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B Proctor

Publications and source records attributed to B Proctor.

At least 19 recordsLinked to original sources

Is short stature a handicap? A comparison of the psychosocial functioning of referred and nonreferred children with normal short stature and children with normal stature.

OBJECTIVES: Normal short stature (NSS), defined as height below the 5th percentile for age and sex norms that is not due to illness, hormonal deficiency, or part of a dysmorphic syndrome, has been thought to have a deleterious effect on psychosocial functioning based on observations of referred populations. Recent studies of nonreferred children with NSS, however, have demonstrated normal function. This study directly compared the psychosocial functioning of referred children with NSS, nonreferred children with NSS, and children with normal stature. STUDY DESIGN: Participants, 90 children (46 boys, 44 girls) between 6 and 12 years of age (mean, 9. 6 years), were administered intelligence and achievement tests. Parents and teachers assessed adaptive and problem behaviors. Family adaptability and cohesiveness were measured. RESULTS: Intelligence and achievement for referred and nonreferred children with NSS were average. Referred children with NSS were reported to have more externalizing behavior problems and poorer social skills than nonreferred children with NSS and children in the control group. Family adaptability and cohesiveness were comparable across groups. CONCLUSIONS: Children with NSS have normal psychosocial function, and results suggest that externalizing behavior problems, attention problems, and poor social skills in children referred to clinics for NSS are inappropriately attributed to short stature.

Achievement↗

Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

PURPOSE: To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS: All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 cells and accessibility of the galactose residues on particle surface was demonstrated by a competition assay using 125I-labeled asialoorosomucoid and RCA lectin agglutination assay, respectively. DNA plasmid encoding chloramphenicol acetyl transferase (CAT) gene was complexed with a tri-galactosylated peptide (GM245.3) or tri-galactosylated lipopeptide (GM246.3) in the presence of an endosomolytic peptide (GM225.1) or endosomolytic lipopeptide (GM227.3) to obtain DNA particles of 100-150 nm in size. The plasmid/peptide complexes were added to HepG2 cell cultures or intravenously administered by tail vein injection into normal mice or rats. Plasmid uptake and expression was quantified by qPCR and ELISA, respectively. RESULTS: Multiple antennary glycopeptides that have the ability to condense and deliver DNA plasmid to hepatocytes were synthesized and complexed with DNA plasmid to obtain colloidally stable DNA/peptide complexes. Addition of DNA/GM245.3/GM225.1 peptide complexes (1:3:1 (-/+/-)) to HepG2 cell cultures yielded CAT expression in transfected cells. The transfection efficiency was significantly reduced in the absence of galactose ligand or removal of endosomolytic peptide. Intravenous administration of DNA/GM245.3 peptide complexes (1:0.5 (-/+)) into the tail vein of normal rats yielded DNA uptake in the liver. Substitution of GM245.3 by galactosylated lipopeptide GM246.3 resulted in more stable DNA particles, and a 10-fold enhancement in liver plasmid uptake. CAT expression was detectable in liver following intravenous administration of DNA/GM246.3 complexes. Addition of endosomolytic lipopeptide GM227.3 into the complexes (DNA/ GM246.3/GM227.3 (1:0.5:1 (-/+/-))) yielded a 5-fold increase in CAT expression. Liver expression was 8-fold and 40-fold higher than lung and spleen, respectively, and localized in the hepatocytes only. The transfection efficiency in liver was enhanced by increasing DNA dose and injection volume. The plasmid uptake and expression in liver using DNA/GM246.3/GM227.3 complexes was 100-200-fold higher than DNA formulated in glucose. Tissue examination and serum biochemistry did not show any adverse effect of the DNA/GM246.3/ GM227.3 (1:0.5:1 (-/+/-)) complexes after intravenous delivery. CONCLUSIONS: Gene targeting to hepatocytes was achieved by systemic administration of a well-tolerated synthetic glycopeptide-based delivery system. The transfection efficiency of this glycopeptide delivery system was dependent on peptide structure, endosomolytic activity, colloidal particle stability, and injection volume.

Amino Acid Sequence↗

Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration.

The impact of a localized application of ultrasound on gene transfer to primary tumors following systemic administration of cationic lipid based transfection complexes was investigated. We have previously shown that systemic administration of DOTMA (N-[(1-(2-3-dioleyloxy) propyl)]-N-N-N-trimethylammonium chloride):cholesterol-based transfection complexes to tumor-bearing mice resulted in expression in the tumor and other tissues, primarily the lungs. Application of ultrasound to the tumor before or after the injection resulted in a significant increase in gene transfer to the tumor with no increase observed in other tissues. The magnitude of increased expression ranged from three- to 270-fold depending upon the DNA dose. The following parameters were optimized for maximal increase: duration of ultrasound application, the time interval between plasmid injection and sonoporation, and plasmid dose. A combination of plasmid quantitation and fluorescence microscopy showed that ultrasound increased tumor uptake of the plasmid and that uptake was limited to the tumor vasculature. Using an IL- 12 expression plasmid, the combination of a single plasmid dose (10 microg) and ultrasound treatment produced significantly higher levels of IL-12 in tumor. This increased expression was sufficient to inhibit tumor growth compared with the control conditions. These data demonstrate the potential application of sonoporation as an effective method for enhancing the expression of systemically administered genes in tumor endothelium for cancer gene therapy.

Animals↗

Optimization of cationic lipid/DNA complexes for systemic gene transfer to tumor lesions.

Intravenous (i.v.) administration of cationic lipid N-[( 1-(2-3-dioleyloxy)propyl)]-N-N-N-trimethylammonium chloride (DOTMA)-based transfection complexes in mice with subcutaneous squamous cell tumors yielded plasmid delivery and expression in tumor lesions. The efficiency of gene transfer in tumors was significantly lower than in the lung. This was consistent with low plasmid levels associated with the tumor, suggesting that plasmid delivery to the tumor site was a limiting factor. Lowering the lipid/DNA charge ratio from 5:1 to 0.8:1 (+/-) did not change DNA levels in tumor but significantly reduced DNA levels in lung. However, expression levels were significantly reduced in both tissues at lower lipid/DNA charge ratios. Complexes prepared from small unilamellar liposomes gave significantly lower expression levels in the lungs but similar expression levels in tumors when compared to complexes prepared from larger unilamellar liposomes. The small liposome complexes were better tolerated than large liposome complexes. Varying the cationic lipid to colipid (cholesterol or DOPE) molar ratio from 4: 1 to 1: 1 significantly reduced expression levels in both tumor and lung. Cationic lipid substitution, using a cholesterol cationic lipid, diethyldiamino-carbamyl-cholesterol instead of DOTMA, produced reduced expression in all other tissues except tumor. Incorporation of PEG into preformed transfection complexes reduced DNA delivery to lung, increased circulation half-life, and enhanced DNA delivery to tumor. In a lung metastatic mouse tumor model, where the accessibility of the i.v. administered transfection complexes to tumor lesions should be less challenging, DOTMA: CHOL complexes (4: 1 lipid to colipid molar ratio, 3: 1 +/- lipid to plasmid charge ratio) were preferentially localized in tumor lesions. These data demonstrate that systemic gene transfer to distal tumor sites by lipid/ DNA complexes may be limited by low plasmid delivery. Modifying the chemical surface properties of transfection complexes enhanced both DNA delivery and expression in tumor and is one approach that may overcome limitations.

Animals↗

Synergistic effect of formulated plasmid and needle-free injection for genetic vaccines.

PURPOSE: A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS: Human growth hormone (hGH) or bacterial beta-galactosidase gene expression plasmids driven by a cytomegalovirus (CMV) promoter were formulated in saline or complexed with a PINC polymer, polyvinylpyrrolidone (PVP), and intramuscularly or subcutaneously administered into dogs and pigs using a 22-gauge needle or a NFID. The hGH-specific IgG titers in serum were measured by an ELISA. Beta-galactosidase expression was measured in injected muscles by an enzymatic assay or immunohistochemistry. The effect of NFID on DNA stability and topology was assessed by gel electrophoresis. RESULTS: Intramuscular (i.m.) or subcutaneous (s.c.) injection of a hGH expression plasmid pCMV-hGH (0.05-0.5 mg/kg) in dogs and pigs elicited antigen-specific IgG antibody titers to expressed hGH. With both routes of injection, pDNA delivery by a NFID was superior to pDNA injection by needle. The magnitude of hGH-specific IgG titers with NFID was 15-20-fold higher than needle injection when pDNA was complexed with PVP, and only 3-4-fold higher with pDNA in saline. The transfection efficiency in the injected muscle, as measured by beta-galactosidase expression, following i.m. injection of pCMV-betagalactosidase/PVP, was not significantly different between needle and NFID-injected groups. CONCLUSIONS: These data demonstrate that the combination of pDNA/ PVP complexes and a NFID act synergistically to achieve high and sustained levels of antigen-specific IgG response to expressed antigen. This gene delivery approach may offer advantage over needle injection of naked DNA for the development of genetic vaccines.

Animals↗

Etiology and treatment of fluid retention (hydrops) in Ménière's syndrome.

For years low sodium diets have been recommended in the treatment of Ménière's syndrome. Elevated levels of insulin play an important role in sodium retention in renal tubules. Insulin production is stimulated by high carbohydrate diets. Adrenaline, cortisone, and glucagon levels may be increased by stress or food or inhalant allergies, further elevating insulin levels. The end result of prolonged hyperinsulinemia includes vasoconstriction and eventually arterial smooth muscle hypertrophy. Individual susceptibility to Ménière's syndrome may occur as a result of inflammatory changes in the endolymphatic sac or cochlear aqueduct secondary to primary or latent viral infections, thus predisposing to fluid retention. Long term medical treatment of Ménière's should be directed towards preventing sodium retention through sodium restriction and carbohydrate management. Other factors including stress and allergy should also be considered.

Dietary Carbohydrates↗

The anatomy of the facial nerve.

The course of the facial nerve from its origin in the human brain-stem to the termination of its end fibers in the muscles of facial expression is reviewed in detail. The relation of the facial nerve to important adjacent structures is emphasized so that the aural surgeon is better prepared to explore in this intricate area.

Ear, Middle↗

Anatomic variations and anomalies involving the facial canal.

Congenital bony dehiscences in the facial canal result from incomplete closure during development and are observed in approximately 55% of temporal bones. Anomalies involving the facial canal frequently are encountered in malformations of the temporal bone. These anomalies include aberrations of the course of one or all of the segments of the canal; abnormal relation to the oval and round window; bifurcations and trifurcations of the nerve; and associations with dysplasia of the stapes, oval window, external ear canal, and auricle. Rarely, the facial nerve may be hypoplastic or totally absent. Two abnormal vessels occasionally may accompany the facial nerve in the Fallopian canal: a persistent stapedial artery and a persistent lateral capital vein.

Chorda Tympani Nerve↗

The hypotympanum.

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Ear, Inner↗

Insensitivity of ubiquinone biosynthesis in glioblastoma cells to an epileptogenic drug, U18666A.

To investigate the perturbation of ubiquinone biosynthesis by a hypocholesterolemic drug, 3 beta-(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride (U18666A), we measured the incorporation of radioactive mevalonate, methionine, tyrosine, and 4-hydroxybenzoic acid into ubiquinone in glioblastoma cells. These four precursors unanimously showed that ubiquinone biosynthesis was not significantly altered by U18666A, which blocked cholesterol biosynthesis at steps beyond mevalonate formation. The fluctuation of the endogenous mevalonate level had little effect on ubiquinone biosynthesis, implying the relative stability of cellular ubiquinone biosynthesis. Furthermore, exogenously added mevalonate did not have an appreciable effect on ubiquinone biosynthesis. The major ubiquinone produced in rat glioblastoma cells was identified as ubiquinone-9. The mevalonate-derived products accumulated in the U18666A-treated cells differed significantly from those reported in a broken cell study, suggesting the existence of delicate mechanisms regulating the formation of cholesterol intermediates.

Androstenes↗

The extratemporal facial nerve.

The extratemporal course of the facial nerve must be completely understood if surgery is required for the removal of parotid and other tumors in the infratemporal space and skull base or if the nerve itself must be exposed when it has been severed. The key to mastering this surgery is to understand the anatomy of the parotid space and its relations to surrounding structures so that the facial nerve can be found during surgery and preserved intact. Tumor masses or scar tissue may distort normal structures and relations to adjacent structures; this must be kept in mind while operating in this complicated anatomic area.

Arteries↗