tbuckley/cabot-search huggingface dataset:
Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam.
Authors: D Razavi, N Delvaux, C Farvacques, F De Brier, C Van Heer, L Kaufman, M P Derde, M Beauduin, M Piccart
Journal: Journal of Clinical Oncology (1993)

Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy (CT) has been reported, little has been done to develop strategies to prevent these problems. A double-blind, placebo-controlled study was therefore designed to assess the usefulness of adding low-dose alprazolam (0.5 mg to 2 mg per day) to a psychologic support program including progressive relaxation training designed to prevent the aforementioned conditions. Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment, which was conducted at four time points: before starting CT, 6 weeks after CT, before the fourth CT, and after the fourth CT. The Hospital Anxiety and Depression Scale (HADS), Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAS), Revised Symptom Checklist (SCL-90-R), Morrow Assessment of Nausea and Emesis (MANE), and World Health Organization (WHO) grading of acute and subacute toxicities were used to compare the alprazolam (AA) and placebo (PA) arms of the study.At the second evaluation, the results showed a higher rate of anticipatory nausea (18% v 0%) in the PA compared with the AA arm (P = .038). These differences were no more significant at each of the further assessments. Significant differences were found for the intake of hypnotics at each assessment visit, with the rate of hypnotic users being significantly higher in the PA (19%) compared with the AA (0%) arm at the fourth assessment (P < .05). Anxiety and depression scores of self- and observer-report were similar in the two arms. A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline. The average HADS total score at baseline was 15.33 (SD = 6.56) for patients who developed anticipatory nausea and 11.23 (SD = 6.67) for other patients.The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT. Although studies are needed to improve the efficacy reported here, physicians may already consider the use of alprazolam for cancer patients undergoing CT.
Abstract 264: Therapeutic Hypothermia Cardioprotection Is Associated with Enhanced pAMPK but Not ATP Preservation
Authors: Willard W Sharp, Zuo-Hui Shao, Mei Han, Chang-Qing Li, Kimm Hamann, David Beiser, Terry Vanden Hoek
Journal: Circulation (2011)

Introduction: Therapeutic Hypothermia (TH) is cardioprotective following ischemia/reperfusion (I/R) injury and improves survival following cardiac arrest in an Akt dependent manner. AMP activated protein kinase (AMPK) is a highly conserved, cardioprotective, sensor of cellular energetic stress and ATP depletion that is activated by ischemia. Phosphorylated AMPK (pAMPK) is also a significant inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) that is activated by Akt but inhibited by TH. In this study we hypothesized that TH enhances pAMPK independent of cellular ATP while increasing cell survival. We further hypothesized that strategies to enhance pAMPK would mimic TH cardioprotection by inhibiting mTORC1. Methods: Cardiomyocytes isolated from 1-2-day old C57BL6/J mice, were exposed to simulated Ischemia (90 min) followed by reperfusion. For TH, cells were cooled from 37C to 32C during ischemia and the first hour of reperfusion. Protein lysates were collected at serial time points for changes in pAMPK by western blot analyses. ATP measurements were made using a standard bioluminescence assay. Results: pAMPK was significantly increased during ischemia as compared to controls. During reperfusion, pAMPK decreased but was maintained by TH (n=5, p&lt;.05). Total AMPK was unchanged. Total cellular ATP decreased significantly with ischemia and TH to 6% and 13% of controls (n=5, p&lt;.05). Following 30 minutes of reperfusion, ATP increased to 9% (IR) and 26% (TH) of controls. Although total cellular ATP increased with TH, these changes were not significant and remained substantially reduced from controls. Cardiomyocyte cell death during ischemia was minimal but increased during reperfusion (4% vs. 46%, p.05, n=5). This cell death was attenuated by TH (24%, p&lt;.05, n=5). The pAMPK activator metformin (100um) similarly attenuated reperfusion associated cell death (22%, p&lt;.05, n=4) while inhibiting mTORC1. Conclusions: TH is associated with enhanced cardiomyocyte survival and pAMPK following IR. These events were not associated with enhanced ATP preservation during ischemia. Pharmacologic strategies to mimic TH effects on AMPK may be beneficial to enhance survival following cardiac arrest.
Description of a Permeable Eukaryotic Cell System to Study Agents Affecting DNA Synthesis: Demonstration That Cytembena is a Direct Inhibitor of Replicative DNA Synthesis 2
Authors: Nathan A. Berger, Georgina Weber
Journal: JNCI Journal of the National Cancer Institute (1977)

Cells were made permeable to DNTP's by a 15-minute treatment with 0.01 M Tris/HCl (pH 7.8), 0.25 M sucrose, 1 mM EDTA, 30 mM 2-mercaptoethanol, and 4 mM MgCl2 at 4 degrees C. These cells used exogenously supplied dNTP's to carry out semiconservative, replicative DNA synthesis. This system could be used to identify inhibitors of DNA synthesis and to determine whether chemotherapeutic agents affect precursor synthesis or whether they have a direct effect on the DNA replication complex. Thus DNA synthesis in the permeable cells was not inhibited by hydroxyurea or by the nucleoside analogue arabinofuranosyl cytosine. In contrast, the active form of the nucleoside analogue, arabinofuranosyl cytosine triphosphate, and daunorubicin promptly inhibited DNA synthesis in the permeable cells. Cytembena, sodium cis-beta-4-methoxybenzoyl-beta-bromoacrylate, also inhibited DNA synthesis in the permeable cells; this demonstrated that this agent functioned as a direct inhibitor of the DNA replication complex.
Pulmonary function abnormalities in Egyptian sickle cell disease patients
Authors: Amany Abou Zeid, Mona El Ghamarawy
Journal: European Respiratory Journal (2011)

Background:  Pulmonary complications account for significant morbidity and mortality in sickle cell disease (SCD) patients. Abnormal pulmonary functions (PFTs) in these patients include airway obstruction, restriction, abnormal diffusing capacity, and hypoxemia. This study was carried out to assess PFTs among SCD patients, and the effects of different clinical and laboratory variables on PFTs.   Methods:  Forty five steady state SCD patients, previously diagnosed and followed up at the Hematology Outpatient Clinic of New Children Hospital; Cairo University, were included. Twenty seven were homozygous for HbSS and 18 sickle β thalassemia. Their mean age was 15.1 years with a range of 5-33years. Clinical, laboratory and PFTs were performed.   Results:  Abnormalities of PFTs were found in 57.8% of our patients (n=26, 23 having restrictive and 3 obstructive patterns). According to severity of affection, 44.4%, 8.9% and 4.4% had mild, moderate and moderate to severe abnormalities respectively. Patients9 age was the only clinical variable that showed a statistically significant difference between SCD patients with normal and abnormal PFTs (p=0.02) and between those with normal and restrictive patterns (p =0.05). Frequency of vaso-occlusive crisis and serum ferritin level showed a statistically significant relation with severity of pulmonary affection (p=0.01 and 0.01 respectively). No statistically significant difference in parameters of PFTs of patients on hydroxyurea (HU) and those not.   Conclusion:  Pulmonary function abnormalities, mostly mild and restrictive, were found among our SCD patients. These changes may be more prominent with increasing age. Severity of pulmonary affection was related to frequency of VOC.
Tumorigenicity and Other Properties of Cells From Ten Continuous Human Esophageal Carcinoma Cell Lines in Nude Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: K M Robinson, L Maistry
Journal: JNCI Journal of the National Cancer Institute (1983)

A total of 239 6-week-old nude mice of BALB/c origin were inoculated sc with human esophageal carcinoma cells of lines Hcu 10, Hcu 18, Hcu 37, and B5 (derived from poorly differentiated tumors), of lines Hcu 39, Hcu 57, and B17 (derived from moderately differentiated tumors), and of lines Hcu 13, Hcu 33, and Hcu 35 (derived from well-differentiated tumors), as well as with esophageal carcinoma lines 13.M1, 13.M5, 13.M7, 13M9, and 13.M1.M11 passaged through the mouse. Tumor take rates varied from 5 to 90% with an overall take rate of 21.9% (56 tumors). Latent periods ranged from 4 weeks to 9 months, and cells of each line gave rise to tumors of varying histologic differentiation. Cells of the poorly differentiated and well-differentiated lines gave rise to 23 infiltrating tumors, with metastasis being observed in a single mouse. All other tumors (33) were encapsulated and mobile. Thirty mice were observed for 6 months following removal of the primary tumor, and a single instance of recurrent carcinoma was noted. Cells from the nude mouse tumor xenografts adapted well to in vitro conditions and developed into continuous lines. The investigations confirmed the tumorigenic potential of 10 human esophageal carcinoma cell lines and provided information about properties of esophageal carcinoma cells in vivo and in vitro.
Effects of Sublethal Irradiation on Changes in Crypts of the Mouse Colon During Treatment With 1,2-Dimethylhydrazine&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: T C Richards, D E Tacha
Journal: JNCI Journal of the National Cancer Institute (1982)

The effects of low-dose X-irradiation on the progression of early neoplastic changes induced in the colon by 1,2-dimethylhydrazine (DMH) were assessed. Outbred female Swiss-Webster mice were treated with DMH only, DMH-irradiation, irradiation only, or 0.001 M EDTA. Animals were pulsed with [3H]thymidine for 1 hour, and the distal colon was radioautographed. The number of labeled cells per crypt in animals tested with DMH-irradiation was greater (P less than 0.01) than the number in "DMH-only" animals, but a corresponding increase in the length of the crypts did not occur. After 16 weeks of treatment, the percentage of animals with focal atypia was similar in the DMH-irradiation group (87%), and the DMH-only group (100%), but there were more focal atypias per animal in the DMH-only group. After 20 weeks, 14% of the DMH-irradiation group had visible tumors compared to 63% of the DMH-only group. The results suggest that DMH increased the number of cells at risk for irradiation; thus the surge in proliferation subsequent to cell depletion was amplified. However, the development of precancerous lesions was not promoted.
PAX6 Alone and Synergistically with PTEN Suppresses the Expression of Vascular Endothelial Growth Factor in Glioblastoma Cells
Authors: Debra A. Mayes, Xiaosong Wu, Tj Liu, W. K. Alfred Yung, Yi-Hong Zhou
Journal: Cancer Research (2006)

1057   Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. High expression of vascular endothelial growth factor ( VEGF ) has been a hallmark of GBM. However, the regulation of  VEGF  expression in malignant gliomas is not well understood. We have previously reported that the transcription factor PAX6 suppresses the tumorigenecity of glioblastoma cells. In addition, there is a reverse correlation between the expression level of  PAX6  and  VEGF  when human glioma tumors and the surrounding normal tissues were compared, suggesting that PAX6 might regulate  VEGF  expression. In this study, several techniques such as real-time quantitative reverse transcription PCR, enzyme-linked immunosorbent assay and immunohistochemistry were used to investigate if PAX6 regulates  VEGF  expression in glioma cell lines. Our results showed a significant reduction of  VEGF  expression in the PAX6 stable-transfected glioma cell line U251HF grown both  in vitro  and in subcutaneous xenografts in nude mice. We further demonstrated in two glioma cell lines (U251HF and U87) that  VEGF  expression was markedly suppressed by adenoviral-mediated overexpression of PAX6, as well as PTEN. Interestingly, in cells when both genes were overexpressed together,  VEGF  expression was further suppressed. Co-immunoprecipitation identified the existence of physical association between PAX6 and PTEN in the situation where the enhanced suppression of  VEGF  expression occurred. This discovery revealed a novel mechanism underlying the tumor-suppression functions of both PAX6 and PTEN in malignant gliomas. Data from this study are consistent with our previous finding in which patients with malignant gliomas have significantly more favorable outcomes when their tumors have high  PAX6  and  PTEN  expression levels compared to patients with low expression values for either or both genes.
Functional variability of the adenosine A3 receptor (<i>ADORA3</i>) gene polymorphism in aspirin-induced urticaria
Authors: S.-H. Kim, E.-J. Nam, Y.-K. Kim, Y.-M. Ye, H.-S. Park
Journal: British Journal of Dermatology (2010)

To improve understanding of aspirin hypersensitivity, this study focused on adenosine as a noncyclooxygenase target molecule of aspirin. Adenosine may affect the release of histamine from cutaneous mast cells through a mechanism mediated by the adenosine A3 receptor.To investigate the genetic contribution of adenosine A3 receptor gene (ADORA3) polymorphisms in the pathogenesis of aspirin-induced urticaria (AIU) in a case-control association study in a Korean population.A case-control association study was performed in 385 patients with AIU and 213 normal controls from a Korean population. The functional variability of genetic polymorphisms in the ADORA3 gene was analysed in in vitro studies that included a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA), and ex vivo studies that included real-time polymerase chain reaction for mRNA expression in peripheral blood mononuclear cells and a histamine release assay.A significant association of ADORA3 promoter polymorphism at -1050G/T was found with the phenotype of AIU. Patients with AIU showed higher frequency of the haplotype, ht1 (T(-1050) C(-564) ), compared with normal healthy controls. Moreover, ht1 (TC) was found to be a high-transcript haplotype by the luciferase activity assay, and a -564C allele-specific DNA binding protein was found by EMSA. Increased basophil histamine release was noted in subjects who had the high-transcript haplotype, ht1 (TC).These results suggest that the high-transcript haplotype, ht1 (TC), of the ADORA3 gene may contribute to the development of cutaneous hyper-reactivity to aspirin, leading to the clinical presentation of AIU.
Concepts in psoriasis: psoriasis and the extracellular matrix
Authors: J. McFadden, L. Fry, A.V. Powles, I. Kimber
Journal: British Journal of Dermatology (2012)

Post-streptococcal guttate psoriasis only sometimes progresses to the persistent plaque psoriasis. We have previously proposed that psoriasis is driven by multiple extradomain A+ fibronectin (EDA+ FN) 'feedback loops'. The psoriasis-specific loop, the 'keratinocyte loop', depends upon expression by keratinocytes of α5β1 integrin. In normal skin, α5β1 expression is minimal or absent in resting epithelial cells, where basal cells are anchored to the laminin component of the basement membrane (via integrins α6β4 and α3β1). However, when the laminin layer is disrupted, due to wounding for instance, α5β1 is then strongly expressed by basal cells as a means for anchoring. At uninvolved skin sites in patients with psoriasis the laminin layer within the basement membrane is disrupted, with a consequential increase in the expression by basal keratinocytes of EDA+ FN and α5β1. We are postulating that in guttate psoriasis streptococcal lytic enzymes, and in particular streptokinase, may - via plasminogen activation - initiate a disruption of the laminin layer in the basement membrane. It is also possible that the expression by proliferating keratinocytes of plasminogen-activating factor might result in additional laminin digestion. The suggestion is that progression of guttate psoriasis to full-blown plaque psoriasis, or to its spontaneous resolution, is governed largely by the triggering of humoral immune responses. Thus, if streptococcal lytic enzymes are neutralized by host antibodies in advance of irreversible and lasting damage to the basement membrane of the dermal papillae, then guttate psoriasis will resolve spontaneously. In contrast, if permanent damage is induced prior to effective neutralization of the relevant bacterial toxins, then keratinocytes will become chronically destabilized. The consequence will be to liberate keratinocytes to proliferate in response to various stimuli, and to continue to elaborate plasminogen activation enzymes; the combined effect being, in concert with immunological priming, to precipitate and sustain plaque psoriasis.
Typing of Panton-Valentine leukocidin-encoding phages carried by methicillin-susceptible and methicillin-resistant Staphylococcus aureus from Italy
Authors: A. Sanchini, M. Del Grosso, L. Villa, M.G. Ammendolia, F. Superti, M. Monaco, A. Pantosti
Journal: Clinical Microbiology and Infection (2014)
Occupational asthma due to heated polypropylene
Authors: JL Malo, A Cartier, L Pineault, M Dugas, A Desjardins
Journal: European Respiratory Journal (1994)

A 35 year-old nonatopic woman was referred to the hospital for possible work-related asthma. She had worked as an operator, at a plant producing polypropylene bags, for the previous four yrs. Her main complaint was a productive cough with dyspnoea and wheezing, as well as rhinitis over the past 3 yrs. She had been absent from work for 6 months on maternity leave, and had improved greatly. She was on a beta 2-adrenergic agent and had to take it at least four times daily. Baseline spirometry whilst at work showed marked airflow obstruction (forced expiratory volume in one second (FEV1) of 43% predicted (pred). After two months away from work FEV1 improved to 89% pred; provocative concentration of histamine causing a 25% fall in FEV1 (PC20) was 3.6 mg.ml-1 (mild airway hyperresponsiveness). Return to work resulted in a marked deterioration in FEV1, and serial peak expiratory flow (PEFR) values. PC20 was 0.11 mg.ml-1 (severe airway hyperresponsiveness) one week after she had returned to work. Specific inhalation challenges with polypropylene heated to 250 degrees C resulted in a late asthmatic reaction. As formaldehyde is one of the degradation products of heating polypropylene, we exposed her to it for up to 2 h, but we elicited no bronchospastic reaction. We conclude that heated polypropylene should be listed as one of the agents that causes occupational asthma.
Subinhibitory concentrations of gentamicin reduce production of listeriolysin, the main virulence factor of Listeria monocytogenes
Authors: Thomas Nichterlein, Eugen Domann, Martin Bauer, Alexander Hlawatsch, Marianne Kretschmar, Trinad Chakraborty, Herbert Hof
Journal: Clinical Microbiology and Infection (1997)
Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP.
Authors: M A Rodriguez, F C Cabanillas, W Velasquez, F B Hagemeister, P McLaughlin, F Swan, J E Romaguera
Journal: Journal of Clinical Oncology (1995)

PURPOSE We report the results of a prospective trial in which patients with relapsing non-Hodgkin's lymphomas were sequentially treated with two regimens (mesna, ifosfamide, mitoxantrone, and etoposide [MINE], and etoposide, methylprednisolone, cytarabine, and cisplatin [ESHAP]) if they had no history of disease resistance to these drugs. PATIENTS AND METHODS Ninety-two patients received MINE (mesna 4 g/m2, ifosfamide 4 g/m2, mitoxantrone 8 mg/m2, and etoposide 195 mg/m2) for a maximum of six courses followed by ESHAP (etoposide 240 mg/m2, methylprednisone 500 mg/d, high-dose cytarabine 2 g/m2, and cisplatin 100 mg/m2) for three courses to consolidate complete response (CR) or for a maximum of six cycles after a partial response (PR) or no response to MINE. Pretreatment serum levels of lactate dehydrogenase (LDH) and beta 2-microglobulin (beta 2M) were documented in 80 of 92 patients. RESULTS The response rate to MINE-ESHAP was 69% (48% CRs and 21% PRs), with a median survival time of 24 months and median time to treatment failure of 12 months. The median time to treatment failure according to histology was as follows: low-grade histologies, 16 months; low-grade transformed to intermediate-grade, 8 months; and intermediate-grade, 5 months. The most serious complication was myelosuppression, which resulted in two deaths due to neutropenic sepsis. A risk factor model based on beta 2M and LDH levels before salvage treatment showed three categories of risk, with 36-month survival rates as follows: low (beta 2M &lt; 3 mg/dL and LDH normal), 61%; intermediate (beta 2M &gt; or = 3 mg/dL or LDH above normal), 23%; and high (beta 2M &gt; or = 3 mg/dL and LDH above normal), 0%. CONCLUSION MINE-ESHAP is an effective salvage strategy for patients with recurrent lymphoma. Toxicity was acceptable. Factors that determine prognostic categories at relapse merit further study.
Late-breaking abstract: Soluble immune complex exaggerates LPS-Induced acute lung injury (ALI) by transfusion – A novel mechanism of transfusion-related acute lung injury (TRALI)
Authors: Ming-Cheng Chan, Chieh-Liang Wu
Journal: European Respiratory Journal (2011)

Rationale:  TRALI is a major cause of morbidity and mortality related to transfusion therapy. Soluble immune complex (ICx) could aggravate LPS-induced lung injury. We speculate that ICx formation during transfusion may play a role in the pathogenesis of TRALI.   Method:  We designed a double-hit mice model to simulate TRALI development. The first hit is LPS i.t. injection. The second hit is transfusion of conditioned blood 24 hours after LPS injection. Mice were sacrificed 6 hours later. The conditioned blood was generated by transfusing 0.1cc/day C57 mice blood to BALB/C mice consecutively for two weeks. Animal were divided into four groups XX, XB, LP and LB (X: no treatment, L: LPS i.t.; B: transfusion of conditioned blood, P: transfusion with PBS)   Result:  1. The LB group has higher protein, TNF-α and MIP-2 level in BALF.  2. Soluble ICx is present in LB only.   Conclusion:  We demonstrated that transfusion with 2cc conditioned blood aggravated LPS-induced ALI and generated soluble ICx in plasma. This probably indicates ICx may aggravate pre-existing ALI which implys a novel mechanism of the pathogenesis of TRALI.
Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study
Authors: N. Sicot, N. Khanafer, V. Meyssonnier, O. Dumitrescu, A. Tristan, M. Bes, G. Lina, F. Vandenesch, P. Vanhems, J. Etienne, Y. Gillet
Journal: Clinical Microbiology and Infection (2012)