tbuckley/cabot-search huggingface dataset:
DNA Repair: a Double-Edged Sword
Authors: Qingyi Wei, Marsha L. Frazier, Bernard Levin
Journal: JNCI Journal of the National Cancer Institute (2000)

It has been estimated that there is a 90% overlap between mutagenicity and carcinogenicity of environmental chemicals (1) and that environmental exposure to carcinogens contributes to the development of more than 80% of human cancers (2). Cancer is also considered to be a genetic disease because genetic alterations at either chromosomal or gene levels have been identified in most cancers. In multistep carcinogenesis (3), initial damage to DNA may lead to tumorigenesis and/or carcinogenesis due to functional imbalance between oncogenes (4), tumor suppressor genes (5), and DNA repair genes (6), perhaps as a result of mutation fixation of the damage. During carcinogenesis, both endogenous and exogenous exposures to carcinogens or genotoxic agents cause cell cycle delays (7) that allow cells to repair DNA damage, suggesting that efficient DNA repair is central to maintaining normal cell cycle and growth. Evidence from molecular epidemiology supports the notion that DNA repair capacity is one of the determinants of genetic susceptibility to cancer (8). Individuals with defective DNA repair genes have up to 1000-fold increased risk for developing cancer . This is exemplified by the presence of defective nucleotide excision repair genes in xeroderma pigmentosum (9), defective mismatch repair genes in patients with hereditary nonpolyposis colon cancer (10), and defective BRCA1 and BRCA2 genes in breast cancer (11). This etiologic association between deficient DNA repair and increased cancer risk is also supported by evidence from studies of sporadic cancers of the skin (12), lung (13), colon (14), and breast (11). These data strongly suggest that it is important for normal tissues to have efficient DNA repair so as to eradicate DNA lesions caused by carcinogens, thereby reducing the risk of mutation fixation and subsequent development of cancer. Clues are beginning to emerge with regard to the mechanism by which defects in hMSH6, hMSH2, and hMLH1genes can give rise to resistance to chemotherapeutic agents. In humans, an hMSH2/hMSH6 heterodimer (MutSa) recognizes mismatches of DNA as well as insertion and deletion loops (15–17). It can also recognize damaged DNA base pairs containing Omethylguanine, O-methylthymine, or the cisplatin–d(GpG) adduct (18). hMSH2 also forms a heterodimer with hMSH3, and this complex (MutSb) mediates the repair of insertion and deletion loops (15–17). hMLH1 forms heterodimers with hPMS1, hPMS2, and hMLH3; however, at the present time, hMLH1/ hPMS2 (MutLa) is the only heterodimer for which there is evidence for participation in the mismatch repair function. The hMutLa protein forms a complex with hMutSa or hMutSb, and the repair complex directs the DNA repair process (16,17,19). Normally, the hMutLa–hMutSa complex triggers G2–M arrest followed by an apoptotic response in normal cells (20). It is thought that this is due, at least in part, to signaling by the complex that represents the first step in a damage-signaling cas-
A Teacher Rating Scale for Use in Drug Studies with Children
Authors: C. KEITH CONNERS
Journal: American Journal of Psychiatry (1969)

The author describes and emphasizes the value of a symptom and behavior rating checklist for teachers' use in drug studies with children. Factor analysis of the scale produced five factors that gave reliable subscales over a one-month period. A treatment study of dextroamphetamine with a group of children having learning and/or behavior disorders showed significant changes in all factors compared with a placebo group in a double-blind study.
Hemispheric laterality in animals and the effects of early experience
Authors: Victor H. Denenberg
Journal: Behavioral and Brain Sciences (1981)

Abstract A review of research with chicks, songbirds, rodents, and nonhuman primates indicates that the brain is lateralized for a number of behavioral functions. These findings can be understood in terms of three hypothetical brain processes derived from a brain model based on general systems theory: hemispheric activation, interhemispheric inhibition, and interhemispheric coupling. Left-hemisphere activation occurs in songbirds and nonhuman primates in response to salient auditory or visual input, or when a communicative output is required. The right hemisphere is activated in rats when spatial performance is required, and in chicks when they are placed in an emotion-provoking situation. In rats and chicks interhemispheric activation and inhibition occur when there is an affective component in the environment (novelty, aversive conditioning) or when an emotional response is emitted (copulation, attack, killing). An interhemispheric coupling (correlation) found in rats and rabbits implies that the hemispheres are two major components in a control system with a negative feedback loop. Early-experience variables in rats can induce laterality in a symmetric brain or facilitate its development in an already biased brain. It is predicted that functional lateralization, when present, will be similar across species: the left hemisphere will tend to be involved in communicative functions while the right hemisphere will respond to spatial and affective information; both hemispheres will often interact via activation-inhibition mechanisms when affective or emotional processes are involved. Homologous brain areas and their connecting callosal fibers must be intact at birth and must remain intact throughout development for lateralization to reach its maximum level. Injury to any portion of this unit will result in hemispheric redundancy rather than specialization. One major function of early experience is to provide stimulation during development, which acts to enhance the growth and development of the corpus callosum, thereby giving rise to a more specialized brain.
A Case of Fulminant Type 1 Diabetes With Strong Evidence of Autoimmunity
Authors: Akira Shimada, Yoichi Oikawa, Toshikatsu Shigihara, Tomoko Senda, Keiichi Kodama
Journal: Diabetes Care (2002)

We have recently reported (1) that T-cell autoimmunity may be involved in so-called “fulminant” type 1 diabetes (characterized by diabetic ketoacidosis [DKA], low HbA1c level at onset, insulin deficiency, and negative islet-associated autoantibodies), which was originally proposed as a novel subtype of type 1B diabetes (2). In our previous report (1), we found a high serum level of interferon-inducible protein-10 (IP-10), an important chemokine inducing migration of activated T-cells to local lesions (3), and GAD-reactive CD4+ cells in the periphery of a patient, even though no islet-associated antibody was detected.

Here, we report another case of fulminant type 1 diabetes, a 48-year-old man who was proven to have not only a high serum IP-10 level and GAD-reactive CD4+ cells in the periphery but also …
Phytophthora capsici-tomato interaction features dramatic shifts in gene expression associated with a hemi-biotrophic lifestyle
Authors: Julietta Jupe, Remco Stam, Andrew JM Howden, Jenny A Morris, Runxuan Zhang, Pete E Hedley, Edgar Huitema
Journal: Genome biology (2013)

Abstract Background Plant-microbe interactions feature complex signal interplay between pathogens and their hosts. Phytophthora species comprise a destructive group of fungus-like plant pathogens, collectively affecting a wide range of plants important to agriculture and natural ecosystems. Despite the availability of genome sequences of both hosts and microbes, little is known about the signal interplay between them during infection. In particular, accurate descriptions of coordinate relationships between host and microbe transcriptional programs are lacking. Results Here, we explore the molecular interaction between the hemi-biotrophic broad host range pathogen Phytophthora capsici and tomato. Infection assays and use of a composite microarray allowed us to unveil distinct changes in both P. capsici and tomato transcriptomes, associated with biotrophy and the subsequent switch to necrotrophy. These included two distinct transcriptional changes associated with early infection and the biotrophy to necrotrophy transition that may contribute to infection and completion of the P. capsici lifecycle Conclusions Our results suggest dynamic but highly regulated transcriptional programming in both host and pathogen that underpin P. capsici disease and hemi-biotrophy. Dynamic expression changes of both effector-coding genes and host factors involved in immunity, suggests modulation of host immune signaling by both host and pathogen. With new unprecedented detail on transcriptional reprogramming, we can now explore the coordinate relationships that drive host-microbe interactions and the basic processes that underpin pathogen lifestyles. Deliberate alteration of lifestyle-associated transcriptional changes may allow prevention or perhaps disruption of hemi-biotrophic disease cycles and limit damage caused by epidemics.
The specificity of the diffuse pattern of cardiac uptake in myocardial infarction imaging with technetium-99m stannous pyrophosphate.
Authors: R Prasquier, M R Taradash, E H Botvinick, D M Shames, W W Parmley
Journal: Circulation (1977)

To analyze the specificity of the diffuse pattern of cardiac uptake with technetium-99m stannous pyrophosphate (TcPYP), we evaluated the bone scans of 1,383 noncardiac patients and the myocardial scintigrams of 120 cardiac patients. Seventy (14.4%) of 483 bone scans performed on a scintillation camera revealed diffuse TcPYP cardiac uptake. Among the total 603 camera bone scans and myocardial scintigrams, the incidence of diffuse cardiac uptake was 16% among patients with clinical coronary disease but 13% among those patients without clinical symptoms. Discrete myocardial uptake was seen in 25 of 26 patients with transmural infarction. Femoral vasculature was more frequently visualized (84% vs 3%, P less than 0.001) and left mastectomy occurred more often (30% vs 1%, P less than 0.001) among patients with diffuse cardiac uptake than among patients with negative images, indicating possible blood pool imaging. The diffuse pattern of cardiac uptake appeared nonspecific and may be due to unintentional cardiac blood pool imaging.
Validity of Prototype Diagnosis for Mood and Anxiety Disorders
Authors: Jared A DeFife, Joanne Peart, Bekh Bradley, Kerry Ressler, Rebecca Drill, Drew Westen
Journal: JAMA Psychiatry (2012)

CONTEXT With growing recognition that most forms of psychopathology are best represented as dimensions or spectra, a central question becomes how to implement dimensional diagnosis in a way that is empirically sound and clinically useful. Prototype matching, which involves comparing a patient's clinical presentation with a prototypical description of the disorder, is an approach to diagnosis that has gained increasing attention with forthcoming revisions to both the DSM and the International Classification of Diseases. OBJECTIVE To examine prototype diagnosis for mood and anxiety disorders. DESIGN, SETTING, AND PATIENTS In the first study, we examined clinicians' DSM-IV and prototype diagnoses with their ratings of the patients' adaptive functioning and patients' self-reported symptoms. In the second study, independent interviewers made prototype diagnoses following either a systematic clinical interview or a structured diagnostic interview. A third interviewer provided independent ratings of global adaptive functioning. Patients were recruited as outpatients (study 1; N = 84) and from primary care clinics (study 2; N = 143). MAIN OUTCOME MEASURES Patients' self-reported mood, anxiety, and externalizing symptoms along with independent clinical ratings of adaptive functioning. RESULTS Clinicians' prototype diagnoses showed small to moderate correlations with patient-reported psychopathology and performed as well as or better than DSM-IV diagnoses. Prototype diagnoses from independent interviewers correlated on average r = .50 and showed substantial incremental validity over DSM-IV diagnoses in predicting adaptive functioning. CONCLUSIONS Prototype matching is a viable alternative for psychiatric diagnosis. As in research on personality disorders, mood and anxiety disorder prototypes outperformed DSM-IV decision rules in predicting psychopathology and global functioning. Prototype matching has multiple advantages, including ease of use in clinical practice, reduced artifactual comorbidity, compatibility with naturally occurring cognitive processes in diagnosticians, and ready translation into both categorical and dimensional diagnosis.
Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register
Authors: E M Camacho, M Harrison, T M Farragher, M Lunt, D K Bunn, S M M Verstappen, D P M Symmons
Journal: Annals of the Rheumatic Diseases (2011)

Objective To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). Methods 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. Results 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16–35). Parous women had significantly lower HAQ scores over time than nulliparous women (−0.19, 95% CI −0.32 to −0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. Conclusion Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.
Phase II Randomized Study of Figitumumab plus Docetaxel and Docetaxel Alone with Crossover for Metastatic Castration-Resistant Prostate Cancer
Authors: Johann S. de Bono, Josep M. Piulats, Hardev S. Pandha, Daniel P. Petrylak, Fred Saad, Luis Miguel A. Aparicio, Shahneen K. Sandhu, Peter Fong, Silke Gillessen, Gary R. Hudes, Tao Wang, Judith Scranton, Michael N. Pollak
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Figitumumab is a human IgG2 monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R), with antitumor activity in prostate cancer. This phase II trial randomized chemotherapy-naïve men with progressing castration-resistant prostate cancer to receive figitumumab every 3 weeks with docetaxel/prednisone (Arm A) or docetaxel/prednisone alone (Arm B1). At progression on Arm B1, patients could cross over to the combination (Arm B2). Experimental Design: Prostate-specific antigen (PSA) response was the primary endpoint; response assessment on the two arms was noncomparative and tested separately; H0 = 0.45 versus HA = 0.60 (α = 0.05; β = 0.09) for Arm A; H0 = 0.05 versus HA = 0.20 (α = 0.05, β = 0.10) for Arm B2. A comparison of progression-free survival (PFS) on Arms A and B1 was planned. Results: A total of 204 patients were randomized and 199 treated (Arm A: 97; Arm B1: 102); 37 patients crossed over to Arm B2 (median number of cycles started: Arm A = 8; B1 = 8; B2 = 4). PSA responses occurred in 52% and 60% of Arms A and B1, respectively; the primary PSA response objective in Arm A was not met. Median PFS was 4.9 and 7.9 months, respectively (HR = 1.44; 95% confidence interval, 1.06–1.96). PSA response rate was 28% in Arm B2. The figitumumab combination appeared more toxic, with more treatment-related grade 3/4 adverse events (75% vs. 56%), particularly hyperglycemia, diarrhea, and asthenia, as well as treatment-related serious adverse events (41% vs. 15%), and all-causality grade 5 adverse events (18% vs. 8%). Conclusion: IGF-1R targeting may merit further evaluation in this disease in selected populations, but combination with docetaxel is not recommended. Clin Cancer Res; 20(7); 1925–34. ©2014 AACR.
Does This Dyspneic Patient in the Emergency Department Have Congestive Heart Failure?
Authors: Charlie S Wang, J Mark FitzGerald, Michael Schulzer, Edwin Mak, Najib T Ayas
Journal: JAMA (2005)

ContextDyspnea is a common complaint in the emergency department where physicians must accurately make a rapid diagnosis.ObjectiveTo assess the usefulness of history, symptoms, and signs along with routine diagnostic studies (chest radiograph, electrocardiogram, and serum B-type natriuretic peptide [BNP]) that differentiate heart failure from other causes of dyspnea in the emergency department.Data SourcesWe searched MEDLINE (1966-July 2005) and the reference lists from retrieved articles, previous reviews, and physical examination textbooks.Study SelectionWe retained 22 studies of various findings for diagnosing heart failure in adult patients presenting with dyspnea to the emergency department.Data ExtractionTwo authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality.Data SynthesisMany features increased the probability of heart failure, with the best feature for each category being the presence of (1) past history of heart failure (positive LR = 5.8; 95% confidence interval [CI], 4.1-8.0); (2) the symptom of paroxysmal nocturnal dyspnea (positive LR = 2.6; 95% CI, 1.5-4.5); (3) the sign of the third heart sound (S3) gallop (positive LR = 11; 95% CI, 4.9-25.0); (4) the chest radiograph showing pulmonary venous congestion (positive LR = 12.0; 95% CI, 6.8-21.0); and (5) electrocardiogram showing atrial fibrillation (positive LR = 3.8; 95% CI, 1.7-8.8). The features that best decreased the probability of heart failure were the absence of (1) past history of heart failure (negative LR = 0.45; 95% CI, 0.38-0.53); (2) the symptom of dyspnea on exertion (negative LR = 0.48; 95% CI, 0.35-0.67); (3) rales (negative LR = 0.51; 95% CI, 0.37-0.70); (4) the chest radiograph showing cardiomegaly (negative LR = 0.33; 95% CI, 0.23-0.48); and (5) any electrocardiogram abnormality (negative LR = 0.64; 95% CI, 0.47-0.88). A low serum BNP proved to be the most useful test (serum B-type natriuretic peptide &lt;100 pg/mL; negative LR = 0.11; 95% CI, 0.07-0.16).ConclusionsFor dyspneic adult emergency department patients, a directed history, physical examination, chest radiograph, and electrocardiography should be performed. If the suspicion of heart failure remains, obtaining a serum BNP level may be helpful, especially for excluding heart failure.
Multiple disturbances of free fatty acid metabolism in noninsulin-dependent diabetes. Effect of oral hypoglycemic therapy.
Authors: M R Taskinen, C Bogardus, A Kennedy, B V Howard
Journal: Journal of Clinical Investigation (1985)

To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free fatty acid appears to be closely related to diabetic control. Furthermore, the increase in fractional clearance rate, despite a marked decrease in lipid oxidation, suggests that the clearance defect in the diabetics is due to an impairment in reesterification, which is restored after therapy.
Possible applications of a non-contact 1.48 μm wavelength diode laser in assisted reproduction technologies
Authors: T Ebner, M Moser, G Tews
Journal: Human Reproduction Update (2005)

Recently, one laser system has been introduced in IVF fulfilling all safety requirements, while achieving a high standard of reproducibility in terms of ablation diameter. This 1.48 μm wavelength indium-gallium-arsenic-phosphorus (InGaAsP) semiconductor laser offers a variety of laser applications to the embryologist. On the one hand, zona pellucida of oocytes or embryos can be manipulated in order to facilitate ICSI or biopsy and assist hatching, and on the other, spermatozoa may be paralysed or immobilized prior to usage. To conclude, the 1.48 μm diode laser provides a promising tool for the microdissection of subcellular targets. The diode laser stands out due to the rapidity, the simplicity and the safety of the procedure which is supported by healthy offspring after laser application.
Salaries and Cardiographers
Authors: S. Nevin
Journal: BMJ (1966)

p. 1482) questions the factual basis for my tentative conclusion (21 May, p. 1301) that general practice may be the most appropriate setting for conducting clinical trials.Two types of defaulting in respect of adherence to treatment schedules must be distinguished, and perhaps should have been distinguished in my original letter.The first group are the " overt defaulters," and the second the " occult defaulters."The former fail to complete the trial for reasons which are obvious to the doctor-for example, volunteering that they have stopped the tab- lets, leaving the district, failing to reattend, etc. Being readily identifiable, their presence can be allowed for in the final assessment.It is the " occult defaulters " who may, and probably usually do, invalidate a trial.This group, having persevered, may appear to the unwary to have been entirely consonant to the treatment schedule, but in fact they have been dissonant.If my figures are examined, bearing in mind this distinction, then it can be seen that out of 29 " completers " 22 (76%) were available for assessment, and that only three of these patients were suspected as being definite defaulters.Can these figures be matched by any hospital outpatient trial ?I am, etc., Camberley,
Adrenoceptor-mediated responses in human skin studied by iontophoresis
Authors: R. HORNOQVIST, O. BACK, R. HENRIKSSON
Journal: British Journal of Dermatology (1984)

The adrenoceptor-mediated responses in human skin (bnlanching and erythema) were studied by an iontophoretic technique. It is concluded that the receptors in superficial dermal blood vessels belong to the subclasses α1 and β2.