bluuebunny/crossref_metadata_2025 huggingface dataset:
Water and enzyme secretion are tightly coupled in pancreatic secretion stimulated by food or CCK-58 but not by CCK-8
Authors: Yamamoto M. , Reeve J. R. , Keire D. A. , Green G. M.
Published: November 2004

Pancreatic secretion of protein, water, chloride, and bicarbonate under basal conditions and in response to intravenous and intraduodenal stimuli were studied in awake rats fully recovered from surgery. During the basal phase of pancreatic secretion, protein output and water output were weakly correlated or uncorrelated, consistent with separate regulation and distinct cellular origin of enzyme (acinar cells) and water (duct cells), referred to as the two-component paradigm of pancreatic secretion. When pancreatic secretion was stimulated physiologically, water and protein output abruptly became strongly and significantly correlated, suggesting that protein secretion and water secretion are tightly coupled or that protein secretion is dependent on water secretion. The apparent function of this coupling is to resist or prevent increases in protein concentration as protein output increases. This pattern of secretion was reproduced by intravenous infusion of the CCK-58 form of cholecystokinin, which strongly stimulates pancreatic water and chloride secretion, but not by CCK-8, which only weakly stimulates water and chloride secretion in a non-dose-dependent manner. The remarkably tight association of water and protein secretion in food-stimulated and CCK-58-stimulated pancreatic secretion is consistent with a single cell type as the origin of both water and enzyme secretion, i.e., the acinar cell, and is not consistent with the two-component paradigm of pancreatic secretion. Because CCK-58 is the only detectable endocrine form of cholecystokinin in the rat and its bioactivity pattern is markedly and qualitatively different from CCK-8, actions previously recorded for CCK-8 should be reexamined.
Functional effects of C-type natriuretic peptide and nitric oxide are attenuated in hypertrophic myocytes from pressure-overloaded mouse hearts
Authors: Su Jun , Zhang Qihang , Moalem Jacob , Tse James , Scholz Peter M. , Weiss Harvey R.
Published: November 2004

Increases in the myocardial level of cGMP usually exert negative inotropic effects in the mammalian hearts. We tested the hypothesis that the negative functional effects caused by nitric oxide (NO) or C-type natriuretic peptide (CNP) through cGMP would be blunted in hypertrophied cardiac myocytes. Contractile function, guanylyl cyclase activity, cGMP-dependent protein phosphorylation, and calcium transients were assessed in ventricular myocytes from aortic stenosis-induced hypertrophic and age-matched control mice. Basal percentage shortening was similar in control and hypertrophic myocytes. S-nitroso- N-acetyl-penicillamine (SNAP, an NO donor, 10−6and 10−5M) or CNP (10−8and 10−7M) reduced percentage shortening in both groups, but their effects were blunted in hypertrophic myocytes. Maximal rates of shortening and relaxation were depressed at the basal level, and both reagents had attenuated effects in hypertrophy. Similar results were also found after treatment with guanylin and carbon monoxide, other stimulators of particulate, and soluble guanylyl cyclase, respectively. Guanylyl cyclase activity was not significantly changed in hypertrophy. Addition of Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine (an inhibitor of cGMP-dependent protein kinase, 5 × 10−6M) blocked SNAP or the effect of CNP in control mice but not in hypertrophy, indicating the cGMP-dependent kinase (PKG) may not mediate the actions of cGMP induced by NO or CNP in the hypertrophic state. Calcium transients after SNAP or CNP were not significantly changed in hypertrophy. These results suggest that in hypertrophied mice, diminished effects of NO or CNP on ventricular myocyte contraction are not due to changes in guanylyl cyclase activity. The data also indicated that PKG-mediated pathways were diminished in hypertrophied myocardium, contributing to blunted effects.
Adult sterol metabolism is not affected by a positive sterol balance in the neonatal Golden Syrian hamster
Authors: Yao Lihang , Woollett Laura A.
Published: November 2004

Dietary components impact metabolism early in life. Some of the diet-induced effects are long lasting and can lead to various adult-based diseases. In the current studies, we examined the short-term effects of dietary cholesterol on neonatal hepatic sterol metabolism and the long-term effects that those early-life diets had on sterol metabolism in adulthood. Neonatal hamsters began consuming solid food as a supplement to milk by 5 days of age; diets contained 0 or 2% added cholesterol (wt/wt). By 10 days of age, plasma and liver cholesterol concentrations were 3.2- and 2.5-fold greater, respectively, in the neonates fed cholesterol. Hepatic sterol synthesis rates were suppressed 65% in cholesterol-fed neonates compared with control neonates. By 20 days of age, plasma and liver cholesterol concentrations were still greater and sterol synthesis rates were now suppressed maximally in neonates fed cholesterol compared with control neonates. The expression level of an apolipoprotein B-containing lipoprotein receptor (low-density lipoprotein receptor-related protein) was greater and the mature form of the sterol regulatory element-binding protein-2 was similar in livers of 20-day-old control neonates compared with control neonates at 10 days of age. To test whether the change in sterol balance in the neonatal period had a lasting effect on hepatic sterol metabolism, all animals were weaned on a low-cholesterol diet. At 70 days of age, hepatic sterol synthesis rates, plasma lipoprotein and liver cholesterol concentrations, and bile acid pool sizes and compositions were measured. Sterol balance in the adults was similar between animals fed either diet early in life, as demonstrated by a lack of difference in any parameter measured. Thus, even though dietary cholesterol suppressed hepatic sterol synthesis rates dramatically in the neonatal hamster, the change has little impact on sterol balance later in life.
Glucose does not activate nonadrenergic, noncholinergic inhibitory neurons in the rat stomach
Authors: Shi Min , Jones Allison R. , Ferreira Manuel , Sahibzada Niaz , Gillis Richard A. , Verbalis Joseph G.
Published: November 2004

We reported previously that intravenously administered d-glucose acts in the central nervous system to inhibit gastric motility induced by hypoglycemia in anesthetized rats. The purpose of this study was to determine whether this effect is due to inhibition of dorsal motor nucleus of the vagus (DMV) cholinergic motoneurons, which synapse with postganglionic cholinergic neurons, or to excitation of DMV cholinergic neurons, which synapse with postganglionic nonadrenergic, noncholinergic (NANC) neurons, particularly nitrergic neurons. Three approaches were employed: 1) assessment of the efficacy of d-glucose-induced inhibition of gastric motility in hypoglycemic rats with and without inhibition of nitric oxide synthase [10 mg/kg iv nitro-l-arginine methyl ester (l-NAME)], 2) assessment of the efficacy of intravenous bethanechol (30 μg·kg−1·min−1) to stimulate gastric motility in hypoglycemic rats during the time of d-glucose-induced inhibition of gastric motility, and 3) determination of c-Fos expression in DMV neurons after intravenous d-glucose was administered to normoglycemic rats. Results obtained demonstrated that l-NAME treatment had no effect on d-glucose-induced inhibition of gastric motility; there was no reduction in the efficacy of intravenous bethanechol to increase gastric motility, and c-Fos expression was not induced by d-glucose in DMV neurons that project to the stomach. These findings indicate that excitation of DMV cholinergic motoneurons that synapse with postganglionic NANC neurons is not a significant contributing component of d-glucose-induced inhibition of gastric motility.
Continuous Recording of Blood Pressure in Cerebrovascular Disease: When Should It Be Done?
Authors: Tejada Javier , Hernández-Echebarría Luís , Ballesteros Beatriz
Published: November 2004

Background and Objectives: Ambulatory blood pressure (BP) monitoring has found some specific clinical indications in the treatment and control of hypertension (HT). As with other target organs exposed to vascular damage dependent on HT, ambulatory BP monitoring can be a useful tool in the prevention of cerebrovascular processes. Method: Review of published articles (Medline database) which have investigated the value of continuous recording of BP in cerebrovascular disease (CVD). Results: Research on the BP patterns and its relationship with stroke has been carried out in subjects with no previous history of CVD (cohort studies and in patients with essential HT, differentiating between adults and elderly patients) and patients after a cerebral ischemic event. The study objectives are aimed at determining its prognostic value in the development of silent and symptomatic CVD, and its prognostic significance regarding functional recovery and the differences of the BP patterns according to the different stroke subtypes. Conclusions: BP monitoring is a useful technique with applications in the control and treatment of the pathological variations of BP in hypertensive patients, with and without a previous history of cerebral ischemia, and mainly in elderly patients, due to the deterioration of the cerebral circulation regulation mechanisms. Clinical research has confirmed the importance of factors related to the circadian rhythm of BP in the primary and secondary prevention of cerebrovascular processes.
A Genetic Approach to Ischemic Stroke Therapy
Authors: Vila Nicolás
Published: November 2004

Stroke therapy will undergo a great revolution in the present decade. The knowledge of the human genome, gene interactions and proteomics will permit a new concept of drug development for stroke. Gene therapy by modification of gene expression will be useful to treat atherosclerosis and hypertensive microangiopathy, or in the acute phase, we will manipulate the acute gene expression induced by ischemia or the apoptotic gene program. However, a single abnormal gene, as in monogenic diseases, is easier to replace than several genes in complex multigenic disorders. Gene therapy, stem cell therapy and neurological grafts for stroke are still in the experimental phase, and many hurdles will have to be jumped before the introduction of these therapies into human clinical stroke trials. A more immediate clinical application of genetics to stroke therapy is the development of pharmacogenetics that analyzes the influence of genetic variability of individuals on drug response. A new era of personalized therapy is dawning where specific DNA biochips will help stroke clinicians to decide on the better use of thrombolytics, neuroprotectants, antithrombotics, statins or antihypertensives.
Usefulness of Anticoagulants in the Prevention of Ischemic Stroke
Authors: Rubio Francisco , Jato Mario
Published: November 2004

Oral anticoagulants are drugs commonly used in the prevention of vascular diseases, especially in embolic-type processes. Although several studies have assessed the possibility of using them in arterial processes, the experience has not been satisfactory so far. Heart diseases with major emboligenic flow are still the main indication, while the prevention of other low-risk heart diseases and treatment of large- or small-artery disease can be based on antiaggregant treatment. Other groups study the problem in large series.
The Endogenous Cannabinoid, Anandamide, Activates the Hypothalamo-Pituitary-Adrenal Axis in CB1 Cannabinoid Receptor Knockout Mice
Authors: Wenger Tibor , Ledent Catherine , Tramu Gérard
Published: November 2004

The purpose of this study was to investigate the effects of the endogenous cannabinoid arachidonoyl-ethanolamide, anandamide (AEA), on the activity of the hypothalamo-pituitary-adrenal (HPA) axis in cannabinoid receptor (CB1 receptor) inactivated (KO) mice. A low dose (0.01 mg/kg i.p.) of AEA significantly increased plasma corticotropin (ACTH) and corticosterone concentrations in both wild-type (+/+) and in mutant (–/–) animals. In each case, hormone levels reached their peaks at 90 min after AEA administration. In a parallel experiment, AEA administration was preceded by the injection of SR 141716A (1.0 mg/kg), a selective and potent CB1 receptor antagonist, or of capsazepine (5.0 mg/kg), a potent vanilloid receptor of type 1 (VR1) antagonist. The latter drugs did not prevent the effects of AEA on the HPA axis. Using Fos protein immunohistochemistry, we observed that the parvocellular part of the hypothalamic paraventricular nucleus (PVN) was activated as early as 45 min after AEA injection and reached peak levels after 60 min in both +/+ and –/– mice. Furthermore, the CB1 and VR1 receptor antagonists did not block the effects of AEA on Fos immunoreactivity. The results strongly support the view that activation of the HPA axis produced by AEA possibly occurs via a currently unknown (CBx) cannabinoid receptor present in PVN.
Rare Quasispecies in the YMDD Motif of Hepatitis B Virus Detected by Polymerase Chain Reaction with Peptide Nucleic Acid Clamping
Authors: Ohishi Waka , Chayama Kazuaki
Published: November 2004

The emergence of drug-resistant mutants of hepatitis B virus (HBV) is a serious problem during antiviral therapy of patients with chronic hepatitis B. Lamivudine-resistant mutants with a mutation in the YMDD motif of reverse transcriptase of HBV emerge in approximately one half of the treated patients within 5 years. To date, the detection of YMDD mutants by polymerase chain reaction (PCR) with peptide nucleic acid (PNA) clamping is most sensitive. In this study, the performance of this method was evaluated in various clinical settings. The PCR-PNA method was able to detect the emergence of YMDD mutants 2–3 months earlier than the previously developed method involving restriction fragment length polymorphism. Further, rare quasispecies were detected by PCR-PNA in patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg). Many previously unrecognized mutants, such as those with YLDD and YMED, were found in them. Although precise sequence analyses of 10 patients identified YVDD and YIDD sequences in 6 of them, only 1 patient had a typical YVDD sequence that was identical with that in the reported lamivudine-resistant strain. All HBV mutants with the YIDD sequence accompanied stop codon(s) in the overlapping envelope (S) gene, suggesting that these strains would have no relevance as regards the emergence of lamivudine resistance. These results suggest that it would be difficult to detect lamivudine-resistant mutants before the therapy and that they would have a greater ability to evade the attack of antiviral drugs by frequent nucleotide substitutions than previously expected.
The Role of c-Jun Protein in Proliferation and Apoptosis of the Endometrium throughout the Menstrual Cycle
Authors: Udou Toshihiro , Hachisuga Toru , Tsujioka Hiroshi , Kawarabayashi Tatsuhiko
Published: November 2004

Proliferation and apoptosis of the endometrium throughout the menstrual cycle were evaluated. Sections from 30 premenopausal women were examined using antibodies of c-jun protein, c-fos protein, estrogen receptors alpha and beta (ER-α and ER-β), progesterone receptor (PR), and Ki-67. Apoptotic cells were identified using a modified terminal deoxynucleotidyl-transferase-mediated biotinylated deoxyuridine triphosphate nick-end labeling (TUNEL) method. The cyclic changes of c-jun protein, c-fos protein, ER-α, PR, and Ki-67 were shown in glandular epithelial cells. Although the stromal expression of ER-α decreased during the secretory phase, a high stromal expression of c-jun protein and PR was still observed during the late secretory phase. The expression of ER-β appeared lower as compared with that of ER-α, without a cyclic change. The apoptotic index was significantly elevated in the glandular epithelial cells of the late secretory phase, whereas a few apoptotic cells were detected in the stromal cells at any stage of the cycle. The cyclic change of c-jun protein probably plays an important role in proliferation and apoptosis of glandular epithelial cells. The persistent stromal expression of c-jun protein and PR is thus considered to prevent stromal cells from entering into apoptosis during the late secretory phase.
Pregnancy Outcome in Patients with a History of Recurrent Spontaneous Miscarriages and Documented Thrombophilias
Authors: Krabbendam Ineke , Dekker Gustaaf A.
Published: November 2004

The aim of this study was to evaluate the effect of treatment in patients analyzed for recurrent spontaneous miscarriage with a diagnosis of a hereditary thrombophilia, the presence of antiphospholipid and/or autoimmune antibodies, and/or hyperhomocystinemia (HHC) with or without methylenetetrahydrofolate reductase (MTHFR) polymorphisms. In total, 76 women with 2 or more embryonic or fetal losses were analyzed. Of these, 49 (64.4%) women were found to have one or more thrombophilias and/or autoimmune antibodies, and 33 (43.4%) women were found to have a MTHFR polymorphism and/or HHC. Since completion of the recurrent miscarriage analysis, 39 women conceived again. All women with a thrombophilia were treated with low-dose aspirin plus low molecular weight heparin. All women with previously diagnosed HHC and/or MTHFR polymorphisms were treated with folate and vitamin B6 and B12 supplementation. In the thrombophilia group, 27 women conceived resulting in 20 successful pregnancies (74.1%) and 7 pregnancy losses (2 trisomy 16, 1 ectopic pregnancy and 4 unexplained miscarriages), i.e. an unexplained pregnancy loss rate of 14.8%. In the HHC/MTHFR group 22 women conceived, resulting in 17 successful pregnancies (77.3%) and 5 pregnancy losses (1 trisomy 16, 1 Turner syndrome and 3 unexplained miscarriages), i.e. an unexplained pregnancy loss rate of 13.6%.
Timing of Fetal Nucleated Red Blood Cell Count Elevation in Response to Acute Hypoxia
Authors: Blackwell Sean C. , Hallak Mordechai , Hotra John W. , Refuerzo Jerrie , Hassan Sonia S. , Sokol Robert J. , Sorokin Yoram
Published: November 2004

We determined the effect of an acute episode of severe hypoxia on peripheral nucleated red blood cell (RBC) counts in the fetal rat. Timed pregnant rats were randomized to a 2-hour exposure to hypoxia (placement in a chamber containing a gas mixture with 9% O2 +3% CO2 + balanced N2) or to a 2-hour exposure to a sham chamber containing room air. Two maternal animals per group underwent cesarean section immediately after the 2-hour period and then 4, 12, 24, 36, 48, and 60 h after exposure. Fetal nucleated RBC counts were compared between groups at each time interval. The nucleated RBC counts were not significantly different in the hypoxia group until 12 h (mean ± SEM 158.0 ± 22.4 RBC/10 high-power fields vs. 90.6 ± 11.0; p = 0.03) and 24 h (133.2 ± 16.0 vs. 84.1 ± 9.0; p = 0.04) after exposure. There were no differences between groups 36, 48, and 60 h after exposure. In the near-term rat fetus, acute hypoxia was associated with a delayed but transient increase in peripheral nucleated RBC counts.
Molecular Signatures of Vascular Injury Are Associated With Early Growth of Intracerebral Hemorrhage
Authors: Silva Yolanda , Leira Rogelio , Tejada Javier , Lainez José M. , Castillo José , Dávalos Antoni ,   by the Stroke Project, Cerebrovascular Diseases Group of the Spanish Neurological Society
Published: November 2004

Background and Purpose—

To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage (ICH).

Methods—

In a multicenter prospective study, we determined concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of <12 hours’ duration. Patients had a neurological evaluation and a computed tomography (CT) scan performed at baseline and at 48±6 hours. Early growth of the ICH was defined as a volume increase >33% between the 2 CT examinations for ICH with a baseline volume <20 mL and >10% for ICH ≥20 mL. Clinical, radiological, and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis.

Results—

Fifty-four (29.5%) patients showed a relevant early growth of ICH. High leukocyte count and fibrinogen levels, low platelet count, and intraventricular bleeding were associated with early ICH growth in bivariate analyses. Plasma concentrations of IL-6 (median [quartiles]: 19.6 [13.6; 29.9] versus 15.9 [11.5; 19.8] pg/mL), TNF-α (13.5 [8.4; 30.5] versus 8.7 [4.7; 13.5] pg/mL), MMP-9 (153.3 [117.7; 204.7] versus 70.6 [47.8; 103.8] ng/mL), and c-Fn (8.8 [6.2; 12.5] versus 2.8 [1.6; 4.2] μg/mL) were significantly higher in patients with early growth of ICH (all
P
<0.001). C-Fn levels >6 μg/mL (OR, 92; 95%CI, 22 to 381;
P
<0.0001) and IL-6>24 pg/mL (OR, 16; 95%CI, 2.3 to 119;
P
=0.005) were independently associated with ICH enlargement in the logistic regression analysis.

Conclusions—

Molecular signatures of vascular injury and inflammatory markers in the early acute phase of ICH are associated with subsequent enlargement of the hematoma.
Religious Conversion, Covert Defiance and Social Identity: A Comparative View
Authors: Nissimi Hilda
Published: November 2004

This article examines the special contribution of forced conversion to the formation of a new social identity. Groups that were forced to convert while struggling to maintain a former-covert religious identity, such as the Moriscos of Spain, the Spanish and Portuguese Jews, and the Huguenots of France, shaped social identities with common traits, despite differences in social, political and religious environments. These groups stressed memory practices, strengthened familistic values, and regendered social roles. Each of these practices set them apart from both of the faith communities they belonged to: the old and the new, the open and the secret. The Mashhadis of Iran are offered as a control group to test this argument, as their community is the farthest in time and space while conforming to the same pattern of social mechanisms. The evolution of the new social-cultural and even ethnic identity was a process whereby religious motifs generated cultural cohesion, and communal ties facilitated both. Thus, even when danger was over a new community was born, more self-conscious, and stronger than before.
Low-Grade Lymphoma
Authors: Winter Jane N. , Gascoyne Randy D. , Van Besien Koen
Published: November 2004

Folicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma, shows considerable heterogeneity in its clinical behavior, representative of a biology that appears increasingly complex and diverse. As our knowledge of the molecular basis of FL increases, we strive for an integration between the bench and clinic that yields treatments based on our scientific understanding and biomarkers that allow us to prescribe treatment rationally.

In Section I, Dr. Randy Gascoyne describes the histologic, cytogenetic and biologic features of FL that underlie its clinical variability. Key aspects of the pathologic diagnosis of FL that have particular relevance to the clinician are highlighted. A proposed model for follicular lymphomagenesis and diffuse large B cell lymphoma transformation has emerged and continues to evolve as the molecular story unfolds. A biologic basis for clinical outcome in FL also appears to be forthcoming.

In Section II, Dr. Jane Winter addresses the complex process of selecting among the many treatment options for patients with FL. Previously a simple matter of deciding between oral or intravenous alkylators, clinicians and patients must now struggle to choose among vastly different approaches ranging from “watch and wait” to stem cell transplantation. The introduction of rituximab and radioimmunoconjugates is changing the treatment paradigm, but the optimal approach to integrating these and other new agents remains to be determined. At every decision point, the best approach is always a clinical trial.

In Section III, Dr. Koen Van Besien provides a well-documented update on outcomes associated with autologous and allogeneic stem cell transplantation for FL. The results of trials of autologous stem cell transplantation in first remission and recent data supporting a role for graft purging are discussed. Based on the premise that a graft-versus-lymphoma effect is operative in FL, reduced-intensity allogeneic transplantation is the preferred approach in many cases, and recently reported results are summarized. Criteria for patient selection and the optimal role of transplantation in the overall therapeutic plan for the patient with FL are presented.
Testicular seminoma after the complete remission of extragonadal yolk sac tumor : a case report
Authors: Kuroda Isao , Ueno Munehisa , Mitsuhashi Tomoko , Nakagawa Ken , Yanaihara Hitoshi , Tsukamoto Takuji , Deguchi Nobuhiro
Published: November 2004

Background

Between 2% and 5% of malignant germ-cell tumors in men arise at extragonadal sites. Of extragonadal germ cell tumors, testicular carcinoma in situ (CIS) are present in 31–42% of cases, and CIS are reported to have low sensitivity to chemotherapy in spite of the various morphology and to have a high likelihood of developing into testicular tumors. A testicular biopsy may thus be highly advisable when evaluating an extragonadal germ cell tumor.

Case presentation

A 36-year-old man was diagnosed as having an extragonadal non-seminomatous germ cell tumor, that was treated by cisplatin-based chemotherapy, leading to a complete remission. In the meantime, testicular tumors were not detected by means of ultrasonography. About 4 years later, a right testicular tumor was found, and orchiectomy was carried out. Microscopically, the tumor was composed of seminoma.

Conclusions

We herein report a case of metachronous occurrence of an extragonadal and gonadal germ cell tumor. In the evaluation of an extragonadal germ cell tumor, a histological examination should be included since ultrasonography is not sufficient to detect CIS or minute lesions of the testis.
Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis
Authors: Rioja Inmaculada , Clayton Chris L , Graham Simon J , Life Paul F , Dickson Marion C
Published: November 2004

Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naïve, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire® profile search and K-mean cluster analysis. Microarray-based data for a subset of genes were validated using real-time PCR TaqMan® analysis. Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression. The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling. Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease. The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development. In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat. These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).
Stabilization and mobility of the head and trunk in vervet monkeys(Cercopithecus aethiops) during treadmill walks and gallops
Authors: Dunbar Donald C.
Published: November 2004

The brain requires internal or external reference frames to determine body orientation in space. These frames may change, however, to meet changing conditions. During quadrupedal overground locomotion by monkeys, the head rotates on a stabilized trunk during walking, but the trunk rotates on a stabilized head during galloping. Do the same movement patterns occur during in-place locomotion? Head and trunk pitch rotations were measured, and yaw and roll rotations estimated from cine films of three adult vervet monkeys(Cercopithecus aethiops L. 1758) walking and galloping quadrupedally on a treadmill. Head and trunk rotational patterns during treadmill walks were comparable to the patterns found during overground walks. The rotational velocities of these segments during both treadmill walks and gallops were also comparable to the velocities found during natural locomotion. By contrast,whereas head and trunk rotational patterns during treadmill gallops did occur that were comparable to the patterns practiced during overground gallops, a significantly different pattern involving large and simultaneous head and trunk rotations was more commonly observed. Simultaneous head and trunk rotations may be possible during treadmill gallops because the fixed visual surround is providing an adequate spatial reference frame. Alternatively, or in addition to this visual information, a re-weighting in other sensory modalities may be occurring. Specifically, the vestibular inputs used during overground locomotion to reference gravity or a gravity-derived vector may become less important than proprioceptive inputs that are using the treadmill belt surface as a reference. Regardless, the spatial reference frame being used, blinks that occur at specific times during the largest head yaw rotations may be necessary to avoid the initiation of unwanted and potentially destabilizing lateral sway brought on by sudden increases in optic flow velocity.
How a low tissue O2 strategy could be conserved in early crustaceans: the example of the podocopid ostracods
Authors: Corbari Laure , Carbonel Pierre , Massabuau Jean-Charles
Published: November 2004

An adaptation strategy whereby O2 partial pressure, PO2, in the tissues is maintained within a low,narrow range of 1–3 kPa, largely independent of the inspired PO2, has been reported in water- and air-breathing poikilotherms and in homeotherms. Based on the postulate that this basic cellular mechanism has been established since the early stages of evolution, it has been hypothesized that it could be the consequence of an early adaptation strategy to maintain cellular oxygenation within the same low and primitive range. To test this hypothesis we studied the basic mechanisms of oxygen regulation in podocopid ostracods, minute crustaceans that have existed on earth for at least 500 million years. Podocopids lack any regulatory mechanism for adapting their ventilation to cope with changes in water oxygenation, and instead adjust their tissue oxygenation status by migrating through the O2 gradient to sediment layers where the PO2 of the water is 3–5 kPa. Experimental manipulation of the O2 profile induced their vertical migration to follow this precise water PO2 and demonstrates the existence of a regulation strategy. This strategy must be associated with the lower PO2 values within the animal's carapace valves, showing that podocopids can actively regulate their tissue PO2 at constant but even lower values than the water. In conclusion, the low tissue PO2strategy could have existed in early crustaceans and, by extension, in early animals.
Metamorphosis inXenopus laevisis not associated with large-scale nuclear DNA content variation
Authors: Freeman Jennifer L. , Rayburn A. Lane
Published: November 2004

Amphibian metamorphosis is a complex process that has been speculated to involve DNA amplification and chromatin rearrangement. While recent studies have concentrated on chromatin rearrangement, only a few studies have dealt with variation in the amount of DNA during amphibian metamorphosis. In this study, nuclei were isolated from Xenopus laevis at various developmental stages. The nuclei were examined in both an unfixed state and a fixed state. The nuclei were stained with propidium iodide and analyzed by flow cytometry to determine their fluorescence intensity. The unfixed nuclei had higher fluorescence variation compared with the fixed nuclei. This increase in variation appeared due to the presence of nuclei of variable fluorescence intensity within the unfixed nuclei. Upon optimum fixation, which has been speculated to result in more homogeneous chromatin conformation and to reduce staining artifacts, the nuclei were observed to have less fluorescence intensity variation. The differential fluorescence observed in this study is consistent with the hypothesis that large-scale intra-individual DNA variation is not associated with amphibian metamorphosis.
Prognostic Value of an Early Soluble L-Selectin (sCD62L) Assay for Risk Assessment in Blunt Multiple Trauma: A Metaanalysis
Authors: Stengel Dirk , Bauwens Kai , Keh Didier , Gerlach Herwig , Ekkernkamp Axel , Tauber Rudolf , Kerner Thoralf
Published: November 2004

Background: After severe trauma, decreased plasma concentrations of the soluble adhesion molecule L-selectin (sCD62L) have been linked to an increased incidence of lung failure and multiorgan dysfunction syndrome (MODS). Individual studies have had conflicting results, however. We examined multiple studies in an attempt to determine whether early sCD62L concentrations are predictive of major complications after severe trauma.

Methods: We performed a systematic review of six electronic databases and a manual search for clinical studies comparing outcomes of multiply injured patients (Injury Severity Score ≥16) depending on their early sCD62L blood concentrations. Because of various outcome definitions, acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) were studied as a composite endpoint. Weighted mean differences (WMDs) in sCD62L concentrations were calculated between individuals with and without complications by fixed- and random-effects models.

Results: Altogether, 3370 citations were identified. Seven prospective studies including 350 patients were eligible for data synthesis. Published data showed the discriminatory features of sCD62L but did not allow for calculation of measures of test accuracy. Three of four studies showed lower early sCD62L concentrations among individuals progressing to ALI and ARDS (WMD = −229 μg/L; 95% confidence interval, −476 to 18 μg/L). No differences in sCD62L concentrations were noted among patients with or without later MODS. Nonsurvivors had significantly lower early sCD62L plasma concentrations (WMD = 121 μg/L; 95% confidence interval, 63–179 μg/L), but little information was available on potential confounders in this group.

Conclusions: Early decreased soluble L-selectin concentrations after multiple trauma may signal an increased likelihood of lung injury and ARDS. The findings of this metaanalysis warrant a large cohort study to develop selectin-based models targeting the risk of inflammatory complications.
Metrologic Traceability of Total Thyroxine Measurements in Human Serum: Efforts to Establish a Network of Reference Measurement Laboratories
Authors: Thienpont Linda M , Van Uytfanghe Katleen , Marriot John , Stokes Peter , Siekmann Lothar , Kessler Anja , Bunk David , Tai Susan
Published: November 2004

Background: Assuring/demonstrating metrologic traceability of in vitro diagnostics necessitates the availability of measurand-specific reference measurement systems (RMSs) and the possibility for industry to work with competent reference measurement laboratories (RMLs). Here we report the results of a European project to investigate the feasibility of developing a RMS for serum total thyroxine.

Methods: Four candidate RMLs (cRMLs) developed/implemented variants of a candidate reference measurement procedure (cRMP) based on isotope dilution–liquid chromatography–mass spectrometry. The sole constraint implemented was calibration with a common thyroxine primary calibrator. The RMPs were externally validated and assessed for comparability in round-robin trials using common samples, i.e., 5 lyophilized and 33 frozen native sera. At the same time, the performance of the cRMLs organized in a network was assessed. For uniform external quality assessment, common performance specifications were agreed on.

Results: All cRMLs performed the cRMPs with fulfillment of the predefined specifications: total and between-laboratory CVs ≤2.0% and 2.5%, respectively, and a systematic deviation ≤0.9%, estimated with a target assigned from the mean of means obtained by the cRMLs. The mean expanded uncertainty for value assignment to the native sera was 2.1%.

Conclusions: A network of cRMLs, with externally conformed competence to properly perform RMPs, has been established. Performance specifications were defined and will form the basis for admittance of new network members. A serum panel, successfully targeted during the validation process, is available for split-sample measurements with commercial routine measurement procedures. The model can now be used for other measurands for which traceability to the Système International d’Unités is needed.
Cysteine cathepsins in human cancer
Authors: Jedeszko Christopher , Sloane Bonnie F.
Published: November 2004

Proteases play causal roles in the malignant progression of human tumors. This review centers on the roles in this process of cysteine cathepsins, i.e., peptidases belonging to the papain family (C1) of the CA clan of cysteine proteases. Cysteine cathepsins, most likely along with matrix metalloproteases (MMPs) and serine proteases, degrade the extracellular matrix, thereby facilitating growth and invasion into surrounding tissue and vasculature. Studies on tumor tissues and cell lines have shown changes in expression, activity and distribution of cysteine cathepsins in numerous human cancers. Molecular, immunologic and pharmacological strategies to modulate expression and activity of cysteine cathepsins have provided evidence for a causal role for these enzymes in tumor progression and invasion. Clinically, the levels, activities and localization of cysteine cathepsins and their endogenous inhibitors have been shown to be of diagnostic and prognostic value. Understanding the roles that cysteine proteases play in cancer could lead to the development of more efficacious therapies.
A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma kallikrein, plasmin and factor XIIa
Authors: Cruz-Silva Ilana , Gozzo Andrezza J. , Nunes Viviane A. , Carmona Adriana K. , Faljoni-Alario Adelaide , Oliva Maria Luiza V. , Sampaio Misako U. , Sampaio Claudio A. M. , Araujo Mariana S.
Published: November 2004

Caesalpinia echinata is a tree belonging to the Leguminosae family. The red color of the trunk, looking like burning wood (‘brasa’ in Portuguese), is the origin of the name Brazil. Seeds of leguminous plants contain high amounts of serine proteinase inhibitors that can affect different biological processes. Here we show that a protein isolated from seeds of C. echinata is able to inhibit enzymes that participate in blood coagulation and fibrinolysis. This inhibitor (CeKI) was purified to homogeneity by ion exchange and reversed-phase chromatography. SDS-PAGE indicated a single polypeptide chain with a molecular mass of 20 kDa. CeKI inhibits human plasma kallikrein (K
i=3.1 nM), plasmin (K
i=0.18 nM), factor XIIa (K
i=0.18 nM), trypsin (K
i=21.5 nM) and factor Xa (K
i=0.49 mM). CeKI inhibited kinin release from highmolecular- mass kininogen by kallikrein in vitro. The N-terminal sequence, determined by automatic Edman degradation, identified the inhibitor as a member of the Kunitz family. The secondary structure, determined by circular dichroism, is mainly a random coil followed by β-sheet structure. The action of CeKI on enzymes of the blood-clotting intrinsic pathway was confirmed by prolongation of the activated partial thromboplastin time.
Zhongguancun and China's High-Tech Parks in Transition: “Growing Pains” or “Premature Senility”?
Authors: Cao Cong
Published: November 2004

This essay examines the development of China's high-tech parks and, in particular, the challenges they have encountered. It concludes that lack of institutional support for innovation and the indigenous technological capabilities necessary to be competitive, unclear ownership, lack of venture capital, and the overwhelming role of government have impeded the efforts of China's high-tech parks to duplicate the success of role models such as Silicon Valley.
The Determinants of Foreign Aid Allocation across China: The Case of World Bank Loans
Authors: Zhang Guang
Published: November 2004

This paper studies the determinants of the provincial allocation of World Bank loans during the reform era in China. It shows that neither humanitarian concerns nor donors' commercial interests are a significant determinant. The central leadership's preferences and provincial bureaucrats' interests together explain most of China's use of foreign aid.
The U.S. Congress and North Korea during the Clinton Years: Talk Tough, Carry a Small Stick
Authors: Hathaway Robert M. , Tama Jordan
Published: November 2004

This essay explores the striking gap between Republican rhetoric and congressional action on North Korea between 1995 and 2001, when the GOP held majorities in both houses of Congress. While historical in nature, this inquiry offers lessons for President Bush—or, if elected president, John Kerry—as he struggles to meet the North Korea challenge.
The J-Delay Scale: A Measure of the Likelihood of Patient Delay in Breast Cancer
Authors: Facione Noreen C.
Published: November 2004

Patient delay in seeking treatment for breast cancer is a major contributing factor to morbidity and mortality. No instruments have previously been developed to predict the likelihood of patient delay. This report describes the development and testing of the J-Delay scale, designed to estimate a woman’s risk of making the judgment to delay versus to seek immediate evaluation of self-discovered breast symptoms that might signal breast cancer. The J-Delay scale items were developed in four qualitative studies (28 focus groups, combined N = 147 women). The J-Delay scale was tested in 2 large, community-based samples varying across age, income, and ethnicity (combined N = 1,290). Content validity was supported by narrative analysis. Criterion validity was supported by the correct prediction of patient delay in 69%-86% of surveyed and interviewed women with symptoms of 3 months’ or more duration. Internal consistency reliability was .83 in English samples (n = 596 and 352) and .81 in a Spanish sample (n = 222). Test-retest reliability after 3-4 months (n = 251) was supported by consistent assignment in 88.8% of cases. The J-Delay is a valid and reliable tool to identify women at risk for patient delay. Women identified as likely to delay medical attention must be targeted for early detection interventions focused on patient delay.
The Relationships Among Racial Identity, Self-Esteem, Sociodemographics, and Health-Promoting Lifestyles
Authors: Johnson Rolanda L.
Published: November 2004

The purpose of this study was to explore the relationships between racial identity, self-esteem, sociodemographic factors, and health-promoting lifestyles in a sample of African Americans. African American mortality rates are disproportionately high. These rates are associated with health behaviors that are driven by many factors including lifestyle practices. Other factors may be self-esteem and racial identity. Research shows gender differences in health behaviors, but no studies have explored a racial identity and gender interaction. Exploring these relationships may lead to the improved health status of African Americans. A convenience sample of 224 was recruited consisting of 48% males (n = 108). The mean age was 37.2 years (SD = 12.6). Regression analyses demonstrated that the internalization racial identity stage (β = .12; p < .001) and self-esteem (β = .50; p < .001) contributed to the variance in health-promoting lifestyles. Self-esteem did not mediate the relationship between immersion and health-promoting lifestyle scores (β = -.16; p = .03). The full model Beta values show that racial identity remains significant with sociodemographics and interactions controlled, but moderators do not. Racial identity, while not a strong predictor, has some impact on health-promoting lifestyles regardless of sociodemographics.
Epoxy Resins
Authors: Pham Ha. Q. , Marks Maurice J.
Published: November 2004

Epoxy resins are reactive intermediates used to produce a versatile class of thermosetting polymers. They are characterized by the presence of a three‐membered cyclic ether group commonly referred to as an epoxy group, 1,2‐epoxide, or oxirane. The most widely used epoxy resins are diglycidyl ethers of bisphenol A derived from bisphenol A and epichlorohydrin. The outstanding performance characteristics of the thermosets derived from bisphenol A epoxies are largely conveyed by the bisphenol A moiety (toughness, rigidity, and elevated temperature performance), the ether linkages (chemical resistance), and the hydroxyl and epoxy groups (adhesive agents). In addition to bisphenol A, other starting materials such as aliphatic glycols and both phenol ando‐cresol novolacs are used to produce specialty resins. Epoxy resins may also include epoxide‐bearing compounds based on aromatic amine, triazine, and cycloaliphatic backbones.

A variety of reagents have been described for converting the liquid and solid epoxy resins to the cured state, which is necessary for the development of the ultimate end‐use properties. The curing agents or hardeners are categorized as either catalytic or coreactive. Catalytic curing agents initiate resin homopolymerization, either cationic or anionic, as a consequence of using a Lewis acid or base in the curing process. Coreactive curing agents are polyfunctional compounds typically possessing active hydrogens that are employed up to stoichiometric quantities with epoxy resins. The important classes of coreactive curing agents include multifunctional amines and their amide derivatives, polyphenols, polymeric thiols, polycarboxylic acids, anhydrides, phenol–formaldehyde novolacs and resoles, and amino–formaldehyde resins.

The largest single use of epoxy resins is in the protective coatings market where high corrosion resistance and adhesion to substrates are important. Epoxies have gained wide acceptance in protective coatings and in electrical and structural applications because of their exceptional combination of properties such as toughness, adhesion, chemical and thermal resistance, and good electrical properties.
Emission Control, Automotive
Authors: Mooney John J.
Published: November 2004

Automotive exhaust gas composition depends on the fuel, the air‐fuel ratio, and on engine type, wear, temperature, etc. Exhaust control systems must be versatile enough to oxidize unburned fuel and partial oxidation products such as carbon monoxide, yet reduce nitrogen oxides, at both engine start‐up and during sustained engine operation. Emission control systems consist of a catalytic converter for the oxidation‐reduction of exhaust gases in conjunction with a fuel ignition system and oxygen sensor to regulate the air‐fuel ratio. Diesel engine emission control technology is discussed briefly.