tbuckley/cabot-search huggingface dataset:
Stemness of B-cell Progenitors in Multiple Myeloma Bone Marrow
Authors: Kelly Boucher, Nancy Parquet, Raymond Widen, Kenneth Shain, Rachid Baz, Melissa Alsina, John Koomen, Claudio Anasetti, William Dalton, Lia E. Perez
Journal: Clinical Cancer Research (2012)

Abstract Purpose: In myeloma, B cells and plasma cells show a clonal relationship. Clonotypic B cells may represent a tumor-initiating compartment or cancer stem cell responsible for minimal residual disease in myeloma. Experimental Design: We report a study of 58 patients with myeloma at time of diagnosis or relapse. B cells in bone marrow were evaluated by multicolor flow cytometry and sorting. Clonality was determined by light chain and/or immunoglobulin chain gene rearrangement PCR. We also determined aldehyde dehydrogenase activity and colony formation growth. Drug sensitivity was tested with conventional and novel agents. Results: Marrow CD19+ cells express a light chain identical to plasma cells and are therefore termed light chain restricted (LCR). The LCR B-cell mass is small in both newly diagnosed and relapsed patients (≤1%). Few marrow LCR B cells (∼10%) are CD19+/CD34+, with the rest being more differentiated CD19+/CD34− B cells. Marrow LCR CD19+ B cells exhibit enhanced aldehyde dehydrogenase activity versus healthy controls. Both CD19+/CD34+ and CD19+/CD34− cells showed colony formation activity, with colony growth efficiency optimized when stroma-conditioned medium was used. B-cell progenitors showed resistance to melphalan, lenalidomide, and bortezomib. Panobinostat, a histone deacetylase inhibitor, induced apoptosis of LCR B cells and CD138+ cells. LCR B cells are CD117, survivin, and Notch positive. Conclusions: We propose that antigen-independent B-cell differentiation stages are involved in disease origination and progression in myeloma. Furthermore, investigations of myeloma putative stem cell progenitors may lead to novel treatments to eradicate the potential reservoir of minimal residual disease. Clin Cancer Res; 18(22); 6155–68. ©2012 AACR.
Modem Transmission of Glucose Values Reduces the Costs and Need for Clinic Visits
Authors: H. Peter Chase, Jerusha A. Pearson, Clare Wightman, Mary D. Roberts, Adam D. Oderberg, Satish K. Garg
Journal: Diabetes Care (2003)

OBJECTIVE—To determine whether modem technology allows for effective management of type 1 diabetes when used in lieu of a clinic visit. RESEARCH DESIGN AND METHODS—A total of 70 adolescent patients with diabetes were prospectively randomized to either a control group or a modem group. Control group patients continued the standard of care of quarterly clinic visits, and modem group patients were instructed to transmit blood glucose data every 2 weeks for 6 months instead of a usual quarterly clinic visit. Health care providers analyzed the data received by modem and contacted patients to discuss diabetes treatment changes. GHbA1c levels were determined at 0 and 6 months, and the number of high and low blood glucose levels and adverse events were tracked. Clinic visit costs, patient expenses, and health care provider times were tracked for cost analysis for both groups. RESULTS—A total of 63 patients (33 control, 30 modem) completed the 6-month study. The GHbA1c values significantly decreased in both groups, with no statistically significant difference between groups (P = 0.96). The occurrence of mild-to-moderate hypoglycemic events were similar in the two groups, and there were no severe hypoglycemic events. The average cost of care for a clinic visit was $305.00, whereas the cost for 6 months of modem transmission was $163.00. CONCLUSIONS—This study shows that electronic transmission of blood glucose levels and other diabetes data every 2 weeks—in lieu of a clinic visit—results in a similar level of glucose control and incidence of acute diabetes complications when compared with current standard care.
Oral acquired non-dystrophic epidermolysis bullosa
Authors: Louis Forman, Fergal F. Nally
Journal: British Journal of Dermatology (1974)

Journal Article Oral acquired non‐dystrophic epidermolysis bullosa Get access Louis Forman, Louis Forman Department of Oral Medicine, Eastman Dental Hospital, London Search for other works by this author on: Oxford Academic Google Scholar Fergal F. Nally Fergal F. Nally Department of Oral Medicine, Eastman Dental Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Page 12, https://doi.org/10.1111/j.1365-2133.1974.tb12472.x Published: 01 July 1974
Phosphotyrosine-Dependent Targeting of Mitogen-Activated Protein Kinase in Differentiated Contractile Vascular Cells
Authors: Raouf A. Khalil, Constance B. Menice, C.-L. Albert Wang, Kathleen G. Morgan
Journal: Circulation Research (1995)

Abstract Tyrosine phosphorylation has been linked to plasmalemmal targeting of src homology-2–containing proteins, activation of mitogen-activated protein (MAP) kinase, nuclear signaling, and proliferation of cultured cells. Significant tyrosine phosphorylation and MAP kinase activities have also been reported in differentiated cells, but the signaling role of tyrosine-phosphorylated MAP kinase in these cells is unclear. The spatial and temporal relation between phosphotyrosine and MAP kinase immunoreactivity was quantified in differentiated contractile vascular smooth muscle cells by using digital imaging microscopy. An initial association of MAP kinase with the plasmalemma required upstream protein kinase C activity but occurred in a tyrosine phosphorylation–independent manner. Subsequent to membrane association, a delayed redistribution of MAP kinase, colocalizing with the actin-binding protein caldesmon, occurred in a tyrosine phosphorylation–dependent manner. The apparent association of MAP kinase with the contractile proteins coincided with contractile activation. Thus, tyrosine phosphorylation appears to target MAP kinase to cytoskeletal proteins in contractile vascular cells. This targeting mechanism may determine the specific destination and thereby the specialized function of MAP kinase in other phenotypes.
Cellular reaction to group A beta-haemolytic streptococcal membrane antigen and its relation to complement levels in patients with rheumatic heart disease.
Authors: R P Sapru, N K Ganguly, S Sharma, R E Chandani, A K Gupta
Journal: BMJ (1977)

Cell-mediated immunity and blood complement activities were studied in 35 patients with chronic rheumatic heart disease (RHD) and 17 normal subjects. The T-cell population in patients with RHD was reduced, as were the CH50 and C3 complement levels. The response to phytohaemagglutinin stimulation was deficient, but the lymphocytes of patients with RHD showed increased avidity for 3H-thymidine when stimulated with specific streptococcal membrane antigen. No differences were found between patients with acute rheumatic activity and those without such activity. The susceptibility of individual patients may be related to the specific sensitisation of lymphocytes, while the fact that this persisted even when T-cell numbers had returned to normal may account for the well-known recrudescenses after streptococcal infections in these patients.
Suppression of cFLIP by Lupeol, a Dietary Triterpene, Is Sufficient to Overcome Resistance to TRAIL-Mediated Apoptosis in Chemoresistant Human Pancreatic Cancer Cells
Authors: Imtiyaz Murtaza, Mohammad Saleem, Vaqar Mustafa Adhami, Bilal Bin Hafeez, Hasan Mukhtar
Journal: Cancer Research (2009)

Overexpression of cellular FLICE-like inhibitory protein (cFLIP) is reported to confer chemoresistance in pancreatic cancer (PaC) cells. This study was designed to investigate the effect of lupeol, a dietary triterpene, on (a) apoptosis of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy-resistant PaC cells overexpressing cFLIP and (b) growth of human pancreatic tumor xenografts in vivo. The effect of lupeol treatment on proliferation and TRAIL/caspase-8/cFLIP machinery in PaC cells was investigated. Next, cFLIP-overexpressing and cFLIP-suppressed cells were tested for sensitivity to recombinant TRAIL therapy in the presence of lupeol. Further, athymic nude mice implanted with AsPC-1 cells were treated with lupeol (40 mg/kg) thrice a week and surrogate biomarkers were evaluated in tumors. Lupeol alone treatment of cells caused (a) decrease in proliferation, (b) induction of caspase-8 and poly(ADP-ribose) polymerase cleavage, and (c) down-regulation of transcriptional activation and expression of cFLIP. Lupeol was observed to increase the TRAIL protein level in cells. Lupeol significantly decreased the viability of AsPC-1 cells both in cFLIP-suppressed cells and in cFLIP-overexpressing cells. Lupeol significantly sensitized chemoresistant PaC cells to undergo apoptosis by recombinant TRAIL. Finally, lupeol significantly reduced the growth of human PaC tumors propagated in athymic nude mice and caused modulation of cFLIP and TRAIL protein levels in tumors. Our findings showed the anticancer efficacy of lupeol with mechanistic rationale against highly chemoresistant human PaC cells. We suggest that lupeol, alone or as an adjuvant to current therapies, could be useful for the management of human PaC.
Phenomenon of Supernormality in the Human Heart
Authors: RASHID A. MASSUMI, EZRA A. AMSTERDAM, DEAN T. MASON
Journal: Circulation (1972)

This report documents five cases of supernormal (SN) conductivity in the sense of unexpected normalization of the previously existing bundle-branch block (BBB) and three cases of SN excitability in which impulses delivered to the ventricles propagated to the myocardium only during a well-defined interval in the cardiac cycles corresponding to the U waves of the preceding beat. In none of the patients could SN be abolished by atropine, suggesting absence of an important vagal role. In the five patients with SN conductivity there were three examples of right BBB in which spontaneous, as well as electrically induced premature atrial beats, were followed by normal QRS complexes only if they reached the right bundle during its SN phase. In the other two patients with bilateral BBB, strategically placed sinus P waves and electrically induced atrial impulses were conducted to the ventricles with normal P-His and His-Q intervals. Analysis of the electrocardiograms and His bundle electrograms indicated that SN conductivity resided in the bundle branches, and not in the A-V node. In one of two patients with bilateral BBB and SN conductivity in the right bundle branch, the SN-conducted beats occurred after both left and right ventricular escape beats, but were coupled to the preceding escape beats by longer intervals after left ventricular escape beats than after right ventricular escape beats. The difference was accounted for by the later activation of the right bundle branch when the preceding escape beat originated from the contralateral left ventricle. These observations favor an electrophysiologic explanation for the phenomenon of supernormality which is most probably related to the increased voltage of the transmembrane action potential in the period commonly known as the period of negative afterpotentials. This study provides no support for the hemodynamic or vagal theory of supernormality.
Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update
Authors: Harold J. Burstein, Sarah Temin, Holly Anderson, Thomas A. Buchholz, Nancy E. Davidson, Karen E. Gelmon, Sharon H. Giordano, Clifford A. Hudis, Diana Rowden, Alexander J. Solky, Vered Stearns, Eric P. Winer, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2014)

To update the ASCO clinical practice guideline on adjuvant endocrine therapy on the basis of emerging data on the optimal duration of treatment, particularly adjuvant tamoxifen.ASCO convened the Update Committee and conducted a systematic review of randomized clinical trials from January 2009 to June 2013 and analyzed three historical trials. Guideline recommendations were based on the Update Committee's review of the evidence. Outcomes of interest included survival, disease recurrence, and adverse events.This guideline update reflects emerging data on duration of tamoxifen treatment. There have been five studies of tamoxifen treatment beyond 5 years of therapy. The two largest studies with longest reported follow-up show a breast cancer survival advantage with 10-year durations of tamoxifen use. In addition to modest gains in survival, extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer.Previous ASCO guidelines recommended treatment of women who have hormone receptor-positive breast cancer and are premenopausal with 5 years of tamoxifen, and those who are postmenopausal a minimum of 5 years of adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor (in sequence). If women are pre- or perimenopausal and have received 5 years of adjuvant tamoxifen, they should be offered 10 years total duration of tamoxifen. If women are postmenopausal and have received 5 years of adjuvant tamoxifen, they should be offered the choice of continuing tamoxifen or switching to an aromatase inhibitor for 10 years total adjuvant endocrine therapy.
Muscular Dystrophy Occurring in Identical Twins
Authors: A. G. Beckett
Journal: BMJ (1955)

We have seen another case through the courtesy of Pro- fessor G. M. Bull in which dressing dyspraxia was a promi- nent feature.Case Report.-Aman aged 59 was first seen in September,1953, with oedema of the legs, ascites, and hypertension (210/ 120).A continuous venous hum was heard in the epigastrium (Cruveilhier-Baumgarten syndrome).A biopsy of the liver showed multiple nodular hyperplasia.He was treated with a high-protein diet and kept well until August, 1954, when his doctor reported: " Yesterday the patient became rather con- fused, and attempts to dress himself were unsuccessful."He was also reported to have melaena.On admission there was jaundice, and he was apathetic and disorientated.On examina- tion there was enlargement of the liver and spleen, and ascites, and the venous hum was very marked.With treatment by low- protein diet he made a good recovery.An annotation in the British Medical Journal (1954) refers to the dual role of liver damage and the effects of a porto- caval shunt in producing mental symptoms.It seems to us, however, that a third factor, not mentioned by the annotator, is important.In the first case described, alco- hol and intercurrent infection, and in the second, gastro- intestinal bleeding, may have played a part in precipitating the confusional episodes.One of us (Allison, 1952) has emphasized how often anoxia, dehydration, alkalaemia, the injudicious use of drugs, and electrolytic imbalance lead to psychiatric disturbances in later life.In both our cases the possible ancillary action of some such factor cannot be excluded.
Memory CD8+ T Cells Use Cell-Intrinsic Lipolysis to Support the Metabolic Programming Necessary for Development
Authors: David O’Sullivan, Gerritje J.W. van der Windt, Stanley Ching-Cheng Huang, Jonathan D. Curtis, Chih-Hao Chang, Michael D. Buck, Jing Qiu, Amber M. Smith, Wing Y. Lam, Lisa M. DiPlato, Fong-Fu Hsu, Morris J. Birnbaum, Edward J. Pearce, Erika L. Pearce
Journal: Immunity (2014)
Familial Aggregation of Delusional Proneness in Schizophrenia and Bipolar Pedigrees
Authors: Franck Schürhoff, Andrei Szöke, Alexandre Méary, Frank Bellivier, Frédéric Rouillon, David Pauls, Marion Leboyer
Journal: American Journal of Psychiatry (2003)

Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands.The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives.Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands.Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies.
Vagal chemoreflex coronary vasodilation evoked by stimulating pulmonary C-fibers in dogs.
Authors: J P Clozel, A M Roberts, J I Hoffman, H M Coleridge, J C Coleridge
Journal: Circulation Research (1985)

We performed experiments on anesthetized, open-chest dogs to determine whether the pulmonary chemoreflex (bradycardia and systemic hypotension) evoked by stimulating pulmonary C-fibers also involves reflex changes in coronary vascular resistance. We perfused the circumflex coronary artery at constant pressure (usually 100 mm Hg) and recorded mean circumflex blood flow. Stimulation of pulmonary C-fibers by right atrial injection of capsaicin (10 micrograms/kg) decreased arterial blood pressure and heart rate and increased circumflex blood flow by 32-109% (P less than 0.001). Circumflex blood flow also increased, by 26-100% (P less than 0.001), when heart rate was kept constant by pacing. Coronary vasodilation was not secondary to the reflex decrease in arterial blood pressure. Injecting capsaicin (10 micrograms/kg) into the left atrium did not increase circumflex blood flow. Reflex coronary vasodilation could still be evoked when myelinated nerve fibers were blocked selectively by cooling the cervical vagus nerves to 7-8 degrees C but was abolished by cooling to 0 degrees C, by cutting the pulmonary vagal branches, or by giving atropine. Reducing coronary perfusion pressure shifted the stimulus (dose of capsaicin)-response (increase in coronary blood flow) curve to the right, but, even at low perfusion pressures, significant reflex vasodilation still occurred. Regional (transmural) distribution of myocardial blood flow was measured by the microsphere technique at various perfusion pressures. The endocardial:epicardial blood flow ratio decreased significantly as perfusion pressure was reduced, but was not altered by right atrial injection of capsaicin at any perfusion pressure. Our results indicate that stimulation of pulmonary C-fibers triggers reflex cholinergic vasodilation in all layers of the myocardium.
IN VITRO STUDIES OF COMPLEMENT FUNCTION IN SERA OF C4-DEFICIENT GUINEA PIGS
Authors: Michael M. Frank, Joseph May, Thelma Gaither, Leonard Ellman
Journal: The Journal of Experimental Medicine (1971)

In vitro studies were performed utilizing sera from a strain of guinea pigs with a total absence of hemolytically active C4. Previous studies in these animals have demonstrated normal complement-dependent inflammatory reactions, suggesting that they are able to bypass their deficiency of C4. In vitro studies with C4-deficient serum also indicate normal activation of late-acting C components. Thus, endotoxin was capable of fixing normal amounts of the late components of complement (C3-9) in these sera, but did not fix C1 and C2. Antigen-antibody complexes fixed both early and late components of complement, although components beyond C4 were fixed less efficiently than in normal sera. Therefore, both in vivo and in vitro evidence indicates that the C4-deficient guinea pigs possess an alternate pathway for activation of late-acting complement components. Antigenic analysis of C4-deficient serum utilizing both guinea pig anti-C4 antibody and rabbit anti-C4 antibody suggests an absolute deficiency of C4-like molecules. Sera from animals with C4-deficiency were found to have one-half the normal level of C2. Sera from five of eight animals tested had 10-20% normal C1 activity. C3-9 assayed as a complex was normal.
Measurement of circulating IgG and IgE food-immune complexes
Authors: Albert L. Sheffer, Phillip L. Lieberman, Donald W. Aaronson, John A. Anderson, Allen P. Kaplan, William E. Pierson, Elliot F. Ellis, Lawrence M. Lichtenstein, Richard F. Lockey, John E. Salvaggio, Burton Zweiman, Barry Zimmerman
Journal: Journal of Allergy and Clinical Immunology (1988)
Ethnicity and academic performance in UK trained doctors and medical students: systematic review and meta-analysis
Authors: K. Woolf, H. W. W. Potts, I. C. McManus
Journal: BMJ (2011)

<b>Objective</b> To determine whether the ethnicity of UK trained doctors and medical students is related to their academic performance. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Online databases PubMed, Scopus, and ERIC; Google and Google Scholar; personal knowledge; backwards and forwards citations; specific searches of medical education journals and medical education conference abstracts. <b>Study selection</b> The included quantitative reports measured the performance of medical students or UK trained doctors from different ethnic groups in undergraduate or postgraduate assessments. Exclusions were non-UK assessments, only non-UK trained candidates, only self reported assessment data, only dropouts or another non-academic variable, obvious sampling bias, or insufficient details of ethnicity or outcomes. <b>Results </b>23 reports comparing the academic performance of medical students and doctors from different ethnic groups were included. Meta-analyses of effects from 22 reports (n=23 742) indicated candidates of “non-white” ethnicity underperformed compared with white candidates (Cohen’s d<i>=</i>−0.42, 95% confidence interval −0.50 to −0.34; P&lt;0.001). Effects in the same direction and of similar magnitude were found in meta-analyses of undergraduate assessments only, postgraduate assessments only, machine marked written assessments only, practical clinical assessments only, assessments with pass/fail outcomes only, assessments with continuous outcomes only, and in a meta-analysis of white <i>v</i> Asian candidates only. Heterogeneity was present in all meta-analyses. <b>Conclusion</b> Ethnic differences in academic performance are widespread across different medical schools, different types of exam, and in undergraduates and postgraduates. They have persisted for many years and cannot be dismissed as atypical or local problems. We need to recognise this as an issue that probably affects all of UK medical and higher education. More detailed information to track the problem as well as further research into its causes is required. Such actions are necessary to ensure a fair and just method of training and of assessing current and future doctors.