Biomedical subjects

A Vaheri

Publications and source records attributed to A Vaheri.

At least 19 recordsLinked to original sources

PubMed2006

Is there an association of Pneumocystis infection with the presence of arena-, hanta-, and poxvirus antibodies in wild mice and shrews in Finland?

As part of studies on the nature of the endemic virus infections in natural rodent hosts, the possible association of cyst forms of Pneumocystis spp. with the presence of hanta-, cowpox-, and arenavirus antibodies in wild mice (Apodemus flavicollis, N=105; Apodemus agrarius, N=63; Micromys minutus, N=50) and the common shrew (Sorex araneus, N=101) was studied in south-central Finland. One hantavirus (Saaremaa virus, SAAV) seropositive A. agrarius, and 2 cowpoxvirus (CPXV) seropositive S. araneus were detected, and antibodies against an arenavirus (Lymphocytic choriomeningitis virus, LCMV) were found in all 3 mouse species but not in shrews. Cyst forms of Pneumocystis spp. were detected in all species except A. agrarius. There was no significant association between virus antibodies (LCMV in mice, and CPXV in shrews) and cyst forms of Pneumocystis in any of the species. Concurrent presence of virus antibodies (LCMV) and cyst forms of Pneumocystis were detected only in 1 M. minutus. In conclusion, we found no evidence of any association between Pneumocystis and antibodies to any of the viruses tested.

Animals↗

PubMed2006

HLA-DRB1, -DQB1 alleles in head and neck carcinoma patients.

Certain HLA class II alleles have been reported to play a role in development or prevention of cervical carcinoma, an epithelial malignancy linked to human papillomavirus (HPV). In head and neck carcinomas, of which a subset is also HPV associated, the impact of HLA genes remains unknown. HLA-DRB1, -DQB1 alleles were determined in a comprehensive series of 162 head and neck carcinoma patients, for which 83 consecutive cadaveric organ donors of Finnish origin served as controls. DRB1*03 was associated with node-negative disease and DRB1*08 and 13 with small tumors; DRB1*04 was protective against disease relapse. Most alleles of borderline significance in this study act similarly in cervical carcinomas.

Alleles↗

PubMed2006

Serological survey for viral pathogens in Turkish rodents.

Wild rodents (n = 330) were trapped around the villages of Altindere and Coşandere (Maçka, Trabzon Province), Ayder, Ortan, and Yolkiyi (Camlihemşin, Rize Province), and Bozdag (Odemiş, Izmir Province) in northeastern and western Turkey during April 2004. Samples were tested for arenavirus, hantavirus, and cowpox virus (family Poxviridae, genus Orthopoxvirus, CPXV) antibodies by using immunofluorescence assays (IFAs). Antibodies against arenaviruses were found in eight of 330 (2.4%) rodents. Arenavirus sero-positive animals were found from all study sites. Antibodies to Puumala virus (family Bunyaviridae, genus Hantavirus, PUUV) were detected in four of 65 Microtus voles tested. Of the PUUV-IFA-positive voles, one Microtus guentheri lydius was caught from Izmir, and one Microtus roberti and two Microtus rossiaemeridionalis were captured near Trabzon. All 264 Apodemus spp. mice tested negative for antibodies to Saaremaa virus (family Bunyaviridae, genus Hantavirus, SAAV); the single Dryomys nitedula tested negative for both PUUV and SAAV antibodies. Only one (0.3%) of the rodents, an Apodemus sylvaticus from Trabzon area, tested seropositive to CPXV. This is the first serologic survey for rodent-borne viruses in their natural hosts in Turkey. Although these preliminary results support presence of several virus groups with zoonotic potential, additional studies are needed to identify the specific viruses that are present in these populations.

Animals↗

PubMed2005

Hantavirus and arenavirus antibody prevalence in rodents and humans in Trentino, Northern Italy.

The spatial and temporal distribution of hantavirus and arenavirus antibody-positive wild rodents in Trentino, Italy, was studied using immunofluorescence assays (IFA) in two long-term sites trapped in 2000-2003, and six other sites trapped in 2002. The overall hantavirus seroprevalence in the bank voles, Clethrionomys glareolus (n=229) screened for Puumala virus (PUUV) antibodies was 0.4%, and that for Apodemus flavicollis mice (n=1416) screened for Dobrava virus (DOBV) antibodies was 0.2%. Antibodies against lymphocytic choriomeningitis virus (LCMV) were found in 82 (5.6%) of the 1472 tested rodents; the seroprevalence being 6.1% in A. flavicollis (n=1181), 3.3% in C. glareolus (n=276), and 14.3% in Microtus arvalis (n=7). Of the serum samples of 488 forestry workers studied by IFA, 12 were LCMV-IgG positive (2.5%) and one DOBV-IgG positive (0.2%), however, the latter could not be confirmed DOBV-specific with a neutralization assay. Our results show a widespread distribution but low prevalence of DOBV in Trentino, and demonstrate that the arenavirus antibodies are a common finding in several other rodent species besides the house mouse.

Adult↗

PubMed2005

Hantavirus nucleocapsid protein: a multifunctional molecule with both housekeeping and ambassadorial duties.

In recent years important progress has been made studying the nucleocapsid (N) protein of hantaviruses. The N protein presents a good example of a multifunctional viral macromolecule. It is a major structural component of a virion that encapsidates viral RNA (vRNA). It also interacts with the virus polymerase (L protein) and one of the glycoproteins. On top of these "house keeping" duties, the N protein performs interactive "ambassadorial" functions interfering with important regulatory pathways in the infected cells.

Actin Cytoskeleton↗

PubMed2004

L protein, the RNA-dependent RNA polymerase of hantaviruses.

L protein of hantaviruses is the RNA transcriptase and replicase that transcribes mRNAs and replicates the genomic RNA using antigenomic RNA as an intermediate. It also appears to have endonuclease activity. In this review, the current knowledge on the hantavirus L protein is presented including sequence motifs conserved in RNA polymerases, mechanisms of RNA synthesis and also the most recent findings on homologous RNA recombination and membrane association.

Amino Acid Motifs↗

PubMed2004

Regulation and interactions in the activation of cell-associated plasminogen.

The main components in plasminogen activation include plasminogen, tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitors-1 and -2 (PAI-1, PAI-2). These components are subject to extensive regulation and interactions with for example, pericellular adhesion molecules. Although uPA and tPA are quite similar in structure and have common inhibitors and physiological substrates, their physiological roles are distinct. Traditionally, the role of tPA has been in fibrinolysis and that of uPA in cell migration, especially in cancer cells. Recently several targets for tPA/plasmin have been found in neuronal tissues. The functional role of the PAIs is no longer simply to inhibit overexpressed plasminogen activators, and PAI-2 has an unidentified role in the regulation of cell death.

Animals↗

PubMed2004

Rapid field test for detection of hantavirus antibodies in rodents.

Puumala virus (PUUV) is the causative agent of nephropathia epidemica, a mild form of haemorrhagic fever with renal syndrome. PUUV is transmitted to humans via aerosolized excreta of the infected bank vole (Clethrionomys glareolus). Current methods for screening of the PUUV prevalence among bank vole populations are laborious, combining sampling in the field and subsequent analyses in the laboratory. In order to facilitate animal testing, a new serological immunochromatographic rapid test was developed. The test uses PUUV nucleocapsid protein as antigen, and it detects anti-PUUV IgG antibodies in rodents. With fresh and undiluted bank-vole blood samples (n = 105) the efficacy of the test was 100%, and with frozen and diluted samples (n = 78) the efficacy was 91%. The test was also shown to detect related hantavirus infections in Norway lemmings and sibling voles (n = 31) with 99% efficacy. The test provides an applicable tool for studying PUUV and related hantavirus infections in arvicoline rodents.

Animals↗

PubMed2004

Cell-cell contacts trigger programmed necrosis and induce cyclooxygenase-2 expression.

Necrosis was induced by cell-cell contacts of human dermal fibroblasts in three-dimensional culture. Dramatic induction of cyclooxygenase-2 (COX-2) expression was found throughout these necrotizing cell clusters, whereas no increase in expression of apoptosis markers was seen. The cells were rapidly committed to necrosis, and the process could not be reversed by allowing them to spread and adhere on a solid substrate. Induction of COX-2 expression was accompanied by greatly enhanced production of the prostaglandins E(2), I(2), and F(2alpha). When applied exogenously on necrotizing clusters, these prostaglandins delayed cell clustering and further enhanced COX-2 expression. Abolishing prostaglandin production by NS-398 or indomethacin reduced cell membrane damage (as measured by lactate dehydrogenase release into the culture medium). We also identified alpha-enolase-mediated plasminogen activation as the major extracellular proteolytic executor of necrotic cell death. In contrast to inhibition of COX-2, inhibition of plasminogen activation failed to inhibit membrane damage associated with necrosis. Intracellular proteolysis, by caspases, was shown to take part in COX-2 induction. Taken together, our results indicate that cell-cell contacts induce an actively programmed necrotic process that functionally involves COX-2, a known hallmark of inflammation and cancer.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers.

BACKGROUND: The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing. It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinolysis. OBJECTIVES: The present study was conducted to characterize the spatial distribution of the various plasminogen activation system components in chronic ulcers and acute, well-granulating wounds. METHODS: The expression of uPA, tPA, urokinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitronectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic venous ulcers, five decubitus ulcers, five well-granulating acute wounds and five normal skin samples. RESULTS: In chronic venous leg ulcers tPA mRNA was detected in basal and suprabasal keratinocytes at the leading wound edge, while in well-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a few keratinocytes. However, tPA was widely expressed in fibroblast- and macrophage-like cells in the stroma of well-granulating wounds, while less tPA was detected in the granulation tissue of chronic ulcers. tPA mRNA and protein were localized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocytes in chronic ulcers vs. normally granulating wounds were found, their expressions were more pronounced in the granulation tissue of well-granulating wounds. CONCLUSIONS: These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the granulation tissue.

Acute Disease↗

PubMed2004

cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-alpha in NCI-H295R adrenocortical cells.

Adrenocorticotropin is the major regulator of adrenocortical development and function. It acts mainly through the cAMP-dependent protein kinase A (PKA) pathway. Our aim was to study the interaction of tumor necrosis factor-alpha (TNFalpha) and the PKA pathway in adrenocortical cell proliferation and apoptosis. The PKA activator Dibutyryl cAMP ((Bu)2cAMP) strongly induced differentiation and inhibited proliferation in the human adrenocortical cell line NCI-H295R (H295R). TNFalpha induced apoptosis of H295R cells. Interestingly, (Bu)2cAMP treatment clearly enhanced TNFalpha-induced apoptosis in H295R cells, but not in another human adrenocortical cell line SW-13, the mouse adrenocortical Y-1 cell line or the human HeLa cell line. This synergistic effect was not due to the (Bu)2cAMP-induced glucocorticoid secretion since dexamethasone had no significant effect on the TNFalpha-induced apoptosis. (Bu)2cAMP treatment rapidly increased the expression of the proto-oncogene c-myc in H295R cells, but not in SW-13, Y-1 or HeLa cells. In transient c-myc transfection assay, c-myc expression associated with decreased expression of the proliferation marker Ki-67 in H295R cells. In conclusion, cAMP-dependent protein kinase activation reduced proliferation and augmented TNFalpha-induced apoptosis in adrenocortical H295R cells, and these effects were associated with increased c-myc expression.

Adrenal Cortex Neoplasms↗

PubMed2004

DNA methylation affects cell proliferation, cortisol secretion and steroidogenic gene expression in human adrenocortical NCI-H295R cells.

Aberrant DNA methylation may be involved in human adrenocortical tumorigenesis, which is often accompanied by abnormal hormone production. In this study, we aimed to clarify the effects of DNA methylation on steroidogenesis using the human adrenocortical NCI-H295R cell line as a model. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (Azad; 10 microM for 7 days) decreased the proliferation rate to approximately 20% and the cell number to 60% of the control, with a simultaneous increase in the expression of the cyclin-dependent kinase inhibitor p57(KIP2) gene. In addition, Azad treatment increased cortisol secretion dose and time dependently, whereas dehydroepiandrosterone sulfate secretion was not affected. Azad treatment decreased basal and (Bu)2cAMP-induced expression of low- and high-density lipoprotein receptor, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme, steroid 17alpha-hydroxylase/17,20-lyase and steroid 21-hydroxylase mRNA, as well as the StAR protein level. In contrast, Azad treatment increased the basal expression of steroid 11beta-hydroxylase and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-isomerase genes, although it inhibited the (Bu)2cAMP-induced expression of these two genes. The expression of steroidogenic factor-1 (SF-1) and DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome 1) genes (both harboring putative CpG islands in their promoters) and the methylation degree of the HpaII recognition site(s) in the SF-1 gene promoter region were reduced by Azad treatment. The immunostaining pattern of the methyl-CpG-binding protein MeCP2 was also modified by Azad treatment. These results suggest that DNA methylation may be implicated in the regulation of cell proliferation and steroidogenesis in human adrenocortical cells.

Adrenal Cortex↗

PubMed2003

Plasminogen activation in neurofibromatosis 2-associated and sporadic schwannomas.

BACKGROUND: Schwannomas are usually benign tumours which occur sporadically or in association with neurofibromatosis 2 (NF2), an autosomal dominant disorder. Invasiveness and higher proliferative potential compared to sporadic tumours are features of NF2-associated schwannomas. METHOD: We studied urokinase (uPA), tissue-type plasminogen activator (tPA), urokinase receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) expression by in situ hybridization and by immunohistochemistry in 14 NF2 and 15 sporadic patients with 34 schwannomas. uPAR and vitronectin immunohistochemistry were also studied. Three sural nerve specimens were included as Schwann cell controls. FINDINGS: Both schwannoma groups expressed prominent levels of uPA and tPA. Semiquantitative analysis of the in situ hybridization and immunoreactivity demonstrated that NF2 schwannomas expressed less PAI-1 at the mRNA level than sporadic schwannomas (score 1.63+/-0.41 vs. 2.05+/-0.75) and less total PAI-1 at the antigen level (score 1.55+/-0.66 vs. 2.07+/-0.56). PAI-1 was mostly in a free form in NF2 schwannomas compared to the sporadic counterparts (score 1.85+/-0.73 vs. 1.46+/-0.58), whereas there was less uPAR antigen in NF2 schwannomas than in the sporadic counterparts (score 1.18+/-0.49 vs. 1.68+/-0.56). Sural nerve Schwann cells did not express detectable level of PAI-1 and at the most a minor amount of tPA. CONCLUSIONS: Schwann cells of tumour cell origin, both in sporadic and NF2 schwannomas, expressed elevated levels of plasminogen activators and PAI-1 compared to normal suralic nerve Schwann cells. Furthermore, there seemed to be an imbalance in the PA-PAI-1 system in NF2-associated schwannomas. Although our methods are more descriptive than quantitative, we suggest that the somewhat more aggressive behavior of NF2-associated schwannomas compared to sporadic schwannomas may be based on the local proteolytic activity.

Antibodies, Monoclonal↗

PubMed2003

Establishment and characterisation of human papillomavirus type 16 DNA immortalised human tonsillar epithelial cell lines.

Oncogenic human papillomavirus (HPV) plays a possible aetiological role in a subset of head and neck cancers, particularly in tonsillar carcinomas. For establishing a model to study mechanisms involved in HPV-associated tonsillar carcinogenesis, normal human tonsillar epithelial (HTE) cells were transfected with full-length HPV-16 DNA. The transfections produced four immortalised cell lines, designated HTE-114/K1, HTE-114/K2, HTE-114/K3 and HTE-114/B. All transfected HTE cell lines were cytogenetically abnormal. They exhibited altered morphology and impaired expression of cytokeratins in organotypic cultures. They failed to form colonies in soft agarose and formed no tumours in nude mice within 6 months. Each of them contained integrated viral DNA in a distinctive pattern as shown by Southern blot hybridisation. Early viral transcripts containing the E7 gene were detected by northern blot hybridisation. In conclusion, primary HTE cells can be immortalised following transfection with full-length HPV-16 DNA; the immortalised cell lines had partially retained epithelial characteristics in their morphology and function. They seem to represent early stages of premalignant epithelial cells and thus provide a useful model for studying further the multistep molecular events of HPV-16-associated tonsillar carcinogenesis.

Animals↗

PubMed2002

Epidemiology of Sindbis virus infections in Finland 1981-96: possible factors explaining a peculiar disease pattern.

Pogosta disease (PD), an epidemic rash-arthritis occurring in late summer is caused by Sindbis virus (SINV) and is transmitted to humans by mosquitoes. Altogether 2183 PD cases were serologically confirmed 1981-96 in Finland, with an annual incidence of 2.7/100000 (18 in the most endemic area of Northern Karelia). The annual average was 136 (varying from 1 to 1282) with epidemics occurring in August-September with a 7-year interval. Studies on 6320 patients with suspected rubella (1973-89) revealed 107 PD cases. The depth of snow cover and the temperature in May-July seemed to predict the number of cases. The morbidity was highest in 45- to 65-year-old females and lowest in children. Subclinical SINV infections were 17 times more common than the clinical ones. The SINV-antibody prevalence in fertile-age females was 0.6% in 1992; the estimated seroprevalence in Finland is about 2%. Among game animals the tetraonids (black grouse and capercaillie) had the highest seroprevalence (65%) in the epidemic year of 1981.

Adolescent↗

PubMed2002

Antibody status to HHV-6 in children with leukaemia.

Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6 (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched children with various neurological diseases of suspected viral origin. Of the children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6 compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of IgG antibodies (based on the resistance to urea treatment) was high in all children with leukaemia. One reference child had HHV-6-specific IgG antibodies with low avidity, which together with his positive IgM indicated an acute infection. The presence of specific IgM antibodies in 40% of children with leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate primary response to HHV-6 infection. The results support the conclusion of the role of the HHV-6 infection at the onset of childhood leukaemia.

Adolescent↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2002

Mapping of B-cell epitopes in the nucleocapsid protein of Puumala hantavirus.

Hantavirus nucleocapsid protein (N) has been proven to induce highly protective immune responses in animal models. The knowledge on the mechanisms behind N-induced protection is still limited, although recent data suggest that both cellular and humoral immune responses are of importance. For a detailed B-cell epitope mapping of Puumala hantavirus (PUUV) N, we used recombinant N derivatives of the Russian strain CG18-20 and the Swedish strain Vranica/Hällnäs, as well as overlapping synthetic peptides corresponding to the Finnish prototype strain Sotkamo. The majority of a panel of monoclonal antibodies (mAbs) reacted with proteins derived from all included PUUV strains demonstrating the antigenic similarity of these proteins. In line with previous results, the epitopes of most mAbs were mapped within the 80 N-terminal amino acids of N. The present study further revealed that the epitopes of four mAbs raised against native viral N were located within amino acids 14-45, whereas one mAb raised against recombinant N was mapped to amino acids 14-39. Differences between the reactivity of the PUUV strains Vranica/Hällnäs and CG18-20 N suggested the importance of amino acid position 35 for the integrity of the epitopes. In line with the patterns obtained by the truncated recombinant proteins, mapping by overlapping peptides (PEPSCAN) confirmed a complex recognition pattern for most analyzed mAbs. Together, the results revealed the existence of several, partially overlapping, and discontinuous B-cell epitopes. In addition, based on differences within the same competition group, novel epitopes were defined.

Amino Acid Sequence↗