tbuckley/cabot-search huggingface dataset:
Voluntary exercise protects against methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood–brain barrier
Authors: Michal Toborek, Melissa J Seelbach, Cetewayo S Rashid, Ibolya E András, Lei Chen, Minseon Park, Karyn A Esser
Journal: Molecular Neurodegeneration (2013)

There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood–brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock lab™ Analysis software. Controls included mice sedentary that did not have access to running wheels and/or injections with saline. METH induced oxidative stress in brain microvessels, resulting in up regulation of caveolae-associated NAD(P)H oxidase subunits, and phosphorylation of mitochondrial protein 66Shc. Treatment with METH disrupted also the expression and colocalization of tight junction proteins. Importantly, exercise markedly attenuated these effects and protected against METH-induced disruption of the BBB integrity. The obtained results indicate that exercise is an important modifiable behavioral factor that can protect against METH-induced cerebrovascular toxicity. These findings may provide new strategies in preventing the toxicity of drug of abuse.
Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial
Authors: Robert Zimmer, Hugo R Scherbarth, Oscar Luis Rillo, Juan Jesus Gomez-Reino, Sylviane Muller
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To evaluate treatment with the peptide-based agent, Lupuzor, in a double-blind, randomised, placebo-controlled study of patients with systemic lupus erythematosus. <h3>Methods</h3> Patients who met ≥4 of the American College of Rheumatology criteria, had a score of ≥6 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and did not have an A score on the British Isles Lupus Assessment Group (BILAG)-2004 scale were eligible. 149 intention-to-treat (ITT) patients were randomly assigned to receive Lupuzor (200 μg) subcutaneously every 4 weeks (n=49; group 1) or every 2 weeks (n=51; group 2) or placebo (n=49; group 3) in addition to standard of care (SOC). A target population (136 ITT patients) consisting of patients having a clinical SLEDAI score ≥6 at week 0 was considered. The clinical SLEDAI score is the SLEDAI-2K score obtained by omitting low complement and increased DNA binding components. <h3>Results</h3> In the ITT overall population, 53.1% in group 1 (p=0.048), 45.1% in group 2 (p=0.18) and 36.2% in the placebo group achieved an SLE Responder Index (SRI) response at week 12. In the target population, the results were more impressive: 61.9% in group 1 (p=0.016), 48.0% in group 2 (p=0.18) and 38.6% in the placebo group achieved an SRI response at week 12. An interim analysis including 114 patients from the target population demonstrated an even better efficacy (according to SLEDAI score) in group 1 compared with placebo (67.6% vs 41.5% (p&lt;0.025) at week 12 and 84.2% vs 45.8% (p&lt;0.025) at week 24). The most common adverse event was a mild injection-site erythema. <h3>Conclusions</h3> Lupuzor/200 µg given three times at 4-week intervals during 12 weeks in addition to SOC is efficacious and generally well tolerated.
PERSISTENT NASAL CATARRH IN CHILDREN
Authors: D. Guthrie
Journal: BMJ (1929)

Research on the chemical.oonstituition of the blood in these patients may be a helpful line which I intend to investigate further.CLASS D. This consists of cases in which operations in the throat had been badly perfoimed, and which cleared up after thorougih rem-val of adenoids. CLASS E.Cases in tlhis class are included merely to show the material onl whiclh this communication is-based.-CONCLUSIONS.The poin1ts which have appealed to me in reviewing these cases are:1.That the presence of pus or muco-pus in the nose must suggest the -possibility of sinus infection, although the presence of adenoids may prodiuce the sameo picture.2. That when dealiog with infection of -the -maxillary antrum ir1 children the possibility of ethmoid ilnfection at an early age rnust be-kept in mind.. *3.That before deciding on any operative form of treat- ment of a child's nose or throat a careful history should be obtained.This mnay form a useful guide to prognosis.-
Long-lived Min Mice Develop Advanced Intestinal Cancers through a Genetically Conservative Pathway
Authors: Richard B. Halberg, Jesse Waggoner, Kristen Rasmussen, Alanna White, Linda Clipson, Amy J. Prunuske, Jeffery W. Bacher, Ruth Sullivan, Mary Kay Washington, Henry C. Pitot, John H.J. Petrini, Donna G. Albertson, William F. Dove
Journal: Cancer Research (2009)

Abstract C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop numerous adenomas along the entire length of the intestine and consequently die at an early age. This short lifespan would prevent the accumulation of somatic genetic mutations or epigenetic alterations necessary for tumor progression. To overcome this limitation, we generated F1 ApcMin/+ hybrids by crossing C57BR/cdcJ and SWR/J females to C57BL/6J ApcMin/+ males. These hybrids developed few intestinal tumors and often lived longer than 1 year. Many of the tumors (24-87%) were invasive adenocarcinomas, in which neoplastic tissue penetrated through the muscle wall into the mesentery. In a few cases (3%), lesions metastasized by extension to regional lymph nodes. The development of these familial cancers does not require chromosomal gains or losses, a high level of microsatellite instability, or the presence of Helicobacter. To test whether genetic instability might accelerate tumor progression, we generated ApcMin/+ mice homozygous for the hypomorphic allele of the Nijmegen breakage syndrome gene (Nbs1ΔB) and also treated ApcMin/+ mice with a strong somatic mutagen. These imposed genetic instabilities did not reduce the time required for cancers to form nor increase the percentage of cancers nor drive progression to the point of distant metastasis. In summary, we have found that the ApcMin/+ mouse model for familial intestinal cancer can develop frequent invasive cancers in the absence of overt genomic instability. Possible factors that promote invasion include age-dependent epigenetic changes, conservative somatic recombination, or direct effects of alleles in the F1 hybrid genetic background. [Cancer Res 2009;69(14):5768–75]
Protection against Mycobacterium ulcerans Lesion Development by Exposure to Aquatic Insect Saliva
Authors: Laurent Marsollier, Estelle Deniaux, Priscille Brodin, Agnès Marot, Christelle Mbondji Wondje, Jean-Paul Saint-André, Annick Chauty, Christian Johnson, Fredj Tekaia, Edouard Yeramian, Pierre Legras, Bernard Carbonnelle, Gilles Reysset, Sara Eyangoh, Geneviève Milon, Stewart T Cole, Jacques Aubry
Journal: PLoS Medicine (2007)

Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%-10% of these aquatic insects captured in endemic areas have M. ulcerans-loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.
Social Control of the Brain
Authors: Russell D. Fernald
Journal: Annual Review of Neuroscience (2012)

In the course of evolution, social behavior has been a strikingly potent selective force in shaping brains to control action. Physiological, cellular, and molecular processes reflect this evolutionary force, particularly in the regulation of reproductive behavior and its neural circuitry. Typically, experimental analysis is directed at how the brain controls behavior, but the brain is also changed by behavior over evolution, during development, and through its ongoing function. Understanding how the brain is influenced by behavior offers unusual experimental challenges. General principles governing the social regulation of the brain are most evident in the control of reproductive behavior. This is most likely because reproduction is arguably the most important event in an animal's life and has been a powerful and essential selective force over evolution. Here I describe the mechanisms through which behavior changes the brain in the service of reproduction using a teleost fish model system.
Response to Comment on Lin et al. Risk Factors for Decline in IQ in Youth With Type 1 Diabetes Over the 12 Years From Diagnosis/Illness Onset. Diabetes Care 2015;38:236–242
Authors: Ashleigh Lin, Elisabeth A. Northam, George A. Werther, Fergus J. Cameron
Journal: Diabetes Care (2015)

Shan and Ji (1) question the reliability of the association between a decline in performance intelligence quotient (PIQ) and younger age of type 1 diabetes (T1D) onset, which we recently reported from our longitudinal study of youth with T1D and healthy controls (HCs) (2). They suggest that if there is a significant association between decline in PIQ and age of onset, then there should also be a significant difference for change in PIQ between participants with T1D and HCs. They also suggest that the association between decline in PIQ and younger age of T1D onset might be attributed to known age-related changes in IQ from adolescence to adulthood or other factors, such as the researcher conducting the tests or the emotional and physical state of participants. We address each of these concerns in turn.

Shan and Ji suggest …
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome
Authors: Gretel B. Kamm, Francisco Pisciottano, Rafi Kliger, Lucía F. Franchini
Journal: Molecular Biology and Evolution (2013)

To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution.
Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy
Authors: M. Campone, I. Bondarenko, S. Brincat, Y. Hotko, P.N. Munster, E. Chmielowska, P. Fumoleau, R. Ward, N. Bardy-Bouxin, E. Leip, K. Turnbull, C. Zacharchuk, R.J. Epstein
Journal: Annals of Oncology (2011)
Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.
Authors: N.J Goulding, S.M Knight, J.L Godolphin, P.M Guyre
Journal: Annals of the Rheumatic Diseases (1992)

The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.
The Direct Renal Vascular Effects of Epinephrine and Norepinephrine before and after Adrenergic Blockade
Authors: MERRILL P. SPENCER, ADAM B. DENISON, HAROLD D. GREEN
Journal: Circulation Research (1954)

By use of a noncannulating electromagnetic flowmeter the direct vasoconstrictor response of the dog renal vasculature to intra-arterial epinephrine was found to bebut slightly greater, weight for weight, than that of norepinephrine. No dilation phase to their reactions was found before or after Ilidar, and this adrenergic blocking drug failed to dilate the renal vasculature in four out of five dogs in the anesthetized and operated state.
Results of Bariatric Surgery
Authors: Erik N. Hansen, Alfonso Torquati, Naji N. Abumrad
Journal: Annual Review of Nutrition (2006)

Overweight and obesity are rapidly growing to epidemic proportions in the United States and globally. Since sustainable weight loss is only achieved by bariatric surgery, medicine has seen an explosion in the diversity and number of bariatric procedures performed over the past few years. Systematic studies of postoperative outcomes and investigations into the physiology and biology of weight loss provide a more comprehensive understanding of the sequelae of bariatric surgery. Adipose tissue is the predominant site of fat stores. Increasing obesity results in an overload of lipids within the body's natural storage sink (i.e., the adipocyte) followed by the necessary deposition of fat within ectopic sites such as muscle, liver, and pancreas. The resulting metabolic derangements are associated with insulin resistance, central obesity, and chronic inflammation as adipose tissue acts as an endocrine organ, producing and secreting a host of biologic mediators. Whereas there are conflicting data on the cardiovascular effects of peripheral, subcutaneous liposuction, malabsorptive bariatric procedures result almost universally in significant amelioration of insulin resistance, hypertension, dyslipidemia, and hepatic steatosis. Concomitant changes in adipocyte-derived hormones may provide mechanistic explanations to the observed improvements.
Is Bendectin a Teratogen?
Authors: José F. Cordero
Journal: JAMA (1981)

We studied the first-trimester exposure to Bendectin for several major categories of birth defects among infants ascertained through the Metropolitan Atlanta Congenital Defects Program from 1968 to 1978. No associations were found between any of these defect categories and Bendectin exposure. An association, however, was found for the amniotic bands cases--a subgroup of limb reductions. We stratified our data to reflect the 1976 change in formulation when one of the three ingredients was removed. An association was found between esophageal atresia and the three-ingredient product and another between encephalocele and the two ingredient product. These statistical associations do not establish a causal relationship between Bendectin and the birth defects we studied. Furthermore, even if the associations are causal, the implied risk is extremely low, approximately one in 1,000 births.
Medicine at the 2000 Sydney Olympic Games: the New Zealand health team: Table 1
Authors: D Robinson, C Milne
Journal: British Journal of Sports Medicine (2002)

A medical team of 14 accompanied the New Zealand team to the 2000 Olympics in Sydney. The team comprised four doctors, seven physiotherapists, a sports psychologist, a chiropractor, and a massage therapist. In addition, two teams (cycling and women's hockey) had dedicated physiotherapists, and sailing brought their own massage therapist.

The month long stay at the Games could be roughly divided into four one week periods. The first week involved the arrival of the medical team over the first weekend that the Games village was open. The sailing team arrived at a similar time and a few other athletes arrived during the week. This week was largely taken up with setting up the medical room in a bare basement area, reconnaissance of the village and Olympic site, attendance at training as required, and providing a service to those already in the …
US cancer mortality may be underestimated
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Cancer mortality in the United States may be underestimated, because deaths within a month of surgery for solid tumours are recorded as deaths related to treatment, according to researchers.

Dr H Gilbert Welch and Dr William Black of Dartmouth Medical School in New Hampshire argue that cancer mortality should include not only deaths from cancer but also deaths caused by treatment for cancer. In the Journal of the National Cancer Institute (2002;94:1066-70) they report that 41% of deaths within a month of treatment for cancer were attributed …
Blood Flow in the Right Coronary Artery of the Dog
Authors: G. Ross
Journal: Cardiovascular Research (1967)

Phasic and mean blood flow in the right coronary artery of either the anesthetized open-chest or the conscious dog is qualitatively similar to that in the left coronary artery. Systolic flow accounts for an appreciable proportion of total flow. Both diastolic and systolic flow are increased following short periods of right coronary artery occlusion. Local injections of adrenaline and noradrenaline resulted in an increase in mean flow despite a reduction or reversal of flow in the isovolumetric phase of systole.
PROTEINURIA RELATED TO HYPERPROTEINEMIA IN DOGS FOLLOWING PLASMA GIVEN PARENTERALLY
Authors: Roger Terry, David R. Hawkins, Edwin H. Church, G. H. Whipple
Journal: The Journal of Experimental Medicine (1948)

Proteinuria in normal dogs can be produced at will by parenteral injections of dog plasma. As the plasma injections are continued the plasma protein concentration rises and at some point protein begins to appear in the urine. The level of plasma protein concentration at which proteinuria appears in normal dogs ranges from 9.6 to 10.4 gm. per cent. This may be termed the renal threshold for proteinuria. Repeat experiments in the same dog show threshold levels to be practically identical. An interval of days (4 to 26 days) has been noted between the start of plasma protein injections and the appearance of the proteinuria. Larger doses of plasma shorten this interval and the critical plasma protein level is attained sooner. Considerable amounts of protein may appear in the urine—298 gm. protein during a 52 day period in one instance studied—yet the urine clears in 1 to 4 days after cessation of protein injections. Autopsy shows undamaged kidneys. Maximal levels of plasma protein concentration range from 10.0 to 11.5 gm. per cent. The highest levels are usually associated with maximal output of protein in the urine. It seems clear that plasma proteins readily pass cell barriers (or membranes) within the body, including the endothelium and epithelium of the renal glomerulus.
Achilles paratendonitis: an evaluation of steroid injection.
Authors: D J DaCruz, M Geeson, M J Allen, I Phair
Journal: British Journal of Sports Medicine (1988)

A prospective, randomised, double-blind study of 28 patients presenting with Achilles paratendonitis was undertaken in order to evaluate the role of peritendonous injection of methy prednisolone acetate (Depo Medrone). At presentation patients were either administered peri-tendonous injection of 40 mgs of methyl prednisolone acetate suspended in 1 ml of 0.25% marcaine or 2 ml of 0.25% marcaine alone. Response was gauged by resolution of pain, tenderness and return to normal activity. Patients who failed to respond to initial treatment were crossed over to the other group at 12 weeks. All patients received standardised physiotherapy. Results indicate that peri-tendonous injection of methyl prednisolone acetate is of no value in Achilles paratendonitis.