tbuckley/cabot-search huggingface dataset:
Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma
Authors: A. Younes, H.A. Preti, F.B. Hagemeister, P. McLaughlin, J.E. Romaguera, M.A. Rodriguez, B.I. Samuels, J.L. Palmer, F. Cabanillas
Journal: Annals of Oncology (2001)

Used as single agents, paclitaxel and topotecan have demonstrated promising activity in treating patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). We conducted a phase II clinical trial to investigate the activity and tolerability of the combination of both drugs.Patients with refractory or relapsed aggressive NHL who had previously been treated with a maximum of two prior chemotherapeutic regimens were given intravenous infusions of paclitaxel 200 mg/m2 over three hours on day one and topotecan 1 mg/m2 over 30 minutes daily from days one to five. All patients received daily subcutaneous injections of filgrastim (granulocyte colony-stimulating factor) 5 microg/kg starting 24 hours after the last dose of chemotherapy until neutrophil recovery. Treatments were repeated every three weeks for a maximum of six courses. Patients who achieved partial remission or complete remission (CR) after at least two courses were offered stem cell transplantation, if eligible.Of the 71 patients eligible for this trial, 66 (93%) were evaluable for treatment response. The median age was 53 years (range 23 to 74 years). Thirty-six percent of the patients had previously been treated with ara-C/platinum-based regimens, and 48% failed to achieve CR after primary induction therapy. Sixty-seven percent of the patients had elevated lactate dehydrogenase levels at the time of treatment initiation. The overall response rate was 48% (95% confidence interval (95% CI): 36%-61%). Patients who had primary refractory disease had a response rate of 31%, compared with 65% for patients who did not. Similarly, the response rate of patients who failed to achieve CR after their most recent previous therapy was 37%, compared with a 65% response rate in patients who relapsed from a first or second CR. The median duration of response was six months. A total of 199 courses were given, with a median of three courses per patient. Neutropenia at levels < or = 500 leukocytes per microliter was observed after 32% of the courses, and thrombocytopenia at levels < or = 20,000 platelets per microliter was observed after 17% of the courses. Grade 3-4 neutropenic fever occurred after 6% of the courses. Non-hematologic toxic effects were predominantly grade 1-2.The combination of paclitaxel and topotecan is an effective first or second line salvage therapy for patients with relapsed or refractory aggressive NHL who had prior anthracycline- or platinum-based chemotherapy.
Bacterial Interference Induced in Embryonated Eggs by Staphylococci*
Authors: William R. McCabe
Journal: Journal of Clinical Investigation (1967)

Studies of experimental infections in embryonated eggs demonstrated that prior allantoic infection with avirulent staphylococci afforded significant protection against subsequent challenge with virulent strains. All strains of coagulase-positive and coagulase-negative staphylococci tested that were relatively avirulent for embryonated eggs were capable of producing interference. The interference induced afforded protection not only against challenge with virulent staphylococci, but also against Diplococcus pneumoniae, Salmonella typhimurium, Escherichia coli, Proteus mirabilis, and one strain of influenza virus (A2J 305). Prior allantoic infection with avirulent staphylococci also protected against intravenous as well as allantoic infection with challenge strains.
Idiopathic Pulmonary Fibrosis: A Degenerative Disease Requiring a Regenerative Approach
Authors: Daniel C. Chambers, Peter M. A. Hopkins
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

We read with interest Toonkel and colleagues' perspective on mesenchymal stem cell (MSC) therapy for idiopathic pulmonary fibrosis (IPF). Based on a thorough review of the available preclinical data and data from human studies for other indications, they, and evidently the U.S. Food and Drug Administration, advocate that the timing is now right for phase 1 studies of MSC therapy for this debilitating lung disease to commence. While we generally agree with their conclusions, we would like to both share our own experience grappling with the same issues they face, and advocate for a coordinated effort from basic scientists and clinicians to facilitate successful translate of this technology...
Immunological dissection of human Ia molecules.
Authors: R Tosi, N Tanigaki, D Centis, G B Ferrara, D Pressman
Journal: The Journal of Experimental Medicine (1978)

The immunochemical analysis of Daudi Ia molecules by a variety of alloantisera led to the recognition of at least three molecular species carrying different antigenic determinants: DRw6, DC-1, and DC-2. Genetic as well as structural evidence indicates that DRw6 and DC-1 molecules are controlled by separate, HLA-linked loci, rather than by alleles at the same locus. The alloantigenic determinants appear to be expressed on the small Ia subunit. DC-1 and DC-2 determinants discussed had not been defined by serological analysis at the population level, but were demonstrated to be present by immunochemical analysis at the molecular level.
Premature Menopause in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Charles A. Sklar, Ann C. Mertens, Pauline Mitby, John Whitton, Marilyn Stovall, Catherine Kasper, Jean Mulder, Daniel Green, H. Stacy Nicholson, Yutaka Yasui, Leslie L. Robison
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Childhood cancer survivors who retain ovarian function after completing cancer treatment are at increased risk of developing premature menopause, defined as cessation of menses before age 40 years. However, published data pertaining to the risk and frequency of premature menopause are limited. Methods: We assessed the incidence of and risk factors for premature menopause in 2819 survivors of childhood cancer who were older than 18 years and were participants in the multicenter Childhood Cancer Survivor Study (CCSS). The comparison group was 1065 female siblings of participants in the CCSS. A multiple Poisson regression model was constructed to determine risk factors for nonsurgical premature menopause. All statistical tests were two-sided. Results: A total of 126 childhood cancer survivors and 33 control siblings developed premature menopause. Of these women, 61 survivors (48%) and 31 siblings (94%) had surgically induced menopause (rate ratio [RR] = 0.8, 95% confidence interval [CI] = 0.52 to 1.23). However, the cumulative incidence of nonsurgical premature menopause was higher for survivors than for siblings (8% versus 0.8%; RR = 13.21, 95% CI = 3.26 to 53.51; P <.001). A multiple Poisson regression model showed that risk factors for nonsurgical premature menopause included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score (based on number of alkylating agents and cumulative dose), and a diagnosis of Hodgkin lymphoma. For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30%. Conclusions: The results of this study will facilitate counseling current survivors about their future risk of premature menopause and aid in designing new regimens that seek to diminish late ovarian toxicity.
Hypothalamic Orexin Neurons Regulate Arousal According to Energy Balance in Mice
Authors: Akihiro Yamanaka, Carsten T Beuckmann, Jon T Willie, Junko Hara, Natsuko Tsujino, Michihiro Mieda, Makoto Tominaga, Ken-ichi Yagami, Fumihiro Sugiyama, Katsutoshi Goto, Masashi Yanagisawa, Takeshi Sakurai
Journal: Neuron (2003)
Effect of Asbestos-Related Pleural Fibrosis on Excursion of the Lower Chest Wall and Diaphragm
Authors: BHAJAN SINGH, PETER R. EASTWOOD, KEVIN E. FINUCANE, JANINE A. PANIZZA, ARTHUR W. MUSK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

To examine mechanisms responsible for reduced lung volumes (restriction) in asbestos-related pleural fibrosis (APF), we studied diaphragm function and lower rib-cage excursion in 26 subjects with previous asbestos exposure and no evidence of asbestosis. Using posteroanterior (PA) and lateral chest radiographs taken at residual volume and at 25%, 70%, and 100% vital capacity (VC) during a slow inspiratory maneuver, we measured fractional expansion of the lower rib cage (FErc), fractional shortening of the diaphragm (FSdi), and changes ( Δ ) in diaphragm dome height (Hdo) and subphrenic volume (Vdi). Vdi was estimated by measuring the major and minor axes of the subphrenic space at 1-cm intervals, assuming an elliptical cross-sectional shape, and correcting for the volume of spinal and paraspinal tissues. Seven subjects had no evidence of APF (control), 12 had pleural plaques (PP), and seven had diffuse pleural thickening with costophrenic obliteration (DPT). Over the range of VC, results (mean ± SEM, normalized for height) in control subjects were VC = 101.2 ± 4.0 % predicted and Δ Vdi = 326 ± 8 ml/m3, and for the right hemithorax and hemidiaphragm on the PA film, FErc = 0.07 ± 0.02, FSdi = 0.32 ± 0.02 and Δ Hdo = 0.8 ± 0.2 cm/m. Relative to controls: DPT subjects had reduced VC (77.4 ± 4.9%, p < 0.01), Δ Vdi (256 ± 2 ml/m3, p < 0.01), FErc (0.01 ± 0.02, p < 0.01), FSdi (0.24 ± 0.01, p < 0.001), and Δ Hdo ( − 0.9 ± 0.06 cm/m, p < 0.01); PP subjects had reduced FSdi (0.25 ± 0.01, p < 0.001) and Δ Vdi (233 ± 47 ml/m3, p < 0.01), and no difference in FErc, Δ Hdo, or VC. We conclude that restriction in DPT is due to obliteration of the zone of apposition, and that by limiting separation of the diaphragm from the rib cage during inspiration, this reduces volume contributed by motion of the diaphragm and lower rib cage. Reduction in the latter contribution was the main cause of restriction, because the reduction in volume contributed by the diaphragm was partly compensated by flattening of its dome. Singh B, Eastwood PR, Finucane KE, Panizza JA, Musk AW. Effect of asbestos-related pleural fibrosis on excursion of the lower chest wall and diaphragm.
INTRACORONARY SALBUTAMOL, SEGMENTAL PLAQUE BURDEN AND FOCAL CORONARY ENDOTHELIAL FUNCTION: NOVEL MECHANISTIC INSIGHTS FROM AN IN VIVO INTRAVASCULAR ULTRASOUND STUDY
Authors: Rishi Puri, Gary Y. Liew, Stephen J. Nicholls, Adam J. Nelson, Darryl P. Leong, Angelo Carbone, Barbara Copus, Dennis T. Wong, John F. Beltrame, Stephen G. Worthley, Matthew I. Worthley
Journal: Journal of the American College of Cardiology (2011)
New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse
Authors: Jean R. Starkey, Aleksander K. Rebane, Mikhail A. Drobizhev, Fanqing Meng, Aijun Gong, Aleisha Elliott, Kate McInnerney, Charles W. Spangler
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols. Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT. Results: Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation. Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.
Antinuclear antibodies in patients with Raynaud's phenomenon: clinical significance of anticentromere antibodies.
Authors: C G Kallenberg, G W Pastoor, A A Wouda, T H The
Journal: Annals of the Rheumatic Diseases (1982)

Antinuclear antibodies (ANA) were detected in the sera of 73 out of 138 patients (53%) referred to us because of Raynaud's phenomenon. When ANA were found, systemic manifestations were likely to be present. The use of human fibroblast monolayers as a nuclear substrate allowed differentiation of several fluorescence patterns, including the discrete speckled variety produced by anticentromere antibodies. These antibodies were detected in the sera of 7 out of 10 patients with CRST syndrome (70%), in 7 out of 40 patients with scleroderma (18%), all without kidney-involvement, in one patient with Sjögren's syndrome and severe Raynaud's phenomenon, and in 7 patients with Raynaud's phenomenon associated with a few symptoms of a connective tissue disease (especially scleroderma). ANA testing on tissue culture monolayers in Raynaud's phenomenon appears to be of value in predicting systemic disease manifestations and the presence or possible future development of distinct clinical patterns, especially the CRST syndrome.
Enhancement of Sensitivity to Tumor Necrosis Factor α in Non–Small Cell Lung Cancer Cells with Acquired Resistance to Gefitinib
Authors: Koichi Ando, Tohru Ohmori, Fumiko Inoue, Tsuyoki Kadofuku, Takamichi Hosaka, Hiroo Ishida, Takao Shirai, Kentaro Okuda, Takashi Hirose, Naoya Horichi, Kazuto Nishio, Nagahiro Saijo, Mitsuru Adachi, Toshio Kuroki
Journal: Clinical Cancer Research (2005)

Abstract Tumor cells that have acquired resistance to gefitinib through continuous drug administration may complicate future treatment. To investigate the mechanisms of acquired resistance, we established PC-9/ZD2001, a non-small-cell lung cancer cell line resistant to gefitinib, by continuous exposure of the parental cell line PC-9 to gefitinib. After 6 months of culture in gefitinib-free conditions, PC-9/ZD2001 cells reacquired sensitivity to gefitinib and were established as a revertant cell line, PC-9/ZD2001R. PC-9/ZD2001 cells showed collateral sensitivity to several anticancer drugs (vinorelbine, paclitaxel, camptothecin, and 5-fluorouracil) and to tumor necrosis factor α (TNF-α). Compared with PC-9 cells, PC-9/ZD2001 cells were 67-fold more sensitive to TNF-α and PC-9/ZD2001R cells were 1.3-fold more sensitive. Therefore, collateral sensitivity to TNF-α was correlated with gefitinib resistance. PC-9/ZD2001 cells expressed a lower level of epidermal growth factor receptor (EGFR) than did PC-9 cells; this down-regulation was partially reversed in PC-9/ZD2001R cells. TNF-α-induced autophosphorylation of EGFR (cross-talk signaling) was detected in all three cell lines. However, TNF-α-induced Akt phosphorylation and IκB degradation were observed much less often in PC-9/ZD2001 cells than in PC-9 cells or PC-9/ZD2001R cells. Expression of the inhibitor of apoptosis proteins c-IAP1 and c-IAP2 was induced by TNF-α in PC-9 and PC-9/ZD2001R cells but not in PC-9/ZD2001 cells. This weak effect of EGFR on Akt pathway might contribute to the TNF-α sensitivity of PC-9/ZD2001 cells. These results suggest that therapy with TNF-α would be effective in some cases of non-small-cell lung cancer that have acquired resistance to gefitinib.
von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.
Authors: D Feng, S E Bursell, A C Clermont, I Lipinska, L P Aiello, L Laffel, G L King, G H Tofler
Journal: Diabetes Care (2000)

OBJECTIVE: Although retinopathy is a common microvascular complication of type 1 diabetes, the mechanism for this complication is still unknown. Changes in retinal circulation have been noted before the development of overt retinal pathology. Because von Willebrand factor (vWF) is a marker for endothelial dysfunction and mediates platelet adhesion, we determined if there was an association between vWF and retinal circulation in the early stages of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Twenty subjects (aged 32.4 +/- 7.8 years) with type 1 diabetes and minimal or no retinopathy were studied. The mean duration of diabetes was 4.7 +/- 2.6 years. Data were collected at baseline and after 4 months of 1,800 IU vitamin E therapy or placebo. Retinal circulation was evaluated by video fluorescein angiography. Plasma vWF antigen levels were measured by enzyme-linked immunosorbent assay and fibrinogen by the Clauss method. RESULTS: Retinal blood flow was negatively correlated with vWF levels (r = -0.44, P = 0.008), whereas retinal circulation time was positively correlated with vWF levels (r = 0.33, P = 0.048). Fibrinogen levels were not significantly associated with either retinal index. However, fibrinogen levels were positively associated with HbA1c levels (r = 0.34, P = 0.01), indicating an association between poor glycemic control and higher fibrinogen levels. CONCLUSIONS: Increased vWF was associated with a prolonged retinal circulation time and reduced retinal blood flow in early-stage retinopathy of type 1 diabetes. Reduced blood flow associated with increased vWF levels may promote stasis in the retinal circulation and lead to local hypoxemia. These changes might contribute to the microvascular complications of diabetes. Whether the vWF levels predict retinal complications deserves further investigation.
DNA/protein complexes delivered in conjunction with adenovirus generate high-efficiencyin vitro transfection: A powerful transfection reagent with potential broad applications
Authors: Fred Askari
Journal: Hepatology (1993)

We have combined a receptor-mediated DNA delivery system with the endosomal lysis ability of adenovirus and shown that DNA can be delivered into primary hepatocytes, resulting in a high level of gene expression. When asialoorosomucoid conjugated with poly(L-lysine) was used to deliver the Escherichia coli β-galactosidase gene into primary hepatocytes through binding with the hepatic asialoglycoprotein receptor, only a low level of β-galactosidase was detectable, with less than 0.1% of the hepatocytes being transfected. This level of activity can be greatly enhanced by the cointernalization of the DNA protein complex with a replication-defective adenovirus, resulting in 100% of the hepatocytes staining blue with 5-bromo-4-chloro-3-indolyI β-D-galactoside. Quantitative analysis of β-galactosdase expression also showed a 1000-fold enhancement of activity. To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and dem-onstrated complete reconstitution of enzymatic activity. This method shows great promise for efficient gene delivery to the liver for correction of hepatic disorders.
Endoscopic Diagnosis of Childhood Burkitt's Lymphoma of the Colon
Authors: Frédéric Millot, Marie-Annick Barboteau, Marie-José Loyer-Lecestre, Françoise Brizard, Pierre Levillain, François Guilhot
Journal: Journal of Clinical Oncology (2010)

A 11-year-old previously healthy girl presented with abdominal pain for 8 weeks. Her physical examination was unremarkable except for a mass located in the right upper quadrant. Abdominal computed tomography scan revealed a 4-cm solid mass arising from the right colon (Fig 1). Positron emission tomography with [F]fluorodeoxyglucose scanning exhibited abnormal uptake in the right upper quadrant of the abdomen (Fig 2). Colonoscopy showed a 4 4 cm near-obstructive nonulcerated wall mass in the right colon (Fig 3). An endoscopic biopsy of the mass was performed. Histology showed a rich cellular infiltrate with medium-sized atypical lymphocytes with round to irregular nuclei, prominent nucleoli, and scant cytoplasm with a starry sky appearance (Fig 4A). Tumor cells showed positive staining for CD45, CD20, and CD10 (Fig 4B, immunostaning for CD20). A diagnosis of Burkitt’s lymphoma was confirmed by cytogenetic analysis of the tumor, with the t(8;14)(q24; q32) translocation being found. Bone marrow and CSF study did not show any malignant cells. The patient underwent four cycles of chemotherapy according to the LMB 96 protocol, with complete disappearance of the palpable abdominal mass confirmed on computed tomography scanning. The patient currently remains free of disease at a follow-up of 5 years. Burkitt’s lymphoma is a mature B-cell neoplasm characterized by the expression of surface immunoglobulins and the presence of characteristic reciprocal chromosomal translocations involving the c-myc oncogene and an immunoglobulin gene. Burkitt’s lymphoma is prevalently a childhood malignancy and represents an oncological emergency because of its high proliferation fraction and short doubling time. Burkitt’s lymphoma is highly sensitive to chemotherapy including cyclophosphamide, vincristine, cytarabine, and methotrexate. The overall cure rates are approximately 90% in children and 65% to 80% in adults with contemporary chemotherapy regimens. Most children with Burkitt’s lymphoma present with primary involvement of the abdomen or the head and neck region. Patients with primary localized disease in the abdomen may present with abdominal pain or swelling, gastrointestinal bleeding, intestinal perforation, or intestinal obstruction resulting from direct compression of the lumen by an expanding mass or by an intussusception triggered by the intraluminal projection of the tumor mass. These abdominal symptoms often lead to emergency laparotomies before a diagnosis of Burkitt’s lymphoma can be made. Surgical resection could be associated with
A comparison between the Farr radioimmunoassay and a new automated fluorescence immunoassay for the detection of antibodies against double stranded DNA in serum
Authors: R H W M Derksen
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To compare test characteristics of the Farr radioimmunoassay and an automated fluorescence immunoassay (ELIA dsDNA test) for the diagnosis of systemic lupus erythematosus (SLE). <b>Methods:</b> A cross sectional study comprising 440 samples from 440 patients, sent to the laboratory over a three month period for anti-dsDNA testing. Chart review was performed, blinded for test results, to count for each patient the number of American College of Rheumatology criteria for the classification of SLE that were fulfilled. At least four criteria were met by 248 (56%) patients (SLE), one to three criteria by 77 (18%) (lupus-like disease, LLD), and no criterion by 115 (26%) (non-SLE/non-LLD). Results from serum samples from the non-SLE/non-LLD and SLE groups were used to calculate receiver operating characteristic curves. <b>Results:</b> For the Farr assay, specificities of 95% and 99% corresponded to sensitivities of 72% and 56% respectively. For the ELIA dsDNA test these levels of specificity corresponded to sensitivities of 44% and 17% respectively. <b>Conclusions:</b> The Farr radioimmunoassay is superior to the ELIA dsDNA test for identifying patients with SLE.