bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinol (vitamin A) is a cofactor in CD3‐induced human T‐lymphocyte activation
Authors: ALLENDE L. M. , CORELL A. , MADRONO A. , GONGORA R. , RODRIGUEZ‐GALLEGO C. , LOPEZ‐GOYANES A. , ROSAL M. , ARNAIZ‐VILLENA A. 
Published: October 2004

SUMMARYImmunomodulatory effects of different retinoids have been demonstrated, both in vivo and in vitro, in different cellular lineages including human and murine thymocytes, human lung fibroblasts, Langerhans' cells, tumoral cells and natural killer (NK) cells; however, any attempt to demonstrate the effect of retinoids on human peripheral blood mononuclear cells (PBMC) resulted in negative results. In the present work, it is shown that retinol and retinoic acid induce a marked increase of proliferation on human PBMC from 32 unrelated healthy individuals, which had previously been stimulated with anti‐CD3 antibodies 48 hr before. Serum‐free medium, specific retinoid concentration (10‐7 M) and a particular timing of retinol addition to the cultures (48 hr after CD3 stimulation) was necessary clearly to detect this retinol‐enhancing effect. The increased proliferative response is specifically mediated via the clonotipic T‐cell receptor–CD3 complex and correlates with the up‐regulation of certain adhesion/activation markers on the T‐lymphocyte surface: CD18, CD45RO and CD25; also Th1‐type of cytokines (interleukin‐2 and interferon‐γ) are found concordantly increased after retinoid costimulation, both measured by a direct protein measurement and by a specific mRNA increase. In addition, it is shown that the in vitro retinol costimulation is only present in immunodeficient patients who have no defect on CD3 molecules and activation pathway. The fact that retinol costimulate lymphocytes only via CD3 (and not via CD2 or CD28) and the lack of response enhancement in immunodeficients with impaired CD3 activation pathway indicates that retinoids may be used as therapeutic agents in immune system deficiencies that do not affect the clonotypic T‐cell receptor.
Cord blood CD4⊃ CD45RA⊃ T cells achieve a lower magnitude of activation when compared with their adult counterparts
Authors: HASSAN J. , REEN D. J. 
Published: October 2004

SUMMARYHighly purified CD4+ CD45RA+ cells from cord blood and peripheral blood from healthy adults were studied. The levels of expression of the CD2, CD3, CD4 and CD28 antigens were similar; however, CD45 and CD45RA antigen expression were slightly lower in cord cells. The reduced expression of the CD45RA antigen on cord CD4+ T cells was confirmed in whole blood. Functional assessment revealed deficiencies in cord CD4+ CD45RA+ T cells. Interleukin‐2 (IL‐2) production in response to specific triggering via CD2 monoclonal antibody (mAb) alone, or CD2 mAb in combination with CD28 mAb showed marked underproduction (about 10% of adult production). When CD25 expression was examined, it was observed that the proportion of activated CD4+ CD45RA+ T cells in cord blood was lower than in adult (about 20% of adult expression). Proliferation to CD2 mAbs or CD2+28 mAbs of cord blood naive cells was similarly depressed. Investigation of IL‐2 mRNA expression under these stimulatory conditions paralleled the results observed for CD25 expression, IL‐2 production and proliferation. When phorbol 12‐myristate 13‐acetate (PMA) was added to the cells triggered with CD2+28mAbs, the responses examined were enhanced in both cord and adult blood with no significant differences between the groups. These findings suggest that under identical conditions of stimulation, purified cord blood CD4+ CD45RA+ T cells do not acquire similar activation status as their adult counterparts. These finding may help in understanding the reduced graft‐versus‐host disease (GVHD) observed in cord blood stem cell transplantation.
Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer
Authors: HARDY C. L. , BHATHAL P. S. , SNIBSON K. J. , ADAMS T. E. 
Published: October 2004

SUMMARYMice expressing an ovine growth hormone–mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T‐lymphocyte expression of activation/memory‐associated markers was compared between liver and blood lymphocytes isolated from METoGH and non‐transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly‐6A/6D at increased density, and were CD45RBlo at later time‐points. Ly‐6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T‐cell receptor (TCR)αβ cells, NK1.1+ TCRαβint CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours.
Factors that influence spontaneous reporting of adverse drug reactions: a model centralized in the medical professional
Authors: Herdeiro María T. , Polonia Jorge , Gestal‐Otero Juan J. , Figueiras Adolfo 
Published: October 2004

AbstractRationale, aims and objectives  The spontaneous reporting of adverse drug reactions (ADRs) through the yellow card and made concrete by the knowledge and attitudes of doctors, has been rousing a great deal of bibliographical interest in recent years. However, there does not seem to be any actual revision in the theme on which the theoretical models that explain the process of decision in reporting are proposed. In this work an explanatory model of the factors that condition reporting is proposed and a revision of the literature on the subject has also been carried out.Methods  The proposed model is centralized in the medical professional and it considers the habit of reporting as the result of the doctor's formation and his interaction with the environment. The combination of knowledge‐attitudes‐practices and the theory of the satisfaction of needs seemed very adequate for ADR systematization.Results and conclusions  The results also indicate that, to improve the participation of health professionals in surveillance systems through spontaneous reporting, it might be necessary to design combined strategies that modify both intrinsic (knowledge, attitudes) and extrinsic (relationship between health professionals and their patients, the national health system and pharmaceutical companies) factors.
Prescription‐related illness – a scandalous pandemic
Authors: McGavock Hugh 
Published: October 2004

AbstractPrescribed drugs are now a major cause of morbidity and mortality, particularly in the elderly. The extent of this pandemic is described and its likely causes in primary care are identified: unnecessary prescribing, imprecise diagnosis, inadequate undergraduate and postgraduate education in pharmacology and therapeutics, the uncritical application of evidence‐based medicine, the outstanding development of new drugs and their sometimes unjustified promotion. Urgent action is recommended under seven headings, by health administration, epidemiologists, medical educators and prescribing doctors.
Molecular investigation of hepatitis E virus infection in domestic and miniature pigs used for medical experiments*
Authors: Tanaka Hozumi , Yoshino Hiroyuki , Kobayashi Eiji , Takahashi Masaharu , Okamoto Hiroaki 
Published: October 2004

Abstract:  Background:  Hepatitis E virus (HEV) infection is highly prevalent among domestic pigs in Japan. It has been reported that pig handlers such as farmers and veterinarians are at increased risk of contracting HEV infection. Pigs are regarded as the most acceptable candidate animals for xenotransplantation and, recently, they are being used as experimental animals.Methods:  We investigated the prevalence of IgG class antibodies to swine HEV (anti‐HEV) and HEV RNA among 152 2‐month‐old domestic pigs and 38 miniature pigs of 4 to 10 months of age that had been brought to our center for medical experiments from five swine farms (A–E) in Japan. Serum samples were tested for anti‐HEV by in‐house enzyme immunoassay, and for HEV RNA by reverse transcription‐polymerase chain reaction using primers targeting the open reading frame 2 (ORF2) region.Results:  One percent (one of 84), 6% (one of 16), and 38% (20 of 52) of the domestic pigs from farms A, B and C, respectively, had detectable HEV RNA, and the 22 HEV isolates recovered from the viremic pigs were 89.8 to 100% identical to each other in the 412‐nucleotide sequence of ORF2 and segregated into three clusters within genotype 3. Although one pig from farm A had detectable HEV RNA reproducibly, the HEV isolate recovered from this pig was up to 100% similar to those recovered from pigs from farm C, and the sera from all 84 pigs from farm A were negative for anti‐HEV. These results suggested that farm A is free from HEV infection. As the viremic pig from farm A had been raised for 1 month in a barn at our center before serum sampling, it is most likely that the pig acquired HEV infection in the barn at our center where HEV‐viremic pigs from farm C had been reared for several days approximately 3 months earlier. The 38 miniature pigs from farms D and E were negative for both anti‐HEV and HEV RNA. In an attempt to further investigate the prevalence of HEV infection, pigs that were being raised in four swine farms (farms A, C, D, and E) were tested for anti‐HEV. Although 96 (86%) of the 112 pigs from farm C were positive for anti‐HEV, none of the 48 pigs in farm A and 138 miniature pigs in farms D and E was positive for anti‐HEV.Conclusions:  These results suggest that three of the five swine farms tested were free from HEV, and that periodic testing for anti‐HEV and HEV RNA of pigs used as experimental animals and pigs raised in swine farms from which pigs are purchased, is useful for providing HEV‐free pigs to researchers who are engaged in studies using pigs.
Reference values for clinical chemistry and clinical hematology parameters in baboons
Authors: Schuurman Henk‐Jan , Smith Harold T , Cozzi Emanuele 
Published: October 2004

Abstract:  Background:  In vivo xenotransplantation modeling in large animal species is often performed in nonhuman primates, including baboons. For proper data interpretation, reference values for clinical chemistry and hematology are required.Methods:  These values are available from baseline levels in animals subjected to tolerability/pharmacokinetic studies. For each individual study two tests for clinical chemistry and hematology were performed before the start of treatment.Results and Conclusion:  We present such data from 17 male and 16 female baboons, with body weights ranging between 4.4 and 14.0 kg (males) and 4.1 and 15.0 kg (females), respectively. The number of duplicate samples per animal determined before each individual study ranged between one and five. These data are reported here to provide baseline values for veterinarians and investigators using baboons in experimental studies, particularly in xenotransplantation.
Public opinion surveys about xenotransplantation
Authors: Hagelin J 
Published: October 2004

Abstract: Background: Xenotransplantation may eventually provide a solution to the worldwide shortage of human organs for transplantation. Xenotransplantation is surrounded by profound ethical issues, both for the potential recipients and for the society as a whole. Concurrent with increased scientific interest, there has been an increasing number of quantitative public opinion surveys conducted about xenotransplantation in the last decade. The aim of the present study was to elucidate these surveys, and to assess some factors that may affect the outcome of them.Materials and methods: Surveys were identified by web and literature searches using key words in Medline and ISI Web of Knowledge. Reference lists of identified surveys were checked. Data was obtained from Inter‐University Consortium for Political and Social Research (ICPSR) and directly from authors whose data were presented in another way than percentages. In total, the present material covered surveys from 35 sources, including 23 countries.Results and discussion: Results showed that almost half of the respondents accept xenotransplantation, whereas the remaining half did either not accept or did not have/state an opinion. Over time, the proportions of acceptance seemed unchanged. The proportion of those who did not accept decreased and the remaining proportion increased. This pattern was evident in Europe and the US, but not in Japan. Gender and education were found to be associated with opinions to xenotransplantation. The influence of religion was not as straightforward. This may partly depend on how religiosity was measured in the polls. Wording of items influenced levels of acceptance. If a xenotransplant was the ‘‘only choice’’ proportions of acceptance increased, and if a ‘‘risk for zoonotic diseases’’ was stated proportions of acceptance decreased. When wording of survey items was somewhat comparable, there were often, but not always, minor differences in proportions of acceptance between surveys from different sources. Trends in opinions are best measured by the use of the same items. It is however difficult to phrase items that will not be affected by external events.
Effects of inactivation of the lateral pulvinar on response properties of second visual area cells in Cebus monkeys
Authors: Soares JGM , Diogo ACM , Fiorani M , Souza APB , Gattass R 
Published: October 2004

Summary1. In the present study, we investigated the influence of the pulvinar nucleus upon response properties of single cells in the second visual area (V2) of Cebus monkeys. The method used consisted of the inactivation of a portion of the lateral pulvinar by GABA injections while studying the response properties of cells in V2 at the same visuotopic location as that of the inactivation.2. After GABA injection in the pulvinar, most cells in V2 (67%) showed changes in spontaneous and/or stimulus‐driven activities. Contrary to the effect found with inactivation of the striate cortex, which promotes a reduction in the response of V2 neurons, we found that the main effect of pulvinar inactivation was an increment in stimulus‐driven responses of V2 cells (39% of units studied). A reduction of responses was observed in 27% of units.3. A change in orientation and/or direction selectivity was found in 91% of cells after inactivation of the pulvinar. Most commonly, the orientation selectivity of a neuron was decreased during pulvinar inactivation.4. The inactivation results indicate that the pulvinar projections have a modulatory effect on the activity of V2 cells.
Changes in endothelium‐derived hyperpolarizing factor in hypertension and ageing: response to chronic treatment with renin–angiotensin system inhibitors
Authors: Goto Kenichi , Fujii Koji , Kansui Yasuo , Iida Mitsuo 
Published: October 2004

Summary1. Endothelial function is impaired in hypertension and ageing and this may be associated with an increase in cardiovascular disease. Several clinical studies have shown that blocking the renin–angiotensin system (RAS) improves endothelial function not only in hypertensive patients, but also in normotensive patients with cardiovascular disease.2. The aim of the present study was to test whether endothelium‐derived hyperpolarizing factor (EDHF)‐mediated smooth muscle hyperpolarization and relaxation are altered in hypertension and ageing and, if so, whether chronic treatment with RAS inhibitors (the angiotensin‐converting enzyme inhibitor enalapril and the angiotensin AT1 receptor antagonist candesartan) would correct such changes.3. Endothelium‐derived hyperpolarizing factor‐mediated responses were examined in mesenteric arteries from 12‐month‐old spontaneously hypertensive rats (SHR) and 3‐, 6‐, 12‐ and 24‐month‐old normotensive Wistar‐Kyoto (WKY) rats. Furthermore, both strains were treated for 3 months with either RAS blockers or a conventional therapy with hydralazine and hydrochlorothiazide from 9 to 12 months of age.4. In arteries of 12‐month‐old SHR, EDHF‐mediated responses were impaired compared with age‐matched WKY rats. In SHR, all antihypertensive treatments improved the impairment of EDHF‐mediated responses; however, RAS inhibitors tended to improve these responses to a greater extent compared with conventional therapy with hydralazine and hydrochlorothiazide.5. In arteries of WKY rats, EDHF‐mediated responses were impaired at the age of 12 and 24 months compared with 3‐ and 6‐month‐old rats, with the response tending to be impaired to a greater extent in 24‐month‐old rats.6. Three months of treatment of WKY rats, until 12 months of age, with RAS inhibitors, but not with conventional therapy with hydralazine and hydrochlorothiazide, improved the age‐related impairment of EDHF‐mediated responses, despite a similar reduction in blood pressure by both treatments.7. These findings suggest that: (i) EDHF‐mediated hyperpolarization and relaxation decline with hypertension and ageing in rat mesenteric arteries; (ii) antihypertensive treatment restores the impaired EDHF‐mediated responses in hypertension; (iii) RAS inhibitors may be more efficacious in improving endothelial dysfunction associated with hypertension; and (iv) chronic treatment with RAS inhibitors improves the age‐related impairment of EDHF‐mediated responses, presumably through the blockade of RAS but not blood pressure lowering alone.
Implication of steady state concentrations of nitrite and nitrate metabolites of nitric oxide in plasma and whole blood in healthy human subjects
Authors: Himeno Mariko , Ishibashi Takaharu , Nakano Shigeru , Furuya Keisuke , Yoshida Junko , Kigoshi Toshikazu , Uchida Kenzo , Nishio Matomo 
Published: October 2004

Summary1. The aim of the present study was to determine whether the steady state NOx concentration reflects NOx formation in vivo.2. A NO3– load study was performed after achieving NOx steady state. Chronological changes in NOx concentrations in plasma and whole blood samples from nine healthy subjects were determined by the HPLC–Griess system and NOx concentrations in erythrocytes were estimated as a possible NOx compartment influential in regulating plasma NOx concentrations.3. Analysis was performed using the first‐order one‐compartment open model and the NOx formation rate was subsequently calculated.4. The mean (±SEM) steady state NOx concentration of plasma (15.5 ± 1.6 µmol/L), whole blood (12.8 ± 1.2 µmol/L) and erythrocytes (11.9 ± 0.7 µmol/L) did not correlate with the NOx formation rate in the compartments (0.50 ± 0.05, 0.61 ± 0.04 and 0.91 ± 0.17 µmol/kg per h, respectively), whereas a significant correlation was found between the steady state NOx concentration and NOx elimination rate (Kel) in plasma (r = −0.69; P = 0.04) and whole blood (r = −0.79; P = 0.01).5. Although there was no direct correlation between steady state NOx concentrations and serum creatinine levels, the correlation between half‐life and serum creatinine levels was significant (plasma: r = 0.60, P = 0.02; whole blood: r = 0.49, P = 0.04).6. Plasma NOx concentrations correlated significantly with erythrocyte NOx concentrations (r = 0.92, P < 0.01; erythrocyte NOx = 0.66 × plasma NOx).7. The results of the present study indicate that NOx does not accumulate excessively into erythrocytes at steady state and during a NO3– load and that the steady state NOx concentration in whole blood and plasma preferentially implies NOx elimination (mainly depending on renal function) rather than NOx formation.
Effect of Anoectochilus formosanus on fibrosis and regeneration of the liver in rats
Authors: Shih Chun‐Ching , Wu Yueh‐Wern , Hsieh Chang‐Chi , Lin Wen‐Chuan 
Published: October 2004

Summary1. The present study examined the effects of an aqueous extract of Anoectochilus formosanus (AFE) on both hepatic fibrosis and regeneration in rats.2. Fibrosis was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for 3 consecutive days per week for 4 weeks.3. In DMN‐treated rats, liver cirrhosis‐associated complications, such as liver atrophy, low concentrations of serum albumin and the accumulation of hepatic collagen, were observed. The AFE protected the liver against DMN‐induced fibrosis, as determined by morphological and biochemical observations.4. In addition, AFE was administered to two‐thirds hepatectomized normal and DMN‐injured rats. Three and 5 days after hepatectomy, AFE increased the extent of liver weight regeneration and the number of S‐phase cells in DMN‐injured rats, but not in normal rats.5. These results show that AFE seems to be useful in the repair of liver injury, improvement of fibrotic changes and promotion of liver regeneration.
Four years of lamivudine treatment in Chinese patients with chronic hepatitis B
Authors: CHANG TING‐TSUNG , LAI CHING‐LUNG , CHIEN RONG‐NAN , GUAN RICHARD , LIM SENG‐GEE , LEE CHUAN‐MO , NG KENG‐YEEN , NICHOLLS GRAHAM J , DENT JULIE C , LEUNG NANCY WY 
Published: October 2004

AbstractBackground and Aims:  This study assessed the efficacy and safety of up to 4 years of lamivudine treatment and the clinical relevance of the emergence of YMDD‐variant hepatitis B virus (HBV).Methods:  Fifty‐eight Chinese adult patients with chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5 years and were monitored for YMDD‐variant HBV, hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine aminotransferase (ALT) concentrations. Four‐year data are reported here.Results:  The rate of HBeAg seroconversion increased with extended therapy and also with higher baseline ALT concentrations. YMDD‐variant HBV was detected in 67% (39/58) of patients at some point during treatment. After 4 years, a total of 47% (27/58) of patients achieved HBeAg seroconversion. Thirty‐three per cent (13/39) of patients with YMDD‐variant HBV achieved HBeAg seroconversion; this increased to 57% (8/14) in patients with moderately elevated (>2–5 × upper limit of normal) pre‐treatment ALT concentrations. The proportion of patients that achieved normal serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years of treatment. That included 68% (23/34) of patients with YMDD‐variant HBV and 73% (8/11) of those without the variant. All patients receiving lamivudine had reduced serum concentrations of HBV‐DNA compared with baseline, despite the emergence of YMDD‐variant HBV in 39 patients. Lamivudine was generally well tolerated; there was little change in the number or type of drug‐related adverse events in the fourth year of the study.Conclusions:  Despite the emergence of YMDD‐variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine.