tbuckley/cabot-search huggingface dataset:
Hybrid resistance to EL-4 lymphoma cells. I. Characterization of natural killer cells that lyse EL-4 cells and their distinction from marrow-dependent natural killer cells.
Authors: V Kumar, E Luevano, M Bennett
Journal: The Journal of Experimental Medicine (1979)

Natural killer (NK) cells from nonimmunized mice capable of lysing EL-4 (C57BL/6 strain H-2b) tissue culture-adapted lymphoma cells have been analyzed and compared with NK cells which lyse YAC-1 (A-strain, H-2a) lymphoma cells. A correlation was seen in the ability of inbred and B6D2F1 mice to reject C57BL/6 (B6) bone-marrow grafts and the ability of their spleen cells to lyse EL-4 cells in vitro. This suggests that hybrid or hemopoietic histocompatibility antigens, (Hh-1b), relevant in the rejection of B6 stem cells may also be the relevant target structures for the anti-EL-4 NK cells. Certain features of these NK cells are similar to the NK cells reactive against YAC-1 cells. Both types of NK cells are present in athymic nude mice, are not affected by treatment with anti-immunoglobulin plus complement, and are not depleted by techniques that remove macrophages. NK activity against both targets is stimulated 3 d after injection of Corynebacterium parvum, and 24 h after challenge with polyinosinic:polycytidylic acid. Hydrocortisone acetate and cyclophosphamide lead to reduction of NK activity within 2-3 d after administration. However, the anti-YAC and anti-EL-4 NK reactivities differed in several important respects. Treatment of mice with 89Sr, the bone-seeking isotope, to deplete marrow-dependent cells, depleted the anti-YAC-1 but not anti-EL-4 cell functions. Anti-EL-4 NK cells were unaffected by silica particles in vivo or in vitro; the NK cells reactive to EL-4 cells matured functionally much earlier in life (5 d of age) and the function did not decline with age. Irradiated mice reconstituted with syngeneic marrow or spleen cells developed functional NK cells against EL-4 targets before they developed anti-YAC-1 NK cells in their spleen. Thus anti-EL-4 NK cells that express hybrid resistance in vitro appear to differ from anti-YAC-1 NK cells and do not require an intact marrow microenvironment for functional differentiation. Despite differences in the NK-cell types involved in the lysis of YAC-1 and EL-4 cells, these two tumor cells share certain common determinants. This was ascertained both by cold competition and by utilization of YAC-1 and EL-4 cell monolayers as immunoadsorbents. We conclude that Hh-1b is the common antigen present in EL-4 and YAC-1 cells, because B6D2F1 anti-B6 (anti-Hh-1b) cytotoxic T lymphocytes lysed both the tumor cells. Our data suggest that Hh-1b antigen is recognized by both types of NK cells, but that additional determinants must be present on YAC-1 cells. Two models of NK cell lysis compatible with the data are presented.
Role of the sympathetic nervous system in the renal response to hemorrhage
Authors: John R. Gill, Alfred G. T. Casper
Journal: Journal of Clinical Investigation (1969)

In 12 studies, a femoral artery and vein of a donor dog treated with desoxycorticosterone were connected by tubing to a renal artery and vein of a recipient dog treated with desoxycorticosterone, and the kidney with its nerve supply intact was perfused at femoral arterial pressure. Infusion of normal saline, which contained albumin, from 2.7 to 3.1 g/100 ml, in the donor produced significant natriuresis in a kidney of the donor (from 112 to 532 muEq/min) and in the perfused kidney (from 60 to 301 muEq/min) of the recipient. Increased sodium excretion in the perfused kidney was associated with an increase in the clearances of inulin and para-aminohippurate (P < 0.01) and a decrease in hematocrit of perfusing blood (P < 0.01). Infusion was continued in the donor while recipient was bled 23 ml/kg, with a decrease in mean arterial pressure from 152 to 130 mm Hg. Sodium excretion in perfused kidney decreased from 301 to 142 muEq/min (P < 0.01), whereas sodium excretion in donor was unchanged (506 VS. 532 muEq/min; P > 0.3). Clearance of inulin by perfused kidney was not significantly affected by bleeding (26 +/-SE 2 VS. 25 +/-SE 2; P > 0.2), but the clearance of para-aminohippurate was decreased by bleeding (P < 0.01), so that filtration fraction increased. As the perfused kidney of the recipient dog continued to receive blood from the natriuretic donor dog when the recipient dog was bled, the decrease in sodium excretion that bleeding produced in the perfused kidney was presumably mediated by renal nerves. Thus, an increase in nervous stimuli to the kidney that is not sufficient to decrease glomerular filtration rate can increase the tubular reabsorption of sodium and thereby significantly decrease its excretion. This property of the sympathetic nervous system to affect tubular reabsorption of sodium suggests that an increase in sympathetic activity may constitute an important mechanism for the renal conservation of sodium when intravascular volume is contracted by hemorrhage or other cause.
Fabry disease and the skin: data from FOS, the Fabry outcome survey
Authors: C.H. Orteu, T. Jansen, O. Lidove, R. Jaussaud, D.A. Hughes, G. Pintos-Morell, U. Ramaswami, R. Parini, G. Sunder-Plassman, M. Beck, A.B. Mehta
Journal: British Journal of Dermatology (2007)

Fabry disease (also known as Anderson-Fabry disease) is a rare, X-linked lysosomal storage disorder that is characterized by accumulation of globotriaosylceramide throughout a range of tissues in the body.To ascertain the prevalence and nature of cutaneous manifestations in patients with Fabry disease and to relate these to the severity of systemic manifestations of the disease.We have documented the dermatological features of this disease with reference to data from 714 patients (345 males, 369 females) registered on the Fabry Outcome Survey (FOS), a multicentre European database.We confirm that the commonest disease manifestation is angiokeratoma. Overall, 78% of males and 50% of females had one or more dermatological abnormality, the commonest being angiokeratoma (66% males, 36% females), hypohidrosis (53% males, 28% females), telangiectasia (23% males, 9% females) and lymphoedema (16% males, 6% females). We demonstrate for the first time that the presence of cutaneous vascular lesions correlates with the severity of the systemic manifestations of the disease (pain, renal failure, cardiac disease, premature cerebrovascular disease) as assessed by a severity scoring system. Although the condition is X linked, there is a surprisingly high prevalence of abnormalities in females.The FOS database is a useful epidemiological tool in establishing the variety and relevance of cutaneous manifestations in Fabry disease. The present study confirms that the presence of dermatological manifestations appears to be a marker of greater severity of systemic disease, which emphasizes the importance of the dermatological assessment of these patients.
Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes
Authors: Dheeraj Kapoor, Hazel Aldred, Stephanie Clark, Kevin S. Channer, T. Hugh Jones
Journal: Diabetes Care (2007)

OBJECTIVE—The aim of our study was to assess the prevalence of clinical hypogonadism, based on both symptoms and biochemical available measures of testosterone deficiency, in men with type 2 diabetes. RESEARCH DESIGN AND METHODS—In a cross-sectional study of 355 type 2 diabetic men aged &amp;gt;30 years, total and bioavailable testosterone, sex hormone–binding globulin, BMI, and waist circumference were measured and free testosterone was calculated. Overt hypogonadism was defined as the presence of clinical symptoms of hypogonadism and low testosterone level (total testosterone &amp;lt;8 nmol/l and/or bioavailable testosterone &amp;lt;2.5 nmol/l). Borderline hypogonadism was defined as the presence of symptoms and total testosterone of 8–12 nmol/l or bioavailable testosterone of 2.5–4 nmol/l. RESULTS—A low blood testosterone level was common in diabetic men, and a significant proportion of these men had symptoms of hypogonadism. Overt hypogonadism was seen in 17% of men with total testosterone &amp;lt;8 nmol/l and 14% with bioavailable testosterone &amp;lt;2.5 nmol/l. Borderline hypogonadism was found in 25% of men with total testosterone 8–12 nmol/l and bioavailable testosterone between 2.5 and 4 nmol/l; 42% of the men had free testosterone &amp;lt;0.255 nmol/l. BMI and waist circumference were both significantly negatively correlated with testosterone levels in men, with the association being stronger for waist circumference. CONCLUSIONS—Testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism. Obesity is associated with low testosterone levels in diabetic men.
Impaired Cholesterol Metabolism and Enhanced Atherosclerosis in Clock Mutant Mice
Authors: Xiaoyue Pan, Xian-Cheng Jiang, M. Mahmood Hussain
Journal: Circulation (2013)

Clock is a key transcription factor that positively controls circadian regulation. However, its role in plasma cholesterol homeostasis and atherosclerosis has not been studied.We show for the first time that dominant-negative Clock mutant protein (Clock(Δ19/Δ19)) enhances plasma cholesterol and atherosclerosis in 3 different mouse models. Detailed analyses revealed that Clk(Δ19/Δ19)Apoe(-/-) mice display hypercholesterolemia resulting from the accumulation of apolipoprotein B48-containing cholesteryl ester-rich lipoproteins. Physiological studies showed that enhanced cholesterol absorption by the intestine contributes to hypercholesterolemia. Molecular studies indicated that the expression of Niemann Pick C1 Like 1, Acyl-CoA:Cholesterol acyltransferase 1, and microsomal triglyceride transfer protein in the intestines of Clk(Δ19/Δ19)Apoe(-/-) mice was high and that enterocytes assembled and secreted more chylomicrons. Furthermore, we identified macrophage dysfunction as another potential cause of increased atherosclerosis in Clk(Δ19/Δ19)Apoe(-/-) mice. Macrophages from Clk(Δ19/Δ19)Apoe(-/-) mice expressed higher levels of scavenger receptors and took up more modified lipoproteins compared with Apoe(-/-) mice, but they expressed low levels of ATP binding casette protein family A member 1 and were defective in cholesterol efflux. Molecular studies revealed that Clock regulates ATP binding casette protein family A member 1 expression in macrophages by modulating upstream transcription factor 2 expression.Clock(Δ19/Δ19) protein enhances atherosclerosis by increasing intestinal cholesterol absorption, augmenting uptake of modified lipoproteins by macrophages, and reducing cholesterol efflux from macrophages. These studies establish that circadian Clock activity is crucial in maintaining low plasma cholesterol levels and in reducing atherogenesis in mice.
Congenital Erythropoietic Porphyria
Authors: Pankaj Madan, Prem Vardhan
Journal: New England Journal of Medicine (2006)

A 32-year-old man presented with severe pain, swelling, and loss of vision in his left eye after excessive exposure to sunlight. He reported multiple, recurrent, discrete blisters developing on sun-exposed areas that healed with scarring and passing red-colored urine for more than 25 years. Multiple hypopigmented scars of variable size were present on his face, the upper part of his chest, his forearms, and the dorsa of his hands and feet. In addition, hypertrichosis of his face and extremities, resorption of the distal phalanges in his hands, destruction of the ear lobules and cartilaginous part of his nose, and hepatosplenomegaly . . .
European Union policy and health
Authors: M. Rayner
Journal: BMJ (1995)

New report leaves much to be desired

In her presentation to the European environment and public health committee the Spanish minister for health, Mrs Angeles Amador, outlined the agenda for the forthcoming meeting of the European Union's health council on 30 November. Although much of this centres on continuing and extending existing programmes, her insistence that health must be an integral part of all union policies and that the recently published audit report on health should be debated in depth is a welcome sign that article 129 of the Maastricht treaty is being taken seriously. This states that “health protection requirements shall form a constituent part of the union's other policies” and in effect means that the European Union has to check that proposals for new policies (in any field) do not have an adverse impact on health or create conditions that undermine the promotion of health.

The audit report on the integration of health protection requirements in community policies was produced by the commission's public health directorate.1 It was compiled from the information obtained after the 23 other directorates had been written to and asked to submit their assessments of how they were taking health into consideration in their policy areas.2 It was published at around the same time as a parallel and much more widely publicised report, produced in conjunction with the World Health Organisation's Regional Office for Europe.3 This includes the main demographic trends and patterns of morbidity and mortality and a discussion of the main determinants of health. It thus provides a useful baseline against which to …
Prognostic and Predictive Impact of Intra- and Peritumoral Immune Infiltrates
Authors: Wolf Herman Fridman, Jérôme Galon, Franck Pagès, Eric Tartour, Catheriné Sautès-Fridman, Guido Kroemer
Journal: Cancer Research (2011)

Leukocyte infiltrates into or around tumor cell nests are found in the context of protumorigenic inflammation and anticancer immunosurveillance. Hence, the detailed composition, density, architecture, and function of leukocyte infiltrates must be analyzed to understand their prognostic impact. The ectopic presence within tumors of high endothelial venule cells, which are normally characteristic for secondary lymphoid organs, correlates with a more pronounced infiltration by T lymphocytes and has a positive predictive impact on local advanced breast cancer treated with neoadjuvant chemotherapy. Recent progress in the field indicates that immune infiltrates of the primary tumors, as well as of metastases, are not only independent prognostic biomarkers but can also constitute predictive factors, suggesting that the pretherapeutic immune response can determine the efficacy of conventional chemotherapies. Moreover, accumulating evidence indicates that chemotherapy can stimulate anticancer immune responses coupled with an increased intratumoral lymphoid infiltration, which correlates with tumor mass reduction and patient survival. Improved methods for the automation of immunohistochemistry and digitalized image analyses will pave the way to an improved understanding of the complex interplay between cancer parenchyma, stroma, and immune effectors, as well as to the routine evaluation of immune-related parameters to the clinical management of cancer patients.
Glucose Intolerance, Insulin Resistance, and Pathological Features of Alzheimer Disease in the Baltimore Longitudinal Study of Aging
Authors: Madhav Thambisetty, E. Jeffrey Metter, An Yang, Hillary Dolan, Christopher Marano, Alan B. Zonderman, Juan C. Troncoso, Yun Zhou, Dean F. Wong, Luigi Ferrucci, Josephine Egan, Susan M. Resnick, Richard J. O’Brien
Journal: JAMA Neurology (2013)

Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear.To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain β-amyloid burden, measured with carbon 11–labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy.Scores calculated from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study.Prospective, serially assessed cohort of community-dwelling subjects.Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography.Autopsy and 11C-PiB positron emission tomography.The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses.We found no significant correlations between measures of brain AD pathology or 11C-PiB β-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole.In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.
Vomiting in the recently anticoagulated patient
Authors: R A Cahill
Journal: Gut (2004)

Background: Crohn's disease is common in highly industrialised Western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms.Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis.Thus exposure to helminths may help prevent or even ameliorate Crohn's disease.Aims: The aim of the study was to determine the safety and possible efficacy of the intestinal helminth Trichuris suis in the treatment of patients with active Crohn's disease.Patients: Twenty nine patients with active Crohn's disease, defined by a Crohn's disease activity index (CDAI) >220 were enrolled in this open label study.Methods: All patients ingested 2500 live T suis ova every three weeks for 24 weeks, and disease activity was monitored by CDAI.Remission was defined as a decrease in CDAI to less than 150 while a response was defined as a decrease in CDAI of greater than 100.Results: At week 24, 23 patients (79.3%) responded (decrease in CDAI .100points or CDAI ,150) and 21/29 (72.4%) remitted (CDAI ,150).Mean CDAI of responders decreased 177.1 points below baseline.Analysis at week 12 yielded similar results.There were no adverse events.Conclusions: This new therapy may offer a unique, safe, and efficacious alternative for Crohn's disease management.These findings also support the premise that natural exposure to helminths such as T suis affords protection from immunological diseases like Crohn's disease.
Effect of Prior Cancer on Outcomes in Advanced Lung Cancer: Implications for Clinical Trial Eligibility and Accrual
Authors: Andrew L. Laccetti, Sandi L. Pruitt, Lei Xuan, Ethan A. Halm, David E. Gerber
Journal: JNCI Journal of the National Cancer Institute (2015)

Prior cancer is a common exclusion criterion in lung cancer trials. This practice reflects concerns that prior cancer may affect trial conduct or outcomes. However, the impact of prior cancer on survival in lung cancer is not known. We identified patients older than age 65 years with stage IV lung cancer diagnosed between 1992 and 2009 in the Surveillance, Epidemiology, and End Results–Medicare linked registry. Prior cancer was characterized by type, stage, and timing. All-cause and lung cancer–specific survival were compared between patients with and without prior cancer using propensity score–adjusted Cox regression. Overall, 102 929 patients with stage IV lung cancer were identified, of whom 14.7% had a history of prior cancer. More than two-thirds (76.0%) of prior cancers were localized or regional stage; most were diagnosed five or fewer years prior to the lung cancer diagnosis. In propensity score–adjusted analysis, patients with prior cancer had better all-cause (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.91 to 0.94) and lung cancer–specific (HR = 0.81, 95% CI = 0.79 to 0.82) survival. In a simulated clinical trial–eligible population (age <75 years, no comorbidity, treated with chemotherapy), similar trends were noted. In subset analyses according to stage, type, and timing of prior cancer, no group of patients with prior cancer had inferior survival compared with patients without prior cancer. Among patients with stage IV lung cancer, prior cancer does not convey an adverse effect on clinical outcomes, regardless of prior cancer stage, type, or timing. Broader inclusion in clinical trials of advanced lung cancer patients with a history of prior cancer should be considered.
Tid1 Negatively Regulates the Migratory Potential of Cancer Cells by Inhibiting the Production of Interleukin-8
Authors: Sung-Woo Kim, Masaaki Hayashi, Jeng-Fan Lo, Colleen Fearns, Rong Xiang, Gwendal Lazennec, Young Yang, Jiing-Dwan Lee
Journal: Cancer Research (2005)

Tid1 is the human homologue of the Drosophila tumor suppressor, Tid56. Reducing the expression of Tid1 in MDA-MB231 breast cancer cells enhanced their migration without affecting their survival or growth rate. From microarray screening, we discovered that after Tid1 depletion, the mRNA level of interleukin-8 (IL-8) was significantly increased in these cancer cells, which consequently increased secretion of IL-8 protein by 3.5-fold. The enhanced migration of these Tid1-knockdown cells was blocked by reducing the IL-8 expression or by adding an IL-8 neutralizing antibody to the culture medium, suggesting that enhancement of cell motility in these Tid1-deficient cells is dependent on the de novo synthesis of IL-8. Subsequently, we found that abrogating the nuclear factor kappaB binding site in the IL-8 promoter completely blocked the Tid1 depletion-induced IL-8 expression in the breast cancer cells. As increased IL-8 levels are known to promote tumor metastasis, we tested the effect of Tid1 knockdown on tumor metastasis and found that Tid1 depletion enhanced the metastasis of breast cancer cells in animals. Together, these results indicate that Tid1 negatively regulates the motility and metastasis of breast cancer cells, most likely through attenuation of nuclear factor kappaB activity on the promoter of the IL8 gene.