tbuckley/cabot-search huggingface dataset:
Evidence for Concurrent Effects of Exposure to Environmental Cadmium and Lead on Hepatic CYP2A6 Phenotype and Renal Function Biomarkers in Nonsmokers
Authors: Soisungwan Satarug, Muneko Nishijo, Pailin Ujjin, Yuvaree Vanavanitkun, Jason R. Baker, Michael R. Moore
Journal: Environmental Health Perspectives (2004)

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 microg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 microg/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (p < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted beta = -0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted beta = 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-beta-D-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously.
Abstract LB-493: Blocking the integrin αvβ3-CRAF axis with Cilengitide arrests glioblastoma cells in pro-metaphase
Authors: Aleksandra Franovic, David A. Cheresh
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is the most prevalent brain tumor subtype, with a particularly high mortality rate due to frequent recurrence and poor response to standard therapies. Improving outcome for these patients will require new therapies which target the unique features of this disease. One such approach is geared toward integrin αvβ3, as high-grade GBM tumors express both the extracellular matrix protein vitronectin and its receptor integrin αvβ3 which drive several key cell signaling pathways to promote cell invasion and survival. Blocking the function of integrin αvβ3 with the antagonist Cilengitide shows potent anti-tumor activity in preclinical models and is currently completing the first Phase III trial for newly-diagnosed GBM. Understanding the mechanisms of activity for Cilengitide will be critical as this drug nears FDA-approval for GBM. Since αvβ3 is highly expressed in both the brain tumor vasculature and on glioma cells, it is not clear whether Cilengitide exerts its effects by disrupting tumor angiogenesis, tumor cell invasion and survival, or other hallmark tumor traits. Focusing on GBM cells, we have made the novel observation that αvβ3 ligation leads to phosphorylation of CRAF on serine 338, an event which we have recently linked to cell survival and cell cycle progression. Pharmacological inhibition or knockdown of integrin αvβ3 reduces activated CRAF levels, causes tumor cells to arrest in pro-metaphase, and suppresses the growth of orthotopic GBM in mice. Activating this pathway by expression of a phospho-mimetic CRAF S338D mutant independently drives cell cycle progression in vitro, accelerates tumor growth in vivo, and renders tumors resistant to the effects of Cilengitide. These findings reveal a previously unappreciated mechanism of action for Cilengitide. In addition to its well-known anti-angiogenic function, it also directly induces cell cycle arrest in GBM cells. The clinical implications of this observation are two-fold as it: 1) provides important insight that could aid in the design of combination treatment regimes; and 2) points at integrin αvβ3 and phosphorylated CRAF S338 expression as potential biomarkers which could serve to help identify the patient populations most likely to benefit from Cilengitide. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-493. doi:1538-7445.AM2012-LB-493
Extended methods of enteroscopy
Authors: M. Austin, A. Rivett, S. Anderson
Journal: Endoscopy (2008)

Single balloon enteroscopy (SBE) allows direct visualization of the small bowel and is important in the evaluation of covert gastrointestinal bleeding. The complication rate for double balloon enteroscopy is 1 %. Complications include acute pancreatitis, perforation, and bleeding [1] [2]. There are no published data of bacteremia following double balloon enteroscopy.
Radiofrequency Ablation of a Tumor Causing Oncogenic Osteomalacia
Authors: Eric Hesse, Herbert Rosenthal, Leonard Bastian
Journal: New England Journal of Medicine (2007)

mice had a significant increase in plasma homocysteine levels (P<0.05, by analysis of variance with Tukey's post hoc multiple-comparison test).In contrast, plasma homocysteine levels in the oxidatively stressed APOE-/-and APOE ε4 mice remained unchanged from values obtained in the presence of dietary folate.These results provide evidence that plasma homocysteine may be an accurate predictor of folate deficiency under otherwise normal conditions but may not reflect folate deficiency in the presence of underlying risk factors known to promote increased oxidative stress.In the future, an accompanying test or series of tests to assess the degree of cellular oxidative stress may be warranted in order to interpret plasma homocysteine values correctly.
SUICIDE AS A MENTAL EPIDEMIC.
Authors: FORBES WINSLOW
Journal: JAMA (1895)

The question of suicide is one which for some time has occupied public attention. During the present year, in consequence of the alarming increase of suicide, I have decided to choose this subject for our consideration, hoping that perhaps what I shall place before the society may prove of interest to its members and draw their serious attention to a grave question. All human actions are under the influence and power of example more than precept, and consequently self-destruction has often been justified by an appeal to the laws and customs of past ages. An undue reverence for the authority of antiquity induces us to rely more upon what has been said or done in former times than upon the dictates of our own feelings and judgment. Many a mistaken individual has formed the most extravagant notions of honor, liberty and courage, and, under the impression that he was imitating
REPORT OF A CASE OF BIFURCATION OF THE RENAL PELVIS
Authors: Leonard A. West
Journal: JAMA (1922)

A blacksmith, aged 48, entered the hospital, July 13, 1922, complaining of pain in the abdomen. Several days before admission, he developed a sharp pain, intermittent in character, over the entire abdomen at first, and later localizing in the right iliac region. There was no nausea or vomiting. The pain was not affected by, nor had it any relation to, the taking of food. Since the onset, the patient had had a gradual increase in frequency of urination, until, at the time of admission, he had a marked daily frequency and urinated five or six times at night. His temperature and pulse were normal on admission, and the leukocyte count was 6,300.  The previous history was negative. The patient had not missed a day from his work on account of sickness in the past thirty years. The physical examination was negative except that there were many abscessed teeth and marked
Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen.
Authors: H Lilja, J Oldbring, G Rannevik, C B Laurell
Journal: Journal of Clinical Investigation (1987)

The comparison of measurements of fibronectin and lactoferrin in ejaculates from vasectomized men, subjects with functional deficiency or aplasia of the seminal vesicles, and reference subjects provided evidence that both the fibronectin and the lactoferrin in human seminal fluid originate from the seminal vesicles and the ampullae. The fibronectin is incorporated in the framework of the seminal gel formed during the immediate postejaculatory phase, whereas the lactoferrin remains in solution. In the seminal gel fibronectin is linked to its predominant structural protein, a high molecular weight seminal vesicle protein (semenogelin). Both the gel-bound fibronectin and semenogelin are progressively fragmented and solubilized by the abundant prostatic kallikrein-like protease (prostate-specific antigen) during and after seminal gel liquefaction. Lactoferrin remains essentially unaffected by the seminal proteases.
Identification of an alternative polyadenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1.
Authors: D Hourcade, D R Miesner, J P Atkinson, V M Holers
Journal: The Journal of Experimental Medicine (1988)

The human C3b/C4b receptor or complement receptor type one (CR1) is an approximately 200-kD single chain membrane glycoprotein of human peripheral blood cells that mediates the binding, processing, and transport of C3b-bearing immune complexes and regulates the activity of the complement cascade. Analysis of partial cDNA clones has shown that the COOH terminus is composed predominantly of three tandemly repeated regions of 450 amino acids each (15). In this report, we present a cDNA sequence that encodes the NH2 terminus of CR1. It appears to have been derived from an alternatively processed transcript, caused by polyadenylation occurring at a site within an intron in the CR1 transcriptional unit. The resulting truncated messenger carries an open reading frame that would produce a short, secreted CR1 form. We present genomic sequences and Northern blots which support this hypothesis and we propose that the NH2-terminal end of CR1 is a likely location for active sites. In addition, we report evidence for a CR1-like sequence in the human genome and we present a model for the organization of CR1.
Finding Pure and Simple Truths With Administrative Data
Authors: Gary E. Rosenthal
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Direct evidence that decreased serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in sickle cell disease is related to antibody deficiency.
Authors: A B Bjornson, J S Lobel
Journal: Journal of Clinical Investigation (1987)

Two approaches were used to demonstrate that reduction in serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in children with sickle cell disease is related to a deficiency of antibodies to pneumococcal capsular polysaccharide. First, opsonization of S. pneumoniae mediated by the alternative pathway in patients' sera was restored to normal by addition of the purified IgG or IgM fraction of goat antiserum to capsular polysaccharide of the homologous serotype. Secondly, IgG antibody titers to capsular polysaccharide in patients' sera correlated significantly with alternative pathway-mediated opsonization; the correlation between titers of IgM anticapsular antibodies and opsonization approached statistical significance. The sum of the IgG and IgM anticapsular antibody titers correlated most significantly with opsonization. Our results suggest that reduction in alternative pathway-mediated opsonization in sera from children with sickle cell disease is related to low levels of both IgG and IgM anticapsular antibodies.
Amino Acid-Dependent Activation of Liver Estrogen Receptor Alpha Integrates Metabolic and Reproductive Functions via IGF-1
Authors: Sara Della Torre, Gianpaolo Rando, Clara Meda, Alessia Stell, Pierre Chambon, Andrée Krust, Cristian Ibarra, Paolo Magni, Paolo Ciana, Adriana Maggi
Journal: Cell Metabolism (2011)
Prevalence and prediction of osteopenia in chronic liver disease
Authors: Herbert L. Bonkovsky, Michael Hawkins, Karen Steinberg, Theodore Hersh, John T. Galambos, J. Michael Henderson, William J. Millikan, John R. Galloway
Journal: Hepatology (1990)

To obtain information on the prevalence and clinical and laboratory correlates of osteopenia in patients with chronic liver disease, we measured bone densities and 30 selected laboratory variables in 133 subjects (70 men, 63 women) with liver disease. Thirty-two had alcoholic liver disease, 18 had primary biliary cirrhosis, 16 had primary sclerosing cholangitis, 48 had other forms of cirrhosis (cryptogenic, posthepatic) and 19 had chronic hepatitis or fibrosis without cirrhosis. Bone densities of the lumbar spine and three sites of the proximal femur (neck, Ward's triangle, greater trochanter) were estimated by dual-photon absorptiometry. Bone densities at all sites were significantly correlated to one another (r = 0.4 to 0.9; 95% confidence intervals = 0.24-0.54 to 0.81-0.90; p less than 0.0001 for all). Compared with an age- and gender-matched reference group, patients with liver disease had highly significant decreases in bone densities (greater than 2 standard deviations below control values; p less than 0.0008 at all sites). Decreases were particularly marked (24% to 42%) at Ward's triangle, the site of the femoral neck particularly prone to fracture. The prevalence of decreased bone densities ranged from 10% to 56%, depending on the site studied and the nature of the liver disease. Among 30 laboratory variables studied, there were significant (p less than 0.05) correlations with bone densities at more than one site for urinary creatinine (r = 0.21, 0.25), urinary calcium (r = -0.18, -0.23), serum total alkaline phosphatase (r = -0.18, -0.27) and the liver-1 isozyme of serum alkaline phosphatase (r = -0.19, -0.26).(ABSTRACT TRUNCATED AT 250 WORDS)
Non-malignant B cells and chronic lymphocytic leukemia cells induce a pro-survival phenotype in CD14+ cells from peripheral blood
Authors: N Bhattacharya, S Diener, I S Idler, T F Barth, J Rauen, A Habermann, T Zenz, P Möller, H Döhner, S Stilgenbauer, D Mertens
Journal: Leukemia (2011)
<i>In Vivo</i>and<i>In Vitro</i>Effects of SAR 943, a Rapamycin Analogue, on Airway Inflammation and Remodeling
Authors: Yasushi Fujitani, Alexandre Trifilieff
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

No current therapy is considered to be satisfactory for severe asthma, and alternative approaches are still required for what is a major unmet medical need. In this study, we compared the effect of a rapamycin derivative, SAR 943, with budesonide, using a murine model of lung inflammation and remodeling. Allergen challenge of ovalbumin-sensitized BALB/c mice induced an increase in the levels of interleukin-5 and interleukin-4; numbers of eosinophil, neutrophil, and lymphocyte; cellular fibronectin; lung epithelial cell proliferation and mucus hypersecretory phenotype; as well as hyperreactivity to methacholine. Both SAR 943 and budesonide, when given intranasally 1 hour before and 24 hours after the aerosol challenge, inhibited all of these parameters with a similar potency (effective dose 50% of 1 mg/kg). In primary cultured smooth muscle cells from human airways, SAR 943 dose dependently inhibited epidermal growth factor-induced proliferation but did not affect the basal cell proliferation. Neither the basal nor stimulated proliferation of a human bronchial epithelial cell line (16HBE14o-) was affected by SAR 943. In conclusion, SAR 943 is as effective as budesonide in inhibiting both lung inflammation and remodeling in a murine model of asthma. Hence, this class of compound could offer beneficial effects in patients with severe asthma.
Trial of ascorbic acid in prevention of colds.
Authors: G. H. Walker, M. L. Bynoe, D. A. Tyrrell
Journal: BMJ (1967)

Bronchitis-Moffat and Sutherland BDCLnJOURNAL 603 seem essential, therefore, that any future investigations into the aetiology of chronic bronchitis should include an intensive search for rhinoviruses along with the more routine virological and bacteriological methods.It is widely accepted that a fourfold or greater rise in antibody titre indicates viral infection, and for this reason virologists are continually stressing the importance of sending paired sera to the laboratory to demonstrate such a rise.The importance of this practice would seem to be supported strongly by our present results, which show that certain viral antibody titres may remain at high levels for several years.This finding does not appear to be restricted to chronic bronchitics, as a recent paper from Glasgow shows similar findings in cases and matched controls (Ross et al., 1967).This persistence of antibodies in individuals over 40 years of age may be due to repeated previous infection, but this does not alter the fact that a single sample of blood sent from such a patient would be of negligible diagnostic value.On the other hand, antibody titres above the persistent levels quoted in this paper may be significant.These levels may hold true only for this laboratory, but it should be possible for each laboratory to find such a level which would be of some help to the clinician anxious to establish a diagnosis on a single sample of serum. SummarySera from 20 patients with chronic bronchitis have been examined for viral complement-fixing antibodies over a period of four years.During this time 68 exacerbations occurred, but only 3 (4.4°/%) of them could be related to viral infection.Elevated antibody titres were found to persist over a long period of time and the significance of this finding is discussed.We would particularly acknowledge the co-operation of the patients involved in this study.
Diversity and Evolution of the Thyroglobulin Type-1 Domain Superfamily
Authors: Marko Novinec, Dušan Kordiš, Vito Turk, Brigita Lenarčič
Journal: Molecular Biology and Evolution (2005)

Multidomain proteins are gaining increasing consideration for their puzzling, flexible utilization in nature. The presence of the characteristic thyroglobulin type-1 (Tg1) domain as a protein module in a variety of multicellular organisms suggests pivotal roles for this building block. To gain insight into the evolution of Tg1 domains, we performed searches of protein, expressed sequence tag, and genome databases. Tg1 domains were found to be Metazoa specific, and we retrieved a total of 170 Tg1 domain–containing protein sequences. Their architectures revealed a wide taxonomic distribution of proteins containing Tg1 domains followed or preceded by secreted protein, acidic, rich in cysteines (SPARC)-type extracellular calcium-binding domains. Other proteins contained lineage-specific domain combinations of peptidase inhibitory modules or domains with different biological functions. Phylogenetic analysis showed that Tg1 domains are highly conserved within protein structures, whereas insertion into novel proteins is followed by rapid diversification. Seven different basic types of protein architecture containing the Tg1 domain were identified in vertebrates. We examined the evolution of these protein groups by combining Tg1 domain phylogeny with additional analyses based on other characteristic domains. Testicans and secreted modular calcium binding protein (SMOCs) evolved from invertebrate homologs by introduction of vertebrate-specific domains, nidogen evolved by insertion of a Tg1 domain into a preexisting architecture, and the remaining four have unique architectures. Thyroglobulin, Trops, and the major histocompatibility complex class II–associated invariant chain are vertebrate specific, while an insulin-like growth factor–binding protein and nidogen were also identified in urochordates. Among vertebrates, we observed differences in protein repertoires, which result from gene duplication and domain duplication. Members of five groups have been characterized at the molecular level. All exhibit subtle differences in their specificities and function either as peptidase inhibitors (thyropins), substrates, or both. As far as the sequence is concerned, only a few conserved residues were identified. In combination with structural data, our analysis shows that the Tg1 domain fold is highly adaptive and comprises a relatively well-conserved core surrounded by highly variable loops that account for its multipurpose function in the animal kingdom.
Joseph Patrick Booth
Authors: Sara Booth, Brian Bartley
Journal: BMJ (2007)

After an education much disrupted by the second world war Joe Booth left school early and volunteered for the army; he was sent to Palestine during the period when the state of Israel was being founded—on which he often reflected in later years. On demobilisation he went to Regent Street Polytechnic as an ex-service student and flourished, gaining excellent marks and obtaining a …
Pharmacology of propranolol in patients with cirrhosis and portal hypertension.
Authors: M J Arthur, A R Tanner, C Patel, R Wright, A G Renwick, C F George
Journal: Gut (1985)

Ten patients with cirrhosis and protal hypertension received an initial 20 mg oral test dose of propranolol and subsequently 160 mg of a slow release preparation, orally, each day for seven days. Protein binding, serial plasma propranolol concentrations and effects on heart rate were studied. Protein binding was slightly reduced (mean 85%, range 78.9-88.1%) compared with four normals (mean 87.9%). In patients with severe liver disease (serum albumin less than 30 g/l) propranolol remained detectable in plasma 24 hours after the single 20 mg dose and high steady state concentrations (mean 266.5 ng/ml, range 84-406) were observed during regular dosing. At steady state there was a significant correlation between log total plasma propranolol concentrations and the percentage fall in heart rate (r = 0.659, p less than 0.05). We suggest that in patients with severe liver chronic disease (serum albumin less than 30 g/l), propranolol therapy should be initiated in hospital. The starting dose should be low (20 mg of the conventional formulation tds or 80 mg of the slow release preparation daily) and that regular monitoring of the heart rate should be carried out.