tbuckley/cabot-search huggingface dataset:
Abstract 4635: The avidity hypothesis: comparing bispecific and monospecific antibodies in preclinical oncology models.
Authors: Kris F. Sachsenmeier, Nazzareno Dimasi, Qihui Huang, Erin Sult, Binyam Bezabeh, Ryan Fleming, Carl Hay, Helen Zhong, Shannon Breen, Changshou Gao, Balaji Agoram, Lutz Jermutus, Robert Hollingsworth
Journal: Cancer Research (2013)

Abstract Bi-specific antibodies are suggested to possess unique advantages when compared with mono-specific antibodies as anti-cancer therapeutics. These advantages include greater efficacy, superior combination with standard of care agents, and evasion of resistance mechanisms. Data are presented supporting the hypothesis that the increased avidity of a tetravalent (non BiTE-like) bi-specific antibody mediates such advantages when compared with conventional bi-valent mono-specific antibodies. Experiments include functional comparisons of antibodies binding the Epidermal Growth Factor (EGFR) and the Insulin-like Growth Factor 1 Receptor (IGF1R) at the biochemical, cellular and tumor xenograft levels. These data support the ongoing use of multi-specific antibodies in oncology research and describe a mechanism that may contribute to superior activity compared to mono-specific antibodies and drug combinations. It is noted that advantages of bi-specific antibody formats remain to be seen clinically in terms of both efficacy and safety. Citation Format: Kris F. Sachsenmeier, Nazzareno Dimasi, Qihui Huang, Erin Sult, Binyam Bezabeh, Ryan Fleming, Carl Hay, Helen Zhong, Shannon Breen, Changshou Gao, Balaji Agoram, Lutz Jermutus, Robert Hollingsworth. The avidity hypothesis: comparing bispecific and monospecific antibodies in preclinical oncology models. [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 4635. doi:10.1158/1538-7445.AM2013-4635
Abstract A11: Regulation of CD133 by the tubulin deacetylase HDAC6 can alter cancer cell state
Authors: Anthony B. Mak, Saranya Kittanakom, Ginny I. Chen, Ralph Mazitschek, Anne-Claude Gingras, Igor Stagljar, Jason Moffat
Journal: Clinical Cancer Research (2010)

Abstract The CD133 antigen AC133/1 is a putative marker for enriching certain stem cells and cancer progenitor cells. Despite its wide application, the function and regulation of its expression remains unclear. Given the presence of its transcript in more differentiated cells, epigenetic regulation of CD133 transcripts alone cannot vouch for its utility as a marker. Therefore, understanding the regulation of CD133 protein expression is important for further defining the cellular state of tumor-initiating cells. We used the MAPLE system (Mak et al, Mol Cell Proteomics, 2010) to identify bona fide protein interaction partners of CD133. We present the microtubule-associated histone deacetylase 6 (HDAC6) as a physical interaction partner of CD133. This interaction was validated by co-immunoprecipitation/Western Blot analyses and by a membrane yeast two-hybrid (MYTH) assay. In order to understand the functional consequence of the HDAC6 and CD133 interaction, we used lentiviral short-hairpin RNAs to knockdown HDAC6 in multiple cell types, including the human epithelial colorectal adenocarcinoma lines Caco- 2 and HT-29 and in the retinoblastoma cell line Weri-Rb-1. Interestingly, we observed a significant reduction of CD133 protein expression. This reduction was shown to be dependent on HDAC6 deacetylase activity using a deacetlyase deficient HDAC6 mutant as well as when using the small molecule inhibitor of HDAC6, tubacin. HDAC6 promotes de-acetylation of alpha-tubulin to influence re-cycling of cell surface proteins. Furthermore, when we performed a CD133 MYTH screen against a cDNA library isolated from an adult human brain, we identified the late endosomal- and lysosomal-associated marker CD63 as an interaction partner of CD133. In fact, treatment of Caco-2 cells with tubacin resulted in trafficking of CD133 into endosomes for lysosomal degradation as determined by increased co-localization with CD63. In an attempt to study the affect of HDAC6 knockdown on cell viability, we noticed that CD133 knockdown significantly impacted cell proliferation and clonogenicity of Caco-2 cells. We determined that the cause of this is likely due to increased differentiation as determined by the level of alkaline phosphatase activity and by quantitative realtime PCR for markers of differentiated colon cells. To assess the tumorigenic potential of Caco-2 cells with reduced CD133 expression in vitro we performed soft agar colony-forming assay, which resulted in the loss of anchorage independent growth, a well-known hallmark of cancer. Together, these results suggest that CD133 can exercise a function in establishing and maintaining a primitive cancer cell state and loss or reduction of its expression marks more differentiated cancer cells that may be nontumorigenic. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A11.
Venodilation in Raynaud's disease
Authors: G.V. Bedarida, D. Kim, T.F. Blaschke, B.B. Hoffman, B.B. Hoffman
Journal: The Lancet (1993)

The pathogenesis of Raynaud's disease is unclear; an enhanced reponse to catecholamines has been hypothesised to contribute to this vasospastic disorder. Impaired endothelium-dependent dilation occurs in other diseases associated with vasospasm, such as coronary atherosclerosis. We investigated both endothelium-dependent and endothelium-independent venodilatory function in Raynaud's disease using the hand-vein compliance technique. Full dose-response curves to noradrenaline were constructed in 10 subjects with primary Raynaud's disease and 10 age and sex matched control subjects. The two groups did not have a different response to noradrenaline. Mean (SD) log values of ED50s (the dose producing half maximum response) were 1·00 (0·59) (geometric mean 10 ng/min) in Raynaud's disease compared with 1·29 (0·66) (20 ng/min) in control subjects (p=0·16). The efficacy of noradrenaline as a venoconstrictor was similar in the two groups: mean maximum dilation (Emax) to noradrenaline was 81 (14)% in the Raynaud's group and 89 (8)% in the control group (p=0·08). Full dose-response curves to the endothelium-dependent dilator bradykinin were constructed. Emax to bradykinin was significantly lower in the Raynaud's group than in the control group (65 [21] vs 91 [29%], p=0·02). ED50 values (doses producing half maximum response) for bradykinin were similar in the two groups. Maximum dilation with nitroprusside, a direct releaser of the vasodilator nitric oxide, was not diminished in the Raynaud's group (94 [23] vs 102 [15]% in controls, p=0·26). These results suggest that endothelium-dependent venodilation is impaired in peripheral vessels in Raynaud's disease, possibly due to diminished release of nitric oxide, and may contribute to the pathogenesis of the disorder.
Intra-epithelial mast cells in human airway epithelium: evidence for smoking-induced changes in their frequency.
Authors: D Lamb, A Lumsden
Journal: Thorax (1982)

A morphological and quantitative study was performed on the respiratory epithelium of human distal airways in 20 lungs removed at operation for the treatment of carcinoma. Using 1 micron araldite sections stained with Toluidine Blue for light microscopy, with further electron microscopic study where required, we have described mast cells in the epithelium of bronchioles, terminal bronchioles, and respiratory bronchioles. Examination of these cells at both microscopic levels demonstrates many of the typical features of mast cells--namely, metachromatic granules on staining with toluidine blue at light microscopic level, surface microvillous processes, and numerous dense intracytoplasmic granules with a whorled substructure at electron microscopy. Furthermore, we have identified cells devoid of granular material which may be recognised as mast cells by virtue of their nuclear and cell surface characteristics--the occurrence of a spectrum of change between those cells devoid of granular material and those with full granule content; and a few cells in which we found both typical dense, whorled granules and large lucent vacuoles devoid of such material. Quantitation of all respiratory epithelial cells by light microscopy shows that mast cells comprise 0-2% of the total population. A higher proportion of mast cells was found in the epithelium of smokers than in non-smokers. Because of the presence of many epithelial mast cells devoid of granule content, we suggest that the use of traditional 4 microns paraffin sections stained with thiazine dyes to study mast cells would lead to a marked underestimation of the epithelial population.
Psychogenic pseudo-Tourette syndrome: one of Dr Johnson's maladies?
Authors: John Grimley Evans
Journal: Journal of the Royal Society of Medicine (2010)

It has been suggested that Dr Samuel Johnson was a sufferer of Tourette's Disorder, now regarded as a distinct syndrome of tics and vocalizations consequent on a neurological abnormality. We describe here a superficially similar syndrome of apparently psychogenic origin that may have underlain some of Dr Johnson's oddities.
PSEUDOMONAS AERUGINOSA PERITONITIS ASSOCIATED WITH CONTAMINATED POLOXAMER-IODINE SOLUTION
Authors: PatriciaL. Parrott, ElizabethN. Whitworth, PamelaM. Terry, LorettaW. Frawley, RebeccaS. Coble, I.Kaye Wachsmuth, JohnE. Mcgowan
Journal: The Lancet (1982)
Anti-nucleic acid antibodies in systemic lupus erythematosus patients and their families. Incidence and correlation with lymphocytotoxic antibodies.
Authors: R J DeHoratius, R Pillarisetty, R P Messner, N Talal
Journal: Journal of Clinical Investigation (1975)

Anti-RNA antibodies were found in 82% of 28 systemic lupus erythematosus (SLE) probands and in 16% of 124 of their family members. The incidence in 76 control family members was only 5%. In the SLE family members, the antibodies were found exclusively in 21% of the 94 close household contacts of the probands. The incidence of anti-native DNA (nDNA) antibodies was 68% for the SLE probands. The incidence of anti-nDNA antibodies in close household contacts of the probands was 6%, which was not significantly different from the 1% incidence found in control families. Lymphocytotoxic antibodies occurred in 57% of the SLE family members as a whole and in 68% of the close household contacts. In the SLE probands, lymphocytotoxic antibodies correlated with anti-single-stranded RNA (poly A) and anti-nDNA but not with anti-double-stranded RNA (poly A-poly U). On the other hand, lymphocytotoxic antibodies in the household contacts correlated with anti-double-stranded RNA (poly A-poly U) but not with anti-poly A or anti-nDNA. The anti-RNA antibodies were present in consanguineous household contacts but not in nonconsanguineous household contacts. These findings strengthen the hypothesis that both an environmental agent, possibly a virus, as well as the genetic response are important in the pathogenesis of SLE. Family members may therefore be a logical population in whom to search for specific antibodies to a viral agent.
Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver*1
Authors: Matthew Golding, Catherine E. Sarraf, El-Nasir Lalani, T.V. Anilkumar, Robert J. Edwards, Peter Nagy, Snorri S. Thorgeirsson, Malcolm R. Alison
Journal: Hepatology (1995)

When hepatocyte regeneration after a two-thirds partial hepatectomy (PH) in rats is blocked by oral gavage of acetylaminofluorene, a proliferation of ductular cells ensues that results in a profusion of neoductules radiating from each portal tract. To examine the possibility that this population of newly emerging cells harbors cells capable of differentiating into hepatocytes, we have looked in these cells for expression of functional markers of hepatocyte commitment at both the RNA and protein levels. Expression of albumin and a-fetoprotein (αFP) messenger RNA (mRNA) transcripts were sought in situ using antisense riboprobes, and the expression of a number of cytochrome P450 enzymes was examined immunohistochemically. Before any signs of differentiation the ductular cells strongly expressed cytokeratins 7, 8, 18, and 19 in the same manner as authentic bile ducts, but unlike the latter also expressed vimentin. In situ hybridization studies showed that small bile ducts close to the limiting plate, as well as the newly formed ducts, expressed albumin and a-fetoprotein messenger RNAs, and immunocytochemistry showed that the distribution of the respective proteins was similar. Beginning at 1 week after partial hepatectomy, areas of differentiation could be found in the new ducts, with cells resembling either columnar intestinal-type epithelia or hepatocytes. Intestinal-like cells expressed neither albumin, α-FP, nor cytochrome P450 enzymes, whereas ductular cells appearing like hepatocytes with the typical membranous distribution of cytokeratin 8 strongly expressed a variety of cytochrome P450 enzymes normally associated with functional hepatocytes. These observations further support the belief that reactive ductules, sprouted from small ducts, can represent an adaptive response of the liver to replenish lost hepatocytes, although some of the newborn cells appear to differentiate along intestinal lines.
Treatment of Haemophilia and Other Coagulation Disorders
Authors: Robert T. Breckenridge
Journal: JAMA (1966)

Doctors Biggs and Macfarlane, in this monograph, summarize their experience with the therapy of hemophilia and other coagulation disorders. They and their colleagues are well qualified to speak on this subject and this book reflects their competence in this area. The first chapter deals with the normal hemostatic mechanism as visualized by Professor Macfarlane. It is imaginatively written and should certainly stimulate interest, if not controversy, among its readers. His "cascade" theory of blood coagulation, while not proven, has gained wide acceptance in this country as well as others. Following this section is a chapter on the diagnosis of hemorrhagic diseases which is somewhat limited in scope and is more adequately covered in other monographs. After the introductory chapters, a large segment deals with the preparation of the therapeutic materials useful in hemophilia and Christmas disease. A great deal of stress is put upon the use of Factor VIII (antihemophilic
Use of cheaper eye drug would save billions, says US study
Authors: M. McCarthy
Journal: BMJ (2014)

If all eye doctors in the United States used the less expensive of the two drugs commonly used to treat neovascular age related macular degeneration and diabetic macular edema, they could save US taxpayers and consumers tens of billions of dollars, a new study concludes.1

In both these conditions the swelling and bleeding resulting from the growth of abnormal retinal blood vessels lead to loss of vision. The conditions affect more than two million Americans and are a leading cause of blindness.

The two drugs, bevacizumab and ranibizumab, are both antivascular endothelial growth factor (anti-VEGF) agents, which, when injected into the eye, cause the abnormal retinal blood vessels to regress, halting or slowing disease …
The House of God
Authors: Richard Smith
Journal: BMJ (2007)

Sex and death are all that matter, argues Philip Roth, perhaps the greatest living writer in English. The early years that doctors spend in hospital thus provide rich material, as the doctors are surrounded by death and obsessed by sex. The House of God by Samuel Shem is the most successful and literary of books describing the initiation of doctors and has sold over two million copies since it was published in 1978. Its bleakness, black humour, and brutishness paved the way for television programmes like Cardiac Arrest , Green Wing , and Bodies . 

The book …
Injection of Bone Marrow Cell Extract Into Infarcted Hearts Results in Functional Improvement Comparable to Intact Cell Therapy
Authors: Yerem Yeghiazarians, Yan Zhang, Megha Prasad, Henry Shih, Shereen A Saini, Junya Takagawa, Richard E Sievers, Maelene L Wong, Neel K Kapasi, Rachel Mirsky, Juha Koskenvuo, Petros Minasi, Jianqin Ye, Mohan N Viswanathan, Franca S Angeli, Andrew J Boyle, Matthew L Springer, William Grossman
Journal: Molecular Therapy (2009)

We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using closed-chest ultrasound-guided injection at a clinically relevant time post-MI. MI was induced in mice and the animals treated at day 3 with either: (i) BMCs from green fluorescent protein (GFP)-expressing mice (n = 14), (ii) BMC extract (n = 14), or (iii) saline control (n = 14). Six animals per group were used for histology at day 6 and the rest followed to day 28 for functional analysis. Ejection fraction was similarly improved in the BMC and extract groups versus control (40.6 +/- 3.4 and 39.1 +/- 2.9% versus 33.2 +/- 5.0%, P < 0.05) with smaller scar sizes. At day 6 but not day 28, both therapies led to significantly higher capillary area and number of arterioles versus control. At day 6, BMCs increased the number of cycling cardiomyocytes (CMs) versus control whereas extract therapy resulted in significant reduction in the number of apoptotic CMs at the border zone (BZ) versus control. Intracellular components within BMCs can enhance vascularity, reduce infarct size, improve cardiac function, and influence CM apoptosis and cycling early after therapy following MI. Intact cells are not necessary and death of implanted cells may be a major component of the benefit.
Intensive Care Unit Admissions With Cirrhosis: Risk–Stratifying Patient Groups and Predicting Individual Survival
Authors: J E Zimmerman, D P Wagner, M G Seneff, R B Becker, X Sun, W A Knaus
Journal: Hepatology (1996)

Prognosis for acutely ill patients with cirrhosis is influenced by the severity of hepatic abnormalities and by dysfunction of other organ systems. The purpose of this study was to examine the usefulness of the Acute Physiology, Age, and Chronic Health Evaluation (APACHE III) prognostic system for risk-stratifying groups of intensive care unit (ICU) patients with cirrhosis and in predicting individual survival. We used data for 17,440 ICU admissions at 40 American hospitals to select 117 of the 537 patients with a history of cirrhosis who were ventilated on ICU day 1, a group known to have a high mortality rate. We then calculated each patient's probability of hospital death on ICU days 1 through 7, using seven previously validated multivariate equations. Hospital mortality was 63% for the 117 study patients. The most important determinants of risk for hospital death on ICU day 1 were the acute physiology score of APACHE III, ICU admission diagnosis, and operative status. Daily changes in the acute physiology score caused a rise or fall in the probability of hospital mortality and was useful in assessing individual response to therapy. APACHE III accurately risk stratifies critically ill patients with cirrhosis because it accounts for many of the factors known to influence prognosis. This capability can be used to assess severity of illness and risk-stratify patients with cirrhosis during clinical trials. Daily prognostic estimates based on physiological changes over time reflect patient response and can help physicians to assess the incremental benefit of therapy.
Association of strength and range of motion with alpha angles in elite youth hockey players
Authors: M J Philippon, R F LaPrade, K K Briggs, J D Stull
Journal: British Journal of Sports Medicine (2011)

Background Increased alpha angle of the hip is associated with femoroacetabular impingement (FAI). Decreased hip range of motion (ROM) and hip adductor/abductor muscular imbalances are reportedly associated with FAI. Objective To determine if there is a relationship between decreased hip ROM and hip muscle imbalances with the degree of observed alpha angle. Design Prospective screening study. Setting Clinical centre screened elite major midget youth hockey players. Participants 20 asymptomatic male (average age of 17.6 years, SD=0.5) ice hockey players who had signed IRB approved consent. Assessment of risk factors Participants underwent hip ROM and strength assessment prior to an MRI (3T) to determine hip alpha angle. Main outcome measurements Positive clinical findings of abduction/adduction strength imbalance and decreased ROM correlate with a high alpha angle. Results The degree of hip alpha angles as determined by MRI were not related to hip abduction/adduction ROM (r2=0.075, p=0.24), flexion/extension ROM (r2=0.012, p=0.64), or external rotation/internal rotation ROM (r2=0.115 p=0.14). Additionally the degree of alpha angle was not related to abduction/adduction strength imbalance (r2=0.013, p=0.64). All 20 participants screened displayed acetabular labral pathology on 3T MRI. Conclusion We found no relationship between hip ROM or abduction/adduction strength imbalances of the hip with the degree of alpha angle in asymptomatic elite major midget hockey players. Therefore, it is important to inspect for muscle weakness and pain in assessing whether patients have clinical symptoms of FAI and not rely solely on MRI for the diagnosis of FAI.
Can sports-minded kids have too many helmets?
Authors: T. B. Cole
Journal: JAMA (1996)

ABSTRACT AS SPRING DAYS grow longer and milder, kids' thoughts are turning to bicycling, roller skating, and in-line skating. But as evidence grows in support of helmets to prevent sports-related head injury, parents may wonder whether an active child needs an extra closet just for sport-specific headgear.The answer may be no, according to Frederick P. Rivara, MD, professor of pediatrics at the University of Washington School of Medicine in Seattle and director of the Harborview Injury Prevention Research Center. Helmets designed for use in one sport generally have not been recommended for use in other sports. But Rivara noted that at least 4 companies have developed multipurpose helmets that can protect children when they ride bicycles and participate in roller sports such as skateboarding and in-line skating.Rivara discussed helmet use last month during the spring session of the American Academy of Pediatrics in Chicago, Ill. The advantage of multipurpose
Concentration of 99mTc-Pyrophosphate in a Benign Leiomyoma of the Uterus
Authors: RAJASHRI S. MANOLI, JAGMEET S. SOIN
Journal: Clinical Nuclear Medicine (1977)

An unusual case of 99mTc(Sn)-pyrophosphate accumulation in a uterine leiomyoma is reported. Although the actual mechanism of uptake is not clear, the concentration of 90mTc(Sn)-pyrophosphate could possibly be related to the increased vascularity of the tumor as demonstrated by a 99mTc-HSA (Human Serum Albumin) study. However, other mechanisms such as calcification or estrogen related hormonal factors may also be responsible. The relationship between 99mTc-pyrophosphate uptake by other estrogen dependent tumors such as breast tumors is also discussed.
TCT-440 Diabetes Mellitus And Early And 2-Year Outcomes of Patients With Cardiogenic Shock And Acute Myocardial Infarction - Results From The PL-ACS Registry
Authors: Marek Gierlotka, Mariusz Gasior, Michal Hawranek, Damian Pres, Mateusz Tajstra, Lukasz Pyka, Marian Zembala, Krzysztof Strojek, Lech Polonski
Journal: Journal of the American College of Cardiology (2013)