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Biomedical subjects

M Dobke

Publications and source records attributed to M Dobke.

At least 19 recordsLinked to original sources

Mutilating facial acne conglobata.

Acne conglobata, a severe form of acne vulgaris, often produces pronounced disfigurement. We describe a 23-year-old man with acne conglobata. Although this type of acne is often more marked on the back rather than on the face, our patient was unusual in that it was localized mainly to the cheeks. Conventional medical therapy was ineffective, or contraindicated. Radical surgical excision with subtotal removal of cheek skin and subcutaneous tissue was performed with an excellent result.

Acne Vulgaris↗

1,25-Dihydroxyvitamin D3 increases collagen production in dermal fibroblasts.

The effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on proliferation and collagen type I and type III production in cultured human fibroblasts was examined. Previous studies have identified receptors for the vitamin in human dermal fibroblasts, and have suggested the skin to be a target tissue. While many studies examining keratinocyte modulation by 1,25-(OH)2D3 have been undertaken, very few have been performed on dermal fibroblasts. Neonatal foreskin fibroblast cultures were examined for cell number, extracellular collagen accumulation, and collagen mRNA levels, after 5 days exposure to 1,25-(OH)2D3 at a concentration of 10(-7) M. The vitamin significantly suppressed (P < 0.01) the proliferation of fibroblasts cultured in the presence of serum. Day 5 cell culture supernatants showed a significant per cell increase in collagen type I (P < 0.05) and type III (P < 0.01) as measured by ELISA. Type I collagen production in exposed cells was 11.64 + 0.531 microgram/10(6) cell vs. 9.53 + 0.500 microgram/10(6) cells in unexposed cells. Type III collagen production was 0.601 + 0.012 microgram/10(6) cell in exposed cells and 0.247 + 0.008 microgram/10(6) cells in unexposed cells. mRNA levels were increased after a 4-day exposure to 10(-7) M 1,25-(OH)2D3 for both type I (2.5-5-fold) and type III (5.5-7.76-fold) collagen. These results suggest a novel effect of increased collagen production by dermal fibroblasts upon exposure to 1,25-(OH)2D3 that is independent of proliferation.

Autoradiography↗

[Attempts at reconstitution of skin continuity].

Biological and clinical principles of living skin equivalents preparation and application are reviewed. Different models of living skin equivalents, based on both autogenic of allogenic elements, are described.

Adolescent↗

Complement activation and the toxicity of stroma-free hemoglobin solutions in primates.

The toxicity of hemoglobin solutions was studied in the context of their ability to activate serum complement (C). Three bovine polymerized hemoglobin solutions (BPHSs) with different degrees of purity were used for experiments in vitro and in vivo. BPHS-1 contained bacterial endotoxins (E) (5 EU/ml) and stromal phospholipids (PLs) (1.2 mg/dl), BPHS-2 contained only PLs (2.0 mg/dl), while BPHS-3 was completely free of both contaminants. C-activation was studied by the direct measurement of C3a, C4a, and C5a des Arg fragments, using commercially available RIA kits. During 1 hour of incubation with fresh monkey plasma, BPHS-1 and -2 activated both pathways of C, while BPHS-3 caused no activation of any factor. In vivo, Hb solutions were used to replace one-third of blood volume in three groups of six Coebus monkeys each, while fresh homologous plasma was used in a control group of four animals. Impure solutions activated the alternative pathway of C and caused significant reactions of the circulating blood (thrombocytopenia, leukopenia, and disseminated intravascular coagulation) associated with multiorgan dysfunction (cardiac arrhythmias, hypoxemia, reduction of renal clearance of endogenous creatinine, and elevation of liver enzyme SGPT). The pure solution neither activated C nor caused any reaction in the circulating blood. However, it caused a moderate degree of direct tissue injury, evidenced by transient reduction of creatinine clearance and elevation of SGPT. These observations suggest that impure and pure Hb solutions carry separate mechanisms of toxicity. Complement, activated by toxic impurities, plays an active role in the toxicity of impure solutions. C-activation in vitro could be used as a screening test of biocompatibility.

Animals↗

Burn wound sepsis may be promoted by a failure of local antibacterial host defenses.

Little attention has been focused on the local burn wound environment, even though burn wound sepsis is a common cause of death in the burn victim. To characterize the effect of the local burn wound environment on neutrophil function and metabolism, the opsonic activity of blister fluid specimens against Pseudomonas aeruginosa was measured as was the effect of blister fluid on control neutrophil oxygen consumption using preopsonized zymosan and f-met-leu-phe (FMLP) as stimuli. Blister fluid did not support the killing of P. aeruginosa by normal neutrophils as well as normal serum. Additionally, blister fluid inhibited zymosan-stimulated, but not FMLP-stimulated, neutrophil oxygen consumption. The inhibitory effect of blister fluid on zymosan-stimulated oxygen consumption correlated with the extent of complement activation, measured as C3d or C3AI (p less than 0.01). That blister fluid did not inhibit the FMLP-mediated respiratory burst supports the concept that the blister fluid inhibitory effect on the zymosan-mediated respiratory burst was mediated through the complement receptor. These findings that blister fluid can affect the bactericidal and metabolic activity of normal neutrophils support the concept that cellular function can be altered by the microenvironment in which the cells are bathed. This potential impairment of host defenses within the burn wound could predispose the burn victim to burn wound sepsis.

Adolescent↗

Failure of local immunity. A potential cause of burn wound sepsis.

Destruction of the skin barrier by thermal injury removes the major local defense barrier to bacteria. To determine whether a local defect in immunity also existed, the opsonic activity of blister fluid against Staphylococcus aureus and Pseudomonas aeruginosa as well as neutrophil chemotaxis were measured. The results of these studies indicated that blister fluid could not opsonize Pseudomonas. A series of repletion experiments indicated that the opsonic defect for Pseudomonas was not due to the presence of inhibitors but was due to the lack of normal serum factor(s). Although both the level of immunoglobulins and complement components in the blister fluid was depressed, the cause of the opsoninopathy appeared to be due to local consumption of complement in the burn wounds. In addition to the opsoninopathy, both neutrophil chemotaxis and random migration were also depressed. In conclusion, a burn injury appears to cause severe impairment of both cellular and humoral local immunity, which could predispose these patients to burn wound sepsis.

Adolescent↗

Circulating fibronectin in burned patients.

Plasma and serum fibronectin levels were determined in a serial study of 24 non-septic burned patients by means of the passive haemagglutination test and electroimmunoassay. The results showed a consistent pattern of observed changes: a decrease of circulating fibronectin in the initial (first 72 hours post-burn), and during post-operatyive period (usually by the end of the first week and during the second week post-injury). Fibronectin level decreases were more remarkable than total serum protein concentration changes following injury, as reflected by decrease of fibronectin/protein ratio.

Adolescent↗

Biomechanics of the pulmonary autograft valve in the aortic position.

Pulmonary autograft valve replacement has been simulated by implanting the pulmonary valve into the aortic position of the same cadaver heart from both human and porcine sources. The forces acting on the pulmonary valve leaflets have been calculated on the basis of a triaxial ellipsoid mathematical model. These forces on the pulmonary autograft valve were shown to be essentially similar to those previously reported for aortic valve leaflets. Biomechanical measurements have been made on the simulated autograft valves and on the isolated pulmonary valve cusps. The tensile strengths of the pulmonary valve cusps in both circumferential and radial directions were roughly three times greater than those of aortic valve cusps. This indicated the ability of the pulmonary valves to accept, ab initio, aortic valve closing pressures. Pressure-induced changes in dimension, calculated on the basis of diameters of the simulated pulmonary autograft root, also indicated that the distensibility of the autograft valve was limited. It reached a maximum at 30 mm Hg (4 kPa) without any suggestion of further distension to the point of distortion and incompetence. The combination of the calculated forces acting on the valve and the biomechanical measurements have shown that pulmonary valves used as autograft aortic valve replacements are able to tolerate aortic pressures from the time of implantation. These experimental results from simulated autografts support the clinical use of this valve over the past 13 years.

Animals↗