tbuckley/cabot-search huggingface dataset:
Missense mutation Thr309Lys in the coagulation factor XII gene in a Spanish family with hereditary angioedema type III
Authors: A. Prieto, P. Tornero, M. Rubio, E. Fernández‐Cruz, C. Rodriguez‐Sainz
Journal: Allergy (2009)

A new type of hereditary angioedema (type III) affecting mainly women with normal C1-inhibitor level and function has been described. Exposition to estrogens is an important precipitating factor. Recently, a missense mutation in the gene of the blood coagulation factor XII (Hageman factor) has been reported in a few families with this type of hereditary angioedema.To study a patient and her family with recurrent swelling attacks during pregnancy.Complement factors C3 and C4 as well as C1-inhibitor level and function were determined. Genomic DNA was isolated from venous blood samples and screened for mutations in the coagulation factor XII gene.C3 and C4 levels as well as C1-inhibitor level and function were normal. A missense mutation Thr309Lys was identified in factor XII gene with a heterozygotic pattern. This mutation was also identified in the mother of the patient, her daughter and her son.These results support that the mentioned mutation in factor XII gene causes hereditary angioedema type III.
Radiation Induction of Endogenous Type C Virus From Mouse Cells Transformed In Vitro by Murine Sarcoma Virus&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: O Niwa, T Sugahara
Journal: JNCI Journal of the National Cancer Institute (1979)

Cell lines from AKR and BALB/c mouse embryos were compared for their sensitivity to X-ray induction of endogenous type C virus. K-Balb cells, a Balb/3T3 cell line nonproductively transformed by Kirsten murine sarcoma virus, were found to be sensitive to X-irradiation. At a dose as low as 50 R, X-rays induced virus expression in K-Balb cells, and the induction frequency increased with increasing dose of X-rays up to 400 R. Among two classes of inducible endogenous viruses carried by K-Balb cells, only Balb:virus-2 was activated by X-irradiation, whereas both Balb:virus-1 and Balb:virus-2 were activated after the cells were treated with 5-iodo-2′-deoxyuridine. UV light and 4-nitroquinoline 1-oxide were also shown to induce virus expression in K-Balb cells. The virus-induction frequency for these physical and chemical carcinogens was much lower (≊3×10-1) than that for 5-bromo-2′-deoxyuridine (≊1×10-1)
Orthostatic Hypertension in Patients With Type 2 Diabetes
Authors: Mototaka Yoshinari, Masanori Wakisaka, Udai Nakamura, Maki Yoshioka, Yuji Uchizono, Masanori Iwase
Journal: Diabetes Care (2001)

The prevalence and clinical importance of orthostatic hypertension (OHT) in diabetic patients has not been elucidated, in contrast to orthostatic hypotension, which is occasionally found in diabetic patients with autonomic neuropathy.The prevalence and severity of orthostatic hypertension was investigated in 277 Japanese male patients with type 2 diabetes, including 90 hypertensive patients and 128 nondiabetic age-matched male subjects. Patients treated with antihypertensive drugs were excluded from the study. OHT was defined as an increase in diastolic blood pressure (DBP) from <90 to >or=90 mmHg and/or an increase in systolic blood pressure (SBP) from <140 to >or=140 mmHg after standing from supine position. Clinical profiles and several serum biochemical parameters were determined in addition to chest X-rays and electrocardiograms.The prevalence of OHT in normotensive and hypertensive diabetic patients was significantly higher than in control subjects (12.8 vs. 1.8%, P < 0.01, for normotensive patients; 12.6 vs. 11.1%, not significant, for hypertensive patients). Orthostasis induced a mean increase of 6.8 +/- 11.4 mmHg in SBP and 9.1 +/- 5.2 mmHg in DBP in diabetic patients with OHT compared with those without OHT (-1.0 +/- 9.0 and 3.8 +/- 6.6 mmHg, respectively). Vibration sensation in the lower limb was reduced in diabetic patients with OHT, but the percent coefficient of variation of RR interval, cardio-to-thoracic ratio on chest X-ray, and serum triglyceride levels were higher in these patients compared with normotensive diabetic patients without OHT.Orthostatic hypertension is a novel complication in normotensive diabetic patients and may associate with early stage neuropathy and development of sustained hypertension.
First-aid-post Work in Air Raids
Authors: L. A. N. Line
Journal: BMJ (1942)

My only reason for venturing on this paper is that eighteen months ago I should have been very grateful for any information, however meagre, about what one might expect to happen at a first-aid post during air raids.As fixed first-aid posts vary according to their locality, structure.and staff, it is advisable, first, briefly to describe the one of which my colleague Dr.
Cytokine-driven Proliferation and Differentiation of Human Naive, Central Memory, and Effector Memory CD4+ T Cells
Authors: Jens Geginat, Federica Sallusto, Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (2001)

Memory T lymphocytes proliferate in vivo in the absence of antigen maintaining a pool of central memory T cells (TCM) and effector memory T cells (TEM) with distinct effector function and homing capacity. We compared human CD4+ naive T, TCM, and TEM cells for their capacity to proliferate in response to cytokines, that have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency TEM, while TCM were less responsive and naive T cells failed to respond. Dendritic cells (DCs) and DC-derived cytokines allowed naive T cells to proliferate selectively in response to IL-4, and potently boosted the response of TCM to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rβ and the common γ chain (γc). The extracellular signal regulated kinase and the p38 mitogen-activated protein (MAP) kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures, some of the proliferating TCM differentiated to TEM-like cells acquiring effector function and switching chemokine receptor expression from CCR7 to CCR5. The sustained antigen-independent generation of TEM from a pool of TCM cells provides a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4+ memory T cells.
Bevacizumab and Postoperative Complications After Hepatic Surgery for Colorectal Metastases
Authors: Nicholas J. Petrelli
Journal: Journal of Clinical Oncology (2009)

from The Univer- sity of Texas M. D. Anderson Cancer Center concerning their recent article in Journal of Clinical Oncology proposing that preoperative bevacizumab does not significantly increase postoperative complications in patients undergoing liver surgery for colorectal cancer metastases.The congratulations are not due to the superiority of their data, but importantly to their self-criticism of the data.The authors concluded that neither the use of bevacizumab nor the timing of bevacizumab administration increases surgical complication rates.However, they qualify their statement by relating that confirmatory prospective studies are required.This is important because in the discussion section of their article, they indeed relate that because their study is retrospective from a single institution with a small number of patients (81 patients in the chemotherapy-plus-bevacizumab group and 44 patients in the chemotherapy-alone group), definitive conclusions about the safety of neoadjuvant bevacizumab and its timing of discontinuation cannot be made.Since the type of chemotherapy, the decision to use bevacizumab, and the duration of chemotherapy and bevacizumab administration, along with the timing of surgical consultation, are at the discretion of the treating physician, the conclusion of their manuscript is preliminary and, as they have stated, must be confirmed prospectively.This group of investigators has a significant experience with hepatic resection of colorectal metastases and continues to recommend waiting at least 6 weeks from discontinuation of bevacizumab before hepatic resection is performed.We certainly can learn from retrospective series, but to the credit of these authors, the self-criticism of their data is laudable.Unfortunately, this is not the case with many
Rationale for Biomarkers and Surrogate End Points in Mechanism-Driven Oncology Drug Development
Authors: John W. Park, Robert S. Kerbel, Gary J. Kelloff, J. Carl Barrett, Bruce A. Chabner, David R. Parkinson, Jonathan Peck, Raymond W. Ruddon, Caroline C. Sigman, Dennis J. Slamon
Journal: Clinical Cancer Research (2004)

Recent progress in understanding the molecular basis of cancer has redefined the landscape for cancer drug discovery and development. Among the most exciting and promising benefits are molecular targeted cancer therapies, which can be seen as progress toward personalized medicine for cancer patients
A survey of the causes of sudden death in sport in the Republic of Ireland
Authors: Fionnuala Quigley
Journal: British Journal of Sports Medicine (2000)

Sudden death in sport is rare, but when it occurs the effects are devastating. There have not been any reports to date describing the frequency and causes of sudden death in sport in the Republic of Ireland.To describe the incidence, possible causes, associated factors, and pathological findings in people who died while exercising in the Republic of Ireland in the 10 year period from January 1987 to December 1996.All 49 regional coroners in the Republic of Ireland were approached and details on all cases of sudden death in sport from 1 January 1987 to 31 December 1996 were requested. A questionnaire was used to document age, sex, participating sport, previous symptoms, previous medical investigations, circumstances of death, and main pathological finding in all reported cases.Of the 49 coroners surveyed, 45 replied. A total of 51 cases of sudden death in sport were identified. The median age was 48 (range 15-78). Fifty of the deaths were of men. Golf was the most popular participating sport. In 42 cases, the pathological cause of death was atherosclerotic coronary artery disease.This is the first time the incidence of sudden death in sport in the Republic of Ireland has been described. The main cause of death in all age groups was atherosclerotic coronary artery disease.
Molecular Staging of Malignant Melanoma
Authors: Steven C. Shivers, Xiangning Wang, Weiguo Li, Emmanuella Joseph, Jane Messina, L. Frank Glass, Ronald DeConti, C. Wayne Cruse, Claudia Berman, Neil A. Fenske, Gary H. Lyman, Douglas S. Reintgen
Journal: JAMA (1998)

For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases.To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma.A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months.A major university-based melanoma referral center at a National Cancer Institute-designated cancer center.A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases.Melanoma recurrence and overall survival.Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival.The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.
Specific systemic nonviral gene delivery to human hepatocellular carcinoma xenografts in SCID mice
Authors: Markus F. Wolschek, Christiane Thallinger, Malgorzata Kursa, Vanessa Rössler, Matthew Allen, Cornelia Lichtenberger, Ralf Kircheis, Trevor Lucas, Martin Willheim, Walter Reinisch, Alfred Gangl, Ernst Wagner, Burkhard Jansen
Journal: Hepatology (2002)

Systemic tumor-targeted gene delivery is attracting increasing attention as a promising alternative to conventional therapeutical strategies. To be considered as a viable option, however, the respective transgene has to be administered with high tumor specificity. Here, we describe novel polyethylenimine (PEI)-based DNA complexes, shielded by covalent attachment of polyethylene glycol (PEG), that make use of epidermal growth factor (EGF) as a ligand for targeting gene delivery to EGF receptor-expressing human hepatocellular carcinoma (HCC) cells. In vitro transfection of luciferase reporter DNA resulted in high levels of gene expression in the human HCC cell lines Huh-7 and HepG2. An excess of free EGF during transfection clearly reduced expression levels, indicating a specific EGF receptor-mediated uptake of the DNA particles. Following intravenous injection into human HCC xenograft-bearing SCID mice, luciferase expression was predominantly found in the tumor, with levels up to 2 logs higher than in the liver, which was the highest expressing major organ. Histologic investigation showed reporter gene expression (β-galactosidase) localized to tumor cells. Assessing DNA distribution within the tumor by immunofluorescence microscopy, rhodamine-labelled transgene DNA was found to be mainly associated with HCC cells. In the liver, DNA was taken up almost exclusively by Kupffer cells and, as indicated by the low expression, subsequently degraded. In conclusion, we have shown that intravenous injection of PEGylated EGF-containing DNA/PEI complexes allows for highly specific expression of a transgene in human HCC tumors.
Variability in the Oral Bioavailability of All-trans-Retinoic Acid
Authors: P. C. Adamson, H. C. Pitot, F. M. Balis, J. Rubin, R. F. Murphy, D. G. Poplack
Journal: JNCI Journal of the National Cancer Institute (1993)

Orally administered all- trans -retinoic acid (all- trans -RA) can induce complete remission in a high proportion of patients with acute promyelocytic leukemia. A previous pharmacokinetic study in patients with acute promyelocytic leukemia raised the possibility that the absorption of orally administered all- trans -RA is a saturable process that would have significant clinical impact on dosing strategies. Purpose : This study was specifically designed to examine the saturability of all- trans -RA absorption by measuring the effect of doubling the oral dose of all- trans -RA on plasma drug concentration in patients receiving long-term oral therapy. Methods : Six patients with solid tumors received oral doses of 10-mg gelatin capsules of all- trans -RA. Patients were studied on 2 consecutive days after they received 28 days of all- trans -RA administered as two daily 78-mg/m 2 doses. The study assigned the patients to two groups. Three patients took a 156-mg/m 2 dose on day 28 and a 78-mg/m 2 dose on day 29; the other three patients took the lower dose on day 28 and the double dose on day 29. Blood samples for the determination of all- trans -RA plasma concentration were obtained at 30-minute intervals starting just prior to drug administration and continuing for a total of 7 hours. The plasma concentration of all- trans -RA was measured by high-performance liquid chromatography. Results : Plasma concentrations following an oral dose of all- trans -RA were highly variable, with peak concentrations ranging from 0.07 to 1.2 μM for the 78-mg/m 2 dose level. Doubling the dose from 78 to 156 mg/m 2 increased plasma concentration in all six patients, but the increase was unpredictable and not related to dose, ranging from less than a 1.2-fold to more than a 10-fold increase. Conclusion : The current study does not support the hypothesis that the gastrointestinal absorption of all- trans -RA involves a saturable process but instead suggests that absorption is highly variable among patients. This wide interpatient variability suggests that pharmacokinetic drug monitoring may have an important role in the management of patients receiving all- trans -RA. [J Natl Cancer Inst 85:993–996, 1993]
Identification and characterization of a bipotent (erythroid and megakaryocytic) cell precursor from the spleen of phenylhydrazine-treated mice
Authors: Alessandro Maria Vannucchi, Francesco Paoletti, Silvia Linari, Cristina Cellai, Roberto Caporale, Pierluigi Rossi Ferrini, Massimo Sanchez, Giovanni Migliaccio, Anna Rita Migliaccio
Journal: Blood (2000)
Association of thromboxane A2 receptor (TBXA2R) with atopy and asthma
Authors: Hyoung Doo Shin, Byung Lae Park, Ji Hyun Jung, Hoe Jin Wang, Hae-Sim Park, Byoung Whui Choi, Soo-Jong Hong, Young Mok Lee, Yong Hoon Kim, Choon-Sik Park
Journal: Journal of Allergy and Clinical Immunology (2003)
Urinary FSP1 Is a Biomarker of Crescentic GN
Authors: Masayuki Iwano, Yukinari Yamaguchi, Takaaki Iwamoto, Kimihiko Nakatani, Masaru Matsui, Atsushi Kubo, Yasuhiro Akai, Toshio Mori, Yoshihiko Saito
Journal: Journal of the American Society of Nephrology (2011)

Fibroblast-specific protein 1 (FSP1)–expressing cells accumulate in damaged kidneys, but whether urinary FSP1 could serve as a biomarker of active renal injury is unknown. We measured urinary FSP1 in 147 patients with various types of glomerular disease using ELISA. Patients with crescentic GN, with or without antinuclear cytoplasmic antibody–associated GN, exhibited elevated levels of urinary FSP1. This assay had a sensitivity of 91.7% and a specificity of 90.2% for crescentic GN in this sample of patients. Moreover, we found that urinary FSP1 became undetectable after successful treatment, suggesting the possible use of FSP1 levels to monitor disease activity over time. Urinary FSP1 levels correlated positively with the number of FSP1-positive glomerular cells, predominantly podocytes and cellular crescents, the likely source of urinary FSP1. Even in patients without crescent formation, patients with high levels of urinary FSP1 had large numbers of FSP1-positive podocytes. Taken together, these data suggest the potential use of urinary FSP1 to screen for active and ongoing glomerular damage, such as the formation of cellular crescents.
Mortality After Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy, or Brachytherapy in Men Without Comorbidity
Authors: Kenneth G. Nepple, Andrew J. Stephenson, Dorina Kallogjeri, Jeff Michalski, Robert L. Grubb, Seth A. Strope, Jennifer Haslag-Minoff, Jay F. Piccirillo, Jay P. Ciezki, Eric A. Klein, Chandana A. Reddy, Changhong Yu, Michael W. Kattan, Adam S. Kibel
Journal: European Urology (2013)
FTY720 Shows Promising <i>In vitro</i> and <i>In vivo</i> Preclinical Activity by Downmodulating Cyclin D1 and Phospho-Akt in Mantle Cell Lymphoma
Authors: Qing Liu, Lapo Alinari, Ching-Shih Chen, Fengting Yan, James T. Dalton, Rosa Lapalombella, Xiaoli Zhang, Rajeswaran Mani, Teresa Lin, John C. Byrd, Robert A. Baiocchi, Natarajan Muthusamy
Journal: Clinical Cancer Research (2010)

Despite the progress that has been made in the treatment of mantle cell lymphoma (MCL), all patients invariably relapse with the currently available therapies. Because of the absence of curative therapy for MCL, we explored FTY720 as a novel agent against MCL.The cytotoxic effect of FTY720 in primary MCL tumor cells and cell lines were evaluated in vitro. The effects of FTY720 on caspase activation, generation of reactive oxygen species, and modulation of Cyclin D1 and Akt, which are implied in the pathogenesis of MCL, were investigated. The in vivo efficacy of FTY720 was evaluated in a Jeko-severe combined immunodeficient xenograft model of human MCL.FTY720 mediated time- and dose-dependent cytotoxicity in primary MCL tumor cells and MCL cell lines in vitro. FTY720-induced cytotoxicity occured independent of caspase activation but dependent on the generation of ROS in MCL. In addition, FTY720 treatment resulted in the time-dependent downmodulation of Cyclin D1 and accumulation of cells in G(0)-G(1) and G(2)-M phases of the cell cycle with concomitant decrease in S-phase entry. Furthermore, concentrations of FTY720 that induced cytotoxicity led to decreased phospho-Akt in primary MCL cells and cell lines. Most importantly, the in vivo therapeutic activity of FTY720 was shown in severe combined immunodeficient mice engrafted with the Jeko MCL cell line.These results provide the first evidence for a potential use of FTY720 in targeting key pathways that are operable in the pathogenesis of MCL and warrant further investigation of FTY720 in clinical trials to treat patients with MCL.
A comparison of the efficacy and tolerability of adapalene 0·1% gel versus tretinoin 0·025% gel in patients with acne vulgaris: a meta‐analysis of five randomized trials
Authors: None Cunliffe, None Poncet, None Loesche, None Verschoore
Journal: British Journal of Dermatology (1998)

The purpose of this meta-analysis was to determine if adapalene 0.1% gel (Differin) provided superior efficacy and better tolerability than tretinoin 0.025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0.1% gel, 450 treated with tretinoin 0.025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran-Mantel-Haenszel test. All statistical tests were two-sided, with the 0.05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.