tbuckley/cabot-search huggingface dataset:
Apoptosis in the ovary: molecular mechanisms
Authors: Mahmoud R. Hussein
Journal: Human Reproduction Update (2005)

Cell death was first described in rabbit ovaries (Graaffian follicles), the phenomenon being called 'chromatolysis' rather than apoptosis. In humans, the ovarian endowment of primordial follicles is established during fetal life. Apoptotic cell death depletes this endowment by at least two-thirds before birth, executed with the help of several players and pathways conserved from worms to humans. To date, apoptosis has been reported to be involved in oogenesis, folliculogenesis, oocyte loss/selection and atresia. Several pro-survival and pro-apoptotic molecules are involved in ovarian apoptosis with the delicate balance between them being the determinant for the final destiny of the follicular cells. This review critically analyses the current knowledge about the biological roles of these molecules and their relevance to the dynamics of follicle development. It also presents the existing literature and assesses the gaps in our knowledge.
Electrically Unexcitable Scar Mapping Based on Pacing Threshold for Identification of the Reentry Circuit Isthmus
Authors: Kyoko Soejima, William G. Stevenson, William H. Maisel, John L. Sapp, Laurence M. Epstein
Journal: Circulation (2002)

We hypothesized that delineating electrically unexcitable scar (EUS) within low-voltage infarct regions will locate reentry circuit isthmuses by defining their borders. The pacing threshold and electrogram amplitude that best determines EUS is unknown.The change in dimension of the virtual electrode was estimated in 11 patients and observed to increase by 4.4+/-2.5 mm as stimulus strength increases from threshold (2.9+/-1.8 mA) to 10 mA. EUS was defined as a threshold >10 mA. In 14 consecutive patients, mapping and ablation of ventricular tachycardia (VT) were performed using an electroanatomic mapping system. During sinus rhythm, unipolar pacing was performed at sites with bipolar electrogram amplitude <1.5 mV. EUS regions were marked on the maps. Reentry circuit isthmuses were identified by entrainment mapping or pace mapping, and ablation was performed. EUS was identified in the infarct in all 14 patients (11.8+/-13.9 cm2). All 20 VT circuit isthmuses identified were adjacent to EUS. Although electrogram amplitude correlated with pacing threshold (r=0.64, P<0.0001), many isthmuses had very low-amplitude electrograms, and EUS could not be identified from electrogram amplitude alone. RF ablation lines connecting selected EUS regions abolished all inducible VTs in 10 patients (71%); spontaneous VT was markedly reduced during follow-up (from 142+/-360 to 0.9+/-2.0 episodes per month, P=0.002).This new method of identifying EUS provides complimentary information to the electrogram amplitude in delineating potential reentry circuit paths, potentially facilitating ablation during sinus rhythm.
Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption, and bone metabolism in vivo and in vitro in rodents.
Authors: A J Yates, G E Gutierrez, P Smolens, P S Travis, M S Katz, T B Aufdemorte, B F Boyce, T K Hymer, J W Poser, G R Mundy
Journal: Journal of Clinical Investigation (1988)

A synthetic peptide corresponding to the first 34 amino acids of the parathyroid hormone-related protein (PTH-rP) produced by a human tumor associated with hypercalcemia was examined for skeletal and renal effects on calcium metabolism in vivo and in vitro. These effects were compared with those of human parathyroid hormone (1-34), hPTH (1-34). Equal doses of PTH-rP(1-34) and hPTH(1-34) produced equivalent stimulation of adenylate cyclase in vitro in bone cells and kidney cells and tubules. Subcutaneous injection of PTH-rP(1-34) in mice caused a significant dose-related increase in blood ionized calcium similar to that seen with hPTH(1-34) at equivalent doses. Repeated injections of equal doses of both peptides caused sustained hypercalcemia which was significantly greater in PTH-rP(1-34)-treated mice, although each induced comparable increases in histomorphometric indices of osteoclastic bone resorption. PTH-rP(1-34) and hPTH(1-34) also caused similar increases in bone resorption when incubated with fetal rat long bones in organ culture. Infusion of either peptide into thyroparathyroidectomized rats suppressed urinary calcium excretion and increased urinary excretion of cyclic AMP. PTH-rP appears to have similar effects to those of PTH on the skeleton, the kidney, and overall calcium homeostasis.
Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins.
Authors: T F Tedder, C M Isaacs, T J Ernst, G D Demetri, D A Adler, C M Disteche
Journal: The Journal of Experimental Medicine (1989)

A cDNA encoding a new human lymphocyte cell surface molecule has been isolated and shown to identify a fourth member of a recently discovered family of adhesion proteins. This lymphocyte-associated molecule (LAM-1) is uniquely composed of multiple distinct domains, one domain homologous with animal lectins, one homologous with epidermal growth factor, and two short consensus repeat units similar to those found in C3/C4 binding proteins. This cDNA clone hybridized with RNAs found in B cell lines and T lymphocytes, but not with RNA from other cell types. The amino acid sequence of LAM-1 is 77% homologous with the sequence of the mouse lymphocyte homing receptor, suggesting that LAM-1 may function in human lymphocyte adhesion. The LAM-1 gene is located on chromosome 1q23-25, as is another member of this adhesion family, suggesting that this new family of proteins may be encoded by a cluster of "adhesion protein" loci.
Does Glucose Variability Influence the Relationship Between Mean Plasma Glucose and HbA1c Levels in Type 1 and Type 2 Diabetic Patients?
Authors: Judith C. Kuenen, Rikke Borg, Dirk J. Kuik, Hui Zheng, David Schoenfeld, Michaela Diamant, David M. Nathan, Robert J. Heine
Journal: Diabetes Care (2011)

The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA(1c) and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-HbA(1c) relationship.Analyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-HbA(1c) relationship.GV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-HbA(1c) relationship in type 1 diabetic patients so that high GV led to a higher HbA(1c) level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the HbA(1c) level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency.In only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with HbA(1c). This effect is more pronounced at higher HbA(1c) levels. However, the impact of GV on the HbA(1c) level in type 1 diabetes is modest, particularly when HbA(1c) is close to the treatment target of 7%.
FSAP reduces risk of repair
Authors: Ruth Williams
Journal: The Journal of Experimental Medicine (2006)

Overenthusiastic repair of damaged blood vessels could cause a fatal blockage. Sedding et al. (page 2801) report that the normal repair-restricting function of factor VII activating protease (FSAP) is disrupted by a common mutation. People carrying the mutation might thus be more at risk of vessel narrowing.






Figure 1

After vascular injury, repair is restricted in the presence of FSAP (right) to prevent narrowing of the blood vessel.




Approximately 5% of the population carries an FSAP polymorphism linked to cardiovascular disease. The authors' previous in vitro evidence suggested that wild-type FSAP, a plasma protein, limits vessel repair processes in part by inactivating PDGF-BB—a growth factor which promotes the proliferation and migration of blood vessel wall cells during repair.

The team isolated and characterized the mutated form of FSAP and discovered that although its ability to bind PDGF-BB was unaltered, it failed to cleave the protein efficiently. Wild-type human FSAP reduced vascular cell proliferation and accumulation at sites of injury in a mouse model—most likely by reducing PDGF-BB activity. The mutant protein, however, provided no such restraint, suggesting that people possessing the mutation might generate excessive scar tissue during vessel repair.

Vessel narrowing occasionally recurs after surgical repair. If, as the team suspects, recurrence correlates with the FSAP polymorphism, then screening cardiovascular patients for the mutation might identify those at risk.
Final results of Australasian Gastrointestinal Trials Group ARCTIC study: an audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines
Authors: D. Ransom, K. Wilson, M. Fournier, R.J. Simes, V. Gebski, D. Yip, N. Tebbutt, C.S. Karapetis, D. Ferry, S. Gordon, T.J. Price
Journal: Annals of Oncology (2013)
Unusual ulceration in diabetes mellitus
Authors: JULIAN VERBOV
Journal: British Journal of Dermatology (1974)

Journal Article Unusual ulceration in diabetes mellitus Get access JULIAN VERBOV JULIAN VERBOV Broadgreen Hospital, Thomas Drive, Liverpool L14 3LB Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 6, 1 December 1974, Pages 699–700, https://doi.org/10.1111/j.1365-2133.1974.tb12457.x Published: 01 December 1974 Article history Accepted: 07 June 1974 Published: 01 December 1974
Signaling at the Slit Diaphragm
Authors: Thomas Benzing
Journal: Journal of the American Society of Nephrology (2004)

<h3>Summary</h3> Microbes are phylogenetically and metabolically diverse. Yet capturing this diversity, assigning functions to host organisms and exploring the biosynthetic potential in natural environments remains challenging. We reconstructed &gt;25,000 draft genomes, including from &gt;2,500 uncharacterized species, from globally-distributed ocean microbial communities, and combined them with ∼10,000 genomes from cultivated and single cells. Mining this resource revealed ∼40,000 putative biosynthetic gene clusters (BGCs), many from unknown phylogenetic groups. Among these, we discovered <i>Candidatus</i> Eudoremicrobiaceae as one of the most biosynthetically diverse microbes detected to date. Discrete transcriptional states structuring natural populations were associated with a potentially niche-partitioning role for BGC products. Together with the characterization of the first Eudoremicrobiaceae natural product, this study demonstrates how microbiomics enables prospecting for candidate bioactive compounds in underexplored microbes and environments.
Gut-hormone profile in totally pancreatectomised patients.
Authors: H G Dammann, H S Besterman, S R Bloom, H W Schreiber
Journal: Gut (1981)

In eight totally pancreatectomised patients the release of the relevant gut hormones was determined after a standard test meal. Plasma levels of pancreatic glucagon were not significantly different from zero in our series of pancreatectomised patients. Pancreatic polypeptide was undetectable. These findings imply the absence of a significant number of normally functioning alpha cells and pancreatic polypeptide cells in extrapancreatic sites in man. Consistent with the antrectomy, duodenectomy, and resection of the upper jejunum that are performed in conjunction with a total pancreatectomy the gastrin release was significantly impaired. In contrast there was a striking post-prandial rise in enteroglucagon probably induced by the rapid intestinal transit time often seen after partial gastrectomy. In contrast plasma motilin and GIP levels were normal. Pancreatectomised man thus presents an interesting model of total deficiency of endogenous insulin, pancreatic polypeptide, and pancreatic glucagon and, in addition, greatly diminished gastrin. The considerable derangement of metabolic and intestinal function that follows total pancreatectomy may, in part, be explained by this gross disturbance of the normal physiology of gut hormone.
Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study
Authors: C. Kenis, D. Bron, Y. Libert, L. Decoster, K. Van Puyvelde, P. Scalliet, P. Cornette, T. Pepersack, S. Luce, C. Langenaeken, M. Rasschaert, S. Allepaerts, R. Van Rijswijk, K. Milisen, J. Flamaing, J.-P. Lobelle, H. Wildiers
Journal: Annals of Oncology (2013)
Regional blood flow and its relationship to lymphocyte and lymphoblast traffic during a primary immune reaction.
Authors: C A Ottaway, D M Parrott
Journal: The Journal of Experimental Medicine (1979)

The relationship of alterations in blood flow with changes in cell distribution has been studied in an inflammatory site and its draining lymph node during the induction of an immune reaction with oxazolone in mice. The cells which move to the site of inflammation are predominantly lymphoblasts and their increased localization in the inflamed ear is significantly correlated with increased regional blood flow to the inflamed tissue. The existence of this correlation is not antigen dependent although there is a relative increment of lymphoblasts which are specifically primed to the inflammatory agent. The localization of nonblastic (small) 51Cr-labeled lymphocytes on the other hand is substantial only in lymphoid tissue and during the induction of an immune reaction after oxazolone application, the increase in localization of these cells in the draining lymph node is positively correlated with increased blood flow to the node. Furthermore, the probability of finding 51Cr labeled lymphocytes in a particular lymph node is related to the regional blood flow which that node receives.
Intensive Insulin Therapy in the Intensive Care Unit
Authors: Christophe De Block, Begoña Manuel-y-Keenoy, Luc Van Gaal, Peter Rogiers
Journal: Diabetes Care (2006)

Hyperglycemia occurs in most critically ill patients. Using continuous glucose monitoring (CGM), we investigated whether intensive insulin therapy based on discontinuous glucose monitoring can achieve normoglycemia (80-110 mg/dl) in a medical intensive care unit (MICU).Fifty adults (men/women 31/19, age 62 +/- 16 years, nondiabetic/diabetic 30/20, intravenous/subcutaneous insulin 22/28, and Acute Physiology and Chronic Health Evaluation II score 22 +/- 7) were prospectively recruited. Forty-eight-hour CGM was performed using a subcutaneous glucose sensor (GlucoDay) and compared with arterial glycemia. Main outcome measures were percent of time in normoglycemia and accuracy/applicability of CGM.During 48-h CGM, glycemia reached target (80-110 mg/dl) in only 22 +/- 18%, was >140 mg/dl in 39 +/- 27%, and was <60 mg/dl in 5 +/- 10% of the time. Patients on subcutaneous versus intravenous insulin had more glycemia readings >110 mg/dl (P = 0.016). Glycemia was higher in diabetic patients (170 +/- 77 vs. 129 +/- 35 mg/dl, P = 0.013). BMI was an independent determinant for bad glycemic control (beta = 0.73, P < 0.0001). Diabetic state (beta = 0.47, P < 0.0001), septic shock (beta = 0.22, P = 0.045), sequential organ failure assessment score (beta = 0.40, P = 0.001), and use of corticoids (beta = 0.28, P = 0.014) and inotropics (beta = -0.24, P = 0.035) were independent determinants of insulin dose. GlucoDay values and arterial glycemia correlated well (r = 0.85, P < 0.0001, n = 555 after six-point calibration), with 97% of data falling in regions A and B of error grid analysis. There were no adverse events using GlucoDay.GlucoDay, a well-tolerated 48-h CGM system, revealed that normoglycemia was only achieved 22% of the time in MICU patients. Further studies should investigate whether application of CGM to titrate insulin therapy can improve patient outcome.
Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries
Authors: Paul Coats, Fiona Johnston, John MacDonald, John J. McMurray, Chris Hillier
Journal: Cardiovascular Research (2001)

In this study we have examined for the first time the signal transduction mechanisms involved in the generation of pressure-dependent myogenic tone in human small resistance arteries from the subcutaneous vascular bed.Myogenic responses and the subcellular mechanisms involved in the generation of this response were studied on a pressure myograph.Human subcutaneous resistance arteries constricted 14.1+/-1.1% in response to an increases in intraluminal pressure from 40 to 80 mmHg and a further 3.5+/-1.7% in response to the 80-120-mmHg pressure step. Ca(2+) depletion or nifedipine abolished this response, whereas BAY K 8644 increased this response to 20.6+/-2.1% (P<0.05, response vs. control). The phospholipase C inhibitor U-73122 reduced the myogenic response to 2.5+/-1.0% at 80 mmHg (P<0.01, response vs. control) and abolished it at 120 mmHg. Diacylglycerol lipase inhibition with RHC-80267 abolished all myogenic responses to pressure. The protein kinase C (PKC) activator phorbol 12,13-dibutyrate increased the maximal myogenic response to 20.9+/-1.8% (P<0.05, response vs. control), whereas the PKC inhibitor calphostin C abolished myogenic responses. These data show that the generation of pressure-dependent myogenic tone in human subcutaneous arteries is dependent on Ca(2+) influx via voltage operated Ca(2+) channels (VOCCs) and a concomitant requirement for the activation of phospholipase C (PLC), diacylglycerol, and PKC.
Abstract 3748: NVP-BYL719, a novel PI3Kalpha selective inhibitor with all the characteristics required for clinical development as an anti-cancer agent
Authors: Christine M. Fritsch, Christian Schnell, Christian Chatenay-Rivauday, Daniel A. Guthy, Alain De Pover, Markus Wartmann, Saskia Brachmann, Sauveur-Michel Maira, Alan Huang, Cornelia Quadt, Francesco Hofmann, Giorgio Caravatti
Journal: Cancer Research (2012)

Abstract Most of the current oncology drug discovery and development work has shifted towards molecularly targeted therapies. A key focus has been on identifying inhibitors against components of pathways that drive tumor cell proliferation, survival, and metastasis such as the PI3K/mTOR pathway, reported to be implicated in many human cancers through various mechanisms, such as, somatic PIK3CA missense mutations that occur at high frequency. These mutations are largely point mutations predominantly clustered within three hotspots in the helical and kinase domains of p110α: E542K, E545K and H1047R, which represent about 80% of the mutations observed, and confirmed to be oncogenic gain-of-function mutations. Based on these findings cancer-specific mutants of p110α appear to be ideal targets for drug development and p110α specific inhibitors, such as NVP-BYL719, could then have potential anti-cancer activity without causing the potential side effects that could be expected from interference with other Class I PI3K isoforms or other members of the PIKK family. NVP-BYL719 is best described as a PI3Kalpha inhibitor as in biochemical assays, it inhibits p110α as well as p110α most common somatic mutations (IC50=5 nM) much more potently than p110α and ≤ and has weak or no activity against p110α, Vps34 and mTOR and is selective against a wide range of protein kinases (&amp;gt; 50-fold). The potency and selectivity profile of NVP-BYL719 is confirmed at the cellular level, is correlated with inhibition of various PI3K/Akt downstream signaling pathway components and is associated with anti-proliferation of breast cancer cell lines harboring PIK3CA mutations. In vivo, NVP-BYL719 shows dose and time-dependent inhibition of the PI3K/Akt pathway which correlates with compound exposure and is associated with good tolerability and significant dose-dependent anti-tumor efficacy in PIK3CA mutant tumor xenograft models in rodents. Moreover, plasma insulin levels are significantly increased while blood glucose levels remained normal at all tested doses and time points indicating on-target effects of NVP-BYL719 on the regulation of metabolism. Overall, as a PI3Kalpha inhibitor, NVP-BYL719 has good drug-like and pharmacological properties and presents all the characteristics required for its ongoing Phase I clinical development in adult patients with advanced solid malignancies whose tumors have an alteration of the PIK3CA gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3748. doi:1538-7445.AM2012-3748
Giant fibromyxoma of the parietal pleura.
Authors: D C Nwafo, F C Adi
Journal: Thorax (1978)

A 23-year-old Nigerian man with a giant (8.5 kg) benign intrathoracic fibromyxoma presented in respiratory distress with what looked clinically and radiologically like a massive left-sided pleural effusion. The correct preoperative diagnosis was suggested by an almost 9dry tap9 together with a solid resistance to the aspiring needle at chest aspiration. Complete removal was successfully accomplished through an extended left thoracotomy. The pathology, clinical features, and treatment of localised pleural fibromas are briefly discussed.
Portal hypertension in acute liver failure.
Authors: M Navasa, J C Garcia-Pagan, J Bosch, J R Riera, R Banares, A Mas, M Bruguera, J Rodes
Journal: Gut (1992)

Twenty five patients with acute liver failure were measured for hepatic venous pressure gradient as an index of portal pressure during the course of a transjugular liver biopsy. Hepatic venous pressure gradient ranged from 4 to 24.5 mm Hg with a mean of 12.8 (5.3) mm Hg (normal values less than 5 mm Hg). All patients but one had increased portal pressure gradient. Portal hypertension correlated with the degree of architectural distortion of the liver, as suggested by a direct correlation between hepatic venous pressure gradient and the area of reticulin collapse, evaluated by means of a morphometric analysis on Sirius red stained liver slides (r = 0.43, p less than 0.05). Hepatic venous pressure gradient was significantly higher in patients with ascites (15.1 (5) mm Hg, n = 15) or renal failure (14.4 (5.3) mm Hg, n = 16) than in those without (9.3 (3.4) mm Hg and 10.1 (4) mm Hg, respectively; p less than 0.05). Portal hypertension was associated with systemic vasodilation and a hyperkinetic circulatory state, with decreased arterial pressure, and peripheral resistance and increased cardiac output.