tbuckley/cabot-search huggingface dataset:
Expression of an insulin/interleukin-1 receptor antagonist hybrid gene in insulin-producing cell lines (HIT-T15 and NIT-1) confers resistance against interleukin-1-induced nitric oxide production.
Authors: N Welsh, K Bendtzen, M Welsh
Journal: Journal of Clinical Investigation (1995)

A hybrid gene consisting of the insulin gene enhancer/promoter region, the signal sequence, the insulin B- and C-chains, and the human interleukin-1 receptor antagonist (IL-1ra) gene was constructed. This hybrid gene was transfected together with the pSV2-neo construct into the insulin-producing cell lines HIT-T15 and NIT-1. One of the geneticin-selected clones, HITra2, expressed a 1.4-kb mRNA, which hybridized both to insulin and IL-1ra-cDNA in Northern blot analysis. Three proteins, with the mol wt 23, 17, and 14 kD, were immunoprecipitated with anti-IL-1ra antibodies from [35S]methionine-labeled HITra2 cells. Both at a low and at a high glucose concentration, 4-5 ng of IL-1ra/10(6) cells (ELISA) was released from these cells. On the other hand, a high glucose concentration evoked a three-fold increase in the release of insulin, suggesting that IL-1ra was released constitutively. Measured by nitrite production, transfected HIT, and NIT-1 cells exhibited a more than 10-fold decrease in IL-1 beta sensitivity. Since the conditioned culture media from the HITra2 cells exhibited an anti-IL-1 beta activity of only 0.5 U/ml, and mixed culture of HITra2 cells and isolated rat islets prevented IL-1 beta induced inhibition of insulin release, it is likely that IL-1ra acts locally at the cell surface. It is concluded that expression of a hybrid insulin/IL-1ra gene confers resistance to IL-1 and that this technique may be used to elucidate the role of IL-1 in autoimmune disorders such as insulin-dependent diabetes mellitus.
Lithotomy Position-Related Rhabdomyolysis of Gluteus Maximus Muscles Demonstrated by Bone Scintigraphy
Authors: Seok Tae Lim, Myung-Hee Sohn, Hwan-Jeong Jeong, Chang-Yeol Yim
Journal: Clinical Nuclear Medicine (2008)

Major urologic surgery performed in the lithotomy position sometimes results in the serious complications of rhabdomyolysis and acute renal failure. A 54-year-old man with prostate cancer (weight, 84 kg; height, 171 cm; body mass index, 28.7) underwent radical perineal prostatectomy in the lithotomy position for 7 hours. On the first postoperative day, the patient complained of numbness and pain of both thighs with oliguria. Serum creatinine kinase and myoglobin levels were elevated. Bone scintigraphy on the second day, which was confirmed by MRI, showed extraosseous increased activity in gluteus maximus muscle regions compatible with rhabdomyolysis.
Cognitive Function in Younger Type II Diabetes
Authors: Jayant Dey, Anoop Misra, Nimesh G Desai, A K Mahapatra, M V Padma
Journal: Diabetes Care (1997)

OBJECTIVE To examine central nervous system involvement as a possible complication of diabetes by performing a comprehensive neuropsychological evaluation of relatively young (age &amp;lt; 55 years) NIDDM patients and a group of control subjects. RESEARCH DESIGN AND METHODS A cross-sectional comparative study of 28 patients, with duration of diabetes 5–18 years (mean ± SD ± 3.2 years), screened for acceptable glycemic control and absence of hypoglycemia on the day of examination, compared with 28 demographically similar, nondiabetic control subjects. Neuropsychometric tests performed were Mini-Mental Status Examination (MMSE), Neurobehavioral Cognitive Status Examination (NCSE), and P300 latencies (endogenous evoked potentials). RESULTS Seven (25.0%) patients reported history suggestive of cognitive impairment during day-to-day activities, and 17 (60.7%) had distal symmetrical polyneuropathy. Average P300 latencies were significantly delayed among the diabetic patients compared with the control subjects (349.5 ± 28.2 vs. 312.9 ± 19.3 ms; t = 5.68, P &amp;lt; 0.001). Although there was no significant difference in MMSE scores, compared with control subjects significantly more patients had impairment in NCSE tests of attention (χ2 = 7.38, P &amp;lt; 0.01), repetition (χ2 = 4.073, P &amp;lt; 0.05), and memory (χ2 = 5.83, P &amp;lt; 0.05), while there was no significant difference in tests of comprehension, naming, construction, and calculation. Duration of diabetes, HbA1c levels, and the presence of distal symmetrical polyneuropathy among patients each did not correlate with any of the parameters of cognitive function evaluated. Higher blood glucose levels during the electrophysiological testing were associated with less delay in P300 latencies among the patients. CONCLUSIONS Central nervous system impairment, manifesting as mild impairments in certain cognitive skills, should be recognized as a possible complication of long-standing NIDDM, even in relatively younger individuals.
ALEUKAEMIC LEUKAEMIA WITH MULTIPLE SKIN TUMOURS.
Authors: JOHN ALEXANDER DRAKE
Journal: British Journal of Dermatology (1925)

Journal Article ALEUKÆMIC LEUKÆMIA WITH MULTIPLE SKIN TUMOURS. Get access JOHN ALEXANDER DRAKE, M.D., M.R.C.P. JOHN ALEXANDER DRAKE, M.D., M.R.C.P. Junior Physician for Diseases of the Skin, King's College Hospital, From the Dermatological Department, King's College Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 8-9, 1 August 1925, Pages 354–364, https://doi.org/10.1111/j.1365-2133.1925.tb09967.x Published: 01 August 1925
Mission hospital medicine
Authors: G. Housden
Journal: BMJ (1979)

<h3>ABSTRACT</h3> Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.
Evidence for a genetic interaction in allergy‐related responsiveness to vitamin <scp>D</scp> deficiency
Authors: K. S. Vimaleswaran, A. Cavadino, E. Hyppönen
Journal: Allergy (2012)

Abstract Background The hormonal form of vitamin D affects both adaptive and innate immune functions involved in the development of allergies. Certain genotypes have been seen to alter the association between vitamin D deficiency ( VDD ) and the risk of food sensitization in children. Methods We examined 27 functional single nucleotide polymorphisms ( SNP s) in/near selected candidate genes for association with total immunoglobulin E ( I g E ) and effect modification by 25‐hydroxyvitamin D in the 1958 British birth cohort (aged 45 years, n = 4921). A cut‐off value of 50 nmol/L was used to define VDD . Results Four SNP s (in FCER1A , IL13 , and CYP24A1 ) and three SNP s (in IL4 and CYP24A1 ) were associated with total I g E and specific I g E , respectively, after correction for multiple testing. As in a previous study, MS4A2 (rs512555, P interaction = 0.04) and IL4 (rs2243250, P interaction = 0.02), and their composite score ( P interaction = 0.009) modified the association between VDD and allergy‐related outcome. Vitamin D deficiency was associated with higher total I g E only in the carriers of the ‘ C ’ allele ( IL4 ), which is present in 86% of white E uropeans, while only 26% of C hinese and &lt;20% of some A frican populations are carriers. Conclusions Our study on white E uropean adults was consistent with a previous study on children from largely non‐white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white E uropeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy‐related responsiveness to VDD .
Coronary and Hemodynamic Effects of Temporary Acute Aortic Insufficiency in Intact Anesthetized Dogs
Authors: JOHN D. FOLTS, GEORGE G. ROWE
Journal: Circulation Research (1974)

In ten dogs with chronically implanted electromagnetic flowmeter probes, phasic aortic and circumflex coronary artery blood flows were measured before, during, and after 15-120 seconds of aortic insufficiency. The dogs were studied in the intact anesthetized state with a cardiac catheter device that produced graded amounts of temporary aortic insufficiency with 18-68% aortic regurgitation. With the onset of aortic insufficiency, there was an immediate increase in pulse pressure with retrograde aortic diastolic blood flow. During the very first cardiac cycle that demonstrated aortic insufficiency, there was a reduction in diastolic coronary blood flow with an increase in systolic coronary blood flow. Mean coronary blood flow fell very low during the first five to ten cardiac cycles. As severe aortic insufficiency continued, systolic coronary blood flow increased, diastolic coronary blood flow remained low or negative, and mean coronary blood flow returned to the normal range. Before the onset of aortic insufficiency, the ratio of diastolic coronary blood flow to systolic coronary blood flow averaged 2.2; after 2 minutes of aortic insufficiency the ratio of diastolic coronary blood flow to systolic coronary blood flow was 0.15. The amount of reduction in diastolic coronary blood flow was related to the amount of aortic regurgitation. Left ventricular work averaged 3.7 kg m/min before and 8.2 kg m/min after 2 minutes of aortic insufficiency with an average of 63% aortic regurgitation; mean coronary blood flow increased from an average of 51 ml/min before to 60 ml/min after 2 minutes of aortic insufficiency. When aortic insufficiency was terminated, coronary blood flow increased to an average of 123 ml/min.
Cultured fibroblast monolayers secrete a protein that alters the cellular binding of somatomedin-C/insulinlike growth factor I.
Authors: D R Clemmons, R G Elgin, V K Han, S J Casella, A J D'Ercole, J J Van Wyk
Journal: Journal of Clinical Investigation (1986)

We studied somatomedin-C/insulinlike growth factor (Sm-C/IGF-I) binding to human fibroblasts in both adherent monolayers and in suspension cultures. The addition of Sm-C/IGF-I in concentrations between 0.5 and 10 ng/ml to monolayers cultures resulted in a paradoxical increase in 125I-Sm-C/IGF-I binding and concentrations between 25 and 300 ng/ml were required to displace the labeled peptide. The addition of unlabeled insulin resulted in no displacement of labeled Sm-C/IGF-I from the adherent cells. When fibroblast suspensions were used Sm-C/IGF-I concentrations between 1 and 10 ng/ml caused displacement, the paradoxical increase in 125I-Sm-C/IGF-I binding was not detected, and insulin displaced 60% of the labeled peptide. Affinity cross-linking to fibroblast monolayers revealed a 43,000-mol wt 125I-Sm-C-binding-protein complex that was not detected after cross-linking to suspended cells. The 43,000-mol wt complex was not detected after cross-linking to smooth muscle cell monolayers, and binding studies showed that 125I-Sm-C/IGF-I was displaced greater than 90% by Sm-C/IGF-I using concentrations between 0.5 and 10 ng/ml. Because fibroblast-conditioned medium contains the 43,000-mol wt complex, smooth muscle cells were incubated with conditioned medium for 24 h prior to initiation of the binding studies. 125I-Sm-C/IGF-I-binding increased 1.6-fold compared to control cultures and after cross-linking the 43,000-mol wt complex could be detected on the smooth muscle cell surface. Human fibroblast monolayers secrete a protein that binds 125I-Sm-C/IGF-I which can be transferred to the smooth muscle cell surface and alters 125I-Sm-C/IGF-I binding.
Closing hospitals with warm sympathy
Authors: R. G. A. Behrman
Journal: BMJ (2011)

Am I alone in being struck by a discrepancy in our current approach to organising healthcare?1 I accept there may be a minimum size for hospitals to be effective. There is nothing new in this sentiment; Aneurin Bevan’s said he “would rather be kept alive in the efficient if cold altruism of a large hospital than expire …
RELATIONSHIP OF NON-OBSTRUCTIVE CORONARY ARTERY DISEASE TO MORTALITY: RESULTS FROM 18,037 PATIENTS WITH &lt;50% STENOSIS IN THE CONFIRM REGISTRY (CORONARY CT ANGIOGRAPHY EVALUATION FOR CLINICAL OUTCOMES: AN INTERNATIONAL MULTICENTER REGISTRY)
Authors: James K. Min, Allison M. Dunning, Fay Y. Lin, Stephan Achenbach, Mouaz Al-Mallah, Daniel S. Berman, Matthew J. Budoff, Filippo Cademartiri, Tracy Q. Callister, Hyuk-Jae Chang, Victor Cheng, Benjamin JW Chow, Augustin Delago, Martin Hadamitzsky, Joerg Hausleiter, Philipp Kaufman, Khurram Nasir, Michael Pencina, Leslee J. Shaw
Journal: Journal of the American College of Cardiology (2011)
Raised pro-inflammatory cytokines interleukin 6 and tumour necrosis factor alpha in coeliac disease mucosa detected by immunohistochemistry.
Authors: R T Przemioslo, M Kontakou, V Nobili, P J Ciclitira
Journal: Gut (1994)

The levels of two pro-inflammatory cytokines, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha), in coeliac disease were studied by immunohistochemistry. Jejunal biopsy specimens from patients with untreated disease, (n = 11), treated disease (n = 9), and normal controls, (n = 11) were stained to detect IL-6, TNF-alpha, CD45 (pan-leukocyte), and CD68 (macrophage surface antigen). Positive cells were identified in the epithelium (per 100 enterocytes) and in the lamina propria (per unit area). There was a significant increase in median IL-6 and TNF-alpha staining in both the lamina propria and the epithelium of untreated coeliac disease patients (lamina propria, 16.2 and 13.0 respectively; epithelium, 0.86 and 1.21, all p &lt; 0.05) when compared with treated coeliac disease patients (lamina propria; 6.0 and 6.2, epithelium; 0.60 and 0.60) and controls (lamina propria; 6.5 and 7.5, epithelium; 0.58 and 0.60). A significant increase in the number of CD45 positive cells was found in the untreated coeliac disease lamina propria and epithelium (p &lt; 0.05) but this was accompanied by a significant rise in CD68 positive cells in the lamina propria only (p &lt; 0.05). Increased IL-6 and TNF-alpha in the lamina propria and epithelium of patients with untreated coeliac disease further supports their role in the immune pathogenesis of this disorder.
Detection of the free acid of bimatoprost in aqueous humor samples from human eyes treated with bimatoprost before cataract surgery
Authors: Carl B. Camras, Carol B. Toris, Birgitta Sjoquist, Monica Milleson, John-Olof Thorngren, Thomas W. Hejkal, Nehal Patel, Edward M. Barnett, Regina Smolyak, S.Fareed Hasan, Courtney Hellman, Jane L. Meza, Martin B. Wax, Johan Stjernschantz
Journal: Ophthalmology (2004)
[747] TNF-ALPHA MEDIATES THE ETHANOL INDUCED PPAR-ALPHA SUPRESSION IN THE LIVER
Authors: P.O. Onder, S. Sengul, R. Calayoglu, B. Savas, K. Cinar, F. Akbiyik, C. Yurdaydin, O. Uzunalimoglu, H. Ataoglu, H. Bozkaya
Journal: Journal of Hepatology (2007)
The Medical Detectives
Authors: Howard Markel
Journal: New England Journal of Medicine (2005)

On a hot and steamy summer day in Berlin — August 4, 1890, to be precise — the 10th International Medical Congress opened with a flair and fanfare that few conference-weary doctors of the 21st century would recognize. At the invitation of Kaiser Wilhelm II, almost 6000 physicians from around the globe flocked to the city that represented the modernity and optimism of medical progress. Perhaps even more enticing was the jam-packed program of lectures delivered by a veritable who's who of medical greats, including Joseph Lister, Rudolf Virchow, and James Paget.Topping the bill two days later, on the . . .
Plasma Vascular Endothelial Growth Factor, Angiopoietin-1, and Angiopoietin-2 in Diabetes
Authors: Hoong Sern Lim, Andrew D. Blann, Aun Yeong Chong, Bethan Freestone, Gregory Y.H. Lip
Journal: Diabetes Care (2004)

OBJECTIVE—Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 are mediators of angiogenesis. More recent data suggest that the balance between these growth factors may affect vascular endothelial integrity. Because diabetes is closely associated with endothelial perturbation, we studied plasma levels of these angiogenic growth factors in patients with diabetes; their relationship with glycemia, inflammation, and endothelial damage/dysfunction; and the effect of intensified cardiovascular risk management. RESEARCH DESIGN AND METHODS—We measured plasma VEGF, Ang-1, and Ang-2 alongside plasma von Willebrand factor (vWf) and urine albumin–to–creatinine ratio (marking endothelial damage/dysfunction) and interleukin (IL)-6 in 94 patients (38 with overt cardiovascular disease [CVD]) with diabetes and 34 normal control subjects. RESULTS—Plasma vWf (P = 0.009), IL-6 (P &amp;lt; 0.001), VEGF (P = 0.001), and Ang-2 (P = 0.001), but not Ang-1 (P = 0.635), were higher in diabetic patients with and without CVD than in control subjects. On multivariate analysis, HbA1c was an independent predictor of plasma VEGF (P = 0.032) and Ang-2 (P = 0.015). Of the 94 patients, a subgroup of 33 patients with and 31 patients without CVD participated in a year of intensified cardiovascular risk management. HbA1c and LDL cholesterol reduced significantly with treatment, along with associated reductions in plasma vWf and VEGF in both groups (P &amp;lt; 0.001). Ang-2 decreased (P &amp;lt; 0.001) only in patients without CVD. There were no significant changes in plasma IL-6 levels in both groups. CONCLUSIONS—Plasma Ang-2 (but not Ang-1), like VEGF levels, are selectively elevated in patients with diabetes and are associated with indexes of endothelial damage/dysfunction, regardless of vascular disease. Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment.
Follicular stimulation and ovarian cancer.
Authors: R. Kulkarni, J. M. McGarry
Journal: BMJ (1989)

on the treatment of benign prostatic.hyperplasiacontained a sentence which cannot pass without comment: "The fact that a recent review has sug- gested that transurethral resection of the prostate may not be as good as urologists have claimed2 does not detract from the important advantages of this technique in treating benign prostatic hyper- plasia."Surely all disadvantages detract somewhat from any advantages, however important?Moreover, readers may not be aware of the nature of the disadvantages that are being cited.These are an excess risk of reoperation and, most importantly, of death in the years after transurethral resection of the prostate when compared with open surgery of around 40%.Obviously there are problems with interpreting the results cited, which are derived from observa- tional and longitudinal data records from three countries among men with no serious concomitant illness and are adjusted as far as possible for case severity.But such data are suggestive and require further investigation by prospective randomised comparison, unless these differences can be unambiguously shown to be attributable to unmeasured aspects of selection or prognosis.It seems slightly cavalier to dismiss implicitly these findings as if they amounted to nothing before such a demonstration.
Five year prospective survey of risk of booking for a home birth in Essex.
Authors: J M Shearer
Journal: BMJ (1985)

A prospective survey was undertaken in 26 practices in Essex to assess the risks associated with a home birth. The 202 women who were booked for a home confinement were compared with a similar group of 185 women who were booked for hospital delivery under consultant care. The principal difference in outcome was the induction rate of 19% in the hospital group compared with 8% in the group booked for delivery at home. A higher rate of episiotomy and second degree tears and more Apgar scores of 7 or below were found in those who were booked for hospital. There were no perinatal deaths in either group. The results of this study showed no evidence of an increased risk associated with home confinements but indicated that there were fewer problems than were encountered in the deliveries in mothers confined in hospital.
A8.25 CARD9 mediates autoantibody-induced autoimmune diseases by linking the SYK tyrosine kinase to CHEMOKINE production
Authors: T Németh, K Futosi, J Weisinger, K Csorba, C Sitaru, J Ruland, A Mócsai
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> CARD9 is a CARMA-like intracellular protein that is highly expressed in innate immune cells. In contrast to its well-defined role in fungal recognition pathways in dendritic cells, its function in non-infectious autoimmune inflammation has not been described yet, despite the fact that a genome-wide association screen raised a possible association between CARD9 gene polymorphisms and a human autoimmune arthritis. Here, we investigated the role of CARD9 in autoantibody-mediated diseases by a transgenic method. <h3>Materials and Methods</h3> We used the neutrophil-, macrophage-, Fc receptor and Syk-mediated K/BxN serum transfer arthritis and the anti-collagen type VII antibody-mediated epidermolysis bullosa acquisita (EBA) models in the presence or absence of CARD9. Bone marrow neutrophils (or cultured bone marrow-derived macrophages) from wild type, Syk- or CARD9-deficient mice were stimulated through their Fcγ receptors, followed by the analysis of the superoxide release (as a <i>short-term response)</i> and chemokine release (as a <i>long-term response</i>). <h3>Results</h3> In contrast to the previously published total resistance of Syk-deficient bone marrow chimeras to experimental arthritis, the absence of CARD9 resulted in a partial, but significant decrease in arthritis severity and CARD9<sup>−/−</sup> mice showed a moderate skin inflammation in the EBA model compared to the wild type animals. Neutrophil (and monocyte) accumulation at the site of inflammation was strongly affected, while CARD9-deficient neutrophils (and monocytes) had normal migratory capacities to the joints in wild type/CARD9<sup>−/−</sup> mixed bone marrow chimeras. Surprisingly, the synovial levels of the chemokines CXCL1 and CXCL2 were dramatically reduced in the absence of CARD9 upon arthritis induction. While Syk<sup>−/−</sup> neutrophils (and macrophages) failed to produce superoxide or release chemokines compared to wild type cells when stimulated through their Fcγ receptors among in vitro conditions, CARD9<sup>−/−</sup> neutrophils showed normal short-term, but strongly reduced long-term responses. Furthermore, Fcγ receptor-mediated phosphorylation of Syk was intact in CARD9<sup>−/−</sup>neutrophils. <h3>Conclusions</h3> CARD9 plays an important role in the development and progression of autoimmune arthritis and autoimmune blistering skin disease in mice, likely by linking the Syk tyrosine kinase to chemokine production in innate immune cells.