tbuckley/cabot-search huggingface dataset:
Histopathology of the Liver - Volume I and II
Authors: B Portmann
Journal: Gut (1994)

At a time when textbooks and atlases on histopathology of the liver abound, any new- comer should be evaluated in perspective with those already available in the field.But Gerald Klatskin and Harold Conn's textbook constitutes a very unique contribution to hepatology, which in my view escapes this rule.
Switch recombination and somatic hypermutation are controlled by the heavy chain 3′ enhancer region
Authors: Wesley A. Dunnick, John T. Collins, Jian Shi, Gerwin Westfield, Clinton Fontaine, Paul Hakimpour, F. Nina Papavasiliou
Journal: The Journal of Experimental Medicine (2009)

Both class switch recombination (CSR) and somatic hypermutation (SHM) require transcription and the trans-acting factor activation-induced cytidine deaminase (AID), and must be up-regulated during antigen-dependent differentiation of B lymphocytes. To test the role of the heavy chain 3′ enhancers in both CSR and SHM, we used a BAC transgene of the entire heavy chain constant region locus. Using Cre-loxP recombination to delete a 28-kb region that contains the four known 3′ heavy chain enhancers, we isolated lines of BAC transgenic mice with an intact heavy chain locus and paired lines in the same chromosomal insertion site lacking the 3′ enhancers. Intact heavy chain transgenes undergo CSR to all heavy chain genes and mutate their transgenic VDJ exon. In paired transgenes lacking the 3′ enhancer region, CSR to most heavy chain genes is reduced to ∼1% of the levels for intact heavy chain loci; SHM is also reduced. Finally, we find that in B cells with a transgene lacking the 3′ enhancers, interchromosomal recombination between the transgenic VDJ exon and the endogenous heavy chain C genes is more easily detected than CSR within the transgene.
c-Abl Expression in Chronic Lymphocytic Leukemia Cells: Clinical and Therapeutic Implications
Authors: Ke Lin, Mark A. Glenn, Robert J. Harris, Andrew D. Duckworth, Sally Dennett, John C. Cawley, Mirko Zuzel, Joseph R. Slupsky
Journal: Cancer Research (2006)

Abstract c-Abl is important for normal B-cell development, but little is known about the function of this nonreceptor tyrosine kinase in chronic lymphocytic leukemia (CLL). Therefore, the aim of the present study was to examine the clinical, therapeutic, and pathogenetic importance of c-Abl in this disease. We show that the malignant cells of CLL predominantly express the type 1b splice variant of c-Abl and that the expression of c-Abl protein is higher in CLL cells than in normal peripheral blood B cells. Moreover, we show that the levels of c-Abl protein expression correlate positively with tumor burden and disease stage, and negatively with IgVH mutation. We also show that STI-571, an inhibitor of c-Abl kinase activity, induces apoptosis of CLL cells with high c-Abl expression levels through a mechanism involving inhibition of nuclear factor κB. We conclude that overexpression of c-Abl is likely to play a pathogenetic role in CLL and that STI-571 may be of potential use in the treatment of this disease. (Cancer Res 2006; 66(15): 7801-9)
Hyperactivated motility of human spermatozoa: a review of physiological function and application in assisted reproduction
Authors: V. Kay
Journal: Human Reproduction Update (1998)

Hyperactivated motility is a specific movement pattern which has been recognized in mammalian spermatozoa for over 25 years. During this time, it has been established that hyperactivation is part of the complex process of sperm capacitation, which is necessary before fertilization can occur. The recent introduction of computed sperm motility analysis has allowed detailed studies of sperm movement characteristics to be undertaken, and evidence is accumulating that hyperactivated motility may correlate with fertility. In this review, the physiological consequences of hyperactivated motility, methods of measurement and their application in assisted reproduction are discussed.
Increased Estrogen Receptor βcx Expression during Mammary Carcinogenesis
Authors: Majida Esslimani-Sahla, Andrew Kramar, Joelle Simony-Lafontaine, Margaret Warner, Jan-Åke Gustafsson, Henri Rochefort
Journal: Clinical Cancer Research (2005)

Abstract Identification of proteins that markedly vary during early steps of mammary carcinogenesis may help to understand its pathophysiology and to develop a prevention strategy. The expression of total estrogen receptor β (ERβ) protein and of its COOH-terminally spliced variant ERβcx (or ERβ2) was compared in 43 invasive breast cancers and in 39 adjacent normal mammary glands and 26 ductal carcinoma in situ (DCIS). Thirty-six breast cancers were ER positive by radioligand binding assay. The analysis was done by immunohistochemistry on adjacent sections of formalin-fixed, paraffin-embedded tumors using polyclonal anti-ERβ 503 IgY and sheep polyclonal ERβcx antibodies that were previously validated. Nuclear staining was quantified using a computerized image analyzer in selected areas of normal and cancer epithelial cells. Total ERβ expression was high in normal glands, decreased in DCIS (P = 0.0004), and increased from DCIS to invasive tumors (P = 0.029). In contrast, the ERβcx expression was low in normal glands, increased significantly in DCIS (P = 0.0014), and continued to increase in invasive carcinomas (P = 0.0027) in both ERα-positive and ERα-negative tumors. This is the first study showing a significant increase of the ERβcx variant protein in DCIS and invasive breast cancer compared with adjacent normal glands. This contrasts with the decrease of the total ERβ level in the same patients and indicates different mechanisms to explain these variations during mammary carcinogenesis. It also suggests a role of the ERβcx variant in carcinogenesis opposite to the protective effect of the wild-type ERβ1.
Fetal Alcohol Syndrome
Authors: Margaret S. Tenbrinck
Journal: JAMA (1975)

A boy born to a known alcoholic mother demonstrated the fetal alcohol syndrome. Although considerably postterm, he weighed less than 1.5 kg (3 lb) at birth and has failed to catch up at 2 1/2 years of age. In addition to continuing prenatal and postnatal growth and developmental deficits, he has many of the other stigmata described as characteristic of this syndrome. To this list have been added other findings from our case.
Myocardial Ca2+- and ATP-cycling imbalances in end-stage dilated and ischemic cardiomyopathies
Authors: P. J. O'Brien, J. K. Gwathmey
Journal: Cardiovascular Research (1995)

We have previously demonstrated deficiencies in myocardial cycling of Ca2+, and ATP turnover, in animals with heart failure (HF). The objective of this study was to determine the relevance of these changes to human HF.We used the Ca2+ dye, indo-1, and the Ca(2+)-channel modulator ryanodine to examine Ca(2+)-cycling in homogenates containing 2.5% myocardium from 12 patients undergoing cardiac transplantations because of ischemic or idiopathic dilated cardiomyopathies (ISCM, DCM), and compared them to homogenates from 11 organ donors who died from noncardiac causes. Key enzymes of ATP production and utilization were also assayed.In HF due to either ISCM or DCM, compared to nonfailing myocardium, rate constants (x 10(-3) s-1) for sarcoplasmic reticulum Ca(2+)-pumping (41.6 +/- 16.0 versus 15.1 +/- 5.9) and Ca(2+)-channel (25.1 +/- 8.3 versus 6.2 +/- 4.1) activities were decreased by 64 and 75%, respectively. These changes in rate constants were associated with a three-fold increase in ionized Ca2+ concentration. Compared to nonfailing myocardium, activities (IU/g) of ATP turnover were also decreased in ISCM and DCM HF by 39%, 30%, and 34%, respectively, for ATP production capacity of creatine kinase (1830 +/- 130 versus 1110 +/- 411) and oxidative phosphorylation (20.0 +/- 3.3 and 14.1 +/- 4.8), and for ATP utilization (28.2 +/- 18.7 versus 18.7 +/- 4.0). Myoglobin, a key component of oxidative phosphorylation, was approximately 50% lower with HF (1.72 +/- 0.30 versus 0.97 +/- 0.20 mg/g).As in animal models, cycling of Ca2+ and ATP turnover were markedly impaired in human heart failure. There were no consistent biochemical differences attributable to difference in etiology, excepting that myoglobin deficiency was 33% greater in ISCM than DCM. We conclude that ATP and Ca2+ cycling are significantly impaired in human HF due to DCM and ISCM.
Leisure-Time Physical Activity Is Associated With the Metabolic Syndrome in Type 1 Diabetes
Authors: Johan Wadén, Lena M. Thorn, Carol Forsblom, Timo Lakka, Markku Saraheimo, Milla Rosengård-Bärlund, Outi Heikkilä, Maija Wessman, Joni A. Turunen, Maija Parkkonen, Heikki Tikkanen, Per-Henrik Groop
Journal: Diabetes Care (2007)

The metabolic syndrome varies in prevalence among different populations. A common feature, however, is a steep increase in prevalence along with a decrease in glucose tolerance (1–2).

We have shown that 39% of adult type 1 diabetic patients have the metabolic syndrome (3), and similar data were recently reported from Italy (4). However, whether the metabolic syndrome observed in type 1 diabetes is the same as in nondiabetic and type 2 diabetic patients is unclear.

Both lifestyle (5–8) and hereditary factors (9) seem to be involved in the development of the metabolic syndrome in nondiabetic and type 2 diabetic subjects. The PPARγ (peroxisome proliferator-activated receptor γ) Pro12Ala polymorphism has been associated with type 2 diabetes, the Ala allele being associated with a lower risk (10), and with the metabolic syndrome in some (11–12) but not all (13) studies. However, whether lifestyle or genetic factors also play a role in the development and treatment of the metabolic syndrome in patients with type 1 diabetes is unknown.

Therefore, to further study the metabolic syndrome in type 1 diabetes, we investigated whether physical activity and/or the PPARγ Pro12Ala polymorphism are associated with metabolic syndrome in patients with type 1 diabetes in the Finnish Diabetic Nephropathy (FinnDiane) …
Animal and in silico models for the study of sarcomeric cardiomyopathies
Authors: D. J. Duncker, J. Bakkers, B. J. Brundel, J. Robbins, J. C. Tardiff, L. Carrier
Journal: Cardiovascular Research (2015)

Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise 'knock-in' models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy.
Medical Costs of Untreated Anemia in Elderly Patients with Predialysis Chronic Kidney Disease
Authors: Patrick Lefebvre, Mei Sheng Duh, Sharon Buteau, Brahim Bookhart, Samir H. Mody
Journal: Journal of the American Society of Nephrology (2006)

The objective of this study was to quantify the incremental medical costs that are associated with untreated anemia among elderly patients with predialysis chronic kidney disease (CKD). An analysis of claims and laboratory data between January 1999 and February 2005 was conducted. Inclusion criteria were age >/=65 yr, two or more hemoglobin readings, one or more claims for CKD, and two or more GFR values of <60 ml/min per 1.73 m(2) (stages 3 to 5 CKD). Patients were excluded when they had cancer or lupus, had received organ transplantation, or were treated for anemia. An open-cohort design was used to classify patients' observation periods into anemia and nonanemia. Both univariate and multivariate analyses were conducted to compare periods of anemia and nonanemia for average monthly medical costs; the latter was adjusted for age, gender, GFR, diabetes, hypertension, liver cirrhosis, coronary artery disease, myocardial infarction, and left ventricular hypertrophy. A subset analysis of patients with moderate CKD (stage 3) was conducted. A total of 2001 patients were identified. Untreated anemia was associated with a significant increase in medical costs, with an unadjusted incremental monthly cost of $1089 (P < 0.0001) and a cost ratio of 1.8:1 relative to nonanemia. After controlling for covariates, untreated anemia remained significantly associated with a cost increase (adjusted incremental monthly cost $503; cost ratio 1.4:1; P < 0.0001). Similar significant cost burden was observed in the subset of patients with moderate CKD. The retrospective observational design may be more susceptible to bias than a randomized, controlled trial. This large study, which was based on real-life practice data, demonstrated that untreated anemia in elderly patients with predialysis CKD was associated with a significant increase in medical costs.
Suicide Risk in Placebo-Controlled Trials of Treatment for Acute Manic Episode and Prevention of Manic-Depressive Episode
Authors: Jitschak G. Storosum, Tamar Wohlfarth, Christine C. Gispen-de Wied, Don H. Linszen, Berthold P.R. Gersons, Barbara J. van Zwieten, Wim van den Brink
Journal: American Journal of Psychiatry (2005)

The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic/depressive episode. If so, this would be a strong ethical argument against the conduct of such studies.All placebo-controlled, double-blind, randomized trials of medication for the treatment of acute manic episode and the prevention of manic/depressive episode that were part of a registration dossier submitted to the regulatory authority of the Netherlands, the Medicines Evaluation Board, between 1997 and 2003, were reviewed for occurrence of suicide and attempted suicide.In 11 placebo-controlled studies of the treatment of acute manic episode, including 1,506 patients (117 person-years) in the combined active compound group and 1,005 patients (71 person-years) in the combined placebo group, no suicides and no suicide attempts occurred. In four placebo-controlled studies of the prevention of manic/depressive episode, including 943 patients (406 person-years) in the combined active compound group and 418 patients (136 person-years) in the combined placebo group, two suicides (493/100,000 person-years of exposure) and eight suicide attempts (1,969/100,000 person-years of exposure) occurred in the combined active compound group, but no suicides and two suicide attempts (1,467/100,000 person-years of exposure) occurred in the combined placebo group.Concern about greater risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials for these indications, provided that appropriate precautions are taken.
The Bowel Cancer Screening Programme: an unusual cause of positive faecal occult bloods
Authors: P G Lidder, D Buckley, R D Pullan
Journal: Gut (2010)

The patient, an asymptomatic 63-year-old gentleman, was invited for colonoscopy through the National Health Service Bowel Cancer Screening Programme (NHS BCSP) after testing positive for faecal occult blood in his stool specimens. Rectal examination was unremarkable; however, colonoscopic examination was limited by an apparent obstruction …
Occurrence and trends in ski injuries in Norway.
Authors: O Ueland, B Kopjar
Journal: British Journal of Sports Medicine (1998)

OBJECTIVES: To provide an overview of ski injuries in Norway and to describe the changes between 1990 and 1996. METHODS: All ski injuries (7966) treated at four hospitals providing health care to a defined population of about 11% of the Norwegian population were registered prospectively from 1990 to 1996. For this study, 6462 injuries sustained in cross country skiing, downhill skiing, telemark skiing, and snowboarding were selected for further analysis. RESULTS: The relative distribution of ski injuries by type of skiing changed significantly from 1990 to 1996 (p&lt;0.001). Injuries from snowboarding showed the highest relative increase, and those sustained during downhill skiing showed a decline. The proportion of fractures in all types of skiing increased during the study period (p=0.001). The proportion of injuries to knee/lower leg decreased and the proportion to the forearm/wrist/hand increased during the study period (p=0.03). The mean age of the injured skiers differed significantly among the different types of skiing activity (p&lt;0.001): cross country skiers were the oldest followed by telemark skiers, downhill skiers, and snowboarders. CONCLUSIONS: Ski injury surveillance results in early detection of changes in temporal injury trends, allowing timely adjustment of injury prevention strategies. Injuries from snowboarding are on the increase in Norway, warranting more effective injury prevention measures.
Response to Letter Regarding Article, “Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium”
Authors: Yoram Amsalem, Micha S. Feinberg, Natalie Landa, Liron Miller, Radka Holbova, Orna Shaharabani-Yosef, Israel M. Barbash, Jonathan Leor, Yael Mardor, Dianne Daniels, Aharon Ocherashvilli
Journal: Circulation (2008)
Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1
Authors: T VONLUEDER, H KJEKSHUS, T EDVARDSEN, E OIE, S URHEIM, L VINGE, M AHMED, O SMISETH, H ATTRAMADAL
Journal: Cardiovascular Research (2004)

Objective: The pulmonary circulation may contribute to elevated plasma levels of endothelin-1 (ET-1) in congestive heart failure (CHF). The aims of the present study were to determine the mechanisms of increased secretion of ET-1 from the pulmonary circulation in CHF. Methods: Juvenile pigs were subjected to sham operation (n=9) or rapid cardiac pacing-induced CHF (215–240 bpm, n=15). Results: Three weeks of rapid pacing led to significant left ventricular dilatation, increased cardiac filling pressures, and reduced contractility (CHF pigs). Arterial plasma ET-1 levels in the CHF pigs were increased 4-fold compared to sham pigs (P<0.001). Single-bolus multiple indicator-dilution experiments revealed that pulmonary synthesis and release of ET-1 was increased in CHF, while pulmonary clearance of plasma ET-1 remained unaltered despite significant reduction of pulmonary fractional extraction of plasma ET-1. Pulmonary ECE-1 isozyme activity (pmol·min−1·mg protein−1) was selectively increased in lower lobe segments of CHF pigs (2.0±0.3) compared to lower lobe segments of controls (1.1±0.1, P<0.02), and to upper lobe segments of CHF pigs (1.1±0.1, P<0.005), and correlated significantly with the wet/dry weight ratios of the pulmonary tissue samples (R=0.75, P<0.001), i.e. a marker of pulmonary congestion. Furthermore, alveolar macrophages in congested lobe segments were identified as likely sites of increased synthesis and release of ET-1. Conclusions: In rapid pacing-induced CHF, a complex cardiopulmonary interaction revealed by pulmonary congestion causes increased pulmonary production and secretion of ET-1 due to enhanced pulmonary ECE-1 activities. Pulmonary secretion of ET-1 during evolving CHF is an important contributor to elevated plasma ET-1 levels in the systemic circulation.
The prevalence of Eye Disease in Elderly Bengalis in Tower Hamlets
Authors: Peter J Gray
Journal: Journal of the Royal Society of Medicine (1996)

The prevalence of eye disease and uncorrected refractive errors in a group of 167 elderly members of the Bangladeshi community which resides in the London Borough of Tower Hamlets was studied. Of the subjects screened 24.6% were found to have a significant and potentially treatable cause of visual loss and a further 32.3% were visually handicapped through the presence of uncorrected refractive errors. A high prevalence (53.3%) of cataract was found in the elderly Bengalis. The high prevalence of eye disease in this ethnic minority group, has important implications for health service planning.
Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth
Authors: Masahiro Akishita, Masaaki Ito, Jukka Y.A. Lehtonen, Laurent Daviet, Victor J. Dzau, Masatsugu Horiuchi
Journal: Journal of Clinical Investigation (1999)

Angiotensin II type 2 (AT2) receptor is abundantly expressed in vascular smooth muscle cells (VSMC) of the fetal vasculature during late gestation (embryonic day 15–20), during which the blood vessels undergo remodeling. To examine directly the influence of AT2 receptor expression in the developmental biology of VSMC, we studied cultures of VSMC from fetal and postnatal wild-type (Agtr2+) and AT2 receptor null (Agtr2–) mice. Consistent with in vivo data, AT2 receptor binding in cultured Agtr2+ VSMC increased by age, peaking at embryonic day 20, and decreased dramatically after birth. Angiotensin II–induced growth in Agtr2+ VSMC (embryonic day 20) was increased by the AT2 receptor blocker PD123319, indicating that the AT2 receptors are functional and exert an antigrowth effect in Agtr2+ VSMC. Growth of VSMC in response to serum decreased age dependently and was higher in Agtr2– than in Agtr2+, inversely correlating with AT2 receptor expression. However, serum-induced growth in Agtr2+ and Agtr2– VSMC and the exaggerated Agtr2– VSMC growth was maintained even in the presence of PD123319 or losartan, an AT1 receptor blocker. Moreover, Agtr2– VSMC showed greater growth responses to platelet-derived growth factor and basic fibroblast growth factor, indicating that Agtr2– cells exhibit a generalized exaggerated growth phenotype. We studied the mechanism responsible for this phenotype and observed that extracellular signal-regulated kinase (ERK) activity was higher in Agtr2– VSMC at baseline and also in response to serum. ERK kinase inhibitor PD98059 inhibited both growth and ERK phosphorylation dose–dependently, while the regression lines between growth and ERK phosphorylation were identical in Agtr2+ and Agtr2– VSMC, suggesting that increased ERK activity in Agtr2– VSMC is pivotal in the growth enhancement. Furthermore, the difference in ERK phosphorylation between Agtr2+ and Agtr2– was abolished by vanadate but not by okadaic acid, implicating tyrosine phosphatase in the difference in ERK activity. These results suggest that the AT2 receptor expression during the fetal vasculogenesis influences the growth phenotype of VSMC via the modulation of ERK cascade.