tbuckley/cabot-search huggingface dataset:
584. Gene Delivery to Primary Neuronal Cells
Authors: Shaomin Zou, Ellen S. Hauck, Michael H. Nantz, James G. Hecker
Journal: Molecular Therapy (2005)

Top of pageAbstract
Neuronal protection under numerous clinical circumstances (i.e. trauma brain injury, stroke, ischemia and circulation arrested surgery, etc.) remains a tough challenge due to the paucity of effective clinical options. Transient gene delivery to CNS neuronal cells may offer an alternative approach to induce neuronal protection. We have previously shown widespread distribution, uptake, and expression in rat brain after non-viral, cationic lipid-mediated delivery of reporter gene vectors to the lateral ventricle 1,2. In order to further develop techniques for, and understand the mechanisms of, non-viral gene delivery, we conducted cationic lipid mediated gene delivery of fire fly luciferase mRNA and DNA to primary rat cortical cells to study the post-transfection transgene expression profiles. The delivery of mRNA resulted in a rapid onset of luciferase expression 1 hour after transfection, peaked at 5- 6 hours post transfection, and diminished to base line 12 hours after transfection. Compared to the delivery of mRNA, DNA delivery resulted in a much later onset of gene expression. Although the transgene expression after DNA delivery was generally one order of magnitude higher than after mRNA delivery, the earliest significant luciferase activity after DNA transfection did not appear until 7 hours after transfection. Peak expression following DNA delivery was 36-48 hours after transfection, and transgene expression persisted at a significant level for at least one week before it dropped to base line. Based on this observation, we attempted the delivery of mRNA and DNA vectors that encode for the heat shock protein gene HSP70. The inducible HSP70 is a chaperone protein and its expression has protective effects under stress conditions. HSP70 was delivered using non-viral cationic lipid-mediated techniques that we have developed to rat primary cortical cells, and analyzed by flow cytometry and immunohistochemistry. Consistent with the luciferase activity results, we detected evenly stained HSP70 expression 5 hours after the delivery of HSP70 mRNA, while expression after the delivery of HSP70 DNA appeared to peak at 36-48 hours.
Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults
Authors: Peter Würtz, Pasi Soininen, Antti J. Kangas, Tapani Rönnemaa, Terho Lehtimäki, Mika Kähönen, Jorma S. Viikari, Olli T. Raitakari, Mika Ala-Korpela
Journal: Diabetes Care (2012)

Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin resistance index in healthy young adults.Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin resistance was estimated by homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed using regression models adjusted for established risk factors. We further examined whether amino acid profiling could augment risk assessment of insulin resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up, while for women only leucine, valine, and phenylalanine predicted 6-year HOMA-IR (P < 0.05). None of the other amino acids were prospectively associated with HOMA-IR. The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men (odds ratio 2.09 [95% CI 1.38-3.17]; P = 0.0005); however, including the amino acid score in prediction models did not improve risk discrimination.Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young, normoglycemic adults, with most pronounced associations for men. These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance.
ALCOHOL AND THE PEDESTRIAN IN TRAFFIC ACCIDENTS
Authors: THOMAS A. GONZALES
Journal: JAMA (1941)

From time to time, publications have appeared on the effect of alcohol on the driving efficiency of operators of motor vehicles. Attempts have been made to correlate the amount of alcohol in the blood, urine or expired air of drivers in traffic accidents and to determine the lowest quantity of the intoxicant in blood, urine and expired air above which it would be reasonably safe to infer that an impairment of reactions and reflexes would occur. Among the observers who have studied this problem are Schwarz,1Heise,2Carlson,3Naville and Rosselet,4Turner5and Selesnick.6The Committee on Tests for Intoxication of the National Safety Council7has recommended that all persons having a level of alcohol in the blood above 0.15 per cent by weight are sufficiently impaired to be unsafe drivers.  With the exception of work by Gerber,8who found a blood
Design of long-acting formulation of protein drugs with a double-layer structure and its application to rhG-CSF
Authors: Hiroo Maeda, Takashi Nakagawa, Noriyuki Adachi, Yasuyuki Sakai, Tomonaga Yamamoto, Akio Matsuoka, Akihiko Sano, Yukihiro Satoh, Teruo Miyata, Keiji Fujioka
Journal: Journal of Controlled Release (2003)
Effect of different bronchodilators on airway smooth muscle responsiveness to contractile agents.
Authors: B Gustafsson, C G Persson
Journal: Thorax (1991)

"Functional antagonism" is often used to describe the general relaxant effect of beta 2 agonists and xanthines and their ability to protect the airways against bronchoconstrictor stimuli. This study in guinea pig isolated trachea addresses the question of whether the capacity of these drugs to protect against constrictor stimuli is related to smooth muscle relaxation. Three antimuscarinic drugs were also examined to determine whether antagonism of mediators other than muscarinic agonists might contribute to bronchodilatation by these antimuscarinic drugs. Terbutaline (1.1 x 10(-7), 2.2 x 10(-7) M), theophylline (2.2 x 10(-4), 4.4 x 10(-4) M), and enprofylline (5.2 x 10(-5), 1.0 x 10(-4) M) relaxed the tracheal tension that remained after indomethacin treatment. They did not, however, alter the carbachol concentration-response curve significantly. In addition, neither theophylline (2.2 x 10(-4) M) nor terbutaline (1.1 x 10(-7) M) altered histamine induced contraction. Atropine sulphate, glycopyrrolate, and ipratropium bromide had EC50 values of 10(-9) - 10(-8) M for relaxation of carbachol induced contractions, whereas concentrations of 10(-6) - 10(-3) M or greater were required to relax contractions induced by allergen and nine other non-muscarinic mediators. It is suggested that bronchodilatation by antimuscarinic drugs in vivo is due to inhibition of acetylcholine induced bronchoconstriction alone and that beta 2 agonists and xanthines have poor ability to protect airway smooth muscle against constrictor stimuli. Hence mechanisms other than bronchodilatation and "functional antagonism" should be considered to explain the protection against constrictor stimuli in asthma seen with beta 2 agonists and xanthines.
Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS.
Authors: B S Peters, E J Beck, D G Coleman, M J Wadsworth, O McGuinness, J R Harris, A J Pinching
Journal: BMJ (1991)

OBJECTIVE--To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN--A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS--347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING--Departments of immunology and genitourinary medicine, St Mary9s Hospital, London. MAIN OUTCOME MEASURES--Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposi9s sarcoma. RESULTS--The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposi9s sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposi9s sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS--The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.
A FEW REMARKS ON THE PATHOLOGY OF SYNOVITIS HYPERPLASTICA GRANULOSA OF THE SHOULDER JOINT.
Authors: E. J. SENN
Journal: JAMA (1896)

kidney are immediate removal of the diseased kidney and its ureter; in case of disease in both kidneys, no operation should be performed.7. The competency of the healthy kidney should be proved by repeated catheterization of the ureters before nephrectomy and the removal of all toxic ele- ments from the blood should be secured by a liquid diet, irrigation of the colon and hydration of the whole system for some days before the removal of the kidney.8. Lumbar, extraperitoneal nephrectomy is the safer operation.9. In women the removal of the ureter should be completed through the vagina.10. Any remaining tuberculosis of the bladder should be treated locally by curetting or cauterization.11. Catheterization of the ureter is not a dangerous procedure and it may easily be accomplished in women with the simple cystoscope of Simon, Pawlik or Kelley, and in men with the more complicated instru- ment of Casper.
Immunopathology of Insulin
Authors: A. R. Colwell
Journal: JAMA (1972)

This compact monograph, sixth of an internationally edited series on endocrinology, reports several years' research on the antigenicity of insulin. Its greatest value is the application of new immunochemical methods to clinical material, yielding information important in dealing with insulin-treated diabetics. The ultimate contribution to allergic patients (one third of the total) would be the administration of synthetic human or purified animal insulin. True insulin resistance appears in only 0.1% of this group. The author reviews the mechanisms of cellular and humoral response to insulin antigen. Details of immune testing techniques, such as immunofluorescence, lymphocyte transformation test, antigen binding by leukocytes, and the immune adherence method, are thoroughly presented. Applied to 14 patients treated in the diabetic clinic in Frankfurt, Germany, and correlated with skin biopsy, they permit interpretation of therapy of the particular allergy. Injection of guinea pigs with bovine insulin failed to induce immunological lesions in pancreas or
Lung injury and oxidoreductases.
Authors: J R Hoidal, P Xu, T Huecksteadt, K A Sanders, K Pfeffer, A B Sturrock
Journal: Environmental Health Perspectives (1998)

Acute lung injury represents a wide spectrum of pathologic processes, the most severe end of the spectrum being the acute respiratory distress syndrome. Reactive oxygen intermediates have been implicated as important in the pathobiochemistry of acute lung injury. The endogenous sources that contribute to the generation of reactive oxygen intermediates in acute lung injury are poorly defined but probably include the molybdenum hydroxylases, NAD(P)H oxidoreductases, the mitochondrial electron transport chain, and arachidonic acid-metabolizing enzymes. Our laboratory has focused, in particular, on the regulation of two of these enzyme systems, xanthine oxidoreductase (XDH/XO) and NAD(P)H oxidase. We observe that gene expression of XDH/XO is regulatory in a cell-specific manner and is markedly affected by inflammatory cytokines, steroids, and physiologic events such as hypoxia. Posttranslational processing is also important in regulating XDH/XO activity. More recently, the laboratory has characterized an NAD(P)H oxidase in vascular cells. The cytochrome components of the oxidase, gp91 and p22, appear similar to the components present in phagocytic cells that contribute to their respiratory burst. In human vascular endothelial and smooth muscle cells, oncostatin M potently induces gp91 expression. We believe that regulation of gp91 is a central controlling factor in expression of the vascular NAD(P)H oxidase. In summary, the studies support the concept that the oxidoreductases of vascular cells are expressed in a highly regulated and self-specific fashion.
Treatment of chronic hepatitis B with interferon alfa-2b
Authors: R. Müller, R. Baumgarten, R. Markus, M. Schulz, H. Wittenberg, B. Hintsche-Kilger, J.-D. Fengler, P. Von Wussow, H. Meisel, H. Klein, K. Malmus, F.W. Schmidt
Journal: Journal of Hepatology (1990)
A comparison of low- with high-osmolality contrast agents in cardiac angiography. Identification of criteria for selective use.
Authors: W H Matthai, W G Kussmaul, J Krol, J E Goin, J S Schwartz, J W Hirshfeld
Journal: Circulation (1994)

BACKGROUND Controversy exists as to whether low-osmolality radiographic contrast agents, which have less detrimental pharmacological effects but are considerably more expensive than high-osmolality agents, should be used universally or only for selected high-risk patients. METHODS AND RESULTS A randomized, double-blind study was used to compare the frequency and severity of adverse events in 2245 consecutive patients undergoing diagnostic cardiac angiography. Two thousand one hundred sixty-six patients were successfully randomized to either iohexol, a low-osmolality contrast agent, or diatrizoate (as Hypaque 76), a high-osmolality agent. The end point event included clinically important adverse events (which jeopardized the patient or required aggressive treatment), contrast agent-related procedure abbreviations, and conversion to open-label contrast agent. Clinically important end point events were associated with increased age, New York Heart Association functional class, left ventricular end-diastolic pressure, arteriovenous oxygen difference, severity of coronary artery disease, and history of a previous reaction to contrast agent. End point events were less frequent in patients receiving iohexol (2.6% versus 4.6%; adjusted odds ratio, 1.59; 95% confidence interval, 0.97-2.60; P = .07). The difference in event frequency between iohexol and diatrizoate was confined to the highest-risk quartile of the patient population. An algorithm was developed to classify patients as being at high or low risk for an event based on patient age, New York Heart Association class, history of a prior contrast reaction, and left ventricular end-diastolic pressure. Application of this algorithm for selective use of low-osmolality agents only for high-risk patients to a theoretical population of 1000 patients reduced contrast agent costs 66% without increasing the frequency of contrast agent-related adverse events. CONCLUSIONS The advantages of low-osmolality contrast agents are clinically important in patients with severe heart disease but are not in less ill patients. Universal use of low-osmolality agents for cardiac angiography in an unselected population is not necessary. Appropriately guided selective use of low-osmolality contrast agents is feasible and has the potential to reduce cost substantially without compromising safety or effectiveness.
The Syndrome of Basal Encephalocele and Hypothalamic-Pituitary Dysfunction
Authors: JEFFREY M. LIEBLICH
Journal: Annals of Internal Medicine (1978)

We documented hypothalamic-pituitary dysfunction in three patients with congenital herniation of the brain through the base of the skull (basal encephalocele). All had growth hormone deficiency, although one has attained normal height. One had diabetes insipidus. Two had hypogonadotropic hypogonadism. Prolactin secretion was elevated in one, normal in another, and borderline low in the third. Two patients were euthyroid, but in response to thyrotropin-releasing hormone (TRH) injection, one patient's thyrotropin (TSH) level increased to levels exceeding normal while the other's did not attain normal levels. In the third patient, TSH response to TRH went from subnormal to normal after treatment with growth hormone and thyroxine. No patient had evidence of ACTH deficiency. These heterogeneous findings do not permit assignment of an unequivocal anatomic or functional site to the endocrine defect (s). Pituitary function should be evaluated in all patients with basal encephalocele, and this entity should be considered in the differential diagnosis of central endocrine malfunction.
BMJ awards honour courage, determination, vision, and insight in medicine
Authors: N. Hawkes
Journal: BMJ (2010)

Health care wears many faces, and most of them were on display at the second annual BMJ Group Awards presentations at the Hilton on Park Lane on March 10. From clinical choices to patients’ voices, the awards seek to celebrate all that is best in the world of medicine.

This year’s were bigger in all respects than the inaugural event in 2009: more entries, a huge vote of 40 000 BMJ readers for the Lifetime Achievement Award, and a larger venue to satisfy the demand for tickets. The common factor among the winners, diverse as they were, was leadership. They had all led in championing new ideas—in the laboratory, the clinic, the hospital, in education, communication and primary care, and in spreading those ideas more equitably across the world.

Fiona Godlee, the BMJ ’s editor, introduced the awards by expressing her delight at the quantity and quality of nominations—700 doctors or teams had been nominated for 11 awards. Professor Gordon Dickson, chief executive officer and secretary of the principal sponsor, MDDUS (the Medical and Dental Defence Union of Scotland), said it was a night for celebration for everybody who worked every day in health care. His organisation’s sponsorship of the awards, he suggested modestly, might go some way to dispel the myth of the mean Scot.

The writer and comedian Tony Hawks was the compere for the evening, remarking that he had once won an award himself. “I won junior musician of the year” he said. “It wasn’t such good news. He was a very irritating nine year old cellist.”

The first category, Research Paper of the Year, went to researchers from the World Health Organization, led by Dr Melba Gomes, for a paper published in the Lancet showing that children with severe malaria unable to take oral treatment could be …
Criticism of a Critic.
Authors: D. Colvin
Journal: JAMA (1897)

Clyde, N. Y., July 28, 1897. <h3>To the Editor:</h3> —In the number for July 24, page 196,I notice under the title " The Jubilee Meeting," that among your exchanges there is one journal,<i>Buffalo Medical and Surgical</i>, which is deeply grieved that the representative of the anarchistic element of the profession of this State—" president of the Medical Society of the State of New York," was not allowed to participate in the proceedings," etc. The writer also laments that " a great medical society" was thus ignored. If the writer was not in his swaddling clothes at the time, does he fail to remember the insurrection in which he and his fellow-revolutionists were engaged—an insurrection the purpose of which those revolutionists boldly proclaimed was the expunging of the Code of Ethics from the Constitution of that "great medical society" by which, since 1807, it had been governed? This mournful state of feeling,
Notes on the Operative Surgery of the Face
Authors: F. Jordan
Journal: BMJ (1868)

psciiple determined the remuneation of the medical man If such Wer the case, there could be no objection to an exclusdve stadard But we know this is not so, either in public apointments or ui priate ptice; and the necesr consequence of suh a stadard would be to starve the public service, and to deny to our teeming population a sufficient supply of qualified medical men.(To k condludd.)OBSTETRIC MEMORANDA.[UNDER this head, we shall, from time to time, as materials come to hand from correspondents, publish records of cases remarkable in themselves, or illustrating points of interest in obstetric practice, the- rapeutic or manipulative.We shall probably in this way preserve from oblivion the notes of very many useful and instructive occurrences in private practice; for the great obstetric experience is that-for the most part hitherto unwritten-of the great body ofgeneral practitioners throughout Great Britain.We will only ask those who may forward cases for record, to relate them with the utmost.brevity,and equally to condense any appended remarks.
α<sub>5</sub> β<sub>1</sub> -integrins are sensors for tauroursodeoxycholic acid in hepatocytes
Authors: Holger Gohlke, Birte Schmitz, Annika Sommerfeld, Roland Reinehr, Dieter Häussinger
Journal: Hepatology (2012)

Ursodeoxycholic acid, which in vivo is converted to its taurine conjugate tauroursodeoxycholic acid (TUDC), is a mainstay for the treatment of cholestatic liver disease. Earlier work showed that TUDC exerts its choleretic properties in the perfused rat liver in an α5 β1 integrin-mediated way. However, the molecular basis of TUDC-sensing in the liver is unknown. We herein show that TUDC (20 μmol/L) induces in perfused rat liver and human HepG2 cells the rapid appearance of the active conformation of the β1 subunit of α5 β1 integrins, followed by an activating phosphorylation of extracellular signal-regulated kinases. TUDC-induced kinase activation was no longer observed after β1 integrin knockdown in isolated rat hepatocytes or in the presence of an integrin-antagonistic hexapeptide in perfused rat liver. TUDC-induced β1 integrin activation occurred predominantly inside the hepatocyte and required TUDC uptake by way of the Na(+) /taurocholate cotransporting peptide. Molecular dynamics simulations of a 3D model of α5 β1 integrin with TUDC bound revealed significant conformational changes within the head region that have been linked to integrin activation before.TUDC can directly activate intrahepatocytic β1 integrins, which trigger signal transduction pathways toward choleresis. (HEPATOLOGY 2013).