tbuckley/cabot-search huggingface dataset:
JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a knock-in mouse model of essential thrombocythemia
Authors: Catherine M. Hobbs, Harriet Manning, Cavan Bennett, Louella Vasquez, Sonia Severin, Lauren Brain, Alexandra Mazharian, Jose A. Guerrero, Juan Li, Nicole Soranzo, Anthony R. Green, Steve P. Watson, Cedric Ghevaert
Journal: Blood (2013)
Angiogenesis in Craniopharyngiomas: Microvascular Density and Tissue Expression of the Vascular Endothelial Growth Factor (VEGF) and Endostatin
Authors: Cristina M. Dallago, Miriam C. Oliveira, Ligia M. Barbosa-Coutinho, Nelson P. Ferreira
Journal: Endocrine Pathology (2005)
Studies on thermoresponsive polymers: Phase behaviour, drug delivery and biomedical applications
Authors: Arijit Gandhi, Abhijit Paul, Suma Oommen Sen, Kalyan Kumar Sen
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The present review aims to highlight the applications of thermoresponsive polymers. Thermo-responsive polymers show a sharp change in properties upon a small or modest change in temperature. This behaviour can be utilized for the preparation of so-called 'smart' drug delivery systems, which mimic biological response behaviour to a certain extent. Such materials are used in the development of several applications, such as drug delivery systems, tissue engineering scaffolds and gene delivery. Advances in this field are particularly relevant to applications in the areas of regenerative medicine and drug delivery. This review addresses summary of the main applications of thermoresponsive polymers which are categorized based on their 3-dimensional structure; hydrogels, interpenetrating networks, micelles, films and particles. The physico-chemical behaviour underlying the phase transition is also discussed in brief.
841. Anti-Tumor Effect of Tumor Specific Replicating Adenovirus Expressing IL-12 and IL-18
Authors: Jing-Hua Huang, Il-Kyu Choi, Sung-Mi Jung, Minjung Kim, Joo-Hyuk Sohn, Chae-Ok Yun, Joo-Hang Kim
Journal: Molecular Therapy (2006)

Cancer immunotherapy denotes a strategy for activating a host's immune response for the treatment of malignancy. Although cancer cells are less immunogenic, immune system is capable of recognizing and eliminating cancer cells. Oncolytic adenoviral vectors are currently being developed as biologic anti-tumor agents, and coupling the lytic function of an oncolytic adenovirus with its ability as a transgene delivery system represents a powerful extension of this methodology. IL-12 is reported to exhibit potent anti-tumor effect by promoting NK cell and cytotoxic T cell activities.
Toxoplasmosis in the Compromised Host
Authors: JOEL RUSKIN
Journal: Annals of Internal Medicine (1976)

In 81 cases of toxoplasmosis in patients with neoplasia, collagen-vascular disorders, and organ allografts, the clinical manifestations were highly variable but neurologic syndromes consistent with diffuse encephalopathy, meningoencephalitis, or cerebral mass lesions predominated. Many concomitant infections with DNA viruses were seen. The diagnosis of toxoplasmosis was not made until postmortem examination in most cases. Biopsy of lymph nodes or brain and serologic tests needed for definitive diagnosis were done infrequently. Twenty patients received antitoxoplasma chemotherapy (pyrimethamine and sulfonamide), 16 (80%) showing marked clinical improvement or complete remission. In immunosuppressed hosts disseminated toxoplasmosis appears to result from defects in cellular immunity that permit recrudescence of latent infection. Because cell-mediated immunity to Toxoplasma gondii can be enhanced in animals by administration of adjuvants, immunotherapy may become a useful adjunct to chemotherapy in immunoincompetent humans suffering potentially lethal infection.
THE EFFECTS OF ADRENAL STEROIDS AND POTASSIUM DEPLETION ON THE ELABORATION OF AN OSMOTICALLY CONCENTRATED URINE*
Authors: Gerhard Giebisch, Rodolfo Lozano
Journal: Journal of Clinical Investigation (1959)

The investigation reported in this paper is concerned with the effects of desoxycorticosterone acetate (DCA), hydrocortisone and dietary potassium depletion on the elaboration of an osmotically concentrated urine in the hydropenic state.Loeb and his associates (1, 2) demonstrated that dogs maintained on large amounts of DCA develop a diabetes insipidus-like picture.Since then, renal function studies in man (3-5), dogs (6) and rats (7, 8) have shown that the ability of the kidney to concentrate the urine is markedly reduced in states of adrenal hyperfunction and potassium deficiency.The mechanism by which polyuria is produced under these conditions has not been es- tablished.In particular, the role of potassium de- ficiency is still a matter of controversy.Thus, contrary to Loeb and co-workers (1, 2), who were unable to prevent the development of polyuria in their DCA-treated animals by feeding potassium chloride, some authors maintain (9) that the increased loss of potassium following the administration of adrenal steroids is responsible for the impairment of water conservation.Also, there is no agreement on the sensitivity of the kidney to vasopressin (Pitressin®) during various states of potassium depletion (7, 9).The present study is an attempt to clarify some of these points.We have, in particular, studied the formation of a concentrated urine during os- motic diuresis in the hydropenic state.According to current concepts, an osmotically concentrated urine can be visualized as being made up of an isosmotic portion less the amount of water ab- stracted from it to produce hypertonicity ( 10, 11 ).
ERCP and Balloon Dilation Is a Valuable Alternative to Surgical Biliodigestive Anastomosis in the Long Common Channel Syndrome in Childhood
Authors: C. Sebesta, A. Schmid, P. Kier, R. Ruckser, E. Tiefengraber, H. Rosen, K. Stelzhammer, K. Geissler, W. Hruby, E. P. Horcher, W. Hinterberger
Journal: Endoscopy (1995)

See also: ERCP and Balloon Dilation is a Valuable Alternative to Surgical Biliodigestive Anastomosis in the Long Common Channel Syndrome in ChildhoodEndoscopy 1996; 28(08): 724-724DOI: 10.1055/s-2007-1005585
Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study.
Authors: S M Haffner, R D'Agostino, L Mykkänen, R Tracy, B Howard, M Rewers, J Selby, P J Savage, M F Saad
Journal: Diabetes Care (1999)

OBJECTIVE: Among nondiabetic subjects, insulin resistance has been associated with increased cardiovascular risk factors, including dyslipidemia, hypertension, impaired fibrinolysis, and coagulation. Less is known about the relationship between insulin resistance and cardiovascular risk factors in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: To examine this issue, we determined insulin sensitivity (SI) in 479 type 2 diabetic subjects by minimal model analyses of frequently sampled intravenous glucose tolerance tests in the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular disease in African-Americans, Hispanics, and non-Hispanic whites. We defined insulin-sensitive subjects as having SI &amp;gt; or = 1.61 x 10(-4) min-1.microU-1.ml-1 (above median in nondiabetic subjects of all ethnic groups in the IRAS). Using this definition, only 37 type 2 diabetic subjects were insulin sensitive, and the remaining 442 were insulin resistant. RESULTS: After adjustment for age, sex, ethnicity, and clinic, insulin resistance was significantly correlated with total triglycerides, VLDL cholesterol, VLDL triglyceride, fibrinogen, PAI-1, and fasting glucose, and was inversely correlated with HDL cholesterol level and LDL size. Carotid intimal-medial thickness was greater in insulin-resistant than in insulin-sensitive subjects, but this difference was not statistically significant. After further adjustment for waist circumference (marker of visceral adiposity), insulin-resistant subjects continued to have higher plasminogen activator inhibitor 1 and VLDL triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size than did insulin-sensitive subjects. After further adjustment for fasting glucose levels, these results were very similar. CONCLUSIONS: We conclude that insulin-resistant type 2 diabetic subjects have more atherogenic cardiovascular risk factor profiles than insulin-sensitive type 2 diabetic subjects and that this is only partially related to increased obesity and an adverse body fat distribution.
Occupational asthma due to gas metal arc welding on mild steel.
Authors: O Vandenplas, F Dargent, J J Auverdin, J Boulanger, J M Bossiroy, D Roosels, R Vande Weyer
Journal: Thorax (1995)

Occupational asthma has been documented in electric arc welders exposed to manual metal arc welding on stainless steel. A subject is described who developed late and dual asthmatic reactions after occupational-type challenge exposure to gas metal arc welding on uncoated mild steel.
Levels and Initial Course of Serum Alanine Aminotransferase Can Predict Outcome of Patients With Budd–Chiari Syndrome
Authors: Pierre–Emmanuel Rautou, Rami Moucari, Dominique Cazals–Hatem, Sylvie Escolano, Cécile Denié, Ludivine Douarin, Claire Francoz, François Durand, Violaine Ozenne, Audrey Imbert, Richard Moreau, Didier Lebrec, Aurélie Plessier, Dominique Valla
Journal: Clinical Gastroenterology and Hepatology (2009)
Maintaining Competency in Advanced Cardiac Life Support Skills
Authors: Jeoffrey K. Stross
Journal: JAMA (1983)

One hundred thirty-two physicians who successfully completed advanced cardiac life support (ACLS) training were randomly placed in a control group or one of two groups receiving interventions designed to provide reinforcement of previously mastered knowledge and skills. These interventions included mailed periodic reprints (group 1) or quarterly patient management problems (group 2). All physicians were retested for knowledge and skills related to ACLS one year later. Fifty-two (39.4%) could successfully ventilate the mannequin, and 62 (47.0%) could perform cardiac compression adequately. No differences were noted among groups. Significant differences in knowledge were found. The control group initiated appropriate therapy in a mock-arrest situation 52% of the time, while group 1 averaged 75% and group 2 averaged 82%. These results indicate that reinforcement after continuing medical education may enhance knowledge retention, but does not maintain motor skills. Yearly recertification in ACLS skills should be considered, and frequent practice sessions should be encouraged for those physicians who are not active participants in ACLS activities.
Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes.
Authors: P J Peters, J Borst, V Oorschot, M Fukuda, O Krähenbühl, J Tschopp, J W Slot, H J Geuze
Journal: The Journal of Experimental Medicine (1991)

Cytotoxic T lymphocytes (CTL) contain granules that are exocytosed during specific interaction with target cells (TC). In this process, the granule contents, including the lethal protein perforin, as well as granzymes, a family of serine esterases, are delivered to the TC. Information regarding the routing of these proteins towards the granule and their exact localization within the granule is of primary importance to resolve the mechanism of granule-mediated TC killing. In this study, the subcellular localization of perforin, granzymes, and known endosomal and lysosomal marker proteins was determined in human and murine CTL, by immunogold labeling of ultrathin cryosections followed by electron microscopy. Perforin and granzymes can be detected in rough endoplasmic reticulum, Golgi complex, trans-Golgi reticulum, and in all cytotoxic granules. Within the granules, they have a similar distribution and are localized not only in the so-called dense core but also over the region containing small internal vesicles. This finding implies that perforin and granzymes can be released in membrane-enveloped and/or -associated form into the intercellular cleft formed upon CTL-TC interaction. On the basis of the present evidence, additional release of these molecules in soluble form cannot be excluded. The lysosomal membrane glycoproteins lamp-1, lamp-2, and CD63, are abundantly present on the granule-delimiting outer membrane, which becomes incorporated into the CTL plasma membrane during lethal hit delivery. In contrast, the cation-dependent mannose 6-phosphate receptor, known to be present in endosomes and absent from lysosomes, is found only in a minority of the granules. Together with our previous findings that the granules are acidic and connected to the endocytic pathway, these observations define CTL granules as secretory lysosomes.
A Longitudinal Study on the Natural History of Serum Hepatitis B Surface Antigen Changes in Chronic Hepatitis B
Authors: Henry Lik-Yuen Chan, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Chi-Hang Tse, Hoi-Yun Chan, Joseph Jao-Yao Sung
Journal: Hepatology (2010)

Serum hepatitis B surface antigen (HBsAg) quantification has been suggested to reflect the concentration of covalently closed circular DNA in the liver. We aimed to investigate the HBsAg levels at different stages of chronic hepatitis B and the changes in HBsAg level during the natural progression of disease. One hundred seventeen untreated patients with chronic hepatitis B were studied with longitudinal follow-up for 99 ± 16 months. HBsAg quantification was performed at the first visit, the last visit, and three visits at each quartile during the follow-up. At the first visit, HBsAg level was higher among patients who were hepatitis B e antigen (HBeAg)-positive (N = 49) than those who were HBeAg-negative (N = 68) (4.01 ± 0.91 log IU/mL versus 2.73 ± 1.25 log IU/mL, P &lt; 0.001). HBsAg level was persistently high at approximately 5 log IU/mL among patients in the immune tolerance phase (N = 7). The HBsAg levels among patients with HBeAg-positive active disease (N = 25) or sustained HBeAg seroconversion (N = 17) were comparable at approximately 3-4 log IU/mL. The HBsAg levels among patients who were HBeAg-negative tended to be higher among patients with active (N = 46) than those with inactive disease (N = 22). The median HBsAg levels decreased in HBeAg-negative patients with active and inactive disease by 0.041 log IU/mL/year and 0.043 log IU/mL/year, respectively. Twenty-two (17%) patients had HBsAg reduction &gt;1 log IU/mL at the last visit; most of them showed reduced hepatitis B virus DNA, and eight had HBsAg loss. Conclusion: HBsAg remained stable in HBeAg-positive patients and tended to reduce slowly in HBeAg-negative patients. Reduction of HBsAg for &gt;1 log IU/mL could reflect improved immune control. (Hepatology 2010)
Comparative Effectiveness Research, Genomics-Enabled Personalized Medicine, and Rapid Learning Health Care: A Common Bond
Authors: Geoffrey S. Ginsburg, Nicole M. Kuderer
Journal: Journal of Clinical Oncology (2012)

Despite stunning advances in our understanding of the genetics and the molecular basis for cancer, many patients with cancer are not yet receiving therapy tailored specifically to their tumor biology. The translation of these advances into clinical practice has been hindered, in part, by the lack of evidence for biomarkers supporting the personalized medicine approach. Most stakeholders agree that the translation of biomarkers into clinical care requires evidence of clinical utility. The highest level of evidence comes from randomized controlled clinical trials (RCTs). However, in many instances, there may be no RCTs that are feasible for assessing the clinical utility of potentially valuable genomic biomarkers. In the absence of RCTs, evidence generation will require well-designed cohort studies for comparative effectiveness research (CER) that link detailed clinical information to tumor biology and genomic data. CER also uses systematic reviews, evidence-quality appraisal, and health outcomes research to provide a methodologic framework for assessing biologic patient subgroups. Rapid learning health care (RLHC) is a model in which diverse data are made available, ideally in a robust and real-time fashion, potentially facilitating CER and personalized medicine. Nonetheless, to realize the full potential of personalized care using RLHC requires advances in CER and biostatistics methodology and the development of interoperable informatics systems, which has been recognized by the National Cancer Institute's program for CER and personalized medicine. The integration of CER methodology and genomics linked to RLHC should enhance, expedite, and expand the evidence generation required for fully realizing personalized cancer care.
A Clinical Interpretation of Bilateral Hilar Adenopathy
Authors: RICHARD H. WINTERBAUER
Journal: Annals of Internal Medicine (1973)

One hundred patients with bilateral hilar adenopathy were reviewed to see if there was a difference between the clinical presentation of granulomatous and neoplastic hilar adenopathy. The 11 patients with neoplastic hilar adenopathy were all symptomatic, and 9 had easily identifiable extrathoracic tumor on physical examination. In symptomatic patients with abnormal examinations, the clinical presentation did not separate granulomatous from neoplastic hilar adenopathy, with the exception that erythema nodosum and uveitis were always a manifestation of sarcoidosis. However, bilateral hilar adenopathy in 30 asymptomatic patients was always caused by sarcoidosis, and 50 of 52 patients with bilateral hilar adenopathy and negative physical examinations had sarcoidosis. We conclude that bilateral hilar adenopathy in asymptomatic patients with negative physical examinations or in association with erythema nodosum or uveitis should be considered a priori evidence of sarcoidosis, and biopsy confirmation of the diagnosis is not necessary.
Sjögren's Syndrome in Progressive Systemic Sclerosis
Authors: JAMES F. CIPOLETTI
Journal: Annals of Internal Medicine (1977)

Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sjögren's syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reported by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sjögren's syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynaud's phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.
Book Review Oxford Textbook of Clinical Hepatology Second edition. Edited by Johannes Bircher, Jean-Pierre Benhamou, Neil McIntyre, Mario Rizzetto, and Juan Rodés. 2148 pp. in two volumes, illustrated. New York, Oxford University Press, 1999. $350. 0-19-262515-2
Authors: Alexander L. Gerbes
Journal: New England Journal of Medicine (1999)
When I'm 64
Authors: James Owen Drife
Journal: BMJ (2011)

Last weekend, the 1971 medical graduates met in Edinburgh. We’ve had reunions before but this one was special. With most of us retired, for the first time in our lives we felt relaxed. The hospital and medical school have moved to the suburbs, so we could admire the new site and reminisce among the luxury apartments that have replaced the old one.

But the real thrill was the rebirth of our student band, the Unbelievable Brass, complete with …
Immunocytologic analysis of nasal cells obtained by nasal lavage: a comparative study with a standard method of cell identification
Authors: J. Prat, A. Xaubet, J. Mullol, V. Plaza, M. Masó, R. Lleonart, C. Picado
Journal: Allergy (1993)

For evaluation of two methods of nasal cell identification, cell morphology and immunocytologic analysis, nasal lavage was performed in 16 healthy subjects and 29 patients suffering from rhinitis. Nasal lavage smears were stained with May‐Grünwald‐Giemsa (MGG), and cells were identified according to their structure as epithelial cells, neutrophils, lymphocytes, eosinophils, and metachromatic cells (basophils and mast cells). Immunocytologic analysis was performed with monoclonal antibodies by the immunoalkaline phosphatase method. The following monoclonal antibodies were used: CK1, EG2, and CD3, which identify epithelial cells, activated eosinophils, and T lymphocytes, respectively; CD 15, which recognizes mature granulocytic cells; and CD 14, which reacts with monocytes and macrophages. A significant difference was observed between the two methods in the number of identified epithelial cells, in both controls (64.6 ± 7.8% with MGG, 14.2 ± 3.5% with CK1 analysis) and patients with rhinitis (56.9 ± 7.6% with MGG, 18.2 ± 3.7% with CK1 analysis). In contrast, no significant differences were found in eosinophil and neutrophil counts when the two methods were compared. After nasal allergic provocation, a significant increase in the number of eosinophils was observed with both methods in seven patients with rhinitis. The results of this study indicate that: 1) MGG staining is a useful method to identify the cells obtained by nasal lavage, and 2) immunocytologic analysis with monoclonal antibodies accurately identifies granulocytic cells, while only a low proportion of epithelial cells are detected, probably because anticytokeratin monoclonal antibody reacts only with viable cells.
Neuropeptides, Appetite Regulation, and Human Obesity
Authors: John F. Wilber
Journal: JAMA (1991)

<h3>SELECTED CASE</h3> A 55-YEAR-OLD married white woman presented with a 30-year history of progressive morbid obesity. Her birth weight was normal, at 3.8 kg. Her weight gain continued progressively, except for two self-induced remissions by means of severe restriction of energy intake (840 to 1680 J/d [1 cal = 4.2 J]). Her usual diet consisted of 18 900 to 21 000 J/d. Associated medical problems included choledocholithiasis, resulting in a cholecystectomy at age 29 years, and severe osteoarthritis involving both knees and the lower vertebral column. Meningitis with encephalitis occurred at age 3 years. The patient had normal urinary free cortisol (70 μg/d) and thyroid function test results. The patient was treated with moderate restriction of energy intake (decrease of 4000 J/d) without anorexigenic medications. She walked 3.3 km/d five times per week. Results of physical examination were as follows: blood pressure, 220/120 mm Hg in the left arm with a
Cutaneous pseudolymphoma, lymphomatoid contact dermatitis type, as an unusual cause of symmetrical upper eyelid nodules
Authors: R.P. Braun, L.E. French, R. Feldmann, P. Chavaz, J-H. Saurat
Journal: British Journal of Dermatology (2000)

We describe a 74-year-old woman who rapidly developed bilateral voluminous nodules on the upper eyelids, following 4 months’ treatment for chalazion. Histological and immunohistochemical findings were suggestive of cutaneous pseudolymphoma (CPL), and extensive screening for malignant lymphoma (ML) remained negative. Cutaneous pseudolymphomas are inflammatory diseases that can simulate ML either clinically, histopathologically, or both. They are a rare cause of nodules of the upper eyelids, usually characterized by a benign evolution, that can be secondary to ultraviolet sensitivity, adverse reactions to systemic medications and contact sensitization, among others. In our case, epicutaneous patch tests were strongly positive for a series of allergens contained in the ophthalmological preparations used; therefore, they were suggestive that the patient had CPL, lymphomatoid contact dermatitis type. In addition, the patient had been treated previously with several drugs, known to cause CPL and immune dysregulation. Complete regression of the lesions required treatment with systemic steroids and chlorambucil. No relapse occurred within a 5-year follow-up period.