tbuckley/cabot-search huggingface dataset:
The Multiple Endocrine Neoplasia Syndromes
Authors: Vipul T. Lakhani, Y. Nancy You, Samuel A. Wells
Journal: Annual Review of Medicine (2006)

Multiple endocrine neoplasia (MEN) type 1 and type 2 exhibit an autosomal dominant pattern of inheritance. In the past two decades the germline mutations that cause these inherited syndromes have been identified. The large majority of patients with MEN1 have mutations in the menin gene. Mutations in the REarranged during Transfection (RET) gene cause MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). Specific codon mutations within RET correlate with disease phenotype and severity. Also, children from families with MEN2A, MEN2B, or FMTC, who are found to have inherited a mutated RET allele, can be managed by prophylactic thyroidectomy, thus preventing the development of medullary thyroid carcinoma (MTC), the dominant endocrinopathy in patients with these hereditary syndromes. New insights into the molecular pathway of RET signal transduction are leading to novel targeted therapies in patients with locally advanced or metastatic hereditary MTC.
Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with weekly high-dose 48-hour continuous-infusion fluorouracil for advanced colorectal cancer: A Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD) study
Authors: E. Aranda, E. Díaz-Rubio, A. Cervantes, A. Antón-Torres, A. Carrato, T. Massutí, J.M. Tabernero, J. Sastre, A. Trés, J. Aparicio, J.M. López-Vega, I. Barneto, J. García-Conde
Journal: Annals of Oncology (1998)
Increased immunoglobulin G production by short term cultured duodenal biopsy samples from HIV infected patients
Authors: T Schneider, T Zippel, W Schmidt, G Pauli, U Wahnschaffe, S Chakravarti, W Heise, E O Riecken, M Zeitz, R Ullrich
Journal: Gut (1998)

Background —Secretory immunity is a major defence mechanism against infections at mucosal surfaces which are common in HIV infected patients. Aims —To analyse intestinal immunoglobulin production in HIV infection in comparison with that in saliva and serum. Patients and methods —Immunoglobulin G (IgG), A (IgA), and M (IgM) concentrations were determined in supernatants of short term cultured duodenal biopsy samples, serum, and saliva from HIV infected patients (n = 28) and controls (n = 14) by radial immunodiffusion. Results —IgG was increased in the supernatants of short term cultured biopsy samples and saliva from HIV infected patients compared with controls (p&lt;0.01), but IgA and IgM levels were normal. In contrast, both IgG and IgA concentrations in serum were higher in HIV infected patients than in controls (p&lt;0.002). No correlation was found between IgA produced by duodenal biopsy specimens and serum IgA. Conclusion —Abnormalities in mucosal immunoglobulin production in HIV infection were suprisingly small, indicating that specific secretory immunity rather than quantitative immunoglobulin production may be impaired. However, increased production of IgG could contribute to mucosal inflammation by complement activation. Our findings of normal mucosal IgA production and the lack of correlation between serum and mucosal IgA argues against an intestinal origin for the increased serum IgA levels in HIV infected patients.
Uridine Diphosphate-Glucuronic Acid-independent Conversion of Bilirubin Monoglucuronides to Diglucuronide in Presence of Plasma Membranes from Rat Liver is Nonenzymic
Authors: Andreas Sieg, Gustaaf P. Van Hees, Karel P. M. Heirwegh
Journal: Journal of Clinical Investigation (1982)

Two routes have been proposed for conversion of bilirubin monoglucuronide to the diglucuronide: glucuronyl transfer (a) from UDP-glucuronic acid to bilirubin monoglucuronide, catalyzed by a microsomal UDP-glucuronyltransferase, and (b) from one molecule of bilirubin monoglucuronide to another (transglucuronidation), catalyzed by an enzyme present in liver plasma membranes. The evidence regarding the role of the latter enzyme for in vivo formation of bilirubin diglucuronide is conflicting. We therefore decided to reexamine the transglucuronidation reaction in plasma membranes and to study the conversion of bilirubin monoglucuronide to diglucuronide in vivo. Purified bilirubin monoglucuronide was incubated with homogenates and plasma membrane-enriched fractions from liver of Wistar and Gunn rats. Stoichiometric formation of bilirubin and bilirubin diglucuronide out of 2 mol of bilirubin monoglucuronide was paralleled by an increase of the IIIα- and XIIIα-isomers of the bilirubin aglycone, thus showing that dipyrrole exchange, not transglucuronidation, is the underlying mechanism. Complete inhibition by ascorbic acid probably reflects intermediate formation of free radicals of dipyrrolic moieties. The reaction was nonenzymic because it proceeded independently of the protein concentration and heat denaturation of the plasma membranes did not result in decreased conversion rates. Collectively, these findings show spontaneous, nonenzymic dipyrrole exchange when bilirubin monoglucuronide is incubated in the presence of rat liver plasma membranes. Because bilirubin glucuronides present in biological fluids contain exclusively the bilirubin-IXα aglycone, formation of the diglucuronide from the monoglucuronide by dipyrrole exchange does not occur in vivo. Rapid excretion of unchanged bilirubin monoglucuronide in Gunn rat bile after injection of the pigment provides confirmatory evidence for the absence of a UDP-glucuronic acid-independent process.
Hodgkin's disease: Complications of therapy and excess mortality
Authors: R.T. Hoppe
Journal: Annals of Oncology (1997)

Background: The long-term survival of patients treated for Hodgkin's disease permits careful evaluation of long-term complications and excess mortality.Patients and methods: Between 1960 and 1995, 2498 patients who were treated for Hodgkin's disease at Stanford University were evaluated.Survival, freedom from relapse, and important complications of therapy (cardiac disease and secondary cancers) were analyzed, and risk of mortality from all causes was calculated utilizing absolute excess risk calculations.Results: The risk of death from Hodgkin's disease is 17% at 15 years of follow-up and increases only slightly thereafter.The risk of death from other causes is also 17% at 15 years, but increases sharply thereafter.The major causes of mortality (other than Hodgkin's disease) are secondary cancers and cardiac disease.Second cancers with significant increase in risk include leukemia (acute nonlymphocytic), non-Hodgkin's lymphoma, lung/pleural cancer, breast cancer, melanoma, soft tissue and bone sarcomas, stomach cancer, salivary gland tumors, thyroid cancer, and pancreatic cancer.The absolute excess risk of death from causes other than Hodgkin's disease increases during each five-year follow-up interval for at least 25 years.However, the absolute excess risk of death during similar followup periods is less for patients treated in more recent years (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995) than in the prior treatment era (1962)(1963)(1964)(1965)(1966)(1967)(1968)(1969)(1970)(1971)(1972)(1973)(1974)(1975)(1976)(1977)(1978)(1979)(1980).Conclusions: Mortality for causes other than Hodgkin's disease is important in the long-term follow-up of patients.Causes of death are often treatment related.Changes in treatment programs can reduce the long-term excess risk of death from complications of therapy.
Recognition and Prevention of Major Mental and Substance Use Disordersedited by Ming T. Tsuang, M.D., Ph.D., D.Sc., William S. Stone, Ph.D., and Michael J. Lyons, Ph.D. Arlington, Va., American Psychiatric Publishing, 2007, 429 pp., $65.00.
Authors: FRANCINE M. BENES
Journal: American Journal of Psychiatry (2007)
Calcineurin Inhibitors Activate the Proto-Oncogene Ras and Promote Protumorigenic Signals in Renal Cancer Cells
Authors: Dipak Datta, Alan G. Contreras, Aninda Basu, Olivier Dormond, Evelyn Flynn, David M. Briscoe, Soumitro Pal
Journal: Cancer Research (2009)

The development of cancer is a major problem in immunosuppressed patients, particularly after solid organ transplantation. We have recently shown that calcineurin inhibitors (CNI) used to treat transplant patients may play a critical role in the rapid progression of renal cancer. To examine the intracellular signaling events for CNI-mediated direct tumorigenic pathway(s), we studied the effect of CNI on the activation of proto-oncogenic Ras in human normal renal epithelial cells (REC) and renal cancer cells (786-0 and Caki-1). We found that CNI treatment significantly increased the level of activated GTP-bound form of Ras in these cells. In addition, CNI induced the association of Ras with one of its effector molecules, Raf, but not with Rho and phosphatidylinositol 3-kinase; CNI treatment also promoted the phosphorylation of the Raf kinase inhibitory protein and the downregulation of carabin, all of which may lead to the activation of the Ras-Raf pathway. Blockade of this pathway through either pharmacologic inhibitors or gene-specific small interfering RNA significantly inhibited CNI-mediated augmented proliferation of renal cancer cells. Finally, it was observed that CNI treatment increased the growth of human renal tumors in vivo, and the Ras-Raf pathway is significantly activated in the tumor tissues of CNI-treated mice. Together, targeting the Ras-Raf pathway may prevent the development/progression of renal cancer in CNI-treated patients.
Acute Wegener's granulomatosis
Authors: D. Leak, G. P. Clein
Journal: Thorax (1967)

Two cases of acute Wegener9s granulomatosis are described. The first ended fatally after an illness of only two weeks. In the second a remission of three years has been obtained with heavy doses of steroid. At present there is evidence of impaired pulmonary gas transfer and also chronic glomerulonephritis, but the patient is asymptomatic. When the disease presents with pulmonary cavitation it may be confused with pulmonary neoplasm, tuberculosis, or lung abscess, and the diagnosis is made by biopsy. The Rose-Waaler was strongly positive in the case tested.
NAD(P)H : quinone Oxidoreductase 1 Deficiency and Increased Susceptibility to 7,12-Dimethylbenz[a]-anthracene-Induced Carcinogenesis in Mouse Skin
Authors: D. J. Long, R. L. Waikel, X.-J. Wang, D. R. Roop, A. K. Jaiswal
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: The phase II enzyme NAD(P)H : quinone oxidoreductase 1 (NQO1) catalyzes quinone detoxification, protecting cells from redox cycling, oxidative stress, mutagenicity, and cytotoxicity induced by quinones and its precursors. We have used NQO1−/− C57BL/6 mice to show that NQO1 protects them from skin cancer induced by the polycyclic aromatic hydrocarbon benzo[a]pyrene. Herein, we used NQO1−/− mice to investigate whether NQO1 also protects them against 7,12-dimethylbenz[a]anthracene (DMBA), where methyl substituents diminish primary quinone formation. Methods: Dorsal skin of NQO1−/− or wild-type C57BL/6 mice was shaved. When tested as a complete carcinogen, DMBA (500 or 750 μg in 100 μL of acetone) alone was applied to the shaved area. When tested as a tumor initiator, DMBA (200 or 400 nmol in 100 μL of acetone) was applied to the shaved area; 1 week later, twice-weekly applications of phorbol 12-myristate 13-acetate (PMA)—10 μg dissolved in 200 μL of acetone—to the same area began and were continued for 20 weeks. Tumor development was monitored in all mice (12–15 per group). All statistical tests were two-sided. Results: When DMBA (750 μg) was tested as a complete carcinogen, about 50% of the DMBA-treated NQO1−/− mice but no DMBA-treated wild-type mouse developed skin tumors. When DMBA (both concentrations) was used as a tumor initiator, NQO1−/− mice developed larger tumors at a greater frequency than their wild-type littermates. Twenty-three weeks after the first PMA treatment in the tumor initiator test, all 30 NQO1−/− mice given 400 nmol of DMBA had developed skin tumors, compared with 33% (10 of 30) of treated wild-type mice (P<.001). Conclusions: NQO1−/− mice are more susceptible to DMBA-induced skin cancer than are their wild-type littermates, suggesting that NQO1 may protect cells from DMBA carcinogenesis.
Prooncogenic Factors miR-23b and miR-27b Are Regulated by Her2/<i>Neu</i>, EGF, and TNF-α in Breast Cancer
Authors: Lianjin Jin, Oliver Wessely, Eric G. Marcusson, Cristina Ivan, George A. Calin, Suresh K. Alahari
Journal: Cancer Research (2013)

miRNAs (miR) are a critical class of small (21-25 nucleotides) noncoding endogenous RNAs implicated in gene expression regulation. We identified miR-23b and miR-27b as miRNAs that are highly upregulated in human breast cancer. We found that engineered knockdown of miR-23b and miR-27b substantially repressed breast cancer growth. Nischarin (NISCH) expression was augmented by knockdown of miR-23b as well as miR-27b. Notably, these miRNAs and Nischarin were inversely expressed in human breast cancers, underscoring their biologic relevance. We showed the clinical relevance of the expression of these miRNAs and showed that high expression of miR-23b and miR-27b correlates with poor outcome in breast cancer. Moreover, intraperitoneally delivered anti-miR-27b restored Nischarin expression and decreased tumor burden in a mouse xenograft model of human mammary tumor. Also, we report for the first time that HER2/neu (ERBB2), EGF, and TNF-α promote miR-23b/27b expression through the AKT/NF-κB signaling cascade. Nischarin was found to regulate miR-27b/23b expression through a feedback loop mechanism by suppressing NF-κB phosphorylation. Because anti-miR-27b compounds that suppress miR-27b inhibit tumor growth, the anti-miR-27b seems to be a good candidate for the development of new antitumor therapies.
Bone Imaging in Metastatic Breast Cancer
Authors: Tsuyoshi Hamaoka, John E. Madewell, Donald A. Podoloff, Gabriel N. Hortobagyi, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2004)

Bone is the most common site to which breast cancer metastasizes. Imaging—by skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imaging—is an essential part, and positron emission tomography or single-photon emission computed tomography have a potential of evaluating bone metastases, but no consensus exists as to the best modality for diagnosing the lesion and for assessing its response to treatment. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor or indirect measurements of bone or tumor metabolism. Although bone metastases can be treated, their response to treatment is considered “unmeasurable” according to existing response criteria. Therefore, the process by which oncologists and radiologists diagnose and monitor the response of bone metastases needs revision, and the current inability to assess the response of bone metastases excludes patients with breast cancer and bone disease from participating in clinical trials of new treatments for breast cancer. In this review of the MEDLINE literature, we discuss the pros and cons of each modality for diagnosing bone metastases and for assessing their response to treatment and we present a practical approach for diagnosis and assessment of bone metastasis.
Interleukin (IL)23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for IL22 but not IL21 in autoimmune experimental arthritis
Authors: A M C Mus, F Cornelissen, P S Asmawidjaja, J P van Hamburg, L Boon, R W Hendriks, E Lubberts
Journal: Annals of the Rheumatic Diseases (2010)

Objective To unravel the role of interleukin 23 (IL23) in subgroup polarisation of IL17α and/or interferon γ (IFNγ) T cells in the prone autoimmune DBA-1 mice with and without collagen-induced arthritis.Methods CD4 T cells were isolated using the MACS system from the spleen of naive and type II collagen (CII) immunised DBA-1 mice.These CD4 T cells were stimulated in vitro under Th0, Th1 or different Th17 conditions.Intracellular staining for IL17A and IFNγ was evaluated by fl ow cytometry.In addition, Th17 cytokines and T-helper-specifi c transcription factors were analysed by ELISA and/or Q-PCR.Results In CD4 T cells from naive DBA-1 mice, IL23 alone hardly induced RORγt, Th17 polarisation and Th17 cytokines but inhibited T-bet expression.In contrast, transforming growth factor (TGFβ)/IL6 was a potent inducer of RORγt, RORα, IL17α, IL17F, IL21 and FoxP3 in these cells.IL23 in contrast to TGFβ/IL6 was critical for the induction of IL22 in CD4 T cells from both naive and CII-immunised DBA-1 mice.In line with these fi ndings, IL23 was more pronounced in inducing the IL17A IFNγ subset in CD4 T cells from CII-immunised mice.However, under naive conditions, IL23 signifi cantly increased the TGFβ/IL6-induced Th17 polarisation including elevated IL17α and IL17F levels and decreased T-bet and FoxP3 expression.Of note, the IL23-induced increase in IL17A and IL17F was prevented in T-bet-defi cient mice.Conclusion IL23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of IL22 but not IL21 in autoimmune arthritis.These data indicate different mechanisms for IL23 and TGFβ/IL6 at the transcription factor level during Th17 differentiation in autoimmune experimental arthritis.
OCCUPATIONAL KOILONYCHIA OF THE TOE NAILS
Authors: B. BENTLEY-PHILLIPS, MARGARET A. H. BAYLES
Journal: British Journal of Dermatology (1971)

SUMMARY.— One hundred and fifty “Ricksha Boys” of Durban. South Africa, whose bare feet are habitually exposed to gross trauma, were examined. A curious type of trauma‐induced, occupational koilonychia, not previously described, was observed in a significant number of the pullers (16%). The clinical appearances are described and the probable aetiological factors are examined.
Pharmacological strategies for self-management of asthma exacerbations
Authors: H. K. Reddel
Journal: European Respiratory Journal (2006)

Written action plans are effective within asthma self-management, but there are few guidelines about the specific medication adjustments which can be recommended for self-treatment of exacerbations. This review examines pharmacological strategies for self-management of asthma exacerbations in adults, including those for inhaled corticosteroid/long-acting β<sub>2</sub>-agonist (ICS/LABA) users. Oral corticosteroids are well-established in clinical practice and clinical trials for the treatment of severe exacerbations, including during combination therapy. Evidence supports 7–10 days treatment, with no need to taper except to reduce side-effects. Doubling the dose of ICS is not effective. Several studies have shown benefit from high-dose ICS (2,400–4,000 µg beclomethasone equivalent) for 1–2 weeks. This may be achieved by adding a high-dose ICS inhaler to maintenance ICS or ICS/LABA therapy. There is inconclusive evidence about acutely increasing the dose of maintenance budesonide/formoterol for exacerbations, and no studies of this approach with fluticasone/salmeterol. For patients taking maintenance budesonide/formoterol, use of the same medication as-needed reduces exacerbations. Short-acting β<sub>2</sub>-agonists are still effective in producing bronchodilation during combination therapy; however, a higher dose may be required. There is a need for further studies to clarify remaining issues about self-management of asthma exacerbations, particularly with regard to side-effects of treatment and patient acceptability.
THE RESULTS OF PROTECTIVE INOCULATION AGAINST INFLUENZA IN THE ARMY AT HOME, 1918-1919
Authors: W. B. Leishman
Journal: BMJ (1920)

to coDsider tile advisability of employing in the army a preventive vaccine against influenza.This conferetice, of which I had tile hionour to be clilairman, agreed thjat such a vaceine mighit be expected to be of service, and made recommendatioins as to its constitution and u.se.Tile vaccine recommyended was accordingly prepared at the Royal Army Medical College, and, in certain com- mainds, used on a considerable scale.In view of the opinion, widely expressed in both medical and lay journals, that we are threatened witlh anothier epidemic wave of influenza, it is felt that the results obtained in tile army commnand(s at hiome last winter withi tile vaccine in question should be made known; not only becausje it is proposed to advocate its employment again in the army, if we sjhould be so unfortunate as to find our- selves in the presence of a serious recrudescence of the disease, but also because the modified vaccine now in army use has, I undlerstand, been adopted by the Ministry of
Premenstrual Dysphoric Disorder What's That?
Authors: Judith H. Gold
Journal: JAMA (1997)

Categorizing the physical and psychological complaints linked to the menstrual cycle is controversial. Some view such efforts as a sociopolitical attempt to minimize, or encapsulate, women's complaints.<sup>1</sup>Others, such as Yonkers et al<sup>2</sup>in this issue, investigate treatments that alleviate these complaints. See also p 983. Premenstrual symptoms have been described for centuries. Many cultures have established rituals and myths related to the menstrual cycle; in North America, cartoons and even lapel buttons about premenstrual syndrome (PMS) are commonplace. Yet it is often unclear what is meant by PMS. Formal investigations of PMS began earlier in this century with the work of Frank in the United States and were furthered by Dalton in Britain.<sup>3</sup>In the last 3 decades, many articles have been published dealing with both the etiology and treatment of premenstrual symptoms. By the mid 1980s, many clinicians had recognized that a small but significant
Oncologic emergencies: Pathophysiology, presentation, diagnosis, and treatment
Authors: Mark A. Lewis, Andrea Wahner Hendrickson, Timothy J. Moynihan
Journal: CA A Cancer Journal for Clinicians (2011)

Abstract Oncologic emergencies can occur at any time during the course of a malignancy, from the presenting symptom to end‐stage disease. Although some of these conditions are related to cancer therapy, they are by no means confined to the period of initial diagnosis and active treatment. In the setting of recurrent malignancy, these events can occur years after the surveillance of a cancer patient has been appropriately transferred from a medical oncologist to a primary care provider. As such, awareness of a patient's cancer history and its possible complications forms an important part of any clinician's knowledge base. Prompt identification of and intervention in these emergencies can prolong survival and improve quality of life, even in the setting of terminal illness. This article reviews hypercalcemia, hyponatremia, hypoglycemia, tumor lysis syndrome, cardiac tamponade, superior vena cava syndrome, neutropenic fever, spinal cord compression, increased intracranial pressure, seizures, hyperviscosity syndrome, leukostasis, and airway obstruction in patients with malignancies. Chemotherapeutic emergencies are also addressed. CA Cancer J Clin 2011. © 2011 American Cancer Society.