tbuckley/cabot-search huggingface dataset:
Analysis of T-cell receptor ? of the T-cell clones reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53 in patients with primary biliary cirrhosis
Authors: Y Ichiki, S Shimoda, H Hara, H Shigematsu, M Nakamura, K Hayashida, H Ishibashi, Y Niho
Journal: Hepatology (1997)

T-cell-mediated autoimmune mechanisms are considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). In the previous study, we identified the immunodominant T-cell epitope on the E2 component of pyruvate dehydrogenase complex (PDC-E2) in patients with PBC who have HLA-DRB4*0101. In this report, we revealed that the frequency of the T cells reactive to the human PDC-E2 163-176 peptide is significantly increased in the peripheral blood of patients with PBC as compared with healthy subjects. We also confirmed that these T cells were all restricted with HLA-DRB4*01 (DR53) by using HLA-DR-transfected L cells. These results together with the evidence that the immunodominant B-cell epitope overlaps with the human T-cell epitope of the PDC-E2 antigen indicate that the T cells reactive to this epitope are closely associated with the pathogenesis of PBC at least in patients who have HLA-DR53. Therefore, we analyzed the T-cell receptor (TCR) Vβ sequence of the five different T-cell clones and the three T-cell clones derived from three patients with PBC and healthy subjects, respectively, which are reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53. The Vβ- and the Jβ-gene usages were diverse among the T-cell clones (Vβ11-Jβ1.4, Vβ8-Jβ1.2, Vβ12-Jβ2.1, Vβ10-Jβ1.5, and Vβ20-Jβ2.1) in patients with PBC. By contrast, in the third complementarity determining region (CDR3), G was frequently found and GXG or GXS motif was identified in all T-cell clones. Moreover, RGXG motif was found in three clones generated from two patients. In healthy subjects, the Vβ- and the Jβ-gene usages were also diverse, and GXG and RGXG motif were found. These results indicate that the T cells may recognize the ligand (the human PDC-E2 163-176 peptide/HLA-DR53 complex) using the limited motif in the CDR3 region and that the design of CDR3-specific immunotherapy would be possible using these motifs.
Glucocorticoid unresponsiveness in severe ulcerative colitis
Authors: C J CORRIGAN
Journal: Gut (1999)

See article on page 382 

Although relatively little is known about the cellular and molecular immunopathology of ulcerative colitis, most would agree that it is an inflammatory disease. There is some support for the hypothesis that this inflammatory process is, at least in part, driven by T cells and their cytokine products. For example, anti-CD4 T cell monoclonal antibodies have been shown to abrogate disease in an animal “model” of colitis1. Anecdotally, monoclonal antibody against tumour necrosis factor α (derived in part from T cells) is effective therapy for ulcerative colitis.2 Finally, the fact that the powerful T cell suppressant cyclosporin A is effective in the treatment of acute severe colitis3 also suggests possible T cell involvement, although it should be borne in mind that cyclosporin A also has inhibitory effects on other inflammatory cells, including monocytes, basophils, and mast cells.

If this hypothesis were correct, one might expect that glucocorticoids, which are very potent inhibitors of T cell activation and cytokine secretion, would be an effective treatment for ulcerative colitis. Yet glucocorticoid therapy for acute exacerbations of ulcerative colitis frequently fails. A recent retrospective study4 of 97 patients with severe ulcerative colitis showed that, despite systemic glucocorticoid therapy, 34% required colectomy within 30 days of presentation. If, then, the “T cell hypothesis” …
A quantitative definition of ventricular asynergy
Authors: N. B. INGELS, G. T. DAUGHTERS
Journal: Cardiovascular Research (1974)

Journal Article A quantitative definition of ventricular asynergy Get access NEIL B. INGELS, JR, NEIL B. INGELS, JR From the Bioengineering and Physiology Division, Palo Alto Medical Research Foundation, 860 Bryant Street, Palo Alto, California 94301, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar GEORGE T. DAUGHTERS, II GEORGE T. DAUGHTERS, II From the Bioengineering and Physiology Division, Palo Alto Medical Research Foundation, 860 Bryant Street, Palo Alto, California 94301, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 5, September 1974, Pages 632–639, https://doi.org/10.1093/cvr/8.5.632 Published: 01 September 1974
The Breast Cancer Susceptibility Mutation <i>PALB2 1592delT</i> Is Associated with an Aggressive Tumor Phenotype
Authors: Tuomas Heikkinen, Hanni Kärkkäinen, Kirsimari Aaltonen, Roger L. Milne, Päivi Heikkilä, Kristiina Aittomäki, Carl Blomqvist, Heli Nevanlinna
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the effect of the breast cancer susceptibility mutation PALB2 1592delT on tumor phenotype and patient survival. Experimental Design: We defined the PALB2 mutation status in 947 familial and 1,274 sporadic breast cancer patients and 1,079 population controls, and compared tumor characteristics and survival in mutation carriers relative to other familial and sporadic cases and to 79 BRCA1 and 104 BRCA2 mutation carrier cases. Results: The PALB2 1592delT mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence interval (95% CI), 2.65-97.78; P &amp;lt; 0.0001] and eight sporadic patients (0.6%; odds ratio, 3.40; 95% CI, 0.68-32.95; P = 0.1207) compared with two (0.2%) control individuals. Tumors of the PALB2 mutation carriers presented triple negative (estrogen receptor negative/progesterone receptor negative/HER negative) phenotype more often (54.5%; P &amp;lt; 0.0001) than those of other familial (12.2%) or sporadic (9.4%) breast cancer patients. They were also more often of higher grade (P = 0.0027 and P = 0.0017, respectively) and had higher expression of Ki67 (P = 0.0004 and P = 0.0490, respectively). Carrying a PALB2 mutation was also associated with reduced survival, especially in familial cases (hazard ratio, 2.30; 95% CI, 1.01-5.24; P = 0.0466) and among familial patients with HER2-negative tumors (hazard ratio, 4.57; 95% CI, 1.96-10.64; P = 0.0004). Carrying a BRCA2 mutation was also found to be an independent predictor of poor survival at 10-year follow-up (P = 0.04). Conclusions: The PALB2 1592delT mutation has a strong effect on familial breast cancer risk. The tumors rising in patients carrying this mutation manifest a phenotype associated with aggressive disease. Our results also suggest a significant impact of carrying a BRCA2 mutation on long-term breast cancer survival.
Contractile function and reserve during acute ischaemia in the canine lateral border zone
Authors: A. D ASKENASE, F. F NACCARELLA, W. S WEINTRAUB, L. W KLEIN, J. B AGARWAL, R. H HELFANT
Journal: Cardiovascular Research (1988)

The hypothesis that there is a lateral border zone with function intermediate to adjacent ischaemic and non-ischaemic tissue was tested in 10 open chest anaesthetised dogs. Four pairs of segment length crystals were placed in parallel so as to span the ischaemic and non-ischaemic zones. Graded occlusion was produced with a screw clamp applied to a carotid to left anterior descending artery cannulation system. Contractile reserve was assessed using postextrasystolic potentiation. A balloon perfusion labelling system was used to label negatively the potentially ischaemic zone and quantify the admixture of ischaemic and non-ischaemic tissue in the lateral border zone, defined by the fraction of normal zone tissue. When the 40 crystal pairs from the 10 dogs were grouped according to fraction of normal zone tissue (FNZT), 13 were in the central ischaemic zone(FNZT<0.1), seven were in the border ischaemic zone (FNZT 0.1−0.5), five were in the border non-ischaemic zone (FNZT 0.5−1.0), and 15 were in the non-ischaemic zone (FNZT 1.0). When the lateral border zone is predominantly non-ischaemic tissue, the tissue behaves as though it is non-ischaemic. Segmental shortening before and after postextrasystolic potentiation in the border non-ischaemic zone and non-ischaemic zone did not change with ischaemia. When tissue in the lateral border zone is predominantly ischaemic, it behaves as though it is ischaemic. Segmental shortening decreased in parallel with progressive ischaemia in the border ischaemic zone and ischaemic zone. At total occlusion, segmental shortening in the border ischaemic zone was −2.3(5.9)% and in the ischaemic zone −3.5(3.6)% (NS). Segmental shortening after postextrasystolic potentiation also decreased in parallel with ischaemia in the border ischaemic zone and ischaemic zone and was 7.0(3.9)% and 8.4(4.5)% respectively at total occlusion (NS). Thus in the heterogeneously perfused lateral border zone function was not intermediate but was determined by the proportions of ischaemic and non-ischaemic tissue.
Understanding the imitation deficit in autism may lead to a more specific model of autism as an empathy disorder
Authors: Tony Charman
Journal: Behavioral and Brain Sciences (2002)

Preston &amp; de Waal are understandably cautious in applying their model to autism. They emphasise multiple cognitive impairments in autism, including prefrontal-executive, cerebellar-attention, and amygdala-emotion recognition deficits. Further empirical examination of imitation ability in autism may reveal deficits in the neural and cognitive basis of perception-action mapping that have a specific relation to the empathic deficit.
Hormones, Cholesterol, and Coronary Atherosclerosis
Authors: GEORGE S. KURLAND, A. STONE FREEDBERG
Journal: Circulation (1960)

Various hormones have been shown to play an important role in lipid metabolism. Clinical and experimental observations implicate the thyroid, adrenal, gonadal, and pituitary glands in atherogenesis. The evidence is strongest that estrogens play a role in human atherosclerosis. The influence of hypothyroidism requires further study and clarification. Hormones and lipids are obviously not the only factors important in atherogenesis; hypertension, local tissue factors, and altered intravascular coagulation in all probability significantly influence the natural history of the disease.
Studies on the Physiology of Awareness: Anoxia and the Levels of Sleep
Authors: J. W. L. Doust, R. A. Schneider
Journal: BMJ (1952)

It has recently been suggested (Lovett Doust, 1951a) that the varying strata of attention and awareness are intim- ately related to the levels of, fhe arterial blood oxygen saturation as determined by the methods of continuous oximetry.It was shown that "attention peaks" of periods of increased concentration and awareness are associated with a rise in the oxygen saturation levels, whereas periods of boredom, decreased concentration, reverie, etc., are correspondingly accompanied by falls in the oximetric values.Considerable work has already been done on the question of anoxia in various pathological and pharma- cological analogues of natural sleep, and its impor- tance in these states appears to be paramount.An impressive parallelism has also been found between many types of fatigue conditions and the clinical syn- drome induced by experimental anoxic anoxia; indeed, Barcroft (1925) suggested many years ago that the symp- tomatology of chronic anoxia was that of mental and bodily fatigue.These phenomena are closely associated with con- sciousness, and it was therefore thought desirable to follow such changes to their logical fulfilment-namely, that of natural sleep.Experimental Procedure Seven normal healthy human subjects were studied and 22 observations made over a period of three months.Six of the subjects were males and the seventh a female.Ages ranged from 22 to 36 years.Arterial blood oxygen saturation levels were measured photo-electrically and continuously by means of a Millikan oximeter (Millikan, 1942), with the sensitive photo-cell attached to the pinna of the ear in the con- ventional manner.The instrument was previously standardized on each occasion by the inhalation of 100% oxygen from a cylinder through a modified B.L.B. mask for at least seven minutes until stationary readings were obtained on the galvanometer.
REMOVAL OF THE STOMACH FOR SARCOMA.
Authors: J. M. BALDY
Journal: JAMA (1898)

TheJournal of the American Medical Association, Feb. 12, 1898, contains an article by Hugo Summa, M.D., and A. C. Bernays, M.D., entitled "The History and Diagnosis of a Case of Carcinoma of the Stomach and the first Operation of Excision of the Stomach in America." In view of this report it may be of interest to recall a case of sarcoma of the stomach for which excision of that organ was performed by me more than four years ago, antedating some years the now famous case of Schatter of Zurich. The case is well known in Philadelphia among my medical friends and has on several occasions been referred to in discussion on abdominal topics. The patient was examined by Dr. S. Solis-Cohen and I think Drs. T. S. K. Morton and Steinbach of the Polyclinic staff. Dr. John B. Roberts and other members of the staff were present at
Expression of Follicle-Stimulating Hormone Receptor in Tumor Blood Vessels
Authors: Aurelian Radu, Christophe Pichon, Philippe Camparo, Martine Antoine, Yves Allory, Anne Couvelard, Gaëlle Fromont, Mai Thu Vu Hai, Nicolae Ghinea
Journal: New England Journal of Medicine (2010)

In adult humans, the follicle-stimulating hormone (FSH) receptor is expressed only in the granulosa cells of the ovary and the Sertoli cells of the testis. It is minimally expressed by the endothelial cells of gonadal blood vessels.We used immunohistochemical and immunoblotting techniques involving four separate FSH-receptor-specific monoclonal antibodies that recognize different FSH receptor epitopes and in situ hybridization to detect FSH receptor in tissue samples from patients with a wide range of tumors. Immunoelectron microscopy was used to detect FSH receptor in mouse tumors.In all 1336 patients examined, FSH receptor was expressed by endothelial cells in tumors of all grades, including early T1 tumors. The tumors were located in the prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis, and ovary. In specimens obtained during surgery performed to remove tumors, the FSH receptor was not expressed in the normal tissues located more than 10 mm from the tumors. The tumor lymphatic vessels did not express FSH receptor. The endothelial cells that expressed FSH receptor were located at the periphery of the tumors in a layer that was approximately 10 mm thick; this layer extended both into and outside of the tumor. Immunoelectron microscopy in mice with xenograft tumors, after perfusion with anti–FSH-receptor antibodies coupled to colloidal gold, showed that the FSH receptor is exposed on the luminal endothelial surface and can bind and internalize circulating ligands.FSH receptor is selectively expressed on the surface of the blood vessels of a wide range of tumors. (Funded by INSERM.).
Definitely not legitimate protest, but probably not child abuse either
Authors: A. Hampson
Journal: BMJ (1996)

The first question raised in the article is that implied in its title. Should the involvement of children in a hunger strike be regarded as a legitimate form of political protest or does it constitute a form of child abuse?

In most developed countries child care legislation aims to strike a balance between the rights of families and communities to bring up their children according to their traditional beliefs and values and the duty of the state to protect children and promote their welfare. In child protection the concept of cultural relativism represents an acknowledgement that there is considerable variation in child rearing practices and few universal standards. In most cases this diversity is to be welcomed. There will be occasions, however, when the obligation to respect variations in cultural norms is overridden by a duty to intervene. It is important to be clear about this principle, but it is only marginally relevant to the present case. The participation of the children in the hunger strike does not derive from any fundamental, culturally determined set of beliefs or values, and it is most unlikely that, under normal circumstances, the withholding of food from children would be considered acceptable within …
Reply to Juan Morote’s Letter to the Editor re: Felix K. Chun, Alexandre de la Taille, Hendrik van Poppel, et al. Prostate Cancer Gene 3 (PCA3): Development and Internal Validation of a Novel Biopsy Nomogram. Eur Urol 2009;56:659–68
Authors: Felix K. Chun, Alexandre de la Taille, Hendrik van Poppel, Michael Marberger, Arnulf Stenzl, Peter F.A. Mulders, Hartwig Huland, Clement-Claude Abbou, Alexander B. Stillebroer, Martijn P.M.Q. van Gils, Jack A. Schalken, Yves Fradet, Leonard S. Marks, William Ellis, Alan W. Partin, Alexander Haese
Journal: European Urology (2009)
Non-surgical Biliary Drainage - Technique, Indications and Results
Authors: J.F. Riemann, G. Lux, W. Rösch, A. Beickert-Sterba
Journal: Endoscopy (1981)

Nonsurgical biliary drainage offers a therapeutic alternative in the palliation of malignant obstructive jaundice. Two basic approaches are available. The percutaneous transhepatic method can be employed either for external drainage or for the placement of an internal endoprosthesis. In the case of the transduodenal, transpapillary approach, either a pigtail catheter can be placed, after prior papillotomy, or - with or without the need to split the papillar - a nasobiliary drainage tube can be introduced. Successful drainage was achieved in 67 patients. In the majority of cases, external drainage was performed as a palliative measure in inoperable carcinoma of the biliodigestive system. In addition, however, pre-operative temporary drainage was also carried out to reduce the risks of surgery in patients with severe obstructive jaundice. The complication rate was low. Apart from biliary peritonitis, cholangitis and minor bleeds were observed. The rate of failure for technical reasons was a relatively low 10%.
Genetic Studies of a Cluster of Acute Lymphoblastic Leukemia Cases in Churchill County, Nevada
Authors: Karen K. Steinberg, Mary V. Relling, Margaret L. Gallagher, Christopher N. Greene, Carol S. Rubin, Deborah French, Adrianne K. Holmes, William L. Carroll, Deborah A. Koontz, Eric J. Sampson, Glen A. Satten
Journal: Environmental Health Perspectives (2006)

In a study to identify exposures associated with 15 cases of childhood leukemia, we found levels of tungsten, arsenic, and dichlorodiphenyldichloroethylene in participants to be higher than mean values reported in the National Report on Human Exposure to Environmental Chemicals. Because case and comparison families had similar levels of these contaminants, we conducted genetic studies to identify gene polymorphisms that might have made case children more susceptible than comparison children to effects of the exposures.
Specific nuclear binding of adenosine 3',5'-monophosphate-binding protein complex with subsequent poly(A) RNA synthesis in embryonic chick cartilage.
Authors: W M Burch, H E Lebovitz
Journal: Journal of Clinical Investigation (1980)

We used embryonic chick pelvic cartilage as a model to study the mechanism by which cyclic AMP increases RNA synthesis. Isolated nuclei were incubated with [32P]-8-azidoadenosine 3,5'-monophosphate ([32P]N3cAMP) with no resultant specific nuclear binding. However, in the presence of cytosol proteins, nuclear binding of [32P]N3cAMP was demonstrable that was specific, time dependent, and dependent on a heat-labile cytosol factor. The possible biological significance of the nuclear binding of the cyclic AMP-protein complex was identified by incubating isolating nuclei with either cyclic AMP or cytosol cyclic AMP-binding proteins prepared by batch elution DEAE cellulose chromatography (DEAE peak cytosol protein), or both, in the presence of cold nucleotides and [3H]uridine 5'-triphosphate. Poly(A) RNA production occurred only in nuclei incubated with cyclic AMP and the DEAE peak cytosol protein preparation. Actinomycin D inhibited the incorporation of [3H]uridine 5'-monophosphate into poly(A) RNA. The newly synthesized poly(A) RNA had a sedimentation constant of 23S. Characterization of the cytosol cyclic AMP binding proteins using [32P]N3-cAMP with photoaffinity labeling three major cAMP-binding complexes (41,000, 51,000, and 55,000 daltons). The 51,000 and 55,000 dalton cyclic AMP binding proteins were further purified by DNA-cellulose chromatography. In the presence of cyclic AMP they stimulated poly(A) RNA synthesis in isolated nuclei. The 51,000-dalton cyclic AMP-binding protein was the predominant one that bound to the nuclei. While cyclic AMP-dependent protein kinsae activity was present in the cytosol and DEAE peak cytosol proteins, it was not present in the DNA-cellulose-bound, cyclic AMP-binding proteins. We conclude that one possible mechanism by which cyclic AMP increases RNA synthesis is by complexing to a 51,000-dalton cytosol cyclic AMP-binding protein and being subsequently translocated to the nucleus, where it is specifically bound and associated with induction of poly(A) RNA synthesis.
Methotrexate and liver toxicity: role of surveillance liver biopsy. Conflict between guidelines for rheumatologists and dermatologists.
Authors: W Hassan
Journal: Annals of the Rheumatic Diseases (1996)

Methotrexate and liver toxicity: role of surveillance liver biopsy Conflict between guidelines for rheumatologists and dermatologists Methotrexate has been used successfully for the treatment of psoriasis since 1951, and over the past decade its use has increased significantly in the treatment of psoriatic arthritis and rheumatoid arthritis.The potential for hepatic toxicity remains a concern to physicians who are increas- ingly using this drug.The American Association of Dermatology has specific guidelines for monitoring the hepatic toxicity of metho- trexate in patients with psoriasis.'These recommend a baseline liver biopsy at or near the beginning of metho- tr-vataP tri-atmPfnt anti aft-r pinih cilmrilttiup ineQp of 1 .a were no published data concerning the liver toxicity of methotrexate in patients with rheumatoid arthritis, many rheumatologists initially followed the dermatology guidelines and obtained biopsy specimens before treatment and frequently thereafter.However, as the use of methotrexate increased, it emerged that clinically serious liver disease was less common in patients with rheumatoid arthritis than in those with psoriasis.The pendulum has consequently now swung to the other extreme, with rheumatologists infrequently performing liver biopsy-a practice that is further enforced by recently published guidelines from the American College of Rheumatology:2 on the basis of findings of a very low incidence of histological abnor- malities in patients with rheumatoid arthritis who are taking methotrexate, surveillance liver biopsying is not recommended (table 2).However, patients with a prior excessive alcohol consumption, persistently increased ab- Table 1 Methotrexate in psoriasis: revised guidelines A. Premethotrexate evaluation 1. Urine analysis 2. Blood urea nitrogen or serum creatinine determination 3. Creatinine clearance determination 4. Serum AST, ALT, alkaline phosphatase, bilirubin, and albumin determinations 5.Those at high risk for AIDS, an HIV antibody determination.6.If long term methotrexate treatment is anticipated, initial (premethotrexate) liver biopsying should be performed.B. Continuing laboratory studies 1. Intervals of 1-4 weeks:Complete blood cell count with differential and platelet count 2. Intervals of 3-4 months:a. Urine analysis b. Blood urea nitrogen or serum creatinine determination c.ALT, AST, alkaline phosphatase, and serum albumin determinations C.More frequent monitoring, which may be useful in the following circumstances:1.