tbuckley/cabot-search huggingface dataset:
Comparison of Fluorescence In Situ Hybridization and Immunohistochemistry for the Evaluation of <i>HER-2</i>/<i>neu</i> in Breast Cancer
Authors: Timothy W. Jacobs, Allen M. Gown, Hadi Yaziji, Melissa J. Barnes, Stuart J. Schnitt
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in the determination of HER-2/neu status of breast cancers. MATERIALS AND METHODS: FISH and IHC for HER-2/neu were performed on formalin-fixed paraffin sections of 100 consecutive invasive breast cancers. FISH was performed at Beth Israel Deaconess Medical Center, Boston, MA, using the Oncor/Ventana INFORM kit (Ventana Medical Systems, Tucson, AZ; formerly sold by Oncor, Inc, Gaithersburg, MD) in a laboratory certified as proficient in this procedure. IHC was performed at PhenoPath Laboratories, Seattle, WA, using a polyclonal antibody to the HER-2/neu protein. FISH and IHC were analyzed in a blinded fashion, and the results were then compared. Procedure and interpretation times and reagent costs for FISH and IHC were also compared. RESULTS: HER-2/neu was amplified by FISH in 26% of cases, and 23% were HER-2/neu–positive by IHC. FISHand IHC were both assessable in 90 cases. Concordance between FISH and IHC results was seen in 82 of these cases (91%, P &lt; .001). The FISH procedure required more technologist time and more interpretation time per case for the pathologist than IHC. Reagent costs were substantially higher for FISH than for IHC. CONCLUSION: There is a high level of correlation between FISH and IHC in the evaluation of HER-2/neu status of breast cancers using formalin-fixed paraffin-embedded specimens. Although the choice of which assay to use should be left for individual laboratories to make based on technical and economic considerations, our results may make it difficult to justify the routine use of FISH for determination of HER-2/neu status in breast cancer.
On the detection of nonrandom associations between DNA polymorphisms in natural populations of Drosophila.
Authors: C Zapata, G Alvarez
Journal: Molecular Biology and Evolution (1993)

The capacity to detect nonrandom associations between restriction-map variants was examined in eight gene regions of Drosophila melanogaster (yellow-achaetescute, white, Zw, Adh, Est6, and rosy) and D. pseudoobscura (Adh and Xdh), on the basis of published population data. The statistical power from individual pairwise tests was both heterogeneous and generally low across gene regions. Sample sizes larger than those currently being used are needed to ensure any power to detect disequilibrium by individual tests. It is found that the heterogeneity in power is mostly explained by large differences in the intensity of sample disequilibrium among regions. The yellow-achaete-scute, Zw, and Adh loci of D. melanogaster displayed both the highest mean power (approximately 0.4) and a very great disequilibrium (mean absolute values of D' were 0.8-1). By contrast, all the other gene regions exhibited lower mean power (approximately 0.2) and moderate levels of disequilibrium (0.4-0.6). Although the proportion of significant pairwise associations, especially for white, Est6, and rosy in D. melanogaster and for Adh and Xdh in D. pseudoobscura, is more or less close to the type I error, simultaneous-inference significance tests show that gametic disequilibrium is occurring at the eight DNA regions examined.
Liver Enzymes Compared With Alcohol Consumption in Predicting the Risk of Type 2 Diabetes
Authors: Kyoko Kogawa Sato, Tomoshige Hayashi, Yoshiko Nakamura, Nobuko Harita, Takeshi Yoneda, Ginji Endo, Hiroshi Kambe
Journal: Diabetes Care (2008)

It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed.The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin.During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT.GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes.
The Clinical Course of Experimental Autoimmune Encephalomyelitis and Inflammation Is Controlled by the Expression of Cd40 within the Central Nervous System
Authors: Burkhard Becher, Brigit G. Durell, Amy V. Miga, William F. Hickey, Randolph J. Noelle
Journal: The Journal of Experimental Medicine (2001)

Although it is clear that the function of CD40 on peripheral hematopoietic cells is pivotal to the development of autoimmunity, the function of CD40 in autoimmune disease outside this compartment is unresolved. In a model of experimental autoimmune encephalomyelitis (EAE), evidence is presented that CD40–CD154 interactions within the central nervous system (CNS) are critical determinants of disease development and progression. Using bone marrow (BM) chimeric mice, the data suggest that the lack of expression of CD40 by CNS-resident cells diminishes the intensity and duration of myelin oligodendrocyte glycoprotein (MOG)-induced EAE and also reduces the degree of inflammatory cell infiltrates into the CNS. Although CNS inflammation is compromised in the CD40+/+→CD40−/− BM chimeric mice, the restricted CD40 expression had no impact on peripheral T cell priming or recall responses. Analysis of RNA expression levels within the CNS demonstrated that encephalitogenic T cells, which entered a CNS environment in which CD40 was absent from parenchymal microglia, could not elicit the expression of chemokines within the CNS. These data provide evidence that CD40 functions outside of the systemic immune compartment to amplify organ-specific autoimmunity.
Mini-Dose Glucagon Rescue for Hypoglycemia in Children With Type 1 Diabetes
Authors: Morey W. Haymond, Barbara Schreiner
Journal: Diabetes Care (2001)

OBJECTIVE—Children with type 1 diabetes are frequently difficult to manage during times of gastroenteritis or poor oral intake of carbohydrates because of mild or impending hypoglycemia. The present study describes the effective use of small doses of subcutaneous glucagon in these children. RESEARCH DESIGN AND METHODS—We analyzed 33 episodes of impending or mild hypoglycemia in 28 children (ages 6.6 ± 0.7 years). All were healthy except for type 1 diabetes and an episode of gastroenteritis. Using a standard U-100 insulin syringe, children ages ≤2 years received two “units” (20 μg) of glucagon subcutaneously and those ages &amp;gt;2 years received one unit/year of age up to 15 units (150 μg). If the blood glucose did not increase within 30 min, the initial dosage was doubled and given at that time. We used patients’ self-glucose monitoring devices, aqueous glucagon, standard insulin syringes, and frequent phone contact with a physician and/or a diabetes nurse educator in this study. RESULTS—Blood glucose was 3.44 ± 0.15 mmol/l before and 8.11 ± 0.72 mmol/l 30 min after glucagon. In 14 children, relative hypoglycemia recurred, requiring retreatment (3.48 ± 0.18 to 6.94 ± 0.72 mmol/l). In four children, a third dose was required. The glucagon was well tolerated. In 28 of the 33 episodes of impending hypoglycemia, the children remained at home and fully recovered. Five children were taken to their local hospital because of concerns of dehydration or fever, but none for hypoglycemia. CONCLUSIONS—Mini-dose glucagon rescue, using subcutaneous injections, is effective in managing children with type 1 diabetes during episodes of impending hypoglycemia due to gastroenteritis or poor oral intake of carbohydrate.
Long-Term Outcomes in Elderly Survivors of In-Hospital Cardiac Arrest
Authors: Paul S. Chan, Brahmajee K. Nallamothu, Harlan M. Krumholz, John A. Spertus, Yan Li, Bradley G. Hammill, Lesley H. Curtis
Journal: New England Journal of Medicine (2013)

Little is known about the long-term outcomes in elderly survivors of in-hospital cardiac arrest. We determined rates of long-term survival and readmission among survivors of in-hospital cardiac arrest and examined whether these outcomes differed according to demographic characteristics and neurologic status at discharge.We linked data from a national registry of inpatient cardiac arrests with Medicare files and identified 6972 adults, 65 years of age or older, who were discharged from the hospital after surviving an in-hospital cardiac arrest between 2000 and 2008. Predictors of 1-year survival and of readmission to the hospital were examined.One year after hospital discharge, 58.5% of the patients were alive, and 34.4% had not been readmitted to the hospital. The risk-adjusted rate of 1-year survival was lower among older patients than among younger patients (63.7%, 58.6%, and 49.7% among patients 65 to 74, 75 to 84, and ≥85 years of age, respectively; P<0.001), among men than among women (58.6% vs. 60.9%, P=0.03), and among black patients than among white patients (52.5% vs. 60.4%, P=0.001). The risk-adjusted rate of 1-year survival was 72.8% among patients with mild or no neurologic disability at discharge, as compared with 61.1% among patients with moderate neurologic disability, 42.2% among those with severe neurologic disability, and 10.2% among those in a coma or vegetative state (P<0.001 for all comparisons). Moreover, 1-year readmission rates were higher among patients who were black, those who were women, and those who had substantial neurologic disability (P<0.05 for all comparisons). These differences in survival and readmission rates persisted at 2 years. At 3 years, the rate of survival among survivors of in-hospital cardiac arrest was similar to that of patients who had been hospitalized with heart failure and were discharged alive (43.5% and 44.9%, respectively; risk ratio, 0.98; 95% confidence interval, 0.95 to 1.02; P=0.35).Among elderly survivors of in-hospital cardiac arrest, nearly 60% were alive at 1 year, and the rate of 3-year survival was similar to that among patients with heart failure. Survival and readmission rates differed according to the demographic characteristics of the patients and neurologic status at discharge. (Funded by the American Heart Association and the National Heart, Lung, and Blood Institute.).
Subjective Experience and D<sub>2</sub>Receptor Occupancy in Patients With Recent-Onset Schizophrenia Treated With Low-Dose Olanzapine or Haloperidol: A Randomized, Double-Blind Study
Authors: Lieuwe de Haan, Marion van Bruggen, Jules Lavalaye, Jan Booij, Peter M A J Dingemans, Don Linszen
Journal: American Journal of Psychiatry (2003)

The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol.Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography.The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group.A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.
New Insights Into Oncogene Addiction Found
Authors: K. Garber
Journal: JNCI Journal of the National Cancer Institute (2007)

Amystery surrounds targeted anticancer drugs like trastuzumab (Herceptin), imatinib (Gleevec), and erlotinib (Tarceva), agents that block the specific signaling pathways thought to drive cancer cell proliferation. For all the molecular sophistication of these new drugs, we know little about why and how they actually work without greatly harming patients. The targets of these drugs are present and active in normal cells as well as tumor cells. So why do targeted drugs kill cancer cells without massive toxic effects? The answer may lie in the study of oncogene addiction, a relatively new area of cancer research. I. Bernard Weinstein , M.D., of Columbia University, conceived the theory of addiction in 1997, after he observed that only partially blocking cyclin D1 (a protein required for cell division) was enough to arrest the growth of cancer cells overexpressing the protein. “These particular cancer cells needed a very high level of oncogene to survive,” Weinstein recalled. “In that sense they were addicted.” Oncogene addiction is the dependence of a cancer cell on one overactive gene or pathway for the cell’s survival and growth. Over the last decade, researchers have accumulated evidence for oncogene addiction, and they are now teasing out exactly how such addiction takes place — and how tumors might escape it. The fi ndings may directly affect how targeted therapies will be used to treat human cancers.
Does ketotifen have a steroid-sparing effect in childhood asthma?
Authors: GJ Canny, J Reisman, H Levison
Journal: European Respiratory Journal (1997)

In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of &lt; or = 1 mg.day-1, were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief. During the baseline period, the mean daily ICS dosage was 432 micrograms in the ketotifen group versus 408 micrograms in the placebo group (NS). Among the-patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled. In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.
Resolved
Authors: Barbara J Ballermann, Radu V Stan
Journal: Journal of the American Society of Nephrology (2007)

There is growing debate as to the primal role of capillary endothelial cells in the barrier function of the glomerular filter. Two experts argue the points for and against. Clearly unresolved is agreement whether glomerular capillary endothelium has fenestrae subtended by diaphragms.
Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: A randomized study
Authors: A. Sobrero, A. Zaniboni, G.L. Frassineti, C. Aschele, A. Guglielmi, R. Giuliani, A. Ravaioli, C. Lanfranco, C. Caroti, E. Arnoldi, S. Barni, L. Gallo, M.A. Pessi, D. Turci, E. Cortesi, F. Grossi, L. Frontini, E. Piazza, P. Bruzzi, R. Labianca
Journal: Annals of Oncology (2000)
Synergistic Interactions of Physiologic Increments of Glucagon, Epinephrine, and Cortisol in the Dog
Authors: Neal Eigler, Luigi Saccà, Robert S. Sherwin
Journal: Journal of Clinical Investigation (1979)

To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones.
Inflammation in acne scarring: a comparison of the responses in lesions from patients prone and not prone to scar
Authors: D.B. Holland, A.H.T. Jeremy, S.G. Roberts, D.C. Seukeran, A.M. Layton, W.J. Cunliffe
Journal: British Journal of Dermatology (2004)

Many patients with inflammatory acne suffer from significant scarring, which is disfiguring and difficult to treat. A cell-mediated immune response is considered to be involved in the pathogenesis of acne, although the extent of this response has been found to differ among patients.To assess whether there were differences in the cell-mediated immune responses at different time points in inflamed lesion development and resolution in patients who were prone (S patients) and those with the same degree of inflamed acne who were not prone (NS patients) to develop scarring.Cellular and vascular markers were investigated using standard immunohistochemical techniques on biopsies of inflamed lesions of known duration, i.e. < 6 h (n = 14), 24 h (n = 14), 48 h (n = 10), 72 h (n = 10) and 6-7 days (n = 11) from the backs of acne patients.In early lesions from NS patients there was a large influx of CD4+ T cells, macrophages and Langerhans cells with a high number of cells expressing HLA-DR. Also there was significant angiogenesis and vascular adhesion molecule expression. Cell recruitment peaked in 48 h lesions, after which leucocyte numbers decreased and vascular activity returned to normal. Of the T cells, only 50% were memory/effector (CD45RO+) and naive (CD45RA+) cells, while the remainder were unclassified (CD45RO-, CD45RA-). In early lesions from S patients, CD4+ T cell numbers were smaller, although a high proportion were skin homing memory/effector cells. Langerhans cell numbers and cellular HLA-DR expression were low, while numbers of macrophages, blood vessels and vascular adhesion molecules were high. In resolving lesions angiogenesis remained high, with a further influx of macrophages and skin homing memory/effector cells and increased cellular HLA-DR expression.The cellular infiltrate was large and active with a greater nonspecific response (few memory T cells) in early lesions of NS patients, which subsided in resolution. In contrast, a predominantly specific immune response was present in S patients, which was initially smaller and ineffective, but was increased and activated in resolving lesions. Such excessive inflammation in healing tissue is conducive to scarring and suggests that the use of topical anti-inflammatory treatments would be appropriate for these patients.
Chronic Thromboembolic Pulmonary Hypertension
Authors: Peter Fedullo, Kim M Kerr, Nick H Kim, William R Auger
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

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