tbuckley/cabot-search huggingface dataset:
Skin as a route of exposure and sensitization in chronic beryllium disease.
Authors: Sally S Tinkle, James M Antonini, Brenda A Rich, Jenny R Roberts, Rebecca Salmen, Karyn DePree, Eric J Adkins
Journal: Environmental Health Perspectives (2003)

Chronic beryllium disease is an occupational lung disease that begins as a cell-mediated immune response to beryllium. Although respiratory and engineering controls have significantly decreased occupational beryllium exposures over the last decade, the rate of beryllium sensitization has not declined. We hypothesized that skin exposure to beryllium particles would provide an alternative route for sensitization to this metal. We employed optical scanning laser confocal microscopy and size-selected fluorospheres to demonstrate that 0.5- and 1.0- micro m particles, in conjunction with motion, as at the wrist, penetrate the stratum corneum of human skin and reach the epidermis and, occasionally, the dermis. The cutaneous immune response to chemical sensitizers is initiated in the skin, matures in the local lymph node (LN), and releases hapten-specific T cells into the peripheral blood. Topical application of beryllium to C3H mice generated beryllium-specific sensitization that was documented by peripheral blood and LN beryllium lymphocyte proliferation tests (BeLPT) and by changes in LN T-cell activation markers, increased expression of CD44, and decreased CD62L. In a sensitization-challenge treatment paradigm, epicutaneous beryllium increased murine ear thickness following chemical challenge. These data are consistent with development of a hapten-specific, cell-mediated immune response following topical application of beryllium and suggest a mechanistic link between the persistent rate of beryllium worker sensitization and skin exposure to fine and ultrafine beryllium particles.
Radioimmunoassay for human follicle—stimulating hormone: physiological studies
Authors: W. D. Odell, A. F. Parlow, C. M. Cargille, G. T. Ross
Journal: Journal of Clinical Investigation (1968)

Most of the information concerning secretion changes in follicle-stimulating hormone (FSH) in humans has been gained with relatively insensitive bioassays of concentrates of pools of urine. We have developed a sensitive and specific radioimmunoassay for FSH that is 500-1000 times more sensitive than the rat ovarianweight augmentation assay and which is capable of quantifying FSH in small volumes of serum. Anti-FSH was prepared by immunizing rabbits with an impure FSH preparation. The majority of antisera showed complete inability to distinguish LH, TSH, and FSH, illustrating the immunological similarities of these hormones. One antiserum was specific when used in a radioimmunoassay. Potency estimates by bioassay were in good agreement, with a single exception, with those obtained with the radioimmunoassay for 10 FSH-containing preparations. Highly purified LH gave a higher potency by immunoassay than by bioassay. Sera from eugonadal men contained 5-25 mIU/ml; sera from castrate men contained over 30 mIU/ml. Sera from eugonadal women contained 7-25 mIU/ml during the follicular phase and 5-15 mIU/ml during the luteal phase of the menstrual cycle. Sera from castrate or postmenopausal women contained 40-250 mIU/ml. FSH was measured throughout the menstrual cycle in 19 women. The general pattern that emerged is summarized as follows: there is a small early follicular phase rise in FSH, and then FSH is relatively constant until mid-cycle; in the majority of women a mid-cycle rise of FSH occurs coincidentally to the mid-cycle LH ovulatory peak; during the luteal phase FSH levels are relatively constant and lower than during the follicular phase. Nonsequential oral contraceptives containing estrogen and progestogen abolish these changes and FSH concentrations remain low throughout treatment. Treatment of castrate men and castrate or postmenopausal women with high doses of oral estrogens results in a fall of FSH to levels found in eugonadal men or women, but not to undetectable levels. Children less than 5 yr of age had undetectable FSH (< 5 mIU/ml).
Addressing Rising Health Care Costs — A View from the Congressional Budget Office
Authors: Peter R. Orszag, Philip Ellis
Journal: New England Journal of Medicine (2007)

Interview with Peter Orszag on the rising cost of health care. (07:58)Download The long-term fiscal balance of the United States will be determined primarily by the future rate of growth of health care costs, as we have recently noted.1 If costs per enrollee in Medicare and Medicaid continued to grow at the same rate as they have over the past four decades, federal spending on those two programs alone would increase from about 5% of the gross domestic product today to about 20% by 2050 — roughly the share of the economy now accounted for by the entire federal budget. Compounding the challenge for policymakers is the difficulty of controlling federal spending . . .
Exodus of medical staff strains Iraq's health facilities
Authors: John Zarocostas
Journal: BMJ (2007)

The exodus of Iraqi doctors fleeing the escalating violence—including targeted threats, kidnappings, and murder of medical staff—is threatening the country's strained health infrastructure, say humanitarian relief experts.

“Health facilities are stretched to the limit as they struggle to cope with daily emergencies caused by mass casualties,” said Angelo Gnaedinger, director general of the International Committee of the Red Cross (ICRC).

Mr Gnaedinger told a recent conference in Geneva on the needs of refugees and internally displaced persons in Iraq and in neighbouring countries, “Patients and medical staff are threatened or targeted. As a result, medical personnel are fleeing the country in large numbers, leaving health facilities short of staff.”

A report by the ICRC published this month on the situation of civilians in Iraq says, “According to the Iraqi Ministry of Health, more than half the doctors have left the country.”

At the end of last year, 18 000 of the 34 000 doctors had left the country, according …
Concomitant Tumor and Minor Histocompatibility Antigen–Specific Immunity Initiate Rejection and Maintain Remission from Established Spontaneous Solid Tumors
Authors: Rodrigo Hess Michelini, Massimo Freschi, Teresa Manzo, Elena Jachetti, Elena Degl'Innocenti, Matteo Grioni, Veronica Basso, Chiara Bonini, Elizabeth Simpson, Anna Mondino, Matteo Bellone
Journal: Cancer Research (2010)

Abstract Nonmyeloablative hematopoietic cell transplantation can cure patients with hematologic malignancies but has reported limited success against solid tumors. This is possibly because of profound peripheral tolerance mechanisms and/or suboptimal tumor recognition by effector T lymphocytes. We report that in mice developing spontaneous prostate cancer, nonmyeloablative minor histocompatibility mismatched hematopoietic stem cell transplantation, and donor lymphocyte infusion of unmanipulated lymphocytes combined with posttransplant tumor-specific vaccination circumvents tumor-specific tolerance, allowing acute tumor rejection and the establishment of protective immunosurveillance. Although donor-derived tumor-specific T cells readily differentiated into effector cells and infiltrated the tumor soon after infusion, they were alone insufficient for tumor eradication, which instead required the concomitance of minor histocompatibiltiy antigen–specific CD8+ T-cell responses. The establishment of protective immunosurveillance was best induced by posttransplant tumor-specific vaccination. Hence, these results provide the proof of principle that tumor-specific T-cell responses have to be harnessed together with minor histocompatibility responses and sustained by posttransplant tumor-specific vaccination to improve the efficacy of allotransplantion for the cure of solid tumors. Cancer Res; 70(9); 3505–14. ©2010 AACR.
830-3 Impact of vessel size on outcomes of different distal protection devices during saphenous vein graft intervention: A FIRE trial substudy
Authors: Aravind Swaminathan, Howard C Hermann, Campbell Rogers, James Hermiller, Robert Feldman, Patrick Hall, Robert Haber, A Masud, Patrick Cambier, Ron P Caputo, David A Cox, Ramona Pop, Martin Fahy, Roxana Mehran, Gregg W Stone
Journal: Journal of the American College of Cardiology (2004)
ETIOLOGY, PATHOLOGY AND DIAGNOSIS OF APPENDICITIS.
Authors: C. E. RUTH
Journal: JAMA (1897)

If we would correctly estimate the tendencies of appendicitis it will be through an understanding of its etiology, pathology and diagnosis. As the varying anatomy and relations of the appendix have much to do with the origin, course and recognition of appendictis they should receive some consideration. The appendix is an organ absolutely without function. For this reason nature is attempting to rid herself permanently of its presence. At the present rate it will be many generations before it is accomplished, and until then physicians must continue its study. All organs without functional activity have less resistance to abnormal processes than those which are functionally active. Every conceivable position is occupied by the appendix, but usually its base is in the right iliac fossa. Its tip may be anywhere that its length, from one to six inches, may enable it to reach. In the female its proximal opening into the
An immunohistochemical study of abnormal keratinocyte proliferation in molluscum contagiosum
Authors: T. Simonart, I. Fayt, J.C. Noel
Journal: British Journal of Dermatology (2002)

Molluscum contagiosum is a common cutaneous tumour that is characterized by usually spontaneous involution and self-limited spreading in immunocompetent individuals.We aimed to investigate the apoptosis and the expression of cell-cycle proteins in molluscum contagiosum lesions.The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL)-based apoptotic index and the expression of the cell-cycle proteins Ki-67, p53, p21WAF and Bcl-2 were investigated in molluscum contagiosum lesions obtained from the trunk of 20 immunocompetent patients and in normal skin samples from the trunk of six healthy volunteers.Whereas molluscum contagiosum lesions displayed a TUNEL-based apoptotic index similar to that of normal skin, they exhibited an increased Ki-67 index, which was confined to the basal and first suprabasal layers (P < 0.001). Compared with normal non-sun-exposed skin, molluscum contagiosum lesions also exhibited increased p53 staining in basal cells (P < 0.01), increased p21WAF in suprabasal cells (P < 0.001) and loss of Bcl-2 expression.These results indicate that molluscum contagiosum lesions exhibit an increased proliferation rate of keratinocytes, which is likely to be partially counteracted by accumulation of p53.
Mechanical Cardiac-Support Devices — Dreams and Devilish Details
Authors: Mariell Jessup
Journal: New England Journal of Medicine (2001)

Statistics on the human and economic impact of the syndrome of heart failure in the United States have been well described, but they deserve further emphasis.1 The incidence of heart failure approaches 10 per 1000 population after the age of 65 years, so that nearly 5 million Americans have this condition today. Despite great advances in medical and surgical management, the five-year mortality rate continues to be about 50 percent; sudden death from cardiac causes occurs among persons with heart failure at six to nine times the rate in the general population. From 1979 to 1998, deaths due to this . . .
Abstract P1-14-03: Overall survival results of a multicenter randomized phase II study in locally advanced breast cancer patients treated with or without neoadjuvant Trastuzumab for HER2 positive tumor (Remagus 02 trial)
Authors: S Giacchetti, J-Y Pierga, B Asselain, S Delaloge, E Brain, M Espié, M-C Mathieu, p Bertheau, P de Cremoux, O Tembo, M Marty
Journal: Cancer Research (2012)

Abstract Background: Trastuzumab is indicated in neoadjuvant setting in locally advanced HER2 positive breast cancer patients (Gianni L. Lancet 2010). There is no data on the impact of the use of neoadjuvant Trastuzumab (T) compared to adjuvant T on survival. Patients and methods: From May 2004 to October 2007, 341 stage II-III breast cancer patients were included in a phase II randomized trial and received 4 cycles (c) of epirubicin (75 mg/m2 d1)–cyclophosphamide (750 mg/m2 d1) q 3 w followed by 4 (c) of docetaxel (100 mg/m2 d1) q 3 w. Pts with HER2+++ tumor (120 pts) were randomized to receive or not neoadjuvant T combined with docetaxel. From September 2005, all pts with HER2+cancer received adjuvant T for a total of 18 c (106 pts). All pts with hormone receptors positive tumor received hormonal treatment according to menopausal status (Pierga et al BCRT 2010). We report here overall survival (OS) and disease free survival (DFS) data at 5 year and associated prognostic factors. Results: At a median follow up of 49 months, the median DFS was not reached for the whole population and was statistically superior for the HER2 positive cancer patients treated with chemotherapy plus neoadjuvant T compared to the other groups, p = 0.018. The median OS is not reached for the whole population and is statistically higher in HER2 positive tumor group compared to HER2 negative group (p = 0.00077). For 106 HER2 positive breast cancer patients who had received one year of complete trastuzumab treatment, there was no significant difference in OS and DFS between pts who started T in neoadjuvant setting versus in adjuvant setting. DFS and OS were not significantly influenced by pathological Complete Response rate (pCR) (respectively, p = 0.22 and p = 0.56). At multivariate analysis including 6 factors (age, tumor size, clinical lymph node, ER, PgR), factors which influenced OS were tumor size (p = 0.03) and ER expression (p = 0.06) and for DFS, clinical lymph node status (p = 0.049) and PgR expression (p = 0.046). Conclusion: pCR is not a surrogate of survival in the HER2+subgroup. HER2 positive breast cancer pts receiving trastuzumab have a significant higher OS than those with HER2 negative tumors. OS and DFS do not seem to differ between the neoadjuvant T group and the T adjuvant group. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-03.
Are Biopsy Forceps Helpful in the Endoscopic Evaluation of Ulcer Diameter?
Authors: F. Cardin, R. Farini, A. Piccoli, A. Martin, F. Vianello, F. Di Mario, R. Naccarato
Journal: Endoscopy (1983)

A hand-made papier-mâché stomach model with hollowed-out ulcers was employed for evaluating the accuracy in estimating ulcer diameters by means of endoscopy. The opened biopsy forceps were also used as a reference marker. Ten endoscopists with various degrees of experience were involved in the study. All the endoscopists underestimated the ulcer diameters; the use of the forceps, resulted in an improvement, in particular in the case of the comparatively inexperienced endoscopists. A stomach model may be helpful in the subjective assessment of the endoscopists' ability to estimate ulcer size.
Abstract 1124: Characterization of a PTEN C2 loop mutation in a human breast cancer cell line
Authors: Andrew M. Chan, Gobind Singh, Leticia Odriozola, Colin Kennedy
Journal: Cancer Research (2010)

Abstract PTEN is a major tumor suppressor gene inactivated in over 30% of human cancer. It encodes a lipid phosphatase with specificity towards phosphatidylinositol (3,4,5) triphosphate (PIP3). PTEN phosphatase activity is crucial to its ability to control cell size, proliferation, motility and survival. The role of PTEN in human breast cancer is well-established. Although the frequency of PTEN mutation in human breast cancer is low (5-10%), a significant fraction of advanced breast cancer has reduced PTEN expression. Furthermore, germ line mutation in PTEN gene constitutes the genetic basis of Cowden's Disease (CD) Syndrome. CD is a harmatoma syndrome with patients displaying aberrant overgrowth of multiple tissue types. Individuals are at a greater risk of developing malignancy of the breast, colon, skin and thyroid. Our laboratory has identified a unique mutation in the C2 loop of PTEN from a human metastatic breast carcinoma cell line, MDA-MB-453. A G to A change substitutes the glutamate (GAG) at codon 307 (E307) to a lysine (AAA). The PTEN C2 loop (aa282-312) is a region on the cytosolic side of the C2 membrane-binding domain. Mono-ubiquitination at K289 within the C2 loop has been shown to promote nuclear translocation. More importantly, unlike the wild-type protein, the E307K mutant is almost undetectable in the nuclear compartment of MDA-MB-453. Biochemically, PTEN E307K mutant displayed similar phosphatase activity towards soluble lipid substrates. More importantly, PTEN E307K displays a striking ability to form an affinity complex with the p53 tumor suppressor. Consistent with this finding, the expression of E307K exerts chemoprotective effect against cisplatinum induced cell death. Based on this preliminary data, we hypothesize that the negatively-charged glutamate residues of PTEN C2 loop play regulatory roles in nuclear translocation and p53-binding. Mutating those residues to lysine creates cryptic ubiquitination sites that subvert the natural ubiquitination at K289, and thus impedes nuclear translocation. Funding: DOD - DAMD17-03-1-0682 (AMC); NCI - RO1CA095063 (AMC), T32CA078207 (GS); Midwest Athletes against Childhood Cancer (AMC); Advancing Healthy Wisconsin Funds (AMC) Acknowledgement: Dr. Xuejun Jiang (Memorial Sloan Kettering Cancer Center, NY) and Dr. Zhen-Qiang Pan (Mount Sinai School of Medicine, NY) for providing the NEDD4-1 and ubiquitination reagents 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 1124.
Altered vascular responses to platelets from hypercholesterolemic humans.
Authors: S Kaul, B J Waack, R C Padgett, R M Brooks, D D Heistad
Journal: Circulation Research (1993)

Activated platelets release potent vasoactive factors. Previous studies have focused on mechanisms by which vascular abnormalities lead to altered responses of atherosclerotic arteries. We tested the hypothesis that the activation of platelets from hypercholesterolemic humans produces abnormal vascular responses. Responses to intraluminal and abluminal activation of platelets from normal subjects and type II hypercholesterolemic patients (total cholesterol, 274 +/- 16 [mean +/- SEM] mg/dl) were examined in carotid arteries from normal rabbits perfused in vitro. Intraluminal activation of normal platelets produced pronounced dilatation of arteries preconstricted with phenylephrine. Vasodilator responses to intraluminal activation of platelets from hypercholesterolemic patients were greatly impaired. Vasodilator responses to platelets from hypercholesterolemic patients were not restored to normal by LY53,857 (10(-5) M), a 5-hydroxytryptamine2-serotonergic antagonist, by SQ29,548 (10(-5) M), a thromboxane A2/prostaglandin H2 receptor antagonist, or by apyrase (1.5 units/ml), an enzyme with ADPase activity. Abluminal activation of normal platelets produced modest constriction in quiescent arteries, and abluminal activation of platelets from hypercholesterolemic patients produced augmented vasoconstrictor responses. The major finding is that vasodilator responses to platelets from hypercholesterolemic patients are profoundly impaired, and vasoconstrictor responses to platelets from hypercholesterolemic patients are augmented. Mechanisms in addition to increased release of serotonin, thromboxane, and ADP appear to contribute to impaired vasodilator responses to hypercholesterolemic platelets. Thus, alteration of platelets by hypercholesterolemia, as well as altered vascular reactivity, may contribute to abnormal vascular responses in atherosclerosis.
Uninsured Dutch patients are being denied hospital care, say doctors
Authors: Tony Sheldon
Journal: BMJ (2006)

guidance for the NHS published this week.The National Institute for Health and Clinical Excellence (NICE) advises on the use of treatments by the NHS in England and Wales.It recommended that the choice of treatment for oestrogen receptor positive breast cancer should be made after discussion between the patient and their doctor about the risks and benefits of the options available.The options are primary adjuvant treatment with an aromatase inhibitor; switching from tamoxifen to an aromatase inhibitor; or use of an aromatase inhibitor after completion of five years of treatment with tamoxifen.This discussion should include whether the patient has received tamoxifen as part of their treatment so far, the side effects of the individual drugs, and, in particular, the assessed risk of recurrence.
Tc-99m MIBI Uptake in Pulmonary Sarcoidosis
Authors: CUMALI AKTOLUN, HIKMET BAYHAN
Journal: Clinical Nuclear Medicine (1994)

During tumor imaging research, the authors incidentally discovered that Tc-99m MIBI is taken up by pulmonary sarcoidosis. In order to evaluate this uptake, they performed Tc-99m MIBI planar and SPECT imaging in 7 patients and compared it with Ga-67. Six out of 7 patients showed evident uptake of Tc-99m MIBI in enlarged hilar lymph nodes. One of the patients, who had been on corticosteroid treatment, showed only faint uptake (negative result), in whom Ga-67 uptake was seen in hilar lymph nodes although it was less evident than the uptake in the other patients. The lymph nodes were better demonstrated with Tc-99m MIBI. The fact that enlarged hilar lymph nodes in a patient on corticosteroid treatment showed faint uptake suggests that Tc-99m MIBI could be helpful for assessing the response to treatment. The preliminary experience in a limited number of patients showed that Tc-99m MIBI is taken up by pulmonary sarcoidosis and it appears to be a potential alternative to Ga-67. Further study is necessary to evaluate its ultimate role in pulmonary sarcoidosis imaging.
Terrence Noel Joseph Alles
Authors: Remy Perumal
Journal: BMJ (2004)

Epidemiologist who discovered the Lassa fever virus-and nearly died from it Jordi Casals-Ariet, an epidemiologist and virologist, was hailed by scientists around the world when he discovered the virus that causes Lassa fever.He was nearly killed by the disease in 1969 while working with the virus in his Yale laboratory.In a high-stakes gamble and with no known treatment, his doctors decided to transfuse him with blood from a nurse who had survived Lassa fever.The blood saved his life.But colleagues say that Dr Casals' contributions are far greater than his discovery of the Lassa fever virus."He did a yeoman's work in establishing useful methods of classifying viruses," said Dr Gregory Tignor, professor emeritus at Yale, who worked with Dr Casals.Little was known about many viruses when Dr Casals started his work at Yale. "Everybody has forgotten how bad it was back then," said Dr Tignor."People didn't know what was causing encephalitis.We had no way of telling the difference between rabies encephalitis, polio encephalitis, or other causes of encephalitis.But Jordi found ways, using antigens and antibodies, to figure it out.His work was so meticulous that to this day nobody has changed his classifications because they have all held up."
INSULIN-LIKE SUBSTANCE FROM PLANTS
Authors: Lewis William Fetzer
Journal: JAMA (1923)

<h3>To the Editor:</h3> —I was much interested in the editorial "Progress With Insulin" (The Journal, August 4, p. 397). I found an insulin-like substance in yeasts (<i>Saccharomyces ellipsoideus</i>and<i>cerevisiae</i>) and in some green corn stalks, and reported my findings in a general way to the Dallas County Medical Society. A record of the report will be found in the<i>Dallas Medical Journal</i>(<b>5</b>:54) and<i>Texas State Journal of Medicine</i>(<b>19</b>:53). I also mentioned the fact that I had noted an insulin-like substance in plant material, while discussing another's paper, before the last meeting of the Texas State Medical Association, held on May 8-10, in Fort Worth. Most of my work up to date has been done on rabbits, a few dogs and cats, and two human beings.