tbuckley/cabot-search huggingface dataset:
456. HOXB4 Overexpression Expands Short-Term Repopulating Cells in Nonhuman Primates and Dogs
Authors: Xiao-Bing Zhang, Laura J. Peterson, Alixandra A. Knapp, Brian C. Beard, R. Keith Humphries, Hans-Peter Kiem
Journal: Molecular Therapy (2005)

Human HOXB4 overexpression is able to extensively expand hematopoietic repopulating stem cells in murine models. Here we examined the effect of HOXB4 in two commonly used large-animal models using competitive repopulation assay. Three macaques and five dogs were transplanted with peripheral blood CD34+ cells transduced with a HOXB4/GFP or a control YFP gammaretroviral vector after lethal irradiation. Two dogs and one monkey died from transplant related complications. Follow-ups for the other three dogs and two monkeys are eight months and nine months, respectively. For all animals pretransplant gene transfer efficiencies in CD34+ cells were similar between HOXB4/GFP and YFP transduced cells: 45% (range 36-55%) and 38% (range 36- 40%) in macaque cells, and 48% (range 23-69%) and 51% (range 31-62%) in dog cells. In all 3 monkeys the initial gene transfer levels in vivo one week after transplantation were higher with the control YFP vector (average, 32% vs 25%). A similar trend was observed for three of the five dogs (average, 21% vs 11% for YFP vs GFP). In all the animals, dogs and monkeys, we observed a dramatic increase in HOXB4/GFP marked cells from 5-30% to 10-62% during the early engraftment period resulting in a significant difference between HOXB4/GFP and YFP marked granulocytes. The peak ratio between HOXB4-overexpressing to YFP-expressing in the three surviving dogs was approximately four at 5-6 weeks post-transplant. In the monkeys the peak ratio was up to ten at 5 weeks post-transplant. Interestingly, in all the dogs the HOXB4/GFP transduced cells decreased to within 2 fold of the control vector by week 15. Taqman PCR analysis of samples at the latest time point in all animals confirmed that the decrease in gene-marked cells was not due to transgene silencing. Subset analysis showed that the ratios of HOXB4-overexpressing cells to YFP-expressing cells were obviously higher for granulocytes than for lymphocytes in macaques and dogs, indicating that HOXB4 overexpression may inhibit lymphoid differentiation or/and promote higher level expansion of myeloid progenitors than lymphoid progenitors. In conclusion, our preclinical studies show that HOXB4 overexpression in CD34+ cells can expand hematopoietic cells that boost short-term engraftment.
(Not so) positive illusions
Authors: Justin Kruger, Steven Chan, Neal Roese
Journal: Behavioral and Brain Sciences (2009)

Abstract We question a central premise upon which the target article is based. Namely, we point out that the evidence for “positive illusions” is in fact quite mixed. As such, the question of whether positive illusions are adaptive from an evolutionary standpoint may be premature in light of the fact that their very existence may be an illusion.
Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo.
Authors: C A Head, C Brugnara, R Martinez-Ruiz, R M Kacmarek, K R Bridges, D Kuter, K D Bloch, W M Zapol
Journal: Journal of Clinical Investigation (1997)

The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; P < 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.
Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models
Authors: Swapnil S. Desale, Srikumar M. Raja, Jong Oh Kim, Bhopal Mohapatra, Kruti S. Soni, Haitao Luan, Stetson H. Williams, Timothy A. Bielecki, Dan Feng, Matthew Storck, Vimla Band, Samuel M. Cohen, Hamid Band, Tatiana K. Bronich
Journal: Journal of Controlled Release (2015)
Variation in the alpha2B-adrenoceptorgene as a risk factor for prehospitalfatal myocardial infarction and sudden cardiac death
Authors: Amir Snapir, Jussi Mikkelsson, Markus Perola, Antti Penttilä, Mika Scheinin, Pekka J Karhunen
Journal: Journal of the American College of Cardiology (2003)
UN seeks $160m to help a million people affected by Libyan crisis
Authors: J. Zarocostas
Journal: BMJ (2011)

The United Nations and partner agencies have launched a regional flash appeal for $160m (£100m; €115m) to scale up humanitarian assistance to a million people affected by the Libyan crisis.

Valerie Amos, the UN’s emergency relief coordinator, said, “This appeal is based on a planning scenario projecting up to 400 000 people leaving Libya—including the 200 000 who have left to date—and another 600 000 people inside Libya expected to need humanitarian aid to varying degrees.” 

The appeal includes $11m for health and nutrition, $48m for food security, and $6m for water, sanitation, and hygiene.

Fierce fighting between forces of Colonel Muammar …
Effect of astemizole on antigen‐mediated histamine release from the blood of patients with allergic rhinitis
Authors: B. A. Faraj, R. T. Jackson
Journal: Allergy (1992)

The main objective of this study was to test the effectiveness of astemizole in vitro in blocking the release of histamine from blood of patients with allergic rhinitis. The results of this investigation indicated that astemizole inhibited allergen‐mediated histamine release from blood basophils of patients with this allergic disorder. The inhibition by astemizole (33–156 μmol) was immediate, requiring no pre‐incubation of the cells, and was dose‐dependent, with maximal inhibition of about 91%. The relatively high potency of astemizole in inhibiting the immunologic release of histamine may provide an additional measure in the treatment of allergic rhinitis with this H i‐receptor antagonist.
The Abused Child
Authors: John B. Reinhart, Elizabeth Elmer
Journal: JAMA (1964)

The Children's Bureau has proposed a law requiring physicians to report instances of suspected child abuse. Value of the model legislation lies in ordering conflicting values held by physicians, extending rational management of abuse problems, and facilitating detection of dangerous situations. But the proposed law has drawbacks: Focus is on the patient to the exclusion of siblings who may also be mistreated. Hazards for the injured child may be augmented by the caretakers' fear of prosecution. Reporting to a social agency appears preferable to reporting to the police. Physicians have much to contribute toward effective laws to protect children from abuse.
Highly Drug-Resistant Tuberculosis
Authors: Alfredo Ponce de Leon
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The beautiful demonstration by Dr Frieden and colleagues<sup>1</sup>that transmission of a single strain of<i>Mycobacterium tuberculosis</i>accounted for much of the recent increase in multidrug-resistant tuberculosis (TB) in New York City raises the question of the generalizability of this finding to other cities. We perform drug susceptibility testing on approximately 180 isolates each year in our clinical microbiology laboratory, located in a tertiary care referral center in Mexico City. Between January 1990 and December 1991, 178 initial isolates from 178 patients referred from Mexico's National Institutes of Health were tested for resistance to 9 antibiotics using the Bactec system (Becton: Dickerson, Cockeyville, Md). Although this is not a systematic sampling for TB in Mexico City, it included isolates from a wide variety of settings, including 26 cases infected with human immunodeficiency virus (HIV). Of these 178 isolates, 40 were resistant to isoniazid and rifampin. Knowing
In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.
Authors: B D Hoit, Y Shao, M Gabel, R A Walsh
Journal: Circulation (1994)

BACKGROUND Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P &lt; .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.
Capsule Endoscopy Is Not as Accurate as Esophagogastroduodenoscopy in Screening Cirrhotic Patients for Varices
Authors: Disaya Chavalitdhamrong, Dennis M. Jensen, Bhavneet Singh, Thomas O.G. Kovacs, Steven H. Han, Francisco Durazo, Sammy Saab, Jeffrey A. Gornbein
Journal: Clinical Gastroenterology and Hepatology (2011)
A Placebo-Controlled, Four-Way Crossover Study Comparing Azelastine Nasal Spray, Cetirizine and Loratadine in Adult Subjects with Ragweed-Induced Seasonal Allergic Rhinitis in the Environmental Exposure Unit (EEU)
Authors: J.D. Ratz, J.H. Day, M.P. Briscoe
Journal: Journal of Allergy and Clinical Immunology (2009)
Excess coronary heart disease in South Asians in the United Kingdom
Authors: Velmurugan C Kuppuswamy, Sandeep Gupta
Journal: BMJ (2005)

The problem has been highlighted, but much more needs to be done 

Health inequality between ethnic groups in the United Kingdom is widening.1 Death rates from coronary heart disease in South Asians (immigrants from India, Pakistan, Bangladesh, and Sri Lanka) have declined at a slower rate than in the indigenous population.2 Accumulating evidence shows that second and third generation South Asians seem to be displaying many of the same risk characteristics that make them prone to coronary heart disease as their parents and grandparents.3 The first published evidence of elevated risk of coronary heart disease in South Asians appeared as early as 1959—from a study based on expatriate Indians in Singapore.w1 Numerous subsequent studies corroborated the findings. However, the topic of ethnicity and disparities in outcomes from coronary heart disease in the United Kingdom has only recently been given the importance it deserves.w2

We still do not have an explanation for excess deaths from coronary heart disease in South Asians, but several plausible hypotheses have been generated (box).w3 w4 The increased prevalence of the metabolic syndrome (comprising insulin resistance, hypertension, central obesity, and hyperlipidaemia) and diabetes mellitus in this population is the most convincing and consistent explanation to date.w3 None of the hypotheses has been studied systematically, and current understanding …
Computer-Assisted Learning and Evaluation in Medicine
Authors: Thomas E. Piemme
Journal: JAMA (1988)

The use of the computer in medical education has been in evolutionary development since the early 1960s; its adoption, however, has been less widespread than the promise of the medium should warrant. Computer-assisted instruction enhances learning, allowing the student the discretion of content, time, place, and pace of instruction. Information conveyed can take several forms, some better suited to undergraduate medical education, others more applicable to graduate and continuing education. The use of the computer in certification and licensure could, within a decade, transform the way competence is assessed. Its greatest promise, however, may lie in providing pertinent information at the time when, and in the place where, patient care takes place. New developments in data storage and retrieval forecast applications that could not have been imagined even a year or two ago. (<i>JAMA</i>1988;260:367-372)
Protective Effect of an SDF-1 Variant in HIV Disease
Authors: Nelson L. Michael
Journal: JAMA (1998)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a
coreceptor with CD4 for T lymphocyte cell line–tropic human immunodeficiency
virus–type 1 (HIV-1). A common polymorphism, SDF1-3′A, was identified in an evolutionarily conserved segment of the 3′
untranslated region of the SDF-1 structural gene transcript. In the homozygous
state, SDF1-3′A/3′A delays the onset
of acquired immunodeficiency syndrome (AIDS), according to a genetic association
analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive
protective effect of SDF1-3′A was increasingly
pronounced in individuals infected with HIV-1 for longer periods, was twice
as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants
in these populations, and was complementary with these mutations in delaying
the onset of AIDS.
Exercise-induced Asthma
Authors: A. Seaton, G. Davies, D. Gaziano, R. O. Hughes
Journal: BMJ (1969)

Tests in three patients with asthma occurring only on exertion showed that F.E.V.(1) fell progressively on exercise, to reach a minimum after 10 minutes. All patients showed a striking metabolic acidosis, with an accumulation of the products of anaerobic metabolism.
Anti-CD20 antibody-mediated apoptosis of B cells is a lipid raft-dependent process
Authors: J.-O. Pers, M. Hammadi, F. Dalbies, A. Tempescul, C. Berthou, A. Bordron, P. Youinou
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> B cell depletion has become a classics in approved conditions and off-label indications. Anti-CD20 have been classified into type-I, such as rituximab (RTX), and type-II monoclonal antibodies (mAbs), such as tositumomab (B1). Since the effects of RTX are variable in autoimmune diseases, the authors have tested those of B1 on the easily accessible B cells of chronic lymphocytic leukaemia (CLL) and marginal zone lymphoma (MZL). This mAb requires translocation of its target into lipid rafts (LR) containing cholesterol, sphingomyelin (SM), ganglioside M1 (GM1) and proteins associated such as Cbp/P-glycoprotein (PAG) implicated in signalling. <h3>Material and methods</h3> B lymphocytes were obtained from 36 untreated CLL patients and 8 MZL used as disease controls. B cells were cultured in 24-well plates at 37°C with or without B1. Apoptosis was investigated using annexin V/propidium iodide. GM1 and SM, were quantified by flow cytometry and Western blotting as well as Cbp/PAG and PGP. Modulation activity of tositumomab by rifampicin, an activator of Pgp was visualised by annexin V/propidium iodide. Characterisation of LR-associated proteins was performed by confocal microscopy. <h3>Results</h3> B1-binding induced B cell apoptosis in 50% of CLLs, and in all MZL tested. A higher CD20 expression was not correlated with sensitivity to B1-induced apoptosis. In fact, apoptosis was associated with a higher GM1 and extramembrane expression of SM leading to the recruitment of Cbp/PAG. The authors observed by confocal microscopy that, in this case, CD20, SM and Cbp/PAG were colocalized. In contrast, those CLL B cells resisting B1-mediated apoptosis, sequestrated SM in the cytoplasm, due to a decrease of Pgp activity. Pgp are indeed implicated in SM exportation to the outer leaflet of the membrane and can be activated by rifampicin. Restored Pgp activity with rifampicin in anti-CD20 resistant B cell leads to an increased location of SM at the outer side of the cell membrane, the recruitment of Cbp/PAG and the induction of apoptosis. <h3>Conclusions</h3> This data supports the view of a fine regulation of lipids implicated in survival or apoptotic signals in B cells. Acting on the lipid distribution at the cell membrane will permit to improve anti-CD20 mAb efficacy.
Quantitative Metrics of Net Proliferation and Invasion Link Biological Aggressiveness Assessed by MRI with Hypoxia Assessed by FMISO-PET in Newly Diagnosed Glioblastomas
Authors: Mindy D. Szeto, Gargi Chakraborty, Jennifer Hadley, Russ Rockne, Mark Muzi, Ellsworth C. Alvord, Kenneth A. Krohn, Alexander M. Spence, Kristin R. Swanson
Journal: Cancer Research (2009)

Glioblastoma multiforme (GBM) are aggressive and uniformly fatal primary brain tumors characterized by their diffuse invasion of the normal-appearing parenchyma peripheral to the clinical imaging abnormality. Hypoxia, a hallmark of aggressive tumor behavior often noted in GBMs, has been associated with resistance to therapy, poorer survival, and more malignant tumor phenotypes. Based on the existence of a set of novel imaging techniques and modeling tools, our objective was to assess a hypothesized quantitative link between tumor growth kinetics [assessed via mathematical models and routine magnetic resonance imaging (MRI)] and the hypoxic burden of the tumor [assessed via positron emission tomography (PET) imaging]. Our biomathematical model for glioma kinetics describes the spatial and temporal evolution of a glioma in terms of concentration of malignant tumor cells. This model has already been proven useful as a novel tool to dynamically quantify the net rates of proliferation (rho) and invasion (D) of the glioma cells in individual patients. Estimates of these kinetic rates can be calculated from routinely available pretreatment MRI in vivo. Eleven adults with GBM were imaged preoperatively with (18)F-fluoromisonidazole (FMISO)-PET and serial gadolinium-enhanced T1- and T2-weighted MRIs to allow the estimation of patient-specific net rates of proliferation (rho) and invasion (D). Hypoxic volumes were quantified from each FMISO-PET scan following standard techniques. To control for tumor size variability, two measures of hypoxic burden were considered: relative hypoxia (RH), defined as the ratio of the hypoxic volume to the T2-defined tumor volume, and the mean intensity on FMISO-PET scaled to the blood activity of the tracer (mean T/B). Pearson correlations between RH and the net rate of cell proliferation (rho) reached significance (P < 0.04). Moreover, highly significant positive correlations were found between biological aggressiveness ratio (rho/D) and both RH (P < 0.00003) and the mean T/B (P < 0.0007).
Thyroid Hormone Action at the Cell Level
Authors: Kenneth Sterling
Journal: New England Journal of Medicine (1979)

(Second of Two Parts)Inter-relation between Thyroid Hormone, Catecholamines and β-Adrenergic ReceptorsPrevious speculation and many data in this area are omitted for the sake of brevity. Some of the manifestations of clinical thyrotoxicosis resemble excessive adrenal medullary activity. Moreover, the β-adrenergic blocking agent, propranolol, has been successfully employed in the management of some manifestations of thyrotoxicosis.91 It is therefore appropriate to mention recent findings suggesting an increased number of β-adrenergic receptor sites in the cardiac plasma membranes of experimental hyperthyroid rats.92 93 94 Cardiac membranes (in a mixture including microsomes) from rats rendered toxic with excess thyroid hormone exhibited an increased . . .
Therapeutic thrombolysis for acute ischaemic stroke
Authors: C. Warlow
Journal: BMJ (2003)

Therapeutic thrombolysis for acute myocardial infarction is standard practice, but not so for ischaemic stroke, the “brain attack” equivalent of heart attack. This is partly because stroke is more complicated: intracerebral haemorrhage must be excluded by imaging, and more vascular pathologies than atheroma underly ischaemic stroke (for example, intracranial small vessel disease and embolism from the heart). Furthermore, coronary care units make research on heart attacks relatively easy, whereas research on acute stroke still often takes place in general medical wards. With stroke units, this will be less of a problem. Research on strokes is woefully underfunded in comparison to research on heart attacks.1 But, if thrombolytic “unblocking the pipes” works for acutely occluded coronary arteries, it should work for acutely occluded brain arteries, provided reperfusion does not make matters worse by increasing cerebral oedema and haemorrhagic transformation. As usual, the balance of benefit and risk is best determined by randomised trials—facts, not opinions and theories.

Here again there is a difference between heart attack and brain attack. For the former, about 60 000 patients …