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Biomedical subjects

R C Butler

Publications and source records attributed to R C Butler.

At least 19 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

Non-toxic endotoxin polysaccharide induces soluble mediators which potentiate antibody production by murine retrovirus-suppressed splenocytes.

Mice infected with Friend leukemia virus show marked acquired immunodeficiency characterized by the impairment of immune function of spleen cells to various antigens, both in vivo and in vitro. The large mol. wt. endotoxin derived from Serratia marcescens, as well as a smaller non-toxic polysaccharide derivative, were found to augment the antibody responsiveness of spleen cells from normal as well as FLV-infected mice. In addition, serum from normal donor mice pretreated with BCG and injected either with endotoxin or the polysaccharide derivative potentiated the antibody response of spleen cells from both normal and FLV-infected mice. Similar enhancement was induced by "antibody response helper factor(s)" present in 3-5 day spleen culture supernatants from endotoxin or polysaccharide-treated spleen cells from normal mice. Enhancement of the antibody response of spleen cells from FLV-infected mice by the antibody helper activity was due to stimulation of B-lymphocytes and reversal of a defect in antibody helper factor(s) formation by macrophages. Similar antibody response enhancing activity was induced by both endotoxin and the non-toxic polysaccharide derivative in cultures of normal spleen cells, adherent spleen cell populations, peritoneal cells and the P388D1 macrophage cell line.

Animals

Humoral immunity to link protein in patients with inflammatory joint disease, osteoarthritis, and in non-arthritic controls.

Cartilage link protein of high purity was prepared and used in an enzyme linked immunosorbent assay (ELISA). Antibodies to link protein were sought in the sera of 98 patients with rheumatic disorders; 38 with rheumatoid arthritis (RA), 29 with osteoarthritis (OA), 13 with psoriatic arthritis (PA), nine with ankylosing spondylitis (AS), nine with systemic lupus erythematosus (SLE), and in 83 healthy controls. Antibodies were detected in all groups with the following prevalences: 21/83 normals, 9/38 RA, 7/29 OA, 7/13 PA, 3/9 AS, and 4/9 SLE. No statistically significant differences existed between the groups with regard to either prevalence or mean titre of anti-link antibodies. Serum antibodies to proteoglycan link protein appear to be no more common in patients with rheumatic disorders than in healthy controls.

Arthritis

The arthropathy of cystic fibrosis.

Musculoskeletal symptoms are frequent in cystic fibrosis (CF). Here the clinical features of 29 patients with CF who had significant arthropathy are described. Twelve had episodic arthritis (EA) characterised by repeated short attacks of severe, incapacitating polyarthritis, which in seven was associated with fever and erythema nodosum. Ten patients had hypertrophic pulmonary osteoarthropathy (HPOA). The onset of symptoms in the group with HPOA was usually later (mean age 20 years v 16 years for EA) and was associated with significantly worse lung function than in patients with CF, either without arthropathy or with EA. Seven patients had arthropathies which could not be classified as EA or HPOA.

Adolescent

Susceptibility of Campylobacter jejuni and Yersinia enterocolitica to UV radiation.

Two enteric pathogens, Campylobacter jejuni and Yersinia enterocolitica serogroup O:3, together with Escherichia coli, were investigated for susceptibility to UV radiation at 254 nm. The UV dose required for a 3-log reduction (99.9% inactivation) of C. jejuni, Y. enterocolitica, and E. coli was 1.8, 2.7, and 5.0 mWs/cm2, respectively. Using E. coli as the basis for comparison, it appears that C. jejuni and Y. enterocolitica serogroup O:3 are more sensitive to UV than many of the pathogens associated with waterborne disease outbreaks and can be easily inactivated in most commercially available UV reactors. No association was found between the sensitivity of Y. enterocolitica to UV and the presence of a 40- to 50-megadalton virulence plasmid.

Campylobacter fetus

Enhanced antibody response in retrovirus-infected mice treated with endotoxin or nontoxic polysaccharide derivative.

Friend leukemia virus (FLV) is a retrovirus which causes marked suppression of the immune response of genetically susceptible mice. In the present study the depressed antibody response to sheep erythrocytes by spleen cells from FLV-infected mice was partially reversed by injection of either a bacterial endotoxin or a nontoxic polysaccharide derivative directly into infected mice or by addition to spleen cell cultures from these mice immunized in vitro with sheep red blood cells (SRBC). The endotoxin and PS in a dose-related manner markedly increased the antibody responsiveness of the spleen cells to SRBC. Thus these results indicate that the nontoxic polysaccharide derivative has properties equivalent to the toxic endotoxin in enhancing the antibody responsiveness of FLV-suppressed spleen cells to a T-cell-dependent antigen like SRBC.

Animals

Alpha-adrenoreceptor reagents. 3. Synthesis of some 2-substituted 1,4-benzodioxans as selective presynaptic alpha 2-adrenoreceptor antagonists.

The synthesis and pharmacological activity of a series of 2-substituted derivatives of the selective alpha 2-adrenoreceptor antagonist idazoxan (RX 781094) is described. Substitution in this position by alkyl, alkenyl, cycloalkenyl, and alkoxy groups in many cases gives compounds whose potencies and selectivities are significantly greater than those of the parent compound.

Adrenergic alpha-Antagonists

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