tbuckley/cabot-search huggingface dataset:
Beyond Appearance: Reflections of a Plastic Surgeon
Authors: Richard C. Schultz
Journal: JAMA (1987)

Using the vehicle of a typical work-week, Dr Goldwyn conveys his philosophy of medicine with special insights into the disciplines of plastic surgery and psychiatry. He does this by probing introspectively the social and religious significance of his routine professional activities. Leaving his driveway for the hospital parking lot at 7 AM Monday, he introduces the reader to his colleagues, his patients, and his conflicts and anxieties stemming from his relations with them. The book ends Friday evening after Dr Goldwyn has touched on each event of his week and discussed its meaning to him. He manages to explore the significance of many aspects of medical ethics as well as analyze the way his religious beliefs relate to the socioeconomic aspects of medicine and the ambiguities of contemporary civilization. Goldwyn is a seasoned author and editor, and therefore this book is well crafted and extremely easy to read. However, it
Ribozyme-mediated selective induction of new gene activity in hepatitis C virus internal ribosome entry site-expressing cells by targeted trans-splicing
Authors: Kyung-J.u Ryu, Jung-Hye Kim, Seong-Wook Lee
Journal: Molecular Therapy (2003)

Although hepatitis C virus (HCV) causes worldwide health problems, efficient and specific therapy is not available so far. In this study, we describe a new genetic approach to the specific HCV therapy that is based upon trans-splicing ribozymes that can selectively replace HCV transcripts with a new RNA that exerts anti-HCV activity. We have developed a group I intron-based ribozyme targeting the internal ribosome entry site (IRES) of HCV with high fidelity and specificity. The ribozyme was designed to trans-splice its 3' tagging sequence comprising a new coding RNA, such as firefly luciferase transcript, that is linked to the 3' part of the HCV 5' UTR encompassing the downstream sequence of the targeted residue in the IRES. This ribozyme was then demonstrated to induce HCV IRES-dependent translation of the firefly luciferase gene selectively in HCV IRES-expressing cells with trans-splicing reaction. Moreover, a specific ribozyme with the coding sequence of the diphtheria toxin A chain in place of the firefly luciferase selectively triggered expression of the cytotoxin in cells expressing HCV IRES and specifically activated apoptosis of the cells. These results suggest that the trans-splicing ribozyme could be a potent anti-HCV agent to deliver therapeutic new gene activities specifically and selectively in HCV-infected cells.
The effect of erythrocyte membrane on the birefringence formation of sickle cell hemoglobin
Authors: H. Mizukami, D. E. Bartnicki, S. Burke, G. J. Brewer, I. F. Mizukami
Journal: American Journal of Hematology (1986)

Abstract The birefringence formation of sickle cell hemoglobin (HbS) in a thin liquid layer was observed while its environment was deoxygenated at different rates, and the effect of membrane was examined. Under slow rate of deoxygenation at 37°C, at pH 7.4, the birefringence of purified HbS appeared at a concentration higher than 24% and its relative magnitude increased as the concentration was increased. Similarly, the partial presure of oxygen, at which the birefringence formation was evident, increased from 0 to 27 torr as the concentration of HbS was increased from 24 to 28%, but it remained the same above this protein concentration. In all the samples tested relative birefringence was largest at the slow rate of deoxygenation (30 torrO 2 /min) and the magnitude decreased as the rate of deoxygenation was increased. The samples showed different sensitivity to the rate of deoxygenation. For example, while the total untreated hemolysate made by freeze‐thawing of packed sickle cells was most resistant to the increased rates of deoxygenation, purified HbS was not. Washed open ghosts partially restored the birefringence formation pattern of purified HbS. The results indicate that the inner surface of the membranes of erythrocytes could behave as a template for large HbS polymer formation at relatively higher rates of deoxygenation.
Pervasive sequence patents cover the entire human genome
Authors: Jeffrey A Rosenfeld, Christopher E Mason
Journal: Genome Medicine (2013)

The scope and eligibility of patents for genetic sequences have been debated for decades, but a critical case regarding gene patents (Association of Molecular Pathologists v. Myriad Genetics) is now reaching the US Supreme Court. Recent court rulings have supported the assertion that such patents can provide intellectual property rights on sequences as small as 15 nucleotides (15mers), but an analysis of all current US patent claims and the human genome presented here shows that 15mer sequences from all human genes match at least one other gene. The average gene matches 364 other genes as 15mers; the breast-cancer-associated gene BRCA1 has 15mers matching at least 689 other genes. Longer sequences (1,000 bp) still showed extensive cross-gene matches. Furthermore, 15mer-length claims from bovine and other animal patents could also claim as much as 84% of the genes in the human genome. In addition, when we expanded our analysis to full-length patent claims on DNA from all US patents to date, we found that 41% of the genes in the human genome have been claimed. Thus, current patents for both short and long nucleotide sequences are extraordinarily non-specific and create an uncertain, problematic liability for genomic medicine, especially in regard to targeted re-sequencing and other sequence diagnostic assays.
Ablating CAR and Integrin Binding in Adenovirus Vectors Reduces Nontarget Organ Transduction and Permits Sustained Bloodstream Persistence Following Intraperitoneal Administration
Authors: Masaki Akiyama, Stephen Thorne, David Kirn, Peter W Roelvink, David A Einfeld, C.Richter King, Thomas J Wickham
Journal: Molecular Therapy (2003)

To create tumor-targeted Ad vectors, ablation of native CAR and integrin receptor binding is crucial to enhance the specificity of tumor transduction. Toward this aim, we have previously created base vectors in which binding to CAR (single-ablated) or to both CAR and integrins (double-ablated) has been ablated. In this study, the biodistribution of the conventional (CAR and integrin binding intact), single-ablated, and double-ablated vectors was evaluated following intraperitoneal administration. The mesothelial lining of the peritoneal organs was the principle site of CAR-dependent gene transfer by the conventional vector. Surprisingly, the single-ablated vector strongly transduced the liver parenchyma rather than the mesothelium, while the double-ablated vector did not significantly transduce the parenchyma or mesothelium. The high level of parenchymal transduction by the single-ablated vector suggested that it efficiently entered the bloodstream from the peritoneal cavity. Consistent with this hypothesis, a large proportion of active particles distributed and persisted in the bloodstream following intraperitoneal administration of either the single- or the double-ablated vector. The above results suggest that the double-ablated vector backbone may not only significantly improve targeting to cancers located in the peritoneal cavity, but may also significantly improve targeting to metastatic tumors located throughout the body by virtue of its enhanced bloodstream persistence.
Pneumonia Associated with the TWAR Strain of Chlamydia
Authors: Thomas J. Marrie, J. Thomas Grayston, San-Pin Wang, Cho-Chou Kuo
Journal: Annals of Internal Medicine (1987)

From November 1981 to August 1984, 301 adult patients with community-acquired pneumonia were admitted to the major referral hospital of Nova Scotia. Serologic tests done on these patients included microimmunofluorescence using the TWAR strain of Chlamydia and all Chlamydia trachomatis serovars as antigens. The TWAR strain has been shown to cause mild pneumonia in teenagers and young adults. Of the 301 patients, 18 (6%) had serologic evidence of recent infection with the TWAR organism. Their mean age was 64 years. Pneumonia associated with the presence of acute TWAR antibody had no characteristic clinical or radiographic features when compared with pneumonia without acute chlamydia antibody. Six patients, who all had preexisting serious chronic disease, had severe illness, and 2 died. Both patients who died had complicated hospital courses and other concomitant infections. We conclude that the TWAR organism may cause pneumonia in older adults and persons with chronic diseases that require hospitalization.
Preventive Therapy for Multidrug-Resistant Tuberculosis
Authors: Larry R. Kirkland
Journal: JAMA (1996)

<h3>To the Editor.</h3> —A more accurate title for the Editorial, "Preventing Multidrug-Resistant Tuberculosis," by Dr Bloch and colleagues,<sup>1</sup>would have been "Preventing Multidrug Resistance in Tuberculosis," since the main focus was strategies to prevent already infected persons from developing resistant <h3>Requirements for Letters</h3> Letters will be published at the discretion of the editors as space permits and are subject to editing and abridgment. Letters will be considered if they are typewritten double-spaced and do not exceed 500 words of text and 5 references. Please include a word count. Letters discussing a recent<i>JAMA</i>article should be received within 4 weeks of the article's publication. Letters must not duplicate other material published or submitted for publication. A signed statement for authorship criteria and responsibility, financial disclosure, copyright transfer, and acknowledgment is essential for publication. Letters not meeting these specifications are generally not considered. Letters will not be returned unless specifically
Selenium and Mercury in the Brazilian Amazon: Opposing Influences on Age-Related Cataracts
Authors: Mélanie Lemire, Myriam Fillion, Benoît Frenette, Annie Mayer, Aline Philibert, Carlos José Sousa Passos, Jean Rémy Davée Guimarães, Fernando Barbosa, Donna Mergler
Journal: Environmental Health Perspectives (2010)

Age-related cataracts (ARCs) are an important cause of blindness in developing countries. Although antioxidants may be part of the body's defense to prevent ARC, environmental contaminants may contribute to cataractogenesis. In fish-eating populations of the lower Tapajós region, elevated exposure to mercury (Hg) has been reported, and blood levels of selenium (Se) range from normal to very high (> 1,000 microg/L).We examined ARCs in relation to these elements among adults (> or = 40 years of age) from 12 riverside communities.Participants (n = 211) provided blood samples and underwent an extensive ocular examination. Inductively coupled plasma mass spectrometry was used to assess Hg and Se in blood and plasma.One-third (n = 69; 32.7%) of the participants had ARC. Lower plasma Se (P-Se; < 25th percentile, 110 microg/L) and higher blood Hg (B-Hg; > or = 25th percentile, 25 microg/L) were associated with a higher prevalence odds ratio (POR) of ARC [adjusted POR (95% confidence interval), 2.69 (1.11-6.56) and 4.45 (1.43-13.83), respectively]. Among participants with high P-Se, we observed a positive but nonsignificant association with high B-Hg exposure, whereas among those with low B-Hg, we observed no association for P-Se. However, compared with the optimum situation (high P-Se, low B-Hg), the POR for those with low P-Se and high B-Hg was 16.4 (3.0-87.9). This finding suggests a synergistic effect.Our results suggest that persons in this population with elevated Hg, the cataractogenic effects of Hg may be offset by Se. Because of the relatively small sample size and possible confounding by other dietary nutrients, additional studies with sufficient power to assess multiple nutrient and toxic interactions are required to confirm these findings.
Regulation of intestinal lactase in adult hypolactasia.
Authors: M Lloyd, G Mevissen, M Fischer, W Olsen, D Goodspeed, M Genini, W Boll, G Semenza, N Mantei
Journal: Journal of Clinical Investigation (1992)

Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine.
US lags in health care despite largest investment, survey shows
Authors: Nellie Bristol
Journal: BMJ (2006)

Ill people in the United States were more likely than those in other countries to report receiving the wrong drugs and incorrect or delayed test results, shows a survey of similar patients in six developed countries.

The survey, which was conducted by the New York based Commonwealth Fund, a private foundation that works towards improving healthcare coverage and quality, showed that the United States scored last in four of six categories—efficiency, …
Guidelines for Drug Therapy in Renal Failure
Authors: WILLIAM M. BENNETT
Journal: Annals of Internal Medicine (1977)

Five tables are presented that provide guidelines for drug usage in patients with renal insufficiency. The data are derived from the current medical literature. If specific information about a drug is unavailable, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity or adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.
Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP
Authors: Mamta Gupta, Matthew J. Maurer, Linda E. Wellik, Mark E. Law, Jing Jing Han, Nazan Ozsan, Ivana N. Micallef, Ahmet Dogan, Thomas E. Witzig
Journal: Blood (2012)
Influence of Inhaled Iloprost on Transpulmonary Gradient of Big Endothelin in Patients With Pulmonary Hypertension
Authors: H. Wilkens, M. Bauer, N. Forestier, J. König, A. Eichler, S. Schneider, H.J. Schäfers, G.W. Sybrecht
Journal: Circulation (2003)

The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown.In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment.An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.
550 Progression and severity of liver fibrosis in HIV-HCV co-infected patients with normal CD4 cell count: Comparison with HCV-infected patients
Authors: D. Roulo, N. Bonilla, N. Barget, M. Andrieu, A. Rosenberg, M. Bentata, B. Jarrousse, V. Jeantils, F. Roudot-Thoraval, M. Ziol
Journal: Journal of Hepatology (2006)
Multiplicity of cross‐reactive epitopes on <i>Bet v</i> I as detected with monoclonal antibodies and human IgE
Authors: J. H. Akkerdaas, R. van Ree, M. Aalbers, S. O. Stapel, R. C. Aalberse
Journal: Allergy (1995)

Six monoclonal antibodies against Bet v I, the major cross‐reactive allergen of birch pollen ( Betula verrucosa ), were obtained. Four did not react with fruits, but two monoclonal antibodies (mAbs) (5H8 and 9C11) were reactive with apple and other fruits. These two cross‐reactive antibodies reacted with identical or overlapping sites, but differed in their relative degree of cross‐reactivity toward various fruits and hazelnut. Cross‐reactive human IgE antibodies reacted with a nonoverlapping epitope, as indicated by results of a two‐site radioimmunoassay (RIA) with the fruit‐reactive mAb 9C11. By isoelectric focusing (IEF) in conjunction with immunoblotting, a maximum of seven isoforms could be distinguished. Depletion of birch‐pollen extract for Bet v I with the most reactive mAb (7F7) removed approximately 95% of the IgE cross‐reactivity between birch pollen and apple extract. The remaining 5% cross‐reactive material was still capable of inhibiting the binding of IgE to apple allergen completely, and was reactive with mAbs 5H8 and 3C4. By means of IEF/immunoblot, it was shown that these mAbs recognize an isoform of Bet v I that is poorly, if at all, recognized by mAb 7F7. These results illustrate the heterogeneity of Bet v I, both with respect to the cross‐reactive sites as well as to the backbone structure. This type of heterogeneity has possible implications for the use of monoclonal antibodies in allergen standardization.
404 DOSE REDUCTION OF PEGINTERFERON ALFA-2A (PEG) IN COMBINATION WITH RIBAVIRIN (RBV) IN CHRONIC HEPATITIS C (CHC) PATIENTS: IMPACT ON VIROLOGICAL RESPONSE UNDER REAL LIFE CONDITIONS
Authors: K. Boeker, S. Mauss, D. Hueppe, M. Schuchmann, W. Schiffelholz, A. Baumgarten, C. Eisenbach, M. Roessle, P. Buggisch, J. Lohmeyer, T. Witthoeft, B. Möller, H. Loehr, E. Schott, U. Alshuth, E. Zehnter
Journal: Journal of Hepatology (2011)
Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma
Authors: G Srivastava, V Rana, M Q Lacy, F K Buadi, S R Hayman, A Dispenzieri, M A Gertz, D Dingli, S Zeldenrust, S Russell, A McCurdy, P Kapoor, R Kyle, S V Rajkumar, S Kumar
Journal: Leukemia (2013)
A teenager in love
Authors: A. Ward
Journal: BMJ (2003)

When I came out of hospital, paralysed by a lymphoma on my spine (at T10), my temporary hosts nicknamed me “the teenager” because I didn't do much, had lots of telephone calls, and needed lifts. I was 52 at the time.

The teenager tag was reinforced when I slept a lot and spent mornings in bed. This provoked dinner table comments (“He's a growing lad”) and typical shouts up the stairs (“It's time to get up. Do you want some lunch?”).

During the next two years, as I slowly progressed from wheelchair to sticks, the health service did everything possible to help me to stand on my own two feet, while my hosts wondered …
Long-term native liver fibrosis in biliary atresia: Development of a novel scoring system using histology and standard liver tests
Authors: Hirofumi Tomita, Yohei Masugi, Ken Hoshino, Yasushi Fuchimoto, Akihiro Fujino, Naoki Shimojima, Hirotoshi Ebinuma, Hidetsugu Saito, Michiie Sakamoto, Tatsuo Kuroda
Journal: Journal of Hepatology (2014)
Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans. Effects of N-acetylcysteine administration.
Authors: S Ghio, S de Servi, R Perotti, E Eleuteri, C Montemartini, G Specchia
Journal: Circulation (1992)

Tolerance to the effects of organic nitrates develops rapidly during continuous exposure to these drugs; its main mechanism seems to be an intracellular sulfhydryl group depletion. However, the relative susceptibility to the development of nitroglycerin tolerance of the arterial or venous circulation in humans is still a matter of dispute.Twenty patients with coronary artery disease underwent a continuous 24-hour nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24-hour infusion, and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure divided by flow. After 24 hours of nitroglycerin infusion, the initial increase in venous volume was reduced 48% (p less than 0.01), whereas the acute effects on vascular resistance were not attenuated in the whole group. N-Acetylcysteine completely restored nitroglycerin venodilator effects in all 10 patients in whom attenuation of the venous effects was observed during the infusion period.The data indicate that the susceptibility to the development of nitrate tolerance in humans is higher in the venous than in the arterial circulation, and that the sulfhydryl group donor N-acetylcysteine is extremely effective in reversing nitroglycerin tolerance in the venous circulation in humans.
Adult rhabdomyosarcoma of the gall bladder: case report and review of published works.
Authors: T M al-Jaberi, N al-Masri, A Tbukhi
Journal: Gut (1994)

A 90 year old woman with alveolar rhabdomyosarcoma of the gall bladder is described. The patient died with tumour metastasis four months after diagnosis despite complete excision of the tumour. The histological, immunohistochemical, and ultrastructural features of the tumour are summarised and published works are reviewed.
A Method of Abdominal Palpation
Authors: P. L. Deshmukh
Journal: BMJ (1948)

MEDCAL JOUNAAnother point is that I have followed up a number of patients who have suffered from non-pulmonary tuberculosis and who later married, and have found that pregnancies were unusual among them.This difference between patients with phthisis and patients with other forms of tuberculosis offers an interest- ing commentary on the pathogenesis of the disease.-Iam, etc.,