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Biomedical subjects

A L Armstrong

Publications and source records attributed to A L Armstrong.

32 records · Page 2Linked to original sources
PubMed1990

In vitro and in vivo effects of metal chelators on cartilage metabolism.

The effect of metallic chelating agents (EDTA, EGTA) on cartilage metabolism was studied both in vitro, on calf cartilage, and in vivo, in rabbits. The question asked was whether it was possible to affect neutral protease activity, and not also inhibit beneficial synthetic systems. In vitro, EDTA suppressed anabolic processes, while EGTA had no effect. However, EDTA in vivo did not suppress glycosaminoglycan or RNA production, but paradoxically stimulated them. At the same time, EDTA inhibited neutral protease activity in normal animals.

Animals↗
PubMed1989

Comparison of the in vitro characteristics of von Willebrand factor in British and commercial factor VIII concentrates.

Qualitative/quantitative analysis of von Willebrand factor antigen (vWf:Ag) in either heat or solvent/detergent treated factor VIII concentrates, used for haemophilia replacement therapy, was undertaken to assess their suitability for the treatment of vWD. For the first time immunoaffinity purified vWf:Ag (Monoclate by-product) was also evaluated by in vitro assessment. Potencies of vWf:Ag varied considerably but were consistently higher (28.9-420.5 iu/ml) than factor VIII:C (one-stage) activity (8.13-42.44 iu/ml). The functional activity of vWf was assessed by either Ristocetin Cofactor (vWf:RCo) or collagen binding methods (vWf:CBA) with typical vWf:RCo/vWf:Ag ratios ranging from 0.08 to 0.94. Multimeric analysis confirmed that in vitro biological activity was dependent on the presence of the high molecular weight forms of vWf:Ag. A significant correlation (r = 0.95) between vWf:RCo activity and collagen binding was observed in all of the concentrates with the exception of the immunopurified product. The data suggest that either NHS 8Y (mean vWfRCo/vWf:Ag = 0.94), Haemate P (mean vWf:RCo/vWf:Ag = 0.69) and high purity Octapharma V.I (vWf:RCo/vWf:Ag = 0.82) which contain medium/high MW vWf:Ag multimers are likely to be most cost-effective in the treatment of symptomatic severe vWD patients than other currently available concentrates.

Chemical Phenomena↗
PubMed1988

Transfusion-induced specific anti-factor XI inhibitor in a patient with previously unrecognized factor XI deficiency.

This article reports the rare occurrence and investigation of a specific anti-factor XI inhibitor that arose after fresh-frozen plasma infusion into a patient with previously unrecognized Factor XI deficiency. The IgG fraction of the patient's plasma that contained anti-Factor XI antibody was isolated by chromatography on DEAE-Affigel and concentrated. It was shown to exert inhibitory effect on purified Factor XI and XIa both in the activated and nonactivated partial thromboplastin time assay.

Aged↗
PubMed1987

Electron microscopic analysis of articular cartilage proteoglycan degradation by growth plate enzymes.

To assess the effect of intracellular growth plate chondrocyte enzymes on proteoglycan structure, we examined enzyme-treated articular cartilage proteoglycans and untreated articular cartilage proteoglycans with the electron microscopic monolayer technique. The untreated proteoglycan monomers ranged in length from less than 20 nm to more than 700 nm, with a mean length of 224.5 +/- 101.6 nm in one experiment and 224.6 +/- 95.7 nm in a second experiment. Incubation with growth plate enzymes reduced proteoglycan monomers to fragments with lengths that varied from less than 5 nm to 143 nm, increased the variability in monomer length, and destroyed proteoglycan aggregates. The enzyme treated monomers had an average length of 29.5 +/- 17.9 nm in one experiment and 35.2 +/- 17.0 nm in a second experiment. The smallest common fragments were 15 nm long and would be expected to contain about 15 glycosaminoglycan chains. This experiment demonstrates that enzymes extracted from growth plate chondrocytes can degrade the chondroitin sulfate-rich region of proteoglycan monomer core proteins, produce a range of monomer fragment sizes with less than 2% of the fragments shorter than 5 nm or longer than 100 nm, increase the variability in monomer length, and degrade proteoglycan aggregates.

Animals↗
PubMed1987

The role of proteases in the pathogenesis of osteoarthritis.

It is proposed that the cartilage contains enzymes which are responsible for the degradation of the principle components of the matrix, the proteoglycan and collagen. Measurement of acid, lysosomal bound proteases, or neutral proteases shows increases in proportion to the severity of the disease. Collagenase activity also increases in human osteoarthritic cartilage in the same manner. In an experimental model of osteoarthritis, induced by mechanical factors, enzymatic activity also increased. By inhibiting the enzyme activity with chelators, the arthritic process could be slowed.

Animals↗
PubMed1986

Degradative enzyme systems in cartilage.

There appears to be a final common pathway in the pathogenesis of osteoarthritis, regardless of the initiating cause. This involves an increase in degradative enzymes that arise from the cartilage. Both proteoglycan- and collagen-degrading enzymes, active at a neutral pH, increase in proportion to the severity of the arthritis until a final end-stage state is reached. This increase in enzyme activity may be triggered by release of a synovial messenger protein similar to interleukin-1. It is suggested by studies in an animal model that inhibition of these enzymes could lead to treatment of osteoarthritis.

Animals↗
PubMed1985

Comparative study of neutral proteoglycanase activity by growth plate zone.

The degradation of proteoglycans has been considered an essential step in the process of endochondral ossification. Neutral proteases, described in the growth plate, have been implicated in this process. If these neutral proteases are important in the endochondral process, their level of activity should be highest at the point where calcification is occurring. This study measures neutral protease activity with a quantitative viscometric assay throughout all zones of the bovine growth plate. The results demonstrate that the enzyme is present throughout all zones of the growth plate. However, enzyme levels in the lower hypertrophic and calcifying zones are significantly higher than anywhere else. The enzymes came from the cartilage cells and not from the invading vasculature. This implied proof of the role of neutral proteases in the endochondral process implies that by inhibiting this class of enzymes, one should be able to block endochondral ossification.

Animals↗
PubMed1984

Partial purification and characterization of a proteoglycan-degrading neutral protease from bovine epiphyseal cartilage.

Degradation of the proteoglycan matrix is considered an essential step in the process of calcification in the growth plate. This laboratory has just described the presence of a protease in human growth plate cartilage that degrades proteoglycan at neutral pH. We report here the isolation, partial purification, and characterization of these proteoglycan-degrading neutral proteases of bovine epiphyseal cartilage. It appears that there is more than a single enzyme active at neutral pH. These enzymes are of low molecular weight (below 30,000), poorly charged, and inhibited by metal chelating agents. Activity is best restored in the presence of zinc. This represents the first characterization of this important enzyme group.

Animals↗
PubMed1982

Patterns of proteoglycan degradation by a neutral protease from human growth-plate epiphyseal cartilage.

The hypothesis is widely held that proteolytic degradation of proteoglycans in the lower hypertrophic zone of the growth plate may be involved in the initiation of mineralization in the zone of provisional calcification. However, a neutral protease that is responsible for the degradation of proteoglycans in the growth plate has not been identified, isolated, and characterized. In the work reported here, neutral protease activity in the growth plate is demonstrated for the first time, and some of the properties of the enzyme are described. Proteoglycans subunits were prepared from bovine nasal cartilage and calf costal cartilage by equilibrium density-gradient centrifugation under dissociative conditions. The proteoglycan subunits were labeled with 14C-formaldehyde. Homogenates from human growth plates were examined for neutral protease activity using the proteoglycan subunits as substrates. Following incubation of the proteoglycan subunits with growth-plate homogenates at pH 5.3 and at pH 7.5 in the presence and absence of ten-millimolar magnesium chloride and calcium chloride, the digestion products were examined by gel chromatography on Sepharose-2B and 6B columns. Column eluants containing proteoglycan-subunit degradation products were monitored for uronic acid, hexose, and radio-activity. Maximum extensive degradation of proteoglycan subunits occurred at pH 7.5 in the presence of ten-millimolar magnesium chloride and calcium chloride.

Animals↗
PubMed1978

Palliation of inoperable head and heck cancer: combined intra-arterial infusion chemotherapy and irradiation.

Palliation of unresectable head and neck cancer remains a difficult problem. Because of excellent results reported by others with infusion of vinblastine, methotrexate, and 5-fluorouracil into the external carotid artery followed by irradiation before curative surgery, we applied this technic to 22 patients with advanced head and neck cancer. Fifteen patients from this group who had chemotherapy infusion followed by radiation therapy are compared with 21 patients who received radiation therapy alone. Both groups were similar in distribution of primary site, histology, and TNM stage. Of 15 patients, 14 (93%) had partial or complete tumor regression after both arterial chemotherapy infusion and irradiation, while 14 of 17 patients (82%) receiving primary irradiation had partial or complete response. Drug toxicity and complications related to infusion occurred in all patients. Most patients in both groups had short survivals (mean of 14.1 months in infusion chemotherapy and radiation vs 9.1 months in primary irradiation). One patient remains alive in the infusion group and two in the control group; however, all have recurrent disease. Results indicate a slight increase in survival time with the addition of infusionchemotherapy to irradiation in palliative treatment of head and heck cancer.

Adolescent↗
PubMedDate not supplied

Role of pin protrusion in the etiology of chondrolysis: a surgical model with radiographic, histologic, and biochemical analysis.

We studied a model of pin protrusion in rabbit hips to determine if chondrolysis is produced. Enzymatic degradation of the articular cartilage remote from the pin site and mechanical destruction of the acetabulum occurred. Loss of proteoglycans in the articular cartilage averaged approximately 30%, and matched the increase in neutral protease activity. This presumably accounts for the loss of height that occurs in chondrolysis, but throughout the study, the joint space did not narrow; instead, it increased. This suggests that some other factor is needed to produce chondrolysis, such as a slip or an immune response.

Animals↗