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Biomedical subjects

M G Peterson

Publications and source records attributed to M G Peterson.

At least 19 recordsLinked to original sources
PubMed1998

High-throughput screening assay for helicase enzymes.

We have developed a novel 96-well microtiter plate high-throughput screening filtration assay for the detection of helicase activity. In this paper we present data for detection of helicase activity of the UL5/8/52 helicase-primase complex from herpes simplex virus 1 (HSV1). The assay involves the detection of radioactively labeled oligonucleotide annealed to a single-stranded circular DNA following capture of the annealed complex on silica beads. We have screened over 200,000 samples containing small organic molecules and natural products and identified T157602, a two-amino thiazole, as a specific inhibitor of HSV replication.

Base Sequence↗
PubMed1998

One-year followup of patients with osteoarthritis of the knee who participated in a program of supervised fitness walking and supportive patient education.

OBJECTIVE: To determine whether gains in functioning observed immediately following participation in an 8-week program of supervised fitness walking for patients with knee osteoarthritis were sustained at 1-year followup. METHODS: Twenty-nine (61.1%) of 47 original intervention program patients and 23 (51.1%) of 45 original control patients were interviewed by telephone at 1-year followup. Patients completed the Arthritis Impact Measurement Scales physical activity, arthritis impact, pain, medication use, and general health perceptions subscales, as well as a separate visual analog pain scale and measures of perceived self-efficacy to cope with arthritis pain and other symptoms. RESULTS: Adherence to walking was low, and there were no statistically significant differences between intervention and control patients at one year. CONCLUSIONS: The failure of intervention patients to maintain regular walking resulted in loss of functional benefits that were observed at 8 weeks in the original study. Long-term adherence to walking is critical to maintenance of initial gains in functional outcomes.

Activities of Daily Living↗
PubMed1998

Inhibition of herpes simplex virus replication by a 2-amino thiazole via interactions with the helicase component of the UL5-UL8-UL52 complex.

With the use of a high-throughput biochemical DNA helicase assay as a screen, T157602, a 2-amino thiazole compound, was identified as a specific inhibitor of herpes simplex virus (HSV) DNA replication. T157602 inhibited reversibly the helicase activity of the HSV UL5-UL8-UL52 (UL5/8/52) helicase-primase complex with an IC50 (concentration of compound that yields 50% inhibition) of 5 microM. T157602 inhibited specifically the UL5/8/52 helicase and not several other helicases. The primase activity of the UL5/8/52 complex was also inhibited by T157602 (IC50 = 20 microM). T157602 inhibited HSV growth in a one-step viral growth assay (IC90 = 3 microM), and plaque formation was completely prevented at concentrations of 25 to 50 microM T157602. Vero, human foreskin fibroblast (HFF), and Jurkat cells could be propagated in the presence of T157602 at concentrations exceeding 100 microM with no obvious cytotoxic effects, indicating that the window between antiviral activity and cellular toxicity is at least 33-fold. Seven independently derived T157602-resistant mutant viruses (four HSV type 2 and three HSV type 1) carried single base pair mutations in the UL5 that resulted in single amino acid changes in the UL5 protein. Marker rescue experiments demonstrated that the UL5 gene from T157602-resistant viruses conferred resistance to T157602-sensitive wild-type viruses. Recombinant UL5/8/52 helicase-primase complex purified from baculoviruses expressing mutant UL5 protein showed complete resistance to T157602 in the in vitro helicase assay. T157602 and its analogs represent a novel class of specific and reversible anti-HSV agents eliciting their inhibitory effects on HSV replication by interacting with the UL5 helicase.

Amino Acid Sequence↗
PubMed1997

Users evaluate LupusLine, a telephone peer counseling service.

OBJECTIVE: To assess the impact of LupusLine during its pilot phase of operation by determining patterns of utilization and user satisfaction. LupusLine is a peer counseling service designed to provide ongoing emotional support from home to home by telephone appointment. METHODS: One hundred fifty-three respondents were surveyed, using a 72-item structured questionnaire administered over the telephone by interviewers separately trained and hired specifically for this purpose. The questionnaire was pilot tested on 10 volunteers with systemic lupus erythematosus (SLE), and a panel of related health professionals reviewed the questionnaire for face validity. RESULTS: Most users were women (94.5%) who had SLE themselves (87.5%) and who called the service because of recent changes in their physical functioning and reported feelings of depression and anxiety about their illness. Forty-one percent of respondents made 6 or more calls to their assigned peer counselor. Respondents reported high levels of satisfaction across 5 highly correlated measures, with 92% of callers reporting at least moderate satisfaction with the service. Over 60% of respondents who reported a change in 6 "feeling" categories attributed this change to using LupusLine. Fewer users reported a change in 4 specific behaviors since using the service, but more respondents attributed changes, when they occurred, to LupusLine. CONCLUSIONS: Based on these initial findings, we believe that telephone networks similar to the LupusLine model may be able to offer substantial benefit to people coping with the complex, ongoing psychosocial challenges of SLE. Further, the at-home accessibility and low cost of such volunteer-based interventions may play an ever more needed role in the present health care environment.

Adult↗
PubMed1997

Patients' expectations and satisfaction with total hip arthroplasty.

Although there have been many studies focusing on the increasingly important assessment of patients' satisfaction, few studies have specifically addressed this tissue for total hip arthroplasty (THA). The goals of this study were to measure patients' satisfaction with THA and to evaluate the relationships of expectations and outcome to patients' satisfaction. A total of 180 patients were surveyed 2 to 3 years after THA about their experiences with THA. Patients cited 45 different expectations, which were grouped into five categories reflecting improvement in pain, walking, psychological state, essential activities, and nonessential activities. Overall, 89% of patients were satisfied with the results of surgery. Lower rates of satisfaction were found in patients who had a better preoperative condition (as measured by the surgeons with The Hospital for Special Surgery Hip Scale), in patients who expected improvement in nonessential activities, and in patients who reported worse postoperative condition (as measured by self-assessment with the Hip Rating Questionnaire and the Medical Outcomes Study Short-form General Health Survey). Patients were also asked how they came to THA. Nearly 50% of patients were first referred to an orthopaedist by family or friends or based on their own knowledge. Seventy-four percent either had subsequently referred others for THA or would have done so if they knew someone with hip pain. This study demonstrates that satisfaction with THA is a complex phenomenon, affected by expectations, outcome, and what patients know about the procedure from their community network. A better understanding of THA satisfaction will enable better future selection of patients and an additional dimension of outcome, both of which are important to patients and payers.

Adolescent↗
PubMed1997

A point mutation abolishes the helicase but not the nucleoside triphosphatase activity of hepatitis C virus NS3 protein.

The NS3 protein of hepatitis C virus contains a bipartite structure consisting of an N-terminal serine protease and a C-terminal DEAD box helicase. We show that the C-terminal domain has ATPase and panhelicase activities. The integrity of the helicase function is dependent on the conserved DEAD motif and can be abolished by a His-Ala point mutation, leaving a fully functional nucleoside triphosphatase.

Acid Anhydride Hydrolases↗
PubMed1997

Action of the peroneus longus tendon on the first metatarsal against metatarsus primus varus force.

A medially directed force was applied to the first metatarsal in 10 cadaver feet. The peroneus longus tendon was subjected to a pull of 5 pounds. The soft tissues between the first and second metatarsals were cut sequentially, starting with the skin on the dorsal and plantar aspect, followed by the intermetatarsal ligament and adductor hallucis tendon, and, finally, the peroneus longus tendon at its distal insertion. Dorsoplantar radiographs while weightbearing were taken after each sectioning. A statistically significant varus displacement of the first metatarsal was observed only after transection of the peroneus longus tendon. It was concluded that the peroneus longus tendon is a strong retaining mechanism of the first metatarsal.

Biomechanical Phenomena↗
PubMed1997

The utility of high-resolution magnetic resonance imaging in the evaluation of the triangular fibrocartilage complex of the wrist.

We performed a prospective study in order to assess the utility of high-resolution magnetic resonance imaging in the detection and specific localization of tears of the triangular fibrocartilage complex. Seventy-seven patients who had pain in the wrist were studied with use of a dedicated surface coil and three-dimensional gradient-recalled techniques with a field of view of eight centimeters and a slice thickness of one millimeter. The patients had pain on the ulnar side of the wrist, ligamentous instability, occult ganglia, or a combination of these. Magnetic resonance images were assessed for radial or ulnar avulsion, or both; central defects; degenerative intrasubstance changes; and complex tears of the triangular fibrocartilage complex. Partial tears were differentiated from complete tears. The findings on the magnetic resonance images were then compared with the arthroscopic findings. Fifty-seven of the fifty-nine tears that were suspected on magnetic resonance images were confirmed with arthroscopy; the two suspected tears that were not confirmed had been interpreted as small partial tears on the magnetic resonance images. With use of arthroscopy as the standard, magnetic resonance imaging had a sensitivity of 100 per cent (fifty-seven of fifty-seven), a specificity of 90 per cent (eighteen of twenty), and an accuracy of 97 per cent (seventy-five of seventy-seven) for the detection of a tear (kappa = 0.93, p < 0.00001). Fifty-three of the fifty-seven tears were localized correctly with use of magnetic resonance imaging. With regard to the location of the tear, magnetic resonance imaging had a sensitivity of 100 per cent (fifty-three of fifty-three), a specificity of 75 per cent (eighteen of twenty-four), and an accuracy of 92 per cent (seventy-one of seventy-seven) (kappa = 0.9, p < 0.0001). We concluded that high-resolution magnetic resonance imaging permits accurate depiction and localization of tears of the triangular fibrocartilage complex. When the appropriate pulse sequence is used, magnetic resonance imaging is an accurate and effective method for the non-invasive evaluation of pain in the wrist.

Adolescent↗
PubMed1997

A self-administered questionnaire for assessment of symptoms and function of the shoulder.

A self-administered questionnaire was designed to assess the severity of symptoms related to and the functional status of the shoulder. It includes domains of global assessment, pain, daily activities, recreational and athletic activities, work, satisfaction, and areas for improvement. Each domain is graded separately and is weighted to arrive at the total score. The over-all scale and each domain were prospectively tested for validity, reliability, and responsiveness to clinical change. One hundred patients who were seen for evaluation of the shoulder were enrolled in the study. The validity of the scale was demonstrated by moderate-to-high correlation of the domains and individual questions of the Shoulder Rating Questionnaire with those of the Arthritis Impact Measurement Scales 2. Validity was supported further by significant correlation of the scores in each domain with the level of satisfaction in that domain and by significantly lower scores in domains that patients selected as areas important for improvement. The over-all scale and each domain were internally consistent (Cronbach alpha, 0.71 to 0.90). Reproducibility was evaluated by repeated administration of the questionnaire after a mean of three days to forty patients whose condition was clinically stable. Reproducibility of the over-all questionnaire and individual domains was excellent (Spearman-Brown index, 0.94 to 0.98). Individual questions were reproducible, with a weighted kappa value of more than 0.7 for each. Responsiveness was evaluated by comparison of the preoperative and postoperative scores of thirty patients who had a satisfactory result one year after an operation on the shoulder. The over-all Shoulder Rating Questionnaire and each domain were responsive to clinical change as demonstrated by favorable standardized response means (range, 1.1 to 1.9) and indices of responsiveness (range, 1.1 to 2.0). Similar analysis performed for individual diagnostic groups supported the validity, reliability, and responsiveness of the questionnaire in each group. The self-administered shoulder questionnaire was found to be valid, reliable, and responsive to clinical change. These qualities should make it a useful instrument for the prospective assessment of the outcome of treatment of disorders related to the shoulder.

Activities of Daily Living↗
PubMed1996

Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans.

Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc gamma RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc gamma RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene. The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans.

Alleles↗
PubMed1996

Balloon photodynamic therapy of esophageal cancer: effect of increasing balloon size.

BACKGROUND AND OBJECTIVE: Photodynamic therapy is currently being used to treat various malignancies including esophageal cancer. The effect of photodynamic therapy depends upon the concentration of photosensitizing drug, light energy delivered to tissue, and the presence of oxygen in the targeted tissue. We have found that an esophageal centering balloon improves light delivery to esophageal mucosa. However, balloon pressure on esophageal mucosa could possibly reduce mucosal blood flow and oxygenation, therefore reducing the effect of photodynamic therapy. This study was conducted to investigate the effect of balloon pressure on the esophageal wall during photodynamic therapy in the canine esophageal model. STUDY DESIGN/MATERIALS AND METHODS: Studies were performed in the canine esophagus of ten animals to investigate whether increasing the size of the centering balloon, and hence the pressure on esophageal mucosa, would alter the tissue effect of PDT. Porfimer sodium 4 mg/Kg was administered and 630 nm light was delivered via a 1 cm diffuser located in the center of a 360 degrees 2 cm windowed balloon. Mucosal light measurements were made to ascertain equivalent mucosal light dosing of approximately 25 J/cm2. Endoscopic and necropsy findings obtained following photodynamic therapy with 25 mm, 33 mm, and 35 mm balloons were compared. RESULTS: In larger dogs (groups A and B), increasing the size of the esophageal centering balloon from a 25-33 mm size did not result in an overly tight fit nor was the increase associated with significant change in the PDT effect. In contrast, increasing the balloon size to 35 mm in smaller dogs (group C) resulted in a tight fit of the balloon in the esophagus and in significant reduction in the PDT effect on mucosal damage when mucosal equivalent light dose was administered during photodynamic therapy in the canine esophageal model. CONCLUSION: Increasing centering balloon size resulted in reduced tissue damage when mucosal equivalent light dose was administered during photodynamic therapy in the canine esophageal model. Proper sizing of centering balloons will be necessary for balloon PDT of esophageal mucosal dysplasia or cancer in humans.

Animals↗
PubMed1996

Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2.

The Notch/Lin-12/Glp-1 receptor family participates in cell-cell signaling events that influence cell fate decisions. Although several Notch homologs and receptor ligands have been identified, the nuclear events involved in this pathway remain incompletely understood. A truncated form of Notch, consisting only of the intracellular domain (NotchIC), localizes to the nucleus and functions as an activated receptor. Using both an in vitro binding assay and a cotransfection assay based on the two-hybrid principle, we show that mammalian NotchIC interacts with the transcriptional repressor CBF1, which is the human homolog of Drosophila Suppressor of Hairless. Cotransfection assays using segments of mouse NotchIC and CBF1 demonstrated that the N-terminal 114-amino-acid region of mouse NotchIC contains the CBF1 interactive domain and that the cdc10/ankyrin repeats are not essential for this interaction. This result was confirmed in immunoprecipation assays in which the N-terminal 114-amino-acid segment of NotchIC, but not the ankyrin repeat region, coprecipitated with CBF1. Mouse NotchIC itself is targeted to the transcriptional repression domain (aa179 to 361) of CBF1. Furthermore, transfection assays in which mouse NotchIC was targeted through Gal4-CBF1 or through endogenous cellular CBF1 indicated that NotchIC transactivates gene expression via CBF1 tethering to DNA. Transactivation by NotchIC occurs partially through abolition of CBF1-mediated repession. This same mechanism is used by Epstein-Barr virus EBNA2. Thus, mimicry of Notch signal transduction is involved in Epstein-Barr virus-driven immortalization.

Amino Acid Sequence↗
PubMed1995

The HCF repeat is an unusual proteolytic cleavage signal.

The herpes simplex virus VP16-associated protein HCF is a nuclear host-cell factor that exists as a family of polypeptides encoded by a single gene. The mature HCF polypeptides are amino- and carboxy-terminal fragments of a large approximately 300-kD precursor protein that arise through cleavage at one or more centrally located sites. The sites of cleavage are the HCF repeats, highly conserved 26-amino-acid sequences repeated six times in the HCF precursor protein. The HCF repeat alone is sufficient to induce cleavage of a heterologous protein, and cleavage occurs at a defined site--PPCE/THET--within the HCF repeat. Alanine-scan mutagenesis was used to identify a large 18-amino-acid segment of the HCF repeat that is important to induce cleavage of a heterologous protein. Even though HCF is cleaved, the majority of amino- and carboxy-terminal cleavage products remain tightly, albeit noncovalently, associated. Modulation of this noncovalent association may provide a mechanism for regulating HCF activity. For example, the cleaved products of an alternative mRNA splicing variant of HCF do not remain associated.

Alternative Splicing↗
PubMed1995

Diminished material properties and altered bone structure in rat femora during pregnancy.

Pregnancy and lactation are known to cause structural and mechanical changes in bone, but the effects of pregnancy alone have not been evaluated thoroughly. This study used radiographic measurements, torsion testing, mineral analyses, and histological evaluation to determine whether there are changes in bone material and geometric properties during pregnancy in the growing rat, as implied by earlier biochemical and histological studies. The bones of pregnant 9 to 12-week-old rats and controls that were not pregnant and were matched by age (but not weight) were evaluated at times corresponding to 5, 10, 15, and 20 days of the 23-day gestation period to address the following questions: (a) How is the growth of whole bone affected by pregnancy in the growing rat (as determined by radiographic analyses)? (b) How are the mechanical properties (structural and material) of whole bone affected by pregnancy (as assessed by torsion testing)? (c) Are there changes in the characteristics of bone mineral during pregnancy (as determined by measurement of mineral content and x-ray diffraction analyses)? and (d) Are there detectable morphological or ultrastructural differences between the bones of pregnant and control rats (as assessed by analyses based on histology and back-scattered electron imaging)? The presence of statistically significant differences in this study was determined initially on the basis of a two-factor analysis of variance. In general, significant differences were noted only at late gestation (day 20), when the bones were longer and had a greater outer radius and cortical thickness; this indicates that more growth occurred during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Tibial intramedullary alignment in total knee arthroplasty.

This article describes a study that assessed the accuracy of a tibial intramedullary alignment device in 44 adult cadaveric tibiae. The results suggest that greater accuracy is achieved if the device is inserted fully to the level of the distal epiphyseal scar and if used in the nonvalgus tibia. When seating of the tibial guide rod is incomplete or when the tibia has a valgus anatomic bow, cross-checking with extramedullary alignment devices is recommended to maximize accuracy of tibial component position.

Adult↗
PubMed1994

Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa.

The Epstein-Barr virus (EBV) transactivator protein, termed Epstein-Barr virus nuclear antigen 2 (EBNA2), plays a critical role in the regulation of latent viral transcription and in the immortalization of EBV-infected B cells. Unlike most transcription factors, EBNA2 does not bind directly to its cis-responsive DNA element but requires a cellular factor, termed C-promoter binding factor 1 (CBF1). Here, CBF1 was purified and was found to directly interact with EBNA2. CBF1 is identical to a protein thought to be involved in immunoglobulin gene rearrangement, RBPJ kappa. Contrary to previous reports, CBF1-RBPJ kappa did not bind to the recombination signal sequences but instead bound to sites in the EBV C-promoter and in the CD23 promoter.

Amino Acid Sequence↗