tbuckley/cabot-search huggingface dataset:
Collateral Artery Growth (Arteriogenesis) After Experimental Arterial Occlusion Is Impaired in Mice Lacking CC-Chemokine Receptor-2
Authors: Matthias Heil, Tibor Ziegelhoeffer, Shawn Wagner, Borja Fernández, Armin Helisch, Sandra Martin, Silvia Tribulova, William A. Kuziel, Georg Bachmann, Wolfgang Schaper
Journal: Circulation Research (2004)

Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. Induced macrophage migration in vivo is driven by the binding of monocyte chemoattractant protein-1 (MCP-1, or CCL2 in the new nomenclature) to the CCR2-chemokine receptor on macrophages. To determine whether the CCL2-CCR2 signaling pathway is involved in the accumulation of macrophages in growing collateral vessels, we used mice that are deficient in CCR2 in a model of experimental arterial occlusion and collateral vessel growth. In an in vitro CCL2-driven chemotaxis assay, mononuclear cells isolated from wild-type BALB/c mice exhibited CCL2 concentration-dependent migration, whereas this migration was abolished in cells from CCR2(-/-) mice on a BALB/c genetic background. In vivo, blood flow recovery as measured by laser Doppler (LDI) and MRI (MRI) was impaired in CCR2(-/-) mice on either the BALB/c or C57BL/6 genetic backgrounds. Three weeks after femoral artery ligation, LDI perfusion ratio of operated versus nonoperated distal hindlimb in BALB/c wild-type mice increased to 0.45+/-0.06 and in CCR2(-/-) animals only to 0.21+/-0.03 (P<0.01). In C57BL/6 mice, ratio increased to 0.96+/-0.09 and 0.85+/-0.08 (P<0.05), respectively. MRI at 3 weeks (0.76+/-0.06 versus 0.62+/-0.01; P<0.05) and hemoglobin oxygen saturation measurements confirmed these findings. Active foot movement score significantly decreased and gastrocnemius muscle atrophy was significantly greater in CCR2(-/-) mice. Morphometric analysis showed a lesser increase in collateral vessel diameters in CCR2(-/-) mice. Importantly, the number of invaded monocytes/macrophages in the perivascular space of collateral arteries of CCR2(-/-) animals was dramatically reduced in comparison to wild-type mice. In conclusion, our results demonstrate that the CCR2 signaling pathway is essential for efficient collateral artery growth.
MEDICAL DEPARTMENTS IN PUBLIC LIBRARIES.
Authors: C. D. SPIVAK
Journal: JAMA (1901)

In the world of industry we witness a tendency toward co-operation, unification and centralization. The one line store passes out of existence and its place is taken by the department store. The same tendency is prevailing in the educational world. The medical school proper is slowly disappearing and in its stead comes the medical department of the university. The libraries in large cities like New York, Chicago, Boston and elsewhere are becoming in one way or another merely departments of one great library system. The state libraries of several states have discarded the idea that its books are intended only for the delectation of the state solons—a law library pure and simple. These progressive libraries collect, preserve and make available for the citizens of the state books on agriculture in its various subdivisions, mining, engineering, natural philosophy, etc. Medical departments in public libraries were but few until 1898,<sup>1</sup>when
Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease
Authors: M. Funke, J-M. Fellrath
Journal: European Respiratory Journal (2008)

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient9s environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.
Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. I. T lymphocyte requirement for B cell tumor generation.
Authors: M L Veronese, A Veronesi, E D'Andrea, A Del Mistro, S Indraccolo, M R Mazza, M Mion, R Zamarchi, C Menin, M Panozzo
Journal: The Journal of Experimental Medicine (1992)

Mechanisms of tumor development were studied in SCID mice injected with human lymphoid cells from Epstein-Barr virus-positive (EBV+) donors. About 80% of peripheral blood mononuclear cell (PBMC)-injected animals developed a lymphoproliferative disease associated with oligoclonal EBV+ tumors of human B cell origin. No change in tumor development rate occurred when monocyte-depleted PBMC were inoculated. No tumors developed when purified B cells were injected. B cell lymphoproliferative disease was also prevented in most cases when PBMC-injected animals were treated with agents that prevent T cell activation, such as cyclosporin A. Both CD4+ and CD8+ T cell subpopulations were able to provide putative factor(s) necessary for EBV+ B cell expansion and progression to tumors. These data suggest that the transfer alone of potentially tumorigenic human cells into an immunodeficient environment, such as the SCID mouse, might not be sufficient for cell progression to tumor, and raise the possibility that chronic activation events could play a major role in the pathogenesis of some EBV+ lymphomas in the immunocompromised host.
Significantly Longer Progression-Free Survival With <i>nab</i>-Paclitaxel Compared With Docetaxel As First-Line Therapy for Metastatic Breast Cancer
Authors: William J. Gradishar, Dimitry Krasnojon, Sergey Cheporov, Anatoly N. Makhson, Georgiy M. Manikhas, Alicia Clawson, Paul Bhar
Journal: Journal of Clinical Oncology (2009)

In patients with metastatic breast cancer (MBC), nab-paclitaxel produced significantly higher antitumor activity compared with patients who received solvent-based paclitaxel. This phase II study examined the antitumor activity and safety of weekly and every 3 week (q3w) nab-paclitaxel compared with docetaxel as first-line treatment in patients with MBC.In this randomized, multicenter study, patients (N = 302) with previously untreated MBC received nab-paclitaxel 300 mg/m(2) q3w, 100 mg/m(2) weekly, or 150 mg/m(2) weekly or docetaxel 100 mg/m(2) q3w.nab-Paclitaxel 150 mg/m(2) weekly demonstrated significantly longer progression-free survival (PFS) than docetaxel by both independent radiologist assessment (12.9 v 7.5 months, respectively; P = .0065) and investigator assessment (14.6 v 7.8 months, respectively; P = .012). On the basis of independent radiologist review, both 150 mg/m(2) (49%) and 100 mg/m(2) (45%) weekly of nab-paclitaxel demonstrated a higher overall response rate (ORR) than docetaxel (35%), but this did not reach statistical significance. This trend was supported by statistically significant investigator ORR for both weekly nab-paclitaxel doses versus docetaxel. nab-Paclitaxel q3w versus docetaxel was not different for PFS or ORR. On the basis of both the independent radiologist and investigator review, disease control rate was significantly higher for patients receiving either dose of weekly nab-paclitaxel compared with docetaxel. Grade 3 or 4 fatigue, neutropenia, and febrile neutropenia were less frequent in all nab-paclitaxel arms. The frequency and grade of peripheral neuropathy were similar in all arms.This randomized study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel, with a statistically and clinically significant prolongation of PFS (> 5 months) in patients receiving nab-paclitaxel 150 mg/m(2) weekly compared with docetaxel 100 mg/m(2) q3w.
Cushing's syndrome
Authors: J. K. Prague, S. May, B. C. Whitelaw
Journal: BMJ (2013)

A 45 year old woman was being regularly reviewed in primary and secondary care because of a five year history of type 2 diabetes that had required early insulin treatment; refractory hypertension; and subsequent chronic kidney disease. She had previously described other symptoms, including weight gain, bruising, flushes, and low mood, all of which had been attributed to obesity and menopause. She was not taking any glucocorticoids. After presenting to her local emergency department with a Colles' fracture after a low impact fall, she was referred to the endocrinology department for suspected Cushing's syndrome; subsequent investigation confirmed the diagnosis. Cushing's syndrome describes the clinical consequences of chronic exposure to excess glucocorticoid irrespective of the underlying cause. Endogenous causes of Cushing's syndrome are rare and include a cortisol-producing adrenal tumour, which may be benign or malignant; excess secretion of adrenocorticotrophic hormone (ACTH) from a pituitary tumour (Cushing's disease); or an ectopic ACTH-producing tumour (ectopic Cushing's syndrome). More commonly, prolonged administration of supraphysiological glucocorticoid treatment (including tablets, inhalers, nasal sprays, and skin creams) can also cause the same clinical condition1 2 (also known as exogenous or iatrogenic Cushing's). #### How common is Cushing's syndrome?
Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy
Authors: Christopher J. Nirschl, Charles G. Drake
Journal: Clinical Cancer Research (2013)

The expression of immune checkpoint molecules on T cells represents an important mechanism that the immune system uses to regulate responses to self-proteins. Checkpoint molecules include cytotoxic T lymphocyte antigen-4, programmed death-1, lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, and several others. Previous studies have identified individual roles for each of these molecules, but more recent data show that coexpression of checkpoint molecules occurs frequently on cancer-specific T cells as well as on pathogen-specific T cells in chronic infections. As the signaling pathways associated with each checkpoint molecule have not been fully elucidated, blocking multiple checkpoints with specific monoclonal antibodies results in improved outcomes in several chronic viral infections as well as in a wide array of preclinical models of cancer. Recent clinical data suggest similar effects in patients with metastatic melanoma. These findings support the concept that individual immune checkpoint molecules may function through nonoverlapping molecular mechanisms. Here, we review current data regarding immune checkpoint molecule signaling and coexpression, both in cancer and infectious disease, as well as the results of preclinical and clinical manipulations of checkpoint proteins.
Microsatellite instability in patients with multiple primary cancers of the gastrointestinal tract
Authors: K Yamashita
Journal: Gut (2000)

Little is known about the genetic alterations in multiple primary cancers of the gastrointestinal tract. Microsatellite instability (MSI) is frequently observed in hereditary non-polyposis colorectal cancer (HNPCC), and multiple primary cancers is a feature of this syndrome.To identify MSI incidence, target gene mutation, and mismatch repair (MMR) protein status in patients with multiple primary cancers of the gastrointestinal tract.Fifty seven cancers from 22 Japanese patients with multiple primary cancers of the stomach, duodenum, colon, and rectum.MSI was examined at 5-7 microsatellite loci. Mutation analysis for TGFbetaRII, IGFIIR, and BAX was performed in cancers with MSI. MMR protein status was examined by immunohistochemical analysis using a monoclonal antibody against hMSH2 and hMLH1.MSI was observed in 16 of 22 patients (73%) and in 29 of 57 lesions (51%). High frequency MSI (MSI-H) was found often in patients with multiple cancers in the same organ (p = 0.042), especially in multiple gastric cancer patients (p = 0.038). In contrast, patients with multiple cancers in different organs had a tendency to show low frequency MSI (MSI-L) or microsatellite stable (MSS) phenotype. Both target gene mutation and decreased expression of MMR protein were found only in seven lesions of three patients with MSI at more than four microsatellite loci.These results suggest that genetic instability may play an important role in the development of multiple gastrointestinal cancers but there may be different genetic alterations between multiple gastrointestinal cancers of the same and different organs.
Increased prevalence of ocular glaucomatous abnormalities in systemic sclerosis
Authors: Y Allanore, C Parc, D Monnet, A P Brézin, A Kahan
Journal: Annals of the Rheumatic Diseases (2004)

Cardiovascular diseases, vasospasm, and dysimmunity have been implicated in normal tension glaucoma (NTG).To investigate the prevalence of ocular abnormalities suggestive of glaucoma damage in systemic sclerosis (SSc).61 patients with SSc (mean (SD) age 56.2 (12) years, mean (SD) disease duration 9.9 (9) years; 41 with limited cutaneous disease) and 37 control subjects with osteoarthritis (mean (SD) age 55.9 (12) years) were studied. They were systematically referred to an ophthalmologist. The evaluation was based on aplanation tonometry, ophthalmoscopy with retinal photography (evaluation of cup/disc ratio (c/d)), and automated static perimetry (determination of mean defects (MD)). Statistical analyses were performed with the chi(2), Mann-Whitney, and Spearman tests.The mean visual acuity and intraocular pressure were similar in both groups. An excavation with a c/d >0.3 was found in 27 eyes from patients with SSc and 5 eyes from controls (p = 0.009); a c/d >0.7 was found in 4 eyes from patients with SSc and none in the controls (NS). Visual field defects (MD <-2 dB) were found in 55 eyes from patients with SSc and in 18 eyes from controls (p<0.0001). A concomitant c/d >0.3 and MD <-2 dB was found in 21 eyes from 12 patients with SSc but in none of the control eyes (p<0.0001).Ocular abnormalities suggesting glaucomatous neuropathy without ocular hypertension were dramatically more prevalent in patients with SSc. These abnormalities seem to be mild but justify long term follow up. They are consistent with the vascular pathogenic hypothesis for NTG.
Adrenocorticotropin Insensitivity Syndromes
Authors: Adrian J. L. Clark, Angela Weber
Journal: Endocrine Reviews (1998)

I. Introduction II. Familial Glucocorticoid Deficiency A. Clinical presentation B. Investigation C. Treatment D. Pathogenesis III. Triple A Syndrome A. Clinical features B. Treatment C. Pathogenesis D. Mapping of triple A syndrome gene E. Candidate genes IV. Acquired ACTH Resistance V. Conclusions
Brief Report: Ankylosing Spondylitis or Diffuse Idiopathic Skeletal Hyperostosis in Royal Egyptian Mummies of the 18th–20th Dynasties? Computed Tomography and Archaeology Studies
Authors: Sahar N. Saleem, Zahi Hawass
Journal: Arthritis & Rheumatology (2014)

Objective. To study the computed tomography(CT) images of royal Ancient Egyptian mummies dated to the 18th to early 20th Dynasties for the claimed diagnoses of ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) and to correlate the findings with the archaeology literature.Methods. We studied the CT images of 13 royal Ancient Egyptian mummies (1492–1153 BC) for evidence of AS and DISH and correlated our findings with the archaeology literature.Results. The findings of the CT scans excluded the diagnosis of AS, based on the absence of sacroiliac joint erosions or fusion of the facet joints. Four mummies fulfilled the diagnostic criteria for DISH:Amenhotep III (18th Dynasty), Ramesses II, his son Merenptah, and Ramesses III (19th to early 20th Dynasties).The diagnosis of DISH, a commonly a symptomatic disease of old age, in the 4 pharaohs is in concordance with their longevity and active lifestyles.Conclusion. CT findings excluded the diagnosis of AS in the studied royal Ancient Egyptian mummies and brought into question the antiquity of the disease. The CT features of DISH during this ancient period were similar to those commonly seen in modern populations,and it is likely that they will also be similar in the future.The affection of Ramesses II and his son Merenptah supports familial clustering of DISH. The process of mummification may induce changes in the spine that should be considered during investigations of disease in ancient mummies.
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID: I. RELATIONSHIP OF SKIN SENSITIVITY TO PURIFIED DIPHTHERIA TOXOID TO THE PRESENCE OF CIRCULATING, NON-PRECIPITATING ANTITOXIN
Authors: W. J. Kuhns
Journal: The Journal of Experimental Medicine (1952)

Among a group of 131 young adults tested, there was a high degree of correlation between the occurrence of immediate skin reactions of the wheal and erythema type produced by purified diphtheria toxoid and personal or familial history of allergy of the hay-fever type. Of 39 Schick-negative subjects who received a "booster" dose of purified diphtheria toxoid, 19 showed no immediate skin reactions before immunization. The development of skin sensitivity in these subjects was associated with the production of non-precipitating circulating antitoxin. Three subjects produced 20 units or more antitoxin per cc. serum following immunization, without demonstrable precipitins. Despite the fact that none showed immediate skin reactions to Schick toxoid prior to immunization, all 3 possessed a high degree of skin sensitivity to toxoid following immunization.
Lung Cancer Histologic Type in the Surveillance, Epidemiology, and End Results Registry Versus Independent Review
Authors: R. W. Field, B. J. Smith, C. E. Platz, R. A. Robinson, J. S. Neuberger, C. P. Brus, C. F. Lynch
Journal: JNCI Journal of the National Cancer Institute (2004)

Because few studies have assessed the accuracy of lung cancer histologic diagnoses reported by state cancer registries, we examined whether the Iowa Surveillance, Epidemiology, and End Results Cancer Registry (i.e., the Iowa Cancer Registry)–reported lung cancer histologic diagnoses were reliable. We investigated agreement between lung cancer histologic types reported for 413 patients with lung cancer by the Iowa Cancer Registry and those obtained through an independent review of diagnostic slides. Among lung cancer histologic types, small-cell carcinoma had the highest sensitivity (94.1%, 95% confidence interval [CI] = 85.6% to 98.4%), positive predictive value (94.1%, 95% CI = 85.6% to 98.4%), negative predictive value (98.8%, 95% CI = 96.9% to 99.7%), and highest percent exact agreement (98.0%, 95% CI = 96.6% to 99.4%). The lowest sensitivity (21.9%, 95% CI = 9.3% to 40.0%) and positive predictive value (23.3%, 95% CI = 9.9% to 42.3%) were noted for large-cell carcinoma, probably because other more specific features of adenocarcinoma or squamous carcinoma were absent. Adenocarcinoma had the lowest specificity (84.4%, 95% CI = 79.0% to 88.9%), negative predictive value (85.2%, 95% CI = 79.9% to 89.6%), and percent exact agreement (82.9%, 95% CI = 79.2% to 86.6%). Samples collected by cytologic examination (odds ratio [OR] = 2.4, 95% CI = 1.1 to 5.2) or biopsy examination (OR = 2.2, 95% CI = 1.1 to 4.2) were more likely to be misclassified than samples obtained via resection. Thus, the histologic type obtained by the Iowa Cancer Registry is reasonably reliable, but independent slide review is needed for precise histologic typing of lung cancer.
Treatment of Intracerebral Neoplasia and Neoplastic Meningitis with Regional Delivery of Oncolytic Recombinant Poliovirus
Authors: Hidenobu Ochiai, Stephanie A. Moore, Gary E. Archer, Tatsunori Okamura, Tracy A. Chewning, Jeffrey R. Marks, John H. Sampson, Matthias Gromeier
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Spread to the central nervous system (CNS) and the leptomeninges is a frequent complication of systemic cancers that is associated with serious morbidity and high mortality. We have evaluated a novel therapeutic approach against CNS complications of breast cancer based on the human neuropathogen poliovirus (PV). Experimental Design: Susceptibility to PV infection and ensuing rapid cell lysis is mediated by the cellular receptor of PV, CD155. We evaluated CD155 expression in several human breast tumor tissue specimens and cultured breast cancer cell lines. In addition, we tested an oncolytic PV recombinant for efficacy in xenotransplantation models of neoplastic meningitis and cerebral metastasis secondary to breast cancer. Results: We observed that breast cancer tissues and cell lines derived thereof express CD155 at levels mediating exquisite sensitivity toward PV-induced oncolysis in the latter. An association with the immunoglobulin superfamily molecule CD155 renders breast cancer a likely target for oncolytic PV recombinants. This assumption was confirmed in xenotransplantation models for neoplastic meningitis or solitary cerebral metastasis, where local virus treatment dramatically improved survival. Conclusions: Our findings suggest oncolytic PV recombinants as a viable treatment option for CNS complications of breast cancer.
Relation of Nonalcoholic Hepatic Steatosis to Early Carotid Atherosclerosis in Healthy Men
Authors: Giovanni Targher, Lorenzo Bertolini, Roberto Padovani, Luciano Zenari, Giacomo Zoppini, Giancarlo Falezza
Journal: Diabetes Care (2004)

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome that is closely associated with obesity, dyslipidemia, insulin resistance, and type 2 diabetes, thus suggesting that NAFLD represents another component of the metabolic syndrome (1,2). Because it is now recognized that individuals with the metabolic syndrome are at increased cardiovascular risk (3–5), it is possible to hypothesize that NAFLD patients might portend a greater cardiovascular disease (CVD) risk. Ultrasonographically measured carotid intima-media thickness (CIMT), as a reliable index of subclinical atherosclerosis (6), can be used to characterize the CVD risk of patients with NAFLD. However, the available data on this specific topic are lacking.

We compared CIMT values in subjects with and without nonalcoholic hepatic steatosis (HS) and examined whether such differences were mediated by one or more metabolic disorders typically clustering in these subjects.

We studied 85 male volunteers who were randomly selected among those who agreed to have an evaluation of their liver and intra-abdominal fat by ultrasonography and computed tomography (CT) scan, respectively. The exclusion criteria were as follows: age >50 years combined with an alcohol consumption ≥20 g/day, taking any drugs, and a history of recent acute illness or clinical evidence suggestive of any cardiovascular events, diabetes, or kidney or liver disorders. All individuals were clinically healthy. Most subjects were abstainers ( n = 68) or drank minimally …