Search PubMed⌕ Search

Biomedical subjects

G Russ

Publications and source records attributed to G Russ.

At least 19 recordsLinked to original sources
PubMed2006

FTY720/cyclosporine regimens in de novo renal transplantation: a 1-year dose-finding study.

FTY720 is a novel immunomodulator being investigated for rejection prophylaxis in renal transplantation when combined with full-dose cyclosporine (CsA; FDC). This 1-year phase II study compared FTY720 plus FDC (Neoral) with FTY720 plus reduced-dose CsA (RDC) and mycophenolate mofetil (MMF) plus FDC in de novo renal transplant patients. Patients were randomized 2:2:2:1 to FTY720 5 mg plus RDC (n = 72); FTY720 2.5 mg plus RDC (n = 74); FTY720 2.5 mg plus FDC (n = 76); or MMF plus FDC (n = 39) for 12 months. CsA exposure in the RDC group was reduced on average by 50% as assessed by C(2) monitoring. The primary efficacy endpoint was the composite incidence of biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation. The incidences for this composite endpoint were 24% and 22%, respectively, for FTY720 5 mg plus RDC and FTY720 2.5 mg plus FDC versus 39% for MMF plus FDC. Patients receiving FTY720 2.5 mg plus RDC were discontinued from treatment due to risk of under-immunosuppression. FTY720 2.5 mg plus FDC and FTY720 5 mg plus RDC were safe and effective in de novo renal transplant patients over 12 months.

Adult↗
PubMed2006

Effect of proteasome inhibitors on expression of HLA-G isoforms.

HLA-G primary transcript is alternatively spliced into a number of mRNAs. In addition to full length HLA-G1 protein isoform these mRNAs might also encode truncated HLA-G protein isoforms lacking one or two extracellular domains. Whereas HLA-G1 protein isoform is regularly identified, truncated HLAG protein isoforms are not detected even if all alternative spliced mRNAs are present in cells. The absence of entire domain(s) renders the truncated HLA-G protein isoforms incapable of binding peptide and beta2-microglobulin. These features of truncated HLA-G protein isoforms may result in their rapid degradation by proteasomes. Here we show that despite the presence of all alternatively spliced HLA-G transcripts in JEG-3 cells pretreated with proteasome inhibitors only a full length HLA-G1 protein isoform was regularly detected. Interestingly, immunoblot analysis showed slight increase of HLA-G1 protein in cells pretreated with proteasome inhibitors, although the expression of HLA-G1 transcript was basically not affected. Expression of HLA-G3 transcript increased in JEG-3 cells pre-incubated with LLL, however, neither HLA-G3 nor other HLA-G short protein isoform was regularly detected. In K562 transfectants proteasome inhibitor LLL greatly enhanced expression of the HLA-G1 and -G2 transcripts as well as corresponding protein isoforms. Flow cytometry analysis showed that in cells pre-treated with proteasome inhibitors cell surface expression of HLA-G1 protein decreased but the quantity of intracellularly localized HLA-G antigens increased. Altogether our results suggest that truncated HLA-G proteins isoforms are not detected in JEG-3 cells as a result of their instability and the low translation efficiency of truncated HLA-G transcripts.

Choriocarcinoma↗
PubMed2006

PB1-F2 gene in influenza a viruses of different hemagglutinin subtype.

The second ORF frame (+1) of PB1 polymerase gene of Influenza A virus (IAV) encodes the PB1-F2 protein. The length of PB1-F2 encoded by the A/Puerto Rico/8/34 (H1N1) (PR8) virus is 87 aa. The analysis of nucleotide sequences of PB1 gene of 626 IAV isolates available in GenBank and Influenza Sequence Database revealed that this gene has mostly the capacity to encode a putative protein of 90 aa. The predicted extra three amino acids in the 90-aa PB1-F2 are to a great extent conservative. Some IAV isolates, particularly human, avian and swine with hemagglutinin (HA) of H1 subtype can potentially encode a C-terminally truncated PB1-F2 of various lengths. The C-terminally truncated PB1-F2 in H1 isolates is lacking the region responsible for mitochondrial targeting and apoptosis. About 50% of avian isolates of H9 subtype possess an ORF for truncated PB1-F2. Eighteen aa, 10 at the N-terminus and 8 at the C terminus are strictly conservative in all 148 human isolates.

Animals↗
PubMed2005

Immunity in latent Herpes simplex virus infection.

Immune responses against productive Herpes simplex virus 1 (HSV-1) and/or Herpes simplex virus 2 (HSV-2) (HSV) infection together with associated immune escape mechanisms are to a great degree understood. Due to a limited RNA expression and lacking a convincing evidence for production of virus proteins during latency, HSV in latently infected neurons had been for a long period considered invisible to immune system. This review analyzes currently accumulating data indicating an important role of immune response to HSV-1 latency and/or to early steps of HSV-1 reactivation process. Although this review focuses on HSV-1, it is likely that general concepts apply to both HSV-1 and HSV-2, since they share a great deal of similarity in their biological features including a high degree of sequence similarity at the nucleic acid level.

Animals↗
PubMed2004

Phase II study of single-agent pegylated liposomal doxorubicin HCl (PLD) in metastatic breast cancer after first-line treatment failure.

OBJECTIVES: Aim of this study was to evaluate the clinical benefit and the toxicity of pegylated liposomal doxorubicin. PATIENTS AND METHODS: Patients with metastatic breast cancer (n = 30) who failed a prior chemotherapy regimen for metastatic disease received 45 mg/m2 pegylated liposomal doxorubicin (PLD) every 4 weeks following prophylactic administration of metoclopramide (10 mg) and dexamethasone (8 mg). RESULTS: 29 of 30 patients were assessed for clinical benefit and time to progression. All patients were assessed for toxicity and analysis of overall survival. 9 patients (31%) had a partial response, and 16 patients (55%) responded with stable disease, resulting in a clinical benefit rate of 86% (n = 25). Median time to progression was 4 months (95% CI: 2.8-5.2), median duration of response was 7 months (95% CI: 4.7-8.2), and median survival was 12 months (95% CI: 6.7-17.2). Skin toxicity was the most common adverse event (30%, all < or = grade 2). Other toxicities were remarkably low in occurrence. CONCLUSION: PLD is a well-tolerated, second-line monotherapy with a high rate of clinical benefit.

Adult↗
PubMed2003

Binding analysis of HLA-G specific antibodies to hematopoietic cells isolated from leukemia patients.

Expression of HLA-G on the surface of malignant hematopoietic cells isolated from leukemia patients was analyzed by flow cytometry using monoclonal antibodies (mAbs) recognizing both, intact HLA-G complex (87G, 01G and MEM-G9) as well as HLA-G free heavy chain (4H84, MEM-G/1 and MEM-G/2). Prerequisite of HLA-G detection by mAbs specific to free heavy chain was mild acid treatment, which dissociates intact HLA-G complex. All mAbs, with the exception of 4H84 mAb, did not indicate the presence of HLA-G antigen in leukemia cells. Positive staining with 4H84 mAb was detected in acid-treated cells isolated from 16 out of 30 patients. Intensity of staining increased after IFN-g pre-incubation in most cases. Immunoblot analyses and RT-PCR, however, failed to detect HLA-G antigen or HLA-G transcripts in cells that bind 4H84 mAb after acid-treatment. The binding of 4H84 mAb can be explained by the acid-induced cross-reactivity of this HLA-G specific mAb with classical HLA class I molecules [15]. The results described here further demonstrate that the HLA-G molecule is not expressed in freshly isolated human leukemia cells.

Adolescent↗
PubMed2003

Sexually transmitted infections among prostitutes in Bratislava, Slovakia.

Sera from 18 prostitutes from Bratislava were examined for the presence of antibodies to several sexually transmitted pathogens, namely Herpes simplex virus 2 (HSV-2), Human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2), Hepatitis B and C viruses (HBV and HCV), Chlamydia trachomatis, and Treponema pallidum. Results of this screening indicated that 11 prostitutes (61%) carried 1 or more sexually transmitted infections. The most prevalent antibodies were directed against HSV-2 (9 cases, i.e. 50%), which represents the most common sexually transmitted infection agent.

Antibodies, Bacterial↗
PubMed2002

Live donor renal transplantation in Australia 1964-1999: an evolving practice.

BACKGROUND: Australia has a low cadaver organ donor (CD) rate by international standards, leading to the increasing use of live donor (LD) renal grafts. AIMS: To review the Australian experience with LD transplants from 1964 to 1999. METHODS: Data were obtained from the Australian and New Zealand Dialysis and Transplant Registry. Survival was assessed by the Kaplan-Meier method. RESULTS: A total of 1584 LD and 10 252 CD transplants was performed between 1964 and 1999. While the CD rate dropped over the last decade, the LD rate increased, maintaining the overall transplantation rate. Only 3.6% of grafts before 1980 were LD, increasing to 28.4% during 1995-1999. Patient and graft survival of LD grafts was superior to CD grafts. Most LD grafts were from live related donors (LRD), most commonly parents or siblings. The number of transplants from live unrelated donors (LURD) has risen (1980-1989, n = 6; 1990-1999, n = 143), primarily due to more spousal donation, with no difference in survival between LRD and LURD groups. Grafts from older donors (> 50 years of age) increased, with no graft survival difference between donors < 50 years and donors > 50 years. LD transplants performed prior to commencement of dialysis increased, with survival similar to grafts performed after dialysis. CONCLUSION: The pattern of renal transplantation in Australia has changed, with increasing numbers of LD transplants, growing use of unrelated and older donors, and more transplants before dialysis commences. Long-term patient and graft survival advantages have been maintained, supporting the growing use of live donors to expand the donor pool.

Adult↗
PubMed2002

Colorectal cancer in patients with chronic renal failure: the effect of dialysis or renal transplantation.

OBJECTIVE: This study reports the characteristics and surgical outcome of colorectal cancer in patients with chronic renal failure treated either by renal transplantation or dialysis. METHODS: Two thousand four hundred and seventeen patients with CRF (1387 transplant and 1030 dialysis) were treated at The Queen Elizabeth Hospital, South Australia, between January 1967 and September 2000. RESULTS: Fourteen have developed colorectal cancer and had their clinical records reviewed. Nine patients were renal transplant recipients and 5 patients were treated with dialysis. Eight patients had surgery. Chemotherapy was given palliatively to 3 patients. One patient died in hospital postoperatively. Seven patients with a renal transplant had notes available. Six presented with late stage disease and all were dead within 9 months of presentation from their disease. In the dialysis patients, tumour stage at presentation was not so advanced and although all the patients have died, the cause of death was secondary to the colorectal cancer in only 2 patients. CONCLUSIONS: This study highlights the poor outcome of patients who have had renal transplant and develop colorectal cancer. Immunosuppression and late diagnosis are implicated in this poor outcome.

Journal Article↗
PubMed2001

Analysis of the extracellular processing of HIV-1 gp160-derived peptides using monoclonal antibodies specific to H-2Dd molecule complexed with p18-I10 peptide.

The immunodominant peptide of human immunodeficiency virus 1 gp 160 for murine cytotoxic T cells of H-2d haplotype, has been originally identified as a 15 amino acid residue peptide P18IIIB (RIQRGPGRAFVTIGK) (Takahashi et al., 1988). Further studies have indicated that a more active form of the peptide is generated by removal of the C-terminal dipeptide by angiotensin-I-converting enzyme (ACE), and additional detailed studies have shown that the actual immunodominant peptide is a decamer P18-I10 (RGPGRAFVTI) (Kozlowski et al., 1993). The effect of proteolytic processing on the antigenicity of P18IIIB peptide and its analogs was investigated by functional T cell assays based on the ability of T cell receptor (TCR) to recognize a specific major histocompatibility complex class I (MHC-I)/peptide complex. Recently we described a new monoclonal antibody (MAb) KP15 directed against the MHC-I molecule H-2Dd complexed with the 10-mer peptide P18-I10. Using this MAb, the cell surface H-2Dd/P18-I10 complex can be easily detected by flow cytometry (Polakova et al., 2000). Here we examined whether peptides longer than P18-I10 decamer form H-2Dd complexes recognized by KP15 MAb. Further we also analyzed how the ACE processing of P18IIIB-related peptides of different length affects their ability to form complexes with H-2Dd recognized by MAb KP15. These experiments confirmed that the ACE digestion of 15-mer peptide P18IIIB is the most effective in the production of a peptide capable of forming complex with H-2Dd recognized by KP15 MAb. The ACE digestion of longer peptides (16-mer to 19-mer) did not produce a significant quantity of peptides, capable of forming H-2Dd complexes recognizable with by MAb KP15. Peptides shorter than P18IIIB (13-mer to 10-mer), notably the optimally sized P18-I10 peptide lost most of their capacity to form H-2Dd complexes recognized by KP15 MAb. Our results show that the extracellular processing of MHC-I-restricted peptides, which cannot be overlooked in designing peptide-based vaccines, can be also studied by as simple and rapid assay as flow cytometry, provided MAbs specific to a particular MHC-I/peptide complex are available.

Animals↗
PubMed2000

The strong positive correlation between effective affinity and infectivity neutralization of highly cross-reactive monoclonal antibody IIB4, which recognizes antigenic site B on influenza A virus haemagglutinin.

Monoclonal antibody (MAb) IIB4 displays a rare combination of virus neutralization (VN) activity and broad cross-reactivity with influenza A virus strains of the H3 subtype isolated in a period from 1973 to 1988. The epitope of this antibody has been identified as around HA1 residues 198, 199 and 201. Here we report that residues 155, 159, 188, 189 and 193 also influence the binding of this antibody. We have used this antibody to study the relationship between antibody affinity and VN activity. Using one MAb and a single epitope on the haemagglutinin (HA) of different influenza viruses we found a strong positive correlation between effective affinity and VN activity of MAb IIB4. A 10-fold increase in effective affinity corresponded to the 2000-fold increase in VN titre. It follows from the law of mass action that for an effective affinity K=9x10(8) l/mol, 50% VN was achieved at approx. 10% occupation of HA spikes with antibody. In contrast, for an effective affinity K=6x10(7) l/mol, to achieve 50% VN, occupation of up to 98% of HA spikes was required. An effective affinity about K=6x10(7) l/mol thus represents the limiting value for VN because a further decrease in the affinity cannot be compensated by a higher concentration of antibody.

Amino Acid Sequence↗
PubMed2000

Expression of the non-classical HLA-G antigen in tumor cell lines is extremely restricted.

It has been proposed that tumor cells frequently associated with partial or total loss of HLA class Ia expression may abnormally express HLA-G class Ib antigen. Such peculiar HLA class I expression would allow tumor cells to escape not only from CD8+T but also from NK-cell cytotoxicity. We studied the cell surface expression of HLA-G using flow cytometry with two HLA-G specific monoclonal antibodies (87G, 01G). The JEG-3 choriocarcinoma cell line, which constitutively expresses HLA-G antigens was used as a positive control. We did not detect the cell-surface HLA-G antigens in the following 75 tumor cell lines: melanoma (22), neuroblastoma (7), retinoblastoma (1), glioma (2), breast carcinoma (3), ovarian carcinoma (3), cervical carcinoma (1), colon carcinoma (3), bladder carcinoma (2), hepatocarcinoma (1), sarcoma (2) and leukemia cell lines: T-lymphocytes (6), B-lymphocytes (13) and myelo-monocytes (9). We found that some myelomonocytic cell lines express on their surface high affinity FcgammaRI (CD64) that may result in the binding of HLA-G specific mabs to their cell surface even in the absence of HLA-G molecules. Our panel of HLA-G negative tumor cell lines accommodated 62 cell lines for which similar analysis have not been reported and also contained 13 cell lines with total or partial loss of HLA class Ia molecules. Our observation imply that under normal culture conditions the cell surface HLA-G reactive with 87G and 01G mabs is absent in most tumor cell lines of different origin.

Antibodies, Monoclonal↗
PubMed1999

Monoclonal antibodies suitable for type-specific identification of herpes simplex viruses by a rapid culture assay.

Eight monoclonal antibodies (MAbs) to herpes simplex viruses 1 and/or 2 (HSV-1, HSV-2) were tested for their reactivity with 190 previously typed HSV-positive clinical specimens in order to determine their suitability for use as type-specific reagents. Using a rapid culture assay we found that two MAbs (T51 and T96) identified HSV-1 in all the 94 specimens, previously found HSV-1-positive, but did not react with the 96 specimens, previously found HSV-2-positive. In contrast, one MAb (303) confirmed the presence of HSV-2 in all the specimens, previously found HSV-2-positive, but did not react with any of the 94 specimens, previously found HSV-1-positive. These three type-specific MAbs allow for a rapid type-specific identification of HSV in infected cultures. One type-common MAb (T111) reacted with all HSV-positive cultures. This MAb can be used as an excellent reagent for detection of HSV infection.

Antibodies, Monoclonal↗
PubMed1998

P-glycoprotein plays an insignificant role in the presentation of antigenic peptides to CD8+ T cells.

Most antigenic peptides presented to CD8+ T cells are generated from cytosolic precursors and are translocated by TAP into the endoplasmic reticulum, where they associate with MHC class I molecules. TAP-deficient cells exhibit a limited capacity to deliver peptides from cytosolic proteins to class I molecules. One candidate for an alternative peptide transporter is P-glycoprotein, which transports numerous substances, including peptides, across membranes. Elevation of P-glycoprotein expression is partially responsible for the resistance developed by neoplasias to chemotherapeutic drugs. Overexpression of P-glycoprotein has been reported to enhance the expression of class I molecules. Here, we investigated the role of P-glycoprotein in the generation of peptide-MHC complexes. We were unable to detect P-glycoprotein-mediated transport of synthetic peptides into the endoplasmic reticulum of either T2 cells (TAP-deficient) infected with a recombinant vaccinia virus (rVV) expressing P-glycoprotein or drug-resistant cells in which TAP is inactivated by a peptide from the herpes simplex virus ICP47 protein. Expression of rVV-encoded P-glycoprotein in T2 cells was unable to enhance cell surface expression of any of three MHC class I allomorphs tested. rVV-mediated expression of P-glycoprotein enabled T2 cells to produce limited amounts of class I-peptide complexes from cytosolic antigens, but this was not blocked by a drug that inhibits its transporter function, and a similar degree of presentation was mediated by functionally inactive mutated forms of P-glycoprotein. Thus, this was a nonspecific effect that we attributed to diminished membrane integrity resulting from P-glycoprotein overexpression. Taken together, our findings cast serious doubts that P-glycoprotein is a biologically significant transporter of cytosolic peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

An endoplasmic reticulum-targeting signal sequence enhances the immunogenicity of an immunorecessive simian virus 40 large T antigen cytotoxic T-lymphocyte epitope.

An immunological hierarchy among three H-2Db-restricted cytotoxic T lymphocyte (CTL) determinants in simian virus 40 (SV40) large T antigen (Tag) was described previously: determinants I and II/III are immunodominant, whereas determinant V is immunorecessive. To assess the immunogenicity of each determinant individually and define mechanisms that contribute to the immunorecessive nature of determinant V, we constructed a panel of recombinant vaccinia viruses (rVVs) expressing minigenes encoding these determinants in various polypeptide contexts. We found the following. (i) Immunization of mice with an rVV encoding full-length SV40 Tag resulted in priming for CTL responses to determinants I and II/III but not determinant V. (ii) rVVs encoding peptide I or II/III in the cytosol or targeted to the endoplasmic reticulum (ER) were highly antigenic and immunogenic. (iii) rVVs encoding peptide V minigenes were antigenic and immunogenic if the peptide was targeted to the ER, expressed in the cytosol with short flanking sequences, or expressed from within a self-protein, murine dihydrofolate reductase. (iv) Presentation of the nonflanked peptide V (preceded by a Met codon only) could be enhanced by using a potent inhibitor of the proteasome. (v) H-2Db-epitope V peptide complexes decayed more rapidly than complexes containing epitope I or II/III peptides. In brefeldin A blocking experiments, functional epitope V complexes were detected longer on targets expressing ER-targeted epitope V than on targets expressing forms of epitope V dependent on the transporter associated with antigen processing. Therefore, limited formation of relatively unstable cell surface H-2Db complexes most likely contributes to the immunorecessive nature of epitope V within SV40 Tag. Increasing the delivery of epitope V peptide to the major histocompatibility complex class I presentation pathway by ER targeting dramatically enhanced the immunogenicity of epitope V.

Animals↗
PubMed1998

Antibody responses to the herpes simplex virus type 2 glycoprotein G in sera of human immunodeficiency virus-infected patients in Slovakia.

Thirty sera of human immunodeficiency virus-positive (HIV+) and 37 sera of HIV-negative (HIV-) individuals in Slovakia were tested for the presence of antibodies to herpes simplex virus type 2 (HSV-2) glycoprotein G (gG). A notable difference between the prevalence of HSV-2-specific antibodies in HIV+ and that in HIV- individuals was found (37% vs. 11%) confirming and extending previous reports that HSV-2 infection is an important risk factor for HIV transmission. Efforts toward the detection of HSV-2 infection and its therapy by anti-HSV drugs should be considered an important factor in decreasing the risk of contracting and spreading of HIV in Slovakia.

Animals↗