tbuckley/cabot-search huggingface dataset:
Retrospective Assessment of Islet Cell Autoantibodies in Pancreas Organ Donors
Authors: Stavros Diamantopoulos, Gloria Allende, Joseph M. Ferreira, Gaetano Ciancio, George W. Burke, Alberto Pugliese
Journal: Diabetes Care (2008)

Of deceased pancreas donors, 3-4% may have autoantibodies (AAb) to pancreatic islet cell antigens; these autoantibodies are well-established markers of type 1 diabetes. We investigated whether donor AAb positivity could affect the outcome of pancreas transplantation.We retrospectively tested AAb in 135 donors whose pancreata and kidneys were transplanted in type 1 diabetes patients. We measured AAb to glutamic acid decarboxylase (GAD-AAb), the tyrosine-phosphatase-like protein IA2 (IA2-AAb), and insulin (insulin-AAb). We then evaluated pancreas transplant outcome data.Four of 135 (2.96%) donors were AAb positive: three donors had GAD-AAb, and one donor had insulin-AAb. Their respective recipients became insulin independent on follow-up. Three of the four recipients had normal, insulin-producing grafts 3-5.8 years after transplant. The recipient of the insulin-AAb-positive donor pancreas developed chronic rejection following discontinuation of immunosuppression 3.3 years after transplant.Single AAb positivity did not affect the outcome of pancreas transplantation in our study.
Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow
Authors: Yoshihiro Ueda, Motonari Kondo, Garnett Kelsoe
Journal: The Journal of Experimental Medicine (2005)

The coordinated production of leukocytes in bone marrow is crucial for innate and adaptive immunity. Inflammation alters normal leukocyte production by promoting granulopoiesis over lymphopoiesis, a response that supports the reactive neutrophilia that follows infection. Here we demonstrate that this specialization for granulopoiesis is determined by inflammation-induced reductions of growth and retention factors, most significantly stem cell factor and CXCL12, which act preferentially to inhibit lymphoid development. These hierarchical effects suggest that the normal equilibrium of leukocyte production in bone marrow is determined by lymphopoiesis' higher demand for specific growth factors and/or retention signals. Inflammation regulates this balance by reducing growth factors that have less impact on developing neutrophils than lymphocytes. We demonstrate that granulopoiesis and lymphopoiesis are coupled specifically in the bone marrow by development in a common niche and propose that the leukopoietic equilibrium is specified by limiting amounts of developmental resources.
Renal Function and Nutritional Status at the Start of Chronic Dialysis Treatment
Authors: MAARTEN A. M. JANSEN, JOHANNA C. KOREVAAR, FRIEDO W. DEKKER, KITTY J. JAGER, ELISABETH W. BOESCHOTEN, RAYMOND T. KREDIET
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Early start of dialysis has been hypothesized to prevent deterioration of nutritional status and to lead to a better clinical outcome. According to the National Kidney Foundation/Dialysis Outcomes Quality Initiative guidelines, dialysis should be started when renal Kt/V urea falls below 2.0/wk or the protein equivalent of total nitrogen appearance normalized to body weight (nPNA) falls below 0.8 g/kg per d. The present study was performed 0 to 4 wk before the start of dialysis treatment in 114 incident Dutch patients with chronic renal failure who all had received pre-end-stage renal disease care. The objectives were ( 1 ) to analyze the relationship of different levels of residual renal function with parameters of nutritional status and ( 2 ) to investigate the relationship of renal Kt/V urea and nPNA in this population. The mean GFR at the start of dialysis treatment was 6.2 ml/min per 1.73 m 2 , and the Kt/V urea was 1.3/wk. Only 10% of the patients fulfilled the Dialysis Outcomes Quality Initiative criterion of Kt/V urea &gt; 2.0/wk. In contrast, 69% met the nPNA norm of 0.8 g/kg per d. Seventy-one percent of these patients had a normal nutritional status as scored by subjective global assessment and also other parameters of nutritional status, such as body mass index, and serum albumin fell within the normal range in the majority of the patients. Dutch predialysis patients reached a higher nPNA with the same level of Kt/V urea compared with U.S. predialysis patients. Implications of these findings are that guidelines on the initiation of dialysis treatment derived from one population are not necessarily valid in other populations.
STUDIES ON THE TRANSFERRINS OF ADULT SERUM, CORD SERUM, AND CEREBROSPINAL FLUID
Authors: W. Carey Parker, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1962)

Nine of the twelve known variants of human transferrin have been resolved by the action of neuraminidase into stepwise patterns of four additional slower moving components whose relative intensities depended upon the concentration of enzyme. These components appeared to represent the stepwise removal of the four sialic acid residues from the transferrin molecule, and at large enzyme concentrations, almost all of the transferrin was reduced to the position of the slowest moving component. In contrast, the electrophoretic mobilities of haptoglobin, ceruloplasmin, and alpha(2)-macroglobulin showed a gradual decrease with increasing neuraminidase concentration. The transferrins of chimpanzees, rhesus and cynomolgus monkeys, and cattle were resolved by neuraminidase into two slower moving components. These experiments suggested that the primate and cattle transferrins contained only two sialic acid residues accessible to the enzyme. Transferrins C, B(2), and D(1) and a cynomolgus monkey transferrin were purified from serum by starch block electrophoresis and cellulose chromatography. Ultracentrifugal analysis could detect no difference in sedimentation rate between transferrin C, the primate transferrin, and neuraminidase-treated transferrin C. The human transferrins showed no variation in amino acid composition, but the cynomolgus transferrin was approximately 20 per cent higher in serine content and 50 per cent lower in glucosamine than human transferrin C. Reactions of antigenic identity were obtained among five human transferrin variants but a reaction of only partial identity was obtained between transferrin C and the cynomolgus transferrin. The transferrin pattern of cord blood showed a prominent band in the position of transferrin C, accompanied by four faint slower moving bands which coincided with the four transferrin components produced by the action of neuraminidase on transferrin C. The transferrin pattern of cerebrospinal fluid in individuals homozygous for serum transferrin C showed two principal components, one of which appeared to contain no sialic acid. Haptoglobin, ceruloplasmin, and alpha(2)-macroglobulin were also present in cerebrospinal fluid.
Explaining the Decline in Early Mortality in Men and Women With Type 2 Diabetes
Authors: Judith Charlton, Radoslav Latinovic, Martin C. Gulliford
Journal: Diabetes Care (2008)

The purpose of this study was to test the hypothesis that changing utilization of lipid-lowering, antihypertensive, and oral hypoglycemic drugs may be associated with trends in all-cause mortality in men and women with type 2 diabetes.This was a cohort study in 197 general practices in the U.K. General Practice Research Database including 48,579 subjects with type 2 diabetes first diagnosed between 1996 and 2006. Measures included all-cause mortality and prescription of hypoglycemic, lipid-lowering, and antihypertensive drugs.From 1996 to 2006, incidence of type 2 diabetes increased and the mean age at diagnosis declined in women. Prescription of statins within 12 months of diagnosis increased (1996, women 4.9%, men 5.1%; 2005, women 63.5%, men 71.0%), as did drugs acting on the renin-angiotensin system (1996, women 19.4%, men 21.5%; 2005, women 45.5%, men 54.6%) and metformin (1996, women 19.1%, men 15.8%; 2005, women 45.5%, men 42.8%), whereas prescription of sulfonylureas declined. All-cause mortality in the first 24 months after diabetes diagnosis declined in men from 47.9 per 1,000 person-years for subjects with diabetes diagnosed in 1996 to 25.2 for subjects with diabetes diagnosed in 2006 and in women from 37.4 in 1996 to 27.6 in 2006. In a multiple regression model adjusting for age and comorbidity, prescription of statins before or after diagnosis, renin-angiotensin system drugs before or after diagnosis, and metformin after diagnosis were associated with lower mortality.Widespread implementation of more effective prescribing to control lipids, blood glucose, and blood pressure may have contributed to recent declines in early mortality in men and women with type 2 diabetes.
Answer to ‘COPD and IPF: it's all about regulation and balance’
Authors: Jia Hou, Yongchang Sun, Hui Zeng
Journal: Thorax (2014)

We thank Tzouvelekis and Bouros1 for their interest in our recent article in Thorax .2 The theory of Hippocrates reminds us of the balance theory informing traditional Chinese medicine. Ancient Chinese scholars believed there were two natural, complementary yet contradictory forces in our universe: yin and yang, with the former being feminine or negative and the latter masculine or positive. Both of them are always in a state of dynamic balance. A balanced state …
Race, Prostate Cancer Survival, and Membership in a Large Health Maintenance Organization
Authors: A. S. Robbins, A. S. Whittemore, S. K. Van Den Eeden
Journal: JNCI Journal of the National Cancer Institute (1998)

Population-based cancer registry data have shown that black men with prostate cancer have poorer stage-specific survival than white men, while studies in equal-access health care systems have not found racial differences in stage-specific survival. This study was designed to test the hypothesis that black men and white men with prostate cancer have equal stage-specific survival in equal-access health care systems.We conducted a cohort study using cancer registry data from all incident cases of prostate cancer occurring in a five-county San Francisco Bay Area region. Incident cases occurred among members (5263 cases, from January 1973 through June 1995) and nonmembers (16,019 cases, from January 1973 through December 1992) of the Kaiser Permanente Medical Care Program, a large health maintenance organization. Death rate ratios (DRRs, black men versus white men) for Kaiser members and nonmembers were computed for all stages combined (adjusting for age and stage) and for each stage (adjusting for age).Among Kaiser members, adjusted DRRs comparing black men with white men were as follows: all stages combined, 1.28 (95% confidence interval [CI] = 1.14-1.44); local stage, 1.23 (95% CI = 1.01-1.51); regional stage, 1.30 (95% CI = 0.97-1.75); and distant stage, 1.27 (95% CI = 1.07-1.50). Corresponding DRRs for nonmembers were as follows: all stages combined, 1.22 (95% CI = 1.14-1.30); local stage, 1.24 (95% CI = 1.09-1.41); regional stage, 1.48 (95% CI = 1.29-1.68); and distant stage, 1.01 (95% CI = 0.91-1.12).These results show poorer prostate cancer survival for black men compared with white men in an equal-access medical care setting. The findings are most consistent with the hypothesis of increased tumor virulence in blacks.
<i>In silico</i> Estimates of Tissue Components in Surgical Samples Based on Expression Profiling Data
Authors: Yipeng Wang, Xiao-Qin Xia, Zhenyu Jia, Anne Sawyers, Huazhen Yao, Jessica Wang-Rodriquez, Dan Mercola, Michael McClelland
Journal: Cancer Research (2010)

Tissue samples from many diseases have been used for gene expression profiling studies, but these samples often vary widely in the cell types they contain. Such variation could confound efforts to correlate expression with clinical parameters. In principle, the proportion of each major tissue component can be estimated from the profiling data and used to triage samples before studying correlations with disease parameters. Four large gene expression microarray data sets from prostate cancer, whose tissue components were estimated by pathologists, were used to test the performance of multivariate linear regression models for in silico prediction of major tissue components. Ten-fold cross-validation within each data set yielded average differences between the pathologists' predictions and the in silico predictions of 8% to 14% for the tumor component and 13% to 17% for the stroma component. Across independent data sets that used similar platforms and fresh frozen samples, the average differences were 11% to 12% for tumor and 12% to 17% for stroma. When the models were applied to 219 arrays of "tumor-enriched" samples in the literature, almost one quarter were predicted to have 30% or less tumor cells. Furthermore, there was a 10.5% difference in the average predicted tumor content between 37 recurrent and 42 nonrecurrent cancer patients. As a result, genes that correlated with tissue percentage generally also correlated with recurrence. If such a correlation is not desired, then some samples might be removed to rebalance the data set or tissue percentages might be incorporated into the prediction algorithm. A web service, "CellPred," has been designed for the in silico prediction of sample tissue components based on expression data.
Celiac Disease and Type 1 Diabetes
Authors: Francesca Lazzarotto, Daniela Basso, Mario Plebani, Alessandro Moscon, Renato Zanchetta, Corrado Betterle
Journal: Diabetes Care (2003)

Type 1 diabetes is a chronic autoimmune disorder with varying degrees of insulin deficiency resulting from an immune-mediated destruction of pancreatic β-cells, usually starting in young individuals with an acute onset (1).

Type 1 diabetes can be associated with other clinical, subclinical, or potential organ-specific autoimmune diseases, mainly of thyroid, stomach, adrenals, and intestine, contributing to depict the constellation of autoimmune polyglandular syndromes (2,3).

Celiac disease is an autoimmune enteropathy characterized by small intestinal lesions of variable severity (4). In genetically predisposed individuals, the disease is triggered by ingestion of gluten. Celiac disease is diagnosed by small-bowel biopsy and is …
Leisure Activities and the Risk of Dementia in the Elderly
Authors: Joe Verghese, Richard B. Lipton, Mindy J. Katz, Charles B. Hall, Carol A. Derby, Gail Kuslansky, Anne F. Ambrose, Martin Sliwinski, Herman Buschke
Journal: New England Journal of Medicine (2003)

Participation in leisure activities has been associated with a lower risk of dementia. It is unclear whether increased participation in leisure activities lowers the risk of dementia or participation in leisure activities declines during the preclinical phase of dementia.We examined the relation between leisure activities and the risk of dementia in a prospective cohort of 469 subjects older than 75 years of age who resided in the community and did not have dementia at base line. We examined the frequency of participation in leisure activities at enrollment and derived cognitive-activity and physical-activity scales in which the units of measure were activity-days per week. Cox proportional-hazards analysis was used to evaluate the risk of dementia according to the base-line level of participation in leisure activities, with adjustment for age, sex, educational level, presence or absence of chronic medical illnesses, and base-line cognitive status.Over a median follow-up period of 5.1 years, dementia developed in 124 subjects (Alzheimer's disease in 61 subjects, vascular dementia in 30, mixed dementia in 25, and other types of dementia in 8). Among leisure activities, reading, playing board games, playing musical instruments, and dancing were associated with a reduced risk of dementia. A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia (hazard ratio, 0.93 [95 percent confidence interval, 0.90 to 0.97]), but a one-point increment in the physical-activity score was not (hazard ratio, 1.00). The association with the cognitive-activity score persisted after the exclusion of the subjects with possible preclinical dementia at base line. Results were similar for Alzheimer's disease and vascular dementia. In linear mixed models, increased participation in cognitive activities at base line was associated with reduced rates of decline in memory.Participation in leisure activities is associated with a reduced risk of dementia, even after adjustment for base-line cognitive status and after the exclusion of subjects with possible preclinical dementia. Controlled trials are needed to assess the protective effect of cognitive leisure activities on the risk of dementia.
Sports medicine in New Zealand.
Authors: C J Milne
Journal: British Journal of Sports Medicine (1992)

Sports medicine in New Zealand is characterized by a team approach. Experienced professionals work together to the benefit of athletes, be they elite performers or those in sport for purely recreational purposes. A no-fault accident compensation scheme is used to provide speedy access to treatment services for those injured in sport and also for advice on accident prevention. Recent initiatives include a task force on drugs in sport and the creation of regional sports foundations. Sports medical education is a prominent part of the New Zealand scene.
Is <scp>ITP</scp> a thrombophilic disorder?
Authors: Francesco Rodeghiero
Journal: American Journal of Hematology (2015)

Immune thrombocytopenia (ITP) represents the epitome of acquired bleeding diseases for the hematologist. Stemming from the interest for the safety of thrombopoietin-receptor agonists (TPO-ra) romiplostim and eltrombopag, recent data have investigated if thrombotic risk is also increased in this disorder. In patients not treated with TPO-ra, a slightly higher risk of venous thrombosis (VTE) is consistently found in ITP, but not to a rate demanding special attention in the generality of cases. No significant increase of arterial thrombosis (AT) is apparent. However, age, splenectomy, and personal risk factors may put some ITP patient to a particularly higher risk of venous and arterial thrombosis (three to four times higher than the average subject). Patients exposed to TPO-ra present indirect evidence of a much higher risk of both AT and VTE. Unfortunately, no matched control population is available and the prospective and registrative nature of these studies may have emphasized the incidence of thrombosis, which was recorded as adverse event. The clinician should be able to individualize the best treatment for the patient, taking also into account the thrombotic risk, limiting active treatment of ITP to those patients really at risk of bleeding.
Magnetic Resonance Spectroscopy Monitoring of Mitogen-Activated Protein Kinase Signaling Inhibition
Authors: Mounia Beloueche-Babari, L. Elizabeth Jackson, Nada M.S. Al-Saffar, Paul Workman, Martin O. Leach, Sabrina M. Ronen
Journal: Cancer Research (2005)

Abstract Several mitogen-activated protein kinase (MAPK) signaling inhibitors are currently undergoing clinical trial as part of novel mechanism-based anticancer treatment strategies. This study was aimed at detecting biomarkers of MAPK signaling inhibition in human breast and colon carcinoma cells using magnetic resonance spectroscopy. We investigated the effect of the prototype MAPK kinase inhibitor U0126 on the 31P-MR spectra of MDA-MB-231, MCF-7 and Hs578T breast, and HCT116 colon carcinoma cells. Treatment of MDA-MB-231 cells with 50 μmol/L U0126 for 2, 4, 8, 16, 24, 32, and 40 hours caused inhibition of extracellular signal–regulated kinases (ERK1/2) phosphorylation from 2 hours onwards. 31P-MR spectra of extracted cells indicated that this was associated with a significant drop in phosphocholine levels to 78 ± 8% at 8 hours, 74 ± 8% at 16 hours, 66 ± 7% at 24 hours, 71 ± 10% at 32 hours, and 65 ± 10% at 40 hours post-treatment. In contrast, the lower concentration of 10 μmol/L U0126 for 40 hours had no significant effect on either P-ERK1/ 2 or phosphocholine levels in MDA-MB-231 cells. Depletion of P-ERK1/2 in MCF-7 and Hs578T cells with 50 μmol/L U0126 also produced a drop in phosphocholine levels to 51 ± 17% at 40 hours and 23 ± 12% at 48 hours, respectively. Similarly, in HCT116 cells, inhibition with 30 μmol/L U0126 caused depletion of P-ERK1/2 and a decrease in phosphocholine levels to 80 ± 9% at 16 hours and 61 ± 4% at 24 hours post-treatment. The reduction in phosphocholine in MDA-MB-231 and HCT116 cells correlated positively with the drop in P-ERK1/2 levels. Our results show that MAPK signaling inhibition with U0126 is associated with a time-dependent decrease in cellular phosphocholine levels. Thus, phosphocholine has potential as a noninvasive pharmacodynamic marker for monitoring MAPK signaling blockade.
EFFECT OF TOPICAL TETKAYNOIC ACID ON SEBUM EXCRETION
Authors: T. S. HAROON, J. HALL, A. HAROON
Journal: British Journal of Dermatology (1972)

SUMMARY.— The topical application of 2% tetraynoic acid in ethanol +20% of propylene glycol failed to produce a significant reduction in sebum excretion in subjects with acne.
Enoxaparin versus Unfractionated Heparin in Elective Percutaneous Coronary Intervention
Authors: Gilles Montalescot, Harvey D. White, Richard Gallo, Marc Cohen, P. Gabriel Steg, Philip E.G. Aylward, Christoph Bode, Massimo Chiariello, Spencer B. King, Robert A. Harrington, Walter J. Desmet, Carlos Macaya, Steven R. Steinhubl
Journal: New England Journal of Medicine (2006)

Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI.