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Biomedical subjects

D L Montgomery

Publications and source records attributed to D L Montgomery.

At least 37 records · Page 2Linked to original sources
PubMed1997

Economic benefit of breast-feeding infants enrolled in WIC.

OBJECTIVES: To determine whether breast-feeding of infants enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is associated with a reduction in Medicaid expenditures during the first 6 months of life; if so, to determine whether the reduction in Medicaid expenditures represents a positive economic benefit to society when WIC costs for these infants and their mothers are considered. DESIGN: Cohorts of exclusively breast-fed and formula-fed infants were tracked for 6 months to compare WIC costs and Medicaid expenditures. SUBJECTS: The sample consisted of 406 healthy infants who were breast-fed exclusively for at least 3 months and 470 healthy infants who were formula-fed exclusively. The infants, born between August 1, 1993, and December 31, 1993, were enrolled in WIC and Medicaid. COST AND BENEFIT MEASURES: WIC costs included redeemed WIC vouchers for formula and foods for infants and mothers, plus administrative expenses for 6 months, minus manufacturers' rebates for formula. Benefit was determined from Medicaid expenditures for health care initiated in the first 180 days of each infant's life. STATISTICAL AND BENEFIT-COST ANALYSES: Economic benefit was calculated as net benefit and as benefit-cost ratios. Regression techniques were used to estimate Medicaid expenditures associated with breast-feeding, adjusted for demographic and prenatal care variables. RESULTS: Compared with formula-feeding, breast-feeding each infant enrolled in WIC saved $478 in WIC costs and Medicaid expenditures during the first 6 months of the infant's life, or $161 after consideration of the formula manufacturer's rebate. A Medicaid cost saving of $112 per infant was realized by the breast-feeding cohort, and Medicaid pharmacy reimbursement costs for breast-fed infants were significantly lower-half that of formula-fed infants. APPLICATIONS: The promotion of breast-feeding among low-income populations through nutrition programs such as WIC is an effective cost-containment measure.

Adult↗
PubMed1997

DNA vaccines.

In just a few years, injection of plasmid DNA to elicit immune responses in vivo has developed from an interesting observation to a viable vaccine strategy. DNA vaccines have been shown to elicit both cellular and humoral immune responses and to be effective in a variety of preclinical bacterial, viral, and parasitic animal models. This review will discuss the current knowledge of vector design, methods of plasmid delivery, immune responses elicited by various DNA vaccines, safety issues, and production and release of plasmid as a vaccine product. The potential of this new vaccine strategy and its future prospects is summarized.

Animals↗
PubMed1997

Expression and immunogenicity of Mycobacterium tuberculosis antigen 85 by DNA vaccination.

Plasmid DNA expression vectors encoding Mycobacterium tuberculosis antigen 85 (Ag85) were tested as vaccines in preclinical animal models. Expression of secreted and nonsecreted forms of Ag85 was observed after transient transfection of cells in vitro. In mice, both types of Ag85 DNA constructs induced strong humoral and cell-mediated immune responses, as measured by ELISA of sera and recall responses of spleen cells restimulated in vitro, respectively, Therefore, DNA vaccination is an effective means of expressing mycobacterial proteins in eukaryotic cells leading to the induction of potent immune responses.

Acyltransferases↗
PubMed1997

Immunogenicity and efficacy of a tuberculosis DNA vaccine encoding the components of the secreted antigen 85 complex.

BALB/c and C57BL/6 mice were injected intramuscularly with plasmid DNA encoding the three components of the immunodominant 30-32 kDa antigen 85 complex (Ag85A, Ag85B, and Ag85C) from Mycobacterium tuberculosis culture filtrate, in order to investigate the utility of nucleic acid vaccination for induction of immune responses against mycobacterial antigens. Ag85A and Ag85B encoding plasmids induced a robust Th1-like response towards native Ag85, characterized by elevated levels of interleukin (IL)-2, interferon-gamma, and TNF-alpha. Levels of IL-4, IL-6, and IL-10 were low or undetectable. Plasmid encoding Ag85C was not effective. Cytotoxic T cell activity was also generated in in vitro restimulated splenocyte cultures from Ag85A and Ag85B DNA vaccinated mice. Finally, Ag85A and Ag85B DNA vaccination conferred significant protection against mycobacterial replication in lungs from B6 mice, subsequently challenged. Therefore, this technique may be useful for the definition of protective antigens of M. tuberculosis and the development of a more effective tuberculosis vaccine.

Animals↗
PubMed1997

Induction of humoral and cellular immune responses by vaccination with M. tuberculosis antigen 85 DNA.

DNA vaccines have been demonstrated to be effective in inducing protective cell-mediated immune responses in animal models of infectious disease. In order to investigate this approach for potential use as a vaccine for tuberculosis, DNA constructs encoding Mycobacterium tuberculosis antigen 85A (Ag85A) were prepared. Expression of Ag85A in mammalian cells was demonstrated by transient transfection of cells in vitro. Intramuscular injection of Ag85A DNA vaccines resulted in the generation of anti-Ag85A antibodies and robust cell-mediated immune responses, as measured by lymphoproliferation of spleen cells in vitro upon specific antigen restimulation, leading to protection in animal challenge models. Therefore, the technique of DNA vaccination is effective in inducing relevant immune responses for protection against tuberculosis and may be used to identify the protective antigens of M. tuberculosis.

Animals↗
PubMed1997

Induction of immunity by DNA vaccination: application to influenza and tuberculosis.

DNA vaccination is an effective means of inducing both humoral and cell-mediated immunity in animal models of infectious disease. Presented here are data generated in two distinct disease models; one viral (influenza) and one bacterial (tuberculosis). Specifically, plasmid DNA encoding an influenza virus antigen (nucleoprotein; NP) and a Mycobacterium tuberculosis antigen (antigen 85; Ag85) were prepared and tested as DNA vaccines in mice. In both cases, high titer antibody responses and robust cell-mediated immune responses were induced against the respective antigens. With respect to the latter, lymphocyte proliferation, Th1-type cytokine secretion, and cytotoxic T lymphocyte responses were observed upon restimulation with antigen in vitro. Furthermore, protective efficacy in animal challenge models was demonstrated in both systems. The data support the hypothesis that DNA vaccination will prove to be a broadly applicable technique for inducing immunity against various infectious diseases.

Animals↗
PubMed1996

Immunogenicity and protective efficacy of a tuberculosis DNA vaccine.

Tuberculosis is the most widespread and lethal infectious disease affecting humans. Immunization of mice with plasmid DNA constructs encoding one of the secreted components of Mycobacterium tuberculosis, antigen 85 (Ag85), induced substantial humoral and cell-mediated immune responses and conferred significant protection against challenge with live M. tuberculosis and M. bovis bacille Calmette-Guérin (BCG). These results indicate that immunization with DNA encoding a mycobacterial antigen provides an efficient and simple method for generating protective immunity and that this technique may be useful for defining the protective antigens of M. tuberculosis, leading to the development of a more effective vaccine.

Animals↗
PubMed1996

Protection against papillomavirus with a polynucleotide vaccine.

Genital infections with human papillomavirus (HPV) are increasingly recognized as a significant source of human disease; HPV is now implicated in up to 90% of cervical carcinomas. Neutralizing antibodies against papillomaviruses recognize conformational epitopes formed when viral capsid proteins assemble into virions or virus-like particles. Immunization with plasmid DNA encoding the major viral capsid protein L1 was studied as a means of inducing neutralizing antibodies and protection against virus challenge. In a cottontail rabbit papillomavirus (CRPV) model, immunization with plasmid DNA encoding L1 elicited conformationally specific neutralizing antibodies and provided immunity against papilloma formation upon challenge with CRPV. Immunization with DNA encoding the capsid protein may provide a means of protecting humans against HPV and would simplify the production of multivalent vaccines by combining plasmids that encode the viral capsid proteins of different strains. This may be of importance given the multiplicity of HPV types capable of causing disease.

Animals↗
PubMed1995

Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus.

Vaccination with plasmid DNA expression vectors encoding foreign proteins elicits antibodies and cell-mediated immunity and protects against disease in animal models. We report a comparison of DNA vaccines, using contemporary human strains of virus, and clinically licensed (inactivated virus or subvirion) vaccines in preclinical animal models, to better predict their efficacy in humans. Influenza DNA vaccines elicited antibodies in both non-human primates and ferrets and protected ferrets against challenge with an antigenically distinct epidemic human influenza virus more effectively than the contemporary clinically licensed vaccine. These studies demonstrate that DNA vaccines may be more effective, particularly against different strains of virus, than inactivated virus or subvirion vaccines.

Animals↗
PubMed1995

Effect of prolonged exercise at 65 and 80% of VO2max on running economy.

The purpose of this study was to investigate the effect of prolonged exercise at 65 and 80% of VO2max on running economy. Fourteen male long distance runners performed two 90-min runs on an outdoor 400 m track at velocities of 65 and 80% of VO2max. Prior to and following each 90-min run, running economy was measured as the steady-state VO2 during treadmill runs at speeds of 188 and 228 m/min. During the 90-min run at 65% of VO2max, the mean weight loss was 1.3 kg. HR increased from 143 bpm between minutes 5-10 to 150 bpm between minutes 85-90. During the 90-min run at 80% of VO2max, the mean weight loss was 1.4 kg. The HR was 161 bpm between minutes 5-10 and increased to 165 bpm between minutes 85-90. When the post running economy test was conducted following each 90-min run, there was a significant increase in VO2 expressed in both l/min and ml/kg min. The increase in VO2 following the 90-min run at 80% of VO2max. These results suggest that 90-min runs at 65 and 80% of VO2max alter running economy with a significant increase in oxygen cost.

Adult↗
PubMed1995

Vitamin E toxicity in neonatal piglets.

Intravenous vitamin E was associated with the deaths of 38 infants in the US in 1984. Because the vitamin E preparation used contained both vitamin E and a high level of polysorbate detergent, the etiology of the syndrome remains unknown. In this study, we determined the tissue disposition of an intravenous preparation of vitamin E solubilized with polysorbate (E-Ferol) in neonatal piglets. One to two-day-old piglets were injected daily with 50 IU/kg/d of vitamin E for a period of 13 days. Other groups were injected intramuscularly, or with a slow, 7 h intravenous infusion with 50 IU/kg/d vitamin E for six days. Massive splenic accumulation of vitamin E (16,004 micrograms/g vs 73 micrograms/g in controls) occurred following rapid injection, with far lesser concentrations in the liver and lung. Levels of vitamin E in the kidney and heart were only slightly above control. Tissue changes correlated with dosage and duration of vitamin E administration and suggested massive accumulation of vitamin E in cells of the mononuclear phagocyte system. Following slow intravenous infusion the highest levels of vitamin E occurred in the liver rather than spleen. Intramuscular injections at similar doses produced slight, but insignificant changes in tissue levels of vitamin E. We speculate that rapid intravenous injection of vitamin E emulsions produces massive accumulation in phagocytic cells of the spleen and to a lesser extent liver and lung, possibly leading to increased susceptibility to sepsis and/or abnormal pulmonary function. Slow infusions of vitamin E produce major accumulations in the liver rather than spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Characterization and evaluation of a recombinant hepatitis B vaccine expressed in yeast defective for N-linked hyperglycosylation.

The hepatitis B (HB) virus preS2 + 2 polypeptide (the M or middle envelope polypeptide) is N-glycosylated at the N4 residue of the preS2 domain when expressed in recombinant yeast. Hyperglycosylation at this amino acid residue (the addition of a large number of mannose residues to the core oligosaccharide), which occurs in common yeast strains, results in an HB vaccine with diminished immunogenicity. Hyperglycosylation can be prevented by expressing the preS2 + S polypeptide in mutant yeast strains (e.g. mnn9) which limit N-linked glycosylation to the addition of only core saccharide residues. An HB vaccine prepared from recombinant yeast expressing the non-hyperglycosylated preS2 + 2 polypeptide was of similar immunogenicity in mice to a licensed HB vaccine and was much more immunogenic in humans than the hyperglycosylated preS2 + 2 vaccine.

Adult↗
PubMed1994

Protein expression in vivo by injection of polynucleotides.

Over the past few years, intramuscular injection of non-replicating DNA expression vectors has been demonstrated to be generally applicable as an effective method of producing functional proteins in vivo. This technique has been useful in the study of growth factors, regulation of protein expression, transplantation rejection, gene therapy, immune regulation and the production of monoclonal antibodies. The most successful application of DNA injection has, however, been the generation of immune responses in animal models, with the ultimate goal of developing vaccines for humans. Therefore, this approach has the potential to be a new vaccine technology, in addition to its utility in other areas of research.

Animals↗
PubMed1994

Astrocytes: form, functions, and roles in disease.

Astrocytes, once relegated to a mere supportive role in the central nervous system, are now recognized as a heterogeneous class of cells with many important and diverse functions. Major astrocyte functions can be grouped into three categories: guidance and support of neuronal migration during development, maintenance of the neural microenvironment, and modulation of immune reactions by serving as antigen-presenting cells. The concept of astrocytic heterogeneity is critical to understanding the functions and reactions of these cells in disease. Astrocytes from different regions of the brain have diverse biochemical characteristics and may respond in different ways to a variety of injuries. Astrocytic swelling and hypertrophy-hyperplasia are two common reactions to injury. This review covers the morphologic and pathophysiologic findings, time course, and determinants of these two responses. In addition to these common reactions, astrocytes may play a primary role in certain diseases, including epilepsy, neurological dysfunction in liver disease, neurodegenerative disorders such as Parkinson's and Huntington's diseases, and demyelination. Evidence supporting primary involvement of astrocytes in these diseases will be considered.

Animals↗
PubMed1993

Heterologous and homologous protection against influenza A by DNA vaccination: optimization of DNA vectors.

We have recently shown that direct injection of DNA can be an effective vaccine strategy eliciting both humoral and cell-mediated immune responses. Vectors were designed specifically for vaccination by direct DNA injection and refined to improve plasmid production in Escherichia coli. The vectors consist of a pUC-19 backbone with the cytomegalovirus (CMV) IE1 enhancer, promoter, and intron A transcription regulatory elements and the BGH polyadenylation sequences driving the expression of the reporter gene CAT or influenza A nucleoprotein (NP) or hemagglutinin (HA). The respective vectors expressed high levels of chloramphenicol acetyltransferase (CAT) and NP in tissue culture, and yielded 14-15 mg of purified plasmid per liter of Escherichia coli culture. Immunization of mice with the NP and HA expression vectors resulted in protection from subsequent lethal challenges of influenza using either heterologous or homologous strains, respectively.

Animals↗