bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAM Receptors Regulate Stem Cell Specification and Organ Development Through Complex Interactions With CLAVATA Signaling
Authors: DeYoung Brody J , Clark Steven E 
Published: September 2008

Abstract
The CLAVATA1 (CLV1) receptor kinase regulates stem cell specification at shoot and flower meristems of Arabidopsis. Most clv1 alleles are dominant negative, and clv1 null alleles are weak in phenotype, suggesting additional receptors functioning in parallel. We have identified two such parallel receptors, BAM1 and BAM2. We show that the weak nature of the phenotype of clv1 null alleles is dependent on BAM activity, with bam clv mutants exhibiting severe defects in stem cell specification. Furthermore, BAM activity in the meristem depends on CLV2, which is required in part for CLV1 function. In addition, clv1 mutants enhance many of the Bam− organ phenotypes, indicating that, contrary to current understanding, CLV1 function is not specific to the meristem. CLV3 encodes a small, secreted peptide that acts as the ligand for CLV1. Mutations in clv3 lead to increased stem cell accumulation. Surprisingly, bam1 and bam2 mutants suppress the phenotype of clv3 mutants. We speculate that in addition to redundant function in the meristem center, BAM1 and BAM2 act to sequester CLV3-like ligands in the meristem flanks.
22q11 Deletion Syndrome and Limb Anomalies: Report on Two Brazilian Patients
Authors: Mizue Kokitsu-Nakata Nancy , Leine Guion-Almeida Maria , Richieri-Costa Antonio 
Published: September 2008

Objective: To report on two Brazilian patients with chromosome 22q11 deletion who presented with velopharyngeal insufficiency, congenital heart anomalies, developmental delay, and limb anomalies. The pattern of limb anomalies in these patients, which range from ectrodactyly to limb synostosis, is very uncommon in 22q11 deletion syndrome. Conclusion: These patients widen the spectrum of clinical signs of the 22q11 deletion syndrome and alert researchers to conduct additional investigation in patients with limb involvement with velopharyngeal insufficiency and/or cardiac anomalies, along with developmental delay.
A Study of Speech, Language, Hearing, and Dentition in Children with Cleft Lip Only
Authors: Vallino Linda D. , Zuker Ronald , Napoli Joseph A. 
Published: September 2008

Objective: To examine the prevalence of speech, language, hearing, and dental problems in children with an initial diagnosis of isolated cleft lip only (CL), for which evidence-based practice can be developed. Design: Retrospective chart review of 95 patients with cleft lip (age range, 2.8 to 3.7 years; mean, 3.1 years). Results: Speech and language impairment was documented in 13% and 18% of the patients, respectively. Thirty-three percent of the children presented with middle ear effusion. Thirteen percent had abnormal hearing. With one exception, the type and degree of hearing loss was a mild conductive loss most often attributed to the presence of effusion. Dental and/or occlusal anomalies were documented in 62% of the patients. A supernumerary tooth was the most frequently occurring dental anomaly and crossbite the most frequently occurring occlusal anomaly. Two children had a submucous cleft palate. Resonance was abnormal in 5% of the children. Conclusion: Children with an initial diagnosis of CL need to be monitored by the interdisciplinary team for speech, language, ear disease, hearing, and dentition beginning in infancy and followed until all management needs are met.
Comparative Osseous and Soft Tissue Morphology following Cleft Lip Repair
Authors: Seidenstricker-Kink Lynn M. , Becker Devra B. , Govier Daniel P. , DeLeon Valerie B. , Lo Lun-Jou , Kane Alex A. 
Published: September 2008

Objective: To quantify comparative improvement between osseous and soft tissue asymmetry following primary lip repair. Design: Retrospective analysis of preoperative and postoperative computed tomography scans of infants with unilateral cleft lip and palate. Sixteen soft tissue landmarks were placed using an exploratory two-/three-dimensional image processing system and compared for asymmetry. Patients: Computed tomography scans were obtained on 26 patients (13 boys, 13 girls) of Chinese ethnicity (mean age  =  0.25 years) prior to Millard lip repair. Nineteen of these contributed to follow-up comparative studies prior to palatoplasty at a mean age of 0.92 years. There were 18 left-sided and eight right-sided clefts. Main Outcome Measure: Euclidean distance matrix asymmetry analysis was used to determine the amount of soft tissue asymmetry pre- and postlip repair. Similar analyses of the same scans were performed for 41 osseous landmarks. Results: Soft tissue landmarks had 36/39 (92%) preoperative and 13/39 (33%) postoperative asymmetric pairs. Osseous distances demonstrated 77/125 (61%) asymmetric pairs preoperatively and 60/125 (48%) postoperatively. Soft tissue and osseous distances of the lip region demonstrated 32% and 39% postoperative asymmetry, respectively. Soft tissue and osseous distances of the nasal region demonstrated 52% and 72% postoperative asymmetry, respectively. Soft tissue and osseous distances of the facial landmarks demonstrated 24% and 34% postoperative asymmetry, respectively. Conclusions: Primary lip repair appears to effect gains in symmetry in soft tissue and provides sufficient molding forces to cause correlating symmetry changes in underlying osseous structures.
Anatomical Basis for Apparent Subepithelial Cleft Lip: A Histological and Ultrasonographic Survey of the Orbicularis Oris Muscle
Authors: Rogers Carolyn R. , Weinberg Seth M. , Smith Timothy D. , Deleyiannis Frederic W. B. , Phil M. , Mooney Mark P. , Marazita Mary L. 
Published: September 2008

Objective: To determine if there is an anatomic basis for subepithelial orbicularis oris muscle defects by directly comparing ultrasonographic images of the upper lip with corresponding histological sections obtained from cadavers. Methods: Ultrasound was performed on the upper lips of previously frozen, unpreserved cadaver heads (n  =  32), followed by dissection and sectioning of the upper lips. The ultrasound sequences were scored by a panel of raters, classifying the orbicularis oris muscle as negative, positive, or unknown for the presence of an orbicularis oris discontinuity (subepithelial defect). Based on ultrasound, six lip specimens were chosen for histological sectioning, were stained with hematoxylin-eosin and Gomori trichrome stain, and were evaluated with light microscopy at low (8×) and intermediate (100×) magnification. Results: One cadaver was scored positive for an orbicularis oris muscle discontinuity based on ultrasound; whereas, the remaining cadavers were scored negative. Of the cadavers with negative ultrasound scores, two were noted to have orbicularis oris muscles with “irregular” features (e.g., excessive localized thinning or asymmetry). From histology, the area of discontinuity as visualized on the positively scored ultrasound was characterized by both disorganized orbicularis oris muscle fibers and excess connective tissue within the muscle belly. In contrast, the localized thinning observed on some of the negatively scored ultrasounds was not confirmed by histology. Conclusions: Abnormalities of the orbicularis oris muscle visualized by ultrasound have an anatomic basis as revealed through histology. Ultrasound is a useful tool for noninvasively identifying discontinuities of the orbicularis oris muscle.
DNA Methylation Changes during Cleft Palate Formation Induced by Retinoic Acid in Mice
Authors: Kuriyama Motone , Udagawa Akikazu , Yoshimoto Shinya , Ichinose Masaharu , Sato Koji , Yamazaki Koji , Matsuno Yoshiharu , Shiota Kunio , Mori Chisato 
Published: September 2008

Objectives: The aim of this study was to analyze epigenetic (specifically, DNA methylation) participation in the mechanisms of cleft palate only induced by maternal exposure to all-trans retinoic acid in mice. Design: Cleft palate only was induced in fetuses by maternal exposure to all-trans retinoic acid. Their secondary palates were excised for analysis. Cytosine extension assay and restriction landmark genomic scanning were performed to analyze DNA methylation status. The expression levels of the DNA methyltransferases were examined by real-time reverse transcriptase–polymerase chain reaction. Results: Using cytosine extension assay, on gestation day 14.5, the status of DNA methylation within CpG islands and in global DNA was decreased significantly in all-trans retinoic acid–treated groups compared with the controls (p < .01 and p < .05). In the controls, the status within CpG islands on gestation day 14.5 was significantly increased compared with gestation days 13.5 and 18.5 (p < .01). Using real-time reverse transcriptase–polymerase chain reaction, there was no significant change in the expression of DNA methyltransferases, except on gestation day 18.5. Using restriction landmark genomic scanning on gestation day 18.5, five spots (0.49%) in the controls and one spot (0.1%) in all-trans retinoic acid–treated groups were specifically detected. Conclusions: These results indicate that changes in DNA methylation may play an important role in the manifestation of cleft palate only caused by environmental factors such as maternal exposure to all-trans retinoic acid.
CD138/Syndecan-1 and SSEA-1 Mark Distinct Populations of Developing Ciliary Epithelium That Are Regulated Differentially by Wnt Signal
Authors: Koso Hideto , Iida Atsumi , Tabata Yoko , Baba Yukihiro , Satoh Shinya , Taketo Mark M. , Watanabe Sumiko 
Published: September 2008

Abstract
Ciliary epithelium (CE), which consists of nonpigmented and pigmented layers, develops from the optic vesicle. However, the molecular mechanisms underlying CE development have not been closely examined, in part because cell-surface markers suitable for specific labeling of subregions of the retina were unknown. Here, we identified CD138/syndecan-1 and stage specific embryonic antigen-1 (SSEA-1) CD15 as cell-surface antigens marking nonpigmented and pigmented CE, respectively. During retinal development, both CD138 and SSEA-1 were expressed in the early stage, and segregation of these markers in the tissue began at around embryonic day (E) 10. As a result, CD138-positive (CD138+) cells were found at the most distal tip of the retina, and SSEA-1+ cells were found in the periphery adjacent to the area of CD138 expression. In vitro characterization of isolated CD138+ or SSEA-1+ cell subpopulations revealed that CD138+ cells lose their retinal progenitor characteristics between E13 and E16, suggesting that they commit to becoming nonpigmented CE cells within this period. By in vivo mouse models, we found that stabilized β-catenin expanded the area of CD138+ nonpigmented CE and that elimination of β-catenin inhibited development of nonpigmented CE cells. These findings are the first to use cell-surface markers to ascertain the spatial and temporal transitions that occur in developing CE.
Disclosure of potential conflicts of interest is found at the end of this article.
Herpes Simplex Virus-Mediated Expression of Pax3 and MyoD in Embryoid Bodies Results in Lineage-Related Alterations in Gene Expression Profiles
Authors: Craft April M. , Krisky David M. , Wechuck James B. , Lobenhofer Edward K. , Jiang Ying , Wolfe Darren P. , Glorioso Joseph C. 
Published: September 2008

Abstract
The ability of embryonic stem cells to develop into multiple cell lineages provides a powerful resource for tissue repair and regeneration. Gene transfer offers a means to dissect the complex events in lineage determination but is limited by current delivery systems. We designed a high-efficiency replication-defective herpes simplex virus gene transfer vector (JDββ) for robust and transient expression of the transcription factors Pax3 and MyoD, which are known to be involved in skeletal muscle differentiation. JDββ-mediated expression of each gene in day 4 embryoid bodies (early-stage mesoderm) resulted in the induction of unique alterations in gene expression profiles, including the upregulation of known target genes relevant to muscle and neural crest development, whereas a control enhanced green fluorescent protein expression vector was relatively inert. This vector delivery system holds great promise for the use of gene transfer to analyze the impact of specific genes on both regulatory genetic events and commitment of stem cells to particular lineages.
Disclosure of potential conflicts of interest is found at the end of this article.
Health-Related Quality of Life Impact of Bevacizumab When Combined with Irinotecan, 5-Fluorouracil, and Leucovorin or 5-Fluorouracil and Leucovorin for Metastatic Colorectal Cancer
Authors: Kabbinavar Fairooz F. , Wallace Joel F. , Holmgren Eric , Yi Jing , Cella David , Yost Kathleen J. , Hurwitz Herbert I. 
Published: September 2008

Abstract

Purpose.
To compare the time to deterioration in health-related quality of life (HRQoL) in patients with previously untreated metastatic colorectal cancer receiving a 5-fluorouracil (5-FU)-based chemotherapy regimen with or without the addition of bevacizumab (BV) in two randomized, placebo-controlled studies.

Patients and Methods.
Prespecified HRQoL endpoints in the phase II (Study 2192) and phase III (Study 2107) studies were time to deterioration in HRQoL, measured by the Functional Assessment of Cancer Therapy–Colorectal (FACT-C) Colorectal Cancer Subscale (CCS), Trial Outcome Index (TOI-C), and FACT-C total score. Time to deterioration in HRQoL was evaluated for patients with baseline and postbaseline assessments, using the stratified log-rank test.

Results.
In the pivotal phase III trial, HRQoL baseline and postbaseline CCS scores were available for 127 patients receiving irinotecan, 5-FU, and leucovorin (LV) (IFL) and 122 patients receiving IFL plus BV. The time to deterioration in HRQoL did not differ significantly between treatment groups as measured by the CCS, TOI-C, or FACT-C total score. In the phase II study, baseline and postbaseline CCS scores were available for 77 and 89 patients receiving 5-FU and LV and 5-FU and LV plus BV, respectively. In that study, the time to deterioration in HRQoL was similar between groups as measured by the CCS and TOI-C scores, but was significantly longer in the 5-FU and LV plus BV arm than in the 5-FU and LV plus placebo arm for the FACT-C total score.

Conclusions.
When added to 5-FU chemotherapy, BV significantly prolonged overall survival and progression-free survival without compromising HRQoL.
Neoplastic Meningitis
Authors: Chamberlain Marc C. 
Published: September 2008

Abstract

Learning Objectives
After completing this course, the reader should be able to: Describe the epidemiology of leptomeningeal metastasis.Participate in the diagnosis of leptomeningeal metastasis.Engage in the treatment of leptomeningeal metastasis.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
Neoplastic meningitis (NM) is a common problem in neuro-oncology, occurring in approximately 5% of all patients with cancer.

Methods.
Notwithstanding frequent focal signs and symptoms, NM is a disease affecting the entire neuraxis, and therefore staging and treatment need encompass all cerebrospinal fluid (CSF) compartments.

Results.
Central nervous system staging of NM includes contrast-enhanced cranial computerized tomography or magnetic resonance imaging (MR-Gd), contrast-enhanced spine magnetic resonance imaging or computerized tomographic myelography and radionuclide CSF flow study. Treatment of NM incorporates involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (i.e., methotrexate, cytosine, arabinoside, and thio-TEPA) administered by a variety of schedules either by intralumbar or intraventricular drug delivery.

Conclusions.
Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.
Fatty Acid Synthase Inhibitors Modulate Energy Balance via Mammalian Target of Rapamycin Complex 1 Signaling in the Central Nervous System
Authors: Proulx Karine , Cota Daniela , Woods Stephen C. , Seeley Randy J. 
Published: September 2008

OBJECTIVE—Evidence links the hypothalamic fatty acid synthase (FAS) pathway to the regulation of food intake and body weight. This includes pharmacological inhibitors that potently reduce feeding and body weight. The mammalian target of rapamycin (mTOR) is an intracellular fuel sensor whose activity in the hypothalamus is also linked to the regulation of energy balance. The purpose of these experiments was to determine whether hypothalamic mTOR complex 1 (mTORC1) signaling is involved in mediating the effects of FAS inhibitors.
RESEARCH DESIGN AND METHODS—We measured the hypothalamic phosphorylation of two downstream targets of mTORC1, S6 kinase 1 (S6K1) and S6 ribosomal protein (S6), after administration of the FAS inhibitors C75 and cerulenin in rats. We evaluated food intake in response to FAS inhibitors in rats pretreated with the mTOR inhibitor rapamycin and in mice lacking functional S6K1 (S6K1−/−). Food intake and phosphorylation of S6K1 and S6 were also determined after C75 injection in rats maintained on a ketogenic diet.
RESULTS—C75 and cerulenin increased phosphorylation of S6K1 and S6, and their anorexic action was reduced in rapamycin-treated rats and in S6K1−/− mice. Consistent with our previous findings, C75 was ineffective at reducing caloric intake in ketotic rats. Under ketosis, C75 was also less efficient at stimulating mTORC1 signaling.
CONCLUSIONS—These findings collectively indicate an important interaction between the FAS and mTORC1 pathways in the central nervous system for regulating energy balance, possibly via modulation of neuronal glucose utilization.
Role of theENPP1K121Q Polymorphism in Glucose Homeostasis
Authors: Baratta Roberto , Rossetti Paola , Prudente Sabrina , Barbetti Fabrizio , Sudano Dora , Nigro Angela , Farina Maria Grazia , Pellegrini Fabio , Trischitta Vincenzo , Frittitta Lucia 
Published: September 2008

OBJECTIVE— To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy.RESEARCH DESIGN AND METHODS— We conducted case-control studies in 764 adults (from two independent samples of 289 nonobese and 485 obese individuals) and 240 overweight/obese children undergoing oral glucose tolerance testing (OGTT). Early-phase insulin secretion and insulin sensitivity (the insulinogenic index and the insulin sensitivity index) and their interplay (the disposition index) were calculated.RESULTS— In adult subjects, glucose profiles during OGTT were significantly (P = 2 × 10−2) different across K121Q genotype groups and higher in QQ than KK individuals (P = 5 × 10−2). The insulinogenic index was significantly reduced in QQ (18.5 ± 3.4) compared with both KK (31.6 ± 1.0; P = 2.2 × 10−7) and KQ (30.5 ± 1.5; P = 3.2 × 10−6) individuals. KQ individuals also showed a reduced insulin sensitivity index compared with KK subjects (P = 3.6 × 10−2). The disposition index was lower in QQ carriers than in KQ and KK individuals (P = 8 × 10−3 and 4 × 10−4, respectively) and lower in KQ than in KK individuals (P = 3 × 10−2). Data obtained in overweight/obese children were very similar to those observed in adults, with QQ individuals showing (compared with KQ and KK subjects) a reduced insulinogenic index (P = 7 × 10−3 and 2 × 10−2, respectively) and disposition index (P = 2 × 10−2 and 7 × 10−3, respectively).CONCLUSIONS— Homozygous carriers of the ENPP1 Q121 variant are characterized by an altered glucose homeostasis. Reduced early-phase insulin secretion and inefficient interplay between insulin secretion and sensitivity, which occur at early ages, are major determinants of this defect.
Ghrelin Infusion in Humans Induces Acute Insulin Resistance and Lipolysis Independent of Growth Hormone Signaling
Authors: Vestergaard Esben Thyssen , Gormsen Lars Christian , Jessen Niels , Lund Sten , Hansen Troels Krarup , Moller Niels , Jorgensen Jens Otto Lunde 
Published: September 2008

OBJECTIVE—Ghrelin is a gut-derived peptide and an endogenous ligand for the growth hormone (GH) secretagogue receptor. Exogenous ghrelin stimulates the release of GH (potently) and adrenocorticotropic hormone (ACTH) (moderately). Ghrelin is also orexigenic, but its impact on substrate metabolism is controversial. We aimed to study direct effects of ghrelin on substrate metabolism and insulin sensitivity in human subjects.
RESEARCH DESIGN AND METHODS—Six healthy men underwent ghrelin (5 pmol · kg−1 · min−1) and saline infusions in a double-blind, cross-over study to study GH signaling proteins in muscle. To circumvent effects of endogenous GH and ACTH, we performed a similar study in eight hypopituitary adults but replaced with GH and hydrocortisone. The methods included a hyperinsulinemic-euglycemic clamp, muscle biopsies, microdialysis, and indirect calorimetry.
RESULTS—In healthy subjects, ghrelin-induced GH secretion translated into acute GH receptor signaling in muscle. In the absence of GH and cortisol secretion, ghrelin acutely decreased peripheral, but not hepatic, insulin sensitivity together with stimulation of lipolysis. These effects occurred without detectable suppression of AMP-activated protein kinase phosphorylation (an alleged second messenger for ghrelin) in skeletal muscle.
CONCLUSIONS—Ghrelin infusion acutely induces lipolysis and insulin resistance independently of GH and cortisol. We hypothesize that the metabolic effects of ghrelin provide a means to partition glucose to glucose-dependent tissues during conditions of energy shortage.
Lymphocytes From Patients With Type 1 Diabetes Display a Distinct Profile of Chromatin Histone H3 Lysine 9 Dimethylation
Authors: Miao Feng , Smith David D. , Zhang Lingxiao , Min Andrew , Feng Wei , Natarajan Rama 
Published: September 2008

OBJECTIVE—The complexity of interactions between genes and the environment is a major challenge for type 1 diabetes studies. Nuclear chromatin is the interface between genetics and environment and the principal carrier of epigenetic information. Because histone tail modifications in chromatin are linked to gene transcription, we hypothesized that histone methylation patterns in cells from type 1 diabetic patients can provide novel epigenetic insights into type 1 diabetes and its complications.
RESEARCH DESIGN AND METHODS—We used chromatin immunoprecipitation (ChIP) linked to microarray (ChIP-chip) approach to compare genome-wide histone H3 lysine 9 dimethylation (H3K9me2) patterns in blood lymphocytes and monocytes from type 1 diabetic patients versus healthy control subjects. Bioinformatics evaluation of methylated candidates was performed by Ingenuity Pathway Analysis (IPA) tools.
RESULTS—A subset of genes in the type 1 diabetic cohort showed significant increase in H3K9me2 in lymphocytes but not in monocytes. CLTA4, a type 1 diabetes susceptibility gene, was one of the candidates displaying increased promoter H3K9me2 in type 1 diabetes. IPA identified two high-scoring networks that encompassed genes showing altered H3K9me2. Many of them were associated with autoimmune and inflammation-related pathways, such as transforming growth factor-β, nuclear factor-κB, p38 mitogen-activated protein kinase, toll-like receptor, and interleukin-6. IPA also revealed biological relationships between these networks and known type 1 diabetes candidate genes.
CONCLUSIONS—The concerted and synergistic alteration of histone methylation within the identified network in lymphocytes might have an effect on the etiology of type 1 diabetes and its complications. These studies provide evidence of a novel association between type 1 diabetes and altered histone methylation of key genes that are components of type 1 diabetes–related biological pathways and also a new understanding of the pathology of type 1 diabetes.