tbuckley/cabot-search huggingface dataset:
Enhanced susceptibility to pancreatitis in severe hypertriglyceridaemic lipoprotein lipase-deficient mice and agonist-like function of pancreatic lipase in pancreatic cells
Authors: Y Wang, L Sternfeld, F Yang, J A Rodriguez, C Ross, M R Hayden, F Carriere, G Liu, W Hofer, I Schulz
Journal: Gut (2008)

<h3>Background and aims:</h3> Recurrent pancreatitis is a common complication of severe hypertriglyceridaemia in patients with various gene mutations in lipoprotein lipase (LPL) or apolipoprotein CII. However, the exact pathogenetic mechanism has not yet been defined. <h3>Methods:</h3> Susceptibility to pancreatitis in LPL-deficient mice was compared with that of wild-type mice after intraperitoneal injections of caerulein by determination of amylase release and pancreatic pathological scores. The effect of chylomicrons and fatty acids on enzyme release, Ca<sup>2+</sup> signalling and cell injury in isolated pancreatic acinar cells from wild-type and LPL-deficient mice was investigated. <h3>Results:</h3> Caerulein induced higher levels of serum amylase and more severe inflammation in the pancreas of LPL-deficient mice than in wild-type mice. Addition of free fatty acids or chylomicrons to isolated pancreatic acinar cells led to the release of amylase and caused cell injury at higher concentrations. The effect of chylomicrons was partially blocked by orlistat, an inhibitor of pancreatic lipase. These results suggest that increased concentrations of free fatty acids from chylomicron hydrolysis by pancreatic lipase can induce acinar cell injury. Surprisingly, pancreatic lipase, whether in its active or inactive state could act like an agonist by inducing amylase secretion without cell injury. It caused an increase in cGMP levels and conversion of cell-damaging sustained elevations of [Ca<sup>2+</sup>] to normal Ca<sup>2+</sup> oscillations. <h3>Conclusions:</h3> LPL-deficient mice with severe hypertriglyceridaemia display enhanced susceptibility to acute pancreatitis. High levels of chylomicrons and free fatty acids result in pancreatic cell injury. Pancreatic lipase has a dual effect: generating free fatty acids from chylomicrons and preventing Ca<sup>2+</sup> overload in pancreatic acinar cells.
Left Ventricular Hypertrophy
Authors: Steven G. Achinger, Juan Carlos Ayus
Journal: Journal of the American Society of Nephrology (2006)

Cardiovascular disease occurs in ESRD patients at rates that are far higher than is seen in the general population, and cardiovascular deaths account for the majority of deaths among dialysis patients. Abnormal mineral metabolism is a novel cardiovascular risk factor among dialysis patients. Recently published results demonstrated that even with good control of BP and anemia, conventional hemodialysis is associated with significant left ventricular hypertrophy (LVH); however, daily hemodialysis was associated with a significant reduction in LV mass index (LVMI). Furthermore, it was shown that control of serum phosphorus correlates with the reduction in LVMI. These data suggest a novel mechanism for the deleterious effect of elevated serum phosphorus on cardiovascular outcomes among hemodialysis patients: LVH. Other investigators have noted an association of hyperphosphatemia and LVH; however, this study was the first to demonstrate that improvement in serum phosphorus is associated with reduction in LVM. In addition, it is shown that daily hemodialysis is an effective modality in improving serum phosphorus through significantly improved phosphorus removal. Elevated serum phosphorus leads to vascular calcification, which can lead to LVH by decreasing vascular compliance. However, our study showed an improvement in LVMI during a 12-mo period. Because vascular calcification is unlikely to remit over this time period, it is proposed that serum phosphorus has a reversible, cardiotoxic effect that leads to LVH that can be reversed successfully with good control of serum phosphorus.
EZC-Prostate Models Offer High Sensitivity and Specificity for Noninvasive Imaging of Prostate Cancer Progression and Androgen Receptor Action
Authors: Mamatha R. Seethammagari, Xiaoming Xie, Norman M. Greenberg, David M. Spencer
Journal: Cancer Research (2006)

Abstract In vivo imaging advances have greatly expanded the use of animal cancer models. Herein, we describe two new models that permit prostate imaging ex vivo, in vivo, and in utero. Further, we show the use of these models for detecting small metastasis and testing reagents that modulate the androgen receptor (AR) axis. A luciferase reporter gene was directed to the prostate epithelium using three composite promoters called human kallikrein 2 (hK2)-E3/P, PSA-E2/P, and ARR2PB, derived from hK2, PSA, and rat probasin regulatory elements, to generate the EZC1, EZC2, and EZC3-prostate mice, respectively. EZC2 and EZC3-prostate display robust expression in the prostate with only minimal detectable expression in other organs, including testes and epididymis. Luciferase expression was detected as early as embryonic day 13 (E13) in the urogenital track. To image prostate cancer progression, lines of EZC mice were bred with prostate cancer models TRAMP and JOCK1, and imaged longitudinally. When crossed with prostate cancer models, EZC3 facilitated detection of metastatic lesions although total prostate luciferase expression was static or reduced due to weakening of AR-regulated promoters. Castration reduced luciferase expression by 90% and 97% in EZC2 and EZC3 mice, respectively, and use of GnRH antagonist also led to extensive inhibition of reporter activity. The EZC-prostate model permits prostate imaging in vivo and should be useful for imaging prostate development, growth, metastasis, and response to treatment noninvasively and longitudinally. These models also provide powerful new reagents for developing improved drugs that inhibit the AR axis. (Cancer Res 2006; 66(12): 6199-209)
HIV Transmission Through Donor Artificial Insemination
Authors: M R Araneta, L Mascola, A Eller, L O'Neil, M M Ginsberg, M Bursaw, J Marik, S Friedman, C A Sims, M L Rekart
Journal: JAMA (1995)

<h3>Objective.</h3> —To investigate and report cases of human immunodeficiency virus (HIV) transmission through donor artificial insemination (Al) before 1986 at five infertility clinics. <h3>Design.</h3> —Two types of look-back studies were performed: (1) identification of an HIV-infected woman who reported previous Al, followed by identification of the infected donor(s) and contact tracing of women who were inseminated with his semen, and (2) identification of an HIV-infected donor and subsequent examination of women receiving AI procedures using his semen. <h3>Setting.</h3> —Five infertility clinics in Los Angeles County, California; San Diego County, California; Arizona; and Vancouver, British Columbia. <h3>Patients.</h3> —A total of 230 women were inseminated with semen from any one of the five identified HIV-infected donors; 199 (87%) consented to HIV testing. <h3>Main Outcome Measure.</h3> —Seropositivity for HIV among Al recipients. <h3>Results.</h3> —Seven (3.52%) of the 199 women (95% confidence interval, 1.55% to 7.41% who were artificially inseminated with semen from any of five HIV-infected donors and consented to HIV testing tested HIV-seropositive. Information on HIV risk was available for three of the five donors; all three reported a history of having sex with men. Four HIV-infected women were identified through uncommon circumstances, rather than through routine look-back studies of donors. <h3>Conclusion.</h3> —Infection with HIV through donor Al performed before routine HIV screening of semen donors represents a potentially serious threat to women who underwent Al procedures. Public health policies requiring retrospective identification of HIV-infected semen donors and patients receiving Al before 1986, especially in acquired immunodeficiency syndrome (AIDS)—prevalent areas, should be considered routine. Women diagnosed with AIDS or HIV infection, in whom no identified risk of HIV acquisition is established, should be questioned about previous Al procedures. (<i>JAMA</i>. 1995;273:854-858)
Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension
Authors: Rajkumar Savai, Hamza M Al-Tamari, Daniel Sedding, Baktybek Kojonazarov, Christian Muecke, Rebecca Teske, Mario R Capecchi, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Ralph Theo Schermuly, Soni Savai Pullamsetti
Journal: Nature Medicine (2014)
Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men
Authors: H. E. Chemes
Journal: Human Reproduction Update (2003)

Sperm pathology is presented as the discipline of characterizing structural and functional deficiencies in abnormal spermatozoa. This concept complements that of sperm morphology mainly concerned with the appearance of spermatozoa. These two notions collaborate in providing correlations of prognostic value with sperm fertilizing capacity, explaining the mechanisms of sperm inefficiency, suggesting strategies to improve fertilization and opening a door to molecular genetic studies. Phenotypes of genetic origin involving sperm heads, flagella and the neck region are presented describing their clinical manifestations, sperm structure, cytochemistry and genetic background. When available, animal models are used to highlight possible genetic mechanisms. Sperm pathologies secondary to andrological conditions or environmental factors are described, stressing the non‐specific nature of the sperm response to noxious agents. The available literature on the prognostic value of sperm pathologies in ICSI is also reviewed. Flagellar anomalies bear a good prognosis, but those affecting the acrosome, sperm chromatin and the neck region entail an increasing chance of failure, which highlights the differential roles played by specific sperm components in fertilization, implantation and early embryonic development. A final discussion is devoted to genetic counselling and the risks involved in using immotile or abnormal spermatozoa in assisted reproduction.
Tone-dependent waterfall behavior during venous pressure elevation in isolated canine hearts.
Authors: E R Farhi, F J Klocke, R E Mates, K Kumar, R M Judd, J M Canty, S Satoh, B Sekovski
Journal: Circulation Research (1991)

We examined the "vascular waterfall" hypothesis, which proposes that coronary flow is unaffected by elevations in outflow pressure until the latter reaches a critical threshold level, in 29 isolated canine hearts. In fibrillating hearts vasodilated with adenosine or carbocromen, coronary flow and the coronary pressure-flow relation were not affected by changes in great cardiac vein pressure (PGCV) below a threshold value of 11 +/- 0.9 (mean +/- SEM) mm Hg. Further elevations of PGCV reduced flow and shifted the pressure-flow relation to the right, increasing its pressure-axis intercept (Pf=0). When vasomotor tone was augmented with vasopressin, threshold PGCV increased to 25 +/- 2.7 mm Hg (p less than 0.001). Once again, the pressure-flow relation was unaffected by changes in PGCV below the threshold value and shifted to the right when this value was exceeded. The amount by which spontaneous values of Pf=0 exceeded threshold values of PGCV was greater when vasomotor tone was augmented than during vasodilation. Pf=0 continued to exceed PGCV when the latter was raised above the threshold level. Both Pf=0 and threshold values of PGCV were less during a long diastole than during ventricular fibrillation. We reached the following conclusions. 1) During changes in PGCV below a threshold value, the coronary circulation exhibits traditional waterfall behavior. 2) The threshold pressure for altering waterfall behavior is affected by vascular tone and mechanical activity. 3) Pf=0 remains above PGCV when the latter is increased above the threshold value needed to alter flow.
Essential Role for Thymosin β4 in Regulating Vascular Smooth Muscle Cell Development and Vessel Wall Stability
Authors: Alex Rossdeutsch, Nicola Smart, Karina N. Dubé, Martin Turner, Paul R. Riley
Journal: Circulation Research (2012)

Rationale: Compromised development of blood vessel walls leads to vascular instability that may predispose to aneurysm with risk of rupture and lethal hemorrhage. There is currently a lack of insight into developmental insults that may define the molecular and cellular characteristics of initiating and perpetrating factors in adult aneurismal disease. Objective: To investigate a role for the actin-binding protein thymosin β4 (Tβ4), previously shown to be proangiogenic, in mural cell development and vascular wall stability. Methods and Results: Phenotypic analyses of both global and endothelial-specific loss-of-function Tβ4 mouse models revealed a proportion of Tβ4-null embryos with vascular hemorrhage coincident with a reduction in smooth muscle cell coverage of their developing vessels. Mechanistic studies revealed that extracellular Tβ4 can stimulate differentiation of mesodermal progenitor cells to a mature mural cell phenotype through activation of the transforming growth factor-beta (TGFβ) pathway and that reduced TGFβ signaling correlates with the severity of hemorrhagic phenotype in Tβ4-null vasculature. Conclusions: Tβ4 is a novel endothelial secreted trophic factor that functions synergistically with TGFβ to regulate mural cell development and vascular wall stability. These findings have important implications for understanding congenital anomalies that may be causative for adult-onset vascular instability.
Effects of the new karate rules on the incidence and distribution of injuries
Authors: J Macan, D Bundalo-Vrbanac, G Romić
Journal: British Journal of Sports Medicine (2006)

To evaluate the incidence and distribution of injuries in karate before and after the implementation of new rules established by the World Karate Federation in 2000.Injury incidence was followed up during the official karate competition seasons of 1997 and 2002 in Croatia. A questionnaire was used to collect data on the age and sex of the competitor and localisation and severity of injury. Data were analysed separately for female and male competitors and age categories < 18 and > or = 18 years.A total of 2023.5 and 2584 minutes of active fighting (exposure time) was assessed for 1997 and 2002 respectively. The overall injury incidence rate (IR) was similar in 1997 and 2002 (10.28 and 9.82/100 exposure minutes respectively). The relative risk (RR) of injury was significantly higher in 1997 than in 2002 for competitors younger than 18 years (RR 1.55, 95% confidence interval (CI) 1.11 to 2.16). The overall RR of head injury was significantly higher in 1997 than in 2002 (RR 1.96, 95% CI 1.54 to 2.49), but the RR of leg injury was significantly lower in 1997 than in 2002 (RR 0.16, 95% CI 0.09 to 0.28). Most injuries (> 98%) were categorised as mild (grade 1) in both periods studied.The results of this study confirm the importance of the new competition rules in the distribution and prevention of injuries in martial arts. Strict judging and heavy penalties for uncontrolled blows, particularly for the youngest competitors, can significantly decrease the risk of injury.
Purification and characterization of a human membrane protein that activates the alternative complement pathway and allows the deposition of homologous complement C3.
Authors: M Matsumoto, F Yamashita, K Iida, M Tomita, T Seya
Journal: The Journal of Experimental Medicine (1995)

A human myeloid cell subline, P39+, is found to be a target for human complement (C) via the alternative pathway and to allow the deposition of multiple C3 fragments on its membranes, though expressing the complement regulatory proteins decay-accelerating factor and membrane cofactor protein. The parent cell line, P39-, which is phenotypically similar to the P39+ subline, does not allow the deposition of homologous C3 fragments. In this study, we established a monoclonal antibody, M161 Ab, which reacted with P39+ but not P39- cells. This Ab recognized a 43-kD protein in P39+ cell lysate transblotted onto nitrocellulose. Using this Ab as a probe, we purified the 43-kD protein, namely, M161 antigen (Ag). M161 Ag had a basic isoelectric point (pI), 9.3-9.4 by chromatofocusing, and was precipitated as an insoluble material at the pI point. The purified M161 Ag was a single-chain protein and did not possess N- or O-linked carbohydrates. When the purified M161 Ag was transblotted onto nitrocellulose and incubated with Mg(2+)-EGTA serum, human C3 fragments were efficiently deposited on M161 Ag. The major species of the deposited C3 fragments was C3b. Furthermore, the C3 fragments bound to the M161 Ag were detached by 1 M hydroxylamine, suggesting that a covalent ester linkage sustains M161 Ag-C3b interaction. NH2-terminal amino acid analysis revealed that M161Ag is a novel membrane protein. Hence, it appeared that M161 Ag is a potent activator of human alternative complement pathway on human cells that activates homologous C3 and allows the deposition of C3b on itself. Thus, under some conditions, homeostasis of complement is maintained even on human cells, not only by the complement regulatory proteins, but also by membrane C3-activating molecules on which C3b is deposited.
Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort
Authors: Nicholas J. Ollberding, Gertraud Maskarinec, Shannon M. Conroy, Yukiko Morimoto, Adrian A. Franke, Robert V. Cooney, Lynne R. Wilkens, Loïc Le Marchand, Marc T. Goodman, Brenda Y. Hernandez, Brian E. Henderson, Laurence N. Kolonel
Journal: Blood (2012)
Soft tissue sore spots of an unknown origin
Authors: Adam Meakins
Journal: British Journal of Sports Medicine (2015)

Trigger points are common clinical diagnoses in the musculoskeletal profession. However, questions have been raised about what they are and how they are treated.1 Trigger points were first described by Travell and Simons as tender, painful areas found in myofascial tissue when palpated. These are often described as muscle ‘knots’ or taut bands, and are considered to be areas of adverse sustained muscular contraction caused either from direct trauma to myofascial tissue or through repeated microtrauma from postural or activity-related stresses/strains. This is believed to cause a crisis at the motor end plates, creating a sustained adverse muscular contraction that is then felt as pain either locally or referred elsewhere.

However, despite widespread acceptance of this theory, and a large and diverse industry built around the treatment of trigger points, including various deep tissue massage and acupressure techniques and more recently, the growing popularity of dry needling, the theory of adverse muscle knots and taut bands as a cause of soft tissue pain has never been adequately explained.

More and more clinicians …
Molecular signatures define two main classes of meningiomas
Authors: Lucia Helena Carvalho, Ivan Smirnov, Gilson S Baia, Zora Modrusan, Justin S Smith, Peter Jun, Joseph F Costello, Michael W McDermott, Scott R VandenBerg, Anita Lal
Journal: Molecular Cancer (2007)

Abstract Background Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant) and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis. Results We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH) to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs) compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups. Conclusion Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.
Crohn's disease management after intestinal resection: a randomised trial
Authors: Peter De Cruz, Michael A Kamm, Amy L Hamilton, Kathryn J Ritchie, Efrosinia O Krejany, Alexandra Gorelik, Danny Liew, Lani Prideaux, Ian C Lawrance, Jane M Andrews, Peter A Bampton, Peter R Gibson, Miles Sparrow, Rupert W Leong, Timothy H Florin, Richard B Gearry, Graham Radford-Smith, Finlay A Macrae, Henry Debinski, Warwick Selby, Ian Kronborg, Michael J Johnston, Rodney Woods, P Ross Elliott, Sally J Bell, Steven J Brown, William R Connell, Paul V Desmond
Journal: The Lancet (2014)
Inhibition of Extracellular Signal–Regulated Kinase Enhances Ischemia/Reoxygenation–Induced Apoptosis in Cultured Cardiac Myocytes and Exaggerates Reperfusion Injury in Isolated Perfused Heart
Authors: Tian-Li Yue, Chuanlin Wang, Juan-Li Gu, Xin-Ling Ma, Sanjay Kumar, John C. Lee, Giora Z. Feuerstein, Heath Thomas, Beverly Maleeff, Eliot H. Ohlstein
Journal: Circulation Research (2000)

Three major mammalian mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal protein kinase (JNK), have been identified in the cardiomyocyte, but their respective roles in the heart are not well understood. The present study explored their functions and cross talk in ischemia/reoxygenation (I/R)-induced cardiac apoptosis. Exposing rat neonatal cardiomyocytes to ischemia resulted in a rapid and transient activation of ERK, p38, and JNK. On reoxygenation, further activation of all 3 mitogen-activated protein kinases was noted; peak activities increased (fold) by 5.5, 5.2, and 6.2, respectively. Visual inspection of myocytes exposed to I/R identified 18.6% of the cells as showing morphological features of apoptosis, which was further confirmed by DNA ladder and terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL). Myocytes treated with PD98059, a MAPK/ERK kinase (MEK1/MEK2) inhibitor, displayed a suppression of I/R-induced ERK activation, whereas p38 and JNK activities were increased by 70.3% and 55.0%, respectively. In addition, the number of apoptotic cells was increased to 33.4%. With pretreatment of cells with SB242719, a selective p38 inhibitor, or SB203580, a p38 and JNK2 inhibitor, I/R+PD98059-induced apoptotic cells were reduced by 42.8% and 63.3%, respectively. Hearts isolated from rats treated with PD98059 and subjected to global ischemia (30 minutes)/reoxygenation (1 hour) showed a diminished functional recovery compared with the vehicle group. Coadministration of SB203580 attenuated the detrimental effects of PD98059 and significantly improved cardiac functional recovery. The data taken together suggest that ERK plays a protective role, whereas p38 and JNK mediate apoptosis in cardiomyocytes subjected to I/R, and the dynamic balance of their activities is critical in determining cardiomyocyte fate subsequent to reperfusional injury.