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Biomedical subjects

M Zukowski

Publications and source records attributed to M Zukowski.

26 records · Page 2Linked to original sources
PubMed1997

The effect of chemosurgical peels and dermabrasion on dermal elastic tissue.

Chemosurgical peel is a technique that has been used widely by plastic surgeons and dermatologists to remove fine and deep wrinkles of the skin. However, the reaction of elastic tissue to the cutaneous application of commonly used chemical peeling agents has not been defined. This study comparatively assessed the alteration in dermal histology and mechanical properties of skin following treatment with 25% and 50% trichloroacetic acid, Baker's phenol solution, and dermabrasion. Yucatan minipigs served as the animal model. The skin was analyzed at five intervals over 6 months after treatment using histologic, quantitative, and mechanical analysis (hematoxylin and eosin, elastic tissue, and Sirius red stains, computerized digital morphometry, and a tensiometer). At 6 months we found no change in the quality, structure, or arrangement of elastic fibers in skin treated with a single application of 25% and 50% trichloroacetic acid or dermabrasion when compared with untreated skin. Skin treated with Baker's phenol solution showed a marked morphologic change in the elastic fibers. The fibers within the regenerated zone of dermis were sparse, wispy, and immature at 6 months after treatment. Preliminary tensiometric analysis of phenol-treated skin at 6 months indicated that the skin was stiffer and weaker. This study questions the possibility of long-term change to the skin by the deep penetration of caustic chemicals to remove wrinkles and rejuvenate the skin.

Animals↗
PubMed1996

Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase.

Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. We report herein the isolation of a cDNA encoding a novel protein kinase designated MAPKKK5 from a human macrophage library. The nucleotide sequence predicts that MAPKKK5 encodes an open reading frame of 1374 amino acids with all 11 kinase subdomains. The putative catalytic domain of MAPKKK5 shows significant sequence homology to the kinase domains of the MAPKKK/MEKK level protein kinases from mouse MEKK2 and -3, Drosophila melanogaster PK92B, Saccharomyces cerevisiae STE11, and Schizosaccharomyces pombe BYR2. Northern blot analysis showed that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. When transiently expressed in COS and 293 cells, MAPKKK5 markedly activated c-Jun N-terminal kinase or stress-activated protein kinase, but not MAPK/ERK. Furthermore, MAPKKK5 that was immunoprecipitated from transfected 293 cells was able to phosphorylate and activate MKK4 in vitro, suggesting that MAPKKK5 may be an upstream activator of MKK4 in the c-Jun N-terminal kinase pathway.

Amino Acid Sequence↗
PubMed1996

Treatment of stretch marks with the 585-nm flashlamp-pumped pulsed dye laser.

BACKGROUND: Striae, or stretch marks, are very common skin disorders that do not impair bodily function, but are of considerable cosmetic concern to many patients. Traditionally, treatment options have been very limited. This study examines the results of treating striae using the 585-nm pulsed dye laser. Stimulation of a variety of wound healing processes has been attributed to low energy laser therapy. Clinically, improvement of hypertrophic and erythematous scars with the 585-nm pulsed dye laser at energy densities of 6-7 J/cm2 is well established. Since striae are dermal scars, evaluation of this same therapy to treat striae was undertaken. OBJECTIVE: To evaluate the effectiveness of the 585-nm flashlamp-pumped pulse dye laser in treating cutaneous striae. METHODS: Thirty-nine striae were treated with four treatment protocols. These treated striae were compared with untreated striae controls in the same patient. The patients ages ranged from 23 to 52 years, with an average age of 36 years. The average age of the treated striae prior to initial treatment was 14 years (range, 8 months to 32 years). Treatment parameters included spot sizes of 7 and 10 mm and fluences of 2.0, 2.5, 3.0, and 4.0 J/cm2. Response to therapy was evaluated through clinical grading, sequential photography, and optical profilometry at a blinded laboratory. Skin biopsies were also examined with light microscopy from two of the 39 striae that were treated. RESULTS: Subjectively, striae appeared to return toward the appearance of normal skin with all protocols. However, the protocol with 10-mm spot size using 3.0 J/cm2 fluence improved the appearance of striae better than the other treatment protocols. Objectively, shadow profilometry revealed that all treatment protocols reduced skin shadowing in striae. This result corresponds with surface patterns of striae returning to that closely resembling adjacent normal skin surface patterns. Histologically, using hematoxylin and eosin stains as well as elastin strains, striae treated with a low fluence pulsed dye laser treatment protocol regained normal appearing elastin content when compared with normal (non-striae) skin adjacent to the treated striae. CONCLUSION: Treatment with the 585-nm pulsed dye laser at low energy densities was shown to improve the appearance of striae. Apparent increased dermal elastin was also observed 8 weeks posttherapy and possibly contributed to the improvement seen in the study patients.

Adult↗
PubMed1991

Enhanced stability of subtilisin by three point mutations.

This study was undertaken to characterize the effect of three point mutations made on aprA-subtilisin on the stability of the protein to both heat- and detergent-induced denaturation. Asparagine residues at positions 109 and 218 were replaced with serine residues to prevent the possible cyclization between these asparagines and the adjacent glycine residues and hence to increase the long-term stability. The effect of these substitutions on conformational stability was examined by thermal denaturation. At high calcium concentrations, the Ser109-substituted analog showed a 3 degrees C higher transition temperature than that of aprA-subtilisin, while the Ser218 substituted analog had a 4 degrees C higher transition temperature. The analog with both changes had a 7 degrees C higher transition temperature than that of the original aprA-subtilisin, indicating that the contributions of the individual mutations were additive. The analog with both mutations also exhibited increased stability in the presence of sodium dodecyl sulfate (SDS) when compared to aprA-subtilisin. In addition to the above two mutations, the asparagine at position 76, located in the high affinity Ca(2+) binding loop of subtilisin, was changed to aspartic acid. The effect of this mutation on the thermal stability of the protein was examined at different calcium concentrations. The analog with all three mutations exhibited little dependence on calcium concentration below 1 mM levels, while the proteins without the mutation at asparagine-76 displayed a strong dependence of melting temperature on Ca(2+) concentration in this range. At much higher calcium concentrations, the analog with three mutations showed an increase in stability similar to that observed with aprA-subtilisin. The analog with three mutations also exhibited greater stability to SDS-induced denaturation than both aprA-subtilisin and the Ser109- and Ser218-substituted analogs. The activation energy barrier for loss of structure in 1% SDS for the analog with all three mutations was increased over that for aprA-subtilisin by 16 kcal/ml. These results suggest that the mutation of asparagine-76 to aspartic acid increases the affinity of the primary Ca(2+) binding site.

Circular Dichroism↗
PubMed1988

Stability of aprA-subtilisin in sodium dodecyl sulfate.

The effect of sodium dodecyl sulfate (SDS) on the structure and activity of aprA-subtilisin, a secreted bacterial serine protease which is 85% homologous to subtilisin BPN', was examined. The addition of SDS resulted in the slow conversion of the subtilisin from the intact protein to the completely unfolded form of the enzyme. No intermediates between these two populations were detected. This conversion was accompanied by decreased activity, disruption of tertiary structure, a change in the mobility of the protein when subjected to SDS-polyacrylamide gel electrophoresis, and an increase in the apparent Stokes radius of the protein. After 2 h in 1% SDS at 20 degrees C, 25% of the subtilisin was still intact and active. The amount of protein existing in the unfolded form was increased by increasing the length of time in SDS, by increasing the concentration of SDS, and by increasing the temperature of the subtilisin-SDS solution. Analysis of the dependence of the rate of unfolding on SDS concentration indicated that one SDS micelle can destroy two protein molecules. The activation energy for the SDS-induced denaturation of aprA-subtilisin was 20 kcal mol-1, indicating that unfolding of the protein could be the rate-limiting step.

Bacillus subtilis↗
PubMed1987

Chest-wall deformity following soft-tissue expansion for breast reconstruction.

We have presented a case in which the presumed pressure effects of tissue expansion caused multiple nondisplaced rib fractures of the anterior thorax in a patient undergoing breast reconstruction. Although the deformity was severe, a satisfactory cosmetic result was obtained and there have been no clinically significant sequelae during a 1-year follow-up period. The degree of bony deformation was most likely enhanced by the combination of this patient's severe osteoporosis, chronic steroid use, and peripheral vascular disease. The fragility and ease of fracture in the bones of osteoporotic postmenopausal females and the long-term effects of steroids on tissues is well known. We believe this observation to be important, since many reconstructed patients are postmenopausal and have variable degrees of osteoporosis. Many undergo adjuvant chemotherapy with steroids and antihormonal agents, and this group of women may therefore be at a greater risk for the occurrence of pressure deformities. The incidence and long-term significance of such deformities are not known. The reconstructive surgeon should be alert to the possibility of this phenomenon occurring as a result of tissue expansion in the patient with severe osteoporosis, peripheral vascular disease, or chronic steroid use.

Breast↗