tbuckley/cabot-search huggingface dataset:
Preparing the “Soil”: The Premetastatic Niche
Authors: Rosandra N. Kaplan, Shahin Rafii, David Lyden
Journal: Cancer Research (2006)

Current focus on cancer metastasis has centered on the intrinsic factors regulating the cell autonomous homing of the tumor cells to the metastatic site. Specific up-regulation of fibronectin and clustering of bone marrow-derived cellular infiltrates coexpressing matrix metalloproteinases in distant tissue sites before tumor cell arrival are proving to be indispensable for the initial stages of metastasis. These bone marrow-derived hematopoietic progenitors that express vascular endothelial growth factor receptor 1 mobilize in response to the unique array of growth factors produced by the primary tumor. Their arrival in distant sites represents early changes in the local microenvironment, termed the "premetastatic niche," which dictate the pattern of metastatic spread. Focus on the early cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to detect and prevent metastasis at its earliest inception.
Degradation of blood group antigens in human colon ecosystems. II. A gene interaction in man that affects the fecal population density of certain enteric bacteria.
Authors: L C Hoskins, E T Boulding
Journal: Journal of Clinical Investigation (1976)

The autosomal dominant ABH secretor gene together with the ABO blood type gene control the presence and specificity of A, B, and H blood group antigens in human gut mucin glycoproteins. Certain obligate anaerobes in feces produce extracellular antigen-specific glycoside structures. We estimated the populations of these bacteria in feces of 22 healthy subjects by determining the greatest dilution of feces that yielded A, B, or H blood group-degrading enzyme activity after 24 h incubation in anaerobic cultures. Comparatively small populations of fecal bacteria produce blood group-degrading enzymes; their estimated populations were 10(8) per g or less in 21 subjects. Fecal populations of B-degrading bacteria were stable over time, and their population density averaged 50,000-fold greater in blood group B secretros than in other subjects. We present evidence that the greater fecal populations of B-degrading bacteria in B secretors is due in part to a competitive nutritional advantage gained by their ability to enzymatically cleave the B antigenic determinant alpha-D-galactose from gut mucins of B secretors. Fecal populations of bacteria producing A and H antigen-degrading enzyme activities were comparable in all subjects to the fecal population of B-degrading bacteria in B secretors. The large populations of fecal anaerobes may be an additional source of A antigen substrate for A-degrading bacteria; thus, antigens cross-reacting with A antigen were detected on cell walls of anaerobic bacteria from 3 of 10 cultures inoculated with 10(-10) g feces. Bacteria producing B-degrading activity likely represent a separate population from those producing A- or H-degrading activity since their fecal populations differed numerically in 14 subjects. These findings suggest that adaptation of blood group-degrading enzymes to mucin structures in human colon ecosystems is chiefly by mutation-selection of comparatively small populations of constitutive enzyme-producing strains rather than by substrate induced enzyme synthesis in many strains.
Continuity of care: a multidisciplinary review
Authors: J. L Haggerty
Journal: BMJ (2003)

The concept-and reality-of continuity of care crosses disciplinary and organisational boundaries.The common definitions provided here should help healthcare providers evaluate continuity more rigorously and improve communication Patients are increasingly seen by an array of providers in a wide variety of organisations and places, raising concerns about fragmentation of care.Policy reports and charters worldwide urge a concerted effort to enhance continuity, 1-3 but efforts to describe the problem or formulate solutions are complicated by the lack of consensus on the definition of continuity.To add to the confusion, other terms such as continuum of care, coordination of care, discharge planning, case management, integration of services, and seamless care are often used synonymously.This synthesis was commissioned by three Canadian health services policy and research bodies.The aim was to develop a common understanding of the concept of continuity as a basis for valid and reliable measurement of practice in different settings.
In Vivo Confocal Microscopy Evaluation of Meibomian Gland Dysfunction in Atopic-Keratoconjunctivitis Patients
Authors: Osama M.A. Ibrahim, Yukihiro Matsumoto, Murat Dogru, Enrique Sato Adan, Tais Hitomi Wakamatsu, Jun Shimazaki, Hiroshi Fujishima, Kazuo Tsubota
Journal: Ophthalmology (2012)
Immunogenetic and Clinical Characterization of Slowly Progressive IDDM
Authors: Tetsuro Kobayashi, Koji Tamemoto, Koji Nakanishi, Norihiro Kato, Minoru Okubo, Hiroshi Kajio, Tadao Sugimoto, Toshio Murase, Kinori Kosaka
Journal: Diabetes Care (1993)

OBJECTIVE To examine the clinical and immunogenetic heterogeneity of IDDM. RESEARCH DESIGN AND METHODS We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (&amp;lt;3 mo, acute clinical-onset group, n = 134), group B (3–12 mo, intermediate group, n = 31), and group C (&amp;gt;13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C. RESULTS The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C uhan in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were assocciated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQAl*0301-DQBl*0302, and DQA1 *0301-DQB 1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1* 0301-DQB 1*0401 were more common in this group than in control subjects. CONCLUSIONS These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved β-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe β-cell destruction in group A patients.
Pasteurella multocida Arthritis and Osteomyelitis
Authors: David B. Bell
Journal: JAMA (1969)

Six months after a cat bit his wrist, a patient with rheumatoid arthritis was found to have septic arthritis of the joint and osteomyelitis of the greater multangulum. Pasteurella multocida was cultured from the purulent joint fluid. The arthritis responded readily to penicillin G potassium therapy given parenterally, but curettage of the affected carpal bone was necessary to restore wrist function. Three of the six patients with P multocida arthritis had preexisting rheumatoid arthritis and were receiving antiinflammatory drugs.
An Integrative Meta-Analysis of MicroRNAs in Hepatocellular Carcinoma
Authors: Mahmoud ElHefnawi, Bangli Soliman, Nourhan Abu-Shahba, Marwa Amer
Journal: Genomics Proteomics & Bioinformatics (2013)

Abstract We aimed to shed new light on the roles of microRNAs (miRNAs) in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises: (1) the overlap of prediction results by four out of five target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB (combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives), (2) evidence from previous microarray analysis on the expression of these targets, (3) gene ontology (GO) and pathway enrichment analysis of the miRNA targets and their pathways and (4) linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are significantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFβ and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development. By analyzing their complete interactome, we proposed new categorization for some of these miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of these miRNAs may be addressed as therapeutic targets or used as therapeutic agents. Such dual roles thus expand the view of miRNAs as active maintainers of cellular homeostasis.
Angiotensin II Augments Cytokine-Stimulated Nitric Oxide Synthesis in Rat Cardiac Myocytes
Authors: Uichi Ikeda, Yoshikazu Maeda, Yasuhiro Kawahara, Mitsuhiro Yokoyama, Kazuyuki Shimada
Journal: Circulation (1995)

Background Nitric oxide (NO) has been shown to modulate cardiac function. We investigated the effect of angiotensin II (Ang II) on NO synthase activity in cardiac myocytes. Methods and Results Using the Griess reagent, we measured the production of nitrite, a stable metabolite of NO, by cultured neonatal rat cardiac myocytes. The expression of inducible NO synthase (iNOS) mRNA was assayed by Northern blotting. Incubation of cardiac myocytes for 24 hours with interleukin-1β (IL-1β) caused a significant increase in NO production. Ang II significantly augmented NO synthesis in IL-1β–stimulated but not in unstimulated cells in a dose-dependent manner. The angiotensin type I receptor antagonist CV 11974 inhibited the effect of Ang II dose-dependently. Simultaneous incubation of Ang II with N G -monomethyl- l -arginine or actinomycin D also completely inhibited the effect of Ang II. The Ang II–induced NO production by IL-1β–stimulated cells was accompanied by increased iNOS mRNA accumulation. Phorbol 12-myristate 13-acetate (PMA) also augmented NO synthesis in IL-1β–stimulated but not in unstimulated cells in a dose-dependent manner. The protein kinase C inhibitor calphostin C dose-dependently blocked the effect of Ang II. After protein kinase C activity was functionally depleted by treatment of cells with PMA for 24 hours, Ang II did not augment IL-1β–induced NO production. Conclusions These results indicate that Ang II upregulates IL-1β–induced iNOS expression in cardiac myocytes, which is mediated at least partially via activation of protein kinase C.
Analogy of Electronic Pacemaker and Ventricular Parasystole with Observations on Refractory Period, Supernormal Phase, and Synchronization
Authors: HOWARD B. BURCHELL
Journal: Circulation (1963)

The artificial pacemaker has been compared to a physiologic ventricular parasystolic focus. In hearts being driven by a pacemaker, in the absence of atrioventricular (AV) block, capture (interference) phenomena are constantly seen. While variations in QRS complexes have been observed when the external pacemaker stimulus occurs early in the T-wave period of a sinus conducted beat, no sequence of aberrant beats has been observed. One patient showed occasional sinus beats interpolated between ventricular beats arising from the artificial pacemaker, and these occurred at a very narrow time band suggesting that AV conduction was permitted by phenomenon of a supernormal phase. At a later date this patient showed also retrograde conduction believed related to a supernormal phase during recovery of junctional tissue penetrated by an impulse entering from above, though the impulse itself was blocked. Records of two patients are used to illustrate grossly aberrant QRS complexes produced by the stimulus of the electric pacemaker when this fell in the semirefractory period. Noteworthy was the presence of a latent period before potentials of the propagated impulse were recorded, there being evident stimulus-to-QRS delays. The situation wherein the rhythm is most chaotic is that where AV block is absent, the sinus rate is fast, and the electric pacemaker rate is relatively slow. In two patients, retrograde activation of the atria occurred as a stable mechanism. In one patient, nodal rhythm of the RP type occurred, and sequences of the records suggested that the AV node might have become synchronized with the extrinsic pacemaker cycle. In this last instance three independent centers of effective impulse formation coexisted, the sinus node, AV node, and stimulating electrodes of the electronic pacemaker. A marked increase in the refractory period of the ventricle, as measured by its response to the set stimulus of the electric pacemaker delivered at varying instants with respect to the sinus mechanism, occurred in one case within a few days. The possibility that reserpine therapy contributed to this change is possible but has not been established, for the effective refractory period, as measured, later remained constant over a period of many weeks.
Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation
Authors: Kristin Baudiß, Cemil Korcan Ayata, Zsofia Lazar, Sanja Cicko, Jessica Beckert, Anja Meyer, Andreas Zech, Rodolfo Paula Vieira, Robert Bittman, Antonio Gómez-Muñoz, Irmgard Merfort, Marco Idzko
Journal: European Respiratory Journal (2015)

Sphingolipids are involved in the pathogenesis of inflammatory diseases. The central molecule is ceramide, which can be converted into ceramide-1-phosphate (C1P). Although C1P can exert anti- and pro-inflammatory effects, its influence on cigarette smoke (CS)-induced lung inflammation is unknown. We aimed to clarify the role of C1P in the pathogenesis of CS-triggered pulmonary inflammation and emphysema in humans and mice. The effects of C1P were addressed on CS-induced lung inflammation in C57BL/6 mice, CS extract-triggered activation of human airway epithelial cells (AECs) and neutrophils from patients with chronic obstructive pulmonary disease. Differential cell counts in bronchoalveolar lavage fluid were determined by flow cytometry and pro-inflammatory cytokines were measured by ELISA. Expression and DNA binding of nuclear factor (NF)-κB and neutral sphingomyelinase (nSMase) were quantified by PCR, electrophoretic mobility shift and fluorometric assays. C1P reduced CS-induced acute and chronic lung inflammation and development of emphysema in mice, which was associated with a reduction in nSMase and NF-κB activity in the lungs. nSMase activity in human serum correlated negatively with forced expiratory volume in 1 s % predicted. In human AECs and neutrophils, C1P inhibited CS-induced activation of NF-κB and nSMase, and reduced pro-inflammatory cytokine release. Our results suggest that C1P is a potential target for anti-inflammatory treatment in CS-induced lung inflammation.
Book Review Obstetrics in the 1990s: Current Controversies (Clinics in Developmental Medicine. Nos. 123/124.) Edited by T. Chard and M.P.M. Richards. 249 pp. London, Mac Keith, 1992. $54.95. 0-521-41282-X (Distributed in the U.S. by Cambridge University Press, New York.)
Authors: Gregory L. Goyert
Journal: New England Journal of Medicine (1993)
Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.
Authors: G S Liu, J Thornton, D M Van Winkle, A W Stanley, R A Olsson, J M Downey
Journal: Circulation (1991)

BACKGROUND Preconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection. METHODS AND RESULTS We examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-isopropyl)adenosine, an A1-selective adenosine receptor agonist, at a dose that delayed conduction but did not dilate the coronary vessels, also limited infarct size. The protection disappeared when we reduced the coronary concentration of drug by intravenous infusion of adenosine, indicating that cardiac rather than peripheral receptors were involved in the protection. CONCLUSIONS We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.
Controlled Study of the Cytotoxic Food Test
Authors: Phil Lieberman
Journal: JAMA (1975)

The cytotoxic food test was not found to be an accurate method for diagnosing atopic reactions to foods. Claims that the test correlated with other untoward reactions to foods (eg, headache, diarrhea, fatigue) could not be corroborated. The test itself is time-consuming, dependent on subjective interpretation, and inconsistent in results when repetitive runs are performed on the same patient.
Seeing wood because of the trees? A case of failure in reverse-engineering
Authors: Philip J. Benson
Journal: Behavioral and Brain Sciences (1998)

Failure to take note of distinctive attributes in the distal stimulus leads to an inadequate proximal encoding. Representation of similarities in Chorus suffers in this regard. Distinctive qualities may require additional complex representation (e.g., reference to linguistic terms) in order to facilitate discrimination. Additional semantic information, which configures proximal attributes, permits accurate identification of true veridical stimuli.
Alcohol and the fetus in the west of Scotland
Authors: J T Wright, P J Toplis
Journal: BMJ (1983)

re-exploration after failed parathyroidectomy and unsuccessful venous sampling.We correctly located the parathyroid tissue in three of the four patients.The scans from the two most recent cases (figs 1 and 2) speak for themselves.Dr Corcoran and others should gain experience in the technique and perform a proper trial before dismissing it on the basis of preliminary results.They will need to provide data of sufficient quality to stand against the results
Effect of interval between neutron radiation and diethylstilbestrol on mammary carcinogenesis in female ACI rats.
Authors: C J Shellabarger, J P Stone, S Holtzman
Journal: Environmental Health Perspectives (1983)

Both radiation and diethylstilbestrol (DES) are carcinogens for the mammary gland of ACI female rats. When DES is given at about the same time as radiation, DES and radiation interact in a synergistic fashion particularly in regard to the number of mammary adenocarcinomas per rat. We have studied the effect of increasing the time interval between radiation and DES on the capacity of DES to enhance (promote?) radiation-induced mammary carcinogenesis. DES, in the form of a compressed pellet containing a mixture of cholesterol and DES, formulated to average 1.25 mg of DES/100 gr body weight, was given to groups of approximately 28 rats at 2 days before, or 50, 100 or 200 days after 0.064 Gy of 0.43 MeV neutron radiation. At each time that DES was given to irradiated rats, DES was also given to nonirradiated rats. All rats were studied for 375 days after the date of the DES administration. When the total number of mammary adenocarcinomas was calculated as a percentage of 24 sites per rat at-risk, DES and radiation always produced a response that was larger than the sum of the responses of DES alone plus radiation alone. This result suggests that these two agents can interact in a synergistic fashion. The interaction between radiation and DES did not decline as the time interval between radiation and DES was lengthened. This result suggests that radiation-induced (initiated?) mammary carcinogenesis is not subject to repair since DES enhancement (promotion?) continues to be effective over long time intervals.
Thoracic Bone Imaging After the Heimlich Maneuver
Authors: JEAN LETTE, ANDRE LEVASSEUR, CHANTAL LABONTE, MARIE-CLAIRE EYBALIN, MICHEL CERINO
Journal: Clinical Nuclear Medicine (1990)

LETTE, JEAN M.D., F.R.C.P.(C), F.A.C.P.; LEVASSEUR, ANDRE M.D.; LABONTE, CHANTAL M.D.; EYBALIN, MARIE-CLAIRE M.D.; CERINO, MICHEL M.D. Author Information
Peak Plantar Pressure and Shear Locations
Authors: Metin Yavuz, Ahmet Erdemir, Georgeanne Botek, Gordon B. Hirschman, Lynn Bardsley, Brian L. Davis
Journal: Diabetes Care (2007)

Diabetic foot ulcers burden the U.S. health care system with an annual cost of approximately $6 billion (1). Based on the mechanical etiology of diabetic foot lesions, investigators tried to establish a relationship between ulcer occurrence and plantar pressures. Mostly, peak pressure has been chosen as an ulcer predictor. However, previous studies have yielded only moderate correlations between peak pressure and the occurrence of diabetic foot lesions (2–4).

Surprisingly, in one study that examined whether plantar ulcer locations matched peak pressure sites (4), only 38% of the ulcers developed under the peak pressure area. Therefore, foot pressure was labeled as a “poor” predictor of diabetic ulcer occurrences and their location (3).

Effectiveness of diabetic ulcer prediction and prevention depends on an understanding of plantar soft tissue mechanics and the complete nature of foot-ground interactions. Further investigation of plantar shear in addition to pressure is essential to minimize the neuropathic ulcer prevalence.

The purpose of this study was to find whether the peak pressure and shear under the feet of diabetic patients occur at different locations. If confirmed, shear distribution may explain the deviation between peak pressure and ulcer locations and potentially help researchers design more effective interventions.

Thirty volunteers were recruited, among whom 10 had diabetic neuropathy. The remaining nondiabetic subjects served as control subjects. Subjects with gross foot deformities (except minor toe clawing), prior foot surgeries, and …