tbuckley/cabot-search huggingface dataset:
The Effect of Progesterone on the Regulatory Mechanisms of Biliary Cholesterol Secretion in the Rat
Authors: Flavio O. Nervi, Reginald Del Pozo, Carmen F. Covarrubias, Beatriz O. Ronco
Journal: Hepatology (1983)

We tested the hypothesis that progesterone, an inhibitor of cholesterol esterification in liver microsomes, increases biliary cholesterol output by increasing the availability of cholesterol. Initial bile samples of 20 min were obtained from acute bile fistula rats after seven daily doses of progesterone (5 to 55 mg per kg of body weight). Biliary cholesterol output correlated with the doses of progesterone, r = 0.64 (p &lt; 0.005). A 100% increment in biliary cholesterol output was obtained with progesterone doses of 30 to 55 mg per kg of body weight. Under these conditions, biliary phospholipid output increased 50% (p &lt; 0.02), but bile salt output remained normal. The relationship between biliary cholesterol and phospholipids as a function of bile salt output was studied after acute depletion of the bile salt pool. A rectangular hyperbola was the best curve fitting for the experimental data in control and progesterone-injected rats. In the physiological range of bile salt output, between 60 and 120 nmoles per gm per min, progesterone-injected rats secreted 100% more biliary cholesterol than did cntrols. The calculated theoretical maximal cholesterol and phospholipid outputs were significantly increased in progesterone-injected animals. Serum and hepatic cholesterol pool, free and ester fractions, remained normal. The acyl-CoA: cholesterol acyltransferase reaction was 30% inhibited in hepatic microsomes of progesterone-injected rats, (p &lt; 0.05). The changes in biliary phospholipids and cholesterol output produced by progesterone were rapidly reversed by either 0.5% cholesterol feeding or 2 mg per kg of body weight ethynyl estradiol injection. These manipulations simultaneously produced a 100% increment in the microsomal acyl-CoA: cholesterol acyltransferase activity (p &lt; 0.005) and increased 4-fold the concentration of hepatic cholesterol esters. This experimental model suggests a functional interrelationship between biliary cholesterol output and the rate at which the liver esterifies cholesterol.
Influence of adenosine receptor blockade on renal function and renal autoregulation.
Authors: A M Ibarrola, E W Inscho, R C Vari, L G Navar
Journal: Journal of the American Society of Nephrology (1991)

Experiments were conducted in anesthetized dogs to evaluate the effects of adenosine receptor blockade on renal function and on autoregulation of total RBF and outer cortical blood flow. After control measurements, the adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfophenylxanthine (PSPX) was infused intrarenally for 45 min at 2 or 6 microM/min. Responses to PSPX were compared with those obtained during infusions of either aminophylline or theophylline. PSPX infusion led to substantial increases in urine flow and sodium excretion (four- to fivefold). RBF increased significantly; however, outer cortical blood flow and GFR were not significantly altered. PRA increased twofold during PSPX infusion. The vasoconstrictor responses to bolus injections of 2-chloroadenosine (100 mumol) were attenuated by 58 and 86% during the low and high doses of PSPX and to a lesser extent with aminophylline/theophylline infusions. At renal arterial pressures above the inflection point, the slope of the average pressure-flow relationship during PSPX infusion was close to zero and was not significantly different from control. Similarly, autoregulatory capability was not altered during infusions of theophylline or aminophylline. These data provide further evidence that endogenous adenosine contributes substantially to the control of renin release but only modestly to the control of RBF and GFR and to renal autoregulatory capability. The natriuretic responses during adenosine blockade, which occurred in the face of elevated renin levels, support the hypothesis that endogenous adenosine enhances tubular sodium reabsorption rate.
Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas
Authors: Christine H. Chung, Kim Ely, Loris McGavran, Marileila Varella-Garcia, Joel Parker, Natalie Parker, Carolyn Jarrett, Jesse Carter, Barbara A. Murphy, James Netterville, Brian B. Burkey, Robert Sinard, Anthony Cmelak, Shawn Levy, Wendell G. Yarbrough, Robbert J.C. Slebos, Fred R. Hirsch
Journal: Journal of Clinical Oncology (2006)

High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC.EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points.Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors.High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.
A Prospective Analysis of Marital Relationship Factors and Quality of Life in Diabetes
Authors: Paula M. Trief, Michael J. Wade, Kirsten Dee Britton, Ruth S. Weinstock
Journal: Diabetes Care (2002)

To prospectively assess the relation between marital relationship domains (i.e., intimacy and adjustment) and health-related quality of life (HRQoL) and glycemic control of individuals with diabetes.A previous cross-sectional study assessed the relationship between marital quality and adaptation to diabetes for 78 insulin-treated adults. Each participant completed two marital quality measures (Spanier Dyadic Adjustment Scale and Personal Assessment of Intimacy in Relationships Scale) at time 1 (T1). A total of 61 subjects were contacted two years later (time 2 [T2]) and re-administered four HRQoL measures (Diabetes Quality of Life Scale, Medical Outcomes Study Health Survey-SF36, Problem Areas in Diabetes Scale, and Positive and Negative Affect Schedule). Glycemic control was assessed by HbA(1c). Demographic data (age, sex, type and duration of diabetes, years married, other medical problems, family history, and years of education) were gathered from charts and questionnaires. Linear regression analyses were used to assess the ability of the two marital measures at T1 to predict HRQoL at T2, controlling for confounding HRQoL and baseline subject variables.Both of the marital quality measures at T1 were prospective predictors of aspects of HRQoL at T2. Less diabetes-related distress at T2 was predicted by better marital adjustment at T1. Greater satisfaction with aspects of the diabetes care regimen at T2 was predicted by better marital adjustment and greater perceived marital intimacy at T1. Neither marital measure predicted general HRQoL or glycemic control.For insulin-treated adults with diabetes, quality of marriage prospectively predicts diabetes-related quality of life. This study highlights the sensitivity of diabetes-specific measures. Future work should explore the value of interventions that target the spouse and/or couple.
Effect of increased pressure on tracheal ciliary beat frequency
Authors: J.H. Calvet, F Verra, J. Maleine, M.c Millepied, A. Harf, E. Escudier
Journal: European Respiratory Journal (1999)

Effects of increased ambient pressure on mucociliary clearance have been poorly investigated. The effects of increasing pressures on ciliary beat frequency (CBF) of guinea-pig tracheal rings were studied in vitro. Increased pressures of 25 and 100 kPa induced a significant and equivalent enhancement of CBF from 30 min after the pressure increase. The increase in CBF observed after a pressure increase of 50 kPa (inspiratory oxygen fraction = 21%), was significantly greater than that observed with an equivalent oxygen tension at atmospheric pressure, i.e. with a gas mixture containing 30% oxygen. Addition of N(G)-nitro-L-arginine methylester (L-NAME) inhibited the enhancement in CBF observed after the 25 kPa pressure increase. Addition of L-arginine reversed the effect of L-NAME. These results demonstrate that a pressure increase applied to tracheal rings, in vitro, induces an enhancement of ciliary beat frequency and that generation of nitric oxide may be involved in this ciliary stimulation.
Inhibition of Cytochrome P450ω-Hydroxylase
Authors: Kasem Nithipatikom, Eric R. Gross, Michael P. Endsley, Jeannine M. Moore, Marilyn A. Isbell, John R. Falck, William B. Campbell, Garrett J. Gross
Journal: Circulation Research (2004)

Cytochrome P450s (CYP) and their arachidonic acid (AA) metabolites have important roles in regulating vascular tone, but their function and specific pathways involved in modulating myocardial ischemia–reperfusion injury have not been clearly established. Thus, we characterized the effects of several selective CYPω-hydroxylase inhibitors and a CYPω-hydroxylase metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), on the extent of ischemia–reperfusion injury in canine hearts. During 60 minutes of ischemia and particularly after 3 hours of reperfusion, 20-HETE was produced at high concentrations. A nonspecific CYP inhibitor, miconazole, and 2 specific CYPω-hydroxylase inhibitors, 17-octadecanoic acid (17-ODYA) and N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), markedly inhibited 20-HETE production during ischemia–reperfusion and produced a profound reduction in myocardial infarct size (expressed as a percent of the area at risk) (19.6±1.7% [control], 8.4±2.5% [0.96 mg/kg miconazole], 5.9±2.2% [0.28 mg/kg 17-ODYA], and 10.8±1.8% [0.40 mg/kg DDMS], P &lt;0.05, respectively). Conversely, exogenous 20-HETE administration significantly increased infarct size (26.9±1.9%, P &lt;0.05). Several CYPω-hydroxylase isoforms, which are known to produce 20-HETE such as CYP4A1, CYP4A2, and CYP4F, were demonstrated to be present in canine heart tissue and their activity was markedly inhibited by incubation with 17-ODYA. These results indicate an important endogenous role for CYPω-hydroxylases and in particular their product, 20-HETE, in exacerbating myocardial injury in canine myocardium. The full text of this article is available online at http://circres.ahajournals.org.
The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation.
Authors: N W Lukacs, S L Kunkel, R M Strieter, K Warmington, S W Chensue
Journal: The Journal of Experimental Medicine (1993)

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a 6-8-kD, lipopolysaccharide-inducible monocyte and neutrophil chemotactic protein that may be important in acute and chronic inflammation. The present study determined the sequential production, source, and in vivo contribution of murine MIP-1 alpha in synchronized Schistosoma mansoni egg pulmonary granuloma formation. Granulomas were examined under conditions of primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1 alpha was measured in 24-h supernatants from intact granulomas (700/ml) cultured with or without soluble egg antigen (SEA). Primary granulomas isolated from naive mice over a 16-d period showed low spontaneous MIP-1 alpha production (&amp;lt; 1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1 alpha production was observed beginning at day 4 and peaking at day 16. Intact vigorous (isolated from 8-wk-infected mice) and modulated (isolated from 20-wk-infected mice) secondary pulmonary granulomas demonstrated comparable spontaneous MIP-1 alpha production. Addition of SEA to vigorous stage granulomas augmented expression of MIP-1 alpha at all time points, whereas stimulated modulated stage granulomas did not increase production. The latter observation is likely related to endogenous immunoregulatory mechanisms reported for modulated stage animals. Immunohistochemical localization of MIP-1 alpha in granuloma sections and cytocentrifuge preparations from vigorous lesions localized MIP-1 alpha production to macrophages within granulomas. Treatment of mice with rabbit anti-mouse MIP-1 alpha antibodies significantly decreased 8-d primary granuloma formation (&amp;gt; 40%) when compared with control mice. Anti-MIP-1 alpha sera also decreased vigorous (&amp;gt; 20%), but not modulated granuloma formation. These findings demonstrate that MIP-1 alpha contributes to cellular recruitment during schistosome egg granuloma formation.
Antisense oligonucleotide therapy for neurodegenerative disease
Authors: R. A. Smith
Journal: Journal of Clinical Investigation (2006)

Neurotoxicity from accumulation of misfolded/mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Since decreasing levels of proteins responsible for such accumulations is likely to ameliorate disease, a therapeutic strategy has been developed to downregulate almost any gene in the CNS. Modified antisense oligonucleotides, continuously infused intraventricularly, have been demonstrated to distribute widely throughout the CNS of rodents and primates, including the regions affected in the major neurodegenerative diseases. Using this route of administration, we found that antisense oligonucleotides to superoxide dismutase 1 (SOD1), one of the most abundant brain proteins, reduced both SOD1 protein and mRNA levels throughout the brain and spinal cord. Treatment initiated near onset significantly slowed disease progression in a model of amyotrophic lateral sclerosis (ALS) caused by a mutation in SOD1. This suggests that direct delivery of antisense oligonucleotides could be an effective, dosage-regulatable means of treating neurodegenerative diseases, including ALS, where appropriate target proteins are known.
Phase II Trial of Preoperative Chemoradiation in Patients With Localized Gastric Adenocarcinoma (RTOG 9904): Quality of Combined Modality Therapy and Pathologic Response
Authors: Jaffer A. Ajani, Kathryn Winter, Gordon S. Okawara, John H. Donohue, Peter W.T. Pisters, Christopher H. Crane, John F. Greskovich, P. Rani Anne, Jeffrey D. Bradley, Christopher Willett, Tyvin A. Rich
Journal: Journal of Clinical Oncology (2006)

Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points.Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points.Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified.For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.
Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer
Authors: G. Lurje, W. Zhang, A.M. Schultheis, D. Yang, S. Groshen, A.E. Hendifar, H. Husain, M.A. Gordon, F. Nagashima, H.M. Chang, H.-J. Lenz
Journal: Annals of Oncology (2008)
Psychological Characteristics of Frequent Short-Notice Cancellers of Diabetes Medical and Education Appointments
Authors: Katie Weinger, Sheila J. McMurrich, Joyce P. Yi, Susan Lin, Myriel Rodriguez
Journal: Diabetes Care (2005)

Failure to attend scheduled medical appointments increases the cost of medical care (1) and may impact successful diabetes management (2). Short-notice cancellations of medical or educator appointments (no-shows and cancellations made within 24 h of an appointment) cannot be easily filled, resulting in lost revenue without a corresponding reduction in labor and facilities costs. Short-notice cancellations also impact the quality of overall patient care. Such cancellations reduce the number of appointments available to all patients, thus some patients needing more prompt medical attention may be placed on a waitlist. Furthermore, less frequent attendance at a diabetes clinic has been associated with poorer glycemic control (3). Finally, health professionals may develop negative attitudes toward those patients who frequently cancel appointments (4), which may undermine the clinician-patient relationship.

Although previous studies have attempted to identify demographic characteristics of patients who either did not schedule, cancelled, or did not attend appointments (2,5–12), we focused on psychological characteristics of patients with short-notice cancellations and the impact of these cancellations on successful diabetes management and cost of care. Specifically, in a prospective study, we asked whether short-notice cancellers differed in risk appraisal, coping processes, attitudes toward diabetes, and diabetes self-management from those who never cancelled.

We followed 134 diabetes patients …
LOCALIZATIONS OF THE VIRUS OF POLIOMYELITIS IN THE CENTRAL NERVOUS SYSTEM DURING THE PREPARALYTIC PERIOD, AFTER INTRANASAL INSTILLATION
Authors: Harold K. Faber, Louis P. Gebhardt
Journal: The Journal of Experimental Medicine (1933)

1. About 4 days after intranasal instillation, the virus of poliomyelitis establishes its initial focus, within the central nervous system, in the olfactory bulbs. It apparently reaches this structure through the axons of the olfactory nerves after primarily infecting the olfactory cells of the nasal mucosa. 2. From this initial focus, the virus spreads (on the 5th and 6th days) through the olfactory tracts and their connections in the brain stem. A secondary focus in the hypothalamus is first established. From this, two main channels can be discerned: first, to the medulla; second, to the thalamus and midbrain. 3. On the 7th day, virus can first be detected in the spinal cord. It is widespread but is found in larger amounts in the cervical than in the lumbar segments. It is present in both the anterior and posterior horns, either in equal amounts or in slightly larger amounts in the posterior. It is also present in the intervertebral ganglia. The surmise is presented that the main route of infection of the cord is not from the medulla (which had been infected as early as the 5th day) but along the sensory tracts, presumably from the thalamus (spinothalamic tracts). 4. Certain portions of the central nervous system were never found to contain demonstrable quantities of virus: these were the cortex of the frontal and parietal lobes (neopallium), and the cerebellum. The olfactory (archipallial) cortex (hippocampus) was only once found to contain virus; this occurred on the 7th day and in small amounts, and presumably had its source in the olfactory bulbs. 5. The experiments of the 7th day suggest that virus had died out in areas previously infected (in the hypothalamus and thalamus, particularly), while continuing, apparently undiminished, in the midbrain and medulla, and spreading to the cord. These observations are in harmony with the general contentions of Fairbrother and Hurst that virus is better adapted to survival in the lower portions of the cerebrospinal axis than in the higher. 6. The conception here presented of the manner of entrance and routes of propagation of the virus of poliomyelitis in the experimental animal appears to be in essential agreement with the clinical and pathological characteristics of the disease in man. Both the experimental disease and the disease as it occurs in man appear to present the features of an infection spread through nervous tissue only. It is unnecessary to assume that at any stage of its progress, during the incubation period or later, systemic or general extranervous infection is present.