tbuckley/cabot-search huggingface dataset:
Superiority of Alternating Non-Cross-Resistant Chemotherapy in Extensive Small Cell Lung Cancer
Authors: W. K. EVANS
Journal: Annals of Internal Medicine (1987)

The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. "Standard" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%p < 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p < 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.
Radioimmunoassay of human intestinal goblet cell mucin. Investigation of mucus from different organs and species.
Authors: R Qureshi, G G Forstner, J F Forstner
Journal: Journal of Clinical Investigation (1979)

We have developed a double-antibody radioimmunoassay for the quantitative measurement of human goblet cell mucin (GCM) in order to study intestinal mucus in human and other species. The assay used 3H-labeled mucin as the antigen, rabbit antisera, and sheep anti-rabbit IgG antisera as the second antibody. A number of applications of the assay were investigated. A survey of human tissues revealed that mucins of the rectum, colon, and small intestine had identical affinity for the rabbit antibody, whereas lung eyelid conjunctiva, esophagus, and stomach reacted less strongly. GCM concentration ranged from 1.9 to 14 microgram mucin protein/mg tissue protein in the small and large intestine, respectively. The radioimmunoassay was also found to be useful as a marker during the isolation of GCM from human ileal extracts, where it indicated that a 10,000-fold purification had been achieved. Antigenic determinants of the mucin did not rely upon ABH blood group-specific terminal sugars in oligosaccharide chains. A comparison of mucins among various species revealed a partial species specificity of the GCM antibody. Human GCM cross-reacted with dog, monkey, and rabbit mucins, but not with mucins of rat, pig, toad, and oyster. Organ distributions of cross-reactive mucins in rabbit tissues indicated a pattern that was qualitatively similar to that seen in human tissues. Possible implications of these findings for autoimmune diseases are briefly discussed.
An Early Clinical Evaluation of Clopenthixol in Treatment-Resistant Female Schizophrenic Patients
Authors: ARTHUR WOLPERT, CHARLES SHEPPARD, SIDNEY MERLIS
Journal: American Journal of Psychiatry (1967)

Some published results from the European literature regarding the therapeutic and untoward effects of clopenthixol therapy were replicated. Therapeutic response was demonstrated at a daily dosage of 50 mg. An initial drowsiness was noted within a few days of therapy. No laboratory abnormalities were noted. The global impressions of the ward physician were confirmed by the statistical evaluation of the rating data. A significant improvement was demonstrated in this sample of treatment-resistant, chronic female schizophrenics. This has encouraged us to formulate a further, more extensive investigation of clopenthixol in a larger double-blind comparative study.
Left Ventricular Filling and Diastolic Pressure-Volume Relations in the Conscious Dog
Authors: MARK I. M. NOBLE, ERIC N. C. MILNE, R. JON GOERKE, ERIK CARLSSON, RAUL J. DOMENECH, KENNETH B. SAUNDERS, JULIEN I. E. HOFFMAN
Journal: Circulation Research (1969)

In 7 conscious dogs, left ventricular diastolic volume (V) was estimated by taking biplane cineradiographs with the left ventricular cavity previously outlined by permanent radiopaque markers. Left ventricular pressure (P) was measured with an implanted miniature transducer. There were two rapid filling periods during early and late diastole; little filling occurred during the middle third of diastole (diastasis). The diastolic pressure-volume relationship was approximately exponential and was fitted by the equation P=- a+be c v , where, a, b , and c are positive constants; the relationship appeared to be determined principally by the elastic properties. The effects of infusions of saline, isoproterenol, calcium gluconate, and methoxamine suggested that viscous and inertial properties are also important determinants of diastolic left ventricular mechanics. No significant series viscosity was observed. Plastic properties were not detected. The elastic properties were not affected by agents having a positive inotropic effect. End-diastolic pressure often differed from that predicted by the exponential equation above, suggesting that it is not a reliable index of enddiastolic volume and left ventricular compliance.
Are We Using the Correct Dose of Metronidazole in Colorectal Surgery?
Authors: J H Hobbiss, N D Carr, P F Schofield
Journal: Journal of the Royal Society of Medicine (1988)

In a series of 20 patients undergoing elective colorectal surgery, 10 received an infusion of metronidazole 500 mg and 10 an infusion of 1500 mg commencing at the induction of anaesthesia. The concentrations of metronidazole in the plasma, rectus muscle and colon of the two groups during the course of the operation were compared. In those patients who received 1500 mg, the plasma and tissue concentrations were all well above the minimum inhibitory concentration (MIC) of metronidazole against Bacteroides fragilis. In those patients who received 500 mg, serum and tissue concentrations were at or only just above the MIC. It may be that 1500 mg would be a more effective dose of metronidazole for prophylactic use in colorectal surgery.
Increasing Incidence of Oral Tongue Squamous Cell Carcinoma in Young White Women, Age 18 to 44 Years
Authors: Sagar C. Patel, William R. Carpenter, Seth Tyree, Marion Everett Couch, Mark Weissler, Trevor Hackman, D. Neil Hayes, Carol Shores, Bhishamjit S. Chera
Journal: Journal of Clinical Oncology (2011)

To evaluate the incidence of oral cavity squamous cell carcinoma (OCSCC) and oral tongue squamous cell carcinoma (OTSCC) in young white women, age 18 to 44 years.We analyzed incidence and survival data from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1975 to 2007 for OCSCC and OTSCC. Three cohorts were examined: all ages, age 18 to 44 years (ie, "young"), and age > 44 years. Individuals were stratified by sex and/or race. Percentage change (PC) and annual percentage change (APC) were calculated. Joinpoint regression analyses were performed to examine trend differences.Overall, incidence of OCSCC was decreasing for all ages. However, incidence was increasing for young white women (PC, 34.8; APC, 2.2; P < .05). Incidence of OTSCC was decreasing for all ages except in the age 18 to 44 years group (PC, 28.8; APC, 1.8; P < .05). Young white individuals had increasing incidence trends of OTSCC (white women: PC, 111.3; APC, 4; P < .05; young white men: PC, 43.7; APC, 1.6; P < .05). The APC of OTSCC was significantly greater in young white women compared with that in young white men (P = .007). Furthermore, incidence of SCC in all other subsites of the oral cavity was decreasing. Nonwhites had a decreasing incidence of OCSCC and OTSCC. Cause-specific survival was similar among whites age 18 to 44 and individuals older than age 44 years.OTSCC is increasing among young white individuals age 18 to 44 years, particularly among white women. Young white women may be a new, emerging head and neck cancer patient population.
Notes on Rubella. With Special Reference to Certain Rheumatic Sequelae
Authors: R. A. Bennett, W. S. C. Copeman
Journal: BMJ (1940)

Miss A., aged 29.-Admitted 3/3/40; discharged 14/3/40.Rash appeared 3/3/40.Throat and gums normal; swelling of occipital glands.Pains in joints began 4/3/40 in wr-ists, knees, and ankles.No swelling of joints. ,;>ash disappeared in three days and pains in joints improved,,on disappearance of rash.Temperature 99°on admission; normal since.Miss B., aged 24.-Admitted 8 / 3 / 40; discharged 17 / 3 / 40.Rash appeared 8/3/40, with severe pains in gums.Throat normal; occipital glands enlarged; gums appeared normal.Pains in joints 10/3/40-in wrists and ~.nkles-which kept
Postural Hypotension
Authors: PHILIP L. DERN
Journal: Circulation (1958)

Clinical experience suggests that there are differences in the extent to which hypertensive patients respond with falls in blood pressure after administration of effective doses of ganglionic-blocking drugs. In this study attempts are made to define the relative magnitudes of the postural and nonpostural falls in blood pressure that are produced by these drugs. Frequent measurements of the blood pressure were made in hypertensive human subjects before and after the administration of ganglion-blocking agents. Drug-induced falls in blood pressure are calculated with reference to the baseline levels of blood pressure established in various ways for the individual patients.
Modeling the Health Effects of Expanding e-Cigarette Sales in the United States and United Kingdom
Authors: Sara Kalkhoran, Stanton A. Glantz
Journal: JAMA Internal Medicine (2015)

The prevalence of electronic cigarette (e-cigarette) use is increasing. Population health effects will depend on cigarette smoking behaviors, levels of dual use with conventional cigarettes, and e-cigarette toxicity.To evaluate potential health effects of various scenarios of increasing promotion and use of e-cigarettes.A base case model was developed using data on actual cigarette and e-cigarette use patterns that quantifies transitions from an initial state of no cigarette or e-cigarette use to 1 of 5 final states: never use of cigarettes or e-cigarettes, cigarette use, e-cigarette use, dual use of cigarettes and e-cigarettes, or quit. Seven scenarios were created that cover a range of use patterns, depending on how the e-cigarette market might develop, as well as a range of possible long-term health effects of e-cigarette use. Scenarios for changes from the base case were evaluated using Monte Carlo simulations. Separate sets of base case model parameters were evaluated for the US and UK populations.We assigned unitless health "costs" for each final state on a scale of 0 to 100. Population health "costs" were compared with the base case (status quo) assuming e-cigarette use health "costs" from 1% to 50% as dangerous as conventional cigarette use health costs.Compared with the base case, a harm reduction scenario in which e-cigarette use increases only among smokers who are interested in quitting with more quit attempts and no increased initiation of e-cigarette use among nonsmokers, and another scenario in which e-cigarettes are taken up only by youth who would have smoked conventional cigarettes, had population-level health benefits regardless of e-cigarette health costs in both the United States and United Kingdom. Conversely, scenarios in which e-cigarette promotion leads to renormalization of cigarette smoking or e-cigarettes are used primarily by youth who never would have smoked showed net health harms across all e-cigarette health costs. In other scenarios, the net health effect varied on the basis of the health cost of e-cigarettes.According to this analysis, widespread promotion of e-cigarettes may have a wide range of population-level health effects, depending on both e-cigarette health risks and patterns of use. Absent the primary effect of e-cigarette promotion being only to divert current or future conventional cigarette smokers to e-cigarette use, the current uncertainty about the health risks of e-cigarettes, increasing e-cigarette use among youth, and the varying health effects at different e-cigarette health costs suggest a potential for harm.
Overcoming Temozolomide Resistance in Glioblastoma via Dual Inhibition of NAD+ Biosynthesis and Base Excision Repair
Authors: Eva M. Goellner, Bradford Grimme, Ashley R. Brown, Ying-Chih Lin, Xiao-Hong Wang, Kelsey F. Sugrue, Leah Mitchell, Ram N. Trivedi, Jiang-bo Tang, Robert W. Sobol
Journal: Cancer Research (2011)

Abstract Glioblastoma multiforme (GBM) is a devastating brain tumor with poor prognosis and low median survival time. Standard treatment includes radiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ). However, a large percentage of tumors are resistant to the cytotoxic effects of the TMZ-induced DNA lesion O6-methylguanine due to elevated expression of the repair protein O6-methylguanine-DNA methyltransferase (MGMT) or a defect in the mismatch repair (MMR) pathway. Although a majority of the TMZ-induced lesions (N7-methylguanine and N3-methyladenine) are base excision repair (BER) substrates, these DNA lesions are also readily repaired. However, blocking BER can enhance response to TMZ and therefore the BER pathway has emerged as an attractive target for reversing TMZ resistance. Our lab has recently reported that inhibition of BER leads to the accumulation of repair intermediates that induce energy depletion–mediated cell death via hyperactivation of poly(ADP-ribose) polymerase. On the basis of our observation that TMZ-induced cell death via BER inhibition is dependent on the availability of nicotinamide adenine dinucleotide (NAD+), we have hypothesized that combined BER and NAD+ biosynthesis inhibition will increase TMZ efficacy in glioblastoma cell lines greater than BER inhibition alone. Importantly, we find that the combination of BER and NAD+ biosynthesis inhibition significantly sensitizes glioma cells with elevated expression of MGMT and those deficient in MMR, two genotypes normally associated with TMZ resistance. Dual targeting of these two interacting pathways (DNA repair and NAD+ biosynthesis) may prove to be an effective treatment combination for patients with resistant and recurrent GBM. Cancer Res; 71(6); 2308–17. ©2011 AACR.
Updated survival and outcomes for older adults with inoperable stage III non-small-cell lung cancer treated with cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel: analysis of a phase III trial from the Hoosier Oncology Group (HOG) and US Oncology
Authors: S.I. Jalal, H.D. Riggs, A. Melnyk, D. Richards, A. Agarwala, M. Neubauer, R. Ansari, R. Govindan, D. Bruetman, W. Fisher, T. Breen, C.S. Johnson, M. Yu, L. Einhorn, N. Hanna
Journal: Annals of Oncology (2011)
Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease.
Authors: N Domloge-Hultsch, W R Gammon, R A Briggaman, S G Gil, W G Carter, K B Yancey
Journal: Journal of Clinical Investigation (1992)

Epiligrin, the major component of human keratinocyte extracellular matrix, serves as the preferred integrin ligand for alpha 3 beta 1 in plasma membranes and focal adhesions, and colocalizes with alpha 6 beta 4 in hemidesmosomes. In human skin, epiligrin is found in the lamina lucida subregion of epidermal basement membrane, where it is thought to be associated with anchoring filaments. We have identified three patients with an acquired mucosal predominant subepidermal blistering disease who have IgG anti-basement membrane autoantibodies that bind the lamina lucida/lamina densa interface of epidermal basement membrane, stain cultured human keratinocyte extracellular matrix, and immunoprecipitate disulfide linked polypeptides of 170, 145, 125, and 95 kD in human keratinocyte culture media in a pattern identical to that of P1E1, a murine monoclonal antiepiligrin antibody. Comparative immunoprecipitation studies of patient sera, P1E1, and GB3 monoclonal antibody show that epiligrin is identical to the antigen (i.e., BM600 or GB3 antigen) previously reported to be absent from the skin of patients with lethal junctional epidermolysis bullosa, an inherited subepidermal blistering disease. Moreover, skin from a fetus with this disease shows no evidence of reactivity to patient antiepiligrin autoantibodies or P1E1. These studies show that antiepiligrin autoantibodies are a specific marker for a novel autoimmune blistering disease and that the epidermal basement membrane antigen absent in patients with lethal junctional epidermolysis bullosa is epiligrin.
Endosialin Protein Expression and Therapeutic Target Potential in Human Solid Tumors: Sarcoma versus Carcinoma
Authors: Cecile Rouleau, Maritza Curiel, William Weber, Robert Smale, Leslie Kurtzberg, James Mascarello, Carol Berger, Gina Wallar, Rebecca Bagley, Nakayuki Honma, Kazumasa Hasegawa, Isao Ishida, Shiro Kataoka, Beth L. Thurberg, Khodadad Mehraein, Bruce Horten, Glenn Miller, Beverly A. Teicher
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Endosialin/CD248/tumor endothelial marker 1 is expressed in stromal cells, endothelial cells, and pericytes in various tumors; however, few studies have focused on expression in malignant cells. Experimental Design: We studied expression of endosialin in clinical specimens, cell culture, and animal models and designed an anti-endosialin therapeutic prototype. Results: Fifty human tumor cell lines and 6 normal cell types in culture were assayed by reverse transcription-PCR and/or flow cytometry for endosialin. Cell surface protein was found on 7 sarcoma lines, 1 neuroblastoma, and 4 normal cell types in culture. A fully human anti-endosialin antibody bound to human A-673 Ewing's sarcoma cells and SK-N-AS neuroblastoma cells but not HT-1080 cells. Exposure of cells to an anti-human IgG conjugated to saporin resulted in growth inhibition only of endosialin-expressing cells. Endosialin expression was assessed by immunohistochemistry in 250 clinical specimens of human cancer including 20 cancer subtypes. Endosialin is frequently found in human cancers. Endosialin expression is mainly a perivascular feature in carcinomas, with some expression in stromal cells. In sarcomas, endosialin is expressed by malignant cells, perivascular cells, and stromal cells. Development and characterization of experimental models for studying endosialin biology in sarcomas and evaluating anti-endosialin therapies is presented. Conclusions: Findings suggest that an anti-endosialin immunotoxin might be a promising therapeutic approach for endosialin-positive neoplasia, especially synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, and osteosarcoma. Thus, a diagnostic/therapeutic targeted therapeutic approach to treatment of endosialin-expressing tumors may be possible.
Replacing Antibodies: Engineering New Binding Proteins
Authors: Scott Banta, Kevin Dooley, Oren Shur
Journal: Annual Review of Biomedical Engineering (2013)

Nature's reliance on proteins to carry out nearly all biological processes has led to the evolution of biomolecules that exhibit a seemingly endless range of functions. Much research has been devoted toward advancing this process in the laboratory in order to create new proteins with improved or unique capabilities. The protein-engineering field has rapidly evolved from pioneering studies in engineering protein stability and activity to an application-driven powerhouse on the forefront of emerging technologies in biomedical engineering and biotechnology. A classic protein-engineering technique in the medical field has focused on manipulating antibodies and antibody fragments for various applications. New classes of alternative scaffolds have recently challenged this paradigm, and these structures have been successfully engineered for applications including targeted cancer therapy, regulated drug delivery, in vivo imaging, and a host of others. This review aims to capture recent advances in the engineering of nonimmunoglobulin scaffolds as well as some of the applications for these molecular recognition elements in the biomedical field.
Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages
Authors: S. Hodge, G. Hodge, S. Brozyna, H. Jersmann, M. Holmes, P. N. Reynolds
Journal: European Respiratory Journal (2006)

Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AMs). The present study investigated the effects of low-dose (500 ng·mL -1 ) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array. Baseline phagocytosis was reduced in COPD subjects compared with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls. The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91, αvβ3 integrin). At higher doses, azithromycin decreased levels of pro-inflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease.
Nucleotide sequence of the Xdh region in Drosophila pseudoobscura and an analysis of the evolution of synonymous codons.
Authors: M A Riley
Journal: Molecular Biology and Evolution (1989)

The nucleotide sequence of the Xdh region of Drosophila pseudoobscura is presented. The Xdh gene structure and organization are compared with the homologous region in D. melanogaster. This locus is shown to have similar organization in the two species, although an additional intron and three insertion/deletion events are described for the D. pseudoobscura coding region. The encoded proteins are predicted to have very similar charges and hydrophobic/hydrophilic domains even though 11% of the amino acids are different. A gene 5' to Xdh, putative l(3)s12, is suggested from sequence similarity between the species. Synonymous differences at the Xdh locus between the two species are analyzed using a new method described in the preceding paper by Lewontin. This analysis shows that synonymous positions within the Xdh locus are evolving at very different rates, being dependent on level of codon redundancy. A comparison of synonymous divergence between D. melanogaster and D. pseudoobscura in five additional genes reveals variation in the level of synonymous substitution.