tbuckley/cabot-search huggingface dataset:
The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.
Authors: Guirong Wang, Todd M Umstead, David S Phelps, Hamid Al-Mondhiry, Joanna Floros
Journal: Environmental Health Perspectives (2002)

Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP-A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP-A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo.
General practitioner's view on the aged.
Authors: E P Wyatt
Journal: BMJ (1979)

Personal ViezvMy morning's visiting list consisted entirely of patients over 80; one was over 90.They were all women, and all widows.The nonagenarian was the best.She was alert, not deaf, and conducted an excellent conversation.She did not move much from her chair, however, because of a bad leg.It had been pinned after a fall 19 years ago, and she thought, probably with justification, that it was beginning to "come loose."The sun was streaming in at her front window but she preferred to sit in her chair in her dark back room, with an outlook on the most dismal of yards.She enjoyed some of her life, she said.The worst thing was not being able to do the tasks that needed doing.She also missed going for long walks."I think my next walk will be along the golden pavements," she said.I hoped that she got plenty of long walks there."I hope so too," she said simply.
Environmental contaminants and intestinal function
Authors: John G. Banwell
Journal: Environmental Health Perspectives (1979)

The environmental contaminants which have their major effects on the small intestine may be classified into five major categories: (1) bacterial, viral, and parasitic agents, (2) food and plant substances, (3) environmental and industrial products, (4) pharmaceutical agents, and (5) toxic agents whose metabolic effects are dependent on interreaction with intestinal bacterial flora, other physical agents (detergents), human intestinal enzyme deficiency states, and the nutritional state of the host.Bacterial, viral, and parasitic agents are the most important of all such agents, being responsible for significant mortality and morbidity in association with diarrheal diseases of adults and children. Several plant substances ingested as foods have unique effects on the small bowel as well as from contaminants such as fungi on poorly preserved grains and cereals. Environmental and industrial products, in spite of their widespread prevalence in industrial societies as contaminants, are less important unless unexpectedly intense exposure occurs to the intestinal tract. Pharmaceutical agents of several types interreact with the small bowel mucosa causing impairment of transport processes for fluid and electrolytes, amino acid, lipid and sugars as well as vitamins. These interreactions may be dependent on bacterial metabolic activity, association with detergents, mucosal enzyme deficiency state (disaccharidases), and the state of nutrition of the subject.
Commercial versus Native Surfactants
Authors: WOLFGANG BERNHARD, JASMIN MOTTAGHIAN, ANDREAS GEBERT, GUNNAR A. RAU, HORST von der HARDT, CHRISTIAN F. POETS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Despite their broad clinical use, there is no standardized comparative study on the functional, biochemical, and morphologic differences of the various commercial surfactants in relation to native surfactant. We investigated these parameters in Alveofact, Curosurf, Exosurf, and Survanta, and compared them with native bovine (NBS) and porcine (NPS) surfactant. For Curosurf and Alveofact the concentrations necessary for minimal surface tensions < 5 mN/m were six to 12 times higher (1.5 and 3 mg/ml, respectively) than with NPS and NBS. Exosurf and Survanta only reached 22 and 8 mN/m, respectively. Increasing calcium to nonphysiologic concentrations artificially improved the function of Alveofact and Curosurf, but it had little effect on Exosurf and Survanta. Impaired surface activity of commercial versus native surfactants corresponded with their lack in surfactant protein SP-A and decreased SP-B/C. The higher surface activity of Curosurf compared with Alveofact corresponded with its higher concentration of dipalmitoylphosphatidylcholine (DPPC). Despite their enrichment in DPPC Survanta and Exosurf exhibited poor surface activity because of low or absent SP-B/C. Ultrastructurally, Curosurf and Alveofact consisted mainly of lamellar and vesicular structures, which were also present in NPS and NBS. Exosurf contained crystalline structures only, whereas the DPPC-enriched Survanta contained separate lamellar/vesicular and crystalline structures. We conclude that in vitro surface activity of commercial surfactants is impaired compared with native surfactants at physiologic calcium concentrations. In the presence of SP-B/C, surface activity corresponds to the concentration of DPPC. Our data underscore the importance of a standardized protocol at physiologic calcium concentrations for the in vitro assessment of commercial surfactants.
Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA
Authors: J. Yun, J. Adam, D. Yerly, W. J. Pichler
Journal: Allergy (2012)

Recent publications have shown that certain human leukocyte antigen (HLA) alleles are strongly associated with hypersensitivity to particular drugs. As HLA molecules are a critical element in T-cell stimulation, it is no surprise that particular HLA alleles have a direct functional role in the pathogenesis of drug hypersensitivity. In this context, a direct interaction of the relevant drug with HLA molecules as described by the p-i concept appears to be more relevant than presentation of hapten-modified peptides. In some HLA-associated drug hypersensitivity reactions, the presence of a risk allele is a necessary but incomplete factor for disease development. In carbamazepine and HLA-B*15:02, certain T-cell receptor (TCR) repertoires are required for immune activation. This additional requirement may be one of the 'missing links' in explaining why most individuals carrying this allele can tolerate the drug. In contrast, abacavir generates polyclonal T-cell response by interacting specifically with HLA-B*57:01 molecules. T cell stimulation may be due to presentation of abacavir or of altered peptides. While the presence of HLA-B*58:01 allele substantially increases the risk of allopurinol hypersensitivity, it is not an absolute requirement, suggesting that other factors also play an important role. In summary, drug hypersensitivity is the end result of a drug interaction with certain HLA molecules and TCRs, the sum of which determines whether the ensuing immune response is going to be harmful or not.
Defining the Good Doctor
Authors: Robert G. Petersdorf
Journal: JAMA (1993)

When I was a young man, it was common to refer to one of our colleagues as a "good doctor." This was an impressionistic description of a physician who excelled at the art as well as the science of medicine, one who cared deeply about his or her patients, who worried about the family, the home situation, the economic impact of the illness, and the patients' understanding of their disease—all while employing the soundest and most appropriate diagnostic and therapeutic methods. A "good doctor" was a physician to whom we would send a member of our family or to whom we would entrust our personal care. See also p 1655. While the term "good doctor" may have passed from the scene, the concept has not. On the contrary, more objective, scientifically sound, and statistically valid methods for defining what a clinically competent, compassionate, communicative physician really is, are constantly being
Disease remission in rheumatoid arthritis.
Authors: A.R Cabral
Journal: Annals of the Rheumatic Diseases (1989)

average 12 years younger than the EPO group, the initial value was more favourable at 371 mg/I.But the rise was much smaller, to only 383 mg/i.On this basis EPO might be considered to have a more favourable protective action than olive oil.Moreover, EPO also significantly lowered the concentration of apolipoprotein B, a risk factor for coronary disease.The strongest prediction of cardiovascular risk may be provided by the formula: (total cholesterolxO-42)-(HDLcholesterol), where HDL=high density lipoprotein.5If this formula is used EPO and olive oil produced almost the same reductions in risk factors, 23% in the case of EPO and 25% in the case of olive oil.At the end of the discussion the authors say that polyunsaturated fatty acids decrease HDL-cholesterol.They imply that because EPO is rich in polyunsaturated fatty acids it also will lower the desirable HDL-cholesterol.The paper they quote, however, says nothing whatsoever about EPO.The authors' own findings show a slight rise in HDL-cholesterol in response to EPO.Other studies have shown that EPO either has no effect on HDL-cholesterol6 7 or that it significantly increases it.8 9There is therefore no evidence at all that EPO reduces HDL-cholesterol and some evidence that it raises it.
Seductions of the WHO safe surgery checklist
Authors: P. J Mahaffey
Journal: BMJ (2010)

It is worrying that those furthest from surgical practice seem to be embracing the new WHO surgical checklist most enthusiastically. Thus, it is ironic that Atul Gawande’s book The Checklist Manifesto is reviewed by a physician rather than a surgeon.1 In espousing its philosophy, the reviewer omits to tell …
Abstract 2340: Disentangling the Myc:Max from the Mad:Max network
Authors: Ana Paula Rebocho, Trevor Littlewood, Gerard I. Evan
Journal: Cancer Research (2014)

Abstract The Myc family comprises three basic helix loop helix leucine zipper (bHLHLZ) transcription factors - C-myc, N-myc and L-myc - which regulate a plethora of intra and extracellular processes. Myc, when bound to Max, another bHLHLZ transcription factor, is able to bind specific DNA sequences, recruit coactivator complexes and promote transcriptional activation. Max can also promote transcriptional repression by dimerizing with distinct transcription factors such as Mad. Previous work has shown that Myc expression promotes proliferation whereas Mad expression leads to differentiation, implying that Myc and Mad have opposing roles in cells. Myc and Mad share the same heterodimeric partner, Max, suggesting that the cell proliferation/differentiation fate is determined by a Myc:Max:Mad network. To understand how this equilibrium is maintained, we are investigating the effects of separating the Myc:Max from the Mad:Max network. To separate these networks we have made use of specific Myc and Max mutant proteins in which reciprocal exchanges at the e and g positions of the leucine zipper have been introduced. Whereas the MycEG and MaxEG proteins dimerize with each other they are unable to associate with their wild type counterparts. Using these mutants we will determine whether cell fate is dictated by a balanced Myc:Max:Mad network or whether Max is simply a common binding partner for both Myc and Mad. In order to validate the EG mutants in vitro, we have used mouse embryonic fibroblasts derived from a c-Myc ER/ER mouse model generated in our laboratory, in which ER is fused to endogenous c-terminus, allowing Myc to be toggled on and off at will. These cells have to be cultured in the presence of the ER ligand, 4-hydroxytamoxifen (4OHT), so that C-myc is functional and the cells proliferate normally. Whereas MycEG or MaxEG alone are unable to support growth of these cells in the absence of 4OHT, the proliferative arrest phenotype observed without 4OHT is rescued by co-expression of MycEG and MaxEG. We are currently generating mouse models where C-mycEG and MaxEG will replace the endogenous proteins in order to separate the roles of Myc:Max and Mad:Max in development and adult tissues. Citation Format: Ana Paula Rebocho, Trevor Littlewood, Gerard I. Evan. Disentangling the Myc:Max from the Mad:Max network. [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 2340. doi:10.1158/1538-7445.AM2014-2340
Echocardiographic manifestations of pandemic 2009 (H1N1) influenza a virus infection
Authors: İsmail Erden, Emine Cakcak Erden, Hakan Özhan, Cengiz basar, Mustafa Yildirim, Subhan Yalçin, Leyla Yılmaz Aydin, Talha Dumlu
Journal: Journal of Infection (2010)
(19) Systemic mastocytosis
Authors: W.F.G. Tucker, C.I. Harrington
Journal: British Journal of Dermatology (1986)

Journal Article (19) Systemic mastocytosis Get access W.F.G. Tucker, Drs, W.F.G. Tucker, Drs Search for other works by this author on: Oxford Academic Google Scholar C.I. Harrington C.I. Harrington Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 64–65, https://doi.org/10.1111/j.1365-2133.1986.tb07714.x Published: 01 July 1986
Abstract 5428: Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) tyrosine kinase enhances cytotoxicity of anti-mesothelin immunotoxin
Authors: Fatima Ali-Rahmani, David Fitzgerald, Scott Martin, Paresma Patel, Craig Thomas, Ira Pastan
Journal: Cancer Research (2014)

Abstract Discoidin domain receptor 1 (DDR1) is an emerging anti-cancer target that belongs to the family of tyrosine kinases that are activated by collagen, the most abundant component of extracellular matrix (ECM). Collagen mediated induction of DDR1 facilitates cell adhesion, migration, proliferation and matrix remodeling. The collagen/DDR1 axis is also thought to modulate tumor-stromal interaction and potentially can affect tumor response to therapy. Mesothelin is a cell-surface tumor-associated antigen over-expressed in several human cancers including mesothelioma, ovarian, lung, breast, and pancreatic cancers with limited expression on normal cells. RG7787 is a second-generation less immunogenic recombinant immunotoxin (RIT) consisting of an Fv portion of an anti-mesothelin antibody attached to a portion of Pseudomonas exotoxin A in which immunogenic B cell epitopes were silenced. Activation of tyrosine kinase mediated signaling in tumor cells has been shown to modulate the activity of RITs. Therefore, we hypothesized that DDR1 regulates RIT action and its inhibition might enhance the activity of RG7787. Knockdown of DDR1 by siRNA or its inhibition with a novel and specific inhibitor, ‘7rh’, synergistically enhanced the cytotoxic activity of RG7787 in several cancer cell lines. Investigation into the mechanism of action showed increased inhibition of protein synthesis in cells treated with combination of ‘7rh’ and RG7787. Furthermore, stimulation of DDR1 activity by collagen treatment protected cancer cells from killing by RG7787. In conclusion, we report that collagen protects cells from killing by RITs through DDR1 and that lowering DDR1 protein or inhibiting DDR1 kinase activity enhances the cytotoxic activity of RITs. Our data suggest that the combination of ‘7rh’ and RG7787 represents a novel therapeutic strategy to target mesothelin-expressing cancers. Citation Format: Fatima Ali-Rahmani, David Fitzgerald, Scott Martin, Paresma Patel, Craig Thomas, Ira Pastan. Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) tyrosine kinase enhances cytotoxicity of anti-mesothelin immunotoxin. [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 5428. doi:10.1158/1538-7445.AM2014-5428
Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice
Authors: Shin-ichiro Matsumura, Shiro Iwanaga, Satsuki Mochizuki, Hiroyuki Okamoto, Satoshi Ogawa, Yasunori Okada
Journal: Journal of Clinical Investigation (2005)

MMPs are implicated in LV remodeling after acute myocardial infarction (MI). To analyze the role of MMP-2, we generated MI by ligating the left coronary artery of MMP-2–KO and WT mice, the latter of which were administered orally an MMP-2–selective inhibitor or vehicle (TISAM). The survival rate was significantly higher in MMP-2–KO and TISAM-treated mice than in control WT mice. The main cause of mortality in control WT mice was cardiac rupture, which was not observed in MMP-2–KO or TISAM-treated mice. Control WT mice, but not MMP-2–KO or TISAM-treated mice, showed activation of the zymogen of MMP-2, strong gelatinolytic activity, and degradation of ECM components, including laminin and fibronectin, in the infarcted myocardium. Although infarcted cardiomyocytes in control WT mice were rapidly removed by macrophages, the removal was suppressed in MMP-2–KO and TISAM-treated mice. Macrophage migration was induced by the infarcted myocardial tissue from control WT mice and was inhibited by treatment of macrophages with laminin or fibronectin peptides prior to migration assay. These data suggest that inhibition of MMP-2 activity improves the survival rate after acute MI by preventing cardiac rupture and delays post-MI remodeling through a reduction in macrophage infiltration.
Possible defects in triacylglycerol and phosphatidyl- choline metabolism in psoriatic epidermis
Authors: R. SUMMERLY, ELIZABETH ILDERTON, G. M. GRAY
Journal: British Journal of Dermatology (1978)

Biopsies of normal skin, psoriatic lesions and the adjacent psoriatic skin were incubated with I-14C-acetate, 32P-orthophosphate and U-14C-glycerol. Total incorporation of I-14C-acetate into psoriatic lesions (17 samples) was 50% higher than in the adjacent uninvolved epidermis (9 samples) and 120% higher than into normal epidermis (10 samples). In the psoriatic lesion a much higher proportion of the total incorporation was into the neutral lipids and was due mainly to a very high incorporation of I-14C-acetate into the triacylglycerols. The I-14C-acetate incorporated into the phospholipids and especially phosphatidylcholine was proportionally much less in the psoriatic lesion and uninvolved psoriatic epidermis than in normal epidermis even though the incorporation of 32P-orthophosphate and U-14C-glycerol, both representing de novo synthesis, into the phospholipids in the psoriatic lesions and uninvolved epidermis were higher (four-fold in lesion) than in normal epidermis. Our findings (1) are evidence for a much increased triacylglycerol synthesis in psoriatic epidermis which would account for the long-known observation of lipid droplet accumulation in psoriatic cells; (2) suggest that in psoriatic epidermis there is a defect in phospholipid metabolism mainly involving phosphatidycholine and the deacylation (phospholipase A)-reacylation (phospholipid acyltransferase) cycle for fatty acid transfer.
Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group.
Authors: P Kulmala, K Savola, J S Petersen, P Vähäsalo, J Karjalainen, T Löppönen, T Dyrberg, H K Akerblom, M Knip
Journal: Journal of Clinical Investigation (1998)

An unselected population of 755 siblings of children with insulin-dependent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid decarboxylase (GADA), insulin autoantibodies (IAA), and combinations of these markers. We also evaluated whether the histochemical ICA test could be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or close to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively. In contrast to the other three antibody specificities, GADA levels were not related to the risk for IDDM. The risk for IDDM in siblings with four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8%, respectively. Combined screening for IA-2A and GADA identified 70% of all ICA-positive siblings, and all of the ICA-positive progressors were also positive for at least one of the three other markers. The sensitivity of the combined analysis of IA-2A and GADA was 81%, and the positive predictive value was 41%. In conclusion, combined screening for IA-2A and GADA may replace the ICA assay, giving comparable sensitivity, specificity, and positive predictive value. Accurate assessment of the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with only one or no antibodies initially will progress to IDDM.