tbuckley/cabot-search huggingface dataset:
Role of Bruton's tyrosine kinase in myeloma cell migration and induction of bone disease
Authors: Rakesh Bam, Wen Ling, Sharmin Khan, Angela Pennisi, Sathisha Upparahalli Venkateshaiah, Xin Li, Frits van Rhee, Saad Usmani, Bart Barlogie, John Shaughnessy, Joshua Epstein, Shmuel Yaccoby
Journal: American Journal of Hematology (2013)

Myeloma cells typically grow in bone, recruit osteoclast precursors and induce their differentiation and activity in areas adjacent to tumor foci. Bruton's tyrosine kinase (BTK), of the TEC family, is expressed in hematopoietic cells and is particularly involved in B-lymphocyte function and osteoclastogenesis. We demonstrated BTK expression in clinical myeloma plasma cells, interleukin (IL)-6- or stroma-dependent cell lines and osteoclasts. SDF-1 induced BTK activation in myeloma cells and BTK inhibition by small hairpin RNA or the small molecule inhibitor, LFM-A13, reduced their migration toward stromal cell-derived factor-1 (SDF-1). Pretreatment with LFM-A13 also reduced in vivo homing of myeloma cells to bone using bioluminescence imaging in the SCID-rab model. Enforced expression of BTK in myeloma cell line enhanced cell migration toward SDF-1 but had no effect on short-term growth. BTK expression was correlated with cell-surface CXCR4 expression in myeloma cells (n = 33, r = 0.81, P < 0.0001), and BTK gene and protein expression was more profound in cell-surface CXCR4-expressing myeloma cells. BTK was not upregulated by IL-6 while its inhibition had no effect on IL-6 signaling in myeloma cells. Human osteoclast precursors also expressed BTK and cell-surface CXCR4 and migrated toward SDF-1. LFM-A13 suppressed migration and differentiation of osteoclast precursors as well as bone-resorbing activity of mature osteoclasts. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibited osteoclast activity, prevented myeloma-induced bone resorption and moderately suppressed myeloma growth. These data demonstrate BTK and cell-surface CXCR4 association in myeloma cells and that BTK plays a role in myeloma cell homing to bone and myeloma-induced bone disease. Am. J. Hematol. 88:463-471, 2013. © 2013 Wiley Periodicals, Inc.
Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery.
Authors: J C Horrow, D F Van Riper, M D Strong, I Brodsky, J L Parmet
Journal: Circulation (1991)

BACKGROUND Desmopressin-induced release of tissue plasminogen activator from endothelial cells may explain the absence of its hemostatic effect in patients undergoing cardiac surgery. Prior administration of the antifibrinolytic drug tranexamic acid might unmask such an effect, and combination therapy might thereby improve postoperative hemostasis. METHODS AND RESULTS A double-blinded design randomly allocated 163 adult patients undergoing coronary revascularization, valve replacement, both procedures, or repair of atrial septal defect to four treatment groups: placebo, tranexamic acid given as 10 mg/kg over 30 minutes followed by 1 mg.kg-1.hr-1 for 12 hours initiated before skin incision, desmopressin given as 0.3 micrograms/kg over 20 minutes after protamine infusion, and both drugs. One surgeon performed all operations. Blood loss consisted of mediastinal tube drainage over 12 hours. Follow-up visits sought evidence of myocardial infarction and stroke. Desmopressin decreased neither the 12-hour blood loss nor the amount of homologous red cells transfused. Tranexamic acid alone significantly reduced 12-hour blood loss, by 30% (mean, 318 versus 453 ml; p less than 0.0001), without enhancement by desmopressin. Tranexamic acid also decreased the proportion of patients receiving homologous blood within 12 hours of operation (8% versus 21%, p = 0.024) and within 5 days of operation (22% versus 41%, p = 0.011). CONCLUSIONS Desmopressin exerts no hemostatic effect, with or without prior administration of antifibrinolytic drug. Prophylactic tranexamic acid alone appears economical and safe in decreasing blood loss and transfusion requirement after cardiac surgery.
Respiratory effort perception at rest and during carbon dioxide rebreathing in patients with dystrophia myotonica.
Authors: J E Clague, J Carter, J Coakley, R H Edwards, P M Calverley
Journal: Thorax (1994)

Breathlessness appears to be closely related to the perception of the outgoing motor command to breathe and should be increased in the presence of muscle weakness. However, breathlessness is not a common symptom in patients with chronic muscle disease who have weak respiratory muscles. The factors that determine the perception of respiratory effort in such patients have not been examined.The inspiratory effort sensation during resting breathing and progressive hypercapnia was investigated in 12 patients with dystrophia myotonica with weak respiratory muscles (nine men and three women of mean (SD) age 41.1 (10.5) years; maximum inspiratory pressure 43.1 (17.2) cm H2O) and an age and sex matched control group of normal subjects of mean age 39.6 (10.6) years and a maximum inspiratory pressure of 123 (15.2) cm H2O.During resting breathing with a mouthpiece no differences were seen in inspiratory effort sensation, mouth occlusion pressure, or tidal volume, but inspiratory time and cycle duration were significantly shorter in the patients with dystrophia. Minute ventilation (VE) was significantly higher in the patients (15.8 (4.0) l/min v 12.5 (2.6) l/min), while resting breathing was no more variable in the patients than in controls. The ventilatory response to carbon dioxide (VE/PCO2) was not significantly lower in the patients (14.9 (6.9) l/min/kPa) than in the controls (17.4 (4.3) l/min/kPa). Effort sensation responses to carbon dioxide driven breathing were similar in the control subjects and the patients. With regression analysis of pooled data neither maximum inspiratory pressure nor disease state contributed to perceived inspiratory effort during hypercapnia.Moderately severe global respiratory muscle weakness does not appear to influence the ventilatory response to rising carbon dioxide tension or the perception of inspiratory effort in patients with dystrophia myotonica.
Treatment centres may destabilise NHS, doctors claim
Authors: Madeleine Brettingham
Journal: BMJ (2005)

The introduction of NHS treatment centres, dedicated exclusively to elective surgery and diagnostic tests, means that patients are being seen and treated faster, according to a report released by the health secretary, John Reid, this week.

But the BMA has raised concerns that if such centres continue to siphon off patients, traditional hospitals may become unsustainable in the long run.

Waiting lists are at their lowest since records began, according to Mr Reid, or at least at their lowest since 1987, when the Department of Health first began collecting comparable data. They have been reduced by 144 000 in the last year, and the centres …
Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema.
Authors: A Yoshioka, T Betsuyaku, M Nishimura, K Miyamoto, T Kondo, Y Kawakami
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.
Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model.
Authors: E Allaire, R Forough, M Clowes, B Starcher, A W Clowes
Journal: Journal of Clinical Investigation (1998)

Although matrix metalloproteinases (MMPs) are expressed in abundance in arterial aneurysms, their contribution to arterial wall degeneration, dilation, and rupture has not been determined. We investigated MMP function in a rat model of aneurysm associated with arterial dilation, elastin loss, medial invasion by mononuclear inflammatory cells, and MMP upregulation. Rupture was correlated with increased gelatinase B (MMP-9) and activated gelatinase A (MMP-2). Syngeneic rat smooth muscle cells retrovirally transfected with tissue inhibitor of matrix metalloproteinases (TIMP)-1 cDNA (LTSN) or with the vector alone as a control (LXSN) were seeded onto the luminal surface of the vessels. The seeding of LTSN cells resulted in TIMP-1 local overexpression. The seeding with LTSN cells, but not LXSN cells, decreased MMP-9, activated MMP-2 and 28-kD caseinase and elastase activity, preserved elastin in the media, and prevented aneurysmal degeneration and rupture. We conclude that MMP overexpression is responsible for aneurysmal degeneration and rupture in this rat model and that local pharmacological blockade might be a reasonable strategy for controlling the formation of aneurysms in humans.
The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1
Authors: Liuliang Qin, Dezheng Zhao, Jianfeng Xu, Xianghui Ren, Ernest F. Terwilliger, Sareh Parangi, Jack Lawler, Harold F. Dvorak, Huiyan Zeng
Journal: Blood (2013)
Interhospital Patient Transfer
Authors: A L Kellermann, T F Ackerman
Journal: New England Journal of Medicine (1988)

Increasing pressure to contain health care costs has led many hospitals to transfer poor and uninsured emergency department patients to other institutions. The transfer of patients for primarily economic reasons — a practice known as "patient dumping" — has become a serious problem nationwide.1 2 3 4 Amid growing concern that many transfers involve patients in unstable or even critical condition, several professional organizations and hospital associations have formulated voluntary guidelines to encourage responsibility in interhospital transfers.5 6 7 8 Recently, several state legislatures and the federal government have also enacted laws to control the worst abuses of patient dumping.9 , 10 Patient-transfer guidelines and laws have generally . . .
Abstract 473: TRIM59, a novel prognostic marker for gastric cancer, promotes tumorigenesis via ubiquitination and degradation of the p53 tumor suppressor
Authors: Zhicheng Zhou, You Wang, Jian Li, Hui Cao, Helen H. Zhu, Wei-Qiang Gao
Journal: Cancer Research (2014)

Abstract As a key tumor suppressor, p53 plays crucial roles in gastric cancer initiation and progression. However, the underlying mechanisms for the down-regulation of p53 in gastric cancer patients are not fully understood. Several tripartite motif (TRIM) family proteins are identified to be involved in the tumorigenesis of multiple cancer types, but the significance and biological function of a new TRIM family protein, TRIM59, in terms of whether and how it affects p53 signaling in gastric cancer are largely unknown. We analyzed multiple microarray datasets from the Oncomine database and tested the expression level of TRIM59 in gastric tumors vs. their matched normal tissues and in gastric carcinoma cell lines using quantitative-polymerase chain reactions (Q-PCR) and immunohistochemical staining. We found Expression of TRIM59 was significantly up-regulated in gastric cancer and strongly associated with poor prognosis. TRIM59 knockdown led to significantly attenuated gastric cancer cell proliferation, clone formation, migration, and in vivo xenograft tumorigenicity, whereas over-expression of TRIM59 showed the opposite effects. Mechanistically, TRIM59 interacted with p53 and enhanced ubiquitination and degradation of the p53 protein. In addition, elevated expression of TRIM59 correlated with down-regulation of p53 target genes in human gastric tumors. In summary, TRIM59 is a novel prognostic marker for gastric cancer and promotes tumorigenesis through facilitating p53 ubiquitination and degradation. Citation Format: Zhicheng Zhou, You Wang, Jian Li, Hui Cao, Helen He Zhu, Wei-Qiang Gao. TRIM59, a novel prognostic marker for gastric cancer, promotes tumorigenesis via ubiquitination and degradation of the p53 tumor suppressor. [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 473. doi:10.1158/1538-7445.AM2014-473
Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation
Authors: Edward V. Loftus, Humberto I. Aguilar, William J. Sandborn, William J. Tremaine, Ruud A. Krom, Alan R. Zinsmeister, Ivo W. Graziadei, Russell H. Wiesner
Journal: Hepatology (1998)

Several centers have identified colorectal cancer in patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) who have undergone orthotopic liver transplantation. Increased frequency of surveillance colonoscopy and prophylactic colectomy has been recommended. To address these concerns, we reviewed the posttransplantation experience with colorectal neoplasia in patients with PSC and UC at our institution. All patients with PSC and UC who underwent liver transplantation at Mayo Clinic between April 1985 and December 1993 were followed up through their complete history for colorectal dysplasia, cancer, or death. Eighty-one of 108 patients with PSC (75%) had concomitant inflammatory bowel disease (all but 1 had UC). Proctocolectomy had been performed before transplantation in 24 (30%). Median follow-up after transplantation was 4.2 years. Among the 57 patients with intact colons, 3 developed colorectal cancer, an incidence of approximately 1% per person per year. The cumulative incidence of dysplasia was 15% at 5 years and 21% at 8 years. Overall actuarial survival stratified by presence or absence of an intact colon at transplantation was similar (86% and 86%, respectively, at 5 years). The risk of carcinoma after transplantation compared with that expected for patients during a comparable (pretransplantation) period was increased fourfold but was not statistically significant. The risk of colorectal neoplasia (dysplasia and cancer) after liver transplantation in patients with PSC and UC is clinically important. However, this risk had no impact on patient survival. Prophylactic proctocolectomy does not appear necessary, but annual surveillance colonoscopy is recommended.
Effect of colony stimulating factor on murine macrophages. Induction of antitumor activity.
Authors: E J Wing, A Waheed, R K Shadduck, L S Nagle, K Stephenson
Journal: Journal of Clinical Investigation (1982)

Colony stimulating factor (CSF) was assessed for its capacity to stimulate antitumor activity in macrophages. Murine peritoneal macrophages incubated with CSF for 48 h inhibited [3H[thymidine (TdR) incorporation by P815 tumor cells to approximately 20% of control values. Inhibition of CSF-stimulated macrophages was significantly greater than inhibition by unstimulated macrophages (P less than 0.001). CSF had little direct effect on the proliferation of either tumor cells or macrophages alone, indicating that the antitumor activity of CSF was mediated by macrophages. it is unlikely that impurities in the CSF preparations were responsible for the effect since CSF that had been purified to homogeneity was as active as crude preparations. Furthermore the activity of CSF on macrophages was blocked by addition of purified anti-CSF antibodies. In addition to being tumoristatic, CSF-stimulated macrophages were tumoricidal as determined by a tumor colony growth assay. Tumor cells that had been incubated with CSF-stimulated macrophages showed a significant reduction in tumor colony-forming units (P less than 0.01). Thus, in addition to its effect on hemopoietic stem cells, CSF induces certain effector functions in mature macrophages that may enhance endogenous antitumor host defenses.
Selection of medical students
Authors: P. Tutton
Journal: BMJ (2002)

Mazindol has been explored as a possible agent in cocaine addiction pharmacotherapy. The tetracyclic compound inhibits both the dopamine transporter and the serotonin transporter, and simple chemical modifications considerably alter target selectivity. Mazindol, therefore, is an attractive scaffold for both understanding the molecular determinants of serotonin/dopamine transporter selectivity and for the development of novel drug abuse treatments. Using molecular modeling and pharmacologic profiling of rationally chosen serotonin and dopamine transporter mutants with respect to a series of mazindol analogs has allowed us to determine the orientation of mazindol within the central binding site. We find that mazindol binds in the central substrate binding site, and that the transporter selectivity can be modulated through mutations of a few residues in the binding pocket. Mazindol is most likely to bind as the <i>R</i>-enantiomer. Tyrosines 95 and 175 in the human serotonin transporter and the corresponding phenylalanines 75 and 155 in the human dopamine transporter are the primary determinants of mazindol selectivity. Manipulating the interaction of substituents on the 7-position with the human serotonin transporter Tyr175 versus dopamine transporter Phe155 is found to be a strong tool in tuning the selectivity of mazindol analogs and may be used in future drug design of cocaine abuse pharmacotherapies.
Hypersensitivity to Hymenoptera Stings
Authors: Theodore M. Freeman
Journal: New England Journal of Medicine (2004)

A 29-year-old man reports that he has been stung by a bee or wasp outside his door, where he had previously noted a nest. Skin itching, diffuse hives, swelling of his arms and legs, tightness in his throat, dizziness, and difficulty talking developed immediately, and he was taken to a local clinic where he received epinephrine and antihistamines. He was observed for two hours, and all symptoms resolved. How should his case be managed subsequently?
THE EFFECT OF ANTIBODY ON INTRACELLULAR PARASITISM OF SALMONELLA TYPHIMURIUM IN MONONUCLEAR PHAGOCYTES IN VITRO
Authors: Justus Gelzer, Emanuel Suter
Journal: The Journal of Experimental Medicine (1959)

The effect of antibody on the fate of Salmonella typhimurium within mononuclear phagocytes (MN) of rabbits was studied in vitro. Monocytes and bacteria were incubated either in absence or presence of antibody. After 45 minutes during which phagocytosis occurred infected cells were washed to remove extracellular bacilli and free antibody. The cells were then reincubated in a medium without addition of antibody, and the interaction between the MN and bacteria was followed, correlating bacterial viability and the morphology of the mixture. The following results were obtained. The anti-Salmonella antibody was not bactericidal even in presence of complement and did not enhance phagocytosis. Regardless of whether antibody was present or absent during phagocytosis, the bacteria appeared to multiply within the cells. When no antibody was present during phagocytosis the infected cells were severely damaged within a few hours of incubation, and extensive extracellular multiplication was dominating. When antibody was present during phagocytosis MN packed with bacteria persisted for a long time. Little or no extracellular growth occurred. It was possible to demonstrate the presence of the antibody within the infected MN, using the fluorescent antibody technique. The antibody appeared as a coat around the bacteria. Antibody entered the cells only during phagocytosis, presumably attached to the bacteria. The active factor of the immune serum was found in the gamma globulin fraction and reacted specifically with the somatic antigen of Salmonella typhimurium. The antiflagellar portion of the antiserum was not involved in the phenomenon described. It is concluded that this antibody protects monocytes against the effect of intracellularly located Salmonella.
Dutch GP in euthanasia case will not go to prison
Authors: T. Sheldon
Journal: BMJ (1997)

A Dutch court has rejected demands by the public prosecutor for a one year prison sentence for premeditated murder against a Frisian general practitioner, Dr Sippe Schat. Instead Dr Schat was found guilty of the lesser charge of euthanasia and of depriving his patient of life at her request and was given a six month suspended prison sentence.

Dr Schat was originally charged with murder and held on …
Today's Scabies
Authors: Milton Orkin
Journal: JAMA (1975)

In the past several years there has been a noticeable increase of scabies in the United States; the magnitude of this is not known. An expanding epidemic continues in most parts of the world. Scabies is frequently seen in many guises that may be difficult to diagnose: scabies in the clean, scabies incognito, nodular scabies, animaltransmitted scabies, scabies in infants, scabies with syphilis, and Norwegian scabies. If the diagnosis cannot be confirmed by identifying the mite, synthesis of suggestive features may establish the diagnosis. Recently adopted children from foreign countries, especially southeastern Asia, have had a high frequency of scabies, which may appear after the children arrive in the United States. Acute glomerulonephritis may develop in patients whose scabetic lesions are complicated by a virulent nephritogenic streptococcal strain. (<i>JAMA</i>233:882-885, 1975)
Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology
Authors: David Chou
Journal: JAMA (1985)

To complement its two other dictionaries for the health professions (eg,<i>Dorland's, Miller and Keane</i>), Saunders has introduced one addressed to both providers and consumers of medical laboratory services. Laboratory services, for the purposes of this book, include pathology, radiology, and related areas. The vocabulary covered by this dictionary refreshingly integrates traditional medical, as well as relevant technical, chemical, and engineering terms. This integration clearly demonstrates the wide impact other areas have had on medicine, as well as the importance in understanding them. The contents cover a mixture of definitions and explanations. According to the preface, "important aspects of laboratory medicine are covered in detail," frequently including some of the newer technologies. Almost a full page is devoted to an excellent description of nuclear magnetic resonance; three pages cover the subject of bacterial pathogenicity. There are also a surprising number of definitions and explanations relating to computer technologies and genetic
SERIAL OCT ANALYSIS OF NEOINTIMAL HYPERPLASIA AND COVERAGE ON THE SIROLIMUS ELUTING STENT STRUTS CROSSING OVER THE SIDE-BRANCH VESSELS
Authors: Tairo Kurita, Kenya Nasu, Euihong Ko, Tsuyoshi Ito, Maoto Habara, Yoshihisa Kinoshita, Mitsuyasu Terashima, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2011)