tbuckley/cabot-search huggingface dataset:
Statins and Musculoskeletal Adverse Events
Authors: Murray M. Finkelstein
Journal: JAMA Internal Medicine (2014)

To the Editor Mansi and colleagues1 have published an analysis of musculoskeletal conditions, arthropathies, and injuries among users and nonusers of statins. They reported higher adjusted odds ratios (ORs) for statin users in all outcome groups. Are their findings clinically significant?
Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells
Authors: Hajime Isomoto, Shogo Kobayashi, Nathan W. Werneburg, Steve F. Bronk, Maria Eugenia Guicciardi, David A. Frank, Gregory J. Gores
Journal: Hepatology (2005)

Interleukin 6 (IL-6) contributes to the pathogenesis of cholangiocarcinoma by upregulating myeloid cell leukemia-1 (Mcl-1), a key antiapoptotic Bcl-2 family member protein. IL-6 can alter gene transcription via Janus kinases (JAK) and signal transducer and activator of transcription (STAT) signal cascade. We examined this cascade in IL-6 regulation of Mcl-1 transcription in human cholangiocarcinoma cell lines. STAT3 was constitutively activated (i.e., tyrosine-phosphorylated) in cholangiocarcinoma cells but not in nonmalignant cholangiocytes. Treatment with anti–IL-6 antisera or the JAK inhibitor AG490 or transfection with dominant negative STAT3 diminished Mcl-1 messenger RNA and protein levels. Likewise, these attempts to interrupt the STAT3 cascade also reduced Mcl-1 promoter activity. Site-directed mutagenesis of a putative STAT3 consensus binding sequence decreased Mcl-1 promoter activity. Chromatin immunoprecipitation analysis demonstrated a direct binding of STAT3 to the putative STAT3 binding sequences in the Mcl-1 promoter. Downregulation of Mcl-1 by AG490 sensitized the cells to apoptosis mediated by tumor necrosis factor–related apoptosis-inducing ligand. In conclusion, we have directly demonstrated a STAT3 regulatory element in the Mcl-1 promoter. Downregulation of Mcl-1 transcription by inhibiting this cascade is a potential strategy for the treatment of this cancer.(HEPATOLOGY 2005;42:1329–1338.)
Facts and Artifacts About Anemia and Preterm Delivery
Authors: Mark A. Klebanoff
Journal: JAMA (1989)

The effect of anemia (hematocrit less than or equal to 0.34) on subsequent preterm birth was prospectively studied in 35,423 pregnancies. The incidence of preterm birth among women with and without anemia at each week during the third trimester was compared. Early in the third trimester, there was a weak association between anemia and preterm delivery. However, anemia early in the third trimester did not account for the substantial increase in preterm birth seen among black women. Anemia after 30 weeks' gestation was not associated with preterm birth. Among women delivering term infants weighing 2500 g or more, the mean hematocrit rose 0.029 among black women and 0.021 among white women from 25 weeks to term. Compared with hematocrits at 40 weeks' gestation, the odds ratios for anemia reached a maximum at 28 weeks and fell sharply as term approached. When the hematocrits of women in term labor were compared with those of women in preterm labor, a spurious dose-response effect for anemia was created. We conclude that anemia is not a strong factor in the pathogenesis of preterm birth and that comparison of hematocrits from women who are in preterm and term labor produces biased results.
Public sponsors must follow ethical rules too
Authors: I. S. Kristiansen
Journal: BMJ (1999)

EDITOR—Bero's editorial on commercial sponsorship for research is important1 because commercial interests can bias the conduct and reporting of research.2 It may, however, leave the impression that pressure on research is an issue only in relation to commercial sponsorship.

I used to believe that public sponsors would allow the independent conduct of research, but experiences have taught me otherwise. Recent stories …
Incidence, Neutrophil Kinetics, and Natural History of Neonatal Neutropenia Associated with Maternal Hypertension
Authors: Joyce M. Koenig, Robert D. Christensen
Journal: New England Journal of Medicine (1989)

Neutropenia occurs often among the newborns of women with hypertension, but its cause, mechanism, and clinical consequences have not been adequately studied. Of 72 infants whose mothers had hypertension during pregnancy, 35 (49 percent) had neutropenia, which persisted from 1 hour to 30 days. The disorder was more prevalent among newborns whose growth had been retarded in utero (P less than 0.01), those who had been delivered prematurely (P less than 0.001), and those whose mothers had had severe hypertension (P less than 0.002) or hypertension and the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) (P less than 0.01). Kinetic investigations of circulating, marginated, storage, and proliferative neutrophils and their progenitors suggested that the neutropenia was the result of diminished neutrophil production. Noscomial infections occurred during the first 2 1/2 weeks of life in eight (23 percent) of the newborns with neutropenia, but in only one (3 percent) of those without this disorder (P less than 0.01). We conclude that the neonatal neutropenia associated with maternal hypertension is due to transiently reduced neutrophil production and is associated with an increased risk of noscomial infection. Its basic cause remains unknown.
Paranoid psychosis with indomethacin.
Authors: V Gotz
Journal: BMJ (1978)

49including at least three sets of identical twins.3The pattern of aggregation in these families has suggested an inherited basis for a pro- portion of patients with vesicoureteric reflux, but no uniform pattern of inheritance has been apparent.In Christchurch we have investigated the immediate family of 42 patients with reflux nephropathy and in 12 of these families there were one or more affected members.4To assess whether there may be an easily delineated genetic marker for reflux nephropathy we have looked at the tissue typing of all patients presenting recently to our departments with chronic renal failure due to reflux nephropathy and compared this with the tissue types of patients with renal failure due to other causes.The results are showni in the accompanying table and indicate that HLA- B12 is occurring with significantly greater frequency in patients with reflux nephropathy.Presence of HLA-B12 in patients according to aetiology of renal failure Cause of renal No of No with failure patients HLA-B12 Reflux nephropathy 19 9 All other causes 46 8X2 test with Yatesis correction: Z2=4.9; 0-02 <P <0-05.In larger centres it may be possible to confirm whether this is a valid observation and therefore possibly a genetic marker for a disease that not infrequently results in end-stage renal failure.
Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis.
Authors: M R Bennett, G I Evan, A C Newby
Journal: Circulation Research (1994)

We have investigated the requirement for c-myc downregulation in the growth arrest of vascular smooth muscle cells (VSMCs). Rat VSMCs were infected with a retrovirus vector directing constitutive expression of either the complete human c-Myc protein (VSM-myc cells) or the c-Myc deletion mutant D106-143, which is inactive in cotransformation and autosuppression assays (VSM-D106-143 myc cells). Clones of transfected VSM-myc cells were isolated that constitutively expressed a range of levels of c-Myc protein from that observed in normal proliferating VSMCs to approximately seven times normal. The growth rates of these clones and their responses to growth inhibitors were then assessed. VSM-myc clones possessed a shorter mean intermitotic time than normal cells, which was inversely correlated (P &lt; .05) with the level of c-Myc protein expressed. VSM-myc cells also expressed lower levels of alpha-smooth muscle actin mRNA and protein and exhibited an altered morphology. The proliferation of normal VSMCs and VSM-D106-143 myc cells was inhibited by serum reduction (0.5% fetal calf serum) and also by treatment with interferon-gamma (100 IU/mL), heparin (50 micrograms/mL), 8-bromo-cAMP (0.1 mmol/L), or 8-bromo-cGMP (0.1 mmol/L). In contrast, proliferation of VSM-myc cells was not inhibited by any of these agents, even if present at 10-fold higher concentrations. However, approximately 75% of VSM-myc cells expressing levels of c-Myc protein seen in normal proliferating VSMCs underwent apoptosis after 4 days of serum reduction or treatment with interferon-gamma. The results show that constitutive c-myc expression induces continuous cell proliferation, reduction in alpha-smooth muscle actin expression and apoptosis in VSMCs. We conclude that downregulation of c-myc is a prerequisite for growth arrest and subsequent survival of VSMCs. Conversely, deregulated c-myc expression may be important in the proliferation and death of VSMCs--characteristics of the pathogenesis of atherosclerosis.
Myxedema in Hyperthyroidism
Authors: Frederick A. J. Kingery
Journal: JAMA (1965)

Myxedema, strictly speaking, is a boggy swelling of the skin and subcutaneous tissue which results from the deposition of mucin. It traditionally occurs in hypothyroid states, and recognition of this generalized nonpitting edema provides the physician with a reason to suspect hypothyroidism. The lesions of<i>localized myxedema</i>which usually occur in the pretibial areas are also collections of mucin in the skin, as the name implies. These circumscribed lesions develop<i>not</i>in the hypothyroid patient as one might expect, but rather in the hyperthyroid individual who almost invariably has exophthalmos. The lesions usually appear after medical or surgical suppression of thyroid activity. Mucin in either type of myxedema appears to be the same. It represents an increase of the mucin normally present in the ground substance of the dermal connective tissue, and it can be demonstrated histochemically with a stain for acid mucopolysaccharides, such as Alcian blue, methylene blue, or
Whistleblower was unfairly dismissed, tribunal finds
Authors: Caroline White
Journal: BMJ (2004)

An employment tribunal unanimously ruled last week that the “whistleblower” who alleged that a London teaching hospital had “fiddled” one of its performance target figures, had been unfairly dismissed.

But the tribunal, which took seven months to publish its verdict, nevertheless decided that had the dismissal procedures been conducted fairly; that there was a “100% chance” that Ian Perkin, former finance director of St George's Healthcare NHS Trust, would still have lost his job; and that he “had contributed to his dismissal to the extent of 100%.”

The tribunal said that the dismissal was unfair because the trust had not followed the …
Science, Ethics, and Due Process
Authors: JOHN R. DURANT
Journal: Annals of Internal Medicine (1981)

Editorials1 July 1981Science, Ethics, and Due ProcessJOHN R. DURANT, M.D.JOHN R. DURANT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-1-116 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe absurdities resulting from the application of due process to novel therapeutic endeavors in humans are strikingly illustrated by two recent events. Standing in stark contrast are the legalization of laetrile by more than 20 state legislatures and the administrative censure of one of the nation's most imaginative scientists for his attempts to use recently developed techniques of genetic engineering to cure several patients of inevitably fatal genetic disorders. In the first case, outlandish claims, presented by persons of doubtful credibility, eventually resulted in an National Institutes of Health (NIH)-funded, one-half million dollar, predictably negative clinical trial approved by four...References1. MOERTELRUBINSARNAYOUNGJONESFLEMING CJGCST. A phase II trial of amygdalin (laetrile) in the treatment of human cancer. Proc AACR/ASCO. 1981;22:383. Abstract. Google Scholar2. WADE N. Gene therapy caught in more entanglements. Science. 1981;212:24-25. CrossrefMedlineGoogle Scholar3. ABRAM M. Living with cancer. In: 1979 Medical and Health Annual. Chicago: Encyclopedia Britannica, Inc.; 1979:158-70. Google Scholar4. . FDA drug approval—a lengthy process that delays the availability of important new drugs. In: GAO Report. Washington D.C.: General Accounting Office; May 28, 1980. (HRD-80-64.) Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Alabama in Birmingham Birmingham, Alabama PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPublic regulation of recombinant DNA gene therapyCorrection: Dr. Pellegrino's Name 1 July 1981Volume 95, Issue 1Page: 116-117KeywordsClinical trialsGenetic diseasesGenetic engineeringScientists Issue Published: 1 July 1981 PDF downloadLoading ...
Borrelia burgdorferi bind to epithelial cell proteoglycans.
Authors: R D Isaacs
Journal: Journal of Clinical Investigation (1994)

Borrelia burgdorferi adhere to mammalian cells in vitro but neither the ligand(s) nor the receptor(s) has (have) been clearly established.Using an in vitro attachment-inhibition as- say, a B. burgdorferi attachment mechanism has been identi- fied.Heparin, heparan sulfate, and dermatan sulfate reduced the attachment of virulent B. burgdorferi strain 297 to HeLa cells by -60%.In addition, virulent, but not avirulent, B. burgdorferi strains B31, N40, and HB19 demonstrated heparin at- tachment-inhibition.Attachment to Chinese hamster ovary cells deficient in heparan sulfate proteoglycans was reduced by 68% compared to attachment to wild-type cells and was identi- cal to attachment at maximum heparin inhibition to the wild- type cells.Pretreatment of HeLa cell monolayers with heparitinase, heparinase, and chondroitinase ABC, but not with chon- droitinase AC, reduced borrelial attachment by -50%.A moderately high affinity, low copy number, promiscuous B. burgdorferi glycosaminoglycan receptor was demonstrated by equilibrium binding studies.A 39-kD polypeptide, purified by heparin affinity chromatography from Triton X-100 extracts derived from virulent borrelia, was a candidate for this recep- tor.These studies indicate that one mode of B. burgdorferi attachment to eukaryotic cells is mediated by a borrelial glycosaminoglycan receptor attaching to surface-exposed proteoglycans on mammalian cells.(
Clinical Usefulness of Imaging the Distribution of the Reticuloendothelial System.
Authors: Patricia A. McIntyre
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Clinical Usefulness of Imaging the Distribution of the Reticuloendothelial System.Patricia A. McIntyre, M.D., F.A.C.P., Monica B. Spaulding, M.D., Pablo Dibos, M.D., Henry N. Wagner Jr., M.D., F.A.C.P.Patricia A. McIntyre, M.D., F.A.C.P.Search for more papers by this author, Monica B. Spaulding, M.D.Search for more papers by this author, Pablo Dibos, M.D.Search for more papers by this author, Henry N. Wagner Jr., M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-794_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRadioactive colloids have been used for several years as liver scanning agents. Although the major proportion of the injected colloid localizes in the reticuloendothelial (RE) cells of the liver, smaller but significant amounts are cleared by the RE cells of the spleen and bone marrow. This study was undertaken to evaluate the usefulness of imaging the distribution of radioactive colloids in the spleen and bone marrow, together with the liver. Spleen scans obtained with technetium-99m sulfur colloid were found to be useful in detecting splenomegaly, focal lesions of the spleen, and decreased function of the RE system of the spleen.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Patricia A. McIntyre, M.D., F.A.C.P.; Monica B. Spaulding, M.D.; Pablo Dibos, M.D.; Henry N. WagnerJr., M.D., F.A.C.P.Affiliations: Baltimore, Md. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 794-795KeywordsBone imagingBone marrowCellsLesionsLiverSpleenSplenomegaly ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Effect of Human Papillomavirus 16/18 L1 Viruslike Particle Vaccine Among Young Women With Preexisting Infection
Authors: Allan Hildesheim, Rolando Herrero, Sholom Wacholder, Ana C. Rodriguez, Diane Solomon, M. Concepcion Bratti, John T. Schiller, Paula Gonzalez, Gary Dubin, Carolina Porras, Silvia E. Jimenez, Douglas R. Lowy, for the Costa Rican HPV Vaccine Trial Group
Journal: JAMA (2007)

NOWLEDGE THAT INFECTIONwith 1 of approximately 15 oncogenic human papillomavirus (HPV) types is required for the development of cervical cancer has permitted primary prevention efforts via vaccination. 1][4][5] One vaccine (Gardasil) is a quadrivalent HPV-16/18 cervical cancer candidate vaccine that contains VLPs from 2 oncogenic HPV types, HPV-16 and HPV-18, and also contains VLPs from HPV types 6 and 11, which are not involved in cervical cancer pathogenesis but are linked to benign genital warts.
Beta transforming growth factors are potential regulators of B lymphopoiesis.
Authors: G Lee, L R Ellingsworth, S Gillis, R Wall, P W Kincade
Journal: The Journal of Experimental Medicine (1987)

Members of the transforming growth factor beta (TGF-beta) family of polypeptides were found to be potent in vitro inhibitors of kappa light chain expression on normal bone marrow-derived and transformed cloned pre-B cells, and of the maturation of these cells to mitogen responsiveness. The inhibition by TGF-beta was selective in that Ia expression was not blocked. Together with the observations that LPS, IL-1, NZB serum factors, IL-4, and IFN-gamma preferentially induced either kappa or Ia, or both, on a pre-B cell line, these results further suggest that acquisition of Ig and class II molecules is independently controlled by different antagonists as well as agonists. In addition, kappa chain induction by IFN-gamma does not appear to be as sensitive to TGF-beta downregulation as that stimulated by other factors tested, and this raises the possibility that activation of the same gene may result from different transmembrane signaling pathways. In contrast to the inhibitory effects of TGF-beta on kappa acquisition by pre-B cells and on kappa increase after exposure of mature B cells to LPS, as measured by kappa RNA levels and/or surface fluorescence, no inhibition was observed on unstimulated spleen B cells or on two cloned B cell lines that constitutively produce kappa. Thus, TGF-beta may function during specific stages of B cell differentiation by inhibiting initiation of, or increased transcription of Ig genes, and therefore, may be an important negative regulator of B lymphopoiesis. It is the first natural substance found to have this effect.
Dangers of Dioctyl Sodium Sulfosuccinate in Mixtures
Authors: Harold Godfrey
Journal: JAMA (1971)

To the Editor.—  In their recent letter ( 213 :2273, 1970) your correspondents Drs. Reynolds and Redeker quote six cases of patients with liver disease following the prolonged administration of oxyphenisatin. Clearly, these point to the dangers of prolonged treatment with this substance, but they lead us away from Dr. Naess's warning about the inherent dangers of dioctyl sodium sulfosuccinate combinations.  In US patent 2,851,394 granted in 1958 to Joseph B. Vaughan (assignor to Lloyd Brothers Inc) the following paragraph occurs:  It was further found in our laboratory that the oral administration of 1, 8 dihydroxyanthraquinone (Danthron) did not produce death in rats even in quantities of as much as 22 mg/kg. On the other hand, when this substance was administered in combination with non-toxic amounts of dioctyl sulfosuccinate only 9 mg/kg was sufficient to give a 50 percent kill in rats. This effect can only be due to increased absorption
797 EASY TO ASSESS ON-TREATMENT PARAMETERS CORRELATE WITH DEGREE OF VIROLOGICAL RESPONSE AFTER 12 WEEKS OF TREATMENT
Authors: D. Jensen, B. Freilich, P. Andreone, A. DiBisceglie, C.E. Brandao, K.R. Reddy, A. Craxi, A. Olveira, G. Teuber, D. Messinger, G. Hooper, M. Popescu, A. Tietz, P. Marcellin
Journal: Journal of Hepatology (2008)
Antibodies elicited by pneumococcal antigens bear an anti-DNA--associated idiotype.
Authors: A Grayzel, A Solomon, C Aranow, B Diamond
Journal: Journal of Clinical Investigation (1991)

There is evidence in both murine and human lupus that the production of anti-DNA antibodies may be triggered by environmental antigens. To explore this further, we studied the serum of 10 nonautoimmune individuals immunized with a polyvalent pneumococcal polysaccharide vaccine. All 10 patients showed a rise in the titer of antipneumococcal antibodies bearing an anti-DNA-associated idiotype. The antipneumococcal response was specific as no idiotypic antitetanus antibodies were detected. Furthermore, no anti-DNA antibodies were present in postvaccination sera. The molecular analysis of antipneumococcal and anti-DNA antibodies bearing a common idiotype will help elucidate how foreign antigen might lead to the production of anti-DNA antibodies in susceptible individuals.