tbuckley/cabot-search huggingface dataset:
Prospects in Asthma Therapy: Disodium Cromoglycate and Diethylcarbamazine
Authors: Robert P. Orange, K. Frank Austen
Journal: New England Journal of Medicine (1968)

Asthma is a syndrome of varying etiology in which the principal pathologic features include bronchospasm, mucosal edema and hypersecretion of mucus resulting in ventilatory insufficiency manifested clinically as wheezing, dyspnea, cough and mucoid expectoration.1 The pathogenesis of extrinsic asthma may involve the immunologic release of various chemical mediators of inflammation, including histamine and slow reacting substance of anaphylaxis (SRS-A). The finding that the lungs of allergic human beings challenged in vitro with specific pollen antigen results in the release of histamine and SRS-Ahu2 does not exclude the possible role of other mediators not yet studied. Passive sensitization of normal human . . .
Abstract 237: MET receptor is a potential new target for cervical carcinoma treatment
Authors: Katarzyna Miekus, Marta Pawlowska, Marcin Majka
Journal: Cancer Research (2011)

Abstract Introduction: Cervical carcinoma (CC) is the major cause of death among women suffering from neoplastic disease especially in the developing countries. The highest mortality is observed in patients with late diagnosis and metastatic disease. MET protooncogene encodes a tyrosine kinase receptor for hepatocyte growth factor (HGF). MET activation triggers a complex biological program including stimulation of cell proliferation, motility and protection from apoptosis. This program plays an important role during embryonic development and wound healing, but abnormal MET activity contribute to cancer development and progression. Therefore, new therapeutic strategies inhibiting MET signaling have been sought. Objectives: The aim of this study was to examine the influence of MET inhibition on growth and metastatic ability of cervical carcinoma cell. Materials and Methods: CC cell line (HTB35) was transduced with MET shRNA and LacZ shRNA expressing viruses and selected with blasticidin. To check genes expression real-time PCR, western blot and flow cytometry were used. Proliferation, cell cycle and apoptosis was studied. Stress fibers organization, adhesion and migration were evaluated using using falloidin staining, adhesion assay and chemotaxis assay respectively. The level of various protein phosphorylation was estimated by western blot. Results: We showed that downregulation of MET expression in HTB-35 cell line causes: (i) the reduction in cell proliferation resulting from altered cell cycle progression, but not from enhanced apoptosis, (ii) changes in actin cytoskeleton organization, (iii) the increased expression of E-cadherin, (iv) the decrease of mRNA levels in the genes responsible for malignant phenotype (such as c-myc, CXCR4 and Slug), and (v) the increased expression of genes involved in EMT and metastasis (including Snail, Slug, Twist, MMP-2, MMP-9 and HIF-1α). Performed in vitro studies have not shown any significant effect of MET inhibition on adhesive ability of HTB-35 cervical carcinoma cell line. However, the decreased migration of MET negative cells was observed. Summary: Our results strongly, indicate that MET receptor plays an important role in stimulating growth and metastasis of HTB-35 cervical carcinoma cell line. Thus, inhibition of HGF-MET receptor axis could be used in the future as the new therapeutic strategy to block cervical carcinoma development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 237. doi:10.1158/1538-7445.AM2011-237
<i>S</i>-adenosyl methionine regulates ubiquitin-conjugating enzyme 9 protein expression and sumoylation in murine liver and human cancers
Authors: Maria Lauda Tomasi, Ivan Tomasi, Komal Ramani, Rosa Maria Pascale, Jun Xu, Pasquale Giordano, José M. Mato, Shelly C. Lu
Journal: Hepatology (2012)

Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and is overexpressed in several malignancies, but its expression in hepatocellular carcinoma (HCC) is unknown. Hepatic S-adenosyl methionine (SAMe) levels decrease in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop HCC, and in ethanol-fed mice. We examined the regulation of Ubc9 by SAMe in murine liver and human HCC, breast, and colon carcinoma cell lines and specimens. Real-time polymerase chain reaction and western blotting measured gene and protein expression, respectively. Immunoprecipitation followed by western blotting examined protein-protein interactions. Ubc9 expression increased in HCC and when hepatic SAMe levels decreased. SAMe treatment in Mat1a KO mice reduced Ubc9 protein, but not messenger RNA (mRNA) levels, and lowered sumoylation. Similarly, treatment of liver cancer cell lines HepG2 and Huh7, colon cancer cell line RKO, and breast cancer cell line MCF-7 with SAMe or its metabolite 5'-methylthioadenosine (MTA) reduced only Ubc9 protein level. Ubc9 posttranslational regulation is unknown. Ubc9 sequence predicted a possible phosphorylation site by cell division cycle 2 (Cdc2), which directly phosphorylated recombinant Ubc9. Mat1a KO mice had higher phosphorylated (phospho)-Ubc9 levels, which normalized after SAMe treatment. SAMe and MTA treatment lowered Cdc2 mRNA and protein levels, as well as phospho-Ubc9 and protein sumoylation in liver, colon, and breast cancer cells. Serine 71 of Ubc9 was required for phosphorylation, interaction with Cdc2, and protein stability. Cdc2, Ubc9, and phospho-Ubc9 levels increased in human liver, breast, and colon cancers. Cdc2 expression is increased and Ubc9 is hyperphosphorylated in several cancers, and this represents a novel mechanism to maintain high Ubc9 protein expression that can be inhibited by SAMe and MTA.
Self testing for diabetes mellitus.
Authors: M Davies, H Alban-Davies, C Cook, J Day
Journal: BMJ (1991)

OBJECTIVE--To develop a simple, economically viable, and effective means of population screening for diabetes mellitus. DESIGN--A postal request system for self testing for glycosuria with foil wrapped dipsticks. Preprandial and postprandial tests were compared with a single postprandial test. The subjects were instructed how to test, and a result card was supplied on which to record and return the result. All those recording a positive test result and 50 people recording a negative result were invited for an oral glucose tolerance test. SETTING--General practice in east Suffolk, list size 11534. PATIENTS--All subjects aged 45-70 years registered with the practice were identified by Suffolk Family Health Services Authority (n = 3057). The 73 subjects known to have diabetes from the practice9s register were excluded, leaving 2984 subjects, 2363 (79.2%) of whom responded. 1167 subjects completed the single test and 1196 the two tests. MAIN OUTCOME MEASURES--Response rate and number of patients with glycosuria. Sensitivity, specificity, and positive predictive value of a single postprandial test and preprandial and postprandial tests. Number of new cases of diabetes identified and cost of screening. RESULTS--Of the patients completing the single postprandial test, 29 had a positive result, an oral glucose tolerance test showed that eight (28%) had diabetes, six (21%) impaired glucose tolerance, and 14 (48%) normal glucose tolerance. 44 of the group who tested before and after eating had a positive result; nine (20%) had diabetes, five (11%) impaired tolerance, and 26 (11%) normal tolerance. Screening cost 59p per subject and 81 pounds per case detected. Of the 17 people with previously undiagnosed diabetes, eight were asymptomatic and 11 had not visited their general practitioner in the past three months. CONCLUSIONS--A postal request system for self testing for postprandial glycosuria in people aged 45-70 is a simple and effective method of population screening for diabetes mellitus.
Crohn disease was not associated with increased risk for mortality
Authors: Paul Moayyedi
Journal: Annals of Internal Medicine (2013)

Source Citation Hovde Ø, Kempski-Monstad I, Småstuen MC, et al. Mortality and causes of death in Crohn's disease: results from 20 years of follow-up in the IBSEN study. Gut. 2013 Jun 6. [Epub ahead of print] 23744613
A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with α<sub>1</sub>-antitrypsin deficiency
Authors: Elena Miranda, Juan Pérez, Ugo I. Ekeowa, Nedim Hadzic, Noor Kalsheker, Bibek Gooptu, Bernard Portmann, Didier Belorgey, Marian Hill, Susan Chambers, Jeff Teckman, Graeme J. Alexander, Stefan J. Marciniak, David A. Lomas
Journal: Hepatology (2010)

Abstract Alpha1-antitrypsin is the most abundant circulating protease inhibitor. The severe Z deficiency allele (Glu342Lys) causes the protein to undergo a conformational transition and form ordered polymers that are retained within hepatocytes. This causes neonatal hepatitis, cirrhosis, and hepatocellular carcinoma. We have developed a conformation-specific monoclonal antibody (2C1) that recognizes the pathological polymers formed by α1-antitrypsin. This antibody was used to characterize the Z variant and a novel shutter domain mutant (His334Asp; α1-antitrypsin King's) identified in a 6-week-old boy who presented with prolonged jaundice. His334Asp α1-antitrypsin rapidly forms polymers that accumulate within the endoplasmic reticulum and show delayed secretion when compared to the wild-type M α1-antitrypsin. The 2C1 antibody recognizes polymers formed by Z and His334Asp α1-antitrypsin despite the mutations directing their effects on different parts of the protein. This antibody also recognized polymers formed by the Siiyama (Ser53Phe) and Brescia (Gly225Arg) mutants, which also mediate their effects on the shutter region of α1-antitrypsin. Conclusion: Z and shutter domain mutants of α1-antitrypsin form polymers with a shared epitope and so are likely to have a similar structure.
Risks of interrupting drug treatment before surgery
Authors: D. W Noble
Journal: BMJ (2000)

Millions of patients worldwide have surgery each year. As well as using a variety of recreational drugs, such as caffeine, tobacco, and alcohol, many of these patients are prescribed therapeutic drugs for concurrent diseases. These drugs are taken for their positive therapeutic benefits, and abrupt interruptions lead at best to a loss of effect and at worst to rebound exacerbations of diseases.1

Unfortunately, surgery, and major abdominal surgery in particular, can cause patients to abstain from their usual drug treatment. After major abdominal surgery gastric emptying is delayed, making administration of drugs by the oral or nasogastric routes unreliable.2-4 Surgical patients may be particularly vulnerable to complications caused by abstention from drug treatment because of the adaptive and maladaptive physiological and psychological stresses related to surgical trauma that may increase the risk of organ dysfunction. 5 6 However, there is little systematic evidence that quantifies the risks of the abrupt withdrawal of therapeutic drugs in the postoperative setting.

An observational study by Kennedy and colleagues of over 1000 admissions for general surgery and vascular surgery has made an important preliminary contribution …
The Pan-B Cell Marker CD22 (siglec 2) Is Expressed On Gastro-intestinal (GI) Eosinophils And Negatively Regulates GI Eosinophil Survival
Authors: T. Wen, C. Blanchard, B. Wahl, O. Pabst, M.E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2011)
Endoscopic ultrasound-guided fine-needle tissue acquisition from a subepithelial lesion in the distal ileum using the forward-viewing echoendoscope
Authors: Domenico Galasso, Fabia Attili, Franco Scaldaferri, Giuseppe Vanella, Frediano Inzani, Guido Costamagna, Alberto Larghi
Journal: Endoscopy (2014)

In a context of rapidly expanding indications for endoscopic ultrasound (EUS)-guided procedures, a dedicated forward-viewing linear therapeutic echoendoscope (FV-EUS) has been developed and tested for different clinical indications [1] [2] [3]. The frontal endoscopic view combined with the exit of the working channel at the tip of the echoendoscope offers some unique advantages over the standard curvilinear echoendoscope. This has opened up new possibilities for EUS-guided fine-needle aspiration and tissue acquisition (EUS-FNTA) from difficult targets and combined endoscopic/EUS treatment [3] [4].
PHYSICAL AND IMMUNOLOGICAL DIFFERENCES AMONG STREPTOKINASES
Authors: Hugh C. Dillon, Lewis W. Wannamaker
Journal: The Journal of Experimental Medicine (1965)

Two strains of Group A streptococci have been shown to produce streptokinases with different physical and immunologic characteristics. These streptokinases have been designated SK-A and SK-B. Examination of additional strains of Group A streptococci has indicated that SK-A is the more commonly encountered streptokinase. Studies comparing the two Group A streptokinases with streptokinase of Group C origin have indicated that the latter streptokinase is intermediate between SK-A and SK-B in regard to its electrophoretic mobility. Immunological data suggest that the Group C streptokinase differs from SK-B but is closely related to SK-A.
Illustrations of the Antiseptic Principle of Treatment in Surgery
Authors: J. Syme
Journal: BMJ (1868)

THE following cases of wounds, compound fractures, and abscesses, selected from those that have been treated under my care in the clinical surgical wards of the Royal Infirmary, will, I hope, tend to illustrate and recommend the antiseptic principles of practice introduced by Mr. Lister, which, although of the greatest value, there is reason to fear are not yet generally understood or adopted.In the old days of surgery all the steps of a healing process were attributed to the effects of so- called " mundifying," " incarning," and "cicatrising" applications.In more recent times, lotions, simple, astringent, or stimulating, have
Loss of Myocardial Ischemic Postconditioning in Adenosine A <sub>1</sub> and Bradykinin B <sub>2</sub> Receptors Gene Knockout Mice
Authors: Lei Xi, Anindita Das, Zhi-Qing Zhao, Vanessa F. Merino, Michael Bader, Rakesh C. Kukreja
Journal: Circulation (2008)

Background— Ischemic postconditioning (PostC) is a recently described cardioprotective modality against reperfusion injury, through series of brief reflow interruptions applied at the very onset of reperfusion. It is proposed that PostC can activate a complex cellular signaling cascade, in which cell membrane receptors could serve as the upstream triggers of PostC. However, the exact subtypes of such receptors remain controversial or uninvestigated. To this context, the purpose of present study was to determine the definitive role of adenosine A 1 and bradykinin B 1 and B 2 receptors in PostC. Methods and Results— The hearts isolated from adult male C57BL/6J wild-type mice or the mice lacking adenosine A 1 , or bradykinin B 1 or B 2 receptors subjected to zero-flow global ischemia and reperfusion in a Langendorff model. PostC, consisting of 6 cycles of 10 seconds of reperfusion and 10 seconds of ischemia, demonstrated significantly reduced myocardial infarct size (22.8±3.1%, mean±SEM) as compared with the non-PostC wild-type controls (35.1±2.8%, P &lt;0.05). The infarct-limiting protection of PostC was absent in adenosine A 1 receptor knockout mice (34.9±2.7%) or bradykinin B 2 receptor knockout mice (33.3±1.7%) and was partially attenuated in bradykinin B 1 receptor-deficient mice (25.6±2.9%; P &gt;0.05). On the other hand, PostC did not significantly alter postischemic cardiac contractile function and coronary flow. Conclusions— With the use of three distinctive strains of gene knockout mice, the current study has provided the first conclusive evidence showing PostC-induced infarct-limiting cardioprotection could be triggered by activation of multiple types of cell membrane receptors, which include adenosine A 1 and bradykinin B 2 receptors.
Endoskopische und histologische Bilder eines Sarkoidoseulkus des Magens
Authors: W. Schmidt, R. Nommels
Journal: Endoscopy (1972)

Case-report on a 1.5×2 cm gastric ulcer in a patient with chronic sarcoidosis for 23 years which grossly looked primarily malignant but proved to be due to gastric involvement of the underlying disease in scopic biopsy. Epitheloid cell granulomata were especially prominent and dense at the ulcer border.
Can laboratory animal carcinogenicity studies predict cancer in exposed children?
Authors: D P Rall
Journal: Environmental Health Perspectives (1995)

A key to the prevention of childhood cancer is the control of carcinogens to which children are exposed. The first step in this process is to identify those chemicals that are likely to cause cancer in children. The best way to identify carcinogens, today, is the use of the rodent lifetime cancer test--the bioassay. The test has vocal critics, but is adequately reliable if properly used. Perhaps the major criticism concerns the use of the maximum tolerated dose as the highest dose tested. Critics claim that this dose causes cellular killing. The resultant cellular proliferation "fixes" preexisting mutations that can lead to cancer. This occurs but in a small fraction of the tests, and the high dose is necessary to achieve statistical sensitivity. All human carcinogens have been shown, when properly studied, to be carcinogenic in rodents. Many human carcinogens were first shown to cause cancer in rodent tests. Regulators rarely ban chemicals that have been demonstrated to be carcinogenic. Further, most chemicals in use today have not been properly tested. The potential errors in the rodent cancer test seem small when compared to the errors in the economic projections of the effects of restricting chemicals. Although not perfect, the rodent cancer test, when used properly, can help protect our children, and us, from cancer.
The mean predicts the number of deviants
Authors: S J Senn
Journal: BMJ (1990)

because they contain added iron and vitamin D and have limited saturated fat and sodium contents, without limiting energy content.Regarding cost we can quibble over figures, but let's accept an extra cost ofE l.43 a week of using a follow on milk (or infant formula) instead of cows' milk.This is the equivalent each day of one to two disposable nappies, or a newspaper, or two cigar- ettes, or 28 ml beer.Nevertheless, for some families even this extra cost may be the proverbial straw-but the answer to this is to change other aspects of public policy, not to continue to recom- mend substandard child feeding customs that are being abandoned by many other countries in the developed world.
Effects of Cyclosporin A and Low Dosages of Steroid on Posttransplantation Diabetes in Kidney Transplant Recipients
Authors: Hidefumi Yamamoto, Shoichi Akazawa, Yoshihiko Yamaguchi, Atsushi Yokota, Hironori Yamasaki, Toshiaki Nakanishi, Daigo Tahara, Fukuzo Matsuya, Yutaka Saito, Shigenobu Nagataki
Journal: Diabetes Care (1991)

Objective To investigate the adverse effects of cyclosporin A (CsA) on pancreatic beta-cell function in kidney transplant recipients. Research Design and Methods The study consisted of 73 patients without a history of diabetes mellitus who had undergone kidney transplantation in our clinic. Results We experienced a higher incidence of posttransplantation diabetes mellitus (PTDM) in patients receiving CsA and low dosages of methylprednisolone (6/20, 30%, P &amp;lt; 0.05) than in patients receiving conventional therapy of azathioprine methylprednisolone (4/53, 7.5%) since the introduction of CsA. In all 6 patients in the CsA-treated group, PTDM occurred within 3 mo after transplantation. The CsA level during the initial 3 mo posttransplant was significantly higher in diabetic than nondiabetic subjects, and the highest CsA level was observed shortly (1 mo) before the development of PTDM. After an average of 71 days of insulin therapy, there was complete remission of PTDM in 5 of 6 diabetic patients, with a corresponding decrease in CsA level. For the patients who were in remission for &amp;gt; 1 yr, a significant improvement of glucose intolerance was observed in association with a significantly higher insulin response to oral glucose load; however, their glycemic profile still showed a significantly higher plasma glucose concentration and a prolonged continuous elevation without initial peak of the insulin-response curve in contrast to the normal pattern found in nondiabetic subjects in the CsA-treated group. Conclusions This study suggests that CsA in combination with low dosages of steroid may have adverse effects on glucose metabolism, which may lead to effects similar to those in non-insulin-dependent diabetes mellitus.
Marrow grafts between canine siblings matched by serotyping and mixed leukocyte culture
Authors: Rainer Storb, Robert H. Rudolph, E. Donnall Thomas
Journal: Journal of Clinical Investigation (1971)

Marrow grafts were carried out between 16 canine sibling donor-recipient pairs. The pairs were matched by serological histocompatibility testing and were nonreactive in a one-way mixed leukocyte culture. Recipients were prepared for transplantation by 1500-1580 R of total body irradiation. Donor marrow was infused within 4 hr of irradiation. Recipients were not given immunosuppressive drug therapy after grafting. All 16 recipients showed evidence of prompt and sustained allogeneic marrow engraftment. Six died between 30 and 128 days after grafting with graft-versus-host disease, and three died between days 72 and 230 with pneumonia but no evidence of graft-versus-host disease with the exception of lymphoid atrophy. Seven recipients survived without graft-versus-host disease and are in excellent health between 200 and 684 after grafting.
... And More About Receptors
Authors: Samuel Vaisrub
Journal: JAMA (1977)

"If you're not into receptors, you may as well pack up and go home." The whispered remark, overheard at an assembly of endocrinologists, could have just as easily been passed at a gathering of immunologists, oncologists or—as the preceding editorial by Bell and Malick clearly illustrates—of clinical pharmacologists. Receptors are the "in" thing in medicine of the 1970's. It is not too long since "receptors" were hypothetical constructs in Ehrlich "side-chain" theory of immunity (1885). They were conceived as a part of a cell that combines with and anchors a haptophore group of a toxin, which is neutralized when the receptor-containing side-chain is cast off into the circulation. No longer linked to the outdated theory and no longer hypothetical—many have been characterized, identified, and isolated —receptors have been frequently shown to be more than mere passive recipients of exogenous or endogenous substances. The process is often that of interaction with
THE PREVENTION AND TREATMENT OF CARBON TETRACHLORIDE INTOXICATION
Authors: P. D. LAMSON
Journal: JAMA (1928)

In the last ten years great advances have been made in the treatment of hookworm disease. These have been due largely to two factors: the campaign carried out by the International Health Board of the Rockefeller Foundation, making it possible to treat very large numbers of cases and to study the best methods of treatment, and the discovery in 1921 by Dr. Maurice C. Hall<sup>1</sup>of the anthelmintic properties of carbon tetrachloride, which is relatively so harmless and so effective that it can be given to whole communities in which hookworm is prevalent, with the assurance that it will remove from 95 to 100 per cent of the hookworms harbored by infested individuals. On account of this certainty of action, it became unnecessary to reexamine the patients for hookworm after treatment, as had been the case previously. The increase in the number of persons treated by this new method