tbuckley/cabot-search huggingface dataset:
Long-Term and Therapeutic-Level Hepatic Gene Expression of Human Factor IX after Naked Plasmid Transfer in Vivo
Authors: Carol H. Miao, Arthur R. Thompson, Keith Loeb, Xin Ye
Journal: Molecular Therapy (2001)

Naked DNA transfer of a high-expressing human factor IX (hFIX) plasmid yielded long-term (over 1 1/2 years) and therapeutic-level (0.5-2 microg/ml) gene expression of hFIX from mouse livers. The expression cassette contained a hepatic locus control region from the ApoE gene locus, an alpha1-anti-trypsin promoter, hFIX cDNA, a portion of the hFIX first intron, and a bovine growth hormone polyadenylation signal. In contrast, a hFIX plasmid containing the expression cassette without effective regulatory elements produced initially low-level gene expression that rapidly declined to undetectable levels. Southern analyses of the cellular DNA indicated that the majority of the input genome from either vector persisted as episomal forms of the original plasmids. Together with RT-PCR analyses of the transcripts, these data indicated that at least two processes are critical for sustained gene expression: persistence of vector DNA and transcriptional/posttranscriptional activation. Liver regeneration after partial hepatectomy resulted in a significant decline in transgene expression, further suggestive of decreased episomal plasmid maintenance rather than transgene integration. Transaminase levels and liver histology showed that rapid intravenous plasmid injection into mice induced transient focal acute liver damage (< 5% of hepatocytes), which was rapidly repaired within 3 to 10 days and resulted thereafter in histologically normal tissue. No significant differences were observed between rapid injection of plasmid and saline control solutions. Transient, very low level antibodies directed against hFIX did not prevent the circulation of therapeutic levels of the protein. Gene transfer of hFIX plasmid DNA into liver elicited neither transgene-specific cytotoxic effect nor long-term toxicity. These results demonstrate that long-term expression of hFIX can be achieved by nonviral plasmid transfer and suggest that this occurs independent of integration.
Abstract 2483: Molecular mechanisms underlying chemopreventive activities of glycyrrhizic acid against UVB-induced carcinogenesis in SKH-1 hairless mouse epidermis
Authors: Jaw-Ming Cherng, Kuen-Daw Tsai, James C. Wei, Daw-Shyong Perng, Alice Y. Yu, Jung-Chung Lin
Journal: Cancer Research (2011)

Abstract Glycyrrhizic acid (GL) has been shown to possess anti-inflammation, antiviral, and chemoprotective activity against tumors. We assessed the protective effects of GL in UVB-induced skin tumor formation in SKH-1 hairless mice and the early molecular biomarkers. Mice irradiated at 180 mJ/cm2 twice per week elicited 100% tumor incidence in 20 weeks. Feeding of GL prior to UVB irradiation caused a strong protection against photocarcinogenesis in terms of delay in tumor appearance, multiplicity, and size. It took 24 weeks to get 100% tumor incidence in GL plus UVB treated-group; the first tumor appearance in UVB-treated animals occurred at 16th week, which was delayed by 3 weeks in GL plus UVB-treated group. Feeding of GL for 2 weeks before a single UVB (180mJ/cm2) irradiation resulted in a strong and significant decrease in UVB-induced thymine dimer-positive cells (p &amp;lt; 0.004), proliferative cell nuclear antigen PCNA (p &amp;lt; 0.01), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells (p &amp;lt; 0.01) together with an increase in p53 and p21/Cip1-positive cell population in epidermis (p &amp;lt; 0.02 ∼ 0.003). Simultaneously, GL also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels (p &amp;lt; 0.01-0.004). Taken together, these results suggest that GL causes a strong protective effect against photocarcinogenesis via down-regulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-kB and of inflammatory responses involving COX-2, PGE2, and NO, while up-regulation of p53, p21/Cip1 to prevent DNA damage. These results provide a focus for the rational development of GL as a novel chemopreventive agent against UV-induced human skin cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2483. doi:10.1158/1538-7445.AM2011-2483
Oregons governor apologises for forced sterilisations
Authors: D. Josefson
Journal: BMJ (2002)

In a historic gesture Oregon's governor, John Kitzhaber, has apologised to thousands of Oregonians who were forcibly sterilised while in the care of the state.

Between 1923 and 1981 Oregon actively practised eugenics and forcibly sterilised people who were mentally ill, had epilepsy, were criminals, or were homosexual. The state also sterilised residents of reform schools and girls who were considered promiscuous. A total of 2648 people were subjected to sterilisation by castration, tubal ligation, hysterectomy, or vasectomy.

Oregon's eugenics bill was introduced into the state legislature in 1907 and was passed in its initial form in 1913. A Board of Eugenics …
Time-Motion Study of Six Pediatric Office Assistants
Authors: Patricia K. Patterson, Abraham B. Bergman
Journal: New England Journal of Medicine (1969)

Abstract Observation of the assistants in six private pediatric offices (four registered nurses and two "medical assistants") for three days with a stopwatch to determine their work patterns showed an average of only 21 per cent of the work day spent "with patients." Nurses trained for three years performed the same functions as "medical assistants" trained for six months. Nurses are inefficiently used in private offices, a fact that should be remedied by more specific training in nursing school, and more appropriate task delegation by physician employers.
Jonas &amp; Kovner's Health Care Delivery in the United States
Authors: David H. Howard
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
Proprotein-processing endoprotease furin controls the growth and differentiation of gastric surface mucous cells.
Authors: Y Konda, H Yokota, T Kayo, T Horiuchi, N Sugiyama, S Tanaka, K Takata, T Takeuchi
Journal: Journal of Clinical Investigation (1997)

Gastric surface mucous cells originate from progenitor cells at the isthmus of the gastric gland, from where the cells migrate to the luminal surface. With migration they form secretory granules and express TGF alpha. We found that proprotein-processing endoprotease furin-positive cells were layered around the upper one fourth of the gastric glands of adult rats, whereas they were distributed along an outer epithelial layer in fetal rats. Because the furin-positive cell layer was localized from the upper cell proliferating zone to the less proliferating pit-cell region in the gastric gland unit, we examined the role of furin in the growth and differentiation of surface mucous cells by using the cell line, GSM06. This cell line is derived from the gastric surface mucous cells of transgenic mice harboring the temperature-sensitive simian virus 40 T antigen. At T antigen-active temperature (33 degrees C), the cells grew to confluency, whereas at T antigen-inactive temperature (39 degrees C), the cells ceased growing. At 33 degrees C, the cells exhibited a high level of furin expression with a negligible level of periodic acid Schiff (PAS)-positive materials and a low level of TGF alpha. In contrast, at 39 degrees C the cells produced a high level of PAS-positive materials, TGF alpha, and secretory granules, with a negligible level of furin expression. To further examine the role of furin, we established a GSM06 cell line introduced with either a sense or an antisense furin cDNA. The cells with sense furin expression produced fewer PAS-positive materials and a low level of TGF alpha even at 39 degrees C, whereas the cells with antisense furin expression exhibited more PAS-positive materials and TGF alpha even at 33 degrees C. When furin expression was suppressed by its antisense oligonucleotide, the cell growth was retarded with enhanced expression of the differentiated characteristics. Thus, we conclude that furin is instrumental in controlling the growth of the surface mucous cells.
Manual of Surgical Nutrition
Authors: Wayne Callaway
Journal: JAMA (1976)

In spite of a commendable purpose and several worthy chapters, this manual fails to achieve its aim. It does<i>not</i>"provide a... concise and portable review of the nutritional principles and practices for the practicing surgeon." Neither is it "a series of chapters carefully coordinated into a single manual." Were either of these claims true, it could be heartily welcomed. How does it fail? Or, rather, supposing there is to be a second edition, how should it be improved? First, reduce the size by half. This could be done without sacrifice of factual content. The chapters by Brennan and Moore, Kinney, Scott, Duke and Dudrick, and several others could be retained but condensed by deleting extraneous words and phrases. Secondly, reduce the number of authors by half. The invited contributors should be knowledgeable in their assigned subjects, or they should be willing to verify their memories by returning to the
Tezosentan, a dual endothelin receptor antagonist, decreases mortality and liver injury in rats with cirrhosis following endotoxin administration
Authors: Waldemar Urbanovicz, Philippe Sogni, Khalid Tazil, Dominique Cazals-Hatem, Eric Barriere, Odile Poirel, Richard Moreau, Didier Lebrec
Journal: Journal of Hepatology (2002)
THE CLASSIFICATION OF DISEASES OF THE EYE FOR HOSPITAL STATISTICS.Read in the Section on Ophthalmology at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: EDWARD JACKSON
Journal: JAMA (1893)

The custom has become general among hospitals and dispensaries, of publishing Annual Reports, showing the number of cases treated. The principal value of such statistics, from the scientific point of view, is that they may throw light on the etiology of certain diseases, by showing their comparative frequency in different places and at different times. This can only attach to such statistics when the classification they employ is comparatively uniform, and their value, as well as the ease with which they can be handled in combination, will be enormously increased if the classifications be exactly uniform. On consulting the reports of the principal ophthalmic hospitals of the country, it will be found that in the main they pretty closely agree as to the naming and relative frequency of the mass of conditions mentioned. There are, however, points of divergence which render the comparison of statistics obtained in the different large
Acid and Basics: A Guide to Understanding Acid-Base Disorders
Authors: Deepak M. Kaji
Journal: JAMA (1994)

Among the many intellectual challenges encountered by medical students, residents, and practitioners, that of interpreting clinical acid-base disorders remains one of the most difficult challenges to master. This short book is an attempt "to lead the uninitiated and the timid to an understanding of acid-base disorders." The author was encouraged to write yet another book on the subject of acid-base disorders because of "explosion in knowledge regarding the molecular basis for membrane transport" in the last decade. To acquaint the beginning reader with the basic molecular mechanisms, the author provides an excellent, albeit brief, description of the importance of pH in life and the role played by various primary and secondary active transport pathways involved in regulation of intracellular pH. The discussion of transport pathways involved in proton secretion is laudable and unusual for a short primer and accounts for the strength of the book. I gave a copy to
Jeremy Bentham's self image: an exemplary bequest for dissection.
Authors: R Richardson, B Hurwitz
Journal: BMJ (1987)

transfusion or injections, and there was no history of venereal infection or genital ulceration.The other antibody positive heterosexual man was an intravenous drug user.When the beginning of October was compared with mid- November there was an increase of over 300% in people attending the clinic who required counselling for the HIV antibody test.By the end of December this had fallen slightly, but with the surge in publicity at the end of February we are expecting a further dramatic increase in requests for testing.Our clinic staff, in particular the health advisers, are working under enormous pressure at present.We do not foresee our workload decreasing, rather the opposite.The recent increase in public awareness and anxiety about AIDS, which will probably continue with further public health education, surely indicates that it is time for an urgent reappraisal of staffing levels in clinics for sexually transmitted diseases.
Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene.
Authors: T Lindner, C Gragnoli, H Furuta, B N Cockburn, C Petzold, H Rietzsch, U Weiss, J Schulze, G I Bell
Journal: Journal of Clinical Investigation (1997)

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic disorder characterized by autosomal dominant inheritance, onset usually before 25 yr of age, and abnormal pancreatic beta-cell function. Mutations in the hepatocyte nuclear factor(HNF)-4alpha/MODY1, glucokinase/MODY2, and HNF-1alpha/MODY3 genes can cause this form of diabetes. In contrast to the glucokinase and HNF-1alpha genes, mutations in the HNF-4alpha gene are a relatively uncommon cause of MODY, and our understanding of the MODY1 form of diabetes is based on studies of only a single family, the R-W pedigree. Here we report the identification of a second family with MODY1 and the first in which there has been a detailed characterization of hepatic function. The affected members of this family, Dresden-11, have inherited a nonsense mutation, R154X, in the HNF-4alpha gene, and are predicted to have reduced levels of this transcription factor in the tissues in which it is expressed, including pancreatic islets, liver, kidney, and intestine. Subjects with the R154X mutation exhibited a diminished insulin secretory response to oral glucose. HNF-4alpha plays a central role in tissue-specific regulation of gene expression in the liver, including the control of synthesis of proteins involved in cholesterol and lipoprotein metabolism and the coagulation cascade. Subjects with the R154X mutation, however, showed no abnormalities in lipid metabolism or coagulation except for a paradoxical 3.3-fold increase in serum lipoprotein(a) levels, nor was there any evidence of renal dysfunction in these subjects. The results suggest that MODY1 is primarily a disorder of beta-cell function.
IMPACT OF POST–DILATATION STRATEGIES AND STENT MATERIALS ON CHRONIC STENT AREA PRESERVATION: AN EXPERIMENTAL STUDY USING OPTICAL COHERENCE TOMOGRAPHY
Authors: Hideki Kitahara, Katsuhisa Waseda, Ryotaro Yamada, Kaori Nakagawa, Fumiaki Ikeno, Peter J. Fitzgerald, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2013)
Dietary Composition, Body Weight, and NIDDM: Comparison of high-fiber, high-carbohydrate, and modified-fat diets
Authors: Karen Z Walker, Kerin O'Dea, Geoffrey C Nicholson, Jane G Muir
Journal: Diabetes Care (1995)

OBJECTIVE To examine the effects of a high-carbohydrate low-fat (HCLF) and a modified-fat (MF) diet on body weight and metabolic control in subjects with non-insulin-dependent diabetes mellitus (NIDDM) living at home. RESEARCH DESIGN AND METHODS Twenty-four NIDDM patients followed HCLF and MF diets alternately and in random order for a 3-month period while at home, with a 1-month baseline and washout between diets. Before and after each diet, fasting glucose and lipids, HbAlc, blood pressure, and body weight were measured. Dietary preferences were assessed by questionnaire. RESULTS Subjects consumed 50% of energy as carbohydrate and 23% as fat on the HCLF diet and 40% of energy as carbohydrate and 36% as fat (over half of which was monounsaturated fat) on the MF diet. Subjects lost weight on both HCLF and MF diets (mean loss 0.7 and 1.3 kg, respectively). Although the MF diet resulted in a small decrease in fasting glucose levels, there was no significant change in HbA1c. Similarly, there was no significant difference between the diets in changes in blood pressure or fasting blood lipids. Most subjects (65%) preferred the MF diet. CONCLUSIONS Although the MF diet is not a low-fat diet, it did not appear to facilitate weight gain in subjects with NIDDM living at home. The MF diet provides an alternative for individuals unable to comply with HCLF diets.
A 47-year-old woman with ductal carcinoma in situ of the breast
Authors: J. Kaufman
Journal: JAMA (1996)

To the Editor.  —The Clinical Crossroads article by Dr Morrow 1 was clinically informative regarding treatment options and outcomes for breast ductal carcinoma in situ (DCIS). It would have been useful if the discussion also included the mammographic evaluation that led to the biopsy. Primary care physicians who routinely advise their patients to have screening mammography not infrequently receive a reading with a recommendation for a 6-month follow-up examination. Mrs Y may have saved herself from such follow-up by seeking a second opinion—is it appropriate to wait 6 months for follow-up?  The American College of Radiology has suggested a standardized nomenclature for mammography and, in effect, has categorized the level of suspicion for malignancy. 2 Why did the second group of physicians described in the article recommend biopsy when the original radiologist recommended a 6-month reexamination? Indeed, for indeterminant or probably benign abnormalities, the latter approach is expected to yield
Clonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd.
Authors: R Abe, J J Ryan, R J Hodes
Journal: The Journal of Experimental Medicine (1987)

Only two sets of antigenic determinants are recognized by T lymphocytes at uniquely high precursor frequencies: those encoded by the MHC and those encoded by Mls. The structural as well as functional characteristics of MHC products have been extensively analyzed. In contrast, little information concerning the nature of Mls genes or their products is available. Although it was originally described (5, 6) that the Mls locus on chromosome 1 is composed of four alleles that encode polymorphic cell surface structures, the issues of polymorphism and allelism in the Mls system have been controversial for some time. In the present study, T cell clones were generated by continuous stimulation of B10.BR (H-2k, Mlsb) T cells by CBA/J (H-2k, Mlsd) stimulators and they were used to analyze the relationship of putative Mlsa, Mlsc, and Mlsd determinants. All clones proliferated in response to determinants expressed by CBA/J stimulators. In addition, each of these clones exhibited a second reactivity to either AKR/J (H-2k, Mlsa) or C3H/HeJ (H-2k, Mlsc) stimulators. No clone responded to both AKR/J and C3H/HeJ. These second specificities were defined to be for Mlsa or Mlsc determinants, respectively, by the response patterns of clones and unprimed T cells to stimulators derived from congenic strains, recombinant inbred (RI) strains, and backcross mice. Moreover, a segregation analysis of the (CBA/J X B10.BR)F1 X B10.BR backcross indicated that the Mlsa-like and Mlsc-like determinants expressed on CBA/J (Mlsd) cells are in fact encoded by nonallelic, unlinked genes. These findings suggest a new concept of the polymorphism and genetics of the Mls system. It is proposed that two distinct and nonallelic gene products express, respectively, the noncrossreacting Mlsa and Mlsc determinants, and that the Mlsd phenotype does not represent an independent genotype but rather reflects the concurrent expression of Mlsa and Mlsc. The Mls system, therefore, consists of at least two systems that are distinct both genetically and antigenically, and that may be of different biologic or physiologic significance as well.
The mutational landscape of paroxysmal nocturnal hemoglobinuria revealed: new insights into clonal dominance
Authors: Stanley Chun-Wei Lee, Omar Abdel-Wahab
Journal: Journal of Clinical Investigation (2014)

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of hematopoietic stem cells that has largely been considered a monogenic disorder due to acquisition of mutations in the gene encoding PIGA, which is required for glycosylphosphatidylinositol (GPI) anchor biosynthesis. In this issue of the JCI, Shen et al. discovered that PNH is in fact a complex genetic disorder orchestrated by many genetic alterations in addition to PIGA mutations. Some of these mutations predate the acquisition of PIGA mutations, while others occur later. Surprisingly, this work indicates that PNH has a clonal evolution and architecture strikingly similar to that of other myeloid neoplasms, highlighting a potentially broader mechanism of disease pathogenesis in this disorder.
Psychiatrist is cleared of misconduct in his care of 14 year old
Authors: C. Dyer
Journal: BMJ (2011)

A child and adolescent psychiatrist has been cleared of any misconduct in the case of a 14 year old girl whom he discharged from a specialist treatment centre earlier than initially planned ( BMJ 2011;342:d2773, 28 Apr, doi:10.1136/bmj.d2773).

A General Medical Council fitness to practise panel held that Tony Livesey, an expert on deliberate self harm, had not undermined the teenager’s stability by discharging her earlier than had been originally planned. The panel also decided that allegations that the discharge …