bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing the Nucleotide Sequence of a Meiotic Recombination Hotspot in Schizosaccharomyces pombe
Authors: Steiner Walter W , Smith Gerald R 
Published: February 2005

Abstract
The ade6-M26 mutation of Schizosaccharomyces pombe created a meiotic recombination hotspot. Previous analyses indicated that the heptamer 5′-ATGACGT-3′ was necessary and sufficient for hotspot activity; the Atf1-Pcr1 transcription factor binds to this sequence and activates M26. After finding cases in which the M26 heptamer in ade6 was, surprisingly, not active as a hotspot, we used an in vitro selection method (SELEX) that revealed an 18-bp consensus sequence for Atf1-Pcr1 binding, 5′-GNVTATGACGTCATNBNC-3′, containing the M26 heptamer at its core. Using this consensus sequence as a guide, we made mutations on each side of the heptamer at two separate sites in ade6. These mutations increased the intracellular hotspot activity of the heptamer, in some cases by &gt;15-fold. These results show that M26, the eukaryotic recombination hotspot with the most precisely defined nucleotide sequence, is larger than previously thought, and they provide valuable information for clarifying the role of M26, and perhaps other hotspots, in meiotic recombination.
Identification of Zebrafish Insertional Mutants With Defects in Visual System Development and Function
Authors: Gross Jeffrey M , Perkins Brian D , Amsterdam Adam , Egaña Ana , Darland Tristan , Matsui Jonathan I , Sciascia Salvatore , Hopkins Nancy , Dowling John E 
Published: February 2005

Abstract
Genetic analysis in zebrafish has been instrumental in identifying genes necessary for visual system development and function. Recently, a large-scale retroviral insertional mutagenesis screen, in which 315 different genes were mutated, that resulted in obvious phenotypic defects by 5 days postfertilization was completed. That the disrupted gene has been identified in each of these mutants provides unique resource through which the formation, function, or physiology of individual organ systems can be studied. To that end, a screen for visual system mutants was performed on 250 of the mutants in this collection, examining each of them histologically for morphological defects in the eye and behaviorally for overall visual system function. Forty loci whose disruption resulted in defects in eye development and/or visual function were identified. The mutants have been divided into the following phenotypic classes that show defects in: (1) morphogenesis, (2) growth and central retinal development, (3) the peripheral marginal zone, (4) retinal lamination, (5) the photoreceptor cell layer, (6) the retinal pigment epithelium, (7) the lens, (8) retinal containment, and (9) behavior. The affected genes in these mutants highlight a diverse set of proteins necessary for the development, maintenance, and function of the vertebrate visual system.
Drosophila Signal Peptide Peptidase Is an Essential Protease for Larval Development
Authors: Casso David J , Tanda Soichi , Biehs Brian , Martoglio Bruno , Kornberg Thomas B 
Published: February 2005

Abstract
We identified the Drosophila melanogaster Signal peptide peptidase gene (Spp) that encodes a multipass transmembrane aspartyl protease. Drosophila SPP is homologous to the human signal peptide peptidase (SPP) and is distantly related to the presenilins. We show that, like human SPP, Drosophila SPP can proteolyze a model signal peptide and is sensitive to an SPP protease inhibitor and that it localizes to the endoplasmic reticulum. Expression of Drosophila SPP was first apparent at germ band extension, and in late embryos it was robust in the salivary glands, proventriculus, and tracheae. Flies bearing mutations in conserved residues or carrying deficiencies for the Spp gene had defective tracheae and died as larvae.
Effect of Recombinant Human Bone Morphogenetic Protein‐4 Dose on Bone Formation in a Rat Calvarial Defect Model
Authors: Pang Eun‐Kyoung , Im Se‐Ung , Kim Chang‐Sung , Choi Seong‐Ho , Chai Jung‐Kiu , Kim Chong‐Kwan , Han Soo‐Boo , Cho Kyoo‐Sung 
Published: February 2005

Background: Bone morphogenetic proteins (BMPs) are being evaluated for periodontal and bone regenerative therapy. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein‐4 (rhBMP‐4) dose on local bone formation in a rat calvaria defect model.Methods: Calvarial, 8 mm diameter, critical‐size osteotomy defects were created in 140 male Sprague‐Dawley rats. Seven groups of 20 animals each received either 1) rhBMP‐4 (2.5 µg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP‐4 (5 µg)/ACS, 3) rhBMP‐4 (2.5 µg) in a β‐tricalcium phosphate (β‐TCP) carrier, 4) rhBMP‐4 (5 µg)/β‐TCP, 5) ACS or 6) β‐TCP carrier controls, or 7) a sham‐surgery control, and were evaluated by histologic and histometric parameters following a 2‐ or 8‐week healing interval (10 animals/group/healing interval).Results: Surgical implantation of rhBMP‐4/ACS and rhBMP‐ 4/β‐TCP resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose range examined, rhBMP‐4 did not exhibit an appreciable dose‐dependent response. Defect closure was not significantly different between the rhBMP‐4/ACS and rhBMP‐4/β‐TCP groups. New bone area of the rhBMP‐4/ β‐TCP group was significantly greater than that of the rhBMP‐4/ ACS group; however, bone density in the rhBMP‐4/ACS group was significantly greater than that in the rhBMP‐4/β‐TCP group at 8 weeks (P <0.05).Conclusions: rhBMP‐4 combined with ACS or β‐TCP has a significant potential to induce bone formation in the rat calvaria defect model. Within the selected rhBMP‐4 dose range and observation interval, there appeared to be no meaningful differences in bone formation. J Periodontol 2004;75:1364‐1370.
Patients' Experience of Pain and Discomfort During Instrumentation in the Diagnosis and Non‐Surgical Treatment of Periodontitis
Authors: van Steenberghe Daniel , Garmyn Peter , Geers Lut , Hendrickx Elke , Maréchal Marina , Huizar Karin , Kristofferson Ann , Meyer‐Rosberg Karin , Vandenhoven Guy 
Published: February 2005

Background: The present multicenter study aimed to survey the patients' experiences in relation to the diagnosis and nonsurgical treatment of periodontitis according to current treatment routine.Methods: Patients (N = 268) treated for plaque‐related periodontitis were enrolled in two groups: group 1 received primary probing of pocket depths (PD 1) and/or primary scaling and root planing (SRP 1); group 2 consisted of patients who were scheduled in the different centers for recall PD/scaling/subgingival instrumentation. Data collection included a full periodontal status, anesthesia employed, procedure time, and patient self‐completed questionnaires to assess their previous and current experience of pain and discomfort during anesthesia and periodontal treatment.Results: Ninety percent of the patients received infiltration anesthesia during primary SRP, compared to only 2% during recall scaling/instrumentation and none during PD. Many patients (40% in SRP group 1 and 52% in the recall scaling/instrumentation group) were most bothered by the scaling procedure, while others (35% in the primary SRP patients) by the anesthetic injection. Painful experiences during previous primary PD and present SRP were highly correlated (r = 0.6).Conclusions: From these results, it is evident that subgingival instrumentation causes pain and discomfort, an aspect that should be considered in periodontal therapy. Unfortunately, the use of local infiltration anesthesia to reduce pain is in itself a cause of discomfort. Attractive alternatives for anesthetic applications are much needed. J Periodontol 2004;75:1465‐1470.
Association Between Human Herpesviruses and the Severity of Periodontitis
Authors: Ling Li‐Jane , Ho Chuan‐Chen , Wu Ching‐Yi , Chen Yen‐Ting , Hung Shan‐Ling 
Published: February 2005

Background: Herpesviruses may play roles in the development of periodontal diseases. The present study evaluated the relationships between herpesviruses and the severity of periodontitis.Methods: Periodontal status in terms of gingival inflammation, bleeding on probing, probing depth, and clinical attachment loss of 20 participants was evaluated. The presence of herpes simplex virus (HSV), human cytomegalovirus (HCMV), or Epstein‐Barr virus type 1 (EBV‐1) in six subgingival plaques from each participant was examined by nested‐polymerase chain reaction techniques.Results: Among the 120 sites examined, the prevalence of HCMV (51.7%) was higher than HSV (30.8%) followed by EBV‐1 (4.2%). The prevalence of HSV or HCMV was significantly higher in the subgroups that had lower plaque index (<1). However, the prevalence of HSV was significantly higher in the subgroup that had higher gingival index (≥2), positive bleeding on probing, deeper probing depth (≥4 mm), or higher clinical attachment loss (≥4 mm). Moreover, the prevalence of EBV‐1 was significantly higher in the subgroup that had higher probing depth (≥4 mm). Coinfection of HSV and HCMV was significantly associated with the sites that had higher gingival index (≥2) or positive bleeding on probing. Coinfection of any two herpesviruses was also associated with higher probing depth (≥4 mm) or higher clinical attachment loss (≥4 mm).Conclusions: This study demonstrated that HSV is related to the severity of periodontal diseases in terms of clinical attachment loss. Coinfection of any two herpesviruses may also play roles. J Periodontol 2004;75:1479‐1485.
Commensal Bacteria Influence Innate Status Within Gingival Tissues: A Pilot Study
Authors: Dixon Douglas R. , Reife Robert A. , Cebra John J. , Darveau Richard P. 
Published: February 2005

Background: The objective of this study was to determine the contribution of commensal bacteria to the innate defense status of gingival tissue by examining the expression of innate host defense mediators in germ‐free and conventionally reared groups in both BALBc/ByJ and SCID C.B17 mice.Methods: Semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR) was utilized to determine the constitutive levels within each gingival tissue set (N = 5) for: E‐selectin, P‐selectin, interleukin‐(IL)‐8 homologue, tumor necrosis factor‐α, IL‐1β, intercellular adhesion molecule‐(ICAM)‐1, ICAM‐2, and vascular adhesion molecule‐(VCAM)‐1. In addition, IL‐1β protein content was determined by enzyme‐linked immunosorbent assay (ELISA).Results: Gingival samples revealed that only IL‐1β mRNA expression among all mediators examined was significantly reduced in conventionally reared mice (P <0.01) compared to germ‐free mice. In contrast, IL‐1β protein levels were significantly (P <0.001) higher in conventionally reared mice compared to germ‐free animals. Conventionally reared and germ‐free SCID C.B17 mice revealed a similar pattern in regard to reduced IL‐1β mRNA and significantly increased IL‐1β protein (P <0.0001).Conclusion: Commensal microbial colonization influences innate host defense mediator expression of IL‐1β at both the mRNA and protein levels in healthy periodontal tissue in mice. J Periodontol 2004;75:1486‐1492.
Root Trunk Concavities as a Risk Factor for Regenerative Procedures of Class II Furcation Lesions in Humans
Authors: Villaça José Henrique , Rodrigues Débora C. , Novaes Arthur B. , Taba Mário , Souza Sérgio L.S. , Grisi Márcio F.M. 
Published: February 2005

Background: The purpose of this study was to evaluate the influence of root trunk concavities on guided tissue regeneration in humans and to determine if a modification in membrane design could improve the results.Methods: Ten patients who provided 10 pairs of similar Class II furcation defects were recruited for the study. Each defect was randomly assigned to treatment with either a normal expanded polytetrafluoroethylene (ePTFE) membrane (NM) or a modified ePTFE membrane (MM). The MM were made by removing the collar from an NM, cutting it into 2 mm segments, and suturing each of the segments to the collar of each MM. Following basic therapy, baseline clinical measurements were recorded using an acrylic stent, including probing depth (PD) and clinical attachment level (CAL). Full flaps were elevated, the defects were carefully debrided, and the root surfaces were decontaminated with manual and ultrasonic instruments. Hard tissue measurements were performed during surgery to determine vertical (VD) and horizontal defect (HD) depths. Then, NM and MM were sutured to their corresponding tooth and the flaps sutured. Membranes remained in position for 6 weeks. After 1 year, all sites were re‐entered and soft and hard tissue measurements were recorded.Results: After 1 year, there were no statistically significant differences (Mann‐Whitney test) between NM and MM groups in percentages of PD reduction (P = 0.27), CAL change (P = 0.26), or VD resolution (P = 0.13). However, percentage of HD resolution (NM: 24.3 ± 11.8; MM: 44.8 ± 16.0) was significantly different between groups (P = 0.008).Conclusions: The modified membranes resulted in greater horizontal resolution of Class II furcation defects. The collars of the membranes should be modified to improve results when root trunk concavities are present. J Periodontol 2004;75:1493‐1499.
Association of Interleukin‐1 Polymorphisms With Aggressive Periodontitis
Authors: Quappe Leticia , Jara Lilian , López Néstor J. 
Published: February 2005

Background: Genetic polymorphisms for interleukin (IL)‐1α and ‐1β have been proposed as potential genetic markers for periodontal diseases. Since the prevalence of these polymorphisms could be race‐related, and no data exist about the frequency of these polymorphisms in the Chilean population, the aim of the current study was to investigate the association of the interleukin‐1 gene polymorphisms with aggressive periodontitis (AgP).Methods: Thirty‐six patients with AgP, 75 healthy controls, and 75 subjects of unknown periodontal status (reference population) were genotyped for the IL‐1A –889 and IL‐1B +3954 loci, by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion and gel electrophoresis. Data were analyzed using the chi‐square test, calculating odds ratios (OR) and confidence intervals (CI).Results: The prevalence of the positive composite IL‐1 genotype was higher in patients (25%) than in healthy controls (12%), but the difference was not significant (P = 0.14). The IL‐1B +3954 homozygous for allele 1 frequency was higher in controls than in patients suggesting a protective factor for AgP. The heterozygous for allele 2 of the IL‐1B showed a significant association with AgP (OR = 2.86, 95% CI 1.06 to 7.71, P = 0.030). No association was observed in localized AgP and generalized AgP between the extent of disease and the presence of the composite positive genotype. Because the number of smokers was too small in patients and in controls, no other analyses were performed.Conclusion: The results of the present study support a positive association between AgP and the presence of the IL‐1B +3954 allele 2 polymorphism. J Periodontol 2004;75:1509‐1515.
Effects of Combined Systemic Administration of Low‐Dose Doxycycline and Alendronate on Endotoxin‐Induced Periodontitis in Rats
Authors: Buduneli Eralp , Vardar Saynur , Buduneli Nurcan , Berdeli Afig Huseyinov , Türkog͠lu Oya , Başkesen Aykut , Atilla Gül 
Published: February 2005

Background: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti‐enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), leukotriene B4 (LTB4), and platelet‐activating factor (PAF) in endotoxin‐induced periodontal breakdown in rats.Methods: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague‐ Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7‐day study period. At the end of the 1‐week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2α, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests.Results: Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2α (P <0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05).Conclusions: Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice. J Periodontol 2004;75:1516‐1523.
Favorable Periodontal Regenerative Outcomes From Teeth With Presurgical Mobility: A Retrospective Study
Authors: Trejo Pedro M. , Weltman Robin L. 
Published: February 2005

Background: The relevance of tooth mobility on periodontal healing is still controversial. The purpose of the present study was to evaluate the effect of presurgical tooth mobility on periodontal regenerative outcomes.Methods: The data in this study were derived from three randomized clinical trials which evaluated regenerative procedures. Sixty‐four patients with one intraosseous periodontal defect each received one of the following treatments: guided tissue regeneration (GTR) using expanded polytetrafluoroethylene (ePTFE), GTR using a bioabsorbable membrane with or without demineralized freezedried bone allograft (DFDBA), or enamel matrix derivative with or without DFDBA. Probing depth (PD), clinical attachment level (CAL), recession (REC), and tooth mobility (TM) were recorded at baseline and 1 year after treatment by a calibrated examiner. The post‐surgical follow‐up and maintenance periods were designed to optimize plaque control. The teeth were grouped according to their baseline Miller index TM score. The grouping yielded 36 teeth with minimal mobility, score 0; 13 teeth with score 1; and 15 with score 2. The mean changes in PD, CAL and REC from baseline to 1 year were calculated for each group. One‐way analysis of variance (ANOVA) was performed to assess differences between the tooth mobility groups considering changes in PD, CAL, and REC at 1 year.Results: The mean PD reduction from baseline to 1 year for teeth with TM score 0 was 3.67 mm; for TM score 1, 2.81 mm; and for score 2, 3.73 mm. The corresponding values for the gain in CAL were 2.73, 1.96, and 2.36 mm, respectively. According to ANOVA, the probing depth reductions and clinical attachment level gains found in each group were not statistically different, P = 0.218 and P = 0.252, respectively.Conclusion: Within the limitations of this analysis, it can be concluded that interproximal, intraosseous defects of teeth with limited presurgical tooth mobility; i.e., teeth with Miller's Class 1 and 2 mobility, will respond favorably to regenerative therapy. J Periodontol 2004;75:1532‐1538.
Resistance to caspase‐dependent, hypoxia‐induced apoptosis is not hypoxia‐inducible factor‐1 alpha mediated in prostate carcinoma cells
Authors: Coffey Ronan N. T. , Morrissey Colm , Taylor Cormac T. , Fitzpatrick John M. , Watson R. William G. 
Published: February 2005

AbstractBACKGROUNDHypoxia occurs in association with cancer development, the result being a more aggressive and metastatic cancer phenotype. Hypoxia, which activates hypoxia‐inducible factor‐1 alpha (HIF‐1α), is associated with a number of cellular changes including increased apoptotic resistance. The authors hypothesized that HIF‐1α is central to the cell's ability to resist apoptosis induced during the hypoxia selection process.METHODSPWR‐1E, LNCaP, LNCaP‐HOF, PC‐3, and DU‐145 cells were cultured in normoxic and hypoxic conditions. Apoptosis was assessed by propidium iodide DNA staining. Cleavage of specific substrates was used to assess caspase activity and Western blotting was used to assess mitochondrial release of cytochrome c and second mitochondria‐derived activator caspase (SMAC)/Diablo. A dominant negative HIF‐1α construct was transfected into the PC‐3 and LNCaP cells to block HIF‐1α activity.RESULTSPC‐3 and DU‐145 were resistant to apoptosis induced by exposure to hypoxia, but the PWR‐1E and LNCaP cells were susceptible. This induction of apoptosis in the LNCaP cells was caspase dependent but independent of cytochrome c release. Blocking the activity of HIF‐1α had no effect on increased apoptotic susceptibility in the PC‐3 cells. LNCaP‐HOF cells, which were resistant to hypoxia‐induced apoptosis, showed no increase in HIF‐1α expression or activity.CONCLUSIONSApoptotic resistance is already established in cells that survive a hypoxic insult and whereas increased HIF‐1α activity may be essential for the development of a more aggressive cancer phenotype, it may not be responsible for the initial selection of an apoptotic resistance phenotype. Cancer 2005. © 2005 American Cancer Society.
Sequential topotecan and oral etoposide in recurrent ovarian carcinoma pretreated with platinum‐taxane
Authors: Gronlund Bo , Engelholm Svend A. , Horvath György , Mäenpää Johanna , Ridderheim Mona 
Published: February 2005

AbstractBACKGROUNDThe objectives of this study were to determine the maximum tolerable dose (MTD), toxicity, efficacy, and feasibility of a sequential regimen of fixed‐dose topotecan (1.00 mg/m2 on Days 1–5) and increasing doses of oral etoposide (50 mg, 75 mg, and 100 mg on Days 6–12 or Days 6–19) in patients with recurrent ovarian carcinoma.METHODSThis multicenter, open‐label study was planned as a Phase I–II study that included patients with epithelial ovarian carcinoma who failed or who developed recurrent disease < 12 months after the end of platinum and taxane‐containing chemotherapy. Dose‐limiting toxicity (DLT) was defined as follows: Grade 4 neutropenia for > 1 week, or neutropenic fever 38.5 °C for > 24 hours/sepsis, or Grade 4 thrombocytopenia for > 1 week, or thrombocytopenia with bleeding, or Grade 3–4 nonhematologic toxicity.RESULTSThe MTD, as defined in the protocol, could not be settled because of unpredictable toxicity, because DLT was found at all dose levels except the starting dose level. In 28 patients (Phase I), 155 cycles were evaluable for toxicity. The main DLT was neutropenia Grade 4 for > 1 week or neutropenic fever/sepsis. Overall, neutropenia Grade 4 that lasted > 1 week and sepsis were noticed in 3% and 2% of cycles, respectively. Because no MTD was reached, the planned Phase II trial was not initiated. However, the patients from Phase I were followed until they developed progressive disease and, among them, 9 patients (32%) obtained an objective response (according to Response Evaluation Criteria in Solid Tumors (RECIST) or CA125 response criteria).CONCLUSIONSCombined topotecan and oral etoposide was inappropriate in patients with recurrent ovarian carcinoma because of unpredictable hematologic toxicity. However, the high objective response rate highlighted the potential additive effect of topoisomerase I and II inhibitors. Cancer 2005. © 2005 American Cancer Society.