tbuckley/cabot-search huggingface dataset:
Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline
Authors: Konrad Talbot, Hoau-Yan Wang, Hala Kazi, Li-Ying Han, Kalindi P. Bakshi, Andres Stucky, Robert L. Fuino, Krista R. Kawaguchi, Andrew J. Samoyedny, Robert S. Wilson, Zoe Arvanitakis, Julie A. Schneider, Bryan A. Wolf, David A. Bennett, John Q. Trojanowski, Steven E. Arnold
Journal: Journal of Clinical Investigation (2012)

While a potential causal factor in Alzheimer’s disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway. Reduced insulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS616) and IRS-1 pS636/639. In the HF, these candidate biomarkers of brain insulin resistance increased commonly and progressively from normal cases to mild cognitively impaired cases to AD cases regardless of diabetes or APOE ε4 status. Levels of IRS-1 pS616 and IRS-1 pS636/639 and their activated kinases correlated positively with those of oligomeric Aβ plaques and were negatively associated with episodic and working memory, even after adjusting for Aβ plaques, neurofibrillary tangles, and APOE ε4. Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβ oligomers and yet promoting cognitive decline independent of classic AD pathology.
Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15
Authors: Yang Xu, Ming Zhang, Carlos A. Ramos, April Durett, Enli Liu, Olga Dakhova, Hao Liu, Chad J. Creighton, Adrian P. Gee, Helen E. Heslop, Cliona M. Rooney, Barbara Savoldo, Gianpietro Dotti
Journal: Blood (2014)
A Facile Nonviral Method for Delivering Genes and siRNAs to Skeletal Muscle of Mammalian Limbs
Authors: James E. Hagstrom, Julia Hegge, Guofeng Zhang, Mark Noble, Vladimir Budker, David L. Lewis, Hans Herweijer, Jon A. Wolff
Journal: Molecular Therapy (2004)

Delivery is increasingly being recognized as the critical hurdle holding back the tremendous promise of nucleic acid-based therapies that include gene therapy and more recently siRNA-based therapeutics. While numerous candidate genes (and siRNA sequences) with therapeutic potential have been identified, their utility has not yet been realized because of inefficient and/or unsafe delivery technologies. We now describe an intravascular, nonviral methodology that enables efficient and repeatable delivery of nucleic acids to muscle cells (myofibers) throughout the limb muscles of mammals. The procedure involves the injection of naked plasmid DNA or siRNA into a distal vein of a limb that is transiently isolated by a tourniquet or blood pressure cuff. Nucleic acid delivery to myofibers is facilitated by its rapid injection in sufficient volume to enable extravasation of the nucleic acid solution into muscle tissue. High levels of transgene expression in skeletal muscle were achieved in both small and large animals with minimal toxicity. Evidence of siRNA delivery to limb muscle was also obtained. The simplicity, effectiveness, and safety of the procedure make this methodology well suited to limb muscle gene therapy applications.
To Save or Let Die
Authors: Richard A. McCormick
Journal: JAMA (1974)

ON Feb 24, the son of Mr. and Mrs. Robert H. T. Houle died following court-ordered emergency surgery at Maine Medical Center. The child was born Feb 9, horribly deformed. His entire left side was malformed; he had no left eye, was practically without a left ear, had a deformed left hand; some of his vertebrae were not fused. Furthermore, he was afflicted with a tracheal esophageal fistula and could not be fed by mouth. Air leaked into his stomach instead of going to the lungs, and fluid from the stomach pushed up into the lungs. As Dr. Andre Hellegers recently noted, "It takes little imagination to think there were further internal deformities" (<i>Obstetrical and Gynecological News</i>, April 1974). As the days passed, the condition of the child deteriorated. Pneumonia set in. His reflexes became impaired and because of poor circulation, severe brain damage was suspected. The tracheal esophageal fistula,
Hirsutism — Beyond the Steroidogenic Block
Authors: David A. Ehrmann, Robert L. Rosenfield
Journal: New England Journal of Medicine (1990)

Hirsutism is a common condition that presents unique diagnostic and therapeutic challenges, and the assessment of patients with hirsutism requires both clinical and biochemical evaluation. The former is relatively straightforward; the latter, however, can be a formidable process, as described in this issue of the Journal.1 , 2 Clinical assessment involves first distinguishing abnormal hair growth that is androgen-dependent (hirsutism) from that which is androgen-independent (hypertrichosis). Small amounts of male-pattern hair growth in women are normal. A woman is considered to have hirsutism when she has a score of 8 or more on the Ferriman and Gallwey scale, in which hair . . .
Mefenamic acid nephropathy: further evidence.
Authors: P L Drury, L G Asirdas, G V Bulger
Journal: BMJ (1981)

~~~~~~~~~~~~~' .7 ~~~A Disrupted crypts distended by mucin and polymorphs and loss of the epithelial surface.Haematoxylin and eosin x 100 (original magnification).Clostridium perfringens, and Cl difficile.Biopsy material from the second sigmoidoscopy was cultured on the medium described by George et al' and yielded a growth of Cl cadaveria.Cl difficile was not isolated.Faecal specimens and biopsy material were examined by tissue culture assay for the presence of a cytotoxin that could be neutralised by Cl sordellii antitoxin, but no toxin was shown.The strain of Cl cadaveria isolated also failed to produce a cytopathic change.Despite these negative cultural and toxicological findings, we decided to treat the patient with vancomycin 500 mg four times daily for five days.At the end of this period her illness had completely resolved clinically, and appearances on sigmoidoscopy were normal.We thank Mr A J Mack for allowing us to report this case and Dr W McNaught for his helpful comments.
AN EASY METHOD OF REMOVING PLASTER CASTS
Authors: Ralph J. Malott
Journal: JAMA (1933)

Essentially, this method consists in creating, at the time of application, free channels between the gauze or wadding and the plaster, enabling one to saw through the plaster with a gigli saw, along a predetermined line. Waterproof paper tubules (soda straws or similar casings) are threaded on a stout cord or a flexible wire of considerable tensile strength and applied over the gauze or wadding surrounding the part to be covered by the cast. At intervals of no greater than 12 inches the tubules, with encased cord or wire, are looped outward for a slightly greater length than the proposed thickness of the plaster cast. These loops are passed through perforated gummed paper strips, which, attached to the gauze, maintain their position. The line of cleavage of the cast is determined at this time and may be a straight line or may be laid to meet the exigencies of the
The Danish Microbiology Database (MiBa) 2010 to 2013
Authors: M Voldstedlund, M Haarh, K Mølbak, None the MiBa Board of Representatives
Journal: Eurosurveillance (2014)

The Danish Microbiology Database (MiBa) is a national database that receives copies of reports from all Danish departments of clinical microbiology. The database was launched in order to provide healthcare personnel with nationwide access to microbiology reports and to enable real-time surveillance of communicable diseases and microorganisms. The establishment and management of MiBa has been a collaborative process among stakeholders, and the present paper summarises lessons learned from this nationwide endeavour which may be relevant to similar projects in the rapidly changing landscape of health informatics.
Healthcare Disparities at the Crossroads With Healthcare Reform
Authors: Lenny Lopez, Eric G. Campbell
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Dispensing with prescriptions
Authors: R E Ferner
Journal: BMJ (1994)

Pharmaceutical products are licensed as prescription only medicines; non -prescription medicines available only from a pharmacy; or products on the general sales list, which can be sold in any shop. The licences of several medicines have recently been switched from prescription only to pharmacy only, and all prescription only medicines will now be reviewed every few years to see whether restriction on their sale remains justified. From 1983 to 1992, 11 products made the transition; by the end of 1994, 26 will have done so. The categories of drugs that can now be bought without prescription include non -sedating antihistamines, corticosteroids for topical use in hayfever, oral and topical non-steroidal anti-inflammatory drugs, nicotine patches, and H2 antagonists.

The change of status brings several advantages. Patients can benefit from more effective treatments for a wider range of minor ailments without needing to see their doctor. Similarly, general practitioners will be pleased that …
Money, Sex, and Religion — The Supreme Court's ACA Sequel
Authors: George J. Annas, Theodore W. Ruger, Jennifer Prah Ruger
Journal: New England Journal of Medicine (2014)

Interview with Prof. George Annas on the Supreme Court’s Hobby Lobby decision and its context and implications. (11:10)Download In Hobby Lobby, the Supreme Court ruled that the ACA burdens the exercise of religion by imposing fines if a company does not provide insurance coverage for all FDA-approved contraception. The authors argue that this undermines the ACA's goal of universal access to health care.
Peritoneovenous (LeVeen) Shunt
Authors: Marlys H. Witte, Charles L. Witte, Shannon Jacobs, Robin Kut
Journal: JAMA (1978)

Because of the unusual clinical course of a patient with hepatic cirrhosis, refractory ascites, and hepatorenal syndrome, we were able to examine the complex interrelationships between massive ascites, renin-aldosterone activity, and renal and hepatic function before and after placement of a peritoneojugular vein (LeVeen) shunt. Measurements indicated that when the shunt was functioning, renin-aldosterone production was suppressed, the hepatorenal syndrome was reversed, and ascites remitted. These data suggest that hyperreninemia, hyperaldosteronism, and functional renal abnormalities of this disorder are potentially reversible and arise primarily from the imbalance between formation and drainage of hepatosplanchnic lymph rather than from hepatocellular dysfunction, lowered plasma oncotic pressure, or portal hypertension. (<i>JAMA</i>239:31-33, 1978)
Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells
Authors: Nathalie Scamuffa, Geraldine Siegfried, Yannick Bontemps, Liming Ma, Ajoy Basak, Ghislaine Cherel, Fabien Calvo, Nabil G. Seidah, Abdel-Majid Khatib
Journal: Journal of Clinical Investigation (2008)

The proprotein convertases (PCs) are implicated in the activation of various precursor proteins that play an important role in tumor cell metastasis. Here, we report their involvement in the regulation of the metastatic potential of colorectal tumor cells. PC function in the human and murine colon carcinoma cell lines HT-29 and CT-26, respectively, was inhibited using siRNA targeting the PCs furin, PACE4, PC5, and PC7 or by overexpression of the general PC inhibitor α1-antitrypsin Portland (α1-PDX). We found that overexpression of α1-PDX and knockdown of furin expression inhibited processing of IGF-1 receptor and its subsequent activation by IGF-1 to induce IRS-1 and Akt phosphorylation, all important in colon carcinoma metastasis. These data suggest that the PC furin is a major IGF-1 receptor convertase. Expression of α1-PDX reduced the production of TNF-α and IL-1α by human colon carcinoma cells, and incubation of murine liver endothelial cells with conditioned media derived from these cells failed to induce tumor cell adhesion to activated murine endothelial cells, a critical step in metastatic invasion. Furthermore, colon carcinoma cells in which PC activity was inhibited by overexpression of α1-PDX when injected into the portal vein of mice showed a significantly reduced ability to form liver metastases. This suggests that inhibition of PCs is a potentially promising strategy for the prevention of colorectal liver metastasis.
THE IMPACT OF DRUG–ELUTING STENT TYPE ON LATE RESTENOSIS AND LATE REGRESSION
Authors: Yusuke Hyodo, Kazushige Kadota, Yasushi Fuku, Koshi Miyake, Yuki Hayakawa, Naoki Saito, Hideaki Otsuji, Suguru Otsuru, Daiji Hasegawa, Yoshikazu Shigemoto, Seiji Habara, Hiroyuki Tanaka, Takeshi Tada, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2013)
THE CONCENTRATION OF THE PLASMA PROTEINS IN NEPHRITIS
Authors: G. C. Linder, C. Lundsgaard, D. D. Van Slyke
Journal: The Journal of Experimental Medicine (1924)

In nephrosclerosis (Volhard and Fahr classification of nephritis) there was no decrease in the plasma proteins. With heart failure the ratio of albumin to globulin fell from the normal 1.7 ± 0.3 to about 1. There is a sharp difference between the two types of glomerulonephritis in the effect on plasma proteins. In the vascular-interstitial type the effect was the same as in nephrosclerosis. There was no decrease in the plasma proteins until shortly before death. In the glomerulotubular or nephrotic type, active or recently active, the total plasma proteins were less than 5 gm. per 100 cc. This decrease from the normal 5.5 to 7.5 occurred whether edema was present or absent. The decrease affected chiefly the albumin, the globulin being usually diminished but little, and sometimes slightly increased. Consequently the ratio of albumin to globulin was reduced to less than 1, and occasionally to 0.6. In nephrosis similar changes were found in the total protein concentration but in severe cases the decrease in albumin was greater than in nephrotic glomerulonephritis while the globulin was either very slightly reduced or was increased. The albumin : globulin ratio was therefore lower than in nephrotic glomerulonephritis, ranging down to 0.26. With the disappearance of edema there was usually an increase in the plasma protein concentration, but this was not invariable, and concentrations of 4.5 per cent or less were compatible with the persistent absence of edema. The ratio of albumin to globulin showed an irregular tendency to rise. Whenever the total concentration was less than 4 per cent there was some edema present, but it was sometimes slight in amount. With recovery in acute cases, and remission with decrease of proteinuria in chronic cases, normal concentrations were regained. The albumin : globulin ratio remained low in some instances for a longer period on account of an absolute increase in globulin concentration. In "functional proteinuria" no change in plasma proteins was found. Low plasma protein concentrations were always associated with considerable losses of protein in the urine, but these losses did not provide an explanation for all our observations. A disturbance in the production of the plasma proteins appears probable.
PT-06 * RANDOMIZED TRIAL OF HIGH-PRECISION CONFORMAL RADIATION THERAPY COMPARED TO CONVENTIONAL RADIOTHERAPY IN PRESERVATION OF LONG-TERM NEURO-COGNITIVE OUTCOMES IN YOUNG PATIENTS WITH PROGRESSIVE OR RESIDUAL BENIGN/LOW-GRADE BRAIN TUMORS
Authors: R. Jalali, T. Gupta, S. Goswami, U. Krishna, D. Dutta, J. Deodhar, S. Kannan, R. Sarin
Journal: Neuro-Oncology (2014)

BACKGROUND: To report neuro-psychological outcomes in young patients with progressive benign and low-grade brain tumors treated with high-precision stereotactic conformal radiotherapy (SCRT) versus conventional radiotherapy (Conv RT) (NCT00517959). METHODS: Between 2001-10, 200 patients (median age 13 years, commonest histology craniopraryngioma) were randomized to SCRT (n = 105; 6MV, non-coplanar fields using micromultileaf collimators) or Conv RT (n = 95; 6MV, 2-4 open fields) to 54 Gy/30 fractions. Neuropsychological battery included full-scale IQ (FSIQ), verbal quotient (VQ), performance quotient (PQ), memory quotient (MQ in patients > 16 years) by Wechsler scores, LOTCA battery and state-trait Anxiety Inventory and Hamilton Anxiety-Depression Scales. Serial evaluations were performed at baseline (pre-RT), 6-months and 2, 3, 4, and 5-years post-RT and analyzed using generalized linear-mixed model (GLMM). RESULTS: Pre- RT baseline revealed considerable proportion of patients with low intelligence in both arms indicating effects of tumor and prior treatments. GLMM for repeated measures demonstrated significantly better preservation of FSIQ over time in SCRT versus Conv RT arm at 3 years (p = 0.0003) and 5 years (p = 0.012). There was significantly better preservation of VQ (age < 16 years) (p = 0.047) and MQ (age > 16 years) (p = 0.049) in SCRT than Conv RT arm. Anxiety scores between two arms was not significant at 5 years but mean depression scores at 5 years in age group <16 years was found significantly higher in Conv RT arm (p = 0.01). Patients in Conv RT also had significantly more neurocognitive decline in LOTCA battery at 5 years (p = 0.019), particularly in visuomotor organization and attention-concentration domains. CONCLUSIONS: We demonstrate high-precision conformal radiotherapy superior to conventional radiotherapy in preservation of neuropsychological functions in young patients with benign/low grade brain tumors. This is among few trials generating evidence for use of modern conformal RT from an appropriately-powered trial with clinically relevant endpoints and act as suitable benchmark for testing newer RT- technologies.
Thalidomide for Malignant Melanoma
Authors: Ganesh C. Kudva, Brian T. Collins, Frank R. Dunphy
Journal: New England Journal of Medicine (2001)

To the Editor: Ridker and colleagues (June 28 issue) 1 demonstrated that the rate of acute coronary events among subjects with a base-line low-density lipoprotein (LDL) cholesterol level below 149.1 mg per deciliter and a C-reactive protein level above 0.16 mg per deciliter was higher among those given placebo than among those treated with lovastatin in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).The authors conclude that C-reactive protein measurements may be useful in targeting statin therapy in patients with relatively low lipid levels.This conclusion is based on a difference of 15 events between the treatment groups and is unlikely to be valid.The interpretation of the C-reactive protein level is wholly dependent on the subsequent use of aspirin, as Ridker and colleagues previously demonstrated in the Physicians' Health Study. 2 The relation between the subsequent nonuse of aspirin and the inflation of the relative risk associated with the high C-reactive protein level is a form of effect modification.Once effect modification has been found, it should be handled in all future analyses by stratification -in this case, according to the use or nonuse of aspirin.Simply put, the authors must demonstrate that it was the high C-reactive protein level, and not the nonuse of aspirin, that created the 15-event difference.It is disturbing that Ridker and colleagues continue to publish analyses of a variety of data sets and fail to account for aspirin use, hence inflating the perceived value of C-reactive protein as a tool for risk prediction.Conventional risk factors have stood the test of time because of their independence from other risk factors and concurrent therapy.Given that the relative risk associated with elevated levels of C-reactive protein is increased by the nonuse of aspirin and that the level of C-reactive protein falls with statin therapy, it is unlikely that C-reactive protein will be useful for the valid prediction of cardiovascular risk.
Biliary Scanning Interpretations Using Technetium-99m DISIDA
Authors: PETER W. BLUE
Journal: Clinical Nuclear Medicine (1985)

The use of the Tc-99m iminodiacetic acid (IDA) derivatives has significantly enhanced the role of nuclearmedicine in the evaluation of biliary disorders (1-3).Now that Tc-99m DISIDA is commercially available, biliary scintigraphy is increasingly popular. In order to simplify interpretation in the majority of cases, an interpretative scheme and flow sheet for diagnosis of non-postoperative biliary disorders and examples are presented.
DNA-based prenatal diagnosis in a Chinese family with xeroderma pigmentosum group A
Authors: Y. Yang, B. Ding, K. Wang, D. Bu, P. Tu, X. Zhu
Journal: British Journal of Dermatology (2004)

Background Xeroderma pigmentosum (XP) is a group of autosomal recessive diseases characterized by hypersensitivity to ultraviolet rays. Among its eight complementation groups, XP group A (XPA) is the most severe type. The XPAC gene has been identified as the defective gene in XPA patients. Objectives To examine genomic DNA from a Chinese family with XPA, to determine the XPAC mutation and, after genetic counselling, to undertake DNA‐based prenatal diagnosis in a subsequent pregnancy. Methods Fetal DNA was extracted from amniotic fluid and used to amplify exon 5 of XPAC containing the potential mutation. Direct sequencing and restriction endonuclease digestion were used for prenatal diagnosis. Results We identified a homozygous nonsense XPAC mutation of 631C→T, which results in an R211X mutation in XPA protein, in the proband. Both her parents are heterozygous. Prenatal diagnosis demonstrated a heterozygous sequence predicting an unaffected child, and a healthy girl was born. Conclusions These data provide the first example of a DNA‐based prenatal test for genodermatosis in China.