tbuckley/cabot-search huggingface dataset:
Cloning of a liver-specific MRP-homologue which is deficient in the TR rat
Authors: C PAULUSMA
Journal: Hepatology (1995)

A phospholipid translocating protein from rat liver has been expressed in Xenopus laevis oocytes. Injection of oocytes with total rat liver messenger RNA (mRNA) resulted in the function expression of saturable uptake of the water soluble phophatidylcholine derivative L-alpha- dibutyroylglycero-3-phophatidylcholine (diC4PC), Kinetic studies revealed an apparent Km value of approximately 10 mmol/L, which is similar to the value previously obtained in isolated rat liver canalicular plasma membrane vesicles for an adenosine triphosphate (ATP)-independent phosphatidylcholine translocator. Size fractionation of total rat liver mRNA yielded an active mRNA species between 1.8 and 2.6 kb, that stimulated the expressed phophatidylcholine uptake activity approximately fivefold as compared with differently sized mRNA subfractions. This active mRNA size class is too small to code for the mdr2 P-glycoprotein, which has been suggested to function as an ATP- dependent canalicular phosphatidylcholine translocator. Hence, the data indicate that there are at least two separate polypeptides involved in phospholipid translocation from hepatocytes into bile. (Hepatology 1996 May;23(5):1254-9)
Annual Review of Gerontology and Geriatrics
Authors: Owen W. Beard
Journal: JAMA (1981)

This volume is planned as the first in a series of annual reviews designed "to encompass the broad spectrum of concerns in aging, from empirical and theoretical literature to clinical studies and services for the elderly" and is expected to "become a dependable source of scholarly information." This reviewer found the published effort to fall short of these high aims, unless they can be realized in the extensive references found at the end of each chapter. One cannot escape the thought that too many authors have chosen to write as if they were only addressing their own discipline and using the jargon of that discipline. There are several well-written chapters using words and phrases that communicate across many disciplines, because the words used are common ones, or have meanings congruent with those that can be found in a good college dictionary, or in a medical dictionary. In fact, the chapter
IS THE ACTION OF BACILLUS ACIDOPHILUS A STRICTLY BACTERIOLOGIC PHENOMENON?
Authors: NICHOLAS KOPELOFF
Journal: JAMA (1923)

The relief from chronic constipation and diarrhea by the ingestion of milk fermented with Bacillus acidophilus is a phenomenon worthy of further study. 1 The beneficial effects obtained by such therapy might be due to a multiplicity of factors. It has been held that chief among these is the ingestion of an increased volume, and more particularly the addition of considerable water to the daily diet. As against this physical or mechanical interpretation, there is a chemical explanation, based on the presence of a considerable amount of lactic acid, together with the disintegration products of the organism B. acidophilus . Finally, there is the strictly bacteriologic interpretation, which holds the living B. acidophilus organisms responsible for all benefits. The experiments here described, which are still in progress, were devised in the hope of arriving at some definite conclusion regarding this phenomenon.    EXPERIMENTAL DATA  Patients with a history of chronic constipation were
Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration
Authors: Leah C. Byrne, Deniz Dalkara, Gabriel Luna, Steven K. Fisher, Emmanuelle Clérin, Jose-Alain Sahel, Thierry Léveillard, John G. Flannery
Journal: Journal of Clinical Investigation (2014)

Alternative splicing of nucleoredoxin-like 1 (Nxnl1) results in 2 isoforms of the rod-derived cone viability factor. The truncated form (RdCVF) is a thioredoxin-like protein secreted by rods that promotes cone survival, while the full-length isoform (RdCVFL), which contains a thioredoxin fold, is involved in oxidative signaling and protection against hyperoxia. Here, we evaluated the effects of these different isoforms in 2 murine models of rod-cone dystrophy. We used adeno-associated virus (AAV) to express these isoforms in mice and found that both systemic and intravitreal injection of engineered AAV vectors resulted in RdCVF and RdCVFL expression in the eye. Systemic delivery of AAV92YF vectors in neonates resulted in earlier onset of RdCVF and RdCVFL expression compared with that observed with intraocular injection using the same vectors at P14. We also evaluated the efficacy of intravitreal injection using a recently developed photoreceptor-transducing AAV variant (7m8) at P14. Systemic administration of AAV92YF-RdCVF improved cone function and delayed cone loss, while AAV92YF-RdCVFL increased rhodopsin mRNA and reduced oxidative stress by-products. Intravitreal 7m8-RdCVF slowed the rate of cone cell death and increased the amplitude of the photopic electroretinogram. Together, these results indicate different functions for Nxnl1 isoforms in the retina and suggest that RdCVF gene therapy has potential for treating retinal degenerative disease.
Intradermal Delivery of Plasmid VEGF165 by Electroporation Promotes Wound Healing
Authors: Bernadette Ferraro, Yolmari L Cruz, Domenico Coppola, Richard Heller
Journal: Molecular Therapy (2009)

Skin flaps are extensively used in reconstructive surgeries to repair large defects and deep wounds, but severe ischemia and necrosis often results in loss of the transplanted tissue. Thus, skin flap models are often used to study the biology of healing and necrosis of acute ischemic wounds. Delivery of exogenous vascular endothelial growth factor (VEGF) to areas of ischemia has shown promise for promoting therapeutic angiogenesis, but its expression must be tightly regulated to avoid adverse effects. In this study, plasmid DNA encoding VEGF165 (pVEGF) was delivered to the ischemic skin of a rat skin flap model by intradermal injection followed by electroporation (EP) (pVEGFE+). Treatment with pVEGFE+ significantly increased VEGF expression for 5 days after delivery compared to injection of pVEGF without EP (pVEGFE−). The short-term increase in VEGF was sufficient to mediate an upregulation of endothelial nitric oxide synthase, an angiogenic factor that increases vascular permeability. pVEGFE+ significantly increased skin flap perfusion at both days 10 and 14 postoperatively. The observed increase in perfusion with pVEGFE+ correlated with an increase in skin flap healing and survival. Our results demonstrate that pVEGFE+ is a potential nonviral noninvasive therapy to increase perfusion and healing of skin flaps and ischemic wounds. Skin flaps are extensively used in reconstructive surgeries to repair large defects and deep wounds, but severe ischemia and necrosis often results in loss of the transplanted tissue. Thus, skin flap models are often used to study the biology of healing and necrosis of acute ischemic wounds. Delivery of exogenous vascular endothelial growth factor (VEGF) to areas of ischemia has shown promise for promoting therapeutic angiogenesis, but its expression must be tightly regulated to avoid adverse effects. In this study, plasmid DNA encoding VEGF165 (pVEGF) was delivered to the ischemic skin of a rat skin flap model by intradermal injection followed by electroporation (EP) (pVEGFE+). Treatment with pVEGFE+ significantly increased VEGF expression for 5 days after delivery compared to injection of pVEGF without EP (pVEGFE−). The short-term increase in VEGF was sufficient to mediate an upregulation of endothelial nitric oxide synthase, an angiogenic factor that increases vascular permeability. pVEGFE+ significantly increased skin flap perfusion at both days 10 and 14 postoperatively. The observed increase in perfusion with pVEGFE+ correlated with an increase in skin flap healing and survival. Our results demonstrate that pVEGFE+ is a potential nonviral noninvasive therapy to increase perfusion and healing of skin flaps and ischemic wounds.
Renal disease. I.
Authors: J. S. Cameron
Journal: BMJ (1966)

It is of course impossible in an article of this length to review all the growing points in the study of renal disease at the moment.My choice has been to discuss, first, advances in the fields of acute and chronic renal failure ; and then to consider nephritis, the nephrotic syndrome, and related topics.Recent progress has rested largely on two factors.First, technical advances, which have enabled the principle of dialysis to be applied to treating acute and chronic renal failure.Another major technical advance has been the exploitation of safe biopsy of the kidney.The second factor has been the application to clinical medicine of biochemical and physiological knowledge, particularly the former.No other branch of medicine is at the moment so dependent for its daily conduct upon applied biochemistry as the study of renal disease.
Conjunctival FOXP3 Expression in Trachoma: Do Regulatory T Cells Have a Role in Human Ocular Chlamydia trachomatis Infection?
Authors: Nkoyo Faal, Robin L Bailey, David Jeffries, Hassan Joof, Isatou Sarr, Mass Laye, David C. W Mabey, Martin J Holland
Journal: PLoS Medicine (2006)

Trachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission can be successfully interrupted using antibiotics and improvements in public and personal hygiene, the long-term success of the control programmes advocated by the World Health Organization are still uncertain. For the complete control and prevention of trachoma, a vaccine would be highly desirable. Currently there are no licensed vaccines for trachoma, and no human vaccine trials have been conducted since the 1960s. A barrier to new attempts to design and introduce a vaccine is the identification of immunologic correlates of protective immunity or immunopathology. We studied important correlates of the immune response in a trachoma-endemic population in order to improve our knowledge of this disease. This is essential for the successful development of a vaccine against both ocular and genital C. trachomatis infection.We used quantitative real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The expression of IFN-gamma, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We evaluated the role of immune effector and regulatory responses in the control of chlamydial infection and in the resolution of clinical signs of trachoma in endemic communities in Gambia. All host transcripts examined were detectable even in normal conjunctiva. The levels of these transcripts were increased, compared to normal uninfected conjunctiva, when infection was detected, with or without clinical disease signs. Interestingly, when clinical disease signs were present in the absence of infection, the expression of a regulatory T cell transcription factor, FOXP3, remained elevated.There is evidence of an increase in the magnitude of the local anti-chlamydial cytokine immune responses with age. This increase is coupled to a decline in the prevalence of infection and active trachoma, suggesting that effective adaptive immunity is acquired over a number of years. The anti-chlamydial and inflammatory immune response at the conjunctival surface, which may control chlamydial replication, is closely matched by counter inflammatory or regulatory IL-10 expression. Differences in the level of FOXP3 expression in the conjunctiva may indicate a role for regulatory T cells in the resolution of the conjunctival immune response, which is important in protection from immunopathology. However, the expression of cytokines that control chlamydial replication and those that regulate the conjunctival immune response is not simply juxtaposed; the interaction between the infection and the clinical disease process is therefore more complex.
Targeted Genome Modifications Using Integrase‐deficient Lentiviral Vectors
Authors: Tatjana I Cornu, Toni Cathomen
Journal: Molecular Therapy (2007)

Gene correction aims at repairing a defective gene directly in the cellular genome, which warrants tissue-specific and sustained expression of the repaired gene through its endogenous promoter. We have developed a novel system based on integrase-deficient lentiviral vectors (IDLVs) that allows us to correct an endogenous mutation using a strategy based on homologous recombination (HR). In a proof-of-concept approach, an IDLV encoding a repair template was co-delivered with an I-SceI nuclease expression vector to rescue a defective enhanced green fluorescent protein (EGFP) gene. Expression of the nuclease created a double-strand break within the target locus, which was crucial for stimulating IDLV-based gene repair. Stable gene correction was realized in up to 12% of the cells, depending on the vector dose, the nuclease expression levels, and the cell type. Genotypic analyses confirmed that gene correction was the result of genuine HR between the target locus and the IDLV repair template. This study presents IDLVs as valuable tools for introducing precise and permanent genetic modifications in human cells. Gene correction aims at repairing a defective gene directly in the cellular genome, which warrants tissue-specific and sustained expression of the repaired gene through its endogenous promoter. We have developed a novel system based on integrase-deficient lentiviral vectors (IDLVs) that allows us to correct an endogenous mutation using a strategy based on homologous recombination (HR). In a proof-of-concept approach, an IDLV encoding a repair template was co-delivered with an I-SceI nuclease expression vector to rescue a defective enhanced green fluorescent protein (EGFP) gene. Expression of the nuclease created a double-strand break within the target locus, which was crucial for stimulating IDLV-based gene repair. Stable gene correction was realized in up to 12% of the cells, depending on the vector dose, the nuclease expression levels, and the cell type. Genotypic analyses confirmed that gene correction was the result of genuine HR between the target locus and the IDLV repair template. This study presents IDLVs as valuable tools for introducing precise and permanent genetic modifications in human cells.
Glycochenodeoxycholate-induced lethal hepatocellular injury in rat hepatocytes. Role of ATP depletion and cytosolic free calcium.
Authors: J R Spivey, S F Bronk, G J Gores
Journal: Journal of Clinical Investigation (1993)

Chenodeoxycholate is toxic to hepatocytes, and accumulation of chenodeoxycholate in the liver during cholestasis may potentiate hepatocellular injury. However, the mechanism of hepatocellular injury by chenodeoxycholate remains obscure. Our aim was to determine the mechanism of cytotoxicity by chenodeoxycholate in rat hepatocytes. At a concentration of 250 microM, glycochenodeoxycholate was more toxic than either chenodeoxycholate or taurochenodeoxycholate. Cellular ATP was 86% depleted within 30 min after addition of glycochenodeoxycholate. Fructose, a glycolytic substrate, maintained ATP concentrations at 50% of the initial value and protected against glycochenodeoxycholate cytotoxicity. ATP depletion in the absence of a glycolytic substrate suggested impairment of mitochondrial function. Indeed, glycochenodeoxycholate inhibited state 3 respiration in digitonin-permeabilized cells in a dose-dependent manner. After ATP depletion, a sustained rise in cytosolic free calcium (Cai2+) was observed. Removal of extracellular Ca2+ abolished the rise in Cai2+, decreased cellular proteolysis, and protected against cell killing by glycochenodeoxycholate. The results suggest that glycochenodeoxycholate cytotoxicity results from ATP depletion followed by a subsequent rise in Cai2+. The rise in Cai2+ leads to an increase in calcium-dependent degradative proteolysis and, ultimately, cell death. We conclude that glycochenodeoxycholate causes a bioenergetic form of lethal cell injury dependent on ATP depletion analogous to the lethal cell injury of anoxia.
HbA1c and the Risks for All-Cause and Cardiovascular Mortality in the General Japanese Population
Authors: Masaru Sakurai, Shigeyuki Saitoh, Katsuyuki Miura, Hideaki Nakagawa, Hirofumi Ohnishi, Hiroshi Akasaka, Aya Kadota, Yoshikuni Kita, Takehito Hayakawa, Takayoshi Ohkubo, Akira Okayama, Tomonori Okamura, Hirotsugu Ueshima
Journal: Diabetes Care (2013)

OBJECTIVE Associations between HbA1c and cardiovascular diseases (CVD) have been reported mainly in Western countries. It is not clear whether HbA1c measurements are useful for assessing CVD mortality risk in East Asian populations. RESEARCH DESIGN AND METHODS The risk for cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. A total of 7,120 participants (2,962 men and 4,158 women; mean age 52.3 years) free of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95% CIs among categories of HbA1c (&amp;lt;5.0%, 5.0–5.4%, 5.5–5.9%, 6.0–6.4%, and ≥6.5%) for participants without treatment for diabetes and HRs for participants with diabetes were calculated using a Cox proportional hazards model. RESULTS During the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral hemorrhage, and 24 from unclassified stroke). Relations to HbA1c with all-cause mortality and CVD death were graded and continuous, and multivariate-adjusted HRs for CVD death in participants with HbA1c 6.0–6.4% and ≥6.5% were 2.18 (95% CI 1.22–3.87) and 2.75 (1.43–5.28), respectively, compared with participants with HbA1c &amp;lt;5.0%. Similar associations were observed between HbA1c and death from coronary heart disease and death from cerebral infarction. CONCLUSIONS High HbA1c levels were associated with increased risk for all-cause mortality and death from CVD, coronary heart disease, and cerebral infarction in general East Asian populations, as in Western populations.
Defining, Counting Traffic Injuries No Easy Task as Nation Assesses Toll From This Violence
Authors: Charles Marwick
Journal: JAMA (1992)

INJURIES in traffic violence may outnumber deaths by 70 to 1 in this country. It may even be over 90 to 1. Nonfatal injuries can range from minor scratches to nearly fatal. So to answer the question of how many injuries requires defining each specific level of injury, points out Leonard Evans, DPhil, General Motors Research Laboratories, Warren, Mich. <h3>Injury Scales</h3> A number of scores and scales have been developed to determine injury severity, such as the Injury Severity Score and the Trauma Index. One of the two primary systems for injury assessment used by the National Highway Traffic Safety Administration in Washington, DC, was developed by the Association for the Advancement of Automotive Medicine, Des Plaines, Ill, principally for measuring the severity of motor vehicle injuries. Called the Abbreviated Injury Scale, this system puts injuries for each region of the body—based on a medical evaluation—into six levels of severity
Gene Transfer of Endothelial Nitric Oxide Synthase Improves Relaxation of Carotid Arteries From Diabetic Rabbits
Authors: D. D. Lund, F. M. Faraci, F. J. Miller, D. D. Heistad
Journal: Circulation (2000)

Background —Diabetes mellitus is associated with impairment of NO-mediated vascular relaxation. The purpose of this study was to determine whether adenovirus-mediated gene transfer of endothelial NO synthase (eNOS) or Cu/Zn superoxide dismutase (SOD1) improves responsiveness to acetylcholine in alloxan-induced diabetic rabbits. Methods and Results —After 8 weeks, plasma glucose was greater in diabetic rabbits (418±35 mg/dL) (mean±SEM) than in normal rabbits (105±4 mg/dL). Carotid arteries were removed and cut into ring segments. Arteries were incubated for 2 hours with adenoviral vectors driven by a CMV promoter expressing β-galactosidase (β-gal), eNOS, SOD1, or vehicle. After incubation with virus, arteries were incubated for an additional 24 hours to allow transgene expression. Vascular reactivity was examined by recording isometric tension. After precontraction with phenylephrine, responses to the endothelium-independent vasodilator sodium nitroprusside were similar in diabetic and normal arteries. Endothelium-dependent relaxation to acetylcholine (3×10 −6 mol/L) was significantly less in arteries from diabetic animals (68±5%) than in normal vessels (90±3%). Adenoviral transfection of arteries with eNOS improved relaxation in response to acetylcholine in diabetic (EC 50 eNOS=0.64±0.12×10 −7 mol/L versus vehicle =1.70±0.43×10 −7 mol/L) but not normal arteries. Vasorelaxation in response to acetylcholine was inhibited by N ω -nitro- l -arginine (100 μmol/L) in all groups. Responses to acetylcholine were unchanged after gene transfection of SOD1 or β-gal in arteries from diabetic or normal rabbits. Conclusions —Adenovirus-mediated gene transfer of eNOS, but not SOD, improves impaired NO-mediated relaxation in vessels from diabetic rabbits.
The Voice of the Symbol
Authors: Alister Brass
Journal: JAMA (1972)

Throughout history men have sought to squeeze a little logic out of the absurdity of life by making use of symbolic thinking. Unfortunately, ignorance of this often unconscious activity is widespread, and Dr. Grotjahn, with 40 years of psychoanalytic practice behind him, believes it vital for us to understand the extent of this ignorance and to correct it. His book is a collection of essays on symbolic thought in a wide variety of situations—some historical, some contemporary. Naturally, there are chapters on dream symbols and on the symbols in psychoanalytic theory, which follow a Freudian path. There is an interesting biographical study of Georg Groddeck, an unconventional physician. Grotjahn also explores the multiple symbolism in Hieronymus Bosch's masterwork, "The Millennium" (a triptych showing the creation of Eve, the Garden of Earthly Delights, and Hell). This picture he interprets as an illustrated text for a medieval sect called the New Adamites,
Extrinsic allergic alveolitis caused by goose feathers in a duvet.
Authors: T Haitjema, H van Velzen-Blad, J M van den Bosch
Journal: Thorax (1992)

Abstract A patient with extrinsic allergic alveolitis had precipitating antibodies to many avian antigens. A duvet containing goose feathers proved to be the source of antigenic material.
A NOTE ON THE IMMEDIATE EFFECTS OF REDUCTION OF KIDNEY SUBSTANCES
Authors: H. T. Karsner, H. A. Bunker, G. P. Grabfield
Journal: The Journal of Experimental Medicine (1915)

Several investigators have studied the nitrogenous metabolism of animals following reduction of kidney substance; notably, Tuffier, 2 Bradford, a Bainbridge and Beddard, 4 Pearce, s and Pilcher.6 Studies of nitrogen balance and partition have been made and somewhat contradictory results obtained, de Paoli 7 observed that large quantities of kidney substance could be removed without endangering life and that the minimum necessary for life is one-half of one kidney, or one-quarter of the total kidney substance.TuNer, on the other hand, stated that life is possible with only 1.5 gm. of kidney substance per kilo of body weight (the total is about 7 gm.per kilo in the dog).Bradford found the danger limit reached at 2 gm.per kilo; this was confirmed by Pearce and by Pilcher.As regards function Tuffier, as quoted by Bradford, states : " It is possible to remove quantities of kidney substance equal in weight and in volume to those of the sum of the two kidneys in such a way as yet to leave behind a considerable amount of kidney substance, as shown by postmortem examination; that this diminution in the amount of kidney substance is not accompanied by any functional disturbance of the urine, and that the urine and urea, after oscillations due to the operation, return to their normal amount."Bradford found that excision of less than two-thirds of the kidney volume 1 Aided by a grant from The Rockefeller Institute for Medical Research.