tbuckley/cabot-search huggingface dataset:
Production of a Cytotoxin From Phorbol Myristate Acetate-Treated Human Promyelocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: George E. Gifford, Ph.D., David A. Flick, M.D., Na'eem A. AbdAllah, B.S., Harvey Fisch, D.V.M., Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1984)

Human promyelocytic leukemia cells, when differentiated into macrophages by treatment with phorbol myristate acetate, secrete a cytolytic factor. Enhanced production was achieved when the cultures were treated with bacterial lipopolysaccharide (LPS). Production of the factor was inhibited when cultures were treated with dactinomycin immediately after LPS treatment. Tritirachium alkaline proteinase treatment inactivated the factor, indicating that it has an essential protein moiety. The molecular weight was found to be approximately 40,000 by Sephacryl S-200 gel filtration. The factor was stable at 56°C for 30 minutes, but 80% of the activity was inactivated at 70°C in 30 minutes. The factor was destroyed (96%) by dialysis against 0.01 M HCI (pH 2) for 14 hours. The cytolytic factor had little activity on normal fibroblasts, but it was able to significantly kill transformed cells in vitro.
Family caregiver satisfaction with early palliative care for advanced non-small cell lung cancer (NSCLC)
Authors: J. Greer, W. Pirl, T. Lynch, J. Billings, V. Jackson, J. Temel
Journal: Journal of Clinical Oncology (2007)

9027 Background: Historically, there has been no established role for palliative care in treating ambulatory oncology patients who are not at the end of life, but still struggling with the physical, psychosocial and spiritual aspects of cancer. Integrating palliative care services earlier in oncology care may help alleviate the suffering of patients with advanced cancer and family caregivers. This single-arm pilot study examines caregiver satisfaction with early palliative care services in patients with advanced NSCLC. Methods: Sample included patients within 8 weeks of diagnosis of stage IIIb with effusions or IV NSCLC and their family caregivers. Patients met with the palliative care team at least monthly until the time of hospice referral or death, completing assessments of quality of life (FACT-L) and mood (HADS) at baseline, 3, and 6 months. Caregivers rated their satisfaction with palliative care services using the FAMCARE. To identify predictors of caregiver satisfaction with care, patient scores from the FACT-L and HADS were entered into a linear regression model. Results: Fifty-one patients were enrolled (31 female, mean age=64.5 years), with 73% (n=37) identifying a caregiver who consented to participate. Of the 32 caregivers who completed a follow-up assessment, 84% (n=27) reported average FAMCARE scores in the “very satisfied” to “satisfied” range. Patients with worse physical (β=−.49, p=.003) but better social wellbeing (β=.55, p=.001) on the FACT-L at baseline had caregivers who were more satisfied with palliative care services at follow-up. Patient mood symptoms on the HADS were not related to caregiver satisfaction with care. Conclusions: The majority of family caregivers reported being satisfied with oncology care that included early palliative care. Patients with greater physical disability had caregivers who were more satisfied with care, which may be due to increased contact with the palliative care team. Also, patients who felt more supported by their families at baseline had caregivers who were more satisfied with care. While these data are encouraging, controlled longitudinal studies are needed to determine if these findings are actually the result of early palliative care services. [Table: see text]
PTH-072 A local, low cost, effective hepatitis C service in a district general hospital?
Authors: I M Johnston, T D Heymann
Journal: Gut (2010)

<h3>Introduction</h3> Hepatitis C causes life threatening disease which may affect 270 million people worldwide and up to 2% of the UK population. HCV is an RNA virus which usually causes asymptomatic infection but leads to chronic liver disease, and if left untreated, liver failure in the majority of cases. It may be treated successfully with ribavirin and pegylated interferon used in combination. Sustained response to therapy ranges from 50 to 75%, dependant on viral genotype. Treatment is physically and psychologically demanding. As a result, patients are usually treated in dedicated clinics with specialist nurse support. Such clinics may be expensive to staff and are most commonly found in tertiary referral centres. <h3>Methods</h3> Our hospital, a district general in SW London started to treat patients with HCV as part of its general gastroenterology and hepatology work in 2001. Now, an outpatient nurse with a special interest in HCV devotes 4 h a week to run the service with the support of three gastroenterologists. The service undertakes all aspects of hepatitis C diagnosis, treatment and monitoring. About 30 patients are now treated pa. Through auditing the service in 2005 and 2008 against NICE guidelines,1 we aimed to determine whether such a low cost, local model of service provision was effective and safe. <h3>Results</h3> From 2004 to 2007 89 patients were treated. By 2008 all had had their genotype tested and documented before treatment (2005, 92%). 82% had had their viral load recorded (2005, 92%). All patients with genotypes 1 and 4 had their initial response to treatment checked at 12 weeks (2005, 74%). Treatment duration, 24 or 48 weeks, was appropriate in all (2005, 86%). The results of “end of treatment” PCR were recorded for 80% of patients (2005, 74%). 96% of those returned for a HCV PCR 6 months later to ensure a sustained virological response (2005, 85%). None of our patients suffered any serious adverse event during treatment. The 2008 findings demonstrated a clear improvement since the 2005 audit in the six standards assessed, reflecting the introduction of a clearer “pathway” for patients as a result of findings in 2005, and greater staff experience. Of the 89 cases audited, documented sustained virological response rates improved from 25% for genotypes 1 and 4 and 44% for genotypes 2 and 3 in 2005 to 46% and 75%, respectively. The actual response rates are likely to be higher if allowance is made for those lost to follow-up. <h3>Conclusion</h3> It is possible to run a local, safe HCV service with few dedicated resources in a DGH. Audit is useful in focusing attention on areas for improvement; documentation that encourages appropriate, timely testing before, during and after treatment helps.
Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population‐Based Cohort Study
Authors: Carlen Reyes, Kirsten M. Leyland, George Peat, Cyrus Cooper, Nigel K. Arden, Daniel Prieto‐Alhambra
Journal: Arthritis & Rheumatology (2016)

Studies of previous cohorts have demonstrated an association between a status of overweight/obesity and the presence of knee and hand osteoarthritis (OA). However, no data on the effect of these factors on the OA burden are available. The aim of the present study was to analyze the effect of being overweight or obese on the incidence of routinely diagnosed knee, hip, and hand OA.
Abstract B05: Improved therapy for neuroblastoma using small molecule inhibitors in combination with chemotherapy
Authors: Nagendra K. Chaturvedi, McGuire R. Timothy, Don W. Coulter, Ashima Shukla, Erin M. McIntyre, J. Graham Sharp, Shantaram S. Joshi
Journal: Cancer Research (2016)

Abstract Neuroblastoma is the most common pediatric malignancy with poor response to current therapy. The NF-kB/mTOR, hedgehog and PLK1 pathways/molecules are aberrantly expressed and activated in high-risk neuroblastoma, thereby targeting these pathways/molecules is an attractive therapeutic strategy. Therefore, we investigated the efficacy and associated molecular mechanism(s) of NF-kB/mTOR dual inhibitor 13-197, hedgehog inhibitor Vismodegib and PLK1 inhibitor BI2536 alone or in combination with Topotecan against high-risk neuroblastoma in vitro and in vivo. Using three neuroblastoma cell lines, the in vitro efficacy of the inhibitors as single agents or in combination with Topotecan on cell growth and apoptosis along with associated molecular mechanism(s) were investigated. In addition, the combined efficacy of Vismodegib and Topotecan was determined in vivo using a xenograft mouse model. Results showed that 13-197, BI2536 and Vismodegib significantly decreased neuroblastoma cell growth and induced apoptosis by targeting associated pathways and molecules in vitro. The 13-197 and BI2536 as single agents showed similar efficacies and were most potent in inhibiting cell growth and survival of neuroblastoma cells. In combination with Topotecan, BI2536 or Vismodegib further significantly decreased neuroblastoma cell growth/survival and neurospheres formation. Corresponding changes in the expression of targeted molecules following therapy were observed. Together, in vitro data demonstrated that hedgehog pathway inhibitor Vismodegib was most efficacious in potentiating Topotecan-induced antineuroblastoma effects. Therefore, as a next logical step, we tested the combined efficacy of Vismodegib and Topotecan against neuroblastoma in vivo using NOD-SCID Gamma deleted (NSG) mice. Our in vivo results showed that Vismodegib combined with Topotecan significantly (p&amp;lt;0.001) reduced tumor growth and increased survival of xenograft mice compared to single agent activity. This combination not only significantly reduced tumor growth and increased survival of the mice but also significantly enhanced antineuroblastoma efficacy by targeting hedgehog pathway components in neuroblastoma in vivo. Thus our studies lay a foundation for taking this therapeutic strategy to clinical setting to determine their efficacies in high-risk neuroblastoma patients. Citation Format: Nagendra K. Chaturvedi, McGuire R. Timothy, Don W. Coulter, Ashima Shukla, Erin M. McIntyre, J. Graham Sharp, Shantaram S. Joshi. Improved therapy for neuroblastoma using small molecule inhibitors in combination with chemotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B05.
Fibrinolysis and Hemorrhages in Fatal Heatstroke
Authors: Shlomo Shibolet, Sharon Fisher, Tuvia Gilat, Harry Bank, Harry Heller
Journal: New England Journal of Medicine (1962)

IN fatal heatstroke widespread hemorrhages are a constant finding. This fact has been emphasized by many authors.1 2 3 4 5 6 Malamud et al.2 analyzed the autopsy material of 125 cases of heatstroke and found multiple hemorrhages in 122, particularly in the central nervous system, heart, lungs, liver and kidneys. The mechanism of these hemorrhagic phenomena has been variously explained. Wright, Reppert and Cuttino3 state that this is due to an increase of capillary permeability in addition to a fall in the prothrombin level and a decreased platelet count.In the present communication we report in detail the findings in a case of fatal . . .
Ovarian Neoplasms in a Hermaphrodite
Authors: Thomas F. Corriden
Journal: New England Journal of Medicine (1949)

HERMAPHRODITISM in itself is a rare anomaly. The additional occurrence of bilateral gonadal neoplasms is exceedingly uncommon. The present paper reports the case of a "male" hermaphrodite with a pseudomucinous cystadenoma of the right ovary and a dysgerminoma (seminoma) of the opposite gonad.General ConsiderationsHermaphroditism is the term used to designate the congenital possession by one person of both male and female sex organs. Two forms exist, true hermaphroditism and pseudohermaphroditism. Diagnosis of the former requires the presence of both ovary and testis either as separate organs or combined to form unilateral or bilateral ovotestes. In pseudohermaphroditism, on the . . .
The Treatment of Hydrocephalus in Pediatric Patients with a Variable Resistance Valve
Authors: S. Pezzotta, D. Locatelli
Journal: Neuro-Oncology (1991)

Surgical treatment in hydrocephalus has already been well established but we are still looking for a more " physiologic valve". It is still difficult to adapt for every single patient and for every different cause of hydrocephalus the best shunt system without complication due to shunt malfunctioning. An outstanding point in non physiologic functioning of the shunt is a non adaptability to the different dinamic conditions in normal life. We report our experience about a variable resistance valve (Orbis Sigma Valve) shunt system, studied to avoid most of these problems. Three years experience over 33 hydrocephalic children, from 1 day to 9 years old young people, five premature newborn are reviewed. The study with a short follow-up has in any case, made it possible to show up the good adaptability of the system to the diverse hydrodinamic conditions and the different types of hydrocephalus. It has proved itself able to respond to the theoretical functioning requisites, as there were no recorded episodes of overdrainage. This shunt has also proved efficient in treating slit ventricle syndrome.
Evidence against a Single Renal Transport Defect in Cystinuria
Authors: Maurice Fox, Samuel Thier, Leon Rosenberg, William Kiser, Stanton Segal
Journal: New England Journal of Medicine (1964)

SINCE 1810, when Wollaston1 first described a urinary calculus composed entirely of cystine, the pathogenesis of cystinuria has been the subject of controversy. Most current concepts date from the observations that the urine of these patients contains large amounts of lysine, arginine2 , 3 and ornithine4 as well as cystine, whereas the plasma levels of these amino acids are not elevated.3 , 5 , 6 These findings led Dent and Rose3 to conclude that the gross cystinuria characteristic of this disease was due to defective tubular reabsorption rather than impaired metabolism of cystine. The renal clearances of the 4 di-amino acids were shown to be abnormally . . .
Case 18-2010
Authors: Tammy M. Meyers, Thumbi Ndung'u
Journal: New England Journal of Medicine (2010)

A 7-year-old boy was seen for treatment of infection with HIV-1. When he was 3 years of age, pulmonary tuberculosis was diagnosed, and at 5 years of age, a diagnosis of HIV-1 infection was made. Despite 19 months of therapy, viremia persisted. A diagnostic test was performed, and a management decision was made.
Colloidal cDNA encoding recombinant multimodular proteins rMDVA comprising disintegrin/cysteine rich disulfide bond 2RGD, and C-terminal domain (ammodystatin), metalloprotease-domain (ammodylysin), and dimeric disintegrin/MLD-VGD domain (VADD) isolated from vipera ammodytes, exerted synergistic action with vinorelbine against metastatic NSCLC, circumventing chemotherapy-mediated systemic toxicity
Authors: J. Dritsas, J. Giannios, E. Michailakis, N. Alexandropoulos
Journal: Journal of Clinical Oncology (2009)

e19100 Background: We investigate if venom proteome of vipera ammodytes can induce apoptosis in NSCLC. Methods: We developed a large scale expression system with lung cell line (LCL), which we modified genetically by cloning. We expressed cDNA encoding multimodular disintegrin (rMDVA) comprising 3 domains from the venom of vipera ammodytes. The cDNA of rMDVA was cloned into the plasmid vector pcDNA III, which was transferred into LCL. The multimodular peptide rMDVA was encapsulated in the hydrophilic phase of liposomes termed as LIP-rMDVA. The in-vivo studies with human metastatic NSCLC were performed in an orthotopic xenograft model. Results: The venom proteome contained 140 proteins. We isolated the multimodular disintegrin displaying cysteine rich disulfide bond 2RGD, and C-terminal motif (ammodystatin), the dimeric MLD/VGD motif (VADD) and metalloprotease-domain (ammodylysin). Ammodystatin with the 2 (ARG-GLY-ASP) RGD motifs interacts with integrins avb5, a5b1 inhibiting invasion, angiogenesis/vasculogenesis and blocked the bFGF-induced avb3 integrin, and avb5 downregulating VEGF, and Ras. It also disrupts the actin cytoskeleton inducing G1 DNA replicative phase arrest, and blocks endothelial cell (EC) secretion of MMP-2, MMP-9, and urokinase type plasminogen activator with its receptor inhibiting proteolysis, and dissolution of ECM blocking invasion. Ammodystatin and ammodylysin lead to type I PCD/apoptosis of tumor cells in masses up to 2 mm, and EC. Beyond that size, ammodystatin inhibits the development of the required vascular network according to HUVEC, MVD, and IHC. VADD causes burring and blocked adhesion of a4b1 integrin to VCAM1. LDH, BrdU and MTT exhibited inhibition of tumor and EC proliferation. TEM exhibited apoptotic signs of irreversible D2 stage in tumor and ECs. Conclusions: Novel liposomal formulation LIP-rMDVA is an effective angiostatic, and cytostatic agent against metastatic NSCLC minimizing ST. No significant financial relationships to disclose.
DDEL-06PRELIMINARY SAFETY OF TOCA 511, A RETROVIRAL REPLICATING VECTOR, IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA ACROSS THREE SEPARATE PHASE 1 STUDIES
Authors: Steven N. Kalkanis, Manish K. Aghi, Timothy F. Cloughsy, George Kaptain, Jana Portnow, Michael A. Vogelbaum, Santosh Kesari, Tom Mikkelsen, J. Bradley Elder, Clark C. Chen, David Piccioni, David Baskin, Jonathan Engh, Daniella Bota, E. Antonio Chiocca, Greg Foltz, Derek Ostertag, Dawn Gammon, Andreas Niethammer, Joseph Landolfi
Journal: Neuro-Oncology (2015)

High grade glioma (HGG) remains resistant to standard therapies with survival ranging from 7.2-8.1 months. Two Phase 1 clinical studies using a retroviral replicating vector (RRV), Toca 511, in combination with oral Toca FC (extended-release 5-FC) are ongoing to evaluate intracranial delivery of Toca 511 in patients with recurrent HGG. Patients were treated either by administering Toca 511 via intratumoral injection by biopsy needle or convection-enhanced delivery (CED) (NCT01156584), or by injection into the resection cavity wall (NCT01470794). The total safety population included 82 patients. The safety profile was favorable with only 3.7% patients experiencing a treatment related SAE and 1 patient discontinuing treatment due to toxicity (rash). A total of 59 patients who were efficacy evaluable (received Toca 511 and at least one dose of Toca FC) and excluding patients with non-biopsy needle delivery had a mOS of 13.8 months (95% CI 10.8,16.9). Cox-regression was used to examine factors associated with survival outcome. Baseline factors included for univariate analysis were tumor grade (III vs IV), number of recurrences (≤2 vs >2), gender, age (≤55 vs >55), longest diameter of cancerous lesion (continuous), daily dose of Toca FC (≥170 mg/kg vs  80), time between Toca 511 and Toca FC (weeks), and respective study participation (NCT01156584 vs NCT01470794). Of these, tumor grade, number of recurrences, gender and lesion diameter were included for multivariate analysis based on a p value >0.2 in the univariate analysis. Based on the multivariate analysis, the only statistically significant positive prognostic factor was the category of number of recurrences. Excluding patients with >2 recurrences, the observed median overall survival (mOS) is 14 months (95% CI 11.15, 23.36), comparing favorably to historical benchmarks. 60% and 24.7% of patients were alive after 12 and 24 months, respectively.
Enteric Viruses Ameliorate Gut Inflammation via Toll-like Receptor 3 and Toll-like Receptor 7-Mediated Interferon-β Production
Authors: Jin-Young Yang, Min-Soo Kim, Eugene Kim, Jae Hee Cheon, Yong-Soo Lee, Yeji Kim, Su-Hyun Lee, Sang-Uk Seo, Seung-Ho Shin, Sun Shim Choi, Bumseok Kim, Sun-Young Chang, Hyun-Jeong Ko, Jin-Woo Bae, Mi-Na Kweon
Journal: Immunity (2016)
Complete Heart Block in Infants and Children
Authors: Frances F. Nakamura, Alexander S. Nadas
Journal: New England Journal of Medicine (1964)

THE presence of complete heart block in the pediatric age group has been known for many years.1 A sizable number of publications, consisting mostly of reports of a small number of cases, indicates that third-degree heart block is not too uncommon in children.2 3 4 5 6 7 8 9 10 11 Three principal considerations prompted the present report. In the first place, the almost uniformly benign prognosis of congenital heart block, proposed by Campbell et al.,3 , 4 has recently been challenged by the publication of Molthan et al.12 reporting 3 fatal cases with Adams–Stokes attacks. Secondly, we believed that the concept of congenital heart block as a solitary finding, . . .
Hematologic Remission and Cytogenetic Improvement Induced by Recombinant Human Interferon Alpha<sub>A</sub>in Chronic Myelogenous Leukemia
Authors: Moshe Talpaz, Hagop M. Kantarjian, Kenneth McCredie, Jose M. Trujillo, Michael J. Keating, Jordan U. Gutterman
Journal: New England Journal of Medicine (1986)

We treated 17 patients who had Philadelphia-Chromosome-Positive chronic myelogenous leukemia (4 of whom had not received therapy and 13 of whom had been treated with hydroxyurea or busulfan for less than six months) with recombinant human interferon alpha-A (Roferon-A). The interferon was given as 5x106 units per square meter of body-surface area per day intramuscularly during induction therapy. Fourteen patients responded to the treatment, of whom 13 had a hematologic remission and 1 had a partial hematologic remission. The median number of white cells in those patients declined from 60.9x103to 3.4x103 per microliter, and the median number of platelets decreased from 476 x103 to 231 x103 per microliter. Among the five responding patients who had splenomegaly before treatment, the spleen size returned to normal in four and decreased by 75 percent in one, although it remained enlarged. Bone marrow cellularity declined from a median of 92.5 percent to a median of 57.5 percent. In six of the patients with hematologic remission, complete suppression of Philadelphia cells was observed on at least one examination. Of the 14 patients who responded, 11 have received the interferon therapy for 9 to 15 months. One patient relapsed during the treatment, and the treatment has been temporarily interrupted in two patients because of toxicity. These data are preliminary and will need further confirmation, but they suggest that recombinant human interferon alphaA is effective in inducing hematologic remission in most patients with benign-phase chronic myelogenous leukemia and in suppressing the Philadelphia chromosome in some of these patients. (N Engl J Med 1986; 314:1065–9.)
Excess Chromosome #4 in Ethylnitrosourea-Induced Neurogenic Tumor Lines of the Rat 2
Authors: William Au, S. W. Soukup, T. I. Mandybur
Journal: JNCI Journal of the National Cancer Institute (1977)

The chromosomes in 15 cell lines derived from separate tumors induced in rats by ethylnitrosourea (ENU) are described. Thirteen lines were neural (glioma or schwannoma) in origin and type. In 12 of these lines, excess chromosome #4 could be demonstrated by Giemsa banding. One to three extra #4 chromosomes were seen as numerical or structural abnormalities. Also noted were other changes that were not consistent among lines. The 12 lines produced tumors in newborn rats. The 13th neurogenic line lacked excess chromosome #4 and did not produce tumors. The remaining 2 lines were nonneurogenic and lacked excess chromosome #4 but produced tumors. Control studies included chromosome analyses of bone marrow preparations from ENU-treated rats with tumors, cell lines from brains of normal rat embryos, and 2 established nonneurogenic rat tumor lines. No excess chromosome #4 was seen. These results suggest that nondisjunction and/or rearrangement of chromosome #4 is associated with the oncogenic process in neurogenic tumors induced by ENU.