tbuckley/cabot-search huggingface dataset:
β-2-Microglobulin Is an Androgen-Regulated Secreted Protein Elevated in Serum of Patients with Advanced Prostate Cancer
Authors: Mitchell Gross, Irina Top, Isett Laux, Jonathan Katz, John Curran, Charles Tindell, David Agus
Journal: Clinical Cancer Research (2007)

A better understanding of secreted proteins may lead to the discovery of new biomarkers, which, along with prostate-specific antigen (PSA), may be useful in the diagnosis and treatment of prostate cancer patients.Conditioned medium was collected from LNCaP cells following stimulation with methyltrienolone (R1881), 17beta-estradiol (estradiol), or interleukin-6 and analyzed for differential protein expression with surface-enhanced laser desorption/ionization-time of flight mass spectrometry. Quantitative reverse transcription-PCR, immunoblots, and ELISA were used to measure beta-2-microglobulin (B2M) message and protein levels in cells, conditioned medium, and serum.Surface-enhanced laser desorption/ionization-time of flight revealed that many peaks were induced or repressed following stimulation with R1881 or estradiol. A peak of interest centered at 11.8 kDa was chosen for additional analysis. Immunodepletion identified the peak of interest as B2M. Reverse transcription-PCR and immunoblots confirmed that PSA and B2M were induced by R1881. However, unlike PSA, B2M was not increased on stimulation with estradiol or interleukin-6. Human B2M is identified in the serum of mice bearing human prostate cancer xenograft. B2M is expressed in human prostate cancer cell lines and tissues. Serum B2M levels are elevated in patients with metastatic, androgen-independent prostate cancer.B2M is a secreted protein expressed in prostate cancer, which is more specific for androgen stimulation than PSA under the conditions tested. Additional studies are warranted to explore if B2M is as useful marker for prostate cancer. Identification of proteins secreted from cancer cells in preclinical models may be a useful strategy for biomarker discovery.
Analysis of 4-aminobiphenyl-DNA adducts in human urinary bladder and lung by alkaline hydrolysis and negative ion gas chromatography-mass spectrometry.
Authors: D Lin, J O Lay, M S Bryant, C Malaveille, M Friesen, H Bartsch, N P Lang, F F Kadlubar
Journal: Environmental Health Perspectives (1994)

Analysis of carcinogen-DNA adducts has been regarded as a useful means of assessing human exposure to chemical carcinogens. We have established a method for quantitation of 4-aminobiphenyl (4-ABP)-DNA adducts by alkaline hydrolysis and gas chromatography with negative ion chemical ionization mass spectrometry (GC-NICI-MS). Aliquots of DNA (typically 100 micrograms/ml) were spiked with an internal standard, d9-4-ABP, and were hydrolyzed in 0.05 N NaOH at 130 degrees C overnight. The liberated 4-ABP was extracted with hexane and derivatized using pentafluoropropionic anhydride in trimethylamine for 30 min at room temperature prior to GC-NICI-MS. With in vitro [3H]N-hydroxy-4-ABP modified DNA standards, we observed 59 +/- 7% (n = 9) recovery of the 4-ABP and a linear correlation between hydrolyzed 4-ABP and the adduct levels ranging from about 1 in 10(8) to 1 in 10(4) nucleotides (r = 0.999, n = 9). The method was further validated by comparison of the results with that obtained by the 32P-postlabeling method. There was excellent agreement (r = 0.994, p < 0.001) between the two methods for quantitation of the adduct in eight samples of Salmonella typhimurium DNA treated with 4-ABP and rat liver S9, although the 32P-postlabeling method gave slightly higher values. The DNA adducts in 11 human lung and 8 urinary bladder mucosa specimens were then determined by our GC-NICI-MS method. The adduct levels were found to be < 0.32 to 49.5 adducts per 10(8) nucleotides in the lungs and < 0.32 to 3.94 adducts per 10(8) nucleotides in the bladder samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Dose and Time Effects of Caffeine Intake on Human Platelet Adenosine A <sub>2A</sub> Receptors
Authors: Katia Varani, Francesco Portaluppi, Stefania Gessi, Stefania Merighi, Ennio Ongini, Luiz Belardinelli, Pier Andrea Borea
Journal: Circulation (2000)

BACKGROUND-We determined whether repeated caffeine administration at different dosages and for different periods of time (400 or 600 mg/d for 1 week or 400 mg/d for 2 weeks) upregulates human platelet adenosine A(2A) receptors and is accompanied by increases in cAMP accumulation and decreases in aggregation and calcium levels after stimulation of A(2A) receptors by the selective agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA). METHODS AND RESULTS-Platelets were obtained from peripheral venous blood of 45 healthy human volunteers at the end of 2 weeks of caffeine abstinence and at 12, 60, and 108 hours after the last dose of caffeine. The lowest dose of caffeine, when given for only 7 days, had no effect. Increasing the total dose, either by giving 400 mg/d for 14 days or giving 600 mg/d, resulted in binding assays performed with the adenosine A(2A) receptor radioligand [(3)H]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]pyrimidine], in the upregulation of A(2A) receptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a rise in cAMP accumulation, and a decrease in calcium levels was significantly increased. CONCLUSIONS-Chronic caffeine intake can lead to upregulation of adenosine A(2A) receptors, which is accompanied by sensitization, in a time- and dose-dependent manner, to the actions of the agonist HE-NECA.
Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial
Authors: David A. Morrow, Benjamin M. Scirica, Bernard R. Chaitman, Darren K. McGuire, Sabina A. Murphy, Ewa Karwatowska-Prokopczuk, Carolyn H. McCabe, Eugene Braunwald
Journal: Circulation (2009)

Ranolazine is a novel antianginal shown in an exploratory analysis in patients with diabetes mellitus and chronic angina to be associated with a decline in hemoglobin A(1c) (HbA(1c)). We designed a prospective evaluation of the effect of ranolazine on hyperglycemia as part of a randomized, double-blind, placebo-controlled outcomes trial.We compared HbA(1c) (percentage) and the time to onset of a > or =1% increase in HbA(1c) among 4918 patients with acute coronary syndrome randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Ranolazine significantly reduced HbA(1c) at 4 months compared with placebo (5.9% versus 6.2%; change from baseline, -0.30 versus -0.04; P<0.001). In patients with diabetes mellitus treated with ranolazine, HbA(1c) declined from 7.5 to 6.9 (change from baseline, -0.64; P<0.001). Diabetic patients were more likely to achieve an HbA(1c) <7% at 4 months with ranolazine compared with placebo (59% versus 49%; P<0.001) and were less likely to have a > or =1% increase in HbA(1c) (14.2% versus 20.6% at 1 year; hazard ratio, 0.63; 95% confidence interval, 0.51 to 0.77; P<0.001). Moreover, ranolazine reduced recurrent ischemia in diabetic patients (hazard ratio, 0.75; 95% confidence interval, 0.61 to 0.93; P=0.008). Notably, in patients without diabetes mellitus at baseline, the incidence of new fasting glucose >110 mg/dL or HbA(1c) > or =6% was reduced by ranolazine (31.8% versus 41.2%; hazard ratio, 0.68; 95% confidence interval, 0.53 to 0.88; P=0.003). Reported hypoglycemia did not increase with ranolazine (P=NS).Ranolazine significantly improved HbA(1c) and recurrent ischemia in patients with diabetes mellitus and reduced the incidence of increased HbA(1c) in those without evidence of previous hyperglycemia. The mechanism of this effect is under investigation.
Haptoglobin-haemoglobin complex in human plasma inhibits endothelium dependent relaxation: evidence that endothelium derived relaxing factor acts as a local autocoid
Authors: D H EDWARDS, T M GRIFFITH, H C RYLEY, A H HENDERSON
Journal: Cardiovascular Research (1986)

Journal Article Haptoglobin-haemoglobin complex in human plasma inhibits endothelium dependent relaxation: evidence that endothelium derived relaxing factor acts as a local autocoid Get access D H EDWARDS, D H EDWARDS **From the Departments of Cardiology, University of Wales College of Medicine, Cardiff. Search for other works by this author on: Oxford Academic PubMed Google Scholar T M GRIFFITH, T M GRIFFITH **From the Departments of Cardiology, University of Wales College of Medicine, Cardiff. Search for other works by this author on: Oxford Academic PubMed Google Scholar H C RYLEY, H C RYLEY **From the Departments of Cardiology, University of Wales College of Medicine, Cardiff. Search for other works by this author on: Oxford Academic PubMed Google Scholar A H HENDERSON A H HENDERSON **From the Departments of Cardiology, University of Wales College of Medicine, Cardiff. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 20, Issue 8, August 1986, Pages 549–556, https://doi.org/10.1093/cvr/20.8.549 Published: 01 August 1986
Blood Lead Concentration and Thyroid Function during Pregnancy: Results from the Yugoslavia Prospective Study of Environmental Lead Exposure
Authors: Linda G. Kahn, Xinhua Liu, Biljana Rajovic, Dusan Popovac, Sharon Oberfield, Joseph H. Graziano, Pam Factor-Litvak
Journal: Environmental Health Perspectives (2014)

Although maternal hypothyroidism increases the risk of adverse neonatal and obstetric outcomes as well as lower IQ in children, the environmental determinants of maternal thyroid dysfunction have yet to be fully explored.We aimed to examine associations between mid-pregnancy blood lead (BPb) and concomitant measures of thyroid function among participants in the Yugoslavia Prospective Study of Environmental Lead Exposure.As part of a population-based prospective study of two towns in Kosovo-one with high levels of environmental lead and one with low-women were recruited during the second trimester of pregnancy, at which time blood samples and questionnaire data were collected. We measured concentrations of BPb, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibodies (TPOAb) in archived serum samples.Compared with women from the unexposed town, women from the exposed town had lower mean FT4 (0.91 ± 0.17 vs. 1.03 ± 0.16 ng/dL), higher mean TPOAb (15.45 ± 33.08 vs. 5.12 ± 6.38 IU/mL), and higher mean BPb (20.00 ± 6.99 vs. 5.57 ± 2.01 μg/dL). No differences in TSH levels were found. After adjustment for potential confounders, for each natural log unit increase in BPb, FT4 decreased by 0.074 ng/dL (95% CI: -0.10, -0.046 ng/dL), and the odds ratio for testing positive to TPOAb was 2.41 (95% CI: 1.53, 3.82). We found no association between BPb and TSH.Prolonged lead exposure may contribute to maternal thyroid dysfunction by stimulating autoimmunity to the thyroid gland.
CAPILLARITY IN INTESTINAL SUTURES.
Authors: F. GREGORY CONNELL
Journal: JAMA (1906)

The histology of intestinal repair has been most comprehensively studied and described by many investigators, such as Warren,<sup>1</sup>Senn,<sup>2</sup>Murphy<sup>3</sup>and many others. The strength of the union has been determined by its resistance to hydrostatic pressure, in the observations of Chlumsky<sup>4</sup>and of Horsley.<sup>5</sup>The capillary action of the suture material has been spoken of by many writers, but no experimental data have been noted in available literature. The subject of capillarity in intestinal suturing is worthy of consideration and study, for the reason that the fear of infecting the peritoneal cavity by capillarity has been the cause of attempts to include but a part of the intestinal wall in the bight of the stitch and, in consequence, the introduction of stitches that have yielded and so proved to be insecure. Capillarity in this connection is generally understood to mean the seepage, creeping or
Effect of Tachycardia Heart Failure on the Restitution of Left Ventricular Function in Closed-Chest Dogs
Authors: Sumanth D. Prabhu, Gregory L. Freeman
Journal: Circulation (1995)

Cardiac mechanical restitution and relaxation restitution are thought to be physiological correlates of the recovery kinetics of Ca2+ release mechanisms and sequestration capacity of the sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ handling, we sought to delineate changes in mechanical and relaxation restitution produced by heart failure.Six dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions and after tachycardia heart failure (THF) produced by rapid LV pacing for 3 to 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at graded extrasystolic intervals (ESIs). Mechanical response was assessed from single-beat elastance. Relaxation was assessed from the time constant of isovolumic relaxation (tau), the average rate of pressure fall during isovolumic relaxation (Ravg), and peak negative dP/dt, the first derivative of LV pressure. Normalized mechanical and relaxation responses plotted against ESI produced monoexponential curves of mechanical and relaxation restitution. THF depressed baseline contractile and relaxation parameters compared with control (end-systolic elastance, 4.7 +/- 0.4 versus 7.1 +/- 0.5 mm Hg/mL, P < .005; tau, 34.8 +/- 2.2 versus 26.7 +/- 1.2 ms, P < .05; all values mean +/- SEM). THF slowed mechanical restitution and delayed development of peak contractile response, with the time constant of mechanical restitution increasing from 61.8 +/- 6.9 to 100.2 +/- 9.6 ms, P < .01. THF abolished the biphasic behavior of relaxation restitution, and this relation was approximated by a single monoexponential function. There was no difference in the time constants of the first phase of relaxation restitution at control and after THF (TCR1, normalized 1/Ravg, 44.3 +/- 5.6 versus 42.0 +/- 8.5 ms, P = NS; TCR1, normalized (dP/dtmin)-1, 42.2 +/- 6.3 versus 36.7 +/- 4.3 ms, P = NS).These results indicate that THF alters the recovery kinetics of SR Ca2+ release to a significantly greater extent than those of SR Ca2+ sequestration and that the abnormal time course of Ca2+ availability to the myofilaments is the rate-limiting step in the recovery of cardiac function after a depolarization.
Differences in adrenal cholesterol, ascorbic acid, circulating corticosterone and aldosterone during the onset of hypertension in SHR vs WKy rats
Authors: B C WEXLER, J P McMURTRY
Journal: Cardiovascular Research (1982)

Young adult male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were killed under strictly quiescent conditions when they became 24, 32, 44, 60, 90 and 120 days of age. Systolic blood pressure was measured just prior to autopsy. Adrenal glands were assayed for ascorbic acid and total cholesterol content, and examined histologically. At 60 days of age, the blood pressure of the SHR became abnormally elevated, reaching severely elevated levels by 120 days of age. The adrenal glands of SHR were consistently smaller than those of WKy but their zonae glomerulosae stained intensively positive for lipid. Adrenocortical ascorbate and cholesterol content remained consistently and significantly lower in SHR vs WKy as did circulating corticosterone levels. Plasma aldosterone levels rose concomitantly with rising blood pressure in SHR and became progressively lower with age in normotensive WKy. These findings suggest that corticosteroidogenesis is different in SHR vs normotensive WKy rats.
Synchronous Prostate Cancer Incidentally Detected by FDG-PET/CT in Staging a Patient With Newly Diagnosed Nasopharyngeal Cancer
Authors: Guang-Uei Hung, Ching-Yeh Hsiung, Ming-Li Huang, Shang-Tao Lin
Journal: Clinical Nuclear Medicine (2009)

A 59-year-old man with newly diagnosed nasopharyngeal cancer underwent FDG-PET/CT for whole-body survey. In addition to the nasopharyngeal area, the thyroid gland and ischium, abnormal FDG accumulation was also noted in the prostate. Transrectal ultrasound-guided biopsy confirmed the diagnosis of prostate adenocarcinoma. This case reminds us that FDG-PET (or PET/CT) has the potential to detect synchronous malignancies on oncologic work-ups and distal activities from primary tumors are not necessarily metastases from the primary lesion.
Results of Stereotactic Brachytherapy Used in the Initial Management of Patients With Glioblastoma
Authors: J. S. Loeffler, E. Alexander, P. Y. Wen, W. M. Shea, C. N. Coleman, H. M. Kooy, H. A. Fine, L. A. Nedzi, B. Silver, N. E. Riese, P. McL. Black
Journal: JNCI Journal of the National Cancer Institute (1990)

Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation.
917 ON-TREATMENT MONITORING OF HBsAg LEVELS TO PREDICT RESPONSE TO PEGINTERFERON ALFA-2A IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B
Authors: G.K.K. Lau, P. Marcellin, M. Brunetto, T. Piratvisuth, H.-P. Kapprell, D. Messinger, M. Popescu
Journal: Journal of Hepatology (2009)
Hepatic Vein Thrombosis (Budd-Chiari Syndrome)
Authors: Willis C. Maddrey
Journal: Hepatology (1984)

Hepatic vein thrombosis (Budd-Chiari Syndrome) is a rare disorder resulting from obstruction to the outflow of blood from the liver. The characteristic pathologic findings are intense congestion most pronounced around the terminal hepatic venules, cell necrosis, and a scant inflammatory reaction. Major clinical manifestations include hepatomegaly, right upper quadrant abdominal pain, and ascites. Disorders associated with hepatic vein thrombosis include those associated with a thrombotic tendency, such as polycythemia vera and paroxysmal nocturnal hemoglobinuria. Use of oral contraceptive agents probably increases tendency to develop hepatic vein thrombosis. Biochemical tests of the liver are of little value. The hepatic scan may be useful in suggesting the diagnosis with a marked decrease in uptake of isotope over affected areas of the liver. The diagnosis is confirmed by inferior vena caval and attempted hepatic venous catheterization. An associated thrombosis of the inferior vena cava is frequently found. Therapy in hepatic vein thrombosis is directed towards correction, in so far as possible, the underlying disorder, prevention of further extention of thrombosis, and management of ascites. Side-to-side portacaval or mesocaval shunt operation may convert the portal vein into an effective hepatic outflow vessel and reduce intrahepatic pressure and decrease injury. Mesoatrial shunts have proven useful in a few patients with hepatic vein thrombosis and either an inferior vena caval thrombosis or a marked pressure gradient from the abdomen to the thorax from ascites and an hypertrophied caudate lobe of the liver. For patients with extensive hepatocellular disease and portal hypertension, hepatic transplantation would seem to offer the best chance for survival.
Systolic Phases of the Cardiac Cycle in Children
Authors: DAVID GOLDE, LUIS BURSTIN
Journal: Circulation (1970)

The duration of the systolic phases of the cardiac cycle in 390 normal children was determined from high-speed simultaneous recordings of the electrocardiogram, phonocardiogram, apexcardiogram, and carotid pulse. Data were obtained on children 1 mo to 13 years of age and analyzed to define the independent effects of aging and heart rate on the systolic intervals. Electromechanical systole (Q-II) was found to prolong with increasing age in children with the same heart rate. Pre-ejection period was also prolonged in older children and occupied an increased percentage of total systole. The interval from onset of contraction to first sound varied inversely with heart rate and was independent of age. Electromechanical delay and isometric contraction time were directly related to age and independent of rate. Ejection time varied directly with age and inversely with heart rate but occupied a smaller percentage of systole in older children. Alterations in systolic phase duration occurring with maturation reflect the normal functional adaptation of the developing heart. Measurement of these phases can provide useful information relative to cardiac function in children.
Vertebral Coccidioidomycosis Presenting as Pott's Disease
Authors: Lewis J. Wesselius
Journal: JAMA (1977)

HUMAN disease induced by the fungus<i>Coccidioides immitis</i>is endemic to the southwestern United States. In the vast majority of persons affected, coccidioidomycosis affects only the respiratory tree. We report a case in which the condition presented as vertebral osteomyelitis resembles tuberculous spondylitis (Pott's disease). We wish to emphasize the similarities between these two entities and the importance of recognizing coccidioidomycosis in the differential diagnosis of Pott's disease. <h3>Report of a Case</h3> An 82-year-old man entered the Tucson Veterans Administration Hospital on November 15, 1976, with a four-month history of midthoracic back pain. He had first noted this discomfort following heavy exertion and lifting. During the two months prior to hospital admission there had been a 13-pound weight loss. He denied having cough, sputum production, fever, chills, or night sweats. The patient did recall a flu-like illness in January 1976, and in February 1976 a chest film had shown a
HEMORRHAGE CONTROLLED IN TWO CASES BY LOCAL APPLICATION OF HORSE-SERUM
Authors: CHARLES G. LEVISON
Journal: JAMA (1913)

For a number of years it has been an accepted procedure to employ serum hypodermatically in hemorrhage due to a diminished tendency of the blood to coagulate, and experience has proved this remedy very effective. Usually horse-serum has been employed in varying quantities and the results have been excellent in hemophilia, purpura, melena neonatorum and in operations associated with a long-continued icterus. Latterly transfusion has been performed, the donor being preferably one of the relatives.  The present opinion is that these serums undoubtedly have the effect of increasing the coagulability of the blood.  The following case-reports are offered as a contribution to bleeding that was controlled by the local application of the serum:  Case 1.—  History.  —The patient, aged 49, gave a history of having had, several years before, intermittent nose-bleed which was cured only after the turbinates had been removed; he had a moderate degree of arteriosclerosis. He