bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic screen in zebrafish identifies the mutantsvps18, nf2andfoie grasas models of liver disease
Authors: Sadler Kirsten C. , Amsterdam Adam , Soroka Carol , Boyer James , Hopkins Nancy
Published: July 2005

Hepatomegaly is a sign of many liver disorders. To identify zebrafish mutants to serve as models for hepatic pathologies, we screened for hepatomegaly at day 5 of embryogenesis in 297 zebrafish lines bearing mutations in genes that are essential for embryonic development. Seven mutants were identified, and three have phenotypes resembling different liver diseases. Mutation of the class C vacuolar protein sorting gene vps18results in hepatomegaly associated with large, vesicle-filled hepatocytes,which we attribute to the failure of endosomal-lysosomal trafficking. Additionally, these mutants develop defects in the bile canaliculi and have marked biliary paucity, suggesting that vps18 also functions to traffic vesicles to the hepatocyte apical membrane and may play a role in the development of the intrahepatic biliary tree. Similar findings have been reported for individuals with arthrogryposis-renal dysfunction-cholestasis(ARC) syndrome, which is due to mutation of another class C vps gene. A second mutant, resulting from disruption of the tumor suppressor gene nf2,develops extrahepatic choledochal cysts in the common bile duct, suggesting that this gene regulates division of biliary cells during development and that nf2 may play a role in the hyperplastic tendencies observed in biliary cells in individuals with choledochal cysts. The third mutant is in the novel gene foie gras, which develops large, lipid-filled hepatocytes, resembling those in individuals with fatty liver disease. These mutants illustrate the utility of zebrafish as a model for studying liver development and disease, and provide valuable tools for investigating the molecular pathogenesis of congenital biliary disorders and fatty liver disease.
Potential structural role of non-coding and coding RNAs in the organization of the cytoskeleton at the vegetal cortex ofXenopusoocytes
Authors: Kloc Malgorzata , Wilk Katarzyna , Vargas Diana , Shirato Yuri , Bilinski Szczepan , Etkin Laurence D.
Published: July 2005

The localization of RNA within a cell or embryo is crucial for proper cellular function or development. There is evidence that the cytoskeleton and RNA may function in the anchoring of localized RNAs at the vegetal cortex of Xenopus laevis oocytes. We found that the organization of the cytokeratin filaments but not the actin cytoskeleton depends on the presence of intact VegT mRNA and a noncoding RNA, Xlsirts. Destruction of either of these transcripts results in disruption of the cytokeratin cytoskeleton in a transcript-specific manner and interferes with proper formation of the germinal granules and subsequent development of the germline. Analysis of the distribution of endogenous VegT and Xlsirts in live oocytes using molecular beacons showed that these RNAs are integrated into the cytokeratin cytoskeleton. These results demonstrate a novel structural role of coding and noncoding RNAs in the organization of the vegetal cortex of Xenopusoocytes.
Mind bomb 1 is essential for generating functional Notch ligands to activate Notch
Authors: Koo Bon-Kyoung , Lim Hyoung-Soo , Song Ran , Yoon Mi-Jeong , Yoon Ki-Jun , Moon Jin-Sook , Kim Young-Woong , Kwon Min-chul , Yoo Kyeong-Won , Kong Myung-Phil , Lee Jinie , Chitnis Ajay B. , Kim Cheol-Hee , Kong Young-Yun
Published: July 2005

The Delta-Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for cell fate specification. Mind bomb 1 (Mib1) has been identified as a ubiquitin ligase that promotes the endocytosis of Delta. We now report that mice lacking Mib1 die prior to embryonic day 11.5, with pan-Notch defects in somitogenesis, neurogenesis,vasculogenesis and cardiogenesis. The Mib1–/–embryos exhibit reduced expression of Notch target genes Hes5, Hey1, Hey2 and Heyl, with the loss of N1icd generation. Interestingly, in the Mib1–/–mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types, indicating that Mib1 is essential for the endocytosis of Notch ligand. In accordance with the pan-Notch defects in Mib1–/– embryos, Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2,as well as Dll1, Dll3 and Dll4. Our results show that Mib1 is an essential regulator, but not a potentiator, for generating functional Notch ligands to activate Notch signaling.
Immunoquantitative PCR for Prion Protein Detection in Sporadic Creutzfeldt–Jakob Disease
Authors: Gofflot Stéphanie , Deprez Manuel , el Moualij Benaïssa , Osman Awad , Thonnart Jean-François , Hougrand Olivier , Heinen Ernst , Zorzi Willy
Published: July 2005

Background: The most common human prion disorder is Creutzfeldt–Jakob disease (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes. Diagnostic tests aim at detection with the highest specificity of very small deposits of abnormal prion protein (PrP).

Methods: We used immunoquantitative PCR (iqPCR) to detect proteinase K–resistant PrP (PrPRes) in tissue from the middle frontal gyrus of 7 patients with sporadic CJD and 7 non-CJD cases. We compared iqPCR with routine optimized ELISA, Western blotting, and immunohistochemical analyses.

Results: The 4 methods showed similar 100% sensitivity and specificity for the diagnosis of CJD. Along with high specificity, however, iqPCR had a threshold for PrPRes detection at least 10-fold lower than that of the classic ELISA.

Conclusions: iqPCR is a new method for PrPRes detection that combines 100% specificity with a detection threshold at least 10-fold lower than classic techniques. This method may improve the detection of minute PrPRes deposits in tissues and body fluids and thus be useful for diagnostic and sterilization applications.
Influences of Blood Sample Processing on Low–Molecular-Weight Proteome Identified by Surface-Enhanced Laser Desorption/Ionization Mass Spectrometry
Authors: Banks Rosamonde E , Stanley Anthea J , Cairns David A , Barrett Jennifer H , Clarke Paul , Thompson Douglas , Selby Peter J
Published: July 2005

Background: Profiling approaches in proteomics, such as surface-enhanced laser desorption/ionization (SELDI) mass spectrometry, are used in disease marker discovery. The aim of this study was to investigate the potential influence of selected preanalytical factors on the results obtained.

Methods: Plasma samples anticoagulated with EDTA, citrate, or heparin, and serum samples from healthy volunteers were profiled by SELDI on CM10, immobilized metal affinity capture (IMAC) array with copper, and H50 chip surfaces. Using linear mixed-effects models, we examined the influence of elapsed time between venipuncture and sample separation (immediate to 24 h) and the type of serum tube used (Greiner Vacuette activator, gel serum separator, or plain tubes). We analyzed purified platelets, as well as platelet-poor and platelet-rich plasma samples treated with calcium and/or thrombin to determine the platelet contribution, directly or via the clotting process, to the profiles generated. We then used cluster analysis to identify samples with similar peak profiles.

Results: Different plasma types and sera could be distinguished on the basis of cluster analyses of their spectral profiles. Elapsed time between venipuncture and separation of plasma and serum from blood samples altered the profiles obtained, particularly for serum samples and particularly on IMAC chips. The type of serum collection tube also affected the profiles because of differences in clotting time. In vitro manipulation of platelets revealed that specific peaks in IMAC profiles of serum appeared to be derived directly from platelets. Several other peaks, including some of those exhibiting time-dependent changes, arose during the clotting process.

Conclusion: Preanalytical variables, such as sample handling, can markedly influence results.
Difference in the Prevalence of Enamel Alterations Affecting Central Incisors of Children with Complete Unilateral Cleft Lip and Palate
Authors: Maciel Suzana Papile , Costa Beatriz , Gomide Marcia Ribeiro
Published: July 2005

Objective

To evaluate the prevalence of enamel alterations affecting the deciduous and permanent central maxillary incisors of children with complete unilateral cleft lip and palate and to verify their characteristics.

Design

Cross-sectional.

Setting

Hospital for Rehabilitation of Craniofacial Anomalies–University of São Paulo, Bauru, São Paulo, Brazil.

Patients

A sample of 90 patients attending the Hospital for Rehabilitation of Craniofacial Anomalies, presenting with complete cleft lip and palate, of both genders, ages 2 to 11 years old.

Methodology

The buccal surfaces of the maxillary central incisors of patients were analyzed for observation of the presence of enamel defects, their type, number, and location. The prevalence of defects was compared between deciduous and permanent teeth and between the incisors at the cleft and noncleft sides.

Results

There was a higher frequency of defects among incisors on the cleft side for both deciduous and permanent dentitions compared with the noncleft side (p < .05); the permanent central incisor was more frequently affected than the deciduous. Evaluation of the types of defects for both incisors in both dentitions demonstrated a homogeneous distribution, except for a lower proportion of yellow opacity in the permanent dentition on the cleft side. In general, the most affected area in all dentitions was the incisal third.

Conclusion

The prevalence of enamel alterations affecting incisors adjacent to the cleft was higher than for incisors on the noncleft side. This difference also was present in the permanent dentition.
Comparison of Nasalance Scores Obtained with the Nasometer, the NasalView, and the OroNasal System
Authors: Bressmann Tim
Published: July 2005

Objective

To compare nasalance scores obtained with the Nasometer, the NasalView, and the OroNasal System; evaluate test-retest reliability of the three systems; and explore whether three common text passages used for nasalance analysis could be shortened to a sentence each.

Subjects

Seventy-six adults with normal speech and hearing (mean age 26.5 years).

Procedures

Subjects read the complete Zoo Passage, Rainbow Passage, and Nasal Sentences.

Main Outcome Measures

Mean nasalance magnitudes and mean nasalance distances were obtained with the three devices.

Results

The Nasometer had the lowest nasalance scores for the nonnasal Zoo Passage. The NasalView had the highest nasalance scores for the phonetically balanced Rainbow Passage. The OroNasal System had the lowest nasalance scores for the Nasal Sentences. The nasalance distance was largest for the Nasometer and smallest for the OroNasal System. Over 90% of the recordings were within 4% to 6% nasalance for most materials recorded with the Nasometer and the NasalView and within 7% to 9% for materials recorded with the OroNasal System. There were significant differences between the complete Zoo Passage and the Nasal Sentences and the individual sentences from these passages for the Nasometer and the OroNasal System.

Conclusions

The three systems measure nasalance in different ways and provide nasalance scores that are not interchangeable. Test-retest variability for the Nasometer and the NasalView may be higher than previously reported. Individual sentences from the Zoo Passage and the Nasal Sentences do not provide nasalance scores that are equivalent to the complete passages.
Use of Absorbable Poly (D,L) Lactic Acid Plates in Cranial-Vault Remodeling: Presentation of the First Case and Lessons Learned about Its Use
Authors: Acosta Humberto L. , Stelnicki Eric J. , Rodriguez Luis , Slingbaum Lisa A.
Published: July 2005

Objective

To present the first clinical use of a new bioabsorbable material, poly (D,L) lactic acid (PDLLA), in pediatric cranial-vault remodeling procedures. This discussion will highlight the benefits and detriments of PDLLA in comparison with currently used absorbable plating systems.

Design

This was a case study documenting the first North American case in which PDLLA was used to treat craniosynostosis.

Materials and Methods

Evaluation of pure PDLLA, a copolymer product of the mixture of poly L-lactic acid and its D-isomer, was used in an 8-month-old boy with a severe phenotypic expression of sagittal craniosynostosis. No signs of elevated intracranial pressure were present, and the neurological examination did not show impairments. Total cranial-vault remodeling with the “hung-span” technique was performed. The Resorb X system, containing 2.2-mm screws and 0.6- to 1-mm-thick plates, was used to stabilize the reconstructed cranial vault.

Results

No surgical complications occurred. The preoperative cranial index measured 62. The scaphocephalic appearance of the skull was eliminated, and the cranial index was normalized to 77. The screws and plates were less palpable than other plating systems. Twelve months postoperatively, none of the plates and screws were identifiable by external palpation.

Conclusion

Resorb X has been successfully used in the treatment of sagittal craniosynostosis. Its rapid rate of resorption and lower profile make it an advantageous system for pediatric skull reconstruction. This represents the first use of this product in the United States for any pathology.
Early Assessment of Dental Arch Development in Repaired Unilateral Cleft Lip and Unilateral Cleft Lip and Palate versus Controls
Authors: Garrahy Ann , Millett Declan T. , Ayoub Ashraf F.
Published: July 2005

Objective

To evaluate dental arch relationships and dimensions, relative to an age matched noncleft sample, in Caucasian 3-year-old children with repaired unilateral cleft lip (UCL) or unilateral cleft lip and palate (UCLP).

Design

Prospective, cross-sectional, case-control study performed in Scotland, U.K.

Participants

Eleven children with repaired unilateral cleft lip, 16 children with repaired unilateral cleft lip and palate, and 78 children as controls.

Main Outcome Measures

Dental arch relationships and linear arch dimensions.

Results

Prevalence of Class III incisor relationship was 31.3% in children with unilateral cleft lip and palate compared with 9.1% in children with unilateral cleft lip. A buccal crossbite was present in 36% of children with unilateral cleft lip, compared with 75.6% of children with unilateral cleft lip and palate. Mean linear maxillary arch dimensions did not differ significantly between children with unilateral cleft lip and the controls. Except for second intermolar width, statistically significant differences existed in mean linear maxillary arch dimensions between the unilateral cleft lip and the unilateral cleft lip and palate groups; the mean linear maxillary arch dimensions were significantly greater in the control group than in the unilateral cleft lip and palate group. The mean cleft-affected anterior quadrant length appeared to be the arch dimension with the greatest power of discrimination among the three groups. There were no significant differences in mean linear mandibular arch dimensions among the three groups.

Conclusions

Anterior crossbite was almost three times more common in the unilateral cleft lip and palate group than in the unilateral cleft lip group. Mean linear maxillary arch dimensions differed significantly between the unilateral cleft lip and palate group and the control group. There were no significant differences in mean linear maxillary arch dimensions between unilateral cleft lip and controls or between mean linear mandibular arch dimensions for unilateral cleft lip, unilateral cleft lip and palate, and controls.
Experimental Aspects of the Pathogenesis of Robin Sequence
Authors: Schubert Johannes , Jahn Heiko , Berginski Markus
Published: July 2005

Objective

The Pierre Robin Sequence (PRS) is a good example of disturbed embryonic development of the secondary palate involving insufficient mandibular growth, failed forward tongue movement, and, in the case of a cleft, impeded fusion of the secondary palate. Discussion continues regarding which of the involved pathogenetic factors is the primary cause of the induced cascade of signs: insufficient mandibular growth or failed descent of the tongue.

Design

Forty-five randomly selected, 18-day-old formalin-fixed A/WySn mouse fetuses were investigated. The strain is known to have a basic genetic defect and as much as 44% clefts in the offspring. Twenty-four fetuses in the group had a cleft palate. Mandible position was measured relative to the head and to the presence or absence of a cleft. Cleft width and tongue position were also determined. Thirty-eight NMRI mouse fetuses of the same age served as controls.

Results

All A/WySn fetuses showed marked mandibular retrognathia, which was more severe in the cleft group (p < .05), but there was no correlation between the degree of retrognathia and cleft width. The median cleft width was 3.4 mm (1.6 through 6.3 mm). The tongue was in the cleft in all 12 fetuses with wide clefts (>3.4 mm wide), and free in the oral cavity in the other 12. Tongue position did not influence the degree of retrognathia (p < .05). Moreover, the tongue was free in all fetuses with severe retrognathia.

Conclusion

The results support the primary role of retroposition of the mandible in the development of cardinal symptoms of Pierre Robin Sequence.
Cross-Sectional Study of the Length of the Nasal Bone in Cleft Lip and Palate Subjects
Authors: Nielsen Bo Werner , Mølsted Kirsten , Skovgaard Lene Theil , KjæR Inger
Published: July 2005

Objective

The purpose of this study was to analyze the human nasal bone length in newborns and male adults with cleft lip (CL), cleft palate (CP), and unilateral cleft lip and palate (UCLP) and to compare the results to previous findings in prenatal material.

Design

This study was a radiographic profile cephalometric cross-sectional analysis.

Subjects and Methods

Profile radiographs from 60 newborns with a male-to-female ratio of 1:1 in each group (20 CL, 20 CP, and 20 UCLP) and 60 male adults (20 CL, 20 CP, and 20 UCLP) were randomly selected among radiographs, taken for optimizing the treatment planning. The nasal bone lengths (n-na) were measured with a digital caliper on the profile radiographs. To compare the nasal bone lengths in the different cleft groups, Student's t tests at a significant level at 5% were performed.

Results

Nasal bone length was significantly shorter in male adult patients with CL compared with patients with CP. Furthermore, the nasal bone length was significantly shorter in newborns with CL (2 months) compared to newborns with UCLP (2 months). A borderline significance was seen in the comparison of patients with CL and UCLP in male adults. There was no significant difference in the nasal bone length between the patients with CP and UCLP, in either the newborns or the male adults.

Conclusions

Nasal bone length was significantly shorter in subjects with CL compared with subjects in whom the palate was clefted. The results show that the clefted lip in CL is associated with a subjacent skeletal deviation in the upper midface.
Maternal Obesity and the Risk for Orofacial Clefts in the Offspring
Authors: Cedergren Marie , Källén Bengt
Published: July 2005

Objective

To estimate whether obese women have an increased risk of orofacial clefts in their offspring, compared with average-weight women.

Design and Participants

The study was based on information on maternal body mass index (BMI) collected in early pregnancy and on the existence of orofacial clefts in the offspring, ascertained from multiple sources. The study included 1686 women who had infants with an orofacial cleft and as controls all delivered women (n = 988,171) during the study period, 1992 through 2001. Infants with chromosome anomalies were excluded. The women were divided into underweight (BMI <19.8), average weight (reference group, BMI 19.8 to 26), overweight (BMI 26.1 to 29), and obese (BMI >29). Adjustments were made for year of birth, maternal age, parity, and maternal smoking.

Results

Obese (BMI >29) mothers had an overall increased risk for having an infant with orofacial clefts: odds ratio 1.30 (95% confidence interval 1.11 to 1.53). This increased risk was higher when the cleft was associated with other major malformations than when it was isolated. There was no statistically significant difference between the risk estimates for cleft lip and cleft palate.

Conclusions

In this large sample, a positive association appears between maternal obesity in early pregnancy and orofacial clefts in the offspring. The explanation for this association is not known, but a relationship with undetected type 2 diabetes is one possibility.
Psychosocial Adjustment in Children and Adolescents with a Craniofacial Anomaly: Age and Sex Patterns
Authors: Pope Alice W. , Snyder Heather T.
Published: July 2005

Objective

To examine rates of psychosocial adjustment problems and competencies in a sample of children with congenital craniofacial anomalies (CFAs).

Methods

Retrospective chart review.

Setting

Urban hospital plastic surgery primary care unit.

Patients

A total of 724 children aged 2 to 18 years with completed Child Behavior Checklists in their medical charts.

Main Outcome Measure

Child Behavior Checklist.

Results

Higher rates of problems in the clinical range were seen for withdrawn, attention, social, thought, and internalizing problems and lower rates for externalizing and somatic complaints; specific patterns varied according to age and sex. Elevated rates of competency deficits were seen in some groups.

Conclusions

Most children with CFAs do not appear to experience psychosocial adjustment problems. Although elevated risk may be seen for certain problems, this group may be protected in other areas. Research identifying the mechanisms responsible for varying age and sex patterns of adjustment is needed.
Multisite Study of Infants with Single-Suture Craniosynostosis: Preliminary Report of Presurgery Development
Authors: Kapp-Simon Kathleen A. , Leroux Brian , Cunningham Michael , Speltz Matthew L.
Published: July 2005

Objective

To evaluate the cognitive and language development of untreated infants with a single suture craniosynostosis at time of diagnosis.

Design and Participants

The study presents time 1 assessments on the first 100 infants with a single suture craniosynostosis (sagittal, metopic, unilateral coronal, and lambdoid) referred to the Infant Learning Project, a prospective, multisite, longitudinal study evaluating neurocognitive development.

Main Outcome Measures

Infants were assessed with the mental (Mental Development Index [MDI]) and motor scales (Psychomotor Developmental Index [PDI]) of the Bayley Scales of Infant Development and the Preschool Language Scale receptive (PLS-AC) and expressive (PLS-EC) language scales. Mothers completed the Parenting Stress Inventory, a brief measure of intelligence (maternal IQ [MAT-IQ]), and provided information regarding family socioeconomic status (SES).

Results

As a group, infants scored significantly lower than the normative data on the MDI (91.9), PDI (83.5), PLS-AC (90.4), and PLS-EC (95.8), and the distribution of scores differed significantly from the expected distribution. MAT-IQ and SES were significantly correlated (.47, p < .01) with mothers of higher IQ coming from higher SES groups. Both MAT-IQ and SES were significantly negatively correlated with life stress events; however, neither MAT-IQ nor SES was correlated with any of the infant development scores.

Conclusions

There may be a greater developmental risk for infants with a single suture craniosynostosis than previously believed. However, control group data will be necessary to confirm findings.
Two Cases of Tessier No. 4 Cleft with Anophthalmia
Authors: Tokioka Kazuyuki , Nakatsuka Takashi , Park Susam , Okouchi Masayuki , Aiba Emiko
Published: July 2005

Objective

Tessier no. 4 cleft is a very rare craniofacial anomaly, and the primary surgical procedure has not been definitely standardized. The cheek advancement flap, technique, which was first reported by Van der Meulen (1985), has produced cosmetically favorable results. In this report, two cases with Tessier no. 4 cleft, which were treated with the cheek advancement flap technique, are presented.

Design and Patients

The first case was unilateral and the second was bilateral, and both were accompanied with anophthalmia on the cleft side. At the primary operation, dissection of the nasal soft tissue, medial canthopexy, and reconstruction of the lower eyelid and conjunctival fornix were performed. Cleft lip was repaired according to the rotation-advancement procedure.

Results and Conclusions

Postoperative appearances were acceptable in both cases, because the resulting scars were made along the esthetic facial units. However, the soft tissue deficiency of the lower eyelid was prominent. Furthermore, in the unilateral case, caudal displacement of the palpebral fissure and cephalic deviation of the nasal ala was recognized.
Comparative Evaluation of Two Different Vestibuloplasty Surgical Procedures in Cleft Patients: A Pilot Study
Authors: de Almeida Ana Lúcia Pompéia Fraga , Pedro Patrícia Franco , Kogawa Evelyn Mikaela , Pereira Tatiana , de Barros Carrilho Guilherme Paes , Aiello Carlos Alberto , Freitas Patrícia Zambonato
Published: July 2005

Objective

Patients with a cleft lip or palate often present alterations in the labial aspect of the ridge, resulting in a shallow vestibule. This study compares the results of two different surgical procedures on deepening of the labial sulcus.

Interventions

Ten patients with a cleft lip and palate were separated into two groups and underwent different vestibuloplasty procedures. An experimental group used a removable retention splint. Preoperative and 4-month postoperative sulcus heights were measured and analyzed statistically.

Results

No statistically significant differences could be detected between groups.

Conclusion

The results indicated that to reach consistent results, a larger number of patients must be submitted to this evaluation.
Three-Dimensional Nasal Changes following Nasoalveolar Molding in Patients with Unilateral Cleft Lip and Palate: Geometric Morphometrics
Authors: Singh G. Dave , Levy-Bercowski Daniel , Santiago Pedro E.
Published: July 2005

Objective

To evaluate three-dimensional changes in nasal morphology in patients with unilateral cleft lip and palate treated with presurgical nasoalveolar molding (NAM) to correct naso-labio-alveolar deformity.

Design

This was a prospective, longitudinal study. Digital stereophotogrammetry was used to capture three-dimensional facial images, and x, y, and z coordinates of 28 nasal landmarks were digitized.

Sample

Ten patients with unilateral cleft lip and palate.

Main Outcome Measures

Nasal form changes between T1 (age: 28 ± 2 days, pre-NAM) and T2 (age: 140 ± 2 days, post-NAM), using conventional measurements and finite-element scaling analysis.

Results

Overall nasal changes were statistically different (p < .01), but no linear or curvilinear changes were found. Specifically, relative size increases were found on the noncleft side, involving the upper nose (30%), alar depth (20%), alar dome (30%), columella height (30%), and lateral wall of the nostril (17%). On the cleft side, the following showed a size increase: upper nose (8%), alar dome (5%), columella height (30%), and lateral wall of the nostril (30%). The cleft-side alar curvature, however, showed a large decrease in size (80%), but no changes on the noncleft side were found. Corresponding shape changes and angular changes were also found.

Conclusions

Using NAM, bilateral nasal symmetry in patients with unilateral cleft lip and palate was improved before surgical repair. Furthermore, slight overcorrection of the alar dome on the cleft side using pressure exerted by the nasal stent is indicated to maintain the NAM result.
Early Composite Cranioplasty in Infants with Severe Aplasia Cutis Congenita: A Report of Two Cases
Authors: Ploplys Emilia A. , Muzaffar Arshad R. , Gruss Joseph S. , Ellenbogen Richard G.
Published: July 2005

Objective

Severe cutis aplasia congenita has traditionally been treated with initial soft tissue coverage and delayed cranioplasty. We advocate the technique of early composite reconstruction of both bone and soft tissues.

Methods

Two cases of cutis aplasia congenita with large skull defects (6 × 10 cm, 8 × 8 cm) of superficial layers, skull, and dura are presented. In each case, composite reconstruction was undertaken before 2 weeks of age with restoration of bony and soft tissue coverage through autologous, full-thickness cranial bone grafts and scalp flaps. Both children have been followed up over 2 years with clinical examination and computed tomography (CT) scans.

Results

In both cases, defects were completely repaired postoperatively and remained closed 2 years later. Complete regeneration of calvarial bone graft donor sites were documented by CT scan. Head shape and circumference were normal at 2-year follow up.
Stimulation of catecholamine biosynthesis via the PKC pathway by prolactin-releasing peptide in PC12 rat pheochromocytoma cells
Authors: Nanmoku T , Takekoshi K , Fukuda T , Ishii K , Isobe K , Kawakami Y
Published: July 2005

We have previously shown that prolactin-releasing peptide (PrRP) stimulates catecholamine release from PC12 cells (rat pheochromocytoma cell line). However, it is not known whether PrRP also affects catecholamine biosynthesis. Thus, we examined the effect of PrRP on catecholamine biosynthesis in PC12 cells. PrRP31 (>10 nM) and PrRP20 (>100 nM) significantly increased the activity and expression level of tyrosine hydroxylase (TH), a rate-limiting enzyme, in catecholamine biosynthesis. However, the PrRP20-stimulated TH activity was markedly weaker than that of PrRP31. PrRP31 (>1 nM) and PrRP20 (>10 nM) significantly induced an increase in the level of PKC activity. Both Ro 32–0432 (a protein kinase C inhibitor) and H89 (a protein kinase A inhibitor) effectively suppressed the PrRP31 (100 nM )-induced TH mRNA level. Next, we examined the effect of PrRP on mitogen-activated protein kinases (MAPKs). PrRP31 (1 μM) significantly induced an increase in the activity of extracellular signal-related kinases (ERKs) and the stress-activated protein kinase/c-jun N terminal kinase (SAPK/JNK). In contrast to ERKs and JNK, PrRP31 did not affect P38 MAPK activity. Consistent with these findings, pretreatment of cells with the MEK-1-inhibitor, PD-98059 (50 μM), significantly inhibited the PrRP31 (100 nM)-induced increase in TH mRNA. These results indicate that PrRP stimulates catecholamine synthesis through both the PKC and PKA pathways in PC12 cells.
Activation of the p38 MAPK pathway by follicle-stimulating hormone regulates steroidogenesis in granulosa cells differentially
Authors: Yu Fu-Qing , Han Chun-Sheng , Yang Wei , Jin Xuan , Hu Zhao-Yuan , Liu Yi-Xun
Published: July 2005

In the present study, we started out to test whether the follicle-stimulating hormone (FSH)-activated p38 MAPK signaling cascade was involved in the regulation of steroidogenesis in granulosa cells (GCs). GCs were prepared from the ovaries of DES-treated immature rats and cultured in serum-free medium. Treatment of GCs with FSH (50 ng/ml) induced the phosphorylation of p38 MAPK rapidly with the phosphorylation being observed within 5 min and reaching the highest level at 30 min. Such activation was protein kinase A-dependent as indicated by the results using specific inhibitors. FSH stimulated the production of progesterone and estradiol as well as the expression of the steroidogenic acute regulatory protein (StAR) in a time-dependent manner, with a maximum level being observed in the production of progesterone and StAR at 48 h. Moreover, the potent p38 MAPK inhibitor SB203580 (20 μM) augmented FSH-induced progesterone and StAR production, while reduced FSH-induced estradiol production at the same time (P<0.01). RT-PCR data showed that inclusion of SB203580 in the media enhanced FSH-stimulated StAR mRNA production, while decreased the FSH-stimulated P450arom mRNA expression (P<0.05). Immunocytochemical studies showed that FSH treatment together with the inhibition of p38 MAPK activity resulted in a higher expression of StAR in mitochondria than FSH treatment alone. FSH also significantly up-regulated the protein level of LRH-1, a member of the orphan receptor family that activates the expression of P450arom in ovaries and testes. p38 MAPK inactivation down-regulated the basal and FSH-induced LRH-1 expression significantly. The intra-cellular level of DAX-1, another orphan receptor that inhibits StAR expression, also decreased upon p38 MAPK being inactivated. For the first time, the present study suggests that FSH-activated p38 MAPK signal pathway regulates progesterone and estrogen production in GCs differentially, and that the transcription factors LRH-1 and DAX-1 might play important roles in the process.
Coregulatory protein–orphan nuclear receptor interactions in the human adrenal cortex
Authors: Kelly Sinead N , McKenna T Joseph , Young Leonie S
Published: July 2005

The capacity of the adrenal to produce steroids is controlled in part through the transcriptional regulation of steroid enzymes. The orphan nuclear receptor steroidogenic factor 1 (SF-1) is central to the transcriptional regulation of all steroid hydroxylase enzymes, whereas nur77 can preferentially regulate steroid enzyme genes relevant to cortisol production. We hypothesised that, in the presence of secretagogues, SF-1 and nur77 may differentially interact with coregulatory proteins in the human adrenal cortex. Both coregulatory proteins, steroid receptor coactivator (SRC-1) and silencing mediator for retinoid and thyroid hormones (SMRT), were found to be expressed in the zona fasciculata and reticularis in the human adrenal cortex, but were largely absent from the zona glomerulosa. Both coregulatory proteins were colocalised with SF-1 and nur77. In the H295R adrenal tumour cell line, SF-1 and nur77 transcripts were increased in cells in the presence of forskolin, whereas nur77 mRNA was also induced with angiotensin II (AII). The coactivator SRC-1 mRNA was increased in the presence of both forskolin and AII. Forskolin induced recruitment of SRC-1 to the SF-1 response element and induced SRC-1–SF-1 interactions, whereas AII increased recruitment of SRC-1 to the nur77 response element and induced SRC-1–nur77 interactions. The corepressor SMRT interacted with SF-1 in the presence of AII and with nur77 in cells treated with forskolin. Orphan nuclear receptor–coregulatory protein interactions may have consequences for the regulation of key steroidogenic enzymes in the human adrenal cortex.
Microvascular effects of corticotropin-releasing hormone in human skin vary in relation to estrogen concentration during the menstrual cycle
Authors: Clifton V L , Crompton R , Read M A , Gibson P G , Smith R , Wright I M R
Published: July 2005

Females have a significantly greater life expectancy than males, which in part may be due to the cardio-protective effects of the female sex hormone, estrogen, on vascular function. However, the sex-specific mechanisms contributing to these differences are complex and not fully understood. Previously we have reported that corticotropin-releasing hormone (CRH) has potent dilator effects in the female skin circulation via mast cell degranulation. Furthermore the dilator response to CRH was more enhanced in females than in age-matched males, suggesting that estrogens may be involved. In this study we examined whether CRH-induced dilation and endothelial cell-dependent dilation in the skin circulation of pre-menopausal females were associated with changes in estrogen during the menstrual cycle. CRH-induced dilation (1 nM) was enhanced in the presence of high circulating concentrations of estrogen and a positive correlation was identified between CRH-induced dilation and plasma estrogen concentrations. Endothelial cell-dependent dilation was examined using acetylcholine. Acetylcholine-induced dilation (1 nM) was not correlated with circulating concentrations of estrogen. These data suggest the variation in CRH-induced dilation in the skin microvasculature during the menstrual cycle may be due to estrogenic effects on mast cell function and not due to direct changes in endothelial cell function.
Melanin-concentrating hormone induces insulin resistance through a mechanism independent of body weight gain
Authors: Pereira-da-Silva Márcio , De Souza Cláudio T , Gasparetti Alessandra L , Saad Mário J A , Velloso Lício A
Published: July 2005

Transgenic hyperexpression of melanin-concentrating hormone (MCH) produces a phenotype of obesity and glucose intolerance. However, it is not known whether under this specific condition, glucose intolerance develops as a direct consequence of hyperexpressed MCH or is secondary to increased adiposity. Here, rats were treated i.c.v. with MCH or with an antisense oligonucleotide to MCH (MCH-ASO). MCH promoted an increase in blood glucose and a decrease in blood insulin levels during a glucose tolerance test. MCH also caused a decrease in the constant of glucose disappearance during an insulin tolerance test. All these effects of MCH were independent of body weight variation and were accompanied by reduced insulin receptor substrate (IRS)-1 engagement of phosphatidylinositol-3 kinase (PI3-kinase) in white and brown adipose tissues, skeletal muscle and liver and by reduced Akt activation in skeletal muscle. MCH also led to a significant reduction in ERK activation in white adipose tissue. Finally, inhibition of hypothalamic MCH expression promoted a significant increase in ERK activation in brown adipose tissue. We conclude that hypothalamic MCH controls glucose homeostasis through mechanisms that are, at least in part, independent of adiposity.
Stress elevates corticotropin-releasing factor (CRF) and CRF-binding protein mRNA levels in rainbow trout (Oncorhynchus mykiss)
Authors: Doyon C , Trudeau V L , Moon T W
Published: July 2005

The objectives of this study were to characterize rainbow trout (Oncorhynchus mykiss) corticotropin-releasing factor (CRF)-binding protein (CRF-BP) cDNA and to examine the variations in CRF-BP and CRF mRNA levels in response to different intensities of stress. Trout were physically disturbed by a single or three consecutive periods of chasing until exhaustion followed by 2 h of recovery. The pituitary CRF-BP and preoptic area CRF1 mRNA contents were significantly increased only after repeated chasing events. Physical disturbance increased plasma cortisol levels with the largest change occurring in the group of trout that were exposed to repeated chasing events. Trout were also individually isolated in 120 l tanks or confined to 1.5 l boxes for 4, 24 or 72 h. CRF-BP mRNA levels in confined fish were greater than those of isolated fish at 72 h although there were no differences compared with the control group. CRF1 mRNA levels in the preoptic area were greater and remained elevated for a longer period in confined compared with isolated trout. Isolation led to a transient increase in plasma cortisol levels, but the higher cortisol values developed in the confined fish suggest that this treatment was more stressful than isolation. These results demonstrate that the intensity and duration of stress are important factors regulating CRF and CRF-BP mRNA levels in rainbow trout. We hypothesize that pituitary CRF-BP is involved in regulating the activity of the stress axis, possibly by reducing access to CRF1 receptors in the corticotropes.
Osmophoresis of a spherical vesicle in a circular cylindrical pore
Authors: Keh Huan J. , Hsu Yun S.
Published: July 2005

The problem of the osmophoretic motion of a spherical vesicle along the centerline of a circular cylindrical pore is studied theoretically in the quasi‐steady limit of negligible Reynolds and Peclet numbers. The imposed solute concentration gradient is uniform and parallel to the pore wall, which may be either impermeable to the solute molecules or prescribed with the far‐field concentration distribution. The presence of the pore wall causes two basic effects on the vesicle velocity: (1) the local concentration gradients on the vesicle surface are altered by the wall, thereby speeding up or slowing down the vesicle; (2) the wall enhances the viscous interaction effect on the moving vesicle. To solve the equations of conservation of mass and momentum, the general solutions are constructed from the fundamental solutions in both cylindrical and spherical coordinates. The boundary conditions are enforced first at the pore wall by the Fourier transforms and then on the vesicle surface by a collocation technique. Numerical results for the osmophoretic velocity of the vesicle, relative to that under identical conditions in an unbounded solution, are presented for various values of the relevant properties of the vesicle as well as the relative separation distance between the vesicle and the pore wall. The collocation results agree well with the approximate analytical solution obtained by using a method of reflections. The presence of the wall will enhance the vesicle velocity, although its dependency on the ratio of vesicle‐to‐pore radii is not necessarily to be monotonic. In general, the boundary effect on osmophoresis is quite significant. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Carbon combustion synthesis of complex oxides: Process demonstration and features
Authors: Martirosyan K. S. , Luss D.
Published: July 2005

Carbon combustion synthesis of oxides (CCSO) is a novel process to rapidly produce high‐purity, submicron, and porous powders of complex oxides. It is a modified form of self‐propagating high temperature synthesis (SHS) that uses carbon as the fuel instead of a pure metal. The CO2 release increases the porosity and friability of the products. Like SHS, it is much faster (order of minutes) than the calcination processes (order of hours). CCSO has several advantages over SHS (the initial components are less expensive, porosity of the products is up to 70%). CCSO can produce complex oxides, such as LaGaO3, which cannot be produced by SHS. The feasibility and features of CCSO are illustrated by its use in producing barium titanate, lithium manganese, and lanthanum gallium oxides. The carbon concentration enabled control of the moving front temperature and average velocity and the particle size and surface area. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Axial Mixing and Scaleup in Static Packed Liquid Extraction Columns
Authors: Becker O.
Published: July 2005

Static packed extraction columns are of particular advantage when high throughputs at low investment cost have to be handled. Despite the fact that many columns of this type are in operation, it is still a problem to scale up the results from laboratory columns to industrial use. One of the main reasons is the fact that experimental data on axial mixing in the phases of static packed extraction columns is hardly available. Therefore, a stable method for measuring axial mixing effects was selected and applied to extraction columns of diverse scales and operated with various substance systems.
Influence of an Electric Field on Filtration in a Filter Press
Authors: Weber K. , Stahl W.
Published: July 2005

The need to dehydrate finely dispersed products is increasing worldwide. The electrofiltration potential increases with the particle surface area. Therefore the combination of mechanical and electrical filtration seems to be an effective method to enhance filtration kinetics. The attempts at pressure electrofiltration attempted in this work showed, that the residual moisture could only be lowered slightly by the electrical field, which itself is due to the electrolytic gas generated.
Analysis of the Start‐up Process for Reactive Distillation
Authors: Reepmeyer F. , Repke J.‐U. , Wozny G.
Published: July 2005

The start‐up procedure of a distillation column is a time‐ and energy‐consuming process. Further, the products during the start‐up time are off specification and cannot easily be recycled as for conventional distillation but must costly be disposed of. In this paper, a process model to simulate the barely analyzed start‐up procedure for a reactive distillation from the cold and empty state to steady state is presented. The start‐up of a reactive distillation column has been modeled with gPROMS. The advantage of a cold and empty start‐up is the consistent and reproducible initialization. Commercial simulators do not give the opportunity to start form a cold and empty state, e.g., a column modeled with Hysys must be shut down from a steady state to be able to model the complete start‐up process, which is not possible, for example, for a batch process. Also, a change in the describing equations and discontinuities in process variables is difficult to handle within the simulation. In this paper, the start‐up strategies normally used for distillation without reaction are examined and applied to reactive distillation. It will be shown that the widely used strategy of total reflux is not suitable for reactive distillation. A simplified model to derive a time constant which describes the influence of parameter setting changes, like heating power, reflux ratio and feed composition on the start‐up time, is introduced and validated.
Analytic Solution of Diffusion‐Reaction in Spherical Porous Catalyst
Authors: Shi‐Bin L. , Yan‐Ping S. , Scott K.
Published: July 2005

The model for coupled diffusion and nth‐order reaction in a spherical catalyst pellet, which is a strong nonlinear differential equation with boundary values, is solved using the Adomian decomposition method. The explicit solutions for concentration profiles and effectiveness factors, for the model equation, are obtained and compared with the solutions obtained by a finite difference numerical method. For reaction orders less than 1.0, the Adomian polynomial series solution with 4 terms gives comparable results to those obtained with a finite difference numerical procedure. For reaction orders greater than 1.0, series solutions with more than 6 terms, are required for good accuracy.
Mesoporous Silica Nanoreactors for Highly Efficient Proteolysis
Authors: Fan Jie , Shui Wenqing , Yang Pengyuan , Wang Xiaoyan , Xu Yunmin , Wang Honghai , Chen Xian , Zhao Dongyuan
Published: July 2005

Protein digestion inside the nanoreactor channels of mesoporous silica (SBA‐15) is reported, and evaluated by using peptide‐mass mapping. Both proteases and substrates were efficiently captured within these biocompatible nanoreactors. After 10 minutes, the mass spectrum of the protein digests released from the mesoporous‐silica‐based nanoreactors revealed the presence of eight peptides covering 58 % of the protein sequence with an intense signal (signal/noise ratio >70). In comparison, the conventional overnight in‐solution digestion of proteins under otherwise identical conditions generated only three peptides (27 % sequence coverage). We propose that this order‐of‐magnitude increase in the proteolytic reaction rate is mainly attributed to two factors: substrate enrichment within mesoporous silica channels and enzyme immobilization. The surface properties and macrostructure of the mesoporous silica were studied to reveal their significant influence on proteolytic reactions.