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Biomedical subjects

G D Pearson

Publications and source records attributed to G D Pearson.

47 records · Page 3Linked to original sources

Chromatin-like organization of the adenovirus chromosome.

Staphylococcal nuclease (nucleate 3'-oligonucleotidohydrolase; EC 3.1.4.7) cleaved DNA within disrupted adenovirus particles into a regular series of fragments with a repeat unit of 200 base pairs. Since this pattern did not eppear when DNA alone was digested, we postulate that the orderly arrangement of core polypeptides protects discrete regions of DNA from nuclease attack. The 23 X 10(6) dalton adenovirus DNA molecule can accommodate 180 units of roughly 200 base pairs. Based on the stoichiometry of core polypeptides, we calculate that each repeat unit contains six copies of polypeptide VII and a single copy of polypeptide V. This model is bases on proposals for the structure of eukaryotic chromatin. Very brief nuclease digestion generated 1800 base pair fragments (1/20 of the adenovirus chromosome). This result is discussed in terms of a higher order folding of viral DNA within the virus particle.

Adenoviridae↗

Intermediate in adenovirus type 2 replication.

Replicating chromosomes, called intermediate DNA, have been extracted from the adenovirus replication complex. Compared to mature molecules, intermediate DNA had a greater buoyant density in CsCl gradients and ethidium bromide-cesium chloride gradients. Digestion of intermediate DNA with S1 endonuclease, but not with RNase, abolished the difference in densities. These properties suggest that replicating molecules contain extensive regions of parental single strands. Although intermediate DNA sedimented faster than marker viral DNA in neutral sucrose gradients, single strands longer than unit length could not be detected after alkaline denaturation. Integral size classes of nascent chains in intermediate DNA suggest a relationship between units of replication and the nucleoprotein structure of the virus chromosome. Adenovirus DNA was replicated at a rate of 0.7 x 10-6 daltons/min. Although newly synthesized molecules had the same sedimentation coefficient and buoyant density as mature chromosomes, they still contained single-strand interruptions. Complete joining of daughter strands required an additional 15 to 20 min.

Adenoviridae↗

The Pediatric Heart Network: a primer for the conduct of multicenter studies in children with congenital and acquired heart disease.

Most contemporary diagnostic and treatment strategies for pediatric patients with cardiovascular disease are not supported by evidence from clinical trials but instead are based on expert opinion, single-institution observational studies, or extrapolated from adult cardiovascular medicine. In response to this concern, the National Heart, Lung, and Blood Institute established the Pediatric Heart Disease Clinical Research Network (PHN) in 2001. The purposes of this article are to describe the initiation, structure, and function of the PHN; to review the ongoing studies; and to address current and future challenges. To date, four randomized clinical trials and two observational studies have been launched. Design and conduct of complex, multicenter studies in children with congenital and acquired heart disease must address numerous challenges, including identification of an appropriate clinically relevant primary endpoint, lack of preliminary data on which to base sample size calculations, and recruitment of an adequate number of subjects. The infrastructure is now well developed and capable of implementing complex, multicenter protocols efficiently and recruiting subjects effectively. The PHN is uniquely positioned to contribute to providing evidence-based medicine for and improving the outcomes of pediatric patients with cardiovascular disease.

Child↗

A retrospective review of the role of transesophageal echocardiography in aortic and cardiac trauma in a level I Pediatric Trauma Center.

This study examined the role of transesophageal echocardiography in blunt aortic and cardiac trauma in a Pediatric Level I Trauma Center. In a > 5-year retrospective review, we identified 10 children with blunt cardiac (n = 4; tricuspid valve in two; mitral valve in one; aortic valve in one) and aortic (n = 6; aortic rupture in five, subintimal flap in one) trauma. Diagnosis of the cardiac injuries was made with transthoracic echocardiography, with transesophageal echocardiography providing additional anatomic detail and postoperative assessment in three of four children who required surgical intervention. Diagnosis of the aortic injuries was made with transesophageal echocardiography in five of six patients; one patient underwent aortography before transfer. Transesophageal echocardiography also identified depressed myocardial function in one child and aided in surgical management of the five aortic ruptures. In blunt chest trauma, transesophageal echocardiography provides accurate evaluation of cardiovascular structure and function and guides operative repair.

Adolescent↗

Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development.

Nucleotide sequence and deletion analysis have been used to identify the regulatory and coding sequences comprising the cholera toxin operon (ctx). Incorporation of defined in vitro-generated ctx deletion mutations into Vibrio cholerae by in vivo genetic recombination produced strains which have practical value in cholera vaccine development.

Base Sequence↗

Effect of IFN-gamma on the immune response in vivo and on gene expression in vitro.

T lymphocytes produce a variety of immunoregulatory molecules including gamma interferon (IFN-gamma) and antigen-specific suppressor and enhancer factors. During our studies of active substances obtained from cloned T-cell lines, we observed that certain fractions administered to mice resulted in enhancement of immune responses. Preliminary characterization of the substance suggested that it could be IFN-gamma and we therefore undertook a study of the action of IFN-gamma produced by recombinant DNA methodology on immune responses. We found that for several antigens, administration of IFN-gamma to mice leads to two- to five-fold enhancement of antibody formation provided that the IFN-gamma and antigen are administered together. The effect was dose dependent, giving a maximal response at 500-600 anti-viral units per mouse. Preliminary studies suggest that the macrophage may be the target of IFN-gamma action. Addition of IFN-gamma to cultures of a macrophage cell line leads to a greater than 10-fold increase in the level of RNA coding for I-region-encoded cell surface molecules.

Animals↗