tbuckley/cabot-search huggingface dataset:
CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22
Authors: Randy S. Longman, Gretchen E. Diehl, Daniel A. Victorio, Jun R. Huh, Carolina Galan, Emily R. Miraldi, Arun Swaminath, Richard Bonneau, Ellen J. Scherl, Dan R. Littman
Journal: The Journal of Experimental Medicine (2014)

Interleukin (IL)-22–producing group 3 innate lymphoid cells (ILC3) promote mucosal healing and maintain barrier integrity, but how microbial signals are integrated to regulate mucosal protection offered by these cells remains unclear. Here, we show that in vivo depletion of CX3CR1+ mononuclear phagocytes (MNPs) resulted in more severe colitis and death after infection with Citrobacter rodentium. This phenotype was rescued by exogenous IL-22, which was endogenously produced by ILC3 in close spatial proximity to CX3CR1+ MNPs that were dependent on MyD88 signaling. CX3CR1+ MNPs from both mouse and human tissue produced more IL-23 and IL-1β than conventional CD103+ dendritic cells (cDCs) and were more efficient than cDCs in supporting IL-22 production in ILC3 in vitro and in vivo. Further, colonic ILC3 from patients with mild to moderate ulcerative colitis or Crohn’s disease had increased IL-22 production. IBD-associated SNP gene set analysis revealed enrichment for genes selectively expressed in human intestinal MNPs. The product of one of these, TL1A, potently enhanced IL-23– and IL-1β-induced production of IL-22 and GM-CSF by ILC3. Collectively, these results reveal a critical role for CX3CR1+ mononuclear phagocytes in integrating microbial signals to regulate colonic ILC3 function in IBD.
Neuraminidase Inhibitors for Influenza
Authors: Anne Moscona
Journal: New England Journal of Medicine (2005)

he impact of influenza infection is felt globally each year when the disease develops in approximately 20 percent of the world’s population. In the United States, influenza infections occur in epidemics each winter, generally between late December and early March. Recent events, including human cases of avian influenza, have heightened awareness of the threat of a pandemic and have spurred efforts to develop plans for its control. Although vaccination is the primary strategy for the prevention of influenza, there are a number of likely scenarios for which vaccination is inadequate and effective antiviral agents would be of the utmost importance. During any influenza season, antigenic drift in the virus may occur after formulation of the year’s vaccine has taken place, rendering the vaccine less protective, and outbreaks can more easily occur among highrisk populations. In the course of a pandemic, vaccine supplies would be inadequate. Vaccine production by current methods cannot be carried out with the speed required to halt the progress of a new strain of influenza virus; therefore, it is likely that vaccine would not be available for the first wave of spread of virus. 1 Antiviral agents thus form an important part of a rational approach to epidemic influenza and are critical to planning for a pandemic. Four drugs are currently available for the treatment or prophylaxis of influenza infections: the adamantanes (amantadine and rimantadine) and the newer class of neuraminidase inhibitors (zanamivir [Relenza] and oseltamivir [Tamiflu]). The adamantanes interfere with viral uncoating inside the cell. They are effective only against influenza A and are associated with several toxic effects and with rapid emergence of drug-resistant variants. Adamantane-resistant isolates of influenza A are genetically stable, can be transmitted to susceptible contacts, are as pathogenic as wild-type virus isolates, and can be shed for prolonged periods in immunocompromised patients taking the drug. This potential for the development of resistance especially limits the use of the adamantanes for the treatment of influenza, although the drugs still have a place in planning for prophylaxis during an epidemic. The neuraminidase inhibitors zanamivir and oseltamivir interfere with the release of progeny influenza virus from infected host cells, a process that prevents infection of new host cells and thereby halts the spread of infection in the respiratory tract (Fig. 1). Since replication of influenza virus in the respiratory tract reaches its peak between 24 and 72 hours after the onset of the illness, drugs such as the neuraminidase inhibitors that act at the stage of viral replication must be administered as early as possible. In contrast to the adamantanes, the neuraminidase inhibitors are associated with very little toxicity and are far less likely to promote the development of drug-resistant influenza. As a class, the neuraminidase inhibitors are effective against all neuraminidase subtypes t
Vicia villosa agglutinin separates freshly isolated Peyer's Patch T cells into interleukin 5- or interleukin 2-producing subsets.
Authors: S Schoenbeck, M J Hammen, M F Kagnoff
Journal: The Journal of Experimental Medicine (1989)

Murine L3T4 T cells freshly isolated from Peyer's Patch were fractionated based on differential adherence to Vicia villosa agglutinin (VVA). VVA adherent cells secreted IL-5, but not IL-2, after stimulation with Con A and IL-1. In striking contrast, VVA nonadherent PP L3T4 T cells secreted IL-2, but not IL-5, under the same conditions. In addition, supernatants from VVA adherent, but not from VVA nonadherent cells cultures, enhanced IgA secretion by LPS-stimulated splenic B cells to the same extent as purified IL-5. Thus, IL-5-producing T cells are present in PP in situ and may play an important role in the development of mucosal immunity. Further, differential adherence to VVA can be used to separate T cell populations that preferentially secrete IL-5 or IL-2.
Extensively Drug-Resistant Tuberculosis in the United States, 1993-2007
Authors: N. Sarita Shah
Journal: JAMA (2008)

Worldwide emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised global public health concern, given the limited therapy options and high mortality.To describe the epidemiology of XDR-TB in the United States and to identify unique characteristics of XDR-TB cases compared with multidrug-resistant TB (MDR-TB) and drug-susceptible TB cases.Descriptive analysis of US TB cases reported from 1993 to 2007. Extensively drug-resistant TB was defined as resistance to isoniazid, a rifamycin, a fluoroquinolone, and at least 1 of amikacin, kanamycin, or capreomycin based on drug susceptibility test results from initial and follow-up specimens.Extensively drug-resistant TB case counts and trends, risk factors for XDR-TB, and overall survival.A total of 83 cases of XDR-TB were reported in the United States from 1993 to 2007. The number of XDR-TB cases declined from 18 (0.07% of 25 107 TB cases) in 1993 to 2 (0.02% of 13 293 TB cases) in 2007, reported to date. Among those with known human immunodeficiency virus (HIV) test results, 31 (53%) were HIV-positive. Compared with MDR-TB cases, XDR-TB cases were more likely to have disseminated TB disease (prevalence ratio [PR], 2.06; 95% confidence interval [CI], 1.19-3.58), less likely to convert to a negative sputum culture (PR, 0.55; 95% CI, 0.33-0.94), and had a prolonged infectious period (median time to culture conversion, 183 days vs 93 days for MDR-TB; P < .001). Twenty-six XDR-TB cases (35%) died during treatment, of whom 21 (81%) were known to be HIV-infected. Mortality was higher among XDR-TB cases than among MDR-TB cases (PR, 1.82; 95% CI, 1.10-3.02) and drug-susceptible TB cases (PR, 6.10; 95% CI, 3.65-10.20).Although the number of US XDR-TB cases has declined since 1993, coinciding with improved TB and HIV/AIDS control, cases continue to be reported each year.
Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients
Authors: B J Philips, J Redman, A Brennan, D Wood, R Holliman, D Baines, E H Baker
Journal: Thorax (2005)

<b>Background:</b> The risk of nosocomial infection is increased in critically ill patients by stress hyperglycaemia. Glucose is not normally detectable in airway secretions but appears as blood glucose levels exceed 6.7–9.7 mmol/l. We hypothesise that the presence of glucose in airway secretions in these patients predisposes to respiratory infection. <b>Methods:</b> An association between glucose in bronchial aspirates and nosocomial respiratory infection was examined in 98 critically ill patients. Patients were included if they were expected to require ventilation for more than 48 hours. Bronchial aspirates were analysed for glucose and sent twice weekly for microbiological analysis and whenever an infection was suspected. <b>Results:</b> Glucose was detected in bronchial aspirates of 58 of the 98 patients. These patients were more likely to have pathogenic bacteria than patients without glucose detected in bronchial aspirates (relative risk 2.4 (95% CI 1.5 to 3.8)). Patients with glucose were much more likely to have methicillin resistant <i>Staphylococcus aureus</i> (MRSA) than those without glucose in bronchial aspirates (relative risk 2.1 (95% CI 1.2 to 3.8)). Patients who became colonised or infected with MRSA had more infiltrates on their chest radiograph (p&lt;0.001), an increased C reactive protein level (p&lt;0.05), and a longer stay in the intensive care unit (p&lt;0.01). Length of stay did not determine which patients acquired MRSA. <b>Conclusion:</b> The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA.
Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats.
Authors: P G Anderson, S P Bishop, S B Digerness
Journal: Circulation Research (1989)

The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial and coronary vascular function and structure. Twelve-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with and without 12 weeks of vasodilator antihypertensive treatment (hydralazine) were studied using an isolated perfused rat heart model. Hydralazine treatment normalized blood pressure in SHR but did not cause regression of cardiac hypertrophy (heart weight to body weight ratio of SHR + hydralazine 4.33 +/- 0.098 vs. SHR 4.66 +/- 0.091; WKY 3.21 +/- 0.092 and WKY + hydralazine 3.38 +/- 0.152; mean +/- SEM). Coronary flow reserve, elicited by adenosine vasodilation in the perfused heart, was decreased in SHR (29%) compared with WKY (105%) and WKY + hydralazine (100%) and was significantly improved in SHR + hydralazine (75%). Morphometric evaluation of perfusion-fixed coronary arteries and arterioles (30-400 microns diameter) demonstrated a significant increase in the slope of the regression line comparing the square root of medial area versus outer diameter in SHR (0.444) compared with WKY (0.335) and WKY + hydralazine (0.336, p less than 0.05). Blood vessels from SHR + hydralazine were not different from control (0.338). Cardiac oxygen consumption was decreased in SHR (10.9 +/- 0.74 mumols oxygen/min/g/60 mm Hg left ventricular pressure) compared with WKY (22.4 +/- 1.47) and WKY + hydralazine (23.4 +/- 1.90; p less than 0.01), while SHR + hydralazine was intermediate (16.0 +/- 1.60). These studies suggest that significant alterations in myocardial and coronary vascular structure and function occur in hypertension-induced cardiac hypertrophy. The coronary vasculature is responsive to blood pressure, independent of cardiac hypertrophy, although moderate coronary deficits do remain after chronic antihypertensive therapy.
DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population
Authors: Monika Belickova, Michaela Dostalova Merkerova, Eliska Stara, Jitka Vesela, Dana Sponerova, Dana Mikulenkova, Radim Brdicka, Radana Neuwirtova, Anna Jonasova, Jaroslav Cermak
Journal: Journal of Hematology & Oncology (2013)

Interactions between genetic variants and risk factors in myelodysplastic syndromes are poorly understood. In this case-control study, we analyzed 1 421 single nucleotide polymorphisms in 408 genes involved in cancer-related pathways in 198 patients and 292 controls.The Illumina SNP Cancer Panel was used for genotyping of samples. The chi-squared, p-values, odds ratios and upper and lower limits of the 95% confidence interval were calculated for all the SNPs that passed the quality control filtering.Gene-based analysis showed nine candidate single nucleotide polymorphisms significantly associated with the disease susceptibility (q-value<0.05). Four of these polymorphisms were located in oxidative damage/DNA repair genes (LIG1, RAD52, MSH3 and GPX3), which may play important roles in the pathobiology of myelodysplastic syndromes. Two of nine candidate polymorphisms were located in transmembrane transporters (ABCB1 and SLC4A2), contributing to individual variability in drug responses and patient prognoses. Moreover, the variations in the ROS1 and STK6 genes were associated with the overall survival of patients.Our association study identified genetic variants in Czech population that may serve as potential markers for myelodysplastic syndromes.
THE ROLE OF MOTIVATION IN RECOVERY FROM ILLNESS
Authors: PAUL R. HAWLEY
Journal: American Journal of Psychiatry (1948)

Motivation is an extremely important factor in the recovery from illness and in overcoming disability. This is true in many cases of somatic illness and of organic injury, and its influence bears little relation to the gravity of the basic condition. In psychosomatic illness and in psychosomatic sequelæ of organic illness and injury, it is of the greatest importance. Motivation must be inspired and intelligently directed by the physician and his associates on the therapeutic team. Too often its influence is disregarded; and too often it is misdirected by careless, superficial study of the case. The worst employment of this powerful factor, however, is when apprehension is unduly aroused in the patient by ill-advised comments or overcautious advice on the part of his physician. The application of psychiatry in the fields of medicine and surgery is slowly gaining ground. The situation is yet far from satisfactory; but the scientific program of the recent meeting of the American College of Physicians reflects the increasing awareness of internists to the necessity for treating the mind as well as the body. But, until psychiatrists recognize that psychotics often suffer from somatic disorders—which is another story that might prove revealing—and until other physicians recognize that almost all of the organically ill and injured suffer from psychosomatic disorders to a greater or lesser extent, patients will be denied the full potentialities of medicine.
Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going?
Authors: G. Parmiani, C. Castelli, P. Dalerba, R. Mortarini, L. Rivoltini, F. M. Marincola, A. Anichini
Journal: JNCI Journal of the National Cancer Institute (2002)

Many human tumor-associated antigens (TAAs) have recently been identified and molecularly characterized. When bound to major histocompatibility complex molecules, TAA peptides are recognized by T cells. Clinical studies have therefore been initiated to assess the therapeutic potential of active immunization or vaccination with TAA peptides in patients with metastatic cancer. So far, only a limited number of TAA peptides, mostly those recognized by CD8+ T cells in melanoma patients, have been clinically tested. In some clinical trials, partial or complete tumor regression was observed in approximately 10%–30% of patients. No serious side effects have been reported. The clinical responses, however, were often not associated with a detectable T-cell-specific antitumor immune response when patients' T cells were evaluated in ex vivo assays. In this review, we analyze the available human TAA peptides, the potential immunogenicity (i.e., the ability to trigger a tumor-specific T-cell response) of TAA peptides in vitro and ex vivo, and the potential to construct slightly modified forms of TAA peptides that have increased T-cell stimulatory activity. We discuss the available data from clinical trials of TAA peptide-based vaccination (including those that used dendritic cells to present TAA peptides), identify possible reasons for the limited clinical efficacy of these vaccines, and suggest ways to improve the clinical outcome of TAA peptide-based vaccination for cancer patients.
Instantaneous Pressure Distribution Along the Human Aorta
Authors: PETER C. LUCHSINGER, ROBERT E. SNELL, DALI J. PATEL, DONALD L. FRY
Journal: Circulation Research (1964)

Pressures at various points of the human aorta were recorded and resolved into their sinusoidal components by Fourier analysis. A progressively decreasing phase angle with distance along the aorta was found. This was considered compatible with a traveling wave system. The pressure moduli generally increased with distance along the aorta. This was attributed to the progressively increasing stiffness of the aorta peripherally. Minor undulations in moduli could be explained on the basis of superimposed reflections. The apparent phase velocities were calculated for various points along the aorta. They tended to converge at higher frequencies to a value of 5 m/sec.
Vaccination with mRNA-Electroporated Dendritic Cells Induces Robust Tumor Antigen-Specific CD4+ and CD8+ T Cells Responses in Stage III and IV Melanoma Patients
Authors: Erik H. J. G. Aarntzen, Gerty Schreibelt, Kalijn Bol, W. Joost Lesterhuis, Alexandra J. Croockewit, Johannes H. W. de Wilt, Michelle M. van Rossum, Willeke A. M. Blokx, Joannes F. M. Jacobs, Tjitske Duiveman-de Boer, Danita H. Schuurhuis, Roel Mus, Kris Thielemans, I. Jolanda M. de Vries, Carl G. Figdor, Cornelis J. A. Punt, Gosse J. Adema
Journal: Clinical Cancer Research (2012)

Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses to vaccination with mRNA-electroporated DC in stage III and IV melanoma patients.Twenty-six stage III HLA*02:01 melanoma patients scheduled for radical lymph node dissection (stage III) and 19 melanoma patients with irresectable locoregional or distant metastatic disease (referred to as stage IV) were included. Monocyte-derived DC, electroporated with mRNA encoding gp100 and tyrosinase, were pulsed with keyhole limpet hemocyanin and administered intranodally. TAA-specific T-cell responses were monitored in blood and skin-test infiltrating lymphocyte (SKIL) cultures.Comparable numbers of vaccine-induced CD8(+) and/or CD4(+) TAA-specific T-cell responses were detected in SKIL cultures; 17/26 stage III patients and 11/19 stage IV patients. Strikingly, in this population, TAA-specific CD8(+) T cells that recognize multiple epitopes and produce elevated levels of IFNγ upon antigenic challenge in vitro, were significantly more often observed in stage III patients; 15/17 versus 3/11 stage IV patients, P = 0.0033. In stage IV patients, one mixed and one partial response were documented. The presence or absence of IFNγ-producing TAA-specific CD8(+) T cells in stage IV patients was associated with marked difference in median overall survival of 24.1 months versus 11.0 months, respectively.Vaccination with mRNA-electroporated DC induces a broad repertoire of IFNγ producing TAA-specific CD8(+) and CD4(+) T-cell responses, particularly in stage III melanoma patients.
Seroprevalence and Risk Factors for HTLV-I/II Infection Among Female Prostitutes in the United States
Authors: Rima F. Khabbaz
Journal: JAMA (1990)

We tested 1305 female prostitutes from eight areas of the United States for antibodies to human T-cell lymphotropic virus type I/II. Overall, 6.7% were human T-cell lymphotropic virus type I/II seropositive (with antibodies to both gag and env gene products). The seroprevalence rates ranged from 0% in southern Nevada to 25.4% in Newark, NJ. Human T-cell lymphotropic virus type I/II seropositivity was independently associated with race (odds ratio, 4.68), intravenous drug use (odds ratio, 2.94), hepatitis B seropositivity (odds ratio, 2.87), recruitment in Newark (odds ratio, 2.34), and more years of sexual activity (odds ratio, 1.08 per year of sexual activity). Groups with high rates included blacks, Hispanics, and American Indians, and the rates in these groups were significantly higher than among whites and Asian Americans for women both with and without a history of intravenous drug use. Among intravenous drug users, the only other independent associations were more years of sexual activity and recruitment in Newark; and in non-intravenous drug users, hepatitis B seropositivity. These data show that human T-cell lymphotropic virus type I/II infection is present among female prostitutes in some areas of the United States. Further studies are needed to evaluate patterns of transmission and long-term health effects.
Mechanism of pulmonary function changes after surgical correction for funnel chest
Authors: L Derveaux, I Ivanoff, F Rochette, M Demedts
Journal: European Respiratory Journal (1988)

In 24 subjects with pectus excavatum we evaluated whether the previously detected unfavourable effects of corrective surgery on the ventilatory capacity were attributable to pulmonary or to chest wall factors. We found that 12.2 +/- 3.7 yrs postoperatively (i.e. at the age of 23.3 +/- 5.4 yrs) the vital capacity was decreased from 89 +/- 10% predicted (pred) preoperatively to 64 +/- 6% pred (p less than 0.001) and forced expiratory volume in one second from 88 +/- 17 to 66 +/- 11% pred (p less than 0.001). At total lung capacity (TLC; 69 +/- 5% pred) we found an obvious reduction in transpulmonary pressure (59 +/- 23% pred) and in transdiaphragmatic pressure (30 +/- 17 cmH2O) postoperatively. This indicated an extrapulmonary cause of the restrictive defect, attributable to abnormal chest wall mechanics secondary to the extensive surgery on the sternum and parasternal zones.
Burden of itch in epidermolysis bullosa
Authors: J.J.L. Snauwaert, W.Y. Yuen, M.F. Jonkman, P. Moons, G. Naulaers, M.A. Morren
Journal: British Journal of Dermatology (2014)

Itch is an unpleasant feeling that leads to scratching. It is a common, but understudied, problem in patients with epidermolysis bullosa (EB).We measured the prevalence and characteristics of itch in the three major forms of EB: generalized EB simplex (EBS), junctional EB (JEB) and dystrophic EB (DEB).Forty patients with EB were recruited from two tertiary care centres and one patient organization. The sample included 19 patients with EBS, seven with JEB and 14 with DEB. Patients completed the Leuven Itch Scale (LIS), a multidimensional self-report instrument that quantifies the frequency, duration, severity, distress, consequences and surface area of itch. This instrument has good clinimetric properties.Itch occurred in 85% of the patients, with substantial differences across the subtypes (EBS 74%, JEB 100%, DEB 93%). Itch, in all its dimensions, was most pronounced in patients with JEB and DEB, and less prominent in patients with EBS. The scores were significantly different for itch frequency, severity, distress and surface area, and the overall itch scores were comparable with those of atopic dermatitis. Itch mainly occurred in a hot environment (65%) and when sweating (62%). The most prevalent consequences were difficulty in falling asleep (88%) and lesions from scratching (85%). Differences between the three major subtypes were also observed in terms of circumstances, consequences and sensory characteristics.As expected, itch is common among patients with EB. All aspects of itch measured by the LIS were more severe in JEB and DEB than in EBS.