tbuckley/cabot-search huggingface dataset:
Brain Iron Overload, Insulin Resistance, and Cognitive Performance in Obese Subjects: A Preliminary MRI Case-Control Study
Authors: Gerard Blasco, Josep Puig, Josep Daunis-i-Estadella, Xavier Molina, Gemma Xifra, Fernando Fernández-Aranda, Salvador Pedraza, Wifredo Ricart, Manuel Portero-Otín, José Manuel Fernández-Real
Journal: Diabetes Care (2014)

OBJECTIVE The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects. RESEARCH DESIGN AND METHODS We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 ± 7.7 years; BMI 43.7 ± 4.48 kg/m2) and 20 healthy nonobese volunteers (10 women; age 48.8 ± 9.5 years; BMI 24.3 ± 3.54 kg/m2) in whom iron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance. RESULTS A significant increase in iron load was detected at the caudate nucleus (P &amp;lt; 0.001), lenticular nucleus (P = 0.004), hypothalamus (P = 0.002), hippocampus (P &amp;lt; 0.001), and liver (P &amp;lt; 0.001) in obese subjects. There was a positive correlation between HIC and BIO at caudate (r = 0.517, P &amp;lt; 0.001), hypothalamus (r = 0.396, P = 0.009), and hippocampus (r = 0.347, P &amp;lt; 0.023). The area under the curve of insulin was independently associated with BIO at the caudate (P = 0.001), hippocampus (P = 0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P = 0.006), and lenticular nucleus (P = 0.012) were independently associated with worse cognitive performance. CONCLUSIONS Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction.
Of ITAMs and ITIMs: turning on and off the B cell antigen receptor.
Authors: M L Thomas
Journal: The Journal of Experimental Medicine (1995)

F or any given receptor, there are mechanisms that regulate the activation of signal transduction pathways, as well as mechanisms that extinguish those signaling pathways.Responding to environmental signals requires that both positive and negative regulation proceed in an ordered manner.Much research has focused on lymphocyte antigen receptorinduced signal transduction pathways, and an understanding of some of the initial events has been gained.The mechanisms that terminate signaling are equally important but less well understood.The inability to properly extinguish activation cascades may result in inappropriate responses and perhaps even cell death.Concerning lymphocyte antigen receptors, antigen recognition results in the activation of intracellular protein tyrosine kinases, particularly members of the Src family kinases, as well as the ZAP-70/syk kinases.The key to antigeninduced signal transduction is the phosphorylation of critical tyrosines within the cytoplasmic domains of the TCR CD3/g" chain complex or the oe and 3 chains of the B cell antigen receptor (BCR) (1-3).The critical tyrosines are located within a characteristic sequence motif termed immunoreceptor tyrosine-based activation motif (ITAM).Inactivating antigen receptors requires dephosphorylation, yet the involved enzyme(s) or process(es) have not previously been identified.Several recent reports, including one in this issue, provide important information about the mechanisms of BCR inactivation (3a-6).Potential insight into the negative regulation of immunoreceptors was gained by the discovery that the motheaten mice (me) harbor a mutation in the SHP gene (also known as PTP1C, HCP, SH-PTP1) (7, 8).The mutation renders me mice deficient in SHP protein.SHP is an SH2 domain containing protein tyrosine phosphatase (PTPase) and belongs to a subfamily that contains another mammalian member, syp (also known as PTP2C, PTP1D and SH-PTP2), and a Drosophila member, corkscrew (csw) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18).syp is thought to function in the positive regulation of receptor tyrosine kinases and to be the mammalian orthologue of csw.In contrast, the phenotype of the me mice suggests that SHP functions in the negative regulation of leukocyte activation, me mice have numerous immunological disorders, including chronic macrophage and neutrophil activation, lymphopenia, and circulating autoantibodies (19).The B lymphocyte populations are markedly disproportionate; there is an absence of CD5-B lymphocytes (B2 cells), while the CD5 § B lymphocytes (B1 cells) are present and increased in relative numbers in the spleen.The B1 lymphocytes are activated and produce
Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors
Authors: Jean Y. Perentes, Nathaniel D. Kirkpatrick, Satoshi Nagano, Eve Y. Smith, Christine M. Shaver, Dennis Sgroi, Igor Garkavtsev, Lance L. Munn, Rakesh K. Jain, Yves Boucher
Journal: Cancer Research (2011)

Functional roles for the cancer cell-associated membrane type I matrix metalloproteinase (MT1-MMP) during early steps of the metastatic cascade in primary tumors remain unresolved. In an effort to determine its significance, we determined the in vivo effects of RNAi-mediated downregulation in mammary cancer cells on the migration, blood and lymphatic vessel invasion (LVI), and lymph node and lung metastasis. We also correlated the expression of cancer cell MT1-MMP with blood vessel invasion (BVI) in 102 breast cancer biopsies. MT1-MMP downregulation in cancer cells decreased lung metastasis without affecting primary tumor growth. The inhibition of lung metastasis correlated with reduced cancer cell migration and BVI. Furthermore, cancer cell-expressed MT1-MMP upregulated the expression of MT1-MMP in vascular endothelial cells, but did not affect MT1-MMP expression in lymphatic endothelial cells, LVI, or lymph node metastasis. Of clinical importance, we observed that elevated MT1-MMP expression correlated with BVI in biopsies from triple-negative breast cancers (TNBC), which have a poor prognosis and high incidence of distant metastasis, relative to other breast cancer subtypes. Together, our findings established that MT1-MMP activity in breast tumors is essential for BVI, but not LVI, and that MT1-MMP should be further explored as a predictor and therapeutic target of hematogenous metastasis in TNBC patients.
Factors that influence collection and engraftment of autologous peripheral-blood stem cells.
Authors: W Bensinger, F Appelbaum, S Rowley, R Storb, J Sanders, K Lilleby, T Gooley, T Demirer, K Schiffman, C Weaver
Journal: Journal of Clinical Oncology (1995)

To analyze factors that affect the collection of peripheral-blood stem cells (PBSC) before transplant and the tempo of engraftment after transplant.A consecutive series of 243 patients with breast cancer (n = 87), malignant lymphoma (n = 90), multiple myeloma (n = 32), or other malignancies (n = 34) had PBSC collected following stimulation with colony-stimulating factors (CSFs) or after chemotherapy followed by CSF. Infusion of PBSC was performed following myeloablative chemotherapy with chemotherapy with or without total-body irradiation (TBI). Postinfusion CSFs were administered to 72 patients. An analysis of factors that influence CD34+ cell yield was performed by linear regression. Cox regression analysis was used to determine factors that affect the kinetics of granulocyte and platelet recovery following infusion of PBSC.Mobilization with chemotherapy followed by CSF, a diagnosis of breast cancer, absence of marrow disease, no prior history of radiation therapy, and fewer cycles of conventional-dose chemotherapy were associated with a higher average daily yield of CD34+ cells. In the multivariate analysis, the CD34 content of infused cells and the use of a posttransplant CSF influenced neutrophil recovery after infusion of PBSC. CD34 content was also important for predicting platelet recovery. The use of postinfusion CSF was associated with a significant delay in platelet recovery in patients who received less than 5.0 x 10(6) CD34+ cells/kg, but there was no discernable effect in patients who received greater than 5.0 x 10(6) CD34+ cells/kg.Disease status and prior treatment influence the ability to mobilize PBSC. CD34 cell dose is an important predictor of engraftment kinetics after PBSC transplant, regardless of disease or mobilization technique. The use of postinfusion CSF improves neutrophil recovery, but at low CD34 doses can delay platelet recovery.
Mammalian Target of Rapamycin Inhibition Promotes Response to Epidermal Growth Factor Receptor Kinase Inhibitors in PTEN-Deficient and PTEN-Intact Glioblastoma Cells
Authors: Maria Y. Wang, Kan V. Lu, Shaojun Zhu, Ederlyn Q. Dia, Igor Vivanco, Gregory M. Shackleford, Webster K. Cavenee, Ingo K. Mellinghoff, Timothy F. Cloughesy, Charles L. Sawyers, Paul S. Mischel
Journal: Cancer Research (2006)

The epidermal growth factor receptor (EGFR) is commonly amplified, overexpressed, and mutated in glioblastoma, making it a compelling molecular target for therapy. We have recently shown that coexpression of EGFRvIII and PTEN protein by glioblastoma cells is strongly associated with clinical response to EGFR kinase inhibitor therapy. PTEN loss, by dissociating inhibition of the EGFR from downstream phosphatidylinositol 3-kinase (PI3K) pathway inhibition, seems to act as a resistance factor. Because 40% to 50% of glioblastomas are PTEN deficient, a critical challenge is to identify strategies that promote responsiveness to EGFR kinase inhibitors in patients whose tumors lack PTEN. Here, we show that the mammalian target of rapamycin (mTOR) inhibitor rapamycin enhances the sensitivity of PTEN-deficient tumor cells to the EGFR kinase inhibitor erlotinib. In two isogenic model systems (U87MG glioblastoma cells expressing EGFR, EGFRvIII, and PTEN in relevant combinations, and SF295 glioblastoma cells in which PTEN protein expression has been stably restored), we show that combined EGFR/mTOR kinase inhibition inhibits tumor cell growth and has an additive effect on inhibiting downstream PI3K pathway signaling. We also show that combination therapy provides added benefit in promoting cell death in PTEN-deficient tumor cells. These studies provide strong rationale for combined mTOR/EGFR kinase inhibitor therapy in glioblastoma patients, particularly those with PTEN-deficient tumors.
Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy
Authors: T. K. Jensen, N. H. I Hjollund, T. B. Henriksen, T. Scheike, H. Kolstad, A. Giwercman, E. Ernst, J. P. Bonde, N. E Skakkebak, J. Olsen
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective</b> : To examine the effect of alcohol consumption on the probability of conception. <b>Design</b> : A follow up study over six menstrual cycles or until a clinically recognised pregnancy occurred after discontinuation of contraception. <b>Subjects</b> : 430&nbsp;Danish couples aged 20-35&nbsp;years trying to conceive for the first time. <b>Main outcome measures</b> : Clinically recognised pregnancy. Fecundability odds ratio: odds of conception among exposed couples divided by odds among those not exposed. <b>Results</b> : In the six cycles of follow up 64% (179) of women with a weekly alcohol intake of less than five drinks and 55% (75) of women with a higher intake conceived. After adjustment for cycle number, smoking in either partner or smoking exposure in utero, centre of enrolment, diseases in female reproductive organs, woman9s body mass index, sperm concentration, and duration of menstrual cycle, the odds ratio decreased with increasing alcohol intake from 0.61&nbsp;(95% confidence interval 0.40&nbsp;to 0.93) among women consuming 1-5&nbsp;drinks a week to 0.34&nbsp;(0.22&nbsp;to 0.52) among women consuming more than 10&nbsp;drinks a week (P=0.03 for trend) compared with women with no alcohol intake. Among men no dose-response association was found after control for confounders including women9s alcohol intake. <b>Conclusion</b> : A woman9s alcohol intake is associated with decreased fecundability even among women with a weekly alcohol intake corresponding to five or fewer drinks. This finding needs further corroboration, but it seems reasonable to encourage women to avoid intake of alcohol when they are trying to become pregnant.
Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment.
Authors: J A Osborne, P H Lento, M R Siegfried, G L Stahl, B Fusman, A M Lefer
Journal: Journal of Clinical Investigation (1989)

Hypercholesterolemia was induced in New Zealand white rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 2 wk. Half of the cholesterol-fed rabbits were given lovastatin, a potent inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis, and the other half were given its vehicle (i.e., DMSO). At the end of 2 wk, the rabbits underwent experimental myocardial ischemia or a sham ischemia procedure. Ischemic animals fed the cholesterol-enriched diet for 2 wk experienced much greater cardiac damage than ischemic rabbits fed the control diet, despite the absence of any atherosclerosis. Lovastatin was shown to protect the ischemic rabbit myocardium by three different indices of ischemic damage: (a) maintenance of creatine kinase (CK) activity in the ischemic myocardium; (b) reduced loss of free amino-nitrogen containing compounds from the ischemic myocardium; and (c) blunting the rise of plasma CK activity. These effects were not due to differences in myocardial oxygen demand between the groups. Arteries isolated from animals fed the cholesterol-enriched diet developed defects in endothelium-dependent relaxation in both large vessels as well as coronary resistance vessels. Acute hypercholesterolemia increases the severity of myocardial ischemia while at the same time impairing endothelium-dependent relaxation. These deleterious changes can be significantly attenuated by treatment with lovastatin.
Long-term measurement of anti-adalimumab using pH-shift-anti-idiotype antigen binding test shows predictive value and transient antibody formation
Authors: Pauline A van Schouwenburg, Charlotte L Krieckaert, Theo Rispens, Lucien Aarden, Gerrit Jan Wolbink, Diana Wouters
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and objectives</h3> Therapeutic monoclonal antibodies are effective drugs for many different diseases. However, the formation of anti-drug antibodies (ADA) against a biological can result in reduced clinical response in some patients. Measurement of ADA in the presence of (high) drug levels is difficult due to drug interference in most assays, including the commonly used antigen binding test (ABT). <h3>Methods</h3> We recently published a novel method which enables the measurement of complexed antibodies against adalimumab (an anti-TNF antibody) in the presence of drug. Here we use this pH-shift-anti-idiotype ABT (PIA) to measure anti-adalimumab antibodies (AAA) in 99 rheumatoid arthritis (RA) patients treated for up to 3 years with adalimumab. <h3>Results</h3> 53 out of 99 RA patients produced AAA. In 50 of these PIA positive patients, AAA could be detected within the first 28 weeks of treatment. Patients in which AAA could be detected in the PIA after 28 weeks of treatment were more prone to declining adalimumab levels (&lt;5 µg/ml) (p&lt;0.01) and high AAA levels which could be detected in the ABT (p&lt;0.05) at later time points. We observed transient AAA formation in 17/53 patients. <h3>Conclusions</h3> Results show that AAA develop early in treatment. However, levels that completely neutralise the drug may be reached much later in treatment. Furthermore, the patients positive for PIA at 28 weeks have an increased chance to develop clinical non-response due to immunogenicity. In some of the patients, AAA formation is transient.
Cystic Fibrosis: Manual of Diagnosis and Management
Journal: Thorax (1986)

pneumonia is rarely associated with spontaneous pneumo- thorax.8Clearly, however, we cannot be certain that the pneumothorax was not caused by the underlying disease process in our second case.The safety of fibreoptic bronchoscopy, when performed as an outpatient procedure in carefully selected patients, has been clearly documented.7 Hospital admission of patients having transbronchial biopsies is, however, recommended.'We agree with this and suggest that all patients should be assessed for the presence of delayed pneumothorax just before discharge from hospital.Patients should in addition be informed of the possibility of this complication and advised to seek medical assistance early in the event of symptoms that suggest its occurrence.
Hyperglycemia reduces gallbladder emptying and plasma hormone secretion to modified sham feeding and regular feeding
Authors: Sybrand Y. de Boer, Ad A. M. Masclee, Wai Fan Lam, Jaap Schipper, Jan B. M. J. Jansen, Cornelius B. H. W. Lamers
Journal: Hepatology (1993)

The purpose of this study was to investigate the effect of acute stable hyperglycemia on gallbladder motility, plasma cholecystokinin level and pancreatic polypeptide secretion. Gallbladder emptying in response to modified sham feeding and regular feeding was determined in six healthy subjects on two separate occasions during normoglycemia (serum glucose = 5 mmol/L) and during hyperglycemia (serum glucose = 15 mmol/L). Pancreatic polypeptide secretion was determined as an indirect measure of cholinergic tone. Gallbladder contraction in response to sham feeding during hyperglycemia (9% +/- 2%) was significantly (p < 0.05) reduced compared with that in normoglycemia (22% +/- 1%). During hyperglycemia, gallbladder emptying after meal ingestion (29% +/- 9%) was significantly (p < 0.05) less than that in normoglycemia (60% +/- 10%). Sham feeding did not affect plasma cholecystokinin levels. Regular feeding induced significant (p < 0.05) increases in plasma cholecystokinin levels in both experiments. However, integrated postprandial plasma cholecystokinin secretion was significantly (p < 0.05) reduced during hyperglycemia compared with that in normoglycemia (29 +/- 5 pmol.60 min vs. 58 +/- 10 pmol.60 min). Modified sham feeding-and feeding-stimulated pancreatic polypeptide secretion during hyperglycemia (235 +/- 95 pmol.90 min and 1,035 +/- 267 pmol.60 min, respectively) were significantly (p < 0.05) less than levels seen in normoglycemia (434 +/- 71 pmol.90 min and 1,961 +/- 219 pmol.60 min, respectively). This study indicates that gallbladder emptying and plasma hormone secretion in response to sham feeding and regular feeding are affected by blood glucose levels.
Encephalitis in an Infant after Vaccination with 17 D Yellow Fever Virus
Authors: J. H. Smith
Journal: BMJ (1954)

MEDICAL MEMORANDABDIBAJOURNrsL difference being the degree of severity-is put down as a subungual hyperkeratosis, a disturbance of the nail-bed (Swaniker, 1948).Various exciting causes have been blamed, from severe trauma-" Ostler's toes," or more chronic injury due to too short shoes-to peripheral neuritis, syphilis, tabes, leprosy, ichthyosis, hemiplegia, and heart disease with peripheral
The Sounds of Silence: Sexuality Information for Cancer Patients
Authors: Anne Katz
Journal: Journal of Clinical Oncology (2004)

Mary, a 41-year-old woman with endometrial cancer, had a hysterectomy for endometrial cancer and subsequently completed radiation therapy. Having recovered from the operation and radiation, she is doing well physically. Nonetheless, she reports that she had pain on intercourse 3 weeks before and has been too afraid to try again since then. She has been married for 10 years, and sex has always been very important to her and her husband. She becomes very emotional when talking about this and states that she is afraid that if this does not improve, her husband may leave her. She states that she has not been given information about sexual functioning at any point in her treatment and believes that this is bordering on malpractice.
Sequential Follow-Up Results of Catheter Intervention for Coronary Artery Lesions After Kawasaki Disease
Authors: Masahiro Ishii, Takafumi Ueno, Hisao Ikeda, Motofumi Iemura, Tetsu Sugimura, Jun Furui, Yoko Sugahara, Hiromi Muta, Teiji Akagi, Yuichi Nomura, Tomoki Homma, Hiroyoshi Yokoi, Masakiyo Nobuyoshi, Toyojiro Matsuishi, Hirohisa Kato
Journal: Circulation (2002)

Background — The purpose of this study was to assess the sequential follow-up results of catheter intervention in Kawasaki disease by use of quantitative coronary angiography (QCA) and intravascular ultrasound imaging. Methods and Results — Catheter intervention was performed on 23 stenotic lesions in 22 patients (aged 2 to 24 years). Percutaneous balloon angioplasty (PBA) was performed in 4 patients, stent implantation in 7, percutaneous transluminal coronary rotational ablation (PTCRA) in 10, and a combination of PTCRA with stent implantation in 2. A total of 21 lesions (91%) were successfully dilated by catheter intervention without major or minor complications. One patient immediately underwent coronary artery bypass grafting (CABG) surgery because stent implantation failed to resolve his lesion. At 4 to 6 months after catheter intervention, 2 restenotic lesions (9%) were detected by QCA in 2 patients who had undergone PBA, and these patients subsequently underwent CABG surgery. In 6 months to 3 years after catheter intervention, no patients showed evidence of ischemic findings. At 3 to 4 years after catheter intervention, QCA and intravascular ultrasound studies were performed on 15 lesions in 14 patients. Two restenotic lesions (13%) were detected by QCA in 2 patients. One of the 2 had stent implantation and underwent CABG surgery, and the other had undergone PTCRA and underwent re-PTCRA. Thirteen patients demonstrated no ischemic findings at 3 to 8 years after catheter intervention. Conclusion — Catheter intervention for Kawasaki disease can be accomplished and can be effective in the short term, but the long-term efficacy should be verified by further study.
Sentinel-site surveillance of Mycobacterium avium complex pulmonary disease
Authors: J. Maugein, M. Dailloux, B. Carbonnelle, V. Vincent, J. Grosset
Journal: European Respiratory Journal (2005)

The incidence of Mycobacterium avium complex (MAC) pulmonary disease in HIV-negative patients was studied prospectively from January 1, 2000 to December 31, 2002 through 32 sentinel sites distributed all over France. Among the 275 patients who yielded MAC isolates from respiratory clinical specimens, 101 (36.7%) met the bacteriological, radiographical and clinical criteria established by the American Thoracic Society for nontuberculous mycobacterial respiratory disease. Of these 101 patients, 81 had underlying lung disease, mainly previous tuberculosis, bronchectasis or chronic obstructive pulmonary disease. Among the 20 patients with no underlying lung disease, 12 had a predisposing factor such as leukaemia or immunosuppressive treatment and eight had no predisposing factor. All patients with MAC respiratory disease had clinical symptoms, commonly cough and fatigue, and 52 (51.5%) were sputum smear positive for acid-fast bacillus. The ratio of patients with Mycobacterium avium complex pulmonary disease to patients with pulmonary tuberculosis in France was estimated to be 3% and the incidence of Mycobacterium avium complex pulmonary disease in France was 0.2 per 100,000 inhabitants.