tbuckley/cabot-search huggingface dataset:
Morpholino Treatment Improves Muscle Function and Pathology of Pitx1 Transgenic Mice
Authors: Sachchida Nand Pandey, Yi-Chien Lee, Toshifumi Yokota, Yi-Wen Chen
Journal: Molecular Therapy (2013)

Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD). We generated a tet-repressible muscle-specific Pitx1 transgenic mouse model which develops phenotypes of muscular dystrophy after the PITX1 expression is induced. In this study, we attempted to block the translation of PITX1 protein using morpholinos. Three groups of the transgenic mice received intravenous injections of phosphorodiamidate morpholino oligomers (PMO) (100 mg/kg), octaguanidinium dendrimer-conjugated morpholino (vivo-morpholino) (10 mg/kg), or phosphate-buffered saline (PBS) after the PITX1 expression was induced. Immunoblotting data showed that PITX1 expression in the triceps and quadriceps was significantly reduced 70% and 63% by the vivo-morpholino treatment, respectively. Muscle pathology of the mice treated with the vivo-morpholino was improved by showing 44% fewer angular-shaped atrophic myofibers. Muscle function determined by grip strength was significantly improved by the vivo-morpholino treatment. The study showed that systemic delivery of the vivo-morpholino reduced the PITX1 expression and improved the muscle phenotypes. Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. The findings of this study suggest that the same principle may be applied to suppress the aberrantly expressed DUX4 in FSHD. Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD). We generated a tet-repressible muscle-specific Pitx1 transgenic mouse model which develops phenotypes of muscular dystrophy after the PITX1 expression is induced. In this study, we attempted to block the translation of PITX1 protein using morpholinos. Three groups of the transgenic mice received intravenous injections of phosphorodiamidate morpholino oligomers (PMO) (100 mg/kg), octaguanidinium dendrimer-conjugated morpholino (vivo-morpholino) (10 mg/kg), or phosphate-buffered saline (PBS) after the PITX1 expression was induced. Immunoblotting data showed that PITX1 expression in the triceps and quadriceps was significantly reduced 70% and 63% by the vivo-morpholino treatment, respectively. Muscle pathology of the mice treated with the vivo-morpholino was improved by showing 44% fewer angular-shaped atrophic myofibers. Muscle function determined by grip strength was significantly improved by the vivo-morpholino treatment. The study showed that systemic delivery of the vivo-morpholino reduced the PITX1 expression and improved the muscle phenotypes. Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. The findings of this study suggest that the same principle may be applied to suppress the aberrantly expressed DUX4 in FSHD.
Post-Transfusion Anicteric Hepatitis
Authors: Constantine L. Hampers, David Prager, John R. Senior
Journal: New England Journal of Medicine (1964)

HEPATITIS resulting from administration of blood products has been and is a very great problem in both military and civilian populations, but there continues to be considerable controversy over just how common it may be. Estimates of the frequency of serum hepatitis after blood transfusion have varied over a hundredfold, even in recent studies. Grady and Chalmers1 reported last year an attack rate of only 6 cases of hepatitis after transfusion of 10,000 units of blood, in a large study of 9 hospitals in which over 300,000 units of blood were given during the observation period. These results were very . . .
Coeliac disease and dermatitis herpetiformis: further studies of their relationship.
Authors: B B Scott, S Young, S M Rajah, J Marks, M S Losowsky
Journal: Gut (1976)

Using diagnostic criteria which are currently accepted as most reliable we have found that 19% (9/47) of patients with dermatitis herpetiformis (DH) have no evidence of coeliac disease. The incidence of HL-A8 in the DH patients was 78%, which is considerably greater than that in healthy controls and no different from that reported in coeliac disease. Furthermore, the incidence of HL-A8 was just as much increased in those DH patients without evidence of coeliac disease suggesting that HL-A8 is associated with DH per se--that is, regardless of its association with coeliac disease.
Allergic reaction to chlormethiazole.
Authors: N A Halstead, J S Madden
Journal: BMJ (1976)

showed the beneficial effect of dapsone in preventing the spread of the disease.I have also been surprised at the decision by the faculty to teach leprosy to medical students in the leprosarium, especially at Garkida, where there is an emphasis on institutional care, reconstructive surgery, and the making of prostheses and where so much time and money are spent on the patients after they have become crippled and so little on curing the patients and preventing the spread of the disease.The place to teach leprosy is in the outpatient clinic run by auxiliary staff, and the area around the medical school would be ideal for this purpose.Then it could be demonstrated that the disease can be cured, prevented, and eradicated by the administration of dapsone.
The Role of Late-Onset Autoimmune Diabetes in White Familial NIDDM Pedigrees
Authors: Steven C Elbein, Kimberley Wegner, Cindy Miles, Liping Yu, George Eisenbarth
Journal: Diabetes Care (1997)

To determine whether autoimmunity is a prominent feature of NIDDM among diabetic members in families with a strong history of NIDDM or in families with a mixture of NIDDM and IDDM.We determined GAD and islet cell (ICA512) autoantibodies from 215 NIDDM individuals and from 14 individuals with impaired glucose tolerance (IGT) of 68 families, including 1 family with maturity-onset diabetes of the young (MODY) and 3 families ascertained specifically for a mixture of NIDDM and IDDM. We tested 2 control populations: 50 unrelated spouses form Utah families, including 29 spouses with either IGT or NIDDM and 198 random nondiabetic white individuals from Colorado.We detected either GAD or ICA512 autoantibodies in 11 members of seven families and in one spouse used as a control subject. In two families, two affected individuals showed evidence of autoimmunity, but NIDDM individuals in each of the seven families showed no evidence of autoimmunity. Among the five families with both IDDM and NIDDM individuals (three families ascertained for a mixture and two families ascertained with an incidental IDDM child), antibodies were detected in members of only one family. Antibody-positive individuals were significantly younger at diabetes onset and had low waist-to-hip ratios, but were not more likely to be insulin treated.Autoimmunity is an important cause of apparent NIDDM, even among families with a strong history of NIDDM. However, autoimmunity among affected family members appeared to be a chance event and not the manifestation of a different genetic cause of diabetes.
Abstract 2034: Development of 3D bioprinted human breast cancer for <i>in vitro</i> drug screening
Authors: Shelby M. King, Sharon C. Presnell, Deborah G. Nguyen
Journal: Cancer Research (2014)

Abstract As breast cancer is a disease of multiple cell types in which the growth, invasion, and metastasis of epithelial carcinomas is heavily influenced by the surrounding cell types, screening of anti-cancer compounds using cancer cell lines grown in 2D often overestimates drug potency. Regulatory agencies are currently seeking improved preclinical oncology models to overcome hurdles to efficient drug development, including bridging the gap between the use of 2D cell lines and 3D animal models. One way to more accurately determine the effects of anti-cancer compounds is through the use of cancer tissue models that incorporate stromal cells of the tumor microenvironment. Breast stroma, composed of fibroblasts, endothelial cells, and adipocytes, plays a key role in the process of carcinogenesis and metastasis. These cell types secrete extracellular matrix, growth factors, and hormones that affect how therapeutic agents access and target cancer cells. We have used Organovo's NovoGen BioprintingTM Platform to develop a model of human breast cancer in which a core of breast cancer cells is surrounded by a physiologically-relevant stromal milieu consisting of adipocytes, mammary fibroblasts, and endothelial cells. This system has several advantages over current screening tools, including the ability to simultaneously measure the effects of small molecules on cancer cells as well as different cell types in the breast microenvironment. Histological analyses of bioprinted neotissues demonstrated that they were stable and viable for at least 14 days in culture and characterized by interaction between stroma and carcinoma compartments. Incorporation of endothelial cells into the 3D neotissue led to the formation of robust microvascular networks. Breast cancer neotissues were fabricated directly into multi-well plates and used to establish biological response profiles to the standard chemotherapeutic agents cisplatin, paclitaxel, methotrexate, and tamoxifen. The cytotoxic effects of chemotherapeutic drugs on specific cell types within the neotissues were assessed biochemically and histologically. he response of the 3D breast cancer neotissues to chemotherapeutic gents was compared to the response of 2D breast cancer cell lines to determine he relative efficacy of compounds in 2D versus 3D. This model can be used to screen new anti-cancer therapeutics in the context of the in vivo-like microenvironment, leading to enhanced efficiency and accuracy of the drug development process. Citation Format: Shelby M. King, Sharon C. Presnell, Deborah G. Nguyen. Development of 3D bioprinted human breast cancer for in vitro drug screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2034. doi:10.1158/1538-7445.AM2014-2034
Acceleration of the Body Clearance of Phenobarbital by Oral Activated Charcoal
Authors: Mary J. Berg, William G. Berlinger, Mark J. Goldberg, Reynold Spector, George F. Johnson
Journal: New England Journal of Medicine (1982)

We investigated the effect of multiple oral doses of activated charcoal on the pharmacokinetics of intravenously administered phenobarbital in a randomized crossover trial. Six healthy men volunteered to take 200 mg of phenobarbital sodium per 70 kg of body weight intravenously on two separate occasions. On one occasion, each subject received oral activated charcoal (180 g) in divided doses over three days after the infusion of phenobarbital. Serum levels of phenobarbital were measured in all subjects up to 90 hours after the infusion, and urinary excretion of phenobarbital was measured in two subjects 24 to 96 hours after the infusion. A pharmacokinetic analysis showed that the charcoal decreased the serum half-life of phenobarbital from 110±8 to 45±6 hours (S.E.M.) (P<0.01), increased the total body clearance of phenobarbital from 4.4±0.2 to 12.0±1.6 ml per kilogram per hour (P<0.01), and increased the nonrenal clearance from 52 to 80 per cent of the total body clearance. We conclude that oral administration of activated charcoal enhances the nonrenal clearance of phenobarbital. (N Engl J Med. 1982; 307:642–4.)
Key to Organ Donation May Be Cultural Awareness
Authors: Teri Randall
Journal: JAMA (1991)

PROCURING ORGANS for transplantation in a quantity that is sufficient to meet the demand is a challenge made even greater by the variety of cultural norms that coexist in the United States. Whether family members give permission for the removal of organs from potential donors depends largely on their religious and cultural beliefs. In the Hispanic-American community where the need for organs is great, so is the need to find persuasive arguments for donation. The tools to meet this challenge have very little to do with medicine. Rather, they involve the ability to view organ donation through a cultural lens, using understanding and sensitivity to each ethnic group's cultural framework and the ways in which it may influence their decision about whether to donate. Hispanic Americans place close to blacks in the need for organ transplantation. The incidence of non—insulin-dependent diabetes mellitus is three times higher in Hispanic Americans than
Expansion of the Homeostasis Model Assessment of β-Cell Function and Insulin Resistance to Enable Clinical Trial Outcome Modeling Through the Interactive Adjustment of Physiology and Treatment Effects: iHOMA2. Diabetes Care 2013;36:2324–2330
Authors: Nathan R. Hill, Jonathan C. Levy, David R. Matthews
Journal: Diabetes Care (2014)

We have modified the renal equations governing the rate of glucose excretion in the interactive homeostasis model assessment 2 (iHOMA2) model (1). On review of the equations describing the renal excretion, we noted that one of …
Calcium and vitamin D in preventing fractures: Dietary intake of calcium needs to be considered
Authors: Julian R F Walters
Journal: BMJ (2005)

Calcium and vitamin D in preventing fractures Vitamin K supplementation has powerful effectEditor-Porthouse et al conducted a good randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D 3 ) for prevention of fractures in primary care. 1 However, vitamin D and calcium are not enough.No mention was made of the extensive research from Japan and the Netherlands, which shows that vitamin K supplementation has a powerful effect in decreasing osteoporosis and osteoporosis related fractures.Combining vitamin K, vitamin D, and calcium seems ideal.Researchers from Osaka Medical College showed that vitamin K and vitamin D together increased bone density much better than vitamin K alone. 2hen comparing calcium and vitamin D alone with placebo, researchers at the University of Maastricht found little benefit on bone loss.But those randomised to take vitamin K in addition to calcium and vitamin D had significantly less femoral neck bone loss after three years. 3he Yamaguchi osteoporosis prevention study showed that vitamin K alone reduced vertebral fractures by 56% compared to placebo, comparable to the benefit found from etidronate. 4 Researchers at Hirosaki University in Japan showed that vitamin K lowered bone fractures in elderly female patients with Parkinson's by 90%. 5 The same research team showed an 86% decrease in fractures in elderly patients with Alzheimer's treated with a combination of vitamin K, vitamin D, and calcium compared with placebo.w1 If the medical standard became to first use vitamins D and K with calcium before using bisphosphonates or selective oestrogen receptor modulators, the public would save billions of dollars a year.
Reform our libel laws, but not our NHS
Authors: F. Godlee
Journal: BMJ (2010)

We need to reform England’s libel laws, not because suppression of scientific debate is getting worse—it may be; it’s hard to tell—but because it has been going on for so long. Years before Wilmshurst v NMT Medical ( BMJ 2010;340:c967 doi:10.1136/bmj.c967) and Singh v the chiropractors ( BMJ 2009;339:b4269 doi:10.1136/bmj.b4269), there was BMJ v Drummond-Jackson, one of the longest running libel cases in legal history.

As former BMJ editor Richard Smith recounts (doi:10.1136/bmj.c1227), Drummond-Jackson, a Harley street dentist, sued the BMA (as owners of the BMJ ) in 1969 for publishing a study critical of a technique with which he was closely associated. The case cost the BMJ …
Observations on the microvasculature of bone defects filled with biodegradable nanoparticulate hydroxyapatite
Authors: Olaf Kilian, Sabine Wenisch, Srikanth Karnati, Eveline Baumgart-Vogt, Anne Hild, Rosemarie Fuhrmann, Tarja Jonuleit, Elvira Dingeldein, Reinhard Schnettler, Ralf-Peter Franke
Journal: Biomaterials (2008)
Effects of Rapid Smoking
Authors: DAVID P. L. SACHS
Journal: Annals of Internal Medicine (1978)

We studied 24 healthy young male smokers to ascertain the medical safety of a highly effective smoking-abatement technique called rapid smoking. In comparison with results obtained after a 12-h cigarette fast or after normal smoking, statistically significant increases occurred after rapid smoking in heart and respiratory rates, systolic blood pressure, carboxyhemoglobin, and pH (p < 0.05), while arterial PCO2, HCO3, and serum [K+] fell (p < 0.05). Rapid smoking produced alveolar hyperventilation in all subjects. In eight, arterial PO2 increased appropriately, but in 16, fell paradoxically (p < 0.01); seven had arterial PO2 below 80 torr. Because this fall could represent ventilation/perfusion mismatch due to early bronchoconstrictive disease, in subjects with normal flow/volume loops and spirometry rapid smoking may be a simple, provocative screening test for early airway disease. Despite the changes produced there were no arrhythmias. Rapid smoking is safe for healthy subjects but should not now be used for higher-risk patients.
Cigarette Smoking and Risk of Cataracts-Reply
Authors: William G. Christen
Journal: JAMA (1993)

<h3>In Reply.</h3> —Dr Harding mentions an apparent discrepancy in the number of cataracts in our recent study of cigarette smoking and our earlier aspirin study.<sup>1</sup>In the cigarette smoking study we analyzed eyes with cataract, whereas in the aspirin study we analyzed people with cataract. In addition, we were able to identify additional incident cases since the publication of the aspirin results. Dr Salchert questions whether the study medications may have affected the results. All analyses were adjusted for the potential confounding effects of treatment assignment so the relationship of cigarette smoking with cataract was independent of study treatment. Questions concerning cataract and macular degeneration were asked of study participants because of scientific evidence that study medications might lower the risk of these diseases. Finally, Drs Ravenholt, Roy, and Harding propose mechanisms that require further study.
INTEGRATED ANALYSIS IDENTIFIES DIFFERENT METABOLIC SIGNATURES WITHIN BOTH TUMOR-INITIATING CELLS AND STEM CELLS IN A MURINE GLIOBLASTOMA MODEL
Authors: O. Sampetrean, H. Saya
Journal: Neuro-Oncology (2014)

BACKGROUND: The metabolic preference of malignant gliomas for glycolysis as an energy source is a potential diagnostic and therapeutic target. As a result of the cellular heterogeneity of these tumors, however, the relation between glycolytic preference, tumor formation and tumor maintenance has remained unknown. To address this issue, we analyzed the metabolic profiles of isogenic glioma-initiating cells (GICs) and glioma stem cells (GSCs) in a syngeneic mouse model. METHODS: GICs were established by overexpression of H-RasV12-dsRed in Ink4a/Arf–null neural stem cells. Subpopulations of GICs were obtained by single-cell cloning, and clones differing in extracellular acidification potential were used for quantification of intracellular metabolites and related enzymes. Tumors formed after intracranial implantation of the GIC clones in mice were examined for pathological features of glioma and expression of glycolytic enzymes. GSCs were established by sphere culture of dsRed-positive cells from the primary tumors and assessed for metabolic characteristics. RESULTS: Malignant transformation of neural stem cells resulted in a distinct shift in metabolism, with a significant increase in lactic acid production as the most pronounced characteristic of all malignant cells. Interestingly however, both GICs and GSCs could adopt two different metabolic profiles. Some clones displayed high glucose consumption and lactate production, while others consumed more oxygen, produced more ATP and had a higher respiratory capacity. The glycolytic clones exhibited higher levels of key glycolytic enzymes such as hexokinase 2 and pyruvate kinase M2, and the clones relying on oxidative phosphorylation had lower levels of pyruvate dehydrogenase kinase 1. While all GICs had equal tumorigenic ability, the differential expression of the metabolic enzymes persisted in the tumors formed by these clones in vivo, as well as in the GSCs of the respective tumors. CONCLUSIONS: The metabolic characteristics of glioma cells appear early during malignant transformation and persist until the late stages of tumor formation. However, even isogenic clones may be heterogeneous in terms of metabolic features, with both GICs and GSCs being able to satisfy their bioenergetics needs not only through aerobic glycolysis, but also through oxidative phosphorylation. These results suggest that a more detailed understanding of the metabolic profile of glioma is imperative for effective diagnostic and therapeutic targeting. SECONDARY CATEGORY: n/a.
Finding Money for Health Care Reform — Rooting Out Waste, Fraud, and Abuse
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

In their quest to enact health care reform legislation, Democrats' major challenge is securing the money to pay for greatly expanded insurance coverage and more government regulation in the face of strong Republican opposition and an unsettled private sector. President Barack Obama has emphasized time and again, recently in a letter to Senators Max Baucus (D-MT) and Edward Kennedy (D-MA), that “health care reform must not add to our deficits over the next 10 years — it must be at least deficit neutral and put America on a path to reducing the deficit over time.” As the administration and its . . .
Seeking to Detect Hearing Loss at Earlier Age
Authors: Charles Marwick
Journal: JAMA (1991)

A SCREENING procedure called evoked otoacoustic emissions test now is being used to detect hearing loss in some newborns. It generates inner ear vibrations in response to acoustic stimulation from a probe containing a sensitive miniature microphone and miniature loudspeaker placed in the external canal. An acoustic click (50 stimuli per second) is emitted through the middle ear and recorded. Susan J. Norton, PhD, Children's Hospital, Seattle, Wash, says that in the United States the average age at which congenital sensorineural hearing loss is detected is 2.5 years. In Israel, the Scandinavian countries, and Britain, which now use this screening procedure, the average age when hearing impairment is detected is 7 months, she says. Norton spoke at a Washington, DC, seminar on communication disorders sponsored by the Johns Hopkins Center for Hearing and Balance, Baltimore, Md, and the National Institute on Deafness and Other Communication Disorders, National Institutes of Health,
Hyperkalemia due to Salt Substitutes
Authors: Robert E. Hoyt
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Near-fatal hyperkalemia from potassium supplements and salt substitutes continues to be an important clinical problem.<sup>1,2</sup> Although its incidence is unknown, it seems more likely to occur in azotemic patients, diabetics, or patients using drugs that affect potassium homeostasis (β-blockers, nonsteroidal anti-inflammatory drugs, captopril, spironolactone, triamterene, and amiloride).<sup>3</sup>Salt substitutes may be prescribed to reduce sodium or increase potassium intake but are also selfprescribed by an unknown number of patients. We describe a patient who experienced near-fatal hyperkalemia caused by repeated ingestion of soup heavily "seasoned" with a salt substitute. <h3>Report of a Case.—</h3> A 70-year-old woman was admitted to a local hospital for transient severe muscle weakness following dinner. She became so weak she could not stand and noted paresthesias of her hands and mild dyspnea. She denied chest pain or diaphoresis. On arrival to the emergency room she was asymptomatic. She had known angina