tbuckley/cabot-search huggingface dataset:
B7-Dc, a New Dendritic Cell Molecule with Potent Costimulatory Properties for T Cells
Authors: Su-Yi Tseng, Mizuto Otsuji, Kevin Gorski, Xin Huang, Jill E. Slansky, Sara I. Pai, Ahmed Shalabi, Tahiro Shin, Drew M. Pardoll, Haruo Tsuchiya
Journal: The Journal of Experimental Medicine (2001)

Dendritic cells (DCs), unique antigen-presenting cells (APCs) with potent T cell stimulatory capacity, direct the activation and differentiation of T cells by providing costimulatory signals. As such, they are critical regulators of both natural and vaccine-induced immune responses. A new B7 family member, B7-DC, whose expression is highly restricted to DCs, was identified among a library of genes differentially expressed between DCs and activated macrophages. B7-DC fails to bind the B7.1/2 receptors CD28 and cytotoxic T lymphocyte–associated antigen (CTLA)-4, but does bind PD-1, a receptor for B7-H1/PD-L1. B7-DC costimulates T cell proliferation more efficiently than B7.1 and induces a distinct pattern of lymphokine secretion. In particular, B7-DC strongly costimulates interferon γ but not interleukin (IL)-4 or IL-10 production from isolated naive T cells. These properties of B7-DC may account for some of the unique activity of DCs, such as their ability to initiate potent T helper cell type 1 responses.
Effect of Treatment of C57BL/6 Mice With the Methanol Extraction Residue Fraction of BCG on Leukemogenesis Induced by the Radiation Leukemia Virus 2
Authors: Nechama Haran-Ghera, David W. Weiss
Journal: JNCI Journal of the National Cancer Institute (1973)

Treatment of C57BL/6 mice with the methanol extraction residue (MER) fraction of attenuated BCG conferred marked resistance, under the appropriate parameters of administration, against leukemogenesis induced by the radiation leukemia virus. The optimal protective effects of MER treatment were manifested when first administration was at a time at which some neoplastic cells had probably already appeared. The protection optimally bestowed lasted for the life of many animals.
Tissue Resident Cells Play a Dominant Role in Arteriogenesis and Concomitant Macrophage Accumulation
Authors: Eugen Khmelewski, Aileen Becker, Thomas Meinertz, Wulf D. Ito
Journal: Circulation Research (2004)

Collateral growth is characterized by macrophage accumulation, suggesting an important role of circulating cells. To study origin and function of macrophages during arteriogenesis, we related the extent of macrophage accumulation to vascular proliferation and investigated the fate of fluorescently (CMFDA) labeled blood cells that were injected at the time of femoral artery occlusion. The effect of bone marrow depletion via cyclophosphamide before femoral artery occlusion on collateral proliferation and macrophage accumulation was studied, and we looked for the presence of bone marrow-derived stem cells in the vicinity of growing collateral vessels. Finally, we investigated the arteriogenic effect of macrophage activation via MCP-1 in bone marrow-depleted animals. Maximal macrophage accumulation occurred during the first 3 days after femoral artery occlusion and paralleled the extent of vascular proliferation. Fluorescently labeled leukocytes homed to spleen and wound but they were absent in proliferating collateral arteries during maximal macrophage accumulation. Depletion of circulating cells did neither affect macrophage accumulation nor collateral growth. Staining of monocyte-depleted animals for BrdUrd and ED2, alphaSMA, or VE-Cadherin demonstrated local proliferation of macrophages and vascular cells, whereas C-Kit, SSEA1, or Thy1-positive bone marrow-derived stem cells were not detectable. Enhancement of macrophage accumulation via MCP-1 was independent of circulating monocytes and promoted arteriogenesis in the absence of direct effects on vascular cells. We propose that the initial phase of vascular growth is characterized by local proliferation of tissue resident precursors rather than by migration of blood born cells. The full text of this article is available online at http://circres.ahajournals.org.
Peak skeletal muscle perfusion is maintained in patients with chronic heart failure when only a small muscle mass is exercised
Authors: Gi Magnusson, Lennart Kaijser, Christer Sylvén, Karl-Erik Karlberg, Bengt Isberg, Bengt Saltin
Journal: Cardiovascular Research (1997)

The issue to be resolved was whether peripheral leg blood flow in patients with chronic heart failure (CHF) is reduced by low local flow capacity or as a function of the amount of muscle mass activated during exercise.In ten CHF patients (ejection fraction 26 (9)%), and 12 healthy controls central and peripheral circulatory responses were assessed during dynamic one- and two-legged knee extensor work. The patients reached a peak perfusion of 234 (16) ml 100 g-1 min-1 in the one-legged mode, which was similar to the controls (244 (11) ml 100 g-1 min-1). At peak two-legged work muscle perfusion was reduced in the patients by 24% (P < 0.05). In contrast the controls maintained their peak muscle perfusion. The mass of the quadriceps femoris muscle and peak leg blood flow correlated closely for both groups at peak one-legged work (r = 0.85, P < 0.001). Peak oxygen uptake in the active limb during one-legged exercise was similar for patients and controls (0.52 (0.06) vs. 0.63 (0.06) l min-1), but it was 38% lower (P < 0.05) in patients than controls during exhaustive two-legged exercise. Arterial systemic oxygen delivery (cardiac output x arterial oxygen content), at peak exercise was highly correlated with peak one- and two-legged workload for both groups, explaining 70% of the difference in peak workload attained (P < 0.001). At peak two-legged exercise non-exercising tissues of the body in the male CHF patients with the largest limb muscle mass, received a blood flow of only 1.2 (0.7) 1 min-1. Mean arterial blood pressure at peak work in both test conditions was significantly lower for the patients than the controls. A higher sympathetic nerve activity in the patients, as evaluated by arterial noradrenaline concentration (NA) and leg NA spillover, contributed to maintain the perfusion pressure.Patients with moderate CHF can reach a peak skeletal muscle perfusion and a leg oxygen uptake comparable to that of healthy individuals when a sufficiently small muscle mass is activated. Exercise involving a larger muscle mass, for the patients in this study about 4 kg, markedly reduces peak leg blood flow, perfusion and oxygen uptake as well as blood flow to non-exercising organs and tissues.
Gastroparesis and botulinum toxin
Authors: R. Rameshshanker, L. A. Smith, P. Southern, D. Whitelaw, C. Beckett
Journal: Gut (2011)

<h3>Introduction</h3> Gastroparesis is defined as delayed gastric emptying. The common causes are diabetes, post surgical, idiopathic. It s management poses a significant challenge in the practice of Gastroenterology. It is defined as resistant when usual conventional measures (Dietary modification, antiemetics, prokinetics, etc) fail to control the symptoms. We chose the resistant cases who underwent Botox (botulinul toxin A) treatment to the pyloric region. <h3>Methods</h3> It is a retrospective analysis of patients with resistant gastroparesis during Dec 2005–June 2010 in our District Hospital. Their OGD reports, case notes clinic letters were analysed. <h3>Results</h3> Total no of patients 21, Male 06, Female 15 (M:F 2:5). Age range 23–76 years. Mean age 47.8 years. Median and mean follow-up 2 years.81% (17) of them were diabetic, others were idiopathic cases. All of them had vomiting, 60% of them had bloating and early satiety as their presenting symptoms. All had antiemetics and prokinetics, 65% had erythromycin and 20% had amitriptyline. All of them had intrapyloric Botox (200 units) using 23G, 8 mm needle. Treatment repeated when symptoms recur. 61.8% showed good response to botox, 19% showed no response. Mean duration of response was 4.2 months.72% of diabetic gastroparesis showed good response. Significant improvement in GCIS (Gastroparesis Cardinal Symptom Index) noted in diabetic group (p &lt; 0.05).62% of diabetic gained weight and 50% insulin requirements increased post-treatment. <h3>Conclusion</h3> This is probably the first published study with longer follow-up period from UK (mean 2 years, maximum 3.8 years). More beneficial in diabetic gastroparesis. Less effective in idiopathic group. Failures may respond to gastric pacing.
Polymorphism of Inhibitory Renin-Angiotensin System as a Genetic Risk Factor for Atrial Fibrillation
Authors: Akiyoshi Ogimoto, Jitsuo Higaki, Tetsuro Miki
Journal: Circulation (2004)

We read with great interest the study by Tsai et al. 1 The authors showed that patients who have a specific genetic variation or polymorphism in the renin-angiotensin system (RAS) genes may be more likely to develop atrial fibrillation (AF) when exposed to environmental factors that elevate atrial pressure.Although we mostly agree with the authors, we believe AF is associated with reduced activation of the RAS in patients with certain types of cardiovascular disease.We recently reported that the insertion/insertion (I/I) genotype of the angiotensin I-converting enzyme (ACE) gene is a significant risk factor for atrial fibrillation 2 in patients with hypertrophic cardiomyopathy (HCM).Plasma ACE activity is significantly higher in individuals with the deletion allele than in individuals with the I allele.Patients with the ACE I/I genotype can be thought to be in a more circulatory ACE-inhibitory state than patients with the other genotypes.The RAS regulates sodium balance and intravascular volume and interacts with other blood pressure control mechanisms, including the sympathetic nervous system and baroreflexes.Because patients with HCM have a small left ventricular cavity size (SLVC) due to hypertrophy, reduction of intravascular volume may reduce cardiac output, leading to systemic hypotension.Therefore, activating the RAS may be a protective means for maintaining intravascular volume and a normal systemic circulation in these patients.In fact, vasodilator agents were reported to be unhelpful or even dangerous in patients with severe concentric left ventricular hypertrophy. 3 In addition, acute ACE inhibition in patients with obstructive HCM is known to lead to hypotension with significant reductions in both end-diastolic and end-systolic volumes. 4Thomson et al 5 suggested that hypotension during central volume unloading provides an additional or alternative trigger for arrhythmias in some patients with HCM.The mechanism by which central volume unloading would trigger AF is unknown, but it might be related to autonomic effects on pulmonary venous foci.Although in general, excessive volume overload is harmful in most types of cardiovascular disease, it may actually be beneficial to patients with an SLVC and reduction of intravascular volume.Patients with a genotype of inhibitory RAS genes may have unstable systemic circulation due to comparatively reduced intravascular volume compared with patients with another genotype of activating RAS genes in certain types of cardiovascular disease.Therefore, the reduced activation of the RAS in patients with an SLVC may play an important role in the development of AF.
Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial
Authors: Sajid Soofi, Simon Cousens, Aamer Imdad, Naveed Bhutto, Nabeela Ali, Zulfiqar A Bhutta
Journal: The Lancet (2012)
Cutaneous and basophilic sensitivity to substance P and gastrin in non‐atopic versus atopic subjects
Authors: R. E. Louis, M. E. Radermecker
Journal: Allergy (1991)

We compared the Cutaneous reaction to intradermal injection of substance P, gastrin and histamine in asymptomatic atopic subjects with a history of hay fever and/or asthma versus non‐atopk healthy volunteers. We also studied in these two groups the basophilic histamine release induced by substance P and gastrin with that obtained with anti‐human IgE and Con A. Intradermal injection of substance P (3–300 pM) and gastrin (3–30 pM) caused a wheal and flare reaction which was comparable in both groups of subjects. Substance P 10 −4 M caused a mean basophilic histamine release of about 15% in atopic and non‐atopic Subjects. Gastrin was not effective in this model. Anti‐IgE and Con A‐induced histamine release was significantly higher in atopic than in non‐atopic volunteers.
Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial
Authors: Mônica R Gadelha, Marcello D Bronstein, Thierry Brue, Mihail Coculescu, Maria Fleseriu, Mirtha Guitelman, Vyacheslav Pronin, Gérald Raverot, Ilan Shimon, Kayo Kodama Lievre, Juergen Fleck, Mounir Aout, Alberto M Pedroncelli, Annamaria Colao
Journal: The Lancet Diabetes & Endocrinology (2014)
Access to Care for Patients With Insulin-Requiring Diabetes in Developing Countries
Authors: David Beran, John S. Yudkin, Maximilian de Courten
Journal: Diabetes Care (2005)

OBJECTIVE—The objective of this study was to assess the barriers to care for patients with insulin-requiring diabetes in Mozambique and Zambia. RESEARCH DESIGN AND METHODS—We used the Rapid Assessment Protocol for Insulin Access to collect information through interviews, discussions, site visits, and document reviews. Government organizations, health facilities, care givers, and patients were asked about care for people with insulin-requiring diabetes. Between 100 and 200 interviews/discussions per country were undertaken in and around the capital city and the regional capital and in a rural area. RESULTS—Insulin was present in both countries in sufficient quantities, although the financial burden for health services and patients meant that problems with supply exist. There are problems with quantification of needs and equitable distribution of insulin. Problems with availability of syringes and testing equipment were noted, particularly in Mozambique. This lack of tools and infrastructure for diagnosis and follow-up coupled with low levels of health care worker training and lack of diagnostic reagents resulted in a substantial risk of misdiagnosis or failure to detect diabetes. The estimated prevalence of insulin-requiring diabetes differs more than 10-fold between urban and rural areas in Mozambique and 4-fold between Mozambique and Zambia, suggesting that problems in diagnosis and care result in substantial worsening of prognosis for such patients. CONCLUSIONS—Insulin is necessary but not sufficient to improve prognosis for diabetic patients. A Rapid Assessment Protocol methodology can be used to define problems in health care delivery for diabetes. Proper care for insulin-requiring diabetes necessitates health systems able to provide trained personnel, medicines in sufficient quantity, and diagnostic and monitoring facilities.
Height of Kilimanjaro
Authors: N C C Sharp
Journal: British Journal of Sports Medicine (2001)

The football club doctor system EDITOR,-I read with interest the paper by Waddington et al 1 highlighting the inadequacies of the football club doctor system in Britain.This paper confirms the situation that many people already knew to exist.Advertisements for club doctors are rarely published in medical journals, doctors normally being appointed on a "who you know" basis.It is also particularly disappointing that, at a time when the specialty of sports and exercise medicine is being established in this country, the majority of doctors working with professional footballers have no qualifications or little experience in the specialty.However, this is not confined to football clubs and probably also applies to rugby clubs and many other sporting associations.One aspect not mentioned in the paper is medical litigation.It is to be hoped that doctors involved with football clubs have arranged medical defence cover, because, if a situation arises in which a player's sporting career is threatened by medical mismanagement and the doctor involved has no professionally recognised sports medicine qualification, he or she could be found guilty of medical negligence.With the amount of money involved in professional football, this could lead to dire consequences for the medical career of the practitioner involved.From a report commissioned by the Football League on the Hillsborough tragedy, the concept of the "crowd doctor" was introduced, meaning that any doctor involved in the medical care of the crowd at a football stadium would be required to possess at least the Diploma in Immediate Medical Care. 2 Before that, the situation was similar to that of the present club doctor system, and few doctors held any recognisable qualifications or training in medical emergencies and resuscitation.A similar recommendation by sports medicine authorities is required to enhance the quality of service provided to football clubs and increase the stature of the specialty.However, it is not a one sided situation.Football clubs must realise the importance of a medical team in looking after their prime assets, the players.Advertising of jobs in medical journals, insisting on experience and qualifications, adequate remuneration, and the provision of job descriptions and contracts should all be implemented.By working together to improve the current situation, a service can be provided in which both professional football players and the medical profession can have confidence.
Low value of adenosine deaminase in tuberculous pleural effusions
Authors: JM Querol, F Barbe, F Manresa, L Esteban, C Canete
Journal: European Respiratory Journal (1990)

It has been claimed that a value of adenosine deaminase (ADA) activity lower than 43 U·/·1 excludes tuberculous aetiology of pleural effusion [1, 2]. We report nine cases of tuberculous pleurisy with at least one determination of ADA (by Giusti and Galanti) activity less than 43 U-/·1 , and two other cases with an ADA value below 44 U-/·1 , out of 114 ADA determinations (representing 8% or 10%). The tuberculosis diagnosis was confirmed by bacteriological cultures of pleural fluid or biopsy material and the pathological finding of a granulomatous lesion in the pleural tissue. In the literature we have found eighteen cases of tuberculous pleurisy with an ADA activity value <43 U·/·1 [35]; however, among the largest series of ADA and tuberculosis no cases with a value of ADA activity <43 U-/·1 were described [1, 2, 6] . In five of the nine cases reported with low ADA activity values, a second determination a few days later evidenced a rise in the ADA activity over 43 U·/'1 to values well within the range of tuberculous effusion (fig. 1). In another two cases a second ADA determination six and eight days later, respectively, still showed a value below 43 U·/·1. In the last two cases only one determination was obtained.
Collagen Genes and Brittle Bones
Authors: Jay R. Shapiro, David W. Rowe
Journal: Annals of Internal Medicine (1983)

The heritable diseases of connective tissue are caused by known or putative defects in the synthesis of collagens, proteoglycans, glycoproteins, or attachment proteins of the extracellular matrix. Abnormal synthesis of type I collagen has been reported in several clinical variants of osteogenesis imperfecta. Because clinical classification of these variants is limited by genetic heterogenity and variable expression, biochemical criteria should be used for precise definition of the variants. Newly recognized molecular defects in osteogenesis imperfecta include the diminished formation of type I collagen and alpha-1 [I] messenger RNA; abnormal synthesis or faulty assembly of alpha-2 [I]; deletion or insertion of base pairs in the gene for alpha-1 [I] or alpha-2 [I] and failure to secrete type I procollagen; and substitution of cysteine for glycine in the triple helix. These molecular defects are characteristic of several variants. However, the molecular lesion in most cases of severe osteogenesis imperfecta has not been identified; synthesis of type I collagen and alpha-1: alpha-2 chain ratios appears to be normal. Production of an alpha-1 trimer may represent one such lesion in severe disease.
Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial.
Authors: J M Sanchez-Tapias, X Forns, S Ampurdanes, L Tito, R Planas, J M Viver, D Acero, M Torres, P Mas, R Morillas, M Forne, J Espinos, J M Llovet, J Costa, E Olmedo, F X Lopez-Labrador, M T Jimenez de Anta, J Rodes
Journal: Gut (1996)

BACKGROUND--There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS--To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS--One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS--Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS--A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS--Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses.