tbuckley/cabot-search huggingface dataset:
A critical role for extracellular protein disulfide isomerase during thrombus formation in mice
Authors: Jaehyung Cho, Barbara C. Furie, Shaun R. Coughlin, Bruce Furie
Journal: Journal of Clinical Investigation (2008)

Thiol isomerases, including protein disulfide isomerase (PDI), catalyze disulfide oxidation, reduction, and isomerization, thereby playing an important role in protein synthesis. To determine whether extracellular PDI mediates thrombus formation in an animal model, PDI expression, platelet accumulation, and fibrin generation were monitored in the blood vessels of mice by intravital fluorescence microscopy following laser-induced arteriolar injury. A time-dependent increase in PDI was observed in murine thrombi following injury. Infusion of the PDI inhibitor bacitracin or a blocking monoclonal antibody against PDI inhibited platelet thrombus formation and fibrin generation. Fibrin deposition is normal in mice lacking the G protein–coupled platelet receptor Par4, although there is no stable accumulation of platelets. Infusion of monoclonal antibodies against PDI into the circulation of Par4–/– mice prior to vessel wall injury inhibited fibrin generation. These results indicate that PDI is required in vivo in mice for both fibrin generation and platelet thrombus formation.
Effects of vasoactive drugs upon haemodynamic power and input impedance in normal rats
Authors: G. Wright
Journal: Cardiovascular Research (1991)

The objectives were (a) to describe the effects of vasoactive drugs in normal rats upon cardiovascular function assessed by computing aortic haemodynamic power and input impedance, each separated into their component parts, and (b) to study the relationship between left ventricular pulsatile power output and the vascular impedance.Haemodynamic power and input impedance were computed from measurements of aortic blood pressure and flow in normal rats. The rats were then given an infusion of a vasoconstrictor drug (methoxamine) followed by a vasodilator drug (hydralazine) in order to study the effects of changes in vascular impedance upon haemodynamic power.The measurements were made on pentobarbitone anaesthetised male Wistar rats of approximately 400 g body weight (10 infused with Hartmann's solution as controls and 10 infused with the drugs).Aortic total haemodynamic power was between 9.96 mW and 10.37 mW during the control period and reached a maximum of 11.36 mW during the methoxamine infusion, but this difference was not statistically significant. It then decreased significantly to 4.32 mW by the end of the hydralazine infusion. Pulsatile power was only 0.32(SEM 0.08) mW (2.8% of the total power) in the control state and decreased to 0.12(0.1) mW (1.7%) during the methoxamine infusion, but increased to 0.59(0.15) mW (12.5%) by the end of the hydralazine infusion. The vascular effects were complex and involved all four of the input impedance parameters--peripheral resistance, characteristic resistance, arterial compliance, and inertance. Reflex responses of the vascular wall were apparent as temporal changes in characteristic resistance and arterial compliance.Changes in cardiovascular function can be described by computing haemodynamic power and input impedance and then separating these into their component parts. Administration of the vasoactive drugs affected left ventricular mean and pulsatile power output and all four components of the input impedance. The frequency distribution of left ventricular pulsatile power output may be matched to the vascular impedance in order to optimise tissue perfusion.
IKK/NF- B signaling: balancing life and death - a new approach to cancer therapy
Authors: Jun-Li Luo, Hideaki Kamata, Michael Karin
Journal: Journal of Clinical Investigation (2005)

IκB kinase/NF-κB (IKK/NF-κB) signaling pathways play critical roles in a variety of physiological and pathological processes. One function of NF-κB is promotion of cell survival through induction of target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NF-κB can also prevent programmed necrosis by inducing genes encoding antioxidant proteins. Regardless of mechanism, many cancer cells, of either epithelial or hematopoietic origin, use NF-κB to achieve resistance to anticancer drugs, radiation, and death cytokines. Hence, inhibition of IKK-driven NF-κB activation offers a strategy for treatment of different malignancies and can convert inflammation-induced tumor growth to inflammation-induced tumor regression.
Rous Sarcoma Virus-Induced Tumors in Marmosets: Characteristics of Tumor Cells and Host Cell-Virus Interrelationships2
Authors: B. Marczynska, F. Deinhardt, J. Schulien, P. Tischendorf, R. D. Smith
Journal: JNCI Journal of the National Cancer Institute (1973)

Thirty-eight tumors were induced in white-lipped marmosets(Saguinus nigricollis, S. fuscicollis) by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). They were analyzed for viral genome, virus-expressed antigen(s), chromosomal aberrations, and the production of acid mucopolysaccharides (AMPS). Tumors established in cell cultures had morphologic characteristics typical for Roustumor cells of fowl and other mammalian species. The viral genome was demonstrated in 7 of 18 tumors by cocultivation with live, X-irradiated, or disrupted chicken cells. No group-specific antigen was detected by complement fixation tests (COFAL) in tumors examined, and only a few animals with a long latent period developed COFAL antibodies. Although no specific chromosomal aberrations accompanied marmoset SR-RSV-induced tumors, chromosomes were often broken and rearranged, which wasattributed to inadequate cell nutrition in fast-growing and poorly vascularized tumors. Large quantities of AMPS were demonstrated in some tumors, and all tumors had some AMPS on the periphery of tumors infiltrating surrounding muscles. Infectious viruses isolated from marmoset SR-RSV-induced tumors had envelope antigens similar to either subgroup A or D of avian sarcoma-leukosis viruses, as did the original SR-RSV used for marmoset inoculation.
IDIOPATHIC HYPERLIPEMIA: METABOLIC STUDIES IN AN AFFECTED FAMILY*
Authors: Richard J. Havel, Robert S. Gordon
Journal: Journal of Clinical Investigation (1960)

The clinical syndrome of idiopathic hyperlipemia is, characterized by lactescent blood plasma in the postabsorptive state. The milky appearance of the plasma is caused by its abnormally high content of triglyceride-rich lipoproteins of high molecular weight. Omission of fat from the diet of such patients decreases the concentration of triglycerides, suggesting that defective removal of exogenous fat from the circulation may be an important meta
CD4+CD25+ Immunoregulatory T Cells
Authors: José L. Cohen, Aurélie Trenado, Douglas Vasey, David Klatzmann, Benoît L. Salomon
Journal: The Journal of Experimental Medicine (2002)

CD4+CD25+ immunoregulatory T cells play a pivotal role in preventing organ-specific autoimmune diseases and in tolerance induction to allogeneic organ transplants. We investigated whether these cells could also control graft-versus-host disease (GVHD), the main complication after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we show that the few CD4+CD25+ T cells naturally present in the transplant regulate GVHD because their removal from the graft dramatically accelerates this disease. Furthermore, the addition of freshly isolated CD4+CD25+ T cells at time of grafting significantly delays or even prevents GVHD. Ex vivo–expanded CD4+CD25+ regulatory T cells obtained after stimulation by allogeneic recipient-type antigen-presenting cells can also modulate GVHD. Thus, CD4+CD25+ regulatory T cells represent a new therapeutic tool for controlling GVHD in allogeneic HSCT. More generally, these results outline the tremendous potential of regulatory T cells as therapeutics.
Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects
Authors: Rolf F. Barth, Jeffrey A. Coderre, M. Graça H. Vicente, Thomas E. Blue
Journal: Clinical Cancer Research (2005)

Abstract Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer α particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na2B12H11SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (∼20 μg/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boron-containing amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out in Japan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of “debulking” surgery to remove as much of the tumor as possible, followed by BNCT at varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v. have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCT could move forward as a treatment modality.
The lectin-like domain of thrombomodulin protects against ischaemia-reperfusion lung injury
Authors: N. Geudens, M. Van de Wouwer, B. M. Vanaudenaerde, R. Vos, C. Van De Wauwer, G. M. Verleden, E. Verbeken, T. Lerut, D. E. M. Van Raemdonck, E. M. Conway
Journal: European Respiratory Journal (2008)

Ischaemia–reperfusion injury of the lung is a major cause of morbidity and mortality, particularly following lung transplantation, the mainstay treatment for patients with end-stage pulmonary disease. Effective measures to prevent this complication are lacking. Thrombomodulin (TM) is an endothelial cell receptor and cofactor for thrombin-mediated generation of the anticoagulant and anti-inflammatory activated protein C (APC). The N-terminal lectin-like domain (LLD) of TM has no direct effects on coagulation, but has distinct anti-inflammatory properties, interfering with leukocyte adhesion, complement activation and cytokine generation, all of which are hallmarks of ischaemia–reperfusion injury. Using a murine model of lung ischaemia–reperfusion injury (90 min ischaemia, 4 h reperfusion), the present study shows that mice lacking the LLD of TM respond with increased extravasation of neutrophils and macrophages into the lung parenchyma and bronchoalveolar fluid (BALF), with augmented BALF levels of cytokines interleukin (IL)-1β and granulocyte-monocytic colony-stimulating factor (GM-CSF). Pre-treatment of wild-type mice with recombinant LLD, as compared with controls, significantly suppresses protein leakage and accumulation of leukocytes in the BALF. These novel findings support further evaluation of recombinant lectin-like domain of thrombomodulin to protect the lung against tissue-damaging pro-inflammatory responses following ischaemia-reperfusion.
Changes in intracellular free calcium concentration during long exposures to simulated ischemia in isolated mammalian ventricular muscle.
Authors: J A Lee, D G Allen
Journal: Circulation Research (1992)

Intracellular free calcium concentration ([Ca2+]i) was measured in isolated ferret ventricular papillary muscles during and after long exposures to ischemia. All experiments were performed at 37 degrees C, and the muscles were stimulated at 1 Hz. Ischemia was simulated by changing from superfusion with oxygenated Tyrode's solution to superfusion with water-saturated gas (95% N2-5% CO2), thus simultaneously stopping oxygenation and restricting the extracellular space. [Ca2+]i was measured with aequorin, which was microinjected into superficial cells of the preparation. Exposure to ischemia caused a complex series of changes in [Ca2+]i. In the first few minutes the changes in [Ca2+]i were variable; however, after approximately 5 minutes all preparations exhibited a progressive increase in amplitude and duration of the stimulated rise in [Ca2+]i (the calcium transient). The amplitude of the calcium transients peaked after approximately 18 minutes of ischemia, when they were 339% of the control value. After this peak, the calcium transients progressively failed to occur in response to stimulation and declined in amplitude; simultaneously, spontaneous oscillations of [Ca2+]i appeared and increased in size and frequency. The oscillations in turn then gradually became less frequent until a large, prolonged (5-10 minute) increase in [Ca2+]i occurred, after which [Ca2+]i returned to a low level. There were no further oscillations after this event, which was seen on average after 37 minutes of ischemia. A slowly progressive contracture often began to develop at about this time. A gradual rise in resting [Ca2+]i occurred during the remainder of the exposure to ischemia. When muscles were reperfused after long exposures to ischemia, there was a very large and prolonged increase in [Ca2+]i, which was usually associated with a contracture and failure of recovery of developed tension. The large increase in [Ca2+]i could be reduced by the inclusion of 3 mM nickel chloride in the reperfusing solution. Comparison between reperfusion with O2 gas versus reperfusion with anoxic Tyrode's solution indicated that reoxygenation was more beneficial to the muscle than resumption of bulk flow. These results reveal the complex spectrum of changes in [Ca2+]i that occur during ischemia and on reperfusion. These changes in [Ca2+]i are likely to play an important role in the generation of ischemic arrhythmias and muscle damage.
CD8+ lymphocytes respond to different HIV epitopes in seronegative and infected subjects
Authors: Rupert Kaul, Tao Dong, Francis A. Plummer, Joshua Kimani, Timothy Rostron, Peter Kiama, Ephantus Njagi, Erastus Irungu, Bashir Farah, Julius Oyugi, Rana Chakraborty, Kelly S. MacDonald, Job J. Bwayo, Andrew McMichael, Sarah L. Rowland-Jones
Journal: Journal of Clinical Investigation (2001)

HIV-1–specific cytotoxic T-lymphocyte (CTL) responses have been detected at a low frequency in many HIV-1–exposed, persistently seronegative (HEPS) subjects. However, it is unclear how CTLs could protect against HIV acquisition in HEPS subjects, when high levels of circulating CTL fail to prevent disease progression in most seropositive subjects. To address this issue we studied CD8+ lymphocyte responses to a panel of HIV-1 CTL epitopes in 91 HEPS and 87 HIV-1–infected Nairobi sex workers. HIV-specific responses in seropositive women focused strongly on epitopes rarely or never recognized in HEPS subjects, who targeted epitopes that were subdominant or unrecognized in infected women. These differences in epitope specificity were restricted by only those HLA class I alleles that are associated with a reduced risk of HIV-1 infection in this cohort. Late seroconversion in HEPS donors was associated with a switch in epitope specificity and/or immunodominance to those epitopes preferentially recognized by HIV-1–infected women. The likelihood of detecting HIV-1–specific responses in HEPS women increased with the duration of viral exposure, suggesting that HIV-1–specific CD8+ responses are acquired over time. The association between differential recognition of distinct CTL epitopes and protection from HIV-1 infection may have significant implications for vaccine design.
Effect of l-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome
Authors: H Grasemann, SS Gartig, HG Wiesemann, H Teschler, N Konietzko, F Ratjen
Journal: European Respiratory Journal (1999)

Airway nitric oxide concentrations in patients with cystic fibrosis or primary ciliary dyskinesia syndrome have been shown to be lower than in healthy subjects. Decreased NO concentrations may contribute to impaired ciliary clearance, respiratory tract infections, or obstructive lung disease in these conditions. Nasal and exhaled NO concentrations were compared before and after infusion of 500 mg x kg(-1) L-arginine, the substrate of NO synthases, in 11 cystic fibrosis (CF) patients, seven primary ciliary dyskinesia (PCD) syndrome patients, and 11 control subjects. Baseline nasal and exhaled NO concentrations were significantly lower in both CF and PCD syndrome patients than in controls (p&lt;0.01). In controls, the maximum increase of NO was seen immediately after L-arginine infusion in the upper airways (1.8-fold) and 3 h after the infusion in the lower airways (1.4-fold). Although NO concentrations also increased significantly in both CF (1.9-fold and 1.6-fold, respectively) and PCD syndrome patients (1.4-fold and 1.8-fold, respectively), concentrations remained subnormal compared with baseline values of controls. Pulmonary function remained unchanged in both patient groups. In conclusion, the low airway nitric oxide formation in both cystic fibrosis and primary ciliary dyskinesia syndrome patients can be augmented by L-arginine administration. The finding that pulmonary function remained unchanged in both conditions may be due to the fact that normalization of airway nitric oxide concentrations could not be achieved.
Morphological and functional gastric cytoprotection by prostaglandin in rats receiving absolute ethanol orally.
Authors: A Robert, F W Leung, P H Guth
Journal: Gut (1992)

Pretreatment with prostaglandins at non-antisecretory doses protects the gastric mucosa, including the parietal cells, from deep necrosis produced by intragastric administration of necrotising agents such as absolute ethanol. Whether the parietal cells also retained their ability to secrete acid when rats were pretreated with a prostaglandin, in spite of exposure to ethanol, was investigated. Gastric acid secretion was abolished 4 hours after ethanol, and secretion returned to control values only after 5-6 days. Pretreatment with a single, non-antisecretory dose of 16, 16-dimethyl prostaglandin E2 (dm PGE2) maintained acid secretion, in spite of exposure to absolute ethanol. Absolute ethanol caused histological changes - extensive gastric mucosal necrosis (through the muscularis mucosae), oedema, haemorrhages, polymorphonuclear infiltration, and formation of granulation tissue - that were maximal 24-48 hours after ethanol and persisted for 2 to 4 weeks. None of these changes were present in animals treated with the prostaglandin. It is concluded that a single oral pretreatment with dmPGE2 protects the gastric mucosa against not only the morphological damage of absolute ethanol (preventing necrosis, haemorrhages, and polymorphonuclear infiltration) but also the functional damage (maintaining the acid secretory function of parietal cells).
Second primary lung cancer in clinical emergency hospital of Constanta - A prospective study
Authors: Doina Tofolean, Laura Mazilu, Tatiana Adam, Ioan-Tiberiu Tofolean, Andra-Iulia Suceveanu
Journal: European Respiratory Journal (2012)

Background. More people are living with a diagnosis of cancer than ever before. One of the consequences of surviving cancer is the increased likelihood of being diagnosed with a second primary cancer. Aim. To determine the frequency of secondary primary lung cancer (SPLC) in clinical practice. Material and method. A total of 176 patients was diagnosed with lung cancer, between January 2001 and January 2011 in 1st Internal Medical Department of Clinical Emergency Hospital of Constanta; 22 patients (12.50%) were already diagnosed with other cancers. Positive diagnosis of SPLC included chest X-ray, spiral CT, bronchoscopy, EUS+FNA, CEUS. Results. Most patients diagnosed with SPLC were initially diagnosed with Hodgkin9s disease (n=4), head and neck cancer (n=5), bladder cancer (n=3). Gender distribution showed male predominance (n=16). Most patients (n=14) were heavy smokers (>25 Pack Years; P
Marrow Transplantation for Leukemia
Authors: E. Donnall Thomas
Journal: JAMA (1978)

To the Editor.—  The article by Bortin and Rimm (p 1245) reporting the results of the Marrow Transplant Registry indicates that two (4% ) of 57 patients with end-stage acute myelogenous leukemia (AML) are living after marrow transplantation. In comparing the survival curves for the Registry cases with the Seattle cases, there was no significant difference, even though a rather clear separation between the curves emerged. Statistical significance depends strongly on sample size, and the number of longterm survivors in both series of patients is small. This should not obscure the fact that there are some long-term disease-free survivors in a group of patients where no other therapeutic approach is known to produce long-term survivors.  In the Seattle series of 46 patients, 17 cases were in remission 100 days after transplantation and eight were in remission at one year—a result that compares favorably with experimental chemotherapy for this type of patient.
The mother ship has come in
Authors: Liam Farrell
Journal: BMJ (2008)

I read that the Conservative party is proposing an innovative support system for new mothers and their babies. Apparently a “health worker” will attend for six hours each day in the first week after discharge, hang out around the house, and be generally helpful—for example, showing the mother how to breastfeed and bathe their baby, looking after older children, and performing housekeeping duties.

This is obviously a brilliant idea, but we have to tread carefully because the healthcare jungle is full of predators; initially we will be under …