Biomedical subjects

Catherine A Schnabel

Publications and source records attributed to Catherine A Schnabel.

6 recordsLinked to original sources

PubMed2006

Immunogenicity of xenopeptide hormone therapies.

Peptides are a growing class of agents whose therapeutic use originated with non-human treatments such as animal insulins. Xenopeptides continue to be explored for biotherapeutic development using genetic engineering, and through the rich resource of animal and plant polypeptides. One of the major concerns of therapeutic administration of xenopeptides is the potential for untoward immune responses that may lead to loss of drug efficacy or adverse events in recipients. An increased risk of immunogenicity is perceived with xenopeptides, however, human-derived therapies also induce antibody formation that in some cases has been associated with severe clinical sequelae. In this review, antibody responses to xenopeptides are highlighted looking at current hormone therapies used to treat endocrine disorders. Similar to clinical experiences with peptide-based agents in general, antibody responses against xenopeptide hormone therapies in majority of cases have been benign in nature with minimal clinical impact.

Animals↗

PubMed2005

Effects of pramlintide on postprandial glucose excursions and measures of oxidative stress in patients with type 1 diabetes.

OBJECTIVE: Oxidative stress has been shown to be increased in the postprandial period in patients with diabetes and has been implicated in the pathogenesis of micro- and macrovascular complications. The aim of this post hoc analysis was to assess the effects of pramlintide, an amylin analog shown to reduce postprandial glucose excursions in patients with diabetes, on markers of oxidative stress in the postprandial period. RESEARCH DESIGN AND METHODS: In a randomized, single-blind, placebo-controlled, crossover study, 18 evaluable subjects with type 1 diabetes underwent two standardized breakfast meal tests and received pramlintide or placebo in addition to their preprandial insulin. The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period. RESULTS: Compared with placebo, pramlintide treatment significantly reduced postprandial excursions of glucose, nitrotyrosine, and ox-LDL and prevented a decline in TRAP (P < 0.03 for all comparisons). Correlation analyses adjusted for treatment revealed a significant association between postprandial mean incremental area under the curve from 0 to 4 h (AUC(0-4 h)) for glucose and postprandial mean incremental AUC(0-4 h) for each measure of oxidative stress (r = 0.75, 0.54, and -0.63 for nitrotyrosine, ox-LDL, and TRAP, respectively; P < 0.001 for all correlations). CONCLUSIONS: These findings indicate that the postprandial glucose-lowering effect of pramlintide in type 1 diabetes is associated with a significant reduction in postprandial oxidative stress.

Adult↗

PubMed2004

Time-of-flight optophoresis analysis of live whole cells in microfluidic channels.

Optophoresis is a non-invasive cell analysis technique that is based on the interaction of live whole cells with optical gradient fields, typically generated by a near-infrared laser. The magnitude of the interaction depends upon the intrinsic physical properties of the cells, such as their refractive index, composition, size, and morphology. Time-of-flight (TOF) optophoresis is an implementation of this technique in a microfluidic environment. It measures cell travel times through a fixed distance with and without irradiation from a laser beam. The magnitude of the optical force from the laser, and therefore the change in transit time introduced by the presence of the infrared laser provides a signature for the cell. By accumulating such measurements for a population of cells (typically 200-300 cells per population), different cell types, drug treatments, or biological states can be compared quantitatively without the need for external labels or markers. An integrated TOF system has been constructed and characterized. The system typically uses square capillaries with 50-100 microm internal diameter and uses a syringe-pump-based flow system that generates initial bulk flow velocities between 200 and 600 microm/sec. Using this TOF technique, we have been able to consistently detect significant differences between normal skin and melanoma cell lines, CCD-1037 and A375, respectively. We have also been able to measure consistent differences in a cell differentiation model (HL60 cell line with DMSO treatment). These early results indicate the potential biological sensitivity of the TOF measurement technique for cellular analysis and cancer diagnostic applications.

Cell Line, Tumor↗

PubMed2003

Optical forces for noninvasive cellular analysis.

A novel, noninvasive measurement technique for quantitative cellular analysis is presented that utilizes the forces generated by an optical beam to evaluate the physical properties of live cells in suspension. In this analysis, a focused, near-infrared laser line with a high cross-sectional intensity gradient is rapidly scanned across a field of cells, and the interaction of those cells with the beam is monitored. The response of each cell to the laser depends on its size, structure, morphology, composition, and surface membrane properties; therefore, with this technique, cell populations of different type, treatment, or biological state can be compared. To demonstrate the utility of this cell analysis platform, we evaluated the early stages of apoptosis induced in the U937 cancer cell line by the drug camptothecin and compared the results with established reference assays. Measurements on our platform show detection of cellular changes earlier than either of the fluorescence-based Annexin V or caspase assays. Because no labeling or additional cell processing is required and because accurate assays can be performed with a small number of cells, this measurement technique may find suitable applications in cell research, medical diagnostics, and drug discovery.

Apoptosis↗

PubMed2003

Pbx1 regulates nephrogenesis and ureteric branching in the developing kidney.

Pbx1 encodes a TALE homeodomain transcription factor that regulates developmental gene expression in a variety of tissues. Loss-of-function studies have demonstrated a critical role for Pbx1 in cellular proliferation and patterning and suggest its involvement in numerous regulatory pathways. In this study, examination of metanephric development in Pbx1(-/-) embryos was conducted to further elucidate Pbx1-dependent processes during organogenesis. Prior to death at E15.5, Pbx1(-/-) embryos displayed kidneys that were reduced in size, axially mispositioned, and in more severe cases, exhibited unilateral agenesis. Analysis with molecular markers revealed the effective induction of tubulogenic mesenchyme; however, Pbx1(-/-) kidneys contained fewer nephrons and were characterized by expanded regions of mesenchymal condensates in the nephrogenic zone. Despite the restricted expression of Pbx1 in metanephric mesenchyme, developing nephrons, and stroma, decreased branching and elongation of the ureter were also observed. Moreover, heterologous recombination studies with explant cultures verified that Pbx1(-/-) renal defects arose exclusively from mesenchymal dysfunction. Taken together, these data establish a role for Pbx1 in mesenchymal-epithelial signaling and demonstrate that Pbx1 is an essential regulator of mesenchymal function during renal morphogenesis.

Animals↗

PubMed2003

Pbx1 is essential for adrenal development and urogenital differentiation.

Pbx1 encodes a TALE (three amino acid loop extension) class homeodomain protein that participates in multimeric transcriptional complexes to regulate developmental gene expression. Previous studies demonstrate a critical role for Pbx1 as a developmental regulator whose absence results in embryonic lethality and multiple tissue and organ system abnormalities. Here we report a requirement for Pbx1 in the differentiation of urogenital organs, where Pbx1 is widely expressed in mesenchymal tissues. The complete lack of adrenal glands and formation of gonads displaying rudimentary sexual differentiation correlated with decreased cellular proliferation in Pbx1(-/-) genital ridges. Furthermore, expression of steroidogenic factor-1 (SF-1), a nuclear receptor essential for adrenal organogenesis, was reduced to minimal levels in Pbx1 mutants, indicating an upstream function for Pbx1 in adrenocortical development. Finally, loss of Pbx1 markedly reduces urogenital ridge outgrowth and results in impaired differentiation of the mesonephros and kidneys and the absence of Müllerian ducts. These findings establish a Pbx1-dependent pathway that regulates the expansion of SF-1 positive cells essential for adrenal formation and gonadal differentiation and demonstrate an early requirement for Pbx1 in urogenital development.

Adrenal Glands↗