tbuckley/cabot-search huggingface dataset:
Randomised trial of prophylactic daily aspirin in British male doctors
Authors: E. Weber
Journal: BMJ (1988)

SIR,-There can be no doubt that the British trial (30 January, p 313) has made a great contribution to research into the effect of aspirin on the frequency of primary infarction and stroke. Both the extent and the duration of this study deserve peer recognition, and these results, acknowledged the world over, are of great scientific interest. In contrast to the results obtained by the British research group, those produced by the American group clearly show a significant reduction in the rate of infarction in doctors who took aspirin, a result which ultimately led to the premature termination of the study. ' An attempt to explain these discrepancies reveals fundamental differences in the way in which these two major studies were carried out. The American study featured not only a considerably larger number of volunteers but also a true control group which took placebos according to a double blind study design. The British control group was merely recommended to avoid taking aspirin. Furthermore, during the six year study about 12% of the British control group changed over to the group taking aspirin, while 30% of the aspirin group stopped taking it. Also, part of the aspirin group transferred to a different formulation during the study and reduced the dose from 500 to 300 mg, thus destroying the comparability of the two groups. Moreover, the results of the study were projected arbitrarily on to a reference value of 10 000 man years. It is at this point, if not sooner, that we must question the binding nature of a scientific study protocol. What is the claim to validity ofa scientific study which is carried out according to criteria that change so frequently? The authors themselves are apparently aware of the shortcomings of their study and in their discussion readily refer to their American colleagues, whose results they consider more significant. They observe that an unbiased and qualified evaluation ofthe side effects can be carried out only on the basis of a placebo group. Why did the British research group pass up the opportunity of gaining such important results? It is regrettable that the necessary further scientific analysis of the range of activity of aspirin in the primary prevention of infarction should be endangered so easily by a study protocol which is equivocal to say the least. This is all the more tragic if we consider the pioneering character of this British study in the discussion surrounding the use of aspirin in the primary prophylaxis of myocardial infarction.
The mutation spectrum in Indian patients with Gaucher disease
Authors: Vartika Bisariya, Pramod K Mistry, Jun Liu, Madhumita Roy Chaudhari, Neerja Gupta, Madhulika Kabra
Journal: Genome biology (2011)

Gaucher disease is the most common lysosomal storage disorder. It results from an inherited deficiency of the enzyme glucocerebrosidase (GBA); accumulation of the substrate of this enzyme has many clinical manifestations. Since the discovery of the GBA gene, more than 200 mutations have been identified, but only a handful of mutations are recurrent (L444P, N370S, IVS2, D409H and 55Del). To determine the spectrum of mutations in the Indian population, we performed mutational screening in children with Gaucher disease.

Twenty-four patients from twenty families were enrolled in this study, after written informed consent was obtained. The diagnosis of Gaucher disease was based on mandatory clinical and biochemical analysis. An initial screening for five common mutations was carried out using PCR-RFLP. Patients who were negative for common mutations were screened by sequencing exons 9 to 11 (a mutation hotspot region) [1].

We identified common mutations (L444P, N370S, IVS2 and D409H [2], and 55Del [3]) in approximately 50% of the patients. L444P (c.1448T>C) was the most frequently identified, followed by D409H in our patients. Western data shows that N370S is the most common mutation in Romanian patients [4]. One polymorphism (E340K) was identified in two patients who were compound heterozygotes for A456P/R463C and S237F/A269P, respectively. Our data highlight the spectrum of mutations that lead to Gaucher disease in the Indian population.
Genome-Wide, High-Resolution Detection of Copy Number, Loss of Heterozygosity, and Genotypes from Formalin-Fixed, Paraffin-Embedded Tumor Tissue Using Microarrays
Authors: Sharoni Jacobs, Ella R. Thompson, Yasuhito Nannya, Go Yamamoto, Raji Pillai, Seishi Ogawa, Dione K. Bailey, Ian G. Campbell
Journal: Cancer Research (2007)

Abstract Formalin-fixed, paraffin-embedded (FFPE) material tends to yield degraded DNA and is thus suboptimal for use in many downstream applications. We describe an integrated analysis of genotype, loss of heterozygosity (LOH), and copy number for DNA derived from FFPE tissues using oligonucleotide microarrays containing over 500K single nucleotide polymorphisms. A prequalifying PCR test predicted the performance of FFPE DNA on the microarrays better than age of FFPE sample. Although genotyping efficiency and reliability were reduced for FFPE DNA when compared with fresh samples, closer examination revealed methods to improve performance at the expense of variable reduction in resolution. Important steps were also identified that enable equivalent copy number and LOH profiles from paired FFPE and fresh frozen tumor samples. In conclusion, we have shown that the Mapping 500K arrays can be used with FFPE-derived samples to produce genotype, copy number, and LOH predictions, and we provide guidelines and suggestions for application of these samples to this integrated system. [Cancer Res 2007;67(6):2544–51]
IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling
Authors: Clinton B. Mathias, Suejy A. Hobson, Maria Garcia-Lloret, Greg Lawson, Dimitri Poddighe, Eva-Jasmin Freyschmidt, Wei Xing, Michael F. Gurish, Talal A. Chatila, Hans C. Oettgen
Journal: Journal of Allergy and Clinical Immunology (2010)
Operation of platinum-palladium catalysts with leaded gasoline.
Authors: D M Teague, L B Clougherty, A N Speca
Journal: Environmental Health Perspectives (1975)

The effect of various fuel additives on the ability of platinum-palladium catalytic converters to remove the carbon monoxide and hydrocarbon components of automotive exhaust has been examined. Engine dynamometer studies suggest that these catalysts may be successfully used in conjunction with fuels of relatively high tetraethyllead concentrations, provided the ethylene dibromide portion of the scavenger is excluded.
Gerald "Charlie" Westbury
Authors: D. Payne
Journal: BMJ (2014)

<h3>Objectives</h3> To investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and all-cause mortality among middle-aged and elderly Chinese population. <h3>Design</h3> Prospective cohort study. <h3>Setting</h3> This study used data from the China Health and Retirement Longitudinal Study. <h3>Participants</h3> Middle-aged and elderly participants with complete data were enrolled for a 4-year follow-up of total mortality and plasma levels of LDL-C, including 4981 male respondents and 5529 female respondents. <h3>Results</h3> During a 4-year follow-up, there were 305 and 219 deaths in men and women, respectively. Compared with the first quintile (Q1) of LDL-C, the adjusted HRs (95% CIs) were 0.818 (0.531 to 1.260) for Q2, 0.782 (0.507 to 1.208) for Q3, 0.605 (0.381 to 0.962) for Q4 and 0.803 (0.506 to 1.274) for Q5 in men. The results from restricted cubic spine (RCS) showed that when the 20th percentile of LDL-C levels (84 mg/dL) was used as the reference, a lower LDL-C concentration (&lt;84 mg/dL) was associated with a higher 4-year all-cause mortality risk. By contrast, both quintile analysis and RCS analysis did not show a statistically significant association in women. <h3>Conclusions</h3> Compared with moderately elevated LDL-C (eg, 117–137 mg/dL), a lower plasma level of LDL-C (eg, ≤84 mg/dL) was associated with an increased risk of 4-year all-cause mortality in middle-aged and elderly Chinese men. The results suggest the potential harmful effect of a quite low level of LDL-C on total mortality.
What is pain facial expression for?
Authors: Nico H. Frijda
Journal: Behavioral and Brain Sciences (2002)

A functional interpretation of facial expressions of pain is welcome. Facial expressions of pain may be useful not only for communication, such as inviting help. They may also be of direct use, as parts of writhing pain behavior patterns, serving to get rid of pain stimuli and/or to suppress pain sensations by something akin to hyperstimulation analgesia.
Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats
Authors: Yulian Lin, Takeo Fujimori, Naoko Kawaguchi, Yuiko Tsujimoto, Mariko Nishimi, Zhengqi Dong, Hidemasa Katsumi, Toshiyasu Sakane, Akira Yamamoto
Journal: Journal of Controlled Release (2010)
James Wylie Beattie
Authors: B. Payne, N A. Green
Journal: BMJ (2009)

After a distinguished scholastic record at the Royal Belfast Academical Institution, James Wylie Beattie (“Wylie”) entered Belfast, on a scholarship. After qualification and house appointments in Belfast, he moved via Scotland to academic training posts in Sheffield and Cardiff. Given the intense competition for general medical consultant posts at that time, …
Abstract 3609: Generation and characterization of a novel monoclonal antibody recognizing both the blood and tissue form of human PCBP-1
Authors: Özge Alper, Alexander O. Vortmeyer, Marille Herrmann, Achille Akoa, Özgül M. Alper, Aaron Auerbach, Cui P. Chen
Journal: Cancer Research (2012)

Abstract Background: Poly(rC)-binding protein-1 (PCBP-1) is a nucleic-acid-binding protein that localizes in nucleus and/or cytoplasm of cells. Shuttling between nucleus and cytoplasm has been related to its function in regulation of RNA transcription, translation and also implicated its involvement in cancer metastasis, progression and chemoresistance. In the present study, we investigated the levels and expression of PCBP-1 in breast carcinoma and its potential use as a biomarker in breast carcinoma differential diagnosis. Methods/Results: We generated a novel monoclonal antibody (mAb), AB-PCBP-1 using hybridoma technology and native protein in cell culture medium as immunogen. This mAb is of IgG1 (kappa) type. It specifically recognized both native and denatured human PCBP-1 protein and displayed high affinity as assessed by ELISA, immunohistochemistry assay, western blot and flow cytometry applications. Using this mAb in competitive ELISA, we showed for the first time that soluble PCBP-1 level is significantly increased in the plasma of metastatic breast cancer patients’ plasma. PCBP-1 is also expressed in metastatic breast carcinoma tissue by immunohistochemistry. Seventy percent of normal breast ducts and lobules expressed strong nuclear staining whereas cytoplasmic staining was less specific and found in most cancer tissues. We examined 90 cases of breast carcinoma tissues classified as either ductal and lobular carcinoma. To evaluate the immunoreactivity of PCBP-1, the staining intensity and intracellular distribution were compared and scored as 0, 1+, 2+ and 3+ based on intensity. Seventy nine % (60 out of 76) of ductal carcinomas showed strong cytoplasmic staining (2+ and 3+) and 45% also exhibited strong nuclear localization for PCBP-1. Lobular carcinomas (n=14), on the other hand, showed an exclusively nuclear staining pattern.Conclusion: AB-PCBP-1 mAb showed high performance in blood and tissue assays. PCBP-1 levels were significantly increased in blood and demonstrated a distinct pattern of expression related to histological tumor types, suggesting that PCBP-1 may be involved in a regulatory mechanism that differs in various subtypes of breast carcinoma. The results suggest the potential clinical use of PCBP-1 as a therapeutic target and/or a biomarker in blood and tissue for the diagnosis and prognosis of breast carcinoma. 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 3609. doi:1538-7445.AM2012-3609
On or Off Target: Mutations, Models, and Predictions
Authors: Levi A. Garraway, William C. Hahn
Journal: Science Translational Medicine (2010)

In a series of articles published in February 2010, The New York Times chronicled, from a personal perspective, the rollercoaster experience of those associated with clinical trials of a RAF inhibitor for the treatment of melanoma. In this issue of Science Translational Medicine, Whittaker et al. describe research that reconciles some of the bewildering aspects of the discovery and development of drugs that inhibit such protein kinase targets in cancer.
Activation patterns in healed experimental myocardial infarction.
Authors: A Kadish, C W Balke, J F Levine, E N Moore, J F Spear
Journal: Circulation Research (1989)

The maximum amplitude of vector loops formed by summing orthogonally recorded bipolar electrograms has been shown to reflect the direction of activation in cardiac muscle. To investigate whether components of vector loops could provide information about different activation directions in local areas of myocardium, we correlated "instantaneous vectors" with isochronal activation patterns in an in vitro preparation of experimental myocardial infarction. In thirteen 3 mm x 3 mm regions studied (from 11 tissues), at least 16 microelectrode impalements with a minimum density of 0.8 mm between sites were made. In seven situations in which notched, irregular, and prolonged duration electrograms were present, vector loops pointed in the same general direction throughout their entire time course. In these preparations, microelectrode impalements demonstrated only a single major direction of activation. In five of six areas in which multidirectional vector loops were present, two or more separate local directions of activation corresponded to the directions of the vector loop. Instantaneous vectors were then used to analyze propagation patterns in vivo in 10 animals with 2-4-week-old experimental myocardial infarction. Of 150 sites in the 10 animals, 13% contained more than one major local direction of activation. In 11 markedly abnormal sites, electrograms were recorded during pacing from four sites around the recording probe. When comparing electrogram characteristics from the four sites, a mean difference of 5.9 mV in electrogram amplitude and 19.1 msec in electrogram duration (coefficient of variation, 27% for amplitude and 22% for duration) was found. In only two of the 11 sites was it found that the same number of activation directions occurred from all pacing sites. We conclude: 1) Instantaneous components of vector loops accurately represent local directions of cardiac activation at differing times. 2) Most areas of experimental myocardial infarction have only one major direction of activation despite the presence of abnormal electrograms. 3) In some regions, however, two major local directions of activation can be identified within a relatively local area. 4) Geometric activation patterns in experimental myocardial infarction are markedly dependent on initial activation direction.
Hair Theory Pelted
Authors: Howard B. Sprague
Journal: JAMA (1964)

<h3>To the Editor:—</h3> For some time I have used a simple test to determine the literary quality of a medical journal. This is the observed frequency of the misspelling of the word "desiccation." Naturally I was shaken to the core when I saw it in Ashley Montagu's communication in your well-known trade journal. "Desiccate" comes from the Latin<i>siccus,</i>meaning dry, as you well recognize. The offending proofreader, including the author, should stand in a corner with this inscription around his or her neck—"There are only three words in the English language beginning with dess:<i>dess,</i>a Scottish term meaning a layer, such as stones;<i>dessa,</i>a village community in Java; and<i>dessert,</i>the course at the end of a meal." If they find any of these in a medical paper they can have them.
Abstract 5532: A pro-fluorescent membrane integrity dye for the real-time assessment of cytotoxicity.
Authors: Richard L. Somberg, Andrew Niles, Tracy Worzella, Dan Lazar
Journal: Cancer Research (2013)

Abstract Cell-based assay models are now universally employed as a routine means of establishing and ranking on- and off-target toxicities. It is well appreciated, however, that individual cytotoxic phenotypes are shaped not only by compound dosage, but by the length of compound-cell exposure. In addition to compound-specific attributes, inherent cellular factors such as biotransformation capacity, cell cycle susceptibility, and receptor expression often dictate the kinetics of cytotoxicity. Unfortunately, the majority of conventional cytotoxicity assays are performed at a terminal endpoint (48-72h) which at worst can underestimate cytotoxicity due to biomarker degradation, or at best, fail to reveal important features of the cytotoxic event which may be important for establishing mechanism-of-action. We have developed a pro-fluorescent, cell-impermeant probe which can be applied to cells at the time of dosing to report changes in membrane integrity as they occur in real-time. The dye enters cells with impaired membrane integrity, greatly enhancing fluorescence which is proportional to non-viable cell number. The dye can be used in traditional plate based formats using standard fluorometry or with image based readers (Essen Bioscience Incucyte™) to establish the dose-dependent kinetics of cytotoxicity. Here we describe the dye's utility using mechanistically distinct cytotoxins with both cancer cell lines (on-target) and terminally differentiated cells (off-target) and correlate this dead cell fluorescence activity to other cytotoxicity biomarkers by same-well multiplexed methods. Citation Format: Richard L. Somberg, Andrew Niles, Tracy Worzella, Dan Lazar. A pro-fluorescent membrane integrity dye for the real-time assessment of cytotoxicity. [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 5532. doi:10.1158/1538-7445.AM2013-5532
A Prognostic Role of Mean 24-h Pulse Pressure Level for Cardiovascular Events in Type 2 Diabetic Subjects Under 60 Years of Age
Authors: Shigeru Nakano, Kazunori Konishi, Keisuke Furuya, Keigo Uehara, Makoto Nishizawa, Atsushi Nakagawa, Toshikazu Kigoshi, Kenzo Uchida
Journal: Diabetes Care (2005)

To assess the prognostic role of ambulatory 24-h pulse pressure (PP) on various vascular events in relatively young type 2 diabetic subjects under 60 years of age.In this prospective study, 237 type 2 diabetic subjects without any history of vascular complications were analyzed. After excluding 9 dropout subjects, 228 subjects (mean age, 46 years; 69% men; mean follow-up period, 100 months) entered the study.Distribution of 24-h PP for all subjects showed left skewed data, indicating that there may be a diabetic subgroup that had a wide PP. Therefore, further analysis was performed by stratifying the diabetic subjects by quartile of 24-h PP. Outcomes for the widest quartile (n = 58; cut point = 53.3 mmHg) was then compared with those from the other narrower quartiles (n = 170). In the diabetic subjects with a wide PP, cardiovascular events occurred more frequently than those in the diabetic subjects with a narrow one (20.7 vs. 4.1%; P < 0.001), resulting in the significant difference in the cumulative incidence of cardiovascular events (P < 0.001, log-rank test), but not cerebrovascular events, between the two subgroups. The Cox model revealed that a wide 24-h PP at baseline independently predicted subsequent cardiovascular events but not cerebrovascular events. By contrast, only duration of diabetes was the risk factor for cerebrovascular events.This study showed that a wide 24-h PP is predictive for cardiovascular events in relatively young diabetic subjects.
Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates
Authors: Ibrahim Dagher, Tuan Huy Nguyen, Marie‐Thérèse Groyer‐Picard, Panagiotis Lainas, Sylvie Mainot, Catherine Guettier, Danièle Pariente, Dominique Franco, Anne Weber
Journal: Hepatology (2008)

The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as hepatocytes, and portal vein occlusion increases hepatocyte engraftment. We investigated whether reversible portal vein embolization combined with ex vivo lentivirus-mediated gene transfer is an effective approach for successful hepatocyte engraftment in nonhuman primates and whether the transgene remains expressed in the long term in transplanted hepatocytes in situ. Simian hepatocytes were isolated after left lobe resection, and the left and right anterior portal branches of animals were embolized with absorbable material. Isolated hepatocytes were labeled with Hoechst dye or transduced in suspension with lentiviruses expressing green fluorescent protein under the control of the human apolipoprotein A-II promoter and transplanted via the inferior mesenteric vein. The whole procedure was well tolerated. The embolized liver was revascularized within 2 weeks. The volume of nonembolized liver increased from 38.7% ± 0.8% before embolization to 55.9% ± 1% after embolization and hepatocytes significantly proliferated (10.5% ± 0.4% on day 3 after embolization). Liver repopulation after transplantation with Hoechst-labeled hepatocytes was 7.4% ± 1.2%. Liver repopulation was 2.1% ± 0.2% with transduced hepatocytes, a proportion similar to that obtained with Hoechst-labeled cells, given that the mean transduction efficacy of simian hepatocyte population was 34%. Transgene expression persisted at 16 weeks after transplantation. Conclusion: We have developed a new approach to improve hepatocyte engraftment and to express a transgene in the long term in nonhuman primates. This strategy could be suitable for clinical applications. (HEPATOLOGY 2009.)
Kidney Transplantation in Identical Twin Minors — Justice Is Done in Connecticut
Authors: William J. Curran
Journal: New England Journal of Medicine (1972)

IT is now 15 years since the Supreme Judicial Court of Massachusetts, in a decision not published, first sanctioned a transplant of a kidney from a well child to his dying identical twin brother.1,2 The children were minors. In 1969 the State of Kentucky joined Massachusetts in allowing parental consent to sanction a transplant between brothers where the donor was a 28-year-old mental incompetent.3 Now the State of Connecticut has followed the rulings of these states and allowed a transplant between identical twins aged seven years.*4 In a superbly drafted opinion, the procedure has been ordered by Judge Robert J. . . .