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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

Supervised fitness walking in patients with osteoarthritis of the knee. A randomized, controlled trial.

OBJECTIVE: To assess the effect of a program of supervised fitness walking and patient education on functional status, pain, and use of medication in patients with osteoarthritis of the knee. DESIGN: An 8-week randomized, controlled trial. SETTING: Inpatient and outpatient services of an orthopedic hospital in an academic medical center. PATIENTS: A total of 102 patients with a documented diagnosis of primary osteoarthritis of one or both knees participated in the study. Data were obtained on 47 of 51 intervention patients and 45 of 51 control patients. INTERVENTIONS: An 8-week program of supervised fitness walking and patient education or standard routine medical care. MEASUREMENTS: Patients were evaluated and outcomes assessed before and after the intervention using a 6-minute test of walking distance and scores on the physical activity, arthritis impact, pain, and medication subscales of the Arthritis Impact Measurement Scale (AIMS). RESULTS: Patients randomly assigned to the walking program had a 70-meter increase in walking distance relative to their baseline assessment, which represents an improvement of 18.4% (95% Cl, 9.8% to 27.0%). In contrast, controls showed a 17-meter decrease in walking distance relative to their baseline assessment (P less than 0.001). Improvements in functional status as measured by the AIMS physical activity subscale were also observed in the walking group but not in the control group (P less than 0.001); patients assigned to the walking program improved 39% (Cl, 15.6% to 60.4%). Although changes in scores on the arthritis impact subscale were similar in the two groups (P = 0.093), the walking group experienced a decrease in arthritis pain of 27% (Cl, 9.6% to 41.4%) (P = 0.003). Medication use was less frequent in the walking group than in the control group at the post-test (P = 0.08). CONCLUSIONS: A program of supervised fitness walking and patient education can improve functional status without worsening pain or exacerbating arthritis-related symptoms in patients with osteoarthritis of the knee.

Adult

Cloning and analysis of the RESA-2 gene: a DNA homologue of the ring-infected erythrocyte surface antigen gene of Plasmodium falciparum.

We have cloned and sequenced a homologue of the ring-infected erythrocyte surface antigen (RESA) gene from Plasmodium falciparum designated RESA-2. Two reading frames with high homology to exon 1 and exon 2 of RESA at both the nucleotide and amino acid levels were identified in the RESA-2 sequence. However, RESA-2 does not contain either of the blocks of tandem repeats present in RESA. The lack of an RNA transcript in either asexual or sexual stage parasites and the presence of an in-frame stop codon in the second reading frame suggests RESA-2 could be a pseudogene. Its lack of expression in asexual stages demonstrates that it does not complement the RESA deletion in isolate FCR3.

Amino Acid Sequence

A computerized cancer information system.

Cancer information was made available via a computer to patients visiting the University of Connecticut Dental Clinics. The computer program was menu driven. An option allowed users to leave messages for the system owners. The computer program generated a log of usage, user comments and items chosen. The user could choose from the following topics: (1) general information on cancer; (2) diet, nutrition and cancer; (3) smoking; (4) the environment, occupations and cancer; and (5) physical checkups. An option to leave a message for the system operators was the option chosen least. Analysis of the usage log shows that the system was used substantially while people were waiting in the clinic and that at least three or four individuals used the system every clinic day. Such information systems can provide important information to the public. The novelty of the system and the lack of supervision did not deter public use.

Connecticut

Geographic variations in the rates of elective total hip and knee arthroplasties among Medicare beneficiaries in the United States.

We analyzed the variations in the rates of elective total hip and total knee arthroplasties for 1988 in the United States to determine whether the rates correlated with the numbers of surgeons. There were 56,204 total hip arthroplasties and 68,491 total knee arthroplasties, performed in the home states of the patients among all of the Medicare beneficiaries. Medicare beneficiaries include most people who are more than sixty-five years old in the United States and a small proportion of younger people who are eligible for Medicare for other reasons. Seventy-nine per cent of the patients who had had a total hip arthroplasty and 89 per cent of those who had had a total knee arthroplasty had been managed with the operation because of osteoarthrosis. Both operations were most common in the seventy to seventy-four-year age-group. We calculated the rate of operations per 100 beneficiaries for each state and age-adjusted the results. Across all of the states, bilateral procedures constituted 1.6 per cent of the total hip arthroplasties and 4.8 per cent of the total knee arthroplasties. The in-hospital rates of mortality were 0.72 per cent for total hip arthroplasties and 0.45 per cent for total knee arthroplasties. The destinations after discharge from the hospital were similar for the two groups of patients, with more than 65 per cent of the patients being discharged directly to their homes. There were no significant differences among states in terms of the length of stay in the hospital or reimbursement of the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Structure and functional properties of human general transcription factor IIE.

The general transcription factor IIE (TFIIE) is an essential component of the eukaryotic RNA polymerase II initiation complex. We have isolated human complementary DNA clones for both the subunits of TFIIE. Using purified recombinant proteins we find that both subunits are essential to form a stable preinitiation complex and to reconstitute basal-level and Sp1-activated transcription in vitro. Analysis of their predicted amino-acid sequences reveals several intriguing structural motifs that could provide insight into the role of TFIIE in transcription initiation.

Adenosine Triphosphate

Expression of a foreign gene in cats reconstituted with retroviral vector infected autologous bone marrow.

A Moloney murine leukemia virus based retroviral vector was used to transfer the bacterial neomycin resistance gene (neoR) into feline hematopoietic cells. We reconstituted four cats that had been lethally irradiated with autologous bone marrow that had been infected with the N2 or SAX retroviral vector. Bone marrow cells from all four cats expressed the neoR gene 30 days posttransplant and three of four cats still had the neoR gene and a low level of drug resistant colony-forming unit granulocyte-macrophage after more than 200 days. Two of the four cats unexpectedly developed diabetes mellitus 90 days posttransplantation. The expression of a foreign gene in cats, albeit at a low level, demonstrates that retroviral vectors can be used for gene transfer in noninbred large animal species and may be useful for gene therapy of humans. The development of diabetes mellitus in two of the subjects emphasizes the value of animal models for the study of possible deleterious effects of retroviral vector-mediated gene transfer.

Animals

Failure of recombinant vaccinia viruses expressing Plasmodium falciparum antigens to protect Saimiri monkeys against malaria.

Saimiri sciurus monkeys were immunized at multiple sites with recombinant vaccinia viruses expressing Plasmodium falciparum antigen genes and boosted 4 weeks later. Control monkeys were immunized with a thymidine kinase-negative vaccinia virus mutant. Two weeks later, all of the monkeys were challenged by intravenous inoculation of P. falciparum (Indochina strain) parasites. A group of unimmunized monkeys was challenged in parallel. All of the monkeys that received vaccinia virus recombinants or the control virus produced good anti-vaccinia virus antibody responses. However, those that received a single construct containing ring-infected erythrocyte surface antigen (RESA) given at eight sites did not produce significant antibody to any of the three major RESA repeat epitopes after immunization but were primed for an enhanced antibody response after challenge infection with P. falciparum. Most of the monkeys produced detectable antibodies to the RESA epitopes after challenge infection. One group of monkeys was immunized with four constructs (expressing RESA, two merozoite surface antigens [MSA-1 and MSA-2], and a rhoptry protein [AMA-1]), each given at two sites. While these monkeys failed to produce significant antibody against MSA-2 or AMA-1 after immunization, they produced enhanced responses against these antigens after challenge infection. Immunization involved an allelic form of MSA-2 different from that present in the parasite challenge strain, so that the enhanced responses seen after challenge infection indicated the presence of T-cell epitopes common to both allelic forms. No groups of monkeys showed any evidence of protection against challenge, as determined by examination of the resulting parasitemias.

Animals

Simplified colorimetric analysis of polymerase chain reactions: detection of HIV sequences in AIDS patients.

We have previously described a colorimetric test, designated an amplified DNA assay (ADA), for specific segments of DNA amplified by polymerase chain reactions (PCRs), suited to diagnostic applications. This relied on binding the amplified DNA via a sequence in one oligodeoxyribonucleotide (oligo) to the DNA-binding protein GCN4 coated on the wells of a microtiter dish. Avidin-peroxidase was then bound to biotin at the 5' end of the other oligo and detected colorimetrically. Two successive PCRs with nested oligos were utilized. We describe here several modifications that greatly simplify the ADA. First, we bind the DNA to a glutathione S-transferase-GCN4 fused polypeptide (GST-GCN4) and avidin-peroxidase simultaneously, rather than successively. Second, we carry out the two successive PCRs in the one reaction mixture, using the thermal stabilities of oligos of differing lengths to separate the two reactions. Third, PCRs can be performed in the wells of a microtiter dish and the amplified DNA captured and detected via GST-GCN4 immobilized on beads attached to the lid of the microtiter dish. Hence it is only necessary to pipette the DNA sample once, and up to 96 samples can then be handled simultaneously.

Acquired Immunodeficiency Syndrome

Isolation and characterization of the Drosophila gene encoding the TATA box binding protein, TFIID.

To investigate the biochemical mechanisms involved in interactions between regulatory factors and the general transcription complex, we have cloned, expressed, and characterized the Drosophila gene encoding the TATA binding protein, dTFIID. Comparison of the protein sequences of the Drosophila and yeast TATA binding proteins reveals a bipartite organization consisting of a highly conserved, basic carboxy-terminal domain and a nonconserved amino-terminal region rich in Gln, Gly, Ser, and Met residues. Purified dTFIID protein binds specifically to the TATA sequence and activates basal-level transcription, and the conserved carboxy-terminal half of the molecule is sufficient for both activities. Partially purified TFIID from Drosophila cells mediates activation by the transcription factor Sp1. In contrast, purified dTFIID expressed from the cloned gene is unable to support Sp1-dependent activation, suggesting that other factors may be required to mediate interactions between upstream activators like Sp1 and the TATA binding protein.

Amino Acid Sequence

Functional domains and upstream activation properties of cloned human TATA binding protein.

The TATA binding protein, TFIID, plays a central role in the initiation of eukaryotic mRNA synthesis. Here, we present a human cDNA clone for this factor. Comparison of its predicted protein sequence with those from Drosophila and yeast reveals a highly conserved carboxyl-terminal 180 amino acids. By contrast, the amino-terminal region of TFIID has diverged in both sequence and length. A striking feature of the human protein is a stretch of 38 glutamine residues in the NH2-terminal region. Expression of human TFIID in both Escherichia coli and HeLa cells produces a protein that binds specifically to a TATA box and promotes basal transcription; the conserved COOH-terminal portion of the protein is sufficient for both of these activities. Recombinant TFIID forms a stable complex on a TATA box either alone or in combination with either of the general transcription factors, TFIIA or TFIIB. Full-length recombinant TFIID is able to support Sp1 activated transcription in a TFIID-depleted nuclear extract, while a deletion of the NH2-terminal half of the protein is not. These results indicate the importance of the NH2-terminal region for upstream activation functions and suggest that additional factors (co-activators) are required for mediating interactions with specific regulators.

Amino Acid Sequence

Nonulcerative keratouveitis in five horses.

Five horses with severe nonulcerative keratouveitis had corneal lesions characterized by a pink stromal infiltrate that initially appeared in the stroma near the limbus. Unremitting iridocyclitis also was evident. In 3 horses, microscopic lesions consisted of marked corneal stromal fibrosis, with mild to severe inflammatory cellular infiltration. Corticosteroids and mydriatic/cycloplegics applied topically and corticosteroids and nonsteroidal anti-inflammatory medications administered parenterally were used with varying degrees of success to control pain and retain vision.

Animals

Structural diversity in the 45-kilodalton merozoite surface antigen of Plasmodium falciparum.

An integral membrane protein associated with the merozoite surface of Plasmodium falciparum termed merozoite surface antigen 2 (the 45-kDa merozoite surface antigen), occurs in antigenically diverse forms. Here we report the sequences of the MSA 2 gene from two other isolates of P. falciparum. The 43 N-terminal residues and the 74 C-terminal residues of all three MSA 2 sequences are highly conserved, but between these conserved regions there are dramatic differences among the alleles. Instead of the two copies of a 32-amino-acid repeat present in the MSA 2 of isolate FC27, MSA 2 from clone 3D7 and isolate Indochina 1 contain 5 and 12 copies respectively of the four amino acid sequence Gly Gly Ser Ala. The sequences flanking the repeats also differ among the three antigens. The repeats in MSA 2 appear to be immunodominant during natural infection, and antibodies to the repeat regions of different alleles react with a restricted number of parasite isolates.

Amino Acid Sequence

Correlation of anti-Ro antibody with photosensitivity rash in systemic lupus erythematosus patients.

We studied 131 patients with systemic lupus erythematosus (SLE) to determine the relationship between the presence of anti-Ro antibody in these patients and specific manifestations of SLE. There was a significant correlation between anti-Ro and photosensitivity rash in SLE patients, regardless of the type of rash. No significant association was found between anti-Ro and other SLE criteria or between anti-Ro and demographic variables.

Adult