tbuckley/cabot-search huggingface dataset:
Isolated hapten-binding receptors of sensitized lymphocytes. II. Receptors from nylon wool-enriched rabbit T lymphocytes lack serological determinants of immunoglobulin constant domains but carry the A locus allotypic markers.
Authors: U Krawinkel, M Cramer, R G Mage, A S Kelus, K Rajewsky
Journal: The Journal of Experimental Medicine (1977)

Hapten-binding receptor material was isolated from sensitized rabbit lymphocytes by a method described previously for murine receptor material. The material was separated into a fraction expressing immunoglobulin determinants (anti-Ig+ fraction) and a fraction lacking known class and type-specific determinants of Ig constant domains (anti-Ig- fraction). We present evidence in support of the notion that--in analogy to the mouse system--the anti-Ig+ fraction is B-cell-derived, whereas the anti-Ig- fraction originates from T lymphocytes. Receptors of the anti-Ig- phenotype are found to express a locus allotypic determinants and, thus, appear to carry variable portions of immunoglobulin heavy chains.
Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype
Authors: Patrícia Henriques Domingues, Pablo Sousa, Álvaro Otero, Jesus Maria Gonçalves, Laura Ruiz, Catarina de Oliveira, Maria Celeste Lopes, Alberto Orfao, Maria Dolores Tabernero
Journal: Neuro-Oncology (2014)

Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse.
Increased plasma levels of the VEGF<sub>165</sub>b splice variant are associated with the severity of nailfold capillary loss in systemic sclerosis
Authors: Mirko Manetti, Serena Guiducci, Eloisa Romano, Silvia Bellando-Randone, Gemma Lepri, Cosimo Bruni, Maria Letizia Conforti, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

In systemic sclerosis (SSc), Raynaud's phenomenon is the earliest clinical manifestation paralleled by nailfold capillaroscopic alterations that may occur months or even years before the onset of fibrosis.1 This evidence suggests a crucial role of microangiopathy characterised by a progressive loss of capillaries with the formation of avascular areas.1 ,2 Consequent chronic tissue hypoxia leads to skin ulcers and gangrene that heavily burden patients’ quality of life.1 ,2 Vascular endothelial growth factor-A (VEGF-A) is overexpressed in SSc skin, and increased circulating levels of VEGF-A correlate with the severity of nailfold capillary loss.2–4 It has been demonstrated that the VEGF-A primary transcript can be alternatively spliced in its terminal exon, producing two distinct mRNA splice variants that are translated to the proangiogenic VEGF165 and antiangiogenic VEGF165b isoforms.5 These two isoforms bind to the tyrosine kinase receptor VEGFR-2 with the same affinity, but binding of VEGF165b results in an insufficient tyrosine phosphorylation/activation of VEGFR-2 and incomplete or transient downstream signalling, which lead to an impaired angiogenic response.5 ,6 Recently, we have provided the first evidence that dermal expression and plasma levels of VEGF165b are raised in SSc patients, and VEGF165b overexpression prevents SSc dermal microvascular endothelial …
Letter: Epipodophyllotoxin VP 16213 in acute non-lymphoblastic leukaemia.
Authors: F Cavalli, R Sonntag, K W Brunner
Journal: BMJ (1975)

jouRNAL 25 ocTOBER 1975 22?out accurate fracture reduction, and move- ment of bone within the wires can take place.In a bone as heavily stressed as the tibia this is almost impossible to avoid.In other situa- tions, as for instance the fibular component of certain ankle fracture-dislocations, they can be of very great value.It would be a pity for the appropriate use of encirclage wiring in fracture treatment to be discredited by further repetition of this long-standing misapprehension concerning the reasons for its failure when used inappropriately.
Bedside Capillary Glucose Monitoring in the General Hospital
Authors: Barbara Barr, Steven B Leichter, Lindley Taylor
Journal: Diabetes Care (1984)

We assessed the accuracy and reliability of capillary glucose monitoring (CGM) for 20 hospitalized patients as an alternative to repeated venipunctures for laboratory blood glucose (LBG) determination. A total of 330 pairs of observations was obtained. Pearson correlation between patient estimates using Chemstrip bG and the laboratory glucose-oxidase method was 0.87. The mean LBG determination was 197 +/- 5 mg/dl compared with 176.4 +/- 4.3 mg/dl for patient CGM estimates. The mean deviation was 17.6 +/- 2.9 mg/dl or 8.9%, which is well within the 20% range that is generally accepted as sufficiently accurate. Certain individual patients may require relatively more instruction and supervision to reliably carry out these measurements. These patients may represent 10-25% of all diabetic patients. Neither age nor years of schooling is a useful index to identify these patients. Therefore, we suggest as a routine that 10 or more CGM be checked against simultaneous LBG to confirm accuracy before relying on bedside CGM estimates alone in managing the hospitalized patient. Patients who can carry out CGM accurately may be managed with CGM alone.
Efficacy of Letrozole Extended Adjuvant Therapy According to Estrogen Receptor and Progesterone Receptor Status of the Primary Tumor: National Cancer Institute of Canada Clinical Trials Group MA.17
Authors: Paul E. Goss, James N. Ingle, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Dongsheng Tu, Lois E. Shepherd, Kathleen I. Pritchard, Robert B. Livingston, Nancy E. Davidson, Larry Norton, Edith A. Perez, Jeffrey S. Abrams, David A. Cameron, Michael J. Palmer, Joseph L. Pater
Journal: Journal of Clinical Oncology (2007)

Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR-than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status.Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy.The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgR-tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR-subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09).These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.
Low Rates of Physicians Counseling Adolescents About Smoking: a Critical Wake-Up Call
Authors: H. A. Lando, D. K. Hatsukami
Journal: JNCI Journal of the National Cancer Institute (1999)

The report by Thorndike et al. (1) in this issue of the Journal is an important wake-up call to physicians, academic teachers, and researchers. The overall results from this study are discouraging, especially given efforts in recent years to educate practicing physicians to identify and to treat smokers, to develop evidence-based guidelines for smoking cessation treatment (2), and to encourage the development of systems to identify smokers. Although smoking status was identified at approximately 70% of adolescent patient visits, counseling was provided at only 1.7% of all visits and 16.9% of visits of patients identified as smokers. Furthermore, and equally discouraging, there was no improvement in these percentages between 1991 through 1996 despite an article written in 1991 providing a guide for physicians on preventing tobacco use during childhood and adolescence (3). Also of concern was the finding that smoking is less likely to be addressed with minority patients. Intervention with adolescents is critical. Ninety percent of smokers initiate smoking in adolescence, with 70% of smokers becoming nicotine dependent before the age of 18 years (4). Physicians and other clinicians are missing a potentially vital teachable moment in failing to address smoking and other tobacco use in their adolescent patients. In the adult literature, even minimal treatment intervention of 3 minutes or less has been shown to increase treatment success by 20% (2). Effective intervention should involve identification and counseling of not only young smokers but also all adolescent patients. For never smokers, counseling should include strong encouragement not to start; for experimental smokers, it should include advice and support in avoiding the transition to regular smoking. In addi
Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
Authors: Alejandro V. Villarino, Cristina M. Tato, Jason S. Stumhofer, Zhengju Yao, Yongzhi K. Cui, Lothar Hennighausen, John J. O'Shea, Christopher A. Hunter
Journal: The Journal of Experimental Medicine (2007)

Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common gamma chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6. Collectively, these findings establish that IL-2 production is limited by a network of autocrine and paracrine signals that are readily available during acute inflammatory responses and, thus, provide a cellular and molecular basis for its transient pattern of expression.
<i>CHEK2</i>*1100delC Genotyping for Clinical Assessment of Breast Cancer Risk: Meta-Analyses of 26,000 Patient Cases and 27,000 Controls
Authors: Maren Weischer, Stig Egil Bojesen, Christina Ellervik, Anne Tybjærg-Hansen, Børge Grønne Nordestgaard
Journal: Journal of Clinical Oncology (2008)

Purpose CHEK2*1100delC heterozygosity may be associated with an increased risk of breast cancer; however, it is unclear whether the evidence is sufficient to recommend genotyping in clinical practice. Patients and Methods We identified studies on CHEK2*1100delC heterozygosity and the risk of unselected, early-onset, and familial breast cancer through comprehensive, computer-based searches of PubMed, EMBASE, and Web of Science. Aggregated risk estimates were compared with previous estimates for BRCA1 and BRCA2 mutation heterozygotes. Results By using fixed-effect models for CHEK2*1100delC heterozygotes versus noncarriers, we found aggregated odds ratios of 2.7 (95% CI, 2.1 to 3.4) for unselected breast cancer, 2.6 (95% CI, 1.3 to 5.5) for early-onset breast cancer, and 4.8 (95% CI, 3.3 to 7.2) for familial breast cancer. For familial breast cancer, this corresponds to a cumulative risk of breast cancer at age 70 years in CHEK2*1100delC heterozygotes of 37% (95% CI, 26% to 56%), which compares with similar previous estimates of 57% (95% CI, 47% to 66%) for BRCA1 mutation heterozygotes and 49% (95% CI, 40% to 57%) for BRCA2 mutation heterozygotes. Conclusion These meta-analyses emphasize that CHEK2*1100delC is an important breast cancer–predisposing gene, which increases the risk three- to five-fold. Because the cumulative risk of breast cancer at age 70 years among familial patient cases for CHEK2*1100delC heterozygotes is almost as high as that for BRCA1 and BRCA2 mutation heterozygotes, genotyping for CHEK2*1100delC should be considered together with BRCA1 and BRCA2 mutation screening in women with a family history of breast cancer.
Biorobotics researcher: To be or not to be?
Authors: Carolina Chang
Journal: Behavioral and Brain Sciences (2001)

Much confusion exists within the robotics and the biology communities regarding the definition of biorobotics and the aims and strategies that characterize this approach. Not even the basic criteria for identifying biorobotic research are being applied consistently. Barbara Webb has taken a crucial step towards setting a common ground from which biorobotic systems can be described, analyzed, and compared.
Quantitative analysis of intercellular connections by immunohistochemistry of the cardiac gap junction protein connexin43.
Authors: R A Luke, E C Beyer, R H Hoyt, J E Saffitz
Journal: Circulation Research (1989)

Polyclonal antisera directed against epitopes in the cytoplasmic domain of rat connexin43, the predominant cardiac gap junction protein, were used to delineate immunohistochemically the distribution of gap junctions in sections of canine left ventricle. Antigen-antibody binding and tissue structure were preserved after paraformaldehyde fixation and paraffin embedment of canine myocardium. Specific binding of antibody to the cytoplasmic surfaces of ultrastructurally identified gap junctions was confirmed with electron microscopy. Light microscopic morphometric analysis of immunostained sections in five separate experiments revealed a mean gap junction surface density of 0.0052 micron2/micron3 myocyte volume, which is consistent with previously reported values determined by use of quantitative electron microscopy. This new method permits quantitative determinations of gap junction surface density and distribution in relatively large heterogeneous areas of myocardium in which ultrastructural morphometry would be impractical. This approach should facilitate analysis of the relation between potential alterations in electrical coupling of myocytes and abnormalities of myocardial conduction occurring at the macroscopic scale in regions such as structurally heterogeneous infarct border zones.
Neurocognitive Effects of Clozapine, Olanzapine, Risperidone, and Haloperidol in Patients With Chronic Schizophrenia or Schizoaffective Disorder
Authors: Robert M Bilder, Robert S Goldman, Jan Volavka, Pal Czobor, Matthew Hoptman, Brian Sheitman, Jean-Pierre Lindenmayer, Leslie Citrome, Joseph McEvoy, Michal Kunz, Miranda Chakos, Thomas B Cooper, Terri L Horowitz, Jeffrey A Lieberman
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. METHOD: The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. RESULTS: Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. CONCLUSIONS: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.
Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102
Authors: Barbara Sennino, Beverly L. Falcón, Dilara McCauley, Tom Le, Thomas McCauley, Jeffrey C. Kurz, Amy Haskell, David M. Epstein, Donald M. McDonald
Journal: Cancer Research (2007)

Abstract Inhibition of platelet derived growth factor (PDGF) can increase the efficacy of other cancer therapeutics, but the cellular mechanism is incompletely understood. We examined the cellular effects on tumor vasculature of a novel DNA oligonucleotide aptamer (AX102) that selectively binds PDGF-B. Treatment with AX102 led to progressive reduction of pericytes, identified by PDGF receptor β, NG2, desmin, or α-smooth muscle actin immunoreactivity, in Lewis lung carcinomas. The decrease ranged from 35% at 2 days, 63% at 7 days, to 85% at 28 days. Most tumor vessels that lacked pericytes at 7 days subsequently regressed. Overall tumor vascularity decreased 79% over 28 days, without a corresponding decrease in tumor size. Regression of pericytes and endothelial cells led to empty basement membrane sleeves, which were visible at 7 days, but only 54% remained at 28 days. PDGF-B inhibition had a less pronounced effect on pancreatic islet tumors in RIP-Tag2 transgenic mice, where pericytes decreased 47%, vascularity decreased 38%, and basement membrane sleeves decreased 21% over 28 days. Taken together, these findings show that inhibition of PDGF-B signaling can lead to regression of tumor vessels, but the magnitude is tumor specific and does not necessarily retard tumor growth. Loss of pericytes in tumors is an expected direct consequence of PDGF-B blockade, but reduced tumor vascularity is likely to be secondary to pericyte regression. [Cancer Res 2007;67(15):7358–67]
Intracellular calcium and ventricular fibrillation. Studies in the aequorin-loaded isovolumic ferret heart.
Authors: Y Kihara, J P Morgan
Journal: Circulation Research (1991)

To elucidate the role of changes in [Ca2+]i in the induction of ventricular fibrillation (VF), Ca2+i signals, epicardial electrical potentials, and isovolumic left ventricular pressure were simultaneously recorded in isolated intact ferret hearts loaded with aequorin, a bioluminescent protein. When the preparations were perfused with 3 microM acetylstrophanthidin and 8 mM Ca2+, or with a low Na+ solution (18 mM Na+, 100 mM Li+), spontaneous transitions to the VF state were consistently observed within a short period of time. The initiation of spontaneous VF was preceded by development of a Ca2+i overload state, coincidental with the ascending phase of diastolic Ca2+i oscillations, and was followed by further elevation in Ca2+i levels, which were associated with augmented Ca2+i oscillations of a saw-toothed pattern. Pretreatment with 10 microM ryanodine, which blocked Ca2+i oscillations in the preparation, did not eliminate inducibility of VF by means of AC electrical stimulations; however, VF no longer occurred spontaneously, and the threshold for VF induction increased markedly. In the absence of a state of Ca2+i overload, spontaneous defibrillation occurred within a minute after the initiation of VF. We conclude that 1) VF can be induced in the absence of Ca2+i oscillations; however, 2) Ca2+i oscillations play a crucial role as a trigger for VF and therefore are an important determinant of the vulnerability to VF; and 3) the augmented Ca2+i oscillations after the transition to VF state may support the maintenance of this type of arrhythmia.