tbuckley/cabot-search huggingface dataset:
Collateral Genome Instability by DNA Damage in Mitosis
Authors: Nannette Jelluma, Geert J.P.L. Kops
Journal: Cancer Discovery (2014)

Abstract Summary: Chromosome segregation errors and DNA damage are in a vicious cycle in cancer cells. Bakhoum and colleagues show that the molecular response to damaged DNA during mitosis impairs the chromosome segregation machinery, adding a new level to the already dangerous relations between different kinds of genomic instability. Cancer Discov; 4(11); 1256–8. ©2014 AACR. See related article by Bakhoum et al., p. 1281
Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment
Authors: P.O. Chappuis, E. Donato, J.R. Goffin, N. Wong, L.R. Bégin, L.R. Kapusta, J.-S. Brunet, P. Porter, W.D. Foulkes
Journal: Annals of Oncology (2005)
Synthesis of hemoglobin F in adult simian erythroid progenitor-derived colonies.
Authors: R M Macklis, J Javid, J M Lipton, M Kudisch, P K Pettis, D G Nathan
Journal: Journal of Clinical Investigation (1982)

The simian hematopoietic system is known to respond to anemic stress with the production of erythrocytes containing large amounts of fetal hemoglobin. To determine the regulatory mechanism responsible for hemoglobin F (HbF) production in stress erythropoiesis, adult simian bone marrow cells were cultured in plasma clots in the presence or absence of erythropoietin and burst-promoting activities, and the HbF content of progenitor-derived colonies was determined by radioimmunoligand assay. Three classes of erythroid progenitors were detected: BFU-E, CFU-E, and a very mature cohort of dense highly erythropoietin-responsive cells (HERC). These classes varied in inverse proportion to their maturity with respect to their potential for HbF accumulation in the colonies to which they give rise. Both erythropoietin and burst-promoting activity stimulated HbF production, particularly in colonies derived from immature progenitors. For example, under conditions of high erythropoietin stimulation, BFU-E colonies contained 13.7-37.7% HbF, CFU-E colonies contained 2.8-13.5% HbF, and HERC colonies 0-1% HbF. These results suggest that under nonstress conditions simian erythrocytes are derived almost entirely from HERC progenitors and proerythroblasts in which gamma chain synthesis is suppressed. During stress erythropoiesis, augmented HbF accumulation could be explained by the rapid entrance into the marrow of proerythroblasts directly derived from immature progenitors. Gamma chain production in these proerythroblasts is additionally regulated by the changes in environmental erythropoietin and burst-promoting activities.
<i>In vivo</i> Significance of the G2 Restriction Point
Authors: Floris Foijer, Elly Delzenne-Goette, Marleen Dekker, Hein te Riele
Journal: Cancer Research (2007)

Abstract Loss of activity of the retinoblastoma pathway is a common event in human cancer. Mouse models have revealed that tumorigenesis by loss of Rb was accelerated by concomitant loss of the cell cycle inhibitor p27KIP1. This has been attributed to reduced apoptosis and weakening of the G1 checkpoint. However, the role of p27KIP1 in a recently identified G2 restriction point may offer an alternative explanation for this synergy. Here, we have investigated the significance of the G2 restriction point in Rb-deficient pituitaries. We show that Rb loss in the pituitary gland activated the G2 restriction point, as evidenced by the appearance of cyclin B1–p27KIP1 complexes. Somewhat unexpectedly, these complexes remained present in Rb-deficient tumors. These results indicate that the G2 restriction point does operate in vivo. However, in the pituitary gland, this mechanism seems to retard rather than to prevent tumor growth. [Cancer Res 2007;67(19):9244–7]
Cancer cachexia is regulated by selective targeting of skeletal muscle gene products
Authors: Swarnali Acharyya, Katherine J. Ladner, Lori L. Nelsen, Jeffrey Damrauer, Peter J. Reiser, Steven Swoap, Denis C. Guttridge
Journal: Journal of Clinical Investigation (2004)

Cachexia is a syndrome characterized by wasting of skeletal muscle and contributes to nearly one-third of all cancer deaths. Cytokines and tumor factors mediate wasting by suppressing muscle gene products, but exactly which products are targeted by these cachectic factors is not well understood. Because of their functional relevance to muscle architecture, such targets are presumed to represent myofibrillar proteins, but whether these proteins are regulated in a general or a selective manner is also unclear. Here we demonstrate, using in vitro and in vivo models of muscle wasting, that cachectic factors are remarkably selective in targeting myosin heavy chain. In myotubes and mouse muscles, TNF-alpha plus IFN-gamma strongly reduced myosin expression through an RNA-dependent mechanism. Likewise, colon-26 tumors in mice caused the selective reduction of this myofibrillar protein, and this reduction correlated with wasting. Under these conditions, however, loss of myosin was associated with the ubiquitin-dependent proteasome pathway, which suggests that mechanisms used to regulate the expression of muscle proteins may be cachectic factor specific. These results shed new light on cancer cachexia by revealing that wasting does not result from a general downregulation of muscle proteins but rather is highly selective as to which proteins are targeted during the wasting state.
Underweight and Breast Cancer Recurrence and Death: A Report From the Korean Breast Cancer Society
Authors: Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh
Journal: Journal of Clinical Oncology (2009)

Purpose The association between body mass index and breast cancer outcome is controversial. Furthermore, the impact of underweight on breast cancer recurrence and death has not been adequately addressed. Patients and Methods We investigated this issue using a large nationwide database of 24,698 Korean breast cancer patients. The association between body weight status and breast cancer recurrence was further explored using a single-institution database containing information on 4,345 patients. Results The results from the nationwide database showed significantly lower overall survival (OS) and breast cancer-specific survival (BCSS) in underweight patients compared with survival in patients of normal weight after adjusting for known prognostic factors such as age, tumor size, lymph node metastasis, hormone receptor status, histologic grade, and lymphovascular invasion (hazard ratio [HR], 1.48; 95% CI, 1.15 to 1.90 for OS; HR, 1.49; 95% CI, 1.15 to 1.93 for BCSS), which were not observed in obese patients. In an analysis of recurrence data from the single institution, underweight women had a significantly higher risk of both distant metastasis and local recurrence of breast cancer (HR, 1.93; 95% CI, 1.04 to 3.58 and HR, 5.13; 95% CI, 2.66 to 9.90, respectively). Conclusion Our study suggests that underweight should be considered to be a high risk factor for death and recurrence after breast cancer surgery, especially in Asian breast cancer patients.
Dramatic improvement of psoriatic erythroderma after acute hepatitis: analysis of cytokine synthesis capability in peripheral blood T cells
Authors: Y. Kano, Y. Teraki, T. Shiohara
Journal: British Journal of Dermatology (2006)

We report a patient with psoriasis and hepatitis C virus infection who initially presented with psoriatic erythroderma and eventually showed complete clearance of psoriatic lesions following acute hepatitis induced by etretinate treatment. Cytokine synthesis capabilities in peripheral blood T cells obtained at different stages were evaluated in this patient. A dramatic increase in the frequency of interferon‐γ‐producing CD8+ T cells in peripheral blood was observed during the erythrodermic stage. In contrast, the frequencies of interleukin (IL)‐4‐ and IL‐13‐producing CD4+ T and CD8+ T cells were remarkably high at the resolution stage. These results clearly indicate that a shift towards type 2 cytokine predominance contributes to the resolution of severe psoriasis.
Both immunity and hyperresponsiveness to Pneumocystis carinii result from transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice.
Authors: J B Roths, C L Sidman
Journal: Journal of Clinical Investigation (1992)

The opportunistic pathogen Pneumocystis carinii (Pc) is considered to be the leading cause of morbidity in patients with AIDS. It is important, therefore, to determine the immunological mechanisms of resistance to Pc. We have taken advantage of the lack of both T and B lymphocytes in severe combined immunodeficiency (scid) mice to determine the critical factors in resistance to spontaneously acquired Pc pneumonia. Using adoptive transfer of unfractionated or fractionated lymphocyte subsets or hyperimmune serum from congenic normal donors, we have demonstrated that effective immunity to Pc results from the action of CD4+ but not CD8+ T cells (in the absence of antibody) or from humoral immunity (in the absence of T cells). However, responses of CD4+ T cells (but not antibody) to already well-established burdens of Pc are often accompanied by a fatal hyperinflammatory reaction. The activity of CD4+ T cells against Pc thus illustrates a broadly applicable principle that T cell immunity represents a critical balance between consequences beneficial and harmful to the host.
Outcome After Surgery Alone or With Restricted Use of Chemotherapy for Patients With Low-Risk Neuroblastoma: Results of Children's Oncology Group Study P9641
Authors: Douglas R. Strother, Wendy B. London, Mary Lou Schmidt, Garrett M. Brodeur, Hiroyuki Shimada, Paul Thorner, Margaret H. Collins, Edward Tagge, Stanton Adkins, C. Patrick Reynolds, Kevin Murray, Robert S. Lavey, Katherine K. Matthay, Robert Castleberry, John M. Maris, Susan L. Cohn
Journal: Journal of Clinical Oncology (2012)

The primary objective of Children's Oncology Group study P9641 was to demonstrate that surgery alone would achieve 3-year overall survival (OS) ≥ 95% for patients with asymptomatic International Neuroblastoma Staging System stages 2a and 2b neuroblastoma (NBL). Secondary objectives focused on other low-risk patients with NBL and on those who required chemotherapy according to protocol-defined criteria.Patients underwent maximally safe resection of tumor. Chemotherapy was reserved for patients with, or at risk for, symptomatic disease, with less than 50% tumor resection at diagnosis, or with unresectable progressive disease after surgery alone.For all 915 eligible patients, 5-year event-free survival (EFS) and OS were 89% ± 1% and 97% ± 1%, respectively. For patients with asymptomatic stage 2a or 2b disease, 5-year EFS and OS were 87% ± 2% and 96% ± 1%, respectively. Among patients with stage 2b disease, EFS and OS were significantly lower for those with unfavorable histology or diploid tumors, and OS was significantly lower for those ≥ 18 months old. For patients with stage 1 and 4s NBL, 5-year OS rates were 99% ± 1% and 91% ± 1%, respectively. Patients who required chemotherapy at diagnosis achieved 5-year OS of 98% ± 1%. Of all patients observed after surgery, 11.1% experienced recurrence or progression of disease.Excellent survival rates can be achieved in asymptomatic low-risk patients with stages 2a and 2b NBL after surgery alone. Immediate use of chemotherapy may be restricted to a minority of patients with low-risk NBL. Patients with stage 2b disease who are older or have diploid or unfavorable histology tumors fare less well. Future studies will seek to refine risk classification.
Cardiac herniation following intrapericardial pneumonectomy
Authors: A. K. Deiraniya
Journal: Thorax (1974)

<b>Deiraniya, A. K. (1974).</b><i>Thorax</i>, <b>29</b>, 545-552. <b>Cardiac herniation following intrapericardial pneumonectomy.</b> Cardiac herniation is a rare and catastrophic complication of intrapericardial pneumonectomy. Untreated it is invariably fatal. This paper reports three cases of cardiac herniation following intrapericardial pneumonectomy. In two cases massive haemorrhage complicated the cardiac herniation. All three cases were re-explored with two immediate survivals. The diagnosis, aetiology, haemodynamic effects, and management of this complication are discussed, and previously reported cases are reviewed.
Cutaneous collision tumour (melanocytic naevus, basal cell carcinoma, seborrhoeic keratosis): a clinical, dermoscopic and pathological case report
Authors: V. de Giorgi, D. Massi, S. Sestini, B. Alfaioli, G. Carelli, P. Carli
Journal: British Journal of Dermatology (2005)

The association of contiguous or 'collision' tumours in the same biopsy specimen is not uncommon and is often reported in the literature. The most common association, basal cell carcinoma (BCC) and naevus, is very difficult to diagnose clinically. We describe a 38-year-old woman with a previous history of melanoma, who presented with a modified pigmented lesion of the hip that had begun to change 6 months earlier. Histologically, the lesion was a melanocytic compound naevus and a BCC with a seborrhoeic keratosis. The case was investigated clinically and by focusing on the dermoscopic features and their pathological correlates. Cutaneous collision tumours are extremely difficult to diagnose preoperatively, even with the help of dermoscopy, in particular when one of the lesions is melanocytic.
The permeability of the small intestinal mucosa: A study using iron
Authors: C. A. Loehry, D. Parish, J. Baker
Journal: Gut (1973)

Various substances containing iron were injected into the lumen of the small intestine in rabbits and into the mesenteric arterial supply.Sections of the mucosa were stained for ferric ions by immersing for 30 minutes into equal parts of 2% HCI and 2% potassium ferrocyanide (Prussian Blue reaction).The ferric ion is bound to various cell structures and its passage through the mucosa could therefore be demonstrated.Iron appeared to pass from the blood into epithelial cells, especially near the tips of the villi, and also between cells as far as the junctional membrane.Studies using 59Fe demonstrated the rapidity of transfer of iron from the blood into the intestinal lumen.After a period of ischaemia epithelial cells in other situations also appeared permeable to iron.The implications of the loss of substances from the blood into the lumen by these routes is discussed.There is a continuous passage of substances from the blood out into the intestinal lumen.It has been demonstrated that mucosal permeation rate both in animals and man depends directly upon the plasma concentration of any substance and inversely upon its molecular size (Loehry, Axon, Hilton, Hider, and Creamer, 1970; Loehry, 1973).How these macro- molecular substances actually permeate the intestinal mucosa is not fully understood; theoretically it is possible that they pass through epithelial cells, between them, or through gaps left by extruded cells at the tips of the villi.In order to study this further we injected substances into the arterial supply to the small intestine that could be directly visualized in the mucosa.In the present experiments we have used solutions containing iron as the ferric molecule becomes rapidly fixed to various mucosal and connective tissue constituents and is therefore not removed during fixing and staining procedures. MethodsThe experiments were performed on albino rabbits weighing between 2.5 and 3.5 kg under nembutal anaesthesia.The abdomen was opened by a midline incision and loops of small intestine were gently drawn out.Two-inch segments of intestine were clamped off and 0.25 ml of various iron preparations
Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart
Authors: Dario Leosco, Giuseppe Rengo, Guido Iaccarino, Luca Golino, Massimo Marchese, Francesca Fortunato, Carmela Zincarelli, Emma Sanzari, Michele Ciccarelli, Gennaro Galasso, Giovanna Giuseppina Altobelli, Valeria Conti, Gianfranco Matrone, Vincenzo Cimini, Nicola Ferrara, Amelia Filippelli, Walter J. Koch, Franco Rengo
Journal: Cardiovascular Research (2007)

Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart.We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise.Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups.Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol.At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion.In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted.In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation.This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization.Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.
Prostasomes—their effects on human male reproduction and fertility
Authors: H.P. Burden, C.H. Holmes, R. Persad, K. Whittington
Journal: Human Reproduction Update (2005)

The prostate is a glandular male accessory sex organ vital for normal fertility. It provides the prostatic component of seminal plasma which nourishes and protects sperm following ejaculation. Prostasomes are small (40–500 nm) membrane-bound vesicles produced by epithelial cells lining the prostate acini and are a component of prostatic secretions. Although the existence of these particles has been known for many years, their full function and relevance to reproductive health are largely unknown. Proteomic studies have shown a wide range of proteins (enzymes, structural proteins and novel, unannotated proteins) present in or on the surface of prostasomes providing them with a diverse nature. Interestingly prostasomes are able to fuse with sperm, this event and the associated transfer of proteins lies at the heart of many of their proposed functions. Sperm motility is increased by the presence of prostasomes and their fusion prevents premature acrosome reactions. Prostasomes have been shown to aid protection of sperm within the female reproductive tract because of immunosuppressive, antioxidant and antibacterial properties. Clinically these functions imply a role for prostasomes in male factor infertility. However, the very functions that promote fertility may have negative connotations in later life; recent work has suggested that prostasomes are involved in prostate cancer. Clearly more work is needed to clarify the role of these novel particles and their impact on men’s health.
Coronary pressure-flow relation in left ventricular hypertrophy. Importance of changes in back pressure versus changes in minimum resistance.
Authors: D J Duncker, J Zhang, R J Bache
Journal: Circulation Research (1993)

Perfusion abnormalities in the pressure-overloaded hypertrophied left ventricle could result from an increase in minimum coronary resistance or an increase in effective back pressure due to increased extravascular compressive forces. Since the pressure-flow relation of the maximally vasodilated coronary bed allows dissociation of minimum resistance (inverse slope [1/alpha PF]) and back pressure (pressure at zero flow [Pf = 0]), the present study was undertaken to examine the coronary pressure-flow relation in left ventricular hypertrophy (LVH). Ascending aortic banding in eight dogs at 6-8 weeks of age (LVH group) increased the left ventricular to body weight ratio to 8.7 +/- 0.6 g/kg as compared with 4.8 +/- 0.2 g/kg in nine normal dogs (p &lt; 0.05). Maximum coronary vasodilation was produced by infusion of adenosine (1 mg/kg per minute i.v.). The slope of the coronary pressure-flow relation (alpha PF) was 5.8 +/- 0.5 10(-2) (ml/min per gram)/mm Hg in the LVH group and 9.3 +/- 0.6 10(-2) (ml/min per gram)/mm Hg in the normal group (p &lt; 0.05). alpha PF was significantly correlated with the left ventricular to body weight ratio but not with coronary pressure, suggesting that the degree of hypertrophy and not exposure to high coronary pressure was responsible for the observed decrease in alpha PF. Pf = 0 was 24.1 +/- 2.6 mm Hg in the LVH group and 11.7 +/- 1.2 mm Hg in the normal group (p &lt; 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Asthmatic Granulomatosis
Authors: Sally E. Wenzel, Catherine A. Vitari, Manisha Shende, Diane C. Strollo, Allyson Larkin, Samuel A. Yousem
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Severe asthma represents 5–10% of all asthma, yet remains problematic and poorly understood. Although it is increasingly recognized as consisting of numerous heterogenous phenotypes, their immunopathology, particularly in the distal airways and interstitium, remains poorly described.Objectives: To identify the pathobiology of atypical difficult asthma.Methods: We report 10 from a total of 19 patients (17 women and 2 men) meeting asthma and severe asthma definitions, requiring daily systemic corticosteroid (CS) use, with inconsistent abnormalities on chest computed tomography scans, who underwent video-assisted thoracoscopic biopsies for further diagnosis and management.Measurements and Main Results: The pathology of 10 of the 19 cases revealed small airway changes consistent with asthma (eosinophilia, goblet cell hyperplasia), but with the unexpected finding of interstitial nonnecrotizing granulomas. These patients had no evidence for hypersensitivity pneumonitis, but 70% of cases had a personal or family history of autoimmune-like disease. The 10 cases were treated with azathioprine, mycophenolic acid, methotrexate, or infliximab. Nine of 10 showed decreased CS requirements and improved or maintained FEV1 despite lower CS doses. Of the remaining nine patients, six manifested asthmatic small airway disease, alone or in combination with alveolar septal mononuclear cells, but no granulomas, whereas three manifested other pathologic findings (aspiration, pneumonia, or thromboemboli).Conclusions: These data suggest that a subset of severe "asthma" manifests a granulomatous pathology, which we term "asthmatic granulomatosis." Although identification of this disease currently requires a thorascopic biopsy, alternative approaches to therapy lead to improvement in outcomes.