tbuckley/cabot-search huggingface dataset:
Tumor necrosis factor alpha (TNFalpha) promotes growth of virulent Mycobacterium tuberculosis in human monocytes iron-mediated growth suppression is correlated with decreased release of TNFalpha from iron-treated infected monocytes.
Authors: T F Byrd
Journal: Journal of Clinical Investigation (1997)

The human immune response to Mycobacterium tuberculosis is not well characterized. To better understand the cellular immune response to tuberculosis, a human mononuclear phagocyte culture system using a low-infecting inoculum of M. tuberculosis to mimic in vivo conditions was developed. Using this system, monocytes treated with IFNgamma/TNFalpha/ calcitriol (CytD) were permissive for the growth of virulent M. tuberculosis. In the presence of iron, however, these monocytes suppressed the growth of M. tuberculosis. The enhanced permissiveness of CytD-preincubated monocytes was found to be due to TNFalpha, however, the ability of iron to suppress M. tuberculosis growth also required preincubation with TNFalpha. Iron-mediated growth suppression was correlated with selective suppression of TNFalpha release from infected monocytes. In addition, removal of TNFalpha from CytD-treated monocytes 2 d after infection mimicked the suppressive effect of iron, suggesting that iron may also be decreasing monocyte sensitivity to exogenously added TNFalpha. In the absence of iron, permissive, CytD-treated monocytes formed large infected cellular aggregates. With iron treatment, aggregation was suppressed, suggesting that the iron-suppressive effect on M. tuberculosis growth may be related to suppression of monocyte aggregation and diminished cell-to-cell spread of M. tuberculosis. The results of this study indicate that TNFalpha preincubation is required for human monocytes to exert an iron-mediated suppressive effect on M. tuberculosis growth. In the absence of iron, however, the continued presence of TNFalpha has a growth-promoting effect on M. tuberculosis in human monocytes. Iron may be an important early modulator of M. tuberculosis growth via its effects on TNFalpha.
Correction of Postoperative Metabolic Alkalosis and Renal Failure by Hemodialysis
Authors: RICHARD D. SWARTZ
Journal: Annals of Internal Medicine (1977)

Three postoperative patients with oliguirc renal failure and hypochloremic metabolic alkalosis were treated with hemodialysis using a specailly prepared high-chloride, low-acetate dialysate. This mode of therapy corrected the metabolic abnormalities and was significantly more effective than treatment with commercially available high-acetate dialysate at increasing the serum chloride and hydrogen ion concentration. Furthermore, hemodialysis with high-chloride, low-acetate dialysate corrected the clinical sequelae of hypoventilation, cardiac arrhythmia, and neuromuscular irritability associated with metabolic alkalosis while treating uremia simultaneously.
Cell-free nucleic acids as non-invasive biomarkers of gynecological cancers, ovarian, endometrial and obstetric disorders and fetal aneuploidy
Authors: S. Traver, S. Assou, E. Scalici, D. Haouzi, T. Al-Edani, S. Belloc, S. Hamamah
Journal: Human Reproduction Update (2014)

Proper folliculogenesis is fundamental to obtain a competent oocyte that, once fertilized, can support the acquisition of embryo developmental competence and pregnancy. MicroRNAs (miRNAs) are crucial regulators of folliculogenesis, which are expressed in the cumulus–oocyte complex and in granulosa cells and some can also be found in the bloodstream. These circulating miRNAs are intensively studied and used as diagnostic/prognostic markers of many diseases, including gynecological and pregnancy disorders. In addition, serum contains small amounts of cell-free DNA (cfDNA), presumably resulting from the release of genetic material from apoptotic/necrotic cells. The quantification of nucleic acids in serum samples could be used as a diagnostic tool for female infertility. An overview of the published literature on miRNAs, and particularly on the use of circulating miRNAs and cfDNA as non-invasive biomarkers of gynecological diseases, was performed (up to January 2014). In the past decade, cell-free nucleic acids have been studied for potential use as biomarkers in many diseases, particularly in gynecological cancers, ovarian and endometrial disorders, as well as in pregnancy-related pathologies and fetal aneuploidy. The data strongly suggest that the concentration of cell-free nucleic acids in serum from IVF patients or in embryo culture medium could be related to the ovarian hormone status and embryo quality, respectively, and be used as a non-invasive biomarker of IVF outcome. The profiling of circulating nucleic acids, such as miRNAs and cfDNA, opens new perspectives for the diagnosis/prognosis of ovarian disorders and for the prediction of IVF outcomes, namely (embryo quality and pregnancy).
THE RELATION OF POSTGRADUATE MEDICAL INSTRUCTION TO PUBLIC HEALTH
Authors: LEROY E. PARKINS
Journal: JAMA (1934)

Public health service originated in the minds of doctors who recognized the need of the community for this important branch of medicine. Jenner and Waterhouse were practitioners of medicine as well as the founders of preventive medicine and the forerunners of modern public health service. Oliver Wendell Holmes was likewise an ardent champion of preventive medicine as well as a practitioner of the medical art. Austin Flint, the eminent physician and cardiologist, was one of the earliest epidemiologists; he conclusively established the source of an epidemic of typhoid in New York State when there was error and much confusion of thought in regard to the etiology. The practitioner of medicine by tradition is interested in public health problems. His enthusiasm for and cooperation in public health programs has varied from time to time. By training, the physician is taught to individualize his knowledge to a great degree. However, it is
CLINICAL USE OF CORTISONE, HYDROCORTISONE, AND CORTICOTROPIN
Authors: Edward W. Boland
Journal: JAMA (1952)

Less than four years ago, the potential range of usefulness of cortisone and corticotropin was unforeseen, and they seemed destined for small therapeutic roles as replacement agents in a few endocrine disorders. In 1948, this perspective quickly changed when Hench, Kendall, Slocumb, and Polley demonstrated that the manifestations of rheumatoid arthritis and some related nonhormonal conditions were powerfully, though temporarily, suppressed by their administration.<sup>1</sup>Early clinical trials with cortisone and corticotropin were restricted largely to diseases of the collagen type, and favorable responses in rheumatoid arthritis, rheumatic fever, disseminated lupus erythematosus, and periarteritis nodosa suggested at first that their beneficial action might be group specific. Soon, however, many apparently disparate diseases were found to be affected by the hormones, and laboratory data were accumulated that showed clearly that the hormones were widespread in their action, affecting the metabolic and physiological functions of many tissues and organs. Thus, it became
Melanotropin receptors demonstrated in situ in human melanoma.
Authors: J B Tatro, M Atkins, J W Mier, S Hardarson, H Wolfe, T Smith, M L Entwistle, S Reichlin
Journal: Journal of Clinical Investigation (1990)

Although some cultured human melanoma cell lines are responsive to melanotropins (melanocyte-stimulating hormones [MSH]), the prevalence and tissue distribution of MSH receptors in melanoma are unknown. We report here the use of an in situ binding technique to demonstrate specific MSH receptors in surgical specimens of human melanoma. The distribution and binding properties of specific MSH binding sites were determined by autoradiography and image analysis after incubation of frozen tumor tissue sections with a biologically active, radiolabeled analogue of alpha-MSH, [125I]iodo-Nle4, D-Phe7-alpha-MSH ([125I]NDP-MSH). In melanoma specimens from 11 patients, 3 showed high levels of specific binding, 5 showed low levels, and in 3 patients specific binding of [125I]NDP-MSH was not detectable. Specific MSH binding sites were present in melanoma cells, but not in adjacent connective or inflammatory tissues. Melanotropins, including alpha-MSH, NDP-MSH, and ACTH, inhibited [125I]NDP-MSH binding in a concentration-dependent manner, whereas unrelated peptides (somatostatin and substance P) did not. The apparent affinity of alpha-MSH for this binding site was in the nanomolar range (EC50 = 2 X 10(-9) M for inhibition of [125I]NDP-MSH binding in situ), similar to that recently described for the murine melanoma receptor. In one patient, analysis of multiple intratumor samples and tumors excised on three separate occasions revealed high levels of specific MSH binding in all samples. These results suggest that endogenous melanotropins may modulate the activities of human melanoma cells in vivo.
Royal Society predicts that personalised medicines are still decades away
Authors: Susan Mayor
Journal: BMJ (2005)

The clinical use of personalised medicines, where patients are prescribed treatments based on their genetic make-up, will not occur for at least another 15-20 years, according to a report published this week by the Royal Society, the UK's national academy of science.

The report was developed by a Royal Society working group to provide a balanced assessment of the future potential and limitations of pharmacogenetics—how genetic make-up affects response to medicines.

The group heard evidence from a wide range of organisations and individuals, in addition to views from three public workshops. It concluded that pharmacogenetics has a promising future but that it will …
Abstract 2443: Tetraspanin CD151 as a target for antibody-based cancer therapy
Authors: Jean-François F. HAEUW
Journal: Cancer Research (2010)

Abstract The tetraspanin CD151 is known to be functionally linked to cancer metastasis. In human, increased expression of CD151 is indicative of a poor prognosis in different cancer types. Whereas its precise mechanism of action remains obscure, CD151 was shown to regulate cell motility and adhesion through association with laminin-binding integrins such as α3β1 or α6β4, and more recently the communication between endothelial and tumor cells. Overexpression of CD151 in tumor cells enhances cell migration, cell invasion and experimental metastasis. Silencing of CD151 with specific siRNA was shown to delay tumour formation in vivo in a mouse model of breast cancer. Several anti-CD151 monoclonal antibodies (Mabs) were shown to display anti-metastatic activity in vivo. Inhibition of metastasis was not attributed to any effect of these Mabs on tumor cell growth but was essentially linked to inhibition of cell motility. However, a more direct effect could be expected. For these reasons, we generated different anti-CD151 Mabs via immunisation with transfectant cells and evaluated their anti-tumor activity in xenograft and orthotopic mouse models to further investigate the role of CD151 in cancer progression in vivo. Interestingly, anti-CD151 Mabs inhibited potently primary tumor growth in different xenograft models including prostate, lung and breast cancer models. These results demonstrate that CD151 could be of importance for controlling tumor cell proliferation. In addition, as anticipated, we showed that anti-CD151 Mabs were also able to inhibit metastasis in vivo in an orthotopic A549 lung cancer model with well characterized lung metastases. The mechanism of action of these Mabs on tumor cells is under investigation and preliminary in vitro data will be presented. Altogether, our results strongly suggest that CD151 could function at multiple cancer stages, including not only metastasis cascade steps but also earlier steps of primary tumor growth, reinforcing thus the interest of this innovative target in oncology. Mabs targeting CD151 may be of significant interest for cancer biotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2443.
Mandatory Insulin-to-Glucose Ratios to Pinpoint the Inherited Lesion of Diabetes Mellitus.
Authors: Holbrooke S. Seltzer
Journal: Annals of Internal Medicine (1968)

s1 May 1968Mandatory Insulin-to-Glucose Ratios to Pinpoint the Inherited Lesion of Diabetes Mellitus.Holbrooke S. Seltzer, M.D., F.A.C.P.Holbrooke S. Seltzer, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1190_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe following analysis of published data resolves a 20-year controversy concerning whether the inherited defect in both juvenile and adult diabetes mellitus is the same, or whether they are fundamentally different diseases. The crucial point is that, when insulin release after glucose loads is measured in normal persons and mild diabetics, comparison of insulin outputs alone yields faulty conclusions because the magnitude of insulin response has to be corrected for the intensity of glycemic stimulus that evoked it.Six experimentally similar studies (two by the author) were analyzed identically. Oral glucose tolerance test (GTT) values and corresponding insulin values were... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Dallas, Texas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1190-1190KeywordsDiabetes mellitusGlucoseInsulinLesionsOral glucose tolerance test Issue Published: 1 May 1968 PDF DownloadLoading ...
Use of AIDS antibody test
Authors: Charles Marwick
Journal: JAMA (1985)

Licensure and increasingly widespread use of tests for antibodies—in donor blood—to the retrovirus associated with acquired immunodeficiency syndrome (AIDS), should permit much more detailed study of the AIDS problem.  Earlier this month, the Department of Health and Human Services and Food and Drug Administration announced that Abbott Laboratories, North Chicago, Ill, is the first to be licensed to market screening test kits for checking for the presence of antibodies to AIDS. Shipments of the kits—at a charge of between $2 and $3 apiece—began that same day (March 2) to blood banks.  The availability of the test opens the door to a whole series of epidemiologic studies, says Harold Jaffe, MD, of the Centers for Disease Control, Atlanta, and a member of that agency's AIDS task force. Jaffe spoke—on the eve of test licensure—at a workshop on AIDS viral antibody detection held by the Food and Drug Administration (Rockville, Md) and
Episiotomy rates in primiparous women in Latin America: hospital based descriptive study
Authors: F. Althabe
Journal: BMJ (2002)

What initially seems to be a democratic or "liberal" stance in awarding all the same access to healthcare technology could in actuality be a conservative and medically radical solution to the social inequalities that have led to an increase in caesarean section rates.Additional research is needed in settings where the economically based distribution of caesarean sections is not as discrepant as in Brazil.Even modest inequalities in healthcare provision might create a market for unnecessary interventions among women who feel marginalised from access to medical technology.
Design of Noninflammatory Synthetic siRNA Mediating Potent Gene Silencing in Vivo
Authors: Adam D. Judge, Gurneet Bola, Amy C.H. Lee, Ian MacLachlan
Journal: Molecular Therapy (2005)

Targeted silencing of disease-associated genes by synthetic short interfering RNA (siRNA) holds considerable promise as a novel therapeutic strategy. However, unmodified siRNA can be potent triggers of the innate immune response, particularly when associated with delivery vehicles that facilitate intracellular uptake. This represents a significant barrier to the therapeutic development of siRNA due to toxicity and off-target gene effects associated with this inflammatory response. Here we show that immune stimulation by synthetic siRNA can be completely abrogated by selective incorporation of 2'-O-methyl (2'OMe) uridine or guanosine nucleosides into one strand of the siRNA duplex. These noninflammatory siRNA, containing less than 20% modified nucleotides, can be readily generated without disrupting their gene-silencing activity. We show that, coupled with an effective systemic delivery vehicle, 2'OMe-modified siRNA targeting apolipoprotein B (apoB) can mediate potent silencing of its target mRNA, causing significant decreases in serum apoB and cholesterol. This is achieved at therapeutically viable siRNA doses without cytokine induction, toxicity, or off-target effects associated with the use of unmodified siRNA. This approach to siRNA design and delivery should prove widely applicable and represents an important step in advancing synthetic siRNA into a broad range of therapeutic areas.
Activity of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Small Cell Lung Cancer
Authors: Radosław Polański, Cassandra L. Hodgkinson, Alberto Fusi, Daisuke Nonaka, Lynsey Priest, Paul Kelly, Francesca Trapani, Paul W. Bishop, Anne White, Susan E. Critchlow, Paul D. Smith, Fiona Blackhall, Caroline Dive, Christopher J. Morrow
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use. Experimental Design: AZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray (TMA) from 78 patients with SCLC. Results: AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors. Conclusions: This study provides a rationale to test AZD3965 in patients with SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond. Clin Cancer Res; 20(4); 926–37. ©2013 AACR.
Symptomatology and Diagnosis of Multiple Sclerosis
Authors: S. Poser
Journal: JAMA (1982)

<h3>To the Editor.—</h3> In the article "The Diagnosis of Multiple Sclerosis," by Hart and Sherman (1982;247:498), the authors try to give guidelines regarding the diagnostic process in patients suspected of having multiple sclerosis (MS). They point out the importance of history-taking and clinical examination, but the information given about frequency and value of clinical symptomatology is misleading. In Table 3 ("Common Symptoms and Signs in Multiple Sclerosis Suspects"), the symptoms of blurred vision and paresthesias are common early disturbances,but the others mentioned are not. Fecal incontinence, for instance, is a rare and late symptom (5% in established cases), and does not support an initial diagnosis of MS.<sup>1</sup> Among the signs listed in Table 3, impaired visual acuity, asymmetric brisk tendon reflexes, and Babinski's signs are relatively common, but pareses—not even mentioned in Table 3—are the most common<sup>2</sup>(Table). Some of the common signs are so nonspecific, however,
COMPARISON OF 3F8 RADIOIMMUNODECTION WITH MIBG AND MDP IN NEUROBLASTOMA
Authors: Samuel D. J. Yeh, Steven M. Larson, Brian Kushner, Michael LaQuaglia, Leslie Burch, Nei-Kong V. Cheung
Journal: Clinical Nuclear Medicine (1990)

Yeh, Samuel D. J.; Larson, Steven M.; Kushner, Brian; LaQuaglia, Michael; Burch, Leslie; Cheung, Nei-Kong V. Author Information
Computers in general practice
Authors: I G Cox
Journal: BMJ (1982)

upper gastrointestinal endoscopy are to enable the examination to be carried out safely and comfortably and to ensure adequate amnesia so that the frequent necessity of repeat endoscopy is never unacceptable to the patient.It seems unnecessary to perform neuroticism inventories, which in any case are not predictive of unfavourable or violent reactions, when safe and simple agents are almost always efficacious.ROGER JONES Andover, Hants JP10 3LI)Elderly patients in a general surgical unit: do they block beds?
Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate
Authors: P. Rytilä, A. S. Pelkonen, T. Metso, K. Nikander, T. Haahtela, M. Turpeinen
Journal: Allergy (2004)

Background: There are few controlled studies on the effects of anti‐inflammatory treatment on airway inflammation in newly diagnosed childhood asthma. Methods: Sixty children with newly diagnosed mild persistent asthma, 5–10 years of age, and 17 healthy control subjects were studied. Asthmatic children were randomized into an open study with two treatment groups: (1) budesonide 400 μ g twice daily for 1 month, 200 μ g twice daily for 5 months and (2) disodium cromoglycate (DSCG) 10 mg three‐times daily for 6 months. All exacerbations were treated with budesonide 400 μ g twice daily for 2 weeks. Symptoms and lung function were recorded throughout the study. Results: Sputum induction was safe and the overall success rate was 71%. This improved with age and decreased after treatment. At baseline, the asthmatic children had more eosinophils in blood (0.26 vs 0.18 × 10 9 /l, P = 0.03) and sputum (1.1 vs 0.0 %, P = 0.0001) than the control subjects. The numbers of sputum eosinophils correlated with bronchial responsiveness ( R = −0.58, P = 0.0002). Eosinophils were higher in children with atopic asthma than with nonatopic asthma ( P &lt; 0.0001), and in children with a history wheezing than in children without wheezing ( P = 0.02). Six months of budesonide treatment, but not of DSCG, improved lung function ( P = 0.007), decreased symptoms ( P = 0.007) and sputum eosinophils ( P = 0.003). The effects of budesonide were pronounced in children with intense sputum eosinophilia (&gt;3%). Conclusion: Sputum eosinophilia is present in children with newly diagnosed mild persistent asthma. Treatment with inhaled budesonide, but not with DSCG, decreases sputum eosinophils along with clinical and functional improvement.