tbuckley/cabot-search huggingface dataset:
Neuropathy, Womens’ Health, and Socioeconomic Aspects of Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2002)

This is the eighth and final in a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions in Philadelphia, PA, in June, 2001.

At a symposium on neuropathy sponsored by the University of Texas Southwestern at the American Diabetes Association meeting in San Antonio, Texas, Soroku Yagihashi (Hirosaki, Japan) discussed aspects of the pathogenesis of distal symmetric polyneuropathy. In a recent survey in Tohoku, Japan, of 32,955 individuals with diabetes, history or symptoms of neuropathy made it the most common complication, occurring in 27% of patients.

There are two major histologic findings in nerve biopsy from patients with distal symmetric polyneuropathy. Myelinated fiber density decreases, falling by approximately one-third with mild neuropathy and by two-thirds with severe neuropathy, reflecting loss of nerve fibers with degeneration of remaining fibers. There is also evidence of microangiopathy in the vasa nervosum. Nerve capillary density again decreases in proportion to the severity of the neuropathy, with capillary basement membrane area nearly doubled with mild neuropathy and tripled with severe neuropathy. The susceptibility of peripheral nerve to ischemia may be partly related to its great axon length with sparse blood supply.

As with retinopathy and nephropathy, poor glycemic control is a major cause of neuropathy, with nerves not showing insulin-mediated glucose uptake, but rather allowing direct glucose entry, which increases with hyperglycemia. In the Tohoku survey, the likelihood of neuropathy increased 2.7-, 1.7-, and 1.2-fold in individuals whose HbA1c was ≥10, 7.5–9.9, and 6.5–7.49%, in comparison to those with HbA1c <6.5%. In the nerve, glucose is metabolized through the polyol pathway to sorbitol via the enzyme aldose reductase (AR). Sorbitol can cause osmotic stress and can lower nerve myoinositol and taurine levels, with decreases in Na+/K+-ATPase, which is involved in intracellular energy homeostasis. In addition, conversion …
The Involvement of Interleukin (IL)-15 in Regulating the Differentiation of Granulated Metrial Gland Cells in Mouse Pregnant Uterus
Authors: Weiguo Ye, Li-Mou Zheng, John Young, Chau-Ching Liu
Journal: The Journal of Experimental Medicine (1996)

Previous studies have suggested that granulated metrial gland (GMG) cells are bone marrow– derived lymphoid cells, which differentiate in situ in the mouse pregnant uterus into natural killer (NK)–like cells. Similar to NK cells, GMG cells express an abundant level of cytolytic mediators such as perforin. The factor(s) regulating the differentiation of GMG cells remain(s) to be identified, although cytokines previously implicated in the stimulation/activation of NK cells (e.g., IL-2, IL-6, IL-7, and IL-12) can be considered as potential candidates. Recently, IL-15, a novel cytokine, which displays biological activities similar to IL-2, has also been shown to be capable of activating NK cells. Using reverse transcription–polymerase chain reaction (RT-PCR) analysis, we have demonstrated in the present study that IL-15 and its cognate receptor, but not the other cytokines, are expressed in the mouse pregnant uterus, with a time course concomitant with those of cytolytic mediators in differentiated GMG cells. Moreover, IL-15, though not IL-2, is capable of inducing the expression of perforin and granzymes in pregnant uterine tissues explanted in vitro. Data obtained from in situ hybridization study have suggested that the macrophages present in the pregnant uterus may be responsible for the production of IL-15. These results suggest that IL-15 is involved in regulating the differentiation of GMG cells during mouse pregnancy.
Growth Factor and Cytokine-Regulated Hyaluronan-Binding Protein TSG-6 Is Localized to the Injury-Induced Rat Neointima and Confers Enhanced Growth in Vascular Smooth Muscle Cells
Authors: Li Ye, Rosalia Mora, Nahid Akhayani, Christian C. Haudenschild, Gene Liau
Journal: Circulation Research (1997)

Abstract Hyaluronan (HA) and HA-binding proteins have been implicated in a diverse array of biological processes, including development, tissue repair, and tumor invasion. However, the role of HA and HA-binding proteins in atherosclerosis and restenosis is poorly understood. PS4 (TSG-6) is a HA-binding protein expressed by cultured vascular smooth muscle cells (SMCs) in response to serum and growth factor stimulation. To delineate a possible role for TSG-6 in vascular disease progression, we have characterized its expression in cultured SMCs and in a rat vascular injury model, and we have studied the effect of constitutive overexpression of TSG-6 on SMC behavior. We found that interleukin-1 (IL-1) but not tumor necrosis factor or interleukin-6 was able to stimulate TSG-6 expression in SMCs. The IL-1 pathway could be distinguished from the growth factor pathway by its insensitivity to protein synthesis inhibitors. Furthermore, epidermal growth factor, fibroblast growth factor-1, and transforming growth factor-β1 were all capable of augmenting maximum IL-1–induced expression of TSG-6. To gain further insight into the function of TSG-6 in SMCs, we examined the effect of constitutive overexpression of TSG-6 on these cells. We found that TSG-6–overexpressing cells grew &gt;50% faster than control cells. Furthermore, this growth advantage became more evident in the absence of serum growth factors, with an average increase in cell number of 118% over control cells after 6 days. Consistent with these in vitro data, we observed intense immunostaining for TSG-6 in proliferating SMCs in the rat neointima after injury, whereas only an occasional cell was positive for TSG-6 in the medial layer and in nonballooned arteries. We conclude that the expression of TSG-6 is tightly controlled by growth factors and cytokines via two distinct pathways in SMCs and that overexpression of TSG-6 confers a growth advantage to these cells.
Prenatal screening for carriers of cystic fibrosis should screen both partners individually
Authors: M. De Braekeleer
Journal: BMJ (1996)

prevalence ofresistance of Streptococcus pneumoniae to common antimicrobial agents in two consecu- tive periods in east London.In our first study we determined the antimicrobial susceptibilities of sequential clinical isolates of pneumococci obtained during January to September 1994.Seven (12%) of 60 isolates had reduced susceptibility to penicillin (either intermediate resistance (minimum inhibitory concentration 0.1-1 mg/l) or high resistance (minimum inhibitory concentration ¢2 mg/l)).In view of this high prevalence we then collected all isolates from October 1994 until April 1995 and established the minimum inhibitory concentrations for a range of antimi- crobial agents and the serological type.2Seventy five isolates were obtained during this period, of which nine (12%) had reduced susceptibility to penicillin.We believe that this is the highest reported prevalence of pneumococci with reduced susceptibility to penicillin in Britain.All strains were typable and are represented in the vaccine that is currently used.During the overall study period 16 pneumo- coccal strains of reduced susceptibility (12% of the 135 isolates) were collected from 16 patients.Two isolates had minimum inhibitory concentra- tions ofpenicillin of >1 mg/l but were sensitive to erythromycin.Four isolates were also resistant to at least two of the three agents commonly tested in vitro-namely, tetracycline, erythromycin, and chloramphenicol.Nine (7%) of the 135 isolates were resistant to erythromycin.The sources of the samples were predominantly sputum or respiratory samples (65 isolates), blood cultures (38), and eye (15) and ear swabs (9).Two patients yielded multiple isolates.Our results confirm that the prevalence of resistant strains of pneumococci varies considerably in Britain and that continued monitoring of antimicrobial resistance at a local level is essential for the continuing optimal management of infections due to this organism.Many pneumococcal infections, even when caused by an organism with reduced susceptibility to penicillin, will respond to penicillin as long as adequate doses are used.3This does not, however, apply to pneumococcal meningitis, as adequate concentrations of penicillin in the cerebrospinal fluid may not be achieved.The increasing prevalence of resistance to penicillin means that this drug will no longer be useful for empirical treatment of this condition, and it is vital that the individual susceptibilities of the causative organism are determined for each patient.
Food Insecurity and Metabolic Control Among U.S. Adults With Diabetes
Authors: Seth A. Berkowitz, Travis P. Baggett, Deborah J. Wexler, Karen W. Huskey, Christina C. Wee
Journal: Diabetes Care (2013)

OBJECTIVE We sought to determine whether food insecurity is associated with worse glycemic, cholesterol, and blood pressure control in adults with diabetes. RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of data from participants of the 1999–2008 National Health and Nutrition Examination Survey. All adults with diabetes (type 1 or type 2) by self-report or diabetes medication use were included. Food insecurity was measured by the Adult Food Security Survey Module. The outcomes of interest were proportion of patients with HbA1c &amp;gt;9.0% (75 mmol/mol), LDL cholesterol &amp;gt;100 mg/dL, and systolic blood pressure &amp;gt;140 mmHg or diastolic blood pressure &amp;gt;90 mmHg. We used multivariable logistic regression for analysis. RESULTS Among the 2,557 adults with diabetes in our sample, a higher proportion of those with food insecurity (27.0 vs. 13.3%, P &amp;lt; 0.001) had an HbA1c &amp;gt;9.0% (75 mmol/mol). After adjustment for age, sex, educational attainment, household income, insurance status and type, smoking status, BMI, duration of diabetes, diabetes medication use and type, and presence of a usual source of care, food insecurity remained significantly associated with poor glycemic control (odds ratio [OR] 1.53 [95% CI 1.07–2.19]). Food insecurity was also associated with poor LDL control before (68.8 vs. 49.8, P = 0.002) and after (1.86 [1.01–3.44]) adjustment. Food insecurity was not associated with blood pressure control. CONCLUSIONS Food insecurity is significantly associated with poor metabolic control in adults with diabetes. Interventions that address food security as well as clinical factors may be needed to successfully manage chronic disease in vulnerable adults.
Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits
Authors: Jian Yang, Teresa Ferreira, Andrew P Morris, Sarah E Medland, Pamela A F Madden, Andrew C Heath, Nicholas G Martin, Grant W Montgomery, Michael N Weedon, Ruth J Loos, Timothy M Frayling, Mark I McCarthy, Joel N Hirschhorn, Michael E Goddard, Peter M Visscher
Journal: Nature Genetics (2012)
Endothelin-1 Secretion by Alveolar Macrophages in Systemic Sclerosis
Authors: CHRISTINE ODOUX, BRUNO CRESTANI, GAËLLE LEBRUN, CORINNE ROLLAND, PHILIPPE AUBIN, NATHALIE SETA, MARCEL-FRANCIS KAHN, JEAN FIET, MICHEL AUBIER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Endothelin-1 (ET-1), a potent fibroblast/smooth muscle cells mitogen, has been implicated in the pathogenesis of systemic sclerosis lung disease (SSc). Since monocytes and macrophages are thought to be activated in SSc, we hypothesized that alveolar macrophages (AM) and their precursors blood monocytes from patients with SSc produced more ET-1 than cells from healthy subjects. ET-1 and big ET-1 concentrations were measured in plasma, in bronchoalveolar lavage (BAL) fluids and in cell culture supernatants from monocytes and alveolar macrophages derived from 13 patients with definite SSc with lung involvement and from 10 control subjects. Plasma and BAL fluid ET-1 and big ET-1 levels were similar in both controls and patients with SSc. ET-1 and big ET-1 concentrations in unstimulated alveolar macrophage supernatants were similar in both groups. In contrast, LPS-stimulated alveolar macrophages from patients with SSc secreted higher amounts of ET-1 and big ET-1 than control subjects. ET-1 and big ET-1 concentrations in monocyte supernatants (either LPS-stimulated or not) were not different in patients and controls. These results show that AM from patients with SSc are hyperresponsive to LPS in vitro in terms of ET-1 and big ET-1 production and suggest that AM could participate in vivo in the overproduction of this potentially profibrotic mediator in patients with SSc.
Functional Analysis of Novel <b> <i>Sonic Hedgehog</i> </b> Gene Mutations Identified in Basal Cell Carcinomas from Xeroderma Pigmentosum Patients
Authors: Sophie Couvé-Privat, Marc Le Bret, Elisabeth Traiffort, Sophie Queille, Josée Coulombe, Bakar Bouadjar, Marie Françoise Avril, Martial Ruat, Alain Sarasin, Leela Daya-Grosjean
Journal: Cancer Research (2004)

Abstract Altered sonic hedgehog (SHH) signaling is crucial in the development of basal cell carcinomas (BCC), the most common human cancer. Mutations in SHH signal transducers, PATCHED and SMOOTHENED, have already been identified, but SHH mutations are extremely rare; only 1 was detected in 74 sporadic BCCs. We present data showing unique SHH mutations in BCCs from repair-deficient, skin cancer-prone xeroderma pigmentosum (XP) patients, which are characterized by high levels of UV-specific mutations in key genes involved in skin carcinogenesis, including PATCHED and SMOOTHENED. Thus, 6 UV-specific SHH mutations were detected in 5 of 33 XP BCCs. These missense SHH alterations are not activating mutations for its postulated proto-oncogene function, as the mutant SHH proteins do not show transforming activity and induce differentiation or stimulate proliferation to the same level as the wild-type protein. Structural modeling studies of the 4 proteins altered at the surface residues, G57S, G64K, D147N, and R155C, show that they do not effect the protein conformation. Interestingly, they are all located on one face of the compact SHH protein suggesting that they may have altered affinity for different partners, which may be important in altering other functions. Additional functional analysis of the SHH mutations found in vivo in XP BCCs will help shed light on the role of SHH in skin carcinogenesis. In conclusion, we report for the first time, significant levels of SHH mutations found only in XP BCCs and none in squamous cell carcinomas, indicating their importance in the specific development of BCCs.
Genome-wide approaches to antidepressant treatment: working towards understanding and predicting response
Authors: Karen Hodgson, Shaista Mufti, Rudolf Uher, Peter McGuffin
Journal: Genome Medicine (2012)

Antidepressants are among the most commonly prescribed drugs, and a range of medications are available. However, treatment response to a particular drug varies greatly between patients, with only 30% of patients responding well to the first treatment administered. Given evidence that antidepressant treatment response is a heritable trait, together with technological advances in genetic research, three recently published genome-wide investigations into antidepressant responses have examined the determinants of variability in treatment outcomes between depressed patients. Here, we review these studies within the context of wider research efforts to identify treatment response predictors. Some interesting genes have been implicated, but no variants have yet been robustly and reliably linked to response. This may suggest that genetic effect sizes are smaller than originally anticipated. Candidate gene approaches in these samples have lent support to the involvement of serotonergic, glutamatergic and stress-response systems in treatment response, although corroborative evidence from genome-wide analyses indicates these results should be interpreted cautiously. Closer examination of antidepressant response, considering it as a complex trait, has indicated that multiple genes of small effect are likely to be involved. Furthermore, there is some evidence that genetic influence on response to treatment may vary between patients with different symptom profiles or environmental exposures. This has implications for the translation of pharmacogenetic findings into clinical practice: genotypic information from multiple loci and data on non-genetic factors are likely to be needed to tailor antidepressant treatment to the individual patient.
73 ADMINISTRATION OF THE ENTRY INHIBITOR MYRCLUDEX-B AFTER ESTABLISHMENT OF HEPATITIS B VIRUS INFECTION PREVENTS VIRAL SPREADING AMONG HUMAN HEPATOCYTES IN UPA MICE
Authors: M. Ben M'Barek, T. Volz, M. Lutgehetmann, T. Bornscheuer, L. Allweiss, A.W. Lohse, A. Alexandrov, S. Urban, J. Petersen, M. Dandri
Journal: Journal of Hepatology (2011)
SCLEROTHERAPY IN BLEEDING OESOPHAGEAL VARICES
Authors: H.S. Rogers, G. Hamilton, K.E.F. Hobbs, B.R.D. Macdougall, D. Westaby, J.B. Saunders, Roger Williams, E.-H. Egberts, H. Schomerus, R. Heinrich, F. Hartmann
Journal: The Lancet (1982)
What is wrong with prototypes
Authors: Peter Földiák
Journal: Behavioral and Brain Sciences (1998)

Representing objects and concepts as points in low-dimensional shape space defined by distances to other complete object exemplars or prototypes, expressed as single numbers, misses the key advantages of representation in terms of hierarchically constructed, meaningful features of the environment. Generalisation along statistically significant, near-independent, sparse, cooperative features that stand directly for various aspects of a concept is essential.
PROCESS, SCHIZOPHRENIC AND THERAPEUTIC: SOME MISCONCEPTIONS RESULTING FROM LANGUAGE AND PHILOSOPHY
Authors: EDWARD S. DEAN
Journal: American Journal of Psychiatry (1961)

The task of the therapist, then, is a close attention to the experience of his patient, but not interpretation, explanation, or evaluation. What is needed for good treatment is that the therapist be "tuned in" on his patient, receive him clearly, and let him know that he is understood. If he keeps close to the phenomenal, the psychiatrist can avoid the hazard of thinking in essences.
Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD
Authors: A. R. Pons, A. Noguera, D. Blanquer, J. Sauleda, J. Pons, A. G. N. Agustí
Journal: European Respiratory Journal (2005)

Alveolar macrophages (AM) participate actively in the inflammatory response that characterises chronic obstructive pulmonary disease (COPD). The present study investigated potential changes in AM phenotypes in patients with COPD. Using flow cytometry, the surface expression of receptors implicated in phagocytosis (CD44, CD36, CD51, CD61, CD14), antigen-presenting capacity (human leukocyte antigen (HLA)-DR), costimulatory molecules (CD80, CD86, CD40) and complement receptor type 3 were assessed in AM from 18 patients with COPD, 14 smokers with normal lung function and nine nonsmokers. When compared to smokers with normal lung function and nonsmokers, the surface expression of HLA-DR and CD80 was lower in AM of patients with COPD. In addition, these patients had a higher percentage of AM with a low level surface expression of CD44. There did not appear to be any difference in the other receptors studied in AM between the three groups. The expression of all these receptors in peripheral blood monocytes also did not differ between groups. In conclusion, these observations suggest that the cell-mediated immune function of alveolar macrophages can be reduced in chronic obstructive pulmonary disease, and that this is a local rather than a systemic event.
Immunoglobulin Light Chains Activate Tubular Epithelial Cells through Redox Signaling
Authors: Kolitha Basnayake, Wei-Zhong Ying, Pei-Xuan Wang, Paul W. Sanders
Journal: Journal of the American Society of Nephrology (2010)

The renal proximal tubule metabolizes circulating low-molecular-weight proteins such as Ig free light chains. In the setting of plasma cell dyscrasias, the burden of filtered protein can be very high. Endocytosis of certain nephrotoxic light chains induces H(2)O(2) production and monocyte chemoattractant protein-1 (MCP-1) release, leading to recruitment of inflammatory cells and interstitial fibrosis, but how these processes are linked mechanistically is not well understood. This study investigated the relationship between H(2)O(2) generated after light chain endocytosis by human proximal tubular (HK-2) cells and activation of c-Src, a redox-sensitive tyrosine kinase. HK-2 cells exposed to two different light chains upregulated c-Src activity, which increased the production of MCP-1. In parallel, we observed a time-dependent oxidation of c-Src. Inhibition of c-Src activity and silencing c-Src expression abrogated the light chain-induced MCP-1 response, but had no effect on H(2)O(2), indicating that production of H(2)O(2) is upstream of c-Src in the signaling cascade. Silencing megalin and cubilin expression inhibited the MCP-1 response, whereas extracellular catalase did not, indicating that endocytosis is required and that intracellular generation of reactive oxygen species activates c-Src. These data show that intracellular H(2)O(2) induced by endocytosis of monoclonal free light chains oxidizes and activates c-Src, which promotes release of MCP-1.
Clusters, classification and epidemiology of interstitial lung diseases: concepts, methods and critical reflections
Authors: J M Antó, P Cullinan
Journal: European Respiratory Journal (2001)

The present article reports on two conceptual and methodological issues concerning interstitial lung disease (ILD) about which there is a lot of misunderstanding and contradiction: the investigation of epidemics and clusters and the classification and epidemiology of ILD. In general, an epidemic is the occurrence of cases of an illness in excess of normal expectancy. The investigation of an epidemic often demands a number of sequential studies: first descriptive, then aetiological. Clusters consist of an increase in incidence of much smaller magnitude, perhaps excluding the possibility that this is merely a result of chance. In recent years, more valid statistical methods for the assessment of clusters have developed. For interstitial lung disease in particular, different classifications exist that are sometimes inconsistent and may change with time. All diseases require a process of ascertainment, whereby they are identified, classified and perhaps registered. The two most employed epidemiological techniques for testing aetiological hypotheses are the cohort and case-referent approaches.
A phase II clinical trial of sunitinib following hepatic transarterial embolization for metastatic neuroendocrine tumors
Authors: J.R. Strosberg, J.M. Weber, J. Choi, T.L. Campos, T.L. Valone, G. Han, M.J. Schell, L.K. Kvols
Journal: Annals of Oncology (2012)
Measurement of Collagen and Smooth Muscle Cell Content in Atherosclerotic Plaques Using Polarization-Sensitive Optical Coherence Tomography
Authors: Seemantini K. Nadkarni, Mark C. Pierce, B. Hyle Park, Johannes F. de Boer, Peter Whittaker, Brett E. Bouma, Jason E. Bressner, Elkan Halpern, Stuart L. Houser, Guillermo J. Tearney
Journal: Journal of the American College of Cardiology (2007)