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Andrzej Górski

Publications and source records attributed to Andrzej Górski.

At least 19 recordsLinked to original sources
PubMed2006

Effects of bacteriophages on free radical production and phagocytic functions.

Reactive oxygen species (ROS) play a major role in mediating antibacterial functions of phagocytic cells. However, excessive ROS production may cause oxidative stress and tissue damage. Uncompensated ROS release has been implicated in a variety of disorders. Novel means of controlling elevated ROS production are urgently needed. We showed that homologous but not the heterologous phages inhibited, in a dose dependent manner, the degree of chemiluminescence in phagocytes induced by Escherichia coli. Treatment of the cells with the phages alone resulted in a small increase in ROS production. Homologous phages also facilitated phagocytosis when preincubated with bacteria. On the other hand, both homologous and heterologous phages inhibited phagocytosis following preincubation with phagocytic cells. The treatment of infected and uninfected mice with phages did not significantly alter the rate of phagocytosis by blood granulocytes and monocytes. In conclusion, we showed that bacteriophages can decrease ROS production by phagocytes. Although in some in vitro experimental models the phages tended to diminish phagocytosis, this phenomenon may be of little significance in clinical situations, since the process of eliminating bacteria in phage-treated patients is predominantly accomplished by both phages and phagocytes.

Animals↗
PubMed2006

Bacteriophage translocation.

The occurrence of phages in the human body, especially in the gastrointestinal tract, raises the question of their potential role in the physiology and pathology of this system. Especially important is the issue of whether phages can pass the intestinal wall and migrate to lymph, peripheral blood, and internal organs and, if so, the effects such a phenomenon could have (such passage by bacteria, known as bacterial translocation, has been shown to cause various disturbances in humans, from immune defects to sepsis). Available data from the literature support the assumption that phage translocation can take place and may have some immunomodulatory effects. In addition, phages of the gut may play a protective role by inhibiting local immune reactions to antigens derived from gut flora.

Animals↗
PubMed2006

Bacteriophage endolysins as a novel class of antibacterial agents.

Endolysins are double-stranded DNA bacteriophage-encoded peptidoglycan hydrolases produced in phage-infected bacterial cells toward the end of the lytic cycle. They reach the peptidoglycan through membrane lesions formed by holins and cleave it, thus, inducing lysis of the bacterial cell and enabling progeny virions to be released. Endolysins are also capable of degrading peptidoglycan when applied externally (as purified recombinant proteins) to the bacterial cell wall, which also results in a rapid lysis of the bacterial cell. The unique ability of endolysins to rapidly cleave peptidoglycan in a generally species-specific manner renders them promising potential antibacterial agents. Originally developed with a view to killing bacteria colonizing mucous membranes (with the first report published in 2001), endolysins also hold promise for the treatment of systemic infections. As potential antibacterials, endolysins possess several important features, for instance, a novel mode of action, a narrow antibacterial spectrum, activity against bacteria regardless of their antibiotic sensitivity, and a low probability of developing resistance. However, there is only one report directly comparing the activity of an endolysin with that of an antibiotic, and no general conclusions can be drawn regarding whether lysins are more effective than traditional antibiotics. The results of the first preclinical studies indicate that the most apparent potential problems associated with endolysin therapy (e.g., their immunogenicity, the release of proinflammatory components during bacteriolysis, or the development of resistance), in fact, may not seriously hinder their use. However, all data regarding the safety and therapeutic effectiveness of endolysins obtained from preclinical studies must be ultimately verified by clinical trials. This review discusses the prophylactic and therapeutic applications of endolysins, especially with respect to their potential use in human medicine. Additionally, we outline current knowledge regarding the structure and natural function of the enzymes in phage biology, including the most recent findings.

Animals↗
PubMed2006

[The presence of bacteriophages in human feces and their potential importance].

Bacteriophages are widely distributed throughout the environment as well as in the bodies of humans and animals (feces, urine, saliva, sputum). Higher presence of Escherichia coli phages compared with Bacteroides fragilis and Salmonella phages was noticed in the feces of healthy human individuals and patients, mainly those with gastro-intestinal tract diseases. A strict correlation exists between the number of bacteria and of phages in the feces of healthy individuals as well as of patients with different diseases. The presence of phages in human feces correlates with the character of the coexisting disease. The frequency of phages in the feces depends on the different indicator bacterial host strains and the numbers of indicator strains. The role of bacteriophages in protecting against pathogenic microorganisms and controlling bacterial flora in the human organism is of major significance.

Animals↗
PubMed2005

The potential role of endogenous bacteriophages in controlling invading pathogens.

Bacteriophages (phages) are omnipresent in our environment, and recent studies highlight their potential impact on the microbial world. Phages can also be present in mammalian organisms, including man (intestines, oral cavity, urine, sputum and serum). Data are available which suggest that those endogenous phages could play an important role in eliminating bacteria and regulating the body ecosystem. Furthermore, our most recent findings suggest that phages can exert immunosuppressive action in the gut, helping control local inflammatory and autoimmune reactions, and demonstrate anticancer activity. We hypothesize that phages could act in concert with the immune system in immunosurveillance against bacteria, viruses and cancer.

Anti-Bacterial Agents↗
PubMed2005

[Bacterial translocation and its clinical significance].

Bacterial translocation (BT) is defined as the passage of indigenous bacteria colonizing the intestine through the epithelial mucosa to the mesenteric lymph nodes and other sites. It can even cause the development of lethal sepsis. BT is being studied extensively, most research being conducted on animal, mostly murine, models. The cause of BT is not well known. Despite advances in antimicrobial therapy, the mortality rate associated with bacteremia is still high, and sepsis can often originate from the patient's own intestinal flora. Consequently, a better understanding of the mechanisms of BT as well as mechanisms operating to prevent bacteria from translocating from the gastrointestinal tract may provide more logical treatment of particular patients. BT may be promoted by immunosuppression (probably one of the most important factors causing the increase in BT), disturbances in the normal ecology of the gastrointestinal tract, allowing some indigenous bacteria to overgrow others, and by mucosal injuries. This article discusses the potential role of various factors responsible for BT and the relationship between BT and neoplastic disease. It also emphasizes the significance of the immune system, which appears to play a role in the ontogeny of gut-associated lymphoid tissue (GALT), including the role of IL-2 (which induces an increase in BT) and the macrophage, which participates in the transport of bacteria from the intestinal lumen to mesenteric lymph nodes. A better understanding of the immunopathology of BT may contribute to the development of novel means of therapy for sepsis and other serious complications of bacterial infection.

Animals↗
PubMed2004

[Phage-display technology and its application to experimental oncological therapy].

One of the biggest challenges facing modern oncology is that of delivering drugs selectively to cancer cells and tumor endothelial cells. To achieve this goal, one can use peptides binding certain molecules on these cells. The most often used method of creating such peptides is phage-display. Peptides obtained from phage display technology can exert anti-cancer effect by inhibiting angiogenesis, decreasing tumor metastatic activity, or inhibiting enzymes important for neoplastic cell spread. They can also be used as components of antitumor vaccines or vehicles delivering cytokines, chemotherapeutics, or anti-sense oligonucleotides to tumors. Phage display technology has also enabled the development of anti-cancer recombinant antibodies, most often used as scFv molecules. ScFv-s can be further modified to increase their affinity and avidity. They can also be conjugated with molecules inducing different anti-cancer effector functions.

Animals↗
PubMed2004

Extracellular Matrix Protein-dependent Apoptosis of T Cells in Women with a History of Recurrent Spontaneous Abortion.

PROBLEM: The purpose of the study was to determine the role of T-cell apoptosis in extracellular matrix (ECM) environment in pregnancy maintenance in women with a history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Thirty-nine non-pregnant women with the history of RSA (anatomic, genetic, endocrine and microbiologic causes were excluded) and 22 healthy women with the previous successful pregnancy outcome were studied. In addition, 21 women with the history of RSA were also studied at the beginning of their next pregnancy. We studied apoptosis of peripheral blood T cells after culture with monoclonal antibody (mAb) OKT-3 alone or with mAb OKT-3 following ECM proteins: collagen IV (C-IV) or fibronectin (Fn). We used Cell Death Detection ELISA for studying cell death in cell population. In addition, apoptotic peripheral blood T cells were identified by annexin V-PE staining protocol using flow cytometry. CD29+ and CD95+ T-cell surface receptors were also analyzed by flow cytometry. RESULTS: The significantly higher values of enrichment factor: mU of the sample (dying/dead cells) per mU of the corresponding control (viable cells) were observed after peripheral blood T-cell culture with C-IV (P = 0.0002) or Fn (P = 0.004) in samples of non-pregnant women with the history of RSA when compared with control women. The significantly higher values of enrichment factor were observed after peripheral blood T-cell culture with C-IV in samples of pregnant women with the history of RSA with successful pregnancy outcome when compared with pregnant women with the history of RSA with failed pregnancy outcome (P = 0.01). However, the percentage of apoptotic T cells stained by annexin V was significantly lower in non-pregnant RSA women compared with control (P = 0.0001). CD95 expression was significantly lower in non-pregnant RSA women compared with control (P = 0.01). CONCLUSIONS: Apoptosis of T cells might be an interesting possible explanation of successful pregnancy outcome in women with the history of RSA.

Abortion, Habitual↗
PubMed2004

Preparation of endotoxin-free bacteriophages.

Bacteriophages (phages) are bacterial viruses that interact with bacterial walls and invade bacterial cells. Moreover, they disturb bacterial metabolism and lead to bacteria lysis. In the case of Gram-negative bacteria crude phage cultures, apart from the phages themselves, the bacterial debris, bacterial proteins and nucleic acids contain endotoxins. These endotoxins (lipopolysaccharides) posses a high degree of toxicity in vitro and in vivo, and their removal is essential for safety in antibacterial bacteriophage therapy. An effective, scaleable purification of bacteriophages from endotoxins was accomplished by sequential ultrafiltration through polysulfone membrane (30 nm) followed by chromatography on sepharose 4B and Matrex Cellulofine Sulfate. The phage fraction after gel filtration chromatography routinely contained endotoxins in the 150-2500 EU/ml range. The procedure yielded bacteriophages contaminated with as little as 0.4-7 EU/ml (Limulus assay). This value lies within the permitted level for intravenous applications (5 EU/kg/h by European Pharmacopoeia, 1997).

Animals↗
PubMed2003

Bacteriophages provide regulatory signals in mitogen-induced murine splenocyte proliferation.

The aim of this investigation was to reveal the regulatory properties of bacteriophage preparations in a model of mitogen-induced splenocyte proliferation in mice. We showed that sepharose 4B-purified preparations of the Staphylococcus aureus phage A20/R exhibited costimulatory activity in splenocyte proliferation induced by suboptimal (0.25 microg/ml) concentrations of ConA. On the other hand, the purified phage fraction was regulatory with regard to splenocyte proliferation induced by the optimal (2.5 microg/ml) ConA concentration. We also showed that the phage preparation can elicit IL-6 production in splenocyte cultures and enhance ConA-induced production of that cytokine. Furthermore, the phages preferentially induced IL-6 production in adherent splenocytes and increased levels of that cytokine in cultures of peritoneal cells from mice and rats. This phenomenon may explain the costimulatory activity of phages in the model described.

Animals↗
PubMed2003

The impact of pretransplant erythropoietin therapy on late outcomes of renal transplantation.

OBJECTIVES: The introduction of recombinant erythropoietin (rHu-EPO) has been shown to reverse anemia of chronic renal failure and was able to almost completely obviate the need for repeated blood transfusions (BT), the most potent cause of allostimulation in renal transplant candidates. The series describes single center experience of the pretransplant BT and rHu-EPO therapy effects on late outcomes of cadaveric renal transplantation. METHODS: We retrospectively analyzed data of 502 adult recipients of primary renal allograft between 1990-1997 whose graft survived > 6 months. In the study group 51 patients were treated prior to transplantation with de novo rHu-EPO therapy, 207 patients received BT, 184 patients were switched from BT to rHu-EPO therapy, and 60 patients did not require treatment. The groups were compared in respect to pretransplant % PRA, frequency of acute rejections and graft survival. RESULTS: At one-year graft survival was similar between groups, however at five years recipients of de novo rHu-EPO and those who have converted from BT to rHu-EPO experienced only 7% graft loss, as compared to 22% of patients treated with BT, and 18% of patients who did not require treatment, p < 0.001. The pretransplant therapy with rHu-EPO was associated with decreased frequency of late episodes of rejection from 0.42 to 0.27, p = 0.03. There were no differences between groups in the number of highly sensitized (PRA > 20%) at the time of transplantation. CONCLUSIONS: The use of rHu-EPO as de novo therapy or conversion from BT treatment to rHu-EPO prior to transplantation was associated with a decline in late posttransplant alloreactivity and improved late renal graft survival.

Adult↗
PubMed2003

Influence of clindamycin, metronidazole and polymyxin B on the expression of cell adhesion molecules stimulated by endotoxin and enterotoxin of Bacteroides fragilis.

The aim of this study was to compare the influence of antimicrobials (clindamycin, metronidazole and polymyxin B) on the expression of adhesion molecules (VCAM-1, ICAM-1 and E-selectin) on the HMEC-1 cell line stimulated by LPS and enterotoxin of B. fragilis. LPS was extracted from two reference: ATCC 43858 and NCTC 11295 and one isolated in our laboratory (W2) enterotoxigenic strains, and one nonenterotoxigenic reference strain--IPL E 323. Enterotoxin preparations (Tox 1 and Tox 2) were isolated from supematant of B. fragilis ATCC 43858 culture and purified. HMEC-1 cell line was stimulated with bacterial preparations at concentration of 10 mg/ml. For measuring the expression of adhesion molecules we used ELISA test. Clindamycin, metronidazole and polymyxin B supressed the ICAM-1 expression when endothelium was stimulated with B. fragilis LPS and augmented ICAM-1 expression by Tox 1 and Tox 2. The expression of VCAM-1 was augmented by antimicrobials when endothelium was stimulated with LPS or enterotoxin preparations. The expression of E-selectin was differentiated.

Anti-Bacterial Agents↗
PubMed2002

Effect of phage therapy on the turnover and function of peripheral neutrophils.

The aim of this investigation was to establish the impact of phage therapy on the turnover and function of circulating neutrophils in 37 patients with suppurative bacterial infections. We determined the levels of circulating neutrophils and their precursors before therapy, after 3 weeks of therapy, and at a distant time interval (3 months) following the beginning of therapy. In addition, we measured the ability of neutrophils to phagocytize Staphylococcus aureus in vitro. Eight healthy blood donors served as a control group. The results showed that, among the studied parameters, the significant changes involved neutrophil precursor count and the ability of neutrophils to phagocytize bacteria. The percentage of neutrophils in patients before therapy was lower than in healthy donors (mean 58.0, versus 61.4). This value dropped further in patients after 3 months of following the therapy (mean 55.6). The content of neutrophil precursors, on the other hand, was lower in healthy donors than in patients before therapy (mean 2.5, versus 3.8). After 3 weeks of the therapy and after 3 months, the levels of neutrophil precursors were significantly higher (mean 4.8 and 4.9, respectively) than in control donors. The phagocytic index was lower in patients before therapy than in control donors (mean 66.3, versus 70.1) and decreased further after 3 weeks of therapy (mean 59.0) and after 3 months (mean 59.6). The results of this investigation indicate that successful phage therapy accelerates the turnover of neutrophils, accompanied by a decrease in their ability to phagocytize bacteria.

Adult↗