tbuckley/cabot-search huggingface dataset:
The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells
Authors: Lionel Franz Poulin, Sandrine Henri, Béatrice de Bovis, Elisabeth Devilard, Adrien Kissenpfennig, Bernard Malissen
Journal: The Journal of Experimental Medicine (2007)

Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express the lectin langerin and that reside in their immature state in epidermis. Paradoxically, in mice permitting diphtheria toxin (DT)–mediated ablation of LCs, epidermal LCs reappeared with kinetics that lagged behind that of their putative progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed that a major fraction of the langerin+, skin-derived DCs found in LNs originates from a developmental pathway that is independent from that of epidermal LCs. This pathway, the existence of which was unexpected, originates in the dermis and gives rise to langerin+ dermal DCs (DDCs) that should not be confused with epidermal LCs en route to LNs. It explains that after DT treatment, some langerin+, skin-derived DCs reappear in LNs long before LC-derived DCs. Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin+ DDCs were found to coexist in wild-type mice. Moreover, DT-mediated ablation of epidermal LCs opened otherwise filled niches and permitted repopulation of adult noninflammatory epidermis with BM-derived LCs. Our results stress that the langerin+ DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models.
The Literature and History of Internal Medicine
Authors: W. BRUCE FYE
Journal: Annals of Internal Medicine (1977)

This bibliography includes 58 books on the history of various medical subspecialties and general reference works useful in obtaining historical and biographical material relevant to internal medicine and related areas. In addition to a brief review of the contents of each volume, information is included on their publication and availability. It is designed to serve as an introduction to the history of internal medicine as well as a source of reference.
Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005
Authors: L Annemans, E Spaepen, M Gaskin, M Bonnemaire, V Malier, T Gilbert, G Nuki
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To investigate and compare the prevalence, comorbidities and management of gout in practice in the UK and Germany. <h3>Methods:</h3> A retrospective analysis of patients with gout, identified through the records of 2.5 million patients in UK general practices and 2.4 million patients attending GPs or internists in Germany, using the IMS Disease Analyzer. <h3>Results:</h3> The prevalence of gout was 1.4% in the UK and Germany. Obesity was the most common comorbidity in the UK (27.7%), but in Germany the most common comorbidity was diabetes (25.9%). The prevalence of comorbidities tended to increase with serum uric acid (sUA) levels. There was a positive correlation between sUA level and the frequency of gout flares. Compared with those in whom sUA was &lt;360 μmol/l (&lt;6 mg/dl), odds ratios for a gout flare were 1.33 and 1.37 at sUA 360–420 μmol/l (6–7 mg/dl), and 2.15 and 2.48 at sUA &gt;530 μmol/l ( &gt;9 mg/dl) in the UK and Germany, respectively (p&lt;0.01). <h3>Conclusions:</h3> The prevalence of gout in practice in the UK and Germany in the years 2000–5 was 1.4%, consistent with previous UK data for 1990–9. Chronic comorbidities were common among patients with gout and included conditions associated with an increased risk for cardiovascular disease, such as obesity, diabetes and hypertension. The importance of regular monitoring of sUA in order to tailor gout treatment was highlighted by data from this study showing that patients with sUA levels ⩾360 μmol/l (⩾6 mg/dl) had an increased risk of gout flares.
Regional Variation in Health Care Intensity and Treatment Practices for End-stage Renal Disease in Older Adults
Authors: Ann M O'Hare, Rudolph A Rodriguez, Susan M Hailpern, Eric B Larson, Manjula Kurella Tamura
Journal: JAMA (2010)

<h3>Context</h3>An increasing number of older adults are being treated for end-stage renal disease (ESRD) with long-term dialysis.<h3>Objectives</h3>To determine how ESRD treatment practices for older adults vary across regions with differing end-of-life intensity of care.<h3>Design, Setting, and Participants</h3>Retrospective observational study using a national ESRD registry to identify a cohort of 41 420 adults (of white or black race), aged 65 years or older, who started long-term dialysis or received a kidney transplant between June 1, 2005, and May 31, 2006. Regional end-of-life intensity of care was defined using an index from the Dartmouth Atlas of Healthcare.<h3>Main Outcome Measures</h3>Incidence of treated ESRD (dialysis or transplant), preparedness for ESRD (under the care of a nephrologist, having a fistula [vs graft or catheter] at time of hemodialysis initiation), and end-of-life care practices.<h3>Results</h3>Among whites, the incidence of ESRD was progressively higher in regions with greater intensity of care and this trend was most pronounced at older ages. Among blacks, a similar relationship was present only at advanced ages (men aged ≥80 years and women aged ≥85 years). Patients living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to be under the care of a nephrologist before the onset of ESRD (62.3% [95% confidence interval {CI}, 61.3%-63.3%] vs 71.1% [95% CI, 69.9%-72.2%], respectively) and less likely to have a fistula (vs graft or catheter) at the time of hemodialysis initiation (11.2% [95% CI, 10.6%-11.8%] vs 16.9% [95% CI, 15.9%-17.8%]). Among patients who died within 2 years of ESRD onset (n = 21 190), those living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to have discontinued dialysis before death (22.2% [95% CI, 21.1%-23.4%] vs 44.3% [95% CI, 42.5%-46.1%], respectively), less likely to have received hospice care (20.7% [95% CI, 19.5%-21.9%] vs 33.5% [95% CI, 31.7%-35.4%]), and more likely to have died in the hospital (67.8% [95% CI, 66.5%-69.1%] vs 50.3% [95% CI, 48.5%-52.1%]). These differences persisted in adjusted analyses.<h3>Conclusion</h3>There are pronounced regional differences in treatment practices for ESRD in older adults that are not explained by differences in patient characteristics.
Concomitant Overexpression of Cyclooxygenase-2 in HER-2–Positive on Smad4-Reduced Human Gastric Carcinomas Is Associated with a Poor Patient Outcome
Authors: Hirokazu Okano, Hisashi Shinohara, Akiko Miyamoto, Kyoichi Takaori, Nobuhiko Tanigawa
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The expression of cyclooxygenase-2 (COX-2) is known to be involved in gastric carcinogenesis and tumor progression, but little is known about the mechanisms responsible for the up-regulation of COX-2. We examined the involvement of two growth factor-signaling systems, HER-2 and transforming growth factor (TGF)-β, in the induction of COX-2 in human gastric cancer tissue. Experimental Design: COX-2 expression was detected by immunohistochemistry in surgical specimens obtained from 166 patients with advanced gastric cancer; possible correlations between the expression of COX-2 and the expression of HER-2, TGF-β1, and Smad4, an intracellular mediator that transmits the TGF-β signal, were then analyzed. Results: COX-2 protein was overexpressed in 91 (54.8%) tumors; COX-2 overexpression was correlated with a differentiated histologic type, deep invasion, and positive lymph node metastasis. COX-2 was frequently overexpressed in HER-2–positive tumors (19 of 22, 86.4%) and in Smad4-reduced tumors (67 of 104, 64.4%) but irrelevant to the TGF-β1 expression status. The expression levels of COX-2 and HER-2 and the reduction in Smad4 were all associated with a poor patient outcome. A multivariate analysis demonstrated a significantly poor outcome for the concomitant overexpression of COX-2 in patients with Smad4-reduced tumors. Conclusions: These results support the possibility that signal transduction via HER-2 and the TGF-β/Smad system may be implicated in COX-2 expression and that the reduction of Smad4 may be, in part, of causal significance in the TGF-β-initiated overexpression of COX-2, which is associated with a poor prognosis for patients with gastric cancer.
Antiangiogenic and Antitumor Activity of 6-(2-Aminoethyl)Amino-5-Chlorouracil, a Novel Small-Molecule Inhibitor of Thymidine Phosphorylase, in Combination with the Vascular Endothelial Growth Factor-Trap
Authors: Haiyan Lu, Robert S. Klein, Edward L. Schwartz
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Tumors produce multiple proangiogenic factors, making it unlikely that agents targeting a single angiogenic pathway will be sufficient to treat the spectrum of tumors that occur clinically. Platelet-derived endothelial cell growth factor has angiogenic activity in vitro and in vivo and is overexpressed in most human cancers, where its expression has been correlated with increased microvessel density, more aggressive tumors, and poorer patient prognosis. Platelet-derived endothelial cell growth factor is identical to the enzyme thymidine phosphorylase (TP), and unlike other angiogenic factors, the proangiogenic actions of TP are dependent on its enzyme activity. Experimental Design: A potent and specific small-molecule inhibitor of the catalytic activity of TP, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), was tested for antiangiogenic and antitumor activity in human cancer xenografts in vivo. Results: Oral administration of AEAC caused 40% to 50% reductions in the growth of A549 non–small cell lung cancer and PANC-1 pancreatic cancer xenografts, but it was not active against a second pancreatic tumor, BxPC-3. AEAC reduced the microvessel density in the tumors, providing evidence for an antiangiogenic action. Equal or better activity was seen when the mice were treated with the vascular endothelial growth factor (VEGF)-Trap, a soluble VEGF decoy receptor, and the combination of AEAC and VEGF-Trap produced additive antitumor activity that was significantly greater than the VEGF-Trap alone. In the A549 tumors, the combination produced tumor regressions. Conclusion: These studies show antitumor activity for a drug targeting TP and suggest that inhibitors of TP could be used to augment the clinical efficacy of drugs targeting the VEGF pathway. (Clin Cancer Res 2009;15(16):5136–44)
B Cells and Humoral Immunity in Atherosclerosis
Authors: Dimitrios Tsiantoulas, Cody J. Diehl, Joseph L. Witztum, Christoph J. Binder
Journal: Circulation Research (2014)

Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our understanding of this disease. Although the role of T cells has been extensively studied for decades, only recently has the role of B cells gained more attention. Recent studies have identified differential effects of different B-cell subsets and helped to clarify the still poorly understood mechanisms by which these act. B1 cells have been shown to prevent lesion formation, whereas B2 cells have been suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells, have been shown to mediate atheroprotective effects, but the functional role of other immunoglobulin classes, particularly IgG, still remains elusive. In this review, we will focus on recent insights on the role of B cells and various immunoglobulin classes and how these may mediate their effects in atherosclerotic lesion formation. Moreover, we will highlight potential therapeutic approaches focusing on B-cell depletion that could be used to translate experimental evidence to human disease.
Choices of Curative and Palliative Care for Cancer Patients
Authors: J. Lynn
Journal: CA A Cancer Journal for Clinicians (1986)

Decision-making in cancer treatment is a complex art that requires specific attention by the physician who is principally responsible for the patient. Whenever possible, the aim should be to advance the patient's interests as the patient defines them. To achieve this, the patient must understand the situation and the likely outcomes of treatment options that might be of benefit, must be free of coercion and manipulation and capable of self-determination, and must be capable of reasoning. When a patient cannot collaborate in the decision-making, the physician needs to recognize this and a surrogate should be chosen to speak on the patient's behalf. The range of treatment options must not be unduly narrowed by lack of consideration, incorrect understanding of the governing moral and legal prohibitions, or unreflective use of imprecise categories.
Anti-TNF Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious Infections and Malignancies
Authors: Tim Bongartz, Alex J. Sutton, Michael J. Sweeting, Iain Buchan, Eric L. Matteson, Victor Montori
Journal: JAMA (2006)

Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies.To assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy.A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies.We included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo.Data on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors.We calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF-treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months.There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.
Unusual erythema elevatum diutinum with fibrohistiocytic proliferation
Authors: M. PORNEUF, M. DUTERQUE, A. SOTTO, J. JOURDAN
Journal: British Journal of Dermatology (1996)

A 78-year-old woman with a history of symmetrical erythematous plaques on the arms, and a monoclonal gammopathy, developed a strange striped reticulate papular dermatosis with central atrophy. Histological examination was compatible with a very late stage of erythema elevatum diutinum (EED), showing a fibrohistiocytic proliferation with areas of granulation tissue. This fibrosis may result from the chronic dermal injury of leucocytoclastic vasculitis and is sometimes the predominant histology of EED. Investigations for underlying haematological anomalies, such as paraproteinaemia and infection with human immunodeficiency virus, must be performed. Dapsone is ineffective once the fibrous nodules have appeared.
Expression of Hepatoma-Derived Growth Factor Is a Strong Prognostic Predictor for Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Hening Ren, Ximing Tang, J. Jack Lee, Lei Feng, Allen D. Everett, Waun Ki Hong, Fadlo R. Khuri, Li Mao
Journal: Journal of Clinical Oncology (2004)

Hepatoma-derived growth factor (HDGF), which is unrelated to hepatocyte growth factor, can stimulate DNA synthesis and cell proliferation on entering the nucleus. We hypothesize that HDGF plays an important role in biologic behavior of early-stage non-small-cell lung cancer (NSCLC).Ninety-eight patients with pathologic stage I NSCLC who underwent curative surgery were studied. Immunohistochemistry was used to determine the expression level of HDGF in the tumor specimens. The intensity of the protein staining and percentage of stained tumor cells were used to determine a labeling index. Statistical analyses, all two-sided, were performed to determine the prognostic effect of HDGF expression levels on clinical parameters and outcomes.The mean +/- standard deviation HDGF labeling index in the 98 tumors was 185 +/- 41. Patients whose tumors had higher HDGF indexes (>/= 185) had a significantly poorer probability of overall survival at 5 years after surgery than did those with lower HDGF indexes (0.26 v 0.82; P <.0001). Similarly, the 5-year disease-specific and disease-free survival probabilities were lower in those with higher HDGF indexes (0.42 v 0.92, and 0.34 v 0.71; P <.0001 and P =.0008; respectively). Multivariate analysis indicated that HDGF level was an independent predictor of overall, disease-specific, and disease-free survivals.Overexpression of HDGF is common in early-stage NSCLC. The expression level in tumor cells is strongly correlated with poor overall, disease-specific, and disease-free survivals, suggesting HDGF may be a powerful prognostic marker for patients with early-stage NSCLC.
Nail changes in a patient with leukaemia
Authors: M. E. Bhaskar
Journal: BMJ (2011)

A 60 year old retired soldier presented to our primary care department with progressive nail pigmentation in both hands over the preceding year. No history of mucosal bleeding or nail trauma was elicited. He had been diagnosed with type 2 diabetes and hypertension three years ago and chronic myeloid leukaemia two years ago. He had been taking losartan and atorvastatin for three years, plus metformin, glimepiride, and hydoxyurea (500 mg twice daily) for two years. Treatment with hydroxyurea had induced a sustained haematological remission for the past 18 months. On examination his vital signs were stable. All nails on his hands were affected (figs 1⇓ and 2⇓), but the rest of his skin was normal.







### 1 How would you describe the abnormality?

#### Short answer

Greyish brown pigmentation can be seen on the proximal nail plate of all fingers. These nail changes are often described as melanonychia (nail hyperpigmentation as a result of melanin accumulation in the epithelium). Onycholysis of the left little finger nail is also seen.

#### Long answer

Greyish brown pigmentation of the proximal nail plate of all fingers. These nail changes are often described as melanonychia (nail …
Requirement for CD4+ cells in resistance to Pneumocystis carinii pneumonia in mice.
Authors: A G Harmsen, M Stankiewicz
Journal: The Journal of Experimental Medicine (1990)

The importance of CD4+ cells in resistance to Pneumocystis carinii (PC) in PC-susceptible severe combined immunodeficient (SCID) mice that were made resistant to PC by immunocompetent spleen cell transfer, and in conventional PC-resistant mice, was investigated. SCID mice with naturally acquired PC pneumonia (PCP) were given infusions of spleen cells from immunocompetent donors. This reconstitution caused the recipients to resolve their PCP. Treatment of reconstituted SCID mice with anti-CD4 monoclonal antibodies (mAbs) to deplete them of CD4+ cells eliminated their ability to resolve PCP, whereas treating them with anti-CD8 mAb to deplete CD8+ cells had no effect. The findings indicate, therefore, that resistance to PCP in immunologically reconstituted SCID mice is dependent on CD4+ cells. To determine whether CD4+ cells enable conventional mice to resist PCP, B6D2 mice were treated with anti-CD4 mAb to deplete them of CD4+ cells in an attempt to induce PCP. After 10-11 wk of treatment, these mice developed progressive PCP. Taken together, these results indicate that loss of CD4+ cells predisposes mice to PC infection.
Targeting Oncogenic Drivers and the Immune System in Melanoma
Authors: Grant A. McArthur, Antoni Ribas
Journal: Journal of Clinical Oncology (2012)

Melanoma is one of the most common cancers in Western countries but has defied the trend of reductions in age-adjusted mortality observed in most other cancers in recent years. Biologically, melanoma is characterized by a high propensity to metastasize at low tumor volumes necessitating the need for effective drug therapies to support efforts in prevention and early detection for reducing mortality. Efforts to study the clinical biology of melanoma have led to a new understanding of the disease, with genomic studies identifying several targetable oncogenes, in particular the protein kinases BRAF and KIT. Biologic studies have also identified a variety of immunologic targets, including the programmed death 1 (PD-1) and cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitory molecules expressed on T lymphocytes. After several decades of clinical trials that failed to demonstrate improvement in overall survival in patients with advanced melanoma, small molecule inhibitors of BRAF or MEK and inhibition of CTLA-4 can improve survival in patients with advanced disease. These early clinical studies have provided a great opportunity to improve mortality in melanoma with the significant potential of combinations of signaling inhibitors or signaling inhibitors combined with immunologic agents, particularly when used in the adjuvant setting, and to transform the care of patients with this most challenging of cancers.