tbuckley/cabot-search huggingface dataset:
Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide
Authors: Adrian Zai, M. Audrey Rudd, Anne Ward Scribner, Joseph Loscalzo
Journal: Journal of Clinical Investigation (1999)

Since thiols can undergo nitrosation and the cell membrane is rich in thiol-containing proteins, we considered the possibility that membrane surface thiols may regulate cellular entry of NO. Recently, protein disulfide isomerase (PDI), a protein that catalyzes thio–disulfide exchange reactions, has been found on the cell-surface membrane. We hypothesized that cell-surface PDI reacts with NO, catalyzes S-nitrosation reactions, and facilitates NO transfer from the extracellular to intracellular compartment. We observed that PDI catalyzes the S-nitrosothiol–dependent oxidation of the heme group of myoglobin (15-fold increase in the rate of oxidation compared with control), and that NO reduces the activity of PDI by 73.1 ± 21.8% (P < 0.005). To assess the role of PDI in the cellular action of NO, we inhibited human erythroleukemia (HEL) cell-surface PDI expression using an antisense phosphorothioate oligodeoxynucleotide directed against PDI mRNA. This oligodeoxynucleotide decreased cell-surface PDI content by 74.1 ± 9.3% and PDI folding activity by 46.6 ± 3.5% compared with untreated or “scrambled” phosphorothioate oligodeoxynucleotide–treated cells (P < 0.0001). This decrease in cell-surface PDI was associated with a significant decrease in cyclic guanosine monophosphate (cGMP) generation after S-nitrosothiol exposure (65.4 ± 26.7% reduction compared with control; P < 0.05), with no effect on cyclic adenosine monophosphate (cAMP) generation after prostaglandin E1 exposure. These data demonstrate that the cellular entry of NO involves a transnitrosation mechanism catalyzed by cell-surface PDI. These observations suggest a unique mechanism by which extracellular NO gains access to the intracellular environment.
Tumour necrosis factor antagonists and tocilizumab have a higher impact on rheumatoid arthritis osteoclastogenic stimuli than methotrexate
Authors: I Perpetuo, D Fernandes, R Cascao, R Moura, J Caetano-Lopes, A Rodrigues, J Polido-Pereira, M Viana Queiroz, J E Fonseca, H Canhao
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is a systemic disease characterised by hyperactivation of the immune system leading to chronic inflammation and joint damage. The inflammatory environment potentiates bone resorption, modulating the balance between RANKL and osteoprotegerin (OPG). Prednisone (PDN), methotrexate (MTX), anti-tumour necrosis factor (TNF) and anti-interleukin 6 (IL6) receptor therapies reduce disease activity, but their differential biological impact …
Jewish Law and the Obligation of the Physician to Heal Patients With AIDS
Authors: Peter Shalit
Journal: JAMA (1989)

<h3>To the Editor.—</h3> As a gay man, a Jew, and a physician who takes care of people with acquired immunodeficiency syndrome, I was offended and angered by the recent letter by Dr Rosner.<sup>1</sup>While it is noble for him to feel obligated to treat patients ("homosexuals and drug addicts") who (he feels) are "evil," maybe he should look for another line of work. There are plenty of dedicated physicians who do not consider their patients "evildoers" who "should be helped to repent from their evil practices." People with acquired immunodeficiency syndrome need care givers who do not make moral judgments about them. It's hard enough to have a life-threatening illness without being advised by one's physician to "repent" something that, in the case of homosexual orientation, is a God-given characteristic and not a chosen "evil practice." Fortunately, Dr Rosner's view represents only the extreme fringe of modern Jewish philosophy.
Differences in Mortality From Coronary Artery Bypass Graft Surgery
Authors: James C. Maher
Journal: JAMA (1991)

<h3>To the Editor.</h3> — article by Williams et al<sup>1</sup>is a fascinating exploration of a complex and important topic. Mortality was not adequately explained by the methods typically used to justify hospital mortality differences. There did, however, seem to be some correlation between operating surgeon and mortality for diagnosis related group 106. Since all these procedures were done at teaching hospitals in the city of Philadelphia, and since it is well known that some attending physicians allow house staff to participate more actively in the care of some patients than of others, I wonder whether the degree of involvement of the house staff either in the operative or the postoperative phase might help explain the mortality rates. In addition, might the economic or referral status of the patients be important in explaining variations in mortality? For example, if the patient was referred by a cardiologist on staff who had
Benign Epithelial Cyst Mimicking Thyroid Cancer Metastasis
Authors: Gonca Gul Bural, Robert L. Peel, James M. Mountz
Journal: Clinical Nuclear Medicine (2011)

A 65-year-old man with a suspicious thyroid nodule underwent total thyroidectomy. Pathology revealed papillary thyroid carcinoma. He received 48 mCi of radioiodine for ablation. On post-therapy whole-body I-131 radioiodine scan, an abnormal focus of uptake was observed in the abdominal left upper quadrant which prompted a SPECT/CT scan for localization. The uptake correlated to a 1.6-cm soft-tissue lesion in the mesentery adjacent to the left diaphragmatic crus, which was surgically removed. Pathology revealed a benign epithelial cyst with no histologic or immunohistological features for thyroid tissue. The exact mechanism of I-131 accumulation in a cyst remains unclear.
The Source of Plasma Dihydrotestosterone in Man
Authors: T. Ito, R. Horton
Journal: Journal of Clinical Investigation (1971)

The source of plasma dihydrotestosterone (DHT) (17β-hydroxy-5α-androstan-3-one) in humans has been investigated by infusing two potential peripheral precursors, testosterone (T) and androstenedione (A). Metabolic clearance rates (MCR), conversion ratios (CR), transfer constants (ρ), and blood production rates (PB) were calculated. Plasma testosterone and dihydrotestosterone were measured by competitive binding techniques. The MCRDHT was 652 ±35 (SD) liters/day in five males and 314 ±63 (SD) liters/day in four adult females. In each individual, the MCRDHT was significantly lower than MCRT as predicted by testosterone-binding protein affinity studies. The PBDHT was 302 ±65 (SD) μg/day in males and 56 ±26 μg/day in females. Testosterone and androstenedione are precursors (prehormones) for plasma dihydrotestosterone. The conversion ratio CRBBT-DHT, calculated as the ratio of counts per minute per liter of plasma of product to precursor after infusion of labeled precursor, was 5.6 ±0.6 (SD)% (six subjects) in the male and 3.5 ±0.4 (SD)% (four subjects) in the female. CRBBA-DHT after androstenedione infusion to three female subjects averaged 9.2%. No dihydrotestosterone back conversion was detected (< 0.2%). The transfer constants were [ρ]BBT-DHT, 3.9 ±1.0% (male) and 1.7 ±0.6% (female), and [ρ]BBA-DHT average was 13.3% in three female subjects. Using either plasma testosterone and dihydrotestosterone values from our subjects and mean androstenedione values as reported in the literature, approximate contributions can be calculated. Testosterone conversion accounts for at least 70% of plasma DHT in the male, but less than 20% in the normal female. Androstenedione appears to be a major prehormone of plasma dihydrotestosterone accounting for at least two-thirds plasma dihydrotestosterone by peripheral conversion in adult females. In three normal women undergoing tubal ligation, there was an unimpressive gradient between ovarian vein and peripheral plasma dihydrotestosterone. It is suggested that dihydrotestosterone in the blood does not arise from direct secretion but may reflect events occurring in peripheral androgen target tissues.
AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features
Authors: Claudia Haferlach, Cristina Mecucci, Susanne Schnittger, Alexander Kohlmann, Marco Mancini, Antonio Cuneo, Nicoletta Testoni, Giovanna Rege-Cambrin, Antonella Santucci, Marco Vignetti, Paola Fazi, Maria Paola Martelli, Torsten Haferlach, Brunangelo Falini
Journal: Blood (2009)
P10.03 * OPSOCLONUS MYOCLONUS SYNDROME ASSOCIATED WITH LUNG ADENOCARCINOMA
Authors: A. F. M. R. Matas, A. S. B. T. Veiga, J. P. M. S. Gabriel, M. R. Silva
Journal: Neuro-Oncology (2014)

INTRODUCTION: The diagnosis of a neurological paraneoplasic syndrome is, in the absence of a known oncologic disease, difficult. It implies the recognition of the neurological syndrome, the diagnosis of the oncologic disease, and the establishment of a relationship between both of them, mediated by a congruent profile of antineuronal antibodies. We report a case that exemplifies the diagnostic challenge that this entity poses. CASE REPORT: A 61-year-old woman, non smoker, presented with depressive humour beginning six months earlier, that evolved sub acutely to irritability, insomnia, tremor, visual disturbances e gait difficulties that resulted in inability to walk in the weak previous to the hospital admission. On the neurological exam, it was noticed encephalopathy, ophtalmoparesis, incessant multidirectional nystagmus, pancerebellar syndrome and axial and multi segmental myoclonus. The brain TC and MRI were normal. CSF study revealed monocytic pleocytosis (22/uL), with increased protein levels (89.0 mg/dL) and normal glucose levels. It was identified by TC an image compatible with pulmonary neoplasm of the right inferior lobe, metastasized to the contra lateral lung and invading the pleural and the loco regional lymph nodes. It was determined seropositivity to the antineuronal antibody ANNA 2 (anti-Ri) and raised levels of tumoral markers CA 125 and CA 15-3. The pulmonary lesion was submitted to transthoracic biopsy and the histological exam confirmed the diagnosis of a lung adenocarcinoma. There was not any neurological improvement after treatment with human immunoglobulin (0.4g/Kg/d, during 7 days). The patient died two months after the diagnosis was made. It is highlighted the absence of any respiratory symptoms contemporaneous to the neurological manifestations. CONCLUSION: The case presented is consistent with the diagnosis of opsoclonus myoclonus syndrome associated with lung adenocarcinoma. It is not usual for this entity, rarely seen in adults, to be associated with this histological variety of pulmonary neoplasm.
Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: lessons learned from other inflammatory diseases?
Authors: R. Moseley, J.E. Stewart, P. Stephens, R.J. Waddington, D.W. Thomas
Journal: British Journal of Dermatology (2004)

The new era of pharmacogenetics has identified a potential for individuals to receive customized treatments for a variety of disease states. For such individualized treatments to fulfil their potential, it will be essential for clinicians to be able to monitor disease activity, ideally in a rapid, noninvasive fashion. The accessibility of the skin offers much potential to develop noninvasive tests of metabolic and disease activity for clinical use. Impaired human wound healing in the skin is a chronic inflammatory disorder in which the development of such tests has considerable potential, aiding clinical decision making and monitoring responses to treatment. This review article discusses how studies in other human diseases have highlighted potential biochemical markers (biomarkers) of disease activity in secreted biofluids, as aids to determining disease and metabolic activity within tissues. Using, as examples, lessons learned in the study of disease activity and prognosis of other chronic inflammatory conditions, such as osteoarthritis and periodontal disease, this review highlights the potential of dermal extracellular matrix (ECM) components (collagens, proteoglycans, hyaluronan and glycoproteins) for such uses. The limitations of currently utilized techniques and the concept that analysis of ECM components in wound fluid may represent useful biomarkers of disease activity are also discussed.
Changing Aspects of the Natural History of Valvular Aortic Stenosis
Authors: Arthur Selzer
Journal: New England Journal of Medicine (1987)

During the past few decades, valvular heart disease has changed in type and character. The two principal reasons for the changes are a decline in the prevalence of rheumatic heart disease and the longer survival of the population in general and of patients with heart disease in particular. The two stenotic lesions of the cardiac valves on the left side have been particularly affected by the change. There has been a gradual decline in the incidence of mitral stenosis — a lesion almost entirely related to rheumatic fever. The types of aortic stenosis seen have shifted from rheumatic to nonrheumatic. . . .
Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients
Authors: Janet S. Kinney, James H. Conway, Margaret W. Hilgartner, Barbara Clayman, Kumudini Mayur, Robert H. Yolken, Raphael P. Viscidi
Journal: American Journal of Hematology (1991)

Abstract Solid‐phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic patients were studied. A cross‐sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P &lt; .0004). In a longitudinal study, antibody levels in sera from 11 asymptomatic patients with gag antibody log units ≦ 1.5 were compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients with gag antibody &gt;1.5. These patient groups were followed for comparable periods of time (67.1‐71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV‐1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progression to AIDS.
Public health medicine after district mergers
Authors: H. Gordon
Journal: BMJ (1993)

in his example has now been discarded to cope with the problems of fixed length codes and a single hierarchy.2It is also a mistake to underestimate the challenge of moving from individual terms to the complexity of the contextual information in a medical record:The broader patient centred aims of the information technology strategy are to be welcomed.As with all scientific endeavour, however, it is essential to have a clear vision of the true goal and to have critically appraised the steps required to achieve it.
Abstract LB-284: The novel therapeutic monoclonal antibody VGX-100 neutralises VEGF-C and inhibits tumor growth and metastasis in subcutaneous and orthotopic models of human cancer.
Authors: Megan E. Baldwin, Angus M. Tester, David Phelan, Robert Klupacs
Journal: Cancer Research (2011)

Abstract Angiogenesis and lymphangiogenesis are important processes facilitating tumor growth and metastasis. Growth factors that stimulate blood and lymphatic proliferation within tumors are therefore potential targets for anti-cancer therapies. Proof of concept of the clinical utility of anti-angiogenic drugs was first established by the FDA/EMEA-approved drug bevacizumab (Avastin®) which blocks VEGF binding to its receptors VEGFR-1 and VEGFR-2, the latter being the key receptor signaling for angiogenesis. However, patients treated with bevacizumab may be refractory or develop resistance to bevacizumab, suggesting upregulation of alternative pro-angiogenic proteins that allow tumors to bypass the inhibition of VEGF signalling. VEGF-C is a logical candidate for inducing resistance to bevacizumab via this mechanism since it is also a ligand for the angiogenic receptor VEGFR-2 and for VEGFR-3 which is upregulated on tumor-associated vascular endothelium. VGX-100 is a highly specific, fully human monoclonal antibody for VEGF-C that blocks VEGF-C binding to both VEGFR-2 and VEGFR-3. Here we demonstrate that VGX-100 has an additive effect in combination with docetaxel and/or anti-VEGF (bevacizumab) in several tumor models, suggesting that VEGF-C may be an important mediator of the resistance to existing anti-VEGF therapies. Further, we demonstrate that in an orthotopic model of prostate cancer, that inhibition of VEGF-C alone by VGX-100 monotherapy is sufficient to inhibit tumor growth and significantly reduce the incidence of tumor metastasis to local lymph nodes. These data indicate that VGX-100 has exciting potential as a cancer therapeutic by targeting a key factor involved in angiogenesis, lymphangiogenesis and tumor metastasis and is expected to complement chemotherapy and/or other anti-angiogenic compounds in the clinic. 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 LB-284. doi:10.1158/1538-7445.AM2011-LB-284
Mini-Mental State Examination
Authors: Jeffrey L. Cummings
Journal: JAMA (1993)

The Mini-Mental State Examination (MMSE), first introduced by Folstein and colleagues in 1975,<sup>1</sup>has become a standard tool for cognitive assessment in the clinical setting. The MMSE facilitates the detection of mental status changes, particularly in the elderly, and thereby enhances patient care. Bedside mental status testing without a standardized approach is subject to considerable interpretive bias, dependent on the skill and experience of the examiner, and often completely neglected. The MMSE provides a structured approach to mental status testing that screens for intellectual impairment and allows comparison of performance across time and among patients or studies.<sup>2</sup>The publication in this issue of<i>JAMA</i>of new data from Crum et al<sup>3</sup>regarding the influence of age and education on the interpretation of the MMSE is welcome and further improves the utility of this instrument. See also p 2386. <h3>MMSE Elements</h3> The MMSE comprises 30 questions with 10
Coarctation of the Aorta With Poststenotic Aneurysm in a 71-Year-Old Man
Authors: James R. Stone
Journal: JAMA (1965)

AT AUTOPSY, a 71-year-old man who had died of pneumonia was found to have severe coarctation of the aorta, with concomitant hypertrophy of the collateral vessels and a poststenotic aneurysm. Since there have been very few recorded cases of coarctation of the aorta in patients surviving to this age, this case was thought to be worth reporting. <h3>Report of a Case</h3> A 71-year-old Mexican man was admitted to the hospital for the first time with complaint, by relatives, of extreme weakness of two years' duration and fever of recent onset. History from the patient was unobtainable as he was moribund. His temperature was 103 F (39.4 C) and blood pressure, 200/80 mm Hg. Rales were heard bilaterally. A chest film taken with a portable unit showed a mass in the region of the thyroid, a calcified mass in the left hilum, and rib notching. He died, in spite of receiving
P719 INDEPENDENT PREDICTORS OF PATIENT-REPORTED OUTCOMES (PROS) AND QUALITY OF LIFE (QOL) IN CHRONIC HEPATITIS C PATIENTS RECEIVING INTERFERON (IFN)-FREE VERSUS IFN-CONTAINING REGIMENS WITH SOFOSBUVIR (SOF)
Authors: Z.M. Younossi, M. Stepanova, F. Nader, D. Nelson, E. Lawitz, I.M. Jacobson, E. Gane, S.L. Hunt
Journal: Journal of Hepatology (2014)
Family Disruption in Childhood and Risk of Adult Depression
Authors: Stephen E. Gilman, Ichiro Kawachi, Garrett M. Fitzmaurice, Stephen L. Buka
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors examined the risk that family disruption and low socioeconomic status in early childhood confer on the onset of major depression in adulthood. METHOD: Participants were 1,104 offspring of mothers enrolled during pregnancy in the Providence, R.I., site of the National Collaborative Perinatal Project. Measures of childhood family disruption and socioeconomic status were obtained before birth and at age 7. Structured diagnostic interviews were used to assess respondents' lifetime history of major depressive episode between the ages of 18 and 39. Survival analysis was used to identify childhood risks for depression onset. RESULTS: Parental divorce in early childhood was associated with a higher lifetime risk of depression among subjects whose mothers did not remarry as well as among subjects whose mothers remarried. These effects were more pronounced when accompanied by high levels of parental conflict. Independent of the respondents' adult socioeconomic status, low socioeconomic status in childhood predicted an elevated risk of depression. CONCLUSIONS: Family disruption and low socioeconomic status in early childhood increase the long-term risk for major depression. Reducing childhood disadvantages may be one avenue for prevention of depression. Identification of modifiable pathways linking aspects of the early childhood environment to adult mental health is needed to mitigate the long-term consequences of childhood disadvantage.
Geographic Variation of Lower-Extremity Major Amputation in Individuals With and Without Diabetes in the Medicare Population
Authors: James S. Wrobel, Jennifer A. Mayfield, Gayle E. Reiber
Journal: Diabetes Care (2001)

OBJECTIVE—To describe geographic variation in rates of lower-limb major amputation in Medicare patients with and without diabetes. RESEARCH DESIGN AND METHODS—This cross-sectional population-based study used national fee-for-service Medicare claims from 1996 through 1997. The unit of analysis was 306 hospital referral regions (HRRs) representing health care markets for their respective tertiary medical centers. Numerators were calculated using nontraumatic major amputations and the diabetes code (250.x) for individuals with diabetes. Denominators for individuals with diabetes were created by multiplying the regional prevalence of diabetes (as determined using a 5% sample of Medicare Part B data identifying at least two visits with a diabetes code for 1995–1996) by the regional Medicare population. Denominators for individuals without diabetes were the remaining Medicare beneficiaries. Rates of major amputations were adjusted for age, sex, and race. RESULTS—Rates of major amputations per year were 3.83 per 1,000 (95% CI 3.60–4.06) individuals with diabetes compared with 0.38 per 1,000 (95% CI 0.35–0.41) individuals without diabetes. Marked geographic variation was observed for individuals with and without diabetes; however, patterns were distinct between the two populations. Rates were high in the Southern and Atlantic states for individuals without diabetes. In contrast, rates for individuals with diabetes were widely varied. Variation across HRRs for individuals with diabetes was 8.6-fold compared with 6.7-fold in individuals without diabetes for major amputations. CONCLUSIONS—Diabetes-related amputation rates exhibit high regional variation, even after age, sex, and race adjustment. Future work should be directed to exploring sources of this variation.