tbuckley/cabot-search huggingface dataset:
Increased formation of ursodeoxycholic acid in patients treated with chenodeoxycholic acid.
Authors: G Salen, G S Tint, B Eliav, N Deering, E H Mosbach
Journal: Journal of Clinical Investigation (1974)

The formation of ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, was investigated in three subjects with cerebrotendinous xanthomatosis and in four subjects with gallstones. Total biliary bile acid composition was analyzed by gas-liquid chromatography before and after 4 months of treatment with 0.75 g/day of chenodeoxycholic acid. Individual bile acids were identified by mass spectrometry. Before treatment, bile from cerebrotendinous xanthomatosis (CTX) subjects contained cholic acid, 85%; chenodeoxycholic acid, 7%; deoxycholic acid, 3%; allocholic acid, 3%; and unidentified steroids, 2%; while bile from gallstone subjects contained cholic acid, 45%; chenodeoxycholic acid, 43%; deoxycholic acid, 11%, and lithocholic acid, 1%. In all subjects, 4 months of chenodeoxycholic acid therapy increased the proportion of this bile acid to approximately 80% and decreased cholic acid to 3% of the total biliary bile acids, the remaining 17% of bile acids were identified as ursodeoxycholic acid. After the intravenous injection of [3H]chenodeoxycholic acid, the specific activity of biliary ursodeoxycholic acid exceeded the specific activity of chenodeoxycholic acid, and the resulting specific activity decay curves suggested precursor-product relationships. When [3H]7-ketolithocholic acid was administrated to another patient treated with chenodeoxycholic acid, radioactivity was detected in both the ursodeoxycholic acid and chenodeoxycholic acid fractions. These results indicate that substantial amounts of ursodeoxycholic acid are formed in patients treated with chenodeoxycholic acid. The ursodeoxycholic acid was synthesized from chenodeoxycholic acid presumably via 7-ketolithocholic acid.
P15.10 * COGNITIVE AND FUNCTIONAL STATUS OF PATIENTS AND QUALITY OF LIFE OF CAREGIVERS: A PROSPECTIVE STUDY IN A COHORT OF RECURRENT GLIOBLASTOMAS
Authors: A. Malabaila, E. Trevisan, M. Magistrello, L. Bertero, A. Pellerino, R. Ruda, R. Torta, R. Soffietti
Journal: Neuro-Oncology (2014)

INTRODUCTION: The diagnosis and treatment of brain tumors are often associated with physical, emotional and social wellness interruption and represent a life-changing event for patients and their families. High levels of psychological distress were found among patients and caregivers; conversely, social support has been identified as a powerful factor increasing life satisfaction of caregivers. Therefore, the primary purpose of this prospective study was to assess the relationships between cognitive and functional status of patients with recurrent glioblastoma receiving intravenous chemotherapy (bevacizumab and fotemustine) and quality of life of caregivers. Secondly, we analyzed changes in cognitive, functional and emotional status during the study period. PATIENTS AND METHODS: All couples patient/caregiver were evaluated 3 times during the assessment period (T0: before the start of chemotherapy; T1: 3 months later; T2: 6 months later). Each patient was assessed by the Mini Mental State Examination (MMSE) and Karnofsky Performance Status (KPS) to estimate cognitive and functional status. To investigate depression, anxiety and quality of life of caregivers we used the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A) and the Caregiver Quality of Life Cancer Scale (CQLCS). RESULTS: Thirty-five patients (17 M, 18 F; mean age = 53,74 ± 9,71) and thirty-five caregivers (15M, 20F; mean age = 52,54 ± 12,70) initially participated into the study, but thirty pairs only completed all assessments; as for the five patients who dropped out, two stopped chemotherapy due to myelotoxicity and three patients died for tumor progression. After regression analysis - including CQLCS score at baseline, HAM-A, HAM-D, MMSE and KPS scores and the response to treatment - quality of life of caregivers at T1 was significantly determined by CQLCS score at T0 (p = 0,001) and MMSE score at T1 (p = 0,011), while at T2 was determined by KPS score at T2 (p = 0,01). Furthermore, we found that scores obtained at MMSE and KPS declined during the evaluation period, as well as HAM-D and CQLCS, while HAM-A didn't change significantly. CONCLUSIONS: These data suggest that quality of life of caregivers after 3 months from the start of chemotherapy primarily are influenced by the initial quality of life and cognitive status of the patient, while after 6 months it depends on the functional status of the patient. One can hypothesize that cognitive decline of the patient has a strong impact on quality of life of caregiver only initially as at a later stage it is hidden by the functional status worsening. Anxiety changes during the evaluation period seem less important that the severity of anxiety in the early stage of the disease.
Divergent mechanisms for the insulin resistant and hyperresponsive glucose transport in adipose cells from fasted and refed rats. Alterations in both glucose transporter number and intrinsic activity.
Authors: B B Kahn, I A Simpson, S W Cushman
Journal: Journal of Clinical Investigation (1988)

The effects of fasting and refeeding on the glucose transport response to insulin in isolated rat adipose cells have been examined using 3-O-methylglucose transport in intact cells and cytochalasin B binding and Western blotting in subcellular membrane fractions. After a 72-h fast, basal glucose transport activity decreases slightly and insulin-stimulated activity decreases greater than 85%. Following 48 h of fasting, insulin-stimulated glucose transport activity is diminished from 3.9 +/- 0.5 to 1.3 +/- 0.3 fmol/cell per min (mean +/- SEM). Similarly, the concentrations of glucose transporters are reduced with fasting in both the plasma membranes from insulin-stimulated cells from 38 +/- 5 to 18 +/- 3 pmol/mg of membrane protein and the low density microsomes from basal cells from 68 +/- 8 to 34 +/- 9 pmol/mg of membrane protein. Ad lib. refeeding for 6 d after a 48-h fast results in up to twofold greater maximally insulin-stimulated glucose transport activity compared with the control level (7.1 +/- 0.4 vs. 4.5 +/- 0.2 fmol/cell per min), before returning to baseline at 10 d. However, the corresponding concentration of glucose transporters in the plasma membranes is restored only to the control level (45 +/- 5 vs. 50 +/- 5 pmol/mg of membrane protein). Although the concentration of glucose transporters in the low density microsomes of basal cells remains decreased, the total number is restored to the control level due to an increase in low density microsomal protein. Thus, the insulin-resistant glucose transport in adipose cells from fasted rats can be explained by a decreased translocation of glucose transporters to the plasma membrane due to a depleted intracellular pool. In contrast, the insulin hyperresponsive glucose transport observed with refeeding appears to result from (a) a restored translocation of glucose transporters to the plasma membrane from a repleted intracellular pool and (b) enhanced plasma membrane glucose transporter intrinsic activity.
Long-term Outcomes of Patients With Primary Biliary Cirrhosis and Hepatocellular Carcinoma
Authors: Mohamad H. Imam, Marina G. Silveira, Emmanouil Sinakos, Andrea A. Gossard, Roberta Jorgensen, Jill Keach, Alisha C. DeCook, Keith D. Lindor
Journal: Clinical Gastroenterology and Hepatology (2011)
Laboratory testing for cryoglobulins
Authors: Gabriela Motyckova, Mandakolathur Murali
Journal: American Journal of Hematology (2011)

Cryoglobulins are immunoglobulins that precipitate below 37°C and can cause multiorgan damage. There are three types of cryoglobulins: Type I (also called simple), which is mostly associated with monoclonal gammopathy and/or other hematologic disorders and Type II and Type III (known as mixed cryoglobulins), which are associated with infectious and systemic diseases. Testing for cryoglobulins is complicated by lack of reference range, standards, and stringency in maintaining testing temperature conditions. Identification of cryoprecipitate can be critical for patient care; therefore, correct testing conditions are crucial for reliable cryoglobulin testing. The patient's blood sample should be kept at 37°C initially to avoid premature precipitation of cryoglobulins and thereby decreasing the yield for subsequent identification. This could cause a false negative result. After warm centrifugation or warm cell precipitation, the clear serum is observed at 4°C for formation of cryoprecipitate. The cryoprecipitate is then washed in cold buffer, and the resulting precipitate is warmed to 37°C and subjected to further analysis by immunodiffusion and immunofixation. In addition to Meltzer's triad of purpura, weakness and arthralgias, cryoglobulinemias have protean manifestations involving skin, joints, kidney, nervous system, as well as the hematopoietic system. The management of cryoglobulinemia especially in patients with organ damage remains difficult. Treatment of cryoglobulinemia focuses on management of the underlying lymphoproliferative disorder or infectious or systemic causes. Medical management may also include corticosteroids and other immunosuppressive agents and plasmapheresis. Rituximab therapy seems to abrogate the aberrant B cell response.
Coarse Particles and Heart Rate Variability among Older Adults with CoronaryArtery Disease in the Coachella Valley, California
Authors: Michael J. Lipsett, Feng C. Tsai, Linda Roger, Mary Woo, Bart D. Ostro
Journal: Environmental Health Perspectives (2006)

Alterations in cardiac autonomic control, assessed by changes in heart rate variability (HRV), provide one plausible mechanistic explanation for consistent associations between exposure to airborne particulate matter (PM) and increased risks of cardiovascular mortality. Decreased HRV has been linked with exposures to PM10 (PM with aerodynamic diameter<or=10 microm) and with fine particles (PM with aerodynamic diameter<or=2.5 microm) originating primarily from combustion sources. However, little is known about the relationship between HRV and coarse particles [PM with aerodynamic diameter 10-2.5 microm (PM10-2.5)], which typically result from entrainment of dust and soil or from mechanical abrasive processes in industry and transportation. We measured several HRV variables in 19 nonsmoking older adults with coronary artery disease residing in the Coachella Valley, California, a desert resort and retirement area in which ambient PM10 consists predominantly of PM10-2.5. Study subjects wore Holter monitors for 24 hr once per week for up to 12 weeks during spring 2000. Pollutant concentrations were assessed at nearby fixed-site monitors. We used mixed models that controlled for individual-specific effects to examine relationships between air pollutants and several HRV metrics. Decrements in several measures of HRV were consistently associated with both PM10 and PM10-2.5; however, there was little relationship of HRV variables with PM2.5 concentrations. The magnitude of the associations (approximately 1-4% decrease in HRV per 10-microg/m3 increase in PM10 or PM10-2.5) was comparable with those observed in several other studies of PM. Elevated levels of ambient PM10-2.5 may adversely affect HRV in older subjects with coronary artery disease.
Abstract 309: Loss of IL-6 or Stat3 drives advanced prostate cancer by promoting p53 inactivation.
Authors: Jan Pencik
Journal: Cancer Research (2013)

Abstract Prostate cancer is the second most common cause of death in men. Approximately 258000 men in worldwide die each year from prostate cancer. The Jak/Stat pathway (Jak - Janus kinase, Stat - signal transducer and activators of transcription) is an important signaling cascade in prostate cancer. Stat3 seems to play a fundamental role in the regulation of proliferation, apoptosis, angiogenesis and hormone-resistance in prostate cancer. Although there has been evidence for an oncogenic function of Stat3, observations from several laboratories suggest the opposite. Under certain conditions activation of Stat3 leads to decreased growth of prostate cancer cells in vitro (LNCaP) and can exert an inhibitory effect on prostate cancer xenografts. To elucidate the role of IL-6/Stat3 signaling in prostate cancer (PCa), we have established Pten-deficient (Ptenpc-/−) PCa mouse models with additional deletion of IL-6 or Stat3. Ablation of IL-6 in Ptenpc-/− mice led to increased tumor formation and signs of massive chronic inflammation. In addition, Ptenpc-/- IL-6−/- mice showed decreased expression of p53-dependent cellular senescence markers when compared to PCa in Ptenpc-/- mice. The concomitant Pten and Stat3 inactivation (Pten/Stat3pc-/−) enhanced cell proliferation and accelerated the prostate cancer progression as well as production of inflammatory cytokines. Pten/Stat3pc-/− mice showed also significant downregulation of crucial components of the p53-dependent cellular senescence pathway. Furthermore, Pten/Stat3pc-/- PCa mice revealed high expression of AR and P-Akt correlated with advanced prostate cancer. These data suggest that disruption of IL-6/Stat3 signaling promotes tumorigenesis in Ptenpc-/- induced prostate cancer via p53 inactivation. Citation Format: Jan Pencik. Loss of IL-6 or Stat3 drives advanced prostate cancer by promoting p53 inactivation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 309. doi:10.1158/1538-7445.AM2013-309
Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia
Authors: Kazuko Miyazaki, Norimasa Yamasaki, Hideaki Oda, Takeshi Kuwata, Yohei Kanno, Masaki Miyazaki, Yukiko Komeno, Jiro Kitaura, Zen-ichiro Honda, Søren Warming, Nancy A. Jenkins, Neal G. Copeland, Toshio Kitamura, Takuro Nakamura, Hiroaki Honda
Journal: Blood (2009)
A novel long-pentraxin PTX3, C-reactive protein, NT-Pro-BNP and troponin-T during the first six months after heart transplant
Authors: Roberto Latini, Pasquale Fratto, Maria Frigerio, Fabrizio Oliva, Giuseppe Peri, Alberto Mantovani, Fabio Pasqualini, Stefano Signorini, Tarcisio Vago, Aldo P. Maggioni, Ettore Vitali
Journal: Journal of the American College of Cardiology (2003)
Cellular and genetic control of antibody responses in vitro. II. Ir gene control of primary IgM responses to trinitrophenyl conjugates of poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys and poly-L-(His,Glu)-poly-D,L-Ala--poly-L-Lys.
Authors: A Singer, H B Dickler, R J Hodes
Journal: The Journal of Experimental Medicine (1977)

The in vitro primary IgM anti-hapten responses to trinitrophenyl (TNP) conjugates of poly-L-(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys (T,G)-A--L and poly-L(His,Glu)-poly-D,L-Ala--poly-L-Lys (H,G)-A--L were shown to be T-cell dependent and under autosomal dominant H-2-linked Ir gene control which mapped within the K or I-A regions of the H-2 complex. The in vitro response to TNP-keyhole limpet hemocyanin, while T-dependent, was not under demonstrable genetic control. The genes governing the in vitro primary IgM anti-hapten responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L resemble the Ir genes controlling the in vivo secondary IgG responses to (T,G)-A--L and (H,G)-A--L in that they are autosomal dominant, map identically within the H-2 complex, and have identical responder and nonresponder haplotypes. It is concluded that Ir genes can govern the ability to generate an IgM response upon initial exposure to antigen.
Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome
Authors: Claudia S. Huettner, Steffen Koschmieder, Hiromi Iwasaki, Junko Iwasaki-Arai, Hanna S. Radomska, Koichi Akashi, Daniel G. Tenen
Journal: Blood (2003)
Cancer Incidence in a Population of Jewish Women at Risk of Ovarian Cancer
Authors: A. Liede
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the incidence and clinical characteristics of ovarian and other cancers in a cohort of women at risk of developing ovarian cancer. PATIENTS AND METHODS: The Gilda Radner Ovarian Cancer Detection Program in Los Angeles, CA, was established in 1991 to study the efficacy of screening in the early detection of ovarian cancer. We present findings from a historical cohort of 290 Jewish women who were offered BRCA testing for three common founder mutations (BRCA1 185delAG and 5382insC and BRCA2 6174delT). RESULTS: In 10 years, 17 cancers were observed (1,111 per 100,000 per year), including six breast and eight ovarian or related cancers. A high proportion of cancers of peritoneal origin was observed. The majority (86%) of women with incident breast or ovarian/peritoneal cancer carried a mutation in the BRCA1 gene. The overall cancer incidence among carriers of mutations in the BRCA1 gene was estimated to be 5,450 per 100,000 per year, corresponding to a cumulative incidence of 47.5% at 10 years. In contrast, the cumulative incidence of cancer among noncarriers was 2.5% (P < 10−8). After adjustment for sampling, the risks to BRCA1 mutation carriers at 10 years were estimated to be 21% for ovarian/peritoneal/tubal cancer, 16% for breast cancer, and 36% for all cancers. CONCLUSION: The excess risk of breast and ovarian cancer in Jewish women with a family history of ovarian cancer is largely attributable to mutations in BRCA1. Intensive surveillance by use of CA-125 and ultrasound does not seem to be an effective means of diagnosing early-stage ovarian cancer in this high-risk cohort.
Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the united states population
Authors: George N. Ioannou, Olivia B. Morrow, Marah L. Connole, Sum P. Lee
Journal: Hepatology (2009)

Abstract Little is known about the impact of dietary factors on the progression of liver disease. Our aim was to determine whether dietary intake was associated with the risk of cirrhosis-related or liver cancer–related death or hospitalization in the U.S. population. Participants included 9221 persons aged 25-74 years without evidence of cirrhosis at entry into the study or during the first 5 years of follow-up, who were subsequently followed for a mean of 13.3 years as part of the first National Health and Nutrition Examination Survey. Dietary intake was ascertained at baseline using a 24-hour dietary recall questionnaire. During follow-up, 123 of 9221 participants had a diagnosis of cirrhosis (n = 118) or liver cancer (n = 5) in hospitalization records or death certificates, including 36 who were diagnosed only on the basis of death certificates. Participants who reported a diet high in protein were at a higher risk of hospitalization or death due to cirrhosis or liver cancer ( P = 0.001), whereas those who reported a diet high in carbohydrates were at a lower risk ( P = 0.003), after adjusting for potential confounders (daily consumption of protein, carbohydrate, fat, tea or coffee, and alcohol, gender, race, age, educational attainment, U.S. geographical region, diabetes, body mass index, and subscapular-to-triceps skinfold ratio). Although total fat consumption was not significantly associated with the risk of cirrhosis or liver cancer, cholesterol consumption was associated with higher risk ( P = 0.007), whereas serum cholesterol level was not associated with risk of cirrhosis or liver cancer. Conclusion: Diet may be an important and potentially modifiable determinant of liver disease. (Hepatology 2009.)
P328Investigating the cause of transposition of great arteries
Authors: WU Bada, MJ Miossec, R Hussain, J Goodship, B Keavney
Journal: Cardiovascular Research (2014)

Introduction: Congenital heart disease (CHD) is the most common congenital abnormality, affecting approximately 7 in 1,000 live births. Transposition of the great arteries (TGA) is the most commonly diagnosed cyanotic heart defect in neonates. We propose that TGA has a genetic cause, likely to be de novo or in genes causing heterotaxy syndrome. Purpose: Exomes of 9 subjects diagnosed with TGA with no family history of CHD and their unaffected parents (trios) were subject to sequencing. The project aims were to: implement the exome bioinformatic analysis pipeline to identify de novo mutations (DNMs) and validate variants called by the pipeline. This is the first study investigating de novo changes in TGA patients. Methods: Bioinformatic pipeline was set up to analyse sequencing performed on Illumina GAIIX following exon capture. Programs used included Casava-Gerald after base calling, NovoAlign/BWA for alignment, SAMtools for variant calling. Integrated Genomics Viewer was used to inspect the variants. Polymerase chain reactions were performed prior to sending off for validation by Sanger sequencing. Results: Bioinformatic pipeline identified on average 188 DNMs per trio. 17 variants were chosen for validation. 1 trio had 2 de novo mutations: 1 nonsense in ZNF227 and 1 missense in PHLPP2. 1 trio had a de novo change in RBP5 gene. 1 trio had an inherited splice site change in RTTN, a candidate gene. Conclusions: The presence of de novo and inherited mutations suggests a complex polygenic cause of TGA.
Incomplete Reiter's Syndrome: Discriminating Features and HL-A W27 in Diagnosis
Authors: Frank C. Arnett, O. Edwin McCLUSKY, Bernice Z. Schacter, Robert E. Lordon
Journal: Annals of Internal Medicine (1976)

Reiter's syndrome (nonspecific urethritis, conjunctivitis, and arthritis) may present with arthritis alone. There are, however, other discriminating clinical features that contribute to diagnosis. Additionally, the presence of HL-A W27 provides a new diagnostic aid. Thirteen patients were studied and support the validity of the concept of incomplete Reiter's syndrome. Peripheral arthritis was the presenting complaint in all, and none had urethritis or conjunctivitis. The majority were young white men. The arthritis was oligoarticular and asymmetric with lower extremity involvement predominating. Heel pain was a prominent symptom in 10, with periostitis of other sites in 5, and "sausage digits" in 8. Mucocutaneous lesions occurred in 1 and significant weight loss in 6. Only 2 had sacro-illiitis. Chronicity has characterized the course in 12. HL-A W27 was present in 12 of 13. Additional data suggest that Reiter's syndrome may be one of the most common forms of inflammatory arthritis in young men.