tbuckley/cabot-search huggingface dataset:
B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?
Authors: P J Hengeveld, M J Kersten
Journal: Blood Cancer Journal (2015)

Abstract Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC’s capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC’s BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916).
Sensitivity Chest Diseases
Authors: Stanley Cohen
Journal: JAMA (1965)

The editors have taken the laudable responsibility of bringing together in one volume all the facets of hypersensitivity mechanisms involved in chest diseases. Using the talents of 17 contributors, the text begins with an excellent coverage of the immunological reactions of hypersensitivity. It is unfortunate that this is not followed by a discussion of tissue hormones or chemical mediators of the allergic reaction. A short but lucid description of lung-function tests and their clinical application is included. The major portion of the book deals with the practical aspects of allergic respiratory disease, particularly bronchial asthma. The subject is presented from the viewpoint of sensitizing agents, diagnostic tests, drugs for symptomatic control, inhalation therapy, and specific allergic desensitization. A chapter by Overholt discusses surgery in bronchial asthma, with particular reference to the debatable procedure of glomectomy (removal of the carotid body). Excellent chapters on pulmonary diseases of suspected allergic etiology, roentgenography
Core to Rind Distribution of Severe Emphysema Predicts Outcome of Lung Volume Reduction Surgery
Authors: YASUTAKA NAKANO, HARVEY O. COXSON, SOREL BOSAN, ROBERT M. ROGERS, FRANK C. SCIURBA, ROBERT J. KEENAN, KEITH R. WALLEY, PETER D. PARÉ, JAMES C. HOGG
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Computed tomography (CT) has shown that emphysema is more extensive in the inner (core) region than in the outer (rind) region of the lung. It has been suggested that the concentration of emphysematous lesions in the outer rind leads to a better outcome following lung volume reduction surgery (LVRS) because these regions tend to be more surgically accessible. The present study used a recently described, computer-based CT scan analysis to quantify severe emphysema (lung inflation > 10.2 ml gas/g tissue), mild/moderate emphysema (lung inflation = 10.2 to 6.0 ml gas/g tissue), and normal lung tissue (lung inflation < 6.0 ml gas/g tissue) present in the core and rind of the lung in 21 LVRS patients. The results show that the quantification of severe emphysema independently predicts change in maximal exercise response and FEV1. We conclude that a greater extent of severe emphysema in the rind of the upper lung predicts greater benefit from LVRS because it identifies the lesions most accessible to removal by LVRS.
Extractable nuclear antigen effect on the DNA anti-DNA reaction and NZB/NZW mouse nephritis.
Authors: A D Morris, C Littleton, L C Corman, J Esterly, G C Sharp
Journal: Journal of Clinical Investigation (1975)

Extractable nuclear antigen (ENA) is composed of at least two components, one a ribonucleo-protein sensitive to ribonuclease or heat and the other a protein. Antibodies to ENA are associated with a relatively benign clinical course in patients with systemic lupus erythematosus (SLE) in which DNA anti DNA complexes are thought pathogenic. The effect of ENA and anti-ENA on DNA anti-DNA reactions in vitro was studied. ENA effectively inhibited an anti-DNA hemagglutination reaction but no effect was found on binding of radioactive DNA or on the anti-hemocyanin hemagglutination reaction. The inhibitory effect was not abolished by yeast ribonuclease (RNase), heating, or DNase. Anti-ENA HAD NO EFFECT ON ANTI-DNA hemagglutination. In vivo, ENA altered the NZB/NZW mouse nephritis thought to be a model for human SLE nephritis. These results suggest the possiblity of a role for ENA in alteration of diseases due to pathogenic DNA anti-DNA complexes.
Sudden Myelopathy Secondary to Therapeutic Total-Body Hyperthermia after Spinal-Cord Irradiation
Authors: Michal A. Douglas, Leon C. Parks, Jose Bebin
Journal: New England Journal of Medicine (1981)

HYPERTHERMIA is a new method of treatment receiving increasing clinical attention in cancer therapy. Its efficacy has been well demonstrated in animals, but its indications, contraindications, and appropriate place in cancer therapy have yet to be defined.1 2 3 4 We report three cases of acute myelopathy in patients undergoing hyperthermia after spinal-cord irradiation within the preceding two months. Post-mortem examination in one case revealed findings similar to those seen in myelopathy resulting from long-term irradiation. Several neurologic side effects have been reported previously with total-body hyperthermia — most commonly peripheral neuropathy, but not myelopathy.1 2 3 The mechanism of action of hyperthermia in cancer . . .
Abstract P4-12-08: Final efficacy results from a single-arm multicenter phase II study evaluating first-line trastuzumab, bevacizumab, and capecitabine (HAX) therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC)
Authors: M Martín, A Makhson, J Gligorov, M Lichinitser, A Lluch, V Semiglazov, S de Ducla, L Mitchell, S Tjulandin
Journal: Cancer Research (2013)

Abstract Background: After median follow-up of 8.8 months, the primary efficacy results from the HAX study [Martín et al., Oncologist 2012] demonstrated a 73% overall response rate (ORR) according to RECIST (primary endpoint), median progression-free survival (PFS) of 14.4 months and a safety profile typical of the component agents; overall survival (OS) data were immature at that time. We present final efficacy results. Methods: Patients with measurable HER2-positive LR/mBC who had received no prior chemotherapy for LR/mBC received bevacizumab 15 mg/kg day 1, trastuzumab 6 mg/kg day 1 (8 mg/kg loading dose in cycle 1), and capecitabine 1000 mg/m2 bid days 1–14, repeated every 3 weeks until progression, unacceptable toxicity, or withdrawal of consent. Results: At the time of data cut-off, median follow-up was 31.8 months (range 1.2–44.5 months). Median duration of study therapy was 9.0, 9.4, and 10.3 months for bevacizumab, capecitabine, and trastuzumab, respectively. More than 8 cycles were administered in 67%, 65%, and 70%, respectively. Efficacy results in the intent-to-treat population (n = 88) and clinically important subgroups are shown below. Patient subgroupBest ORR,% (95% CI)PFS events, n (%)Median PFS, months (95% CI)Deaths, n (%)Median OS, months (95% CI)1-year OS rate,% (95% CI)All patients (n = 88)75 (65-84)70 (80)14.2 (10.5-14.9)40 (45)31.8 (26.3-38.2)94 (86-98)ER and/or PgR positive (n = 37)73 (56-86)32 (86)14.1 (8.5-17.0)19 (51)31.8 (24.4-42.6)100 (*-*)ER and PgR negative (n = 51)77 (63-87)38 (75)14.5 (10.5-18.9)21 (41)33.1 (23.6-44.5)90 (77-96)No prior chemotherapy (n = 37)81 (65-92)27 (73)14.9 (10.5-24.8)14 (38)31.8 (26.3-44.4)94 (80-99)Prior chemotherapy (n = 51)71 (56-83)43 (84)13.6 (8.5-14.8)26 (51)30.9 (24.3-42.1)94 (82-98)Taxane pretreated (n = 28)57 (37-76)26 (93)9.5 (5.2-14.0)17 (61)27.4 (21.4-33.2)93 (74-98)Prior anti-HER2 therapy (n = 22)73 (50-89)18 (82)12.1 (5.2-17.0)11 (50)30.9 (24.3-*)95 (72-99)Age &amp;gt;60 years (n = 25)72 (51-88)16 (64)14.2 (10.5-21.7)11 (44)33.2 (22.0-*)100 (*-*)*Not reached The most common grade ≥3 adverse events were hand-foot syndrome (26% of patients), diarrhea (11%), and hypertension (11%). The majority of deaths (38/40) were from progressive/underlying disease. The cause of the two remaining deaths was described as unknown; one was reported at the primary analysis and the other occurred 19 months after last study drug administration, following progression. Detailed long-term safety results will be presented. Conclusion: Long-term follow-up results from the HAX study show that this is an active and tolerable first-line triplet therapy for HER2-positive mBC, demonstrating median OS of 31.8 months. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-08.
Consultant found guilty of failing to act on colleague
Authors: C. Dyer
Journal: BMJ (1994)

A senior consultant was found guilty of serious professional misconduct by the General Medical Council (GMC) last week for failing to investigate complaints that a locum was endangering patients. The professional conduct committee found Dr Sean Dunn, 45, who is chairman of the anaesthetics division of East Yorkshire Hospitals NHS Trust, guilty for not having acted on concerns that colleagues had expressed about the competence of Dr Behrooz Irani. But the committee took into account a shortage of anaesthetists and problems in procedures for locum appointments and imposed no sanction …
PD05-03: Impact of Quantitative Measurement of HER2, HER3, HER4, EGFR, ER and PTEN Protein Expression on Benefit to Adjuvant Trastuzumab in Early-Stage HER2+ Breast Cancer Patients in NCCTG N9831.
Authors: EA Perez, KV Ballman, MM Reinholz, AC Dueck, H Cheng, RB Jenkins, AE McCullough, B Chen, NE Davidson, S Martino, PA Kaufman, LA Kutteh, GW Sledge, XJ Geiger, JN Ingle, KS Tenner, LN Harris, JR Gralow, DL Rimm
Journal: Cancer Research (2011)

Abstract Background: Prediction of benefit from trastuzumab in patients (pts) with HER2+ breast cancer remains an important goal. We sought to investigate the predictive value of quantitative measurement of HER2, HER3, HER4, EGFR, ER and PTEN protein expression on the benefit of trastuzumab in the phase III HER2+ adjuvant N9831 study for pts randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C). Methods: For each marker, we evaluated quantitative expression, relationship with demographic data, and association with disease-free survival (DFS) of pts. Freshly cut tissue microarray slides with up to three-fold redundancy per specimen from the N9831 cohort were treated identically using the AQUA (Camp, et al; Nat Med 2002, JCO 2008) method of quantitative immunofluorescence for each marker. HER2 was tested with CB11 (mouse monoclonal, Biocare, Inc.) and preliminary results were available for 698 of nearly 1400 pt specimens to be tested. The minimum value per pt was used in statistical analysis. Specimens were classified with high versus low expression based on a median value cutpoint for each marker. Median follow-up was 7.0 yrs. Results: Quantitative HER2 was compared with centrally performed HER2 testing by IHC and FISH. Median quantitative HER2 via AQUA was 10,017 units for the HER2 IHC 3+ group (n=607) versus 1058, 831, and 970 for the HER2 IHC 2+ (n=68), 1+ (n=11), and 0 (n=11) groups, respectively. The Spearman correlation between quantitative HER2 and FISH HER2/CEP17 ratio was 0.32 (p&amp;lt;0.001). High quantitative HER2 was associated with lower percentage of hormone receptor positivity (48% vs 59%, chi-sq p=0.003) but not associated with age, race, nodal positivity, tumor histology, grade, or size. High HER2 did not impact DFS in any arm of the study (See Table). Data for additional HER2 testing, HER3, HER4, EGFR, ER and PTEN are in process and will be ready by September, 2011. Conclusions: Similar to results based on standard HER2 testing by IHC and FISH in N9831, quantitative HER2 did not impact benefit from adjuvant trastuzumab. Results for additional markers will be presented. Our complete quantitative results for a second epitope on HER2, HER3, HER4, ER and EGFR will be the first report of these markers in a large patient cohort in the adjuvant setting. Disease Free Survival Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-03.
The Interrelations of the Pulmonary Arterial and Venous Wedge Pressures
Authors: RUSSELL H. WILSON, WAYNE HOSETH, MARY DEMPSEY
Journal: Circulation Research (1955)

Pulmonary venous wedge pressure closely reflects the pulmonary arterial mean pressure. Pulmonary arterial wedge pressure is not significantly different from the left atrial mean pressure. Neither the former nor the latter is an approximation of the pulmonary capillary pressure.
REPORT OF CASES TREATED WITH ROENTGEN RAYS.
Authors: Wm. ALLEN PUSEY
Journal: JAMA (1902)

<h3>TUBERCULOSIS OF THE SKIN.</h3><h3>Case 1.</h3> —Referred to me by Prof. H. B. Favill of Rush Medical College. Woman, aged 38, with extensive lupus involving the chin, cheeks, and neck of four years' duration; healed with healthy soft white scars after five months. This patient has been well now a year and a half and shows no sign of recurrence. This case has been reported in detail.<sup>1</sup> <h3>Case 2.</h3> —Referred to me by Prof. A. J. Ochsner of the University of Illinois. Lupus of the nose in a girl 10 years old of two years' duration; healed with healthy scars after five months; practically no deformity. This patient has been well for a year and there is no evidence of recurrence. The case has been reported in detail.<sup>2</sup> <h3>Case 3.</h3> —Mrs. A., aged 38, fifteen years married, was referred to me in March, 1901, by Dr. E. A.
MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma #
Authors: Shuai Li, Hanjiang Fu, Yulan Wang, Yi Tie, Ruiyun Xing, Jie Zhu, Zhixian Sun, Lixin Wei, Xiaofei Zheng
Journal: Hepatology (2008)

MicroRNAs (miRNAs) have recently been proposed as a versatile class of molecules involved in regulation of various biological processes. Although there is emerging evidence that some microRNAs can function as oncogenes or tumor suppressors, the specific role of miRNA in human hepatocellular carcinoma (HCC) is unclear at this point. In this study, we examined the microRNA expression profiles in a set of 20 human HCC specimens by miRNA microarray and quantitative real-time polymerase chain reaction. The results showed that among the 20 HCC samples analyzed, microRNA-101 was significantly down-regulated twofold or more (twofold to 20-fold) in 16 samples compared with the matching nontumoral liver tissues. Using both a luciferase reporter assay and Western blot analysis, we showed that microRNA-101 repressed the expression of v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene, a key component of the activator protein-1 (AP-1) transcription factor. Moreover, using a luciferase expression vector (pAP-1-Luc) driven by seven copies of an AP-1 cis-element, we observed that microRNA-101 expression inhibited phorbol 12-myristate 13-acetate (PMA)-induced AP-1 activity. In in vitro Matrigel invasion and Transwell migration assays, enhanced microRNA-101 expression inhibited the invasion and migration of cultured HCC cells, respectively. These findings suggest that microRNA-101 may play an important role in HCC.MicroRNA-101, which is aberrantly expressed in HCC, could repress the expression of the FOS oncogene.
Multiple Punctures for Oedema
Authors: M. Sein
Journal: BMJ (1937)

Cases crop up now and again in medical practice where obstinate oedema defies treatment by medical means.Such cases are seen in the late stages of cardio-renal failure when, apart from the discomfort arising from the oedema, the patients suffer from attacks of nocturnal dyspnoea.Prognosis in these cases is extremely poor, but any treatment which enables life to be prolonged in fair comfort and also reduces the suffering should be wel- come.
Antibody Response to Measles-Mumps-Rubella Vaccine of Children With Mild Illness at the Time of Vaccination
Authors: Gail E. King
Journal: JAMA (1996)

To examine the response to measles-mumps-rubella (MMR) vaccine among children with and without mild illness.Prospective cohort.A total of 386 children aged 15 to 23 months.Seroconversion rates to measles, mumps, and rubella in ill and well children.Six public health immunization clinics in two counties in the greater metropolitan Atlanta, Ga, area from February 1992 to April 1993.Acute upper respiratory tract infection, otitis media, and diarrhea were observed in 128 (33%), 41 (11%), and 13 (3%) of the children (groups are not mutually exclusive); 157 children had one of these mild illnesses and 229 were well. Overall seroconversion rates were 98% for measles, 83% for mumps, and 98% for rubella antigens. Measles seroconversion rates for ill children compared with well children, respectively, were as follows: upper respiratory tract infection, 99% vs 97%; mild fever, 98% vs 97%; otitis media, 98% vs 98%; diarrhea, 100% vs 98%; and any mild illness, 99% vs 97%. Estimates of the magnitude of antibody response to measles, mumps, and rubella antigens were the same for children with and without mild illness. There was no association of mild illness with increased rates and severity of adverse events reported in the 2 weeks after vaccination.Vaccinating children who present with mild illnesses with MMR vaccine is a safe and efficacious practice. These results support recommendations of the Advisory Committee on Immunization Practices and the American Academy of Pediatrics.
LAD-1/variant syndrome is caused by mutations in FERMT3
Authors: Taco W. Kuijpers, Edith van de Vijver, Marian A. J. Weterman, Martin de Boer, Anton T. J. Tool, Timo K. van den Berg, Markus Moser, Marja E. Jakobs, Karl Seeger, Özden Sanal, Sule Ünal, Mualla Çetin, Dirk Roos, Arthur J. Verhoeven, Frank Baas
Journal: Blood (2008)
Multiple Muscular Ventricular Septal Defects
Authors: WILLIAM F. FRIEDMAN, ALI MEHRIZI, ALLEN L. PUSCH
Journal: Circulation (1965)

Defects in the muscular portion of the interventricular septum are frequently multiple. Although their incidence is significant, scant attention has been paid them as a distinct entity. This report concerns seven patients with multiple muscular ventricular septal defects seen between 1956 and 1962. The patients ranged in age from 4 months to 9 years; five were less than 2 years old. Symptoms and signs of growth retardation, failure to thrive, and marked cardiac decompensation were present in each case. Electrocardiographic evidence of combined ventricular hypertrophy and incomplete right bundle-branch block was noted in each instance. Right heart catheterization demonstrated marked pulmonary hypertension of the high-flow, low-resistance type. These routine studies could not distinguish multiple muscular ventricular septal defects from the more usual membranous septal defect. All patients had cardiac surgery. There was one survivor. In three instances difficulty in identifying all of the multiple fenestrations prevented complete surgical repair. Postmortem examination was done in six patients. The sievelike appearance of the muscular ventricular septum was the most striking gross finding in the majority of the cases. Histologic analysis of the pulmonary vascular structural alterations did not reveal marked changes in any of the cases. In contrast to the widespread belief that most isolated muscular septal defects are innocuous, these seven examples of multiple muscular defects were associated with a picture of severe heart disease. Every effort should be made to diagnose the lesion prior to surgery. Recognition of the multiple nature of the defect is a necessary preliminary to successful therapy. It is hoped that preoperative left heart angiocardiography will successfully demonstrate the multiple lesions.
Abstract 158: Sustained adrenergic signaling activates pro-inflammatory networks in ovarian carcinoma
Authors: Archana S. Nagaraja, Guillermo Armaiz-Pena, Julie Allen, Nouara C. Sadaoui, Behrouz Zand, Peiying Yang, Lin Tan, Steve Cole, Susan Lutgendorf, Anil K. Sood
Journal: Cancer Research (2014)

Abstract Purpose: To determine the role of adrenergic activation in driving tumor inflammation through COX-2/Prostaglandin E2 (PGE2) axis as PGE2 is known to play an important role in the induction of a pro-inflammatory signature in the tumor microenvironment that promotes tumor growth and metastasis. Methods We first analyzed global metabolic changes in tumors isolated from patients with known Center for Epidemiologic Studies Depression Scale (CES-D; depressive) scores and tumoral norepinephrine (NE) levels. Beta-adrenergic receptor (ADRB) positive cells (Skov3 and HeyA8) were used to study mechanism at gene and protein levels of PTGS2 (cyclooxygenase2), PTGES (prostaglandin E synthase) and metabolite levels (all prostaglandins, PGs) in vitro and in vivo. Results Our results revealed that levels of PGs were significantly increased in patients with high CESD scores (&amp;gt;16). PGE2 was upregulated by 2.38 fold when compared to the low CES-D scores. A similar trend was also observed with other pro-inflammatory eicosanoids, such as 6-keto prostaglandin F1 Alpha (2.03), prostaglandin A2 (1.39) and prostaglandin E1 (1.39). Exposure to NE resulted in increased PTGS2 and PTGES (prostaglandin E2 synthase) gene expression in adrenergic receptor positive cell lines. Mass-spectroscopy analyses confirmed that upon treatment with NE and arachidonic acid (substrate), PGE2 levels were increased in conditioned medium from Skov3 cells. Treatment with a broad ADRB agonist (isoproterenol) or ADRB2 specific agonist (terbutaline) led to increases in expression of PTGS2 and PTGES. Conversely, treatment with a broad antagonist (propranolol) or an ADRB2 specific antagonist (butoxamine) in the presence of NE abrogated gene expression changes of PTGS2 and PTGES. Silencing PTGS2 resulted in significantly decreased migration (40%) and invasion (25%) of Skov3 and HeyA8 cells in the presence of NE. Importantly, silencing PTGS2 in a restraint stress orthotropic model decreased tumor burden by 70% and metastasis (tumor confined to the ovary) in Skov3-ip1 orthotopic mouse model as compared to control siRNA with restraint stress. Conclusion Increased adrenergic stimulation results in a pro-inflammatory milieu that drives tumor progression and metastasis. Citation Format: Archana S. Nagaraja, Guillermo Armaiz-Pena, Julie Allen, Nouara C. Sadaoui, Behrouz Zand, Peiying Yang, Lin Tan, Steve Cole, Susan Lutgendorf, Anil K. Sood. Sustained adrenergic signaling activates pro-inflammatory networks in ovarian carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 158. doi:10.1158/1538-7445.AM2014-158
September 11 might be shock treatment for addressing global health inequalities
Authors: N. Awofeso
Journal: BMJ (2002)

EDITOR—Smith's editorial rightly points to the heightened interest in global health issues by world leaders but overemphasises the impact of the recent report on macroeconomics on health for bringing this about. 1 2

World development reports and indicators and human development reports have been published for decades by the World Bank and United Nations Development Programme, respectively. These annual reports detail global health inequalities and can be accessed on the internet. For example, the Human Development Report 1997 , commenting on globalisation and …