tbuckley/cabot-search huggingface dataset:
Abstract 2240: Structural variant of osteoprotegerin lacking TRAIL binding for therapeutic bone remodeling in osteolytic malignancies.
Authors: Jerome T. Higgs
Journal: Cancer Research (2013)

Abstract Current treatments for osteolytic cancer pathology include a combination of radiation and chemotherapy, but toxic side effects are still of major concern. Studies have shown that osteoclast activity is increased in patients with osteolytic cancers such as multiple myeloma, breast and prostate cancer through increased expression of Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) leading to RANKL/RANK signaling, resulting in osteoclast activation and ultimately bone resorption. Moreover, Osteoprotegerin (OPG), a decoy receptor for RANKL, is disproportionately expressed in these patients who present with bone lesions. Thus, the use of OPG as a therapeutic molecule would greatly decrease osteolytic damage and reduce morbidity. However, despite the potential of OPG in inhibiting the activation of osteoclast, OPG also binds to tumor necrosis factor related apoptosis-inducing ligand (TRAIL) making tumor cells resistant to apoptosis. TRAIL binds to the Death Receptor 4 and 5 (DR4, DR5) and initiate cell death of transformed cells such as MM. The goals of this study was to designed and develop a therapeutic approach to the treatment of osteolytic bone damage by use of genetically altered OPG retaining RANKL binding but abolished in TRAIL binding. Towards uncoupling the events of TRAIL binding of OPG and to improve its utility for bone remodeling without inducing tumor resistance to apoptosis, we created a genetic variant of OPG through structural homology model based on interactive domain identification and by superimposing structural models of TRAIL, OPG and DR5 to identify regions of OPG for rational design. The mutant OPG (mut-OPG) was purified and extensively characterized for its ability for decreasing osteoclast damage without affecting tumor apoptosis pathway both in vivo and in vitro indicating its potential for therapy targeting bone lesions in osteolytic malignancies. Citation Format: Jerome T. Higgs. Structural variant of osteoprotegerin lacking TRAIL binding for therapeutic bone remodeling in osteolytic malignancies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2240. doi:10.1158/1538-7445.AM2013-2240
Purification of a human liver cytochrome P-450 immunochemically related to several cytochromes P-450 purified from untreated rats.
Authors: S A Wrighton, P E Thomas, P Willis, S L Maines, P B Watkins, W Levin, P S Guzelian
Journal: Journal of Clinical Investigation (1987)

Among characterized forms of liver microsomal cytochromes P-450 in rats are four related isozymes (P-450f-i) notable for their lack of inducibility. Immunoblot analyses demonstrated that human livers microsomes contained several proteins related to these rat P-450s. A human liver P-450, termed HLx, was purified and found by immunochemical assays to resemble rat P-450g. Analysis of the NH2-terminal amino acid sequence of HLx indicates that it is related to rat P-450s f-i and human liver P-450MP. A monoclonal antibody was used to measure the amounts of HLx in 21 human liver specimens. No correlation between the levels of HLx protein in these specimens and the patients' environmental histories was observed. However, statistical analysis of the data suggests that the distribution of HLx is at least bimodal. We conclude that HLx is a member of a family of human liver P-450s that resembles in its structure, and possibly in its distribution, several liver P-450s found in other animals.
Outcomes of Stereotactic Radiosurgery in the Management of Brain Metastasis in Patients with HER2 Positive Metastatic Breast Cancer.
Authors: S. Raza, A. Narayana, A. Morsi, E. Parker, S. Rush, J. Golfinos, Y. Novik
Journal: Cancer Research (2009)

Abstract Background:We present single institution experience on the effect of Her 2 status on results of Gamma knife radiosurgery (SRS) for brain metastases (BM) as to local control, pattern of relapse and survival.Material and Methods:From 2004 to 2008, 65 patients with metastatic breast cancer (MBC) were treated with GK-SRS at our center, 52 had documented Her 2 status. We performed analysis based on Her 2 status of the original tumor defined as positive by 3+ DAKO or FISH. SRS was delivered using cobalt leksell GKS to a median dose of 20Gy (range 16-20 Gy) at 50% isodose line. Responses were evaluated by gadolinium enhanced MRI. We analyzed the data as to: objective response (OR) defined as radiologic response or stable disease, and local progression –free survival (PFS) defined as freedom from progression of treated BM, appearance of new brain metastases and/or leptomeningeal progression, as well as overall survival (OS) measured from the time of SRS .ResultsTwenty-eight patients were identified as HER2 positive (Group A) and 24 patients were HER2 negative (Group B). Median time to develop BM in group A was 60 months (4 -240 months) versus 48 months (4-156) in group B. Median follow-up was 12 months (1-48) from the time of onset of BM. 66% patients in group A and 82% patients in group B have no more than 2 BM at the time of SRS.In group A, OR was 78.6% (22 pts)and 21.4%(6 pts) had progressive disease (PD) where as in group B the OR was 83% (20 pts) and 17%(4 pts) had PD. Median time to local recurrence of the treated lesion in group A was 13 months (95% CI 5.84 to 20.15) compared to 8 months (95%CI 6.75 to 9.25) in group B. Local PFS at 1 year for Group A vs. B was: control of the treated lesions 69% versus 41.2% respectively, p= 0.97 by log rank test; and development of new BM 67% compared to 86% (p=0.2).Out of all CNS relapses, almost a quarter of patients in both groups received second SRS whereas 25% patients in group A and 31% patients in group B received whole brain irradiation respectively. Interestingly, 28% (9 pts) failed as leptomeningeal disease following SRS, 7 of them with Her 2 positive tumors. Leptomeningeal relapses were seen both as only pattern of recurrence (4 pts) or associated with other types of CNS progression: local re-growth or new BM (5pts).ConclusionsSRS provides high rate of objective response and local control for BM from both Her 2 positive and Her 2 negative breast cancer. No statistically significant difference in local PFS was seen. More frequent pattern of relapse as leptomeningeal disease was seen in Her 2 positive after SRS. Evaluation of novel systemic targeted therapies in conjunction with local therapies is needed for effective management of BM from breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6152.
Utilization of data from human population studies for setting air quality standards: evaluation of important issues.
Authors: M D Lebowitz
Journal: Environmental Health Perspectives (1983)

Epidemiological studies of community populations are highly relevant to the process of setting national ambient air quality primary standards, as criteria for those standards are the protection of human populations against adverse effects on health. Nevertheless, because of the difficulties of performing adequate community population studies of a quality commensurate with the needs of standard setting, the use of data derived from studies is problematic. This paper addresses the important issues of appropriate exposure assessment and health assessment, and discusses the problems of multiplex variables and colinearity as they are critical in assessments of exposure-effect relationships. It is concluded that a major problem in the use of data from such studies for standard setting is not necessarily one of scientific reliability or validity, but arises from the attempt of translating adequate science into policy decisions.
Effects of Cabozantinib, a small molecule tyrosine kinase inhibitor, on the immune permissiveness of the tumor microenvironment and immune-mediated killing of tumor cells
Authors: Anna R Kwilas, Andressa Ardiani, Renee N Donahue, Dana Aftab, James W Hodge
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Combination therapy for the treatment of cancer is becoming increasingly important as the complexity of carcinogenesis and the availability of targeted therapies continues to expand. Successful combination therapy would target the primary tumor and distant metastases from multiple
Necrobiosis Lipoidica Diabeticorum
Authors: Sigfrid A. Muller
Journal: JAMA (1966)

To determine the effect of cortisone acetate on the standard glucose-tolerance test as a means of appraising insulinogenic reserve and to evaluate more completely the relationship of necrobiosis lipoidica diabeticorum (NLD) to diabetes mellitus, the authors reexamined 19 patients who had NLD but who had not been found to have diabetes mellitus during previous examinations at the Mayo Clinic. Standard glucose-tolerance tests gave abnormal results in three cases, including that of one patient who was taking hydrochlorothiazide. Cortisone glucose-tolerance tests gave abnormal results in five of the remaining 16 cases. Six of the 11 patients without evidence of carbohydrate intolerance gave family histories of diabetes. These findings confirm the close relationship between NLD and diabetes mellitus and suggest a relation to the prediabetic state, perhaps independent of carbohydrate metabolism.
Inhibitory effect of gastrin and cholecystokinin fragments on the secretion of triacylglycerol in rat hepatocytes
Authors: Marie Lindholm, Anders Eklund
Journal: Hepatology (1993)

In this investigation we studied the influence of two gastrin fragments, pentagastrin and nonsulfated heptadecagastrin, and two cholecystokinin fragments, sulfated and desulfated cholecystokinin 26-33, on intracellular and secreted triacylglycerol in isolated hepatocyte cultures. Both gastrin fragments inhibited triacylglycerol release in a biphasic manner, exhibiting maximal effect at 0.1 nmol/L (nonsulfated heptadecagastrin) and 0.3 nmol/L (pentagastrin). At these concentrations triacylglycerol secretion was 42% (nonsulfated heptadecagastrin, p < 0.001) and 62% (pentagastrin, p < 0.001) lower than in cells untreated with gastrin. Sulfated cholecystokinin 26-33 caused a 35% decrease in triacylglycerol secretion at 0.1 nmol/L (p < 0.01), and desulfated cholecystokinin 26-33 caused a 53% decrease at 0.2 nmol/L (p < 0.001). In all experiments, the hormone-induced decrease in triacylglycerol secretion was accompanied by an increase in intracellular triacylglycerol content. The cholecystokinin-A receptor antagonist L-364, 718 did not affect the decrease in triacylglycerol secretion induced by 0.3 nmol/L pentagastrin, whereas the cholecystokinin-B receptor antagonist L-365, 260 inhibited the pentagastrin effect at concentrations above 50 nmol/L. These results suggest that gastrin, cholecystokinin or some other gastrinlike hormone (or all three) may play a previously unrecognized regulatory role with respect to hepatic very low density lipoprotein secretion.
Fluorescein Microangiography of the Ocular Fundus
Authors: Albert M. Potts
Journal: JAMA (1974)

Dr. Shimizu was junior author with Professor Shikano of an<i>Atlas of Fluorescence Fundus Angiography</i>in 1968 (209:421, 1969). The present volume is not a revision of the first one but represents a close view of one aspect of fluorescein angiography. It describes the events in the ocular capillary circulation in health and disease that the technique is able to demonstrate. The degree of detail is indicated by the separate chapters on the peripapillary capillaries and the disk itself. There are further chapters on occlusive retinal angiopathies, on capillary circulatory dynamics, and on inflammatory disease. Particularly notable are sizable sections on pulseless disease and Harada disease—entities that are rare enough in the United States so that a good series of pictures is welcome. Many of the photographs are enlarged six diameters in the plates. The excellence of the printing and the quality of the paper allow most of the detail of
Inhibition of Photocarcinogenesis by Platelet-Activating Factor or Serotonin Receptor Antagonists
Authors: Coimbatore S. Sreevidya, Noor M. Khaskhely, Atsushi Fukunaga, Polina Khaskina, Stephen E. Ullrich
Journal: Cancer Research (2008)

Abstract The UV radiation in sunlight is the primary cause of nonmelanoma skin cancer. Moreover, UV exposure induces immune suppression. Early steps in the cascade of events leading to immune suppression are the binding of UV-induced platelet-activating factor (PAF) to its receptor and the binding of cis-urocanic acid, a photoreceptor for UVB radiation, to the serotonin (5-HT2A) receptor. Here, we tested the hypothesis that blocking the binding of PAF and 5-HT2A to their receptors would also block skin cancer induction. Hairless mice were injected with PAF or serotonin receptor antagonists and then exposed to solar-simulated UV radiation. We noted a significant and substantial decrease in skin cancer incidence in mice treated with the PAF or 5-HT2A receptor antagonists. Also, the PAF and/or serotonin receptor antagonists blocked skin cancer progression. The PAF and serotonin receptor antagonists worked in a synergistic fashion to block skin cancer induction. We also measured the effect that injecting PAF and 5-HT2A receptor antagonists had on UV-induced skin damage after a single UV exposure. We noted a significant decrease in UV-induced hypertrophy, sunburn cell formation, and apoptosis when the mice were injected with PAF and/or 5-HT2A receptor antagonists. These data indicate that treating UV-irradiated mice with PAF and 5-HT2A receptor antagonists blocks skin cancer induction in vivo, in part by reversing UV-induced damage to the skin and by preventing the induction of immune suppression. [Cancer Res 2008;68(10):3978–84]
An open letter to the Prince of Wales: with respect, your highness, you've got it wrong
Authors: Michael Baum
Journal: BMJ (2004)

Twenty years ago, on the 150th anniversary of the BMA, you were appointed its president and used your position to admonish my profession for its complacency. You also used this platform to promote “alternative” medicine. Shortly after that I had the privilege of meeting you at a series of colloquia organised to debate the role of complementary and alternative medicine (CAM). Of course, you won't remember me but the event is indelible in my memory. I was the only one of my colleagues unequivocally to register dissent.

A few days later you had a four page supplement in the London Evening Standard , promoting unproven cures for cancer, and the paper invited me to respond. I requested the same space but was only allowed one page, which at the last minute was cut by a quarter to make space for an advert for a new release by Frankie Goes to Hollywood. Furthermore, the subeditors embarrassed me with the banner headline, “With respect your Highness, you've got it wrong” (13 August 1984). As I have nothing more to lose I'm happy for that headline to grace the BMJ today.

Over the past 20 years I have …
Nosocomial transmission of HCV in the liver unit of a tertiary care center
Authors: Xavier Forns, Eva Martínez-Bauer, Anna Feliu, Montserrat García-Retortillo, Marta Martín, Eugeni Gay, Miquel Navasa, Jose María Sánchez-Tapias, Miquel Bruguera, Juan Rodés
Journal: Hepatology (2004)

Despite its medical and legal implications, there are no prospective studies analyzing the incidence and mechanisms involved in the nosocomial transmission of hepatitis C virus (HCV) in liver units. This study prospectively investigates the nosocomial transmission of HCV in the liver unit of a tertiary care center from August 2000 to October 2002. The median prevalence of HCV infection among hospitalized patients was 50%. Anti-HCV–negative patients admitted to the liver unit during the study period were prospectively followed, and serum markers of HCV infection were repeated 6 months after discharge. All known risk factors for HCV transmission (including the physical allocation of HCV-infected and noninfected patients during hospitalization) were recorded. Complete follow-up data were available in 1,301 (84.5%) of 1,540 patients. Six patients (0.46%) acquired HCV infection (annual incidence: 0.27/100 admissions). Phylogenetic analyses of recovered HCV sequences identified the source of infection as an HCV-infected roommate (3 cases) and a patient receiving care by the same nurse team (1 case). The most relevant risk factors associated with HCV acquisition were duration of hospitalization (>10 days; OR, 35; 95% CI, 1.96-622) and hospitalization with an HCV-infected roommate (>5 days; OR, 12; 95% CI, 1.39-103). In fact, HCV infection occurred in 1.7% of the 357 patients hospitalized longer than 10 days. In conclusion, HCV nosocomial infection appears to occur via patient-to-patient transmission in liver units, particularly in individuals who require long hospitalizations. Continuous reinforcement of universal prevention measures and, when possible, isolation of patients at higher risk might further reduce nosocomial HCV transmission. (HEPATOLOGY 2005;41:115–122.)
Effects of Asbestos in Dockyard Workers
Authors: G. Sheers, A. R. Templeton
Journal: BMJ (1968)

The prevalence of pleural and pulmonary abnormalities attributed to asbestos among 15,000 workers in a naval dockyard has been studied by means of a one-in-ten sample. Ninety-four per cent. of the men in the sample were examined. Of these, 3% had experienced continuous occupational exposure to asbestos and half of the remainder (representing approximately 6,800 men) had been exposed intermittently. The prevalence of pleural fibrosis ranged from 28% in continuously exposed workers to 1.9% in those with least exposure.Most cases of pulmonary fibrosis occurred in laggers and sprayers who had been continuously exposed for between 15 and 20 years. Pulmonary fibrosis was also seen in a variety of intermittently exposed trades, and had been preceded by extensive pleural thickening in some cases. Ten cases of pleural mesothelioma have occurred in the last three years and a large number of men appear to be potentially at risk.
Points from Letters: Bronchodilator Preparations
Authors: P. W. S. Gray
Journal: BMJ (1974)

1) That this commnittee agrees to ap- point an appropriate number of members to serve on its two District Medical Committees."(2) That if the General Medical Services Committee so advises, these members will not participate in-the work of the District Medical Committees until the ques- tion of remuneration or reimbursement for loss of earnings is agreed with the Depart- ment of Health and Social Security."-Weare, etc.,
Temporal and Geographic Trends in the Autopsy Frequency of Blunt and Penetrating Trauma Deaths in the United States
Authors: Daniel A. Pollock
Journal: JAMA (1993)

<h3>Objective.</h3> —To examine national trends in the percentage of blunt and penetrating trauma deaths autopsied. <h3>Design, Setting, and Participatns.</h3> —For each year from 1980 through 1989, we used national mortality data files to determine the autopsy frequency (percentage of deaths autopsied) of all deaths in the United States. We analyzed variation in the autopsy frequency of blunt and penetrating trauma deaths by cause of injury and place of occurrence of death. <h3>Results.</h3> —The autopsy frequency of blunt and penetrating trauma deaths in the United States increased by 14.3% during the 1980s to 58.9% in 1989 (62 004 of 105 309 deaths autopsied), while the autopsy frequency of all deaths decreased by 23.6% during the same period to 11.5% in 1989 (248 272 of 2153859 deaths autopsied). Among trauma deaths, homicides remained far more likely to be autopsied than nonhomicides (deaths due to unintentional injuries, suicides, and injuries of undetermined intentionality). The autopsy frequency of homicidal trauma deaths in 1989 was 90.0% or higher in 44 states and ranged from 79.6% in Mississippi to 100.0% in six states. The autopsy frequency of nonhomicidal trauma deaths in 1989 was 90.0% or higher in two states and ranged from 10.3% in Oklahoma to 94.5% in Hawaii. Nationwide, we found significant differences in the autopsy frequency of trauma deaths in 1989 between metropolitan and nonmetropolitan counties, both for homicides (97.7% vs 89.3%;<i>P</i>&lt;.001) and nonhomicides (58.2% vs 29.9%;<i>P</i>&lt;.001). <h3>Conclusions.</h3> —The percentage of blunt and penetrating trauma deaths autopsied has increased recently in the United States, but extensive geographic variation in autopsy frequency suggests that the benefits of autopsy findings for trauma care quality improvement and public health surveillance of injuries are distributed unevenly throughout the nation. (<i>JAMA</i>. 1993;269:1525-1531)
Amputee Clinic in a Rural Setting
Authors: Oswald V. Clark
Journal: JAMA (1964)

THIS REVIEW is an effort to expose the need for, and the problems encountered in, developing an amputee clinic in a rural area. The staff of James Decker Munson Hospital, a 250-bed general hospital with an adjacent 90-bed Tricounty Medical Care facility, located in Traverse City, Mich, originated a progressive plan for total patient care with the organization of the Department of Rehabilitation Medicine. The hospital is in a rural setting more than 150 miles from the nearest city with facilities for amputees. The community approximates 18,000 people and the immediate tricounty rural area approximates 50,000 people. The northern one third of the lower peninsula, served in part by the hospital and its facilities, has an estimated population of 100,000 people. In the surrounding several counties there are many small, well-staffed rural hospitals serving sparsely populated areas. Within the confines of the hospital, the concepts of intensive, intermediate, long-intermediate, ambulatory,
Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model
Authors: Paulo C.F. Marotto, Albert I. Ko, Cristiane Murta-Nascimento, Antonio C. Seguro, Rogerio R. Prado, Marcia C. Barbosa, Sergio A. Cleto, José Eluf-Neto
Journal: Journal of Infection (2009)
BENIGN AND MALIGNANT HYPERTENSION AFTER ADRENAL ENUCLEATION IN THE RAT
Authors: C. E. Hall, O. B. Holland, O. Hall
Journal: The Journal of Experimental Medicine (1967)

Adrenal-enucleated, mononephrectomized rats given a high salt diet rapidly develop malignant hypertension, characterized by the presence of necrotizing vascular lesions in a number of organs and tissues. If a normal salt intake is provided, or if hydrochlorothiazide is given together with a high salt diet, there is, instead, the delayed onset of benign hypertension which either stabilizes or increases in intensity extremely slowly; Such animals display few, if any, pathologic vascular changes other than occasional focal glomerular hyalinization, show insignificant cardiac enlargement, and do not exhibit alterations in the serum sodium or potassium. Occasional animals behave atypically and develop malignant hypertension despite normal salt consumption, demonstrating that in susceptible rats excess salt is not essential to this disorder. Hydrochlorothiazide given to rats that imbibed distilled water postoperatively prevented hypertension entirely for 97 days, when one of eight rats developed mild hypertension and some others reached what is regarded as a prehypertensive range. It is concluded that adrenal regeneration provides a physiological milieu favorable to the development of benign hypertension, which is not, as a rule, manifest until regeneration is complete. Salt excess converts the response into one in which malignant hypertension begins during regeneration and worsens rapidly thereafter until death. The course and findings are compared with those of the benign and malignant phases of clinical essential hypertension, and the implications of the similarities are discussed.