabetes risk factors were age ≥45 years, non-Caucasian ethnicity, physical inactivity, BMI ≥25 kg/m2, hypertension, and cardiovascular disease. RESULTS—A total of 73% of adults with diabetes were told by a health professional to exercise more versus 31% of adults without diabetes. The proportion receiving advice increased as the number of diabetes risk factors increased until reaching similar rates as people with diabetes. After adjustment for sociodemographic and clinical factors, the strongest correlates of receiving advice were BMI and cardiovascular risk factors. Among respondents with diabetes, the likelihood of receiving advice did not vary by age, sex, education, or income level but was less likely in Hispanics. CONCLUSIONS—Health professionals advised most patients with or at highest risk for diabetes to exercise, suggesting recognition of its importance for disease management. As risk factors declined, fewer patients were advised to exercise, suggesting missed opportunities for disease prevention. However, exercise has not increased proportional to exercise advice. The challenge remains converting patient awareness into behavior change.