tbuckley/cabot-search huggingface dataset:
Prediction of Graft-Versus-Host Disease in Humans by Donor Gene-Expression Profiling
Authors: Chantal Baron, Roland Somogyi, Larry D Greller, Vincent Rineau, Peter Wilkinson, Carolyn R Cho, Mark J Cameron, David J Kelvin, Pierre Chagnon, Denis-Claude Roy, Lambert Busque, Rafick-Pierre Sékaly, Claude Perreault
Journal: PLoS Medicine (2007)

Background Graft-versus-host disease (GVHD) results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (AHCT). Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be "stronger alloresponders" than others, and consequently more likely to elicit GVHD. Methods and Findings To this end, we measured the gene-expression profiles of CD4+ and CD8+ T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the "dangerous donor" trait (occurrence of GVHD in the recipient) is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-β signaling and cell proliferation. Conclusions These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine.
Transforming Growth Factor β–induced Protein Promotes Severe Vascular Inflammatory Responses
Authors: Jong-Sup Bae, Wonhwa Lee, Ju-Ock Nam, Jung-Eun Kim, Shin-Woo Kim, In-San Kim
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Sepsis is a systemic inflammatory condition resulting from bacterial infections; it has a high mortality rate and limited therapeutic options. Despite extensive research into the mechanisms driving bacterial sepsis, the target molecules controlling vascular leakage are still largely unknown. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins.The aim of this study was to determine the roles of TGFBIp in vascular proinflammatory responses, and the mechanisms of action driving these responses.Circulating levels of TGFBIp were measured in patients admitted to the hospital with sepsis, severe sepsis, and septic shock and in cecal ligation and puncture (CLP)-induced septic mice. Effects of TGFBIp knockout on CLP-induced septic mortality and effects of TGFBIp on multiple vascular proinflammatory responses were determined.Circulating levels of TGFBIp were significantly elevated compared with healthy controls, and were strongly correlated with disease severity. High blood TGFBIp levels were also observed in CLP-induced septic mice. The absence of the TGFBIp gene in mice attenuated CLP-induced sepsis. TGFBIp enhanced vascular proinflammatory responses including vascular permeability, adhesion and migration of leukocytes, and disruption of adherence junctions through interacting with integrin αvβ5.Collectively, our findings demonstrate that the TGFBIp-αvβ5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.
Increased Body Lead Burden — Cause or Consequence of Chronic Renal Insufficiency?
Authors: Philip A. Marsden
Journal: New England Journal of Medicine (2003)

Greek physicians first recognized the association between exposure to lead and disease over two millennia ago. The sources of lead have changed since ancient times, but exposure is still largely preventable,1 which underscores the need for caregivers in modern industrialized societies to be especially vigilant for environmental sources of lead that can cause illness in persons at high risk. Although the level of environmental exposure to lead is decreasing, toxic effects of lead remain the most common environmental illness among children in the United States. The report by Lin and colleagues in this issue of the Journal 2 compels us to . . .
Yes‐associated protein regulation of adaptive liver enlargement and hepatocellular carcinoma development in mice
Authors: Marta A. Kowalik, Christian Saliba, Monica Pibiri, Andrea Perra, Giovanna M. Ledda-Columbano, Ivana Sarotto, Elena Ghiso, Silvia Giordano, Amedeo Columbano
Journal: Hepatology (2011)

The Hippo kinase cascade, a growth-suppressive pathway that ultimately antagonizes the transcriptional coactivator Yes-associated protein (YAP), has been shown in transgenic animals to orchestrate organ size regulation. The purpose of this study was to determine whether in non-genetically modified mice (1) the Hippo pathway is involved in the regulation of adaptive liver enlargement caused by the mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), an agonist of constitutive androstane receptor and (2) a dysregulation of this pathway occurs during the development of chemically induced hepatocellular carcinoma (HCC). We show that liver enlargement caused by TCPOBOP was associated with an increase of YAP protein levels that paralleled the increase in 2-bromodeoxyuridine incorporation. Interestingly, when a second dose of TCPOBOP was given to mice with enlarged livers, no further increases in liver mass or YAP protein levels were observed, suggesting that the Hippo pathway prevents further growth of the hyperplastic liver. Viral-mediated exogenous expression of active YAP in mouse livers was able to partially overcome the block of hepatocyte proliferation. We also show that HCCs developed in mice given diethylnitrosamine and then subjected to repeated treatments with TCPOBOP had increased levels of YAP that were associated with down-regulation of microRNA 375, which is known to control YAP expression, and with enhanced levels of alpha-fetoprotein and connective tissue growth factor, two target genes of YAP.These results suggest that the Hippo pathway regulates adaptive liver enlargement and is probably inactivated in initiated cells that escape the suppressive constrain exerted on the surrounding normal tissue, thus allowing clonal expansion to HCC.
Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction
Authors: S. Matthijs Boekholdt, Nick R. Bijsterveld, Arno H.M. Moons, Marcel Levi, Harry R. Büller, Ron J.G. Peters
Journal: Circulation (2001)

Background — It is pathophysiologically conceivable that genetic variations in coagulation and fibrinolytic proteins are associated with the risk of myocardial infarction. Methods and Results — We performed a literature search to identify published case-control studies correlating the factor V Leiden or prothrombin G20210A mutations or fibrinogen G−455A or plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphisms with the risk of myocardial infarction. Studies were included only if they used solid diagnostic criteria and complied with published methodological criteria. A common OR with corresponding 95% CI was calculated for the risk of myocardial infarction in a fixed-effect model according to Mantel-Haenszel. The factor V Leiden and prothrombin G20201A mutations did not significantly correlate with myocardial infarction (OR 1.26, 95% CI 0.94 to 1.67, P =0.12 and OR 0.89, 95% CI 0.59 to 1.35, P =0.6, respectively). Inclusion of the studies that investigated young patients (&lt;55 years) made the association significant for factor V Leiden (OR 1.29, 95% CI 1.03 to 1.61, P =0.02). Homozygosity for the fibrinogen −455A allele was significantly associated with a decreased risk of myocardial infarction (OR 0.66, 95% CI 0.44 to 0.99, P =0.04), whereas the PAI-1 4G4G genotype was significantly associated with increased risk (OR 1.20, 95% CI 1.04 to 1.39, P =0.04). Conclusions — Associations between these genetic variations and myocardial infarction were weak or absent. In the absence of clinical implications, our results indicate that screening of patients with myocardial infarction for these genetic variations is not warranted.
Clinical Considerations in the Surgical Management of Strokes
Authors: JESSE E. THOMPSON, MARK M. KARTCHNER, DALE J. AUSTIN, CLARENCE G. WHEELER, RALPH D. PATMAN
Journal: Circulation (1966)

Four hundred carotid endarterectomies were performed on 320 private patients with cerebrovascular insufficiency during an eight-year period. Patients are classified into four groups: frank stroke (135 patients), transient cerebral ischemia (151 patients), chronic cerebral ischemia (13 patients), and asymptomatic bruit (21 patients). Over-all operative procedure mortality was 3.5%. In frank strokes it was 7.4%; in transient ischemia, 1.02%; and in the other two groups was zero. As a safety factor during operation, the routine use of an inlying bypass shunt is advocated. Of 60 long-term deaths, six (10%) were due to strokes. Among frank stroke survivors, 42.8% are normal, and 48.4% are improved. One patient had a mild subsequent stroke. In transient ischemia survivors, 88.4% are normal, and 7% are improved. Three patients had strokes due to unoperated lesions. Surgery appears to have lowered the incidence of strokes in these groups. There were no strokes in the other two groups. Indications for and timing of operative procedures are suggested on the basis of the clinical results. Transient ischemia, chronic ischemia, and asymptomatic bruit patients may be operated upon electively unless an imminent total occlusion demands emergency operation. Acute and rapidly progressing strokes should not be operated upon as an emergency, but allowed to stabilize and be considered for surgery at a delayed time. The concept of total cerebral blood flow is discussed in relation to its therapeutic implications and the reversibility of neurological deficits. Carotid endarterectomy is a safe, definitive therapy in selected patients with cerebrovascular insufficiency.
Minimally invasive and robotic treatment of atrial fibrillation using microwave energy
Authors: Mathew R. Williams, Mauricio Garrido, Jennifer Casher, L. Wiley Nifong, Kimberly Klein, Deon W. Vigilance, Mehmet Oz, Yoshifumi Naka, W. Randolph Chitwood, Michael Argenziano
Journal: Journal of the American College of Cardiology (2003)
Death sentence against Sudanese doctor sparks widespread protest
Authors: P. Moszynski
Journal: BMJ (2014)

Outrage has been mounting worldwide over a death sentence imposed on a Sudanese doctor. 

Muslim-born Meriam Yehya Ibrahim, who is eight months pregnant, was last week convicted of apostasy for converting to Christianity and sentenced to death by hanging after she refused to recant her faith. The Khartoum court also annulled her marriage—to South Sudanese born Daniel Wani, a US citizen—and sentenced her to 100 lashes for adultery, because Sudanese law forbids Muslim women …
Stories of Illness and Healing: Women Write Their Bodies
Authors: Delese Wear
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Interpretation of lung function tests in the sickle-cell haemoglobinopathies.
Authors: G J Miller, G R Serjeant, M J Saunders, C Richardson, R J Gilson
Journal: Thorax (1978)

Prediction equations have been evolved for the assessment of vital capacity, total lung capacity, and the single breath carbon monoxide transfer factor in haemoglobin SS and haemoglobin SC disease. These relationships take account of the growth disorder and anaemia in the sickle-cell states. The results suggest that, in the clinically stable state, any effects of alveolar capillary sickling and haemoconcentration and any altered reactivity of haemoglobins S and C with the test gas are of no significance for clinical respiratory physiology. Sex differences in lung function appear independent of haemoglobin type.
Teaching Problem-Oriented Therapy
Authors: C. Ringer, A. Blaser, M. Thommen, E. Heim
Journal: Psychotherapy and Psychosomatics (1990)

The therapeutic concept is problem- and patient-oriented. In analogy to it the didactic concept is problem- and therapist-oriented. The essential point is learning in groups from practical cases. Problem-oriented in this context means that the problem-solving process in which the patient and the therapist are engaged is supported by the observer group. Therapist-oriented means that the learning process should take account of the different preferences and experiences of the therapists. That can only be accomplished by problem-oriented learning. Each psychotherapy training group consists of 4 assistant doctors and a supervisor and stays together about 1 year. The strongly structured concept of problem-oriented therapy (POT) [Blaser et al., 1988] offers the beginner a framework by which he can guide the dialogue with the patient. The eclecticism of POT allows the more experienced therapist to try out new methods without losing track of the problem. The constantly changing role of being observer or therapist supports the group coherence, and furthermore it promotes an important element of therapeutic competence, the ability to get into a close relation with the patient and at the same time being able to observe oneself, the patient and the therapeutic process from a more distant view. In addition to the POT training group tutorials in special psychotherapy methods and single supervision sessions are offered.
Abstract LB-2: Structure-based design of G-quadruplex ligands leads to enhanced potency against pancreatic cancer cells
Authors: Marialuisa Micco, Gavin Collie, Mekala Gunaratnam, Stephen A. Ohnmacht, Anthony P. Reszka, Stephen Neidle
Journal: Cancer Research (2012)

Abstract Certain small molecules can sequester the single-stranded overhang of human telomeric DNA into higher-order quadruplex structures. Such quadruplex-ligand complexes interfere with telomerase activity and inhibit its ability to maintain telomere integrity in many cancer cell types. This approach to selectivity interfering with cancer cell viability has been demonstrated for several classes of quadruplex-binding molecules in cells and in xenograft experiments. We have previously described a series of tetra-substituted naphthalene diimide (ND) compounds with high affinity for human telomeric quadruplex DNA. These also have high potency for growth inhibition in a panel of cancer cell lines, concomitant with telomerase inhibition. Those compounds with N-methyl-piperazine (NMP) end-groups have shown exceptional potency in a pancreatic cancer cell line panel, with the lead compound having typical IC50 values of 100-200 nM. It has significant anti-tumor activity in a pancreatic cancer xenograft model, with a 50% reduction in tumor volume on ip administration, along with inhibition of telomerase activity. We report here a structure-based design study in which the four positive charges of the tetra-NMP compound have been modulated by substituting NMP groups on two of the four side-arms of the ND core with more weakly basic groups, in order to improve drug-like features. A diminution in the highly cationic nature of these ND compounds may improve cellular uptake and tumor distribution properties, while retaining quadruplex affinity. The morpholine group has been used because it is less basic than the NMP group. We hypothesized that the presence of four NMP groups is non-essential in order to retain effective quadruplex binding, since the morpholine group is of equivalent size and so could be bound in the same way. Three co-crystals structures of NMP and morpholino-containing ND compounds with a human telomeric quadruplex have been determined. These show that the morpholino group binds in quadruplex grooves in a closely-similar manner to the NMP group and has the same hydrogen-bonding. Accordingly, several hybrid morpholino-NMP ND compounds have been synthesized and shown high quadruplex affinity, exceptional potency in selectively inhibiting growth in pancreatic cancer cell lines, with IC50 values of &amp;lt;10 nM, together with potent telomerase inhibition in these cells. Lead compounds from this study are currently being taken into further in vivo evaluation, with a view to identifying a compound suitable for pre-clinical development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-2. doi:1538-7445.AM2012-LB-2
The molecular mechanisms of arsenic-induced cell transformation and apoptosis.
Authors: Zigang Dong
Journal: Environmental Health Perspectives (2002)

Arsenic is a well-documented human carcinogen associated with cancers of the skin, lung, liver, and bladder. Interestingly, arsenic has also been used as an effective chemotherapeutic agent in the treatment of certain human cancers. However, the mechanisms by which arsenic induces proliferation of cancer cells or cancer cell death are not well understood. We found that exposure of JB6 P+ cells to low concentrations of arsenic induces cell transformation, whereas higher concentrations of arsenic induce cell apoptosis. Arsenite induces phosphorylation of extracellular signal-regulated protein kinases (Erks) and c-Jun NH(2)-terminal kinases (JNKs). Arsenite-induced Erk activation was markedly inhibited by introduction of dominant-negative Erk2 into cells, whereas expression of dominant-negative Erk2 did not inhibit JNKs or mitogen-activated protein kinase Erk kinase 1/2. Furthermore, arsenite-induced cell transformation was blocked in cells expressing dominant-negative Erk2. In contrast, overexpression of dominant-negative JNK1 increased cell transformation even though it inhibited arsenite-induced JNK activation. Arsenic also induced AP-1 and nuclear factor kappa B (NF-kappaB) activation. Blocking NF-kappaB activation by dominant-negative inhibitory kappa Balpha inhibited arsenic-induced apoptosis and enhanced arsenic-induced cell transformation. Arsenic induced activation of JNKs at a similar dose range that was effective for induction of apoptosis in JB6 cells. In addition, we found that arsenic did not induce p53-dependent transactivation. Similarly, apoptosis induction was not different between p53 wild-type (p53(+/+)) or p53-deficient (p53(-/-)) cells. In contrast, arsenic-induced apoptosis was almost totally blocked by expression of a dominant-negative mutant of JNK. Taken together with previous findings that p53 mutations are involved in approximately 50% of all human cancers and nearly all chemotherapeutic agents kill cancer cells mainly by apoptotic induction, we suggest that arsenic may be a useful agent for the treatment of cancers with p53 mutations. These results suggest that the activation of Erks is required for arsenic-induced cell transformation, whereas the activation of JNKs and NF-kappaB is involved in arsenic-induced apoptosis of JB6 cells.
Lithotripsy of an impacted calcified stone in the cystic duct accompanied by cholecystitis in severe Crohn's disease.
Authors: U Stolzel, C Koszka, M Gregor, K Ziegler, T Zimmer, E O Riecken
Journal: Gut (1993)

A 35 year old women patient with Crohn9s disease and previous multiple abdominal operations presented with a calcified stone of 12 mm diameter in the cystic duct giving rise to cholecystitis. The surgeons declined to operate because of extensive intra-abdominal adhesions caused by multiple intestinal resections and chronic enterocutaneous fistulas. It was possible to fragment the stone in three lithotripsy sessions. The fragments were excreted spontaneously through the ductus choledochus and the cholecystitis was cured by antibiotic treatment. The patient remained symptom free after 12 months.
Timely Addition of Insulin to Oral Therapy for Type 2 Diabetes
Authors: Matthew C. Riddle
Journal: Diabetes Care (2002)

The U.K. Prospective Diabetes Study (UKPDS) has shaped our view of the management of type 2 diabetes more than any other trial. It proved that glycemic control limits retinopathy (and probably other microvascular complications) as much for type 2 diabetic patients as had previously been shown for type 1 diabetic patients (1). It defined the progressive natural history of type 2 diabetes, with declining β-cell function over time and a need for progressively more active treatment to maintain glycemic control (2). In addition, it has offered important insights into the effects of several forms of treatment.

For example, newly diagnosed patients entering the UKPDS who did not need immediate insulin therapy received intensive dietary therapy, but only 15% of them were able to reach target levels of glycemic control (fasting blood glucose ≤108 mg/dl) after 3 months, and the results were even worse after a year (3). This disappointing result indicates that lifestyle intervention alone will only occasionally be successful for patients presenting with overt diabetes. The UKPDS also reassured us that insulin and sulfonylureas do not increase cardiovascular mortality, as had been feared. It showed that glyburide caused more hypoglycemia than chlorpropamide and glipizide (1) and that metformin (4) was the one drug used that did not cause weight gain compared with therapy based on lifestyle. These insights have helped us deploy these treatments more effectively.

One of the main conclusions the UKPDS investigators themselves have drawn from their findings is that combinations of treatments will routinely be needed for type 2 diabetes (5). In this issue of Diabetes Care , they report the results of a …