Biomedical subjects

W L Olszewski

Publications and source records attributed to W L Olszewski.

At least 19 recordsLinked to original sources

PubMed2005

The effectiveness of long-acting penicillin (penidur) in preventing recurrences of dermatolymphangioadenitis(DLA) and controlling skin, deep tissues, and lymph bacterial flora in patients with "filarial" lymphedema.

Dermatolymphangioadenitis (DLA) is a common and serious complication of so-called "filarial" and bacterial non-filarial lymphedema of the limb, affecting skin, lymphatics and lymph nodes. In our previous studies, we demonstrated that more than 60% of patients revealed presence of bacterial isolates in deep tissues, tissue fluid and lymph from the lymphedematous limbs. The question remained open whether elimination or suppression of bacteria dwelling in lymphedematous tissues by administration of low doses of penicillin for long time periods would prevent recurrence of DLA attacks. In this study, we retrospectively evaluated a self/community-selected group of patients with lymphedema of the lower limbs with respect to the efficacy of long-acting penicillin in preventing episodes of DLA. There were no microfilariae or anti-filarial antibodies detected in the investigated group. The questions we asked were: (a) how effective is the benzathine penicillin in preventing recurrences of DLA attacks and (b) how does its long-term administration influence the bacterial spectrum of leg skin, deep tissues, lymph and lymph nodes and sensitivity to antibiotics. Two randomly selected groups of patients, receiving and not receiving penicillin during the same period of time, were compared. Evidently lower recurrence rate of DLA was observed in the treated group (p < 0.002). There was increased prevalence of cocci and gram-positive bacilli with a concomitant decrease of gram-negative bacilli on the foot and calf skin surface. Simultaneously, decreased prevalence of gram-positive cocci and gram-negative bacilli isolates in limb deep tissues and lymph was seen. No resistance to penicillin and other tested antibiotics developed in isolates from the skin surface, deep tissues and lymph. We conclude that long-lasting penicillin is effective in preventing recurrent DLA attacks.

Adult↗

PubMed2004

Profiling of normal human leg lymph proteins using the 2-D electrophoresis and SELDI-TOF mass spectrophotometry approach.

The parenchymatous cells are supplied by nutrients transported in fluid from blood across the capillary wall. This fluid, called tissue fluid (TF), contains proteins originating from plasma as well as those synthesized and secreted by tissue cells. The protein composition of TF remains largely unknown. The TF which has entered lymphatics is called lymph (L). Harvesting L and measuring its proteins concentrations and identifying them provide an insight into biochemical processes in the TF. Here we describe our initial evaluation of the normal human prenodal L protein profile of m.w. 2.5 to 12.5 kDa using the ProteinChip SELDI MS system and compare it with that of plasma (P) protein. This is the first study in the literature providing evidence for the presence of the so far non-identified proteins in L as well as proteins identified in L but absent from P and conversely present in P but not in L. Evident differences between paired L and P samples have been found, along with similarities. Thirteen proteins were detected in P and seven in L in the region of 2.5 to 12.5 kDa. Five identical proteins, although of different relative intensity, were found in L and P. The proteins specific for L but not P had 7070 and 8619 ion values. P proteins absent from L were of 3890, 3969, 4078, 6863, 7676, 7778, 7847 and 7937 ion values. In addition to detecting some so far unknown proteins in L, these preliminary findings throw a new light on our understanding of the mechanism of transcapillary transport of low m.w. proteins. They challenge the commonly accepted notion of unlimited free diffusion of peptides across the capillary membrane.

Adult↗

PubMed2004

DNA released from ischemic and rejecting organs as an indicator of graft cellular damage.

Donor cellular debris contains fragments of nuclei with genetic material. The question arises whether the amount of donor graft released DNA accumulating in the recipient lymphoid tissues after transplantation could be a measure of donor organ damage caused by ischemia and preservation as well as rejection. We found that donor heart passenger cells do not contribute to the DNA disseminated in the recipient. All donor DNA was, then, derived from the damaged graft cells. Immediately and 1 day after transplantation, it was present in blood (plasma and cells) to accumulate later in the spleen. Higher values of donor DNA in the syngeneic than allogeneic combination, most evident on day 7, were presumably due to better perfusion of graft not undergoing rejection. Immunosuppression attenuated donor DNA release and accumulation in recipient tissues, nevertheless, relatively high concentrations could still be detected. Further studies are in progress on the usefulness of measuring DNA concentration for evaluation of the graft damage.

DNA↗

PubMed2003

Clinical and experimental transplantation of isolated organ or tissue cells indications problems from the Polish perspective.

Clinical cell transplantation remains as a clinical experiment. Morphologically intact and functional cells transplanted into their tissue of origin undergo rapid disintegration by attacking granulocytes and macrophages, leading to the so-called early graft dysfunction. When transplanted to sites remote from their origin, the process of elimination is even faster. Among millions of transplanted cells, only a few survive in an autologous or syngeneic recipient, not to mention an allogeneic combination. What is the mechanism of elimination of the majority of transplanted cells? Which cells survive and what is their genotype and phenotype? There are several problems that should be investigated: (1) the mechanism of anoikis, namely, detachment-induced apoptosis, (2) the reaction of the innate immune system to transplanted cells, (3) the microchimerism created by the transplanted cells, and (4) the "niche" for transplanted cells within the local cell chemical environment and signalling. Our experience with transplantation of hepatocytes illustrates current problems in isolated cell grafting. Proposals to increase the in vivo survival rate of transplanted syngeneic hepatocytes are essential to the vision of the future of cell transplantation.

Anoikis↗

PubMed2003

Transplantation of hepatocytes: elimination of recipient natural killer cells with irradiation and bone marrow reconstitution prevent early graft dysfunction.

Transplanted isolated syngeneic and allogeneic hepatocytes rapidly disintegrate, irrespective of the origin or the site of engraftment namely spleen, liver, portal vein, peritoneum, or subcutaneous tissues. Although various methods have been applied to attenuate this reaction, none have been found effective. We applied a combined protocol consisting of administration of anti-asialoGM1 antiserum (eliminating NK cells), sublethal whole-body irradiation, and reconstitution with syngeneic bone marrow cells to intrasplenic hepatocyte transplantation and 3 consecutive partial hepatectomies. This method overcame the early disintegration of grafted hepatocytes. Ninety days after transplantation numerous hepatocyte clusters and dilated bile canaliculae, occupying two thirds of the spleen, were observed, with some hepatocytes adhering to the bile ducts forming Hering's canals. Mitotic figures were noticed. There were no recipient mononuclear infiltrates around the hepatocyte clusters.

Animals↗

PubMed2003

Repopulation of donor heart by recipient bone marrow-derived dendritic cells prior to transplantation causes acute rejection by both the allogeneic and syngeneic recipient.

Experimental studies on allogeneic transplantation have shown that recipient dendritic cells (DC) play a role in peripheral tolerance as well as in rejection of allografts. It is not known whether DC exert their tolerogenic function in recipient lymphoid tissue, and whether they process shed alloantigen in the graft itself. To answer this question we created a chimeric heart model deprived of its own DC and repopulated by recipient DC. The rationale for this model was to observe whether recipient DC located in the graft attenuate recruitment and stimulation of recipient lymphocytes, subsequently prolonging graft survival. Vascularized bone marrow transplants (VBMTx) from the prospective recipient to the lethally irradiated heart donor, which function for a period of 14 days, were used to replace donor DC with prospective recipient DC. Hearts from chimeric LEW rats (with BN DC) were transplanted to untreated BN rats. Also, hearts from chimeric LEW rats (with BN DC) were returned to untreated LEW rats. Replacement of the donor heart with recipient DC did not prolong graft survival. Rather, it initiated a rejection reaction that was already present in the donor. Recipient DC retained their immunogenic properties also when the graft was returned back to a donor strain animal.

Animals↗

PubMed2003

Inhibition of formation of synapses between dendritic cells and lymphocytes in skin lymph in an allogeneic reaction by cyclosporine and tacrolimus.

Skin, an important component of composite tissue allografts is considered to be among the most immunogenic of tissues. The mechanisms of resistance of skin allografts to pharmacological immunosuppression remain unknown. We investigated this problem at the level of antigen presentation by graft dendritic cells (DC) to recipient lymphocytes (L). Cells obtained from lymph draining skin were examined for formation of synapses, necessary for antigen presentation, in the presence of cyclosporine (CsA) or tacrolimus (FK 506). In culture the frequency of DC-L synapses was greater in allogeneic than syngeneic combinations. Cells treated with FK 50% showed a decreased rate of formation of autologous or allogeneic DC-L synapses and lower expression of CD49d. The suppressive effect of FK 506 on DC-L synapse formation may explain the effectiveness of this drug for skin allograft survival.

Animals↗

PubMed2003

The effect of cyclosporine and tacrolimus on indigenous bacterial flora in human skin grafts.

Allogeneic skin transplants require intensive immunosuppressive therapy. Treatment protocols used for parenchymal organ grafts are not satisfactory to prevent skin graft rejection. Another factor responsible for the destruction of allogeneic skin transplants is bacterial inflammation. Temporary ischemia and the allogeneic reaction in transplanted skin cause increased permeability of the epidermis and the dermal capillaries, making skin grafts vulnerable to bacterial penetration. Moreover, immunosuppressive therapy compromises the host immune response. The present study assessed the effects of immunosuppression by cyclosporine (CsA) or tacrolimus (Tac) on the indigenous bacterial flora of transplanted human skin. We found that a 6-day course of treatment with CsA or Tac was followed by an increased prevalence of bacterial isolates, mostly evidenced by a change in the spectrum of graft bacterial flora from Staphylococcus aureus and coagulase-negative staphylococci toward more pathogenic strains such as Escherichia coli, Enterococcus faecium, micrococcus, and pseudomonas. The mouse skin adjacent to the graft remained sterile, precluding the possibility of graft contamination with mouse flora.

Animals↗

PubMed2003

The normal and metastases-bearing livers retain various specific subsets of live lymphocytes from portal circulation.

The liver is among the organs that trap lymphocytes flowing through their blood vasculature. These cells, marginated in sinusoids, participate in the liver's anti-viral and anti-tumor processes. The molecular mechanism of this lymphocyte margination and cooperation with resident sinusoidal cells remains obscure and inadequately studied due to the difficulties in obtaining samples of sinusoidal blood from a living animal. To overcome these shortcomings, we have worked out an in situ rat liver perfusion model in exsanguinated animals that enables quantitative observations of blood lymphocyte trapping in sinusoids. The cell populations trapped by the liver and retained in the perfusing blood were characterized with respect to their phenotypes and cytotoxicity. Perfused livers, previously washed out of sinusoidal lymphocytes, halted leukocytes from normal perfusing blood. The numbers of halted post-perfusion CD5+, CD4+, CD8+, CD56+ (ED1) and MHC class II+ (OX6) subsets did not differ statistically from the pre-perfusion population, which suggests active extraction of leukocytes during perfusion. Moreover, cytotoxicity of post- and preperfusion populations against CC531 and K562 remained at a similar level. The perfused livers with CC531 colon adenocarcinoma metastases halted higher numbers of the CD14 and MHC class II+ and fewer of CD11b+ and CD54+ normal blood leukocytes than normal livers. The phenotypes of cells retrieved from sinusoids after perfusion were almost identical to those obtained prior to perfusion. Interestingly, the post-perfusion populations displayed higher cytotoxic capacity than before perfusion. Taken together, the in situ liver perfusion method allows the study of the specificity and kinetics of recruitment of specific populations of host leukocytes in metastatic tumor tissue and evaluation of their cytotoxicity levels.

1,2-Dimethylhydrazine↗

PubMed2003

Immune changes in lymph nodes after skin grafting. I. Effects of bacterial antigens.

Transplantation of skin brings about response of the regional lymph nodes. Lymph node cells (B and T lymphocytes, dendritic cells, imigrating monocytes, high endothelial venous cells) respond to three types of antigens: allogeneic, bacterial and self-antigens. Allogeneic reaction is induced by contact of antigen presenting cells (APC) with donor antigens. Bacteria penetrate rejecting graft epidermis and travel along lymphatics to the nearest lymph node. Rejecting graft debris is phagocytized by macrophages and dendritic cells and transported to lymph nodes. These different type antigens induce different reaction of node cells. In this review we present data from literature and own studies on the effect of bacteria normally residing on skin surface on lymph node after penetration of epidermis. Further reviews will be dealing with the response of lymph nodes to allo- and autoantigens.

Animals↗

PubMed2003

Similar response of dendritic cells to bacterial and allogeneic antigens.

The dendritic cells (DC) of an allograft recipients become engaged not only in an allogeneic but also antibacterial reaction. They react to the alloantigens and microorganisms which colonize the rejecting grafts. This leads to overstimulation of DCs what may non-specifically intensity the rejection process. We investigated the effects of allogeneic and bacterial antigens on splenic DCs phenotypes. In vitro stimulation of spleen DC-enriched population by E. coli, LPS and CpG DNA brought about an increase in expression of OX6 (MHC class II) from 47.4% in the control population to 65% in the E. coli stimulated group (p < 0.05) and to 85% in the LPS and CpGDNA groups (p < 0.05). Interestingly, a significant drop in the frequency of OX62+ antigen was observed after incubation with LPS. Allogeneic heart transplants brought about an increase of OX6+ (MHC class II) DCs to 100% and a decrease of EDI+ cells. Simultaneously, an increase in expression of W3/13 on DC-enriched splenic cells was observed. There was no significant change in the frequency of OX62+ expression in conclusion, both bacterial and alloantigens strongly activate splenic DCs what may add to the intensity of the rejection process.

Animals↗

PubMed2002