tbuckley/cabot-search huggingface dataset:
Antibodies to human gastric epithelial cells and heat shock protein 60 in Helicobacter pylori positive mucosa associated lymphoid tissue lymphoma
Authors: Y Kawahara, K Yokota, M Mizuno, N Yunoki, T Uesu, H Okada, K Kobayashi, Y Hirai, K Oguma, T Tsuji
Journal: Gut (1999)

<h3>BACKGROUND</h3> Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to<i>Helicobacter pylori</i>. <h3>AIM</h3> To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by <i>H pylori</i> and human gastric epithelial cells. <h3>METHODS</h3> Sera were obtained from <i>H pylori</i> positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; non-ulcer dyspepsia, n = 20) and from<i>H pylori</i> negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. <h3>RESULTS</h3> Antibody titres to HGC-27 cells were significantly elevated in<i>H pylori</i> positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and <i>H pylori</i> HspB was documented by immunoblotting experiments. <h3>CONCLUSIONS</h3> Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between <i>H pylori</i> HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.
Managing Cystic Fibrosis
Authors: Malena Cohen-Cymberknoh, David Shoseyov, Eitan Kerem
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

The survival of patients with cystic fibrosis (CF) continues to improve. The discovery and cloning of the CFTR gene more than 21 years ago led to the identification of the structure and function of the CFTR chloride channel. New therapies based on the understanding of the function of CFTR are currently under development. The better clinical status and improved survival of patients with CF is not only a result of understanding of the molecular mechanisms of CF but also a result of the development of therapeutic strategies that are based on insights into the natural course of the disease. Current CF treatments that target respiratory infections, inflammation, mucociliary clearance, and nutritional status are associated with improved pulmonary function and reduced exacerbations. Patients benefit from treatment at a specialized CF center by a multidisciplinary dedicated team with emphasis being placed on frequent visits, periodic testing, and monitoring adherence to therapy. The purpose of this review is to survey recent developments in CF care that are responsible for the improved survival and quality of life of patients with CF.
Pharyngeal stimulation in treatment of arrhythmias
Authors: A. A. El Etr
Journal: JAMA (1968)

To the Editor:—  In a recent article by Salem et al,1a new technique for the treatment of hiccups was described. I have been working closely with Dr. Salem in the last few years and have been impressed by the efficiency of his technique of pharyngeal stimulation in the treatment of hiccups. Moreover, I have been able to treat a variety of supraventricular arrhythmias with the same method. The usefulness of this technique was first noted during suctioning the pharynx to remove secretions prior to induction of anesthesia for cardioversion. The preexisting supraventricular tachycardia converted to a normal sinus rhythm. This, coupled with the effectiveness of pharyngeal stimulation in the treatment of hiccups, led me to investigate its use in the treatment of arrhythmias, mainly of reflex origin, during anesthesia. The arrhythmias treated consisted of two cases of paroxismal atrial tachycardia, two cases with premature ventricular contractions, three cases
P53 Mediates the Apoptotic Response to GTP Depletion after Renal Ischemia-Reperfusion
Authors: K. J. Kelly, Zoya Plotkin, Stacey L. Vulgamott, Pierre C. Dagher
Journal: Journal of the American Society of Nephrology (2003)

Ischemic injury to the kidney is characterized in part by nucleotide depletion and tubular cell death in the form of necrosis or apoptosis. GTP depletion was recently identified as an important inducer of apoptosis during chemical anoxia in vitro and ischemic injury in vivo . It has also been shown that GTP salvage with guanosine prevented apoptosis and protected function. This study investigates the role of p53 in mediating the apoptotic response to GTP depletion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion. p53 protein levels increased significantly in the medulla over 24 h post-ischemia. The provision of guanosine inhibited the increase in p53. Pifithrin-α, a specific inhibitor of p53, mimicked the effects of guanosine. It had no effect on necrosis, yet it prevented apoptosis and protected renal function. Pifithrin-α was protective when given up to 14 h after the ischemic insult. The effects of pifithrin-α on p53 included inhibition of transcriptional activation of downstream p53 targets like p21 and Bax and inhibition of p53 translocation to the mitochondria. Similar results were obtained in cultured renal tubular cells. It is concluded that p53 is an important mediator of apoptosis during states of GTP depletion. Inhibitors of p53 should be considered in the treatment of ischemic renal injury. E-mail: pdaghe2@iupui.edu
Inhibition of Binding of E- and P-selectin to Sialyl-Lewis X Molecule Suppresses the Inflammatory Response in Hypersensitivity Pneumonitis in Mice
Authors: LI-HUA PAN, KOHEI YAMAUCHI, TAKASHI SAWAI, TOSHIHIDE NAKADATE, YUKI KOJIMA, NAOFUMI TAKAHASHI, KEISUKE ADACHI, AKIHIKO KAMEYAMA, HIROSHI INOUE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The carbohydrate structure of sialyl-Lewis X (SLex) can function as a ligand for E- and P-selectin, which play important roles in mediating the initial interactions of leukocytes with the endothelium in inflammatory responses. In this study we evaluated the effects of inhibiting E- and P-selectin function with the SLex molecule on the inflammatory response in an experimental murine model of hypersensitivity pneumonitis (HP). Antigen exposure induced marked interstitial and especially perivascular and peribronchiolar infiltration with lymphocytes and granuloma formation, in murine lung sensitized with Saccaropolyspora rectivirgula. These pathologic changes were significantly suppressed with SLex ganglioside analogues through a reduction in the numbers of lymphocytes in bronchoalveolar lavage fluid, as evidenced by the lung index and histologic scores indicating the severity of the inflammatory response. Using specific antibodies, we also evaluated the immunohistochemical localization of SLex in mononuclear cells in granulomas, and of E- and P-selectin in vascular endothelium. Our findings suggest that the molecular interaction between SLex, and E- and P-selectin mediates lymphocyte recruitment into the lung parenchyma, which is critical for the inflammatory response in experimental murine models of HP.
Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels.
Authors: T Doi, L J Striker, K Kimata, E P Peten, Y Yamada, G E Striker
Journal: The Journal of Experimental Medicine (1991)

Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis.
Decreased β-Cell Function in Overweight Latino Children With Impaired Fasting Glucose
Authors: Marc J. Weigensberg, Geoff D.C. Ball, Gabriel Q. Shaibi, Martha L. Cruz, Michael I. Goran
Journal: Diabetes Care (2005)

OBJECTIVE—To determine whether overweight Latino children with impaired fasting glucose (IFG) (≥100 mg/dl) have increased insulin resistance or decreased β-cell function compared with those with normal fasting glucose (NFG). RESEARCH DESIGN AND METHODS—We studied 207 healthy overweight Latino children, aged 8–13 years, with a family history of type 2 diabetes. Fasting and 2-h glucose and insulin were assessed by oral glucose tolerance test. Insulin sensitivity (Si), the acute insulin response to glucose (AIRg), and the disposition index (DI; an index of β-cell function) were determined using the insulin-modified intravenous glucose tolerance test and minimal modeling. Body composition was determined by dual-energy X-ray absorptiometry. RESULTS—There were no differences in body composition between NFG (n = 182) and IFG (n = 25) children. Compared with children with NFG, children with IFG had higher fasting and 2-h glucose values and higher fasting insulin. After adjusting for covariates, children with IFG had no difference in Si but 15% lower DI than NFG children (2,224 ± 210 vs. 2,613 ± 76, P &amp;lt; 0.05). Multivariate linear regression showed that AIRg and DI, but not Si, were significant predictors of fasting blood glucose. CONCLUSIONS—In overweight Latino adolescents with a family history of type 2 diabetes, IFG is associated with impaired β-cell function and therefore may identify children likely to be at risk for progression to type 2 diabetes. The actual risk of progression of IFG to type 2 diabetes remains to be determined by prospective longitudinal studies.
HLA‐DR‐dependent increased mannan‐induced lymphoproliferative response in atopic eczema dermatitis syndrome
Authors: J. Savolainen, J. Kosonen, O. Kortekangas‐Savolainen, H. Yssel, J. Bousquet
Journal: Allergy (2003)

Background: In yeast‐sensitive atopic eczema dermatitis syndrome (AEDS), yeast mannan induces highly elevated specific IgE levels and lymphoproliferative responses. In healthy individuals the involvement of both human leukocyte antigen (HLA)‐dependent T‐cell activation and non‐HLA‐dependent activation, e.g. by crosslinking of the cell surface mannose receptors, has been suggested. In the present study the HLA dependence and the role of crosslinking in the lymphoproliferative response to mannan in AEDS has been analyzed. Methods: Twenty patients with AEDS and 12 controls with no history of allergic diseases were included in the study. Mannan from Candida albicans was prepared according to the Cetavlon method. Following isolation using Ficoll‐Hypaque, peripheral blood mononuclear cells (PBMC) were incubated with the mannan preparation in the absence and presence of different concentrations of neutralizing anti‐HLA antibodies and α‐methylmannoside for 6 days and proliferative responses were measured by 3 H‐thymidine incorporation and scintilloradiography. Results: In AEDS patients with elevated mannan‐specific serum IgE, the C. albicans mannan induced lymphoproliferation. Mannan‐induced lymphoproliferative responses could be inhibited, dose‐dependently, by neutralizing anti‐HLA‐DR, but not anti‐HLA‐DQ antibodies in AEDS patients and healthy controls. The addition of α‐methylmannoside, that blocks binding to mannose receptors, inhibited lymphoproliferative responses in a dose‐dependent way by 50% only in healthy controls, but not in AEDS patients. Levels of inhibition of the proliferation by α‐methylmannoside correlated inversely with the yeast‐ and mannan‐specific IgE levels. Conclusions: These results show that in healthy subjects yeast mannan activates lymphocytes both in an HLA‐DR‐dependent manner and as a result of direct crosslinking of the cell surface. However, in AEDS the elevated lymphoproliferative response is HLA‐DR‐dependent, although only a slight proportion of this response results from direct crosslinking.
Hypnotic behavior: A social-psychological interpretation of amnesia, analgesia, and “trance logic”
Authors: Nicholas P. Spanos
Journal: Behavioral and Brain Sciences (1986)

Abstract This paper examines research on three hypnotic phenomena: suggested amnesia, suggested analgesia, and “trance logic.” For each case a social-psychological interpretation of hypnotic behavior as a voluntary response strategy is compared with the traditional special-process view that “good” hypnotic subjects have lost conscious control over suggestion-induced behavior. I conclude that it is inaccurate to describe hypnotically amnesic subjects as unable to recall the material they have been instructed to forget. Although amnesics present themselves as unable to remember, they in fact retain control over retrieval processes and accommodate their recall (or lack of it) to the social demands of the test situation. Hypnotic suggestions of analgesia do not produce a dissociation of pain from phenomenal awareness. Nonhypnotic suggestions of analgesia and distractor tasks that deflect attention from the'noxious stimuli are as effective as hypnotic suggestions in producing reductions in reported pain. Moreover, when appropriately motivated, subjects low in hypnotic suggestibility report pain reductions as large as those reported by highly suggestible hypnotically analgesic subjects. Finally, the data fail to support the view that a tolerance for logical incongruity (i.e., trance logic) uniquely characterizes hypnotic responding. So-called trance-logic-governed responding appears to reflect the attempts of “good” subjects to meet implicit demands to report accurately what they experience.
Nonsteroidal anti‐inflammatory drugs in the treatment of hemophilic arthropathy
Authors: Patricia Thomas, Bonnie Hepburn, Hugh C. Kim, Parvin Saidi
Journal: American Journal of Hematology (1982)

Abstract This study was undertaken to investigate the safety and efficacy of nonaspirin, nonsteroidal anti‐inflammatory drugs (NSAIDs) in controlling the pain and stiffness of hemophilic arthropathy. Data were collected from eight adult hemophilic patients in successive double‐blind controlled studies using choline magnesium trisalicylate (CMT) and ibuprofen (IPF). In seven patients, neither drug consistently affected bleeding times, platelet aggregation studies, frequency of joint hemorrhages, or frequency of factor infusions. In one patient, platelet aggregation appeared to be affected by CMT and bleeding time became markedly prolonged after IPF therapy. Three patients taking CMT and four patients taking IPF reported greater relief of pain and stiffness with the drugs than with placebos. Our results suggest that IPF and CMT can benefit the hemophiliac and that they can be used safely in most hemophilic patients under closely supervised conditions.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: N. Kretchmer, Francis J. Cherot
Journal: The Journal of Experimental Medicine (1954)

Parenteral injection of amino acids resulted in the formation of Gram-positive droplets in the cytoplasm of the proximal convoluted tubule cells of the kidney of the rat within 15 minutes after intravenous administration. At this time the free alpha amino nitrogen in the cortex of the kidney had increased 2-fold. At the end of 1 hour this level was still somewhat higher than that of the control animals. The administration of increasing amounts of the amino acid disclosed the existence of a maximal concentration level in the renal cortex. When it was reached droplets appeared. Fractionation of the cells 15 minutes after the injection of lysine resulted in the recovery of free amino acid in the supernatant fluid but 1 hour after the injection lysine was contained within the particulate protein of the fractions which contain droplets. The increase in lysine was of the order of 2- 3-fold. It is concluded that the mitochondria-droplet complex is a locus of amino acid concentration and metabolism within the cytoplasm of the renal cell. A method is described for the determination of lysine in micro quantities.
Calpain system protein expression in basal-like and triple-negative invasive breast cancer
Authors: S.J. Storr, K.W. Lee, C.M. Woolston, S. Safuan, A.R. Green, R.D. Macmillan, A. Benhasouna, T. Parr, I.O. Ellis, S.G. Martin
Journal: Annals of Oncology (2012)

BackgroundBasal-like and triple-negative breast tumours encompass an important clinical subgroup and biomarkers that can prognostically stratify these patients are required.Materials and methodsWe investigated two breast cancer tissue microarrays for the expression of calpain-1, calpain-2 and calpastatin using immunohistochemistry. The first microarray was comprised of invasive tumours from 1371 unselected patients, and the verification microarray was comprised of invasive tumours from 387 oestrogen receptor (ER)-negative patients.ResultsThe calpain system contains a number of proteases and an endogenous inhibitor, calpastatin. Calpain activity is implicated in important cellular processes including cytoskeletal remodelling, apoptosis and survival. Our results show that the expression of calpastatin and calpain-1 are significantly associated with various clinicopathological criteria including tumour grade and ER expression. High expression of calpain-2 in basal-like or triple-negative disease was associated with adverse breast cancer-specific survival (P= 0.003 and <0.001, respectively) and was verified in an independent cohort of patients. Interestingly, those patients with basal-like or triple-negative disease with a low level of calpain-2 expression had similar breast cancer-specific survival to non-basal- or receptor- (oestrogen, progesterone or human epidermal growth factor receptor 2 (HER2)) positive disease.ConclusionsExpression of the large catalytic subunit of m-calpain (calpain-2) is significantly associated with clinical outcome of patients with triple-negative and basal-like disease.
Treatment Center and Geographic Variability in Pre-ESRD Care Associate with Increased Mortality
Authors: William M. McClellan, Haimanot Wasse, Ann C. McClellan, Adam Kipp, Lance A. Waller, Michael V. Rocco
Journal: Journal of the American Society of Nephrology (2009)

Late referral of patients with chronic kidney disease is associated with increased morbidity and mortality, but the contribution of center-to-center and geographic variability of pre-ESRD nephrology care to mortality of patients with ESRD is unknown. We evaluated the pre-ESRD care of >30,000 incident hemodialysis patients, 5088 (17.8%) of whom died during follow-up (median 365 d). Approximately half (51.3%) of incident patients had received at least 6 mo of pre-ESRD nephrology care, as reported by attending physicians. Pre-ESRD nephrology care was independently associated with survival (odds ratio 1.54; 95% confidence interval 1.45 to 1.64). There was substantial center-to-center variability in pre-ESRD care, which was associated with increased facility-specific death rates. As the proportion of patients who were in a treatment center and receiving pre-ESRD nephrology care increased from lowest to highest quintile, the mortality rate decreased from 19.6 to 16.1% (P = 0.0031). In addition, treatment centers in the lowest quintile of pre-ESRD care were clustered geographically. In conclusion, pre-ESRD nephrology care is highly variable among treatment centers and geographic regions. Targeting these disparities could have substantial clinical impact, because the absence of ≥6 mo of pre-ESRD care by a nephrologist is associated with a higher risk for death.
Structural-functional relationships in Alport syndrome.
Authors: K H Kim, Y Kim, M C Gubler, M W Steffes, P H Lane, C E Kashtan, J T Crosson, S M Mauer
Journal: Journal of the American Society of Nephrology (1995)

Renal morphometric analysis was performed in 15 (13 male) Alport syndrome patients ages 4 to 26 years, along with 10 controls ages 3 to 26 years, to better understand the structural basis of renal dysfunction in Alport syndrome. The glomerular basement membrane (GBM) width class frequencies of controls were normally distributed; those of Alport syndrome patients were slightly skewed, especially toward thicker classes, although there was also an increase in the proportion of thinner classes. Mesangial volume fraction was not different between Alport syndrome patients (0.21 +/- 0.09) and controls (0.19 +/- 0.04). There was an inverse correlation between mesangial volume fraction and creatinine clearance in Alport syndrome patients (r = -0.72, P < 0.01); however, the creatinine clearances in Alport syndrome patients were far less than in insulin-dependent diabetic patients with similar mesangial volume fraction. Similarly, there was no significant difference in the surface density of the peripheral GBM (in square micrometers per cubic micrometer) in Alport syndrome patients (0.12 +/- 0.04) versus controls (0.13 +/- 0.02). The surface density of the peripheral GBM correlated with creatinine clearance in Alport syndrome patients (r = 0.71, P < 0.01). However, there was a greater reduction in creatinine clearance as related to declining the surface density of the peripheral GBM in Alport syndrome than in diabetic patients. The cortical interstitial volume fraction was highly inversely correlated with creatinine clearance in Alport syndrome patients (r = -0.85, P < 0.01). Global glomerular sclerosis was 0% in five and 5 to 61% in nine Alport syndrome patients and correlated inversely with creatinine clearance (r = -0.74, P < 0.01). However, the creatinine clearance was lower in Alport syndrome than in diabetic patients with similar cortical interstitial volume fraction and percent glomerular sclerosis. There was no significant difference in an index of glomerular number between Alport syndrome patients and controls. Thus, changes in mesangial volume fraction, cortical interstitial volume fraction, percent glomerular sclerosis, and surface density of the peripheral GBM in Alport syndrome patients only partially account for the reduction in creatinine clearance. It was speculated that decreased glomerular capillary wall hydraulic conductivity in Alport syndrome could explain many of these observations.