tbuckley/cabot-search huggingface dataset:
Ulcer of the Stomach, Opening into the Left Ventricle of the Heart
Authors: J. M. Finny
Journal: BMJ (1886)

THE specimen which I exhibit is one illustrating a disease of very great rarity, no similar case having been recorded in the United King- dom, and demonstrating features, in the clinical and pathological his- tory of gastric ulcer, of unusual interest.It is a specimen of an oval ulcer of the stomach (1l + --inch), situated on the anterior wall, two and a half inches from the cardiac orifice, which perforated the gastric wall and the diaphragm, opened into the left ventricle of the heart, and caused death by hiemorrhage directly from the heart into the stomach.The clinical history of the patient from whom the specimen was removed is as follows.A farm-labourer, aged 19, was admitted, under my care, into Sir Patrick Dun's Hospital,-at the end of October, 1885, suffering from articular rheumatism, of a subacute type, of a month's duration.He was well nourished, though somewhat pale ; the knees were painful and swollen, and a pericardial friction-sou-nd, limited to the sternum, was discovered.In a few days, the rheumatic symptoms disappeared, and the pericardial inflammation abated.The friction-sound was not followed by evidences of serous effusion, nor accompanied by endocar- dial valvulitis.It was thought, therefore, that the pericardial inflammation had ended in resolution or adhesion.The febrile disturbance (99°to 101°) which existed at the time of admission diminished, but never disap- peared, during the five weeks of the patient's life in hospital.He felt, however, so well, the first fortnight after admission, that, at his urgent request, he was allowed to sit up for a day or two; and his diet was sufficiently liberal, including eggs, bread and butter, and puddings- meat was not allowed, though asked for.There were no symptoms pointing to disease of the stomach, with, perhaps, one exception.There was no pain in the epigastrium or baclk ejther before or after food, nor, any sickness of stomach ; and there was a complete absence of any history of his ever having vomited or passed blood, or of ever having had any gastric distress.The only symptom which might have awakened a suspicion of what was going on in the stomach was a pain, which he referred to a small area, cor- respeding to the cartilage of the sixth rib on the left side, and also to theiin near the coracoid process, under the clavicle, on the right side.Tls pain, he stated, he had suffered from during the last five years, at varying intervals; at times, it was so severe as to necessitate his aving up his rwork, and lying down.'Strong pressure with the folded arm always relieved it.It was seemingly in no way connected with the introduction of food, and was not accompanied or followed by
Autoimmune and Inflammatory Mechanisms in Atherosclerosis
Authors: Georg Wick, Michael Knoflach, Qingbo Xu
Journal: Annual Review of Immunology (2004)

The present review focuses on the concept that cellular and humoral immunity to the phylogenetically highly conserved antigen heat shock protein 60 (HSP60) is the initiating mechanism in the earliest stages of atherosclerosis. Subjecting arterial endothelial cells to classical atherosclerosis risk factors leads to the expression of HSP60 that then may serve as a target for pre-existent cross-reactive antimicrobial HSP60 immunity or bona fide autoimmune reactions induced by biochemically altered autologous HSP60. Endothelial cells can also bind microbial or autologous HSP60 via Toll-like receptors, providing another possibility for targetting adaptive or innate immunological effector mechanisms.
Interleukin‐33 in allergy
Authors: Tatsukuni Ohno, Hideaki Morita, Ken Arae, Kenji Matsumoto, Susumu Nakae
Journal: Allergy (2012)

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family, which includes IL-1 and IL-18, and is considered to be important for host defense against nematodes by inducing Th2 cytokine production via the IL-33 receptor. IL-33 receptor is a heterodimer of IL-1 receptor-like 1 (IL-1RL1; also called ST2, T1, Der4, and fit-1) and IL-1 receptor accessory protein (IL-1RAcP). On the other hand, excessive and/or inappropriate production of IL-33 is considered to be involved in the development of various disorders, such as allergic and autoimmune diseases. Unlike IL-1β and IL-18, IL-33 does not seem to be secreted through the activation of inflammasomes in events such as apoptosis. However, IL-33 is localized in the nucleus of cells and is released during tissue injury associated with necrosis. This suggests that it acts as an alarmin, like IL-1α and high-mobility group box chromosomal protein-1 (HMGB-1). This review summarizes current knowledge regarding the roles of IL-33 in the functions of various cell types and the pathogenesis of allergy.
Concerted and Nonconcerted Evolution of the Hsp70 Gene Superfamily in Two Sibling Species of Nematodes
Authors: Nikolas Nikolaidis, Masatoshi Nei
Journal: Molecular Biology and Evolution (2004)

We have identified the Hsp70 gene superfamily of the nematode Caenorhabditis briggsae and investigated the evolution of these genes in comparison with Hsp70 genes from C. elegans, Drosophila, and yeast. The Hsp70 genes are classified into three monophyletic groups according to their subcellular localization, namely, cytoplasm (CYT), endoplasmic reticulum (ER), and mitochondria (MT). The Hsp110 genes can be classified into the polyphyletic CYT group and the monophyletic ER group. The different Hsp70 and Hsp110 groups appeared to evolve following the model of divergent evolution. This model can also explain the evolution of the ER and MT genes. On the other hand, the CYT genes are divided into heat-inducible and constitutively expressed genes. The constitutively expressed genes have evolved more or less following the birth-and-death process, and the rates of gene birth and gene death are different between the two nematode species. By contrast, some heat-inducible genes show an intraspecies phylogenetic clustering. This suggests that they are subject to sequence homogenization resulting from gene conversion-like events. In addition, the heat-inducible genes show high levels of sequence conservation in both intra-species and inter-species comparisons, and in most cases, amino acid sequence similarity is higher than nucleotide sequence similarity. This indicates that purifying selection also plays an important role in maintaining high sequence similarity among paralogous Hsp70 genes. Therefore, we suggest that the CYT heat-inducible genes have been subjected to a combination of purifying selection, birth-and-death process, and gene conversion-like events.
Relation of pyloric motility to pyloric opening and closure in healthy subjects.
Authors: G Tougas, M Anvari, J Dent, S Somers, D Richards, G W Stevenson
Journal: Gut (1992)

The relation between pyloric motor activity, opening, and closure was examined in eight healthy men. Manometry was performed with an assembly combining 13 side holes and a sleeve sensor positioned astride the pylorus. Simultaneous with manometry, pyloric opening and closure and antroduodenal contractions were observed fluoroscopically with the antrum filled with barium. During intraduodenal normal saline infusion, coordinated antral pressure waves swept over the pylorus and ejected barium into the duodenum. No localised pyloric motor pattern was observed under these conditions. In contrast, the intraduodenal triglyceride infusion was associated with the absence of antral pressure waves and virtual absence of antral wall movement. At the pylorus, there was a zone of luminal occlusion less than 1 cm long that persisted for the period of observation. This zone of luminal occlusion corresponded precisely with manometric recordings of a narrow zone of pyloric phasic and tonic activity. During the duodenal triglyceride infusion, the pylorus was closed for 98.5% of the measurement period when basal pyloric pressure was 4 mm Hg or more, and during this motor pattern, barium did not traverse the pylorus. Localised pyloric contractions cause sustained pyloric closure, whether these contractions are phasic or tonic. These contractions occur independently of antral or duodenal contractions and may interrupt gastric emptying.
Stroke patients are not treated quickly enough
Authors: Adrian O'Dowd
Journal: BMJ (2005)

The NHS needs an increase of 400-500% in the number of stroke specialists to improve stroke care to acceptable standards, it has been claimed. The National Sentinel Stroke Audit 2004 , published this week, found that standards of stroke care had undergone “dramatic improvement” in recent years but that huge problems remained.

The audit of all hospitals in England, Wales, and Northern Ireland found that 82% of hospitals in England had stroke units by April 2004, when the survey was done, while the proportion of hospitals that had stroke units in Northern Ireland was …
Cellular Histone Modification Patterns Predict Prognosis and Treatment Response in Resectable Pancreatic Adenocarcinoma: Results From RTOG 9704
Authors: Ananya Manuyakorn, Rebecca Paulus, James Farrell, Nicole A. Dawson, Sheila Tze, Gardenia Cheung-Lau, Oscar Joe Hines, Howard Reber, David B. Seligson, Steve Horvath, Siavash K. Kurdistani, Chandhan Guha, David W. Dawson
Journal: Journal of Clinical Oncology (2010)

PURPOSE Differences in cellular levels of histone modifications have predicted clinical outcome in certain cancers. Here, we studied the prognostic and predictive value of three histone modifications in pancreatic adenocarcinoma. METHODS Tissue microarrays (TMAs) from two pancreatic adenocarcinoma cohorts were examined, including those from a 195-patient cohort from Radiation Therapy Oncology Group trial RTOG 9704, a multicenter, phase III, randomized treatment trial comparing adjuvant gemcitabine with fluorouracil and a 140-patient cohort of patients with stage I or II cancer from University of California, Los Angeles Medical Center. Immunohistochemistry was performed for histone H3 lysine 4 dimethylation (H3K4me2), histone H3 lysine 9 dimethylation (H3K9me2), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathologic parameters and clinical outcome measures. Results Low cellular levels of H3K4me2, H3K9me2, or H3K18ac were each significant and independent predictors of poor survival in univariate and multivariate models, and combined low levels of H3K4me2 and/or H3K18ac were the most significant predictor of overall survival (hazard ratio, 2.93; 95% CI, 1.78 to 4.82) in the University of California, Los Angeles cohort. In subgroup analyses, histone levels were predictive of survival specifically for those patients with node-negative cancer or for those patients receiving adjuvant fluorouracil, but not gemcitabine, in RTOG 9704. CONCLUSION Cellular levels of histone modifications define previously unrecognized subsets of patients with pancreatic adenocarcinoma with distinct epigenetic phenotypes and clinical outcomes and represent prognostic and predictive biomarkers that could inform clinical decisions, including the use of fluorouracil chemotherapy.
Fetal Macrosomia and Neonatal Hyperinsulinemic Hypoglycemia Associated With Transplacental Transfer of Sulfonylurea in a Mother With <i>KCNJ11</i>-Related Neonatal Diabetes
Authors: Nele Myngheer, Karel Allegaert, Andrew Hattersley, Tim McDonald, Holger Kramer, Frances M. Ashcroft, Johan Verhaeghe, Chantal Mathieu, Kristina Casteels
Journal: Diabetes Care (2014)

OBJECTIVE Sulfonylureas (SUs) are effective at controlling glycemia in permanent neonatal diabetes mellitus (PNDM) caused by KCNJ11 (Kir6.2) mutations. RESEARCH DESIGN AND METHODS We report the case of a woman with PNDM who continued high doses of glibenclamide (85 mg/day) during her pregnancy. The baby was born preterm, and presented with macrosomia and severe hyperinsulinemic hypoglycemia requiring high-rate intravenous glucose infusion. RESULTS Postnatal genetic testing excluded a KCNJ11 mutation in the baby. Glibenclamide was detected in both the baby's blood and the maternal milk. CONCLUSIONS We hypothesize that high doses of glibenclamide in the mother led to transplacental passage of the drug and overstimulation of fetal β-cells, which resulted in severe hyperinsulinemic hypoglycemia in the neonate (who did not carry the mutation) and contributed to fetal macrosomia. We suggest that glibenclamide (and other SUs) should be avoided in mothers with PNDM if the baby does not carry the mutation or if prenatal screening has not been performed, while glibenclamide may be beneficial when the fetus is a PNDM carrier.
TGF-β–dependent CD103 expression by CD8+ T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease
Authors: Riham El-Asady, Rongwen Yuan, Kechang Liu, Donghua Wang, Ronald E. Gress, Philip J. Lucas, Cinthia B. Drachenberg, Gregg A. Hadley
Journal: The Journal of Experimental Medicine (2005)

Destruction of the host intestinal epithelium by donor effector T cell populations is a hallmark of graft-versus-host disease (GVHD), but the underlying mechanisms remain obscure. We demonstrate that CD8+ T cells expressing CD103, an integrin conferring specificity for the epithelial ligand E-cadherin, play a critical role in this process. A TCR transgenic GVHD model was used to demonstrate that CD103 is selectively expressed by host-specific CD8+ T cell effector populations (CD8 effectors) that accumulate in the host intestinal epithelium during GVHD. Although host-specific CD8 effectors infiltrated a wide range of host compartments, only those infiltrating the intestinal epithelium expressed CD103. Host-specific CD8 effectors expressing a TGF-β dominant negative type II receptor were defective in CD103 expression on entry into the intestinal epithelium, which indicates local TGF-β activity as a critical regulating factor. Host-specific CD8 effectors deficient in CD103 expression successfully migrated into the host intestinal epithelium but were retained at this site much less efficiently than wild-type host-specific CD8 effectors. The relevance of these events to GVHD pathogenesis is supported by the finding that CD103-deficient CD8+ T cells were strikingly defective in transferring intestinal GVHD pathology and mortality. Collectively, these data document a pivotal role for TGF-β–dependent CD103 expression in dictating the gut tropism, and hence the destructive potential, of CD8+ T cells during GVHD pathogenesis.
TCT-77 Safety of provocative tests to detect coronary artery spasm. Results from a French registry including 2,430 patients.
Authors: Helene Aelion, Aures Chaib, Emmanuel Salengro, Stephane Manzo-Silberman, Marie Caroline Chenilleau, Julien Rosencher, christophe Meune, Alain Cariou, Simon Weber, Olivier Varenne
Journal: Journal of the American College of Cardiology (2013)
Macrophage-colony-stimulating factor selectively enhances macrophage scavenger receptor expression and function.
Authors: W J de Villiers, I P Fraser, D A Hughes, A G Doyle, S Gordon
Journal: The Journal of Experimental Medicine (1994)

Regulation of macrophage scavenger receptor (MSR) activity may be an important determinant of the extent of atherogenesis. The effect of macrophage-colony-stimulating factor (M-CSF) on this pathway was studied using a recently developed monoclonal antibody to murine MSR. M-CSF markedly and selectively increased MSR synthesis in murine macrophages: posttranslationally, the receptor appeared more stable and shifted to a predominantly surface distribution. Functionally, M-CSF enhanced modified lipoprotein uptake and increased divalent cation-independent adhesion in vitro. These results suggest a plausible mechanism whereby M-CSF production in the atheromatous plaque microenvironment could promote the recruitment and retention of mononuclear phagocytes and subsequent foam cell formation.
Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*
Authors: RUSSEL J. REITER
Journal: Endocrine Reviews (1991)

UNTIL 35 yr ago, most scientists did not take research on the pineal gland seriously. The decade beginning in 1956, however, provided several discoveries that laid the foundation for what has become a very active area of investigation. These important early observations included the findings that, 1), the physiological activity of the pineal is influenced by the photoperiodic environment (1–5); 2), the gland contains a substance, N-acetyl-5-methoxytryptamine or melatonin, which has obvious endocrine capabilities (6, 7); 3), the function of the reproductive system in photoperiodically dependent rodents is inextricably linked to the physiology of the pineal gland (5, 8, 9); 4), the sympathetic innervation to the pineal is required for the gland to maintain its biosynthetic and endocrine activities (10, 11); and 5), the pineal gland can be rapidly removed from rodents with minimal damage to adjacent neural structures using a specially designed trephine (12). Since the mid 1960s, research on the pineal gland has increased exponentially, and its association with a wide variety of physiological systems has been documented (13–18). Proof that melatonin is the hormone of pineal origin that accounts for many of the endocrine manifestations of the gland, however, came somewhat later. Thus, whereas some early studies certainly suggested that melatonin had modulatory effects on the neuroendocrine- reproductive axis (19, 20), these actions were questioned when it was observed that in hamsters bearing sc placed melatonin pellets, which release the indole continuously, the ability of short day exposure and the pineal to suppress reproductive physiology was unexpectedly negated (21–23). These observations were, however, followed closely by studies showing that melatonin, administered as a single daily injection at a precise time with regard to the light-dark cycle, induced quiescence of the neuroendocrine-reproductive axis just as did short day exposure (24, 25).
Platelet Glycoprotein IIb/IIIa Receptor Inhibition in Non–ST-Elevation Acute Coronary Syndromes
Authors: Eric Boersma, K. Martijn Akkerhuis, Pierre Théroux, Robert M. Califf, Eric J. Topol, Maarten L. Simoons
Journal: Circulation (1999)

Background —Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. Methods and Results —We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction ( P &lt;0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4.9% versus 8.0%; 41% reduction; P &lt;0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. Conclusions —There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.
Pulmonary nodules due to Corynebacterium ulcerans
Authors: RB Dessau, M Brandt-Christensen, OJ Jensen, P Tonnesen
Journal: European Respiratory Journal (1995)

A 53 year old male with symptoms of coughing for 6 months presented with bilateral multiple pulmonary nodules suggestive of metastatic disease. By surgical resection 4 out of 6 nodules were removed. Histopathological examination showed granulomatous necrotizing inflammation with growth of Corynebacterium ulcerans, which did not produce diphtheria toxin. The patient was treated with penicillin for 1 week. Follow-up for 2 yrs showed no sign of recurrence.
Single channel recordings from human cardiac sarcoplasmic reticulum.
Authors: S R Holmberg, A J Williams
Journal: Circulation Research (1989)

Native membrane vesicles of human cardiac sarcoplasmic reticulum have been fused with artificial lipid bilayers to obtain recordings of single chloride and calcium release channels. Tissue was obtained from the explanted hearts of patients with end-stage cardiac failure undergoing heart transplantation. Although previous studies of calcium uptake and release have shown that the function of the sarcoplasmic reticulum is abnormal in end-stage cardiac failure, the basic properties of the channels are similar to those reported for equivalent channels from normal animal tissue.
Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene.
Authors: H Karasuyama, N Tohyama, T Tada
Journal: The Journal of Experimental Medicine (1989)

We introduced a mouse IL-2 cDNA expression vector into an IL-2-dependent mouse helper T cell line HT-2. Transfected cells secreted substantial amounts of IL-2, to which they themselves responded by proliferating without further requirement for exogenous IL-2. The proliferation was a direct function of the cell density and was inhibitable by antibodies against IL-2 or IL-2-R, indicating the autocrine nature of the proliferation. Those producing higher amounts of IL-2 were found to be tumorigenic when inoculated into nude mice. The latency period of tumor development correlated inversely with the level of IL-2 secreted. Tumor cells proliferated in vitro in an IL-2 autocrine fashion indistinguishable from that of the inoculated cells. We thus provide evidence that the aberrant activation of the IL-2 autocrine circuit can lead T cells to malignant transformation.
Chromosome Patterns in the AKR Mouse: Spontaneous Leukemia, Ascites Transfers, and Tissue Culture Cell Lines23
Authors: Relda Cailleau, Miriam Matthews Munro
Journal: JNCI Journal of the National Cancer Institute (1964)

Chromosomes were analyzed from various tissues of 14 AKR mice with spontaneous leukemia. Only 4 mice showed an apparently normal pattern and a modal diploid number of 40 chromosomes. In the remaining animals abnormal markers were present or the modal chromosome number was 41. Ascites lines established from leukemic lymph nodes and thymus tissues or from a tissue culture line showed predominantly aneuploid cells with modes of 41, 42, and 43 chromosomes. One ascites line transformed to hypotetraploidy by the 40th transfer and has retained this mode ever since. Two or 3 types of marker chromosomes (metacentrics, trans-locations, and minute) have been noted in the different ascites lines and sometimes have persisted through 40 or more transfers. Tissue-cultured cell lines have been grown on 3 or 4 different media and have given rise to lines with various chromosome complements. Most tissue culture lines range from 39 to 42 chromosomes, and one line has retained a mode of 40 chromosomes for more than 130 subcultures. Other lines have transformed so that the modal chromosome number ranges from 70 to 80. The type of growth media used seems to influence the chromosome numbers in these tissue culture lines.