tbuckley/cabot-search huggingface dataset:
Intestinal carcinogenesis: IKK can go all the way
Authors: Yoshiaki Sunami, Thomas Wirth
Journal: Journal of Clinical Investigation (2011)

Chronic inflammation has long been suspected to support tumorigenesis in a variety of cancers. The IκB kinase (IKK)/NF-κB pathway is the critical signal transduction pathway regulating inflammation, and loss-of-function studies have demonstrated its involvement in tumorigenesis. In this issue of the JCI, Vlantis et al. present evidence that persistent genetic activation of IKK/NF-κB signaling in intestinal epithelial cells not only accelerates tumorigenesis in models of both carcinogen- and mutation-induced colorectal cancer, but also is sufficient to induce intestinal tumors.
Altered Folate Metabolism in Early HIV Infection-Reply
Authors: Richard S. Beach
Journal: JAMA (1988)

<h3>In Reply.</h3> —We appreciate the comments by Tilkian et al regarding our finding of elevated serum and red blood cell folate levels in early HIV infection. We, too, considered vitamin B<sub>12</sub>deficiency and the vitamin B<sub>12</sub>—folate trap as a possible cause of the apparent elevation of folate levels.<sup>1</sup>However, there was no significant correlation between folate and serum vitamin B<sub>12</sub>levels in our patients (<i>r</i>=.12;<i>P</i>=.51). While approximately 25% of our patients were vitamin B<sub>12</sub>deficient, they were not consistently the same subjects with the elevated folate levels (Figure). Consequently, an alternative explanation should be sought. As pointed out by Tilkian and coworkers, cellular lysis might result in transient elevation of serum nutrient levels. However, our patients had elevated levels of both serum and, most notably, erythrocyte folate. Therefore, release of intracellular folate alone cannot explain our findings. The binding of folate
Interval between insulin injection and eating in relation to blood glucose control
Authors: S D Slater
Journal: BMJ (1985)

human parvovirus in pregnancy are en- couraging and substantiate previous epidemiological studies that have failed to reveal any evidence of teratogenicity.'Indeed, the severe fetal infections described recently3 4 may well represent rare events.Nevertheless, we agree with Dr Wright and colleagues on the need for serological identification of additional cases if the effects of human parvovirus in pregnancy are to be defined more precisely.Our experi- ence suggests, however, that infection in some adults may be subclinical, as illustrated by our third case.It may be prudent, therefore, to consider human parvovirus serology not only in pregnant women who develop a non-rubella rash but also in those who are close contacts of children with erythema infectiosum.
Ascending Hemorrhagic Signs after a Bite from a Copperhead
Authors: James R. Roberts, Michael I. Greenberg
Journal: New England Journal of Medicine (1997)

To the Editor: Rubin and colleagues (Nov.7 issue) 1 conclude that advanced epithelial ovarian cancers in patients with germ-line BRCA1 mutations have a better prognosis than their sporadic counterparts.Although this may eventually prove to be correct, the methods used in this study raise several questions.Important prognostic information about the patients with BRCA1 mutations, such as the status of residual disease and the type of chemotherapy used, was said to be unavailable from the patients' charts, although these data are critical in choosing a proper control group.Did the authors attempt to check the original operative reports; to make direct contact with the surgeons, the medical oncologists, or both; and, when possible, to ask the patients?Since many patients and family members know what kind of chemotherapy was administered, I am surprised that this basic information was not available.Histology and disease stage are important prognostic factors in ovarian tumors, yet in only 14 cases were slides reviewed to confirm the diagnosis.Why were slides from the remaining 39 patients unavailable?Is it possible that the distribution of histologic subtypes and grades shown in Table 1 of the article would have differed if the authors had undertaken a centralized review of all available slides?The authors make no direct mention of how rigorously they assessed survival status.Was this done by reviewing the charts, calling patients directly, or examining death certificates?Readers should be given enough information for them to have confidence in the quality of the data presented.In view of these uncertainties in the BRCA1 -mutation group, I am at a loss to know how the authors can confidently choose a representative control group for comparison.It is not enough to select the control group on the basis of age and stage alone, because there are many other influences on outcome that could easily bias the results.The median survival of 29 months in the control group suggests that those patients represent a group at particularly high risk, with suboptimally debulked disease, 2 and this may therefore artifactually magnify any potential survival advantage associated with the presence of a BRCA1 mutation.These concerns lead me to believe that the authors have drawn conclusions about the influence of BRCA1 mutations on prognosis that are not entirely justified by their data.
Intrarenal mechanisms of salt retention after bile duct ligation in rats.
Authors: W E Yarger, N W Schrader, M A Boyd
Journal: Journal of Clinical Investigation (1976)

In order to study renal salt-retaining mechanisms during the early stages of ascites formation, rats were subjected to bile duct ligation. After this procedure, plasma volumes were found to be reduced and hematocrits slightly increased. The whole-kidney glomberular filtration rate and plasma flows were reduced to 59 and 57% of control values, but the filtration fraction was unchanged. Absolute sodium excretion, as well as the fraction of the filtered sodium load excreted, was also significantly reduced. When micropuncture techniques were used to examine the function of single superficial nephrons, the glomerular filtration rate in these nephrons was found to be reduced to 70% of controlled values, and fractional reabsorption was found to be increased at all accessible sites along the nephron. Filtration by intermediate and juxtamedullary nephrons, determined by Hanssen's technique, was reduced to 55 and 48% of control values. By the use of radioactive microspheres, it was demonstrated that blood flow to superficial, intermediate, and juxtamedullary nephrons was reduced to 49, 59, and 73% of control values. Filtration by superficial nephrons decreased much more than plasma flow--a finding which suggests that the measured increase in fractional reabsorption was associated with an increase in the superficial nephron filtration fraction. From this study, it appears that two factors play an important part in the sodium retention observed in the initial stages of ascites formation following bile duct ligation in rats: (a) a decrease in the filtered sodium load and (b) increased fractional reabsorption by the superficial nephrons--the nephrons which show the least decrease in filtration.
Diffuse Heterotopic Cystic Malformation of the Stomach
Authors: Harold A. Oberman, John G. Lodmell, Norman D. Sower
Journal: New England Journal of Medicine (1963)

IN 1947 Scott and Payne1 reported a unique case of diffuse thickening of the distal half of the gastric wall by multiple, small cysts of the mucosa and submucosa. This occurred in a fifty-eight-year-old man who had experienced anorexia and weight loss, and who was found to have achlorhydria and a roentgenographic filling defect in the antrum.We recently encountered similar involvement of the stomach in a fifty-four-year-old man, who also presented clinical findings simulating diffuse mucosal thickening by carcinoma or malignant lymphoma.Case ReportF.R., a 54-year-old man, was admitted to Walter Reed General Hospital in June, 1962, with . . .
Autografts of peripheral blood stem cells
Authors: C L Rist
Journal: BMJ (1994)

contents and then swallowed as a glass of water is drunk.4If swallowing is impaired, nasogastric administration of the capsule's contents is indeed an alternative, albeit less accurate.Rather than sublingual nifedipine being prescribed, it would be clearer and more accurate to prescribe nifedipine for oral administration, with additional instructions that the patient should bite the capsule before swallowing it while drinking a glass ofwater.
James Malone-Lee responds to the media flurry over safety of anticholinergic drugs in elderly people
Authors: J. Malone-Lee
Journal: BMJ (2011)

The intemperate hubbub over anticholinergic safety in elderly people, championed by the BBC on the morning of 24 June 2011, merits sober reflection.1 The focus was a paper by Fox and colleagues that was unavailable until 4 pm,2 when placed on the website of the Journal of the American Geriatrics Society . By then the media squall had dissipated. Recent UK history should deter such ill advised announcement of data through television, before it is published for peer scrutiny.

The article in question was a post hoc analysis of epidemiological data collected from older adults enrolled in the Medical Research Council Cognitive Function and Ageing Study. Participants were assessed using the mini-mental state examination (MMSE) in 1991 and 1993. The paper was published as an early online brief report, short on detail.

Anticholinergic exposure was measured crudely using a ranked …
Abstract B9: Cost effectiveness of gene expression profiling for tumor site origin
Authors: John Hornberger, Irina Degtiar, Hialy Gutierrez, Ashwini Shewade, W. David Henner, Shawn Becker, Stephen Raab
Journal: Clinical Cancer Research (2012)

Abstract Background: Gene expression profiling (GEP) reliably supplements traditional clinicopathological information on the tissue of origin (TOO) in metastatic or poorly differentiated cancer. A cost-effectiveness analysis of GEP TOO testing versus usual care was conducted from a third-party payer perspective in the United States. Methods: A retrospective, observational study examined treatment changes in patients whose physicians had received the GEP TOO test results to help diagnose the tissue-site of their patient's malignancy and to guide appropriate therapy. Changes in planned chemotherapy, surgery, radiation therapy, added blood tests, imaging investigations, and referral to hospice care before and after the GEP TOO test results were recorded. The effect of changes in chemotherapy on survival were based on randomized controlled trials informing appropriate use of chemotherapy cited in National Comprehensive Cancer Network (NCCN) and Up-to-Date guidelines. Drug and administration costs were based on average doses reported in NCCN guidelines. Centers for Medicare and Medicaid Services (CMS) fee schedules were used to obtain other unit costs. Quality-of-life weights were obtained from literature sources. Changes in overall survival, costs, and cost per quality-adjusted life year (QALY) gained were estimated using bootstrap methods. Results: Use of chemotherapy regimens consistent with guidelines for the final tumor-site diagnosis increased significantly from 42% to 65% (net difference 23%; p&amp;lt; 0.001). Overall survival was projected to increase from 15.9 months to 19.5 months (mean difference 3.6 months, 95%CI [2.0, 5.1]). The average increase in survival adjusted for quality of life was 2.7 months (95%CI [1.4, 3.9]), and average third-party payer costs per patient increased by $10,360 (95% CI [$5,668, $15,053]). The cost per QALY gained was $46,858 (95% CI [$17,995, $75,718]). Conclusions: GEP TOO testing significantly altered clinical practice patterns for treating metastatic cancer of uncertain primary. It is projected to increase overall survival, QALYs, and costs, resulting in an expected cost per QALY of less than $50,000.
The Importance of Biopsy Procedures
Authors: George E. Moore
Journal: JAMA (1969)

Biopsy procedures of all kinds should be used far more frequently, not only for establishing initial diagnoses but also for providing more accurate clinical surveillance of the disease process. Frozen section and other techniques for rapid processing should be adopted in order to supply the clinician with more current pathological information. In the future, it is hoped that all biopsy reports can be made available within a few hours after the procedure itself.
VASCULAR RESPONSE IN THE ISOLATED RAT LIVER
Authors: James P. Nolan, Cornelius J. O'Connell
Journal: The Journal of Experimental Medicine (1965)

Sublethal doses of E. coli endotoxin were shown to cause direct slowing of blood flow in the isolated perfused rat liver. Concentrations as low as SO ng per ml elicited this vasoconstrictive response. The decrease in flow after the initial lipopolysaccharide injection was immediate and lasted from. 5 to 15 minutes before recovering to baseline values. Succeeding injections of the same concentration, however, had little or no circulatory effects, and this tachyphylaxis persisted through 5 hours of perfusion. The replacement of the perfusate with fresh whole blood after several hours partially restored the ability of the hepatic vasculature to respond to the lipopolysaccharide. However, the presence of plasma or formed blood elements was not essential to the response, as brisk decreases occurred after endotoxin when a modified Ringer's solution was the sole perfusate. Catecholamines or serotonin did not appear to be key mediators in the primary vascular effect of endotoxin as phentolamine and methysergide administration did not appreciably modify the response. On the other hand, hydrocortisone when given in large doses with the endotoxin or in smaller doses 15 to 45 minutes prior to the lipopolysaccharide completely blocked vasoconstriction. The isolated preparation seems to be an excellent model for the study of direct circulatory effects of various substances in the liver.
Reproductive impairment in the Florida panther: nature or nurture?
Authors: C F Facemire, T S Gross, L J Guillette
Journal: Environmental Health Perspectives (1995)

Many of the remaining members of the endangered Florida panther (Felis concolor coryi) population suffer from one or more of a variety of physiological, reproductive, endocrine, and immune system defects including congenital heart defects, abnormal sperm, low sperm density, cryptorchidism, thyroid dysfunction, and possible immunosuppression. Mercury contamination, determined to be the cause of death of a female panther in 1989, was presented as the likely cause of thyroid dysfunction. As genetic diversity in the species was less than expected, all of the other abnormalities have been attributed to inbreeding. However, exposure to a variety of chemical compounds, especially those that have been identified as environmental endocrine disrupters (including mercury, p,p'-DDE, and polychlorinated biphenyls), has elicited all of the listed abnormalities in other species. A number of these contaminants are present in South Florida. An exposure pathway has been identified, and evidence presented in this paper, including the fact that there appears to be no significant difference between serum estradiol levels in males and females, suggests that many male panthers may have been demasculinized and feminized as a result of either prenatal or postnatal exposure. Thus, regardless of the effects of inbreeding, current evidence seems to indicate that environmental contaminants may be a major factor contributing to reproductive impairment in the Florida panther population.
Hepatitis C virus and the threshold of natural killer cell inhibition
Authors: Golo Ahlenstiel, Barbara Rehermann, Hartmut Jaeschke, Kevin Mullen, Darius Moradpour
Journal: Hepatology (2005)

Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.
Oxidative modification of low-density lipoproteins and the outcome of renal allografts at 11/2 years
Authors: Jean-Louis Bosmans, Paul Holvoet, Simonne E.H. Dauwe, Dirk K. Ysebaert, Thierry Chapelle, Angelika Jürgens, Vera Kovacic, Eric A. Van Marck, Marc E. De Broe, Gert A. Verpooten
Journal: Kidney International (2001)
Aristotle's Anomaly-Reply
Authors: Robert A. Kyle
Journal: JAMA (1982)

In Reply.—  We appreciated seeing the comments of Dr Harnes concerning Aristotle's anomaly.  The following  additional definitions of Aristotle's anomaly have come to our attention:   1. When the first and second fingers are crossed and a small object such as a pencil is placed between them the false impression is gained that there are  objects (Butterworth's Medical Dictionary).    2. When a small object is held between the first and second fingers crossed in such a way that it touches or presses upon skin surfaces which ordinarily are not pressed upon simultaneously by a single object, it is perceived falsely as two (Stedman's Medical Dictionary).   Perhaps Dr Harnes can use these additional definitions to test Aristotle's anomaly further.
Cyclic Premenstrual Unconjugated Hyperbilirubinemia
Authors: KAKUTARO YAMAGUCHI
Journal: Annals of Internal Medicine (1975)

Two young women developed unconjugated hyperbilirubinemia that fluctuated with the menstrual cycle. They were otherwise healthy, and there was no evidence of hematologic or chronic liver disease. Serum unconjugated bilirubin rose concomitant with the rise of basal temperature during the premenstrual period, and it declined immediately after the end of menses. Administration of progesterone during the postmenstrual period elevated unconjugated bilirubin. A close relation of hyperbilirubinemia to female hormones was suggested. The condition may be called "constitutional unconjugated hyperbilirubinemia with a menstrual cycle."
The Pressure Gradient in Ventricular Outflow Obstruction: Influence of Peripheral Resistance
Authors: E. D. Silove, J. H. K. Vogel, R. F. Grover
Journal: Cardiovascular Research (1968)

When flow of fluid in elastic tubing is pulsatile, as in the cardiovascular system, the magnitude of the pressure gradient across a fixed stenosis can be substantially decreased by an increase in the downstream resistance. This is possibly due to an uneven transfer of energy. Clinical implications are cited.
Studies on the Distribution of Surface Immunoglobulins on Human B-Lymphocytes
Authors: Kenneth A. Ault, Morris J. Karnovsky, Emil R. Unanue
Journal: Journal of Clinical Investigation (1973)

Normal human peripheral blood lymphocytes were studied with fluorescent anti-immunoglobulin antibodies and shown to have a patchy distribution of immunoglobulin on their surfaces that does not form a cap after complexing with antibody. Use of freeze-etch electron microscopy confirmed the distribution of immunoglobulin in isolated patches on the membrane. Evidence is presented that this distribution may explain the absence of capping of these human cells as compared with mouse B-lymphocytes.Studies of the metabolism of antibody bound to the cell surface revealed rapid shedding of complexes from the cell and also rapid endocytosis with subsequent degradation of the antibody. Several attempts to alter this distribution of immunoglobulin on the surface were unsuccessful. Possible mechanisms by which cell surface elements may be organized are discussed, as well as the significance of the results in terms of the immune response and the classification of certain lymphoproliferative diseases.
Estrogen regulates Hippo signaling via GPER in breast cancer
Authors: Xin Zhou, Shuyang Wang, Zhen Wang, Xu Feng, Peng Liu, Xian-Bo Lv, Fulong Li, Fa-Xing Yu, Yiping Sun, Haixin Yuan, Hongguang Zhu, Yue Xiong, Qun-Ying Lei, Kun-Liang Guan
Journal: Journal of Clinical Investigation (2015)

The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.
TCT-766 Prevalence and prognostic significance of early left ventricular reverse remodeling in high-risk patients with severe aortic stenosis undergoing transcatheter aortic valve implantation
Authors: Stylianos A. Pyxaras, Thomas Schmitz, Alexander Wolf, Yuan Zhang, Illkyu-Oliver Lee, Christoph Johann, Christoph Naber
Journal: Journal of the American College of Cardiology (2014)
Intestinal alkaline phosphatase in the diagnosis of liver disease.
Authors: T W Warnes, P Hine, G Kay
Journal: Gut (1977)

Alkaline phosphatase isoenzymes have been studied by acrylamide gel disc electrophoresis in 76 patients with liver disorders comprising 15 with an extrahepatic lesion, 53 with an intrahepatic lesion, and eight patients who had features of both intra- and extrahepatic disease. No intestinal band was found in the 15 cases of extrahepatic liver disease, in marked contrast to the patients with intrahepatic lesions in whom an intestinal band was found in 45% of cases. The intrahepatic group was heterogeneous, a high incidence of intestinal bands being found in patients with cirrhosis of the liver. It is concluded that where a raised serum alkaline phosphatase is found in a patient with jaundice, and a gut band is present on electrophoresis, the lesion is likely to be intrahepatic.
Tobacco Smoking and Bladder Cancer—Reply
Authors: Neal D. Freedman
Journal: JAMA (2011)

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