tbuckley/cabot-search huggingface dataset:
Antigen-specific immune responses to influenza vaccine in utero
Authors: Deepa Rastogi, Chaodong Wang, Xia Mao, Cynthia Lendor, Paul B. Rothman, Rachel L. Miller
Journal: Journal of Clinical Investigation (2007)

Initial immune responses to allergens may occur before birth, thereby modulating the subsequent development of atopy. This paradigm remains controversial, however, due to the inability to identify antigen-specific T cells in cord blood. The advent of MHC tetramers has revolutionized the detection of antigen-specific T cells. Tetramer staining of cord blood after CMV infection has demonstrated that effective CD8+ antigen-specific immune responses can follow intrauterine viral infections. We hypothesized that sensitization to antigens occurs in utero in humans. We studied cord blood B and T cell immune responses following vaccination against influenza during pregnancy. Anti-Fluzone and anti-matrix protein IgM antibodies were detected in 38.5% (27 of 70) and 40.0% (28 of 70), respectively, of cord blood specimens. Using MHC tetramers, HA-specific CD4+ T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father. Matrix protein–specific CD8+ T cells were detected among 10.0% (2 of 20) of HLA-A*0201+ newborns. These results suggest that B and T cell immune responses occur in the fetus following vaccination against influenza and have important implications for determining when immune responses to environmental exposures begin.
Dose-Intense Chemotherapy Every 2 Weeks With Dose-Intense Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone May Improve Survival in Intermediate- and High-Grade Lymphoma: A Phase II Study of the Southwest Oncology Group (SWOG 9349)
Authors: Douglas W. Blayney, Michael L. LeBlanc, Thomas Grogan, Ellen R. Gaynor, Robert A. Chapman, C. Harris Spiridonidis, Sarah A. Taylor, Scott I. Bearman, Thomas P. Miller, Richard I. Fisher
Journal: Journal of Clinical Oncology (2003)

To test the hypothesis that therapy of intermediate- and high-grade (excluding Burkitt lymphoblastic) lymphoma with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) could be safely dose-intensified with routine filgrastim support.Eligible patients were those who were previously untreated and who had either bulky stage II, or stage III or IV lymphoma with working formulation histology D, E, F, G, H, or J; performance status < or = 2; and acceptable end organ function. No upper age limit was specified. Therapy was dose-intensified CHOP (CHOP-DI) with filgrastim support. Each course was repeated every 14 days for six planned courses.Eighty-eight eligible patients were treated with CHOP-DI and had a median follow-up of 5.1 years on this phase II study, designated Southwest Oncology Group (SWOG) 9349. The progression-free survival was 51% at 2 years and 41% at 5 years. The overall survival was 60% at 5 years. Three fatal treatment-related events occurred. One patient with myelodysplastic syndrome was reported.Treatment with CHOP-DI can be safely administered in the cooperative group setting and results in improved survival. Estimated overall survival at 5 years was 14% better than that of patients treated with standard-dose CHOP in an earlier SWOG study, although progression-free survival of 60% at 2 years-the prespecified end point-was not achieved. CHOP-DI, given every 2 weeks at escalated doses, is a strategy that should be tested in a future randomized clinical trial in lymphoma.
Mammographic Screening-Reply
Authors: Susan M. Love
Journal: JAMA (1994)

<h3>In Reply.</h3> —Dr Gambrell raises some interesting issues but appears to miss the fundamental conclusions of meta-analyses of screening mammograms: there is no evidence that mammographic screening reduces deaths from breast cancer in women younger than 50 years, and there is clear evidence that it increases the social, psychological, and economic costs of care.<sup>1</sup>The fact that four of 15 of the cancers diagnosed in his practice were in patients younger than 50 years does not mean that this is a risk-free, cost-effective, or lifesaving procedure for this age group. Under no circumstances can individual clinical experience provide a scientifically valid assessment of screening practices in large populations. No amount of wishful thinking can supplant randomized controlled studies, which remain the gold standard. Indeed, Gambrell does not indicate whether the cases he diagnosed were found by screening mammograms, nor does he tell us whether this diagnosis saved their lives.
Trimming of antigenic peptides in an early secretory compartment.
Authors: H L Snyder, J W Yewdell, J R Bennink
Journal: The Journal of Experimental Medicine (1994)

Major histocompatibility complex (MHC) class I molecules bind peptides of 8-10 residues in the endoplasmic reticulum (ER) and convey them to the cell surface for inspection by CD8-expressing T cells (TCD8+). Antigenic peptides are predominantly derived from a cytosolic pool of polypeptides. The proteolytic generation of peptides from polypeptides clearly begins in the cytosol, but it is uncertain whether the final proteolytic steps occur before or after peptides are transported into the ER by the MHC-encoded peptide transporter (TAP). To study the trimming of antigenic peptides in the secretory pathway in the absence of cytosolic processing, we used an NH2-terminal signal sequence to target to the ER of TAP-deficient cells, "tandem" peptides consisting of two defined TCD8+ determinants arranged from head to tail. We find that in contrast to cytosolic proteases in TAP-expressing cells, which are able to liberate antigenic peptides from either end of a tandem peptide, proteases (probably aminopeptidases) present in an early secretory compartment preferentially liberate the COOH-terminal determinant. These findings demonstrate that proteolytic activities associated with antigen processing are not limited to the cytosol, but that they also exist in an early secretory compartment. Such secretory aminopeptidases may function to trim TAP-transported peptides to the optimal size for binding to class I molecules.
Sudden death after treatment with pulsed methylprednisolone.
Authors: P V Gardiner, I D Griffiths
Journal: BMJ (1990)

1982, was controlled with metformin 500 mg twice daily.At laparotomy the duodenal nodule was resected and the liver appeared clear.Histology confirmed a non-argyrophilic, non-argentophilic, trabecular carcinoid tumour which had not invaded the muscularis propria.A urinary screen for 5hydroxyindole acetic acid gave a negative result.Although carcinoid tumours are the most common primary tumour of the small intestine, duodenal carcinoids are rare.'In the case of gastric carcinoids gastrin may play a part as it appears to act as a trophic hormone.2The relation between drug induced hypergastrinaemia and carcinoids remains the subject of much debate.'Carcinoid tumours found in patients with chronic atrophic gastritis or pernicious anaemia,4 or in rats given long term H2 antagonists, appear to be confined to the gastric fundus.5Nevertheless, the occurrence of such an unusual tumour in a patient receiving long term treatment with ranitidine leads us to suspect that the two may be interrelated.Neither the manufacturer nor the Committee on Safety of Medicines is aware of any previous reports of such an association.1 Barclay I'HC, Schapira DVI.Malignant tumours of the small
Gouty arthritis in the manubriosternal joint
Authors: F PEREZ-RUIZ, M CALABOZO, A ALONSO-RUIZ
Journal: Annals of the Rheumatic Diseases (1997)

No transmission risk was found except for spinal surgery one year before the symptoms and signs of the disease began.She had not received any blood, and there was no abnormality in the liver function tests during her follow up.We found no significant diVerence between healthy population and SLE patients in terms of prevalence of anti-HCV (p>0.05).In the medical literature, we could not find any study about the prevalence of anti-HCV in SLE patients.However, Michel et al 10 in their study about anti-GOR and HCV in autoimmune liver diseases have reported no anti-HCV in 10 SLE patients.Our results showed that the prevalence of the anti-HCV in patients with SLE was not higher than that of the general population, and the relation between HCV and SLE could not be established.
Screening for Mild Thyroid Failure at the Periodic Health Examination
Authors: Mark D. Danese
Journal: JAMA (1996)

To estimate the cost-effectiveness of periodic screening for mild thyroid failure by measurement of serum thyroid stimulating hormone (TSH) concentration.Cost-utility analysis using a state-transition computer decision model that accounted for case finding, medical consequences of mild thyroid failure, and costs of care during 40 years of simulated follow-up.Periodic health examinations in offices of primary care physicians.Hypothetical cohorts of women and men screened every 5 years during the recommended periodic examination, beginning at age 35 years.Adding the serum TSH assay to total serum cholesterol screening was compared to cholesterol screening alone.Discounted quality-adjusted life years (QALYs) and direct medical costs from a societal perspective.The cost-effectiveness of screening 35-year-old patients with a serum TSH assay every 5 years was $9223 per QALY for women and $22595 per QALY for men. The cost-effectiveness became more favorable when age at first screening was increased for both sexes and was always more favorable for women than men. Reduced progression to overt hypothyroidism and relief of symptoms increased QALYs, but did not substantially reduce direct medical costs. Finding hypercholesterolemia induced by mild thyroid failure reduced direct medical costs, but did not substantially increase QALYs. The cost of a TSH assay and the importance to patients of symptoms associated with thyroid failure were the most influential factors in sensitivity analyses.The cost-effectiveness of screening for mild thyroid failure compares favorably with other generally accepted preventive medical practices. Physicians should consider measuring serum TSH concentration in patients aged 35 years and older undergoing routine periodic health examinations. The cost-effectiveness of screening is most favorable in elderly women.
Delay in diagnosis and long-term survival in breast cancer.
Authors: J M Elwood, W P Moorehead
Journal: BMJ (1980)

The records of all 1591 women with a histologically confirmed primary breast neoplasm who received their primary treatment at the main referral centre in British Columbia and were diagnosed in the years 1945, 1950, 1955, 1960, 1965, 1970, or 1975 were reviewed. The interval from appearance of the first symptom to diagnosis decreased from 1945 to 1960, but no change was seen from 1960 to 1975. An analysis of survival from the date of first symptom showed that long-term survival was greater in patients with a shorter delay between the appearance of symptoms and diagnosis. The demonstration that shorter delay does improve survival, even when assessed from the appearance of the first symptom, yet delay times have not been falling recently, suggests that educational efforts are inefficient.
Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice.
Authors: N S Shachter, T Hayek, T Leff, J D Smith, D W Rosenberg, A Walsh, R Ramakrishnan, I J Goldberg, H N Ginsberg, J L Breslow
Journal: Journal of Clinical Investigation (1994)

We have generated transgenic mice expressing the human apolipoprotein CII (apoCII) gene under the transcriptional control of the human cytochrome P-450 IA1 (CYPIA1) promoter. Human apoCII transgenic (HuCIITg) mice exhibited significant basal expression of the transgene (plasma apoCII level = 26.1 +/- 4 mg/dl) and showed further induction of transgene expression after treatment with beta-naphthoflavone. Unexpectedly, HuCIITg mice were hypertriglyceridemic and human apoCII levels correlated strongly to triglyceride levels (R = 0.89, P < 0.0001). Triglyceride levels (mg/dl +/- SEM) were elevated compared to controls in both the fed (804 +/- 113 vs 146 +/- 18, P < 0.001) and fasted (273 +/- 39 vs 61 +/- 4, P < 0.001) states. HuCIITg mice accumulated triglyceride-rich very low density lipoproteins (VLDL) with an increased apoC/apoE ratio. Tracer kinetic studies indicated delayed clearance of VLDL-triglyceride, and studies using Triton inhibition of VLDL clearance showed no increase in VLDL production. Plasma from these mice activated mouse lipoprotein lipase normally and radiolabeled VLDL were normally hydrolyzed. However, HuCIITg VLDL showed markedly decreased binding to heparin-Sepharose, suggesting that apoCII-rich, apoE-poor lipoprotein may be less accessible to cell surface lipases or receptors within their glycosaminoglycan matrices. HuCIITg mice are a promising model of hypertriglyceridemia that suggests a more complex role for apoCII in the metabolism of plasma triglycerides.
Medical students at risk from needlestick injury
Authors: D. Josefson
Journal: BMJ (1999)

Needlestick injuries are common among medical students and pose a significant health risk, according to a new study (Annals of Internal Medicine 1999;130:45-51).

Although occupational exposure to bloodborne pathogens is now widely recognised as a hazard for healthcare workers, medical students may be at particular risk, according to researchers at the University of California at San Francisco (UCSF).

In the first comprehensive, long term study of the subject, researchers led by Dr Emilie Osborn found that 11.7% of medical students surveyed had sustained needlestick injuries or mucosal exposures to blood. …
Nanowell‐Trapped Charged Ligand‐Bearing Nanoparticle Surfaces: A Novel Method of Enhancing Flow‐Resistant Cell Adhesion
Authors: Phat L. Tran, Jessica R. Gamboa, Katherine E. McCracken, Mark R. Riley, Marvin J. Slepian, Jeong‐Yeol Yoon
Journal: Advanced Healthcare Materials (2012)

Abstract Assuring cell adhesion to an underlying biomaterial surface is vital in implant device design and tissue engineering, particularly under circumstances where cells are subjected to potential detachment from overriding fluid flow. Cell–substrate adhesion is a highly regulated process involving the interplay of mechanical properties, surface topographic features, electrostatic charge, and biochemical mechanisms. At the nanoscale level, the physical properties of the underlying substrate are of particular importance in cell adhesion. Conventionally, natural, pro‐adhesive, and often thrombogenic, protein biomaterials are frequently utilized to facilitate adhesion. In the present study, nanofabrication techniques are utilized to enhance the biological functionality of a synthetic polymer surface, polymethymethacrylate, with respect to cell adhesion. Specifically we examine the effect on cell adhesion of combining: 1. optimized surface texturing, 2. electrostatic charge and 3. cell adhesive ligands, uniquely assembled on the substrata surface, as an ensemble of nanoparticles trapped in nanowells. Our results reveal that the ensemble strategy leads to enhanced, more than simply additive, endothelial cell adhesion under both static and flow conditions. This strategy may be of particular utility for enhancing flow‐resistant endothelialization of blood‐contacting surfaces of cardiovascular devices subjected to flow‐mediated shear.
Abstract 3606: Dynamic expression of pepsinogen I in gastric diseases sequence and relationship with Helicobacter pylori infection
Authors: Ping Li, Liping Sun, Yuan Yuan
Journal: Cancer Research (2012)

Abstract Serum PG I and PG I /PGII levels seemed to be related to the functional changes in the stomach, and their use as ‘serological biopsy’ in gastric cancer and precancerous diseases has been reported over 20 years. But the dynamic expression of pepsinogen I in situ of gastric mucosa and the value to detect gastric cancer and precancerous diseases, relative to the serum pepsinogen I is still unclear. Helicobacter pylori is a gram-negative bacterium that colonizes the stomach. More than 50% of the adult population are infected with H. pylori worldwide. Numerous studies have reported that healthy volunteers and gastric ulcer patients with H pylori infection have increased serum pepsinogen I levels which decrease after H pylori eradication. The evidence whether expression of pepesinogen I in situ affected by H pylori infection is not available. We thus conducted this study to investigate the dynamic expression of pepsinogen I in superficial gastritis, atrophic gastritis, gastric cancer and also H.pylori-associated gastric lesions and evaluate the application value of pepsinogen I in classifying gastric cancer and its precancerous diseases, and also the influence of H pylori on pepsinogen I expression. The expression of pepsinogen I was determined by immunohistochemistry method in 185 cases with mucosa taken from gastric corpus as well as from antrum. H.pylori infection was determined by histological examination and ELISA. Serum pepsinogen I and II were determined by ELISA. We found that Pepsinogen I was only expressed in the gastric corpus. There were 185 cases from gastric corpus and the positive rate of pepsinogen I expression in superficial gastritis, atrophic gastritis and gastric cancer decreased significantly in sequence (P&amp;lt;0.05;100% vs. 83.3%vs0.0%), and the over-expression rate also decreased along with the sequence: normal, superficial gastritis, atrophic gastritis and gastric cancer (p&amp;lt;0.05; 93.3%vs72.9% vs22.2vs0.0%). The over-expression rate of pepsinogen I in superficial gastritis with H pylori infection was higher than that without H pylori infection (P=0.035; β2 = 4.46).The serum expression of Pepsinogen I had no statistical difference (P&amp;gt;0.05) and the ratio of sPGA to sPGC decreased along with the above groups. (P&amp;lt;0.05). In conclusion, expression of PGI in situ has positive correlation with the degree of malignancy of gastric mucosa. and it is good biomarker for the diagnosis of gastric cancer and precancerous diseases. Also, The expression of PGI has positive correlation with H.pylori infection, and maybe is an important part in the H pylori- related damage or a good marker for screening H.pylori infection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3606. doi:1538-7445.AM2012-3606
Cutaneous Gangrene Following Massive Self-administration of Adrenaline
Authors: R. B. Coles, W. M. M. Douglass
Journal: BMJ (1955)

MEDICAL MEMORANDA MBICHJOLA close watch should be kept for the onset of collapse in infants at this time, since it may appear with remarkable rapidity.It is suggested that disappearance of the skin lesions to a greater degree than that to be reasonably ex- pected from routine therapy may be a valuable warning sign, and that a rise in the respiratory rate to 60 a minute or over, without evidence of chest or other disease, is a signal for urgent therapy.Cortisone appears to be a rational therapeutic approach in eczema collapse.We are grateful to Dr. J.
Gordon Robert Bruce Skinner
Authors: C. G. Fink
Journal: BMJ (2014)

There are always those who have been regarded as pestilential nuisances by their medical colleagues. Gordon Robert Bruce Skinner was from the very start the iconoclast’s iconoclast. A Glaswegian boy, he was described at the age of 8, by a primary school teacher whose car tyres he let down, as educationally subnormal. Despite such well supported beginnings he attended Kelvinside Academy Grammar School and qualified in medicine. He came to the University of Birmingham to train in the obstetrics department of Hugh McLaren, another Glaswegian, and quickly established himself as a larger than life character with an irrepressible Glaswegian humour and evidently was a very talented and decidedly awkward member of the department. Training in obstetrics completed, Gordon was seconded to a research fellowship in the virology department under Peter Wildy, with whom he worked closely and whom he respected. In 1976 he became a senior lecturer in microbiology with consultant status in the Queen Elizabeth Hospital.

He …
Abstract 4268: Breast cancer stem cells play a role in trastuzumab resistance in mouse xenograph models
Authors: Korkaya Hasan, Amanda K. Paulson, Qin Zen, Hayley J. Smithkort, Ahmet A. Quraishi, Shivani Patel, Suling Liu, Amber Heath, Shawn G. Clouthier, Max S. Wicha
Journal: Cancer Research (2010)

Abstract One of the most significant advances in breast cancer therapeutics has been the development of HER2 targeted therapies for treatment of HER2 overexpressing breast cancer. The use of HER2 inhibitors such as trastuzumab have improved patient outcome in both the adjuvant and advanced setting. However, one-third of HER2-positive tumors do not respond to HER2 targeted agents and resistance may develop in patients with chronic exposure. Nearly 50% of patients who respond to HER2 targeted agents relapse within a year. The mechanism of resistance to HER2 targeted agents is not entirely clear. However, increasing evidence indicates that this resistance may be associated with loss of PTEN (phosphotase and tensin homolog), the gain of function of somatic mutations of PI3KA or truncation of the extracellular domain of HER2. We have recently demonstrated that trastuzumab reduces the cancer stem cell (CSC) population in trastuzumab sensitive but not trastuzumab resistant cell lines. In order to elucidate the mechanisms of trastuzumab resistance we engineered MCF7 cells to overexpress HER2, knockdown PTEN or both. HER2 overexpression or PTEN knockdown increased the proportion of CSC's as assessed by the Aldefluor assay and tumor initiation in NOD/SCID mice. Cell lines with both HER2 overexpression and PTEN knockdown contained a significantly higher proportion of Aldefluor positive (3.2 %) compared to either alteration alone (1.7%, 1.9% respectively and 0.5 % in parental cells). In addition, cells with both PTEN deletion and HER2 overexpression showed several fold increase in their invasive properties in vitro as compared cells with either alteration alone. Furthermore, cells with the combined alterations but not those with either alone were highly metastatic in NOD/SCID mice consistent with the demonstrated role of CSC's in mediating tumor metastasis. Trastuzumab treatment significantly reduced the Aldefluor positive population in HER2 overexpressing cells. In contrasts trastuzumab had no effect on the Aldefluor positive population in cells with both HER2 overexpression and PTEN knockdown. These studies suggest that PTEN deletion renders Her 2 overexpressing MCF7 breast cancers resistant to trastuzumab by regulating the CSC population. Strategies aimed at blocking downstream signaling through PI3K or Akt inhibition may effectively target this important cell population in trastuzumab resistant tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4268.