tbuckley/cabot-search huggingface dataset:
“Toxic memory” via chaperone modification is a potential mechanism for rapid mallory-denk body reinduction
Authors: Pavel Strnad, Guo-Zhong Tao, Phillip So, Kenneth Lau, Jim Schilling, Yuquan Wei, Jian Liao, Bishr M. Omary
Journal: Hepatology (2008)

Abstract The cytoplasmic hepatocyte inclusions, Mallory-Denk bodies (MDBs), are characteristic of several liver disorders, including alcoholic and nonalcoholic steatohepatitis. In mice, MDBs can be induced by long-term feeding with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 3 to 4 months or rapidly reformed in DDC-induced then recovered mice by DDC refeeding or exposure to a wide range of toxins for only 5 to 7 days. The molecular basis for such a rapid reinduction of MDBs is unknown. We hypothesized that protein changes retained after DDC priming contribute to the rapid MDB reappearance and associate with MDB formation in general terms. Two-dimensional differential-in-gel-electrophoresis coupled with mass spectrometry were used to characterize protein changes in livers from the various treatment groups. The alterations were assessed by real-time reverse-transcription polymerase chain reaction and confirmed by immunoblotting. DDC treatment led to pronounced charged isoform changes in several chaperone families, including Hsp25, 60, 70, GRP58, GRP75, and GRP78, which lasted at least for 1 month after discontinuation of DDC feeding, whereas changes in other proteins normalized during recovery. DDC feeding also resulted in altered expression of Hsp72, GRP75, and Hsp25 and in functional impairment of Hsp60 and Hsp70 as determined using a protein complex formation and release assay. The priming toward rapid MDB reinduction lasts for at least 3 months after DDC discontinuation, but becomes weaker after prolonged recovery. MDB reinduction parallels the rapid increase in p62 and Hsp25 levels as well as keratin 8 cross-linking that is normally associated with MDB formation. Conclusion: Persistent posttranslational modifications in chaperone proteins, coupled with protein cross-linking and altered chaperone expression and function likely contribute to the “toxic memory” of DDC-primed mice. We hypothesize that similar changes are important contributors to inclusion body formation in several diseases. (Hepatology 2008.)
Cell lines with heterogeneous phenotypes result from a single isolation of albumin-sv40 T-antigen transgenic rat hepatocytes
Authors: S J Bulera, M J Haas, C A Sattler, Y Li, H C Pitot
Journal: Hepatology (1997)

Several immortalized cell lines were established from the livers of two transgenic rats expressing the simian virus protein large T antigen under the control of the albumin promoter. Hepatocytes from transgenic rats were isolated by a two-step perfusion procedure from a normal- appearing liver and from a liver that contained a single neoplasm. Cells were also isolated from the dissociated liver neoplasm. After 5 weeks in culture, cell colonies were isolated and subcloned as individual cell lines. Electron microscopy revealed that all cell lines had a high nuclear-to-cytoplasmic ratio compared with normal hepatocytes. The cytoplasm contained numerous organelles, including smooth and rough endoplasmic reticulum, Golgi, mitochondria, peroxisomes, and annulate lamellae. However, the lines exhibited a variety of different cell morphologies. All cell lines, including those derived from neoplastic cells, exhibited a similar doubling time of 26 hours and the ability to grow in soft agar. Northern blot analysis revealed that the cell lines differentially expressed hepatocyte markers. Large T antigen was expressed in the cultured cell lines at much higher levels than was observed in transgenic hepatocytes in vivo. This suggests that the viral protein is required to maintain cell viability in culture. In addition, the tumor suppressor proteins, p53 and Rbp105, were detected in all cultured cell lines. In contrast, these same proteins were not detected by Western blot in transgenic hepatocytes in vivo. All cell lines expressed the oncogene c-myc, yet growth factor-dependent and independent growth were observed. The data presented show for the first time the establishment and characterization of a number of cell lines derived from hepatocytes isolated from an alb-SV40 large T-antigen transgenic rat. These cell lines exhibited varied morphological and biochemical hepatocellular characteristics in vitro, suggesting that the expression of the transgene in hepatocytes leads to considerable phenotypic diversity analogous to that seen in hepatocellular carcinomas induced by chemical carcinogenesis.
Surgical Therapy of Chronic Glaucoma in Aphakia and Pseudophakia
Authors: Ronald L. Gross, Robert M. Feldman, George L. Spaeth, William C. Steinmann, Detlev Spiegel, L. Jay Katz, Richard P. Wilson, Rohit Varma, Marlene R. Moster, Steven Marks
Journal: Ophthalmology (1988)
Urine neutrophil gelatinase–associated lipocalin levels do not improve risk prediction of progressive chronic kidney disease
Authors: Kathleen D. Liu, Wei Yang, Amanda H. Anderson, Harold I. Feldman, Sevag Demirjian, Takayuki Hamano, Jiang He, James Lash, Eva Lustigova, Sylvia E. Rosas, Michael S. Simonson, Kaixiang Tao, Chi-yuan Hsu
Journal: Kidney International (2013)
Mapping of immunodominant CD4+ T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection
Authors: Robert M. Hoffmann, Helmut M. Diepolder, Reinhart Zachoval, Franz-Maximilian Zwiebel, Maria-Christina Jung, Siegfried Scholz, Hans Nitschko, Gert Riethmüller, Gerd R. Pape
Journal: Hepatology (1995)

In acute and chronic viral disease the specific response of CD4+ T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4+ T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4+ T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4+ immune reaction to hepatitis C viral antigens (P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P < .05). In general, a CD4+ T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon-alpha as compared with nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
Robert George Dalton
Authors: J. Ropner
Journal: BMJ (2004)

Consultant haematologist Cheltenham General Hospital (b 1954; q Bristol 1978; FRCP, FRCPath), d 31 October 2003.​2003.




Figure 1




Those who knew Bob would not be surprised to learn that when, in 2002, he found himself being outpaced on a bike by his teenage daughter he sought a medical explanation. The finding of anaemia was rapidly followed by a diagnosis of gastric malignancy with established liver spread. Bob was appointed as a singlehanded consultant to the General Hospital, Cheltenham, in 1988. He swiftly established specialist clinics and close links with oncology colleagues. Bob was co-founder of Cheltenham's Leukaemia and Intensive Chemotherapy Charity (LINC) and a force behind fund raising to provide a new outpatient suite. He leaves a wife, Rosie, and two children.
Short intensive radiation courses may work as well as standard ones
Authors: David Spurgeon
Journal: BMJ (2008)

A shorter, more intense course of radiation works as well as the longer standard course, two studies presented at a meeting of the American Society for Therapeutic Radiology and Oncology indicate.

In one of the studies Canadian researchers found that radiation treatment called accelerated hypofractionated whole breast radiation, which took one to three weeks rather than the usual five to seven weeks, produced a return of cancer in 6.2% of patients after 10-12 years, similar to the 6.7% of patients in the standard treatment. …
The Prognostic Value of Chromosome 7 Polysomy in Non-small Cell Lung Cancer Patients Treated with Gefitinib
Authors: Lela E. Buckingham, John S. Coon, Larry E. Morrison, Kristine K.B. Jacobson, Susan S. Jewell, Kelly A. Kaiser, Ann M. Mauer, Tariq Muzzafar, Clayton Polowy, Sanjib Basu, Meryl Gale, Victoria M. Villaflor, Philip Bonomi
Journal: Journal of Thoracic Oncology (2007)
The Challenges of Reforming Graduate Medical Education Payments
Authors: Gail Wilensky
Journal: JAMA (2014)

example, where does the sensory information encoding location in place cells, spatial geometry in grid cells, or head direction in head direction cells come from, and how is it combined?” Researchers are actively investigating howgridcell activity influencesplacecell activity and vice versa and how these interactionsmaygowrong inAlzheimerdiseaseand other brain conditions. In a mouse model of Alzheimer disease, O’Keefe and his colleagues have shown that place cell degradation correlates with deterioration of animals’ spatial memory (Cacucci F et al. ProcNatlAcadSciUSA.2008;105[22]:78637868). Edvard Moser is excited to be an active part of the effort to find clinical applications for the field. “We wish to understand how gr id cel ls interact with other cell types to produce a sense of location. This will lead to knowledge that can hopefully be used by others to work out strategies to detect dysfunctions in the positioning system early on and to prevent further progression of disease.”
Treating COPD — The TORCH Trial, P Values, and the Dodo
Authors: Klaus F. Rabe
Journal: New England Journal of Medicine (2007)

In the United States, the overall, age-standardized death rate decreased from 1242 deaths per 100,000 population in 1970 to 845 deaths per 100,000 in 2002. This good news must be viewed against the doubling during the same interval of the age-standardized death rate among persons with chronic obstructive pulmonary disease (COPD),1 which makes COPD a major cause of death (Figure 1).COPD is the diagnostic term for a group of disorders that are characterized by respiratory symptoms — dyspnea, cough, and sputum production; airflow limitation; and chronic inflammation of the lung.2 Risk factors include exposure to a wide variety of . . .
Heart transplantation in children.
Authors: D P Taggart, J H Dark
Journal: BMJ (1991)

with emphasis being placed on developing outlets for basic research, which continues to be strong in Britain.Thus Professor Peckham is keen that there should, for example, be means to develop vaccines to exploit new technologies like magnetic resonance imaging.The strategy will be implemented through the management executive and the regions, each of which will be required to produce a research and development plan.The research will have to be multidisciplinary with input from NHS professional staff, managers, and scientists, and because the NHS lacks many of the skills necessary universities will play a central part.All regional plans will need to include proposals for training.Professor Peckham foresees two tensions: firstly, between getting everybody involved and spreading the effort too thin; and, secondly, between the top down and bottom up approaches.All research organisations struggle with these tensions, but Professor Peckham believes that the NHS can achieve a balance.Thus many of the proposals for research will come from regions, but at the same time some half a dozen national priorities will be set.There will be a national research and development committee, and it may be that the committee will need a subcommittee to award grants.In order to implement the strategy Professor Peckham and his team have been busy forming links with the Medical Research Council, the medical research charities, industry, and international organisations.Thus he imagines that the United Kingdom Coordinating Committee for Cancer Research might provide a model for other categories of research, and one is already being talked of for cardiovascular research.Working groups have also been set up to look at priorities, technology assessment, clinical evaluation, and screening, and there are other groups concerned with implementation and data handling.What Professor Peckham and his team have produced is not a fully formed strategy, it is a bold sketch; and now begins the difficult part of trying to make it work.As every business school graduate knows, thinking up strategies is the easy part.It's making them work that is hard, and there are some worries about this one.Firstly, it's not clear how the research strategy will relate to the overall health strategy that the Department of Health is about to produce.The World Health Organisation argues that all countries should have a research strategy-but it should underpin the overall health strategy.
Why the Dying Need Wills
Authors: Gary Stein
Journal: JAMA (1999)

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
Phase I Trial of Lenalidomide in Pediatric Patients With Recurrent, Refractory, or Progressive Primary CNS Tumors: Pediatric Brain Tumor Consortium Study PBTC-018
Authors: Katherine E. Warren, Stewart Goldman, Ian F. Pollack, Jason Fangusaro, Paula Schaiquevich, Clinton F. Stewart, Dana Wallace, Susan M. Blaney, Roger Packer, Tobey MacDonald, Regina Jakacki, James M. Boyett, Larry E. Kun
Journal: Journal of Clinical Oncology (2010)

A phase I trial of lenalidomide was performed in children with recurrent, refractory, or progressive primary CNS tumors to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile and pharmacokinetics.Lenalidomide was administered by mouth daily for 21 days, repeated every 28 days. The starting dose was 15 mg/m(2)/d orally, and the dose was escalated according to a modified continuous reassessment method. Correlative studies included pharmacokinetics obtained from consenting patients on course 1, day 1, and at steady-state (between days 7 and 21).Fifty-one patients (median age, 10 years; range, 2 to 21 years) were enrolled. Forty-four patients were evaluable for dose finding, and 49 patients were evaluable for toxicity. The primary toxicity was myelosuppression, but the MTD was not defined because doses up to 116 mg/m(2)/d were well-tolerated during the dose-finding period. Two objective responses were observed (one in thalamic juvenile pilocytic astrocytoma and one in optic pathway glioma) at dose levels of 88 and 116 mg/m(2)/d. Twenty-three patients, representing all dose levels, received ≥ six cycles of therapy. Pharmacokinetic analysis demonstrated that the lenalidomide area under the concentration-time curve from 0 to 24 hours and maximum plasma concentration increased with dosage over the range studied.Lenalidomide was tolerable in children with CNS tumors at doses of 116 mg/m(2)/d during the initial dose-finding period. The primary toxicity is myelosuppression. Antitumor activity, defined by both objective responses and long-term stable disease, was observed, primarily in patients with low-grade gliomas.
Plateletpheresis vs Plateletapheresis or Thrombocytapheresis
Authors: Basil S. Strates
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In the report on donor RBC lysis by Howard and Perkins (236:289,1976), the term "plateletpheresis" was included in the title and appeared several times in the text. It was also present in the titles of three of the four references cited. This etymologically incorrect term appeared in print as early as 1968.<sup>1</sup>Since that time, plateletpheresis has been used to denote removal of platelets from blood, in both spoken and written English, instead of the etymologically correct terms "plateletapheresis" or "thrombocytapheresis" (platelet or thrombocyte + Greek<i>aphairesis</i>[removal]).<sup>2(p1169)</sup> In a similar situation back in the early 1950s, the compound word "plasmopheresis" was coined and used in an internal Atomic Energy Commission report of the University of Rochester School of Medicine and Dentistry. On my recommendation, the term was changed to "plasmapheresis" and henceforth appeared in the medical literature in its corrected form. Subsequently, terms such as
Age at Diagnosis and Transmission of Invasive Melanoma in 23 Families With Cutaneous Malignat Melanoma/Dysplastic Nevi
Authors: A. M. Goldstein, M. C. Fraser, W. H. Clark, M. A. Tucker
Journal: JNCI Journal of the National Cancer Institute (1994)

Familial melanoma patients tend to have an earlier age at first melanoma diagnosis, thinner lesions, a different histologic distribution, and a higher frequency of multiple primary melanomas than patients with nonfamilial melanoma. Previous examination of a large melanoma kindred from Texas suggested that although cutaneous malignant melanoma (CMM) was transmitted in an autosomal dominant fashion, there were sex differences in penetrance and disease expression.This study further evaluated the age at diagnosis, sex difference in penetrance and disease expression, and segregation of familial CMM.We evaluated the age at diagnosis and transmission of CMM in 23 U.S. white families with CMM/dysplastic nevi who had been followed 5-17 years. We estimated the median and mean ages at diagnosis of invasive melanoma for all individuals, for men and women separately, and by generation. Using the computer program BMDP1L, we also estimated the cumulative probability of an offspring developing CMM as a function of age according to whether the mother or father had melanoma. In addition, we used a life-table approach to estimate the probability that offspring of CMM parents were affected with CMM (penetrance).The median age at diagnosis in the 23 kindreds (n = 106) was 33 years, substantially less than that of patients with sporadic melanomas in the U.S. white population. For females, the median age at diagnosis was 29 years; for males, it was 36 years. Nine percent of the case patients developed CMM before age 20 compared with 2% in the general population. There was little difference in the transmission pattern of melanoma between males and females in the 23 families, although sons of CMM parents had a higher risk of CMM than daughters of CMM parents. This difference was, however, based on small numbers and was not statistically significant. The penetrance estimates for CMM were high. They rose rapidly from 6% at age 18 to 85% by age 48. The median age at diagnosis of invasive melanoma decreased dramatically in successive generations; the reduction was 11-16 years per generation and was statistically significant (P < .0001).Although this reduction in median age at diagnosis may result partly from increased surveillance in hereditary melanoma families and the fact that individuals in the younger generations have not yet reached the highest at-risk ages for developing melanoma, the possibility of changes in melanoma risk and risk factors, genetic and/or environmental, across generations should be considered.
Commensal Bacteroides Species Induce Colitis in Host-Genotype-Specific Fashion in a Mouse Model of Inflammatory Bowel Disease
Authors: Seth M. Bloom, Vinieth N. Bijanki, Gerardo M. Nava, Lulu Sun, Nicole P. Malvin, David L. Donermeyer, W. Michael Dunne, Paul M. Allen, Thaddeus S. Stappenbeck
Journal: Cell Host & Microbe (2011)
Effects of Sulindac and Ibuprofen in Patients with Chronic Glomerular Disease
Authors: Giovanni Ciabattoni, Giulio A. Cinotti, Alessandro Pierucci, Bianca M. Simonetti, Massimo Manzi, Francesco Pugliese, Paola Barsotti, Gabriella Pecci, Franco Taggi, Carlo Patrono
Journal: New England Journal of Medicine (1984)

Original Article from The New England Journal of Medicine — Effects of Sulindac and Ibuprofen in Patients with Chronic Glomerular Disease — Evidence for the Dependence of Renal Function on Prostacyclin
Lysophosphatidylcholine up-regulates IL-1β-induced iNOS expression in rat mesangial cells
Authors: Mayumi Taniuchi, Haruhisa Otani, Naoya Kodama, Yoshinori Tone, Michiko Sakagashira, Yoichi Yamada, Masatoshi Mune, Susumu Yukawa
Journal: Kidney International (1999)
Fluphenazine and Postherpetic Neuralgia-Reply
Authors: Terence M. Murphy
Journal: JAMA (1990)

<h3>In Reply.—</h3> Dr Hurtig is correct in expressing his concerns about the extrapyramidal side effects of fluphenazine hydrochloride. I had prefaced my suggestions about its use with the fact that therapy for postherpetic neuralgia is often less than satisfactory and had followed my treatment suggestions with the caveat about extrapyramidal side effects and particularly warned against using this medication in dosages greater than 10 mg/d. I well recognize that the use of fluphenazine has not passed any litmus test, but few of the therapies for chronic pain treatment have. In rereading my paragraph, I should perhaps have stressed more the tricyclic antidepressant component of this particular combination, which, as Dr Hurtig correctly states, has been validated in appropriate trials. The use of fluphenazine was first suggested by Taub<sup>1</sup>at the first meeting of the International Association for the Study of Pain. We have used the medication at the University of
Treadmill Exercise Testing in Hypertensive Patients Treated With Hydrochlorothiazide and β-Blocking Drugs
Authors: Albert J. Miller
Journal: JAMA (1983)

Twelve patients with hypertension who did not become normotensive after treatment with hydrochlorothiazide alone were studied. Treadmill exercise testing was done before and after additional treatment to standing resting normotension with beta-blocker drugs. The double product (peak mean BP times peak heart rate) at peak performance fell significantly because of decreases in systolic arterial BP and heart rate, but diastolic pressures still rose with exercise in ten of the 12 patients, in seven of them to 100 mm Hg or higher. Thus, the data show that patients with hypertension treated to resting normotension with hydrochlorothiazide and a beta-blocker still often demonstrate a significant diastolic BP rise with exercise. In such patients, a rise in diastolic BP with exercise cannot be used as evidence of coronary atherosclerosis. The measurement of the arterial BP response to exercise is probably important in the assessment of the effectiveness of individual antihypertensive regimens.