tbuckley/cabot-search huggingface dataset:
A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule.
Authors: F Sanchez-Madrid, J A Nagy, E Robbins, P Simon, T A Springer
Journal: The Journal of Experimental Medicine (1983)

The human lymphocyte function-associated antigen-1 (LFA-1), the complement receptor-associated OKM1 molecule, and a previously undescribed molecule termed p150,95, have been found to be structurally and antigenically related. Each antigen contains an alpha- and beta-subunit noncovalently associated in an alpha 1 beta 1-structure as shown by cross-linking experiments. LFA-1, OKM1, and p150,95 alpha-subunit designations and their molecular weights are alpha L = 177,000 Mr, alpha M = 165,000 Mr, and alpha X = 150,000 Mr, respectively. The beta-subunits are all = 95,000 Mr. Some MAb precipitated only LFA-1, others only OKM1, and another precipitates all three antigens. The specificity of these MAb for particular subunits was examined after subunit dissociation by high pH. MAb specific for LFA-1 or OKM1 bind to the alpha L- or alpha M-subunits, respectively, while the cross-reactive MAb binds to the beta-subunits. Coprecipitation experiments with intact alpha 1 beta 1-complexes showed anti-alpha and anti-beta MAb can precipitate the same molecules. In two-dimensional (2D) isoelectric focusing-SDS-PAGE, the alpha subunits of the three antigens are distinct, while the beta-subunits are identical. Biosynthesis experiments showed alpha L, alpha M, and alpha X are synthesized from distinct precursors, as is beta. The three antigens differ in expression on lymphocytes, granulocytes, and monocytes. During maturation of the monoblast-like U937 line, alpha M and alpha X are upregulated and alpha L is downregulated. Some MAb to the alpha subunit of OKM1 inhibited the complement receptor type three. LFA-1, OKM1, and p150,95 constitute a novel family of functionally important human leukocyte antigens that share a common beta-subunit.
Plasma Glucose Levels Throughout the Day and HbA1c Interrelationships in Type 2 Diabetes
Authors: Enzo Bonora, Francesco Calcaterra, Simonetta Lombardi, Nicoletta Bonfante, Gianni Formentini, Riccardo C. Bonadonna, Michele Muggeo
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate the extent of plasma glucose excursions with meals, the relations between plasma glucose levels at different times of the day, and the relations between the latter and HbA1c in non–insulin-treated type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—Daily glucose profiles were assessed in non–insulin-treated type 2 diabetic patients. Outpatients at the diabetes clinic (n = 371; one daily plasma glucose profile) and at home (n = 30; five daily blood glucose profiles over 1 month) as well as inpatients (n = 455; profile of plasma glucose on the day of admission) were examined. Subjects had plasma/blood glucose assessment before and 2–3 h after breakfast, lunch, and dinner. HbA1c was also measured. RESULTS—After the meals many subjects had glucose levels &amp;gt;8.9 mmol/l (160 mg/dl) and/or glucose excursions &amp;gt;2.2 mmol/l (40 mg/dl). This was also often found when HbA1c was satisfactory (&amp;lt;7%). The coefficients of simple correlation among plasma/blood glucose at different times of the day ranged from 0.52 to 0.88. Correlations between HbA1c and plasma/blood glucose at different times of the day ranged from 0.44 to 0.67. The strongest correlation was between HbA1c and mean daily glucose (r = 0.57–0.69). Multiple regression analyses showed that premeal but not postmeal plasma/blood glucose levels were independent predictors of HbA1c. CONCLUSIONS—These results suggest that 1) the majority of non–insulin-treated type 2 diabetic patients have exaggerated plasma/blood glucose excursions with meals, and many of them have higher-than-recommended glucose concentrations 2 h after the meals; 2) plasma/blood glucose levels throughout the day are not as strongly interrelated as one might believe; and 3) HbA1c is more related to preprandial than postprandial plasma/blood glucose levels. These findings have potential implications for treatment and monitoring of metabolic control in type 2 diabetes.
518 THE VALUE OF SERUM HBSAG LEVELS IN THE PREDICTION OF RELAPSE IN THE CHB PATIENTS WHO MET NAS ENDPOINT CRITERIA
Authors: I.N. Jiang, X.H. Huang, Y.X. Liang, W.W. Guo, M.H. Su, L.X. He, S.H. Zhong, Z.H. Liu, W.D. Fu, Y.M. Deng, B.M. Liao
Journal: Journal of Hepatology (2012)
Endoscopic markers of impending varceal hemorrhage: Correlation with the pressure in the varices
Authors: Kazushige Beppu, Makoto Hashizume
Journal: Hepatology (1990)

In 40 patients with cirrhosis and esophageal varices, transmural variceal pressure was assessed endoscopically by fine needle puncture and related to endoscopicsigns as well as to the severity of liver disease. Transmural pressure was significantly (p &lt; 0.01) higher in the presence of a red color sign (26.7[7.8] cm H 2 O) than in its absence (19.1 [6.6] cm H 2 ). Transmural pressure, however, was not significantly related to diameter or number of varices (diameter &gt;5mm: 23.7 [8.4], diameter ≤5 mm: 22.2 [7.9] cm H 2 0; number &gt; 3: 23.2 [8.0], number ≤3: 22.2 [7.8] cm H 2 O. The Child status (Child A: 23.9 [8.0], Child B/C: 21.3 [8.1] cm H 2 O) and individual Child–Pugh parameters including ascites (ascites present: 23.2 [8.3] cm H 2 O, ascites absent: 22.8 [8.1] cm H 2 O) were not significantly related to transmural variceal pressure. We conclude that the endoscopic visibility of a red color sign on the varices is associated with a high transmural esophageal variceal pressure. Our results favor the hypothesis that variceal pressure may be of major importance for the development of the red color sign.
Relationship Between Potassium and Vagal Action on Atrioventricular Transmission
Authors: KALMAN GREENSPAN, CHARLES M. WUNSCH, CHARLES FISCH
Journal: Circulation Research (1965)

The relationship between the effects of potassium and vagal stimulation on transmission through the atrioventricular transmission system was investigated. It was observed that infusion of isotonic potassium chloride alleviated atrioventricular block induced by vagal activity. This occurred at plasma potassium levels ranging from 4.8 to 6.9 mEq/liter. This antagonism does not appear to be mediated by catecholamine release since infusion of epinephrine (0.23 µg/min) did not relieve the block. At plasma levels higher than those capable of inhibiting vagal action, potassium enhances parasympathomimetic actions on A-V transmission and, at still higher levels, potassium is capable of inducing A-V block which is independent of the vagus.
S104 Targeting the bacterial cytoskeleton of CF pathogens for antimicrobial development–A cautionary tale?
Authors: SC Carnell, JD Perry, D Vollmer, J Biboy, M Facchini, A Bragonzi, A Vergunst, W Vollmer, CMA Khan, A De Soyza
Journal: Thorax (2013)

<h3>Background</h3> <i>Burkholderia cepacia </i>complex (BCC) bacteria are opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult due to the inherent multidrug resistance of BCC. There is a pressing need to find new bacterial targets for antimicrobials. We have previously shown that the novel compound Q22, which is related to A22 and inhibits the bacterial cytoskeletal protein MreB, inhibits growth of BCC bacteria. <h3>Aims</h3> We aimed to further analyse the phenotypic effects of Q22 treatment on BCC virulence traits to assess its feasibility as an antimicrobial. <h3>Methods</h3> BCC bacteria were grown in the presence of Q22 and a broad phenotypic analysis was performed, including resistance to H<sub>2</sub>O<sub>2</sub> induced oxidative stress, changes in inflammatory potential of cell surface components and <i><i>in vivo</i></i> drug toxicity studies. The influence of Q22 treatment on inflammatory potential was measured by monitoring the cytokine responses of BCC whole cell lysates, purified lipopolysaccharide and purified peptidoglycan extracted from bacterial cultures grown in the presence or absence of Q22 in differentiated THP-1 cells. Compound Q22 was also assessed for toxicity in both zebrafish and mouse infection models. <h3>Results</h3> BCC bacteria grown in the presence of Q22 displayed varying levels of resistance to H<sub>2</sub>O<sub>2</sub> induced oxidative stress with some strains showing increased resistance upon Q22 treatment. An increased response in pro inflammatory activity elected by whole Q22 treated bacterial lysate was observed for cytokines TNFa and IL-1b but this was variable between strains. Further dissection of this response is under investigation. Despite minimal toxicity previously shown <i><i>in vitro</i></i>with primary CF cell lines,<i><i>in vivo</i></i> studies demonstrated Q22 toxicity in both zebrafish and mouse infection models. <h3>Conclusions</h3> In the case of BCC bacteria destabilisation of the bacterial cytoskeleton using compounds such as Q22 can lead to unexpected increases of <i><i>in vitro</i></i> virulence-related traits. These changes appear to vary depending on strain and species. Future development of antimicrobials targeting the BCC bacterial cytoskeleton may be hampered if such effects translate into the <i><i>in vivo</i></i> environment of CF infection. Work supported by Newcastle-Upon-Tyne Hospitals Special Trustees &amp; Italian CF Research Foundation (FFC).
The NAS Perchlorate Review: Questions Remain about the Perchlorate RfD
Authors: Gary Ginsberg, Deborah Rice
Journal: Environmental Health Perspectives (2005)

Human exposure to perchlorate is commonplace because it is a contaminant of drinking water, certain foods, and breast milk. The U.S. Environmental Protection Agency (EPA) conducted a perchlorate risk assessment in 2002 that yielded a reference dose (RfD) based on both the animal and human toxicology data. This assessment has been superceded by a recent National Academy of Science (NAS) review that derived a perchlorate RfD that is 20-fold greater (less stringent) than that derived by the U.S. EPA in 2002. The NAS-derived RfD was put on the U.S. EPA's Integrated Risk Information System (IRIS) database very quickly and with no further public review. In this commentary we raise concerns about the NAS approach to RfD development in three areas of toxicity assessment: the dose that the NAS described as a no observable adverse-effect level is actually associated with perchlorate-induced effects; consideration of uncertainties was insufficient; and the NAS considered the inhibition of iodine uptake to be a nonadverse effect. We conclude that risk assessors should carefully evaluate whether the IRIS RfD is the most appropriate value for assessing perchlorate risk.
The Arg389Gly Beta1-Adrenoceptor Polymorphism and Catecholamine Effects on Plasma-Renin Activity
Authors: Heike Bruck, Kirsten Leineweber, Thomas Temme, Melanie Weber, Gerd Heusch, Thomas Philipp, Otto-Erich Brodde
Journal: Journal of the American College of Cardiology (2005)
SAP102, a Novel Postsynaptic Protein That Interacts with NMDA Receptor Complexes In Vivo
Authors: Bettina M. Müller, Ute Kistner, Stefan Kindler, Wook Joon Chung, Sven Kuhlendahl, Steven D. Fenster, Lit-Fui Lau, Rüdiger W. Veh, Richard L. Huganir, Eckart D. Gundelfinger, Craig C. Garner
Journal: Neuron (1996)

Synapse-associated proteins (SAPs) are constituents of the pre- and postsynaptic submembraneous cytomatrix. Here, we present SAP102, a novel 102 kDa SAP detected in dendritic shafts and spines of asymmetric type 1 synapses. SAP102 is enriched in preparations of synaptic junctions, where it biochemically behaves as a component of the cortical cytoskeleton. Antibodies directed against NMDA receptors coimmunoprecipitate SAP102 from rat brain synaptosomes. Recombinant proteins containing the carboxy-terminal tail of NMDA receptor subunit NR2B interact with SAP102 from rat brain homogenates. All three PDZ domains in SAP102 bind the cytoplasmic tail of NR2B in vitro. These data represent direct evidence that in vivo SAP102 is involved in linking NMDA receptors to the submembraneous cytomatrix associated with postsynaptic densities at excitatory synapses.
Get the Facts Straight
Authors: Daniel B. Kopans
Journal: Journal of Clinical Oncology (2004)

The article by Demicheli et al 1 concludes that premenopausal women should not be screened for breast cancer because they contend that the earlier treatment of breast cancers among these women hastens their demise.It would seem that the authors have a hypothesis that they wish to prove, and that they have misunderstood the facts, thinking that they fit the hypothesis.Peer review should have picked up the important, factually incorrect statements that seem to lend support to their hypothesis.Since their argument is based on factually incorrect information, and this could result in the unnecessary loss of life, the authors should provide corrections.Contrary to their assertions, the randomized controlled trials of mammography screening do not "all" show an early mortality excess for younger women.As with any such trials, the results in the early years reveal very small numbers.There is clearly statistical fluctuation that is to be expected since, even in the absence of screening, women are not expected to die from breast cancer at exactly the same time in the two groups of a trial.If these small numbers had any validity, then large trials would never be necessary.One need only look at the graphs of the survival data from the Malmo I trial 2 and the Gothenberg trial, 3 as well as the combined Swedish data 4 to see this effect.The curves weave back and forth in the early years of followup, consistent with statistical fluctuation.Malmo II shows a clear benefit from the beginning for "younger" women. 2 It has also been suggested that some deaths among the control group that were not counted may have been due to undiagnosed breast cancer.The authors also failed to take into account the fact that deaths among women in the screened group may also include women who refused, and were never screened.The analysis by Cox that is cited represents an artifact of incomplete analysis.Any adjustment for multiple testing would render the observation nonsignificant.The article provides two other importantly incorrect statements.There are, indeed, animal studies suggesting that, for some cancers, following the removal of the primary lesion, the growth rate of metastatic lesions does increase.What the authors neglected to point out is that this effect is transient, lasting for a few hours to, at most, a few days.They provide additional misleading information by suggesting that this results in earlier death.With the possible exception of their reference 15 from 1979, the other laboratory studies specifically state that this phenomenon did not lead to earlier deaths.Their own survival curves fail to show any earlier mortality among the premenopausal women.They do not provide
Iceland breast cancer study questions the risk attributable to gene mutations
Authors: V. Madden
Journal: BMJ (1998)

The risk of breast cancer in carriers of the BRCA2 gene–one of the two major genes associated with the disease–may be lower in some populations than previously suggested, according to a study from Iceland.

The Icelandic study ( Lancet 1998;352:1337-9) estimated that the risk of breast cancer in those with the BRCA2 gene mutation is 37% at the age of 70. This was considerably lower than previous studies, such as the Ashkenazi Jewish study ( New England Journal of Medicine 1997;336:1401-8), which showed …
Oxidized CaMKII: a “heart stopper” for the sinus node?
Authors: Sabine Huke, Björn C. Knollmann
Journal: Journal of Clinical Investigation (2011)

Each normal heart beat is triggered by an electrical impulse emitted from a group of specialized cardiomyocytes that together form the sinoatrial node (SAN). In this issue of the JCI, Swaminathan and colleagues demonstrate a new molecular mechanism that can disrupt the normal beating of the heart: angiotensin II - typically found in increased levels in heart failure and hypertension - oxidizes and activates Ca2+/calmodulin-dependent kinase II via NADPH oxidase activation, causing SAN cell death. The loss of SAN cells produces an electrical imbalance termed the "source-sink mismatch," which may contribute to the SAN dysfunction that affects millions of people later in life and complicates a number of heart diseases.
Pharmacologic Treatment of Alcohol Withdrawal-Reply
Authors: Michael Mayo-Smith
Journal: JAMA (1997)

In Reply.  —Dr Johnson expresses concern about the level of significance in 1 of the 11 statistical analyses we performed. In approaching our topic, we attempted to follow the basic principles of the scientific method as it applies to meta-analyses. Meta-analysis can be viewed as a research project in which the unit of analysis is the individual study rather than an individual patient. As such, we formed our hypotheses and plan for analysis before searching and reviewing the medical literature. We identified criteria for study inclusion, including standards for study design, inclusion and exclusion criteria, treatment protocol, and measurement of outcomes. We identified 4 studies that met these criteria, analyzed them using a conservative approach recommended by our statistical consultants, and report the results. As such, we feel the recommendations are based on the best available evidence and represent reasonable positions. The lack of well-designed trials addressing the relative efficacy of the
The use of Sirolimus should be restricted in liver transplantation
Authors: Omar Massoud, Russell H. Wiesner
Journal: Journal of Hepatology (2011)

Sirolimus and mTOR inhibitors are important additions to the therapeutic armamentarium to prevent allograft rejection, but their role in liver transplantation is evolving. De novo use of Sirolimus in the early post-transplant period has undoubtedly been influenced by the high incidence of hepatic artery thrombosis and decreased patient and graft survival leading to a black box warning. The jury remains undecided on the role of conversion from CNIs to mTOR inhibitors in those developing renal insufficiency and it must be noted that a second warning was issued by the FDA because of decreased survival in those conversion studies. Finally, the anti-atherogenic, antiviral, and anti-neoplastic effects associated with Sirolimus, which might favor their use in certain liver transplant patients, need further evaluation before firm recommendations can be made.
Vein of Galen Malformation With Cutaneous Signs
Authors: Jamie Zussman, Noriko Salamon, Ki-Young Suh
Journal: JAMA Dermatology (2013)

Cutaneous vascular malformations may be the presenting sign of more serious internal abnormalities. This case of vein of Galen malformation (VGAM) illustrates the importance of obtaining imaging studies in select cases.
How on earth do we combat climate change?
Authors: F. Godlee
Journal: BMJ (2011)

The greatest risk to human health is neither communicable nor non-communicable disease, it is climate change. Saying this, as I and others have started doing at conferences, seems to take a certain courage. We’ve been emboldened by clear statements from WHO’s director general Margaret Chan and from the Lancet (www.thelancet.com/climate-change). But this week, at a meeting hosted by the BMJ in collaboration with an extraordinary alliance of organisations (http://climatechange.bmj.com, doi:10.1136/bmj.d6775), it became clear that we are going to have to get braver still.

Let me begin by acknowledging that putting climate change at the top of the list of things to worry about is hard when faced …
Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults
Authors: David Gómez-Almaguer, Miguel A. Herrera-Rojas, José C. Jaime-Pérez, Andrés Gómez-De León, Olga G. Cantú-Rodríguez, César H. Gutiérrez-Aguirre, Luz Tarín-Arzaga, Jesús Hernández-Reyes, Guillermo J. Ruiz-Arguelles
Journal: Blood (2014)
Proinflammatory cytokines in nasal secretions of allergic subjects after antigen challenge.
Authors: T C Sim, J A Grant, K A Hilsmeier, Y Fukuda, R Alam
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

To study the role of cytokines in allergic late-phase reactions (LPR), we measured cytokines (interleukins [IL]-1 beta, IL-2, IL-4, IL-5, IL-6, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in nasal secretions (NS) of eight allergic subjects following antigen or saline provocation. NS were collected hourly for 10 h after challenge by a newly developed matrix method. All subjects recorded hourly symptom scores. Cytokines were measured using specific enzyme-linked immunosorbent assays (ELISA). Compared with prechallenge values, significant levels of IL-1 beta were detected in all subjects during the immediate reaction (peak, 51.0 +/- 22.4 pg/ml) and LPR (peak, 78.5 +/- 22.6 pg/ml) after antigen challenges (p < 0.01) but not saline challenges. In contrast, GM-CSF and IL-6 showed a delayed rise (peak, 26.4 +/- 1.3 pg/ml and 33.8 +/- 10.0 pg/ml, respectively) at hour 4 in the antigen-challenge period (p < 0.01 versus saline). NS from 4 donors also showed detectable IL-5 (7.6 to 155 pg/ml) during the immediate reaction and LPR after allergen challenges (versus saline, p < 0.01). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during the immediate reaction (IL-1 beta) and LPR (IL-1 beta, GM-CSF, and IL-6). IL-2 and IL-4 were not detected in any sample. Thus, IL-1 beta, IL-5, IL-6, and GM-CSF are present in the LPR of allergic rhinitis, and their correlation with clinical responses may suggest their role in allergic inflammation.
British researchers to clone human stem cells to study motor neurone disease
Authors: Kmietowicz Zosia
Journal: BMJ (2005)

The British research team that created Dolly the sheep has been granted a licence to clone human embryos to study motor neurone disease.

The licence will allow researchers at the Roslin Institute in Edinburgh and King's College in London to generate stem cell lines from embryos created using DNA from patients with motor neurone disease. They will focus on uncovering the cause of the motor neurone disease in patients whose condition cannot be linked to the genes already identified as causing the disease.

It is only the second time that the United …