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Waldemar L Olszewski

Publications and source records attributed to Waldemar L Olszewski.

45 records · Page 3Linked to original sources
PubMed2003

Tolerogenic properties of dendritic cells in allografting.

In this review we present current views on the mechanism of prolongation of organ allograft survival mediated by donor dendritic cells. The contemporary research focuses on problems as: a) is the DC microchimerism the cause or consequence of long-term graft acceptance, b) what is the role of DCs, which are derived from bone marrow, with respect to the cell trafficking and dissemination and site-specific function as related to the mechanism of tolerance. There is a large body of evidence indicating that DC play certain regulatory role in the process of induction of tolerance. Immaturity of DCs, bone marrow lineage, method of dissemination by infusion in suspension or from the vascularized bone marrow graft, location after transplantation and environment inhibiting their maturation seem to be the prerequisites for displaying their tolerogenic activity. The subtle balance between induction of tolerance or immunization does not allow today to use immature DC in clinical practice. Further studies, in particular in human recipients, are needed.

Bone Marrow↗
PubMed2002

The soluble tumor necrosis factor receptor I is an early predictor of local infective complications after colorectal surgery.

The clinical implications of increased cytokine levels after major surgery remain unclear. In this study, systemic concentration of a spectrum of cytokines, including interleukins IL-6, IL-8, IL-10, IL-1ra, and soluble tumor necrosis factor receptor-I (sTNF-RI) was examined in patients with and without postoperative septic complications following colorectal surgery. Although there were no significant changes in IL-1beta, TNF-alpha, and IL-8 serum levels during the observation period, there was a significant rise in IL-6, IL-1ra, and sTNF-RI concentrations in the entire group of patients between postoperative day 1 and 14. There were no differences between the group without and with local complications when IL-6, IL-1ra, and IL-10 were examined. The serum levels of sTNF-RI, IL-1ra, and IL-6 were found to be sensitive indicators of the pro- and anti-inflammatory response to the surgical trauma, but only sTNF-RI turned out to be a sensitive early marker of local septic postoperative complications in patients with colorectal carcinoma.

Antigens, CD↗
PubMed2002

The pathomechanism of posttraumatic edema of lower limbs: I. The effect of extravasated blood, bone marrow cells, and bacterial colonization on tissues, lymphatics, and lymph nodes.

BACKGROUND: The mechanical injury of soft tissues and bones of lower extremities is frequently followed by long-lasting edema at the site of trauma and distally. The pathomechanism of this complication remains unclear. Venous thrombosis and interruption of lymphatics are considered to be the main etiologic factors. We propose a concept that protracted healing of injured tissues and bones with involvement of the regional lymphatic system (lymphatics and nodes) is responsible for persistence of edema. The events affecting the first (scavenging) phase of healing of traumatized tissues, such as hematoma, translocation of bone marrow cells to soft tissues, and colonization by microorganisms, and in particular their effects on lymphatics and lymph nodes, were studied. METHODS: Mongrel dogs weighing 15-20 kg were used. Fresh blood or bone marrow cell (BMC) suspension was injected subcutaneously or intralymphatically into the paw. Strains of saprophyte bacteria residing on the skin surface were cultured and injected intradermally. Oil-contrast lymphography was performed before and after injections to evaluate the changes in lymphatics and nodes. Biopsy samples of paw skin, subcutaneous tissue, and regional lymph nodes (LN) were taken. The responsiveness of LN lymphocytes was studied in autologous mixed cultures with peripheral blood lymphocytes (PBL), BMC, and cultured bacteria. RESULTS: The PBL from subcutaneously injected blood were evacuated by the lymphatic route at a rate of 1-3%/6 hr. There was no thrombosis of lymphatic vessels or obstruction of LN sinusoids. The BMC evoked major inflammatory changes in both the skin and the LN. Bacteria caused local inflammation, dilatation of lymphatics, and destruction of node parenchyma. Autologous BMC and PBL stimulated LN lymphocytes in a 6-day culture. The responsiveness of lymph node lymphocytes to previously subcutaneously injected bacterial antigens was increased. CONCLUSION: The extravasated blood did not produce changes in skin, subcutaneous tissue, and lymphatics; however, it stimulated LN lymphocytes. The BMC and saprophyte bacteria caused major local and lymph node inflammatory response. All these factors may contribute to the local edema in the initial phases of healing of traumatized tissues.

Animals↗
PubMed2002

Contractility patterns of normal and pathologically changed human lymphatics.

Human leg lymphatics contract spontaneously, rhythmically propelling lymph. This intrinsic property regulates the fluid environment in the intercellular space in skin, connective tissue, and perivascular spaces. The pressures generated by lymphatic contractions constitute the main force for lymph flow. This mechanism is of utmost importance during night rest, anesthesia, and immobilization, as well as in those with damaged peripheral motor neurons. All supporting forces are only secondary to those created by spontaneous lymphatic contractions. The intrinsically regulated lymph flow depends on tissue fluid and lymph production rate. The transport capacity of lymphatics adjusts to the fluid load. Under physiological conditions, limb activity and position only slightly change lymph flow. In obstructive lymphedema, high lymph pressures can be observed. They are usually generated by leg muscle contraction, whereas the spontaneous contractility of lymphatics becomes ineffective in lymph transport because of low generated pressures and lymphatic valve insufficiency. The knowledge of lymph flow in normal and lymphedematou limbs will be useful in the derivation of rational treatments for lymphedema.

Humans↗
PubMed2002

De novo lymph node formation in chronic inflammation of the human leg.

Organized lymphoid tissue is the first line of antigenic defense. Recruited by antigen located in the non-lymphoid tissues, the infiltrating lymphocytes often organize themselves as follicle-like structures that contain germinal centers, similar to those in secondary lymphoid follicles of lymph nodes. These extranodal tertiary lymphoid follicles are found in various autoimmune diseases. We investigated 153 patients with protracted lymph stasis of the lower limb, caused by lymphatic damage incurred through soft tissue bacterial inflammation or mechanical trauma of soft tissues and bones. In 10% of patients with post-inflammatory, and in 25% with post-traumatic lymph stasis, "newly-formed" lymph nodes were detected by means of lymphoscintigraphy. They were located along the large calf and thigh veins. Although scattered nodes are normally detected in these areas, the number and total mass of visualized nodes substantially exceeded those seen in healthy subjects. The calculated surface area of "newly formed" nodes attained 50-70% of the area of ipsilateral inguinal nodes. Histological evaluation of nodal biopsy specimens in three such patients revealed, in one, a lymph node structure without differentiation into cortical and medullary areas, and in a second, a follicle-like structure within a dilated lymph vessel. Lymph clot removed from another dilated vessel contained a lymphocyte/dendritic cell aggregate. The "newly formed" nodes likely originate from primordial lymphoid follicles and/or lymphoid cell aggregates formed in response to chronic stimulation by microbial products and self-antigens from the damaged tissues. Detection of "newly-formed" lymph nodes in the limb is evidence of an ongoing inflammatory process and requires appropriate therapy.

Chronic Disease↗
PubMedDate not supplied

Low recruitment of immune cells with increased expression of endothelial adhesion molecules in margins of the chronic diabetic foot ulcers.

Diabetic foot skin close to an ulcer shows only a few infiltrating cells compared to nondiabetic inflamed tissues. Diabetes is characterized by thickened basement membrane of the blood arterioles and capillaries. This may affect the transcapillary transport of immune humoral factors and cells to the extravascular space. We analyzed by immunohistochemistry the phenotype and expression pattern of adhesion molecules on leukocyte, dermal fibroblast, and endothelial cells in diabetic foot ulcers. Although there was accumulation of granulocytes on the surface and superficial layers of the granulation tissue, rare perivascular granulocyte infiltrates in the dermis were seen. Moreover, lack of macrophage and CD3+ T cell infiltrates was observed. In contrast, there was increased intensity of CD1a staining of Langerhans cells in the epidermis and papillary dermis (p < 0.05). Fibroblasts revealed increased presence in the ulcer margins compared with normal skin (p < 0.05). Skin endothelial cells expressed stronger von Willebrand factor and E-selectin compared with normal skin (p < 0.05). Our study provides evidence that increased expression of endothelial cell adhesion molecules responsible for immunocyte extravasation is not associated with increased inflammatory cell infiltration of the ulcerated diabetic foot tissue. We suggest that the healing process of diabetic foot ulcers may be hampered by mechanisms decreasing accumulation of leukocytes. This implies that pharmacological or biological stimulation of leukocyte extravasation into the ulcer tissue should be tried.

Adult↗
PubMedDate not supplied

Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers.

Keratinocytes and dermal endothelial cells, excluding leukocytes that infiltrate wounds, are the main source of soluble factors regulating healing of skin ulcers. We used immunohistochemistry to analyze the expression of various chemotactic and growth factors and their receptors in the margin of diabetic foot ulcers and in normal nondiabetic foot skin. Our study found significantly elevated expression of transforming growth factor-beta1 (TGF-beta1) and type I TGF-beta receptors (TGFbetaR1), granulocyte macrophage colony-stimulating factor (GM-CSF), and epidermal growth factor (EGF) in keratinocytes in the ulcer margin (p < 0.05). Significantly increased expression of monocyte chemotactic protein-1, GM-CSF, CXCR1, and TGFbetaRI and decreased expression of interleukin (IL)-10, IL-15, and TGF-beta1 were observed in ulcer dermal endothelial cells (p < 0.05). There was a lack of up-regulation of IL-8, CCR2A, IL-10 receptor, GM-CSF receptor, platelet-derived growth factors and their receptors, vascular endothelial growth factor and its type II receptor, EGF receptor, insulin-like growth factor-1, and nitric oxide synthase-2 in both KCs and endothelial cells in the ulcer. Finally, there was a lack of up-regulation of IL-10 and IL-15 in keratinocytes and of EGF, basic fibroblast growth factor, and nitric oxide synthase-3 in endothelial cells in the ulcer margins. The enhanced expression of some factors responsible for KC behavior could suggest an unimpaired capacity of keratinocytes to reepithelialize the margin of diabetic foot ulcers. However, lack of up-regulation of some angiogenic and leukocyte chemotactic factors, associated with the reduced influx of immune cells, may account for a poor formation of granulation tissue and chronicity of ulcer epithelialization.

Adult↗
PubMedDate not supplied

RNA interference--significance and applications.

RNA interference (RNAi) is a post-transcriptional, highly conserved process in eukaryotes that leads to specific gene silencing through degradation of the target mRNA. This mechanism is mediated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. The dsRNA is processed into small interfering RNA (siRNA) by an enzyme called Dicer, and the siRNAs are then incorporated into a multi-component RNA-induced silencing complex, which finds and cleaves the target mRNA. In plants and worms, amplification of the silencing signal and cell-to-cell RNAi spreading is observed. The proposed biological roles of RNAi include resistance to viruses, transposons (mainly in plants), and the silencing and regulation of gene expression, particularly during development. In developmental gene control, specific small RNAs (micro RNA and small temporal RNA) are involved, which are processed in the same way as dsRNAs but act at the level of translation. RNAi technology has become a powerful tool in functional genomic analyses and may prove to be a useful method to develop highly specific gene-silencing therapeutics against viral infections and cancer in the future.

Animals↗