tbuckley/cabot-search huggingface dataset:
Converting Enzyme Inhibition and the Glomerular Hemodynamic Response to Glycine in Diabetic Rats
Authors: LARRY A. SLOMOWITZ, ORJAN W. PETERSON, SCOTT C. THOMSON
Journal: Journal of the American Society of Nephrology (1999)

Abstract. GFR normally increases during glycine infusion. This response is absent in humans and rats with established diabetes mellitus. In diabetic patients, angiotensin-converting enzyme inhibition (ACEI) restores the effect of glycine on GFR. To ascertain the glomerular hemodynamic basis for this effect of ACEI, micropuncture studies were performed in male Wistar-Froemter rats after 5 to 6 wk of insulin-treated streptozotocin diabetes. The determinants of single-nephron GFR (SNGFR) were assessed in each rat before and during glycine infusion. Studies were performed in diabetics, diabetics after 5 d of ACEI (enlapril in the drinking water), and weight-matched controls. Diabetic rats manifest renal hypertrophy and glomerular hyperfiltration but not glomerular capillary hypertension. ACEI reduced glomerular capillary pressure, increased glomerular ultrafiltration coefficient, and did not mitigate hyperfiltration. In controls, glycine increased SNGFR by 30% due to increased nephron plasma flow. In diabetics, glycine had no effect on any determinant of SNGFR. In ACEI-treated diabetics, the SNGFR response to glycine was indistinguishable from nondiabetics, but the effect of glycine was mediated by greater ultrafiltration pressure rather than by greater plasma flow. These findings demonstrate that: ( 1 ) The absent response to glycine in established diabetes does not indicate that renal functional reserve is exhausted by hyperfiltration; and ( 2 ) ACEI restores the GFR response to glycine in established diabetes, but this response is mediated by increased ultrafiltration pressure rather than by increased nephron plasma flow.
Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients
Authors: Gesine Paul, Olof Zachrisson, Andrea Varrone, Per Almqvist, Markus Jerling, Göran Lind, Stig Rehncrona, Bengt Linderoth, Hjalmar Bjartmarz, Lisa L. Shafer, Robert Coffey, Mikael Svensson, Katarina Jansson Mercer, Anton Forsberg, Christer Halldin, Per Svenningsson, Håkan Widner, Jonas Frisén, Sven Pålhagen, Anders Haegerstrand
Journal: Journal of Clinical Investigation (2015)

BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA).
Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast Cancer
Authors: Allan Lipton, S. M. Ali, K. Leitzel, Laurence Demers, Vernon Chinchilli, L. Engle, Harold Harvey, C. Brady, C. M. Nalin, M. Dugan, W. Carney, J. Allard
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the effect of elevation of serum HER-2/neu on response to hormone therapy. PATIENTS AND METHODS: Seven hundred nineteen metastatic patients with estrogen receptor–positive (ER+), progesterone receptor–positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels. RESULTS: Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with nonelevated and 23% in 217 patients with elevated serum HER-2/neu levels (P < .0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with nonelevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P < .0001). CONCLUSION: Patients with ER+ and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER+ and serum HER-2/neu–negative patients. Their survival duration is also shorter.
Explosive Speciation of Takifugu: Another Use of Fugu as a Model System for Evolutionary Biology
Authors: Y. Yamanoue, M. Miya, K. Matsuura, S. Miyazawa, N. Tsukamoto, H. Doi, H. Takahashi, K. Mabuchi, M. Nishida, H. Sakai
Journal: Molecular Biology and Evolution (2008)

Although the fugu Takifugu rubripes has attracted attention as a model organism for genomic studies because of its compact genome, it is not generally appreciated that there are approximately 25 closely related species with limited distributions in the waters of East Asia. We performed molecular phylogenetic analyses and constructed a time tree using whole mitochondrial genome sequences from 15 Takifugu species together with 10 outgroups to examine patterns of diversification. The resultant time tree showed that the modern Takifugu species underwent explosive speciation during the Pliocene 1.8–5.3 Ma, which is comparable with that of the Malawi cichlids and tropheine cichlids in Lake Tanganyika. Considering their limited distributions and remarkable variations in coloration, morphology, and behavior, the results of the present study strongly suggest that Takifugu species are strong candidates as a model system for evolutionary studies of speciation mechanisms in marine environments where few such organisms are available.
Clocks, genes and sleep
Authors: M. von Schantz, S. N Archer
Journal: Journal of the Royal Society of Medicine (2003)

Do but consider what an excellent thing sleep is; it is soinestimable a jewel that, if a tyrant would give his crownfor an hour’s slumber, it cannot be bought; of sobeautiful a shape is it, that though a man lie with anEmpress, his heart cannot beat quiet till he leaves herembracements to be at rest with the other: yea, sogreatly indebted are we to this kinsman of death, that weowe the better tributary, half of our life to him: andthere is good cause why we should do so: for sleep is thatgolden chain that ties health and our bodies together.—Thomas Dekker (The Gull’s Hornbook, 1609)Circadian rhythms are endogenously generated rhythms thatapproximate the length of a day and a night. They are foundin most organisms whose life span is counted in days orgreater units, rather than hours.
Role of single port medical pleuroscopy using optical biopsy forceps in diagnosing malignant pleural effusion
Authors: Debajyoti Bhattacharyya, M.S. Barthwal, C.D.S Katoch, Anand Arora
Journal: European Respiratory Journal (2012)

Introduction: Medical pleuroscopy is useful in early confirmation of malignant pleural effusion. Optical biopsy forceps helps in getting adequate number and amount of specimen through a single port giving a small incision.  Aims and objectives: To assess the efficacy and safety of single port medical pleuroscopy using optical biopsy forceps in diagnosing malignant pleural effusion.  Methods: This is a retrospective study of all patients who had been histopathologically proved to have malignant pleural effusion by single port diagnostic medical pleuroscopy using optical biopsy forceps between January 2009 and January 2012 in a tertiary care hospital in India.  Results: 39 patients (25 males and 14 females) underwent medical pleuroscopy during the period of study with a possible diagnosis of malignant pleural effusion. Mean age of patients was 54.4 years (range: 38-82 years). 37 patients (94.8%) were confirmed to have malignancy by medical pleuroscopic biopsy. Adenocarcinoma was the commonest malignancy – 15 (40.5%), followed by squamous cell carcinoma – 11 (29.7%), small cell carcinoma – 5 (13.5%), poorly differentiated carcinoma – 3 (8.1%), malignant mesothelioma – 2 (5.4%), and non-Hodgkin9s lymphoma (2.7%). Reports were inconclusive in two patients. VATS biopsy subsequently confirmed them to be adenocarcinoma and mesothelioma respectively. Complications encountered during the perioperative period included: superficial wound infection in one (2.5%), and air leaks more than 7 days in two (5.1%) cases.  Conclusions: Single port medical pleuroscopy using optical biopsy forceps has a high diagnostic rate in malignant pleural effusion. The procedure is also safe.
SAPS 3—From evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description
Authors: Philipp G. H. Metnitz, Rui P. Moreno, Eduardo Almeida, Barbara Jordan, Peter Bauer, Ricardo Abizanda Campos, Gaetano Iapichino, David Edbrooke, Maurizia Capuzzo, Jean-Roger Le Gall
Journal: Intensive Care Medicine (2005)

Risk adjustment systems now in use were developed more than a decade ago and lack prognostic performance. Objective of the SAPS 3 study was to collect data about risk factors and outcomes in a heterogeneous cohort of intensive care unit (ICU) patients, in order to develop a new, improved model for risk adjustment.
Glucocorticoid Effects of Lymphosarcoma P1798 on Dna Replication and Growth of Subcutaneous Tumors in Mice&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: E. Aubrey Thompson, William M. Moore, Roger H. Sawyer
Journal: JNCI Journal of the National Cancer Institute (1980)

Injection of cortisol into BALB/c mice inhibited tritiated thymidine ([3H]dThd) incorporation into ascites cells of lymphosarcoma P1798 but not into cells isolated frm large subcutaneous tumors. The DNA synthetic index (SI), estimated autoradiographically after pulse labeling with [3H]dThd in vitro, was 0.25-0.29 for ascites cells and cells isolated from tumors having a radius squared (r2) less than 200 mm2. Cortisol decreased the SI of ascites cells by 90-95% within 5 hours. Similarly, cortisol decreased the SI of cells from subcutaneous tumors having an r2 less than 90 mm2. Growth and [3H]dThd incorporation were also inhibited by cortisol treatment of tumors with an r2 less than 90 mm2. However, when tumors became larger than 90 mm2, the SI did not decrease after cortisol treatment. Neither growth nor [3H]dThd incorporation was inhibited in tumors with an r2 greater than 90 mm2. These data indicate that tumors of lymphosarcoma P1798 became resistant to cortisol in a size-dependent manner. Loss of sensitivity ws not due to a gradual increase in the percentage of resistant cells.
Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy
Authors: Dawn Hershman, Alfred I. Neugut, Judith S. Jacobson, Jian Wang, Wei-Yann Tsai, Russell McBride, Charles L. Bennett, Victor R. Grann
Journal: JNCI Journal of the National Cancer Institute (2007)

Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G-CSFs) or granulocyte-macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients.Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stages I-III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided.Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15).The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free.
Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis.
Authors: R E Gregg, W E Connor, D S Lin, H B Brewer
Journal: Journal of Clinical Investigation (1986)

Sitosterolemia and xanthomatosis together are a disease characterized by premature cardiovascular disease, and by elevated plasma concentrations of total sterols and of plant sterols, especially sitosterol which is hyperabsorbed. In order to determine whether this abnormal metabolism also involved other sterols, a patient with sitosterolemia was fed a diet high in shellfish that contain significant quantities of noncholesterol sterols, some of which are less well absorbed than cholesterol in humans. Compared with control subjects (n = 8), the sitosterolemic subject had an increased absorption of 22-dehydrocholesterol (71.5% vs. 43.8 +/- 11.4%, mean +/- SD), C-26 sterol (80.6% vs. 49.3 +/- 11.4%), brassicasterol (51.8% vs. 4.8 +/- 4.2%), and 24-methylene cholesterol (60.5% vs. 16.0 +/- 8.3%). This enhanced absorption was associated with an increased plasma total shellfish sterol level (13.1 mg/dl vs. 1.9 +/- 0.7 mg/dl in normals). In the sitosterolemic subject, as in normals, the shellfish sterols were not preferentially concentrated in any lipoprotein class, and 50-65% of these sterols were in the esterified form in plasma. Bile acids and neutral sterols were quantitated in bile obtained by duodenal aspiration. The bile acid composition did not differ significantly in the sitosterolemic subject compared with the normal controls. The sitosterolemic subject, though, was unable to concentrate normally the neutral shellfish sterols in bile. The normal controls concentrated the shellfish sterols in bile 6.3 +/- 1.7-fold relative to the plasma shellfish sterol concentration whereas the study subject was only able to concentrate them 2.1-fold. We propose that sitosterolemia and xanthomatosis occur from a generalized abnormality in the usual ability of the gut mucosa and other tissues of the body to discriminate among many different sterols. This has important implications for the understanding of the pathophysiology of this disease and for therapeutic recommendations.
The Paradox of Disease Prevention
Authors: Harvey V. Fineberg
Journal: JAMA (2013)

Prevention of disease is often difficult to put into practice. Among the obstacles: the success of prevention is invisible, lacks drama, often requires persistent behavior change, and may be long delayed; statistical lives have little emotional effect, and benefits often do not accrue to the payer; avoidable harm is accepted as normal, preventive advice may be inconsistent, and bias against errors of commission may deter action; prevention is expected to produce a net financial return, whereas treatment is expected only to be worth its cost; and commercial interests as well as personal, religious, or cultural beliefs may conflict with disease prevention. Six strategies can help overcome these obstacles: (1) Pay for preventive services. (2) Make prevention financially rewarding for individuals and families. (3) Involve employers to promote health in the workplace and provide incentives to employees to maintain healthy practices. (4) Reengineer products and systems to make prevention simpler, lower in cost, and less dependent on individual action. (5) Use policy to reinforce choices that favor prevention. (6) Use multiple media channels to educate, elicit health-promoting behavior, and strengthen healthy habits. Prevention of disease will succeed over time insofar as it can be embedded in a culture of health.
Axl, A Receptor Tyrosine Kinase, Mediates Flow-Induced Vascular Remodeling
Authors: Vyacheslav A. Korshunov, Amy M. Mohan, Mary A. Georger, Bradford C. Berk
Journal: Circulation Research (2006)

Intima-media thickening (IMT) in response to hemodynamic stress is a physiological process that requires coordinated signaling among endothelial, inflammatory, and vascular smooth muscle cells (VSMC). Axl, a receptor tyrosine kinase, whose ligand is Gas6, is highly induced in VSMC after carotid injury. Because Axl regulates cell migration, phagocytosis and apoptosis, we hypothesized that Axl would play a role in IMT. Vascular remodeling in mice deficient in Axl (Axl(-/-)) and wild-type littermates (Axl(+/+)) was induced by ligation of the left carotid artery (LCA) branches maintaining flow via the left occipital artery. Both genotypes had similar baseline hemodynamic parameters and carotid artery structure. Partial ligation altered blood flow equally in both genotypes: increased by 60% in the right carotid artery (RCA) and decreased by 80% in the LCA. There were no significant differences in RCA remodeling between genotypes. However, in the LCA Axl(-/-) developed significantly smaller intima+media compared with Axl(+/+) (31+/-4 versus 42+/-6x10(-6) microm3, respectively). Quantitative immunohistochemistry of Axl(-/-) LCA showed increased apoptosis compared with Axl(+/+) (5-fold). As expected, p-Akt was decreased in Axl(-/-), whereas there was no difference in Gas6 expression. Cell composition also changed significantly, with increases in CD45+ cells and decreases in VSMC, macrophages, and neutrophils in Axl(-/-) compared with Axl(+/+). These data demonstrate an important role for Axl in flow-dependent remodeling by regulating vascular apoptosis and vascular inflammation.
Specific knockdown of uPA/uPAR attenuates invasion in glioblastoma cells and xenografts by inhibition of cleavage and trafficking of Notch -1 receptor
Authors: Hari Raghu, Christopher S Gondi, Dzung H Dinh, Meena Gujrati, Jasti S Rao
Journal: Molecular Cancer (2011)

Abstract Background uPA/uPAR is a multifunctional system that is over expressed in many cancers and plays a critical role in glioblastoma (GBM) invasion. Previous studies from our lab have also shown that uPA/uPAR down regulation inhibits cancer cell invasion in SNB 19 GBM cells. Methods As Notch 1 is known to be over expressed and promotes invasion in glioblastoma, we therefore tested our hypothesis of whether down regulation of uPA/uPAR, singly or in tandem, attenuates GBM invasion via Notch 1 receptor. Targeted down regulation of uPA/uPAR, either singly or simultaneously, inhibited the anchorage independent growth of U251MG and GBM xenograft cell lines 4910 and 5310 as assessed by soft agar colony formation assay. Expression of all four Notch receptors was confirmed in GBM tissue array analysis by immunohistochemistry. Results Down regulation of uPA/uPAR, either singly or simultaneously, in U251 MG and tumor xenografts inhibited the cleavage of the Notch receptor between the Gly 1743 and Val 1744 positions, thereby suggesting inhibition of activated cytosolic fragment-related Notch gene transcription. Morphological analysis confirmed inhibition of NICD when U251 MG cells were treated with puPA, puPAR or pU2. uPA/uPAR down regulation inhibited Notch 1 mRNA in all three examined cell lines. uPA/uPAR shRNA down regulated nuclear activation of NF-κB subunits and phosphorylation of AKT/mTOR pathway in U251 MG and GBM xenografts. puPA down regulated NICD and HES induced phosphorylation of AKT/ERK and NF-κB. Down regulation of Notch 1 using siRNA inhibited uPA activity as shown by fibrinogen zymography. It also decreased uPA expression levels as shown by western blotting. Exogenous addition of uPA activated Notch 1 in uPAR antisense U251 MG cells and also in uPAR antisense cells transfected with siRNA against Delta and Jagged. The Notch 1 receptor co-localized with LAMP-1, a marker for lysosomes in uPA, uPAR and U2, down regulated U251 MG cells which probably indicates inhibition of Notch 1 receptor trafficking in GBM cells. Notch 1 expression was significantly inhibited in puPA- and pU2-treated pre-established intracranial tumors in mice. Conclusions Overall our results show that down regulation of uPA/uPAR, either singly or simultaneously, could be an effective approach to attenuate Notch 1 receptor cleavage, signaling and endosomal trafficking in U251MG cells and xenografts, and ultimately inhibiting GBM invasion.
Circulating hyaluronate in psoriasis
Authors: A. LUNDIN, A. ENGSTROM-LAURENT, R. HALLGREN, G. MICHAELSSON
Journal: British Journal of Dermatology (1985)

Journal Article Circulating hyaluronate in psoriasis Get access A. LUNDIN, A. LUNDIN Department of Dermatology, Uppsala, Sweden Asa Lundin, M.D., Department of Dermatology, University Hospital, S‐75185 Uppsala, Sweden. Search for other works by this author on: Oxford Academic Google Scholar A. ENGSTRÖM‐LAURENT, A. ENGSTRÖM‐LAURENT Department of Institute of Medical and Physiological Chemistry, Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar R. HÄLLGREN, R. HÄLLGREN Department of Internal Medicine, University Hospital Search for other works by this author on: Oxford Academic Google Scholar G. MICHAËLSSON G. MICHAËLSSON Department of Dermatology, Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 6, 1 June 1985, Pages 663–671, https://doi.org/10.1111/j.1365-2133.1985.tb02334.x Published: 01 June 1985 Article history Accepted: 07 November 1984 Published: 01 June 1985