tbuckley/cabot-search huggingface dataset:
A controlled trial of high dose interferon, alone and after prednisone withdrawal, in the treatment of chronic hepatitis B: long term follow up.
Authors: V Perez, J Findor, H Tanno, J Sorda
Journal: Gut (1993)

This study was designed to evaluate the safety and effectiveness of high dose interferon, with or without prednisone pretreatment, in patients with chronic hepatitis B. Patients were randomised to two treatment groups: group I (n = 26) received six weeks of prednisone followed by a two week, drug free period, and then 10 million units (MU) of interferon alfa-2b three times weekly subcutaneously for 16 weeks; group II (n = 24) were used as controls for 24 weeks and then treated with interferon. Loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV)-DNA, with a return to normal alanine aminotransferase (ALT) activity, was seen in 16 of 26 group I patients (61.5%), in one group II patient (4.2%) during the control phase, and in 13 of 23 group II patients (56.5%) after interferon. Three of 26 (11.5%) in group I and one of 23 (4.3%) in group II eliminated the surface antigen (HBsAg). There were no statistically significant differences in response between groups I and II. Liver biopsies carried out in 20 patients showed that responders had a noticeable reduction in inflammation and disappearance of core antigen in liver tissue, changes not seen in non-responders. On long term follow up (four years), nine out of 28 responders (32.1%) eliminated HBsAg, and four initial non-responders had a late seroconversion.
Antitumour activity of three second-line treatment combinations in patients with metastatic colorectal cancer after optimal 5-FU regimen failure: a randomised, multicentre phase II study
Authors: P. Rougier, D. Lepille, J. Bennouna, A. Marre, M. Ducreux, L. Mignot, A. Hua, D. Méry-Mignard
Journal: Annals of Oncology (2002)
Evolutionary Origins of a Novel Host Plant Detoxification Gene in Butterflies
Authors: Hanna M Fischer, Christopher W Wheat, David G Heckel, Heiko Vogel
Journal: Molecular Biology and Evolution (2008)

Chemical interactions between plants and their insect herbivores provide an excellent opportunity to study the evolution of species interactions on a molecular level. Here, we investigate the molecular evolutionary events that gave rise to a novel detoxifying enzyme (nitrile-specifier protein [NSP]) in the butterfly family Pieridae, previously identified as a coevolutionary key innovation. By generating and sequencing expressed sequence tags, genomic libraries, and screening databases we found NSP to be a member of an insect-specific gene family, which we characterized and named the NSP-like gene family. Members consist of variable tandem repeats, are gut expressed, and are found across Insecta evolving in a dynamic, ongoing birth-death process. In the Lepidoptera, multiple copies of single-domain major allergen genes are present and originate via tandem duplications. Multiple domain genes are found solely within the brassicaceous-feeding Pieridae butterflies, one of them being NSP and another called major allergen (MA). Analyses suggest that NSP and its paralog MA have a unique single-domain evolutionary origin, being formed by intragenic domain duplication followed by tandem whole-gene duplication. Duplicates subsequently experienced a period of relaxed constraint followed by an increase in constraint, perhaps after neofunctionalization. NSP and its ortholog MA are still experiencing high rates of change, reflecting a dynamic evolution consistent with the known role of NSP in plant-insect interactions. Our results provide direct evidence to the hypothesis that gene duplication is one of the driving forces for speciation and adaptation, showing that both within- and whole-gene tandem duplications are a powerful force underlying evolutionary adaptation.
Health Benefits of Long-Term Weight-Loss Maintenance
Authors: Christian F. Rueda-Clausen, Ayodele A. Ogunleye, Arya M. Sharma
Journal: Annual Review of Nutrition (2015)

Obesity is a chronic and complex medical condition associated with a large number of complications affecting most organs and systems through multiple pathways. Strategies for weight management include behavioral, pharmacological, and surgical interventions, all of which can result in a reduction in obesity-related comorbidities and improvements in quality of life. However, subsequent weight regain often reduces the durability of these improvements. The objective of this article is to review evidence supporting the long-term effects of intentional weight loss on morbidity, mortality, quality of life, and health-care cost. Overall, considerable evidence suggests that intentional weight loss is associated with clinically relevant benefits for the majority of obesity-related comorbidities. However, the degree of weight loss that must be achieved and sustained to reap these benefits varies widely between comorbidities.
Optimal Pathologic Staging: Defining Stage II Disease
Authors: Carolyn C. Compton
Journal: Clinical Cancer Research (2007)

Abstract Tumor stage remains the most important determinant of prognosis in colorectal cancer and is the basis of all authoritative patient management guidelines. The pathologic assessment of stage II disease is especially critical because it may help to identify patients at additional risk for whom surgery alone may not be curative. Accurate analysis of regional lymph nodes, extent of tumor penetration, and circumferential resection margins constitute the most crucial issues. For assignment of pN0, adequacy of the surgical resection and thoroughness of the lymph node harvest from the resection specimen are both essential. The minimum number of lymph nodes has been variably determined to be between 12 and 18 for assignment of pN0, but the confidence level increases with increasing numbers of nodes examined. The ability of exhaustive analysis of sentinel lymph nodes using special techniques to substitute for an exhaustive lymph node harvest and standard node examination has not been definitively shown. Although special techniques may facilitate the identification of minute amounts of tumor (i.e., isolated tumor cells) in regional lymph nodes, the prognostic significance of such findings remains unclear. Additional stage-independent pathologic features that have been validated as adverse prognostic factors include involvement by tumor of mural lymphovascular channels, venous vessels, or the surgical resection margin of the operative specimen and high tumor grade. The presence of these features may help to identify patients for whom surgery alone will not be curative and adjuvant therapies may be appropriate.
Upregulation of Fas-signalling molecules in lung epithelial cells from patients with idiopathic pulmonary fibrosis
Authors: T. Maeyama, K. Kuwano, M. Kawasaki, R. Kunitake, N. Hagimoto, T. Matsuba, M. Yoshimi, I. Inoshima, K. Yoshida, N. Hara
Journal: European Respiratory Journal (2001)

The caspase cascade is an executioner of apoptosis, mediated by Fas. Fas-associating protein with death domain (FADD) interacts with Fas and initiates apoptosis through activating caspase-8. It has previously been demonstrated that the Fas-Fas ligand pathway may be involved in the pathophysiology of idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate Fas-signalling molecules in epithelial cells in IPF. The immunohistochemistry for FADD and caspase-1 and -3 and terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick endlabelling (TUNEL) methods were performed in lung tissues from 10 patients with IPF obtained by thoracoscopic biopsy and in seven normal lung parenchyma specimens. The induction of caspases expression and activation by Fas-ligation on lung epithelial cell line A549 was also investigated. The immunoreactivity grade for FADD and caspase-1 and -3, and positive signals for TUNEL were significantly increased in epithelial cells of IPF compared with controls. Fas-ligation induced upregulation of caspase-1 and -3 expression in the nucleus and cytoplasm in A549 cells. Procaspase-1, -3, and -8 were activated in apoptotic cells, but not in viable cells. Although direct measurement of the caspase activity in lung epithelial cells of idiopathic pulmonary fibrosis could not be made, these results suggest that the Fas-signalling pathway is upregulated in lung epithelial cells of idiopathic pulmonary fibrosis.
Abnormal Cytokinesis after X-Irradiation in Tumor Cells that Override the G2 DNA Damage Checkpoint
Authors: Haomin Huang, Lynda Fletcher, Neil Beeharry, Rene Daniel, Gary Kao, Tim J. Yen, Ruth J. Muschel
Journal: Cancer Research (2008)

Abstract X-irradiation–induced DNA damage perturbs the G1, S, and G2 phases of the cell cycle. The behavior of cells after they have experienced a DNA damage checkpoint delay is poorly characterized. We therefore examined the fates of irradiated tumor cells that have overcome a prolonged G2 checkpoint delay. Most irradiated cells progressed through mitosis without significant delay, but failed to complete cytokinesis as they remained tethered to each other at the midbody. We observed that the movement of centrioles at the time of cytokinesis was impaired in the irradiated, bridged cells. We attribute the perturbation of centriole dynamics to the presence of chromatin bridges that spanned the daughter cells. The bridged cells exhibited different fates that included death, fusion that formed multinucleated cells, or another round of mitosis with no noticeable cell cycle delays. The presence of γH2AX foci in the bridge as well as in the separated nuclei indicated that cells were proliferating despite the presence of DNA damage. It seems that DNA damage checkpoints were not reactivated in cells that overrode a prolonged G2 delay. Cells deficient in ATM, H2AX, XRCC3, or ligase 4 exhibited a higher frequency of radiation-induced bridges than controls, suggesting that the DNA bridges resulted from inadequate DNA repair. These data show a previously unappreciated cytologic hallmark of DNA damage in dividing cells. Chromatin bridges that interfere with cytokinesis are likely to contribute to the replication failure and clonogenic death of cells exposed to irradiation. [Cancer Res 2008;68(10):3724–32]
Examination of Msh6- and Msh3-deficient Mice in Class Switching Reveals Overlapping and Distinct Roles of MutS Homologues in Antibody Diversification
Authors: Ziqiang Li, Stefan J. Scherer, Diana Ronai, Maria D. Iglesias-Ussel, Jonathan U. Peled, Philip D. Bardwell, Min Zhuang, KyeRyoung Lee, Alberto Martin, Winfried Edelmann, Matthew D. Scharff
Journal: The Journal of Experimental Medicine (2004)

Somatic hypermutation and class switch recombination (CSR) contribute to the somatic diversification of antibodies. It has been shown that MutS homologue (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base substitutions in somatic hypermutation. However, their roles in CSR have not yet been reported. Here we show that Msh6−/− mice have a decrease in CSR, whereas Msh3−/− mice do not. When switch regions were analyzed for mutations, deficiency in Msh6 was associated with an increase in transition mutations at G/C basepairs, mutations at RGYW/WRCY hotspots, and a small increase in the targeting of G/C bases. In addition, Msh6−/− mice exhibited an increase in the targeting of recombination sites to GAGCT/GGGGT consensus repeats and hotspots in Sγ3 but not in Sμ. In contrast to Msh2−/− mice, deficiency in Msh6 surprisingly did not change the characteristics of Sμ-Sγ3 switch junctions. However, Msh6−/− mice exhibited a change in the positioning of Sμ and Sγ3 junctions. Although none of these changes were seen in Msh3−/− mice, they had a higher percentage of large inserts in their switch junctions. Together, our data suggest that MutS homologues Msh2, Msh3, and Msh6 play overlapping and distinct roles during antibody diversification processes.
Therapeutic advancement of chronic lymphocytic leukemia
Authors: Kang Lu, Xin Wang
Journal: Journal of Hematology & Oncology (2012)

Despite the combinations of chemotherapy with monoclonal antibodies have further improved response rates, chronic lymphocytic leukemia (CLL) remains an incurable disease with an extremely variable course. This article reviews the ongoing clinical advances in the treatment of CLL in both previously untreated and relapsed disease and focuses on the benefit of different therapeutic strategies, the most effective therapy combinations and the potential activity of novel agents. Novel agents and combination therapies have been investigated by several studies in both the upfront and relapsed setting, particularly for patients with 17p deletion, TP53 mutation and fludarabine-refractory CLL. While these agents and combination therapies have improved initial response rates, ongoing studies are continued to determine and improve the efficacy and safety. Despite advancements in the treatment of CLL have led to high response rates, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option and reduced-intensity conditioning (RIC) allo-HSCT must be strongly considered whenever feasible. As such, ongoing studies of these agents and other novel approaches in clinical development are needed to expand and improve treatment options for CLL patients.
Safety of Revaccination With Pneumococcal Polysaccharide Vaccine
Authors: L A Jackson, P Benson, V P Sneller, J C Butler, R S Thompson, R T Chen, L S Lewis, G Carlone, F DeStefano, P Holder, T Lezhava, W W Williams
Journal: JAMA (1999)

Revaccination of healthy adults with pneumococcal polysaccharide vaccine (PPV) within several years of first vaccination has been associated with a higher than expected frequency and severity of local injection site reactions. The risk of adverse events associated with revaccination of elderly and chronically ill persons 5 or more years after first vaccination, as is currently recommended, has not been well defined.To determine whether revaccination with PPV at least 5 years after first vaccination is associated with more frequent or more serious adverse events than those following first vaccination.Comparative intervention study conducted between April 1996 and August 1997.Persons aged 50 to 74 years either who had never been vaccinated with PPV (n = 901) or who had been vaccinated once at least 5 years prior to enrollment (n = 513).PPV vaccination.Postvaccination local injection site reactions and prevaccination concentrations of type-specific antibodies.Those who were revaccinated were more likely than those who received their first vaccinations to report a local injection site reaction of at least 10.2 cm (4 in) in diameter within 2 days of vaccination: 11% (55/513) vs 3% (29/901) (relative risk [RR], 3.3; 95% confidence interval [CI], 2.1-5.1). These reactions resolved by a median of 3 days following vaccination. The highest rate was among revaccinated patients who were immunocompetent and did not have chronic illness: 15% (33/228) compared with 3% (10/337) among comparable patients receiving their first vaccinations (RR, 4.9; 95% CI, 2.4-9.7). The risk of these local reactions was significantly correlated with prevaccination geometric mean antibody concentrations.Physicians and patients should be aware that self-limited local injection site reactions occur more frequently following revaccination compared with first vaccination; however, this risk does not represent a contraindication to revaccination with PPV for recommended groups.
Smoking is associated with urinary albumin excretion: an evaluation of premenopausal patients with type 2 diabetes mellitus
Authors: Futoshi Anan, Takayuki Masaki, Naohiko Takahashi, Mikiko Nakagawa, Hidetoshi Yonemochi, Nobuoki Eshima, Tetsunori Saikawa, Hironobu Yoshimatsu
Journal: Metabolism (2007)
Infectious complications associated with the use of CPAP in patients with sleep apnea-hipopnea sindrome
Authors: Trinidad Silvente Zamora, Pedro Méndez Martínez, Carlos Máximo Verde Colinas, Jose Antonio Ros Lucas, Francisco José Ruiz López, José Hernández Martínez, María Carmen Abellán Martínez, María Cristina Contessotto Avilés, María Jesús Avilés Inglés, Damián Malia Alvarado, José Carlos Vicente López, Inés Vergara Lahuerta, Roberto Bernabeu Mora, Ana María García Medina, Pedro Castell Gallud
Journal: European Respiratory Journal (2012)

INTRODUCTION  CPAP systems can be contaminated by microbes, increasing the risk of respiratory infections. Humidifiers can add a higher risk. Our study evaluates upper respiratory tract colonization and respiratory diseases related to CPAP with or without humidifier.  METHOLOGY  A Prospective study was designed. 100 CPAP-users were randomized: Group A (CPAP without humidifier): 50 patients (41 men, 9 women) between 28 and 87 years (average, 55). GROUP B (CPAP with humidifier): 50 patients (43 men, 7 women) between 41 and 98 years (average, 62). Patients were instructed on good hygienic practices in maintaining their systems. They were asked about respiratory infection symptoms. Swabs were taken from pharyngeal exudates in all patient, and from masks and tubes in Group B.  RESULTS  16 Pharyngeal exudates cultures were positive in Group A and 5 in Group B (32% versus 5%). Results:  Streptococcus group G  6 patients in Group A;  Streptococcus pyogenes group A : 6 in Group A and 1 in Group B;  Streptococcus beta-hemolytic group C:  3 in Group A, 2 in Group B;  Staphylococcus aureus  : 1 in Group A;  Streptococcus group C:  2 in Group B. Respiratory infection symptoms: 3 patients in Group A, 5 in Group B (6% versus 10%). Swabs from masks and tubes in Group B: 31 polymicrobial flora, 2 multiple fungal flora, 3  Turolopsis candida , 1  Aeromona hidrophila , 1  Rodotora rubra , 1  Serratia marcensis  and 1  Pseudomona aeruginosa .  CONCLUSIONS  Upper respiratory airways colonisation has been lower in the humidifier group, even though CPAP systems contamination has been common. Respiratory infection symptoms were low in both groups. Humidifiers have not significantly increased infections.
Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities
Authors: Elizabeth A. Maher, Cameron Brennan, Patrick Y. Wen, Laura Durso, Keith L. Ligon, Aaron Richardson, Deepak Khatry, Bin Feng, Raktim Sinha, David N. Louis, John Quackenbush, Peter McL. Black, Lynda Chin, Ronald A. DePinho
Journal: Cancer Research (2006)

Glioblastoma is classified into two subtypes on the basis of clinical history: "primary glioblastoma" arising de novo without detectable antecedent disease and "secondary glioblastoma" evolving from a low-grade astrocytoma. Despite their distinctive clinical courses, they arrive at an indistinguishable clinical and pathologic end point highlighted by widespread invasion and resistance to therapy and, as such, are managed clinically as if they are one disease entity. Because the life history of a cancer cell is often reflected in the pattern of genomic alterations, we sought to determine whether primary and secondary glioblastomas evolve through similar or different molecular pathogenetic routes. Clinically annotated primary and secondary glioblastoma samples were subjected to high-resolution copy number analysis using oligonucleotide-based array comparative genomic hybridization. Unsupervised classification using genomic nonnegative matrix factorization methods identified three distinct genomic subclasses. Whereas one corresponded to clinically defined primary glioblastomas, the remaining two stratified secondary glioblastoma into two genetically distinct cohorts. Thus, this global genomic analysis showed wide-scale differences between primary and secondary glioblastomas that were previously unappreciated, and has shown for the first time that secondary glioblastoma is heterogeneous in its molecular pathogenesis. Consistent with these findings, analysis of regional recurrent copy number alterations revealed many more events unique to these subclasses than shared. The pathobiological significance of these shared and subtype-specific copy number alterations is reinforced by their frequent occurrence, resident genes with clear links to cancer, recurrence in diverse cancer types, and apparent association with clinical outcome. We conclude that glioblastoma is composed of at least three distinct molecular subtypes, including novel subgroups of secondary glioblastoma, which may benefit from different therapeutic strategies.
Gemcitabine plus etoposide in chemonaive extensive disease small-cell lung cancer: A multi-centre phase II study
Authors: J. Vansteenkiste, U. Gatzemeier, C. Manegold, A. Hanauske, P. Weynants, L. Bosquée, J. Blatter, K. Mansouri, J. von Pawel
Journal: Annals of Oncology (2001)
A Modest Proposal: A Vow of Chastity for Single Physicians in Remote Areas?
Authors: Philip Chan
Journal: JAMA (1992)

<h3>To the Editor.</h3> —In "Sexual Misconduct in the Practice of Medicine,"<sup>1</sup>the Council on Ethical and Judicial Affairs of the American Medical Association concluded that "(1) sexual contact or a romantic relationship concurrent with the physician-patient relationship is unethical; (2) sexual contact or romantic relationship with a former patient may be unethical under certain circumstances." Before initiating a genuine dating or romantic relationship, "a physician's minimum duty would be to terminate his or her professional relationship with the patient." Although the overall intentions of the guidelines are unassailable, it places peculiar restrictions on some unmarried medical practitioners serving remote communities. In some circumstances, a single individual may be the only physician serving a large geographic area. A high percentage of people in that catchment area would be bona fide patients of such a physician. Termination of the professional relationship with anyone in that community could leave that person
Haemolytic Streptococcus Gangrene
Authors: B.S. Simpson
Journal: BMJ (1936)

fDiCAL JOV,,?(AL was tested for agglutinins against pneumococci and streptococci.No agglutinins were detected at the beginning of this course, but now, after four doses, his blood shows agglutinins for pneumococci in 1 in 40 dilution, and for streptococci in 1 in 80 dilution, thus indicating a definite agglutination response after the oral administration of such a combined vaccine.No toxic symptoms were observed with these doses at weekly intervals.
Temporary Treatment of Prepubescent Rats with Angiotensin Inhibitors Suppresses the Development of Hypertensive Nephrosclerosis
Authors: Hideaki Nakaya, Hiroyuki Sasamura, Matsuhiko Hayashi, Takao Saruta
Journal: Journal of the American Society of Nephrology (2001)

Hypertensive nephrosclerosis is a leading cause of end-stage renal disease; therefore, strategies to prevent the development of renal disease require close study. Here it is demonstrated that transient treatment of prepubescent rats with angiotensin inhibitors attenuated their susceptibility to the development of hypertensive nephrosclerosis after maturation. Stroke-prone spontaneously hypertensive Izumo strain rats were divided into four groups, treated with vehicle, the angiotensin-converting enzyme inhibitor (ACEI) delapril (40 mg/kg per d), the angiotensin receptor antagonist (AT1R-Ant) candesartan cilexetil (1 mg/kg per d), or the vasodilator hydralazine (25 mg/kg per d) from weaning to puberty (3 to 10 wk of age), and then monitored without treatment for 6 mo. BP in the ACEI- and AT1R-Ant-treated groups remained significantly decreased, compared with the untreated and hydralazine-treated groups. Moreover, marked proteinuria and nephrosclerosis developed in the untreated and hydralazine-treated groups at 30 wk but were suppressed in the ACEI- and AT1R-Ant-treated groups. Of interest, plasma renin activity, plasma angiotensin II concentrations, and renal renin mRNA levels were reduced by >50% in the ACEI- and AT1R-Ant-treated rats, suggesting that the treatments may have attenuated the development of nephrosclerosis by overcoming the susceptibility of stroke-prone spontaneously hypertensive rats to overactivation of the renin-angiotensin system.