tbuckley/cabot-search huggingface dataset:
Sulforaphane Causes Autophagy to Inhibit Release of Cytochrome <i>c</i> and Apoptosis in Human Prostate Cancer Cells
Authors: Anna Herman-Antosiewicz, Daniel E. Johnson, Shivendra V. Singh
Journal: Cancer Research (2006)

The present study reports a novel response to sulforaphane, a highly promising anticancer constituent of several edible cruciferous vegetables, in PC-3 and LNCaP human prostate cancer cells involving induction of autophagy. Exposure of PC-3 and LNCaP cells to sulforaphane resulted in several specific features characteristic of autophagy, including appearance of membranous vacuoles in the cytoplasm as revealed by transmission electron microscopy and formation of acidic vesicular organelles as revealed by fluorescence microscopy following staining with the lysosomotropic agent acridine orange. The sulforaphane-induced autophagy was associated with up-regulation, processing, and recruitment to autophagosomes of microtubule-associated protein 1 light chain 3 (LC3), which is a mammalian homologue of the yeast autophagy regulating protein Apg8/Aut7p. Treatment of cells with a specific inhibitor of autophagy (3-methyladenine) attenuated localization of LC3 to autophagosomes but exacerbated cytosolic release of cytochrome c as well as apoptotic cell death as revealed by analysis of subdiploid fraction and cytoplasmic histone-associated DNA fragmentation. In conclusion, the present study indicates that induction of autophagy represents a defense mechanism against sulforaphane-induced apoptosis in human prostate cancer cells. To the best of our knowledge, the present study is the first published report to convincingly document induction of autophagy by an isothiocyanate class of dietary chemopreventive agent.
Outcome of attempts to treat rheumatoid arthritis with gold, penicillamine, sulphasalazine, or dapsone.
Authors: K A Grindulis, B McConkey
Journal: Annals of the Rheumatic Diseases (1984)

The outcome of attempts to continue treatment indefinitely with either gold, penicillamine, sulphasalazine, or dapsone was studied in 240 patients with rheumatoid arthritis (RA). The usual reason for discontinuing treatment was the occurrence of an adverse effect. This led to 53% of patients stopping gold, 33% sulphasalazine, 32% penicillamine, and 17% dapsone. The next most frequent reason was that the drug was ineffective, leading to discontinuation in 37% of patients having dapsone, 24% sulphasalazine, 19% penicillamine, and 16% gold. Other reasons for stopping treatment were infrequent. The high discontinuation rate of these drugs over 2 years in part accounts for the conflict of opinion on whether they can alter the course of RA; their efficacy must to a large extent be governed by their acceptability.
BCA-1 is highly expressed in Helicobacter pylori–induced mucosa-associated lymphoid tissue and gastric lymphoma
Authors: Luca Mazzucchelli, Andrea Blaser, Andreas Kappeler, Patrik Schärli, Jean A. Laissue, Marco Baggiolini, Mariagrazia Uguccioni
Journal: Journal of Clinical Investigation (1999)

Infection with Helicobacter pylori (Hp) induces the formation of lymphoid tissue in the stomach and the occasional development of primary gastric B-cell lymphomas. We have studied the expression of 2 chemokines that attract B lymphocytes, BCA-1 and SLC, in gastric tissue samples obtained from patients with chronic gastritis induced by Hp infection or nonsteroidal anti-inflammatory drugs, as well as from patients with Hp-associated low-grade and high-grade gastric lymphomas. High-level expression of BCA-1 and its receptor, CXCR5, was observed in all mucosal lymphoid aggregates and in the mantle zone of all secondary lymphoid follicles in Hp-induced gastric mucosa-associated lymphoid tissue (MALT). Follicular dendritic cells and B lymphocytes are possible sources of BCA-1, which is not expressed by T lymphocytes, macrophages, or CD1a+ dendritic cells. Strong expression of BCA-1 and CXCR5 was also detected in the transformed B cells of gastric MALT lymphomas. By contrast, SLC was confined almost exclusively to endothelial cells in and outside the lymphoid tissue. Only scant, occasional SLC expression was observed in the marginal zone of MALT follicles. Our findings indicate that BCA-1, which functions as a homing chemokine in normal lymphoid tissue, is induced in chronic Hp gastritis and is involved in the formation of lymphoid follicles and gastric lymphomas of the MALT type.
The detection of cell-bound antibody on complement-coated human red cells
Authors: Bruce C. Gilliland, John P. Leddy, John H. Vaughan
Journal: Journal of Clinical Investigation (1970)

This study sought to elucidate the mechanism by which human red cells, in a variety of clinical settings, become coated in vivo with autologous complement components in the absence of anti-red cell autoantibodies demonstrable by standard methods. By means of a newly developed complement-fixing antibody consumption test, previously undetectable red cell-bound gammaG globulin could be detected and quantified. By this technique, the complement-coated red cells of 13 of 16 patients were shown to carry abnormally high numbers of gammaG molecules per cell, which were nevertheless below the level for detection by the direct antiglobulin test. Eluates were made from the red cells of seven of these patients and each eluate, when sufficiently concentrated, was capable of sensitizing normal human red cells (with gammaG antibodies) to give a positive indirect antiglobulin test with anti-gammaG serum. In the presence of fresh normal serum, six of the eluates so tested were capable of fixing complement to normal human red cells. The antibodies in the red cell eluates did not exhibit Rh specificity and did not react with nonprimate red cells. When studied by sucrose gradient ultracentrifugation, the gammaG antibodies to human red cells in these eluates sedimented in the 7S region. It is concluded that in many patients in whom direct antiglobulin tests reveal only cell-bound complement, the complement fixation is mediated in vivo by small quantities of "warm-reacting" erythrocyte autoantibodies of the gammaG class.
Strategies for Safer Liver Surgery and Partial Liver Transplantation
Authors: Pierre-Alain Clavien, Henrik Petrowsky, Michelle L DeOliveira, Rolf Graf
Journal: New England Journal of Medicine (2007)

The liver possesses the unique ability to regenerate within a short period of time, a feature that has led to the development of innovative strategies in liver surgery and transplantation. This review presents both established and novel methods for manipulating liver volume to attain improved liver surgery and transplantation.
Image-Guided Breast Tumor Therapy Using a Small Interfering RNA Nanodrug
Authors: Mohanraja Kumar, Mehmet Yigit, Guangping Dai, Anna Moore, Zdravka Medarova
Journal: Cancer Research (2010)

Iron oxide nanoparticles offer a feasible tool for combined imaging and delivery of small interfering RNA (siRNA) to tumors, stimulating active interest in exploring different imaging and delivery platforms suitable for detection by a variety of modalities. In this study, we describe the synthesis and testing of a tumor-targeted nanodrug (MN-EPPT-siBIRC5) that is designed to specifically shuttle siRNA to human breast tumors. The nanodrug binds the tumor-specific antigen uMUC-1, which is found in >90% of human breast adenocarcinomas. MN-EPPT-siBIRC5 consists of superparamagnetic iron oxide nanoparticles [for magnetic resonance imaging (MRI)], the dye Cy 5.5 (for near-IR optical imaging), peptides (EPPT) that specifically target uMUC-1, and a synthetic siRNA that targets the tumor-specific antiapoptotic gene BIRC5. Nanodrug uptake by human breast adenocarcinoma cells resulted in a significant downregulation of BIRC5. Following i.v. delivery into subcutaneous mouse models of breast cancer, the nanodrug showed a preferential tumor uptake, which could be visualized by MRI and near-IR optical imaging. Furthermore, MRI could be used to quantitatively monitor nanodrug bioavailability in the tumor tissue throughout the course of treatment. Intravenous injection of the agent once a week over 2 weeks resulted in the induction of considerable levels of necrosis and apoptosis in the tumors, translating into a significant decrease in tumor growth rate. Our strategy permits the simultaneous tumor-specific delivery of siRNA to tumors and the imaging of the delivery process. More generally, it illustrates the potential to apply this approach to many human cancer studies, including for basic tumor biology and therapy.
Stratifying Patients at Risk of Diabetic Complications: An integrated look at clinical, socioeconomic, and care-related factors
Authors: Antonio Nicolucci, Fabrizio Carinci, Antonio Ciampi
Journal: Diabetes Care (1998)

OBJECTIVE The aim of this study was to identify subgroups of patients for whom the interactions among clinical, socioeconomic, and care-related factors determine a substantial increase in the risk of developing long-term diabetic complications. RESEARCH DESIGN AND METHODS We performed a case-control study aimed at identifying and quantifying the risk factors for the development of major diabetic complications (eye, renal, and lower limb complications) in type 1 and type 2 diabetic patients. A total of 886 patients with renal, eye, or lower limb complications and 1,888 control subjects were enrolled in 35 diabetes outpatient clinics and 49 general practitioners' offices in 17 out of the 20 Italian regions. The main results were obtained using recursive partitioning and amalgamation (RECPAM), a technique that attempts to integrate the advantages of main effect logistic regression and tree-growing. RESULTS The application of RECPAM led to the detection of important interactions involving clinical, socioeconomic, and care-related characteristics and allowed the identification of internally homogeneous subgroups characterized by a marked difference in the risk of developing major complications. In type 1 diabetic patients, the interaction between hypertension and smoking habits led to a dramatic increase in the complication risk, while in type 2 diabetic subjects, a poor compliance with visit scheduling was the most important predictor of complications. Furthermore, a marked difference in the risk profile was associated with patient characteristics (age, years of education, occupation). CONCLUSIONS In the definition of the risk profile for each individual patient, socioeconomic status and level of education need to be taken under serious consideration, since they can determine a complication risk not dissimilar from hard clinical variables, such as hypertension and diabetes duration. Specific educational interventions, targeted to the socially disadvantaged strata of the population, need to be designed and implemented.
Arthritis patients get long-term help from total lymphoid irradiation
Authors: Milan Korcok
Journal: JAMA (1983)

Total lymphoid irradiation (TLI)—a technique developed at Stanford University Medical Center, California, originally for treatment of stage III Hodgkin's disease—is yielding such "encouraging" results in patients with intractable rheumatoid arthritis that its application to a broader range of autoimmune diseases and organ transplantation is now being investigated. In a keynote address at the recent meeting of the American Society of Therapeutic Radiologists (ASTR) in Orlando, Fla, Henry S. Kaplan, MD, director of the Cancer Biology Research Laboratory at Stanford, said that although use of TLI for autoimmune disease is still very much investigational, it would appear, "based on our limited experience so far, that this will become a new treatment for patients with very far advanced and crippling autoimmune disease." Still, he emphasized the experimental nature of this work, telling the audience: "We would be quite alarmed if there were any widespread move to adopt this as a treatment for
Human Alveolar Wall Fibroblasts Directly Link Epithelial Type 2 Cells to Capillary Endothelium
Authors: Faye E. Sirianni, Fanny S. F. Chu, David C. Walker
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Alveolar wall fibroblasts directly link type 2 (T2) pneumocytes to capillary endothelium through apertures in their respective basal laminae in rabbit lung. These fibroblasts provide a bridge from the capillary to the airway lumen along which leukocytes may migrate without disrupting extracellular matrix. Normal human lungs were examined by transmission electron microscopy and serial section 3D reconstruction. We found contacts between fibroblasts and T2 pneumocytes and between fibroblasts and type 1 pneumocytes that occur at holes in the epithelial basal lamina. The same fibroblast also made contact with pericytes and endothelial cells through similar apertures. A survey of 41 T2 pneumocytes revealed that 54% of T2 pneumocytes had at least one gap in their basal lamina. A morphometric analysis showed these gaps occupied approximately 5.58 +/- 1.51% (mean +/- SE) of the area underneath T2 pneumocytes. We conclude that a population of single fibroblasts link T2 pneumocytes to adjacent capillary endothelial cells in alveolar walls of human lung. We propose that fibroblasts are organized to maintain communication between epithelium and mesenchyme and to provide directional information to migrating leukocytes.
Neck Circumference, Carotid Wall Intima-Media Thickness, and Incident Stroke
Authors: Klara J. Rosenquist, Joseph M. Massaro, Karol M. Pencina, Ralph B. D’Agostino, Alexa Beiser, George T. O’Connor, Christopher J. O’Donnell, Philip A. Wolf, Joseph F. Polak, Sudha Seshadri, Caroline S. Fox
Journal: Diabetes Care (2013)

Locally acting fat depots may contribute to obesity complications, in particular vascular disease, through direct paracrine effects (1,2). The carotid arteries are encased in fat, and total upper-body subcutaneous fat is estimated by neck circumference (NC). NC has been independently correlated with cardiometabolic risk factors above and beyond that of other adiposity measures (3,4). Carotid wall intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and has been associated with cardiovascular and stroke outcomes (5). The aim of this study was to evaluate the association of NC and carotid wall IMT above and beyond traditional cardiovascular risk factors and generalized adiposity.

Framingham Heart Study offspring participants who underwent carotid ultrasonography and NC measurements were included ( n = 3,274; mean age 59 years; 52% women); NC, internal carotid artery (ICA) IMT, and common carotid artery (CCA) IMT were determined as previously described (4,5). Linear regression models evaluated the association between adiposity exposures and IMT. NC, BMI, and …
Deficiency of active natural killer cells in the Chediak-Higashi syndrome. Localization of the defect using a single cell cytotoxicity assay.
Authors: P Katz, A M Zaytoun, A S Fauci
Journal: Journal of Clinical Investigation (1982)

This study investigated the defective natural killer (NK) cell activity in two patients with the Chediak-Higashi syndrome (CHS) using both a standard 51-chromium release microcytoxicity and a single cell-in-agarose assay against K562 and Molt-4 target cells. CHS patients were deficient in overall maximum NK capacity, but had normal percentages of potentially cytotoxic target bindng cells. the relative number of TBC that could kill bound targets (i.e., "active" NK cells) was significantly depressed in CHS patients when compared with normal controls. The diminished CHS active NK cells that were present, however, were capable of recycling and lysing multiple target cells during the assay period. In vitro interferon (INF) treatment of normal and CHS effector cells did not alter target cell binding, but did increase the maximum NK capacity, percentage of active NK cells and the maximum recycling capacity, as well as the rate of lysis. These studies indicate that the depression of NK activity in patients with CHS is secondary to a deficiency of active NK cells. The CHS active NK cells that are present, however, are capable of normal target lysis and recycling. Potentially cytotoxic pre-NK cells, which can bind but not kill target cells, can be activated by in vitro IFN to develop lytic activity. Thus, IFN treatment may be of potential benefit to the immune surveillance network of CHS patients by activating a population of pre-NK cells to express their cytotoxic potential.
So Long, Coffee Shop
Authors: Richard L. Cohen
Journal: JAMA (1989)

At first, watching new grandparents in the Women's Hospital coffee shop is diverting and fills some of my idle time. I can spot them from across the room. They talk incessantly and seem to be the only people smiling. They discuss matters such as "Should we get the bed jacket or the plant?" In the end, they often buy both. Sometimes there are as many as a dozen of them, chattering to anyone who will listen about this miracle in their lives. I belong to a different group of coffee shop regulars... silent, coffee-sipping men whose wives are patients on one of the oncology units. We look like dark silhouettes against the bright backdrop of grandparents. Although we men rarely speak, each of us seems to know who the others are. It is obvious that these men are not good at networking or forming support groups when they are suffering.
CD133+ Melanoma Subpopulations Contribute to Perivascular Niche Morphogenesis and Tumorigenicity through Vasculogenic Mimicry
Authors: Chiou-Yan Lai, Brian E. Schwartz, Mei-Yu Hsu
Journal: Cancer Research (2012)

Tumor cell subpopulations that express cancer stem cell markers such as CD133 (prominin1) or ABCB5 are thought to be crucial for tumor initiation and heterogeneity, but their biological significance in melanoma has been controversial. Here, we report that CD133(+) and ABCB5(+) subpopulations are colocalized in melanomas in perivascular niches that contain CD144 (VE-cadherin)(+) melanoma cells forming vessel-like channels, a phenomenon termed vasculogenic mimicry (VM). RNAi-mediated attenuation of CD133 established its critical function in morphogenesis of these perivascular niches as well as in melanoma tumorigenicity. Niche-associated genes CD144 and ABCB5 were downregulated in tumors derived from CD133 knockdown (KD) melanoma cells compared with controls. CD133KD cells also lacked the ability to form CD144(+) VM-like channels in a manner that was associated with a depletion of the ABCB5(+) cell subpopulation. Finally, CD133 KD cells exhibited poorer tumor growth in vivo. Taken together, our findings corroborate models in which CD133(+)/ABCB5(+) melanoma cells reside in a complex anastomosing microvascular niche that encompasses CD144(+) VM channels as well as authentic endothelial cell-lined blood vessels. Further, they indicate that CD133(+) cells act as stem-like cells, which drive tumor growth by promoting VM and the morphogenesis of a specialized perivascular niche in melanoma.
Enoximone Echocardiography for Predicting Recovery of Left Ventricular Dysfunction After Revascularization
Authors: Chunzeng Lu, Mauro Carlino, Gabriele Fragasso, Francesco Maisano, Alberto Margonato, Alberto Cappelletti, Sergio L. Chierchia
Journal: Circulation (2000)

The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated.Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine.Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.
1118-81 The impact of abciximab on final infarct size and left ventricular function of patients with acute myocardial infarction undergoing primary stenting: Insights from the abcizimab and carbostent evaluation (ACE) trial
Authors: Guido Parodi, Angela Migliorini, Roberto Sciagrà, Gentian Memisha, Renato Valenti, David Antoniucci
Journal: Journal of the American College of Cardiology (2004)
A case of Lassa fever: experience at St Thomas's Hospital.
Authors: C B Cooper, W R Gransden, M Webster, M King, M O'Mahony, S Young, J E Banatvala
Journal: BMJ (1982)

An 18-year-old Nigerian girl, normally resident in Jos, was admitted to hospital for five days before she was diagnosed as having Lassa fever. There were several atypical features in the early stages of here illness, notably the absence of prostration, pharyngitis, or bradycardia and the development of appreciable leucocytosis. Consequent control and surveillance measures required checks for 21 days on 173 people who had had contact with as first line if they had handled her or specimens without taking precautions to avoid direct skin contact with her excretions, secretions, and blood; other contacts were categorised as second line. During her time in hospital she was managed in a single room on a general ward. She visited a number of investigative departments within the hospital, and her specimens were examined in five clinical laboratories. Despite this no secondary cases occurred among either first- or second-line contacts, and there was no serological evidence of subclinical infection among any of the contacts tested (159 people).
Practice, practice, practice
Authors: Douglas Kamerow
Journal: BMJ (2007)

This week's Practice section has a trio of interesting and useful articles.

Giuseppe Lauria and Raffaella Lombardi review recent advances in the use of skin biopsy to diagnose and monitor peripheral neuropathy (doi: 10.1136/bmj.39192.488125.BE). An easy to perform 3 mm punch biopsy can make the diagnosis of small nerve fiber neuropathies, which can be associated with diabetes and other metabolic disorders, sarcoidosis and …
Nitric Oxide Inhalation Improves Microvascular Flow and Decreases Infarction Size After Myocardial Ischemia and Reperfusion
Authors: Xiaoshun Liu, Yanming Huang, Peter Pokreisz, Pieter Vermeersch, Glenn Marsboom, Marc Swinnen, Eric Verbeken, Jose Santos, Marijke Pellens, Hilde Gillijns, Frans Van de Werf, Kenneth D. Bloch, Stefan Janssens
Journal: Journal of the American College of Cardiology (2007)