tbuckley/cabot-search huggingface dataset:
Phase-variable Expression of Lipopolysaccharide Contributes to the Virulence of <i>Legionella pneumophila </i>
Authors: Edeltraud Lüneberg, Ulrich Zähringer, Yuriy A. Knirel, Dorothee Steinmann, Maike Hartmann, Ivo Steinmetz, Manfred Rohde, Jörg Köhl, Matthias Frosch
Journal: The Journal of Experimental Medicine (1998)

With the aid of monoclonal antibody (mAb) 2625, raised against the lipopolysaccharide (LPS) of Legionella pneumophila serogroup 1, subgroup OLDA, we isolated mutant 811 from the virulent wild-type strain RC1. This mutant was not reactive with mAb 2625 and exhibited an unstable phenotype, since we observed an in vitro and in vivo switch of mutant 811 to the mAb 2625–positive phenotype, thus restoring the wild-type LPS. Bactericidal assays revealed that mutant 811 was lysed by serum complement components, whereas the parental strain RC1 was almost serum resistant. Moreover, mutant 811 was not able to replicate intracellularly in macrophage-like cell line HL-60. In the guinea pig animal model, mutant 811 exhibited significantly reduced ability to replicate. Among recovered bacteria, mAb 2625–positive revertants were increased by fourfold. The relevance of LPS phase switch for pathogenesis of Legionella infection was further corroborated by the observation that 5% of the bacteria recovered from the lungs of guinea pigs infected with the wild-type strain RC1 were negative for mAb 2625 binding. These findings strongly indicate that under in vivo conditions switching between two LPS phenotypes occurs and may promote adaptation and replication of L. pneumophila. This is the first description of phase-variable expression of Legionella LPS.
Dietary Antioxidant Intake and Risk of Type 2 Diabetes
Authors: Jukka Montonen, Paul Knekt, Ritva Järvinen, Antti Reunanen
Journal: Diabetes Care (2004)

OBJECTIVE—The intake of antioxidants was studied for its ability to predict type 2 diabetes. RESEARCH DESIGN AND METHODS—A cohort of 2,285 men and 2,019 women 40–69 years of age and free of diabetes at baseline (1967–1972) was studied. Food consumption during the previous year was estimated using a dietary history interview. The intake of vitamin C, four tocopherols, four tocotrienols, and six carotenoids was calculated. During a 23-year follow-up, a total of 164 male and 219 female incident cases occurred. RESULTS—Vitamin E intake was significantly associated with a reduced risk of type 2 diabetes. The relative risk (RR) of type 2 diabetes between the extreme quartiles of the intake was 0.69 (95% CI 0.51–0.94, P for trend = 0.003). Intakes of α-tocopherol, γ-tocopherol, δ-tocopherol, and β-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, β-cryptoxanthin intake was significantly associated with a reduced risk of type 2 diabetes (RR 0.58, 95% CI 0.44–0.78, P &amp;lt; 0.001). No association was evident between intake of vitamin C and type 2 diabetes risk. CONCLUSIONS—This study supports the hypothesis that development of type 2 diabetes may be reduced by the intake of antioxidants in the diet.
Accuracy of the "Breathalyser"
Authors: M. G. Eggleton
Journal: BMJ (1960)

Opinion is divided as to the proportion of accidents which can be ascribed to alcohol, and, if the object of legislation is to make the roads safer, disqualification would seem to be the obvious penalty for dangerous driving, whatever its cause. If, on balance, alcohol is considered so important a contributory factor as to merit special attention and the breathalyser is to be used in its detection, a fixed limit of 50 mg./ 100 ml. is not practicable; for the accuracy of the instrument is only +/-25 mg./100 ml. at the 95% confidence limits. Thus, 50 mg./ 100 ml. reported by the breathalyser would represent values down to 25 mg./100 ml. in nearly half the subjects tested, while five in every 100 might be below 25 or above 75 mg./ 100 ml. Motorists must either forgo alcohol altogether and the instrument be used in a qualitative manner, or some higher fixed limit be set.
Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis
Authors: M. Masoli, M. Weatherall, S. Holt, P. Shirtcliffe, R. Beasley
Journal: European Respiratory Journal (2006)

The dose–response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear. The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose–response studies of ≥4 weeks’ duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range. Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses &gt;1,000 μg were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-μg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01–1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 μg·day -1 . In conclusion, for routine prescribing within the established therapeutic dose–response range (50–500 μg·day -1 ), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate &gt;1,000 μg and by the considerable individual variability in the response.
Regulation of B1 cell migration by signals through Toll-like receptors
Authors: Seon-ah Ha, Masayuki Tsuji, Keiichiro Suzuki, Bob Meek, Nobutaka Yasuda, Tsuneyasu Kaisho, Sidonia Fagarasan
Journal: The Journal of Experimental Medicine (2006)

Peritoneal B1 cells are known to generate large amounts of antibodies outside their residential site. These antibodies play an important role in the early defense against bacteria and viruses, before the establishment of adaptive immune responses. Although many stimuli, including antigen, lipopolysaccharide, or cytokines, have been shown to activate B1 cells and induce their differentiation into plasma cells, the molecular signals required for their egress from the peritoneal cavity are not understood. We demonstrate here that direct signals through Toll-like receptors (TLRs) induce specific, rapid, and transient down-regulation of integrins and CD9 on B1 cells, which is required for detachment from local matrix and a high velocity movement of cells in response to chemokines. Thus, we revealed an unexpected role for TLRs in governing the interplay between integrins, tetraspanins, and chemokine receptors required for B1 cell egress and, as such, in facilitating appropriate transition from innate to adaptive immune responses.
Presence of MBL in airways: is it a disease severity marker or an additional host defence mechanism?
Authors: K C Jambo, S B Gordon
Journal: Thorax (2009)

hay fever 4 and for raised IgE for common inhalation allergens at age 11. 5 It would therefore be most informative if the authors could provide additional data on the differences between the neonatal anthropometric data of the children with and without ceasarean section, and on the indications for caesarean sections themselves.This issue is of significant importance and of clinical relevance because, if indeed a causal relationship exists between mode of delivery and development of asthma, this would certainly make an argument against elective caesarean section for non-medical reasons.It would seem that there is currently insufficient evidence to infer a causal relationship, but it certainly seems worthwhile sorting this out.
Molecular evolution of the human immunoglobulin E response: high incidence of shared mutations and clonal relatedness among epsilon VH5 transcripts from three unrelated patients with atopic dermatitis.
Authors: N van der Stoep, J van der Linden, T Logtenberg
Journal: The Journal of Experimental Medicine (1993)

We have analyzed the nucleotide sequences of 19 epsilon VH5 transcripts derived from in vivo isotype switched peripheral blood B cells of three patients with atopic dermatitis. Comparison with the patients' own germline VH5 gene segments revealed that the epsilon transcripts were derived from both functional members of the human VH5 gene family and harbored numerous somatic mutations (range 5-36 per VH5 gene). In two patients, we detected clonally related but diverged transcripts, permitting the construction of a genealogical tree in one patient. We observed a high proportion of shared silent (S) and replacement (R) mutations among epsilon VH5 sequences derived from all three individuals, even among transcripts descending from the two different germline VH5 gene segments. A remarkably high number of these mutations is shared with previously reported VH5 genes encoding antibodies with defined specificities. The shared S mutations, and likely a fraction of the R mutations, appear to mark preferential sites ("hot spots") of somatic hypermutations in human VH5 genes. The distribution of R and S mutations over complementarity determining region and framework regions in the majority of VH regions deviated from that characteristic of antigen-driven immune response. We hypothesize that the V regions of immunoglobulin E-bearing B cells have accumulated "selectively neutral" mutations over extended periods of clonal expansion, resulting in unusual R/S ratios. We propose that the molecular characteristics of the epsilon VH regions in atopic dermatitis may be representative of antigens that recurrently or chronically stimulate the immune system.
Targeting Galectin-1 Overcomes Breast Cancer-Associated Immunosuppression and Prevents Metastatic Disease
Authors: Tomás Dalotto-Moreno, Diego O. Croci, Juan P. Cerliani, Verónica C. Martinez-Allo, Sebastián Dergan-Dylon, Santiago P. Méndez-Huergo, Juan C. Stupirski, Daniel Mazal, Eduardo Osinaga, Marta A. Toscano, Victoria Sundblad, Gabriel A. Rabinovich, Mariana Salatino
Journal: Cancer Research (2012)

Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.
Effect of cisapride on delayed gastric emptying in gastro-oesophageal reflux disease.
Authors: G J Maddern, G G Jamieson, J C Myers, P J Collins
Journal: Gut (1991)

Some patients with gastro-oesophageal reflux disease have delayed gastric emptying. This study investigates the effect of cisapride on gastric emptying in 34 patients with proved reflux and delayed gastric emptying of solids. They were enrolled in a double blind controlled crossover study. Placebo or cisapride (10 mg) tablets were given three times a day for three days followed by further assessment of gastric emptying. The protocol was repeated with the crossover tablet. Gastric emptying was assessed by a dual radionuclide technique. The percentage of a solid meal remaining in the stomach at 100 minutes (% R100 minutes) and the time taken for 50% of the liquid to empty (T50 minutes) were calculated and analysed by the Wilcoxon matched pairs signed ranks test and expressed as medians (ranges). For gastric emptying of solids the initial % R100 minutes (70 (60-100)%) was not significantly different from placebo (71 (35-100)%). After cisapride treatment a significant acceleration (p less than 0.001) in gastric emptying occurred (% R100 minutes, 50.5 (28-93)%). Similarly with gastric emptying of liquids, the initial T50 minute value was 26.5 (12-82) minutes, after placebo the value was 28 (11-81) minutes, but this was significantly accelerated with cisapride (p less than 0.03) to 22.5 (6-61) minutes. The acceleration in gastric emptying occurred in the proximal portion of the stomach for gastric emptying of both solids and liquids suggesting that this is the principal site of action of cisapride. We conclude that cisapride significantly accelerates gastric emptying of both solids and liquids in patients with gastro-oesophageal reflux disease and delayed gastric emptying.
Cases of Abdominal Surgery
Authors: E. S. Bishop
Journal: BMJ (1897)

I THE BITInHL 9I CASE I.-Mrs.B., aged 34, 3i-para, has had bad health during the whole of pregnancy, with considerable leucorrhcea.She was attended in her confinement by a qualified midwife from the Plaistow Maternity Charity.Confined October zith, z8g6.Breech presentation, which presented no difficulty.In the evening of the day of her confinement her temperature was 1030.I saw her on October 13th, and found the temperature 2030, pulse I20, skin hot and dry, tongue moist with white fur; abdomen distended; uterus on a level with the umbilicus and tender on pressure; lochia normal in quantity and not offensive.Ordered perchloride douches and quinine.October 34th.Morning temperature I02.80; pulse 220 and of good quality; general condition the same.Gave injection of io c.cm. antistreptococcic serum.In the evening the temperature had risen to io30, the abdomen was more distended; another injection of 20 c.cm. serum was given.October 15th.Morning temperature 103.80.Uterus smaller and not so tender, abdomen softer, general condition the same, IO c.cm. serum iniected ; evening temperature 1040, pulse 230; lo c.cm. serum injected.dctober x6th.Morning temperature 2030, even- ing 2o40; general condition worse.No more injections given.Died same evening.No bacteriological examination made.CASE II.-Mrs.B., aged 30, a thin anaemic woman, who has been in a bad state of health lately.Confinea October 2gth, 2896 ; placenta praevia, from which there had been considerable haemorrhage before I was sum- moned.All went well till November 1st, when she had a slight rigor and her temperature rose to 1030.With intrauterine douches of mercuric chloride she did well till November sth, when, owing to illness, I did not see her till November gth.During my absence the douches were omitted for thirty-six hours, and the lochia became offensive, the temperature rising to Io05.Novembergth.Morning temperature 2020, pulse 222.Gave
Pneumonia, with Copious Haemoptysis Treated by Ergot: Speedy Recovery
Authors: C. H. Jones
Journal: BMJ (1879)

posterior cornua of grey matter, is the external band of the posterior column; it is also called the posterior root-zone.Sclerosis of the inner division of the posterior column-the column of Goll-does not appear to give rise to the characteristic phenomena of this disease; while it is always present when the posterior root-zones are affected.Dr. J. Lockhart Clarke has further demonstrated that to the posterior root-zones are principally attached the posterior or sensory roots of the spinal nerves, not to the lateral columns, as was once believed.Usually the posterior cornua of grey matter are to some extent implicated in the sclerosis.The posterior roots of the spinal nerves are almost always found to be atrophied.Similar alterations from degeneration are found in parts within the cranium, which are closely related to the posterior columns of the cord; as, for example, in the lower cerebral peduncles, the restiform bodies, and the optic thalami.The optic nerve is often affected, and the grey degeneration in it may often be detected very early in the disease by means of the ophthalmoscope.Chronic neuritis-the result of implication of the cilio-spinal centre, upon which also depends the contraction of the pupil in these cases- is also frequently met with in this as in other spinal diseases.You must not expect to find the disease always strictly limited to the posterior root-zones and the adjacent grey matter of the spinal cord.Other regions are often invaded in the progress of the disease, and you will then have contractions, paralysis, atrophy, or disease of joints superadded, according to the region involved.[To be conztinuted.]
The 8‐year follow‐up of the PIAMA intervention study assessing the effect of mite‐impermeable mattress covers
Authors: U. Gehring, J. C. de Jongste, M. Kerkhof, M. Oldewening, D. Postma, R. T. van Strien, A. H. Wijga, S. M. Willers, A. Wolse, J. Gerritsen, H. A. Smit, B. Brunekreef
Journal: Allergy (2011)

To cite this article: Gehring U, de Jongste JC, Kerkhof M, Oldewening M, Postma D, van Strien RT, Wijga AH, Willers SM, Wolse A, Gerritsen J, Smit HA, Brunekreef B. The 8‐year follow‐up of the PIAMA intervention study assessing the effect of mite‐impermeable mattress covers. Allergy 2012; 67 : 248–256. Abstract Background: Exposure to high levels of house dust mite (HDM) allergens is associated with the development of allergic sensitization to HDM, a risk factor for the development of asthma, rhinitis, and allergic dermatitis. We studied the effect of an early intervention with mite‐impermeable mattress covers on HDM allergen levels and the development of asthma and mite allergy throughout the first 8 years of life. Methods: High‐risk children (allergic mother) were prenatally recruited and randomly allocated to two groups receiving mite allergen–impermeable ( n = 416) and placebo mattress covers ( n = 394) or no intervention ( n = 472). Asthma and allergies were assessed yearly by questionnaire. Specific immunoglobulin E and bronchial hyper‐responsiveness were measured at the age of 8 years. Mattress dust samples collected at different time points were analyzed for HDM allergens. Results: At the age of 8 years, levels of HDM allergen Der f1 but not Der p1 were lower in the active than the placebo mattress cover group. In repeated measures analyses, we found a temporary decreased risk of asthma symptoms at the age of 2 years in the intervention group compared to the placebo group and a temporary association between higher HDM allergen exposure at the age of 3 months and more asthma symptoms. Conclusion: Early intervention with mite‐impermeable mattress covers is successful in reducing exposure to Der f 1; it only temporarily reduces the risk of asthma symptoms and does not reduce the risk of hay fever, eczema, and allergic sensitization.
Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis
Authors: O. Butovsky
Journal: Journal of Clinical Investigation (2006)

The role of activated microglia (MG) in demyelinating neurodegenerative diseases such as multiple sclerosis is controversial. Here we show that high, but not low, levels of IFN-gamma (a cytokine associated with inflammatory autoimmune diseases) conferred on rodent MG a phenotype that impeded oligodendrogenesis from adult neural stem/progenitor cells. IL-4 reversed the impediment, attenuated TNF-alpha production, and overcame blockage of IGF-I production caused by IFN-gamma. In rodents with acute or chronic EAE, injection of IL-4-activated MG into the cerebrospinal fluid resulted in increased oligodendrogenesis in the spinal cord and improved clinical symptoms. The newly formed oligodendrocytes were spatially associated with MG expressing MHC class II proteins and IGF-I. These results point to what we believe to be a novel role for MG in oligodendrogenesis from the endogenous stem cell pool.
Ontogenetic constraints on the evolution of right-handedness
Authors: George F. Michel
Journal: Behavioral and Brain Sciences (2003)

Ontogenetic factors constrain the evolution of species-typical traits. Because human infants are born “prematurely” relative to other primates, the development of handedness during infancy can reveal important ontogenetic influences on handedness that may have contributed to the evolution of the human species-typical trait of a population-level right-hand dominance.
Double-Negative Feedback Loop between Reprogramming Factor LIN28 and microRNA <i>let-7</i> Regulates Aldehyde Dehydrogenase 1–Positive Cancer Stem Cells
Authors: Xiaojun Yang, Xiaojuan Lin, Xiaomin Zhong, Sippy Kaur, Ning Li, Shun Liang, Heini Lassus, Liping Wang, Dionyssios Katsaros, Kathleen Montone, Xia Zhao, Youcheng Zhang, Ralf Bützow, George Coukos, Lin Zhang
Journal: Cancer Research (2010)

A relatively rare aldehyde dehydrogenase 1 (ALDH1)-positive "stem cell-like" subpopulation of tumor cells has the unique ability to initiate and perpetuate tumor growth; moreover, it is highly resistant to chemotherapy and significantly associated with poor clinical outcomes. The development of more effective therapies for cancer requires targeting of this cell population. Using cDNA microarray analysis, we identified that the expression of the Caenorhabditis elegans lin-28 homologue (LIN28) was positively correlated with the percentage of ALDH1+ tumor cells; this was further validated in an independent set of tissue arrays (n=197). Both loss-of-function and gain-of-function studies showed that LIN28 plays a critical role in the maintenance of ALDH1+ tumor cells. In addition, we found that there is a double-negative feedback loop between LIN28 and let-7 in tumor cells, and that let-7 negatively regulates ALDH1+ tumor cells. Finally, we report that a LIN28/let-7 loop modulates self-renewal and differentiation of mammary gland epithelial progenitor cells. Our data provide evidence that cancer stem cells may arise through a "reprogramming-like" mechanism. A rebalancing of the LIN28/let-7 regulatory loop could be a novel therapeutic strategy to target ALDH1+ cancer stem cells.