Biomedical subjects

John F Schiltz

Publications and source records attributed to John F Schiltz.

4 recordsLinked to original sources

PubMed2003

Hmga2 promoter analysis in transgenic mice.

HMGA2(2) belongs to the high mobility group A (HMGA) family of architectural transcription factors which participate in a wide variety of nuclear processes ranging from transcription to recombination, playing an important role in chromatin remodelling. HMGA2 is expressed during embryogenesis but not by adult somatic tissues, yet it becomes re-expressed following neoplastic transformation. A role in development is underscored by the finding that the inactivation of the Hmga2 gene is responsible for the murine pygmy phenotype. To elucidate mechanisms that control HMGA2 expression, we have previously cloned the gene and identified functional elements involved in its regulation. In this paper, transgenic mice were generated to define genomic regions involved in Hmga2 developmental and tissue-specific transcriptional regulation. A genomic region from -8.1 to -3.7kb upstream from the initiation site has been found to recapitulate most of the spatial and temporal endogenous Hmga2 gene expression.

Animals↗

PubMed2003

Hmga1 is required for normal sperm development.

The Hmgi protein family of chromosomal architectural factors is extensively studied for its roles in embryogenesis and its association with benign mesenchymal tumors. Although the biochemical function of Hmga1 has been studied in vitro, to provide in vivo insight into its biological function, a targeted disruption of Hmga1 was initiated. Chimeric founder mice were derived from embryonic stem (ES) cells harboring a targeted mutation in a single Hmga1 allele. These 14 different chimeric founders produced 494 black progeny. Since none of these 494 progeny were agouti, none of them were derived from ES cells. Control injections of the wild-type ES cell lines resulted in ES cell derived agouti mice, indicating that the ES cells were totipotent. Therefore, our results indicate that one intact Hmga1 allele was not sufficient for germ-line transmission of the ES cells. Seven chimeric founder mice that were examined histologically demonstrated aberrant regions in their reproductive organs. Aberrant regions of seminiferous tubules were reduced in diameter, demonstrated vacuolated Sertoli cells, and had an absolute deficiency of sperm. While the Hmga1(+/-) ES cells were shown to contribute to the formation of the epididymides, they did not significantly contribute to the testes of chimeric founder mice. No sperm isolated from any of the Hmga1(+/-) chimeric mice were shown to arise from the ES cells, as none of them contained the targeted disruption of the Hmga1 gene. Our results suggest that both alleles of Hmga1 are required for normal sperm production in the mouse.

Animals↗

PubMed2002

Hmgi-c-independent Activation of MuRantes in Vivo.

The architectural factor HMGI-C is of considerable interest for its recognized roles in mammalian development and tumorigenesis. As a result, the identification of downstream target genes of HMGI-C is the present focus of active research. In vitro evidence from macrophage cell lines has previously suggested that Hmgi-c is necessary for the inducible activation of MuRantes expression. To attempt to verify this hypothesis, an in vivo analysis was performed that took advantage of the existence of the Hmgi-c null mouse strain. The ability of cells and tissues extracted from Hmgi-c null mice to express the inflammatory chemokine MuRantes was investigated. The investigation examined MuRantes expression in primary embryonic fibroblasts and fresh peritoneal macrophages after Newcastle disease virus induction and whole organs after lipopolysaccharide induction. Each of these systems clearly demonstrates that Hmgi-c is not required for the activation of MuRantes expression.

Animals↗

PubMedDate not supplied

Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis.

BACKGROUND: Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are medical emergencies associated with psychotropic administration. Differentiation and treatment can be complex, especially when features of both syndromes are present and the patient has taken both serotonergic and neuroleptic agents. METHOD: Case analysis of a poly-drug overdose (venlafaxine, topiramate, divalproex sodium, risperidone, and carbamazepine) presenting with mixed SS/NMS features and whose clinical management suggests a practical algorithm for treatment of undifferentiated SS/NMS in critical care settings. RESULTS: The suggested algorithm includes: 1) Supportive care and withdrawal of all potentially offending agents; 2) Laboratory evaluation with prompt initiation of treatment for both disorders--cyproheptadine for SS and dantrolene for NMS; 3) Do not use bromocriptine (contraindicated in SS) or chlorpromazine (contraindicated in NMS) initially; 4) Add bromocriptine when clinical presentation becomes consistent with NMS (SS can be prolonged if serotonergic agent has long half-life). CONCLUSIONS: Prompt and appropriate identification and intervention are essential for successful management of SS and NMS. The suggested treatment algorithm allows for specific treatment of both disorders and avoids potentially exacerbating either one. The algorithm derived from this case could serve as both a practical guideline and impetus for further investigation in light of increasing psychotropic co-administration.

Adult↗