tbuckley/cabot-search huggingface dataset:
Effector cells in allelic H-2 class I-incompatible skin graft rejection.
Authors: T Ichikawa, E Nakayama, A Uenaka, M Monden, T Mori
Journal: The Journal of Experimental Medicine (1987)

The cellular mechanisms of skin graft rejection with allelic H-2 class I differences were studied by examining the effect on graft survival of in vivo administration of anti-Lyt-2.2 mAb, anti-L3T4 mAb, or both to recipient mice. The injections of anti-Lyt-2.2 mAb and anti-L3T4 mAb caused selective depletions of Lyt-2+ cells and L3T4+ cells, respectively. Injection of anti-Lyt-2.2 mAb significantly prolonged graft survival in 7 of 12 combinations of H-2D-end difference, but did not prolong graft survival in 5 other combinations of H-2D-end difference, or in 2 combinations of H-2K-end difference. Injection of anti-L3T4 mAb did not prolong graft survival in any combinations with class I difference tested. Injection of anti-L3T4 mAb plus anti-Lyt-2.2 mAb markedly prolonged graft survival in the combinations with class I difference in which anti-Lyt-2.2 mAb had no effect and overcame the effect of anti-Lyt-2.2 mAb in those in which anti-Lyt-2.2 mAb had an effect in prolonging graft survival. These results indicated that in combinations in which anti-Lyt-2.2 mAb did not prolong graft survival, class I antigen stimulated L3T4+ effector cells when Lyt-2+ cells were blocked and Lyt-2+ effector cells when L3T4+ cells were blocked. On the other hand, in the combinations in which anti-Lyt-2.2 mAb prolong graft survival, these antigens initially caused preferential stimulation of Lyt-2+ but not L3T4+ effector cells, although delayed activation of L3T4+ effector cells occurred when Lyt-2+ cells were blocked. Furthermore, a significant correlation was found between the effect of anti-Lyt-2.2 mAb in prolonging graft survival and the failure of recipient mice to produce H-2 antibody. These results can be taken as evidence that L3T4+ effector cells are not involved in the initial phase of graft rejection in these combinations.
Genome-Wide Interrogation Identifies <i>YAP1</i> Variants Associated with Survival of Small-Cell Lung Cancer Patients
Authors: Chen Wu, Binghe Xu, Peng Yuan, Xiaoping Miao, Yu Liu, Yin Guan, Dianke Yu, Jian Xu, Tongwen Zhang, Hongbing Shen, Tangchun Wu, Dongxin Lin
Journal: Cancer Research (2010)

Abstract Although most patients with small-cell lung cancer respond to chemotherapy, the survival time is highly diverse. We conducted a genome-wide analysis to examine whether germline genetic variations are prognostic factors in small-cell lung cancer patients treated with the same chemotherapy regimen. Genome-wide scan of single nucleotide polymorphisms (SNP) was performed using blood DNA to identify genotypes associated with overall survival in 245 patients treated with platinum-based chemotherapy, and the results were replicated in another independent set of 305 patients. Associations were estimated by Cox models and function of the variants was examined by biochemical assays. We found that rs1820453 T&amp;gt;G SNP within the promoter region of YAP1 on chromosome 11q22 and rs716274 A&amp;gt;G SNP in the region of downstream of DYNC2H1 on chromosome 11q22.3 are associated with small-cell lung cancer survival. In pooled analysis of 2 independent cohorts, the adjusted hazard ratio for patients with the rs1820453 TG or GG genotype was 1.49 (95% CI, 1.19–1.85; P = 0.0004) and 1.65 (95% CI, 1.36–2.01; P = 4.76 × 10−7), respectively, compared with the TT genotype; and for patients with the rs716274 AG or GG genotype was 1.83 (95% CI, 1.47–2.29; P = 8.74 × 10−8) and 2.96 (95% CI, 1.90–4.62; P = 1.59 × 10−6), respectively, compared with the AA genotype. Functional analysis showed that the rs1820453 T&amp;gt;G change creates a transcriptional factor binding site and results in downregulation of YAP1 expression. These results suggest that YAP1 may play an important role in prognosis of small-cell lung cancer patients treated with platinum-based chemotherapy. Cancer Res; 70(23); 9721–9. ©2010 AACR.
Sweat chloride is not a useful marker of clinical response to Ivacaftor
Authors: Peter J Barry, Andrew M Jones, Anthony K Webb, Alexander R Horsley
Journal: Thorax (2013)

Clinical trials have revealed that Ivacaftor significantly reduces sweat chloride in patients with cystic fibrosis who carry the G551D mutation. This finding has been incorporated into the commissioning guidelines in the UK with a sweat chloride reduction of 30% or below 60 mmol/L, specified as the main criteria for continued funding of Ivacaftor for individual patients. In a cohort of 24 adults who were prescribed Ivacaftor, there was no correlation between absolute or relative reductions in sweat chloride and improvements in lung function. This questions the validity of sweat chloride as a surrogate marker of clinical efficacy.
ERYTHEMA NEONATORUM ALLERGICUM*
Authors: B. DUPERRAT, A. J. BRET
Journal: British Journal of Dermatology (1961)

Journal Article ERYTHEMA NEONATORUM ALLERGICUM Get access B. DUPERRAT, B. DUPERRAT Paris Search for other works by this author on: Oxford Academic Google Scholar A. J. BRET A. J. BRET Paris Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 8-9, 1 August 1961, Pages 300–302, https://doi.org/10.1111/j.1365-2133.1961.tb14451.x Published: 01 August 1961
Restricted randomization in randomized controlled trials
Authors: G. ter Riet
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Schulz and colleagues wrote, "In reports of trials that had apparently used unrestricted randomization, the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance."<sup>1</sup>They speculated that "nonrandom manipulation of comparison groups... may have occurred." For example, according to Schulz et al, out of 96 trials, and if unrestricted randomization was used, about half of trials should have had a disparity between the numbers of subjects in the treatment and control groups that fall outside the 50% prediction interval (see Figure 1 in Schulz et al<sup>1</sup>). Only eight did. However, their prediction intervals are based on a cumulative binomial distribution. This model does not reflect randomized trial conduct in practice. Consider a realistic example of a drug trial in which an investigator prepares a random assignment list in advance— usually, but not necessarily, by
Autologous peripheral stem cell transplantation for aggressive hemophagocytic syndrome associated with T‐cell lymphoma: Case study and review
Authors: Davinder S. Jassal, Ken Kasper, Carmen Morales, Morel Rubinger
Journal: American Journal of Hematology (2001)

Abstract Hemophagocytic syndrome (HPS) is a rare clinical presentation infrequently associated with lymphoproliferative disorders. We describe a 29‐year‐old male with aggressive HPS and T‐cell lymphoma managed successfully with high‐dose chemotherapy and autologous peripheral stem cell transplantation (APSCT), in remission at 41 months of follow‐up. In reviewing the literature, this case illustrates the 2nd longest surviving individual post stem cell transplant for aggressive HPS. Am. J. Hematol. 69:64‐66, 2002. © 2002 Wiley‐Liss, Inc.
Explaining How “High-Grade” Systemic Inflammation Accelerates Vascular Risk in Rheumatoid Arthritis
Authors: Naveed Sattar, David W. McCarey, Hilary Capell, Iain B. McInnes
Journal: Circulation (2003)

There is intense interest in mechanisms whereby low-grade inflammation could interact with conventional and novel vascular risk factors to promote the atheromatous lesion. Patients with rheumatoid arthritis (RA), who by definition manifest persistent high levels of inflammation, are at greater risk of developing cardiovascular disease. Mechanisms mediating this enhanced risk are ill defined. On the basis of available evidence, we argue here that the systemic inflammatory response in RA is critical to accelerated atherogenesis operating via accentuation of established and novel risk factor pathways. By implication, long-term suppression of the systemic inflammatory response in RA should be effective in reducing risk of coronary heart disease. Early epidemiological observational and clinical studies are commensurate with this hypothesis. By contrast, risk factor modulation with conventional agents, such as statins, may provide unpredictable clinical benefit in the context of uncontrolled systemic inflammatory parameters. Unraveling such complex relationships in which exaggerated inflammation–risk factor interactions are prevalent may elicit novel insights to effector mechanisms in vascular disease generally.
Reduced Growth Rate of Transplantable Mammary Adenocarcinoma in C3H Mice Fed Eicosa-5,8,11,14-tetraynoic Acid2
Authors: G. Ananda Rao, S. Abraham
Journal: JNCI Journal of the National Cancer Institute (1977)

Female 3-month-old C3H mice were given sc injections of 5-mg pieces of mammary adenocarcinoma and fed a linoleate-containing (15% corn oil) diet in the presence or absence of eicosa-5,8,11,14-tetraynoic acid (TVA), an inhibitor of prostaglandin synthesis. After 6 weeks, the weights of tumors of mice fed the TVA-free linoleate diet were three to five times greater than those of mice fed the TVA-containing linoleate diet. Dietary TVA caused a reduction in the levels of arachidonate and an elevation in the levels of linoleate in mammary tumors and livers. Aspirin, another known inhibitor of prostaglandin synthesis, when added to the linoleate diet, did not affect the tumor size or the composition of fatty acids in the tumors and livers. Thus we concluded that a) the growth of mammary tumors was not related to prostaglandin synthesis but was related to the availability of arachidonate, and b) TVA was an effective inhibitor for the conversion of linoleate to arachidonate.
Fusion of Metabolic Function and Morphology: Sequential [<sup>18</sup>F]Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Studies Yield New Insights Into the Natural History of Bone Metastases in Breast Cancer
Authors: Yong Du, Ian Cullum, Tim M. Illidge, Peter J. Ell
Journal: Journal of Clinical Oncology (2007)

By monitoring bone metastases with sequential [(18)F]fluorodeoxyglucose positron-emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging, this study investigates the clinical relevance of [(18)F]FDG uptake features of bone metastases with various radiographic appearances.Bone metastases were found in 67 of 408 consecutive patients with known/suspected recurrent breast cancer on [(18)F]FDG-PET/CT, characterized by CT morphology changes and/or bony [(18)F]FDG uptake. Twenty-five of the patients had sequential [(18)F]FDG-PET/CT examinations (86 studies) over an average follow-up period of 23 months. The temporal changes in [(18)F]FDG uptake and corresponding CT morphology features of 146 bone lesions identified in these 25 patients were followed up and correlated with therapeutic outcome retrospectively.The 146 lesions were classified as osteolytic (77), osteoblastic (41), mixed-pattern (11), or no change/negative (17) on CT. The majority of the osteolytic (72; 93.5%) and mixed-pattern lesions (nine; 81.8%), but fewer of the osteoblastic lesions (25; 61%), showed increased [(18)F]FDG uptake. After treatment, 58 osteolytic lesions (80.5%) became [(18)F]FDG negative and osteoblastic on CT and only 14 relatively large lesions (19.5%) remained [(18)F]FDG avid. Of the 25 [(18)F]FDG-avid osteoblastic lesions, 13 (52%) became [(18)F]FDG negative, but 12 (48%) remained [(18)F]FDG avid and increased in size on CT. Five of the mixed-pattern lesions remained [(18)F]FDG avid after treatment. All 17 CT-negative lesions became [(18)F]FDG negative; however, nine of them became osteoblastic. None of the initially [(18)F]FDG-negative lesions showed [(18)F]FDG avidity during follow-up.[(18)F]FDG uptake reflects the immediate tumor activity of bone metastases, whereas the radiographic morphology changes vary greatly with time among patients.
Hippocampal Theta Input to the Amygdala Shapes Feedforward Inhibition to Gate Heterosynaptic Plasticity
Authors: Michaël Bazelot, Marco Bocchio, Yu Kasugai, David Fischer, Paul D. Dodson, Francesco Ferraguti, Marco Capogna
Journal: Neuron (2015)

The dynamic interactions between hippocampus and amygdala are critical for emotional memory. Theta synchrony between these structures occurs during fear memory retrieval and may facilitate synaptic plasticity, but the cellular mechanisms are unknown. We report that interneurons of the mouse basal amygdala are activated during theta network activity or optogenetic stimulation of ventral CA1 pyramidal cell axons, whereas principal neurons are inhibited. Interneurons provide feedforward inhibition that transiently hyperpolarizes principal neurons. However, synaptic inhibition attenuates during theta frequency stimulation of ventral CA1 fibers, and this broadens excitatory postsynaptic potentials. These effects are mediated by GABAB receptors and change in the Cl− driving force. Pairing theta frequency stimulation of ventral CA1 fibers with coincident stimuli of the lateral amygdala induces long-term potentiation of lateral-basal amygdala excitatory synapses. Hence, feedforward inhibition, known to enforce temporal fidelity of excitatory inputs, dominates hippocampus-amygdala interactions to gate heterosynaptic plasticity.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0ZWY3MDUwYzM2ZTBhNGI5YTNiYzA4ZGQ1MDQ4ZmFkNiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc5NDU4NjU1fQ.Suh3doK8PR6FUepEDF88av8SwhqD8CXKILLBlNXeRhmy29NX9C6psnasH0mdtQPVCoNTDJP-bvZqnCaCAlUKhPswAALR--1nLDUDhFvP3q2ICmvIlFVP6CvB6k_ySSEz0UDudKeGk00NNkMFcFV-lbxv101UyvNvkoXn_u9V5_z-zr3ok8cAzctNA0p_RvM-MLyWT5Keqcw5OODgBBw5hOMG0IdxF03CobgNqP7-LPuuldKnpLrQOc8lv2IDAmOl3jIinZU1DvD0m5XQ-I1HbUzdJXb9-KJP42hLkl3ZJ-qQV00KQ5wKAMnI7eoxizXEKM1wD2STqvtZWLOjzJ4WCA(mp4, (75.01 MB) Download video
T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity.
Authors: H Wagner, M Röllinghoff
Journal: The Journal of Experimental Medicine (1978)

Secondary murine cytotoxic T lymphocyte responses from alloantigen-primed T cells can be induced in vitro by apparently unrelated regimens, such as addition of either concanavalin A (Con A), conditioned medium from Con A stimulated lymphocyte cultures, conditioned medium from secondary mixed lymphocyte cultures (MLC), or stimulator cells sharing only the I-region with the stimulating cells used for primary sensitization. We now report that upon polyclonal (Con A), or antigen-specific (MLC) stimulation, Lyl+ T cells release a factor, which in turn triggers alloantigen primed Ly23+ T cells to proliferation and cytolytic activity. The secondary cytotoxic T lymphocyte inducing factor (SCIF) is produced within 24 h. For its production, an intact protein metabolism, not DNA metabolism, is required. Once induced, the functional activity of SCIF is nonspecific and not H-2 restricted. SCIF allows exponential growth and long-term propagation of cytolytic Ly23+ T cells with specificity to alloantigens used for primary sensitization. SCIF induced activation of alloantigen primed Ly23+ T cells does not require the presence of alloantigens. The results therefore reveal a process by which Lyl+ T-cell-derived nonspecific factor(s) induce autonomously Ly23+ T-cell-mediated, antigen-specific, cytotoxic T lymphocyte responses.
Expression of type I hair keratins in follicular tumours
Authors: B. Cribier, B. Peltre, L. Langbein, H. Winter, J. Schweizer, E. Grosshans
Journal: British Journal of Dermatology (2001)

Background Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours. Objectives To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin. Methods We performed immunohistochemistry on paraffin sections of formalin‐fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3‐II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17. Results While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti‐hHa3‐II and anti‐hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late‐stage pilomatrixomas. Conclusions These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation‐specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour.
Tackle shortfall in NHS funding, healthcare leaders tell health secretary
Authors: G. Iacobucci
Journal: BMJ (2015)

Healthcare leaders have urged the returning health secretary for England, Jeremy Hunt, to urgently prioritise investment in the NHS to safeguard its future.

Prime Minister David Cameron this week reappointed Hunt to his cabinet after the Conservative Party’s victory in last week’s UK general election, with Hunt to continue in the role he has held since replacing Andrew Lansley in September 2012.

Cameron made two new appointments to the Department of Health, with Ben Gummer replacing Dan Poulter as undersecretary of state for health and Alistair Burt replacing the departing Liberal Democrat minister for care and support, Norman Lamb.

As The BMJ went to press the public health minister, Jane Ellison, minister for health quality, Lord Howe, and life sciences …
Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study.
Authors: G Falkson, R Gelman, C I Falkson, J Glick, J Harris
Journal: Journal of Clinical Oncology (1991)

Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with mitolactol, doxorubicin, vincristine (DAV), tamoxifen, and fluoxymesterone (DAVTH). Nine patients were canceled, and 114 were ineligible (half because of concomitant diseases). Among the 501 eligible patients, the overall response rate was 54% (14% complete response and 5% not assessable). The median time to treatment failure (TTF) was 9.0 months, and the median survival was 20.9 months. Multivariate models were fit on a randomly chosen half of the eligible cases and then verified on the other half. About half of the variables that were significant in the models remained significant in the verification data set. In the verification data set the variables that remained significantly associated with lower probability of response were three or more organ sites of disease and lack of nodal metastases; the variables associated with a significantly shorter TTF were liver metastases, estrogen receptor (ER)-negativity, and prior adjuvant therapy. The variables associated with significantly shorter survival were liver metastases, ER negativity, three or more organ sites of disease, and prior adjuvant chemotherapy. None of the variables in the data set had a significant influence on toxicity. The 125 patients aged over 65 years did not have worse toxicity or worse prognosis than younger patients. Ineligible patients had significantly less response but virtually identical TTF curves, survival curves, and toxicities. Therefore, patient discriminants are of paramount importance in predicting the outcome of treatment. Many of the current criteria for eligibility for entry on study may not be justified.
Nucleus-Encoded, Plastid-Targeted Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) Indicates a Single Origin for Chromalveolate Plastids
Authors: J. T. Harper
Journal: Molecular Biology and Evolution (2003)

Plastids (the photosynthetic organelles of plants and algae) originated through endosymbiosis between a cyanobacterium and a eukaryote and subsequently spread to other eukaryotes by secondary endosymbioses between two eukaryotes. Mounting evidence favors a single origin for plastids of apicomplexans, cryptophytes, dinoflagellates, haptophytes, and heterokonts (together with their nonphotosynthetic relatives, termed chromalveolates), but so far, no single molecular marker has been described that supports this common origin. One piece of evidence comes from plastid-targeted glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which originated by a gene duplication of the cytosolic form. However, no plastid GAPDH has been characterized from haptophytes, leaving an important piece of the puzzle missing. We have sequenced genes encoding cytosolic, mitochondrion-targeted, and plastid-targeted GAPDH proteins from a number of haptophytes and heterokonts and found haptophyte homologs that branch within a strongly supported clade of chromalveolate plastid-targeted genes, being more closely related to an apicomplexan homolog than was expected. The evolution of plastid-targeted GAPDH supports red algal ancestry of apicomplexan plastids and raises a number of questions about the importance of plastid loss and the possibility of cryptic plastids in nonphotosynthetic lineages such as ciliates.