tbuckley/cabot-search huggingface dataset:
Familial dysbetalipoproteinemia associated with apolipoprotein E3-Leiden in an extended multigeneration pedigree.
Authors: P de Knijff, A M van den Maagdenberg, A F Stalenhoef, J A Leuven, P N Demacker, L P Kuyt, R R Frants, L M Havekes
Journal: Journal of Clinical Investigation (1991)

By the careful screening of familial dysbetalipoproteinemic (FD) patients, five probands showing heterozygosity for the APOE*3-Leiden allele were found. Genealogical studies revealed that these probands share common ancestry in the 17th century. In a group of 128 family members, spanning three generations, 37 additional heterozygous APOE*3-Leiden gene carriers were detected. Although with a variable degree of severity, all carriers exhibited characteristics of FD such as (a) elevated levels of cholesterol in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) fractions, (b) elevated ratios of cholesterol levels in these density fractions over total plasma levels of triglycerides, and (c) strongly increased plasma levels of apolipoprotein E (apoE). Multiple linear regression analysis revealed that most of the variability in expression of FD in APOE*3-Leiden allele carriers can be explained by age. Body mass index showed a less significant influence on the expression of FD. Gender had no effect on the expression in E*3-Leiden allele carriers, nor did it influence the age of onset of FD. In the group of APOE*3-Leiden allele carriers, we found that the E*2 allele enhances the expression of FD, whereas the E*4 allele had the opposite effect. Isoelectric focusing of plasma and of isolated VLDL, IDL, and high density lipoprotein density fractions showed that in E*3-Leiden allele carriers the apoE3-Leiden variant largely predominates over its normal apoE counterpart, especially in the VLDL and IDL density fractions. We conclude that in APOE*3-Leiden allele carriers FD is dominantly inherited with a high rate of penetrance, i.e., the presence of normally functioning apoE molecules in the plasma does not prevent the age-related expression of this disease.
Blood stem cell transplantation to treat cystic lung light chain deposition disease
Authors: Aurélie Le Borgne, Grégoire Prévot, Isabelle Rouquette, Anne Huynh, Laurent Têtu, Fabrice Projetti, Miguel Carreiro, Raphaël Borie, Arnaud Jaccard, Christian Recher, Alain Didier
Journal: European Respiratory Journal (2015)

Light chain deposition disease (LCDD) is a rare disease resulting from non-amyloid immunoglobulin (Ig) light chain deposition in tissue. In systemic LCDD, plasma cell dyscrasia is common and renal involvement is almost always present, sometimes with damage to other organ systems (cardiac, hepatic and neurological systems). LCDD can be limited to the lungs, presenting as multiple cystic lung disease, nodules or bronchiectasis. Cystic lung related to LCDD (CL-LCDD) was recently described in patients referred for lung transplantation to treat end-stage multiple cystic lung disease [1]. In the reported cases, blood and bone marrow examinations did not reveal clonal plasma cell proliferation. Here we report the first case of CL-LCDD revealing a B-cell extrapulmonary lymphoproliferative disorder and the results of treatment for the underlying haematological disease with autologous peripheral blood stem cell transplantation during the CL-LCDD. Despite respiratory insufficiency, lung transplantation was actually not considered because of the underlying disease. We report a case of CL-LCDD that was treated with autologous peripheral blood stem cell transplantation <http://ow.ly/NUQOt>
A population-based questionnaire survey on the prevalence of peanut, tree nut, and shellfish allergy in 2 Asian populations
Authors: Lynette Pei-Chi Shek, Elizabeth Ann Cabrera-Morales, Shu E. Soh, Irvin Gerez, Pau Zhing Ng, Fong Cheng Yi, Stefan Ma, Bee Wah Lee
Journal: Journal of Allergy and Clinical Immunology (2010)
Randomized Controlled Trial of the Prophylactic Effect of Urea-Based Cream on Sorafenib-Associated Hand-Foot Skin Reactions in Patients With Advanced Hepatocellular Carcinoma
Authors: ZhengGang Ren, KangShun Zhu, HaiYan Kang, MinQiang Lu, ZengQiang Qu, LiGong Lu, TianQiang Song, WeiPing Zhou, Hui Wang, WeiZhu Yang, Xuan Wang, YongPing Yang, LeHua Shi, YuXian Bai, XiaoFeng Guo, Sheng-Long Ye
Journal: Journal of Clinical Oncology (2015)

To assess whether urea-based cream (UBC) has prophylactic benefits on sorafenib-induced hand-foot skin reaction (HFSR) in patients with advanced hepatocellular carcinoma (HCC).In this randomized, open-label trial, 871 patients with advanced HCC throughout China were treated with 10% UBC three times per day plus best supportive care (BSC; n = 439) or BSC alone excluding all creams (n = 432), starting on day 1 of sorafenib treatment, for up to 12 weeks. HFSR was assessed every 2 weeks and at 14 weeks for patients completing the study. Once HFSR occurred, patients were allowed any cream, including a UBC.The 12-week incidence of any grade HFSR was significantly lower in the UBC group versus the BSC-alone group (56.0% v 73.6%, respectively; odds ratio [OR], 0.457; 95% CI, 0.344 to 0.608; P < .001), as was the incidence of grade ≥ 2 HFSR (20.7% v 29.2%, respectively; OR, 0.635; 95% CI, 0.466 to 0.866; P = .004). Median time to first occurrence of HFSR was significantly longer in the UBC group than the BSC-alone group (84 v 34 days, respectively; hazard ratio, 0.658; 95% CI, 0.541 to 0.799; P < .001). Elevated AST was associated with increased risk of HFSR but did not alter the treatment effect of UBC. UBC plus BSC, compared with BSC alone, did not affect the sorafenib dose reduction or interruption rate (9.1% v 11.8%, respectively; P = .1937), response rate (11.1% v 10.1%, respectively; P = .6674), or disease control rate (98.8% v 98.2%, respectively; P = .5350) at week 12.UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared with BSC. Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HFSR are warranted.
Formation of protein kinase Cε-Lck signaling modules confers cardioprotection
Authors: Peipei Ping, Changxu Song, Jun Zhang, Yiru Guo, Xinan Cao, Richard C.X. Li, Wenjian Wu, Thomas M. Vondriska, Jason M. Pass, Xian-Liang Tang, William M. Pierce, Roberto Bolli
Journal: Journal of Clinical Investigation (2002)

The ε isoform of protein kinase C (PKCε) is a member of the PKC family of serine/threonine kinases and plays a critical role in protection against ischemic injury in multiple organs. Functional proteomic analyses of PKCε signaling show that this isozyme forms multiprotein complexes in the heart; however, the precise signaling mechanisms whereby PKCε orchestrates cardioprotection are poorly understood. Here we report that Lck, a member of the Src family of tyrosine kinases, forms a functional signaling module with PKCε. In cardiac cells, PKCε interacts with, phosphorylates, and activates Lck. In vivo studies showed that cardioprotection elicited either by cardiac-specific transgenic activation of PKCε or by ischemic preconditioning enhances the formation of PKCε-Lck modules. Disruption of these modules, via ablation of the Lck gene, abrogated the infarct-sparing effects of these two forms of cardioprotection, indicating that the formation of PKCε-Lck signaling modules is required for the manifestation of a cardioprotective phenotype. These findings demonstrate, for the first time to our knowledge, that the assembly of a module (PKCε-Lck) is an obligatory step in the signal transduction that results in a specific phenotype. Thus, PKCε-Lck modules may serve as novel therapeutic targets for the prevention of ischemic injury.
Childhood Trauma and Personality Disorder: Positive Correlation With Adult CSF Corticotropin-Releasing Factor Concentrations
Authors: Royce Lee, Thomas D. Geracioti, John W. Kasckow, Emil F. Coccaro
Journal: American Journal of Psychiatry (2005)

To test the hypothesis that early life trauma results in adult stress hormone alterations in individuals with personality disorders, the authors examined the relationship between history of childhood adversity and lumbar CSF corticotropin-releasing factor (CRF).Participants were 20 otherwise healthy men who met DSM-IV criteria for personality disorders. CSF CRF was obtained by lumbar puncture, and childhood adversity was measured by the Childhood Trauma Questionnaire. Correlations were obtained between CSF CRF and the total score on the Childhood Trauma Questionnaire as well as scores on its four subscales.CSF CRF concentrations were positively correlated with the total score on the Childhood Trauma Questionnaire. Analysis of the subscales revealed that CSF CRF was correlated with emotional neglect. Correlations between CSF CRF level and physical and emotional abuse and with physical neglect were not statistically significant.Consistent with the hypothesis that the severity of early life stress is correlated with stress hormone abnormalities in adulthood, Childhood Trauma Questionnaire total scores and emotional neglect scores were significantly correlated with CSF CRF levels in individuals with personality disorders.
Response to Letter Regarding Article, “Incomplete Inhibition of Thromboxane Biosynthesis by Acetylsalicylic Acid: Determinants and Effect on Cardiovascular Risk”
Authors: John W. Eikelboom, Graeme J. Hankey, Jim Thom, Deepak L. Bhatt, P. Gabriel Steg, Gilles Montalescot, S. Claiborne Johnston, Steven R. Steinhubl, Koon-Hou Mak, J. Donald Easton, Christian Hamm, Tingfei Hu, Keith A.A. Fox, Eric J. Topol
Journal: Circulation (2009)
Long-term use of ICS influence TLR2 expression on induced sputum from severe COPD patients
Authors: Haixing Zhu, Guochao Shi, Wei Tang
Journal: European Respiratory Journal (2012)

Objection: To evaluate the influence of long-term use of inhaled corticosteroid on TLR2 expression on and in macrophages from induced sputum in severe COPD patients. Methods: Severe stable smoking male COPD patients treated in OPD of Respirology were divided into2 groups: long-term ICS group (ICS≥500/day futicasone propionate, ≥1 year)(n=21) and ICS naive group(n=29). With flow cytometry, we tested TLR2 expression on macrophages from induced sputum in these COPD patients. We also examined the mRNA expression in the induced sputum.  Result: The TLR2 extracellular expression on the macrophages from induced sputum in long-term ICS treatment group were lower than the ICS naive group(13.69±1.17 vs 20.12±4.37,p=0.019). The TLR2 intracellular expression (5.35±1.67 vs 12.81±4.89), the TLR2mRNAand TNFαmRNA expression also showed decreased trends in ICS long-term treatment group.  There were positive relationship between the expression of TLR2 extracellular and intracellular expression. Conclusion: Long-term use of ICS may have negative influence on TLR2 expression in the airway of COPD patients, which may increase the pneumonia susceptibility in severe COPD patients.
Tivantinib (ARQ197) Displays Cytotoxic Activity That Is Independent of Its Ability to Bind MET
Authors: Cristina Basilico, Selma Pennacchietti, Elisa Vigna, Cristina Chiriaco, Sabrina Arena, Alberto Bardelli, Donatella Valdembri, Guido Serini, Paolo Michieli
Journal: Clinical Cancer Research (2013)

MET, the high-affinity receptor for hepatocyte growth factor, is frequently deregulated in human cancer. Tivantinib (ARQ197; Arqule), a staurosporine derivative that binds to the dephosphorylated MET kinase in vitro, is being tested clinically as a highly selective MET inhibitor. However, the mechanism of action of tivantinib is still unclear.The activity of tivantinib was analyzed in multiple cellular models, including: cells displaying c-MET gene amplification, strictly 'addicted' to MET signaling; cells with normal c-MET gene copy number, not dependent on MET for growth; cells not expressing MET; somatic knockout cells in which the ATP-binding cleft of MET, where tivantinib binds, was deleted by homologous recombination; and a cell system 'poisoned' by MET kinase hyperactivation, where cells die unless cultured in the presence of a specific MET inhibitor.Tivantinib displayed cytotoxic activity independently of c-MET gene copy number and regardless of the presence or absence of MET. In both wild-type and isogenic knockout cells, tivantinib perturbed microtubule dynamics, induced G2/M arrest, and promoted apoptosis. Tivantinib did not rescue survival of cells 'poisoned' by MET kinase hyperactivation, but further incremented cell death. In all cell models analyzed, tivantinib did not inhibit HGF-dependent or -independent MET tyrosine autophosphorylation.We conclude that tivantinib displays cytotoxic activity via molecular mechanisms that are independent from its ability to bind MET. This notion has a relevant impact on the interpretation of clinical results, on the design of future clinical trials, and on the selection of patients receiving tivantinib treatment.
In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-α
Authors: Shwu-Bin Lin, Li-Ching Wu, Siao-Ling Huang, Hui-Lun Hsu, Sung-Hwa Hsieh, Chin-Wen Chi, Lo-Chun Au
Journal: Journal of Hepatology (2000)
Food-Borne Infections and Intoxications
Authors: A Przybylska
Journal: JAMA (1934)

In total were registered 30,515 cases of bacterial foodborne infections and intoxications (salmonelloses of animal source, staphylococcal, botulism, other bacterial and caused by undetermined agents) in 1998. Morbidity amounted 78.9/100,000. In 399 outbreaks of collective illnesses (4 people and more) 8225 cases were registered altogether. S. Enteritidis caused 92.5% cases in outbreaks. The main vehicle of foodborne infections and intoxications in outbreaks was food prepared from raw materials of animal source, which caused 86.8% cases in outbreaks. Dishes from eggs brought about 45.5% of these cases. Among the places of the ready made food production, private homes prevailed (58.1% of the whole amount of outbreaks). Seven epidemics numbering above 100 cases each were registered in 1998.
Expression of Human Somatostatin Receptor Subtype 3 in Pancreatic Cancer In Vitro and In Vivo
Authors: M. Raderer, J. Valencak, W. Scheithauer, T. Pangerl, M. Leimer, A. Kurtaran, I. Virgolini, G. Hamilton
Journal: JNCI Journal of the National Cancer Institute (1998)

Somatostatin analogs have become a focus of interest in clinical oncology, and promising results in patients with gastrointestinal tract cancers have been published in the recent literature (1).While these data suggest a potential survival benefit with the application of somatostatin analogs in advanced pancreatic cancer, results have also been reported that indicate the absence of somatostatin receptors (SSTRs) in pancreatic adenocarcinomas (2).In addition, Fisher et al.(3) have recently reported the detection of messenger RNAs (mRNAs) encoding SSTR1, SSTR2, and SSTR5 in pancreatic cancer cells, but the absence of functional somatostatin binding sites on the cell surface.We have recently investigated both the in vitro and in vivo expression of somatostatin receptors as judged by radioimaging of pancreatic cancer patients with labeled somatostatin analogs that are characterized by distinct receptor affinities.Somatostatin receptor subtype expression was investigated in four human pancreatic cancer cell lines (ASPC-1, BxPC3, Capan-1, and Panc-1).In addition, the in vivo expression of human somatostatin receptors (hSSTRs) was investigated in five patients with metastatic pancreatic adenocarcinoma through scanning with the commercially a v a i l a b l e 1 1 1 I n -D T P A -D -P h e 1octreotide ( 111 In-OCT; OctreoScan®, Mallinckrodt Medical Inc., St Louis, MO), which preferentially targets hSSTR2 and hSSTR5.Three of these
MOUSE COMPLEMENT: THE EFFECT OF SEX HORMONES AND CASTRATION ON TWO OF THE LATE-ACTING COMPONENTS
Authors: Winthrop H. Churchill, Ronald M. Weintraub, Tibor Borsos, Herbert J. Rapp
Journal: The Journal of Experimental Medicine (1967)

The titer of late-acting complement components in sera from male mice is 8-10 times higher than the titer of sera from female mice. Using assays developed to measure the serum content of two of the late-acting components, we have shown that this difference is due to the effect of androgen and estrogen on these two late-acting complement components. These two components have been tentatively identified as C'5 and C'6. Androgen and estrogen have greater effect on C'6 than on C'5. The possibility has not been excluded that still other of the late-acting complement components are affected by androgens and estrogens. The course of homograft rejection was unchanged in mice deficient in C'5 and C'6.
Trastuzumab Down-Regulates Bcl-2 Expression and Potentiates Apoptosis Induction by Bcl-2/Bcl-XL Bispecific Antisense Oligonucleotides in <b> <i>HER-2</i> </b>Gene–Amplified Breast Cancer Cells
Authors: Michele Milella, Daniela Trisciuoglio, Tiziana Bruno, Ludovica Ciuffreda, Marcella Mottolese, Anna Cianciulli, Francesco Cognetti, Uwe Zangemeister-Wittke, Donatella Del Bufalo, Gabriella Zupi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To investigate the possible existence of an antiapoptotic cross-talk between HER-2 and antiapoptotic Bcl-2 family members. Experimental Design: Bcl-2 and Bcl-XL expression and apoptosis induction were analyzed in HER-2gene–amplified (BT474) and nonamplified (ZR 75-1) breast cancer cell lines exposed to trastuzumab, alone or in combination with either Bcl-2/Bcl-XL bispecific antisense oligonucleotides (AS-4625) or the small-molecule Bcl-2 antagonist HA14-1. Results: In addition to HER-2 and epidermal growth factor receptor, trastuzumab down-regulated Bcl-2, but not Bcl-XL, protein, and mRNA expression in BT474 cells. Interestingly, trastuzumab-induced down-regulation of HER-2 and Bcl-2 was also observed in three of five and two of three breast cancer patients undergoing trastuzumab treatment, respectively. Despite Bcl-2 down-regulation, however, trastuzumab only marginally increased the rate of apoptosis (7.3 ± 3.5%). We therefore investigated whether a combination of AS-4625 and trastuzumab might increase proapoptotic efficiency. AS-4625 treatment of BT474 cells decreased both Bcl-2 and Bcl-XL expression, resulting in a 21 ± 7% net apoptosis induction; the combination of AS-4625 followed by trastuzumab resulted in a significantly stronger induction of apoptosis (37 ± 6%, P &amp;lt; 0.01) that was not observed with the reverse treatment sequence (trastuzumab followed by AS-4625). Similar results were obtained with the Bcl-2 antagonist HA14-1; indeed, exposure of BT474 cells to HA14-1 followed by trastuzumab resulted in a striking proapoptotic synergism (combination index = 0.58 ± 0.18), as assessed by isobologram analysis. Conclusions: Altogether our findings suggest that combined targeting of HER-2 and Bcl-2 may represent a novel, rational approach to more effective breast cancer therapy.
During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain
Authors: Jennifer Thompson, Astar Winoto
Journal: The Journal of Experimental Medicine (2008)

Apoptosis accompanying negative selection is a central but poorly understood event in T cell development. The Nur77 nuclear steroid receptor and Bim, a proapoptotic BH3-only member of the Bcl-2 family, are two molecules implicated in this process. However, how they relate to each other and how Nur77 induces apoptosis remain unclear. In thymocytes, Nur77 has been shown to induce cell death through a transcriptional-dependent pathway, but in cancer cell lines, Nur77 was reported to induce apoptosis through conversion of Bcl-2 into a killer protein at the mitochondria. Whether this Nur77 transcriptional-independent pathway actually occurs in vivo remains controversial. Using an optimized fractionation protocol for thymocytes, here we report that stimulation of CD4+CD8+ thymocytes results in translocation of Nur77 and its family member Nor-1 to the mitochondria, leading to their association with Bcl-2 and exposure of the Bcl-2 proapoptotic BH3 domain. In two T cell receptor transgenic models of negative selection, F5 and HY, a conformational change of the Bcl-2 molecule in the negatively selected T cell population was similarly observed. Thus, the Nur77 family and Bim pathways converge at mitochondria to mediate negative selection.
Skip Metastases in Osteosarcoma: Experience of the Cooperative Osteosarcoma Study Group
Authors: Leo Kager, Andreas Zoubek, Ulrike Kastner, Beate Kempf-Bielack, Jenny Potratz, Rainer Kotz, G. Ulrich Exner, Christiane Franzius, Susanna Lang, Rainer Maas, Heribert Jürgens, Helmut Gadner, Stefan Bielack
Journal: Journal of Clinical Oncology (2006)

The outlook for patients with osteosarcoma who present with synchronous regional bone metastases (skip metastases), either in the primary bone site or transarticular, is considered to be extremely poor. This study was conducted to further investigate the prognostic implication of skip metastases in osteosarcoma.The authors retrospectively analyzed the collected data of 1,765 consecutive patients with newly diagnosed high-grade osteosarcoma of bone who were registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies and identified 24 patients (1.4%) with unequivocally proven skip metastases. All 24 patients were treated by an aggressive surgical approach coupled with polychemotherapy. Demographic, diagnostic, tumor, and treatment-related variables and response and survival data were analyzed.Skip metastases were identified preoperatively in 11 of 24 patients by bone scan, eight of 22 patients by plain x-ray, 15 of 18 patients by magnetic resonance imaging, and five of 10 patients by computed tomography. A complete surgical remission (CSR) of all clinically detectable tumor sites was achieved in 22 of 24 patients during front-line therapy. With a median follow-up time of 4.4 years (8 years for survivors) from diagnosis, 12 patients were alive, all of whom were in continuous CSR. Survival did correlate with location of skip metastases and histologic response to neoadjuvant chemotherapy.Synchronous regional bone metastases are rare in osteosarcoma, and preoperative detection relies on appropriate diagnostic imaging. Aggressive multimodal therapy holds the promise to achieve prolonged survival, especially in patients in whom these metastases occur within the same bone as the primary lesion and whose tumors respond well to chemotherapy.
Menopausal hormone therapy and risk of ovarian cancer: systematic review and meta-analysis
Authors: Claudia M. Greiser, Eberhard M. Greiser, Martina Dören
Journal: Human Reproduction Update (2007)

Knowledge about the impact of menopausal hormone therapy (MHT) on the risk of ovarian cancer (OvC) is insufficient, and studies are inconsistent. Mortality from OvC ranks highest among cancer sites in female reproductive organs. We performed meta-analyses to assess the impact of specified types of MHT on the risk of OvC in cohort studies (CS), case-control studies (CCS), randomized controlled trials (RCT) and cancer registry studies (CRS). We used data published 1966–2006 on estrogen therapy (ET), estrogen/progestin therapy (EPT) or MHT (unspecified regimen) identified by a structured, computerized and manual literature search. We identified 42 studies (30CCS, 7CS, 1 RCT and 4 CRS) with 12 238 cases. The risk of OvC (ever-use, annual risk) is increased 1.28-fold by ET [confidence interval (CI) 1.18–1.40] and 1.11-fold by EPT (CI 1.02–1.21) with a suggestion of greater risks with ET. There appears to be no differential impact of any therapy on histological subtypes. Risks were greater in European than North American studies for both ET and EPT. In conclusion, ET as well as EPT, are risk factors for OvC. Given the widespread use of MHT, known benefits should be weighed against the increased risk of OvC, and more studies are warranted, particularly on factors with the greatest apparent risks.