tbuckley/cabot-search huggingface dataset:
Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression
Authors: Shahrokh F. Shariat, Michael W. Kattan, Erica Traxel, Ben Andrews, Kuichun Zhu, Thomas M. Wheeler, Kevin M. Slawin
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We have shown that preoperative plasma levels of transforming growth factor-β1 (TGF-β1), interleukin 6 (IL)-6, and its receptor (IL-6sR) are associated with prostate cancer progression and metastasis. The objectives of this study were to confirm these findings and to examine the association of changes in plasma levels of these markers after surgery with disease progression in a large consecutive cohort of patients. Experimental Design: Plasma levels of TGF-β1, IL-6, and IL-6sR were measured pre- and postoperatively (6–8 weeks after surgery) in 302 consecutive patients who underwent radical prostatectomy for clinically localized disease. Results: Pre- and postoperative levels of TGF-β1 were significantly elevated in patients with extraprostatic extension, seminal vesicle involvement, and metastases to lymph nodes. In contrast, preoperative levels of IL-6 and IL-6sR, but not postoperative levels, were significantly associated with tumor volume, prostatectomy Gleason sum, and metastases to lymph nodes. In a postoperative model that included pre- and postoperative TGF-β1, IL-6, and IL-6sR and standard postoperative parameters, postoperative TGF-β1 and prostatectomy Gleason sum were significant predictors of overall and aggressive disease progression. Although, for all patients, plasma levels of all three markers declined significantly after prostate removal, for patients that experienced disease progression, only IL-6 and IL-6sR levels decreased significantly. Conclusions: For patients undergoing radical prostatectomy, preoperative plasma levels of TGF-β1 and IL-6sR are associated with metastases to regional lymph nodes, presumed occult metastases at the time of primary treatment, and disease progression. After prostate removal, postoperative TGF-β1 level increases in value over preoperative levels for the prediction of disease progression.
BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis
Authors: A. Scheja, K. Larsen, L. Todorova, E. Tufvesson, M. Wildt, A. Åkesson, L. Hansson, S. Ellis, G. Westergren Thorsson
Journal: European Respiratory Journal (2006)

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil–fibroblast interaction in pulmonary fibrosis in systemic sclerosis.
Characteristics and Outcomes of Breast Cancer in Women With and Without a History of Radiation for Hodgkin's Lymphoma: A Multi-Institutional, Matched Cohort Study
Authors: Elena B. Elkin, Michelle L. Klem, Anne Marie Gonzales, Nicole M. Ishill, David Hodgson, Andrea K. Ng, Lawrence B. Marks, Joanne Weidhaas, Gary M. Freedman, Robert C. Miller, Louis S. Constine, Sten Myrehaug, Joachim Yahalom
Journal: Journal of Clinical Oncology (2011)

Purpose To compare characteristics and outcomes of breast cancer in women with and without a history of radiation therapy (RT) for Hodgkin's lymphoma (HL). Patients and Methods Women with breast cancer diagnosed from 1980 to 2006 after RT for HL were identified from eight North American hospitals and were matched three-to-one with patients with sporadic breast cancer by age, race, and year of breast cancer diagnosis. Information on patient, tumor and treatment characteristics, and clinical outcomes was abstracted from medical records. Results A total of 253 patients with breast cancer with a history of RT for HL were matched with 741 patients with sporadic breast cancer. Median time from HL to breast cancer diagnosis was 18 years. Median age at breast cancer diagnosis was 42 years. Breast cancer after RT for HL was more likely to be detected by screening, was more likely to be diagnosed at an earlier stage, and was more likely to be bilateral at diagnosis. HL survivors had an increased risk of metachronous contralateral breast cancer (adjusted hazard ratio [HR], 4.3; 95% CI, 1.7 to 11.0) and death as a result of any cause (adjusted HR, 1.9; 95% CI, 1.1 to 3.3). Breast cancer–specific mortality was also elevated, but this difference was not statistically significant (adjusted HR, 1.6; 95% CI, 0.7 to 3.4). Conclusion In women with a history of RT for HL, breast cancer is diagnosed at an earlier stage, but these women are at greater risk for bilateral disease and are more likely to die as a result of causes other than breast cancer. Our findings support close follow-up for contralateral tumors in these patients and ongoing primary care to manage comorbid conditions.
The domain Archaea in human mucosal surfaces
Authors: F. Matarazzo, A.C. Ribeiro, M. Faveri, C. Taddei, M.B. Martinez, M.P.A. Mayer
Journal: Clinical Microbiology and Infection (2012)

Archaea present distinct features from bacteria and eukaryotes, and thus constitute one of the branches of the phylogenetic tree of life. Members of this domain colonize distinct niches in the human body, arranged in complex communities, especially in the intestines and the oral cavity. The diversity of archaea within these niches is limited to a few phylotypes, constituted in particular by methane-producing archaeal organisms. Although they are possibly symbionts, methanogens may play a role in the establishment of mucosal diseases by favouring the growth of certain bacterial groups.
Melatonin: From Basic Research to Cancer Treatment Clinics
Authors: None Vijayalaxmi, Charles R. Thomas, Russel J. Reiter, Terence S. Herman
Journal: Journal of Clinical Oncology (2002)

ABSTRACT: Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger, an indirect antioxidant, as well as an important immunomodulatory agent. In both in vitro and in vivo investigations, melatonin protected healthy cells from radiation-induced and chemotherapeutic drug–induced toxicity. Furthermore, several clinical studies have demonstrated the potential of melatonin, either alone or in combination with traditional therapy, to yield a favorable efficacy to toxicity ratio in the treatment of human cancers. This study reviews the literature from laboratory investigations that document the antioxidant and oncostatic actions of melatonin and summarizes the evidence regarding the potential use of melatonin in cancer treatment. This study also provides rationale for the design of larger translational research–based clinical trials.
MicroRNA-10 Regulates the Angiogenic Behavior of Zebrafish and Human Endothelial Cells by Promoting Vascular Endothelial Growth Factor Signaling
Authors: David Hassel, Paul Cheng, Mark P. White, Kathryn N. Ivey, Jens Kroll, Hellmut G. Augustin, Hugo A. Katus, Didier Y.R. Stainier, Deepak Srivastava
Journal: Circulation Research (2012)

Rationale: Formation and remodeling of the vasculature during development and disease involve a highly conserved and precisely regulated network of attractants and repellants. Various signaling pathways control the behavior of endothelial cells, but their posttranscriptional dose titration by microRNAs is poorly understood. Objective: To identify microRNAs that regulate angiogenesis. Methods and Results: We show that the highly conserved microRNA family encoding miR-10 regulates the behavior of endothelial cells during angiogenesis by positively titrating proangiogenic signaling. Knockdown of miR-10 led to premature truncation of intersegmental vessel growth in the trunk of zebrafish larvae, whereas overexpression of miR-10 promoted angiogenic behavior in zebrafish and cultured human umbilical venous endothelial cells. We found that miR-10 functions, in part, by directly regulating the level of fms-related tyrosine kinase 1 (FLT1), a cell-surface protein that sequesters vascular endothelial growth factor, and its soluble splice variant sFLT1. The increase in FLT1/sFLT1 protein levels upon miR-10 knockdown in zebrafish and in human umbilical venous endothelial cells inhibited the angiogenic behavior of endothelial cells largely by antagonizing vascular endothelial growth factor receptor 2 signaling. Conclusions: Our study provides insights into how FLT1 and vascular endothelial growth factor receptor 2 signaling is titrated in a microRNA-mediated manner and establishes miR-10 as a potential new target for the selective modulation of angiogenesis.
Hyaluronidase-sensitive halos around adherent cells. Their role in blocking lymphocyte-mediated cytolysis.
Authors: W H McBride, J B Bard
Journal: The Journal of Experimental Medicine (1979)

A variety of adherent sarcoma, carcinoma and normal cells are surrounded in vitro by thick, transparent zones (approximately equal to 9 micron thick) that spleen cells and a variety of other cells and particles cannot penetrate. Seven lymphoblastoid cell lines did not possess such halos. The presence of these halos around adherent fibrosarcoma cells appeared to protect them from lymphocyte-mediated cytolysis. Hyaluronidase treatment, which destroyed the halo and allowed lymphocytes to approach the tumor cell membrane, enhanced the cytotoxic action of immune but not of normal spleen cells. These observations, in addition to highlighting a little-known feature of the cell surface, may also be of general relevance to the in vitro and in vivo killing of tumor cells by immune effector cells.
Natural killer (NK) cells augment atherosclerosis by cytotoxic-dependent mechanisms
Authors: Ahrathy Selathurai, Virginie Deswaerte, Peter Kanellakis, Peter Tipping, Ban-Hock Toh, Alex Bobik, Tin Kyaw
Journal: Cardiovascular Research (2014)

Although natural killer (NK) cells, a key component of the innate immune system, have been identified in human and mouse atherosclerotic lesions, their role in atherosclerosis development remains unclear. To determine their role in atherosclerosis, we used both loss- and gain-of-function experiments in ApoE(-/-) mice fed a high-fat diet.Treatment of ApoE(-/-) mice with anti-Asialo-GM1 antibodies depleted NK cells without affecting other lymphocytes, including natural killer T cells, and greatly attenuated atherosclerosis. These effects were independent of plasma lipids. To confirm the atherogenicity of NK cells, these cells were isolated from mouse spleens for adoptive transfer into lymphocyte-deficient ApoE(-/-)Rag2(-/-)IL2rg(-/-) mice. Transfer of NK cells from wild-type mice into ApoE(-/-)Rag2(-/-)IL2rg(-/-) mice doubled lesion size, confirming a pro-atherogenic role for NK cells. To determine whether their atherogenicity was dependent on production of interferon-γ (IFN-γ) or cytotoxins, we compared the transfer of NK cells deficient in IFN-γ, perforin, and granzyme B with the transfer of wild-type NK cells. Transfer of IFN-γ-deficient NK cells increased lesion size in the lymphocyte-deficient ApoE(-/-) mice as wild-type NK cells. However, granzyme B- and perforin-deficient NK cells did not affect lesion size. Only wild-type NK cells increased necrotic core size, whereas perforin- and granzyme B-deficient NK cells did not. Plasma lipid levels were largely unaffected by the cell transfer.Our loss- and gain-of-function findings provide definitive evidence that NK cells are atherogenic and their production of perforin and granzyme B contributes to atherosclerosis and the expansion of necrotic cores.
A Red and Swollen Eyelid
Authors: Rajesh C. Rao, Victor M. Elner, Hakan Demirci
Journal: JAMA Oncology (2015)

A woman in her 80s complained of fullness near her left eye for 2 months. She denied pain, trauma, or changes in vision. Her right eye had been enucleated 40 years before for choroidal melanoma, and she had been fitted with an ocular prosthesis (Figure 1). Twenty-six years before presentation, she was diagnosed with moderately differentiated, estrogen and progesterone receptor-positive, invasive ductal carcinoma of the left breast (Stage 2, T2, N1, M0). At that time, she underwent modified radical mastectomy, and three lymph nodes were positive for carcinoma. She was then treated with 6 cycles of cyclophosphamide, doxorubicin, and 5-fluorouracil, followed by daily tamoxifen for nearly 5 years. There was no evidence of recurrent disease after this treatment. External examination revealed mild edema, erythema, and ptosis of the left upper lid (Figure 1). Left cervical lymphadenopathy was present. Best-corrected visual acuity was 20/25, and left ocular motility was full.



Figure 1

Erythema, edema, and ptosis of the left upper eyelid. Front (A), left (B), and right (B) aspects of the upper face show the ocular prosthesis (black arrowhead) and asymmetric enlargement, erythema, and ptosis of the left upper eyelid (white arrowheads). ...
Intra-articular pressure profile of the knee joint in a spectrum of inflammatory arthropathies
Authors: S. Jawed, K. Gaffney, D. R Blake
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> The intra-articular pressure (IAP) rises significantly after isometric quadriceps contraction in patients with rheumatoid synovitis, a process that may temporarily impede synovial blood flow and cause oxidative injury. In acute traumatic knee effusions (ATE) pressure rises are trivial. This study compared the IAP profiles of patients with ATE with three different populations—an acute synovitis on the background of a chronic inflammatory arthropathy, a chronic low grade inflammatory arthropathy, and an acute intermittent inflammatory arthropathy. The study objective was to discover if the pressure profiles observed in these groups reflect an influence of the inflammatory process or time or both. <h3>METHODS</h3> Thirty three patients were studied. These were divided into four subgroups; group 1: five acute traumatic knee effusions (ATE); group 2: acute effusions on the background of a chronic inflammatory arthropathy: seven rheumatoid arthritis (RA), five psoriatic arthritis (PsA); group 3: seven osteoarthritis (OA) and group 4: acute effusions on the background of an intermittent inflammatory arthropathy: seven pyrophosphate arthropathy (PA), one amyloid (AA), one Behcet's (B). IAP was measured (mm Hg) at rest and during isometric quadriceps contraction using the hand held portable 295-1 intra-compartmental pressure monitor system (Stryker UK). The volume of synovial fluid aspirated was recorded. <h3>RESULTS</h3> Expressed as medians (interquartile range). Resting IAP was; ATE 6 (2–12), RA 8 (5–47), PsA 18 (11–31), OA 17 (7–21), PA 25 (9–29), AA 14, and B 12. IAP increased in all subjects during isometric contraction; ATE 9 (7–16), RA 56 (33–150), PsA 52 (43–85), OA 56 (20–116), PA 53 (41–65), AA 47, B 57 and the IAP rise was significant (p&lt;0.05) in all except the ATE group (p&gt;0.05). The volume of synovial fluid aspirated in groups 2, 3, and 4 correlated significantly with the magnitude of the IAP change (<i>r</i> = 0.45, p &lt; 0.05). <h3>CONCLUSION</h3> The IAP rise during isometric quadriceps contraction is a feature of all patients with an inflammatory based effusion irrespective of the duration of the effusion. This is not the case in patients with an ATE. In inflammatory synovitis the rise in intra-articular pressure with isometric quadriceps contraction relates to effusion volume. It is concluded that the inflammatory process prevents reflex muscle inhibition, a locally protective mechanism that minimises the potential for intermittent ischaemia/oxidative injury.
Effect of Mean Airway Pressure on Lung Volume during High-frequency Oscillatory Ventilation of Preterm Infants
Authors: ULRICH THOME, ANDREAS TÖPFER, PETER SCHALLER, FRANK POHLANDT
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Measurement of mean lung volume (MLV) in high-frequency oscillatory ventilation (HFO) may be useful for optimizing the high lung volume strategy, but has not been available until now. We have measured MLV by means of the sulfur hexafluoride (SF6) washout method in 13 premature infants ventilated with HFO because of respiratory distress syndrome (gestational age, 23 to 31 wk [median, 25 + 6/7 wk]; birthweight, 630 to 1,140 g [790 g]; age at measurement, 2 to 10 d [4 d]; weight, 675 to 1,250 g [850 g]). To evaluate the relationship between MLV and mean airway pressure (MAP), the latter was systematically varied between the measurements. With clinically selected MAP, MLV was between 23.3 and 41.9 ml/kg (median, 33.5 ml/kg) and was strongly dependent on MAP in each patient; linear regression analyses resulted in slope factors between 1.0 and 6.9 ml/cm H2O/kg (median, 2.83 ml/cm H2O/kg), with correlation coefficients between 0.77 and 0.99 (median, 0.94). Stabilization of MLV after modification of MAP took 2 to 25 min (median, 9 min). We conclude that the selection of MAP on a clinical basis leads to a wide range of different MLVs. Despite the strong dependence of MLV on MAP, the prediction of MLV solely based on MAP was impossible because of large patient to patient variability of linear regressions. Alveolar recruitment and derecruitment may take up to 25 min after MAP changes.
ON THE NATURE OF THE PRESSOR ACTION OF RENIN
Authors: Irvine H. Page
Journal: The Journal of Experimental Medicine (1939)

1. Tachyphylaxis occurs when renin is repeatedly injected into dogs and cats regardless of whether they are normal, anesthetized, pithed, hepatectomized, suprarenalectomized, nephrectomized, or eviscerated. 2. The pressor response to renin in brief experiments is independent of the height of the arterial pressure or the presence of the suprarenals. Evisceration and large doses of ergotamine reduce the response. It is largely uninfluenced by pithing, intracisternal injection of renin, cocaine, strychnine, caffeine, and infusion of sodium bicarbonate or hydrochloric acid. It may be slightly increased by large blood transfusions or hepatectomy but the result is short lived. 3. There is no parallelism between the pressor responses to carotid sinus stimulation, adrenine, and tyramine on the one hand and renin on the other. 4. Section of the brain may be followed by depressor responses to renin. 5. Intracisternal injection of renin elicits no significant rise in blood pressure or other circulatory manifestations. 6. Continuous infusion of renin produces a prolonged rise of arterial pressure in normal and chronically suprarenalectomized dogs, but the pressure ultimately falls despite continued infusion. 7. Tachyphylaxis develops in the isolated rabbit's ear perfused with blood and small doses of renin. The same blood perfused through a second ear causes no vasoconstriction when renin is added. Addition of renin-activator restores the ability of renin to cause constriction. 8. Renin alone causes no vasoconstriction when perfused with Ringer's solution, but renin plus renin-activator restores activity. Tachyphylaxis does not develop when Ringer's solution is employed instead of recirculating blood. 9. Blood from animals made tachyphylactic by repeated injections of renin is lacking in activator and also fails to cause vasoconstriction in the rabbit's ear when renin and renin-activator are added. 10. Renin-activator is lost and tachyphylaxis develops more slowly during continuous infusion of renin. Blood pressure may fall after a period of renin infusion despite the pressure in the blood of excess renin. Injection of partially purified activator restores the activator content of the blood as demonstrated in the rabbit's ear, but no rise in arterial pressure occurs.
Topical opioids for painful ulcers in systemic sclerosis
Authors: I L A van Ingen, M M P M Jansen, P Barrera
Journal: Annals of the Rheumatic Diseases (2007)

Painful cutaneous ulcers are frequent in systemic sclerosis (SSc). They are due to vasoconstriction and fibrosis, and are often located in digits and toes though they also occur at other locations.1 We admitted a 75-year-old patient known to have had limited SSc for 43 years. Her medical history encompassed two earlier admissions for painful digital and leg ulcers during which treatment with opioids resulted in severe obstipation and ileus. This time she presented with a superficial ulcer on the left lower leg with a diameter of 5.5 by 4.5 cm and necrotic borders surrounded by erythaematous and oedematous skin (fig 1 …
Acute-phase response of human hepatocytes: Regulation of acute-phase protein synthesis by interleukin-6
Authors: José V. Castell, Maria José Gómez-lechón, Martina David, Ricardo Fabra, Ramón Trullenque, Peter C. Heinrich
Journal: Hepatology (1990)

Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin1β;, recombinant interleukin-6 and tumor necrosis factor-α. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein—mRNA and C-reactive protein—protein synthesis. Also, fibrinogen and α−1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level. (HEPATOLOGY 1990;12:1179-1186).