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A Sadowska

Publications and source records attributed to A Sadowska.

11 recordsLinked to original sources
PubMed2005

Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-beta levels and histological changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21). METHODS: In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation. RESULTS: We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3 months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL, respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.

Antibodies, Monoclonal↗
PubMed2003

Human herpesvirus-6 in renal transplant recipients: potential risk factors for the development of human herpesvirus-6 seroconversion.

Herpesviruses, including human herpesvirus-6 (HHV-6), reactivate and have the potential to be pathogenic in immunocompromised patients. Little information is available regarding the correlation between immunosuppressive therapy and HHV-6 seroconversion after organ transplantation. Serum samples obtained from 120 kidney and kidney/pancreas transplant recipients were tested to explore the potential risk factors for developing HHV-6 infection including types of immunosuppression and induction/rejection therapy. Stored serum samples obtained prior to and at the 2nd, 4th, 12th and 48th weeks after transplantation were tested for anti-HHV-6 immunoglobulin (Ig)M antibodies using indirect immunofluorescence assay. Prior to transplantation and 48 weeks after transplantation the sera were additionally tested for anti-HHV-6 IgG using enzyme-linked immunoassay. Ninety-one percent of 120 recipients were HHV-6 IgG-positive before transplantation. One hundred seven of 120 patients were anti-HHV-6 IgM-negative before transplantation. Primary/secondary HHV-6 seroconversion occurred in sera of 46.6% of these 107 patients. HHV-6 seroconversion most frequently occurred 2 to 4 weeks after transplantation. There was no significant relationship between HHV-6 seroconversion and the treatment with methylprednisolone (MP). The incidence of HHV-6 seroconversion was significantly higher in subjects who were treated with the regimens including Daclizumab or Sirolimus as compared with those who were on other protocols. HHV-6 seropositivity in the Polish population of organ transplant recipients is very high. We demonstrated a trend toward association of HHV-6 seroconversion with type of immunosuppressive therapy.

Adolescent↗
PubMed2003

Polyomavirus BK infection.

Because it is an important factor affecting renal transplant function, BK infections are significant problem in posttransplant. BK nephropathy develops in 5% of renal allograft recipients, in most cases within the first year after the procedure. The gold standard for BK nephropathy diagnosis is still immunohistochemical staining for large T antigen in graft biopsy specimens. The aim of the present study was to evaluate the incidence of and factors influencing BK nephropathy in our renal allograft population. Among 89 renal or pancreas/kidney allograft recipients, BKV DNA was detected in 1 or more serum samples in 17 patients but BK nephropathy was diagnosed in only 1 case. Plasmacytic tubulitis was an exclusive feature in PCR-positive patients with 2 (20%) cases but no such findings in the PCR-negative group. In 40% of patients in the PCR-positive group at least 1 rejection episode was diagnosed versus 22% in the PCR-negative group. There were no significant differences in both groups according to total ischemia time, immunosuppressive treatments, or mean serum creatinine at 1 year after transplantation.

BK Virus↗
PubMed2001

The impact of immune responses on lung cancer and the development of new treatment modalities.

OBJECTIVE: This presentation covers predominantly review data in relation with immune responses initiating and accompanying lung carcinogenesis or- on the contrary-contributing to novel therapeutic developments. Occasionally, personal findings will be considered. RESULTS 1 OF IMMUNE DEFICIENCY: It is known for several decades that cancer incidence (several sites) is increased in subjects receiving immunosuppressive therapy, e.g. to avoid transplant rejection, or suffering from AIDS. We have observed that in areas heavily polluted by industrial activities, resulting in immune deficiency, cancer incidence is increased, notably for lung cancer. On the other hand, neoplastic cells are able to escape the host's immune responses by inducing apoptosis of the effector T lymphocytes. Apoptosis in T-cells is triggered by the interaction of the membrane receptor Fas with its normal ligand Fas L, or an activating antibody. Now lung carcinoma cells have been shown to express Fas L, enabling them to destroy cytolytic T cells. RESULTS 2 OF IMMUNE TREATMENT: It is well over a century ago that interest in the immunotherapy of cancer was aroused by the observation of tumour regressions concomitant with bacterial infection, an observation leading to the development of 'Coley's toxin', a mixture of killed bacteria (presently known to act through the presence of TNF-alpha). Since these long-standing empirical attempts, a lasting search for immune control of cancer has been initiated, comprising such different approaches as active non-specific immunotherapy, active specific immunotherapy, approaches based on the use of monoclonal antibodies, as well as those depending on cellular immunity and the development of adoptive immunotherapy, and the use of peptide vaccines. These different approaches will be described and their results presented. CONCLUSION: Present state-of-the-art will be discussed and new pathways for development evoked; better understanding of immune mechanisms is opening new avenues for improved treatment efficacy.

Antibodies, Monoclonal↗
PubMed2001

In vitro propagation of Withania somnifera and isolation of withanolides with immunosuppressive activity.

Withania somnifera plantlets were produced in vitro from the shoot-tip of aseptically germinated seedlings. Culture conditions were optimized using different plant growth regulators which gave rise to 120 shoots from a single bud. The plantlets were then transferred to pots and maintained in greenhouse for 4 months. 90% of these in vitro propagated plantlets survived and showed normal growth. Leaves from these plants were used for isolation of the withanolides. Methanolic extract of leaves from plantlets growing in tissue culture and those transferred to the greenhouse were evaluated for immunomodulatory activity. While the extract from greenhouse samples showed potent immunosuppressive activity, those from tissue cultures samples did not show any activity. Fractionation and characterization of withanolides, using HPLC, NMR, MS methods revealed the presence of withaferin A in the greenhouse samples. Our results indicate that Withania species may require longer time and better differentiation and also natural environment for the production of withaferin A.

Adjuvants, Immunologic↗
PubMed2001

Use of higher plants in the biomonitoring of environmental genotoxic pollution.

Genotoxicity is recognised as being the first step in carcinogenesis. Hence the identification ambient genotoxicity represents an important step in cancer risk assessment even if non-genotoxic mechanisms also occur. Genotoxicity can be assessed after exposure of populations to chemical or physical agents, as cytogenetic alterations, mutations or production of DNA/protein adducts. Well defined higher plants represent an excellent basis for cytogenetic evaluations after exposure to genotoxic pollutants, especially that the maturation of their gametes (meiosis) follows the same patterns as in animals and humans. We present a description of the Tradescantia Micronucleus Assay (TRAD-MCN) and results of a series of field evaluations after environmental pollution (urban settings, industrial sites, landfills). A significant correlation is observed between the intensity of the pollution and the ratio of micronuclei appearing at the tetrad stage of meiosis. The method is easy, requiring no special equipment, reproducible, rather inexpensive. It allows the establishment of "genotoxicity maps" and the follow-up monitoring of the polluted sites. In environmental monitoring, we consider the TRAD-MCN assay as the first-line procedure presenting the additional advantage of not involving human populations primary evaluations, thus avoiding psychological stress.

Air Pollutants↗
PubMed1994

Environmental genotoxicity and cancer risk in humans: a combined evaluation correlating the results of the Tradescantia micronucleus assay in the field and human biomarker assessments in serum. I. The TRAD-MCN assay.

It is well documented that environmental pollution from industrial activity, sewage farms, hazardous waste sites, incinerators, etc, contributes to the overall cancer risk and that this contribution can be considerable under certain circumstances. It is important, therefore, to identify the level of genotoxic activity in the environment and to relate it to biomarkers of cancer risk in humans. After reviewing a range of cytogenetic assays, we have selected the Tradescantia micronucleus assay (TRAD-MCN) developed by Ma et al to be used in indoor and field evaluations. The meiotic pollen mother cells of T clone 4430 are particularly sensitive to chemical pollutants; the buds are exposed for 6-8 h. We describe assays made down wind from a coal-fired power station and from the vicinity of two waste sites. Statistically significant results were obtained at 200 m and 600 m down wind from the power station; higher levels of micronucleus frequencies (MN) were found in foggy rather than dry conditions. Similarly, in the vicinity of two waste sites the MN frequencies were significantly increased in both dry and foggy conditions up to 1.5 km down wind; this was despite previous efforts to rehabilitate the sites. The TRAD-MCN assay is sensitive, reproducible, easy to perform, well standardized, inexpensive and undemanding in equipment. We propose that it be the primary test for genotoxicity evaluation and mapping followed, in suspicious areas, by human biomarker assays.

Air Pollution↗
PubMedDate not supplied

Fever, human herpesvirus-6 (HHV-6) seroconversion, and acute rejection episodes as a function of the initial seroprevalence for HHV-6 in renal transplant recipients.

Human herpesvirus-6 (HHV-6) is an opportunistic viral pathogen of emerging clinical significance in immunocompromised patients. We performed a seroepidemiological survey to test the relation between seroprevalence among donors and recipients for HHV-6 at three endpoints. Before transplantation sera obtained from cadaveric donors and from potential recipients were tested for IgG antibodies against HHV-6 using an enzyme-linked immunoassay. The group of recipient sera, including samples obtained before as well as 2, 4, 12, and 48 weeks after transplantation, were tested for anti-HHV-6 IgM antibodies using an indirect immunofluorescence assay. The statistical analysis was performed with the Cox proportional hazards models. The HHV-6 seronegative group (n = 11) compared with the HHV-6 seropositive group (n = 109) showed twice the risk of HHV-6 IgM seroconversion (RR = 2.24; P < .04), with a greater risk of fever, namely 3.8, which was on the verge of statistical significance. The opposite trend toward an association with acute rejection episodes was observed among HHV-6 seronegative patients (RR = 1.81). The presence of IgG antibody in the sera of donors to IgG seropositive recipients had no association with the occurrence of IgM seroconversion. In contrast, IgM antibodies to HHV-6 appeared in four of five seronegative patients who received allografts from IgG seropositive donors. These preliminary data suggest that the effects seem to be the consequence of HHV-6 transmission through a renal allograft.

Antibodies, Viral↗