tbuckley/cabot-search huggingface dataset:
Characterization of marginal zone B cell precursors
Authors: Bhaskar Srivastava, William J. Quinn, Kristin Hazard, Jan Erikson, David Allman
Journal: The Journal of Experimental Medicine (2005)

Selection of recently formed B cells into the follicular or marginal zone (MZ) compartments is proposed to occur by way of proliferative intermediates expressing high levels of CD21/35 and CD23. However, we show that CD21/35high CD23+ splenocytes are not enriched for proliferative cells, and do not contribute substantially to the generation of follicular B cells. Instead, ontogenic relationships, steady-state labeling kinetics, and adoptive transfer experiments suggest that CD21/35high CD23+ splenocytes serve primarily as precursors for MZ B cells, although their developmental potential seems to be broader and is influenced by environmental cues that are associated with lymphopenia. Furthermore, CD21/35high CD23+ splenocytes share several key functional characteristics with MZ B cells, including their capacity to trap T-independent antigen and a heightened proliferative response to LPS. These observations challenge previous models of peripheral B cell maturation, and suggest that MZ B cells develop by way of CD21/35high CD23+ intermediates.
Abstract 11474: Deficiency of Senescence Marker Protein-30 Impairs Collateral Growth by Supressing Nitric Oxide Bioactivity Under Ischemia
Authors: Hiroyuki Yamauchi, Shu-ichi Saitoh, Takashi Owada, Yasuchika Takeishi
Journal: Circulation (2014)

Aging impairs collateral growth under ischemia and reduces the expression of VEGF, however the exact mechanism is unclear. Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate the effect of SMP30 on ischemia-induced collateral growth, we examined the recovery of cutaneous blood flow (CBF) after femoral artery ligation by laser Doppler imaging in mice. Recoveries of CBF and tissue capillary density were suppressed in SMP30 knockout (KO) mice compared to those of wild type (WT) mice (Figure). Acetylcholine (ACh, 1 μM)-induced NO generation, total thiol and reduced glutathione (GSH) levels in aorta of SMP30 KO mice were lower than those of WT mice (NO: 2.6±4.5 vs. 86.2±9.2 nM; total thiol: 6.3±1.6 vs. 33.2±4.6 nmol/mg/protein; GSH: 5.1±0.8 vs. 18.6±2.1 nmol/mg/protein; P&lt;0.01, respectively). Superoxide generation and NADPH oxidase activity were greater in aorta of SMP30 KO mice compared to that of WT mice (superoxide level: 3.3±0.5 vs. 1.6±0.2 nmol/mg protein; NADPH oxidase activity: 3240±254 vs. 982±106 RLU; P&lt;0.01, respectively). Asymmetric dimethylarginine (ADMA) level was higher in aorta of SMP30 KO mice than that of WT mice (6.4±0.8 vs. 2.4±0.4 nmol/mg protein, P&lt;0.01). VEGF content in the crural muscle in SMP30 KO mice did not increase in 14 days post-ischemia compared to that in pre-ischemia (SMP30 KO mice 1.1±0.2 fold vs. WT mice 2.2±0.3 fold, P&lt;0.01). Akt phosphorylation in the crural muscle was attenuated in SMP30 KO mice compared to that of WT mice (p-Akt/Akt: SMP30 KO mice 0.4±0.3 vs. WT mice 1.2±0.4, P&lt;0.01). Thus, SMP30 deficiency exacerbates oxidant stress due to NADPH oxidase activation, which leads to the rarefaction of collateral growth induced by ischemia related to Akt-VEGF pathway. These results suggest that the decrease of SMP30 in aging impairs VEGF/NO-dependent angiogenesis associated with overproduction of superoxide.
Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides
Authors: Raul Harari, Jordi Julvez, Katsuyuki Murata, Dana Barr, David C. Bellinger, Frodi Debes, Philippe Grandjean
Journal: Environmental Health Perspectives (2010)

BackgroundThe long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable.ObjectivesIn northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children's neurobehavioral functions at 6–8 years of age.MethodsWe examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children's current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity.ResultsOf 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5–2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results.ConclusionsThese findings support the notion that prenatal exposure to pesticides—at levels not producing adverse health outcomes in the mother—can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a "silent pandemic" of developmental neurotoxicity.
How infections can modify lung immunity
Authors: L.P. Nicod, M.A. Spiteri
Journal: European Respiratory Journal (2001)

Several studies have reported low rates of allergic sensitization and allergies in children exposed to respiratory tract infections 1, 2 or a rural environment 3. The role of immunity in controlling infections has been well explored in the past, but the long-lasting effect of infections on immunity in health and disease is still largely unknown. It is, therefore, important to consider current knowledge on lung defences in order to find new approaches in identifying how infections may modulate T-helper (Th)1/Th2 immunity.

There has been increasing evidence in previous literature linking host innate immunity, triggered by many infectious agents, and acquired immunity with its specific humoral and cellular responses. Innate immunity is driven through the actions of a variety of cell types, including macrophages, eosinophils, basophils and T-lymphocytes, such as γδ T-cells or natural killer (NK) cells. Innate immunity can be triggered by: lipopolysaccharides via receptors, such as CD14, in conjunction with the Toll 4 receptors; bacterial peptidoglycans interacting with Toll 2 receptors; bacterial deoxyribonucleic acid (DNA) …
Intron gain and loss in segmentally duplicated genes in rice
Authors: Haining Lin, Wei Zhu, Joana C Silva, Xun Gu, C Robin Buell
Journal: Genome biology (2006)

Introns are under less selection pressure than exons, and consequently, intronic sequences have a higher rate of gain and loss than exons. In a number of plant species, a large portion of the genome has been segmentally duplicated, giving rise to a large set of duplicated genes. The recent completion of the rice genome in which segmental duplication has been documented has allowed us to investigate intron evolution within rice, a diploid monocotyledonous species.Analysis of segmental duplication in rice revealed that 159 Mb of the 371 Mb genome and 21,570 of the 43,719 non-transposable element-related genes were contained within a duplicated region. In these duplicated regions, 3,101 collinear paired genes were present. Using this set of segmentally duplicated genes, we investigated intron evolution from full-length cDNA-supported non-transposable element-related gene models of rice. Using gene pairs that have an ortholog in the dicotyledonous model species Arabidopsis thaliana, we identified more intron loss (49 introns within 35 gene pairs) than intron gain (5 introns within 5 gene pairs) following segmental duplication. We were unable to demonstrate preferential intron loss at the 3' end of genes as previously reported in mammalian genomes. However, we did find that the four nucleotides of exons that flank lost introns had less frequently used 4-mers.We observed that intron evolution within rice following segmental duplication is largely dominated by intron loss. In two of the five cases of intron gain within segmentally duplicated genes, the gained sequences were similar to transposable elements.
Chronic treatment with rosuvastatin modulates nitric oxide synthase expression and reduces ischemia–reperfusion injury in rat hearts
Authors: P DINAPOLI, A TACCARDI, A GRILLI, M DELUTIIS, A BARSOTTI, M FELACO, R DECATERINA
Journal: Cardiovascular Research (2005)

Due to reported modulatory effects of statins on nitric oxide synthase (NOS) expression, we tested the hypothesis of protective effects of in vivo chronic treatment with rosuvastatin, a novel 3-hydroxy-3-methyl-glutaryl coenzyme A-reductase inhibitor, on ischemia-reperfusion injury, and investigated mechanisms involved.After 3 weeks of in vivo treatment with rosuvastatin (0.2-20 mg/kg/day) or placebo, excised hearts from Wistar rats were subjected to 15 min global ischemia and 22-180 min reperfusion. We evaluated creatine-phosphokinase and nitrite levels in the coronary effluent, heart weight changes, microvascular permeability (extravasation of fluoresceine-labeled albumin), ultrastructural alterations, and the expression of endothelial (e) and inducible (i) nitric oxide synthase (NOS) (by reverse-transcription polymerase chain reaction and Western blotting).Rosuvastatin 0.2 and 2 mg/kg/day significantly reduced myocardial damage and vascular hyperpermeability, concomitant with a reduction in endothelial and cardiomyocyte lesions. At 2 mg/kg/day, rosuvastatin significantly increased eNOS mRNA and protein compared with untreated hearts, and conversely decreased iNOS mRNA and protein, as well as nitrite production after ischemia-reperfusion. The addition of the NOS inhibitor N(omega)-nitro-L-arginine methylester (L-NAME, 30 micromol/L) significantly reduced cardioprotection against ischemia-reperfusion.Chronic treatment with rosuvastatin before ischemia reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte damage by NO-dependent mechanisms.
Pulmonary function after phrenic nerve transfer for brachial plexus avulsion injury
Authors: Paulo Beraldo, Ricardo Gepp, Lívia Penna, Sergio Ramalho, Regis Silva, Eidmar Neri
Journal: European Respiratory Journal (2011)

Objective: Spirometry was assessed in patients before and after full-length phrenic nerve transfer surgery.

Methods: 16 patients (13 men; 17 to 58 years old) with brachial plexus injury underwent full-length phrenic nerve transfer. By video-assisted thoracic surgery the phrenic nerve was severed at a location just before its entry into the diaphragm, harvested from the thoracic cavity, and transferred to the musculocutaneous nerve. The median time between injury and surgery was 5.5 months (range 2.8 to 10.2). Patients underwent follow-up evaluation 1.4 to 16.4 months with manual muscle testing and spirometry; 3 patients were eventually lost to follow up.

Results: Baseline spirometric parameters were normal. Although no patient experienced pulmonary problems or respiratory complains following the surgery, we observed a significant reduction of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC, respectively, to 69% of predicted values (±13; p<0.001), 68% of predicted values (±17; p<0.001) and 81% (±11; p=0,03). The percent variation of FVC was -22% (±11; range -49% to -6%). We observed a negative dependence between FVC and length of time after surgery (Figure). The majority of patients exhibit motor improvement on the arm.

![Figure][1] 



Conclusion: Although preliminary, our results point to a significant impact of the surgery to spirometric parameters. This impact improves with the time after surgery.

 [1]: pending:yes
Activation of the Canonical Wnt Pathway during Genital Keratinocyte Transformation: A Model for Cervical Cancer Progression
Authors: Aykut Üren, Shannon Fallen, Hang Yuan, Alp Usubütün, Türkan Küçükali, Richard Schlegel, Jeffrey A. Toretsky
Journal: Cancer Research (2005)

Abstract Cervical carcinoma, the second leading cause of cancer deaths in women worldwide, is associated with human papillomavirus (HPV). HPV-infected individuals are at high risk for developing cervical carcinoma; however, the molecular mechanisms that lead to the progression of cervical cancer have not been established. We hypothesized that in a multistep carcinogenesis model, HPV provides the initial hit and activation of canonical Wnt pathway may serve as the second hit. To test this hypothesis, we evaluated the canonical Wnt pathway as a promoting factor of HPV-induced human keratinocyte transformation. In this in vitro experimental cervical carcinoma model, primary human keratinocytes immortalized by HPV were transformed by SV40 small-t (smt) antigen. We show that smt-transformed cells have high cytoplasmic β-catenin levels, a hallmark of activated canonical Wnt pathway, and that activation of this pathway by smt is mediated through its interaction with protein phosphatase-2A. Furthermore, inhibition of downstream signaling from β-catenin inhibited the smt-induced transformed phenotype. Wnt pathway activation transformed HPV-immortalized primary human keratinocytes even in the absence of smt. However, activation of the Wnt pathway in the absence of HPV was not sufficient to induce transformation. We also detected increased cytoplasmic and nuclear staining of β-catenin in invasive cervical carcinoma samples from 48 patients. We detected weak cytoplasmic and no nuclear staining of β-catenin in 18 cases of cervical dysplasia. Our results suggest that the transformation of HPV expressing human keratinocytes requires activation of the Wnt pathway and that this activation may serve as a screening tool in HPV-positive populations to detect malignant progression.
Importance of Radiotherapy in the Outcome of Patients With Primary CNS Lymphoma: An Analysis of the CHOD/BVAM Regimen Followed by Two Different Radiotherapy Treatments
Authors: E. M. Bessell
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen.
The regulation by iron of the synthesis of adhesins and cytoadherence levels in the protozoan Trichomonas vaginalis.
Authors: M W Lehker, R Arroyo, J F Alderete
Journal: The Journal of Experimental Medicine (1991)

Levels of adherence of Trichomonas vaginalis to epithelial cells was found to be modulated by iron. Cytoadherence values were greater than or equal to twofold higher for trichomonads grown in a complex cultivation medium supplemented with iron. This increase in adherence levels was specifically mediated by iron; parasites cultured in a low-iron medium in the presence of salts other than iron were unresponsive to changes in adherence levels. Expression of the higher adherence property, by parasites grown first in low-iron medium followed by supplementation with iron, was a function of time, and the extent of cytoadherence was proportional to the concentration of iron added to the medium. Lactoferrin, an important iron source for trichomonads at the site of infection, elevated adherence of the parasite to epithelial cells, demonstrating the likely in vivo modulation of adherence by iron. The alteration of levels of adherence caused by iron was determined to be a reflection of gene expression of previously characterized trichomonad adhesins. Parasites grown under iron-replete conditions had higher quantities of surface-exposed adhesins, and this was a result of increased synthesis of adhesins. Actinomycin D and alpha-amanitin prevented expression of adhesin molecules, which resulted in decreased cytoadherence, showing that adhesin synthesis was dependent on gene transcription. Data indicated that genes encoding the four trichomonad adhesins are coordinately regulated by iron.
Long term cancer survival rates double in England and Wales in past 40 years
Authors: A. O'Dowd
Journal: BMJ (2010)

Cancer experts have welcomed news that long term survival rates from some cancers have doubled over the past 40 years.

People given a diagnosis of breast, bowel, or ovarian cancer or non-Hodgkin’s lymphoma are now twice as likely to survive for at least 10 years as people with these diagnoses in the early 1970s.

Several factors, including faster diagnosis, better surgery, more effective radiotherapy, personalised treatment, and new drugs, have helped lead to the improvements in survival.

The figures, released this week by the charity Cancer Research UK, show that the proportion of women considered likely to survive breast cancer for at least 10 years rose from 38.9% in …
Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199
Authors: Sylvia Adams, Robert J. Gray, Sandra Demaria, Lori Goldstein, Edith A. Perez, Lawrence N. Shulman, Silvana Martino, Molin Wang, Vicky E. Jones, Thomas J. Saphner, Antonio C. Wolff, William C. Wood, Nancy E. Davidson, George W. Sledge, Joseph A. Sparano, Sunil S. Badve
Journal: Journal of Clinical Oncology (2014)

Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified.The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS.In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids.
Authors: P T Clayton, J V Leonard, A M Lawson, K D Setchell, S Andersson, B Egestad, J Sjövall
Journal: Journal of Clinical Investigation (1987)

Urinary bile acids from a 3-mo-old boy with cholestatic jaundice were analyzed by ion exchange chromatography and gas chromatography-mass spectrometry (GC-MS). This suggested the presence of labile sulfated cholenoic acids with an allylic hydroxyl group, a conclusion supported by analysis using fast atom bombardment mass spectrometry (FAB-MS). The compounds detected by FAB-MS were separated by thin layer chromatography and high performance liquid chromatography. The sulfated bile acids could be solvolyzed in acidified tetrahydrofuran, and glycine conjugates were partially hydrolyzed by cholylglycine hydrolase. Following solvolysis, deconjugation, and methylation with diazomethane, the bile acids were identified by GC-MS of trimethylsilyl derivatives. The major bile acids in the urine were 3 beta,7 alpha-dihydroxy-5-cholenoic acid 3-sulfate, 3 beta,7 alpha,12 alpha-trihydroxy-5-cholenoic acid monosulfate, and their glycine conjugates. Chenodeoxycholic acid and cholic acid were undetectable in urine and plasma. The family pedigree suggested that abnormal bile acid synthesis was an autosomal recessive condition leading to cirrhosis in early childhood.
Human High Molecular Weight–Melanoma-Associated Antigen: Utility for Detection of Metastatic Melanoma in Sentinel Lymph Nodes
Authors: Yasufumi Goto, Soldano Ferrone, Takaaki Arigami, Minoru Kitago, Atsushi Tanemura, Eiji Sunami, Sandy L. Nguyen, Roderick R. Turner, Donald L. Morton, Dave S.B. Hoon
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Detection of micrometastasis in melanoma-draining lymph nodes is important for staging and prognosis. Immunohistochemical staining (IHC) using S-100p-HMB-45–, and MART-1–specfic antibodies is used for detecting metastases in sentinel lymph nodes (SLN). However, improvement in IHC is needed for melanoma micrometastasis detection. Experimental Design: Paraffin-embedded archival tissue (PEAT) specimens were obtained from 42 non-SLN macrometastases, 42 SLN metastases, and 16 tumor-negative SLNs of 100 melanoma patients who underwent SLN biopsy. PEAT specimens were assessed by IHC with high molecular weight−melanoma-associated antigen (HMW-MAA)–specific monoclonal antibodies (mAb) and with S-100p-, HMB-45–, and MART-1–specific antibodies. Quantitative real-time reverse-transcriptase PCR assay was used for HMW-MAA and MART-1 mRNA detection. Results: Expression frequency and immunostaining intensity were higher for HMW-MAA than MART-1 in nodal macrometastases (P &amp;lt; 0.0001 and P &amp;lt; 0.0001, respectively) and micrometastases (P &amp;lt; 0.0001 and P = 0.004, respectively). All 52 (100%) macrometastases were positive with HMW-MAA–specific mAbs, whereas 43 (83%) were positive with MART-1–specific mAbs. In a comparison analysis, 23 of 23 (100%) micrometastases were HMW-MAA–positive, whereas 21 (91%) and 18 (78%) specimens were S-100p– and HMB-45–positive, respectively. Quantitative real-time reverse-transcriptase PCR analysis of 48 nodal metastases showed HMW-MAA mRNA detection in SLNs with metastases. Conclusions: HMW-MAA is more sensitive and specific than MART-1, S-100p, and HMB-45 for IHC-based detection of SLN micrometastases. SLN PEAT–based detection specificity of melanoma micrometastases can be improved by IHC with HMW-MAA–specific mAbs.