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P G Alexander

Publications and source records attributed to P G Alexander.

5 recordsLinked to original sources
PubMed1997

Cloning and characterization of chicken Paraxis: a regulator of paraxial mesoderm development and somite formation.

To investigate the molecular regulation of embryonic somite formation and development, we have cloned the full-length cDNA and characterized the embryonic expression profile of chicken Paraxis, a member of a novel family of basic helix-loop-helix (bHLH) proteins, which has been suggested to play a role in paraxial mesoderm development. Chicken Paraxis encodes a 1.35-kb mRNA and contains a 53-amino-acid residue bHLH domain, identical in sequence to that found in the mammalian Paraxis genes of mouse, hamster, and human. Northern analysis revealed significant Paraxis expression in the early embryo up to the 30- to 35-somite stage, declining from Incubation Day 4 on and becoming undetectable by Day 5. By whole-mount in situ hybridization, Paraxis expression is first seen distinctly in the emerging paraxial mesoderm of the primitive streak stage chick embryo. During gastrulation, Paraxis expression in the mesoderm defines bilaterally symmetric crescents located immediately rostral to Hensen's node and appears to pre-configure the emerging somitic mesoderm. During somite development, Paraxis expression is evident in the rostral segmental plate and the newly formed somites, although the level of expression clearly decreases in the more mature somites. By the 10-12th pair of somites, counting from the caudal end, Paraxis expression appears to be preferentially localized to the medial aspect of individual somites. Histological analysis showed that Paraxis expression is evenly distributed in the newly formed caudal epithelial somites, then localized to the medial portion of maturing somites, and preferentially localized in the dermomyotome of more rostral somites before diminishing to undetectable levels in the most cranial somites. The functional involvement of Paraxis in somite development was assessed by perturbing its expression in somitic stage chick embryos using a Paraxis-specific antisense oligonucleotide. Disruption of somite formation from the paraxial mesoderm was observed in 67% of the surviving topically treated embryos, whereas control embryos treated with sense or random sequence oligonucleotides did not show similar effects. In addition, direct injection of Paraxis-specific antisense oligonucleotide into the paraxial mesoderm produced discrete segmentation anomalies which correlated spatially with the site of injection. Whole-mount in situ hybridization revealed that the regions defective in somite formation displayed perturbed Paraxis expression and a reduction of Pax-1 expression, a marker for epithelial somites and sclerotome. Histological analysis indicated poor condensation and/or epithelization of the somitic mesoderm. Finally, embryos treated with valproic acid, a known teratogen which affects somite segmentation, showed perturbed Paraxis expression, suggesting that the mechanism of action of this teratogen involves a pathway(s) requiring Paraxis activity. These data provide evidence that Paraxis acts as an important regulator of paraxial mesoderm and somite development and functions in axial patterning of the chick embryo.

Amino Acid Sequence↗
PubMedDate not supplied

Hepatitis B vaccination programs for health care personnel in U.S. hospitals.

A random sample of 232 U.S. hospitals was surveyed. Of those hospitals, 75 percent had hepatitis B vaccination programs. The presence of a program was associated with hospital size (60 percent of those with 100 beds, 75 percent with 100-499 beds, 90 percent with 500 or more beds; P = 0.0013) and hospital location (urban 86 percent; rural 57 percent; P less than 0.001). The frequency of needlestick exposures per month among hospital personnel and hospital location were directly related to and best predicted the existence of hepatitis B vaccination programs. All hospitals with programs offered vaccine to high-risk personnel (as defined by the hospital). Seventy-seven percent of hospitals paid all costs for vaccinating high-risk personnel; 19 percent paid for any employee to be vaccinated regardless of risk status. Forty-six percent of hospitals with programs were estimated to have vaccinated more than 10 percent of all eligible personnel, and 13 percent to have vaccinated more than 25 percent of eligible personnel. The highest compliance rates were associated with hospitals paying for the vaccine and requiring vaccination of high-risk personnel. Fifty-four percent of hospitals attributed noncompliance to concern regarding vaccine safety and effectiveness. The reasons why there was no vaccination program in 58 hospitals were (a) low incidence of hepatitis B virus infections among personnel, (b) cost of vaccine, and (c) vaccination being offered as part of a needlestick protocol. Full utilization of hepatitis B vaccine could eliminate the occupational hazard that hepatitis B virus presents to health care personnel.

Economics, Hospital↗