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Biomedical subjects

R M Armstrong

Publications and source records attributed to R M Armstrong.

At least 37 records · Page 2Linked to original sources

Transforming growth factors-beta 1 and beta 2 induce synthesis and accumulation of hyaluronate and chondroitin sulfate in vivo.

Subcutaneous implantation in rats of partially purified transforming growth factor-beta (TGF-beta) derived from bovine bone induced extensive development of connective tissue with associated edema. Subcutaneous injection of pure TGF-beta 1 or TGF-beta 2 also induced connective tissue deposition in mice and guinea pigs. Sustained release of TGF-beta 1 from mini-osmotic pumps implanted subcutaneously in mature guinea pigs promoted connective tissue deposition that encapsulated the pumps. Biochemical analyses of the connective tissue capsule demonstrated that TGF-beta 1 induced a dose-dependent accumulation of glycosaminoglycans (GAGs). The GAG/DNA ratio also increased as a function of the rate of TGF-beta 1 released, suggesting that the factor increased production of GAGs per cell. Cellulose acetate gel electrophoresis of the GAGs and hydrolysis with specific glycosidases revealed that the majority of GAGs consisted of hyaluronate and chondroitin sulfate. These results demonstrate that TGF-beta 1 and TGF-beta 2 stimulate the production of not only collagenous extracellular matrix components, but also dramatically increase the in vivo synthesis of hyaluronate and chondroitin sulfate.

Animals↗

Purification and characterization of a unique osteoinductive factor from bovine bone.

A unique protein that promotes ectopic osteoinduction in the rat has been isolated and characterized. Osteoinductive factor (OIF) was extracted from the organic matrix of bovine bone with 4 M guanidine HCl and purified by gel filtration, ion-exchange chromatography, affinity chromatography, and reversed phase high performance liquid chromatography. OIF is a glycoprotein with an apparent molecular mass of 22-28 kDa based on sodium dodecyl sulfate gel electrophoresis. Enzymatic or chemical deglycosylation of OIF reduces its mass to about 12 kDa with apparent loss of activity. OIF activity in the model used is substantially increased by addition of transforming growth factor (TGF)-beta 1 or TGF-beta 2, suggesting an important role for TGF-beta 1 and -2 in bone regeneration and repair. The N-terminal sequence of OIF has no homology to other reported proteins.

Amino Acid Sequence↗

Experimental infection of eland (Taurotrages oryx), sable antelope (Ozanna grandicomis) and buffalo (Syncerus caffer) with foot-and-mouth disease virus.

The course of experimental infection of a type SAT 1 FMDV strain was studied in buffalo, sable antelope and eland following tongue inoculation and contact and has been compared with that in cattle. All species became infected, although disease was less severe in the game animals and larger amounts of virus were required to infect game animals than cattle. Neutralizing antibody titres were high and were maintained for an extended period in buffalo, sable antelope and eland. The carrier state was demonstrated in buffalo for the longest period. Cattle carried virus for up to 56 days. Virus persistence in sable antelope was transitory and did not occur in eland.

Animals↗

An enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of antibodies against swine vesicular disease virus (SVDV).

A liquid phase blocking sandwich ELISA has been compared with virus neutralisation for testing pig sera for antibodies against swine vesicular disease (SVD) virus. Highest infectivity titre of SVD virus was obtained using a multiplicity of infection of 30 pfu/cell and harvesting after 21 h. Titres obtained for 300 clinically normal animals were assessed by ELISA and 89% were found to be 1/6 or less. Results were skewed and spread up to 1/45. Comparison of known positive sera resulted in a correlation between the two methods of 0.68 and showed that a virus neutralisation titre of 1/16 was equivalent to 1/40 (log10 1.61) by ELISA. Variation in results obtained by replicate testing using ELISA and virus neutralisation was almost identical. Overlap between positive and negative sera was shown to be reduced to 1-1/2 fold in ELISA. Therefore, the ELISA correlated well with virus neutralisation and has several advantages over the latter.

Animals↗

Controlled pilot trial of monthly intravenous cyclophosphamide in multiple sclerosis.

Monthly intravenous cyclophosphamide treatment was compared with placebo treatment for one year in a controlled trial of 14 patients with relapsing/remitting multiple sclerosis. Eight patients received placebo and six patients received cyclophosphamide. The cyclophosphamide group showed a definite trend to have less frequent and less prolonged episodes than the placebo group. When each group served as their own controls, the cyclophosphamide group had a significant decrease in episodes while the placebo group did not. When the placebo group was then given cyclophosphamide, they also had a significant decrease in episodes. When all patients who were receiving cyclophosphamide were combined for analysis, the decrease in episodes was even more evident. Complications were minimal. These results suggest that monthly intravenous doses of cyclophosphamide may influence the frequency and duration of episodes of relapsing/remitting multiple sclerosis.

Adult↗

Osteogenesis in rats with an inductive bovine composite.

Subcutaneous (S.C.) implantation of allogeneic demineralized bone matrix in rats results in endochondral bone formation. In contrast, implants of bovine demineralized bone matrix in rat S.C. tissue show inconsistent cartilage and bone formation, presumably due to an intense inflammatory reaction at the implant site. To overcome this response, a partially purified bone inducing extract was prepared from bovine bone by a series of steps that included demineralization, guanidine/HCl extraction, gel filtration, and cation exchange chromatography. To develop a carrier, the inactive guanidine/HCl-extracted matrix was then trypsinized to remove the inflammatory and immunogenic components, thus yielding a predominantly collagenous matrix. Bovine composites were prepared by combining different amounts of the bone inducing extract with a carrier that consisted of the trypsinized bone matrix and purified soluble bovine dermal collagen. Subcutaneous implantation of the composite preparation resulted in dose-dependent endochondral bone formation in rats. The inductive activity and the low-level inflammatory response were comparable to allogeneic implants.

Animals↗

Botulism in a patient with jejunoileal bypass.

A 45-year-old woman was diagnosed as having the unclassified form of botulism. Her intestines may have been predisposed to colonization with Clostridium botulinum because of a jejunoileal bypass procedure that had been done several years earlier. One other similar case has been reported.

Botulism↗

A rapid enzyme-linked immunosorbent assay for the detection of foot-and-mouth disease virus in epithelial tissues.

A rapid double sandwich enzyme-linked immunosorbent assay (ELISA) has been used for the identification and type differentiation of foot-and-mouth disease (FMD) viruses in epithelial tissue samples submitted for diagnosis from the field. No difficulty was experienced in the direct typing of freshly harvested epithelium from recently ruptured vesicles by the complement fixation (CF) test or ELISA. The ELISA was more sensitive and specific, but proved no more efficient than the traditional CF test in the direct typing of samples of poorer quality from many countries overseas where communications are often difficult. However, when both tests were used concurrently, FMD virus typings were confirmed in 27 more samples. Some possible reasons for the failure of ELISA to detect virus in certain cases are discussed.

Animals↗

Acute toxoplasmic encephalitis in a normal adult.

Acute encephalitis associated with an impressive skin rash developed in an otherwise healthy man. Brain biopsy findings were not diagnostic, but serologic data confirmed the diagnosis of acute toxoplasmosis. The patient improved after antimicrobial therapy with pyrimethamine and sulfadiazine, but he was left with neurologic deficits.

Acute Disease↗

Insulin resistance in patients with myotonic dystrophy.

Evaluation of insulin sensitivity in 12 patients with myotonic dystrophy gave results different from those found in other insulin-resistant conditions. Nine of our subjects were insensitive to exogenous insulin, but only three had elevated fasting insulin concentrations. Eight had an excessive insulin response to a glucose challenge. Monocyte insulin receptor affinity was decreased (myotonics, 1.21 +/- 0.74 X 10(9) liters per mole; controls, 2.62 +/- 1.28 X 10(9)), and this parameter correlated best with the insulin resistance. No circulating receptor antibody or insulin binding inhibitor was found. Our studies suggest that the insulin resistance seen in patients with myotonic dystrophy is related to decreased insulin receptor affinity.

Adult↗