tbuckley/cabot-search huggingface dataset:
The Fv-2r Resistance Gene in Mice: Its Effect on Spleen Colony Formation by Friend Virus-Transformed Cells23
Authors: Kenneth J. Blank, Richard A. Steeves, Frank Lilly
Journal: JNCI Journal of the National Cancer Institute (1976)

To determine the mechanism by which the recessive Fv-2r gene confers complete resistance to spleen focus formation and to the induction of early splenomegaly characteristic of the Friend virus (FV) disease syndrome, we compared the parameters of FV infection in susceptible DBA/2 (D2) (Fv-1n, Fv-2S) and partially congenic D2.Fv-2r (Fv-1n, Fv-2r) mice. After infecting these mice with N-tropic FV complex, we followed the replication of spleen focus-forming virus (SFFV) and the generation of SFFV-transformed tumor colony-forming cells (CFC) in their spleens. By both parameters D2.Fv-2r mice were 20- to 100-fold less susceptible than DBA/2 controls, but the inhibition was only partial. Transplantation of washed spleen cells from SFFV-infected DBA/2 mice resulted In equal growth and recovery. of tumor CFC from both D2.Fv-2r and Fv-2S mice. However, these tumor cells grew as colonies in Fv-2S mice, whereas they grew diffusely in the spleens of D2.Fv-2r hosts and did not develop into macroscopically or microscopically visible colonies. Thus the completeness of the resistance to spleen focus formation that defines the Fv-2r gene was reflected only in the complete suppression of the colonial growth of tumor cells, whereas the other parameters of infection showed no or only partial inhibition.
Functional Neuroprotection and Efficient Regulation of GDNF Using Destabilizing Domains in a Rodent Model of Parkinson’s Disease
Authors: Luis Quintino, Giuseppe Manfré, Erika Elgstrand Wettergren, Angrit Namislo, Christina Isaksson, Cecilia Lundberg
Journal: Molecular Therapy (2013)

Glial cell line–derived neurotrophic factor (GDNF) has great potential to treat Parkinson's disease (PD). However, constitutive expression of GDNF can over time lead to side effects. Therefore, it would be useful to regulate GDNF expression. Recently, a new gene inducible system using destabilizing domains (DD) from E. coli dihydrofolate reductase (DHFR) has been developed and characterized. The advantage of this novel DD is that it is regulated by trimethoprim (TMP), a well-characterized drug that crosses the blood–brain barrier and can therefore be used to regulate gene expression in the brain. We have adapted this system to regulate expression of GDNF. A C-terminal fusion of GDNF and a DD with an additional furin cleavage site was able to be efficiently regulated in vitro, properly processed and was able to bind to canonical GDNF receptors, inducing a signaling cascade response in target cells. In vivo characterization of the protein showed that it could be efficiently induced by TMP and it was only functional when gene expression was turned on. Further characterization in a rodent model of PD showed that the regulated GDNF protected neurons, improved motor behavior of animals and was efficiently regulated in a pathological setting. Glial cell line–derived neurotrophic factor (GDNF) has great potential to treat Parkinson's disease (PD). However, constitutive expression of GDNF can over time lead to side effects. Therefore, it would be useful to regulate GDNF expression. Recently, a new gene inducible system using destabilizing domains (DD) from E. coli dihydrofolate reductase (DHFR) has been developed and characterized. The advantage of this novel DD is that it is regulated by trimethoprim (TMP), a well-characterized drug that crosses the blood–brain barrier and can therefore be used to regulate gene expression in the brain. We have adapted this system to regulate expression of GDNF. A C-terminal fusion of GDNF and a DD with an additional furin cleavage site was able to be efficiently regulated in vitro, properly processed and was able to bind to canonical GDNF receptors, inducing a signaling cascade response in target cells. In vivo characterization of the protein showed that it could be efficiently induced by TMP and it was only functional when gene expression was turned on. Further characterization in a rodent model of PD showed that the regulated GDNF protected neurons, improved motor behavior of animals and was efficiently regulated in a pathological setting.
Victims of Cardiac Arrest Occurring Outside the Hospital: A Source of Transplantable Kidneys
Authors: Ana I. Sánchez-Fructuoso, Maria Marques, Dolores Prats, José Conesa, Natividad Calvo, M. Jesús Pérez-Contín, Jesús Blazquez, Cristina Fernández, Ervigio Corral, Francisco Del Río, Jose R. Núñez, Alberto Barrientos
Journal: Annals of Internal Medicine (2006)

The use of non-heart-beating donors could help shorten the list of patients who are waiting for a kidney transplant. Several reports describe acceptable results of transplantations from non-heart-beating donors who had in-hospital cardiac arrest, but few reports describe results of transplantations from non-heart-beating donors who had cardiac arrest that occurred outside of the hospital (Maastricht type I and type II donors).To compare graft survival rates among patients receiving kidneys from heart-beating donors versus type I or type II non-heart-beating donors.Retrospective cohort study of transplantations performed from January 1989 to December 2004.Kidney transplant program of a teaching hospital in Madrid, Spain.320 patients who received a kidney transplant from non-heart-beating donors (273 type I donors and 47 type II donors) and 584 patients who received a kidney transplant from heart-beating donors divided into 2 groups according to donor age (age <60 years [n = 458] and age > or =60 years [n = 126]).The primary outcome measure was graft survival. The median follow-up time was 68 months (range, 9 to 198 months).One- and 5-year graft survival rates were 90.7% and 85.5%, respectively, for transplants from heart-beating donors younger than 60 years of age; 79.8% and 73.3%, respectively, for transplants from heart-beating donors 60 years of age or older (P < 0.001); and 87.4% and 82.1%, respectively, for transplants from non-heart-beating donors (P = 0.22 [vs. those from heart-beating donors < 60 years of age] and P = 0.014 [vs. those from heart-beating donors >or = 60 years of age]). Graft survival did not differ between patients who received kidneys from heart-beating donors younger than 60 years of age and patients who received kidneys from non-heart-beating donors.This single-site, observational study was retrospective, and immunosuppressive therapy regimens given to transplant recipients varied over time.Outcomes of transplants from non-heart-beating donors and younger heart-beating donors are similar, and results for transplants from non-heart-beating donors improved compared with those from older heart-beating donors. On the basis of these results, the authors encourage other transplant units to adopt the use of type I and type II non-heart-beating donors.
Premorbid Intellectual Functioning in Bipolar Disorder and Schizophrenia: Results From a Cohort Study of Male Conscripts
Authors: Jari Tiihonen, Jari Haukka, Markus Henriksson, Mary Cannon, Tuula Kieseppä, Ilmo Laaksonen, Juhani Sinivuo, Jouko Lönnqvist
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Premorbid intellectual impairment has been described in schizophrenia, but little is known about premorbid intellectual functioning in bipolar disorder or other psychoses. In this study, premorbid intellectual ability was investigated in individuals with bipolar disorder, schizophrenia, or other psychoses. METHOD: Results on verbal, arithmetic, and visuospatial reasoning tests were obtained for 195,019 apparently healthy male subjects conscripted into the Finnish Defense Forces during 1982–1987 (mean age, 19.9 years). Linkage with the Finnish Hospital Discharge Register (mean follow-up time, 7.1 years) identified conscripts later diagnosed with bipolar disorder (N=100), schizophrenia (N=621), or other psychoses (N=527). RESULTS: Poor performance on the visuospatial reasoning test at age 20 was associated with higher risks for all three disorders. The odds ratios indicating the difference in risk of illness between the lowest and highest of nine performance categories were 34.65 (95% confidence interval [CI], 4.05–296.44) for bipolar disorder, 13.76 (95% CI=5.49–34.47) for schizophrenia, and 4.28 (95% CI=2.09–8.77) for other psychoses. In contrast, the higher the score for arithmetic reasoning, the greater the risk of bipolar disorder; a high score was associated with a more than 12-fold greater risk. Verbal test performance was not associated with higher risk for psychiatric disorder. CONCLUSIONS: These results indicate that premorbid visuospatial reasoning is impaired in bipolar disorder and schizophrenia and, to a smaller extent, in other psychoses. This suggests that a subtle neurodevelopmental aberration is involved in the etiology of bipolar disorder and schizophrenia. High arithmetic test performance may be associated with greater risk for bipolar disorder.
Endocrine Tumors of the Pancreas: Recent Advances in Research and Management
Authors: J M Polak
Journal: Gut (1995)

Chapters from 27 onward deal with the nutritional treatment of disease of liver, kid- ney, lungs, bowel, and of patients with HIV infection, cancer, and the elderly.Most authors have accepted a challenge to give 'future perspectives' in their field, and common themes recurr.New substrates and drugs will be developed, the efficacy of nutri- tional support will be better tested by randomised controlled trials, and their colleagues will come to see the value of well trained multidisciplinary nutrition support teams.This is a very informative book, written by leading practitioners of the art, but I fear that clinicians who need it will outnumber clinicians who want it.
Taking the 'sting' out of local anaesthetics
Authors: C.C. LONG, R.J. MOTLEY, P.J. HOLT
Journal: British Journal of Dermatology (1991)

Journal Article Taking the 'sting' out of local anaesthetics Get access C.C. LONG, C.C. LONG Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW, U.K. Dr C.C.Long. 452 Search for other works by this author on: Oxford Academic Google Scholar R.J. MOTLEY, R.J. MOTLEY Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.J. HOLT P.J. HOLT Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 5, 1 November 1991, Pages 452–455, https://doi.org/10.1111/j.1365-2133.1991.tb14771.x Published: 01 November 1991
Prognostic significance of human papillomavirus in recurrent or metastatic head and neck cancer: an analysis of Eastern Cooperative Oncology Group trials
Authors: A. Argiris, S. Li, M. Ghebremichael, A.M. Egloff, L. Wang, A.A. Forastiere, B. Burtness, R. Mehra
Journal: Annals of Oncology (2014)
Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth
Authors: Jiyuan Ke, R Lakshman Chelvarajan, Vishal Sindhava, Darrell A Robertson, Lazaros Lekakis, C Darrell Jennings, Subbarao Bondada
Journal: Molecular Cancer (2009)

Previously we have shown that B cell receptor (BCR) expression and B cell receptor signaling pathways are important for the basal growth of B lymphoma cells. In particular we have shown that the activation of Syk, a non-src family protein tyrosine kinase and the mitogen activated protein kinases (MAPK), ERK and JNK that mediate BCR signals are required for the constitutive growth of B lymphoma cells. Since src family protein tyrosine kinases (SFKs) like Lyn are known to be needed for the phosphorylation of BCR co-receptors, Ig-alpha and Ig-beta, we hypothesized that one or more SFKs will be constitutively activated in B lymphoma cells and may be necessary for B lymphoma growth.Src kinase activity was found to be constitutively high in many murine and human B lymphoma cell lines and primary lymphoma samples. The specific pharmacological inhibitors of SFKs, PP1 and PP2 inhibited the proliferation of a number of both murine and human B lymphomas in a dose-dependent manner. Importantly, dasatinib (BMS-354825), an oral dual BCR-ABL and SFK specific inhibitor inhibited the growth of B lymphomas in the nanomolar range in vitro and strongly inhibited a mouse lymphoma growth in vivo. Among the SFKs, Lyn is predominantly phosphorylated and Lyn-specific small interfering RNA inhibited the growth of B lymphomas, supporting an important role for Lyn in B lymphoma growth. Suppression of SFK activity blocks BCR mediated signaling pathways. PMA or CpG can partially reverse the growth inhibition induced by SFK inhibition. Although blocking SFK activity inhibited the growth of a number of B lymphomas, some lymphomas such as SudHL-4, SudHL-6, OCI-Ly3 and OCI-Ly10 are more resistant due to an increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL.These studies further support our concept that BCR signaling pathways are important for the continued growth of established B lymphoma cells. Some of the intermediates in this BCR pathway are potential immunotherapeutic targets. In particular, inhibition of SFK activity alone or in synergy with inhibition of the prosurvival Bcl-2 proteins holds promise in developing more effective treatments for B lymphoma patients.
A case of linear IgA buUous dermatosis with IgA anti-type VII collagen autoantibodies
Authors: T. HASHIMOTO, A. ISHIKO, H. SHIMIZU, T. TANAKA, H.J. DODD, B.S. BHOGAL, M.M. BLACK, T. NISHIKAWA
Journal: British Journal of Dermatology (1996)

In this study we present a patient with the sublamina densa type of linear IgA bullous dermatosis (LABD), with IgA autoantibodies reactive with the 290-kDa type VII collagen (the epidermolysis bullosa acquisita (EBA) antigen) and with immunoblotting of normal human dermal extracts. The clinical and histological features of the present case were compatible with those of LABD but quite different from those of EBA. Although EBA sera reacted with the bacterial fusion protein of the N-terminal globular (NC1) domain of type VII collagen, this patient's serum did not show reactivity. Furthermore, ultrastructural localization of target epitopes on the anchoring fibrils in this patient was considerably different from EBA. These results indicate that, whereas EBA antibodies react with the NC1 domain of type VII collagen, the epitope in this case is different from that of EBA (and is most likely on the central triple helical domain). This difference may be responsible for the clinical presentation in this patient being distinct from that of EBA.
Cellular Immune Response Against Autologous Human Malignant Melanoma: Are In Vitro Studies Providing a Framework for a More Effective Immunotherapy?
Authors: G. Parmiani, A. Anichini, G. Fossati
Journal: JNCI Journal of the National Cancer Institute (1990)

Data concerning the in vitro lymphocyte response against autologous tumors are reviewed, with a particular emphasis on melanoma. Evidence for such an immune response to tumors has been accumulating over the last 10 years through the work of several groups of investigators. Proliferative and/or cytotoxic responses are detectable in approximately 70% of patients with primary tumors, whereas the in vitro reaction with metastatic lesions is much less frequent. This response is mainly mediated by T lymphocytes obtained from peripheral blood, tumor lesions, and lymph nodes, but patients' suppressor cells and factors have been reported to inhibit such response. Clonal analysis revealed a low but consistent frequency of antimelanoma-specific T-cytotoxic and/or proliferating cells even in metastatic melanoma patients; such effectors are major histocompatibility complex restricted and use the T-cell receptor for tumor recognition of unique and, possibly, cross-reacting melanoma-restricted antigens. The chemical and genetic nature of such molecules remains to be defined. After the limited but biologically fundamental clinical responses achieved by adoptive immu-notherapy with interleukin-2 and lymphokine-activated killers, T cells appear to lend themselves as crucial new effectors in adoptive immunotherapy of human cancer and, in particular, of melanoma. [J Natl Cancer Inst 82: 361–370, 1990]
Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer
Authors: J.L. Oh, E.E. Vokes, M.S. Kies, B.B. Mittal, M.E. Witt, R.R. Weichselbaum, D.J. Haraf
Journal: Annals of Oncology (2003)
Anthropometry of young competitive sport rock climbers
Authors: P B Watts, L M Joubert, A K Lish, J D Mast, B Wilkins
Journal: British Journal of Sports Medicine (2003)

Background: Adult elite competitive rock climbers are small in stature with low body mass and very low body fat percentage. These characteristics have generated concern that young climbers may attempt body mass reduction to extreme levels with adverse consequences for health and performance. No published anthropometry data for young competitive climbers exist. Objective: To describe the general anthropometric characteristics of junior US competitive rock climbers. Methods: Ninety subjects (mean (SD) age 13.5 (3.0) years) volunteered to participate. All competed at the Junior Competition Climbers Association US National Championship. Anthropometric variables, including height, mass, body mass index (BMI), arm span, biiliocristal and biacromial breadths, skinfold thickness at nine anatomical sites, forearm and hand volumes, and handgrip strength, were measured. Selected variables were expressed as ratio values and as normative age and sex matched centile scores where appropriate. A control group (n = 45) of non-climbing children and youths who participated in a variety of sports activities, including basketball, cross country running, cross country skiing, soccer, and swimming, underwent the same testing procedures in the Exercise Science Laboratory of Northern Michigan University. Results: Mean (SD) self reported climbing ability was 11.80 (1.20), or about 5.11d on the Yosemite decimal system scale. The mean (SD) experience level was 3.2 (1.9) years, and subjects competed in 10 (5) organised competitions over a 12 month period. Despite similarity in age, there were significant differences (p&lt;0.01) between climbers and control subjects for height, mass, centile scores for height and mass, ratio of arm span to height (“ape index”), biiliocristal/biacromial ratio, sum of seven and sum of nine skinfolds, estimated body fat percentage, and handgrip/mass ratio. Despite significantly lower skinfold sums and estimated body fat percentage, no differences were found between climbers and controls for absolute BMI or BMI expressed as a centile score. Conclusions: Young competitive climbers have similar general anthropometric characteristics to elite adult climbers. These include relatively small stature, low body mass, low sums of skinfolds, and high handgrip to mass ratio. Relative to age matched athletic non-climbers, climbers appear to be more linear in body type with narrow shoulders relative to hips. Differences in body composition exist between climbers and non-climbing athletes despite similar BMI values.
Effect of Changing the Priority for HLA Matching on the Rates and Outcomes of Kidney Transplantation in Minority Groups
Authors: John P. Roberts, Robert A. Wolfe, Jennifer L. Bragg-Gresham, Sarah H. Rush, James J. Wynn, Dale A. Distant, Valarie B. Ashby, Philip J. Held, Friedrich K. Port
Journal: New England Journal of Medicine (2004)

HLA typing and the time a patient has spent on the waiting list are the primary criteria used to allocate cadaveric kidneys for transplantation in the United States. Candidates with no HLA-A, B, and DR mismatches are given top priority, followed by candidates with the fewest mismatches at the HLA-B and DR loci; this policy contributes to a higher transplantation rate among whites than nonwhites. We hypothesized that changing this allocation policy would affect graft survival and the racial balance among transplant recipients.We estimated the relative rates of kidney transplantation according to race resulting from the current allocation policy and racial differences in HLA antigen profiles, using a Cox model for the time from placement on the waiting list to transplantation. Another model, also adjusted for HLA-B and DR antigen profiles, estimated the relative rates of kidney transplantation that would result if the distribution of these antigen profiles were identical among the racial and ethnic groups. We also investigated the effect of HLA matching on the risk of graft failure, using a Cox model for the time from the first transplantation to graft failure. The results of the two analyses were used to estimate the change in the racial balance of transplantation and graft-failure rates that would result from the elimination of HLA-B matching or HLA-B and DR matching as a means of assigning priority.Eliminating the HLA-B matching as a priority while maintaining HLA-DR matching as a priority would decrease the number of transplantations among whites by 4.0 percent (166 fewer transplantations over a one-year period), whereas it would increase the number among nonwhites by 6.3 percent and increase the rate of graft loss by 2.0 percent.Removing HLA-B matching as a priority for the allocation of cadaveric kidneys could reduce the existing racial imbalance by increasing the number of transplantations among nonwhites, with only a small increase in the rate of graft loss.
Phase I Dose-Escalation Study of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer
Authors: Thomas P. Boike, Yair Lotan, L. Chinsoo Cho, Jeffrey Brindle, Paul DeRose, Xian-Jin Xie, Jingsheng Yan, Ryan Foster, David Pistenmaa, Alida Perkins, Susan Cooley, Robert Timmerman
Journal: Journal of Clinical Oncology (2011)

To evaluate the tolerability of escalating doses of stereotactic body radiation therapy in the treatment of localized prostate cancer.Eligible patients included those with Gleason score 2 to 6 with prostate-specific antigen (PSA) ≤ 20, Gleason score 7 with PSA ≤ 15, ≤ T2b, prostate size ≤ 60 cm(3), and American Urological Association (AUA) score ≤ 15. Pretreatment preparation required an enema and placement of a rectal balloon. Dose-limiting toxicity (DLT) was defined as grade 3 or worse GI/genitourinary (GU) toxicity by Common Terminology Criteria of Adverse Events (version 3). Patients completed quality-of-life questionnaires at defined intervals.Groups of 15 patients received 45 Gy, 47.5 Gy, and 50 Gy in five fractions (45 total patients). The median follow-up is 30 months (range, 3 to 36 months), 18 months (range, 0 to 30 months), and 12 months (range, 3 to 18 months) for the 45 Gy, 47.5 Gy, and 50 Gy groups, respectively. For all patients, GI grade ≥ 2 and grade ≥ 3 toxicity occurred in 18% and 2%, respectively, and GU grade ≥ 2 and grade ≥ 3 toxicity occurred in 31% and 4%, respectively. Mean AUA scores increased significantly from baseline in the 47.5-Gy dose level (P = .002) as compared with the other dose levels, where mean values returned to baseline. Rectal quality-of-life scores (Expanded Prostate Cancer Index Composite) fell from baseline up to 12 months but trended back at 18 months. In all patients, PSA control is 100% by the nadir + 2 ng/mL failure definition.Dose escalation to 50 Gy has been completed without DLT. A multicenter phase II trial is underway treating patients to 50 Gy in five fractions to further evaluate this experimental therapy.