tbuckley/cabot-search huggingface dataset:
Targeted Inhibition of Prostate Cancer Metastases with an RNA Aptamer to Prostate-specific Membrane Antigen
Authors: Justin P Dassie, Luiza I Hernandez, Gregory S Thomas, Matthew E Long, William M Rockey, Craig A Howell, Yani Chen, Frank J Hernandez, Xiu Ying Liu, Mary E Wilson, Lee-Ann Allen, Daniel A Vaena, David K Meyerholz, Paloma H Giangrande
Journal: Molecular Therapy (2014)

Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed to effectively treat some cancers. However, many cancers such as metastatic prostate cancer (PC) have yet to be treated with current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions as a smart drug for PC by inhibiting the enzymatic activity of prostate-specific membrane antigen (PSMA). Treatment of PC cells with A9g results in reduced cell migration/invasion in culture and metastatic disease in vivo. Importantly, A9g is safe in vivo and is not immunogenic in human cells. Pharmacokinetic and biodistribution studies in mice confirm target specificity and absence of non-specific on/off-target effects. In conclusion, these studies provide new and important insights into the role of PSMA in driving carcinogenesis and demonstrate critical endpoints for the translation of a novel RNA smart drug for advanced stage PC.
The velocity profile in the canine ascending aorta and its effects on the accuracy of pulsed Doppler determinations of mean blood velocity
Authors: C. L LUCAS, B. A KEAGY, H. S HSIAO, T. A JOHNSON, G. W HENRY, B. R WILCOX
Journal: Cardiovascular Research (1984)

The velocity profile in the ascending aorta, which has been variously reported as parabolic, skewed or flat, was measured using an intraluminal probe equipped with a miniature piezoelectric crystal activated by a 20 MHz pulsed Doppler with a 1 mm3 sample volume size. Phasic velocities, determined via spectral analyses, were obtained at 2 mm intervals across the aortic lumen of anaesthetised open-chest dogs by sequentially moving the crystal between posterior and anterior walls, maintaining the ultrasound beam parallel to the flow axis. Range-gating allowed data acquisition 3.5 mm proximal to the crystal, thus eliminating probe induced turbulence. Time and spatial distributions of velocities over the cross-section were computed. Expected errors in vessel mean velocity estimates based on point measurements were calculated. Analysis of phasic waveforms showed increased posterior velocities during systole but third order regression analysis of normalised point mean velocities across the lumen showed the best fit was a statistically flat straight line. Centreline referenced analyses indicated the expected difference between point mean velocity and vessel mean velocity was maximal (19.3 +/- 10.1%) 4 mm toward the posterior wall and minimal (4.7 +/- 9.1%) 5 mm toward the anterior wall. Anterior posterior wall referenced analyses indicated the most reliable position for estimating vessel mean velocity from point mean velocity along this axis was 5 mm from the anterior wall.
Gene Expression Profiling of Progressive Papillary Noninvasive Carcinomas of the Urinary Bladder
Authors: Peter J. Wild, Alexander Herr, Christoph Wissmann, Robert Stoehr, Andre Rosenthal, Dirk Zaak, Ronald Simon, Ruth Knuechel, Christian Pilarsky, Arndt Hartmann
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of the present study was to define gene expression profiles of noninvasive and invasive bladder cancer, to identify potential therapeutic or screening targets in bladder cancer, and to define genetic changes relevant for tumor progression of recurrent papillary bladder cancer (pTa). Experimental Design: Overall, 67 bladder neoplasms (46 pTa, 3 pTis, 10 pT1, and 8 pT2) and eight normal bladder specimens were investigated by a combination of laser microdissection and gene expression profiling. Eight of 16 patients with recurrent noninvasive papillary bladder tumors developed carcinoma in situ (pTis) or invasive bladder cancer (≥pT1G2) in the course of time. RNA expression results of the putative progression marker cathepsin E (CTSE) were confirmed by immunohistochemistry using high-throughput tissue microarray analysis (n = 776). Univariate analysis of factors regarding overall survival, progression-free survival, and recurrence-free survival in patients with urothelial bladder cancer was done. Results: Hierarchical cluster analyses revealed no differences between pTaG1 and pTaG2 tumors. However, distinct groups of invasive cancers with different gene expression profiles in papillary and solid tumors were found. Progression-associated gene profiles could be defined (e.g., FABP4 and CTSE) and were already present in the preceding noninvasive papillary tumors. CTSE expression (P = 0.003) and a high Ki-67 labeling index of at least 5% (P = 0.01) were the only factors that correlated significantly with progression-free survival of pTa tumors in our gene expression approach. Conclusions: Gene expression profiling revealed novel genes with potential clinical utility to select patients that are more likely to develop aggressive disease.
Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study
Authors: E. Lahat
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. <b>Design:</b> Prospective randomised study. <b>Setting:</b> Paediatric emergency department in a general hospital. <b>Subjects:</b> 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. <b>Interventions:</b> Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). <b>Main outcome measures:</b> Time from arrival at hospital to starting treatment and cessation of seizures. <b>Results:</b> Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7.9 to 8.3). No significant side effects were observed in either group. <b>Conclusion:</b> Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home.
Dead children from problem families
Authors: P. R Hay
Journal: BMJ (1983)

Renal artery thrombosis caused by antihypertensive treatment SIR,-The letter by Dr Lawrence E Ramsay (1 January, p 62) contained a somewhat misleading speculation based on a presentation of mine.The lctter suggested that thrombosis of the renal artery during medical therapy of renovascular hypertension with captopril might be more common than information available suggests.In the 269 patients with renovascular hypertension I reviewed, as cited by Dr Ramsay, in fact none developed thrombosis of the renal artery.The follow up interval was up to two years.As pointed out by Oelkers,' such a calamity can occur, but it must be uncommon.
Agricultural lung diseases.
Authors: S R Kirkhorn, V F Garry
Journal: Environmental Health Perspectives (2000)

Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards. Animal confinement operations with increasing animal density, particularly swine confinement, have contributed significantly to increased intensity and duration of exposure to indoor air toxins. Ongoing research has implicated bacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper and lower airway inflammation and as immunologic agents in both grain and animal production. Animal confinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additional sources of respiratory irritants. It has become evident that a significant percentage of agricultural workers have clinical symptoms associated with long-term exposure to organic dusts and animal confinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis, organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and asthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focus upon the emerging respiratory health issues in a changing agricultural economic and technologic environment. Environmental and occupational hazards and exposures will be emphasized rather than clinical diagnosis and treatment. Methods of prevention, from both engineering controls and personal respiratory perspectives, are also addressed.
Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a ligand for attachment of group A Streptococcus to CD44 on human keratinocytes.
Authors: H M Schrager, S Albertí, C Cywes, G J Dougherty, M R Wessels
Journal: Journal of Clinical Investigation (1998)

We used wild-type and isogenic mutant strains of group A Streptococcus (GAS) that expressed M protein, capsule, or both to study the function of M protein and the hyaluronic acid capsular polysaccharide in attachment of GAS to human keratinocytes. Types 6 and 24, but not type 18, M protein were found to mediate attachment of GAS to soft palate or skin keratinocytes, but this interaction was prevented by the hyaluronic acid capsule on highly encapsulated, or mucoid, strains. Monoclonal antibody to CD44, the principal hyaluronic acid-binding receptor on keratinocytes, inhibited attachment of both highly encapsulated and poorly encapsulated wild type strains of GAS, but not the attachment of acapsular mutants. Transfection of K562 cells with cDNA encoding human CD44 conferred the capacity to bind each of six wild-type strains of GAS, but not to bind acapsular mutants. Because, in contrast to other potential adhesins, the group A streptococcal capsule is both highly conserved and surface-exposed, it may serve as a universal adhesin for attachment of diverse strains of GAS to keratinocytes of the pharyngeal mucosa and the skin.
SERUM IMMUNOGLOBULINS IN PSORIASIS BEFORE AND AFTER ULTRA VIOLET LIGHT THERAPY
Authors: A. VARELZIDIS, A. THEODORIDIS
Journal: British Journal of Dermatology (2006)

SUMMARY.— A significant increase of the mean IgA globulin value was noted in 105 patients with ordinary psoriasis whereas the mean IgG and IgM globulin levels remained normal. Thirty-two of these patients received u.v. light therapy which resulted in resolution of the skin lesions. At this stage the IgA levels fell to the normal range. The possibility of the skin eruption influencing the IgA serum levels is discussed.
Laboratory Procedures and Therapy in Coronary Thrombosis
Authors: Paul W. Boyles
Journal: JAMA (1961)

Recently interest has been expressed in the possibility of reducing the damage to the myocardium after an infarction by the use of fibrinolytic therapy. At this time activator appears to be the ideal thrombolytic agent. Data obtained from 3 patients with acute myocardial infarction are presented. All were treated with fibrinolytic therapy. A rise in the level of fibrinolytic activity was manifested by changes in several components of the clotting system and by increased areas of lysis on heated fibrin plates. Other evidence of improvement included a rapid fall in serum transaminase values.
ISOPRAL AND CHLORAL HYDRATE.
Authors: E. IMPENS
Journal: JAMA (1907)

In an exhaustive paper which I published in 1903<sup>1</sup>I was the first to draw attention to the hypnotic properties of trichlorisopropylic alcohol, or isopral. I have made numerous experiments which show that the drug acts more effectively than chloral, while at the same time the range of the dose is greater. The results of my experiments have been confirmed by Dr. Schmitt, professor of therapeutics in the University of Nancy. He says:<sup>2</sup>"My experiments have led to results which correspond closely with those obtained by Impens.... " With reference to its rapid action—one of the characteristic properties of isopral—he expresses himself in the following terms: "The rapidity of absorption is demonstrated by the fact that the effects of the drug appear very quickly, from two to three minutes sufficing for an intraperitoneal injection, and when given by the mouth five or six minutes being sufficient with slightly larger
Burning-Feet Syndrome: Case Due to Malabsorption and Responding to Riboflavine
Authors: C. S. Lai, G. A. Ransome
Journal: BMJ (1970)

A woman with the burning-feet syndrome was found on investigation to have malabsorption. The syndrome responded rapidly to intramuscular injections of 6 mg. of riboflavine daily. It is suggested that deficiency of this substance, due to malabsorption and aggravated by a defective diet and repeated pregnancies, was responsible for the syndrome in this case.
Treatment of Heat Stroke With Dantrolene
Authors: James S. Lydiatt
Journal: JAMA (1981)

<h3>To the Editor.—</h3> A number of similarities between malignant hyperthermia and heat stroke syndrome exist.<sup>1,2</sup>Disorders of electrolyte balance, renal function, bleeding diathesis, plasma enzyme levels, as well as temperature control are common in both syndromes. We recently treated a case of extreme heat stroke syndrome with intravenous (IV) dantrolene sodium, currently the accepted treatment of choice for malignant hyperthermia,<sup>2,3</sup>with excellent results. The following is a report on that experience. <h3>Report of a Case.—</h3> A 41-year-old 80-kg man was brought to the emergency room with a rectal temperature greater than 42 °C after working in a hot environment before collapsing. On physical examination, the patient's skin was blotchy, hot, and dry. The respiratory rate was 40 to 45/min, and brachial artery blood pressure was 105/50 mm Hg. Blood was drawn for laboratory studies (Table) followed by rapid intravascular volume expansion (4,000 mL of lactated Ringer's solution over two
PROLIFERATIVE ACTIVITY OF THE LYMPHATIC TISSUES OF RATS AS STUDIED WITH TRITIUM-LABELED THYMIDINE
Authors: Charles G. Craddock, George S. Nakai, Hajime Fukuta, Louise M. Vanslager
Journal: The Journal of Experimental Medicine (1964)

Cytokinetic data are presented, employing quantitation of H3DNA in the lymphatic tissues of normal rats serially sacrificed after H3Tdr administration. A marked difference in the patterns of initial labeling and label loss was observed between the thymus and peripheral lymphatic tissue. The data are compatible with other indications of rapid cell renewal in the thymus. There is suppression of initial uptake of H3Tdr into the DNA of each large lymphocytic progenitor cell in the thymus, apparently because of a feedback of thymidine containing material from small lymphocytes in the thymus. Depletion of the thymus of small cells, as by operative stress or whole body x-ray, leads to a marked increase in the uptake of H3Tdr into the DNA of large thymocytes. This finding, which is in agreement with the previous findings of Sugino et al. (33, 34) suggesting transfer of thymine nucleotides from small thymus lymphocytes to precursor cells, may or may not be related to the apparent transfer of DNA label between thymic cells. The evidence for the latter consists of the curvilinear dilution of the DNA label in the thymus proliferating cell population and the relationship between the rate of DNA label dilution in large cells and the H3DNA in the small cells in the thymus. After the DNA label in progenitor cells in the thymus and lymph nodes has entered the small cell population, the subsequent dilution of grains in these dividing cells follows the same slope as the loss of radioactivity from the entire lymph node. There is a long retention of some H3DNA label in the dividing lymph node cell population. This suggests that the loss of radioactivity from the dividing cells and from the small cell population as a whole occurs equally. This pattern prevails regardless of whether the percentage of large and small cells is altered experimentally. These findings can be explained by an interchange of the DNA nuclear label between small lymphocytes and large lymphocytes. This could occur by some process such as phagocytosis or pinocytosis, or by transformation of the small lymphocyte into a large, dividing cell. The data fit best with the latter possibility. All or any of these mechanisms would lead to an equilibration of the DNA label between large and small cells. This finding prevents the assignment of a finite life span to lymphocytes on the basis of DNA labeling kinetics. Nevertheless, there appear to be at least two different types of lymphocytes. One, the "thymus-type" lymphocyte, is found in the thymus cortex, bone marrow and germinal centers of lymphoid follicles. The other type, found abundantly in the widespread peripheral lymphatic tissue, shows a very prolonged retention of DNA label and is believed to be the recirculating, "immunologically committed" cells described by others. These cells do not appear to enter the thymus cortex.
Electrical potential difference between basal cell carcinoma, benign inflammatory lesions and normal tissue
Authors: R. E. WOODROUGH, G. CANTI, B. W. WATSON
Journal: British Journal of Dermatology (2006)

Measurement of the resting electrical potential difference on the surface of the skin has been made on patients with suspected basal cell carcinoma. It was demonstrated that in fifty-five lesions from forty-nine patients, the mean electrical potential difference from thirty-six basal cell carcinomas was found to be +II mV, from nineteen benign inflammatory lesions it was found to be +2 mV, and from normal skin, contra-lateral to the lesions in both groups, it was found to be -3 mV. All the measurements are relative to a reference electrode placed under the tongue. The difference between the means for the inflammatory lesions and for the normal skin was found to be statistically insignificant, but the difference between these means and the mean potential difference for the basal cell carcinoma group was found to be highly significant (P less than 0-1%). However, the populations overlap to such an extent as to make the measurement, in its present form, useless as a diagnostic technique.
The absorption of carbenoxolone administered orally as a positioned-release capsule
Authors: W. E. Lindup, D. V. Parke, D. Colin-Jones
Journal: Gut (1970)

Carbenoxolone administered in a position-released capsule is as readily absorbed as when administered by tablets, although not necessarily from the same site. It is therefore reasonable to suppose that the same systemic pharmacological actions will be observed with either preparation.
DIAGNOSIS IN DISEASES OF INFANTS AND CHILDREN.
Authors: C. G. SLAGLE
Journal: JAMA (1896)

Candor compels me to admit that upon more exten-extensive investigation than I have hitherto made, I found that much more had been done and said, and better done and said, upon this subject than I was previously aware of, but found the subject matter widely scattered throughout voluminous medical literature.  Inasmuch as we are compelled to study and practice every department of medicine before we can become at all skillful in pediatrics, it would be most unsatisfactory to attempt to discuss diagnosis in this special department without first reviewing the subject of diagnosis in general, as it applies more or less to all ages and conditions of life. For we must and do endeavor to instruct our students, that pediatrics can never become a specialty, as that term can only and properly be applied to thestudyandtreatmentof diseases of special organs or parts of the body, while
P918 miRNA BASED SCORE FOR THE CORRECT DIAGNOSIS OF REJECTION VS RECURRENT HEPATITIS C IN LIVER TRANSPLANTED PATIENTS
Authors: P. Fytili, T. Krech, S. Zell, L. Bockmeyer, D. Jonigk, F. Lehner, H. Kreipe, M.P. Manns, J.U. Becker, H. Wedemeyer
Journal: Journal of Hepatology (2014)
Towards the therapeutic use of vascular smooth muscle progenitor cells
Authors: T. Merkulova-Rainon, D. Broqueres-You, N. Kubis, J.-S. Silvestre, B. I. Levy
Journal: Cardiovascular Research (2012)

Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.
Large Artery Involvement in Giant Cell (Temporal) Arteritis
Authors: ROBERT G. KLEIN
Journal: Annals of Internal Medicine (1975)

Of 248 patients with giant cell arteritis, 34 had evidence that the disease affected the aorta or its major branches. Symptoms suggestive of large artery involvement were intermittent claudication of an extremity, paresthesias, and Raynaud's phenomenon. Physical findings included absent or decreased large artery pulses and bruits over large arteries. Four patients presented with decreased upper extremity pulses as the initial manifestation of their arteritis. Nine other patients under treatment for temporal arteritis or polymyalgia rheumatica first developed evidence of large artery involvement as corticosteroid therapy was tapered or discontinued. Angiography, performed in 10 patients, was helpful in indicating arteritis rather than atherosclerosis as the cause of large artery disease. Three patients died with aortic rupture, and, at autopsy, widespread giant cell arteritis was found. However, when corticosteroids were given in adequate doses, the response was favorable in most patients; intermittent claudication decreased and the pulses improved.