tbuckley/cabot-search huggingface dataset:
DDT and Related Compounds and Risk of Pancreatic Cancer
Authors: D H Garabrant, J Held, B Langholz, J M Peters, T M Mack
Journal: JNCI Journal of the National Cancer Institute (1992)

A cohort mortality study among 5886 chemical manufacturing workers was completed in 1987 and showed increased mortality due to pancreatic cancer.We conducted a nested case-control study of pancreatic cancer among these chemical manufacturing workers to identify risk factors for this disease.Twenty-eight verified cases of pancreatic cancer and 112 matched controls were studied. Next of kin of each subject were interviewed to determine lifestyle factors, including tobacco, alcohol, and coffee consumption. Written work records and interviews with co-workers were used to determine chemical exposures at the plant under study.DDT was associated with pancreatic cancer (risk ratio [RR] for ever exposed compared with never exposed = 4.8; 95% confidence interval = 1.3-17.6). Among subjects who had a mean exposure to DDT of 47 months, the risk was 7.4 times that among subjects with no exposure. Two DDT derivatives, Ethylan and DDD, were additionally associated with pancreatic cancer (RR = 5.0 and 4.3, respectively); exposures to these two chemicals were correlated, and it was not possible to determine whether each acted independently of the other. Smoking was identified as an independent risk factor, but controlling for smoking (and other potential confounders) in the analyses did not appreciably alter the risks seen for DDT, DDD, or Ethylan.Exposure to DDT was associated with pancreatic cancer. The association was not explained by exposure to lifestyle factors or other chemicals, and risk increased with both duration of exposure and latency since first exposure.These results may indicate that DDT can cause pancreatic cancer in humans under circumstances of heavy and prolonged exposure.
GENE TRANSFER TO HEMATOPOIETIC STEM CELLS: Implications for Gene Therapy of Human Disease
Authors: Cynthia E. Dunbar, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Transfer of new genetic material to hematopoietic stem cells and expression of the gene product in daughter cells of various lineages is an exciting approach to the treatment of congenital and acquired human diseases. This review summarizes the current status of retroviral and adeno-associated viral vectors for gene transfer to human hematopoietic cells, including extensive preclinical data as well as preliminary results from ongoing clinical trials.
Anti-Immunoglobulin E (Omalizumab) Therapy in Allergic Asthma
Authors: WILLIAM W. BUSSE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<DOSE JUSTIFICATIONANTI-IgE (OMALIZUMAB) PHA...ANTI-IgE (OMALIZUMAB) PHA...CONCLUSIONReferencesCITING ARTICLES
Defective secretion of an immunoglobulin caused by mutations in the heavy chain complementarity determining region 2.
Authors: C Chen, T M Martin, S Stevens, M B Rittenberg
Journal: The Journal of Experimental Medicine (1994)

We have investigated four secretion-deficient antibodies (Abs) derived from a panel of 46 mutant T15 anti-phosphocholine Abs, all of which have point mutations in the heavy chain (H) complementarity determining region 2 (CDR2). The level of secretion for these four Abs was &amp;lt; 10% of wild type when expressed together with the T15 light chain (L) in either SP2/0 or P3X63Ag8.653 myeloma cells although normal levels of H and L chain mRNA were produced. Moreover, abundant intracellular H and L chain proteins were detected. Three of the four mutants had little or no assembled H and L complexes intracellularly whereas one had a significant amount of intracellular immunoglobulin (Ig) which was shown to be capable of binding Ag. Thus, we demonstrate for the first time that point mutations confined to CDR2 of the H chain variable (V) region can impede Ab assembly and secretion. We then introduced the same CDR2 mutations into a related H chain which is encoded by the same T15 VH gene but different diversity (D) and joining (J) genes. When these H chains were expressed with a non-T15 L chain, the resulting Abs were secreted normally. The results thus suggest that the effects of the CDR2 mutations on Ab secretion are dependent on their interactions with L and/or H chain D-J sequences. These results also reveal a novel mechanism that could contribute to B cell wastage.
Identification of a ferrochelatase mutation in a Chinese family with erythropoietic protoporphyria
Authors: Xiao-Fei Kong, Jing Ye, De-Yong Gao, Qi-Ming Gong, Dong-Hua Zhang, Zhi-Meng Lu, Yi-Ming Lu, Xin-Xin Zhang
Journal: Journal of Hepatology (2007)
Ig RNA expression in normal B cells stimulated with anti-IgM antibody and T cell-derived growth and differentiation factors.
Authors: K Nakanishi, D I Cohen, M Blackman, E Nielsen, J Ohara, T Hamaoka, M E Koshland, W E Paul
Journal: The Journal of Experimental Medicine (1984)

An increase in mRNA encoding the secretory form of the mu heavy (H) chain (mus) and in the ratio of mus mRNA to the mRNA encoding the membrane form of the microH chain (micron) occurs in normal B cells stimulated with anti-IgM and BSF-p1 together with the two B cell differentiation factors B15-TRF and EL-TRF. Stimulation of cells with anti-IgM and BSF-p1 with either B15- or EL-TRF causes no change in mus levels or mus/micron ratios. The requirements for induction of high rate IgM synthesis in normal B cells stimulated with anti-IgM were precisely the same as those required for elevation of mus, mRNA levels and for increase in mus/micron mRNA ratios. A very close correlation also exists between induction of mRNA for J chain and increase in mus mRNA levels. Similarly, the increase in J chain protein concentration and percent of cells with cytoplasmic IgM were correlated to each other and to levels of mus and J chain mRNA. These results indicate that elevation of mus mRNA and mus/micron mRNA ratios occur in normal B cells only upon commitment to IgM synthesis, and reaffirm the close relation between IgM synthesis and the presence of J chain.
Long-term ganciclovir chemotherapy for congenital duck hepatitis B virus infection in vivo: Effect on intrahepatic-viral DNA, RNA, and protein expression
Authors: C Luscombe
Journal: Hepatology (1996)

Long-term antiviral chemotherapy using the nucleoside analogue ganciclovir was undertaken with the aim of eliminating hepadnaviral covalently closed circular (CCC) DNA from the livers of ducks that were congenitally infected with the duck hepatitis B virus (DHBV). Twenty- four weeks of ganciclovir therapy caused a substantial reduction in viremia, intrahepatic viral DNA replicative intermediates, and viral core proteins. Unfortunately, ganciclovir therapy did not substantially affect CCC DNA or viral RNA levels, and the treatment resulted in an increase in the intrahepatic expression of the viral envelope proteins, pre-S and S. By the completion of therapy, the viral envelope proteins had assembled into large aggregates within the cytoplasm of most hepatocytes. Viral replication in the bile duct epithelial cells and in the extrahepatic sites was likewise not affected by long-term ganciclovir therapy. In conclusion, 24 weeks of ganciclovir therapy decreased most viral replication markers within the liver, except for those of viral CCC DNA, RNA, and envelope proteins. Long-term therapeutic strategies using nucleoside analogs such as ganciclovir should be used with caution in chronic hepatitis B virus (HBV) infection. The careful monitoring of serum and hepatic markers of viral replication may therefore be important to avoid possible toxic consequences, such as the selective accumulation of viral proteins. (Hepatology 1996 Oct;24(4):766-73)
Does presence of multiple viruses in the stable state predispose COPD patients to exacerbations
Authors: Marijke Vanspauwen, Frits Franssen, Cathrien Bruggeman, Emiel Wouters, Catharina Linssen
Journal: European Respiratory Journal (2011)

Introduction:  Respiratory viruses are associated with acute exacerbations (AE) in patients with COPD, but may also lead to asymptomatic carriership. This study investigates whether co-detection of viruses in the stable state predisposes for AEs in patients with COPD. Since it is known that many viruses circulate during the year we included the most important respiratory viruses in our study.   Material and methods:  From March 2009 until August 2010 sputum samples of COPD patients clinically rehabilitating at the centre of expertise for chronic organ failure (CIRO), were included. Sputum samples were collected during the stable state and during an AE. Real-time polymerase chain reaction for rhinovirus, hMPV, RSV, influenza A and B and parainfluenza 1-4, was performed.   Results:  A total of 498 sputum samples (218 patients) were included. Viruses were detected in 208 samples (42%) of which 106 (51%) were collected during the stable state. In 11% of the samples multiple viruses were found, of which the combination of rhinovirus and hMPV was the most frequent (58%). Patients with multiple viruses in the stable sample did not experience more AEs in the first weeks after stable sample collection than patients with a single virus or without a virus in the stable sample.   Conclusion:  In 11% of sputum samples of COPD patients multiple respiratory viruses were found. The presence of multiple viruses does not predispose these patients to the short-term occurrence of an AE.
Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of the human pancreas
Authors: B Burghardt, M-L Elkaer, T-H Kwon, G Z Rácz, G Varga, M C Steward, S Nielsen
Journal: Gut (2003)

The exocrine pancreas secretes large volumes of isotonic fluid, most of which originates from the ductal system. The role of aquaporin (AQP) water channels in this process is unknown.Expression and localisation of known AQP isoforms was examined in normal human pancreas, pancreatic adenocarcinoma, and pancreatic cell lines of ductal origin (Capan-1, Capan-2, and HPAF) using reverse transcriptase-polymerase chain reaction and immunohistochemistry.Messenger RNAs for AQP1, -3, -4, -5, and -8 were detected in normal pancreas and in pancreatic adenocarcinoma. The cell lines expressed AQP3, -4, and -5 but lacked AQP1 and AQP8. Immunohistochemistry of normal pancreas revealed that AQP1 is strongly expressed in centroacinar cells and in both the apical and basolateral domains of intercalated and intralobular duct epithelia. AQP1 expression declined with distance along the small interlobular ducts and was not detectable in larger interlobular ducts. AQP3 and AQP4 were not detectable by immunohistochemistry. AQP5 was observed at the apical membrane of intercalated duct cells and also in duct associated mucoid glands. AQP8 was confined to the apical pole of acinar cells. Both AQP1 and AQP5 were colocalised with cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of intercalated duct cells.AQP1 and AQP5 are strongly expressed in the intercalated ducts of the human pancreas. Their distribution correlates closely with that of CFTR, a marker of ductal electrolyte secretion. This suggests that fluid secretion is concentrated in the terminal branches of the ductal tree and that both AQP1 and AQP5 may play a significant role.
Chemotherapy With or Without Radiotherapy in Limited-Stage Diffuse Aggressive Non-Hodgkin's Lymphoma: Eastern Cooperative Oncology Group Study 1484
Authors: Sandra J. Horning, Edie Weller, KyungMann Kim, John D. Earle, Michael J. O'Connell, Thomas M. Habermann, John H. Glick
Journal: Journal of Clinical Oncology (2004)

To compare low-dose (30 Gy) radiotherapy (RT) with observation (OBS) in limited-stage aggressive lymphoma patients achieving complete remission (CR) after chemotherapy, and to measure conversion from partial response (PR) to CR with high-dose (40 Gy) RT.From 1984 to 1992, stage I (with risk factors) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomly assigned to 30 Gy involved-field RT or OBS. PR patients received 40 Gy RT.Among 172 CR patients, the 6-year disease-free survival (DFS) was 73% for low-dose RT versus 56% for OBS (two-sided P = .05). Failure-free survival (two-sided P = .06), and time to progression (two-sided P = .06) also favored RT. Intent-to-treat analyses yielded similar results. No survival differences were observed. Three RT versus 15 OBS patients relapsed in initial disease sites. At 6 years, failure-free survival was 63% in PR patients; conversion to CR did not significantly influence clinical outcome.For patients in CR after CHOP, low-dose RT prolonged DFS and provided local control, but no survival benefit was observed. The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities. Future efforts should be directed toward improved imaging and more effective systemic therapies.
Lung infections. 2. Branhamella catarrhalis: epidemiological and clinical aspects of a human respiratory tract pathogen.
Authors: T F Murphy
Journal: Thorax (1998)

The organism was subsequently regarded as an About 1-5% of healthy adults are colonised Diseases of the upper respiratory tract commensal until the by B catarrhalis. [10][1][12][13] Infants and children are Department of Medicine, Department late 1970s.Since then, several lines of evidence colonised at a higher rate. 10 14-17Adults with of Microbiology, State have established its importance as a pathogen.chronic lung diseases appear to have a higher University of NewThe bacterium has undergone several name rate of respiratory tract colonisation than York at Buffalo and the Department of changes as a result of an uncertain taxonomic healthy adults.Several studies have surveyed Veterans Affairs relationship between B catarrhalis and Mor-culture results of sputum samples and ex-Medical Center, axella and other related genera.The changing amined the clinical status of patients from Buffalo, New York, USA and unstable nomenclature of the bacterium whom B catarrhalis has been isolated 11 18 19 and T F Murphy has been a frustration for practising physicians have shown that sputum samples which contain B catarrhalis are more likely to be recovered Correspondence to: Dr T F and investigators working on the organism.It Murphy, Medical Research was first called Micrococcus catarrhalis by Ghon from patients with chronic lung disease than 151, 3495
Video assisted thoracic surgery for spontaneous pneumothorax.
Authors: R G Berrisford, R D Page
Journal: Thorax (1996)

Video-assisted thoracic surgery has been widely used in the treatment of spontaneous pneumothorax despite a paucity of data regarding the relative safety and long-term efficacy for this procedure.We reviewed 113 consecutive patients (68 male and 45 female patients, aged 15 to 92 years, mean 35.1) who underwent 121 video-assisted thoracic surgical procedures during 119 hospitalizations from 1991 through 1993.Recurrent ipsilateral pneumothorax was the most frequent indication for surgery and occurred in 77 patients (65%).The most common method of management was stapling of an identified bleb in the lung, which was undertaken in 105 (87%) patients.No operative deaths occurred.Complications included an air leak lasting longer than 5 days in 10 (8%) patients, two of whom required second procedures for definitive management No episodes of postoperative bleeding or empyema occurred.The postoperative stay ranged from 1 day to 39 days (median 3 days, average 4*3 days) and 99 patients (84%) were discharged within 5 days.Mean follow-up was 13.1 months and ranged from 1 to 34 months.Eleven patients (10%) were lost to follow-up.Ipsilateral pneumothorax recurred after five of 121 procedures (4.1%).Twelve perioperative parameters (age, gender, race, smoking history, site of pneumothorax, severity of pneumothorax, operative indications, number of blebs, site of blebs, bleb ablation, method of pleurodesis, and prolonged postoperative air leak) were entered into univariate and multivariate analysis to identify significant independent predictors of recurrence.The only independent predictor of recurrence was the failure to identify and ablate a bleb at operation, which resulted in a 23% recurrence rate versus a 1-8% rate in those with ablated blebs (p<0.001).These data suggest that video-assisted thoracic surgery is a viable alternative to thoracotomy for the treatment of recurrent spontaneous pneumothorax.It results in a short hospital stay, low morbidity, high patient acceptance, and a low rate of recurrence.(
Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays
Authors: Tamotsu Ichiba, Takanori Teshima, Rork Kuick, David E. Misek, Chen Liu, Yuichiro Takada, Yoshinobu Maeda, Pavan Reddy, Debra L. Williams, Samir M. Hanash, James L. M. Ferrara
Journal: Blood (2003)
Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport
Authors: Alessandro Filosa, Sónia Paixão, Silke D Honsek, Maria A Carmona, Lore Becker, Berend Feddersen, Louise Gaitanos, York Rudhard, Ralf Schoepfer, Thomas Klopstock, Klas Kullander, Christine R Rose, Elena B Pasquale, Rüdiger Klein
Journal: Nature Neuroscience (2009)
Recent Trends in Breast Cancer Among Younger Women in the United States
Authors: Louise A. Brinton, Mark E. Sherman, J. Daniel Carreon, William F. Anderson
Journal: JNCI Journal of the National Cancer Institute (2008)

Increases in the incidence of postmenopausal breast cancers have been linked to screening and menopausal hormone use, but younger women have received less attention. Thus, we analyzed trends in breast cancer incidence (N = 387 231) using the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program 13-Registry database (1992–2004). Whites had higher incidence rates than blacks after age 40 years, but the reverse was true among younger women (black–white crossover). Among younger women, the rate per 100 000 woman-years was 16.8 for black vs 15.1 for white women; the highest black–white incidence rate ratio (IRR) was seen among women younger than 30 years (IRR = 1.52, 95% confidence interval = 1.34 to 1.73). This risk pattern was not observed in other ethnic groups. The black–white crossover among younger women was largely restricted to breast cancers with favorable tumor characteristics. The annual percentage change in the incidence of invasive breast cancers decreased modestly among older women but increased among younger (<40 years) white women. Continued surveillance of trends is needed, particularly for molecular subtypes that preferentially occur among young women.
Mononuclear cell complement receptor blockade in primary biliary cirrhosis.
Authors: M N Al-Aghbar, J Neuberger, R Williams, A L Eddleston
Journal: Gut (1985)

Peripheral blood monocyte and lymphocyte receptors for Fc and C3b fragments were examined in vitro in patients with primary biliary cirrhosis and other chronic liver diseases using sheep red blood cells coated with anti-SRBC IgG1 (to detect Fc receptors) and with anti-SRBC IgM and complement (to detect C3b receptors). The number of C3b receptors detected on 100 monocytes was significantly lower in patients with primary biliary cirrhosis (23.0 +/- 12.0, mean +/- 1 SD) compared with normal controls (57.4 +/- 16.9) and other chronic liver disease (HBsAg negative chronic active hepatitis 62.0 +/- 17.0, alcoholic cirrhosis 50.9 +/- 4.0), while the number of Fc receptors detected on 100 monocytes was not significantly different in all the groups (primary biliary cirrhosis 72.8 +/- 28.6, chronic active hepatitis 74.7 +/- 14.0, alcoholic cirrhosis 58.0 +/- 13.5 and normal controls 69.6 +/- 19.9). When mononuclear cells isolated from normal individuals were pre-incubated with serum from patients with primary biliary cirrhosis before testing their receptor function there was a significant reduction in the number of C3b receptors detected per 100 monocytes (27.6 +/- 10.8) compared with pre-incubation with normal serum (72.0 +/- 18.0). This reduction in C3b-receptor function was again observed when the serum used for pre-incubation was depleted of circulating immune complexes; but when complement was further depleted from these sera, the number of C3b-receptors detected after pre-incubation was similar to normal values (64.0 +/- 11.8). Lymphocyte receptors showed a similar pattern of results. This implies a specific C3b receptor blockade on monocytes and lymphocytes from patients with primary biliary cirrhosis which appears to be because of blocking by serum factor(s) including complement fragments.
Inducible expression of insulin receptors on T lymphocyte clones.
Authors: V L Braciale, J R Gavin, T J Braciale
Journal: The Journal of Experimental Medicine (1982)

This study demonstrates that the insulin receptors are expressed on the surface of some T cell clones after specific antigenic stimulation. The insulin receptors on these lymphocytes are physicochemically similar to insulin receptors present on cells which express the receptors constitutively (adipocytes, hepatocytes, etc.). The kinetics of expression of insulin receptors on cloned, noncytotoxic T cells after specific antigenic stimulation closely parallels that of [3H]thymidine incorporation in such cultures.
Effect of Antiheparin Agents on Venous Thrombosis Following Vascular Injury
Authors: William A. Mersereau
Journal: Circulation Research (1962)

The effect of the antiheparin agents hexadimethrine bromide and protamine sulfate on venous thrombosis have been studied in the rat, rabbit, and dog. Untreated traumatized veins were not thrombosed. Traumatized veins treated with these agents topically, or in some species intravenously, thrombosed. The thrombi so produced consisted of an occluding mass of platelet trabeculae at the site of vascular injury, a red and white proximal tail, and a distal stasis clot. The hexadimethrine bromide-induced thrombus in the rat is prevented by pretreatment with Dicumarol or heparin. It is suggested that the antiheparin agents bring about thrombosis of the injured veins by neutralizing an anticoagulant liberated locally.
Neoadjuvant Docetaxel and Capecitabine and the Use of Thymidine Phosphorylase as a Predictive Biomarker in Breast Cancer
Authors: Rachel M. Layman, Dafydd G. Thomas, Kent A. Griffith, Jeffrey B. Smerage, Mark A. Helvie, Marilyn A. Roubidoux, Kathleen M. Diehl, Lisa A. Newman, Michael S. Sabel, James A. Hayman, Lori J. Pierce, Daniel F. Hayes, Anne F. Schott
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Thymidine phosphorylase (TP) induction by docetaxel is a proposed mechanism for the observed preclinical synergy of docetaxel and capecitabine (DC). We evaluated whether TP protein expression is increased by docetaxel and correlates with pathologic complete response (pCR) in breast cancer patients. Experimental Design: Women with stage II to III breast cancer were given four cycles of neoadjuvant docetaxel 36 mg/m2 i.v. over 30 min on days 1, 8, and 15 and capecitabine 2,000 mg/d, in two divided doses, on days 5 to 21 of a 28-day cycle. Radiology-directed biopsies of the breast tumors were done at baseline and 5 days after the first dose of docetaxel to evaluate TP expression. Following DC therapy, patients had core breast biopsies, and if residual disease was present, received four cycles of standard dose-dense doxorubin and cyclophosphamide (AC). Results: The pCR rate was 26.9% (95% confidence interval, 11.6-47.8). Up-regulation of TP expression was not observed by either quantitative immunofluorescence (QIF) or immunohistochemistry. Radiology-directed core biopsy after neoadjuvant chemotherapy accurately predicted pathologic response in 88% (95% confidence interval, 69.8-97.6) of the cases. Neither level of TP expression nor TP up-regulation correlated with pCR. Significant toxicity resulted in therapy discontinuation in 3 of 26 patients. Conclusions: DC chemotherapy exhibited a similar pCR rate compared with standard taxane regimens, with increased toxicity. TP expression was not up-regulated after docetaxel and did not correlate with therapeutic response. Core breast biopsy after neoadjuvant chemotherapy accurately predicted pathologic response.