tbuckley/cabot-search huggingface dataset:
Methotrexate and cytarabine inhibit progression of human lymphoma in NOD/SCID mice carrying a mutant dihydrofolate reductase and cytidine deaminase fusion gene
Authors: Tulin Budak-Alpdogan, Onder Alpdogan, Debabrata Banerjee, Eunice Wang, Malcolm A.S. Moore, Joseph R. Bertino
Journal: Molecular Therapy (2004)

An SFG-based retroviral bicistronic vector containing a double-mutant dihydrofolate reductase-cytidine deaminase fusion cDNA (F/S DHFR-CD) with IRES-eGFP confers resistance to both methotrexate (MTX) and cytarabine (ara-C). Two weeks after transplantation with marrow transduced with either a fusion or a control gene (eGFP-IRES-NeoR), human lymphoma (SKI-DLCL-1) cells were injected sc into the flanks of nonobese diabetic/severe combined immune deficiency mice. In mock-transplanted mice, maximal tolerated dose (MTD) of posttransplant MTX/ara-C (15/10 mg/kg/day, x3) was unable to control tumor growth. Transfer of the fusion gene allowed doses of MTX/ara-C (25/15 mg/kg/day, x4) twofold higher than the MTD to be tolerated. The tumor burden defined the efficiency of posttransplant chemotherapy; early treatment, 48 h after tumor inoculation, provided tumor-free survival, while starting treatment after having palpable tumor growth (7 days) delayed tumor growth a median time of 28 days. In addition, the early treated group had higher gene expression in peripheral blood and marrow cells than the late treated group (P < 0.05), suggesting that early treatment allowed for enrichment of transduced marrow progenitors. These results encourage clinical studies using this retroviral fusion gene construct.
HEMOPERITONEUM WITH BLUISH DISCOLORED UMBILICUS: REPORT OF CASE
Authors: Melmuth H. Sternberg
Journal: JAMA (1922)

<h3>History.</h3> —S. F., man, aged 61, a German saloonkeeper, was admitted to the hospital, Sept. 5, 1922, with the complaint of "enlarged abdomen." The family history was essentially unimportant. He denied all acute infectious diseases and venereal disease. He was the father of one grown son; his wife denied any miscarriages. Twenty-five years before, he suffered with nonbleeding hemorrhoids, which spontaneously disappeared. Seven years before, he was troubled with varicosities and edema of the lower extremities. He admitted that he indulged heavily in beer, wine, tobacco and coffee. He also enjoyed a voracious appetite, which he satisfied freely. Prior to three months before his entrance into the hospital, he had no complaints. He noticed that his appetite became poor and he was constipated. He complained of pyrosis, belching of gas, fulness after eating, borborygmus and loss of weight and strength. Six weeks before, his abdomen became distended. For this, he
RESPONSIBILITY OF NATION, STATE AND COUNTY FOR RURAL SANITATION
Authors: W. S. RANKIN
Journal: JAMA (1918)

When this paper was written, no appropriate action had been taken to retard or prevent the rapid disor- ganization of public health agencies incidental to our national plan of medical preparedness.At that time, it seemed almost futile to discuss any phase of public health administration.With reliable assurance that this matter of paramount importance, to wit, the maintenance of public health agencies during the war, would be properly dealt with in Washington during the past week, I have selected a subject of national scope and importance, once the maintenance of our public health agencies is assured.My subject, the "Responsibility of Nation, State and County for Rural Sanitation," seems to be logically divisible into three sections: (1) the size and nature of the problem of rural sanitation; (2) the relative responsibility of nation, state and county for rural sanitation, and (3) the coordinate responsibility of nation, state and county for rural sanitation. SIZE AND NATURE OF THE PROBLEM OF RURAL SANITATIONIn size, the problem of rural sanitation has to do with 60,000,000 people, comprising 53 per cent, of our population, and 99 per cent, of the area of this country.It is the larger part of the general problem of sanitation.In nature, rural sanitation is primary and funda¬ mental to sanitation in general ; in the natural order, the country and then the city.The city is made of wood and brick and stone and men and ideas-the built and the builders-all brought in from the coun¬ try.The vital current flows from the country to the
The Philosophy of Consumption.
Authors: J. S. Christian
Journal: JAMA (1891)

<h3>To the Editor:</h3> —A proclamation by an eminent physician that he has discovered a specific cure for consumption in its most prevalent and insiduous form, known as tuberculosis, might well create a deep and universal interest, since there are comparatively few of us that do not have this deadly enemy within the limits of our cousin kinship. And if German slaughter-house statistics are to be taken as representative, no less than ten per cent, of our domesticated-horned cattle, are a prey to the same disease, though seldom discovered during life. This fact would suggest that tubercular consumption is still more prevalent in the human family than has yet been supposed, and that many carry it under the cover of other maladies. But unfortunately for any hope for a specific remedy, the preponderance of evidence points to the fact that consumption is much more a product of individual habits and social
Postsurgical Problems of the Gastrointestinal Tract
Authors: Thomas E. Machella
Journal: JAMA (1960)

The purpose of this article is to describe the clinical manifestations, development, and treatment of some of the undesirable sequelae which sometimes follow subtotal gastric resection. They include the dumping syndrome, postprandial hypoglycemia, loss of weight, diarrhea, anemia, gastroileal fistula, marginal ulcer, gastrojejunocolic fistula, failure of the gastric remnant to empty, the afferent loop syndromes, jejunal obstruction due to herniation internally between the peritoneal rings, rupture of the duodenal stump, leakage at the corner of sorrow, and stasis in a long afferent loop.
Expiratory muscle endurance in chronic obstructive pulmonary disease
Authors: A Ramirez-Sarmiento
Journal: Thorax (2002)

Background: A reduction in expiratory muscle (ExM) endurance in patients with chronic obstructive pulmonary disease (COPD) may have clinically relevant implications. This study was carried out to evaluate ExM endurance in patients with COPD. Methods: Twenty three patients with COPD (FEV<sub>1</sub> 35 (14)% predicted) and 14 matched controls were studied. ExM endurance was assessed using a method based on the use of an expiratory threshold valve which includes two steps. In step 1 the load is progressively increased (50 g every 2 minutes) until task failure is reached, and the pressure generated against the highest tolerated load is defined as the maximal expiratory sustainable pressure (Pthmax). In step 2 subjects breathe against a submaximal constant load (80% of Pthmax) and the time elapsed until task failure is termed the expiratory endurance time (Tth<sub>80</sub>). In addition, the strength of peripheral muscles (handgrip, HGS) and respiratory muscles (maximal inspiratory and expiratory pressures, Pimax and Pemax, respectively) was evaluated. Results: Patients with COPD had lower ExM strength and endurance than controls: Pemax 64 (19)% predicted <i>v</i> 84 (14)% predicted (mean difference 20%; 95% confidence intervals (CI) 14 to 39); Pthmax 52 (27) <i>v</i> 151 (46) cm H<sub>2</sub>O (mean difference 99, 95% CI 74 to 123); and Tth<sub>80</sub> 9.4 (6.3) <i>v</i> 14.2 (7.4) min (mean difference 4.8, 95% CI 1.0 to 10.4; p&lt;0.01 for all). Interestingly, ExM endurance directly correlated with both the severity of airways obstruction (Pthmax with FEV<sub>1</sub>, <i>r</i>=0.794, p&lt;0.01) and the reduction in strength observed in different muscle groups (Pthmax with HG, Pimax or Pemax, <i>r</i>=0.550, p&lt;0.05; <i>r</i>=0.583, p&lt;0.001; and <i>r</i>=0.584, p&lt;0.001, respectively). Conclusions: ExM endurance is decreased in patients with COPD. This impairment is proportional to the severity of the disease and is associated with lower strength in different muscle groups. This suggests that systemic effects are implicated in the impairment observed in ExM function.
REPORT ON SIX CASES OF TONSILLECTOMY IN DIPHTHERIA CARRIERS
Authors: C. C. Ballantyne, B. S. Cornell
Journal: BMJ (1917)

Pyorrboe alveelarisis often present :Stomatitis and g 4igivitis.Quinsy is a not uncommon complication.Gastro.enteritis cases have occurred in which, pO8M mortem, abundant bacilli and -spirochaetes have been foiund in the intestines (Vincent).N6phritis and albuminuria.The uriiie of these patienis .oftencontains a trace of albumin, and.m some cases acute nephritis may occur.To quote one example:A doctor working at a base hospital was three weeks in hos- pita!with Vincent's angina, and on recovery was given three weeks' sick leave.Whilst in England it recurred on the same ,tonsil, the recurrence only lasting a few days.On return to duty he bad a third attack -on the opposite side, and was .admitted to hospital, his urine containing a trace of albumin.'Thr6e -days after admission he developed acute nephritis.Twelve days later the albumin and casts had entirely disappeared.Other complications are ulceration of the pharynx,-on some occasions causing perforation of the carotid artery
Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder
Authors: Mohammed Uddin, Kristiina Tammimies, Giovanna Pellecchia, Babak Alipanahi, Pingzhao Hu, Zhuozhi Wang, Dalila Pinto, Lynette Lau, Thomas Nalpathamkalam, Christian R Marshall, Benjamin J Blencowe, Brendan J Frey, Daniele Merico, Ryan K C Yuen, Stephen W Scherer
Journal: Nature Genetics (2014)
HYPOTHYROIDISM IN CHILDHOOD
Authors: E. KOST SHELTON
Journal: JAMA (1941)

For purposes of clarity, let us assume that there are three types of hypothyroidism during childhood, namely cretinism, juvenile myxedema and borderline hypothyroidism. As a matter of fact they are all one and the same disorder modified according to (<i>a</i>) the severity and (<i>b</i>) the length of time during which the patient has been subjected to the deficiency. Because we are dealing with a hormone whose purpose it is not only to develop the organism during the most plastic period of its existence but also to maintain it in functional equilibrium, one can readily appreciate the diagnostic variables to be encountered in a disruption of such a mechanism at any age. Let us first consider the degree of severity. Until recently the more conservative observers were unwilling to concede any form of hypothyroidism which could not easily be classified under cretinism or myxedema. When analyzed closely, such a stand is
Placebo surgery provokes controversy
Authors: S. Gottlieb
Journal: BMJ (1999)

A researcher from the University of South Florida has prompted a medical controversy after talking to the New England Journal of Medicine to explain his controversial practice of performing placebo surgery on patients with Parkinson's disease in order to test an experimental treatment.

The researcher, Dr Thomas Freeman, director of the neural reconstruction programme at Tampa General Hospital in Florida, writes that “placebo surgery” is the best way to evaluate how people who receive cell transplants compare with those who do not.

In the placebo surgery that he performs Dr Freeman bores into a patient's skull but does not implant any of the fetal nerve cells being studied as a treatment …
High-Dose Intravenous Immune Globulin for Stiff-Person Syndrome
Authors: Marinos C. Dalakas, Mavis Fujii, Mian Li, Bashar Lutfi, Joan Kyhos, Beverly McElroy
Journal: New England Journal of Medicine (2001)

Stiff-person syndrome is a disabling central nervous system disorder with no satisfactory treatment that is characterized by muscle rigidity, episodic muscle spasms, high titers of antibodies against glutamic acid decarboxylase (GAD65), and a frequent association with autoimmune disorders. Because stiff-person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin.
Novel Associations of Multiple Genetic Loci With Plasma Levels of Factor VII, Factor VIII, and von Willebrand Factor
Authors: Nicholas L. Smith, Ming-Huei Chen, Abbas Dehghan, David P. Strachan, Saonli Basu, Nicole Soranzo, Caroline Hayward, Igor Rudan, Maria Sabater-Lleal, Joshua C. Bis, Moniek P.M. de Maat, Ann Rumley, Xiaoxiao Kong, Qiong Yang, Frances M.K. Williams, Veronique Vitart, Harry Campbell, Anders Mälarstig, Kerri L. Wiggins, Cornelia M. Van Duijn, Wendy L. McArdle, James S. Pankow, Andrew D. Johnson, Angela Silveira, Barbara McKnight, Andre G. Uitterlinden, Nena Aleksic, James B. Meigs, Annette Peters, Wolfgang Koenig, Mary Cushman, Sekar Kathiresan, Jerome I. Rotter, Edwin G. Bovill, Albert Hofman, Eric Boerwinkle, Geoffrey H. Tofler, John F. Peden, Bruce M. Psaty, Frank Leebeek, Aaron R. Folsom, Martin G. Larson, Timothy D. Spector, Alan F. Wright, James F. Wilson, Anders Hamsten, Thomas Lumley, Jacqueline C.M. Witteman, Weihong Tang, Christopher J. O'Donnell
Journal: Circulation (2010)

Plasma levels of coagulation factors VII (FVII), VIII (FVIII), and von Willebrand factor (vWF) influence risk of hemorrhage and thrombosis. We conducted genome-wide association studies to identify new loci associated with plasma levels.The setting of the study included 5 community-based studies for discovery comprising 23 608 European-ancestry participants: Atherosclerosis Risk In Communities Study, Cardiovascular Health Study, British 1958 Birth Cohort, Framingham Heart Study, and Rotterdam Study. All subjects had genome-wide single-nucleotide polymorphism (SNP) scans and at least 1 phenotype measured: FVII activity/antigen, FVIII activity, and vWF antigen. Each study used its genotype data to impute to HapMap SNPs and independently conducted association analyses of hemostasis measures using an additive genetic model. Study findings were combined by meta-analysis. Replication was conducted in 7604 participants not in the discovery cohort. For FVII, 305 SNPs exceeded the genome-wide significance threshold of 5.0x10(-8) and comprised 5 loci on 5 chromosomes: 2p23 (smallest P value 6.2x10(-24)), 4q25 (3.6x10(-12)), 11q12 (2.0x10(-10)), 13q34 (9.0x10(-259)), and 20q11.2 (5.7x10(-37)). Loci were within or near genes, including 4 new candidate genes and F7 (13q34). For vWF, 400 SNPs exceeded the threshold and marked 8 loci on 6 chromosomes: 6q24 (1.2x10(-22)), 8p21 (1.3x10(-16)), 9q34 (<5.0x10(-324)), 12p13 (1.7x10(-32)), 12q23 (7.3x10(-10)), 12q24.3 (3.8x10(-11)), 14q32 (2.3x10(-10)), and 19p13.2 (1.3x10(-9)). All loci were within genes, including 6 new candidate genes, as well as ABO (9q34) and VWF (12p13). For FVIII, 5 loci were identified and overlapped vWF findings. Nine of the 10 new findings were replicated.New genetic associations were discovered outside previously known biological pathways and may point to novel prevention and treatment targets of hemostasis disorders.
A Rare Case of Pulmonary Malignant Granular Cell Tumor Detected With 18F-FDG PET/CT Imaging
Authors: Ai-ping Cheng, Meng-jie Dong, Li-ping Fu, Li-Jun Zhao, Xiao-gang Wang, Wei-ying Sun
Journal: Clinical Nuclear Medicine (2013)

Malignant granular cell tumor is rarely involved in the lungs. We present a rare case with 18F-FDG PET/CT images showing a hypermetabolic lesion in the lower lobe of the left lung with posterior mediastinum invasion. Histopathologic study proved it as malignant granular cell tumor.
Morphological investigations of fibrogenic action of Estonian oil shale dust.
Authors: V A Küng
Journal: Environmental Health Perspectives (1979)

A review of morphological investigations carried out to clarify the pathogenicity of industrial dust produced in the mining and processing of Estonian oil shale is given. Histological examination of lungs of workers in the oil shale industry taken at necropsies showed that the inhalation of oil shale dust over a long period (more than 20 years) may cause the development of occupational pneumoconiotic changes in oil shale miners. The pneumoconiotic process develops slowly and is characterized by changes typical of the interstitial form of pneumoconiotic fibrosis in the lungs. Emphysematous changes and chronic bronchitis also occur. The average chemical content of oil shale as well as of samples of oil shale dust generated during mining and sorting procedures is given. The results of experiments in white rats are presented; these studies also indicate a mild fibrogenic action of Estonian oil shale dust.
THE VALUE OF EXCISION OF THE SUPERIOR CERVICAL SYMPATHETIC GANGLION IN GLAUCOMA.
Authors: GEORGE F. SUKER
Journal: JAMA (1901)

The history and modus operandi of this operation, as well as its intended and desired range of purpose, are all familiar to you, hence these points do not merit repetition here. In order to obtain as complete American statistics as possible, the writer has sent out several hundred question blanks to men of repute and experience. However, the returns are a trifle meager, yet of such great importance on account of their uniformity, that a fair and just estimate may be had as to the real merits of the operation in question. There have been only 14 operations performed in America for glaucoma; in addition, several have been done for optic atrophy and Basedow's disease. If there are any more operations for glaucoma the writer has failed to get the report, though every effort was made to obtain same. First, let us take a brief review of the physiology of
Abstract 262: The evolution of diverse cancer stem cells in human liver cancer.
Authors: Taro Yamashita, Masao Honda, Kouki Nio, Yasumasa Hara, Takehiro Hayashi, Naoki Oishi, Hajime Sunakozaka, Hajime Takatori, Shuichi Kaneko
Journal: Cancer Research (2013)

Abstract Cancer stem cells (CSCs) are considered a pivotal target for the eradication of liver cancer. CSCs have been identified by the use of various stem cell markers; however, it remains unclear how individual CSC markers are expressed in individual tumors. We hypothesized that the distinct marker-positive CSCs show unique features of tumorigenicity/metastasis and chemosensitivity which may reflect the heterogeneous nature of hepatocellular carcinoma (HCC). Gene expression profiling and immunohistochemistry analyses were used to analyze 364 tumor specimens. Fluorescence-activated cell sorting (FACS) was used to isolate marker-positive HCC cells, which were tested for hepatic stem/progenitor cell properties. CSC markers EpCAM and CD90 are independently expressed in primary liver cancer. EpCAM+ cells share features with tumorigenic epithelial stem cells, whereas CD90+ cells share those of metastatic vascular endothelial cells with expression of c-Kit. CD90+ cells facilitate metastasis of EpCAM+ cells through activation of TGF-beta signaling, and this effect is abolished by c-Kit inhibitor imatinib mesylate. These distinct tumorigenic/metastatic CSCs can evolve from marker-negative cells de novo, and their frequencies vary dramatically according to the genomic alterations and genotoxic stress. Our results suggest that liver CSCs are not a single, static entity but rather exist heterogeneously and undergo dynamic changes through genomic alteration and genotoxic stress. The evolution of CSCs explains the enrichment of CSCs in advanced cancer and the limitation of targeting marker-positive CSCs alone for tumor eradication. Citation Format: Taro Yamashita, Masao Honda, Kouki Nio, Yasumasa Hara, Takehiro Hayashi, Naoki Oishi, Hajime Sunakozaka, Hajime Takatori, Shuichi Kaneko. The evolution of diverse cancer stem cells in human liver cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 262. doi:10.1158/1538-7445.AM2013-262
Nasal ventilation in acute exacerbations of chronic obstructive pulmonary disease: effect of ventilator mode on arterial blood gas tensions.
Authors: D J Meecham Jones, E A Paul, C Grahame-Clarke, J A Wedzicha
Journal: Thorax (1994)

BACKGROUND--There are no controlled trials of the use of different modes of nasal intermittent positive pressure ventilation (NIPPV) in patients with exacerbations of chronic obstructive pulmonary disease (COPD). This study describes the effect on blood gas tensions of four different modes of nasal ventilation. METHODS--Twelve patients with acute exacerbations of COPD were studied (mean (SD) FEV1 0.59 (0.13) l, PaO2 (air) 5.10 (1.12) kPa, PaCO2 9.28 (1.97) kPa, pH 7.32 (0.03)). Each patient underwent four one-hour periods of nasal ventilation in randomised order: (a) inspiratory pressure support 18 cm H2O; (b) pressure support 18 cm H2O+positive end expiratory pressure (PEEP) 6 cm H2O (IPAP+EPAP); (c) continuous positive airway pressure (CPAP) 8 cm H2O; and (d) volume cycled NIPPV. Arterial blood samples were obtained before each period of ventilation and at one hour. RESULTS--Pressure support, CPAP, and volume cycled NIPPV all produced significant improvements in PaO2; there was no difference between these three modes. The change in PaO2 with IPAP+EPAP did not reach statistical significance. None of the modes produced significant changes in mean PaCO2; patients with higher baseline levels tended to show a rise in PaCO2 whereas those with lower baseline levels tended to show a fall. CONCLUSIONS--Although PaO2 improved in all patients there are differences in efficacy between the modes, while the changes in PaCO2 were variable. The addition of EPAP conferred no advantage in terms of blood gas tensions.
PI-3K/Akt Pathway-Dependent Cyclin D1 Expression Is Responsible for Arsenite-Induced Human Keratinocyte Transformation
Authors: Weiming Ouyang, Wenjing Luo, Dongyun Zhang, Jinlong Jian, Qian Ma, Jingxia Li, Xianglin Shi, Jingyuan Chen, Jimin Gao, Chuanshu Huang
Journal: Environmental Health Perspectives (2007)

Long-term exposure of arsenite leads to human skin cancer. However, the exact mechanisms of arsenite-induced human skin carcinogenesis remain to be defined.In this study, we investigated the potential role of PI-3K/Akt/cyclin D1in the transformation of human keratinocytic cells upon arsenite exposure.We used the soft agar assay to evaluate the cell transformation activity of arsenite exposure and the nude mice xenograft model to determine the tumorigenesis of arsenite-induced transformed cells. We used the dominant negative mutant and gene knockdown approaches to elucidate the signaling pathway involved in this process.Our results showed that repeated long-term exposure of HaCat cells to arsenite caused cell transformation, as indicated by anchorage-independent growth in soft agar. The tumorigenicity of these transformed cells was confirmed in nude mice. Treatment of cells with arsenite also induced significant activation of PI-3K and Akt, which was responsible for the anchorage-independent cell growth induced by arsenite exposure. Furthermore, our data also indicated that cyclin D1 is an important downstream molecule involved in PI-3K/Akt-mediated cell transformation upon arsenite exposure based on the facts that inhibition of cyclin D1 expression by dominant negative mutants of PI-3K, and Akt, or the knockdown of the cyclin D1 expression by its specific siRNA in the HaCat cells resulted in impairing of anchorage-independent growth of HaCat cells induced by arsenite.Our results demonstrate that PI-3K/Akt-mediated cyclin D1 expression is at least one key event implicated in the arsenite human skin carcinogenic effect.