tbuckley/cabot-search huggingface dataset:
Studies on the Development of Mammary Tumors in Dilute-Brown DBAb Mice Without the Agent
Authors: O. Mühlbock, W. van Ebbenhorst Tengbergen, Th. G. van Rijssel
Journal: JNCI Journal of the National Cancer Institute (1952)

Studies on the Development of Mammary Tumors in Dilute-Brown DBAb Mice Without the Agent Get access O. Mühlbock, O. Mühlbock Laboratory of the Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam, Holland Search for other works by this author on: Oxford Academic PubMed Google Scholar W. van Ebbenhorst Tengbergen, W. van Ebbenhorst Tengbergen Laboratory of the Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam, Holland Search for other works by this author on: Oxford Academic PubMed Google Scholar Th. G. van Rijssel Th. G. van Rijssel Laboratory of the Antoni van Leeuwenhoekhuis, The Netherlands Cancer Institute, Amsterdam, Holland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 2, October 1952, Pages 505–531, https://doi.org/10.1093/jnci/13.2.505 Published: 01 October 1952 Article history Received: 06 June 1952 Published: 01 October 1952
Selenium-Dependent Glutathione Peroxidase Expression is Inversely Related to Estrogen Receptor Content of Human Breast Cancer Cells
Authors: A J Townsend, C S Morrow, B K Sinha, K H Cowan
Journal: Cancer Communications (1991)

The absence of estrogen receptors (ER) in human breast tumors has been associated with a poorer prognosis compared to patients with ER positive breast cancer. Previous studies from our laboratory have shown that a multidrug resistant human breast cancer cell line selected for resistance to Adriamycin (ADR) exhibited markedly increased expression of both the pi class glutathione S-transferase (GST-pi) and the selenium-dependent glutathione peroxidase. These studies also revealed that the ER status was inversely related to the expression of GST-pi in six human breast cancer cell lines and primary tumor specimens. In the present study, we have examined the relationship between ER status and several biological properties of these cells, including their levels of glutathione peroxidase (GSH-Px) and catalase expression, their capacity to generate toxic hydroxyl radicals (degrees OH) by redox cycling of ADR, and their sensitivities to the cytotoxic effects of ADR and the oxidant, H2O2. Our results show that expression of GSH-Px, but not catalase, is inversely related to the ER status in these cell lines. Formation of the degree OH induced by treatment of cells with ADR was inversely proportional to the GSH-Px activity in these cell lines, and thus directly related to the ER status. Sensitivity of these cells to ADR or to H2O2, however, was not consistently related to ER status, GSH-Px, or catalase activity, or to ADR induced degree OH radical formation. These results indicate that these parameters are not predictive of cellular susceptibility to oxidative damage in these cell lines under the conditions studied.
Reply
Authors: Charlotte R. Grant, Rodrigo Liberal, Yun Ma, Simon C. Robson, Giorgina Mieli‐Vergani, Diego Vergani, Maria Serena Longhi
Journal: Hepatology (2014)

Potential conflict of interest: Dr. Robson received grants from Pfizer and Dainippon and holds intellectual property rights with Nanopharma. We read with interest the letter by Sebode et al., who report in patients with autoimmune hepatitis (AIH) that the frequency of CD4+CD25+CD39+ cells is lower in treated patients when compared to untreated cases. They further note no differences between untreated AIH patients and healthy individuals. The authors propose that regulatory T cell (Treg) impairment results from immunosuppressive treatment rather than being a disease‐related defect, as we had previously suggested.1 Immunosuppressive treatment may indeed impact lymphocyte numbers, including those of CD39+ Tregs: for example, in our report,1 patients treated with prednisolone and mycophenolate mofetil (MMF) had lower proportions of CD39+ Treg compared with those who were treated with prednisolone alone or with prednisolone and azathioprine. although such direct effects of the immunosuppressive drugs—MMF in our case—on Treg phenotype are indeed possible, we had posited that the lower frequencies of CD39+ Treg observed in the MMF‐treated group may reflect more severe disease, characterized by a more substantial regulatory cell impairment.1 The differences in our results may be due to the fact that, at variance with Sebode et al., we investigated prototypic Tregs that were CD4+CD39+ and CD25high. Although we had studied only three patients prior to starting immunosuppressive treatment, interestingly these individuals did not have higher numbers of CD4+CD39+CD25high Treg when contrasted with patients on immunosuppressive drugs. We should add that the involvement of CD39 in the development of autoimmune conditions is suggested by prior observations that genetic polymorphisms associated with low levels of CD39 expression are enriched in patients with Crohn's disease.2 This prior finding infers that lower levels of expression of CD39 by Treg might be linked to an autoimmune diathesis operative through impairment of adenosine generation and perturbation, at least in part, of Treg function. As suggested by Sebode et al., and agreed to by us, the functional relevance of CD4+CD39+CD25high Treg in AIH merits further investigation in larger prospective studies that include both untreated and treated patients.
Hepatomas in Choline Deficiency&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: W. D. Salmon, D. H. Copeland, M. J. Burns
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article Hepatomas in Choline Deficiency, Get access W. D. Salmon, W. D. Salmon Department of Animal Husbandry and Nutrition, Agricultural Experiment Station of the Alabama Polytechnic Institute, Auburn, Ala. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. H. Copeland, D. H. Copeland Department of Animal Husbandry and Nutrition, Agricultural Experiment Station of the Alabama Polytechnic Institute, Auburn, Ala. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Burns M. J. Burns Department of Animal Husbandry and Nutrition, Agricultural Experiment Station of the Alabama Polytechnic Institute, Auburn, Ala. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue Supplement_5, April 1955, Pages 1549–1568, https://doi.org/10.1093/jnci/15.Supplement_5.1549 Published: 01 April 1955
The dexamethasone suppression test in mixed bipolar disorder
Authors: D L Evans, C B Nemeroff
Journal: American Journal of Psychiatry (1983)

The authors administered the dexamethasone suppression test to 10 patients who met DSM-III criteria for bipolar disorder. All 7 patients with bipolar disorder, mixed type, failed to suppress cortisol; however, the 3 patients with bipolar disorder, manic type, were normal suppressors.
Vagotomy in treatment of duodenal ulcer.
Authors: V N Korzh, N V Koval'chuk, B P Kudriavtsev
Journal: BMJ (1968)

important difference is that Bence Jones protein shows only one type of light chain, either K or A, and there is considerable homogeneity within the type.In myeloma of Bence Jones type the myeloma cells produce only one form of light chain,
AB0887 Influence of Bone Mineral Density at the Femoral Neck on the Probability of Osteoporotic Fractures
Authors: L. Myasoutova, A. Vasilyev, D. Abdulganieva, S. Lapshina
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To rate 10-year probability of osteoporotic fractures based on bone mineral density (BMD) at the femoral neck. <h3>Methods</h3> The study included 70 patients (35 men and 35 women), aged 40-90 years, who applied to the largest clinics in Kazan for various reasons during the period from January to September 2014. In each of the 7 clinics (number locales) were randomly selected 10 patients (5 men and 5 women). All patients were invited for a visit to a rheumatologist for risk assessment and calculation of the 10-year probability of osteoporotic fractures (general and hip) through the FRAX validated for these purposes. Calculated on the basis taken epidemiological prevalence of risk factors in the Russian population. All the patients underwent dual-energy X-ray absorptiometry at Hologic densitometer with the definition of BMD at the femoral neck. Next was calculated the 10-year probability of fracture-adjusted BMD at the femoral neck. Threshold intervention (beginning antiosteoporotic therapy) was considered the 10-year probability of fracture over 20% for all sites of fractures and/or more than 3% for hip fractures. <h3>Results</h3> The average age of the patients was 61,8±21,3 years (women - 59,2±23,5 years, men - 63,5±18,1 years). The probability of fracture in all locations in the next 10 years, more than 20% was observed in 15 (21.4%) patients: 11 (31.4%) women and 4 (11.4%) men. The probability of hip fracture within 10 years more than 3% was detected in 13 (18.5%) patients (10 (28.6%) women and 3 (8.6%) men). After adding in the program FRAX values at the femoral neck BMD increased number of patients with a 10-year probability of fracture in all locations more than 20% (19 (27.1%) patients: 13 (37.1%) women and 6 (17.1%) men) and the femoral neck over 3% (20 (28.6%) patients: 13 (34.3%) and 7 women (20%) men). <h3>Conclusions</h3> The program allows to estimate the FRAX 10-year probability of osteoporotic fractures and to determine the threshold of intervention in individuals at risk. The advantage of this program is the ability to determine the likelihood of fractures in the absence of information about the BMD at the femoral neck. However, knowing the value of BMD significantly increases the sensitivity of the method. <h3>Disclosure of Interest</h3> None declared
Isolation and Characterization of Doxorubicin-Resistant Lewis Lung Carcinoma Variants
Authors: N A Bruno, L A Carver, D L Slate
Journal: Cancer Communications (1990)

A series of drug-resistant variants of the murine Lewis lung carcinoma (3LL-CK) cell line has been isolated using stepwise selection in increasing concentrations of doxorubicin. These variants exhibited classical multidrug resistance as evidenced by decreased doxorubicin accumulation, cross-resistance to vinblastine, reversibility of resistance by verapamil, and overexpression of P-glycoprotein. When the doxorubicin-resistant 3LL-CK cell populations were injected into the tail veins of B6D2F1 mice, their metastatic abilities were consistently reduced compared with that of the parental line.
SP0060 Peripheral Effects of Inflammation: Skeletal Muscle and Fatigue
Authors: H. Westerblad
Journal: Annals of the Rheumatic Diseases (2015)

Repeated activation of skeletal muscle results in impaired contractile function; that is, fatigue develops. Fatigue that limits everyday activities develops more rapidly if muscles are weak already in the unfatigued state. Thus from a practical perspective, muscle weakness and muscle fatigue are closely connected. Muscle weakness and impaired work capacity are commonly observed symptoms in patients with rheumatic diseases. We have studied mechanisms underlying these muscular impairments in animal models of rheumatoid arthritis (RA) and our results indicate key roles of alterations in (i) the metabolism of reactive oxygen and nitrogen species, (ii) cellular calcium handling, and (iii) myofibrillar function. <h3>Disclosure of Interest</h3> None declared
FRI0619-HPR Joint Prostheses and Biologic Therapies in a Rheumatologic Clinic
Authors: A. Lόpez Esteban, M. Montoro, J.C. Nieto González, C. Flor, C.M. González, I. Janta, J. Martínez-Barrio, M. Hinojosa, N. Bello, C. Mata-Martinez, B. Serrano, J. Lόpez-Longo, I. Monteagudo, E. Naredo, L. Carreño
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Biologic therapies (BT) have been changed considerably the treatment of autoimmune and autoinflammatory rheumatic diseases. However, patients with joint prostheses may present adverse effects due to these therapies. <h3>Objectives</h3> To describe clinical features, treatment and complications of patients with joint prosthesis treated with BT. <h3>Methods</h3> We included all patients treated in our BT Unit from January 2010 to December 2014. For each patient we analysed demographic, diagnosis, treatments, number of prostheses and complications. <h3>Results</h3> Eight hundred patients were treated with TB in our TB Unit during the study period of which 77 (9.6%) patients needed joint prosthesis. The diagnosis of patients with joint prosthesis was as follows: 51 (66.2%) rheumatoid arthritis (RA), 16 (20.7%) ankylosing spondylitis (AS), 5 (6.5%) lupus erythematosus, 3 (3.9%) psoriatic arthritis and 2 (2.6%) juvenile idiopathic arthritis. We found 129 prostheses placed in the 77 patients, of which 56 (43.4%) were hip prostheses, 50 (38.7%) were knee prostheses, 5 (3.9%) were MCF prostheses, 4 (3.1%) were ankle prostheses, 3 (2.3%) were wrist prostheses, 2 (1.5%) were IF prostheses, 2 (1.5%) were elbow prostheses and 2 (1.5%) were shoulder prostheses. The mean age of prosthesis placing was 60 years (range 28-85) and the mean disease duration at the moment of prosthesis placing was 20 years. The most used BT were as follows: 28 (36.4%) infliximab, 20 (26%) rituximab, 16 (20.7%) tocilizumab, 9 (11.6%) abatacept and 4 (5.2%) etanercept. Thirty four (44.1%) patients had received more than one biological drug, 44 (57.1%) patients had concomitant synthetic disease-modifying anti-rheumatic drugs (sDMARDs) treatments and 41 (53.2%) patients had steroid treatment associated. We recorded 7 (5.4%) prosthetic infections in 7 (9.1%) patients of which 6 were diagnosed with RA and one with AS. From all infections, 2 occurred in prosthesis placed before the beginning of BT treatment and 5 occurred in prostheses placed during BT treatment. All patients with prosthesis infections were treated with concomitant sDMARDs and steroid treatment. Five patients needed prosthesis replacement for other reasons. <h3>Conclusions</h3> Most frequent prostheses were hip and knee prostheses. The majority of prosthetic infection occurred in patients with prosthetic placement during the BT treatment. All patients with prosthesis infections received also sDMARS and steroid treatments. <h3>Disclosure of Interest</h3> None declared
What information for the patient? Large scale pilot study on experimental package inserts giving information on prescribed and over the counter drugs.
Journal: BMJ (1990)

OBJECTIVE--To compare the acceptability and the degree of understandability of two drug information leaflets on three over the counter and two prescribed drugs. DESIGN--Prospective observational study. SETTING--Random sample of municipal pharmacies throughout Italy. SUBJECTS--A total of 6992 clients of the pharmacies who requested the study drugs over a period of four months. INTERVENTION--Exposure of patients to two information leaflets, one approved by the Ministry of Health, and the other an experimental sheet prepared by the research working group. MAIN OUTCOME MEASURES--The degree of acceptability of the information was assessed by using a pretested questionnaire. Comments concerning information needs were also encouraged and collected. RESULTS--6992 Clients responded to the questionnaire. Non-metropolitan (urban and rural) areas had the highest rate of participation. The participants strongly preferred the experimental leaflets to the approved leaflets, both with respect to accessibility of the contents (overall preference 78.1% v 17.8%) and ease of understanding the contraindications of drug use (90.2% v 73.7%). Basic attitudes related to the use of written information were similar among clients of different age groups, educational levels (though emerging people with primary school or lower educational levels showed slightly lesser understanding), and geographic areas. Up to 50% of those who took over the counter drugs indicated a disposition to change their drug seeking behaviour on the basis of the information in the experimental leaflet. The comments provided a useful complementary set of data on the information needs expressed by participants. CONCLUSIONS--The results of this pilot study indicate that patients will enter active programmes to investigate the provision of problem oriented drug information. Their information needs seem to concern both prescribed and over the counter drugs. More extensive and systematic work is required to develop an improved consumer oriented language for widely used drugs.
“Whatever”
Authors: Des Spence
Journal: BMJ (2007)

“Is that you, Des?” This wasn't a seance but a random email in my mailbox. It was a friend from school with whom I had lost contact over 20 years ago. “Of course it's bloody well me” was my response. Three weeks later I walked into the restaurant and an older, greyer version of the only Mod in Orkney stood before me. Now he is a lawyer in Edinburgh, and we picked up where we left off. I reminded him of his revolting home made wine and he reminded me of the occasion following said wine when we smoked loose tea rolled in sticky labels. He jibed how he got a higher mark in maths, but I pointed out that regularly I thrashed him at cards (practical maths). But we did not brag about our professional success or how much we earnt.

Scoring points seems to matter to people, whether it be about your clothes, your car, your holidays, your weight, your house, or, of course, your children. Medicine is a hotbed of such behaviour, with superiority being our raison d'etre. In the past the pecking order was clear—physician, surgeon, anaesthetist, general practitioner, and lastly the orthopedic surgeon; we all knew where we stood and enjoyed our various sniper positions. But now we have a battalion of different hospital specialists: cardiologists, reflexologists, rheumatologists, acupuncturists, boneologists—God only knows where nurse specialists fit in. The air is now so hot with sneering volleys of bullets that all the sport has gone out of it!

Is it time to put the guns down? “Your GP said WHAT?” “HOW ridiculous,” “The diagnosis was SO obvious,” and all the rest of the rehearsed expressions and phrases need to stop. No doubt, like many GPs, I have taken abuse from patients following such remarks. My clinical acumen may be C+, but most of the time I get it right. This has taught me to bite my tongue when the shoe is on the other foot and colleagues have missed a diagnosis. The reality is that illness evolves, signs change, and patients give completely different histories to different doctors—this is the essence of clinical practice. The sniping has merely served to undermine the whole profession and erode trust with the patients. We are all in this together.

My father once told me “that if you compete then you have lost.” My children have taught me a modern version of this phrase. Next time you receive that condescending letter from a colleague, hold your hands to form a W, cock your head 30 degrees, and say loudly, “Whatever.” Silly, but highly effective.
Renal function in children receiving long-term lithium prophylaxis
Authors: S K Khandelwal, V K Varma, R Srinivasa Murthy
Journal: American Journal of Psychiatry (1984)

Four children who had received lithium carbonate for 3-5 years had unimpaired tubular and glomerular renal functions. Their serum lithium levels had been maintained at 0.5-1.0 meq/liter, and side effects had not been a problem.
LMO2 and IL2RG synergize in thymocytes to mimic the evolution of SCID-X1 gene therapy-associated T-cell leukaemia
Authors: K Ruggero, O Al-Assar, J S Chambers, R Codrington, T Brend, T H Rabbitts
Journal: Leukemia (2016)

The SCID-X1 disease occurs in males that lack a functional X-linked gene encoding the interleukin 2 receptor subunit gamma (IL2RG) and thus are immuno-deficient (reviewed in Rochman et al.1). Gene therapy has been a success in curing SCID-X1 in patients receiving autologous CD34+-bone marrow cells infected with retroviruses expressing IL2RG. This treatment protocol has, however, produced adverse T-cell effects where clonal T-cell leukaemias arose, and four have insertional mutagenesis of the T-cell oncogene LMO2.2, 3, 4, 5 LMO2 is a T-cell oncogene first discovered via chromosomal translocations in T-cell acute leukaemia (T-ALL) (reviewed in Chambers and Rabbitts6). It is unclear if the T-cell neoplasias in the SCID-X1 patients are simply due to insertional activation of the LMO2 gene or reflect synergy between LMO2 and IL2RG.7, 8, 9 Further, the recurrent involvement of LMO2 in SCID-X1 leukaemias is puzzling as other T-cell oncogenes (for example, TAL1/SCL, HOX11 and LYL1) might equally have been targets. This suggests that specific properties of LMO2 per se are required in these adverse events. The oncogenic potential of IL2RG itself also remains controversial. Although it causes T-cell lymphomas in mice transplanted with virally transduced haematopoetic stem cells,10 other studies have indicated that IL2RG is not an oncogene.11 Here we provide evidence that synergy is required between LMO2 and IL2RG proteins specifically in the T-cell lineage to elicit neoplasias and that additional mutations are required such as Notch1 mutations like those in human T-ALL.12
Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality
Authors: Asim Saha, Roddy S. O’Connor, Govindarajan Thangavelu, Scott B. Lovitch, Durga Bhavani Dandamudi, Caleph B. Wilson, Benjamin G. Vincent, Victor Tkachev, Jan M. Pawlicki, Scott N. Furlan, Leslie S. Kean, Kazutoshi Aoyama, Patricia A. Taylor, Angela Panoskaltsis-Mortari, Rocio Foncea, Parvathi Ranganathan, Steven M. Devine, Joel S. Burrill, Lili Guo, Catarina Sacristan, Nathaniel W. Snyder, Ian A. Blair, Michael C. Milone, Michael L. Dustin, James L. Riley, David A. Bernlohr, William J. Murphy, Brian T. Fife, David H. Munn, Jeffrey S. Miller, Jonathan S. Serody, Gordon J. Freeman, Arlene H. Sharpe, Laurence A. Turka, Bruce R. Blazar
Journal: Journal of Clinical Investigation (2016)

Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1–/– donors. PD-L1–deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1–/– donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell–mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD.