bluuebunny/crossref_metadata_2025_split huggingface dataset:
UCN‐01 alters phosphorylation of Akt and GSK3β and induces apoptosis in six independent human neuroblastoma cell lines
Authors: Shankar Sai Latha , Krupski Melissa , Parashar Bhupesh , Okwuaka Chidi , O'Guin Kathy , Mani Sridhar , Shafit‐Zagardo Bridget 
Published: July 2004

AbstractIn this study we evaluated UCN‐01, a small molecule that inhibits protein kinases by interacting with the ATP‐binding site, as a potential anti‐cancer agent for neuroblastoma. UCN‐01 was effective at inducing apoptosis in six neuroblastoma cell lines with diverse cellular and genetic phenotypes. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end‐labeling (TUNEL) assays, detection of active caspase‐3 and cleaved poly ADP‐ribose polymerase (PARP) confirmed that UCN‐01 induced apoptosis. Cell cycle analysis determined that the UCN‐01 treated cells accumulated in S phase by 16 h. Unlike vinblastine and docetaxel that increased survivin expression, UCN‐01 treatment did not increase X‐linked inhibitor of apoptosis protein (XIAP) and survivin levels. Analysis of specific phosphoepitopes on chk1/2, Akt, and GSK3β following UCN‐01 treatment determined that there was no significant change in phospho‐chk1/2. However, there was decreased immunoreactivity at Ser473 and Thr308 of Akt and Ser9 of GSK3β by 4 h indicating that the Akt survival pathway and downstream signalling was compromised. Thus, UCN‐01 was effective at inducing apoptosis in neuroblastoma cell lines.
Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells
Authors: Ohtsuki Sumio , Takizawa Takuya , Takanaga Hitomi , Hori Satoko , Hosoya Ken‐ichi , Terasaki Tetsuya 
Published: July 2004

AbstractOrganic anion transporting polypeptide 3 (oatp3) transports various CNS‐acting endogenous compounds, including thyroid hormones and prostaglandin E2, between extra‐ and intracellular spaces, suggesting a possible role in CNS function. The purpose of this study was to clarify the expression and localization of oatp3 in the mouse brain. RT‐PCR analysis revealed that oatp3 mRNA is expressed in brain capillary‐rich fraction, conditionally immortalized brain capillary endothelial cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2 and 5 mRNAs were detected. Immunohistochemical analysis with anti‐oatp3 antibody suggests that oatp3 protein is localized at the brush‐border membrane of mouse choroid plexus epithelial cells. Furthermore, intense immunoreactivity was detected in neural cells in the border region between hypothalamus and thalamus, and in the olfactory bulb. Immunoreactivity was also detected in brain capillary endothelial cells in the cerebral cortex. These localizations in the mouse brain suggest that oatp3 plays roles in blood–brainand –cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells.
β‐Naphthoflavone disturbs astrocytic differentiation of C6 glioma cells by inhibiting autocrine interleukin‐6
Authors: Takanaga Hiromi , Yoshitake Tomoko , Yatabe Emi , Hara Shuntaro , Kunimoto Manabu 
Published: July 2004

AbstractRegulation of astrocyte differentiation is a key process in the development of the central nervous system (CNS), and disturbance of the differentiation can lead to brain system dysfunction. Here we show that β‐naphthoflavone (βNF), an agonist of the aryl hydrocarbon receptor (AhR), disturbed the cAMP‐induced astrocytic differentiation of C6 glioma by inhibiting autocrine interleukin‐6 (IL‐6). Treatment of cells with βNF reduced the induction of an astrocyte marker glial fibrillary acidic protein (GFAP). This was caused by the inactivation of its upstream transcription factor signal transducer and activator of transcription 3 (STAT3) by βNF. In addition, βNF attenuated the induction of the IL‐6 gene, which leads to the activation of STAT3. Most importantly, the inhibitory effect of βNF on GFAP promoter activity was recovered by the addition of recombinant IL‐6. Taken together, these results indicate that the inhibitory effect of βNF on IL‐6 induction suppresses STAT3 activation. These processes subsequently lead to the attenuation of GFAP induction.
Prejunctional AT1 receptor subtype‐dependent modification of neurotransmitter releases in canine isolated splenic arteries
Authors: Komiyama J. , Yang X.‐P. , Chiba S. 
Published: July 2004

Summary 1 The regulation by angiotensin II (Ang II) formed locally on nerve‐stimulated purinergic and adrenergic components of double‐peaked vasoconstrictions in the canine splenic artery and Ang II receptor subtypes involved were investigated. 2 The perfusion of the precursor angiotensin I (Ang I, 0.1–1 nm) did not affect the vasoconstrictor responses to noradrenaline (NA, 0.03–1 nmol) and adenosine 5′‐triphosphate (ATP, 0.03–1 μmol). The second component vasoconstrictor response to nerve stimulation was dose dependently potentiated by Ang I (0.1–1 nm). The first peaked constriction was slightly, but insignificantly increased. The potentiating effects of Ang I were abolished by KRH‐594 (10 nm), a selective AT1 receptor antagonist, but not by PD 123319 (1–10 nm), an AT2 receptor antagonist. KRH‐594 (10 nm) or PD 123319 (10 nm) never affected the vasoconstrictions to either NA or ATP. 3 The treatment with KRH‐594 (1–10 nm) produced a greater inhibition on the second peaked response than the first one, although both of them were dose dependently inhibited. PD 123319 (1–10 nm) did not affect the vasoconstrictor responses induced by nerve stimulation. 4 Inhibition of angiotensin‐converting enzyme with 10 nm enalaprilat reduced the second peaked response, having no significant inhibition on the first peaked response. A higher dose of enalaprilat (100 nm) produced a greater inhibition of the second peak than the first one. It reduced the second peak by approximately 65%, while the first peak was decreased approximately 35%. After treatment with enalaprilat, Ang I (1 nm) failed to enhance the neuronal vascular response. Enalaprilat at doses used did not affect the vasoconstrictions to either NA or ATP. 5 The present results indicate that endogenously generated Ang II may produce a more marked potentiation of adrenergic transmission than purinergic transmission via activation of prejunctional AT1 receptors.
Coronary and aortic vasoconstriction by cathinone, the active constituent of khat
Authors: Al‐Motarreb A. L. , Broadley K. J. 
Published: July 2004

Summary 1 The psychostimulant constituent of khat leaves, S‐(−)‐cathinone, was examined for vascular activity on the coronary vasculature of guinea‐pig‐isolated perfused hearts and aortic ring preparations. 2 Cathinone caused coronary vasoconstriction, negative inotropy and negative chronotropy in isolated hearts. The major metabolite of cathinone after its ingestion, 1R.2S‐(−)‐norephedrine (norephedrine), also caused coronary vasoconstriction comparable with that by cathinone. Norephedrine, however, had no effect on force or rate of cardiac contractions. 3 Cocaine (10 μm) potentiated the coronary vasoconstriction and positive inotropy by noradrenaline indicating inhibition of neuronal uptake. The vasoconstriction and negative inotropy by cathinone, however, were not affected, indicating that its action was not via release of noradrenaline from sympathetic neurones. 4 The α1‐adrenoceptor antagonist, prazosin, blocked the vasoconstriction by noradrenaline, but not that produced by cathinone in the presence of cocaine. This indicates that the coronary vasoconstriction by cathinone was not due to an action on α1‐adrenoceptors either directly or indirectly through noradrenaline release. 5 Three repeated doses of cathinone displayed the same coronary vasoconstrictor responses, indicating a lack of tachyphylaxis and therefore confirming that the response was unlikely to be due to indirect sympathomimetic activity through release of noradrenaline. 6 In guinea‐pig aortic rings, the order of vasoconstrictor activity was: noradrenaline > norephedrine > cathinone, with each causing approximately equivalent maximum responses. The time to reach plateau contractions was shortest for noradrenaline (5.1 ± 0.5 min), then norephedrine (9.3 ± 1.5 min) and cathinone the longest (25.4 ± 3.2 min, 335 μm dose). 7 These results indicate that cathinone has vasoconstrictor activity which is not due to indirect or direct sympathomimetic activity. The precise mechanism for this vasoconstriction remains to be determined. The coronary vasoconstriction may explain the increased incidence of myocardial infarction in khat chewers, which may arise from coronary vasospasm.
Locally delivered doxycycline improves the healing following non‐surgical periodontal therapy in smokers
Authors: Tomasi Cristiano , Wennström Jan L. 
Published: July 2004

AbstractObjective: The outcome of non‐surgical periodontal therapy is known to be inferior in smokers compared to non‐smokers. In the present study, the question was asked whether such a difference in healing response may be less evident following adjunctive use of locally delivered controlled‐release doxycycline.Methods: One hundred and three patients (42 smokers, 61 non‐smokers), each having at least eight periodontal sites with PPD (probing pocket depth) 5 mm, were following stratification for smoking randomly assigned to two different treatment protocols; non‐surgical scaling/root planing (Control) or ultrasonic instrumentation+application of a 8.5% w/w doxycycline gel (Atridox™) (Test). Instructions in oral hygiene were given to all patients. Clinical examinations of plaque, PPD, clinical attachment level (CAL) and bleeding following pocket probing were performed at baseline and after 3 months. Primary efficacy endpoints were changes in PPD and CAL. Patient mean values were calculated as basis for statistical analysis (multiple regression analyses).Results: The baseline examination revealed no significant difference in mean PPD between treatment groups or between smokers and non‐smokers (mean PPD 5.7–5.9 mm). The mean PPD reduction in the control group at 3‐month was 1.1 mm (SD=0.45) for smokers and 1.5 mm (0.67) for non‐smokers. In the test group the PPD reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non‐smokers, respectively. The mean CAL gain for smokers and non‐smokers amounted to 0.5 mm (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression analysis revealed that smoking and initial PPD negatively influenced the treatment outcome in terms of PPD reduction and CAL gain, while the use of doxycycline had a significant positive effect.Conclusion: Locally applied controlled‐release doxycycline gel may partly counteract the negative effect of smoking on periodontal healing following non‐surgical therapy.
The short‐term effectiveness of non‐surgical treatment in reducing protease activity in gingival crevicular fluid from chronic periodontitis patients
Authors: Figueredo C. M. S. , Areas A. , Miranda L. A. , Fischer R. G. , Gustafsson A. 
Published: July 2004

AbstractObjectives: The aim of this study was to evaluate the short‐term effect of non‐surgical periodontal treatment on protease activity in gingival crevicular fluid (GCF) of patients with chronic periodontitis.Material and Methods: After clinical examination, in which pocket probing depth, probing attachment level, plaque and bleeding indices were recorded, gingival fluid samples from 21 chronic periodontitis patients were collected from gingivitis (GP) and periodontitis (PP) sites with an intracrevicular washing method. Samples were taken in the same way from a group of patients with gingivitis alone (GG). The periodontitis patients received non‐surgical periodontal treatment and were re‐evaluated 30 days later. We compared elastase and collagenase activities before and after treatment. The former activity was measured with a low‐weight substrate (S‐2484) and inhibited by α‐1‐antitrypsin. Matrix‐metalloproteinase‐8 (MMP‐8) was measured with an ELISA and collagenolytic activity with fluorescein‐conjugated collagen type I as substrate.Results: All clinical parameters showed a significant improvement after treatment (p<0.05) which was accompanied by a significant reduction in the values of total elastase activity, free elastase, MPP‐8 and collagenolytic activity in both GP and PP sites (p<0.05). However, the latter sites continued to have higher levels of MMP‐8 and collagenolytic activity than the former ones after treatment. The free elastase activity and the proportion of free elastase in GP and PP samples after treatment remained higher than in untreated GG samples.Conclusion: This study shows that the clinical improvements after non‐surgical treatment are accompanied by reductions in protease and neutrophil activities.
Association of periodontal disease to anxiety and depression symptoms, and psychosocial stress factors
Authors: Solis A. C. O. , Lotufo R. F. M. , Pannuti C. M. , Brunheiro E. C. , Marques A. H. , Lotufo‐Neto F. 
Published: July 2004

AbstractObjective: A cross‐sectional study was conducted to investigate if anxiety, depression and hopelessness symptoms are associated with periodontal disease.Method: A total of 160 subjects took part in this study. Probing depth and clinical attachment level were recorded at six sites per tooth and the gingival and plaque indices were also recorded. The instruments used to assess the psychological variables (anxiety, depression, stress, psychiatric symptoms and hopelessness) were: the State–Trait Anxiety Inventory, the Beck Depression Inventory, the Life Events Scale modified by Savoia, the Self‐Report Screening Questionnaire‐20 and the Beck Hopelessness Scale.Results: There was no difference in scale score means between patients with and without established periodontitis. Results of the Ordinal Logistic Regression Analysis model that included age, plaque index, smoking and psychological factors showed that patients with psychiatric symptoms (odds ratio (OR) 1.24, 95% confidence interval (CI) 0.33–4.78), depression symptoms (OR 0.57, 95% CI 0.15–2.21) and with hopelessness (OR 0.70, 95% CI 0.13–3.84) were not at a greater risk of developing established periodontitis.Conclusion: In this sample, no evidence was found for an association between depression, hopelessness, psychiatric symptoms and established periodontitis. The association of periodontal disease to depression, anxiety and stress should be investigated in psychiatric populations, especially in those with depression and anxiety disorders.
The association of periodontal disease parameters with systemic medical conditions and tobacco use
Authors: Molloy John , Wolff Larry F. , Lopez‐Guzman Angel , Hodges James S. 
Published: July 2004

AbstractObjectives: The objective of this study was to determine if an association existed between periodontal disease and various systemic medical conditions and tobacco use.Material and Methods: The study design was a case‐controlled, retrospective chart review. Patient charts (n=2006) were selected from more than 13,000 active patients attending the University of Minnesota dental clinics. These charts were examined to determine patient's self‐reported systemic condition and smoking history. In addition, the number of missing teeth and bone loss were recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine bone loss and number of missing teeth. Each examiner was blind to the findings of the other.Results: After adjusting for age, sex, diabetes and smoking (yes/no) status, seven conditions were significantly (p=0.0003–0.04) related to bone loss or number of missing teeth (vascular disease, heart surgery, vascular surgery, heart attack, thyroid problems, arthritis, stomach ulcers). From these conditions, thyroid problems and arthritis had a negative association with bone loss.Conclusions: These findings support the results from previous investigators that a number of systemic conditions and smoking are closely associated with missing teeth or bone loss.
Effect of recombinant human bone morphogenetic protein‐12 (rhBMP‐12) on regeneration of periodontal attachment following tooth replantation in dogs
Authors: Sorensen Rachel G. , Polimeni Giuseppe , Kinoshita Atsuhiro , Wozney John M. , Wikesjö Ulf M. E. 
Published: July 2004

AbstractObjectives: Subcutaneous and intramuscular implants of bone morphogenetic protein‐12 (BMP‐12) have been shown to induce formation of tendon and ligament tissue. BMP‐12 induced a new attachment with a distinct fibrocartilaginous zone at the tendon‐bone interface in the rat tendon‐bone attachment model. Surgical controls showed poor healing and failure to reform the appropriate tendon–bone attachment morphologically. Application of recombinant human BMP‐12 (rhBMP‐12) to periodontal defects suggests that rhBMP‐12 has the potential to support regeneration of the periodontal ligament (PDL). The objective of this pilot study was to evaluate this effect of rhBMP‐12 in a tooth replantation model.Methods: Six, young adult, male Hound Labrador mongrel dogs were used. Maxillary and/or mandibular incisor and premolar teeth were extracted and the PDL was either left “intact” or removed by root planing. rhBMP‐12 (1.0 mg/ml) or a buffer control was topically applied to teeth with “intact” PDL in contralateral jaw quadrants in each of 3 animals. The teeth were immersed in 1.0 ml of the rhBMP‐12 or the buffer solution for 10 min and then replanted. The remaining three animals received rhBMP‐12 (1.0 mg/ml) and the buffer control in a similar fashion applied to teeth instrumented to remove the PDL and cementum, and surface demineralized with citric acid. The animals were euthanized at 8 weeks postsurgery and block sections were collected and processed for histopathologic analysis.Results: No dramatic differences were found between teeth receiving topical rhBMP‐12 and the buffer control. Application of rhBMP‐12 did not have an apparent effect on new cementum and PDL formation in the tooth replantation model. Moreover, application of rhBMP‐12 did not increase nor did it decrease the apparent presence and extent of ankylosis along the root surface compared to the control.Conclusions: The observations from this study do not support the use of topical rhBMP‐12 to support the reestablishment of the PDL including regeneration of cementum and functionally oriented fibers, and to prevent ankylosis and root resorption following replantation of teeth.
Baseline radiographic defect angle of the intrabony defect as a prognostic indicator in regenerative periodontal surgery with enamel matrix derivative
Authors: Tsitoura Effie , Tucker Richard , Suvan Jean , Laurell Lars , Cortellini Pierpaolo , Tonetti Maurizio 
Published: July 2004

AbstractIntroduction: The baseline radiographic defect angle has previously been correlated with the clinical outcomes of intrabony defects treated with access flap or guided tissue regeneration. The aim of this study was to investigate whether an association exists between baseline radiographic defect angle and treatment outcome when enamel matrix derivative (EMD) is used in periodontal regenerative surgery.Materials and Methods: Baseline radiographs were collected from the test group of a previously published clinical trial using a population of 166 patients treated for chronic periodontitis. All intrabony defects were 3 mm for inclusion in the original study. Either modified or simplified papilla preservation technique was used to access the defect. The roots were conditioned with an EDTA gel and the primary outcome measure was clinical attachment level (CAL) change, 1 year after surgery.Results: Sixty‐seven radiographs were measurable. The probability of obtaining CAL gain >3 mm was 2.46 times higher (95% confidence interval: 1.017–5.970) when the radiographic defect angle was 22° than when it was 36°.Conclusions: This study showed that there was a significant association between baseline radiographic defect angle and CAL gain at 1 year. The observed increased odds ratio of obtaining CAL gain of 4 mm after regenerative surgery with EMD is used in narrow (22°) intrabony defects, suggests that the baseline radiographic defect angle might be used as a prognostic indicator of treatment outcome.
Modification of stretch tolerance in a stooping position
Authors: Læssøe U. , Voigt M. 
Published: July 2004

A stooping (slump) position is believed to add tension to the nerve tissue complex. This study was designed to determine whether this position would have an effect on the stretch tolerance in a passive knee extension. Thirteen healthy individuals were tested. The knee extension was stopped by the subjects at “onset of pain”. Joint range of motion and passive resistance to the extension were recorded in four test situations: upright sitting and stooping position, with the ankle joint in either the neutral or maximal dorsi‐flexed position.A significant decrease in range of motion was seen when shifting from upright to stooping position: Δangle −2.4° (P<0.01). According to this, the passive tissue tension was accepted at significantly lower values in stooping position: Δtorque −1.2 N m (P<0.01). Testing with maximal dorsi‐flexion of the ankle showed more pronounced changes: Δangle −3.4° (P<0.001); Δtorque −2.3 N m (P<0.001), but the effect of foot position was not significant.Knee joint range of motion was acutely diminished in a stooping position. Thus, stretch tolerance was affected by manipulation of structures, which were not directly mechanically related to this joint. An influence from the nerve tissue complex must be considered to be a factor when describing the mechanisms behind altered stretch tolerance.
Phase and Antigenic Variation in Bacteria
Authors: van der Woude Marjan W. , Bäumler Andreas J. 
Published: July 2004

SUMMARYPhase and antigenic variation result in a heterogenic phenotype of a clonal bacterial population, in which individual cells either express the phase-variable protein(s) or not, or express one of multiple antigenic forms of the protein, respectively. This form of regulation has been identified mainly, but by no means exclusively, for a wide variety of surface structures in animal pathogens and is implicated as a virulence strategy. This review provides an overview of the many bacterial proteins and structures that are under the control of phase or antigenic variation. The context is mainly within the role of the proteins and variation for pathogenesis, which reflects the main body of literature. The occurrence of phase variation in expression of genes not readily recognizable as virulence factors is highlighted as well, to illustrate that our current knowledge is incomplete. From recent genome sequence analysis, it has become clear that phase variation may be more widespread than is currently recognized, and a brief discussion is included to show how genome sequence analysis can provide novel information, as well as its limitations. The current state of knowledge of the molecular mechanisms leading to phase variation and antigenic variation are reviewed, and the way in which these mechanisms form part of the general regulatory network of the cell is addressed. Arguments both for and against a role of phase and antigenic variation in immune evasion are presented and put into new perspective by distinguishing between a role in bacterial persistence in a host and a role in facilitating evasion of cross-immunity. Finally, examples are presented to illustrate that phase-variable gene expression should be taken into account in the development of diagnostic assays and in the interpretation of experimental results and epidemiological studies.