tbuckley/cabot-search huggingface dataset:
Intramuscular Administration of Recombinant Adeno-Associated Virus 2 α-1 Antitrypsin (rAAV-SERPINA1) Vectors in a Nonhuman Primate Model: Safety and Immunologic Aspects
Authors: Sihong Song, Marda Scott-Jorgensen, Jianming Wang, Amy Poirier, James Crawford, Martha Campbell-Thompson, Terence R. Flotte
Journal: Molecular Therapy (2002)

We performed a series of studies in baboons to evaluate the safety of intramuscular administration of rAAV vector expressing the α-1 antitrypsin (AAT) gene (SERPINA1) in a nonhuman primate model. Initial experiments performed with an rAAV vector expressing the human SERPINA1 gene (at doses of up to 5×1012 vector genomes/kg) resulted in the generation of anti-human AAT antibodies, which correlated with a loss of detectable transgene expression. Subsequent studies made use of the baboon SERPINA1 gene tagged with a short (10-amino-acid) c-myc tag. When animals were sacrificed, 4 months after vector injection, transduced myofibers showed efficient transgene expression without detectable humoral immune responses. Mild inflammation was observed in and near the sites of injection in some vector- and saline-injected animals, but serum creatine kinase (CK) values were normal in nearly every case. Real-time PCR was also performed 4 months after injection on gonadal tissue to evaluate the risk of germline transmission. No vector sequences were detected in the gonadal tissues from these animals. These studies indicate that the risks of immune reaction and germline transmission after intramuscular injection of rAAV-SERPINA1 in nonhuman primates are relatively low within the range of vector doses studied. We performed a series of studies in baboons to evaluate the safety of intramuscular administration of rAAV vector expressing the α-1 antitrypsin (AAT) gene (SERPINA1) in a nonhuman primate model. Initial experiments performed with an rAAV vector expressing the human SERPINA1 gene (at doses of up to 5×1012 vector genomes/kg) resulted in the generation of anti-human AAT antibodies, which correlated with a loss of detectable transgene expression. Subsequent studies made use of the baboon SERPINA1 gene tagged with a short (10-amino-acid) c-myc tag. When animals were sacrificed, 4 months after vector injection, transduced myofibers showed efficient transgene expression without detectable humoral immune responses. Mild inflammation was observed in and near the sites of injection in some vector- and saline-injected animals, but serum creatine kinase (CK) values were normal in nearly every case. Real-time PCR was also performed 4 months after injection on gonadal tissue to evaluate the risk of germline transmission. No vector sequences were detected in the gonadal tissues from these animals. These studies indicate that the risks of immune reaction and germline transmission after intramuscular injection of rAAV-SERPINA1 in nonhuman primates are relatively low within the range of vector doses studied.
Clinical and Histologic Determinants of Mortality for Patients With Barrett’s Esophagus–Related T1 Esophageal Adenocarcinoma
Authors: Cadman L. Leggett, Jason T. Lewis, Tsung Teh Wu, Cathy D. Schleck, Alan R. Zinsmeister, Kelly T. Dunagan, Lori S. Lutzke, Kenneth K. Wang, Prasad G. Iyer
Journal: Clinical Gastroenterology and Hepatology (2014)
Immunoreactive β-Endorphin and Adrenocorticotropin in Human Cerebrospinal Fluid
Authors: Kazuwa Nakao, Shogo Oki, Issey Tanaka, Kazuko Horii, Yoshikatsu Nakai, Tomoo Furui, Masanori Fukushima, Akio Kuwayama, Naoki Kageyama, Hiroo Imura
Journal: Journal of Clinical Investigation (1980)

To elucidate the significance of β-endorphin in human cerebrospinal fluid (CSF), CSF levels of β-endorphin-like immunoreactivity (β-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF β-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2±1.3 and 14.6±0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushing's disease (n = 7) had significantly lower CSF β-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF β-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05).
Sheila Anne Robertson (née Martyn)
Authors: Struan Robertson
Journal: BMJ (2004)

A pioneer of hypotensive anaesthesiaHale Enderby is best known for his pioneering work in hypotensive anaesthesia.This is the technique of lowering blood pressure during surgery, making operations safer and more rapid, and enabling more complicated surgery while controlling blood loss from the patient.In 1948-9 the pharmacologists Paton and Zaimis first described a range of new drugs, the methonium compounds, some of which could lower blood pressure.Hale Enderby saw that this fall in blood pressure could be used to lessen bleeding during surgery-the snag was measuring the low blood pressures.Early methods of measurement relied on using a mercury column, but the Korotkov sounds become inaudible below 60 mm Hg systolic.The pulse also becomes impalpable at that pressure.However, this was the level of blood pressure needed to reduce bleeding significantly.Hale Enderby introduced into anaesthesia the oscillometer, an older and largely forgotten method of blood pressure measurement but one that proved capable of measuring accurately these low pressures.He was also responsible for introducing the "anti-trendelenburg" or head-up tilt of the operating table to assist in the lowering of blood pressure.George Edward Hale Enderby was born in Boston, Lincolnshire.At the start of the second world war he joined the emergency medical service after being turned down for active military service because of a duodenal ulcer.He worked initially at Guy's Hospital and then at Pembury Hospital, Kent, to which many of the Guy's facilities were moved after the hospital was bombed at the start of the war.It was there that he was asked to move into anaesthesia.He organised most of his training himself by reading and visiting notable anaesthetists of the day.
Utilization Review of Psychiatric Inpatient Care
Authors: ALEX RICHMAN, HENRY PINSKER
Journal: American Journal of Psychiatry (1973)

The authors describe a utilization review procedure for inpatient care involving the statement of therapeutic goals, predictions about the time required to reach these goals, and the evaluation of care in terms of whether the goals have been met. The effectiveness of the procedure is suggested by the decrease in the number of patients with prolonged stays and the increase in the number of patients cared for. This has been accomplished with no decline in the quality of service.
Abstract 4156: Interaction between the <i>rabphillin-3A-like</i> gene and phosphorylation of mammalian target of rapamycin (<i>mTOR</i>) in colorectal cancer
Authors: Venkat R. Katkoori, Sandeep Choudhary, Abraham R. Butler, Chandrakumar Shanmugam, Liselle L. Bovell, Temesgen Samuel, Mohammed Athar, William E. Grizzle, Upender Manne
Journal: Cancer Research (2012)

Abstract Background: Recently, we demonstrated that, for colorectal carcinomas (CRCs), genetic alterations in the rabphillin-3A-like (RPH3AL) gene are associated with aggressive tumor phenotypes and poor patient survival. The mammalian target of rapamycin (mTOR) pathway regulates tumor growth by integrating diverse signals of growth factors, nutrients, and energy sufficiency. Therefore, we determined the effects of wild-type (w+) and mutated (67w-, 175w-, 290w-) RPH3AL on the mTOR signaling pathway in CRC tissues and in a line of colon cancer cells (LoVo). Materials and Methods: Ninety five prospectively collected, frozen CRC tissues and their matching control tissues were analyzed for the mutational status of RPH3AL using the cDNA polymerase chain reaction and direct sequencing. Expression constructs of RPH3AL w+ and the mutant variants were developed using eukaryotic expression vectors. LoVo cells were stably transfected with the w+ and w- forms of RPH3AL. Western blot analyses were performed on lysates of CRC tissues and LoVo cells to assess expression of p53, p27, and PCNA and proteins in the mTOR pathway. Results: Mutational analysis of RPH3AL detected four missense mutations: at codon 67 (Val &amp;gt; Met) in 2 CRCs, at codon 175 (Pro &amp;gt; Ser) in 1 CRC, and at codon 290 (Arg &amp;gt; Lys) in 1 CRC. Western blot analyses demonstrated that over-expression of wt RPH3AL in LoVo cells or CRC tissues with wt RPH3AL led to decreases in total mTOR and to phosphorylation of Rictor p-mTOR (S2481), Raptor p-mTOR (S2448), p70S6K1, and p70S6K. In contrast, in CRC tissues or LoVo cells with over-expression of mutant forms of RPH3AL, there were higher levels of total mTOR and greater phosphorylation of the Rictor, raptor, P70S6K1 and p70S6K. Additionally, CRC w+ RPH3AL and LoVo cells that over-expressed w+ RPH3AL demonstrated higher levels of p27, and lower levels of PCNA, and p53. In contrast, the CRC tissues or LoVo cells with over-expression of RPH3AL mutants exhibited lower levels of p27 and higher levels of PCNA. Conclusion: The results demonstrate that the RPH3AL gene has a tumor-suppressing effect involving changes in the mTOR pathway and suggest that these changes inhibit progression of CRCs. This work was supported by grants from the NCI/NIH (2U54-CA118948-06, R01-CA98932, and R03-CA139629). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4156. doi:1538-7445.AM2012-4156
THE RELATIVE MERITS OF TRANYLCYPROMINE ALONE AND TRANYLCYPROMINE IN COMBINATION WITH TRIFLUOPERAZINE IN THE TREATMENT OF PATIENTS WITH SEVERE AGITATED DEPRESSIONS
Authors: STANLEY LESSE
Journal: American Journal of Psychiatry (1962)

Tranylcypromine in combination with trifluoperazine is of very significant benefit in severely agitated, depressed patients. Tranylcypromine alone is of little significant worth in this type of patient.
(9) Acanthosis nigricans with carcinoma of the stomach
Authors: A. Navaratnam, G.A. Hodgson
Journal: British Journal of Dermatology (1973)

Journal Article (9) Acanthosis nigricans with carcinoma of the stomach Get access A. Navaratnam, A. Navaratnam Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar G.A. Hodgson G.A. Hodgson Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue s9, 1 July 1973, Pages 46–50, https://doi.org/10.1111/j.1365-2133.1973.tb03442.x Published: 01 July 1973
The Efficacy and Safety of Cholestyramine Therapy in Hyperlipidemic Patients.
Authors: H. Richard Casdorph
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971The Efficacy and Safety of Cholestyramine Therapy in Hyperlipidemic Patients.H. Richard Casdorph, M.D., Ph.D., F.A.C.P.H. Richard Casdorph, M.D., Ph.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-818_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptLongitudinal studies on the hypolipidemic effect of cholestyramine have been conducted on 103 hyperlipidemic patients (representing 1,728 patient-months of therapy). Cholestyramine was administered in doses of 12 to 24 g/day. Various lipid values have been studied. Serum cholesterol was measured by Auto-Analyzer. The average cholesterol for the 103 patients was reduced from 317 to 199.7 mg/100 ml, an average reduction of 117.3 mg/100 ml (-19.8%). Percent reduction by type was 54 type II patients, -19.8%; 1 type III patient, -21%; 33 type IV patients, -20.2%; and 15 untyped hypercholesteremic patients, -21.5%. No significant change in the serum triglycerides was observed.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Long Beach, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug-Induced Acute PancreatitisAdverse Effects of Hypolipidaemic DrugsDrug-induced pancreatitis: A critical reviewPotential Drug Interactions— Fact or Fallacy?4 Antihyperlipidaemic AgentsEffects of colestipol hydrochloride (U-26,597A) on serum and fecal lipids in dogs 1 May 1971Volume 74, Issue 5Page: 818-818KeywordsCholesterolLipidsLongitudinal studiesSafetySerum triglycerides Issue Published: 1 May 1971 PDF downloadLoading ...
Analysis of results of catheter tip cultures in open-heart surgery patients.
Authors: R Freeman, B King
Journal: Thorax (1975)

A statistical analysis of 628 consecutive catheter tip cultures is presented. All were from patients undergoing open-heart surgery. The previously noted effects of early removal are shown to be significant. The possible effects of stasis, flushing, handling, and place of insertion are discussed. The unresolved significance of isolations of aerobic sporing bacilli is noted, and a decreasing incidence of postoperative infective endocarditis in the same group of patients is an encouraging sign.
Magnetic measurement of S-T and T-Q segment shifts in humans. Part II: Exercise-induced S-T segment depression.
Authors: D Cohen, P Savard, R D Rifkin, E Lepeschkin, W E Strauss
Journal: Circulation Research (1983)

The direct-current magnetocardiogram, which shows the T-Q (baseline) shift, is used to clarify the cause of S-T depression induced by stress testing in the human heart. Measurements are made of the amount of baseline shift associated with the S-T depression. Results are presented of a well-documented patient, with typical coronary artery disease, undergoing a two-step exercise test. Before exercise, there was no S-T or baseline shift. During exercise, the S-T segment became depressed and the baseline segment was simultaneously elevated, at about 70% of the S-T amplitude. After termination of exercise, the baseline elevation disappeared somewhat more rapidly than the S-T depression. These results were consistent in repeated tests of this patient. Because the baseline shift is a reflection of an injury current, these results confirm the belief that exercise-induced S-T depression is mostly due to an injury current which is interrupted during the S-T interval. The baseline shift seen here is the first non-invasive measurement of an injury current in the human heart, and its presence and time-course generally agree with measurements in the animal heart. This work also confirms that the direct-current magnetocardiogram, although not practical for clinical purposes, is useful as a research tool.
DEXTER DVT VERSUS SINISTER DVT: WHICH IS THE MORE SINISTER?
Authors: Behnood Bikdeli, Babak Sharif-Kashani, Ehsan Chitsaz, Bavand Bikdeli, Mandana Chitsazan, Saeed Kermani-Randjbar, Neda Behzadnia, Shahram Yazdani, Leila Saliminejad, Mohammad-Reza Masjedi
Journal: Journal of the American College of Cardiology (2011)
Treatment of Haemochromatosis by Repeated Venesection
Authors: D. A. Davey, A. W. H. Foxell, T. A. Kemp
Journal: BMJ (1954)

MEDICAL JOURNALIsoniazid-resistant organisms were isolated at some time from about one-half the patients in the T1H and the T2H groups and from about two-thirds in the H group; but in the T5H group resistant organisms were obtained from only 3 out of the 10 patients, and in none before the end of the fifth month of treatment.No oxytetracycline resistance was encountered.There was no important difference between the four treatment groups as regards clinical or radiological pro- gress over the first three months of treatment.Treatment of one patient in the T5H group had to be stopped after one week because of intractable diarrhoea and vomiting.Apart from this, the toxic effects attributable to oxytetracycline were slight.Owing to the considerable incidence of isoniazid resistance in the T1H and T2H groups, neither method can be recommended as satisfactory in treatment.On the other hand, oxytetracycline in a dosage of 5 g.daily would seem to be of probable value in delaying or pre- venting the onset of isoniazid resistance, but this com- bination is likely to be less effective than that of strepto- mycin or P.A.S. with isoniazid; it is also very expensive.
A lymphocyte homing receptor (L-selectin) mediates the in vitro attachment of lymphocytes to myelinated tracts of the central nervous system.
Authors: K Huang, J S Geoffroy, M S Singer, S D Rosen
Journal: Journal of Clinical Investigation (1991)

Lymphocytes enter lymph nodes by first adhering to high endothelial venules, an adhesive event mediated by a lectinlike lymphocyte receptor (L-selectin). Previously, it was shown with an in vitro assay that lymphocytes preferentially adhere to myelin-rich regions in brain sections. Here, using a recombinant form of L-selectin as an immunohistochemical reagent, we demonstrate potential ligands for L-selectin in myelinated regions of the central but not the peripheral nervous system. Using several antibodies and phorbol ester downmodulation of the receptor, we establish that L-selectin on human lymphocytes has a primary involvement in lymphocyte adherence to the myelinated regions. On mouse lymphocytes, the contribution of L-selectin appears to be partial. These findings raise the possibility that leukocyte targeting to myelin-rich regions, via a L-selectin dependent mechanism, may be a factor in the pathogenesis of certain central nervous system demyelinating diseases.
WHAT NUMBER OF MORPHOLOGICAL TYPES OF VENTRICULAR PREMATURE BEATS PREDICTS POOR PROGNOSIS IN SUBJECTS WITH NON-ISCHEMIC CARDIOMYOPATHY?
Authors: Koya Ozawa, Nobusada Funabashi, Hiroyuki Takaoka, Masae Uehara, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2014)
Steroids in Treatment of the Nephrotic Syndrome in Adults
Authors: H. Gotz, W. T. E. McCaughey, R. A. Womersley
Journal: BMJ (1964)

Crush Injury of Chest-Whitwam and Norman M=o 351with crush injuries of the chest it cannot be assumed that oxygenation is adequate on the basis of the finding of a normal PaCXO2 (2) In these patients the inspired gases should be enriched with oxygen no matter what the mode or amount of ventilation.Even then hypoxaemia may still be present.Further therapy should aim at promoting expansion of the lungs and at restoring to normal the circulating blood volume and the oxygen-carrying capacity of the blood. SummaryArterial blood-gas analyses have been performed on nine patients who had sustained chest injuries.After tracheostomy and in the absence of pulmonary tamponade the lungs were capable of maintaining normal or subnormal carbon dioxide tensions, but in all cases there was a reduction in the percentage saturation with oxygen of the arterial blood, and in some patients this was not corrected fully with oxygen therapy.Some of the implications of these findings are discussed.
Teaching Nursing by Correspondence.
Authors: Walter H. Snyder
Journal: JAMA (1906)

Toledo, Ohio, Jan. 3, 1906. <h3>To the Editor:</h3> —The committee on public health and legislation of the Academy of Medicine of Toledo ask for information based on experience which any of your readers may have as to the advisability of teaching nursing by correspondence courses. We wish especially to procure actual experiences which physicians may have had with such nurses. We do not care for arguments as to the logical possibility of such course, but whether in actual practice such nurses are satisfactory, and we wish replies from those who have tried them. These replies will be considered confidential if the writer requests it. The replies may be sent to the undersigned, the secretary of the society
Effects of Oxandrolone, an Anabolic Steroid, on Hemostasis
Authors: Nighat N. Kahn, Asru K. Sinha, Ann M. Spungen, William A. Bauman
Journal: American Journal of Hematology (2006)

This study evaluated the short-term effects of oxandrolone, an anabolic androgenic synthetic steroid, on blood coagulation and the hemostatic/fibrinolytic system in healthy individuals. Subjects (n = 14) were administered oxandrolone (10 mg twice daily) for 14 days. Blood was obtained on days 0, 1, 3, 7, 9, 14, and then at day 42 (28 days after discontinuation of the drug). Samples were analyzed for the plasma plasminogen, plasminogen activator inhibitor (PAI-1), fibrinogen, and coagulation factors (II, V, VII, VIII, and X). After 7 days of administration of oxandrolone, the plasma plasminogen level significantly increased [100% +/- 21% to 174% +/- 21% (P < 0.0001)]. PAI-1 was significantly decreased at day 3 [16 +/- 9 to 7 +/- 4 mg/dL (P < 0.01)]. Coagulation factors II and V significantly increased at day 14 [88 +/- 15 to 122 +/- 11 (P < 0.005) and 105 +/- 21 to 179 +/- 36% (P < 0.0001)], respectively. Factor VII level decreased by day 3 [91% +/- 26% to 83% +/- 18%, NS], but after 14 days factor VII level returned to baseline (91% +/- 26% to 93% +/- 19%, NS). The increase of factor VIII level was not significant (111% +/- 64% to 125% +/- 55%, NS). Factor X increased steadily over 14 days of drug treatment [96% +/- 11% to 107% +/- 25%, NS] and after discontinuation, decreased and returned to baseline by day 42 [107% +/- 25% to 89% +/- 25%, NS]. Fibrinogen decreased by 22% +/- 12%, (NS). Administration of oxandrolone, to healthy young men was associated with a significant increase in select blood coagulation factors and plasminogen. These changes create a state of potential hypercoagulability that appears to be counterbalanced by increased fibrinolytic activity to maintain homeostasis.
Centrofacial lentiginosis.
Authors: IGOR DOCIU, OLGA GALACTION-NITELEA, NICOLAE ŞIRJIĀ, VLAD MURGU
Journal: British Journal of Dermatology (1976)

Forty patients with centrofacial lentiginosis have been studied. A greater than normal number of bone abnormalities, malformations due to dysraphia, endocrine dysfunctions, and neurological diseases, but not psychiatric impairment, were found.
Altered expression of Bag-1 in Coxsackievirus B3 infected mouse heart
Authors: T Peng
Journal: Cardiovascular Research (2001)

Objective: The mechanisms by which Coxsackie B viruses cause myocarditis or dilated cardiomyopathy are not well understood. This study examined changes in the expression of cardiac genes resulting from Coxsackievirus B3 (CVB3) infection of mice. Methods: Mice (five per group) were experimentally infected with CVB3 or mock-infected with diluent. Altered expression of genes was initially identified by cDNA array, and confirmed by semiquantitative RT-PCR, western blot and immunohistochemistry. Results: Forty-two up-regulated or down-regulated genes were observed in cDNA arrays carrying 588 known mouse genes. Among these, one down-regulated gene, Bag-1, known to be involved in inhibition of apoptosis and modulation of chaperone activity, was investigated further. Semiquantitative RT-PCR showed that Bag-1 expression was down-regulated by up to 30% in virus-infected mouse heart on day 7 compared to the mock-infected. Cell fractionation and western blot analysis confirmed that Bag-1 isoform p32 was predominant in the cytoplasm of mouse myocardium and down-regulated at 4 days or 7 days after CVB3 infection. In contrast, Bag-1 isoform p50 appeared to increase in the nuclear fraction of mouse heart at 7 days after infection. Down regulated expression and distribution of Bag-1 protein or evidence of apoptosis in the infected mouse heart was demonstrated by immunostaining or histochemistry (TUNEL assay), respectively. Conclusion: CVB3 infection induced differential expression of Bag-1 in cytoplasmic and nuclear fractions of mouse heart and apoptosis. This may be important in the pathogenesis of enterovirus heart muscle disease.