tbuckley/cabot-search huggingface dataset:
Watching the lung work: An in vitro 3-D microfluidic device to challenge pulmonary drug delivery strategies with high end microscopy
Authors: Nina Hobi, Maja Gulic, Thomas Haller, Paul Dietl, Manfred Frick
Journal: European Respiratory Journal (2013)

During tissue development, lung cells are exposed to mechanical forces and communicate via biochemical signals directing their shape and function. The unique alveolar-capillary interface relates to cellular transport and cell differentiation and has particular impact on the understanding of pulmonary edema und cystic fibrosis. Our model allows exploring the delicate cellular compositions of lung tissue which is highly intricate and requires advanced technology.  For that, we cultured freshly isolated AT II and immortal AT I cells from rat on the apical side in close contact to the air-liquid interface and HEMC-1 were seeded on the basolateral side. Our preliminary experiments were performed on cell culture inserts, thus we verified the functionality by measuring cell viability, morphogenesis, transepithelial resistance (TER) and tight junction protein expression under different conditions.  The coculture formed a confluent monolayer and TER was significantly increased after two days interface contact. Applying different culture conditions had no effect on tight junction’s expression and cell viability; though adding of dexamethason lead to a concentration dependent TER increase. Next, we will implement our coculture in a transparent microfluidic chamber that mimics the dynamic microenvironment of an intact lung and enables long-term cell culturing at the air-liquid-interface.  Our ‘artificial lung’ model will facilitate the visualization of cellular processes in a live cell imaging manner. This approach will improve the current pathophysiological understanding of alveolar transport in general, and further accelerate pulmonary drug delivery research.
A phase II trial of PS-341 (bortezomib) followed by the addition of doxorubicin at progression in incurable adenoid cystic carcinoma of the head and neck: An Eastern Cooperative Oncology Group study
Authors: A. Argiris, M. A. Goldwasser, B. Burtness, R. Deconti, R. Axelrod, C. Van Waes, A. Forastiere
Journal: Journal of Clinical Oncology (2006)

5573 Background: Adenoid cystic carcinoma (ACC) is usually resistant to chemotherapy. Bortezomib (B) is a highly selective inhibitor of the 26S proteasome which is central for the ubiquitin-proteasome degradation pathway. Inhibition of NF-κB activity achieved by B may be important for inhibition of the growth of ACC. Preclinical studies have shown synergy between B and doxorubicin (D). Methods: Eligibility criteria included incurable ACC, any number of prior therapies but without an anthracycline, unidimensionally measurable disease, ECOG performance status 0–2, ejection fraction within normal limits (WNL), absolute neutrophil count &gt;1500/μL, platelets &gt;100,000/μL, and total bilirubin WNL. Patients (pts) with stable disease (SD) for 9 months or more were excluded. Pts received B 1.3 mg/m 2 IV push on days 1,4,8, and 11, every 21 days, until progression. Doxorubicin 20 mg/m 2 IV on days 1 and 8 was added at the time of progression. Response assessment was performed after every 2 cycles using RECIST. Immunohistochemistry for biomarkers affected by the ubiquitin-proteasome pathway on baseline tumor and measurement of serum inflammatory and angiogenic cytokines before and in response to therapy were performed. Results: 25 pts were enrolled; 18 were females; median age was 56 years (26–73); distant metastatic sites: lung (21), liver (4), bone (2). Best response to single-agent B: 16 pts (64%) had SD, 7 progressed, and 2 were unevaluable (1 with symptomatic deterioration). The median progression-free survival was 8.5 months. In 4 evaluable pts who received B plus D, 1 partial response and 2 SD were observed. 1 pt died 7 months after starting treatment without documented progression. Worst grade (G) 3/4 toxicities with B alone in 22 evaluable pts were: G3 neutropenia 5%, G4 neutropenia 5%, G3 thrombocytopenia 5%, G3 sensory neuropathy 14%; G3 generalized weakness 5%, G3 fatigue 9%, G3 anorexia 5%, G3 diarrhea 5%, G3 hyponatremia 5%, G3 dyspnea 5%. Conclusions: B was well tolerated and resulted in disease stabilization in a high percentage of pts but no objective responses. Updated response data with the addition of D will be available. No significant financial relationships to disclose.
Is the International Prognostic Index for Aggressive Lymphoma patients useful for follicular lymphoma patients?
Authors: Y Bastion, B Coiffier
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.7.1340 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8021723 Is the International Prognostic Index for Aggressive Lymphoma patients useful for follicular lymphoma patients? Y BastionxY BastionSearch for articles by this author , B CoiffierxB CoiffierSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.7.1340 First Page PDF © 1994 by American Society of Clinical Oncology
Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection — United States, 2016
Authors: J. Erin Staples, Eric J. Dziuban, Marc Fischer, Janet D. Cragan, Sonja A. Rasmussen, Michael J. Cannon, Meghan T. Frey, Christina M. Renquist, Robert S. Lanciotti, Jorge L. Muñoz, Ann M. Powers, Margaret A. Honein, Cynthia A. Moore
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

CDC has developed interim guidelines for health care providers in the United States who are caring for infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy. These guidelines include recommendations for the testing and management of these infants. Guidance is subject to change as more information becomes available; the latest information, including answers to commonly asked questions, can be found online (http://www.cdc.gov/zika). Pediatric health care providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (based on travel to or residence in an area with Zika virus transmission [http://wwwnc.cdc.gov/travel/notices]), and review fetal ultrasounds and maternal testing for Zika virus infection (see Interim Guidelines for Pregnant Women During a Zika Virus Outbreak*) (1). Zika virus testing is recommended for 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant; or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. For infants with laboratory evidence of a possible congenital Zika virus infection, additional clinical evaluation and follow-up is recommended. Health care providers should contact their state or territorial health department to facilitate testing. As an arboviral disease, Zika virus disease is a nationally notifiable condition.
A TLR9 CpG immunomodulator in combination with chemotherapy as treatment for advanced non-small cell lung cancer (NSCLS), a randomized, controlled phase II study
Authors: G. Leichman, D. Gravenor, G. Albert, T. Schmalbach
Journal: Journal of Clinical Oncology (2004)

7126 Background: First line chemotherapy for unresectable NSCLC provides partial and short duration responses, and there are still 54,000 deaths/year in the U.S. CPG 7909 (ProMune), a new chemically defined, targeted immunomodulator acting through dendritic cell receptors is synergistic with chemotherapy in non-clinical models, and shows human anti-tumor activity in several cancers. Preclinical data, human safety at active doses, and the need to improve therapy justified a Phase 2 combination trial. Methods: This randomized, controlled study compares chemotherapy [C] (standard of care) alone vs. [C] plus CPG 7909. Seventy-five patients will be randomized 1:2, to [C] alone (taxane and platinum regimen given week 1 of each cycle) versus [C] plus CPG 7909, 0.20mg/kg administered subcutaneously weeks 2 and 3. The primary efficacy endpoint is anti-neoplastic activity determined by overall response rate (RECIST). Secondary efficacy assessments include clinical benefit, duration of response, time to progression, and survival. Multiple biologic responses parameters are compared between responders and non-responders. Results: Forty of 75 patients in 25 centers have been enrolled and treated to date. All have KPS > 70; the age range is 39–82, and 10 are female. Six patients are off-study (2= PD, 1= injection site reaction, 1= pulmonary emphysema, 1=exacerbation of gout, 1= angina and dyspnea) with 31 patients continuing therapy from 4 to 24 weeks. Toxicities of [C] are not complicated by CPG 7909. Tolerability is acceptable; no drug related serious adverse events have been reported to date, ongoing assessments show biologic responses consistent with CPG 7909 immunomodulatory activity, tolerance of the combination, and tumor response. Conclusions: This new combination regimen appears active in NSCLC treatment. Comparative tumor and biologic response profiles will be presented for both treatment groups. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group
Heterozygosity for a Novel Missense Mutation in the<i>ITGB4</i>Gene Associated With Autosomal Dominant Epidermolysis Bullosa
Authors: Iana Turcan, Anna M. G. Pasmooij, Peter C. van den Akker, Henny Lemmink, Gyorgy B. Halmos, Richard J. Sinke, Marcel F. Jonkman
Journal: JAMA Dermatology (2016)

Epidermolysis bullosa (EB) is a group of mechanobullous genodermatoses characterized by the fragility of skin and mucous membranes. Mutations in the ITGA6 and ITGB4 genes, encoding the hemidesmosomal protein α6β4-integrin, have been involved in the pathogenesis of EB. To date, the inheritance of these particular genes is known to be exclusively autosomal recessive. Herein, we report a novel heterozygous missense mutation in the ITGB4 gene exerting a dominant negative effect that cosegregates with the EB phenotype in an extended family.The clinical phenotype of affected individuals is primarily characterized by nail dystrophy and late onset of mild skin fragility and acral blistering. Some patients developed granulation tissue in the larynx, urethra, lacrimal duct, and external auditory canal. Sequencing the complete set of genes associated with EB revealed a heterozygous missense mutation in exon 5 of ITGB4: c.433G>T, p.Asp145Tyr. The mutation was found in the affected relatives and was not present in unaffected relatives and control DNA samples.This study highlights, for the first time to our knowledge, the possibility of a dominant mode of inheritance for a missense ITGB4 mutation in EB, thus expanding the mutational database and genotype-phenotype correlation for this rare disease.
Pathogenesis of glomerular injury in the fawn-hooded rat
Authors: J L Simons, A P Provoost, S Anderson, J L Troy, H G Rennke, D J Sandstrom, B M Brenner
Journal: Journal of the American Society of Nephrology (1993)

Fawn-hooded rats spontaneously develop focal and segmental glomerular sclerosis, systemic hypertension, and proteinuria at a young age. Micropuncture and morphological studies were performed in two inbred strains of fawn-hooded rats, FHH and FHL, with different susceptibilities to develop chronic renal failure. FHH rats have higher values for systolic blood pressure and proteinuria and more rapid development of focal and segmental glomerular sclerosis and subsequent chronic renal failure as compared with genetically closely related FHL rats. FHH and FHL strains and a Wistar control strain, WAG, were matched for age and were studied at 16 wk. FHH, FHL, and WAG-old (WAG-O) strains were matched for weight, and the last group was studied at 22 wk. WAG were also matched for weight to a young group of FHH rats (FHH-Y), and these were studied at 8 wk. In comparison with WAG and WAG-O rats, FHH and FHH-Y rats exhibited an increased in mean glomerular capillary hydraulic pressure (WAG, 52 +/- 1 mm Hg; WAG-O, 47 +/- 2 mm Hg; FHH, 60 +/- 2 mm Hg; FHH-Y, 65 +/- 1 mm Hg), whereas values in FHL animals were intermediate (56 +/- 2 mm Hg). No significant differences in glomerular volume were found among groups. Moderate focal and segmental glomerular sclerosis developed in FHH and FHH-Y rats, with values for older FHH rats being significantly greater than those for WAG, WAG-O, and FHL animals. Thus, the genetically determined sensitivity to develop proteinuria, focal and segmental glomerular sclerosis, and chronic renal failure in fawn-hooded rats correlated with early evidence of glomerular capillary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Frank William Murphy
Authors: Peter Sims
Journal: BMJ (2016)

Frank Murphy was born in Altrincham and attended grammar school, university and medical school in wartime Manchester. He spent the following 10 years as a clinician in west Africa. Initially a national serviceman, he was commissioned as a medical officer with the British Army and spent four years in the Royal West Africa Frontier Force.

He returned to England to enhance his clinical skills at Cromer and to receive training in tropical medicine before returning to Africa. The Colonial Medical Service appointed him district medical officer in northern Nigeria, where he ran a …
Epoetin-alpha compared to standard of care decreases number of packed red blood cell transfusions in patients receiving hyper-CVAD for acute lymphocytic leukemia, lymphoblastic lymphoma, and Burkitt’s lymphoma
Authors: M. E. Cabanillas, D. A. Thomas, H. Kantarjian, G. N. Mattiuzzi, B. N. Bekele, M. C. Foudray, J. L. Cassat, J. E. Cortes
Journal: Journal of Clinical Oncology (2007)

7075 Background: Anemia is common in patients with acute lymphocytic leukemia (ALL), lymphoblastic lymphoma (LL), and Burkitt’s lymphoma (BL) treated with chemotherapy and is associated with poor cancer control. Studies have shown that mild correction of anemia is associated with a significant improvement in quality of life. The current standard of care (SOC) for treatment of anemia in ALL, LL, BL is packed red blood cell (PRBC) transfusions. Objectives: To evaluate if EPO 1)decreases number/frequency of transfusions, and 2) adversely influences the complete remission (CR) rate. Methods: Patients with newly diagnosed ALL, LL, or BL receiving hyper-CVAD were randomized to EPO vs SOC within 14 days of starting chemotherapy. EPO dose was 40,000 units SQ weekly and escalated to 60,000 units after 4 weeks if indicated. Both arms received PRBC transfusions as per guidelines. Patients were considered evaluable if they had been on the study for at least 5 weeks. Results: 46 of 70 patients were evaluable: 16 ALL, 4 BL, and 3 LL on EPO (total 23) and 20 ALL, 1 BL, 2 LL in the SOC arm (total 23). The 2 groups were comparable in baseline hemoglobin and number of courses of chemotherapy completed. Median baseline erythroepoietin level was 299 (r 12–10,532) in the EPO arm vs. 104 (r 7–491; p=0.02) in the SOC arm. Time to neutrophil and platelet recovery was comparable in both arms. All patients with ALL (both arms) achieved a CR. One patient with LL on the EPO arm had no response to chemotherapy while all patients with BL and LL on the SOC arm achieved a CR. Conclusions: 1) EPO significantly decreased the frequency and number of PRBC transfusions in patients with ALL, LL, and BL on hyper-CVAD. 2) EPO does not affect recovery of other cell lines. 3) Use of EPO does not appear to have an adverse impact on CR rates in patients with ALL. No significant financial relationships to disclose. [Table: see text]
Hepatitis B Immune Globulin — Prevention of Hepatitis from Accidental Exposure among Medical Personnel
Authors: G F Grady, V A Lee
Journal: New England Journal of Medicine (1975)

The role of anti-HBs antibody in reducing the probability of hepatitis after accidental exposure to serum from patients with hepatitis or carriers of HBs Ag was studied prospectively among 712 medical workers. One fourth of the workers were anti-HBs positive and less than one per cent of them developed hepatitis, in contrast to 11 per cent among those who were anti-HBs negative. Three coded immune-serum globulin preparations of varying anti-HBs titer were randomly assigned. Among 251 persons passively immunized with globulin having a conventionally low anti-HBs titer, hepatitis developed in 17 (seven per cent) within six months. Comparative rates among those receiving intermediately high titer and high titer globulin, respectively, were five per cent (11 of 208) and two per cent (5 of 253). The significantly lower incidence among the latter (P less than 0.05) was offset by six additional cases, all in recipients of high titer globulin, detected when follow-up was extended to nine months.
Autonomous Megakaryocyte Growth in Essential Thrombocythemia and Idiopathic Myelofibrosis Is Not Related to a c-mpl Mutation or to an Autocrine Stimulation by Mpl-L
Authors: Anne Laure Taksin, Jean-Pierre Le Couedic, Isabelle Dusanter-Fourt, Aline Massé, Stéphane Giraudier, André Katz, Françoise Wendling, William Vainchenker, Nicole Casadevall, Najet Debili
Journal: Blood (1999)
Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group.
Authors: H S Nicholson, M Krailo, M M Ames, N L Seibel, J M Reid, W Liu-Mares, L G Vezina, A G Ettinger, G H Reaman
Journal: Journal of Clinical Oncology (1998)

PURPOSE The Children's Cancer Group conducted a phase I trial of temozolomide stratified by prior craniospinal irradiation (CSI). PATIENTS AND METHODS Children and adolescents with recurrent or progressive cancer were enrolled. Temozolomide was administered orally daily for 5 days, with subsequent courses administered every 21 to 28 days after full hematologic recovery. Dose levels tested included 100, 150, 180, 215, 245, and 260 mg/m2 daily. RESULTS Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the first three dose levels (100, 150, and 180 mg/m2 daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m2 daily had grade 3 hematologic toxicity. Three of eight patients (38%) treated at 245 to 260 mg/m2 daily had dose-limiting toxicity (DLT), which included both neutropenia and thrombocytopenia. Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematologic DLT occurred in one of six patients (17%) at 100 mg/m2 daily and in two of four patients (50%) at 215 mg/m2 daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the patients. After two courses of temozolomide, 10 patients had stable disease (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 months of follow-up. CONCLUSION The maximum-tolerated dose (MTD) of temozolomide for children and adolescents without prior CSI is 215 mg/m2 daily and for those with prior CSI is 180 mg/m2 daily for 5 days, with subsequent courses that begin on day 28. Temozolomide is well tolerated and should undergo phase II testing in children and adolescents.
Cytotoxicity of Carcinogenic Aromatic Amides in Normal and Xeroderma Pigmentosum Fibroblasts With Different DNA Repair Capabilities2
Authors: Veronica M. Maher, Nancy Birch, James R. Otto, J. Justin McCormick
Journal: JNCI Journal of the National Cancer Institute (1975)

The effect of exposure to UV irradiation or to the N-acetoxy-ester derivatives of four carcinogenic aromatic amides, 4-acetylaminobiphenyl (AABP), 2-acetylaminofluorene (AAF), 2-acetylaminophenanthrene, and 4-acetylaminostilbene, on cell survival was compared in strains of cultured human fibroblasts possessing normal rates of excision repair of DNA and in three strains of xeroderma pigmentosum (XP) cells, each differing in its rate of excision repair. The survival of each strain after exposure to UV reflected its capacity to repair DNA. Thus the slope of the survival curve for the XP strain with the poorest capacity for excision repair (XP12BE complementation group A) was 5.8-fold steeper than the exponential portion of the curve for the normally repairing strains; that of XP2BE (complementation group C) was 1.95-fold; and that of XP4BE (a variant capable of a normal rate of dimer excision) was only 1.3-fold steeper. The slope of the survival curves after exposure to each N-acetoxy ester derivative for these same XP strains averaged 6.4, 2.0, and 1.4 times steeper, respectively, than that of the normal strains tested. The excision repair capacity of these lines after exposure to N-acetoxy-AAF (50 muM/ml) was tested with alkaline cesium chloride density gradient centrifugation to detect incorporation of tritiated thymidine into nonreplicated DNA. The normal strains and XP4BE exhibited DNA excision repair by this method, whereas XP patients 2 and 12 did not. The cytotoxic effect of the four parent aromatic amide carcinogens, their N-hydroxy derivatives, as well as the N-acetoxy ester of each of the four N-hydroxy compounds and the N-sulfate ester of N-hydroxy-AAF and N-hydroxy-AABP in the XP2BE strain, was compared with their effect on the normal fibroblasts. The parent amides proved to be noncytotoxic at all doses tested. In contrast, the N-hydroxy derivatives of each aromatic amide were highly cytotoxic, as were the ester compounds. For each active derivative, the slope of the survival curve for XP2BE was 2-2.k times steeper than that of the normally repairing strain.
TGF 3 mutations cause arrhythmogenic right ventricular dysplasia type 1 and open the door to understanding the biological role of TGF 3 (where there's a will, there's a way): EXPERT'S PERSPECTIVE
Authors: J. Tamargo
Journal: Cardiovascular Research (2012)

This editorial refers to an article by G. Beffagna et al . [10][1] published in Cardiovascular Research in 2005. It is accompanied by a retrospective editorial by one of the authors of that original article, A. Rampazzo (doi:10.1093/cvr/cvs221), as part of this Spotlight on Landmark Papers in Cardiovascular Research . 

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited myocardial disease characterized by progressive fibrofatty replacement of the right ventricular myocardium, leading to right ventricular failure and arrhythmias.1,2 The left ventricle can also be involved, and in some patients, it can be the predominant site of involvement. The estimated prevalence of the disease in the general population ranges from 1:1000 to 1:5000.1,2 ARVC/D is a leading cause of sudden cardiac death (SCD), especially in young adults and athletes.1,2 The current diagnostic criteria are based on the presence of major and minor standardized criteria including ECG, ventricular arrhythmias, right ventricular function and morphology, histopathology, and family history.3

ARVC/D is a familial disease in at least 50% of cases, usually transmitted as an autosomal dominant trait, with reduced penetrance and highly variable clinical expression.1,2,4 ARVC/D has been associated with mutations in genes encoding cardiac desmosomal proteins involved in cell-to-cell interaction, including plakophilin-2 ( PKP2 ), desmoplakin ( DSP ), desmoglein-2 ( DSG2 ), desmocollin-2 ( DSC2 ), and plakoglobin ( JUP ).1–4 In addition, two complex cardiocutaneous disorders with autosomal recessive inheritance, the Naxos disease and the Carvajal syndrome, in which ARVC/D is associated with palmoplantar keratoderma and woolly hair, are also associated with homozygous mutations in JUP and in DSP , respectively. These findings confirmed that desmosomal dysfunction might be the final common pathway in the pathogenesis of ARVC/D. Desmosomes are protein complexes in the intercalated disk that are responsible for mechanical coupling of cardiac myocytes. …

 [1]: #ref-10