tbuckley/cabot-search huggingface dataset:
Macula Densa Sensing and Signaling Mechanisms of Renin Release
Authors: János Peti-Peterdi, Raymond C. Harris
Journal: Journal of the American Society of Nephrology (2010)

Macula densa cells in the distal nephron, according to the classic paradigm, are salt sensors that generate paracrine chemical signals in the juxtaglomerular apparatus to control vital kidney functions, including renal blood flow, glomerular filtration, and renin release. Renin is the rate-limiting step in the activation of the renin-angiotensin system, a key modulator of body fluid homeostasis. Here, we discuss recent advances in understanding macula densa sensing and suggest these cells, in addition to salt, also sense various chemical and metabolic signals in the tubular environment that directly trigger renin release.
Prospective Study of Risk Factors for Alzheimer’s Disease: Results at 7.5 Years
Authors: George S. Zubenko, Ethel Winwood, Barbara Jacobs, Ivana Teply, J. Scott Stiffler, Hugh B. Hughes III, F. Jacob Huff, Trey Sunderland, A. Julio Martinez
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE ε4 genotype. METHOD: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE ε4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the ε4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. CONCLUSIONS: These results indicate that increased platelet membrane fluidity is not produced by the APOE ε4 allele. Instead, increased platelet membrane fluidity and the ε4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different.
Plasma Levels of Trefoil Factors are Increased in Patients with Advanced Prostate Cancer
Authors: Else Marie Vestergaard, Michael Borre, Steen Seier Poulsen, Ebba Nexø, Niels Tørring
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer. Experimental Design: In 79 patients with prostate cancer, 23 patients with benign prostatic hyperplasia, and 44 healthy individuals plasma TFF1, TFF2, and TFF3 were determined with ELISAs and compared with clinical stage and prostate-specific antigen (PSA) values. Plasma levels of TFF were compared with the immunohistochemical expression of TFF and chromogranin A in 30 prostate cancer tissue samples. Results: Patients with advanced prostate cancer had significantly higher plasma concentrations of TFF1, TFF2, and TFF3 (P &amp;lt; 0.01) compared with patients with localized disease. Using a cutoff of 200 pmol/L, the sensitivity and specificity of plasma TFF3 in differentiating between patients with localized and advanced disease was 74% (59-85%) and 81% (66-91%). Plasma levels of TFF3 were highest in patients with bone metastases (P = 0.008). Patients with serum PSA &amp;gt;10 μg/L had significantly higher plasma TFF3 values than patients with serum PSA &amp;lt;10 μg/L (P = 0.03) and TFF3 levels were higher in patients with Gleason sums of ≥7 (P = 0.02). Expression of TFF1 and TFF3 determined by immunohistochemistry was increased in patients with prostate cancer but did not correlate with plasma trefoil factor values. Conclusions: Plasma levels of trefoil factors are increased in patients with advanced prostate cancer. Prospective studies are needed to confirm the predictive utility of trefoil factors in prostate cancer.
AZF deletions and Y chromosomal haplogroups: history and update based on sequence
Authors: Peter H. Vogt
Journal: Human Reproduction Update (2005)

AZF deletions are genomic deletions in the euchromatic part of the long arm of the human Y chromosome (Yq11) associated with azoospermia or severe oligozoospermia. Consequently, it can be assumed that these deletions remove Y chromosomal genes required for spermatogenesis. However, these 'classical' or 'complete' AZF deletions, AZFa, AZFb and AZFc, represent only a subset of rearrangements in Yq11. With the benefit of the Y chromosome sequence, more rearrangements (deletions, duplications, inversions) inside and outside the classical AZF deletion intervals have been elucidated and intra-chromosomal non-allelic homologous recombinations (NAHRs) of repetitive sequence blocks have been identified as their major cause. These include duplications in AZFa, AZFb and AZFc and the partial AZFb and AZFc deletions of which some were summarized under the pseudonym 'gr/gr' deletions. At least some of these rearrangements are associated with distinct Y chromosomal haplogroups and are present with similar frequencies in fertile and infertile men. This suggests a functional redundancy of the AZFb/AZFc multi-copy genes. Alternatively, the functional contribution(s) of these genes to human spermatogenesis might be different in men of different Y haplogroups. That raises the question whether, the frequency of Y haplogroups with different AZF gene contents in distinct human populations leads to a male fertility status that varies between populations or whether, the presence of the multiple Y haplogroups implies a balancing selection via genomic deletion/amplification mechanisms.
Selective targeted delivery of TNFα to tumor blood vessels
Authors: Laura Borsi, Enrica Balza, Barbara Carnemolla, Francesca Sassi, Patrizia Castellani, Alexander Berndt, Hartwig Kosmehl, Attila Birò, Annalisa Siri, Paola Orecchia, Jessica Grassi, Dario Neri, Luciano Zardi
Journal: Blood (2003)
Mucosal Administration of Heat Shock Protein-65 Decreases Atherosclerosis and Inflammation in Aortic Arch of Low-Density Lipoprotein Receptor-Deficient Mice
Authors: Ruth Maron, Galina Sukhova, Ana-Maria Faria, Ethan Hoffmann, Francois Mach, Peter Libby, Howard L. Weiner
Journal: Circulation (2002)

Background— Increasing evidence supports the involvement of inflammation and immunity in atherogenesis as well as the role of autoimmunity to heat shock proteins (HSPs) in the progression of atherosclerosis. Mucosal administration of autoantigens decreases organ-specific inflammation and disease in several models of autoimmunity (diabetes, arthritis, and encephalomyelitis) and is also being tested in human clinical trials. Methods and Results— We examined the effect of nasal or oral administration of mycobacterial HSP-65 on atherosclerotic lesion formation in mice lacking the receptor for LDL that were maintained on a high-cholesterol diet. Animals were nasally or orally treated for 1 week with HSP-65, and a high-cholesterol diet was started after the last treatment. The mice were mucosally treated once a week for 8 or 12 weeks, at which time pathological analysis was performed. We found a significant decrease in the size of atherosclerotic plaques, a reduction in macrophage-positive area in the aortic arch, increased interleukin-10 expression, and a reduced number of T cells in nasally treated animals compared with control animals. A similar trend was observed in orally treated mice, but it was not significant. Conclusions— Our results demonstrate that nasal vaccination with HSP reduces the inflammatory process associated with atherosclerosis and provides a new immunologic approach for the treatment of atherosclerosis.
Capsaicin treatment induces histamine release and perfusion changes in psoriatic skin
Authors: None Krogstad, None LÖnnroth, None Larson, None Wallin
Journal: British Journal of Dermatology (1999)

Journal Article Capsaicin treatment induces histamine release and perfusion changes in psoriatic skin Get access A.L. Krogstad, A.L. Krogstad Department of Dermatology, (Clinical Neurophysiology), Sahlgrenska University Hospital, SE‐41345 Göteborg, Sweden, Anne LeneKrogstad E‐mail: anne‐lene.krogstad@nfys.gu.se Search for other works by this author on: Oxford Academic Google Scholar P. LÖnnroth, P. LÖnnroth Department of Internal Medicine, (Clinical Neurophysiology), Sahlgrenska University Hospital, SE‐41345 Göteborg, Sweden, Search for other works by this author on: Oxford Academic Google Scholar G. Larson, G. Larson Department of Clinical Chemistry and Transfusion Medicine, (Clinical Neurophysiology), Sahlgrenska University Hospital, SE‐41345 Göteborg, Sweden, Search for other works by this author on: Oxford Academic Google Scholar B.G. Wallin B.G. Wallin Department of Clinical Neuroscience (Clinical Neurophysiology), Sahlgrenska University Hospital, SE‐41345 Göteborg, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 1, 1 July 1999, Pages 87–93, https://doi.org/10.1046/j.1365-2133.1999.02925.x Published: 01 July 1999
Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery
Authors: William T. Cefalu
Journal: Diabetes Care (2004)

To comprehensively review the progress to date on the development of alternative routes for insulin delivery.Study data were collected through a Medline review.Proof of principle has been established for many routes of administration including dermal, nasal, oral, buccal, and pulmonary insulin delivery.Of all the approaches to date, pulmonary delivery appears to be most feasible. Ongoing phase III studies will ultimately determine safety, tolerability, and efficacy before approval for clinical use.
Renal Monoclonal Immunoglobulin Deposition Disease
Authors: JULIE LIN, GLEN S. MARKOWITZ, ANTHONY M. VALERI, NEERAJA KAMBHAM, WILLIAM H. SHERMAN, GERALD B. APPEL, VIVETTE D. D'AGATI
Journal: Journal of the American Society of Nephrology (2001)

Abstract. This study reports the clinicopathologic findings and outcome in 34 patients with renal monoclonal immunoglobulin deposition disease (MIDD), which included 23 light-chain DD (LCDD), 5 light- and heavy-chain DD (LHCDD), and 6 heavy-chain DD (HCDD). A total of 23 patients had pure MIDD, whereas 11 patients had LCDD with coexistent myeloma cast nephropathy (LCDD &amp; MCN). Renal biopsy diagnosis preceded clinical evidence of dysproteinemia in 68% of all cases. By immunofluorescence, the composition of deposits included 11κ/1λ (LCDD), 3IgGκ/2IgGλ (LHCDD), 5γ/1α (HCDD), and 10κ/1λ (LCDD &amp; MCN). Patients with pure MIDD presented with mean serum creatinine of 4.2 mg/dl, nephrotic proteinuria, and hypertension. Cases of HCDD were associated with a CH1 deletion and frequently had hypocomplementemia and a positive hepatitis C virus antibody but negative hepatitis C virus PCR. LCDD &amp; MCN is a morphologically and clinically distinct entity from pure MIDD, presenting with higher creatinine (mean, 7.8 mg/dl; P = 0.01), greater dialysis dependence (64 versus 26%; P = 0.053), subnephrotic proteinuria, and less nodular glomerulopathy (18 versus 100%; P &lt; 0.0001). Multiple myeloma was more frequently diagnosed in LCDD &amp; MCN than in pure MIDD (91 versus 31%; P = 0.025). Renal and patient survivals were significantly worse in patients with LCDD &amp; MCN (mean, 4 and 22 mo, respectively), compared with patients with pure MIDD (mean, 22 and 54 mo). Chemotherapy stabilized or improved renal function in 10 of 15 patients (67%) with pure MIDD who presented with creatinine of &lt;5.0 mg/dl, emphasizing the importance of early detection. On multivariate analysis, initial creatinine was the only predictor of renal and patient survival in pure MIDD, underscoring the prognostic significance of the renal involvement.
Paroxetine in Human Breast Milk and Nursing Infants
Authors: Zachary N. Stowe, Lee S. Cohen, Amy Hostetter, James C. Ritchie, Michael J. Owens, Charles B. Nemeroff
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The purpose of this study was to determine the extent of infant medication exposure through breast-feeding during maternal treatment with paroxetine. METHOD: Breast milk and paired maternal and infant sera were collected after 10 days of maternal treatment with paroxetine at a stable daily dose (10–50 mg/day). All samples were analyzed by means of high-performance liquid chromatography with ultraviolet detection and a limit of detection of 2 ng/ml. RESULTS: Breast milk paroxetine concentrations were highly variable (2–101 ng/ml) and were present in all breast milk samples (N=108). A significant gradient effect was observed, with greater paroxetine concentrations found in later portions of breast milk (hind milk) than in early portions (fore milk). No clear time course of paroxetine excretion into breast milk was demonstrated, although maternal paroxetine daily dose reliably predicted both trough and peak breast milk concentrations over a 24-hour period. In 16 mother and infant serum pairs, no detectable concentrations of paroxetine were found in the serum of the nursing infants. CONCLUSIONS: This study extends previous data by demonstrating the presence of paroxetine in the breast milk of nursing women treated with this medication. The low concentrations of paroxetine in infant serum and lack of any observable adverse effects after maternal use of this medication while breast-feeding parallels the available data on other selective serotonin reuptake inhibitors.
PREVALENCE AND CLINICAL SIGNIFICANCE OF FUNCTIONAL MITRAL STENOSIS AFTER MITRAL VALVE REPAIR FOR MYXOMATOUS MITRAL REGURGITATION
Authors: Shin-Yee K. Chen, Buu-Khanh Lam, Thierry Mesana, Vincent Chan, Karen Hay, Kwan-Leung Chan
Journal: Journal of the American College of Cardiology (2011)
Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice
Authors: Ludwig Amigo, Hegaly Mendoza, Juan Castro, Verónica Quiñones, Juan Francisco Miquel, Silvana Zanlungo
Journal: Hepatology (2002)

Receptor-mediated endocytosis is one of the major mechanisms for uptake of lipoprotein cholesterol in the liver. Because Niemann-Pick C1 (NPC1) protein is a key component in the intracellular distribution of cholesterol obtained from lipoproteins by the endocytic pathway, it may play a critical role in controlling plasma lipoprotein cholesterol and its biliary secretion. A murine model of Niemann-Pick type C disease (NPC), the NPC1-deficient [NPC1 (−/−)] mouse, was used to evaluate the relevance of hepatic NPC1 expression in regulating plasma lipoprotein cholesterol profile and biliary lipid secretion under chow and high-cholesterol diets. Total plasma cholesterol concentrations were increased in NPC1 (−/−) mice compared with wild-type mice when both mouse strains were fed chow or high-cholesterol diets. The increased plasma cholesterol levels found in NPC1 (−/−) mice were mostly due to elevated cholesterol content in larger and more heterogeneous HDL particles. On the chow diet, biliary lipid secretion was not impaired by NPC1 deficiency. Furthermore, chow-fed NPC1 (−/−) mice showed a small, but significant, increase in biliary cholesterol secretion. On the high-cholesterol diet, wild-type mice increased biliary cholesterol output, whereas NPC1 (−/−) mice did not. Finally, hepatic NPC1 overexpression by adenovirus-mediated gene transfer increased biliary cholesterol secretion by 100% to 150% in both wild-type mice and cholesterol-fed NPC1 (−/−) mice. In conclusion, hepatic NPC1 expression is an important factor for regulating plasma HDL cholesterol levels and biliary cholesterol secretion in mice.
SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma
Authors: Edgar Ben-Josef, Katherine A. Guthrie, Anthony B. El-Khoueiry, Christopher L. Corless, Mark M. Zalupski, Andrew M. Lowy, Charles R. Thomas, Steven R. Alberts, Laura A. Dawson, Kenneth C. Micetich, Melanie B. Thomas, Abby B. Siegel, Charles D. Blanke
Journal: Journal of Clinical Oncology (2015)

The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen.Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m(2) intravenously on days 1 and 8) and capecitabine (1,500 mg/m(2) per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m(2) per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively.A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage.This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.
Chronic traumatic encephalopathy and risk of suicide in former athletes
Authors: Grant L Iverson
Journal: British Journal of Sports Medicine (2013)

Background In the initial autopsy case studies of chronic traumatic encephalopathy (CTE), some researchers have concluded that the proteinopathy associated with CTE is the underlying cause of suicidality and completed suicide in former athletes. Methods A review of the literature on contact sports and risk of completed suicide revealed only one epidemiological study with direct relevant data. Results There are no published cross-sectional, epidemiological or prospective studies showing a relation between contact sports and risk of suicide. One published epidemiological study suggests that retired National Football League players have lower rates of death by suicide than the general population. Outside of sports, there is a mature body of evidence suggesting that the causes of suicide are complex, multifactorial and difficult to predict in individual cases. Conclusions Future research might establish a clear causal connection between the proteinopathy of CTE and suicide. At present, however, there is insufficient scientific evidence to conclude that there is a strong causal relationship between the presence of these proteinopathies and suicide in former athletes. Additional research is needed to determine the extent to which the neuropathology of CTE is a possible mediator or moderator variable associated with suicide.
Changes in N-terminal glucagon-like immunoreactivity and insulin during short-term gluten challenge in childhood coeliac disease.
Authors: D J Carson, J F Glasgow, K D Buchanan, J M Sloan
Journal: Gut (1981)

Sixteen patients (aged 3.5-14.3 years) with normal jejunal mucosa, originally diagnosed as having coeliac disease at least 18 months before, were started on gluten challenge. The 'end point' of challenge was significant deterioration in jejunal mucosa morphologically and morphometrically. Studies carried out both before and after challenge included intestinal absorption of D-xylose and glucose, and release of insulin and N-terminal glucagon-like immunoreactivity (N-GLI). After gluten challenge, there were significant increases in plasma N-GLI at both 45 (P less than 0.05) and 120 minutes (P less than 0.03) after oral glucose. Significant reduction occurred in glucose absorption at 45 minutes (P less than 0.04), in one-hour D-xylose absorption (P less than 0.01) and fasting serum cholesterol (P less than 0.01). Plasma N-GLI showed significant negative correlations with D-xylose absorption (P less than 0.003) and serum cholesterol (P less than 0.004).
The Use and Misuse of Sex Chromatin Screening for `Gender Identification' of Female Athletes
Authors: Albert de la Chapelle
Journal: JAMA (1986)

According to the rules of sports organizations such as the International Olympic Committee, competitors registered as females must undergo a "gender verification" test that consists of screening with sex chromatin, followed by further tests in those with an abnormal or inconclusive result. The aims of the gender verification test have not been published but presumably they are to exclude from women's sports events males or other individuals whose muscle strength or body build gives them an unfair advantage over their competitors. It is shown herein that the sex chromatin screening method reveals only a small proportion of such individuals. Moreover, women with certain congenital chromosome abnormalities and other abnormal conditions without increased muscle strength are found to have "abnormal" sex chromatin. Thus, the present screening method is both inaccurate and discriminatory. It is proposed that the aims of gender identification should be defined and methods chosen that achieve the desired result. (<i>JAMA</i>1986;256:1920-1923)
Examination of the Therapeutic Potential of Delta-24-RGD in Brain Tumor Stem Cells: Role of Autophagic Cell Death
Authors: Hong Jiang, Candelaria Gomez-Manzano, Hiroshi Aoki, Marta M.. Alonso, Seiji Kondo, Frank McCormick, Jing Xu, Yasuko Kondo, B. Nebiyou Bekele, Howard Colman, Frederick F. Lang, Juan Fueyo
Journal: JNCI Journal of the National Cancer Institute (2007)

The eradication of brain tumor stem cells is essential for long-term brain tumor remission after treatment. In this study, we examined the therapeutic potential of an oncolytic adenovirus, Delta-24-RGD, targeted to the abnormal p16INK4/Rb pathway in brain tumor stem cells. Four brain tumor stem cell lines from surgical glioblastoma specimens expressed high levels of adenoviral receptors and allowed for efficient viral infection, replication, and oncolysis in an Rb-dependent manner. Delta-24-RGD induced autophagic cell death, as indicated by accumulation of Atg5 and LC3-II protein and autophagic vacuoles. Treatment of xenografts derived from brain tumor stem cells with Delta-24-RGD statistically significantly improved the survival of glioma-bearing mice (means: 38.5 versus 66.3 days, difference = 27.8 days, 95% confidence interval = 19.5 to 35.9 days, P <.001). Analyses of treated tumors showed that Atg5 expression colocalized with viral fiber protein and delineated a wave front of autophagic cells that circumscribed areas of virally induced necrosis. Our results show for the first time that brain tumor stem cells are susceptible to adenovirus-mediated cell death via autophagy in vitro and in vivo.