tbuckley/cabot-search huggingface dataset:
118. Self-Complementary AAV Vectors Pseudotyped with Either Serotype 5 or 8 Capsids Give Therapeutic Human Factor IX Levels at Significantly Reduced Doses in Non-Human Primates
Authors: John T. Gray, Andrew M. Davidoff, Amit C. Nathwani
Journal: Molecular Therapy (2005)

We have created a novel self-complementary adeno-associated virus (scAAV) vector for Factor IX (hemophilia B) gene therapy, and have tested this vector with multiple serotype capsids in both murine and Rhesus macaque models. A small, liver-specific transcriptional cassette enabled inclusion of the 1386 bp of human Factor IX coding sequence in a single terminal resolution site deleted scAAV vector. At both early and late time points after transduction, self-complementary vector genomes purified from murine liver show striking differences from those produced by conventional single-stranded vectors, and these differences are consistent with the predicted asymmetric hairpin structure of scAAV. Using vectors pseudotyped with serotype 8 capsids (scAAV2/8) in mice, our new vector provides 30|[ndash]|60 fold greater circulating Factor IX (138 |[mu]|g/ml from 1011 particles) than our previous, conventional single-stranded AAV2/8 vector. This enhancement was observed relatively uniformly across a dose range of 109 to 1011 genome copies/mouse, in agreement with previous observations of the non-saturable behavior of AAV2/8 vectors in liver transduction. scAAV2/5 vectors produced |[sim]|50 fold lower levels of human Factor IX than scAAV2/8 in mice, and with somewhat delayed kinetics.
A prospective study of gout in New Zealand Maoris.
Authors: G W Brauer, I A Prior
Journal: Annals of the Rheumatic Diseases (1978)

Results are reported from the first prospective study of gout in New Zealand Maoris based on a sample of 388 males and 378 females. At baseline, high mean levels of serum uric acid (SUA) were found, 0.422 +/- 0.092 mmol/1 (7.05 +/- 1.54 mg/100 ml) in males and 0.350 +/- 0.091 mmol/1 (5.85 +/- 1.52 mg/100 ml) in females. On the basis of traditional criteria (SUA above 0.42 mmol/1 (7.0 mg/100 ml) in males and above 0.36 mmol/1 (6.0 mg/100 ml) in females) the prevalence of hyperuricaemia was 49% in males and 42% in females. The baseline prevalence of gout (8.8% for males and 0.8% for females) and the subsequent 11-year incidence rates (10.3% for males and 4.3% for females) are discussed in relation to specified SUA classes. When traditional, sex-specific criteria for hyperuricaemia were used, no relationship was found between the prevalence of hyperuricaemia and the incidence of gout. There was, however, a sharp increase in the incidence rate of gout in both sexes when SUA levels were above 0.48 mmol/1 (8.0 mg/100 ml). In subjects with a baseline SUA above this level, the age-standardised 11-year incidence rate of gout was 29.1% for males and 37.2% for females. A previously unreported relationship linking muscle size to the incidence of gout in males is presented as a major finding of the study. Other risk factors associated with gout were body mass and blood pressure.
Hughlings Jackson on Psychiatry
Authors: TERRENCE L. Riley
Journal: JAMA (1983)

This is a delightful book that should probably appeal to almost all physicians, many people interested in psychiatry and psychology, and, very likely, many lay people who would be interested in the evolution of modern psychiatric or neurological philosophies. This is far more than a monograph simply praising Hughlings Jackson but is a scholarly assessment of Jackson's contributions to modern psychiatry, as well as neurology. Having had the opportunity to review<i>Epilepsy and Psychiatry</i>by Reynolds and Trimble inThe Journallast year, I enjoyed the comparison of the styles of the two contemporary giants, Jackson and Gowers. In this delightful book, there are dozens of lively descriptions of the interchanges between Jackson and the other authorities in psychiatry and neurology of his era, including Laycock, Horsley, and brilliant followers such as Kinnier Wilson. At the end of this book, one is impressed more than ever at both the remarkable
ON THE HISTIDINE CONTENT OF HUMAN EPIDERMIS
Authors: CLARA NAGY-VEZEKENYI
Journal: British Journal of Dermatology (1969)

SUMMARY.— Histochemical investigations on epidermis of adults and foetuses of different ages have demonstrated that there is a close relationship between histidine content and keratohyalin granules. Where the latter are absent the histidine level is low. Only after the development of the second active protein synthesizing layers of the epithelium does keratinization begin in embryonic life.
Cytogenetic Studies in Reproductive Loss
Authors: Rina Schmidt
Journal: JAMA (1976)

Cytogenetic studies were performed on 57 families with pregnancy wastage (eg, two or more spontaneous abortions or stillbirths). Chromosomal abnormalities were ascertained in 17 couples, through offspring with congenital malformations. Seven families had children with neural tube defects, and five families also had a previous child with Down syndrome. One mother had mosaic Turner syndrome; two additional mothers and one father had balanced chromosome translocations. These findings indicate that chromosome analyses should be performed on every couple with repeated miscarriages or malformed children, and subsequent pregnancies at risk should be monitored by amniocentesis. (<i>JAMA</i>236:369-373, 1976)
Unusual Fatal Complication Following Gastroscopy
Authors: W. Rösch, M. Stolte
Journal: Endoscopy (1974)

Report on a fatal complication 4 hours after an uncomplicated gastroscopy where a benign supra-angular ulcer was found from which several biopsy specimens were taken. The patient died of acute coronary insufficiency induced by intraperitoneal hemorrhage from a torn highly vascularized adhesion at the ulcer base. Bericht uber eine todliche Komplikation nach ambulanter Gastroskopie. Wahrscheinlich durch Luftinsufflation und Biopsie aus dem Ulkusrand eines benignen Ulkus kam es zu einer Rhexisblutung aus einem stark vaskularisierten Adhasionsstrang, der sich bei einer vorausgegangenen Ulkuspenetration gebildet hatte. Die Patientin verstarb an einer akuten Koronarinsuffizienz nach einem Blutverlust von etwa 500 ml bei praexistenter koronarer Herzkrankheit.
Rupture of the Jejunum, from a Fall, in a Girl Eleven Years of Age
Authors: E. Holland
Journal: BMJ (1873)

fused her food, tore her hair, pinched her skin, destroyed her clothing' was violent to those around her in a marked degree, cunning and mali- cious, foul in her language, and raved and fumed with passion, rendering it often necessary, during the paroxysms of excitement, to hold her, or to place her in the padded room for safety's sake.She was sleepless and
Compensatory Molecular Evolution of HC-Pro, an RNA-Silencing Suppressor from a Plant RNA Virus
Authors: C. Torres-Barcelo, J.-A. Daros, S. F. Elena
Journal: Molecular Biology and Evolution (2009)

RNA silencing is a eukaryotic mechanism involved in several cellular processes, one example being a sequence-specific antiviral defense. Many plant viruses have developed counterdefensive proteins that in many instances are multifunctional, such as helper component protease (HC-Pro) of Tobacco etch virus (TEV). In a previous work, a collection of mutants with amino acid replacements in TEV HC-Pro was generated, and their effects in the capacity of suppressing RNA silencing were quantified in a transient expression assay. In this study, three mutations that caused a reduction in suppression activity and three that increased it were used to create replicate experimental lineages that were evolved through serial passages. We have evaluated the number of genotypic changes that occurred during evolution in HC-Pro and their phenotypic effects on virus viability, virulence, and suppression of RNA silencing. In no instance did the original mutation revert to the wildtype (WT) sequence. In several cases, fixed mutations were canonical compensatory changes, returning the suppressor activity to the WT HC-Pro value, pointing to the existence of stabilizing selection pressures and pleiotropic effects of the introduced original mutations. However, in other instances, the fixed mutations were overcompensatory, driving the activity of the mutant beyond the optimal value. Negative epistatic effects among beneficial mutations as well as decompensatory epistasis also play an important role during compensatory evolution of RNA-silencing suppression.
Rapidly Developing Tolerance to Transdermal Nitroglycerin in Congestive Heart Failure
Authors: RANDY A. JORDAN
Journal: Annals of Internal Medicine (1986)

We have reported early attenuation of hemodynamic effects of transdermal nitroglycerin in patients with heart failure. We now report nitroglycerin plasma levels in those same patients. We administered transdermal nitroglycerin, 60 mg/24 h, to eight patients or placebo to seven patients in a double-blind fashion, and monitored pulmonary wedge pressure and nitroglycerin plasma levels for 24 hours. After placebo administration, nitroglycerin plasma levels and pulmonary wedge pressure remained unchanged. During transdermal nitroglycerin administration, the plasma nitroglycerin level rose from 0.04 ± 0.12 ng/mL at baseline to near peak levels at 2 hours (7.43 ± 7.21 ng/mL). Between 2 and 24 hours, levels fluctuated at a steady state. Pulmonary wedge pressure fell from 22 ± 7 mm Hg at control to a nadir of 14 ± 5 mm Hg at 4 hours (p < 0.01). Despite persistently high plasma nitroglycerin levels, by 18 hours pulmonary wedge pressure was no longer significantly reduced (20 ± 9 mm Hg). These results indicate that rapid development of tolerance is the cause of attenuated hemodynamic efficacy of transdermal nitroglycerin.
Openness Between Gay Persons and Health Professionals
Authors: LARRY DARDICK
Journal: Annals of Internal Medicine (1980)

A study of homosexual men and women was undertaken to ascertain what factors contribute toward being open with health professionals about one's sexual orientation and how this openness affects quality of care. Six hundred twenty-two men and women responded to a questionnaire distributed in the Gay Community News. Almost half (49%) had explicitly shared with their primary health professional that they were homosexual, another 11% assumed their health provider knew, and only 7% would not share this information with their health provider under any circumstances. Those who had shared this information were more satisfied with their primary health professional and, if male, were more likely to have been checked for venereal disease. Health professionals' attitudes towards homosexuality were an important concern of respondents; 27% felt that a previous health professional had been prejudiced towards homosexual persons.
Abstract 242: Anti-obesity drugorlistat enhances sensitivity toTRAIL by two different pathways inhormone-refractory prostate cancer cells
Authors: Jun Fujiwara, Yoshihiro Sowa, Mano Horinaka, Makoto Koyama, Miki Wakada, Tsuneharu Miki, Toshiyuki Sakai
Journal: Cancer Research (2012)

Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as one of the expected cancer therapeutics. However, since hormone-refractory prostate cancer (HRPC) cells are sometimes resistant to TRAIL, we need to develop a novel strategy to overcome. We demonstrated that the anti-obesity drug orlistat enhances the sensitivity to TRAIL in HRPC cells. The combination of orlistat and TRAIL remarkably induced apoptosis in DU145 and PC3 cells. Orlistat induced the expression of DR5, which is one of the TRAIL receptors. The suppression of DR5 with siRNA reduced the enhanced apoptosis, suggesting that the enhanced apoptosis was at least partially due to the up-regulation of DR5. Although the up-regulation of DR5 at both mRNA and protein levels by orlistat was observed in both cell lines, the activation of the DR5 promoter in DU145 cells was CHOP-dependent, but that in PC3 cells was CHOP-independent. Moreover, orlistat induced reactive oxygen species (ROS), and a ROS scavenger diminished the sensitivity to TRAIL through the suppression of the CHOP and DR5 expressions in both cell lines. These results suggest that there are two different pathways of up-regulation of DR5 by orlistat, which are ROS-CHOP pathway and ROS-direct pathway. In conclusion, orlistat enhances the sensitivity to TRAIL in the ROS mediated pathways in prostate cancer cells. We believe that the administration of TRAIL and orlistat is considered a promising strategy for cancer therapy in HRPC. 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 242. doi:1538-7445.AM2012-242
Green turtle fibropapillomatosis: challenges to assessing the role of environmental cofactors.
Authors: L H Herbst, P A Klein
Journal: Environmental Health Perspectives (1995)

Green turtle fibropapillomatosis (GTFP) is a growing threat to the survival of green turtle (Chelonia mydas) populations worldwide. Recent transmission studies point to an infectious etiology. Several field studies suggest that high GTFP prevalence is associated with marine habitats that have been impacted by agricultural, industrial, or urban development. Environmental contaminants could be involved in GTFP through several plausible mechanisms including cocarcinogenesis and contaminant-induced immune suppression. However, an association of contaminants with GTFP has not been established. A broader perspective is needed when studying infectious diseases such as GTFP in complex ecosystems. Alternative explanations for high GTFP prevalence in some near-shore habitats include the following: a) these habitats provide an optimum physical environment for survival and transmission of the infectious agent; b) these habitats attract a high density of susceptible turtles or harbor a higher density of potential vectors, facilitating transmission of the pathogen in a density-dependent fashion; and c) these habitats may contain other stressors that render turtles more susceptible to GTFP. Application of scientifically rigorous criteria in the epizootiology of GTFP in free-ranging populations remains a formidable challenge.
Ethicist Faults Human Research Subject Protection
Authors: Charles Marwick
Journal: JAMA (1994)

THE SYSTEM that is supposed to protect human subjects who participate in research studies is flawed. The result is failure to protect such persons adequately, said speakers at a Washington, DC, meeting. Two recently publicized examples illustrate the point: In controlled field trials of the efficacy of pertussis vaccine, some children were denied the benefits of the vaccine; in another study involving schizophrenic patients, the subjects were not told the full extent of the risks of participation. The flaw in the system is the failure to keep in working order the mechanism of open public discussion of difficult cases by the Ethics Advisory Board that was set up in 1977 and allowed to lapse in 1980, says noted medical ethicist Albert R. Jonsen, PhD, of the University of Washington School of Medicine, Seattle. If that mechanism had been in place, Jonsen argued at a meeting of the Congressional Biomedical Research
Bone Marrow Therapy for Myocardial Infarction
Authors: Joshua M. Hare
Journal: JAMA (2011)

The results of the latetime study, 1 reported by Traverse and colleagues in this issue of JAMA, appear 1 decade after the publication of the landmark study by Orlic et al. 2 The authors conducted a rigorous clinical trial to test the hypothesis that intracoronary infusion of autologous bone marrow mononuclear cells (BMCs) in patients with myocardial infarction (MI) would improve left ventricular function.The rationale for using whole bone marrow in this setting derives from numerous sets of experimental studies showing that bone marrow contains cellular constituents that have cardiac reparative ability. 2,3The authors found that among 87 patients with MI and left ventricular dysfunction following reperfusion with percutaneous coronary intervention, compared with placebo intracoronary infusion, intracoronary infusion of BMCs 2 to 3 weeks after percutaneous coronary intervention did not improve global or regional ventricular function at 6 months.Given its rigorous design with placebo control, blinding, and sophisticated magnetic resonance imaging (MRI), the LateTIME trial results are compelling, arguing against the value of intracoronary bone marrow infusion administration 2 to 3 weeks following acute MI.The results of the LateTIME trial are in contrast with several other rigorous clinical trials, notably the Reinfusion of Enriched Progenitor Cell and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) published in 2006, 4 which showed a statistically significant increase in ejection fraction (EF) in response to intracoronary bone marrow given within 3 to 7 days of MI.In that study, the authors found that the benefit increased among patients treated toward the end of the 7-day time frame, with an enhanced effect in the subgroup of patients with EFs less than the median of 48.9%.The results of a meta-analysis 5 substantiated the finding that intracoronary BMCs are associated with an improvement in EF by approximately 3% to 4%.Additionally, a potentially important analysis from the REPAIR-AMI data suggests that intracoronary BMCs may have clinical benefits that exceed those predicted by the increase in EF. 6 Importantly, 2 ongoing current trials-TIME 7 and BAMI (Bone marrow-derived mononuclear cells [BM-MNC] on all-cause mortality in Acute Myocardial Infarction)-will offer important information.The TIME study, 7 conducted by the same investigators as the LateTIME study, will compare the efficacy of bone marrow therapy at 3 vs 7 days, and the
IV. The Family Practice Program at the Baltimore City Hospitals
Authors: Francis P. Chinard
Journal: JAMA (1961)

A FAMILY PRACTICE PROGRAM was started at the Baltimore City Hospitals in July, 1960, when the first house officer assumed his duties under that program. It is too early to evaluate the program. Instead, there follows a description of its setting, the factors which have led to its particular format in Baltimore, and the impact that the program may have, not only on its host hospital, but also eventually on the practice of medicine in the community. <h3>The Community and Medical Settings</h3> Baltimore is a sprawling semi-industrial town with a metropolitan population of the order of a million and a half and with some 2,000 physicians to tend to its medical needs. It has only one municipal hospital, the Baltimore City Hospitals. This is a teaching institution with ties to the 2 medical schools in its area but with a particularly close relationship to the medical school of the Johns
Government figures show rapid increase in NHS staff
Authors: Owen Dyer
Journal: BMJ (2004)

The NHS in England and Wales has seen a year of record growth in staff numbers, according to statistics released last week. The latest figures show that in September 2003 the NHS had recruited an extra 18 800 nurses, 5600 doctors, and 2500 allied health professionals over the previous 12 months.



The NHS chief executive, Nigel Crisp, said: “There are now 1 282 900 people in England working in the NHS. Almost exactly …
Abstract of Lectures on the Structure and Functions of the Brain in Relation to Disease
Authors: D. J. Hamilton
Journal: BMJ (1884)

The present study aimed to quantify which image reconstruction conditions for normal databases and patients affect statistical brain function image analysis using an easy <i>z</i> score imaging system (eZIS) and 3-dimensional stereotactic surface projections (3D-SSP). <b>Methods:</b> We constructed normal databases based on cerebral perfusion SPECT images obtained from 15 healthy individuals. Each normal database was created with the following unique conditions: a variable Butterworth filter cutoff frequency (fc) with and without scatter and attenuation corrections. To simulate patient data, we selected 1 dataset from among those created from the 15 healthy individuals. The simulated patient data were designed to include hypoperfused regions with prespecified volumes. Using 3D-SSP and eZIS, we compared how the above processing conditions affect the distribution of SD in normal database images and the accuracy of detecting specific regions. <b>Results:</b> The SD for the SPECT images increased with the fc of the Butterworth filter. The <i>z</i> score decreased by 30% for 3D-SSP and by 14% for eZIS, indicating that the prefilter significantly affected <i>z</i> scores. The accuracy of detecting the hypoperfused regions was significantly influenced by the fc; 3D-SSP decreased by 7.51%, and eZIS decreased by 55.34%. The detection accuracy with eZIS, which involves a smoothing process, was significantly decreased. The error of the area of hypoperfused regions was minimized when normal database and patient data were both corrected for scatter and attenuation. <b>Conclusion:</b> When the reconstruction conditions (fc, scatter correction, and attenuation correction) at normal database creation differed from those at patient data processing, the <i>z</i> scores widely underestimated the analytic results because the SD varied according to the reconstruction conditions. The accuracy of brain function image analysis can be improved by considering the reconstruction conditions and correcting for scatter and attenuation on both normal databases and patient data.
PRIMARY CHANGES IN EYES OF RATS WHICH RESULT FROM DEFICIENCY OF FAT-SOLUBLE A IN DIET
Authors: SHINNOSUKE MORI
Journal: JAMA (1922)

Of recent years, several investigators have described the eye disease which occurs in rats as the result of diets deficient in fat-soluble A. Various names have been given to this condition. McCollum and Simmonds<sup>1</sup>termed it xerophthalmia. They chose this name after careful study of the development, symptoms and treatment of xerophthalmia as it occurs in rats and man. Osborne and Mendel<sup>2</sup>preferred to use the more general term ophthalmia. Goldschmidt<sup>3</sup>studied the pathology of the disease as it occurred among young rats on Hopkins' diet. His studies convinced him of the identity of the lesion with keratomalacia in man, and he proposed giving this name to the disease in the rat. Stephenson and Clark<sup>4</sup>also preferred this term to xerophthalmia, for the pathologic condition in the eyes of rats seemed to them to resemble keratomalacia more