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Biomedical subjects

S Starr

Publications and source records attributed to S Starr.

At least 19 recordsLinked to original sources
PubMed2001

A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects.

The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.

Adolescent↗
PubMed2000

Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team.

The use of recombinant CD4-IgG2 in pediatric human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log(10) copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1-infected children appears to be well tolerated and capable of reducing HIV-1 burden.

Adolescent↗
PubMed2000

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators.

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

AIDS Vaccines↗
PubMed2000

The Ohio Substance Abuse Monitoring Network: constructing and operating a statewide epidemiologic intelligence system.

Working with the Ohio Department of Alcohol and Drug Addiction Services (ODADAS) and researchers at the University of Akron, Wright State University's Center for Interventions, Treatment, and Addictions Research developed the Ohio Substance Abuse Monitoring (OSAM) Network to provide a statewide summary of substance abuse trends. Ten key informants across the state collect qualitative and statistical data on substance abuse trends in their regions and prepare biannual reports. The OSAM network has a rapid response capability through which key informants can investigate special issues related to substance abuse identified by ODADAS and provide policymakers with timely, statewide reports. Within 12 months after operations began, the key informants produced reports on drug abuse trends and rapid response issues for the state. These reports prepared policymakers to respond more effectively to prevention and substance abuse treatment needs.

Costs and Cost Analysis↗
PubMed1998

CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors.

We have previously shown that using agonist affinity at recombinant receptors selectively expressed in clonal cells as the dependent variable in three-dimensional quantitative structure-activity relationship studies (3D-QSAR) presents a unique opportunity for accuracy and precision in measurement. Thus, a comparison of affinity's structural determinants for a set of compounds at two different recombinant dopamine receptors represents an attainable goal for 3D-QSAR. A molecular database of bound conformations of 16 structurally diverse agonists was established by alignment with a high-affinity template compound for the D1 receptor, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H-benzazepin. A second molecular database of the bound conformations of the same compounds was established against a second template for the D2 receptor, bromocriptine. These aligned structures suggested three-point pharmacophore maps (one cationic nitrogen and two electronegative centers) for the two dopamine receptors, which differed primarily in the height of the nitrogen above the plane of the catechol ring and in the nature of the hydrogen-bonding region. The ln(1/KL) values for the low-affinity agonist binding conformation at recombinant D1 and D2 dopamine receptors stably expressed in C6 glioma cells were used as the target property for the CoMFA (comparative molecular field analysis) of the 16 aligned structures. The resulting CoMFA models yielded cross-validated R2 (q2) values (standard error of prediction) of 0. 879 (1.471, with five principal components) and 0.834 (1.652, with five principal components) for D1 and D2 affinity, respectively. The simple R2 values (standard error of the estimate) were 0.994 (0.323) and 0.999 (0.116), respectively, for D1 and D2 receptor. F values were 341 and 2465 for D1 and D2 models, respectively, with 5 and 10 df. The predictive utility of the CoMFA model was evaluated at both receptors using the dopamine agonists, apomorphine and 7-OH-DPAT. Predictions of KL were accurate at both receptors. Flexible 3D searches of several chemical databases (NCI, MDDR, CMC, ACD, and Maybridge) were done using basic pharmacophore models at each receptor to determine the similarity of hit lists between the two models. The D1 and D2 models yielded different lists of lead compounds. Several of the lead compounds closely resembled high-affinity training set compounds. Finally, homology modeling of agonist binding to the D2 receptor revealed some consistencies and inconsistencies with the CoMFA-derived D2 model and provided a possible rationale for features of the D2 CoMFA contour map. Together these results suggest that CoMFA-homology based models may provide useful insights concerning differential agonist-receptor interactions at related receptors. The results also suggest that comparisons of CoMFA models for two structurally related receptors may be a fruitful approach for differential QSAR.

Animals↗
PubMed1998

Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines.

The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor, we have identified a number of compounds which are the most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT2C receptor model and our proposed binding mode for this class of ligands within that model.

Animals↗
PubMed1997

Thrombolysis and Q wave versus non-Q wave first acute myocardial infarction: a GUSTO-I substudy. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries Investigators.

OBJECTIVES: We assessed the outcomes of patients with a first myocardial infarction with ST segment elevation, with and without the development of abnormal Q waves after thrombolysis. BACKGROUND: Prethrombolytic era studies report conflicting short-versus long-term mortality in the overall non-Q wave population, probably related to its heterogeneity. METHODS: Patients with no electrocardiographic (ECG) confounding factors or evidence of previous infarction were included. Q wave infarction was defined as a Q wave duration > or = 30 ms in lead aVF; R wave > or = 40 ms in lead V1; any Q wave or R wave < or = 10 ms and < or = 0.1 mV in lead V2; or Q wave > or = 40 ms in at least two of the following leads: I, aVL, V4, V5 or V6. In-hospital clinical events and mortality at 30 days and 1 year were assessed. RESULTS: No Q waves developed in 4,601 (21.3%) of the 21,570 patients. This group comprised more women and had a lower Killip class, lower weight and less anterior baseline ST elevation. The non-Q wave group had less in-hospital cardiogenic shock (2.1% vs. 3.3%, p < 0.0001), less heart failure (8.5% vs. 13.9%, p < 0.0001) and a trend toward less stroke (0.7% vs. 1.0%, p = 0.07) but an increased use of angioplasty (28% vs. 24%, p = 0.0001). The unadjusted mortality rate in the non-Q wave group was lower at 30 days (0.9% vs. 1.8%, p = 0.0001) and 1 year (2.7% vs. 4.2%, p = 0.0001), as was the adjusted 30-day mortality rate (4.8% vs. 5.3%, p < 0.0001). CONCLUSIONS: Patients with no ECG confounding factors or evidence of previous infarction who do not develop Q waves after thrombolysis have a better 30-day and 1-year prognosis than patients with a Q wave infarction.

Aged↗
PubMed1997

Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.

Alanine Transaminase↗
PubMed1997

The University of Massachusetts Medical Center office-based continuity experience: are we preparing pediatrics residents for primary care practice?

OBJECTIVE: Surveys of residency graduates and employers have suggested that residency programs do not prepare residents well for practice. Since 1988, pediatric residents at the University of Massachusetts have been paired one-on-one with an office-based pediatrician for their 3-year continuity experience. This survey was conducted to determine if graduates of such a program are prepared to enter pediatric practice. METHODOLOGY: Graduates of the program from 1991 through 1995 who entered primary care practice were surveyed about their preparedness for practice. The questionnaire was also sent to the residents' first employers. The 32 questions were directed to overall sense of preparedness, ability to manage the pace of practice, common illnesses, common behavior problems, anticipatory guidance, office management, and subspecialty problems. RESULTS: Data from all 25 residents who entered practice and the employers of 20 of the 25 residents were obtained and analyzed. Both groups rated overall resident preparedness to be "well-prepared" or "very well-prepared" and gave high scores on working at the pace of practice, diagnosing and treating common illnesses, diagnosing and treating common behavior problems, and providing anticipatory guidance. Areas in which residents were considered to be less well-prepared included anticipatory guidance about nutrition, managing problems by telephone, office management, gynecology, and orthopedics. CONCLUSIONS: The results suggest that continuity experiences in office practices are associated with preparation for the pace and types of visits that occur commonly in primary care practice, abilities which previous surveys of residency alumni and employers have found lacking. Some areas may benefit from a formal curriculum which may be implemented in the office practice, at the medical center, or at both sites. Preceptors may benefit from faculty development and continuing medical education that is directed not only at teaching skills but also at content areas which were not addressed in their own residencies.

Academic Medical Centers↗
PubMed1995

Drug-induced up-regulation of dopamine D2 receptors on cultured cells.

Ligand-induced up-regulation of recombinant dopamine D2 receptors was assessed using C6 glioma cells stably expressing the short (415-amino-acid; D2s) and long (444-amino-acid; D2L) forms of the receptor. Overnight treatment of C6-D2L cells with N-propylnorapomorphine (NPA) caused a time- and concentration-dependent increase in the density of receptors, as assessed by the binding of radioligand to membranes prepared from the cells, with no change in the affinity of the receptors for the radioligand. The effect of 10 microM NPA was maximal after 10 h, at which time the density of D2L receptors was more than doubled. The agonists dopamine and quinpirole also increased the density of D2L receptors. The receptor up-regulation was not specific for agonists, because the antagonists epidepride, sulpiride, and domperidone caused smaller (30-60%) increases in receptor density. Prolonged treatment with 10 microM NPA desensitized D2L receptors, as evidenced by a reduced ability of dopamine to inhibit adenylyl cyclase, whereas treatment with sulpiride was associated with an enhanced responsiveness to dopamine. The magnitude of NPA-induced receptor up-regulation in each of four clonal lines of C6-D2L cells (mean increase, 80%) was greater than in all four lines of C6-D2S cells (33%). Inactivation of pertussis toxin-sensitive G proteins had no effect on the basal density of D2L receptors or on the NPA-induced receptor up-regulation. Treatment with 5 micrograms/ml of cycloheximide, on the other hand, decreased the basal density of receptors and attenuated, but did not prevent, the NPA-induced increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Educating pediatric residents in community settings.

Pediatric training programs have recently witnessed a renewed emphasis on community-based experiences. This change can be attributed partly to the need for a more appropriate foundation for careers in general pediatrics and partly to a call for more generalist physicians as a result of health care reform. Community experiences provide optimal sites for residents to learn community-based primary care, practice management, collaboration with patient care teams, and advocacy on behalf of children's issues. The literature of the past year has focused on the theoretical issues, curricular components, and practical demands of implementing such experiences.

Community Health Services↗
PubMed1994

ECG myocardial infarct size: a gender-, age-, race-insensitive 12-segment multiple regression model. I: Retrospective learning set of 100 pathoanatomic infarcts and 229 normal control subjects.

In this early study of ongoing work with multiple regression modeling for mapping myocardial infarct (MI) into 12 left ventricular (LV) segments, promising results have been presented using electrocardiographic (ECG) QRS variables that are gender, age, and race insensitive (GARI), the GARI-QRS 12-segment multiple regression model. These include Q, R, and S duration, expressed as percentage total QRS duration, and R/Q duration, R/Q amplitude, R/S duration, and R/S amplitude variables. For version I, building 12 regression models using 68 single and 32 multiple MIs, the GARI-QRS variables correlated with pathoanatomic MI in each of 12 segments with r values ranging from .67 to .88. In version II of the model, using all MIs and 229 normal subjects, r = .73-.91. Version II predictions of MI in 12 LV segments for each subject were used to calculate the predicted total percentage LV infarct, which correlated well with that found at autopsy. The r values found were .81 for all single MIs, .73 for multiple MIs, and .80 for all MIs taken together. With refinements of the input ECG variables to include (1) improvement in the GARI-QRS variables, (2) adding a significant number of subjects with hypertrophies and conduction defects with and without MI to an expanded learning set, and (3) applying the enhanced 12-LV-segment regression models to a similar test set, it is to be expected that these regression models can be improved even further in such a way as to be applicable to general clinical populations using routine computerized ECG analysis programs.

Adult↗
PubMed1994

Persistence of cell-mediated and humoral immune responses in healthy children immunized with live attenuated varicella vaccine.

Two hundred fourteen healthy seronegative children immunized with various doses of Oka/Merck varicella vaccine were studied for persistence of varicella-zoster virus (VZV)-specific lymphocyte proliferation and antibodies to VZV as determined by a glycoprotein (gp) ELISA. Of the 140 vaccinees tested for VZV-specific lymphocyte proliferation, 94% had positive responses, with a mean stimulation index of 8.9 (range, 3.0-44.6). Of 214 tested by gpELISA, 95% were positive for up to 6 years after immunization; the geometric mean titer was 30.2 (range, 1.3-3510.0). Of 122 individuals tested both by ELISA and for VZV-specific lymphocyte proliferation, 91% had persistence of both responses. Persistence of cellular and humoral immune responses in a large percentage of vaccinees for up to 6 years after immunization with Oka/Merck varicella vaccine suggests that protection against severe varicella is likely to be similarly long-lasting.

Adolescent↗
PubMed1994

Induced hyporesponsiveness in rat Kupffer cells is not specific for lipopolysaccharide.

The phenomenon of lipopolysaccharide (LPS)-induced hyporesponsiveness has been reported to occur in macrophage cell lines and primary cells. Hyporesponsiveness was evidenced by a diminution or lack of production of tumour necrosis factor-alpha (TNF-alpha) after sequential doses of LPS. In order to characterize the hyporesponsive state in Kupffer cells, the production of TNF-alpha was quantified after varying the concentration of a primary low dose of LPS prior to a challenge with a high, normally stimulatory dose of LPS. The kinetics of establishment of the hyporesponsive state and the effect of varying the bacterial serotype and genus of the challenge dose were determined. The specificity of the hyporesponsive state for LPS was examined. Our results demonstrate that complete hyporesponsiveness with no detectable production of TNF-alpha (< 30 pg/ml) was achieved after a primary dose > or = 10 ng/ml. Establishment of the hyporesponsive state took place within 6 hr. Induction of hyporesponsiveness was not dependent upon the serotype or genus of the challenge dose of LPS and was not specific for LPS. Complete hyporesponsiveness was induced after a primary dose (10 micrograms/ml) of the Gram-positive bacterium Corynebacterium parvum (Cp) and was evident upon challenge with 100 micrograms/ml Cp. The data indicate that the mechanisms by which LPS and Cp induce hyporesponsiveness are not identical in that a primary dose of LPS (10 ng/ml) induced only partial hyporesponsiveness upon challenge with Cp (100 micrograms/ml). These studies improve our understanding of Kupffer cell function.

Animals↗