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Biomedical subjects

A E Baker

Publications and source records attributed to A E Baker.

18 recordsLinked to original sources
PubMed2004

Simian virus 40 infection disrupts p130-E2F and p107-E2F complexes but does not perturb pRb-E2F complexes.

In its native host species, the Rhesus Macaque, simian virus 40 (SV40) forms a persistent infection in the kidneys with no apparent harmful side effects. We show that SV40 infection of growth-arrested monkey kidney epithelial cells results in the specific disruption of certain Rb-E2F family complexes. Throughout the course of infection, p130-E2F and p107-E2F complexes are disrupted, but surprisingly pRb-E2F complexes remain intact. This suggests that the presence of some pRb-E2F complexes is not inhibitory to productive infection. Additionally, while a decrease of p130 steady state levels is observed during the later time points of infection, early during infection, p130 is readily detectable. This suggests SV40 infection overrides p130-mediated growth arrest through a mechanism(s) in addition to the well-documented T antigen-mediated degradation of p130. Finally, infection induces a dramatic relocalization of E2F4 from the nucleus to the cytoplasm. The implications of these observations to the life cycle of the virus are addressed.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

A qualitative assessment of children's farm safety day camp programs.

In order to increase farm safety awareness and teach children good safety habits, farm safety day camp programs have been initiated in many communities. For the most part, the effectiveness of the programs is unknown because few evaluations have been performed. The purpose of this project was to qualitatively assess the overall strengths and weaknesses of farm safety day camp programs and to generate recommendations for future programs. Interviews, a literature search, and observations were used to identify strengths and weaknesses of the farm safety day camp programs. Major strengths of the programs are that: 1) positive attention is given to agriculture and agricultural safety; 2) programs are hands-on, interactive, and fun; 3) children gain knowledge about farm safety; 4) programs bring a community together to work toward a common goal; and 5) children talk to parents about safety. Key weaknesses of farm safety day camp programs are that: 1) there is a lack of parental involvement in many of the programs; 2) it is hard to change patterns of behavior in one day; 3) programs are expensive and time consuming; 4) curricula may include content that is inaccurate or inappropriate for the age of participants; and 5) evaluation is difficult. When done well, farm safety day camp programs can teach children about safety and influence safety practices affecting children on the farm. Recommendations for future farm safety day camp programs are: 1) ensure that child-development principles are applied to all aspects of program activities and curricula; 2) provide session leaders with accurate and relevant content; 3) increase parental involvement; and 4) address safety issues throughout the year.

Accident Prevention↗
PubMed2001

Impact of the change to inactivated poliovirus vaccine on the immunization status of young children in the United States: a study from pediatric research in office settings and the National Medical Association.

OBJECTIVE: To determine whether the change from an all oral poliovirus vaccine (OPV) schedule to an inactivated poliovirus vaccine (IPV)-containing schedule has adversely affected the immunization status of young children in the United States. METHODS: Immunization data were abstracted from the medical records of children 8 to 35 months old seen consecutively for any reason in the offices of practicing pediatricians who are members of the Pediatric Research in Office Settings network of the American Academy of Pediatrics or the National Medical Association. Data on up to 120 eligible children were collected in each practice between March 1998 and January 2000. Patients were classified as fully immunized at 8 months old if they had received 3 diphtheria-tetanus-pertussis, 2 Haemophilus influenzae type b, 2 hepatitis B, and 2 poliovirus vaccines. Study children who were >/=12 months of age at the time that data were collected were categorized as being fully immunized at 12 months if they had received the same vaccines before their first birthday. To assess the effect of type of poliovirus vaccines on these outcomes, study patients were classified as being in an IPV or OPV group based on the initial type of vaccine received. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for IPV as a predictor of being fully immunized at 8 and 12 months of age, after adjusting for race/ethnicity of the patient, maternal education level, year of birth, and method of payment for vaccines. In addition, the effect of clustering of children within practices was accounted for by the use of generalized estimation equation techniques. RESULTS: Data were analyzed on 13 520 children from 177 practices in 42 states; 79.4% of patients were fully immunized at 8 months of age, and 88.7% of those eligible were fully immunized at 12 months of age. A total of 6910 patients (51.1%) were classified as OPV recipients, wheras 5282 (39.1%) received IPV. In addition, 1328 children (9.8%) were documented as having received poliovirus vaccine, but the particular type could not be determined. Compared with OPV recipients and after controlling for the confounding variables and the effect of clustering within practices, children in the IPV group were as likely as were OPV recipients to be fully immunized at 8 months of age (OR: 1.04; 95% CI: 0.88,1.23). At 12 months of age, the OR for IPV as a predictor of being fully immunized was 1.08 (95% CI: 0.90,1.30). When compared with OPV recipients, adjusted ORs for children in the undetermined poliovirus vaccine type group being fully immunized at 8 and 12 months of age were 0.84 (95% CI: 0.68,1.04) and 0.84 (95% CI: 0.67,1.07), respectively. CONCLUSIONS: The results of this national study indicate that the implementation of an IPV-containing poliovirus vaccine schedule has not had an adverse effect on the immunization status of young children who were vaccinated in the offices of practicing pediatricians.

Child, Preschool↗
PubMed2000

Coordination of specialty referrals and physician satisfaction with referral care.

OBJECTIVES: To describe how physicians coordinate patient care for specialty referrals and to examine the effects of these activities on referring physicians' satisfaction with the specialty care their patients receive and referral completion. DESIGN AND METHODS: Prospective study of a consecutive sample of referrals (N = 963) made from the offices of 122 pediatricians in 85 practices in a national practice-based research network. Data sources included a physician survey completed when the referral was made (response rate, 99%) and a physician survey and medical record review conducted 3 months later (response rate, 85%). Referral completion was defined as receipt of written communication of referral results from the specialist. RESULTS: Pediatricians scheduled appointments with specialists for 39.3% and sent patient information to specialists for 50.8% of referrals. The adjusted odds of referral completion were increased 3-fold for those referrals for which the pediatrician scheduled the appointment and communicated with the specialist compared with those for which neither activity occurred. Referring physicians' satisfaction ratings were significantly increased by any type of specialist feedback and were highest for referrals involving specialist feedback by both telephone and letter. Elements of specialists' letters that significantly increased physician ratings of letter quality included presence of patient history, suggestions for future care, follow-up arrangements, and plans for comanaging care; only the inclusion of plans for comanaging patient care was significantly related to the referring physicians' overall satisfaction. CONCLUSIONS: Better coordination between referring physicians and specialists increases physician satisfaction with specialty care and enhances referral completion. Improvements in the referral process may be achieved through better communication and collaboration between primary care physicians and specialists.

Adolescent↗
PubMed2000

Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs.

Estrogen deficiency following ovariectomy or menopause results in bone loss. Although evidence strongly suggests that the immune system is involved in the pathogenesis of estrogen-deficient osteoporosis, it is not clear what role, if any, the T-lymphocyte plays in this process. Therefore, we examined the distribution of T-cell subsets in lymphoid organs and tissues, under varying estrogenic states in the rat. Six-month-old female Sprague-Dawley rats, ovariectomized (Ovx) and sham-operated, were randomized 5 d post-surgery into six groups to receive the following treatments: (A) sham/placebo; (B) sham/low-dose E2; (C) sham/high-dose E2; (D) Ovx/placebo; (E) Ovx/low-dose E2; (F) Ovx/high-dose E2. Half of the treated rats (groups A-F) were sacrificed on d 14; the remainder on d 28. Following euthanasia, mononuclear cells were isolated from the thymus, peripheral blood, spleen, lymph node and bone marrow, and were labeled for flow cytometric analysis using mouse anti-rat monoclonal antibodies directed against CD5, CD4, and CD8 antigenic markers. In the thymus, ovariectomy caused a dramatic increase and E2 treatment caused a dose-dependent decrease in weight that was proportional to the number of thymocytes. In the bone marrow, ovariectomy caused a significant reduction in the percentage of all T-cell subsets examined and this effect persisted throughout the duration of the study. Estrogen replacement therapy at the low-dose reversed the effects of ovariectomy and high-dose E2 treatment caused an increase in T-cell subsets in both the sham and Ovx groups, an effect that was more pronounced at d 14 compared with d 28. Although the percentages of some T-cell subsets in the other lymphoid organs/tissues were altered by ovariectomy or E2 treatment at d 0 and 14, all these changes had normalized by d 28 except for CD5 and CD4 cells in peripheral blood. In summary, with the exception of T-lymphocytes in the bone marrow, the effects of varying estrogenic states on T-cells were variable and transient. The influence of estrogen status on bone marrow T-lymphocytes suggests that these cells may play a role in mediating the effects of estrogen on bone turnover and warrant additional studies focusing on the functional role of T-cells in the bone marrow compartment.

Animals↗
PubMed1999

The pediatric primary-specialty care interface: how pediatricians refer children and adolescents to specialty care.

OBJECTIVE: To describe how pediatricians refer patients to specialists, including frequency of referral decisions, reasons for referral, and types of referrals. DESIGN: We conducted a prospective study of visits (N = 58 771) made to 142 pediatricians in a national primary care practice-based research network. During 20 consecutive practice days, physicians and parents completed questionnaires for referred patients, and office staff kept logs of all visits. Physicians used medical records to complete questionnaires 3 months after referrals were made. RESULTS: Pediatricians referred patients to specialists during 2.3% of office visits. Referrals made during telephone conversations with parents accounted for 27.5% of all referrals. The most common reason for referral was advice on diagnosis or treatment (74.3%). Referrals were made most commonly to surgical subspecialists (52.3%), followed by medical subspecialists (27.9%), nonphysicians (11.4%), and mental health practitioners (8.4%). Physicians requested a consultation or a referral with shared management in 75% of cases. Otitis media was the condition referred most often (9.2%). Fifty other conditions accounted for 84.3% of all referrals. CONCLUSIONS: About 1 in 40 pediatric visits result in referral. Getting advice from a specialist is the most common reason for referral. Pediatricians desire a collaborative relationship with specialists for most of their referred patients. Physician training to increase clinical competence may be most useful for the 50 most commonly referred conditions. Education concerning the referral process should focus on the respective roles of the referring physician and specialist, particularly as they pertain to successful approaches for comanaging referred patients.

Adolescent↗
PubMed1999

Gatekeeping and referral of children and adolescents to specialty care.

OBJECTIVE: In this study we examined how gatekeeping arrangements influence referrals to specialty care for children and adolescents in private and Medicaid insurance plans. DESIGN/PARTICIPANTS: We conducted a prospective study of office visits (n = 27 104) made to 142 pediatricians in 94 practices distributed throughout 36 states in a national primary care practice-based research network. During 10 practice-days, physicians and patients completed questionnaires on referred patients, while office staff kept logs of all visits. Physicians used medical records to complete questionnaires for a subset of patients 3 months after their referral was made. RESULTS: Gatekeeping arrangements were common among children and adolescents with private (57.8%) and Medicaid (43.3%) insurance. Patients in gatekeeping plans were more likely to be referred with private (3. 16% vs 1.85% visits referred) and Medicaid (5.39% vs 3.73%) financing. Increased parental requests for specialty care among gatekeeping patients did not explain the increased referral rate. Physicians' reasons for making the referral were similar between the two groups. Physicians were less likely to schedule an appointment or communicate with the specialist for referred patients in gatekeeping plans. However, rates of physician awareness that a specialist visit occurred and specialist communication back to pediatricians did not differ between the two groups 3 months after the referrals were made. CONCLUSIONS: Gatekeeping arrangements are common among insured children and adolescents in the United States. Our study suggests that gatekeeping arrangements increase referrals from pediatricians' offices to specialty care and compromise some aspects of coordination.

Adolescent↗
PubMed1998

Site-directed mutagenesis probing the catalytic role of arginines 165 and 166 of human cytomegalovirus protease.

Human cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses that also includes herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), human herpes virus-6, 7, and 8 (HHV-6, HHV-7, and HHV-8), and Epstein-Barr virus (EBV). Each member of this family encodes a serine protease that is a potential target for antiviral therapeutic intervention. We recently reported the crystal structure of CMV proteases [Qiu, X., Culp, J. S., DiLella, A. G., Hellmig, B., Hoog, S. S., Janson, C. A., Smith, W. W., and Abdel-Meguid, S. S. (1996) Nature 383, 275-279] and proposed that the highly conserved Arg165 and Arg166 residues are involved in stabilizing the oxyanion intermediate in human herpes protease catalyzed reactions through the backbone NH and side chain, respectively. In the current study, site-directed mutagenesis was carried out to probe the catalytic function of these two amino acid residues. Substitution of Arg166 with an alanine has led to ablation of enzymatic activity without detectable change in CMV protease conformation, supporting suggestions from the crystal structure that Arg166 side chain plays a major role in catalysis. The wild-type has a Km = 138 +/- 17 microM and kcat = 19.9 +/- 1.1 min-1, while R166A has only residual activity, with a kcat = 0.012 +/- 0.001 min-1 and an unaltered Km = 145 +/- 18 microM. In the crystal structure, the side chain of Arg166 was shown previously to hold a water molecule that can act as a hydrogen-bond donor to the oxyanion and was thus proposed to stabilize the oxyanion intermediate. However, kinetic characterization of the mutant R165A only reveals a 2.7-fold lower activity than wild-type, with a Km = 166 +/- 19 microM and a kcat = 7.4 +/- 0.4 min-1. These results confirm that Arg165 side chain is not involved in the stabilization of the oxyanion. It is likely that Arg165 only utilizes the backbone NH for catalysis as suggested by the crystal structure.

Alanine↗
PubMed1998

Quantitative assessment of independent contributions of pericardium and septum to direct ventricular interaction.

In the intact animal, it is difficult to discriminate between the independent effects of series and direct ventricular interaction (DI) or the individual contributions of the pericardium and septum to DI. Left ventricular (LV) venous return (LVVR) and right ventricular (RV) end-diastolic pressure (RVEDP) were varied independently in a right-heart bypass model. LV minor-axis diameters were measured, and the product of the two diameters was used as an index of LV volume (LVVI). At each RVEDP (0, 5, 10, and 15 mmHg), increased LVVR caused an increased LVVI. When RVEDP was increased, increased pump output was required to maintain a given LVVI. RV-to-LV pressure gain (DeltaLVEDP/DeltaRVEDP) reflects coupling and DI. With the pericardium closed, the gain was dependent on RVEDP; when RVEDP was increased from 0 to 5 mmHg, the gain was not statistically different from zero, indicating little or no DI. When RVEDP was increased from 10 to 15 mmHg, the gain was not statistically different from 1.0, indicating approximately 1:1 coupling of the ventricles. Opening the pericardium reduced the gain, but significant interaction remained. When the septal contribution was accounted for, the remaining interaction was eliminated. In conclusion, DI substantially affects LVEDP-volume relations. Considerable increases in RV output may be required to counterbalance increased constraint to LV filling. With the pericardium closed, RV-to-LV coupling is minimal when RVEDP is low and increases to 1:1 coupling when RVEDP is high. Opening the pericardium reduces DI, but significant septum-mediated interaction remains.

Animals↗
PubMed1998

Pediatric research in office settings (PROS): a national practice-based research network to improve children's health care.

OBJECTIVES: To describe the establishment of a national pediatric primary care research network to improve children's health care-Pediatric Research in Office Settings (PROS), and to evaluate the network's progress toward achieving its objectives. SETTING: Pediatric practices in all 50 states and Puerto Rico. PARTICIPANTS: Approximately 1400 pediatric practitioners from more than 470 practices. RESULTS: Beginning in 1986, a core of volunteer pediatrician coordinators from participating American Academy of Pediatrics chapters were identified to oversee local PROS efforts, represent practitioners, and inform the development of proposed research studies. PROS subsequently recruited practitioners from around the country, building a research infrastructure and a system of collaboration between the practitioners, research staff at the AAP, and investigative teams at academic institutions. This PROS collaboration has developed and conducted 10 primary care research studies that have added to the knowledge base of pediatric primary care. CONCLUSIONS: PROS has accomplished two of its initial objectives-development of a structure and process for pediatric practice-based research and provision of research experience to practitioners. Successful and consistent achievement of a third objective-meaningful dissemination of study results to relevant audiences-will depend on meeting several challenges.

Child↗
PubMed1992

Analysis of high complement levels in Mus hortulanus and BUB mice.

BUB/BnJ mice were previously identified as having exceptionally potent complement activity, relative to common mouse strains, in the lysis of antibody-coated human tumor cells. We describe herein our investigation into the molecular and genetic basis for this difference between mouse strains, and also our results with wild mice and mouse strains recently derived from the wild, to determine whether low complement levels are characteristic of wild mice. BUB complement was compared with complement from BALB/c and C57BL/6 mice. BUB mice had higher levels of most individual classical pathway components, except for C1, than the other two strains, but the difference was generally only 2-3-fold, so insufficient to fully explain the difference observed with tumor target cells. CH50 titers on antibody-coated sheep erythrocytes also demonstrated only a 2-4-fold difference. However, CH50 titers on antibody-coated human erythrocyte target cells demonstrated a difference similar in magnitude to that seen with human tumor targets. These results suggest that the difference between mouse strains depends partly on the use of human, rather than sheep, target cells. In an assay for alternative complement pathway activity using neuraminidase-treated human erythrocytes as targets, complements of BALB/c and BUB mice were similar in activity, suggesting that the difference between mouse strains is manifested in the early steps of complement activation. Analysis of F1 and backcross mice suggested that the difference in complement level between BUB and BALB/c or C57BL/6 mice is controlled by semi-dominant genes, and cannot be attributed to a single gene. Wild mice and mice recently derived from the wild generally had low complement levels, similar to most laboratory mice. However, three strains of aboriginal mice, including Mus hortulanus (spicilegus) and Mus spretus, had complement levels higher than that of BUB mice, and as high as sera from the rabbit or rat, which are the most potent known complement sources for the lysis of human tumor cells. In comparison with BUB mouse sera, M. hortulanus sera had at least four-fold higher levels of C3, C6, C8 and C9, and some or all of these differences may explain its higher total complement activity. In the lysis of antibody-coated human erythrocytes, M. hortulanus serum was more potent than any other complement source tested, including sera of the guinea pig, rat, rabbit or human. These strains may be useful in investigating the role of complement in various pathological processes, and in investigating the genetic regulation of the complement system.

Animals↗
PubMed1988

Structure-function analysis of synthetic and recombinant derivatives of transforming growth factor alpha.

Transforming growth factor alpha (TGF-alpha) is a 50-amino-acid peptide that stimulates cell proliferation via binding to cell surface receptors. To identify the structural features of TGF-alpha that govern receptor-ligand interactions, we prepared synthetic peptide fragments and recombinant mutant proteins of TGF-alpha. These TGF-alpha derivatives were tested in receptor binding and mitogenesis assays. Synthetic peptides representing the N terminus, the C terminus, or the individual disulfide constrained rings of TGF-alpha did not exhibit receptor-binding or mitogenic activity. Replacement of the cysteines with alanines at positions 8 and 21, 16 and 32, and 34 and 43 or at positions 8 and 21 and 34 and 43 yielded inactive mutant proteins. However, mutant proteins containing substitutions or deletions in the N-terminal region retained significant biologic activity. Conservative amino acid changes at residue 29 or 38 or both and a nonconservative amino acid change at residue 12 had little effect on binding or mitogenesis. However, nonconservative amino acid changes at residues 15, 38, and 47 produced dramatic decreases in receptor binding (23- to 71-fold) and mitogenic activity (38- to 125-fold). These studies indicate that at least three distinct regions of TGF-alpha contribute to biologic activity.

Amino Acid Sequence↗
PubMedDate not supplied

Isolation of multiple biologically and chemically diverse species of epidermal growth factor.

We have analyzed several lots of epidermal growth factor (EGF) purified from murine submaxillary glands including "receptor grade" EGF from Collaborative Research and EGF from Boehringer Mannheim Biochemicals. New England Nuclear uses "receptor grade" EGF to produce 125I-labeled EGF. Though these reagents are reported to be homogeneous, we found them to be a mixture of six species. A method was developed to separate this mixture into its component parts. The individual components were chemically characterized and tested for biological potency. N-terminal sequence analysis of the unfractionated EGF-mixture reveals three different sequences starting with residues 1, 2, or 3 of the mature peptide. Each component exhibited different degrees of mitogenic and EGF receptor binding activity indicating that the N-terminal region contributes to the biological response. The species representing the complete EGF peptide is the most active species in all biological assays. A rapid method for purification of homogeneous complete EGF from commercial EGF preparations is described.

Amino Acids↗