tbuckley/cabot-search huggingface dataset:
Glycogen Stored in Skeletal but Not in Cardiac Muscle in Acid α-Glucosidase Mutant (Pompe) Mice Is Highly Resistant to Transgene-Encoded Human Enzyme
Authors: Nina Raben, Tejas Jatkar, Alicia Lee, Nina Lu, Sunita Dwivedi, Kanneboyina Nagaraju, Paul H. Plotz
Journal: Molecular Therapy (2002)

Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease. We have addressed the issue of reversibility of the disease in the Gaa(-/-) mouse model. We have made transgenic lines expressing human GAA in skeletal and cardiac muscle of Gaa(-/-) mice, and we turned the transgene on at different stages of disease progression by using a tetracycline-controllable system. We have demonstrated that levels of 20-30% of normal activity are indeed sufficient to clear glycogen in the heart of young Gaa(-/-) mice, but not in older mice with a considerably higher glycogen load. However, in skeletal muscle-a major organ affected in infantile and in milder, late-onset variants in humans-induction of GAA expression in young Gaa(-/-) mice to levels greatly exceeding wildtype values did not result in full phenotypic correction, and some muscle fibers showed little or no glycogen clearance. The results demonstrate that complete reversal of pathology in skeletal muscle or long-affected heart muscle will require much more enzyme than previously expected or a different approach.
Frequent Outpatient Contact and Decreasing Medication Affordability in Patients With Diabetes From 1997 to 2004
Authors: Richard W. Grant, Ellen P. McCarthy, Daniel E. Singer, James B. Meigs
Journal: Diabetes Care (2006)

Despite significant changes in treatment standards for diabetes, there has been little improvement in overall rates of metabolic control (1–5). In recent years, diabetes medical regimen complexity has also increased markedly, with the proportion of U.S. patients taking five or more prescription medicines nearly doubling (from 18 to 30%) from 1994 to 2003 (6). Given the persistent difficulty in achieving ideal metabolic control and the increasing complexity of medical care, further insight into current diabetes outpatient management is required.

We used data from the National Health Interview Survey (NHIS) to examine U.S. annual trends in diabetes care from 1997 to 2004. The NHIS is an annual nationwide in-person household survey conducted by the Census Bureau that includes an in-depth adult health care access and utilization survey. Sampled adults were asked about demographic and socioeconomic information, diagnosed conditions, self-reported ability to afford prescription medications in the prior year, perceived barriers to obtaining clinic appointments (e.g., long waits for appointments, difficulty making appointments, difficulty reaching the clinic by phone), and frequency of outpatient clinical contact (excluding overnight hospitalizations, telephone calls, and emergency room, dental, or home visits). Response rates over this 8-year period varied from 80.8 to 90.3%.

We limited our analyses to adults who self-identified as having a diagnosis of nongestational diabetes. We created a single independent variable for year (numbered 1–8) and used logistic regression for dichotomous and linear …
Bipolar Disorder and Addiction
Authors: Bridget M. Kuehn
Journal: JAMA (2010)

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
STUDIES ON THE EFFECT OF EXPERIMENTAL NONKETOTIC DIABETES MELLITUS ON ANTIBACTERIAL DEFENSE
Authors: Robert H. Drachman, Richard K. Root, W. Barry Wood
Journal: The Journal of Experimental Medicine (1966)

Chronically diabetic nonketotic rats were shown to be more susceptible to experimental Type 25 pneumococcal pneumonia than nondiabetic rats. The cumulative mortality in the diabetic group was significantly higher at infecting doses of 10(3), 10(4), 10(5), and 10(6) organisms, and the LD(50) was less than one twentieth of that for the nondiabetic group. More than ten times as many viable pneumococci were found in the pneumonic lesions of the diabetic animals at 24 and 36 hr as were present in the lesions of the nondiabetic controls, and serial histologic studies revealed that phagocytosis was strikingly depressed in the alveolar exudates of the diabetic animals. The diabetic state was also found to cause a similar depression of in vivo phagocytosis in preformed peritoneal exudates. The results of in vitro experiments indicated that the principal defect in the diabetic animals resided in their serum rather than in their polymorphonuclear leukocytes. The depressive factor in the serum was identified as the abnormally high concentration of glucose. Since equivalent molar concentrations of unmetabolized sugars added to normal serum caused a similar depression of phagocytosis, it was tentatively concluded that the action of the glucose on the leukocytes was primarily osmotic. The sensitivity of the granulocytes to the glucose effect, however, depended upon the conditions of the phagocytic test. Only when the pneumococci were encapsulated and the leukocytes derived from inflammatory exudates were crowded together, as in vivo, was the depressive action of the glucose clearly demonstrable.
Polycystic Kidney Disease: Prospective Analysis of Nonazotemic Patients and Family Members
Authors: PATRICIA A. GABOW
Journal: Annals of Internal Medicine (1984)

To develop a profile of nonazotemic polycystic kidney disease as it occurs in families, we identified and studied 164 persons with autosomal-dominant polycystic kidney disease, 81 persons suspected of having the disease, and 250 family members without the disease. Because symptoms were absent in 32% of patients with the disease but present in 30% of persons without the disease, symptoms are not reliable in screening for the disease. Hypertension and palpable kidneys and liver were significantly commoner in patients with the disease, but systolic murmur unrelated to hypertension (10.5%) and peripheral edema (9.3%) also were common. Normal laboratory values do not exclude the diagnosis of polycystic kidney disease. Ultrasonography appears to be more sensitive than excretory urography in detecting the disease and also can detect hepatic cysts. Berry aneurysms can occur and are an important cause of mortality and morbidity. The relation of renal cysts to signs, symptoms and renal function is discussed.
Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies
Authors: Mamta Gupta, Andrea E. Wahner Hendrickson, Seong Seok Yun, Jing Jing Han, Paula A. Schneider, Brian D. Koh, Mary J. Stenson, Linda E. Wellik, Jennifer C. Shing, Kevin L. Peterson, Karen S. Flatten, Allan D. Hess, B. Douglas Smith, Judith E. Karp, Sharon Barr, Thomas E. Witzig, Scott H. Kaufmann
Journal: Blood (2011)
Drowning Mortality in Los Angeles County, 1976 to 1984
Authors: Patrick W. O'Carroll
Journal: JAMA (1988)

Drowning is the fourth leading cause of unintentional injury death in Los Angeles County. We examined data collected by the Los Angeles County Coroner's Office on drownings that occurred in the county from 1976 through 1984. There were 1587 drownings (1130 males and 457 females) during this nine-year period, for an annual rate of 2.36 drownings per 100,000 persons (3.44 for males and 1.33 for females). The largest proportion of drownings (44.5%) for both sexes, and in almost every age group, occurred in private swimming pools. Children 2 to 3 years of age had the highest swimming-pool drowning rate (7.95). The elderly also experienced high drowning rates, primarily in swimming pools and bathtubs. Drowning-site profiles varied dramatically by age and sex. These findings indicate a need for Los Angeles County to address the problem of drownings among infants and toddlers in private swimming pools and to investigate the failure of regulations requiring fencing of swimming pools to prevent these deaths. These findings also suggest several potential opportunities for preventive intervention by physicians and demonstrate that health professionals cannot rely on national drowning-site profiles when developing local drowning prevention strategies.
Is malaria a predisposing factor for third molar pericoronitis in the tropics?
Authors: Foluso J. Owotade, Kehinde E. Adebiyi, Oladipo A. Aboderin, Olawunmi A. Fatusi, Eyitope O. Ogunbodede, Okechukwu Akueme
Journal: Journal of Infection (2005)
Efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in hepatitis C patients with advanced fibrosis and cirrhosis
Authors: Savino Bruno, Mitchell L. Shiffman, Stuart K. Roberts, Edward J. Gane, Diethelm Messinger, Stephanos J. Hadziyannis, Patrick Marcellin
Journal: Hepatology (2009)

The objective of this study is to determine the efficacy and safety of peginterferon alfa-2a (40KD)/ribavirin in patients with advanced fibrosis. Data from 341 genotype 1/4 patients (99 with bridging fibrosis/cirrhosis) treated for 48 weeks and 1547 genotype 2/3 patients (380 with bridging fibrosis/cirrhosis) treated for 16 or 24 weeks enrolled in three randomized international studies were analyzed. Sustained virological response (SVR) rates decreased progressively from 60% in genotype 1/4 patients without advanced fibrosis to 51% in those with bridging fibrosis and 33% in those with cirrhosis (trend test P = 0.0028); and from 76% to 61% and 57%, respectively, in genotype 2/3 patients treated for 24 weeks (trend test P < 0.0001). Irrespective of genotype, patients without advanced fibrosis were more likely to have an earlier response to treatment that was associated with higher SVR rates and lower relapse rates during untreated follow-up. Among patients with or without a diagnosis of advanced fibrosis, rates of SVR and relapse were similar for patients with similar responses in the first 12 weeks. Conclusion: Compared with patients with less severe disease, SVR rates are significantly lower in patients with advanced fibrosis. However, irrespective of genotype and degree of fibrosis, the time to become hepatitis C virus (HCV) RNA undetectable was the strongest predictor of SVR. (HEPATOLOGY 2010.)
Abstract PR3: The BLM helicase facilitates RNA polymerase l-mediated ribosomal RNA transcription
Authors: Patrick Grierson, Kate Lillard, Gregory Behbehani, Kelly Combs, Saumitri Bhattacharyya, Acharya Samir, Joanna Groden
Journal: Cancer Research (2011)

Abstract Bloom's syndrome (BS) is an autosomal recessive disorder that is invariably characterized by cancer predisposition and idiopathic growth retardation. The BLM helicase, mutations of which lead to BS, localizes to the nucleolus of the cell, the site of RNA polymerase l-mediated ribosomal RNA (rRNA) transcription. rRNA transcription is fundamental for ribosome biogenesis and therefore protein synthesis, cellular growth and proliferation; its inhibition limits cellular growth and proliferation as well as bodily growth. Disorders with defective ribosome biogenesis, such as Diamond-Blackfan anemia and Shwachman-Diamond syndrome, display similar cancer predisposition and growth abnormalities to BS. The objective of this study was to investigate a potential mechanism underlying the proportional dwarfism of BS. We tested the hypothesis that the BLM helicase facilitates rRNA transcription as a component of an RNA polymerase I-associated complex, which when deficient has the potential to lead to proportional dwarfism. We report that nucleolar BLM facilitates RNA polymerase I-mediated rRNA transcription using H3-uridine pulse-chase assays and nuclear run-on assays in cells with an innate or experimentally induced BLM deficiency. In vitro helicase assays demonstrate that BLM unwinds GC-rich hybrid RNA/DNA nucleic acid substrates predicted to form in the nucleolus during rRNA transcription; the persistence of such structures inhibits progression of the RNA polymerase I transcription complex. Immunofluorescence studies using actinomycin D at a concentration that inhibits RNA polymerase I demonstrate the dependence of BLM nucleolar localization upon ongoing RNA polymerase l-mediated rRNA transcription. Finally, in vivo protein co-immunoprecipitation shows that BLM physically associates with RNA polymerase I in the nucleolus. These studies suggest that nucleolar BLM interacts with RNA polymerase I and facilitates rRNA transcription by modulating rDNA structure. Given the intricate relationship between rDNA metabolism and growth, our data may help to understand the etiology of the proportional dwarfism in Bloom's syndrome. Furthermore, this work provides greater understanding of the mechanisms regulating rRNA transcription and ribosome biogenesis, processes currently being exploited in cancer therapeutics. This abstract is also presented as Poster B34. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR3.
BIPLANE FLUOROSCOPY IN THE TREATMENT OF FRACTURES: NEW RADIOLUCENT FRACTURE STRETCHER AND NEW SURGICAL ROENTGEN-RAY UNIT
Authors: Herman B. Philips
Journal: JAMA (1925)

The advantages of simultaneous biplane fluoroscopy in the treatment of fractures is apparent to those experienced in this type of work. To be able to manipulate fragments of a fractured bone, while the limb is in an extension and retention device, and to be able, at any time within a few seconds, to fluoroscope or roentgenograph the bones in two planes, one at right angles to the other, approach the ideal in the treatment of fractures.  To attempt to fluoroscope or roentgenograph a broken bone, in more than one plane, with the patient on a Hawley, Albee or Oppenheimer fracture table, is to invite the keenest disappointment. The construction of these fracture units does not permit such procedures with any degree of success. The extreme weight, the bulkiness and the radiopacity, as well as the dangers of high tension shock, discourage any consistent attempts in this direction. For this reason,
Death Behind Bars
Authors: John E. Smialek
Journal: JAMA (1978)

HUNDREDS of suicides occur each year in small local jails. Nevertheless, the problem is relatively neglected by public officials. While deaths of inmates in federal or state prisons are the subject of analysis, to our knowledge there is no accurate evaluation of most deaths occurring in jails. In an effort to document the severity of the problem, the deaths of 25 prisoners in local Wayne County, Michigan, jails in 1976 and 1977 were studied. Wayne County's inmate population is distributed between the Wayne County jail, with a daily average of 941 prisoners, and 40 local lockups, each containing two to ten cells. These findings were reported in a survey of detention facilities in Wayne County by the Michigan Department of Corrections, Office of Jail Services, on March 24, 1976, and in the Wayne County jail report in 1977. The occurrence of 25 deaths in this population during the study can
Early Factors Associated With Fluid Sequestration and Outcomes of Patients With Acute Pancreatitis
Authors: Enrique de-Madaria, Peter A. Banks, Neftalí Moya-Hoyo, Bechien U. Wu, Mónica Rey-Riveiro, Nelly G. Acevedo-Piedra, Juan Martínez, Félix Lluís, José Sánchez-Payá, Vikesh K. Singh
Journal: Clinical Gastroenterology and Hepatology (2013)
Processing of Tumor Antigen Differentially Impacts the Development of Helper and Effector CD4+ T-cell Responses
Authors: Dannie Bernard, Michael S Ventresca, Laura A Marshall, Carole Evelegh, Yonghong Wan, Jonathan L Bramson
Journal: Molecular Therapy (2010)

CD4(+) T cells contribute to the antitumor T-cell response as both effectors that promote tumor rejection and helpers that facilitate the activation of other antitumor effector cells, such as CD8(+) T cells. Maximal engagement of both effector and helper CD4(+) T-cell responses is a desirable attribute of cancer vaccines. We have employed the B16F10 murine melanoma model and a series of recombinant adenovirus (Ad) vaccines expressing mutant forms of the tumor antigen, dopachrome tautomerase, to investigate the relationship between antigen processing and the antitumor CD4(+) T-cell response. Our results have revealed an unexpected dichotomy in the generation of helper and effector CD4(+) T-cell responses where CD4(+) T effector responses are dependent upon protein processing and trafficking, whereas CD4(+) T helper responses are not. The results have important implications for strategies aimed at augmenting antigen immunogenicity by altering intracellular processing and localization.
A REPLY TO THE EDITOR'S COMMENT
Authors: ARTHUR R. RIDDLE
Journal: British Journal of Dermatology (1935)

Journal Article A REPLY TO THE EDITOR'S COMMENT Get access ARTHUR R. RIDDLE ARTHUR R. RIDDLE Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 47, Issue 10, 1 October 1935, Pages 407–408, https://doi.org/10.1111/j.1365-2133.1935.tb09819.x Published: 01 October 1935
The Development of American Pharmacology: John J. Abel and the Shaping of a Discipline
Authors: Leo E. Hollister
Journal: JAMA (1993)

John Parascandola became a historian of pharmacology after joining the faculty of the University of Wisconsin School of Pharmacy in 1969. His present book, about John Abel and the beginnings of pharmacology in the United States, is based on hitherto unavailable primary sources. It focuses on the role Abel played in the development of the new discipline. Most of us are not aware that pharmacology became a separate discipline in this country only about 100 years ago. Before then, the subject was taught as Materia Medica, a didactic course concerned with the physical and chemical properties of drugs rather than their actions. A few experimental studies of drugs were undertaken by Weir Mitchell and Horatio Wood in the middle of the 19th century, but these were exceptions. John Abel, whose first love was chemistry, was destined to change this course. Abel, a dedicated and ambitious young man, studied extensively in
Massive Hemangioma or Lymphedema? A Case with a Diagnostic Dilemma
Authors: PARUL BHATNAGAR, ARUN BATRA, SANJEEV SHARMA, SAWROOP KRISHAN, NAKESE LAL SONI, RAJENDRA P. TRIPATHY, ASEEM BHATNAGAR
Journal: Clinical Nuclear Medicine (2002)

The authors present an unusual case of massive enlargement of the right lower extremity that was treated as lymphedema secondary to filarial infection. A multiple-method approach beginning with scintigraphy led to the diagnosis of massive hemangioma with probable associated lymphatic proliferation. Abnormal local proliferation of vascular and lymphatic tissue is a developmental anomaly that is difficult to diagnose or characterize, even with histopathologic data. Individual imaging methods may also yield nonspecific findings. Blood-pool scintigraphy, therefore, has a definitive role to play in assessing such complex lesions.
TCT-491 Renal Artery Denervation with a New Simultaneous Multielectrode Catheter for Treatment of Resistant Hypertension: Results from the Symplicity Spyral(tm) First-in-Man Study
Authors: Robert J. Whitbourn, Scott Harding, Martin T. Rothman, Tony Walton
Journal: Journal of the American College of Cardiology (2013)
Mast Cell-Mediated Antigen Presentation Regulates CD8+ T Cell Effector Functions
Authors: Erietta Stelekati, Rajia Bahri, Orietta D'Orlando, Zane Orinska, Hans-Willi Mittrücker, Rabea Langenhaun, Markus Glatzel, Annalena Bollinger, Ralf Paus, Silvia Bulfone-Paus
Journal: Immunity (2009)
The Genetics of Colorectal Cancer
Authors: Paula M. Calvert, Harold Frucht
Journal: Annals of Internal Medicine (2002)

Colon cancer is a common disease that can be sporadic, familial, or inherited. Recent advances have contributed to the understanding of the molecular basis of these various patterns of colon cancer. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer; and, in Ashkenazi Jewish persons, a mutation that was previously thought to be a polymorphism may cause familial colon cancer. Mutations of three different classes of genes have been described in colon cancer etiology: oncogenes, suppressor genes, and mismatch repair genes. Knowledge of many of the specific mutations responsible for colon carcinogenesis allows an understanding of the phenotypic manifestations observed and forms the basis of genetic testing for inherited disease. Although genetic testing is possible and available, it is only an adjunct to the clinical management of persons at risk for colon cancer and patients with colon cancer. As a result of advances in the understanding of the molecular causes of colon cancer and the availability of colon cancer screening methods such as colonoscopy, it should be possible to prevent the vast majority of colon cancer in our society. Practicing clinicians should recognize the patterns of clinical colon cancer, understand its causes, and be able to use genetic testing and endoscopic screening for prevention.
Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program
Authors: Chrysothemis C. Brown, Daria Esterhazy, Aurelien Sarde, Mariya London, Venu Pullabhatla, Ines Osma-Garcia, Raya al-Bader, Carla Ortiz, Raul Elgueta, Matthew Arno, Emanuele de Rinaldis, Daniel Mucida, Graham M. Lord, Randolph J. Noelle
Journal: Immunity (2015)

CD4+ T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells.