tbuckley/cabot-search huggingface dataset:
Abstract 1323: Liver-specific knockout mice and liver-derived cell lines provide insights into potential roles for the GP73/GOLM1 HCC serum biomarker - association with sustained cell proliferation
Authors: Gunisha Arora, Rosalba Flores, Lorinda Wright, Claus J. Fimmel, Barrie P. Bode
Journal: Cancer Research (2012)

Abstract Golgi Protein-73kDa (GP73/GOLM1) is a resident cis Golgi Type II membrane protein that is nearly undetectable in normal liver, but whose expression is upregulated in hepatocellular carcinoma (HCC) and whose circulating levels increase in the plasma of patients with chronic liver disease and HCC. As such, it is the subject of ongoing clinical trials investigating its use as a serum biomarker for HCC. GP73/GOLM1 is cleaved by a proprotein convertase and secreted by proliferating cells, an activity possibly elevated in cancer, yet its biological role in the liver and in the pathogenesis of HCC remains unclear. In order to investigate possible biological roles for GP73/GOLM1, liver-specific knockout mice (C57BL/6) were generated using the Cre-loxP system, characterized by a “floxed” GOLM1 gene and Cre recombinase driven by the albumin promoter. GP73/GOLM1 Cre+/−genotypes were confirmed by PCR analysis. GP73/GOLM1Fl/Fl/Cre(+) animals showed no obvious biological phenotype compared to their Cre(-) littermates, and exhibited normal growth, behavior, and successful mating, suggesting that hepatic GP73/GOLM1 is not vital for normal physiological function, as might be hypothesized from its normally low expression in the liver. Previous studies indicated that GP73/GOLM1 expression was not upregulated in post-hepatectomy liver regeneration, suggesting that its activated expression in the liver is linked to inflammatory or carcinogenic processes rather than transiently increased mitosis. Examination of GP73/GOLM1 expression in 14 human HCC cell lines revealed similar expression levels in epithelial and mesenchymal cell lines, and in an SV40-transformed nontumorigenic human liver epithelial cell line. Rodent in vitro models of hepatocellular transformation revealed equal GP73/GOLM1 expression levels in nontumorigenic parent cell lines and their transformed tumorigenic derivatives. Collectively, the data from the in vivo and in vitro models thus far do not support a direct association of GP73/GOLM1 expression with liver mitogenesis or differentiation, but rather suggest that its expression may be linked to a sustained commitment to cell proliferation - such as occurs in cell lines, liver disease and cancerous transformation, promoted by an inflammatory microenvironment. Possible mechanistic roles for GP73/GOLM1 in HCC development and progression are currently being tested in carcinogenesis models with liver-specific knockout mice. A website on GP73/GOLM1 has also been established as a resource for the research community interested in the study of this protein. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1323. doi:1538-7445.AM2012-1323
Epidermodysplasia verruciformis with severe hands and feet deformity successfully treated by surgical excision
Authors: F. Fang, L. Zhao, M-J. Jiang, Y. Wang, Q-Q. Wang
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, A 39‐year‐old man was admitted to our hospital in November 2000 for treatment of deforming warts of the hands and feet. The disorder started at the age of 19 years as small warty papules on his limbs. Warty lesions, especially on his hands and feet, enlarged to form large vegetating hyperkeratotic masses. Lesions were often complicated by secondary infections. Hand function was severely compromised, affecting his daily activities. Treatments with cryosurgery and laser ablation were unsuccessful. Nobody else in his family was similarly affected. Examination showed flat, brown, warty papules and plaques measuring 2–8 mm in size scattered over the whole body. He had giant vegetating hyperkeratotic warts on his hands (Fig. 1a) and feet. Investigation revealed normal full blood count, liver and renal function tests, and immunoglobulin and complement levels. Hepatitis B surface antigen and human immunodeficiency virus antibody tests were negative. X‐ray of his hands and feet showed no abnormality. Biopsy of a warty lesion showed hyperkeratosis, thickening of the stratum spinosum, and vacuolated cells in the upper layers of the epidermis. Those cells had a clear, light‐blue pale cytoplasm with keratohyaline granules and a central pyknotic nucleus. There was dilatation of dermal blood vessels and perivascular lymphocytic infiltration (Fig. 2). In situ hybridization indicated a positive human papillomavirus (HPV) reaction. A clinical diagnosis of epidermodysplasia verruciformis (EV) was made.
Consumer Choices and the American Health Care System-Reply
Authors: Stanley J. Reiser
Journal: JAMA (1992)

<h3>In Reply.</h3> —Although these responses to my article focus on different aspects of it, I am gratified that all of the commentators agree with my central point: that consumer knowledge and autonomy are significant goods that the medical profession and society should promote. While I agree with Dr Danto on the significance of practice guidelines constructed for physicians, we should develop equally informative guidelines for patients to lead them through the difficult task of understanding and making therapeutic choices. By comparison with guidelines produced for clinicians, those currently being created for patients are brief and do not contain adequate discussion of the relative merits of alternative treatments. This imbalance should be addressed. Dr Gorski in part misreads my article. I indicate that only worker and employer should contribute equal contributions to fund the worker's health care through vouchers. For the unemployed or part-time and full-time workers earning low wages, I
Genetic basis of the polymorphisms of the αI domain of spectrin
Authors: Patrick G. Gallagher, Marc Romana, Clara Wong, Bernard G. Forget
Journal: American Journal of Hematology (1997)

Defects of α spectrin have been identified in many cases of hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP). To aid in the genetic analysis of families with these disorders, the locations of three α-spectrin gene polymorphisms were mapped, the genetic basis of these polymorphisms identified, and PCR-based assays designed for their identification. The frequencies of these polymorphisms were determined in two populations and in patients with αI/50a HE and HPP. These studies identified two distinct haplotypes and provided evidence that two HE/HPP mutations associated with the αI/50a protein phenotype, L207P and L260P, arose on separate chromosomal backgrounds. Am. J. Hematol. 56:107–111, 1997. © 1997 Wiley-Liss, Inc.
Violence in America: Guns-Reply
Authors: Douglas S. Weil
Journal: JAMA (1992)

<h3>In Reply.</h3> —Dr Kohanski identifies several instances in which he believes there are inconsistencies between what we have written and the data that we have used for our article. Kohanski is simply mistaken. He appears to have misread the first table presented in the article. That table shows the percentage of individuals who keep their guns loaded some or all of the time, for any given category, not the actual number of individuals who keep a gun loaded. Read properly, the text and the tables are in agreement. For example, we wrote that "over half of the handgun owners surveyed kept their guns currently loaded." The table indicates that of the surveyed gun owners, 51% sometimes or always kept their guns loaded; not that 51 of 364 respondents sometimes or always kept their guns loaded, as Kohanski writes. Kohanski also questions our ability to draw valid conclusions from a sample
Obesity and Late-Age Survival Without Major Disease or Disability in Older Women
Authors: Eileen Rillamas-Sun, Andrea Z. LaCroix, Molly E. Waring, Candyce H. Kroenke, Michael J. LaMonte, Mara Z. Vitolins, Rebecca Seguin, Christina L. Bell, Margery Gass, Todd M. Manini, Kamal H. Masaki, Robert B. Wallace
Journal: JAMA Internal Medicine (2013)

The effect of obesity on late-age survival in women without disease or disability is unknown.
Coronary thrombolysis in dogs with intravenously administered human pro-urokinase.
Authors: D Collen, D Stump, F van de Werf, I K Jang, M Nobuhara, H R Lijnen
Journal: Circulation (1985)

Coronary thrombolysis was induced by infusion of highly purified human pro-urokinase isolated from a transformed kidney cell line (ACHN) or by infusion of urokinase of urinary origin in anesthetized dogs with 1-hr-old clots in the left anterior descending coronary artery. The clots were induced with a copper coil and thrombolysis was detected by repeat coronary angiography. Intravenous infusion of pro-urokinase at a rate of 10 micrograms/kg/min for 30 min in two dogs did not induce thrombolysis, which was only obtained after 8 and 15 min of its subsequent intracoronary administration. Intravenous infusion of pro-urokinase at a rate of 20 micrograms/kg/min for 30 min in four dogs induced coronary thrombolysis within 23 +/- 2 min (mean +/- SEM). This was not associated with systemic fibrinolytic activation because the alpha 2-antiplasmin and fibrinogen levels did not decrease. Intravenous infusion of urokinase at a rate of 10 micrograms/kg/min for 30 min elicited thrombolysis in four of seven dogs within an average of 19 +/- 2 min. In the other three dogs thrombolysis was only obtained within 11 +/- 3 min of its subsequent intracoronary infusion. Administration of urokinase was associated with systemic fibrinolytic activation as evidenced by a decrease of alpha 2-antiplasmin to about 10% and of fibrinogen to 43 +/- 13% of the preinfusion value. It is concluded that intravenous infusion of pro-urokinase at a sufficiently high rate produces coronary thrombolysis without systemic fibrinolysis in dogs.
Predicting Disease Progression After Regional Therapy for In-Transit Melanoma
Authors: Michael E. Lidsky, Ryan S. Turley, Georgia M. Beasley, Ketan Sharma, Douglas S. Tyler
Journal: JAMA Surgery (2013)

Although approximately 30% to 50% of patients experience a complete response after regional chemotherapy for in-transit melanoma, a subset of patients will develop rapidly progressive disease. In the current era of an expanding armamentarium, including both regional and systemic options for treating advanced melanoma, identifying perioperative factors that predict disease progression may obviate unnecessary morbidity associated with regional therapy and avoid delays in systemic therapy.To identify patient-related clinical and pathological variables, as well as procedural factors, that correlate with disease progression.Using a prospectively maintained database, we identified patients who either underwent first-time melphalan-based isolated limb infusion (ILI) or first-time hyperthermic isolated limb perfusion (HILP) for in-transit melanoma. Response was defined using modified Response Evaluation Criteria in Solid Tumors for cutaneous disease at 3 months after treatment. Survival analyses were performed using the Kaplan-Meier method, with the differences in survival curves compared using a log-rank test. Potential preoperative and procedural predictors of in-field progressive disease were analyzed using logistic regression.Of the 258 patients included in the database, 215 were identified as having undergone first-time regional therapy. Of these 215 patients, 134 underwent ILI, and 81 underwent HILP.Regional therapy (ILI or HILP).Complete response or progressive disease.Of 134 patients who underwent ILI, 43 (32.1%) experienced in-field progressive disease. Of 81 patients who underwent HILP, 9 (11.1%) experienced in-field progressive disease. The median survival for patients with in-field progressive disease was 20.3 months for the ILI cohort and 15.0 months for the HILP cohort. In general, patients with progressive disease were younger, with advanced-stage melanoma and increased tumor burden. Compared with patients who experienced a complete response, patients with in-field progressive disease after ILI were younger (odds ratio, 1.06 [95% CI, 0.90-0.98]; P = .002). For patients who underwent HILP, no clinically relevant preoperative predictors of in-field progressive disease were identified. Procedural variables, including chemotherapeutic dosing, degree of acidosis or base deficit achieved, and peak temperature attained, were not predictors of in-field progressive disease after ILI or HILP.Patient, clinical, and procedural factors are unreliable predictors of in-field progressive disease after regional therapy in patients with in-transit melanoma. Defining the potential utility of molecular markers in predicting response or failure of regional therapy should be the focus of future research efforts.
Esperanto—The International Language.
Authors: W. A. Briggs.
Journal: JAMA (1907)

Sacramento, Cal., Feb. 11, 1907. <h3>To the Editor:</h3> —Kindly permit me to suggest and to urge the early establishment inThe Journalof a department of Esperanto, on the following grounds: 1. Esperanto is the one and only proposed international language which has successfully borne the scrutiny both of scholars and of men of affairs. 2. The adoption of Esperanto as the international language would be the most powerful promoter of universal peace imaginable—infinitely more effective than Dreadnaughts or any other kind of "big stick" and immeasurably less expensive. In blood and treasure what does armed peace cost the world? 3. The adoption of Esperanto as the international language would be the most powerful promoter of the diffusion of knowledge of which it is possible to conceive. Free trade in knowledge! The freedom of the vast realm of science and art and literature for a few days' study! That imagination
Perfusion Recovery After Lung Volume Reduction Surgery
Authors: NAOYUKI WATANABE, SHINYA OKU, YUSUKE INOUE, TOSHIMITSU MOMOSE, TORU OTAKE, SHUJI TANADA, HAJIME MURATA, YASUHITO SASAKI, KEIGO ENDO
Journal: Clinical Nuclear Medicine (1999)

A patient with emphysema was evaluated before and after lung volume reduction surgery by pulmonary perfusion and ventilation imaging. Preoperative imaging showed marked nonhomogeneity of perfusion throughout both lung fields, with more segmental defects in the right lower field involving ventilation abnormalities. After resection of the right lower lobe, pulmonary imaging showed an improvement of matched perfusion and ventilation in the right lower field. This case illustrates perfusion and ventilation recovery after lung volume reduction surgery.
Report of the Librarian
Authors: Henry R. Viets
Journal: New England Journal of Medicine (1951)

THE Librarian herewith presents his annual report to the Boston Medical Library, the thirteenth accounting of the state of the Library since he took office in 1938. This report covers the calendar year 1950, a year of increase in the use of the Library to a point where the circulation and use of our books and periodicals reached nearly 65,000 items. This is the greatest use of the Library in its history, and when considered in relation to the growth during 1948 and 1949 it is noteworthy that in the three-year period the use of the Library has grown from . . .
Systemic chemotherapy for primary breast cancer
Authors: K. Abel
Journal: BMJ (1977)

response.The increasingly widespread use of drugs such as diazepam and the tendency to use Cremophor solubilisation to prevent thrombophlebitis and injection pain must increase the chances of clinical responses occurring.The next few years may well see an increasing number of reports of anaphylactoid phenomena to what have long been considered "safe" drugs.
Cesarean Section Rates in the United States
Authors: Bruce A. Harris
Journal: JAMA (1985)

To the Editor.—  The recent study by Gleicher 1 and the comments on it by Dr Rosen 2 are most interesting.  It appears that all studies on cesarean delivery will be incomplete until the publication of a well-designed study relative to the influence of litigation on the obstetrician's choice of procedure. The consensus conference of 1980 was unable to reach any firm conclusion in this area. This is because there are very few data on this important subject.  When the average obstetrician is faced with a large neonate in the occiput posterior position and a questionable fetal heart tracing, it is much easier for him to do a cesarean than it is to stand by and wait for vaginal delivery—knowing that 20 years hence (when he is in his old age) he may well be the object of a malpractice suit by the child he is about to deliver. Such
Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial — FAT)
Authors: Jan Malik, Vojtech Melenovsky, Dan Wichterle, Tomas Haas, Jan Simek, Richard Ceska, Jaromir Hradec
Journal: Cardiovascular Research (2001)

Objective: It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia. Studies assessing the effects of fibrates on endothelium have been neglected. Therefore, we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia. Methods: 29 otherwise healthy males (aged 47.4±7.8 years) with combined hyperlipidaemia (total cholesterol 7.55±1.20 mmol/l, triglycerides 5.41±4.54 mmol/l) were included into the randomised, single-blind, cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily — each of the drugs for a period of 10 weeks. Analysed biochemical parameters were as follows: serum total-, LDL- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides, fibrinogen, uric acid, C-reactive protein (CRP), insulin, and homocysteine. Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery. Two indices of endothelial-dependent postischaemic changes were used — the recently introduced index of peak blood flow (PBF) representing the level of reactive hyperaemia and traditional flow-mediated dilatation (FMD). Results: We observed a small improvement in FMD after both fenofibrate and atorvastatin (from 2.26% to 2.98% and 2.87%, respectively; NS). PBF increased from 448 ml/min to 536 ml/min after fenofibrate (P=0.04) and to 570 ml/min after atorvastatin (P=0.03). The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly (P-values of 0.82 and 0.47 for FMD and PBF, respectively). Significant correlations (P<0.01) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP (r=−0.60) and between both FMD and PBF, and insulinaemia (r=−0.48 and −0.56, respectively) only during treatment with fenofibrate. Conclusions: Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference. The PBF was superior to FMD for the detection of this improvement. The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy. The improvement of vascular reactivity during treatment with fenofibrate (opposed to atorvastatin) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance. The PBF was more reproducible than FMD because of considerably lower intra-subject variability.
Treatment of poisoning by antidepressant drugs
Authors: C. A. Fuge
Journal: BMJ (1967)

LJU"RNAL response to specific therapy, even when large numbers of tablets are consumed.On the other hand, experience of para- cetamol poisoning is very limited, but acute liver necrosis and death feature prominently in recorded cases."Indeed, the manufacturers of one brand of paracetamol, very responsibly, give in their brochure information relating to a 13-year- old girl who died after taking 30 tablets.Post-mortem examination revealed massive diffuse toxic necrosis of the liver.The onset of liver disease in paracetamol poisoning may be delayed several days, and it is possible that survival from serious intoxication may be complicated by residual liver damage.The toxic effect of 50 aspirin tablets, a com- mon overdose, is very much less than those that might arise from ingestion of a similar number of paracetamol tablets.Moreover, there is no adequate therapy for this type of poisoning.Should the advice of your leader be accepted and paracetamol become as readily available as aspirin is at present, a greatly increased incidence of paracetamol over- dosage is inevitable.We consider that the resulting mortality and morbidity would be greater than that from aspirin poisoning, and certainly would not warrant acceptance of the change you have so strongly advocated.-Weare, etc.,
Abstract 2000: Curcumin prevents human prostate cancer cell invasion by inhibiting of matriptase activity
Authors: Tai-Shan Cheng, Wen-Chi Chen, Ya-Yun Lin, Chia-I Liao, Chun-Jung Ko, Ming-Shyue Lee
Journal: Cancer Research (2012)

Abstract Curcumin has been shown with potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism how curcumin suppresses prostate cancer cell migration and invasion is not well understood. In this study we showed that curcumin could significantly suppress prostate cancer PC3 cell migration and invasion. Moreover, our data also showed that curcumin was able to suppress EGF- or heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment resulted in not only significant reductions on MMP-9 and MMP-2 activities, but also on activated level of matriptase which is a membrane-bound serine protease and has been proposed to play important roles in tumor invasion and malignancy. Matriptase is synthesized as a full length zymogen, which is rapidly stepped into the maturation process, mature form through a cleavage within the SEA domain to from a latent matriptase. Our data further showed that curcumin can inhibit the latent matriptase formation in the maturation process to affect matriptase activity. Furthermore, the reduction of activated matriptase by curcumin was also partly due to curcumin promoting the shedding of activated matriptase into extracellular environment, but not due to curcumin effect on matriptase gene expression. In addition, we established the stable pools of CWR22Rv1 cells with matriptase overexpression and found that expression of matriptase in CWR22Rv1 cells enhanced their invasive ability. With curcumin treatment, the invasive ability induced by matriptase overexpression was significantly suppressed. In summary, the data indicated that curcumin exhibits a suppressive effect on prostate cancer cell invasion, at least in part by down-regulating matriptase activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2000. doi:1538-7445.AM2012-2000