tbuckley/cabot-search huggingface dataset:
SOM230, A New Somatostatin Analogue, Is Highly Effective in the Therapy of Growth Hormone/Prolactin-Secreting Pituitary Adenomas
Authors: Monica Fedele, Ivana De Martino, Rosario Pivonello, Andrea Ciarmiello, M. Laura Del Basso De Caro, Rosa Visone, Dario Palmieri, Giovanna M. Pierantoni, Claudio Arra, Herbert A. Schmid, Leo Hofland, Gaetano Lombardi, Annamaria Colao, Alfredo Fusco
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We have previously shown that transgenic mice ubiquitously overexpressing the HMGA2 gene develop growth hormone/prolactin-secreting pituitary adenomas. This animal model has been used to evaluate the therapeutic efficacy of SOM230, a somatostatin analogue with high affinity for the somatostatin receptor subtypes 1, 2, 3, and 5, on the growth of the pituitary adenomas. Experimental Design: Four groups of 3- and 9-month-old HMGA2 transgenic mice were treated for 3 months with a continuous s.c. injection of two different dosages of SOM230 (5 or 50 μg/kg/h), one dose of octreotide, corresponding to that used in human therapy, and a placebo, respectively. The development of the tumor before and after therapy was monitored by magnetic resonance imaging of the pituitary region and evaluation of the serum prolactin levels. Results: The highest dose of SOM230 induced a drastic regression of the tumor, whereas octreotide was not able to induce any significant tumor regression, although tumor progression was significantly slowed down. No significant differences were observed between the animals treated with the lowest dose of SOM230 and those receiving placebo. Conclusions: These results clearly support the efficacy of the SOM230 treatment in human pituitary adenomas secreting prolactin based on the dramatic tumor shrinkage and fall in prolactin levels. This beneficial effect could be of crucial clinical usefulness in patients bearing tumors resistant to dopaminergic drugs.
Smooth Muscle–Specific Deletion of Nitric Oxide–Sensitive Guanylyl Cyclase Is Sufficient to Induce Hypertension in Mice
Authors: Dieter Groneberg, Peter König, Angela Wirth, Stefan Offermanns, Doris Koesling, Andreas Friebe
Journal: Circulation (2010)

Arterial hypertension is one of the major diseases in industrial countries and a major cause of mortality. One of the main vascular factors responsible for the relaxation of blood vessels and regulation of blood pressure is nitric oxide (NO). NO acts predominantly via NO-sensitive guanylyl cyclase (NO-GC), which is made up of 2 different subunits (alpha and beta). Deletion of the beta(1) subunit leads to a global NO-GC knockout, and these mice are hypertensive. However, global deletion of NO-GC in mice does not allow identification of the cell/tissue type responsible for the elevated blood pressure.To determine the relative contribution of smooth muscle cells to the hypertension seen in NO-GC knockout mice, we generated smooth muscle-specific knockout mice for the beta(1) subunit of NO-GC using a tamoxifen-inducible system. Male mice were investigated because the Cre transgene used is located on the Y chromosome. Tamoxifen injection led to a rapid reduction of NO-GC expression in smooth muscle but did not affect that in other tissues. Parallel to a reduction in NO-induced cGMP accumulation, NO-induced relaxation of aortic smooth muscle was gradually lost after induction by tamoxifen. Concomitantly, these animals developed hypertension within 3 to 4 weeks.We generated a model in which the development of hypertension can be visualized over time by deletion of a single gene in smooth muscle cells. In sum, our data provide evidence that deletion of NO-GC solely in smooth muscle is sufficient to cause hypertension.
Air pollution and hospital admissions for respiratory conditions in Rome, Italy
Authors: D. Fusco, F. Forastiere, P. Michelozzi, T. Spadea, B. Ostro, M. Arcà, C.A. Perucci
Journal: European Respiratory Journal (2001)

Most of the evidence regarding the association between particulate air pollution and emergency room visits or hospital admissions for respiratory conditions and asthma comes from the USA. European time-series analyses have suggested that gaseous air pollutants are important determinants of acute hospitalization for respiratory conditions, at least as important as particulate mass. The association between daily mean levels of suspended particles and gaseous pollutants (sulphur dioxide, nitrogen dioxide, carbon monoxide, ozone) was examined. The daily emergency hospital admissions for respiratory conditions in the metropolitan area of Rome during 1995-1997 were also recorded. Daily counts of hospital admissions for total respiratory conditions (43 admissions day(-1)), acute respiratory infections including pneumonia (18 day(-1)), chronic obstructive pulmonary disease (COPD) (13 day(-1)), and asthma (4.5 day(-1)) among residents of all ages and among children (0-14 yrs) were analysed. The generalized additive models included spline smooth functions of the day of study, mean temperature, mean humidity, influenza epidemics, and indicator variables for day of the week and holidays. Total respiratory admissions were significantly associated with same-day level of NO2 (2.5% increase per interquartile range (IQR) change, 22.3 microg x m(-3)) and CO (2.8% increase per IQR, 1.5 mg x m(-3)). No effect was found for particulate matter and SO2, whereas O3 was associated with admissions only among children (lag 1, 5.5% increase per IQR, 23.9 microg x m3). The effect of NO2 was stronger on acute respiratory infections (lag 0, 4.0% increase) and on asthma among children (lag 1, 10.7% increase). The admissions for all ages for asthma and COPD were associated only with same-day level of CO (5.5% and 4.3% increase, respectively). Multipollutant models confirmed the role of CO on all respiratory admissions, including asthma and COPD, and that of NO2 on acute respiratory infections. Among children, O3 remained a strong indicator of acute respiratory infections. Carbon monoxide and photochemical pollutants (nitrogen dioxide, ozone) appear to be determinants of acute respiratory conditions in Rome. Since carbon monoxide and nitrogen dioxide are good indicators of combustion products from traffic related sources, the detected effect may be due to unmeasured fine and ultrafine particles.
Possible involvement of platelet activating factor in anaphylaxis of passively sensitised, isolated guinea pig hearts
Authors: A. TOSAKI, M. KOLTAI, P. BRAQUET, L. SZEKERES
Journal: Cardiovascular Research (1989)

There is evidence that cardiac tissue may be a target for antigen/antibody reactions. Platelet activating factor (PAF) is released during anaphylaxis and could mediate cardiac damage. To investigate this, guinea pigs were passively sensitised by anti-ovalbumin rabbit serum (6 mg.kg-1 intravenously) and 24 h later their hearts were excised and isolated according to a working heart preparation technique. After a 20 min equilibration period, anaphylactic challenge was induced by a bolus injection of ovalbumin (2 mg in 0.2 ml buffer) via the side arm of the aortic cannula. Heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdp/dtmax) and left ventricular end diastolic pressure (LVEDP) were recorded. After ovalbumin challenge, heart rate and LVEDP were markedly increased, while coronary flow, aortic flow, LVDP, and LVdp/dtmax were profoundly decreased. All these alterations were over within 5 min, and the measured variables returned to approximately the pre-challenge values. BN 52021, a specific PAF receptor antagonist, was dissolved in the perfusion buffer and given in doses of 15, 30 and 60 mumol.litre-1 10 min prior to the induction of anaphylactic challenge until the end of the observation period. BN 52021 inhibited the increase in heart rate and LVEDP and the decrease in coronary and aortic flow, LVDP and LVdp/dtmax in a dose dependent manner. The changes produced by 30 and 60 mumol.litre-1 were statistically significant at the levels of p less than 0.01 and p less than 0.001 when compared to the control values.(ABSTRACT TRUNCATED AT 250 WORDS)
Possible axonal regrowth in late recovery from the minimally conscious state
Authors: H. U. Voss
Journal: Journal of Clinical Investigation (2006)

We used diffusion tensor imaging (DTI) to study 2 patients with traumatic brain injury. The first patient recovered reliable expressive language after 19 years in a minimally conscious state (MCS); the second had remained in MCS for 6 years. Comparison of white matter integrity in the patients and 20 normal subjects using histograms of apparent diffusion constants and diffusion anisotropy identified widespread altered diffusivity and decreased anisotropy in the damaged white matter. These findings remained unchanged over an 18-month interval between 2 studies in the first patient. In addition, in this patient, we identified large, bilateral regions of posterior white matter with significantly increased anisotropy that reduced over 18 months. In contrast, notable increases in anisotropy within the midline cerebellar white matter in the second study correlated with marked clinical improvements in motor functions. This finding was further correlated with an increase in resting metabolism measured by PET in this subregion. Aberrant white matter structures were evident in the second patient’s DTI images but were not clinically correlated. We propose that axonal regrowth may underlie these findings and provide a biological mechanism for late recovery. Our results are discussed in the context of recent experimental studies that support this inference.
Localized unresectable neuroblastoma: results of treatment based on clinical prognostic factors
Authors: A. Garaventa, L. Boni, M.S. Lo Piccolo, G.P. Tonini, C. Gambini, A. Mancini, L. Tonegatti, M. Carli, L.C. di Montezemolo, A. Di Cataldo, F. Casale, K. Mazzocco, G. Cecchetto, A. Rizzo, B. De Bernardi
Journal: Annals of Oncology (2002)
Pathogenesis of Thrombotic Microangiopathies
Authors: X. Long Zheng, J. Evan Sadler
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP has at least three types: congenital or familial, idiopathic, and nonidiopathic. The congenital and idiopathic TTP syndromes are caused primarily by deficiency of ADAMTS13, owing to mutations in the ADAMTS13 gene or autoantibodies that inhibit ADAMTS13 activity. HUS is similar to TTP, but is associated with acute renal failure. Diarrhea-associated HUS accounts for more than 90% of cases and is usually caused by infection with Shiga-toxin-producing Escherichia coli (O157:H7). Diarrhea-negative HUS is associated with complement dysregulation in up to 50% of cases, caused by mutations in complement factor H, membrane cofactor protein, factor I or factor B, or by autoantibodies against factor H. The incomplete penetrance of mutations in either ADAMTS13 or complement regulatory genes suggests that precipitating events or triggers may be required to cause thrombotic microangiopathy in many patients.
DASH-Style Diet Associates with Reduced Risk for Kidney Stones
Authors: Eric N. Taylor, Teresa T. Fung, Gary C. Curhan
Journal: Journal of the American Society of Nephrology (2009)

The impact of the Dietary Approaches to Stop Hypertension (DASH) diet on kidney stone formation is unknown. We prospectively examined the relation between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45,821 men; 18 yr of follow-up), Nurses' Health Study I (n = 94,108 older women; 18 yr of follow-up), and Nurses' Health Study II (n = 101,837 younger women; 14 yr of follow-up). We constructed a DASH score based on eight components: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains and low intake of sodium, sweetened beverages, and red and processed meats. We used Cox hazards regression to adjust for factors that included age, BMI, and fluid intake. Over a combined 50 yr of follow-up, we documented 5645 incident kidney stones. Participants with higher DASH scores had higher intakes of calcium, potassium, magnesium, oxalate, and vitamin C and had lower intakes of sodium. For participants in the highest compared with the lowest quintile of DASH score, the multivariate relative risks for kidney stones were 0.55 (95% CI, 0.46 to 0.65) for men, 0.58 (95% CI, 0.49 to 0.68) for older women, and 0.60 (95% CI, 0.52 to 0.70) for younger women. Higher DASH scores were associated with reduced risk even in participants with lower calcium intake. Exclusion of participants with hypertension did not change the results. In conclusion, consumption of a DASH-style diet is associated with a marked decrease in kidney stone risk.
ORGAN SPECIFICITY OF TISSUES OF THE DOG AND MAN AS SHOWN BY PASSIVE ANAPHYLAXIS IN GUINEA PIGS
Authors: G. Howard Bailey, Sidney Raffel
Journal: The Journal of Experimental Medicine (1941)

The immunization of rabbits for periods of 6 to 8 weeks with sedimented, heat-killed vaccines of Pasteurella boviseptica grown in infusion broths made from six different tissues of the dog and seven tissues of man, caused the production of sera containing antibodies for the broths as well as for the bacteria. The broth made from human fibromyoma of the uterus was the least antigenic of all, as indicated by passive anaphylactic tests in guinea pigs. When these animals were prepared by intraabdominal injection with the rabbit antisera and tested 48 hours later by intravenous injection with autoclaved aqueous extracts of a large number of organs of the dog and man, the guinea pigs were found to be passively sensitized so that severe or fatal anaphylaxis was generally obtained with broths made from the homologous organ and in some instances with those prepared from heterologous organs of the same species. In most instances, the injection of broths from heterologous tissues did not desensitize to later injections of that from the homologous tissue. The most organ-specific antisera were those for striated muscle, small intestine (ileum), kidney, placenta, and fibromyoma, and the least so those for whole blood, liver, and lung. The cross-reactions of the antiserum for blood were mostly with extracts of tissues which normally contain large amounts of blood. The presence of Forssman antigen in the tissues of the dog did not interfere with the demonstration of organ specificity by the methods used. In general, the results indicate that the various tissues of man and the dog contain thermostable, water-soluble, organ-specific substances which can be demonstrated by passive anaphylaxis in guinea pigs. The chemical nature of these substances has not been definitely determined, although there are some indications that they are protein split-products, probably proteoses.
Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy
Authors: Sebastian Oltean, Yan Qiu, Joanne K. Ferguson, Megan Stevens, Chris Neal, Amy Russell, Amit Kaura, Kenton P. Arkill, Kirstie Harris, Clare Symonds, Katja Lacey, Lihini Wijeyaratne, Melissa Gammons, Emma Wylie, Richard P. Hulse, Chloe Alsop, George Cope, Gopinath Damodaran, Kai B. Betteridge, Raina Ramnath, Simon C. Satchell, Rebecca R. Foster, Kurt Ballmer-Hofer, Lucy F. Donaldson, Jonathan Barratt, Hans J. Baelde, Steven J. Harper, David O. Bates, Andrew H.J. Salmon
Journal: Journal of the American Society of Nephrology (2014)

Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A 165 b in diabetic nephropathy. Renal expression of VEGF-A 165 b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A 165 b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A 165 b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A 165 b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A 165 b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A 165 b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.
Targeting Tumor Angiogenesis with Adenovirus-Delivered Anti-Tie-2 Intrabody
Authors: Mikhail Popkov, Nina Jendreyko, Dorian B. McGavern, Christoph Rader, Carlos F. Barbas
Journal: Cancer Research (2005)

Inhibition of tumor angiogenesis is a promising approach for cancer therapy. As an endothelial cell-specific receptor kinase expressed almost exclusively on the surface of vascular endothelium, Tie-2 has an important role in tumor angiogenesis. To explore the therapeutic potential of blocking Tie-2 receptor-interaction pathway, an adenoviral vector was used to deliver a recombinant single-chain antibody fragment rabbit intrabody (pAd-2S03) capable of inhibition of both mouse and human Tie-2 surface expression. pAd-2S03 was given to mice with well-established primary tumors, either a human Kaposi's sarcoma (SLK) or a human colon carcinoma (SW1222). The intrabody significantly inhibited growth of both tumors (75% and 63%, respectively) when compared with pAd-GFP control-treated tumors (P < 0.01). Histopathologic analysis of cryosections taken from mice treated with pAd-2S03 revealed a marked decrease in vessel density, which was reduced by >87% in both tumor models when compared with control-treated tumors (P < 0.01). In contrast, human Tie-2-monospecific pAd-1S05 intrabody did not affect the growth of tumors, indicating that the antitumor effect of pAd-2S03 was due to the inhibition of tumor angiogenesis in these murine models. Our results show that the Tie-2 receptor pathway is essential for both SLK sarcoma and SW1222 colon carcinoma xenograft growth. The present study shows the potential utility of antiangiogenic agents that target the endothelium-specific receptor Tie-2 for down-regulation or genetic deletion.
New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides
Authors: P. Anand, P. Rudge, C.J. Mathias, M. Sharief, V.P. Misra, P.K. Thomas, D.R. Springall, J.M. Polak, S.R. Bloom, M.A. Ghatei, M. Naher-Noe
Journal: The Lancet (1991)
Role of protein kinase C isoforms in bile formation and cholestasis
Authors: Sawkat M. Anwer
Journal: Hepatology (2014)

Transhepatic solute transport provides the osmotic driving force for canalicular bile formation. Choleretic and cholestatic agents affect bile formation, in part, by altering plasma membrane localizations of transporters involved in bile formation. These short-term dynamic changes in transporter location are highly regulated posttranslational events requiring various cellular signaling pathways. Interestingly, both choleretic and cholestatic agents activate the same intracellular signaling kinases, such as phosphoinositide-3-kinase (PI3K), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK). An emerging theme is that choleretic and cholestatic effects may be mediated by different isoforms of these kinases. This is most evident for PKC-mediated regulation of plasma membrane localization of Na+-taurocholate cotransporting polypeptide (NTCP) and multidrug resistance-associated protein 2 (MRP2) by conventional PKCα (cPKCα), novel PKCδ (nPKCδ), nPKCε, and atypical PKCζ (aPKCζ). aPKCζ may mediate choleretic effects by inserting NTCP into the plasma membrane, and nPKCε may mediate cholestatic effects by retrieving MRP2 from the plasma membrane. On the other hand, cPKCα and nPKCδ may be involved in choleretic, cholestatic, and anticholestatic effects by inserting, retrieving, and inhibiting retrieval of transporters, respectively. The effects of PKC isoforms may be mediated by phosphorylation of the transporters, actin binding proteins (radixin and myristoylated alanine-rich C kinase substrate), and Rab proteins. Human NTCP plays an important role in the entry of hepatitis B and D viruses into hepatocytes and consequent infection. Thus, PKCs, by regulating NTCP trafficking, may also play an important role in hepatic viral infections. (Hepatology 2014;60:1090–1097)
Decreased apoptosis and sensitivity to macrophage mediated cytolysis of endometrial cells in endometriosis
Authors: W. Dmowski
Journal: Human Reproduction Update (1998)

Ectopic dissemination of endometrial cells and their subsequent implantation are the mechanisms involved in the development of endometriosis. While the process of dissemination appears to be a phenomenon common to all women, it is unknown what facilitates or prevents ectopic implantation of misplaced endometrial cells. Prior studies by our group and others suggest that cell-mediated immunity in patients with endometriosis is decreased. The present studies evaluated (i) peripheral blood monocyte (PBM) and peritoneal macrophage (PM) mediated cytolysis of autologous eutopic and ectopic endometrial cells and (ii) programmed cell death (apoptosis) in the eutopic and ectopic endometrium. PBM-mediated cytolysis was (mean+/-SD) 23.1+/-13% for the eutopic and 7.8+/-% for the ectopic endometrium (P < 0.004), while the corresponding percentages for PM-mediated cytolysis were 5.4+/-7 and 0.3+/-1 respectively (P < 0.04). This indicates that PBM are much more effective than PM in inducing cytolysis of both eutopic and ectopic endometrium and that ectopic endometrial cells are significantly more resistant to both PBM- and PM-mediated cytolysis. The apoptosis was significantly decreased in the eutopic endometrium of women with endometriosis as compared to fertile controls (0.375+/-0.17 versus 1.57+/-0.3, P < 0.0001). Furthermore, in matched samples apoptosis was significantly lower in the ectopic (0.149+/-0.075) than eutopic (0.375+/-0.17) endometrium (P < 0.001). We conclude from these studies that the decrease in the capacity of monocytes to mediate cytolysis of the misplaced endometrial cells in the peritoneal locations and an increased resistance of these cells to apoptosis are fundamental to the aetiology and/or pathophysiology of endometriosis.