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R C Butler

Publications and source records attributed to R C Butler.

15 recordsLinked to original sources

Bone mineral content in patients with rheumatoid arthritis: relationship to low-dose steroid therapy.

Bone mineral content (BMC) of the distal forearm was measured by single photon absorptiometry in 142 patients with rheumatoid arthritis (RA) of whom 27/54 men and 44/88 women received low-dose steroid therapy (less than 10 mg/day). To study the effect of steroid therapy a case-control analysis was undertaken in patients matched for age, sex and disease duration. Steroid therapy was associated with a reduced BMC in men (1.16 +/- 0.29 versus 1.32 +/- 0.23; P less than 0.05) and post-menopausal (0.76 +/- 0.24 versus 0.91 +/- 0.25; P less than 0.02) but not pre-menopausal women (1.1 +/- 0.28 versus 1.1 +/- 0.17). Symptomatic fractures were more common in steroid-treated patients than in those who had not received steroids (10/71 versus 2/71; P less than 0.05). Serum osteocalcin, an index of bone formation, was measured in 106 cases. It tended to be higher in patients with RA than in controls but the values observed in steroid and non-steroid RA groups did not differ significantly. We conclude that low-dose steroid therapy is associated with increased bone loss and numbers of fractures in patients with RA but this does not appear to be the result of a simple defect in bone formation.

Absorptiometry, Photon

Heteroaromatic analogues of the alpha 2-adrenoreceptor partial agonist clonidine.

A 1,4-dioxane analogue (1) of the alpha 2-adrenoreceptor partial agonist clonidine (2) has previously been shown to possess an interesting but complex pharmacological profile. In this study, from a series of other heterocyclic analogues of clonidine, the 1,4-oxazines 6 and 12 were found to resemble 1 in that they are partial alpha 2-agonists in the periphery and are excluded from the central nervous system. However, when given directly into the brain, they behave as pure alpha 2-antagonists.

Adrenergic alpha-Agonists

Restoration of depressed antibody responses of leukemic splenocytes treated with LPS-induced factors.

Lipopolysaccharide and a nontoxic derivative, PS, from Serratia marcescens were studied in terms of their effects on normal and Friend leukemia virus depressed splenocytes. These materials caused a marked increase in the number of antibody producing cells by both groups of splenocytes. MDP, a synthetic analogue of myobacterial cell walls, produced a similar adjuvant response by normal and leukemic splenocytes. Combinations of PS or LPS and BCG or MDP resulted in synergistic immunostimulatory responses. A soluble factor associated with these materials appeared to mediate the response, since cell-free supernatants from LPS stimulated splenocytes or serum from LPS treated mice resulted in similar immunostimulation.

Acetylmuramyl-Alanyl-Isoglutamine

Studies on the endotoxin induced tumor resistance.

In summary, this report has discussed the immunologic mechanisms involved in the enhancement of nonspecific resistance to tumor by endotoxin. The optimal conditions for tumor protection involved pretreatment with approximately 25 mug LPS administered at the siteof subsequent tumor challenge. In an attempt to relate endotoxin structural components to the ability to enhance TUR, a variety of whole LPS's, endotoxic glycolipids and PS preparations were compared. While all of the intact LPS's and several of the glycolipids were effective in enhancing TUR, some endotoxic glycolipids were totally inactive although they were equally toxic. Some lipid-free PS preparations were also active although less than whole LPS. Evidence was presented to suggest that mechanism for enhancement of TUR involves B cells and macrophages but not T cells. The mechanism also involves the production of soluble factors which are released into the serum of mice in response to LPS or PS. These factors can transfer and mediate the antitumor effects of LPS. The preinfection of mice with BCG enhanced the activity of LPS and PS in the production of antitumor activity.

Animals

Macrophage factors that enhance the antibody response.

The immunological mechanism of the primary in vitro antibody responses to sheep erythrocyte antigens involves soluble immunomodulatory factors. These studies have demonstrated that the stimulation of immunocytes with lipopolysaccharide (LPS) induced the release of a helper factor which appeared to be a monokine. This helper factor was released by stimulated adherent splenocyte cultures but not by nonadherent cell populations. The P388D-transformed macrophage cell line also produced the factor in response to LPS. LPS-induced helper factors were absorbed from solution by bone marrow cells but not by thymocytes, thereby indicating that the factor may selectively bind to B-cells or to undifferentiated stem cells. Mature T-cells did not appear to be involved in the immunostimulatory effects of this macrophage-derived factor as evidenced by the results of several studies. These included observations that splenocytes from athymic BALB/c nu nu mice both produced the factor and responded to it.

Animals

Bone marrow colony-stimulating factor and tumor resistance-enhancing activity of postendotoxin mouse sera.

The passive transfer of postendotoxin mouse serum could enhance nonspecific resistance to the development of TA3-Ha transplantable ascites tumor in mice. The postendotoxin serum was not directly cytotoxic to TA3-Ha tumor cells in vitro, nor did it contain significant amounts of residual endotoxin, but it was rich in colony-stimulating factors (CSFs). High-titer CSF serum could be induced by endotoxic lipopolysaccharide (LPS). Nonendotoxic, lipid-free, and polysaccharide-rich hydrolytic breakdown product of LPS (called PS) was less potent but still active in CSF induction. There was a correlation between the level of CSF stimulation and the capacity of the sera to transfer tumor resistance (TUR). Those LPS preparations that had the highest CSF-inducing capacity were the most potent in TUR enhancement. Suppression of CSF production by treatment with theophylline or epinephrine, enhancers of cyclic AMP/cyclic GMP ratios, lowered the enhancement of TUR by endotoxic LPS. The infection of serum donor mice with bacillus Calmette-Guérin (BCG) 18 days prior to LPS treatment gave the highest serum CSF levels and the most potent TUR-inducing serum preparation. Even more notable was the finding that the nontoxic PS preparation could replace toxic LPS in the above BCG-LPS system. The serum harvested from BCG-infected mice 2 hr after PS injection was similarly effective in the passive transfer of TUR.

Animals

Discussion paper: dual effects of tumor antigens: induction of tumor resistance or tumor growth enhancement.

TA3-HA nonspecific tumors growing in ascites form shed their membrane components into the ascites fluid. This product can induce tumor growth enhancement if given together with or after i.p. tumor inoculation in relatively large quantities, but if given i.m. in small quantities, several days before tumor challenge, the mice show an elevated resistance to the tumor. The strictly strain-specific TA3-St line does not release such membrane components into the ascites fluid. It has also been found that the TA3-HA cells have a larger membrane fluidity than the TA3-St cells, as measured by membrane microviscosity, using the Shinitzki procedure. Isolation and gross chemical analysis of the TA3-Ha ascites fluid component was carried out. Results, so far, indicate that the active site of this product is probably carbohydrate in nature. The possible mode of action of such component in tumor growth enhancement is most probably by overwhelming and neutralizing immunocytes capable of recognition and eventually cytotoxic action.

Animals

Relationship of structure to function in bacterial endotoxins. IX. Differences in the lipid moiety of endotoxic glycolipids.

Chemical, immunochemical, chromatographic, and endotoxic properties of five chromatographically pure glycolipids were compared. The preparations were extracted by chloroform-methanol from three Escherichia coli, one Salmonella minnesota, and one S. typhimurium Re heptoseless mutant strains. The local Shwartzman skin assay, the nonspecific resistance-enhancing effect, and the Limulus assays could not distinguish among the five glycolipids, all five being active in all three assays. Significant differences could be seen when the tumor resistance-enhancing effect of the glycolipids in mice was compared with the nonspecific TA3-Ha murine mammary adenocarcinoma growing in ascites form. Even greater variation was observed in the capacity of the preparations to enhance the nonspecific resistance of mice to virulent S. typhi 0901 infections. The data show that the five glycolipids are quite dissimilar in their biological effects. Similarly, thin-layer chromatography and molecular ratio determinations showed that differences exist in the chemical structure of the glycolipids. Accordingly, we claim that not only the polysaccharide but the lipid moiety as well may vary in various gram-negative endotoxin preparations.

Animals

Antacids.

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Alkalosis