bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular inhibition of histone deacetylation results in major enhancement of the production of IL-1β in response to LPS
Authors: Sato Timothy A. , Mitchell Murray D.
Published: October 2005

It has been postulated that the progression of human pregnancy to term is, in part, the result of a relative maternal Th2immunological state. This can be activated in some cell types by modifying DNA methylation and histone acetylation status. We demonstrate that the molecular inhibition of histone deacetylation, using trichostatin A (TSA), in human choriodecidual explants leads to a massive increase in lipopolysaccharide (LPS)-stimulated IL-1β. The inhibition of histone deacetylation had no effect on LPS-stimulated TNF-α production or production of the other cytokines studied (IL-10, IL-1 receptor antagonist). The molecular inhibition of DNA methylation and histone deacetylation, using 5-aza-2′-deoxycytidine and TSA, respectively, in human choriodecidual explants also results in an increase in the basal production of TNF-α but not that of IL-1β. The differential response is unique, and the relative uncoupling of IL-1β and TNF-α responsiveness may have importance in other biological systems and provide new therapeutic targets for pathologies where upregulation of IL-1β is known to be a causative factor.
A causal role for uric acid in fructose-induced metabolic syndrome
Authors: Nakagawa Takahiko , Hu Hanbo , Zharikov Sergey , Tuttle Katherine R. , Short Robert A. , Glushakova Olena , Ouyang Xiaosen , Feig Daniel I. , Block Edward R. , Herrera-Acosta Jaime , Patel Jawaharlal M. , Johnson Richard J.
Published: October 2005

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.
Redox dependence of glomerular epithelial cell hypertrophy in response to glucose
Authors: Kim Nam-Ho , Rincon-Choles Hernan , Bhandari Basant , Choudhury Goutam Ghosh , Abboud Hanna E. , Gorin Yves
Published: October 2005

Podocytes or glomerular epithelial cells (GECs) are important targets of the diabetic microenvironment. Podocyte foot process effacement and widening, loss of GECs and hypertrophy are pathological features of this disease. ANG II and oxidative stress are key mediators of renal hypertrophy in diabetes. The cellular mechanisms responsible for GEC hypertrophy in diabetes are incompletely characterized. We investigated the effect of high glucose on protein synthesis and GEC hypertrophy. Exposure of GECs to high glucose dose dependently stimulated [3H]leucine incorporation, but not [3H]yhymidine incorporation. High glucose resulted in the activation of ERK1/2 and Akt/PKB. ERK1/2 pathway inhibitor or the dominant negative mutant of Akt/PKB inhibited high glucose-induced protein synthesis. High glucose elicited a rapid generation of reactive oxygen species (ROS). The stimulatory effect of high glucose on ROS production, ERK1/2, and Akt/PKB activation was prevented by the antioxidants catalase, diphenylene iodonium, and N-acetylcysteine. Exposure of the cells to hydrogen peroxide mimicked the effects of high glucose. In addition, ANG II resulted in the activation of ERK1/2 and Akt/PKB and GEC hypertrophy. Moreover, high glucose and ANG II exhibited additive effects on ERK1/2 and Akt/PKB activation as well as protein synthesis. These additive responses were abolished by treatment of the cells with the antioxidants. These data demonstrate that high glucose stimulates GEC hypertrophy through a ROS-dependent activation of ERK1/2 and Akt/PKB. Enhanced ROS generation accounts for the additive effects of high glucose and ANG II, suggesting that this signaling cascade contributes to GEC injury in diabetes.
Serum Levels of TNF‐α, IFN‐γ, IL‐6, IL‐8,IL‐12, IL‐17, and IL‐18 in Patients With Active Psoriasis andCorrelation With Disease Severity
Authors: Arican Ozer , Aral Murat , Sasmaz Sezai , Ciragil Pinar
Published: October 2005

Recent progress in the understanding of psoriasis
has shown that the regulation of local and systemic cytokines
plays an important role in its pathogenesis. The most
often used psoriasis score is the psoriasis area and severity
index (PASI). A simple laboratory test from a blood sample would
be an attractive, patient‐independent, and observer‐independent
marker of disease severity. To this end, we evaluated the
association of serum levels of some proinflammatory cytokines
in vivo and their correlation with severity of psoriasis.
The serum levels of cytokines levels were determined with the use
of the ELISA method. All mean values except IL‐17 levels of
patients were significantly higher than those of controls. There
was a significant correlation between serum levels of IFN‐γ,
IL‐12, IL‐17, and IL‐18, and severity of the disease. Psoriasis
can be described as a T‐cell‐mediated disease, with a
complex role for a variety of cytokines, which has led to
the development of new immunomodulatory therapies. In this study,
serum TNF‐α, IFN‐γ, IL‐6, IL‐8, IL‐12, and IL‐18
levels were significantly higher in active psoriatic patients than
in controls. Furthermore, high levels of IFN‐γ, IL‐12, and
IL‐18 correlated with the clinical severity and activity of
psoriasis, and those measurements of serum levels of these
cytokines may be objective parameters for the disease severity.
Psychological and Quality-of-Life Outcomes from a Comprehensive Stress Reduction and Lifestyle Program in Patients with Coronary Artery Disease: Results of a Randomized Trial
Authors: Michalsen Andreas , Grossman Paul , Lehmann Nils , Knoblauch Nicola T.M. , Paul Anna , Moebus Susanne , Budde Thomas , Dobos Gustav J.
Published: October 2005

Background: Stress reduction and comprehensive lifestyle modification programs have improved atherosclerosis and cardiac risk factors in earlier trials. Little is known about the impact of such programs on quality-of-life (QoL) and psychological outcomes. Given recent significant improvements in cardiac care, we evaluated the current benefit of stress reduction/lifestyle modification on QoL and emotional distress in patients with coronary artery disease (CAD). Methods: 101 patients (59.4 ± 8.6 years, 23 female) with CAD were randomized to a 1-year lifestyle/stress management program (n = 48) or written advice (n = 53). QoL and psychological outcomes were assessed with the SF-36, Beck Depression, Spielberger State/Trait Anxiety, Spielberger State/Trait Anger and Perceived Stress Inventories. Group repeated-measures analyses of variance were performed for all measures. Results: Adherence to the program was excellent (daily relaxation practice 39 ± 5vs. 5 ± 8 min, respectively; p < 0.001). Both groups improved comparably in most dimensions of QoL, and significantly greater improvements for the lifestyle group were found for physical function and physical sum score (p = 0.046 and p = 0.045). Depression, anxiety, anger and perceived stress were reduced similarly in both groups. However, intervention × gender interaction effects revealed greater benefits among women in the lifestyle intervention vs. advice group for depression and anger (p = 0.025 and p = 0.040), but no effects for men. Conclusions: A comprehensive lifestyle modification and stress management program did not improve psychological outcomes in medically stable CAD patients. The program did appear to confer psychological benefits for women but not men. Further trials should investigate gender-related differences in coronary patient responses to behavioral interventions.
Antidepressant Response and Well-Being in Pre-, Peri- and Postmenopausal Women with Major Depressive Disorder Treated with Fluoxetine
Authors: Cassano Paolo , Soares Claudio N. , Cusin Cristina , Mascarini Alessandra , Cohen Lee S. , Fava Maurizio
Published: October 2005

Background: We assessed the impact of menopausal status on treatment response and well-being in a cohort of outpatient women with major depressive disorder (DSM-III-R criteria), who received treatment with fluoxetine (20 mg/day for 8 weeks). Methods: Menopausal status was defined based on age, presence of menstrual irregularity or amenorrhea and vasomotor symptoms. Remission and response of depression were defined as a 17-item Hamilton Depression Rating Scale (HAM-D-17) score ≤7 and a HAM-D-17 decrease ≧50%, respectively. Well-being was assessed by self-rating with the Symptom Questionnaire. Remitters were followed up for 28 additional weeks. Results: No differences in rates of response and remission as well as in levels of well-being were observed among pre- (n = 121), peri- (n = 28) and postmenopausal (n = 35) women at the endpoint of the acute phase, even after adjustment for baseline depression severity. Residual symptoms, however, were significantly more common in postmenopausal women, except for the continuation phase endpoint. Differences in residual symptoms during the acute phase subsided after adjustment for baseline depression severity. Conclusions: Overall, menopausal status did not significantly affect the response to fluoxetine treatment and the degree of posttreatment well-being among major depressive disorder patients.
In-Patient Treatment of Mothers with Depressive Disorders – Does Joint Admission of Their Children Have a Negative Effect on the Results of Treatment?
Authors: Nickel Marius , Nickel Cerstin , Tritt Karin , Lahmann Claas , Leiberich Peter , Muehlbacher Moritz , Egger Christoph , Rother Wolfhardt , Loew Thomas
Published: October 2005

Background: There is disagreement whether in-patient psychotherapeutic treatment results for women whose children are cohospitalised with them would be better if the mothers were hospitalised without children. The purpose of this study was to examine this question in the case of mothers with depressive symptoms. Methods: The treatment results for 43 female in-patients (21 with and 22 without accompanying children) in a prospective, randomised, controlled study were compared. The period of observation was 6 weeks. The Beck Depression Inventory (BDI) and the Changes in Experience and Behaviour Questionnaire (VEV) were used for outcome measures. Results: At 6 weeks, according to the intent-to-treat principle, neither the VEV (p = 0.58) nor the BDI (p = 0.57) yielded significant differences between mothers whose children were admitted jointly and mothers whose children were not. Conclusion: The treatment results for patients with depressive symptoms whoare accompanied by their children for the duration of their in-patient psychotherapy treatment are just as good as those for mothers whose children are not jointly admitted. Additionally, the data have further implications that lend themselves to discussion regarding support for this type of facility.
Coping with Serious Accidental Injury: A One-Year Follow-Up Study
Authors: Hepp Urs , Moergeli Hanspeter , Büchi Stefan , Wittmann Lutz , Schnyder Ulrich
Published: October 2005

Background: The aim of this study was to analyze changes of coping strategies in severely injured accident victims over time and to compare patients with high and low posttraumatic stress disorder (PTSD) symptom levels with regard to their coping patterns and accident-related cognitions. Methods: 106 consecutive patients with severe accidental injuries admitted to a trauma surgery intensive care unit (ICU) were assessed within 1 month after the trauma and 6 and 12 months later. Assessments included a clinical interview, the Freiburg Questionnaire of Coping with Illness, the patients’ accident-related cognitions, the Clinician-Administered PTSD Scale, the 90-item revised Symptom Checklist (SCL-90-R), and the Sense of Coherence Questionnaire (SOC). Patients who met the criteria for either full or subsyndromal PTSD at least once over the observation period (36 subjects; 34.0%) were assigned to a highly symptomatic group (HSG), the remainder (70 subjects; 66.0%) to a less symptomatic group. Results: Overall, active problem-focused coping was predominant immediately after the accident and declined over time, with a stronger decrease in the HSG. Patients in the HSG scored higher on the SCL Global Severity Index and lower on the SOC. The patients’ subjective appraisal of accident severity was higher in the HSG, whereas there was no group difference with regard to accident-related variables such as type of accident, injury severity and mild to moderate traumatic brain injury. Conclusions: Active problem-focused coping, although utilized most frequently and often regarded as protective, might be an inadequate strategy in face of acute stress following a severe accident. Clinicians should not expect their patients to cope very actively in the acute ICU phase. In the subsequent rehabilitation, active coping seems to be more adaptive.
Elevated Aldosterone in Amniotic Fluid and Maternal Blood Has Diagnostic Potential in Pregnancies Complicated with a Fetus of Bartter Syndrome
Authors: Nakanishi Tamao , Suzumori Nobuhiro , Mizuno Haruo , Suzuki Kazutaka , Sato Takeshi , Tanemura Mitsuyo , Suzuki Yoshikatsu , Suzumori Kaoru
Published: October 2005

Pregnancies with fetuses affected with the Bartter syndrome, an autosomal recessive disorder of hyperreninism and hyperaldosteronism, are complicated by early onset of polyhydramnios which results in preterm deliveries. We have assessed biochemical changes in amniotic fluid and the mother’s blood with a view to early diagnosis. Aldosterone levels of both amniotic fluid and the mother’s blood were found to be increased at 27 weeks of gestation, while electrolyte levels did not differ significantly from those reported earlier for controls. After birth the baby suffered from polyuria with hyponatremia, hypomagnesemia and hypercalciuria which could be controlled by treatment with sodium chloride and magnesium. Elevated aldosterone thus might be a useful marker for early diagnostic purposes.
Aminiotic Fluid and Intrauterine Growth Restriction in a Gastroschisis Fetal Rat Model
Authors: Franchi-Teixeira Antonio Roberto , Weber Guimarães Barreto Maria , Nogueira Barbara , Bittencourt Daniel , Violin Luis , Sbragia Lourenço
Published: October 2005

Fetuses with digestive anomalies such as gastroschisis may present intrauterine growth restriction (IUGR) and shortened intestines. Objective: The aim of this study was to assess the influence caused by amniotic fluid (AF) in intestinal length and somatic growth in an experimental gastroschisis fetal model at two distinct gestational ages. Material and Method: Fetal rats were operated according to Correia-Pinto on 2 different days of gestation: day 18.5 (group I) and day 19.5 (group II). Each group was divided into three sub-groups: fetuses with gastroschisis (G), control (C) and sham(S). Body measurements and histological analysis were done. Result: Body measurement analysis showed: average body weight (g) in group I was G = 5.32, C = 5.68, S = 5.86; group II was G = 5.32, C = 5.80, S = 5.66. Average intestine weight (g) in group I was G = 0.283, C = 0.238, S = 0.231; group II was G = 0.272, C = 0.231, S = 0.233. Average intestine length (mm) in group I was G = 125, C = 216, S = 209; group II was G = 148, C = 226, S = 226. Histological analysis showed a decrease in the number and size of the intestinal microvillae and a light edema of serosa. Conclusion: Gastroschisis had a direct correlation with IUGR and the time of exposure of the fetuses to AF had no influence on body weight in gastroschisis fetuses but did interfere with intestinal length.
Periconceptional Clinics: A Medical Health Care Infrastructure of New Genetics
Authors: Czeizel Andrew E. , Gasztonyi Zoltan , Kuliev Anver
Published: October 2005

The necessary paradigm shift of medical prevention and health promotion from general prevention to specific genetic-oriented prevention require two crucial points: the selection of the optimal time for the primary prevention of birth defects and predictive genetic testing and the establishment of the appropriate healthcare infrastructure. The optimal time for the primary prevention of birth defects (e.g. neural-tube defects) and predictive genetic testing is the preconceptionalperiod, i.e. the preparatory time for the planned conception, particularly before the first pregnancy, and the most acceptable time for the concrete diagnosis of the expected serious genetic diseases is the early postconceptional period. Theoretically, preimplantation genetic diagnosis is the optimal option for offspring of couples at high risk including autosomal and X-linked recessive, dominant disorders and chromosomal aberrations. The pre- and early postconceptional health can be addressed jointly in a new type of the health care infrastructure entitled periconceptional clinic. Periconceptional clinics seem to be appropriate for the starting point for the primary prevention of common complex diseases as well.
Antenatal Detection of Arterio-Arterial Anastomoses by Doppler Placental Assessment in Monochorionic Twin Pregnancies
Authors: Fichera Anna , Mor Elisa , Soregaroli Mirella , Frusca Tiziana
Published: October 2005

Objectives: To evaluate the reproducibility of Doppler antenatal detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twin pregnancies. Methods: Between October 2002 and February 2004, 21 MC diamniotic twin pregnancies and one dichorionic triamniotic triplet seen at the Twin Clinic at the University of Brescia were recruited. After routine ultrasonographic assessment, AAA were searched using Color or Power and spectral Doppler. The presence of AAA was confirmed postnatally by placental injection studies. Results: Data of 19 patients were available for the analysis. AAA were detected in 12 cases (63%) antenatally and in 16 (84.2%) at injection study. Sensitivity and specificity of Doppler for detecting AAA were 75 and 100%, respectively. Detection rates increased at advanced gestations and with anterior/fundal placentae. The incidence of twin-twin transfusion syndrome was higher in the group with no AAA detected in vivo compared to the group with AAA found with Doppler (28.5 vs. 16.6%), but the difference was not statistically significant (p = 0.5). Conclusion: This study confirmed the feasibility of AAA Doppler detection in vivo in MC pregnancies.
Systemic Lupus Erythematosus – Associated Acute Severe Thrombocytopenia and Leukopenia First Presented in Pregnancy
Authors: Daskalakis G. , Papantoniou N. , Marinopoulos S. , Vomvolaki E. , Papageorgiou I. , Mesogitis S. , Antsaklis A.
Published: October 2005

We report a rare case of acute severe thrombocytopenia and leukopenia, which first presented at 37 weeks’ gestation. Based on clinical as well as on laboratory findings the diagnosis of systemic lupus erythematosus was made. The patient was successfully managed with an emergency transfusion of 6 units of platelets and intravenous immunoglobulin infusion followed by methylprednisolone administration. A caesarean section was performed at 39 weeks. The neonate was not thrombocytopenic at birth, nor at the age of 1 month.
Efficacy of Two Regimens of Misoprostol for Early Second-Trimester Pregnancy Termination
Authors: Guix Cristina , Palacio Montse , Figueras Francesc , Bennasar Mar , Zamora Luis , Coll Oriol , Cararach Vicenç
Published: October 2005

Objective: To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination. Methods: This is a prospective study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks. Two regimens of misoprostol were used. Group 1: 400 µg of oral plus 400 µg vaginal misoprostol every 8 h (combined regimen) and group 2: 400 µg of vaginal misoprostol every 3 h up to a maximum of five doses (vaginal regimen). Results: The induction-to-abortion interval was significantly longer in group 1 (25.5 ± 24.45 h) than in group 2 (15 ± 7.14 h) (p = 0.016). The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7% in group 2 (p = 0.006). The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders. Conclusions: Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination.
Outcomes of a Non-Operative Caries Treatment Programme for Children and Adolescents
Authors: Ekstrand K.R. , Christiansen M.E.C.
Published: October 2005

This study assessed the effectiveness and performance of a non-operative caries treatment programme (NOCTP) used since 1987 in the municipality of Nexö in Denmark. The NOCTP emphasizes mechanical plaque control and considers the eruption period of molar teeth as a risk factor. The mean DMF-S among 18-year-olds in 1999 and 2000 in Nexö was 1.23 ± 2.26 and 1.25 ± 2.01 (medians 0); 55 and 56% had DMF-S = 0. The mean numbers of sealed surfaces were 4.6 ± 3.25 and 4.0 ± 3.22, respectively. The cost per child per year was marginally and significantly reduced in the years with the NOCTP compared to that before 1988 (p = 0.05). In 4 comparison municipalities with very low caries experience, mean DMF-S scores among 18-year-olds in 1999 were 2.73–3.25 (medians 1–2) and were significantly higher than in Nexö (p < 0.001). The NOCTP differed from the preventive programmes used in the comparison municipalities in the period 1988–1999 in emphasising care for the erupting molars, the use of a firm guideline and stated goals to be achieved, but with less emphasis on diet. The effectiveness and performance of the NOCTP were both considered high, as very low DMF-S and high %DMF-S = 0 had been achieved by 1999, and 18-year-olds in Nexö had significantly less caries than in the comparison municipalities. The latter difference could not be explained by difference in caries-related background variables.
Beyond Anaemia Management: Evolving Role of Erythropoietin Therapy in Neurological Disorders, Multiple Myeloma and Tumour Hypoxia Models
Authors: Boogaerts Marc , Mittelman Moshe , Vaupel Peter
Published: October 2005

Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood–brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results.
Evidence for a Tetrahydrobiopterin Deficit in Schizophrenia
Authors: Richardson M.A. , Read Laura L. , Taylor Clelland Catherine L. , Reilly Margaret A. , Chao Helen M. , Guynn Robert W. , Suckow Raymond F. , Clelland James D.
Published: October 2005

Tetrahydrobiopterin (BH4) is a vital cofactor maintaining availability of the amine neurotransmitters [dopamine (DA), noradrenaline (NA), and serotonin (5-HT)], regulating the synthesis of nitric oxide (NO) by nitric oxide synthase (NOS), and stimulating and modulating the glutamatergic system (directly and indirectly). These BH4 properties and their potential relevance to schizophrenia led us to investigate the hypothesis of a study group (healthy controls, n = 37; schizophrenics, n = 154) effect on fasting plasma total biopterin levels (a measure of BH4). Study analysis showed a highly significant deficit of total biopterins for the schizophrenic sample after partialling out the effects of potential confounds of gender, age, ethnicity, neuroleptic use history and dose of current use, 24-hour dietary phenylalanine/protein ratio (a dietary variable relevant to BH4 synthesis), and plasma phenylalanine (which stimulates BH4 synthesis). A mean decrement of 34% in plasma total biopterins for schizophrenics from control values supports clinical relevance for the finding. In a subsample (21 controls and 23 schizophrenics), sequence analysis was done of the GTP cyclohydrolase I feedback regulatory gene and no mutations were found in the coding region of the gene. A deficiency of BH4 could lead to hypofunction of the systems of DA, NA, 5-HT, NOS/NO, and glutamate, all of which have been independently implicated in schizophrenia psychopathology. Further, evidence has been accumulating which implicates the critical interdependence of these neurotransmitter systems in schizophrenia; this concept, along with the present study finding of a biopterin deficit, suggests that further study of the BH4 system in schizophrenia is warranted and desirable.
Interleukin-6 Genetic Polymorphism and Chinese Major Depression
Authors: Hong Chen-Jee , Yu Younger W.-Y. , Chen Tai-Jui , Tsai Shih-Jen
Published: October 2005

Background: It has been reported that serum concentrations of interleukin-6 (IL-6), a pro-inflammatory cytokine, were significantly higher in major depressive disorder (MDD). Objectives: The aim of the present study was to examine whether the IL-6 genetic variant confers susceptibility to MDD. Methods: We genotyped a functional polymorphism in the promoter region (position –634) of the IL-6 gene in a sample of 257 MDD patients and 105 normal controls. Results: No significant differences were demonstrated for the genotype or allele frequency of the IL-6 polymorphism when comparing the MDD and control groups. Conclusions: Our findings suggested that the investigated IL-6 polymorphism does not affect MDD susceptibility. We propose that other genetic variations of IL-6, relating either to MDD or to the clinical manifestations of MDD, may need further investigation.
A Note on Aphasia in Bilingual Patients: Pitres’ and Ribot’s Laws
Authors: Pearce J.M.S.
Published: October 2005

Johann Gesner in 1770 probably provided the first description of dissociation in reading ability in different languages in a bilingual patient, who after brain damage was able to read Latin but not German. Clinical studies have since shown that bilingual ‘aphasics’ do not necessarily manifest the same language disorders with the same degree of severity in both languages. Superficially, different case findings indicate instances of shared and divergent representation of components of language in the bilingual brain. This paper considers a selection of many empirical studies, which have failed to reconcile the parallel recovery of language in many reported bilingual aphasiacs and the differential recovery in others. It reviews Pitres’ rule (recovery of the most used acquired language) and Ribot’s law (recovery of the native language) that are important concepts during recovery and rehabilitation of bilingual aphasiacs.
Intravenous TPA for Very Old Stroke Patients
Authors: Chen Chin-I , Iguchi Yasuyuki , Grotta James C. , Garami Zsolt , Uchino Ken , Shaltoni Hashem , Alexandrov Andrei V.
Published: October 2005

Background: Although thrombolysis in patients with advanced age is considered more risky, some may benefit from TPA treatment. We studied safety and recanalization/recovery in patients older than 80 years treated with TPA and compared them with younger stroke patients. Methods: We studied patients treated with intravenous TPA and divided them into younger (<80 years) and older (≧80 years) groups for comparison. Diagnostic transcranial Doppler was completed before bolus, and patients were consequently monitored for up to 2 h when feasible. Clinical data included NIH Stroke Scale score, symptomatic intracranial hemorrhage (ICH) and discharge disposition. Results: We studied 127 younger (mean 63 years, range 31–79) and 56 older patients (mean 84 years, range 80–93). Median baseline NIH Stroke Scale score was higher in the older group (18 vs. 14 points, NS). Occlusion locations, onset to needle time (median 130 vs. 120 min) as well as improvement at 24 h (median 5 vs. 4 points) were similar in both groups. Transcranial Doppler monitoring showed similar partial or complete recanalization rates (66 vs. 66%), onset to recanalization time (median 160 vs. 158 min) and reocclusion rates (26 vs. 25%). Symptomatic and fatal ICH was not higher in the older group (7.1 and 3.5% vs. 6.3 and 3.9%, NS). There was higher mortality among older patients (20 vs. 11%, NS). At discharge, 23% of older patients went home, 41% underwent rehabilitation and 16% were transferred to skilled nursing facilities, compared with 31, 43 and 15% respectively, in the younger group. Conclusion: After intravenous TPA treatment, patients over 80 years of age have similar recanalization, short-term improvement and symptomatic ICH rates compared with younger patients. However, older patients tend to have higher in-hospital mortality.
Election 2004 Concession and Victory Speeches
Authors: Willyard Jennifer , Ritter Kurt
Published: October 2005

This analysis of the 2004 presidential election concession-victory ritual shows that generic norms had the greatest influence on the speeches, but presidential candidates John Kerry and George W. Bush occasionally violated generic expectations due to the context of their speeches and their personal inclinations. In particular, Democratic vice presidential candidate John Edwards disrupted the dynamics of the closing ritual of the election with a speech strikingly incongruent with Kerry's concession speech. This study concludes that a full understanding of the quadrennial concession-victory ritual requires attention to context and speakers as well as to genre. Because of the reciprocal nature of the ritual of acknowledging defeat and declaring victory, scholars also need to examine statements by the losing and winning vice presidential candidates.
An Immigrant's Dream and the Audacity of Hope
Authors: Elahi Babak , Cos Grant
Published: October 2005

Smith and Nimmo assert that contemporary political conventions orchestrate an important legitimation ritual. Asignificant part of this ritual is composed of speechmaking. The 2004 Democratic and Republican conventions had a few notable speech moments. Specifically, the speeches by Illinois State Senator Barack Obama and California Governor Arnold Schwarzenegger garnered attention for both them and their party leaders. Along with the excitement these two speakers generated, they shared a common narrative thread in their two speeches. The difference between the speeches, the authors argue, lies in how the speakers enacted different elements of the moralistic and materialistic forms of the American dream. In accordance with Honig, the authors argue that Obama and Schwarzenegger functioned in this iconic way to reenchant, rescue, and reinvigorate each party's sense of purity, innocence, and goodness.
From Sidekick to Sideshow— Celebrity, Entertainment, and the Politics of Distraction
Authors: Weiskel Timothy C.
Published: October 2005

In America, entertainment celebrities have entered politics, and the news media have become part of the entertainment industry. At the same time, political figures cultivate their role as celebrities, with image handlers and engineered media campaigns that treat voters like fans. President Bush has modeled himself on Ronald Reagan—the “western” movie actor as much as the president. The role bears little relation to reality, but it has become commonly accepted by a politically obsequious press and amovie-loving public. The persona is actively promoted by the White House as part of the politics of distraction—a strategy designed to keep the public from learning about what is being done in its name and with its tax dollars. The politics of distraction can explain why the public has failed to perceive the global climate crisis, but Americans will need to awake soon from this dream state if they wish to survive.
Visual Representations of the 2004 Presidential Campaign
Authors: Conners Joan L.
Published: October 2005

Political cartoons are a unique form of media message; they offer voters an opinion on the campaign or candidates encapsulated typically in a single image. However, for those images to be comprehended and appreciated, cartoonists make reference to other events or images to allowreaders to receive and digest the message quickly. This study examines representations of presidential candidates in political cartoons to identify how often references to nonelection themes are made, with particular attention to allusions made to factors from popular culture.
The ETS factor TEL2 is a hematopoietic oncoprotein
Authors: Carella Cintia , Potter Mark , Bonten Jacqueline , Rehg Jerold E. , Neale Geoffrey , Grosveld Gerard C.
Published: October 2005

TEL2/ETV7 is highly homologous to the ETS transcription factor TEL/ETV6, a frequent target of chromosome translocation in human leukemia. Although both proteins are transcriptional inhibitors binding similar DNA recognition sequences, they have opposite biologic effects: TEL inhibits proliferation while TEL2 promotes it. In addition, forced expression of TEL2 but not TEL blocks vitamin D3–induced differentiation of U937 and HL60 myeloid cells. TEL2 is expressed in the hematopoietic system, and its expression is up-regulated in bone marrow samples of some patients with leukemia, suggesting a role in oncogenesis. Recently we also showed that TEL2 cooperates with Myc in B lymphomagenesis in mice. Here we show that forced expression of TEL2 alone in mouse bone marrow causes a myeloproliferative disease with a long latency period but with high penetrance. This suggested that secondary mutations are necessary for disease development. Treating mice receiving transplants with TEL2-expressing bone marrow with the chemical carcinogen N-ethyl-N-nitrosourea (ENU) resulted in significantly accelerated disease onset. Although the mice developed a GFP-positive myeloid disease with 30% of the mice showing elevated white blood counts, they all died of T-cell lymphoma, which was GFP negative. Together our data identify TEL2 as a bona fide oncogene, but leukemic transformation is dependent on secondary mutations.
The kinase insert domain-containing receptor is an angiogenesis-associated antigen recognized by human cytotoxic T lymphocytes
Authors: Sun Yuansheng , Stevanović Stefan , Song Mingxia , Schwantes Astrid , Kirkpatrick C. James , Schadendorf Dirk , Cichutek Klaus
Published: October 2005

Antigen-specific cancer immunotherapy directed toward tumor-nourishing angiogenic blood vessels holds the promise of high efficacy, low toxicity, and ease of application. To evaluate whether the human angiogenic kinase insert domain-containing receptor (KDR) can serve as a target for cellular immunotherapy, 19 peptide sequences with HLA-A*0201 motifs were selected by computer-based algorithms. Five peptides (KDR82-90, KDR288-297, KDR766-774, KDR1093-1101, KDR1035-1044) stimulated specific cytotoxic T lymphocytes (CTLs) from peripheral-blood mononuclear cells (PBMCs) of 3 HLA-A*0201 donors. The decapeptide KDR288-297 was efficient in sensitizing target cells for recognition by a CTL clone at a concentration of 10 nM. More important, KDR288-297 - specific CTLs lysed target cells transfected with HLA-A2/KDR cDNAs and a range of HLA-matched KDR+ angiogenic endothelial cells (aECs) and also recognized CD34+ endothelial progenitor cells. The specificity of CTLs was further confirmed by tetramer assay and cold-target inhibition assay. In addition, ex vivo exposure of aECs to the inflammatory cytokines enhanced CTL reactivity, which is in keeping with up-regulated KDR and HLA class 1 expression. In Matrigel assays, recognition of aECs by specific CTLs triggered an antivascular effect. These findings provide the first proof of the antigenic property of KDR protein and may be useful for devising new immunotherapeutic approaches to human cancers.
Developmental regulation of yolk sac hematopoiesis by Krüppel-like factor 6
Authors: Matsumoto Nobuyuki , Kubo Atsushi , Liu Huixian , Akita Kuniharu , Laub Friedrich , Ramirez Francesco , Keller Gordon , Friedman Scott L.
Published: October 2005

Krüppel-like factor 6 (KLF6) is a member of a growing family of transcription factors that share a common 3 C2H2 zinc finger DNA binding domain and have broad activity in regulating proliferation and development. We have previously established that Klf6 is expressed in neuronal tissue, hindgut, heart, lung, kidney, and limb buds during midgestation. To explore the potential role of Klf6 in mouse development, we analyzed Klf6-/- mice and found that the homozygous mutation is embryonic lethal by embryonic day (E) 12.5 and associated with markedly reduced hematopoiesis and poorly organized yolk sac vascularization. Additionally, mRNA levels of Scl and Gata1 were reduced by approximately 80% in Klf6-/- yolk sacs. To further analyze this phenotype, we generated Klf6-/- embryonic stem (ES) cells by homologous recombination, and compared their capacity to differentiate into the hematopoietic lineage with that of either Klf6+/- or Klf6+/+ ES cells. Consistent with the phenotype in the early embryo, Klf6-/- ES cells displayed significant hematopoietic defects following differentiation into EBs. Prolongation of epiblast-like cells and delays in mesoderm induction were also observed in the Klf6-/- EBs, associated with delayed expression of Brachyury, Klf1, and Gata1. Forced expression of KLF6 using a tet-inducible system enhanced the hematopoietic potential of wild-type EBs. Collectively, these findings implicate Klf6 in ES-cell differentiation and hematopoiesis.
AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML
Authors: Pearce Daniel J. , Taussig David , Zibara Kazem , Smith Lan-Lan , Ridler Christopher M. , Preudhomme Claude , Young Bryan D. , Rohatiner Ama Z. , Lister T. Andrew , Bonnet Dominique
Published: October 2005

The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients, and alternative tissue sources did not cause AML engraftment in most previously nonengrafting AML samples. Homing of AML cells to the marrow was the same between engrafters and nonengrafters. FLT3 internal tandem duplication (ITD) and nucleophosmin mutations occurred at a similar frequency in engrafters and nonengrafters. The only variable that was related to engraftment ability was the karyotypically defined risk stratification of individual AML cases. Of interest, follow-up of younger patients with intermediate-risk AML revealed a significant difference in overall survival between NOD/SCID engrafting and nonengrafting AMLs. Hence, the ability of AML to engraft in the NOD/SCID assay seems to be an inherent property of AML cells, independent of homing, conditioning, or cell frequency/source, which is directly related to prognosis. Our results suggest an important difference between leukemic initiating cells between engrafting and nonengrafting AML cases that correlates with treatment response.
Epstein-Barr virus: the impact of scientific advances on clinical practice
Authors: Williams Hilary , Crawford Dorothy H.
Published: October 2005

Epstein-Barr virus (EBV) is a tumorigenic herpes virus that infects and persists in B lymphocytes in the majority of humans, generally without causing disease. However, in a few individuals the virus is associated with significant pathology, particularly benign and malignant lymphoproliferations. Recently acquired knowledge on the mechanisms of EBV persistence, immune control of primary and persistent infection, and disease pathogenesis is now being translated into the clinic with novel methods of diagnosis, prevention and treatment contributing to improved patient care. This review concentrates on these recent advances in the field of hematology/oncology.
A310 helical turn is essential for the proliferation-inhibiting properties of macrophage inflammatory protein-1 alpha (CCL3)
Authors: Ottersbach Katrin , Mclean John , Isaacs Neil W. , Graham Gerard J.
Published: October 2005

Despite possessing marked structural similarities, the chemokines macrophage inflammatory protein-1α (MIP-1α; CCL3) and RANTES (CCL5) display differential activity in hematopoietic progenitor-cell-inhibitory assays, with MIP-1α being active and RANTES inactive in this context. We have sought to identify the key structural determinants of this property of MIP-1α. This has involved constructing MIP-1α/RANTES chimeras by swapping structural domains between the 2 proteins. Results indicate that, in contrast to other chemokine functions, neither the N nor the C termini are key determinants of inhibitory activity. The motif that appears to be most important for this activity lies between the second and fourth cysteines of MIP-1α and further domain swap analysis has narrowed this down to the 310 helical turn preceding the first β-strand in MIP-1α. More detailed analysis has highlighted the role played by a specific dipeptide motif in the proliferation-inhibitory activity of chemokines. The involvement of the 310 helical-turn motif in chemokine function is unprecedented and this study therefore identifies a novel, functionally essential motif within chemokines. In addition, this study further attests to the alternative mechanisms of action used by MIP-1α in inhibition of hematopoietic progenitor-cell proliferation and regulation of leukocyte migration.
HLA-DPB1 matching status has significant implications for recipients of unrelated donor stem cell transplants
Authors: Shaw Bronwen E. , Marsh Steven G.E. , Mayor Neema P. , Russell Nigel H. , Madrigal J. Alejandro
Published: October 2005

Studies in unrelated donor (UD) hematopoietic stem cell transplantations (HSCT) show an effect of the matching status of HLA-DPB1 on complications. We analyzed 423 UD-HSCT pairs. Most protocols included T-cell depletion (TCD). All pairs had high-resolution tissue typing performed for 6 HLA loci. Two hundred eighty-two pairs were matched at 10 of 10 alleles (29% were DPB1 matched). In 141 HLA-mismatched pairs, 28% were matched for DPB1. In the 10 of 10 matched pairs (n = 282), the 3-year probability of relapse was 61%. This was significantly higher in DPB1-matched pairs (74%) as compared with DPB1-mismatched pairs (56%) (log rank, P = .001). This finding persisted in multivariate analysis. In the group overall (n = 423), relapse was also significantly increased if DPB1 was matched (log rank; P < .001). These results were similar in chronic myeloid leukemia (CML; P < .001) and acute lymphoblastic leukemia (ALL; P = .013). In ALL, DPB1-matched pairs had a significantly worse overall survival (log rank; P = .025). Thus, in recipients of TCD UD-HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status for the other HLA molecules. It is possible that this effect is especially apparent following TCD transplantations and invites speculation about the function of DPB1 within the immune system.
Differential roles for β2 integrins in experimental autoimmune bullous pemphigoid
Authors: Liu Zhi , Zhao Minglang , Li Ning , Diaz Luis A. , Mayadas Tanya N.
Published: October 2005

Bullous pemphigoid (BP) is an autoimmune disease associated with autoantibodies directed against the hemidesmosomal antigens anti-BP230 and anti-B180. Neonatal mice injected with rabbit anti-mouse BP180 (mBP10) IgG develop a BP-like disease. Complement, immune complexes, mast cells, and neutrophils play a key role in subepidermal blistering in this animal model. In this study we investigated the role of β2 integrins in experimental BP. Wild-type (WT) mice pretreated with neutralizing antibody against CD11a (LFA-1), CD11b (Mac-1), CD11a plus CD11b, or CD18 alone failed to develop BP when injected with pathogenic anti-mBP180 IgG. This was associated with a significant reduction in neutrophil accumulation in neutralizing antibody-treated mice. Mac-1-deficient (Mac-1 knockout [KO]) mice were resistant to experimental BP despite normal complement deposition and mast cell and neutrophil degranulation. Neutrophil infiltration in Mac-1 KO mice was severely impaired at 24 hours. However, more neutrophils accumulated in the skin of Mac-1 KO mice compared with WT mice at early time points (2-4 hours), which was associated with an increase in their survival as determined by apoptosis markers. These data suggest that β2 integrins play differential roles in experimental BP: LFA-1 is required for neutrophil recruitment, while Mac-1 mediates late neutrophil accumulation and apoptosis of infiltrating neutrophils.