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Biomedical subjects

Daniel Young

Publications and source records attributed to Daniel Young.

10 recordsLinked to original sources
PubMed2006

Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life.

BACKGROUND: Ventilation with higher PaCO(2) goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO(2) goal than in previous trials. OBJECTIVE: To determine the clinical benefits and safety of higher PaCO(2) goals for ventilated preterm infants. STUDY DESIGN: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO(2) target between 55 and 65 mm Hg (7.3- 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7- 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18-22 months corrected age. RESULTS: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). CONCLUSION: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.

Algorithms↗
PubMed2006

Jet-based methods to print living cells.

Cell printing has been popularized over the past few years as a revolutionary advance in tissue engineering has potentially enabled heterogeneous 3-D scaffolds to be built cell-by-cell. This review article summarizes the state-of-the-art cell printing techniques that utilize fluid jetting phenomena to deposit 2- and 3-D patterns of living eukaryotic cells. There are four distinct categories of jetbased approaches to printing cells. Laser guidance direct write (LG DW) was the first reported technique to print viable cells by forming patterns of embryonic-chick spinal-cord cells on a glass slide (1999). Shortly after this, modified laser-induced forward transfer techniques (LIFT) and modified ink jet printers were also used to print viable cells, followed by the most recent demonstration using an electrohydrodynamic jetting (EHDJ) method. The low cost of some of these printing technologies has spurred debate as to whether they could be used on a large scale to manufacture tissue and possibly even whole organs. This review summarizes the published results of these cell printers (cell viability, retained genotype and phenotype), and also includes a physical description of the various jetting processes with a discussion of the stresses and forces that may be encountered by cells during printing. We conclude the review by comparing and contrasting the different jet-based techniques, while providing a map for future experiments that could lead to significant advances in the field of tissue engineering.

Animals↗
PubMed2004

Nuclear microenvironments support assembly and organization of the transcriptional regulatory machinery for cell proliferation and differentiation.

The temporal and spatial organization of transcriptional regulatory machinery provides microenvironments within the nucleus where threshold concentrations of genes and cognate factors facilitate functional interactions. Conventional biochemical, molecular, and in vivo genetic approaches, together with high throughput genomic and proteomic analysis are rapidly expanding our database of regulatory macromolecules and signaling pathways that are requisite for control of genes that govern proliferation and differentiation. There is accruing insight into the architectural organization of regulatory machinery for gene expression that suggests signatures for biological control. Localized scaffolding of regulatory macromolecules at strategic promoter sites and focal compartmentalization of genes, transcripts, and regulatory factors within intranuclear microenvironments provides an infrastructure for combinatorial control of transcription that is operative within the three dimensional context of nuclear architecture.

Cell Cycle↗
PubMed2003

Intranuclear trafficking of transcription factors: Requirements for vitamin D-mediated biological control of gene expression.

The architecturally associated subnuclear organization of nucleic acids and cognate regulatory factors suggest functional interrelationships between nuclear structure and gene expression. Mechanisms that contribute to the spatial distribution of transcription factors within the three-dimensional context of nuclear architecture control the sorting of regulatory information as well as the assembly and activities of sites within the nucleus that support gene expression. Vitamin D control of gene expression serves as a paradigm for experimentally addressing mechanisms that govern the intranuclear targeting of regulatory factors to nuclear domains where transcription of developmental and tissue-specific genes occur. We will present an overview of molecular, cellular, genetic, and biochemical approaches that provide insight into the trafficking of regulatory factors that mediate vitamin D control of gene expression to transcriptionally active subnuclear sites. Examples will be presented that suggest modifications in the intranuclear targeting of transcription factors abrogate competency for vitamin D control of skeletal gene expression during development and fidelity of gene expression in tumor cells.

Animals↗
PubMed2003

Tumor suppressor pRB functions as a co-repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription.

The CCAAT displacement protein (CDP-cut/CUTL1/cux) performs a key proliferation-related function as the DNA binding subunit of the cell cycle controlled HiNF-D complex. HiNF-D interacts with all five classes (H1, H2A, H2B, H3, and H4) of the cell-cycle dependent histone genes, which are transcriptionally and coordinately activated at the G(1)/S phase transition independent of E2F. The tumor suppressor pRB/p105 is an intrinsic component of the HiNF-D complex. However, the molecular interactions that enable CDP and pRB to form a complex and thus convey cell growth regulatory information onto histone gene promoters must be further defined. Using transient transfections, we show that CDP represses the H4 gene promoter and that pRB functions with CDP as a co-repressor. Direct physical interaction between CDP and pRB was observed in glutathione-S-transferase (GST) pull-down assays. Furthermore, interactions between these proteins were established by yeast and mammalian two-hybrid experiments and co-immunoprecipitation assays. Confocal microscopy shows that subsets of each protein are co-localized in situ. Using a series of pRB mutants, we find that the CDP/pRB interaction, similar to the E2F/pRB interaction, utilizes the A/B large pocket (LP) of pRB. Thus, several converging lines of evidence indicate that complexes between CDP and pRB repress cell cycle regulated histone gene promoters.

Animals↗
PubMed2003

Nuclear microenvironments support physiological control of gene expression.

There is growing recognition that the organization of nucleic acids and regulatory proteins is functionally linked to the assembly, localization and activity of gene regulatory machinery. Cellular, molecular, biochemical and in-vivo genetic evidence support an obligatory relationship between nuclear microenvironments where regulatory complexes reside and fidelity of transcriptional control. Perturbations in mechanisms governing the intranuclear trafficking of transcription factors and the temporal/spatial organization of regulatory proteins within the nucleus occur with compromised gene expression that abrogates skeletal development and mediates leukemogenesis.

Cell Nucleus↗
PubMed2003

Thrombus characterization with intravascular ultrasound: potential to predict successful thrombolysis.

PURPOSE: To define analysis methods using radiofrequency (RF) data from intravascular ultrasound (IVUS) to characterize thrombus so that the success or failure of thrombolysis can be predicted. METHODS: Experimentation was done in 2 phases: first, 40 clots created from platelet-rich (n=20) and platelet-poor (n=20) plasma were imaged with 20 and 30-MHz IVUS probes. The digitized RF signals were analyzed to determine the attenuation and slope of attenuation characteristics as a reference standard for the second part of the study. In this phase, 20 perfusion trials were performed with 10 platelet-rich and 10 platelet-poor samples in an in vitro arterial perfusion model; the composition of the samples was blinded during interrogation with IVUS. Alteplase (0.1 mg) was then infused directly into the thrombus for 1 hour; restoration of flow and amount of lysis were quantified. RESULTS: Significant differences were detected for the integrated attenuation value (p<0.001) between platelet-poor and platelet-rich clots interrogated with a 30-MHz probe, but no differences were noted using the 20-MHz catheter. However, both transducers were capable of differentiating platelet-rich and platelet-poor clots using a slope of attenuation analysis, which was successful in identifying all 20 (100%) of the blinded clots in the in vitro model. The speed and completeness of lysis were significantly higher (p<0.05) for platelet-rich (78%) than platelet-poor (21%) clots. CONCLUSIONS: IVUS preprocessed imaging is capable of differentiating various types of thrombus. This information can be used to predict the success or failure of pharmacological lysis techniques.

Equipment Design↗
PubMed2002

Vascular endothelial growth factor and Kaposi's sarcoma cells in human skin grafts.

Human cancer cells often produce tumors in animal models that incompletely reproduce the histology of the parental tumor. Kaposi's sarcoma (KS) cells, in particular, have not produced durable angiogenic lesions in animal models that resemble those of KS in humans. We investigated the contribution of transformed KS cells, vascular endothelial growth factor (VEGF), and human skin tissue on tumor development in a human skin graft/mouse model. High levels of serum VEGF (322 pg/ml) were seen in HIV-1-infected persons with KS compared with HIV-1-infected persons without KS (115 pg/ml). Human KS lesions expressed VEGF in the spindle cells. Transformed KS cells expressed the mitogenically active 121-amino acid and 165-amino acid isoforms of VEGF. Tumors induced by KS cells implanted in the SCID mice grew preferentially in human skin grafts rather than in ungrafted murine skin. Tumors induced in the presence of human skin grafts developed numerous lumens expressing alpha(v)beta(3) integrin. KS cells inoculated with neutralizing anti-VEGF antibody did not form tumors. This study supports an important role for VEGF in tumor development and shows how a human tissue can preferentially promote tumor growth.

Animals↗
PubMedDate not supplied

Intranuclear organization of RUNX transcriptional regulatory machinery in biological control of skeletogenesis and cancer.

RUNX (AML/CBFA/PEBP2) transcription factors serve as paradigms for obligatory relationships between nuclear structure and physiological control of phenotypic gene expression. The RUNX proteins contribute to tissue restricted transcription by sequence-specific binding to promoter elements of target genes and serving as scaffolds for the assembly of coregulatory complexes that mediate biochemical and architectural control of activity. We will present an overview of approaches we are pursuing to address: (1) the involvement of RUNX proteins in governing competency for protein/DNA and protein/protein interactions at promoter regulatory sequences; (2) the recruitment of RUNX factors to subnuclear sites where the machinery for expression or repression of target genes is organized; and (3) the trafficking and integration of regulatory signals that control RUNX-mediated transcription.

Animals↗