tbuckley/cabot-search huggingface dataset:
Liposomal Delivery of Heat Shock Protein 72 Into Renal Tubular Cells Blocks Nuclear Factor-κB Activation, Tumor Necrosis Factor-α Production, and Subsequent Ischemia-Induced Apoptosis
Authors: Kirstan K. Meldrum, Arthur L. Burnett, Xianzhong Meng, Rosalia Misseri, Matthew B.K. Shaw, John P. Gearhart, Daniel R. Meldrum
Journal: Circulation Research (2003)

Heat shock protein 72 (HSP72) is a stress-inducible protein capable of protecting a variety of cells from toxins, thermal stress, and ischemic injury. The cytoprotective role and mechanism of action of HSP72 in renal cell ischemic injury remain unclear. To study this, HSP72 was introduced (liposomal transfer) or induced (thermal stress, 43°C×1 hour) in renal tubular cells (LLC-PK1) with Western blot confirmation. Cells were subjected to simulated ischemia 24 hours after liposomal HSP72 transfer or thermal stress, and the effect of HSP72 on nuclear factor-κB (NF-κB) activation (electrophoretic mobility shift assay and immunohistochemistry), IκBα production (Western blot), postischemic tumor necrosis factor-α (TNF-α) production (RT-PCR), and apoptosis (TUNEL assay) were determined. In separate experiments, the role of TNF-α in apoptosis was determined (anti-TNF-α neutralizing antibody). Results demonstrated that both liposomal transfer of HSP72 and thermal induction of HSP72 prevented NF-κB activation and translocation, TNF-α gene transcription, and subsequent ischemia-induced renal tubular cell apoptosis. Furthermore, TNF-α neutralization also inhibited ischemia-induced renal tubular cell apoptosis. These results indicate that liposomal delivery of HSP72 inhibits ischemia-induced renal tubular cell apoptosis by preventing NF-κB activation and subsequent TNF-α production. Further elucidation of the mechanisms of HSP-induced cytoprotection may result in therapeutic strategies that limit or prevent ischemia-induced renal damage.
Prospective comparison of secretin-stimulated magnetic resonance cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi dysfunction types II and III
Authors: S. P Pereira, A. Gillams, S. N Sgouros, G. J M Webster, A. R W Hatfield
Journal: Gut (2006)

<b>Background:</b> In sphincter of Oddi dysfunction (SOD), sphincter of Oddi manometry (SOM) predicts the response to sphincterotomy, but is invasive and associated with complications. <b>Aim:</b> To evaluate the role of secretin-stimulated magnetic resonance cholangiopancreatography (ss-MRCP) in predicting the results of SOM in patients with suspected type II or III SOD. <b>Methods:</b> MRCP was performed at baseline and at 1, 3, 5 and 7 min after intravenous secretin. SOD was diagnosed when the mean basal sphincter pressure at SOM was &gt;40 mm Hg. Long-term outcome after SOM, with or without endoscopic sphincterotomy, was assessed using an 11-point (0–10) Likert scale. <b>Results:</b> Of 47 patients (male/female 9/38; mean age 46 years; range 27–69 years) referred for SOM, 27 (57%) had SOD and underwent biliary and/or pancreatic sphincterotomy. ss-MRCP was abnormal in 10/16 (63%) type II and 0/11 type III SOD cases. The diagnostic accuracy of ss-MRCP for SOD types II and III was 73% and 46%, respectively. During a mean follow-up of 31.6 (range 17–44) months, patients with normal SOM and SOD type II experienced a significant reduction in symptoms (mean Likert score 8 vs 4; p = 0.03, and 9 vs 1.6; p = 0.0002, respectively), whereas in patients with SOD type III, there was no improvement in pain scores. All patients with SOD and an abnormal ss-MRCP (n = 12) reported long-term symptom improvement (mean Likert score 9.2 <i>v</i> 1.2, p&lt;0.001). <b>Conclusions:</b> ss-MRCP is insensitive in predicting abnormal manometry in patients with suspected type III SOD, but is useful in selecting patients with suspected SOD II who are most likely to benefit from endotherapy.
Loss-of-function mutation of the SCN3B-encoded sodium channel 3 subunit associated with a case of idiopathic ventricular fibrillation
Authors: C. R. Valdivia, A. Medeiros-Domingo, B. Ye, W. K. Shen, T. J. Algiers, M. J. Ackerman, J. C. Makielski
Journal: Cardiovascular Research (2009)

Loss-of-function mutations in the SCN5A-encoded sodium channel SCN5A or Nav1.5 have been identified in idiopathic ventricular fibrillation (IVF) in the absence of Brugada syndrome phenotype. Nav1.5 is regulated by four sodium channel auxiliary beta subunits. Here, we report a case with IVF and a novel mutation in the SCN3B-encoded sodium channel beta subunit Navbeta3 that causes a loss of function of Nav1.5 channels in vitro.Comprehensive open reading frame mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, GPD1L, four sodium channel beta subunit genes (SCN1-4B), and targeted scan of RYR2 was performed. A novel missense mutation, Navbeta3-V54G, was identified in a 20-year-old male following witnessed collapse and defibrillation from VF. The ECG exhibited epsilon waves, and imaging studies demonstrated a structurally normal heart. The mutated residue was highly conserved across species, localized to the Navbeta3 extracellular domain, and absent in 800 reference alleles. We found that HEK-293 cells had endogenous Navbeta3, but COS cells did not. Co-expression of Nav1.5 with Navbeta3-V54G (with or without co-expression of the Navbeta1 subunit) in both HEK-293 cells and COS cells revealed a significant decrease in peak sodium current and a positive shift of inactivation compared with WT. Co-immunoprecipitation experiments showed association of Navbeta3 with Nav1.5, and immunocytochemistry demonstrated a dramatic decrease in trafficking to the plasma membrane when co-expressed with mutant Navbeta3-V54G.This study provides molecular and cellular evidence implicating mutations in Navbeta3 as a cause of IVF.
Transient suppression of clonal hemopoiesis associated with pregnancy in a patient with a myeloproliferative disorder.
Authors: A G Turhan, R K Humphries, J D Cashman, D A Cuthbert, C J Eaves, A C Eaves
Journal: Journal of Clinical Investigation (1988)

We have used restriction fragment length polymorphism analysis to study the clonal involvement of the blood cells in a woman with myeloproliferative disease, whose initially high platelet count (940,000/microliter) spontaneously decreased during a normal pregnancy but then returned rapidly to the same high level after delivery of her child. Analysis of her erythroid progenitors showed the presence of erythropoietin-independent progenitors before, during, and after her pregnancy, consistent with a diagnosis of myeloproliferative disease, and persistence of the abnormal clone throughout the period of study. Analysis of DNA from her blood granulocytes showed these to be polyclonal at mid-pregnancy, when her platelet count had decreased to normal values, in comparison to the monoclonal pattern exhibited by her blood granulocytes 3 mo postpartum, when her platelet count was again elevated. These results demonstrate a partial conversion to normal, polyclonal hemopoiesis during her pregnancy and suggest a previously unanticipated differential sensitivity of normal and neoplastic hemopoietic cells to physiological changes associated with this state.
A study of platelet Count, body fat and Harvard Step Test Score
Authors: W. P. Marley, A. C. Linnerud
Journal: British Journal of Sports Medicine (1973)

The relationship between platelet count, bodyfat, and Harvard step test score was examined in 15 post-absorptive male subjects. Subjects rested for five minutes at the beginning of the testing period. A fingertip blood sample was then obtained and the platelet count determined by the method of Brecher and Cronkite. One-percent ammonium oxalate was employed as the dilution fluid. Bodyfat was calculated with the Siri formula on the basis of skinfolds obtained by the method of Pascale. Testing was concluded with the Harvard step test in a controlled environment room. Pearson product-moment correlation calculations yielded no significant relationship (P=&gt;.05) between platelet count and bodyfat or platelet count and Harvard step test score. Subjects were equated by age matching into lean (under 9.9%), average (10-14.9%), and overweight (above 15%) bodyfat groups. An analysis of variance (ANOVA) revealed no significant difference (P&gt;.05) between the platelet counts of these groups.
Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial
Authors: Christine Stabell Benn, Birgitte Rode Diness, Adam Roth, Ernesto Nante, Ane Bærent Fisker, Ida Maria Lisse, Maria Yazdanbakhsh, Hilton Whittle, Amabelia Rodrigues, Peter Aaby
Journal: BMJ (2008)

To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality.Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG.Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months.Mortality rate ratios.174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration.Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival.Clinical trials NCT00168597.
Dietary Predictors of Maternal Prenatal Blood Mercury Levels in the ALSPAC Birth Cohort Study
Authors: Jean Golding, Colin D. Steer, Joseph R. Hibbeln, Pauline M. Emmett, Tony Lowery, Robert Jones
Journal: Environmental Health Perspectives (2013)

Background: Very high levels of prenatal maternal mercury have adverse effects on the developing fetal brain. It has been suggested that all possible sources of mercury should be avoided. However, although seafood is a known source of mercury, little is known about other dietary components that contribute to the overall levels of blood mercury.Objective: Our goal was to quantify the contribution of components of maternal diet to prenatal blood mercury level.Methods: Whole blood samples and information on diet and sociodemographic factors were collected from pregnant women (n = 4,484) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). The blood samples were assayed for total mercury using inductively coupled plasma dynamic reaction cell mass spectrometry. Linear regression was used to estimate the relative contributions of 103 dietary variables and 6 sociodemographic characteristics to whole blood total mercury levels (TBM; untransformed and log-transformed) based on R2 values.Results: We estimated that maternal diet accounted for 19.8% of the total variation in ln-TBM, with 44% of diet-associated variability (8.75% of the total variation) associated with seafood consumption (white fish, oily fish, and shellfish). Other dietary components positively associated with TBM included wine and herbal teas, and components with significant negative associations included white bread, meat pies or pasties, and french fries.Conclusions: Although seafood is a source of dietary mercury, seafood appeared to explain a relatively small proportion of the variation in TBM in our UK study population. Our findings require confirmation, but suggest that limiting seafood intake during pregnancy may have a limited impact on prenatal blood mercury levels.Citation: Golding J, Steer CD, Hibbeln JR, Emmett PM, Lowery T, Jones R. 2013. Dietary predictors of maternal prenatal blood mercury levels in the ALSPAC birth cohort study. Environ Health Perspect 121:1214–1218; http://dx.doi.org/10.1289/ehp.1206115
Abstract 2344: 3D extracellular stiffness cues drive localized changes in gene expression
Authors: Russell Bainer, Yoshihiro Yui, Shannon Mumenthaler, Parag Mallick, Ondrej Podlaha, Franziska Michor, Jan Liphardt, Jonathan Licht, Valerie Weaver
Journal: Cancer Research (2014)

Abstract The stiffness of the extracellular matrix (ECM) stimulates mechanotransduction pathways that regulate tissue development and tumor progression. We previously showed that a stiff ECM potentiates cell growth and survival, enhances cell migration to drive tumor cell invasion, and drives malignant progression of the mammary gland in culture and in vivo, but the specific transcriptional and molecular events that occur as cells acquire these phenotypic changes are not well understood. To clarify this process, we used expression microarrays, tandem mass spectrometry, and RNA sequencing to identify changes in gene expression levels, isoform usage, and protein abundance that occur as intact ascini respond to distinct stiffness environments. We found that in stiffer ECM conditions ascini acquire consistent changes in gene expression related to cell adhesion and mRNA splicing, and specifically induce the expression of a set of genes involved in epithelial cell differentiation that includes multiple SPRR and S100 proteins. Remarkably, these genes map to an apparent stiffness-mediated transcriptional hotspot on chromosome 1q21, a region containing elevated transcription in many cancers but whose activity has not been related to mechanotransduction. We then used a heuristic approach to identify additional candidate force-mediated transcriptional hotspots throughout the genome that contain multiple genes that are coordinately activated or silenced in response to elevated ECM stiffness. Provocatively, we find that genes whose expression levels are responsive to ECM stiffness cues are disproportionately located within chromosomal regions that associate with the nuclear lamina, suggesting that these transcriptional changes may be due in part to force-dependent alteration of genomic contacts with the nuclear envelope. These studies provide biological insight into the divergent cellular responses to distinct stiffness environments and suggest that genome regulatory responses to the force environment may specifically target distinct chromosomal regions via a mechanism that remains to be elucidated. Citation Format: Russell Bainer, Yoshihiro Yui, Shannon Mumenthaler, Parag Mallick, Ondrej Podlaha, Franziska Michor, Jan Liphardt, Jonathan Licht, Valerie Weaver. 3D extracellular stiffness cues drive localized changes in gene expression. [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 2344. doi:10.1158/1538-7445.AM2014-2344
Dioxin-receptor ligands in urban air and vehicle exhaust.
Authors: G G Mason
Journal: Environmental Health Perspectives (1994)

The ability of extracts of urban air and vehicle exhaust particulates to bind to the dioxin receptor has been determined. It was shown that such extracts do contain significant amounts of dioxin-receptor binding activity. The level of dioxin-receptor binding found in ambient air reflects its pollution level as determined by mutagenic activity. Furthermore, it was shown that the extracts of both urban air and vehicle exhaust particulates could provoke the induction of cytochrome P450IA1 in cultured rat hepatoma cells. Chemical fractionation of the extracts revealed that the majority of the dioxin-receptor binding activity from urban air and gasoline vehicle samples fractionated with the polycyclic aromatic compounds. However, unknown polycyclic aromatic compounds were responsible for the majority of the binding activity measured. In the case of diesel vehicle exhausts, the majority of the dioxin-receptor binding activity was found to be associated with nitro-polycyclic aromatic compounds. Studies with a variety of diesel fuels showed that the amount of dioxin-receptor ligands present in exhaust emissions are fuel-dependent and that substantial amounts of dioxin-receptor ligands are present in the semivolatile phase of exhaust emissions.
Maxcy-Rosenau Preventive Medicine and Public Health
Authors: George L. Fite
Journal: JAMA (1965)

<i>Rosenau's Preventive Medicine and Hygiene</i>, born in 1913, lives again in its ninth edition, as a 36-authored volume, much revised. The preface acknowledges that the book had already reached the practical limit of size, requiring deletions of older material. This edition is best described as a compendium of everything connected with preventive medicine or public health, with the result that subjects are included, such as genetic aspects of epidemiology, which have minimum relationship. Other subjects are inadequately treated, and the reader needs to go far beyond what is discussed in the present edition to grasp the full public health problems in many of the infectious diseases. The subjects of sanitary engineering, environmental health, rehabilitation, and organization of health services are described; each is worth a substantial volume in its own right, and abbreviations are often too synoptic. The space allocated to subjects seems purely arbitrary. <i>Rosenau</i>, and<i>Maxcy-Rosenau</i>were durable
CASE OF PUERPERAL CONVULSIONS
Authors: R. T. Woodhouse
Journal: BMJ (1856)

twisted a .h all such case he fears amputation is still the remedy; but with the full effects of chloroform, all other caes ar thus manageable under the indication first Stated OPERATION FOR EXTERNAL HIIOZRRHOID8: ACTUAL OAUTERY: ADVANTAGES OP THE 'CECOA5EUR .One of the last operation days at Guy's, Mr. HILTON operated on a very bad case of external hemorrhoids, which had resisted all other treatment.As the heemorrhage threatened at one time to be excessive, it was found necessary to have recourse to the actual cautery.Hs3mor- rhoids, it need hardly be observed, are found of various kinds.Sometimes we find a mere dilated vein or varix covered by mucous membrane; or, again, as in the present instance, a large tumour, consisting of areolar, spongy, soft structure, very liable to hemorrhage, or to repeated attacks of inflammation, with deposit of coagulable lymph.The base of the hsomorrhoidal growth in the present case was so broad that it did not seem possible to apply ligature; indeed, the practical rule in the hospitals seems to be to re- move all external piles by the knife; all internal piles, by strangulation.We may here mention a new instrumentthe &craseur, now very much used in continental hospitals, and men- tioned at Guy's, which is said to be quite perfect in its efficiency in removing hsemorrhoids, without a drop of blood being lost.There is not much experience of its use, at present, at this side of the Channel. VALUE OF SETONS IN CASES OF PARALYSIS FROM DISEASEDvERTEBRE, AS DESCRIBED BY POTT.We alluded recentlv to the disuse of issues, and of setons generally, in hospital practice, of late years, as much perhaps from a matter of fashion or growing opinion in London against the trouble to the patient incident to their proper trial, as from any very positive evidence of their evil effects.Painting with tincture of iodine or acetic tincture of cantharides, as in diseased knee-joints, seems to have superseded issues in many instances.Two cases at present in the London Hospital, under the care of Mr. ADAMS, appear, however, to indicate that, in particular forms of disease, the proper use of the seton is highly beneficial.One case is that of H. B., a young man, aged 20 years, of scrofulous appearance, admitted the first week in April, complaining of paralysis of the lower extremities, induced by diseased vertebrae.The history of the case does not present any special feature of novelty.Mr. Adams
Haemolytic anaemia following rituximab treatment in a patient with pemphigus vulgaris
Authors: W.W. Li, X.X. Chen, J. Yu, Y. Wang, D.F. Bu, P. Tu
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Sir, We report a patient with pemphigus vulgaris (PV) who developed haemolytic anaemia (HA) during rituximab therapy. To our knowledge, HA following rituximab has not been reported previously. A 43‐year‐old Chinese man was hospitalized because of skin rashes over his body and erosions of the oral mucosa for more than 4 years. He had been diagnosed as having PV by skin histopathology 4 years previously, and had been treated with systemic high‐dose corticosteroid in combination with immunosuppressive agents (methotrexate and cyclophosphamide) and intravenous immunoglobulin. However, the disease sometimes relapsed and even worsened, and the morbidity resulting from long‐term use of these drugs became problematic to him. One month before admission, his disease condition had become refractory to prednisolone 80 mg daily and methotrexate 10 mg weekly for 30 days together with moxifloxacin 400 mg daily for 7 days. We then started a therapeutic course of rituximab (infusion of 375 mg m−2 weekly for 4 weeks) in combination with prednisolone 80 mg daily beginning from the second day of his admission. At the third day of admission, the patient experienced fever, and moxifloxacin 400 mg daily was given based on the results of bacterial culture and a susceptibility test from blister liquid. At the seventh day of admission, his haemoglobin dropped from 13·5 to 7·3 g dL−1, but mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, total bilirubin and direct bilirubin were all within normal range. The patient looked pale without any other complaint. The second infusion of rituximab was then postponed. Further examinations carried out at the ninth day of admission were negative for Coombs' test, antinuclear antibody and faecal occult blood, and serum iron, folic acid and vitamin B12 were within normal range. However, haemoglobin dropped further to 6·5 g dL−1, and reticulocyte count was 9·96%, suggesting the presence of HA. Infusion of 400 mL washed red blood cells was prescribed along with intravenous immunoglobulin 87·5 g within 5 days and administration of folic acid and vitamin B12 daily. The second rituximab infusion was performed at the 23rd day of admission when his anaemia improved. Weals appeared on his body transiently after this infusion. Haemoglobin decreased from 8·7 to 7·6 g dL−1 but without any further reduction. The third and fourth doses of rituximab were infused weekly on schedule. After the course of rituximab therapy, dermatological improvement was satisfactory, and prednisolone was decreased to 65 mg daily. The results of laboratory examinations during rituximab treatment are shown in Table 1.