tbuckley/cabot-search huggingface dataset:
Human Podocytes Express Angiopoietin 1, a Potential Regulator of Glomerular Vascular Endothelial Growth Factor
Authors: Simon C. Satchell, Steve J. Harper, John E. Tooke, Dontscho Kerjaschki, Moin A. Saleem, Peter W. Mathieson
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Vascular endothelial growth factor (VEGF) is abundantly expressed by podocytes, but its role in glomeruli is unknown. Angiopoietins are endothelial cell growth factors that function in concert with VEGF but have not previously been observed in human glomeruli. Angiopoietin 1 (Ang1) acts via the endothelial receptor Tie2 to promote maturation and stabilization of blood vessels, resisting angiogenesis and opposing some actions of VEGF. Ang1, Ang2, Tie2, and VEGF expression in normal human renal cortex was examined with immunofluorescence and immunohistochemical analyses. High-power, multiple-color, immunofluorescence analyses and additional antibodies (specific for particular components of the glomerular filtration barrier) were used to determine the exact locations of Ang1 and Tie2 in the glomerular capillary wall. Immuno-electron-microscopic analysis of rat glomeruli was used to further localize endothelial Tie2 expression. RNA and protein extracted from human glomeruli, cultured human podocytes, and cultured human endothelial cells were analyzed for Ang1, Ang2, and Tie2 by using reverse transcription-PCR and Western blotting. Ang1 was detected in podocytes in normal glomeruli and, with VEGF, was concentrated in podocyte foot processes. Tie2 was demonstrated on glomerular capillary endothelial cells, particularly on the abluminal surface. Reverse transcription-PCR and Western blotting analyses confirmed the expression of Ang1 and Tie2 in glomeruli and of Ang1 in cultured podocytes. These findings suggest a role for Ang1 in the maintenance of the glomerular endothelium and make it a good candidate to be a regulator of the actions of VEGF on glomerular permeability, resisting angiogenesis while allowing the induction of high permeability to water and small solutes.
Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma
Authors: John G. Gribben, Nathan Fowler, Franck Morschhauser
Journal: Journal of Clinical Oncology (2015)

Lenalidomide is an orally active immunomodulatory drug that has direct antineoplastic activity and indirect effects mediated through multiple types of immune cells found in the tumor microenvironment, including B, T, natural killer (NK), and dendritic cells. Recently, the E3 ubiquitin ligase cereblon was identified as a molecular target that may underlie the effects of lenalidomide on tumor cells, as well as on cells in the tumor microenvironment. Decreases in cereblon attenuate these effects and also confer resistance to lenalidomide. Tumoricidal effects of lenalidomide are associated with reduced interferon regulatory factor 4, a downstream target of cereblon. Lenalidomide stimulates proliferation and activation of NK cells, thereby enhancing NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. These effects appear to be secondary to cytokine production from T cells. Lenalidomide has been shown to produce synergistic effects in experimental models when evaluated in combination with rituximab, dexamethasone, bortezomib, and B-cell receptor signaling inhibitors, consistent with mechanisms complementary to these agents. These experimental findings have translated to the clinic, where single-agent use displays durable responses in relapsed/refractory non-Hodgkin lymphoma, and combination with rituximab and other agents leads to improved responses at first line and in relapsed/refractory disease. The activity of lenalidomide is evident across multiple lymphoma subtypes, including indolent and aggressive forms. The interaction among cell types in the immune microenvironment is increasingly recognized as important to tumor cell recognition and destruction, as well as to protection of normal immune cells, as reflected by lenalidomide studies across multiple types of B-cell lymphomas.
Queen's speech presages independent board for the NHS
Authors: A. O'Dowd
Journal: BMJ (2010)

Increased power for health professionals and patients in the running of the NHS is to be introduced under the new government’s legislative plans for the next 18 months.

In the Queen’s speech delivered this week, Prime Minister David Cameron set out his plans contained in 22 bills and one draft bill.

Under the Health Bill, the government aims to give health professionals and patients more say over decision making in the NHS. This bill will also create an independent NHS board to allocate resources and provide guidance to allow GPs to commission services; strengthen the role of regulator the Care Quality Commission; axe some health quangos; cut some centrally set targets; and focus more on the problem of health inequalities.

Sales of alcohol below the actual cost …
REACTIONS OF MONKEYS TO EXPERIMENTALLY INDUCED STREPTOCOCCUS HEMOLYTICUS, GROUP C, INFECTION
Authors: Samuel Saslaw, H. E. Wilson, Charles A. Doan, O. C. Woolpert, J. L. Schwab
Journal: The Journal of Experimental Medicine (1946)

Macaca mulatta on a normal diet proved to be resistant on intranasal inoculation with Streptococcus hemolyticus, group C. More than half of the monkeys maintained for various periods on a modified dietary regimen deficient in vitamin B became more or less anemic. All developed a granulopenic leucopenia during which many developed spontaneous infections, and all were extremely susceptible on intranasal instillation of Streptococcus hemolyticus, group C. In normal monkeys, primary inoculation with the streptococcus resulted in an immediate marked neutrophilic leucocytosis. In the nutritionally deficient animals with leucopenia, only an abortive transitory leucocytosis was observed. Following reinoculation with the same strain of hemolytic streptococci in normal healthy monkeys, the prompt leucocytic response originally observed, failed to develop, yet the animals remained asymptomatic. In the first instance the opsonic index remained low at the preinoculation base line level, but in the second, a sharp increase in the opsonic index occurred in several days. This humoral response apparently rendered unnecessary the quantitative granulocytic leucocytosis associated with survival in the first instance. There was no demonstrable difference in time of appearance or titer of the antibody responses, i.e. precipitins, antistreptolysins, and opsonins between the normal and nutritionally deficient monkeys. Synthetic folic acid (L. casei factor) relieved both leucopenia and anemia promptly in the "vitamin M"-deficient monkeys, with increase in resistance to endogenous infection when this supplement was given sufficiently promptly.
Partial Volume Decrease of the Thalamus in Relatives of Patients With Schizophrenia
Authors: Wouter G. Staal, Hilleke E. Hulshoff Pol, Hugo Schnack, Astrid C. van der Schot, René S. Kahn
Journal: American Journal of Psychiatry (1998)

The authors' goal was to compare the thalamic, total brain, and intracranial volumes of patients with schizophrenia, their healthy siblings, and normal comparison subjects.Magnetic resonance imaging (MRI) brain scans were obtained for 32 same-sex siblings who were discordant for schizophrenia and 32 matched normal comparison subjects.Mean total thalamic volume, corrected for total brain volume, was significantly different among affected siblings, unaffected siblings, and comparison subjects. Thalamic volume was smallest in the patients; thalamic volume in their siblings was smaller than that of comparison subjects but larger than that of the patients with schizophrenia.These results suggest that healthy siblings of patients with schizophrenia partially share the thalamic abnormalities of their affected relatives.
Aphasia research and theoretical linguistics guiding each other
Authors: Jeannette Schaeffer
Journal: Behavioral and Brain Sciences (2000)

An elaboration on some loose ends in Grodzinsky's analysis shows that data from the field of aphasia contribute to the formulation of theoretical linguistic principles, and provides extra arguments in favor of Grodzinsky's claim that linguistic theory is the best tool for the investigation of aphasia. This illustrates and emphasizes the importance of communication between researchers in the field of (Broca's) aphasia and of theoretical linguistics.
Diagnosis and Treatment of Discharging Ears
Authors: C. M. Johnston
Journal: BMJ (1966)

Discharge in the ear can come from the external meatus, the middle-ear cleft, or both.A survey of factory workers' made before antibiotics were generally available in general practice showed that otitis externa was not uncommon: 2.6 % of a sample of the workers were found to have otitis externa and 3.3% to have middle-ear discharge.Because permanent deaf- ness or other serious complications may follow otitis media, simple otitis externa should not be diagnosed until it can be shown that the middle ear is healthy.The Medical Research Council's Working Party for research in general practice for the year 1955 reported2 a yearly incidence of 8% of acute otitis media in children.The medical inspections of the school health service show that on entering school nine children out of every 1,000 have chronic discharge from the ear.Chronic ear infection in the adult population is not a notifiable disease and the incidence is unknown.Medical examination of recruits for National Service,3 however, showed an incidence of bilateral dry perforations of the tympanic membrane or active disease in one or both middle ears ranging from 2.2% to 5.9% in different counties of England. Acute Otitis MediaAn accurate history of the time of onset, symptoms, and previous treatment is essential for diagnosis, and will often permit a tentative differentiation between acute or chronic suppurative otitis media.The first symptom is pain in the ear, and this is usually followed by rapid relief or diminution in intensity when the drum perforates and discharge appears at the ear.This is accompanied by subsidence of pyrexia and toxaemia.It is essential to inquire if there has been a previous ear infection in the recent past.If antibiotics were given for the initial attack-and particularly if they were given by the oral route-treatment may have been inadequate and could have masked a latent infection for several weeks.During this time extensive bone disease may have occurred in the mastoid pro- cess, with an intracranial extension or the development of venous sinus thrombosis.These conditions demand immediate surgery.In other cases vertigo, profound deafness, or facial nerve paralysis may occur; but it will then be a problem requiring some experience to decide whether medical or surgical treatment is advisable.If the case is seen within the first 24 hours of the appearance of the discharge, deafness, tinnitus, and occasionally slight vertigo will be present.Pain will have usually subsided.Tenderness of the mastoid process should be sought by firm pressure on the mastoid tip and near Macewen's triangle.Particularly with children, apprehension may give a false impression that tenderness is present.This can be discounted if no movement of the head away from the diseased side results * Otologist, Swindon and Cirencester Hospitals.when simultaneous and equal pressure is made on both mastoid processes.
Circulating CD34+ cells: An adverse prognostic factor in the myelodysplastic syndromes
Authors: Sally A. Sullivan, Katherine A. Marsden, Raymond M. Lowenthal, David M. Jupe, Michael E. Jones
Journal: American Journal of Hematology (1992)

Abstract As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU‐GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients ( P &lt; 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells ( P &lt; 0.03). The Bournemouth score was also significantly associated with transformation to AML ( P &lt; 0.0001) and poor survival ( P &lt; 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU‐GM colony growth.
D-penicillamine withdrawal in rheumatoid arthritis.
Authors: M J Ahern, N D Hall, K Case, P J Maddison
Journal: Annals of the Rheumatic Diseases (1984)

Thirty-eight patients with rheumatoid arthritis in remission on penicillamine were entered into a prospective, randomised, placebo controlled study to determine the effects of gradual penicillamine withdrawal, to find a serological marker capable of predicting relapse, and to assess the effects of reintroduction of penicillamine. 80% of patients attempting gradual penicillamine withdrawal flared. There was no single serological marker capable of predicting outcome consistently. Decreasing SH levels were highly specific for recurrence of active synovitis but were insensitive. Reintroduction of penicillamine was successful. The implications of these findings, particularly concerning duration of therapy with disease modifying drugs, are discussed.
Prevention of suicide
Authors: N.J Birch, D.P Srinivasan, TraolachS Brugha, ChrisR Brewin, PaulE Bebbington, Stuart Checkley, Wolfgang Rutz, Jan Walinder, Göran Eberhard, Anne-Liis Von Knorring, Lars Von Knorring, Börje Wistedt, Anna Åberg-Wistedt
Journal: The Lancet (1992)
A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients
Authors: Katsuya Shiraki, Koujirou Takase, Yukihiko Tameda, Minoru Hamada, Yoshitane Kosaka, Takeshi Nakano
Journal: Hepatology (1995)

Levels of two types of lectin-reactive alpha-fetoprotein (AFP), designated AFP-L3 and AFP-P4+P5, were analyzed with Lens culinaris agglutinin A and AFP-P4+P5 with erythroagglutinating phytohemagglutinin, respectively, in an attempt to determine the utility and significance of these macromolecules as early indicators of hepatocellular carcinoma during the periodic follow-up of cirrhotic patients. The subjects were 51 of 190 consecutive cirrhotic patients in whom hepatocellular carcinoma developed during a 6-year follow-up period and 21 cirrhotic patients without hepatocellular carcinoma. Serum AFP levels were of limited value to diagnose and predict hepatocellular carcinoma. The relative levels of AFP-L3 and AFP-P4+P5 in patients with hepatocellular carcinoma at the time of tumor detection were significantly higher than those in patients with cirrhosis. The sensitivity was 61%, and the specificity was 90%. Fourteen patients (48%) of 29 patients with small hepatocellular carcinomas less than 2 cm in diameter showed elevated percentage of lectin-reactive AFP. Retrospective examination of 21 patients who were positive for lectin-reactive AFP at diagnosis of hepatocellular carcinoma showed that 41% of them had already expressed lectin-reactive AFP 12 months before the direct detection of hepatocellular carcinoma by diagnostic imaging. These results lead us to conclude that the level of lectin-reactive AFP is a suitable predictive marker for the early recognition of hepatocellular carcinoma in the follow-up of patients with cirrhosis, and that measurements of the level of lectin-reactive AFP should be added to the screening methods that are now in use.
Demethylation of Urokinase Promoter as a Prognostic Marker in Patients with Breast Carcinoma
Authors: Pouya Pakneshan, Bernard Têtu, Shafaat A. Rabbani
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Urokinase (uPA) is expressed in a number of highly invasive malignancies including breast cancer. Because production of uPA is associated with breast cancer progression and can serve as a useful prognostic marker, the purpose of this study was to examine the role of uPA promoter methylation as an indicator of uPA production in breast cancer patients. Experimental Design: We examined the methylation status of the uPA promoter and the levels of uPA expression in normal human breast epithelial cells and several human breast cancer cells by bisulfite sequencing analysis and reverse transcription-PCR. We also analyzed the methylation status of the uPA promoter in surgical biopsy samples from patients with breast cancer of different grades, as determined by the Elston-Ellis histological grading system. Results: Expression of uPA mRNA was only detected in the highly invasive estrogen receptor-negative breast cancer cell lines, where the promoter was completely demethylated. In normal and low invasive breast cancer cells, the uPA promoter was methylated, resulting in lack of uPA mRNA expression. Analysis of biopsy samples showed that demethylation of the uPA promoter is associated with malignant transformation. Reverse transcription-PCR analysis revealed that this demethylation of the uPA promoter is directly associated with induction of uPA mRNA expression, which is well known to be associated with poor prognosis in breast cancer patients. Conclusions: This study indicated that uPA expression in breast cancer patients is under epigenetic control via methylation of its promoter. Determination of uPA promoter methylation can therefore serve as an early reliable indicator of uPA production in breast cancer patients.
Assessment of secondary attack rate and effectiveness of antiviral prophylaxis among household contacts in an influenza A(H1N1)v outbreak in Kobe, Japan, May–June 2009
Authors: F Odaira, H Takahashi, T Toyokawa, Y Tsuchihashi, T Kodama, Y Yahata, T Sunagawa, K Taniguchi, N Okabe
Journal: Eurosurveillance (2009)

This report describes the assessment of the secondary attack rate (SAR) and the effectiveness of post-exposure antiviral prophylaxis among household contacts in the first domestic outbreak of a novel influenza A(H1N1)v between mid-May and early June 2009 in Kobe city, Japan. Of the 293 subjects, 14 (4.8%) household contacts met the case definition and most secondary cases were probably infected around the time of symptom onset date of the respective index case. The SAR among household contacts who did not receive prophylaxis was 7.6%, similar to the rate of seasonal influenza, and the attack rate in siblings was significantly higher than that in parents. We conclude that it is important to establish routine infection control measures for households in order to prevent the spread of the virus among household contacts and, possibly, to the community. We could not conclude whether antiviral prophylaxis was effective or not. However, among close contacts with underlying disease who received prophylaxis, nobody developed a severe form of the disease.
Positive Selection on an Acrosomal Sperm Protein, M7 Lysin, in Three Species of the Mussel Genus Mytilus
Authors: C. Riginos
Journal: Molecular Biology and Evolution (2003)

Marine invertebrate sperm proteins are particularly interesting because they are characterized by positive selection and are likely to be involved in prezyogotic isolation and, thus, speciation. Here, we present the first survey of interspecific and intraspecific variation of a bivalve sperm protein among a group of species that regularly hybridize in nature. M7 lysin is found in sperm acrosomes of mussels and dissolves the egg vitelline coat, permitting fertilization. We sequenced multiple alleles of the mature protein-coding region of M7 lysin from allopatric populations of mussels in the Mytilus edulis species group (M. edulis, M. galloprovincialis, and M. trossulus). A significant McDonald-Kreitman test showed an excess of fixed amino acid replacing substitutions between species, consistent with positive selection. In addition, Kolmogorov-Smirnov tests showed significant heterogeneity in polymorphism to divergence ratios for both synonymous variation and combined synonymous and nonsynonymous variation within M. galloprovincialis. These results indicate that there has been adaptive evolution at M7 lysin and, furthermore, show that positive selection on sperm proteins can occur even when postzygotic reproductive isolation is incomplete.
Safety, feasibility and functionality of activated autologous dendritic cells for intratumoral injection in solid tumors: a Phase I clinical trial
Authors: Vivek Subbiah, Ravi Murthy, David Hong, Robert Prins, Chitra Hosing, Robert Brown, McGuire Mary, Aung Naing, Siquing Fu, Anthony Conley, Indreshpaul Kaur, Kyle Hendricks, Deepthi Kolli, Lori Noffsinger, Marnix Bosch
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Dendritic cells (DC) are proficient in initiating adaptive immune responses, through the uptake and subsequent presentation to the immune system of antigenic compounds. In preclinical studies, activated DC (aDC; DCVax®-Direct) were shown to be superior to immature DC in clearing
MicroRNAs As Novel Regulators of Angiogenesis
Authors: Yajaira Suárez, William C. Sessa
Journal: Circulation Research (2009)

MicroRNAs are short noncoding RNAs that function as negative regulators of gene expression. Posttranscriptional regulation by miRNAs is important for many aspects of development, homeostasis, and disease. Endothelial cells are key regulators of different aspects of vascular biology, including the formation of new blood vessels (angiogenesis). Here, we review the approaches and current experimental evidence for the involvement of miRNAs in the regulation of the angiogenic process and their potential therapeutic applications for vascular diseases associated with abnormal angiogenesis.
THE PLACE OF BONE-MARROW TRANSPLANTATION IN ACUTE MYELOGENOUS LEUKÆMIA
Authors: R.L. Powles, H.M. Clink, G. Bandini, J.G. Watson, D. Spence, B. Jameson, H.E.M. Kay, G. Morgenstern, D. Hedley, H. Lumley, D. Lawson, A. Barrett, S. Lawler, T.J. Mcelwain
Journal: The Lancet (1980)