tbuckley/cabot-search huggingface dataset:
Oligoclonal expansion of T cell receptor V beta 2 and 3 cells in the livers of mice with graft-versus-host disease
Authors: Weiran Chen, Charles D. Howell
Journal: Hepatology (2002)

The nonsuppurrative destructive cholangitis lesions in the B10.D2 (donor) into BALB/c (host) mouse graft-versus-host disease (GVHD) model are dependent on CD4 T cells that use a T cell receptor-β chain variable region (Vβ) repertoire, which is heavily biased toward Vβ2 and Vβ3 usage. We hypothesized that liver Vβ2 + and Vβ3 + CD4 T cells originate from donor mice and recognize BALB/c minor histocompatibility alloantigens and BALB/c endogenous retroviral superantigen-6, respectively. To test this hypothesis, we determined the donor:host chimera status of infiltrating liver lymphocytes and the clonal states of liver Vβ2 + and liver Vβ3 + CD4 cells isolated from GVHD mice. A limited donor TCR Vβ repertoire composed of Vβ1 + , 2 + , 3 + , 4 + , 6 + , and 8 + cells infiltrated the livers of GVHD mice on day 3. Consistent with a response to immunodominant host minor histocompatibility antigens, we detected oligoclonal liver Vβ2 + T cells in 40% of GVHD mice studied on day 3 and in 100% of GVHD mice studied on day 14. Typical of superantigen stimulation, extremely polyclonal liver Vβ3 + T cells were detected in 100% of GVHD mice studied on day 3 and 40% of GVHD mice studied on day 14. Yet, the liver Vβ3 + T cells in 60% of the day 14 GVHD mice were oligoclonal, pointing to a response to minor histocompatibility antigens.
Targeted nucleotide exchange in the alkaline phosphatase gene of HuH-7 cells mediated by a chimeric RNA/DNA oligonucleotide
Authors: B T Kren, A Cole-Strauss, E B Kmiec, C J Steer
Journal: Hepatology (1997)

Although a variety of methods has been devised for modification of hepatic genes, none has been effective for long-term correction of genetic disorders. In this study, we employed a recently described novel experimental strategy for site-directed nucleotide exchange in genomic DNA of HuH-7 human hepatoma cells. A chimeric 2′-O-methylated-RNA/DNA oligonucleotide containing sequences complementary to 25 bases of the alkaline phosphatase gene was constructed as a duplex containing a G to A substitution at nucleotide 935. Cells were transfected with oligonucleotides for 48 hours, then harvested for DNA isolation and polymerase chain reaction (PCR) amplification of exon 6 of the alkaline phosphatase gene. Colony lifts were hybridized to 17 mer 32 P-labeled oligonucleotide probes specific to the 935-G and 935-A sequences. Hybridizing colonies were grown, plasmid DNA isolated, and sequenced. Transfection efficiency was determined at 24 hours by nuclear uptake of fluorescein-12-dUTP-labeled chimeric oligonucleotides. Colonies hybridizing with the 935-A probe were identified only from cells transfected with the specific chimeric oligonucleotide; and there was no evidence of cross-hybridization. Conversion of G to A at nucleotide 935 occurred at an overall frequency of up to 11.9% and when corrected for transfection efficiency approached 43%. No other alterations were detected in the sequence of exon 6 with the targeted nucleotide exchange. These results show that a single base pair alteration in the alkaline phosphatase gene of HuH-7 cells can be introduced at a relatively high frequency following transfection with chimeric RNA/DNA oligonucleotides. This technique offers a novel and potentially powerful strategy for site-directed hepatic gene alteration without the use of viral-based vectors.
Long-term Effects of Hydroxyurea in Psoriasis
Authors: M. G. C. Dahl, J. S. Comaish
Journal: BMJ (1972)

Hydroxyurea is an effective treatment for psoriasis but consistently produces macrocytosis in peripheral blood with a fall in haemoglobin levels and white cell counts. In this long-term study of 16 patients anaemia and leukopenia have proved frequent and troublesome side effects requiring discontinuance of treatment in many cases. In view of these findings hydroxyurea cannot be recommended as the drug of first choice even for treating severe and intractable psoriasis, and it is our opinion that methotrexate is safer and at least as effective in these circumstances. The clearest indications for the use of hydroxyurea appear to be in life-ruining psoriasis when methotrexate treatment has either failed or is contraindicated because of liver damage. A great deal more investigative work is required before these indications can be generally extended.
Effects of intracoronary acetylcholine and atropine on basal and dobutamine-stimulated left ventricular contractility.
Authors: J S Landzberg, J D Parker, D F Gauthier, W S Colucci
Journal: Circulation (1994)

BACKGROUND The role of cholinergic pathways in modulating left ventricular contractile function in humans is not known. This study evaluated the effect of a cholinergic agonist (acetylcholine) and antagonist (atropine) on basal and beta-adrenergically stimulated left ventricular contractile function in normal subjects and subjects with denervated hearts after cardiac transplantation. METHODS AND RESULTS Six subjects with normal left ventricular function and seven subjects who were 1 to 3 years after cardiac transplantation were studied. Acetylcholine, atropine, and the beta-adrenergic agonist dobutamine were infused via the left main coronary artery, and changes in left ventricular contractile function were assessed by measurement of peak +dP/dt. Intracoronary dobutamine increased +dP/dt by 70 +/- 15% and 66 +/- 20% in the normal subjects and transplant recipients, respectively. Intracoronary acetylcholine and atropine alone each had no effect on left ventricular +dP/dt in either normal subjects or transplant recipients. The concurrent infusion of acetylcholine with dobutamine reduced the response to dobutamine by 66 +/- 10% and 79 +/- 9% in normal subjects and transplant recipients, respectively. The concurrent infusion of atropine with dobutamine potentiated the response to dobutamine by 25 +/- 7% in normal subjects but had no effect in transplant recipients. CONCLUSIONS Stimulation and inhibition of cholinergic receptors in the human heart can modulate the positive inotropic response to beta-adrenergic stimulation.
Obama's victory
Authors: B. Rechel, M. McKee
Journal: BMJ (2009)

What are the implications for global health?The world looked on in anticipation as a new American president was elected on 4 November 2008.Discussion in American health policy circles focused on the question of how the next president might reform the American health system.1However, the rest of the world will be more concerned about the implications for global health.This is something that demands urgent attention because the first 100 days of the new administration can be expected to set the tone for the rest of the presidential term.
Failed hip replacements.
Authors: R. N. Villar
Journal: BMJ (1992)

divert the air flow through the artificial fistula during forced expiration.This leaves the patients free to gesticulate with both hands to make their points more forcibly.Good functional results with these speech buttons have been reported from all over the world, and long term complications seem to be relatively few.2"22Many patients who have been unable to acquire oesophageal speech have been successfully treated: fluency rates of 90% have been achieved.'8The success of these valves has been so well publicised that the relations ofmany patients in the United Kingdom ask why so few have had speech buttons fitted.Cost is not a limitation-it is similar to that of a routine intermediate procedure in ear, nose, and throat surgery, and the cost of annual maintenance is no more than £150-200.The reason probably lies more in the conservatism ofBritish surgeons and past experience of unplanned and uncontrolled pharyngeal fistulas complicating laryngectomy.No doubt primary punc- ture at the time of laryngectomy will receive the same circumspect approach, though it is being performed in a few British centres.Dedicated and well trained auxiliary staff are necessary to provide a speech button service, but no good reason exists why this cannot be realised in any centre performing a reasonable amount of surgery for cancer of the head and neck.
REST IN THE TREATMENT OF DISEASES OF THE HEART.Read at the Meeting of the Tri-State Medical Society at Jacksonville Ill., Oct. 2-3, 1894.
Authors: ROBERT H. BABCOCK
Journal: JAMA (1894)

For years it has been my custom, both in practice and in teaching, to insist upon absolute rest in bed in cases of heart disease with destroyed compensation. My opinion was based upon the consideration that the only period of rest enjoyed by the heart was during diastole, and since the heart beats more slowly in a recumbent than in an erect position or during exercise, the diseased heart should be encouraged to beat slowly. Moreover, I was supported in my belief by the statements of such weighty authorities in medicine as Balfour and Liebermeister. The latter has reported an instructive case of a business man who had a serious valvular lesion, and who every now and then overstrained his heart to the point of threatened loss of compensation. He would enter the hospital and after three or four days of treatment and upon relief of his most urgent symptoms
Proceedings: Pain threshold (PT) analysis in patients with osteoarthritis of the hip.
Authors: S L O'Driscoll, M I Jayson
Journal: Annals of the Rheumatic Diseases (1975)

of Medicine Section on Rheumatology and Rehabilitation, the following papers were given.* This equals: counts' 100 seconds of tuptake of tritiated thymidine in stimulated cultures divided bv uptake in unstimulated cultures.Normal values ranged from 30 to 110 with an average of 75.t This was monitored by estimating the % release of Cr5l from the target cells.Normal values ranged from 30 to 85 with an average of 62.Cell mediated immunity to synovial antigens in rheumatoid arthritis.
Hypereosinophilia, JAK2V617F, and Budd‐Chiari syndrome: Who is responsible for what?
Authors: Elena Mishchenko, Tamar Tadmor, Elad Schiff, Dina Attias, Aaron Polliack
Journal: American Journal of Hematology (2010)

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction, which sometimes may be life threatening, with the development of fulminant hepatic failure. In cases of this kind, the most frequent underlying cause of BCS, myeloproliferative neoplasms (MPN), should always be excluded first, and molecular analysis of the Janus Kinase 2 (JAK2) mutation must always be performed [1]. While the association of BCS with polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis is well documented, hypereosinophilia has only been described in sporadic cases [2–7]. Furthermore, Jak2 mutation in association with hypereosinophilia has been reported very rarely and its prevalence in this disorder still requires further investigation [8,9]. To the best of our knowledge, cases with the above association occurring together with BCS have not been reported until now. Here, we describe a young woman presenting with idiopathic eosinophilia, JAK2 mutation, and BCS. We also elaborate briefly on the biological mechanism and clinical features of this rare entity. In our opinion, this case supports the formal inclusion of hypereosinophilic syndrome (HES) in the WHO MPN category and also raises the possible pathogenetic contribution of eosinophils, or their products, in MPN-associated splanchnic vein thrombosis.
Shantilal Raghavji Kanani
Authors: K. Somers
Journal: BMJ (2013)

Born in Uganda, Shantilal Raghavji Kanani (“Shanti”) identified an interest in tropical medicine early in his career. Working in the medical unit under Professor Alan Woodruff at the Hospital for Tropical Diseases in London, Kanani became involved in documenting and publishing clinical material that passed through the unit. He coauthored studies on …
Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities
Authors: Julie A. McEarchern, Ezogelin Oflazoglu, Leigh Francisco, Charlotte F. McDonagh, Kristine A. Gordon, Ivan Stone, Kerry Klussman, Eileen Turcott, Nico van Rooijen, Paul Carter, Iqbal S. Grewal, Alan F. Wahl, Che-Leung Law
Journal: Blood (2006)
Case 51-1974
Authors: Richard C. Cabot, Robert E. Scully, Betty U. McNeely, Barry L. Fanburg, Gerald Nash
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 44-year-old man was admitted to the hospital because of dyspnea.He was well until seven years previously, when dyspnea developed, and an x-ray film of the chest (Fig. 1) revealed diffuse parenchymal infiltrates in both lungs and bilateral hilar lymphadenopathy. He entered another hospital, where a scalene-lymph-node biopsy disclosed noncaseating granulomas consistent with sarcoidosis. No medications were given, and he became lost to follow-up examination. The dyspnea gradually increased in severity, and by six months before entry he had to rest after climbing one flight of stairs.Four months before admission he fainted without relation to . . .
Sing a new song. Presidential address delivered before the 72nd Annual Meeting of the American Society for Clinical Investigation, Washington, D. C., 11 May 1980.
Authors: J Roth
Journal: Journal of Clinical Investigation (1980)

You, the members ofThe American Society for Clinical Investigation, have honored me and my fellow officers by electing us and entrusting us with the leadership of the society.We wish to thank you for the privilege and to account to you for our terms in office.I would like to review briefly a few of our accomplishments, some of the problems that we see, and the modest experiments we have undertaken.Also I am going to assign several jobs to every member of The American Society for Clinical Investigation and to all members ofthe clinical research community.Finally, the highlight of this morning's program will be the next speaker, Professor Rolf Luft, who will discuss "
Protection against Exercise-Induced Bronchoconstriction Two Hours after a Single Dose of Montelukast in Children
Authors: Y. Wasfi, J.P. Kemp, C. Villarán, R. Massaad, W. Xin, S.S. Smugar, B.A. Knorr, G. Philip
Journal: Journal of Allergy and Clinical Immunology (2011)
The Risk of West Nile Virus Infection Is Associated with Combined Sewer Overflow Streams in Urban Atlanta, Georgia, USA
Authors: Gonzalo M. Vazquez-Prokopec, Jodi L. Vanden Eng, Rosmarie Kelly, Daniel G. Mead, Priti Kolhe, James Howgate, Uriel Kitron, Thomas R. Burkot
Journal: Environmental Health Perspectives (2010)

At present, the factors favoring transmission and amplification of West Nile Virus (WNV) within urban environments are poorly understood. In urban Atlanta, Georgia, the highly polluted waters of streams affected by combined sewer overflow (CSO) represent significant habitats for the WNV mosquito vector Culex quinquefasciatus. However, their contribution to the risk of WNV infection in humans and birds remains unclear.Our goals were to describe and quantify the spatial distribution of WNV infection in mosquitoes, humans, and corvids, such as blue jays and American crows that are particularly susceptible to WNV infection, and to assess the relationship between WNV infection and proximity to CSO-affected streams in the city of Atlanta, Georgia.We applied spatial statistics to human, corvid, and mosquito WNV surveillance data from 2001 through 2007. Multimodel analysis was used to estimate associations of WNV infection in Cx. quinquefasciatus, humans, and dead corvids with selected risk factors including distance to CSO streams and catch basins, land cover, median household income, and housing characteristics.We found that WNV infection in mosquitoes, corvids, and humans was spatially clustered and statistically associated with CSO-affected streams. WNV infection in Cx. quinquefasciatus was significantly higher in CSO compared with non-CSO streams, and WNV infection rates among humans and corvids were significantly associated with proximity to CSO-affected streams, the extent of tree cover, and median household income.Our study strongly suggests that CSO-affected streams are significant sources of Cx. quinquefasciatus mosquitoes that may facilitate WNV transmission to humans within urban environments. Our findings may have direct implications for the surveillance and control of WNV in other urban centers that continue to use CSO systems as a waste management practice.
Pain and Enlargement of an Amputated-Leg Stump-Reply
Authors: Milton Alter
Journal: JAMA (1984)

<h3>In Reply.—</h3> The patient's lancinating pain is clearly indicative of nerve irritation, which, contrary to Dr Singer's impression, need not result in atrophy of muscle even after many years, as patients with arachnoiditis or herniated disk will attest. Indeed, cases are on record with muscle hypertrophy caused by chronic nerve root irritation. Abnormal vessels rather than a scar might compress or irritate nerves in the stump, as is postulated by some for hemifacial spasm. Both Dr Singer and I agree that recurrent arteriovenous malformation accounts for the limb enlargement and the patient should be investigated angiographically. A properly fitted prosthesis can only benefit the patient, and Dr Singer's suggestion in this regard is well worth following.
Discovery and Mechanistic Characterization of a Novel Selective Nuclear Androgen Receptor Exporter for the Treatment of Prostate Cancer
Authors: Ramesh Narayanan, Muralimohan Yepuru, Adam T. Szafran, Maria Szwarc, Casey E. Bohl, Natalie L. Young, Duane D. Miller, Michael A. Mancini, James T. Dalton
Journal: Cancer Research (2010)

Abstract Despite the success of medical strategies to reduce androgen levels in the treatment of prostate cancer, this disease invariably relapses to a castrate-resistant state that is generally fatal. Although it had been thought that androgen-insensitive cancers no longer relied on the androgen receptor (AR) for growth and survival, it is now clear that this is not the case. Because relapses are known to occur by many mechanisms that keep the AR functionally active, strategies to block AR accumulation in the nucleus may be therapeutically useful. Here, we report the discovery of a selective nuclear androgen receptor exporter (SNARE) that functions to exclude AR from the nucleus. SNARE-1 binds wild-type and mutant ARs and efficiently inhibits their transactivation activity and ability to induce PSA gene expression. SNARE-1 inhibits the androgen-sensitive growth of LNCaP cells and tumor xenografts. Quantitative subcellular localization studies suggest that SNARE-1 inhibits nuclear translocation of AR, but also facilitates export of nuclear AR that has been translocated by an agonist. Mechanistic studies indicate that SNARE-1 rapidly phosphorylates p38 mitogen-activated protein kinase (MAPK) and Ser650 of the AR. Additionally, SNARE-1 was found to promote ubiquitination of AR in LNCaP cells. Lastly, SNARE-1 functions as a tissue-selective AR inhibitor, as it fails to phosphorylate p38 MAPK in U2OS bone cells that are stably transfected with AR. In summary, SNARE-1 inhibits AR function by a mechanism that is distinct from clinically available antiandrogens, such that it might inform novel methods to block AR function in androgen-independent prostate cancer. Cancer Res; 70(2); 842–51
Abstract 2181: Rapid screening of molecular targets using RT-PCR for solid tumor profiling
Authors: Kimberly L. Pouliot, Rudolph Cadet, Brynmor Watkins, Stephen T. Sonis, Edward Fey
Journal: Cancer Research (2010)

Abstract Purpose: The identification of molecular targets will be an essential step in developing mechanistically-based approaches to cancer treatment, as well as for determining tumor response and/or resistance to therapy. Not only will identification of these targets in solid tumors, but in the subsequent metastasis as well. The purpose of this study was to evaluate the utility of a large-scale tumor bank, using both xenograft and orthotopic models, as a source of material for quantification of gene expression as a tumor profiling and screening tool. Experimental Design: Solid tumors representing nine different indications were grown as a xenograft in nude mice. The panel of cell lines included: epidermoid carcinoma (A-431), lung carcinoma (A549, NCI-H460, small cell lung carcinoma: NCI-H82, NCI-H69), pancreatic carcinoma (AsPC-1, BxPC-3 and PANC-1), prostate carcinoma (Du145), breast carcinoma (MDA-MB-231, MDA-MB-435, MCF-7), colon carcincoma (HCT-15, HCT-116 and HT-29), ovarian carcinoma (OVCAR-3 and SK-OV-3) and glioma (U87-MG and U118-MG). In addition, five cell lines representing three indications were grown orthotopically (A549, NCI-H460, MDA-MB-231, MCF-7 and HT-29) in the lung, breast or colon, respectively. When subcutaneously implanted tumors reached a volume of 1500-2000mm3 samples were harvested by aseptic technique. Orthotopically implanted tumors were excised after 25 to 45 days post-implantation and tissues harvested. Animals with mammary fat pad tumors, also had lymph nodes and lungs removed. RNA was purified under sterile conditions. Expression of Akt, phosphoinositide-3 kinase (PI3K), epidermal growth factor receptor (EGFR), p53 and BCL-2 was determined using RT-PCR (Applied BioSystems TaqMan System). Results: Differential expression of target genes within solid tumors was determined using RT-PCR. An emphasis on gene expression in orthotopic and metastatic models will be discussed. Conclusion: Unlike semi-quantitiative methods such as immunohistochemistry (IHC) or Western Blotting, RT-PCR is ideal as screening tool as it is rapid, robust, quantitative and only requires a small amount of starting material. We describe a rapid screening method of gene expression in both xenograft and orthotopic models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2181.
Pharmacokinetics and its role in small molecule drug discovery research
Authors: Graham R. Jang, Robert Z. Harris, David T. Lau
Journal: Medicinal Research Reviews (2001)

Abstract Pharmacokinetics (PK), which describes the disposition of a drug in the body, should be a primary consideration in the selection of a drug candidate, ultimately contributing to its eventual clinical success or failure. Accordingly, a sound understanding of PK concepts and an appreciation of the judicious use of PK and related (e.g., metabolism, transporter) data in drug discovery can be beneficial to those involved in the process. This review defines important PK parameters (e.g., clearance, volume of distribution, half‐life), describes methods of PK data analysis (noncompartmental vs . compartmental) and provides an overview of additional concepts such as allometric scaling, PK/pharmacodynamic modeling, and nonlinear PK. Furthermore, the role and strategic use of PK screens in drug discovery are discussed. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 5, 382–396, 2001