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J A Witkowski

Publications and source records attributed to J A Witkowski.

At least 73 records · Page 4Linked to original sources

Tissue culture studies of muscle disorders: Part 2. Biochemical studies, nerve-muscle culture, metabolic myopathies, and animal models.

This review continues with studies of protein, lipid, and purine metabolism of Duchenne muscular dystrophy (DMD) cells in vitro and of muscle cells in combined culture with nerve cells. In vitro studies of human metabolic myopathies are tabulated. Results using the hamster, chicken, and mouse (dy25, dy, mdg, and mdx) myopathies are discussed. Interesting findings include suggestions of altered collagen synthesis by DMD cells. Analysis of cell proteins by two-dimensional gel electrophoresis and the use of combined nerve-muscle cultures remain important areas of development. It is disappointing that so few attempts have been made to repeat significant findings in this field, and when a number of laboratories have examined the same phenomenon, the results are often contradictory. It remains to be shown how these various abnormalities found in cells in vitro are related to each other and to those pathologic features of diseased muscle observed in vivo.

Animals↗

Behaviour of Duchenne dystrophy fibroblasts in collagen gels.

In order to clarify the possible involvement of the cell surface in the pathogenesis of Duchenne muscular dystrophy, we have examined the behaviour of fibroblasts cultured from Duchenne patients in hydrated collagen lattices. No differences could be found between Duchenne and normal skin fibroblasts, either after initial seeding or following prolonged culture within the collagen gel.

Cell Adhesion↗

Cephalosporins in cutaneous infections. A prospective comparison of two dosage regimens of ceftazidime for therapy of skin and skin structure infections.

The safety and efficacy of ceftazidime administered as 0.5 g every 8 hours (q8h) or 1.0 g q8h for at least 5 days were compared in 197 patients and found to be effective in the treatment of cellulitis, abscesses, skin ulcers, and wound infections. Staphylococcus aureus was the predominant pathogen in both treatment groups with approximately half of the isolates from each treatment group being gram-positive. Pseudomonas aeruginosa was the most common gram-negative isolate. P. aeruginosa, Proteus mirabilis, and Escherichia coli each comprised 5-12% of the isolates from each treatment group. Clinical cure or improvement was achieved in 98.7% of the patients in each treatment group. Concurrently with clinically successful treatment, a high rate of bacteriologic eradication without superinfection was achieved with the 0.5-g regimen (84% of all isolates) and the 1.0-g regimen (92%).

Adolescent↗

The effect of monensin on cell aggregation of normal and dystrophic human skin fibroblasts.

Measurements of aggregation kinetics using couette viscometry show that freshly trypsinized skin fibroblasts from patients with Duchenne muscular dystrophy have values of intercellular adhesiveness approx. 40% those of normal cells. If cells are allowed to recover from the effects of trypsinization (by incubation for 2 h at 37 degrees C in serum-containing medium) the intercellular adhesiveness of both cell types increases, and normal and Duchenne cells aggregate to the same extent. Exposure to the ionophore monensin during the recovery phase leads to suppression of recovery in both cell types, and this effect of the drug is greater in Duchenne fibroblasts. These results are discussed in relation to other data on the reported differential effects of trypsin and monensin on normal and Duchenne fibroblasts.

Cell Aggregation↗

Cell surface abnormality in clones of skin fibroblasts from a carrier of Duchenne muscular dystrophy.

We have previously reported that skin fibroblasts from patients with Duchenne muscular dystrophy (DMD) have a lower intercellular adhesiveness than control cells, and that cells from carriers of DMD have normal adhesiveness instead of the expected intermediate value. We have now cloned skin fibroblasts from a carrier of DMD (subject AS) who is also heterozygous for G6PD B/G6PD Mediterranean and determined the intercellular adhesiveness and G6PD phenotypes of the clones. G6PD activity was determined using the 2d-G6P/G6P ratio method. Normal cells had a percentage utilisation of 7.31% and uncloned cells from AS a value of 25.16%. Of 16 clones, 15 had normal values (mean 8.72%) while one clone was G6PD Med with a value of 57.5%. Mean intercellular adhesiveness of normal and uncloned cells from AS were 2.95 and 2.90 respectively. Of 11 clones tested, nine had normal values of adhesiveness (mean 3.1) and all these clones were G6PD B. The single G6PD Med clone had a value of 0.88, compared with 1.39 for DMD cells. We have no explanation at present for the single clone that was G6PD B but DMD-like on aggregation.

Adhesiveness↗

A novel procedure for pattern analysis of features present on freeze-fractured plasma membranes.

We have used statistical methods for the analysis of two-dimensional point patterns to derive quantitative descriptions of the distributions of caveolae on freeze-fractured muscle fibre membranes. One method was based on a quadrat analysis while the second was a new procedure that we have called the interpoint distance analysis. We show that the latter analysis can unambiguously distinguish random, clustered and dispersed patterns and that a single parameter can be derived that can be used to compare different distributions. It is readily applicable to patterns containing several hundred points. Practical details of the method are given and a simple algorithm that can be implemented on a microcomputer is provided. The interpoint distance analysis should prove generally useful in situations where the two-dimensional distribution of objects has to be quantified.

Cell Membrane↗

Duchenne muscular dystrophy: studies of cell motility in vitro.

Duchenne muscular dystrophy (DMD) is a severe degenerative disorder of skeletal muscle. It has been suggested that an abnormality of the plasma membrane may be responsible for the pathogenesis of DMD, and a number of cell surface changes have been described in DMD muscle fibres and other cell types. Alterations in cell-to-cell and cell-to-substratum adhesiveness have been reported for DMD cells and we have determined whether these alterations in cell adhesiveness affect migration of cells from DMD muscle explants. DMD cells move more rapidly and spend less time at rest than do normal or DMD carrier cells, although the differences were statistically significant only for the latter cells. An inverse relationship between cell speed and contact with surrounding cells was not observed. All cells tended to persist in their direction of movement, and there were no differences between the types of cells studied. Our results support the view that there may be a cell surface defect in DMD.

Cell Adhesion↗

Candidiasis: the isomorphic response.

Two uncontrolled insulin dependent diabetic patients had Candida albicans infection with the unique manifestation of erythematous scaling papulopustules at the sites of excoriation. In one patient, the clinical presentation suggested herpes zoster. Recognition of this picture and the contributing factors, i.e. Candida infected finger nails and elevated blood sugar will permit early use of appropriate antifungal therapy.

Aged↗

Ceforanide compared with cefazolin in skin and soft tissue infections.

The response of serious skin and skin structure infections to ceforanide 1 gm every twelve hours or cefazolin 1 gm every eight hours was evaluated in ninety-six patients hospitalized for treatment. Most of the patients had decubitus ulcers; predominant pathogens were Staphylococcus aureus, Escherichia coli, and Proteus mirabilis. Ceforanide produced a satisfactory clinical response in 89 percent (forty-eight of fifty-four) of the patients evaluated and eradicated 90 percent (seventy-four of eighty-two) of the pathogens. Although the clinical response of forty-two cefazolin-treated patients was similar (satisfactory response in 86 percent, thirty-six patients), only 81 percent (forty-eight of fifty-nine) of the pathogens were eradicated. Both ceforanide and cefazolin were very well tolerated systemically and locally.

Adult↗