tbuckley/cabot-search huggingface dataset:
Identification of a Human Follicular Dendritic Cell Molecule That Stimulates Germinal Center B Cell Growth
Authors: Li Li, Xin Zhang, Sharlotte Kovacic, Andrew J. Long, Karen Bourque, Clive R. Wood, Yong Sung Choi
Journal: The Journal of Experimental Medicine (2000)

The initial interaction between B cells and follicular dendritic cells (FDCs) appears to be essential for germinal center (GC) formation. To identify molecules regulating this interaction, we generated FDC-staining monoclonal antibodies (mAbs) and screened them for their ability to block FDC-mediated costimulation of growth and differentiation of CD40-stimulated B cells. Using one of the inhibitory mAbs, 8D6, we expression cloned the cDNA encoding the 8D6 antigen (Ag) from a human FDC line, HK. The 8D6 Ag is a novel protein of 282 amino acids that is expressed abundantly on FDCs. Monolayers of COS cells transiently transfected with the 8D6 Ag cDNA stimulate B cell growth. The mAb 8D6 blocks the costimulatory function completely. The inhibitory activity of the mAb 8D6 was demonstrated to be due to an inhibition of cell cycle progression of CD40 ligand-stimulated GC B cells. In addition, the mAb 8D6 inhibits the growth of a lymphoma of GC origin, L3055, which depends on FDCs or HK cells for its growth. These findings suggest that the primary function of FDCs in the GC is to stimulate B cell growth. An FDC signal molecule, 8D6 Ag, may be an important molecule to mediate this function.
Multiple connexins colocalize in canine ventricular myocyte gap junctions.
Authors: H L Kanter, J G Laing, E C Beyer, K G Green, J E Saffitz
Journal: Circulation Research (1993)

We have recently shown that adult canine ventricular myocytes express three distinct gap junction channel proteins, connexin40 (Cx40), connexin43 (Cx43), and connexin45 (Cx45). These proteins have unique cytoplasmic domains that likely confer connexin-specific physiological properties. To determine whether the three distinct channel proteins are distributed in identical or different populations of gap junctions, we performed double-label immunofluorescence on disaggregated canine ventricular myocytes incubated simultaneously with a mouse monoclonal anti-Cx43 and affinity-purified polyclonal rabbit antibodies against Cx40 or Cx45. Analysis of double-labeled cardiac myocytes using laser scanning confocal microscopy revealed virtually identical patterns of immunoreactivity for both the Cx43/Cx40 and Cx43/Cx45 pairs. Double-label immunoelectron microscopy confirmed that ultrastructurally identified cardiac myocyte gap junctions contain multiple channel proteins. Thus, three channel proteins colocalize in canine cardiac myocyte gap junctions. The presence of multiple functionally distinct connexins suggests complex possibilities regarding the composition of individual channels and the regulation of intercellular coupling.
Binding of Losartan to Angiotensin AT1 Receptors Increases Dopamine D1 Receptor Activation
Authors: Dong Li, Lena Scott, Susanne Crambert, Sergey Zelenin, Ann-Christine Eklöf, Luis Di Ciano, Fernando Ibarra, Anita Aperia
Journal: Journal of the American Society of Nephrology (2011)

Signaling through both angiotensin AT1 receptors (AT1R) and dopamine D1 receptors (D1R) modulates renal sodium excretion and arterial BP. AT1R and D1R form heterodimers, but whether treatment with AT1R antagonists functionally modifies D1R via allosterism is unknown. In this study, the AT1R antagonist losartan strengthened the interaction between AT1R and D1R and increased expression of D1R on the plasma membrane in vitro. In rat proximal tubule cells that express endogenous AT1R and D1R, losartan increased cAMP generation. Losartan increased cAMP in HEK 293a cells transfected with both AT1R and D1R, but it did not increase cAMP in cells transfected with either receptor alone, suggesting that losartan induces D1R activation. Furthermore, losartan did not increase cAMP in HEK 293a cells expressing AT1R and mutant S397/S398A D1R, which disrupts the physical interaction between AT1R and D1R. In vivo, administration of a D1R antagonist significantly attenuated the antihypertensive effect of losartan in rats with renal hypertension. Taken together, these data imply that losartan might exert its antihypertensive effect both by inhibiting AT1R signaling and by enhancing D1R signaling.
Dopa and Parkinsonism
Authors: J. Watt
Journal: BMJ (1967)

In a nonalcoholic woman with multiple symmetric lipomatosis (MSL), muscle histochemistry showed ragged-red fibers and cytochrome c oxidase negative fibers. Southern blot analysis revealed a single deletion of mitochondrial DNA (mtDNA). We suggest that MSL is an uncommon manifestation of the wide clinical spectrum of mitochondrial disorders, in particular of those associated with single mtDNA deletions. <b>NEUROLOGY 1996;47: </b> 1012-1014
Evidence of clonal variants of Helicobacter pylori in three generations of a duodenal ulcer disease family.
Authors: C U Nwokolo, J Bickley, A R Attard, R J Owen, M Costas, I A Fraser
Journal: Gut (1992)

Nine members of a family with a high incidence of duodenal ulcer disease were studied by interview, examination of hospital records, endoscopy, and antral biopsy. Helicobacter pylori was confirmed by CLO test, histology and culture. DNA extraction from pure isolates of H pylori was possible in six family members and strain typing was performed by restriction fragment length polymorphism. DNA restriction digestion was followed by vacublotting and then DNA hybridisation, using a cDNA probe complimentary to H pylori rRNA cistrons. Eight of the nine family members were H pylori positive by CLO test and histology. Five had duodenal ulcer disease. Three family members (one from each generation) harboured clonal variants of a single parent strain of H pylori but only two had duodenal disease. The other three members harboured different strains. Intrafamilial clustering of clonal variants of H pylori occurs in some duodenal ulcer disease families. Family members however, may develop duodenal disease irrespective of the colonising strain.
Neurovascular dysfunction in diabetic rats. Potential contribution of autoxidation and free radicals examined using transition metal chelating agents.
Authors: N E Cameron, M A Cotter
Journal: Journal of Clinical Investigation (1995)

Oxygen free radical activity is elevated in diabetes mellitus and has been implicated in the etiology of vascular complications. Recent studies have shown that impaired perfusion of nerve endoneurium is a major cause of nerve fiber dysfunction in experimental diabetes. Free radical scavenger treatment prevents the development of nerve conduction abnormalities in diabetic rats. In vitro experiments suggest that autoxidation reactions of glucose, catalyzed by free transition metal ions, are a potential source of free radicals in diabetes. We investigated whether chronic treatment with deferoxamine and trientine, transition metal chelating agents which can prevent autoxidation, could correct nerve conduction and blood flow changes in streptozotocin-diabetic rats. A 20% reduction in sciatic nerve motor conduction velocity after 2 mo diabetes was 90% ameliorated by 2 wk of treatment with deferoxamine or trientine. Sciatic endoneurial nutritive blood flow was 45% reduced by diabetes, but was completely corrected by treatment. In contrast, transition metal chelation had no effect on blood flow or conduction velocity in nondiabetic rats. Thus, the data support the hypothesis that increased free radical activity by glucose autoxidation as a result of impaired transition metal handling is a major cause of early neurovascular deficits in diabetes.
Circumferential Radiofrequency Ablation of Pulmonary Vein Ostia
Authors: Carlo Pappone, Salvatore Rosanio, Giuseppe Oreto, Monica Tocchi, Filippo Gugliotta, Gabriele Vicedomini, Adriano Salvati, Cosimo Dicandia, Patrizio Mazzone, Vincenzo Santinelli, Simone Gulletta, Sergio Chierchia
Journal: Circulation (2000)

The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia.We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography.Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.
Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immunodeficiency
Authors: Tomoki Kawai, Ryuta Nishikomori, Kazushi Izawa, Yuuki Murata, Naoko Tanaka, Hidemasa Sakai, Megumu Saito, Takahiro Yasumi, Yuki Takaoka, Tatsutoshi Nakahata, Tomoyuki Mizukami, Hiroyuki Nunoi, Yuki Kiyohara, Atsushi Yoden, Takuji Murata, Shinya Sasaki, Etsuro Ito, Hiroshi Akutagawa, Toshinao Kawai, Chihaya Imai, Satoshi Okada, Masao Kobayashi, Toshio Heike
Journal: Blood (2012)
The concentration of anticitrullinated protein antibodies in serum and synovial fluid in relation to total immunoglobulin concentrations
Authors: Annemiek Willemze, Jing Shi, Marlies Mulder, Gerrie Stoeken-Rijsbergen, Jan W Drijfhout, Tom W J Huizinga, Leendert A Trouw, Rene E M Toes
Journal: Annals of the Rheumatic Diseases (2013)

Background Anticitrullinated protein antibodies (ACPA) are one of the best predictors for the development of rheumatoid arthritis. Nonetheless, relatively little information is present on the absolute concentration of ACPA in relation to total immunoglobulin (Ig) concentrations. Such information would be of relevance to compare ACPA levels to other antibody levels. Here, we estimated the relative abundance of ACPA Ig in serum and synovial fluid using a quantitative approach. Methods ACPA were purified using HiTrap Streptavidin columns coupled with biotinylated cyclic citrullinated peptide (CCP2). Total Ig and anti-CCP2 isotype reactivities were measured by ELISA. Results ACPA were successfully isolated as substantial antibody amounts were eluted from sera of ACPA-positive patients and neglectable antibody amounts were eluted from sera of ACPA-negative patients. Up to 1 in 80 IgG-molecules were estimated to be ACPA. Strikingly, IgM-ACPA was most abundant in synovial fluid (with the highest enrichment in the range of one IgM-ACPA for every eight IgM-antibodies). Conclusions ACPA-IgG levels are estimated to be within the range of peak levels of protective antibody responses against recall antigens. IgM-ACPA is abundantly present in synovial fluid, suggesting the presence of a continuous ongoing autoimmune response in the synovial compartment.
The Combined Effect of Leisure-Time Physical Activity and Diabetes on Cardiovascular Mortality
Authors: Børge Moe, Eivin Eilertsen, Tom I.L. Nilsen
Journal: Diabetes Care (2012)

To examine if leisure-time physical activity could cancel out the adverse effect of diabetes on cardiovascular mortality.This study prospectively examined the combined effect of clinical diabetes and reported leisure-time physical activity on cardiovascular mortality. Data on 53,587 Norwegian men and women participating in the population-based Nord-Trøndelag Health (HUNT) Study (1995-1997) were linked with the Cause of Death Registry at Statistics Norway.Overall, 1,716 people died of cardiovascular disease during follow-up through 2008. Compared with the reference group of 3,077 physically inactive people without diabetes, 121 inactive people with diabetes had an adjusted hazard ratio (HR) of 2.81 (95% CI 1.93-4.07). The HR (95% CI) among people who reported ≥3 h of light activity per week was 0.89 (0.48-1.63) if they had diabetes (n = 403) and 0.78 (0.63-0.96) if they did not (n = 17,714). Analyses stratified by total activity level showed a gradually weaker association of diabetes with mortality with increasing activity level (P(interaction) = 0.003).The data suggest that even modest physical activity may cancel out the adverse impact of diabetes on cardiovascular mortality.
The Effects of Nitroglycerin on Coronary Collaterals and Myocardial Contractility
Authors: Michael V. Cohen, James M. Downey, Edmund H. Sonnenblick, Edward S. Kirk
Journal: Journal of Clinical Investigation (1973)

Nitroglycerin (TNG) causes a prolonged dilatation of coronary collaterals. To demonstrate a functional significance of this dilatation we measured the effect of TNG on myocardial contractile force in dogs 2½-4 wk after the left anterior descending coronary artery (LAD) had been embolized in closed-chest animals. Development of collaterals was documented by angiography. Via a left thoracotomy the main left coronary artery (LCA) and LAD distal to the embolized plug were cannulated. Coronary flow and perfusion pressure were recorded. Contractile force was measured with gauges sutured to epicardial areas supplied by the left circumflex coronary artery (LCf) and occluded LAD. Coronary perfusion pressure in the LCA was gradually decreased until the contractile force recorded by the LAD gauge diminished while the LCf gauge was unaffected. Under these conditions, with coronary perfusion pressure held constant with the aid of a Starling resistance, TNG (18 μg) injected into the LCA increased peripheral LAD pressure by 3-12 mm Hg and contractile force in the LAD region by 36% (range 20-90%), returning it to near-normal levels, while having minimal effect in the LCf area. These changes persisted for 5 min. When LCf and LAD areas were both ischemic, intracoronary TNG had minimal effect on peripheral LAD pressure and contractile force. Thus, TNG causes prolonged dilatation of coronary collaterals and presumed increased collateral flow with subsequent enhancement of myocardial contractile force in ischemic areas. This effect is seen only when ischemia is limited to an area supplied by the collaterals. When the whole heart is ischemic, collaterals are unresponsive to TNG, suggesting that these collaterals dilate fully when the regions from which they originate become ischemic.
Donor-Derived Ip-10 Initiates Development of Acute Allograft Rejection
Authors: Wayne W. Hancock, Wei Gao, Vilmos Csizmadia, Kerrie L. Faia, Nida Shemmeri, Andrew D. Luster
Journal: The Journal of Experimental Medicine (2001)

An allograft is often considered an immunologically inert playing field on which host leukocytes assemble and wreak havoc. However, we demonstrate that graft-specific physiologic responses to early injury initiate and promulgate destruction of vascularized grafts. Serial analysis of allografts showed that intragraft expression of the three chemokine ligands for the CXC chemo-kine receptor CXCR3 was induced in the order of interferon (IFN)-gamma-inducible protein of 10 kD (IP-10, or CXCL10), IFN-inducible T cell alpha-chemoattractant (I-TAC; CXCL11), and then monokine induced by IFN-gamma (Mig, CXCL9). Initial IP-10 production was localized to endothelial cells, and only IP-10 was induced by isografting. Anti-IP-10 monoclonal antibodies prolonged allograft survival, but surprisingly, IP-10-deficient (IP-10(-/-)) mice acutely rejected allografts. However, though allografts from IP-10(+/+) mice were rejected by day 7, hearts from IP-10(-/-) mice survived long term. Compared with IP-10(+/+) donors, use of IP-10(-/-) donors reduced intragraft expression of cytokines, chemokines and their receptors, and associated leukocyte infiltration and graft injury. Hence, tissue-specific generation of a single chemokine in response to initial ischemia/reperfusion can initiate progressive graft infiltration and amplification of multiple effector pathways, and targeting of this proximal chemokine can prevent acute rejection. These data emphasize the pivotal role of donor-derived IP-10 in initiating alloresponses, with implications for tissue engineering to decrease immunogenicity, and demonstrate that chemokine redundancy may not be operative in vivo.
Chronic Inflammation and Breast Cancer Recurrence
Authors: Steven W. Cole
Journal: Journal of Clinical Oncology (2009)

On page #### of this issue, Pierce and colleagues 1 present some of the most persuasive evidence yet that chronic inflammation might increase the risk of breast cancer recurrence. In a multi-site study of 734 women treated successfully for early stage breast cancer, high levels of circulating acute phase proteins (APPs) ~3 years after treatment were associated with a 2-fold elevation in the risk of subsequent disease recurrence and mortality. Risk ratios were similar across primary tumor types (stage, ER/PR status), and independent of potential confounders such as age, estrogen level, and adiposity. These results are consistent with previous studies linking circulating inflammatory markers to progression of metastatic breast cancer 2–8. However, the findings of Pierce et al. are novel in suggesting that serum inflammatory markers might provide early information about disease recurrence risk in patients with no history of metastatic disease and no current evidence of cancer. If the present findings are replicated in larger cohorts with more recurrent cases, post-treatment APP monitoring could provide new a strategy for assessing the risk of breast cancer recurrence in apparently cured patients.
Some PCTs recommend GPs limit prescriptions to 28 days
Authors: A. O'Dowd
Journal: BMJ (2011)

A total of 215 diabetic children were screened for coeliac disease by determination of class specific serum reticulin antibody. Nine children were positive for reticulin antibody and all underwent biopsy of the small intestine. Four new cases of coeliac disease were found; all of these children had IgA reticulin antibody. Two of three other children with a low titre of IgA reticulin antibody had partial villous atrophy. It was concluded that IgA class reticulin antibody was a good marker of coeliac disease in diabetic children. The prevalence of coeliac disease in these children was 1:43 (including one previously diagnosed case) and we suggest that diabetic children be screened routinely for reticulin antibody.
P102 A survey of home oxygen provision across London
Authors: A. C. Davidson, S. Williams, N. Baxter, E. Morris, L. Restrick
Journal: Thorax (2011)

<h3>Introduction</h3> In preparing for 2012, we undertook a survey of current oxygen provision across London. <h3>Methods</h3> A questionnaire was sent electronically (Survey Monkey) to 100 BTS Oxygen champions, oxygen leads in primary and secondary care, PCT prescribing advisors and community respiratory nurses around London. <h3>Results</h3> From 60 returns the main findings were: 75% of LTOT prescriptions initiated by hospitals yet no follow-up in 35%. 70% community teams reported "not at all" and "only sometimes" being informed about new starters by GPs and hospitals. &lt;50% took action when concordance reports showed variance (under or over use) from prescribed treatment. Lack of ability to detect hypoxic patients with &gt;20% community healthcare sites not having access to an oximeter. Fire safety officers are rarely advised about the persistent smoker (only 16%) despite the potential risk to patients, their families and the general public. Local guidance on appropriate steps to take is rare (35%). 3 HOS units denied LTOT for smokers and one assessed this by exhaled carbon monoxide measurement. A variety of methods for protecting patients from excessive oxygen are favoured but use appears limited. When asked what policy respondents favoured, universal precaution (as promoted by ambulance guidelines) was most popular (60%) while 20% favoured oxygen cards and 20% patient specific protocols (PSP). A specific local policy for removing oxygen when no longer indicated or used is rare (&lt;25%). This, coupled with inadequate follow-up of patients started on oxygen during hospital admission, suggests significant waste with the current oxygen provision. Respondents indicated guidance on oxygen removal, contract monitoring, assessment for ambulatory oxygen and training in arterial or capillary blood gases as being required. <h3>Conclusions</h3> Problems in healthcare coordination, public and patient safety and in removing oxygen once ordered were common. There is a need to integrate hospital and community teams and to prepare for safe mobilisation and contract management so that a quality home oxygen service can be provided in the future.
Melanoma--Part 1: epidemiology, risk factors, and prevention
Authors: V. Bataille, E. de Vries
Journal: BMJ (2008)

#### Summary points

The incidence of melanoma has risen over the past 30 years in most white populations.1 2 However, in some parts of the world incidence rates are stable or falling. Although large scale primary prevention programmes such as public health education campaigns aimed at reducing exposure to sun may lead to reduced incidence, such programmes have not yet been proved effective. However, melanoma is highly amenable to secondary prevention through early detection. Being able to recognise a melanoma early is an important skill for primary healthcare practitioners. In this first article of a two part series on melanoma, we examine the evidence on the genetic epidemiology of melanoma and outline the complex interactions between incidence, mortality, and survival trends; we also discuss the evidence for prevention.

Although melanoma remains a relatively rare tumour, many European countries show an annual increase in incidence above 2%; in some northern European countries, however, no significant increase has been observed.1 Between 1992 and 2005, the annual increase in incidence rates of melanoma in the United States was 2.3% for all races and 2.8% in white populations.3 Queensland in Australia had an increase in incidence of 1.4% for males and 0.7% for females during 1982 to 2001.4 Most recent incidence data show that in some …
Motor cortex fields and speech movements: Simple dual control is implausible
Authors: James H. Abbs, Roxanne DePaul
Journal: Behavioral and Brain Sciences (1998)

We applaud the spirit of MacNeilage's attempts to better explain the evolution and cortical control of speech by drawing on the vast literature in nonhuman primate neurobiology. However, he oversimplifies motor cortical fields and their known individual functions to such an extent that he undermines the value of his effort. In particular, MacNeilage has lumped together the functional characteristics across multiple mesial and lateral motor cortex fields, inadvertantly creating two hypothetical centers that simply may not exist.