tbuckley/cabot-search huggingface dataset:
Toward Brain Tumor Gene Therapy Using Multipotent Mesenchymal Stromal Cell Vectors
Authors: Daniel Bexell, Stefan Scheding, Johan Bengzon
Journal: Molecular Therapy (2010)

Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many characteristics with pericytes and that implanted MSCs localize primarily to perivascular niches within tumors, which might have therapeutic implications. The use of MSC vectors in cancer gene therapy raises concerns, however, including a possible MSC contribution to tumor stroma and vasculature, MSC-mediated antitumor immune suppression, and the potential malignant transformation of cultured MSCs. Nonetheless, we highlight the novel prospects of MSC-based tumor therapy, which appears to be a promising approach. Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many characteristics with pericytes and that implanted MSCs localize primarily to perivascular niches within tumors, which might have therapeutic implications. The use of MSC vectors in cancer gene therapy raises concerns, however, including a possible MSC contribution to tumor stroma and vasculature, MSC-mediated antitumor immune suppression, and the potential malignant transformation of cultured MSCs. Nonetheless, we highlight the novel prospects of MSC-based tumor therapy, which appears to be a promising approach.
A CLINICAL REPORT OF A CASE OF BLASTOMYCOSIS OF THE SKIN FROM ACCIDENTAL INOCULATION.
Authors: NEWTON EVANS
Journal: JAMA (1903)

The subject of this report is a physician, 28 years of age, who has had unusually good health, with no history of specific or venereal disease or tuberculosis or any tuberculosis in the immediate family. On December 4, at an autopsy on a case of systemic blastomycosis, he accidentally inflicted a very slight skin wound with the point of a needle on the palmar surface of the left index finger, just in the fold at the junction of the proximal and middle phalanges. The wound was insignificant and apparently healed. At the end of about one week a very small pustule appeared at this point. This was opened and a small drop of pus removed. It was not noticed again until after several days, when a small pustule again appeared and a small drop of pus was evacuated, as before. The affected area was very small, about the size of a pin head or less. The minute pustule was covered by a very thin layer, probably only the epidermis.
321. Splice-Switching of the Prostate Specific Membrane Antigen (PSMA) in LnCap Prostate Cancer Cells
Authors: Tiffany L. Williams, Ryszard Kole
Journal: Molecular Therapy (2005)

Prostate Specific Membrane Antigen (PSMA) is highly expressed in prostate cancer and the neovasculature of nearly all non-prostate cancers. Its levels may be highest in androgen-independent prostate cancers although the function of PSMA in oncogenesis and/or prostate cancer progression is unknown. The two predominant PSMA splice variants include a membrane-bound full length PSMA and a cytosolic PSMA' which lacks the encoded transmembrane domain located at the end of exon 1. The PSMA:PSMA' mRNA ratio in prostate cancer is substantially higher than that of normal prostate and benign prostate hyperplasia. A lesser known PSMA splice variant lacking exon 6 should produce a truncated and presumably inactive protein. To alter expression of PSMA splice variants we have targeted both the downstream 5' splice site of PSMA's exon 1 and the 5' splice site of exon 6 with two 18-mer antisense 2'-O-methyl splice-switching oligonucleotides (SSOs). The SSO targeted to exon 1 induces the simultaneous downregulation of PSMA and upregulation of PSMA' mRNA in the LnCap prostate cancer cell line, the other decreases mRNA levels of PSMA without increasing PSMA' levels. Splice switching resulted in concomitant changes at the protein level. Both SSO treatments gave led to a decrease in cell proliferation. A marked increase in apoptosis was measured by PARP cleavage assay; the PSMA5'A1 SSO was more efficient at apoptosis induction. Functional studies of PSMA's dipeptidase activity after splice switching are being carried out. This research may link PSMA's ability to hydrolyze poly-glutamyl folate providing readily-transportable mono-glutamyl folate with cell cycle progression concerning purine and methionine metabolism and the one carbon cycle in prostate cancer and tumor neovasculature. Further, a comparison between results from the two SSO treatments will help distinguish which effects are due to changes in PSMA's intracellular localization.
Topical delivery of anti-TNFα siRNA and capsaicin via novel lipid-polymer hybrid nanoparticles efficiently inhibits skin inflammation in vivo
Authors: Pinaki R. Desai, Srujan Marepally, Apurva R. Patel, Chandrashekhar Voshavar, Arabinda Chaudhuri, Mandip Singh
Journal: Journal of Controlled Release (2013)
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder
Authors: Wei Du, Jocelyn F Bautista, Huanghe Yang, Ana Diez-Sampedro, Sun-Ah You, Lejin Wang, Prakash Kotagal, Hans O Lüders, Jingyi Shi, Jianmin Cui, George B Richerson, Qing K Wang
Journal: Nature Genetics (2005)
Hydroxyapatite Orbital Implants Scanning With Technetium-99m MDP
Authors: LEONARD M. NUMEROW, REINHARD KLOIBER, ROBERT J. MITCHELL, CHRISTINE P. MOLNAR, MEL A. ANDERSON
Journal: Clinical Nuclear Medicine (1994)

Porous hydroxyapatite spheres are an ideal prosthetic device for orbital implantation because they are incorporated into soft tissues. Once vascularized, an eye prosthesis can be coupled to the sphere by a peg placed within a central motility hole. This hole should not be drilled while the sphere is avascular because of the risk of infection. Radionuclide scanning with Tc-99m methylene diphosphonate has been used to assess implant vascular ingrowth because radiophosphonate deposition within the sphere parallels vascularization. Using this technique, the authors examined the hydroxyapatite implants of 15 patients 6 months following insertion. Results showed that complete vascularization is best defined by planar imaging rather than SPECT. While the relative intensity of implant activity may be an important feature, uniformity of activity is probably more significant.
Experimental Autoimmune Myocarditis Produced by Adoptive Transfer of Splenocytes After Myocardial Infarction
Authors: Alan Maisel, David Cesario, Stephen Baird, Jalees Rehman, Parviz Haghighi, Steve Carter
Journal: Circulation Research (1998)

One possible mechanism for neurohumoral activation after myocardial infarction may be the generation of an immune response against cardiac self-antigens. We hypothesize that if there is a T cell-mediated reaction to self-antigens, the transfer of splenic lymphocytes from postinfarct rats into syngeneic rats with normal hearts should result in a T cell-mediated autoimmune myocarditis in the healthy syngeneic rats. Rats were killed 6 weeks after coronary ligation. Splenocytes from animals with large and small infarcts were purified from spleens, activated with concanavalin A, and injected in varying doses into normal syngeneic rats. These recipient rats were killed 6 weeks later, and histopathological studies were performed. Our results demonstrate in vivo evidence of lymphocyte-mediated myocardial injury by adoptive transfer of sensitized lymphocytes from rats who developed congestive heart failure after acute myocardial infarction. The amount of infiltrate and necrosis in the recipient rats appeared directly related to the size of the infarct from the donor rats. This suggests that larger infarcts lead to a greater inflammatory response as well as a greater propensity for alteration of cardiac surface antigens or the emergence of previously sequestered antigens. None of the other organs (kidney, liver, lung, or brain) had evidence of infiltrates. Two-dimensional echocardiography did not reveal systolic dysfunction. This study provides direct evidence of autoimmune myocardial injury produced by adoptive transfer of concanavalin A-activated splenocytes after myocardial infarction. We propose that neurohumoral activation early in the postinfarction period triggers a series of specific inflammatory and immunological events that lead to formation of specific clones of T cells. When these are activated and transferred into normal rats, cardiac-specific cellular infiltration occurs, occasionally accompanied by myocardial necrosis. This model should help to further explore the link between neurohumoral activation after myocardial infarction and the subsequent immune alterations that might be associated with the development and/or progression of congestive heart failure. Additionally, this might be a useful model in which to study other immune-mediated cardiomyopathies.
PROCEDURAL AND IN-HOSPITAL OUTCOMES FOR PERCUTANEOUS BALLOON AORTIC VALVULOPLASTY IN PATIENTS WITH SEVERE CALCIFIC AORTIC STENOSIS AND LEFT VENTRICULAR END-DIASTOLIC DIAMETER &lt;4.0 CM
Authors: Pritha P. Gupta, Creighton W. Don, Manoj Kesarwani, Christian Witzke, Roberto J. Cubeddu, Jesus Herrero-Garibi, Eugene Pomerantsev, Angel E. Caldera, David McCarty, Ignacio Inglessis, Igor F. Palacios
Journal: Journal of the American College of Cardiology (2011)
Cellular hyperimmunoreactivity to rubella virus synthetic peptides in chronic rubella associated arthritis.
Authors: L A Mitchell, D Decarie, R Shukin, A J Tingle, D K Ford, M Lacroix, M Zrein
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--Immune recognition of the major structural proteins of rubella virus by peripheral blood mononuclear cells and synovial inflammatory infiltrates of a patient with documented chronic rubella associated arthritis was compared with responses of normal healthy rubella virus immunoreactive subjects to establish if there were unusual response patterns associated with rubella associated arthritis in this subject. METHODS--Synthetic peptides (16-33 amino acids in length) representing selected amino acid sequences of the rubella virus envelope (E1 and E2) and capsid (C) proteins were used in lymphocyte stimulation assays with peripheral blood mononuclear cells or synovial inflammatory infiltrates to determine T lymphocyte recognition of antigenic sites within the synthetic peptides. A rubella virus specific polymerase chain reaction was used to determine the persistence of rubella virus in the patient9s cells. RESULTS--The patient9s peripheral blood mononuclear cells showed abnormally increased lymphoproliferative responses to three E1 synthetic peptides encompassing residues 219-234, 389-411, and 462-481, and one E2 synthetic peptide containing the sequence 50-72, of which the last three were predicted to contain T cell antigenic sites. Although the patient9s peripheral blood mononuclear cells showed positive proliferative responses to C synthetic peptides, these were not unusual. The number of synthetic peptides within the E1, E2, and C panels recognised by the patient9s peripheral blood mononuclear cells was greater than was previously observed in normal healthy subjects. The recognition of synthetic peptides by synovial inflammatory infiltrates was similar to peripheral blood mononuclear cells but the responses measured were lower. The polymerase chain reaction was negative for rubella virus detection in peripheral blood mononuclear cells and synovial inflammatory infiltrates. CONCLUSIONS--Abnormally increased T cell recognition of antigenic sites within rubella virus E1 and E2 proteins observed in this patient with rubella associated arthritis suggests chronic antigenaemia due to persistent rubella virus in tissue sites other than peripheral blood mononuclear cells or synovial inflammatory infiltrates.
ALTERATIONS IN SERUM GLOBULINS DURING THE FORMATION AND RESORPTION OF AMYLOID IN RABBITS
Authors: Goetz W. Richter
Journal: The Journal of Experimental Medicine (1956)

A marked increase of the serum beta globulins was found in rabbits developing amyloidosis as a result of prolonged treatment with ribonucleate administered by subcutaneous injections. Following cessation of treatment the beta globulin levels gradually returned to normal while the gamma globulin levels rose strikingly, the changes being accompanied by a resorption of amyloid from the spleen, and probably also from the kidneys. Electrophoretic studies provided some evidence that the increase in beta globulins which accompanied the development of amyloidosis resulted from the production of a globulin not normally present in rabbit serum. A protein or protein derivative that moved as a beta globulin when subjected to filter paper electrophoresis was excreted in substantial quantities in the urine of several amyloidotic rabbits, along with much smaller quantities of substances moving as albumin, alpha and gamma globulins. Considered as a whole, the findings indicate a causal relationship between the abnormal production of circulating beta globulins and the deposition of amyloid in rabbits treated with ribonucleate. Hence it appears that a beta globulin may be directly involved in the formation of amyloid under the conditions of the experiments here reported.
Risk of congenital malformations in children born after assisted reproduction is higher than previously thought
Authors: S. Mayor
Journal: BMJ (2010)

Children born as a result of assisted reproductive technology (ART) have a higher risk of major congenital malformation than previously thought, show results from a study presented at the annual conference of the European Society of Human Genetics in Gothenburg, Sweden, on 14 June.

The survey of all births between 2003 and 2007 at 33 centres in France registered to provide ART followed up 15 162 children, making it one of the largest studies yet to investigate the effects of fertility treatment.

Questionnaires completed by parents and paediatricians caring for the children showed a prevalence of major congenital malformation of 4.2%, higher than the 2-3% found in previous studies. The results showed that the higher prevalence was due to a higher than expected rate of heart disease and cardiac malformations and malformations of the urogenital system. These were much more common in boys than in girls.

Among the minor …
The Coronary Drug Project
Authors: Broda O. Barnes
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The directors of the Coronary Drug Project (220:996,1972) should be congratulated for including thyroid in an attempt to delay atherosclerosis. For more than 75 years evidence has been mounting that (1) thyroid deficiency promotes both experimental and clinical atherosclerosis, and (2) desiccated thyroid therapy is safe and effective in delaying vascular accidents in patients with advanced arterial damage.<sup>1</sup> By the same token, the directors should be censored for selecting dextrothyroxine sodium, a synthetic preparation of variable activity, which has been listed as contraindicated in coronary disease by the<i>Physicians Desk Reference</i>. Undoubtedly, they were misled by statements that this analogue has less metabolic activity than the natural hormone. Per unit of weight, this is true, but effective dosages of each compound reveal that desiccated thyroid or levothyroxine sodium is superior to dextrothyroxine for the reduction of serum lipids. Best and Duncan<sup>2</sup>found that in the
FATAL HEMORRHAGE FROM ERODED ARTERIA CYSTICA OF THE GALLBLADDER
Authors: RICHARD H. JAFFÉ
Journal: JAMA (1923)

Two acute dangers threaten the life of persons suffering from chronic peptic ulcer: the perforation of the ulcer into the peritoneal cavity, and fatal hemorrhage from eroded blood vessels. Fatal hemorrhages are comparatively rare events in chronic gastric ulcers. Da Costa 1 reports that only 3 to 8 per cent, of persons actually die of hemorrhage. The spread of an ulcer sometimes, though not as often as it is generally considered, causes obstruction of the blood vessels in its base by inflammatory changes in the vessel walls and by thrombosis. In this way larger hemorrhages may be prevented. But, on the other hand, the contractibility of a blood vessel embedded in the firm, cicatrized tissue of the ulcer may be impaired and so increase the possibility of abundant bleeding from smaller vessels.  My own experience is based on fifty-five cases in which the patients have died from peptic ulcer of
Health organisations are urged to end investment in fossil fuels
Authors: J. Wise
Journal: BMJ (2015)

Health sector organisations should end their investment in fossil fuel companies because it is immoral and inconsistent to continue to invest in industries known to harm health, a new report from a group of health organisations and charities has argued.1

The report from the Climate and Health Council, the Centre for Sustainable Healthcare, Medact (an organisation for health professionals that works in such areas as climate change and disarmament), Healthy Planet UK, and the students’ organisation Medsin said that air pollution from coal, oil, and gas …
Clinical and Immunological Effects of Aspirin Desensitization in Patients with Aspirin Exacerbated Respiratory Diseases; A Randomized, Double Blind, Placebo Controlled Trial
Authors: Hossein Esmaeilzadeh, Mohammad Nabavi, Saba Arshi, Mohammad Hassan Bemanian, Morteza Fallahpour, Zahra Aryan
Journal: Journal of Allergy and Clinical Immunology (2015)
Philippines passes antismoking laws
Authors: C. Wallerstein
Journal: BMJ (1998)

Antismoking laws passed last week in the Philippines after a five year struggle are “too little, too late” to stub out the country's addiction to cigarettes, health officials have warned. The country's new legislation leaves Cambodia as the only country in the Western Pacific region still without any antismoking law.

Once ratified by the president, Fidel Ramos, the new bill will …
The effects of oral hydralazine on right ventricular end-diastolic pressure in patients with right ventricular failure.
Authors: L J Rubin, F Handel, R H Peter
Journal: Circulation (1982)

Hydralazine reduces pulmonary vascular resistance in patients with primary and secondary pulmonary hypertension, but the effects on right ventricular function of a change in resistance without a reduction in pulmonary arterial pressure are not known. We evaluated the hemodynamic effects of hydralazine, 50 mg, administered orally every 6 hours for 48 hours in 14 patients with right ventricular failure and pulmonary hypertension resulting from various causes. Hydralazine reduced mean right ventricular end-diastolic pressure from 17.4 +/- 5.6 to 11.6 +/- 5.3 mm Hg (p less than 0.001) and increased cardiac output and stroke volume by more than 40%. In nine patients who had no change in mean pulmonary arterial pressure after hydralazine, total pulmonary resistance decreased from 15.9 +/- 6.0 to 10.6 +/- 4.3 (p less than 0.001) and cardiac index increased from 2.07 +/- 0.51 to 2.97 +/- 0.91 (p less than 0.005). There was a close correlation between the reductions in total pulmonary resistance and right ventricular end-diastolic pressure (r = 0.73)). These data suggest that hydralazine can increase cardiac output and reduce right ventricular end-diastolic pressure even when pulmonary arterial pressure remains unchanged.
Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers
Authors: P Clavien, C A Camargo, R Gorczynski, M K Washington, G A Levy, B Langer, P D Greig
Journal: Hepatology (1996)

Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes (PMN) may play a critical role in ischemia– reperfusion injury. To evaluate whether similar mechanisms are operative in human liver, six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were randomized for utilization of hepatic vascular exclusion (HVE) as a model of ischemia–reperfusion injury. Portal and systemic levels of acute reactant cytokines (interleukin 6 [IL–6], interleukin 1 [IL–1], tumor necrosis factor α [TNF–α]) and neutrophil adhesion in serial liver biopsy specimens were studied. Correlations among mediators, leukocyte adhesion, and markers of liver injury were also evaluated. Hepatic vascular exclusion resulted in substantial and reproducible changes in portal and arterial IL–6 levels in both cirrhotic and noncirrhotic patients. Portal and systemic cytokine levels were comparable in most instances, whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients. Negative correlations were found between IL–6 levels at the time of reperfusion and later TNF–α levels. IL–6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications. Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients. In cirrhotic patients, the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury. This study in humans shows that acute reactant cytokines are released during liver ischemia and, interestingly, that IL–6 levels strongly correlate with clinical and laboratory measures of injury. Further studies to evaluate possible causal relationship with hepatic injury are warranted, with emphasis on the role of IL–6 and PMN adhesion.