Oral polymeric N-acetyl-D-glucosamine and osteoarthritis.

Many patients with arthritis are using alternative modes of therapy, including nutritional supplements, to treat their arthritis. Most patients never tell their doctors that they are taking alternative medications, and few doctors even ask about such activities. Over-the-counter supplements are expensive and consume large amounts of patients' healthcare dollars. Glucosamine has been widely touted as being an effective arthritis treatment. The authors designed and undertook a study to test the efficacy of a polymer of N-acetyl-D-glucosamine (NAG), or POLY-Nag, in a double-blind, placebo-controlled study in patients with osteoarthritis. Results indicate that POLY-Nag may be useful in treating patients with osteoarthritis.

Cooperative ordering in homeodomain-DNA recognition: solution structure and dynamics of the MATa1 homeodomain.

The mating type homeodomain proteins, MATa1 and MATalpha2, combine to form a heterodimer to bind DNA in diploid yeast cells. The a1-alpha2 heterodimer tightly and specifically binds haploid-specific gene operators to repress transcription. On its own, however, the a1 homeodomain does not bind DNA in a sequence-specific manner. To help understand this interaction, we describe the solution structure and backbone dynamics of the free a1 homeodomain. Free a1 in solution is an ensemble of structures having flexible hinges at the two turns in the small protein fold. Conformational changes in the a1 homeodomain upon ternary complex formation are located in the loop between helix 1 and helix 2, where the C-terminal tail of alpha2 binds to form the heterodimer, and at the C-terminus of helix 3, the DNA recognition helix. The observed differences, comparing the free and bound a1 structures, suggest a mechanism linking van der Waals stacking changes to the ordering of a final turn in the DNA-binding helix of a1. The tail of alpha2 induces changes in loop 1 of a1 that push it toward a properly folded DNA binding conformation.

Gastropathy induced by nonsteroidal anti-inflammatory drugs: prescribing patterns among geriatric practitioners.

The objective of this study was to determine patterns among geriatric practitioners in prescribing agents that protect the gastrointestinal tract when nonsteroidal anti-inflammatory drug (NSAID) treatment is started for elderly patients. A questionnaire describing five scenarios of elderly patients requiring NSAID therapy asked respondents to choose gastrointestinal-protective agents for each scenario. Respondents were then asked to what extent four established risk factors for NSAID gastropathy (age, previous peptic ulcer, previous gastrointestinal bleeding, and heart disease) affected their choices. The choice of gastrointestinal-protective agent was compared with the training and experience of the respondents. This self-administered survey was provided to 821 randomly selected physicians from the membership of the American Geriatrics Society throughout the United States and Puerto Rico. Statistical Package for the Social Sciences (SPSS), version 6.1.4, was used to obtain frequencies. Of 821 surveys, 229 (28%) were returned. It was found that well elderly patients and nursing home residents were not treated with any gastrointestinal-protective agent by 64% (well elderly patients) and 32% (nursing home residents) of respondents. Among respondents who would prescribe, about half would choose misoprostol for a well elderly patient or a nursing home resident, whereas half or more preferred histamine H2-receptor antagonists. Twenty-three percent would not prescribe misoprostol when NSAID therapy was resumed after an active ulcer had healed, and 68% preferred H2 antagonists in that setting. The difference in response attributable to training/experience was less than 9%. Factors that did not affect prescribing patterns included the patient's age (15% to 62%) and heart disease (44% to 50%). The study concluded that age and heart disease are risk factors to which physicians give less consideration when choosing gastrointestinal-protective agents. Although misoprostol is the only agent approved by the Food and Drug Administration for prophylaxis against NSAID gastropathy, 23% of respondents chose not to prescribe misoprostol when NSAID therapy was resumed after an active ulcer had healed. Histamine H2-receptor antagonists were preferred over misoprostol for well elderly patients and nursing home residents. Training and experience were not responsible for differences among respondents' prescribing patterns.

High level, context dependent misincorporation of lysine for arginine in Saccharomyces cerevisiae a1 homeodomain expressed in Escherichia coli.

The Saccharomyces cerevisiae a1 homeodomain is expressed as a soluble protein in Escherichia coli when cultured in minimal medium. Nuclear magnetic resonance (NMR) spectra of previously prepared a1 homeodomain samples contained a subset of doubled and broadened resonances. Mass spectroscopic and NMR analysis demonstrates that the heterogeneity is largely due to a lysine misincorporation at the arginine (Arg) 115 site. Arg 115 is coded by the 5'-AGA-3' sequence, which is quite rare in E. coli genes. Lower level mistranslation at three other rare arginine codons also occurs. The percentage of lysine for arginine misincorporation in a1 homeodomain production is dependent on media composition. The dnaY gene, which encodes the rare 5'-AGA-3' tRNA(ARG), was co-expressed in E. coli with the a1-encoding plasmid to produce a homogeneous recombinant a1 homeodomain. Co-expression of the dnaY gene completely blocks mistranslation of arginine to lysine during a1 overexpression in minimal media, and homogeneous protein is produced.

Sweet's syndrome after splenic irradiation for chronic myelogenous leukemia.

Sweet's syndrome is defined as acute febrile neutrophilic dermatosis. Characteristic features are fever; peripheral neutrophilia; and painful cutaneous nodules and plaques on the face, neck, trunk, and limbs. Biopsy specimens of these lesions show a mature neutrophilic infiltrate of the dermis. Vasculitis is absent. Sweet's syndrome is associated with malignancy in approximately 20% of reported cases. The pathogenesis is unknown. The authors describe Sweet's syndrome in a 39-year-old man 5 weeks after splenic irradiation for chronic myelogenous leukemia. Treatment with parenteral corticosteroids resulted in dramatic improvement of the patient's condition. The authors discuss the diagnosis of Sweet's syndrome and the fact that it is thought to be cytokine-induced.

A survey of osteoarthritis of the knee in the elderly.

We evaluated the signs and symptoms suggestive of osteoarthritis (OA) of the knee in 682 elderly people. The results suggest that both the frequency of signs and symptoms and the degree of severity remain constant in the 7th, 8th and 9th decades. Differences between men and women and between blacks and whites were also noted--women and blacks tending to have more frequent and more severe evidence of OA of the knee. These data suggest that OA of the knee is a specific disease that affects only a portion of the population and is not inevitably progressive.

Purulent pericarditis occurring in a patient with cecal carcinoma: report of a case.

We report the unusual concatenation of cecal carcinoma complicated by bacteremia and purulent pericarditis. The organism responsible for the pericarditis was not definitely established. The pericarditis was successfully managed by surgical drainage and antibiotic therapy. Colonic surgery followed eradication of the pericarditis.