tbuckley/cabot-search huggingface dataset:
Oral allergy syndrome (OAS) in pollinosis patients after eating pistachio nuts: Two cases with two different patterns of onset
Authors: G. Liccardi, G. Mistrello, P. Noschese, P. Falagiani, M. D'Amato, G. D'Amato
Journal: Allergy (1996)

We describe two uncommon cases of oral allergy syndrome (OAS) after eating pistachio nuts (p.n.) in subjects (a 54‐year‐old man and a 3‐year‐old girl) with exclusive skin prick test (SPT) positivity to Parietaria (P .) and pistachio nut (p.n.) allergens. Serologic P.‐ and p.n.‐specific IgE determinations were also carried out. A double‐blind, placebo‐controlled food challenge (DBPCFC) was performed, for ethical reasons, only in the adult patient, but we observed a positive intraoral reaction only after slight scratching of the oral mucosa. Since this patient had put three whole p.n. with their shells into his mouth, breaking them with his teeth, before the onset of symptoms, we suggest that slight injury of the oral mucosa may enhance the local response. Preliminary results with SDS‐PAGE and immunoblotting demonstrate the occurrence of a slight degree of cross‐reactivity between these allergens, hut further studies are necessary to obtain a definite conclusion.
Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma
Authors: P S Thomas
Journal: Thorax (2002)

Inhaled tumour necrosis factor alpha (TNF alpha) has previously been shown to induce airway neutrophilia and increased airway reactivity in normal subjects. It was hypothesised that a similar challenge would increase airway reactivity in those with mild asthma, but that the inflammatory profile may differ.Ten mild asthmatic subjects were recruited on the basis of clinical asthma and either a sensitivity to methacholine within the range defined for asthma or a 20% improvement in forced expiratory volume (FEV(1)) after 200 micro g salbutamol. Subjects inhaled either vehicle control or 60 ng recombinant human (rh)TNF alpha and were studied at baseline, 6, 24, and 48 hours later. Variables included spirometric parameters, methacholine provocative concentration causing a 20% fall in FEV(1) (PC(20)), induced sputum differential cell count, relative sputum level of mRNA of interleukins (IL)-4, IL-5, IL-9, IL-14, IL-15 and TNF alpha, and the exhaled gaseous markers of inflammation, nitric oxide and carbon monoxide.PC(20) showed an increase in sensitivity after TNF alpha compared with control (p<0.01). The mean percentage of neutrophils increased at 24-48 hours (24 hour control: 1.1 (95% CI 0.4 to 2.7) v 9.2 (95% CI 3.5 to 14.9), p<0.05), and there was also a rise in eosinophils (p=0.05). Relative levels of sputum mRNA suggested a rise in expression of TNF alpha, IL-14, and IL-15, but no change in IL-4 and IL-5. Spirometric parameters and exhaled gases showed no significant change.The increase in airway responsiveness and sputum inflammatory cell influx in response to rhTNF alpha indicates that TNF alpha may contribute to the airway inflammation that characterises asthma.
Mnk1 is a novel acinar cell-specific kinase required for exocrine pancreatic secretion and response to pancreatitis in mice
Authors: Jaroslaw Cendrowski, Víctor J Sánchez-Arévalo Lobo, Matthias Sendler, Antonio Salas, Jens-Peter Kühn, Xavier Molero, Rikiro Fukunaga, Julia Mayerle, Markus M Lerch, Francisco X Real
Journal: Gut (2014)

<h3>Objective</h3> Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription factor 1 (PTF1) complex. Induction of pancreatitis leads to MAP kinase activation and transient suppression of the acinar differentiation programme. We investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. <h3>Design</h3> Mnk1 expression was analysed using immunohistochemistry, RT-qPCR and western blotting. Ptf1a binding to <i>Mnk1</i> was assessed by chromatin immunoprecipitation and qPCR. Acute pancreatitis was induced in wild type and <i>Mnk1<sup>−/−</sup></i> mice by 7 h intraperitoneal injections of caerulein. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. In vivo secretion was quantified by secretin-stimulated MRI. <h3>Results</h3> Mnk1 is expressed at the highest levels in pancreatic acinar cells and is a direct PTF1 target. Mnk1 is activated upon induction of pancreatitis and is indispensable for eIF4E phosphorylation. The pancreas of <i>Mnk1<sup>−/−</sup></i> mice is histologically normal. Digestive enzyme content is significantly increased and c-Myc and Ccnd1 levels are reduced in <i>Mnk1<sup>−/−</sup></i> mice. Upon induction of acute pancreatitis, <i>Mnk1<sup>−/−</sup></i> mice show impaired eIF4E phosphorylation, activation of c-Myc and downregulation of zymogen content. Acinar cells show defective relocalisation of digestive enzymes, polarity defects and impaired secretory response in vitro and in vivo. <h3>Conclusions</h3> Mnk1 is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and eIF4E phosphorylation. It is required for the physiological secretory response of acinar cells and for the homeostatic response to caerulein administration during acute pancreatitis.
Observations on the Role of Diminished Oxygen Tension in the Functional Hyperemia of Skeletal Muscle
Authors: JOHN ROSS, GERARD A. KAISER, FRANCIS J. KLOCKE
Journal: Circulation Research (1964)

The hypothesis that lowered tissue oxygen tension acting on vascular smooth muscle can explain functional hyperemia in skeletal muscle was examined in ten dogs. A comparison was made between the blood flow increment that accompanied rapid, rhythmic contraction of a gastrocnemius muscle and the flow change that occurred in the same muscle at rest during its perfusion with venous blood obtained from the resting or contracting gastrocnemius muscle of the opposite leg. Blood P O O2 , pH, and P CO CO2 were measured in samples of venous blood from the muscle. There was no evidence that the perfusion circuit traumatized the perfused blood. During functional hyperemia, the increases in blood flow averaged 173%, and the average venous P O O2 , was 25 mm Hg. During venous perfusion, the maximum increases in blood flow averaged 56%, and the average venous P O O2 , was 23 mm Hg. When the muscle was stimulated to contract during its perfusion with venous blood, increases in blood flow occurred which averaged 143%, despite additional falls in venous blood P O O2 that averaged only 3 mm Hg. These studies suggest that the effect of lowered P O O2 on vascular smooth muscle does not produce sufficient vasodilatation to explain functional hyperemia in skeletal muscle.
T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors.
Authors: H M Georgiou, A C Lagarde, D Bellgrau
Journal: The Journal of Experimental Medicine (1988)

Diabetes-prone BB (BB-DP) rats express several T cell dysfunctions which include poor proliferative and cytotoxic responses to alloantigen. The goal of this study was to determine the origin of these T cell dysfunctions. When BB-DP rats were thymectomized, T cell depleted, and transplanted with neonatal thymus tissue from diabetes-resistant and otherwise normal DA/BB F1 rats, the early restoration of T cell function proceeded normally on a cell-for-cell basis; i.e., peripheral T cells functioned like those from the thymus donor. Because the thymus in these experiments was subjected to gamma irradiation before transplantation and there was no evidence of F1 chimerism in the transplanted BB-DP rats, it appeared that the BB-DP T cell precursors could mature into normally functioning T cells if the maturation process occurred in a normal thymus. If the F1 thymus tissue was treated with dGua before transplantation, the T cells of these animals functioned poorly like those from untreated BB-DP rats. dGua poisons bone marrow-derived cells, including gamma radiation-resistant cells of the macrophage/dendritic cell lineages, while sparing the thymic epithelium. Therefore, the reversal of the T cell dysfunction depends on the presence in the F1 thymus of gamma radiation-resistant, dGua-sensitive F1 cells. Conversely, thymectomized and T cell-depleted F1 rats expressed T cell dysfunction when transplanted with gamma-irradiated BB thymus grafts. T cell responses were normal in animals transplanted with dGua-treated BB thymus grafts. With increasing time after thymus transplantation, T cells from all animals gradually expressed the functional phenotype of the bone marrow donor. Taken together these results suggest that BB-DP bone marrow-derived cells that are not T cell precursors influence the maturation environment in the thymus of otherwise normal BB-DP T cell precursors.
Semiautomatic carotid lumen segmentation for quantification of lumen geometry in multispectral MRI
Authors: Hui Tang, Theo van Walsum, Robbert S. van Onkelen, Reinhard Hameeteman, Stefan Klein, Michiel Schaap, Fufa L. Tori, Quirijn J.A. van den Bouwhuijsen, Jacqueline C.M. Witteman, Aad van der Lugt, Lucas J. van Vliet, Wiro J. Niessen
Journal: Medical Image Analysis (2012)
An Adoption Study of Parental Depression as an Environmental Liability for Adolescent Depression and Childhood Disruptive Disorders
Authors: Erin C. Tully, William G. Iacono, Matt McGue
Journal: American Journal of Psychiatry (2008)

Objective: The authors used an adoption study design to investigate environmental influences on risk for psychopathology in adolescents with depressed parents. Method: Participants were 568 adopted adolescents ascertained through large adoption agencies, 416 nonadopted adolescents ascertained through birth records, and their parents. Clinical interviews with parents and adolescents were used to determine lifetime DSM-IV-TR diagnoses of major depressive disorder, oppositional defiant disorder, conduct disorder, attention deficit hyperactivity disorder (ADHD), and substance use disorders in adolescents and major depression in mothers and fathers. Effects of parental depression (either parent with major depression, maternal major depression, and paternal major depression) on adolescent psychopathology were tested in nonadopted and adopted adolescents separately, and interactive effects of parental depression and adoption status were tested. Results: Either parent having major depression and a mother having major depression were associated with a significantly greater risk for major depression and disruptive behavior disorders in both nonadopted and adopted adolescents. Paternal depression did not have a main effect on any psychiatric disorder in adolescents and, with one exception (ADHD in adopted adolescents), did not predict significantly greater likelihoods of disorders in either nonadopted or adopted adolescents. Conclusions: Maternal depression was an environmental liability for lifetime diagnoses of major depression and disruptive disorders in adolescents. Paternal depression was not associated with an increased risk for psychopathology in adolescents.
Long-term safety of Infliximab for the treatment of inflammatory bowel disease: does blocking TNF reduce colitis-associated colorectal carcinogenesis?
Authors: L. Biancone, C. Petruzziello, E. Calabrese, F. Zorzi, P. Naccarato, S. Onali, F. Pallone
Journal: Gut (2009)

We read with interest the article by Fidder et al 1 reporting, in a single-centre cohort study, the frequency of severe adverse events (SAEs) in 734 infliximab- and 666 non-infliximab treated patients with inflammatory bowel disease (IBD) followed-up in the long term (median 58 and 144 months, respectively). While no differences between the two groups were detected in terms of SAEs, mortality, infection rate and malignancies, we do believe that the type of cancer observed deserves further consideration. A comparable cancer incidence was detected in the two groups, confirming previous studies.2 3 However, while in the non-infliximab-treated group 8 out of the 666 (1.2%) patients had a newly diagnosed colorectal cancer, no patients in the infliximab group had a new diagnosis of colorectal cancer (0%) during the study period. In the infliximab group, one metastatic adenocarcinoma of unknown origin was, however, detected in one …
Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients
Authors: M. Mandalà, M. Reni, S. Cascinu, S. Barni, I. Floriani, S. Cereda, R. Berardi, S. Mosconi, V. Torri, R. Labianca
Journal: Annals of Oncology (2007)
Toll-Like Receptor-2 Mediates Inflammation and Matrix Degradation in Human Atherosclerosis
Authors: Claudia Monaco, Scott M. Gregan, Tina J. Navin, Brian M.J. Foxwell, Alun H. Davies, Marc Feldmann
Journal: Circulation (2009)

Background— Inflammation and matrix degradation are the hallmarks of high-risk atherosclerosis that leads to myocardial infarction and stroke. Toll-like receptors (TLRs), key players in innate immunity, are upregulated in atherosclerotic lesions, but their functional role in human atherosclerosis is unknown. We explored the effects of blocking TLR-2, TLR-4, and myeloid differentiation primary response gene 88 (MyD88), a signaling adaptor shared by most TLRs and interleukin-1 receptor (IL-1R), in an in vitro model of human atherosclerosis. Methods and Results— Carotid endarterectomies were obtained from patients with symptomatic carotid disease. Cells were isolated via enzymatic tissue dissociation and cultured in the presence or absence of TLR signaling blockers. A dominant-negative form of MyD88 (MyD88 DN ) decreased the production of monocyte chemotactic protein-1/CCL2 ( P =0.000), IL-8/CXCL8 ( P =0.006), IL-6 ( P =0.002), matrix metalloproteinase-1 (MMP-1; P =0.002), and MMP-3 ( P =0.000), as well as nuclear factor-κB activation ( P &lt;0.05) in atheroma cell cultures. IL-1R antagonist, TLR-4 blocking antibodies, or overexpression of a dominant-negative form of the TLR-4 signaling adaptor TRIF-related adaptor molecule reduced nuclear factor-κB activity but did not have a broad impact on the production of the mediators studied. In contrast, TLR-2 neutralizing antibodies inhibited nuclear factor-κB activation ( P &lt;0.05) and significantly reduced monocyte chemotactic protein-1/CCL2 ( P =0.000), IL-8/CXCL8 ( P =0.009), IL-6 ( P =0.000), and MMP-1 ( P =0.000), MMP-2 ( P =0.004), MMP-3 ( P =0.000), and MMP-9 ( P =0.006) production. Conclusions— Our data indicate that TLR-2 signaling through MyD88 plays a predominant role in inflammation and matrix degradation in human atherosclerosis. TLR-2 blockade may represent a therapeutic strategy for atherosclerosis and its complications.
Thrombotic microangiopathy and retroviral infections: A 13‐year experience
Authors: Antonio Ucar, Hugo F. Fernandez, John J. Byrnes, Eric C‐Y Lian, William J. Harrington
Journal: American Journal of Hematology (1994)

Abstract Eleven of fifty serum samples collected from patients with a diagnosis of thrombotic microangiopathy (TMA), from 1979 to 1991, tested positive for antlretroviral antibodies. Seven had human immunodeficiency virus (HIV) infection, and four had human iymphotrophic virus, type I (HTLV‐I) infection. All patients were treated with plasma exchange and for infusion, but only two of the HIV‐infected patlents obtained a complete response (CR) and one of them died after a few months. Combined results from the ilterature indicate that most patients with HIV infection survive less than one year from the initial diagnosis of TMA. In the setting of HIV infection, TMA Is a treatable condition, but survivai for most patients is less than 12 months. Three of the four HTLV‐I infected patients with TMA had a CR. These observations strongly suggest that both HIV and HTLV‐I infections are associated with TMA, but rigorous epidemiologic studies will be needed to determine the relative risk for each. Retrovirai Infections should be considered In patients with TMA, especially If the patient has associated risk factors and demographic characteristics. © 1994 Wiley‐Liss, Inc.
Focal Adhesion Kinase Expression in Human Neuroblastoma: Immunohistochemical and Real-time PCR Analyses
Authors: Elizabeth A. Beierle, Nicole A. Massoll, Joseph Hartwich, Elena V. Kurenova, Vita M. Golubovskaya, William G. Cance, Patrick McGrady, Wendy B. London
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase important in signaling between cells and their extracellular matrix. Studies have shown that FAK expression is up-regulated in several human tumors and is related to tumor progression. We recently found an increase in p125FAK expression in human neuroblastoma cells lines and wished to determine its expression in human neuroblastoma specimens and evaluate for a possible correlation between p125FAK expression and known prognostic factors for neuroblastoma. We hypothesized that p125FAK expression would be up-regulated in advanced human neuroblastomas. Experimental Design: Using immunohistochemical techniques with monoclonal antibody 4.47 specific for p125FAK expression, we analyzed 70 formalin-fixed, paraffin-embedded human neuroblastoma specimens for p125FAK staining. In addition, real-time PCR was used to determine the abundance of FAK mRNA in 17 matched human neuroblastoma mRNA specimens. Results: FAK staining was present in 51 of the 70 tumor specimens (73%). Immunohistochemical staining of p125FAK in the ganglion-type tumor cells correlated with advanced International Neuroblastoma Staging System tumor stages and FAK mRNA abundance. In addition, p125FAK staining was significantly increased in stage IV tumors with amplification of the N-MYC oncogene. Conclusions: These novel findings provide evidence that FAK is expressed by advanced-stage neuroblastoma and provide a rationale for targeting FAK in the treatment of this tumor.
Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study
Authors: D J Pattison
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To investigate whether, there is an association between consumption of fruit and vegetables and dietary antioxidants and the risk of developing inflammatory polyarthritis (IP). <b>Methods:</b> In a prospective, population based, nested case-control study of residents of Norfolk, UK, men and women aged 45–74 years were recruited, between 1993 and 1997 through general practice age-sex registers to the Norfolk arm of the European Prospective Investigation of Cancer (EPIC-Norfolk). Dietary intake was assessed at baseline using 7 day diet diaries. Seventy three participants who went on to develop IP between 1993 and 2001 and were registered by the Norfolk Arthritis Register (NOAR) were identified. Incident cases of IP, assessed by general practitioners, fulfilled the criteria of two or more swollen joints, persisting for a minimum of 4 weeks. Each case of IP was matched for age and sex with two controls free of IP. <b>Results:</b> Lower intakes of fruit and vegetables, and vitamin C were associated with an increased risk of developing IP. Those in the lowest category of vitamin C intake, compared with the highest, increased their risk of developing IP more than threefold, adjusted odds ratio (OR) with 95% confidence intervals (CI) 3.3 (95% CI 1.4 to 7.9). Weak inverse associations between vitamin E and β-carotene intake and IP risk were found. <b>Conclusion:</b> Patients with IP (cases) consumed less fruit and vitamin C than matched controls, which appeared to increase their risk of developing IP. The mechanism for this effect is uncertain. Thus similar studies are necessary to confirm these results.
Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells.
Authors: T Uchiyama, T Hori, M Tsudo, Y Wano, H Umadome, S Tamori, J Yodoi, M Maeda, H Sawami, H Uchino
Journal: Journal of Clinical Investigation (1985)

We studied the expression of the interleukin-2 (IL-2) receptor and the proliferative response to exogenous IL-2 of peripheral blood leukemic cells from patients with adult T cell leukemia (ATL) in order to see whether IL-2 receptor expressed on ATL cells is different from normal IL-2 receptor and whether it plays a role in the neoplastic growth in ATL. Peripheral blood leukemic cells from 42 patients with ATL examined expressed IL-2 receptors that were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after the culture for 24 or 48 h. The number of anti-Tac binding sites ranged from 3,100 to 11,400 in fresh cells and from 3,600 to 96,000/cell in short-term cultured leukemic cells, whereas phytohemagglutinin-P (PHA-P)-stimulated normal T cells exhibited 6,900-35,000 anti-Tac binding sites per cell. ATL-derived and human T cell leukemia/lymphoma virus, type I (HTLV-I)-infected cell lines such as MT-1 and Hut102 expressed a much higher number of anti-Tac binding sites. Leukemic cells from 15 patients with ATL examined showed no or very poor proliferative response to various concentrations of immunoaffinity-purified IL-2, although they expressed Tac antigen (Ag). Radiolabeled IL-2 binding experiments demonstrated that ATL leukemic cells could bind IL-2, and they expressed both high and low affinity IL-2 receptors, although the number of high affinity IL-2 receptor was much less than that of low affinity IL-2 receptor and that of anti-Tac binding sites. In contrast, leukemic T cells from a patient with T cell chronic lymphocytic leukemia (CLL), in whom HTLV-I infection was not demonstrated, responded as well as PHA-P-stimulated normal T cells, and their IL-2 receptors, unlike ATL cells, were modulated (down regulated) by anti-Tac antibody. No differences were noted between ATL cells and normal activated T cells in one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the IL-2 receptor. Thus, leukemic cells in ATL spontaneously and continuously express IL-2 receptor, which appears to be abnormally regulated and unresponsive to IL-2. These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells.
Peritoneal healing and adhesion formation/reformation
Authors: Y. C. Cheong
Journal: Human Reproduction Update (2001)

Intra-abdominal adhesion formation and reformation after surgery is a cause of significant morbidity, resulting in infertility and pain. The understanding of the pathogenesis of adhesion formation and reformation especially at the cellular and molecular level can help to further develop more effective treatments for the prevention of adhesion formation and reformation. Following an injury to the peritoneum, fibrinolytic activity over the peritoneal surface decreases, leading to changes in the expression and synthesis of various cellular mediators and in the remodelling of the connective tissue. The cellular response to peritoneal injury and adhesion formation and reformation are reviewed. Analysis of the available literature data on the cellular mediators in the peritoneal fluid showed variation in results from different investigators. The potential sources of variability and error are examined. It is still unclear if there is significant individual variation in the peritoneal response to injury.
Who needs Rubik's cube?
Authors: L. Farrell
Journal: BMJ (1999)

I read an article by a diabetologist last week, in which he claimed that in the next millennium diabetes would remain one of the most intellectually satisfying of all illnesses, and that because diabetes involves all organs and ages it gives a “wonderful” spectrum for the clinician.

He didn't claim that people with diabetes would be better managed, or that they would feel better, or have fewer complications, or live longer and have …