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Biomedical subjects

A Vaheri

Publications and source records attributed to A Vaheri.

At least 181 records · Page 10Linked to original sources
PubMed1994

Nephropathia epidemica in Finland: a retrospective study of 126 cases.

A total of 126 (99 males, 27 females) serologically confirmed hospital-treated adult cases of nephropathia epidemica (NE) were studied. The initial diagnosis suggested by the referring physician was correct in only 28%. Some rare clinical manifestations of NE were observed; acute myopericarditis in 3 patients and encephalitis in 1. Pulmonary involvement due to vascular congestion was observed in 16% and liver involvement in 34% of the patients. Thrombocytopenia was present in 75%, leukocytosis in 50% and anemia in 50%. Erythrocyte sedimentation rate (ESR) was 2-108 (mean 38) mm/h and C-reactive protein (CRP) 0-126 (mean 52) mg/l. Proteinuria was observed in 94%, hematuria in 58% and pyuria in 28%. Electrolyte abnormalities (hyponatremia, hypokalemia, hypocalcemia, hyperphosphatemia) were all common but rarely serious. Serum lipid changes caused by the acute infection and renal failure included very low total and HDL-cholesterol as well as high triglyceride levels. Renal function was transiently impaired in 94% of the patients and 7 needed transient dialysis therapy. All recovered.

Adolescent↗
PubMed1994

Activation of interleukin-1 beta gene expression during retinoic acid-induced granulocytic differentiation of promyeloid leukemia cells.

We have examined the expression of the interleukin 1 beta (IL-1 beta) gene during the granulocytic differentiation of two promyeloid leukemia cell lines, HL-60 and NB4. HL-60 is known to differentiate along the granulocytic pathway after treatment with 13-trans-retinoic acid (13-trans-RA), whereas treatment with phorbol myristate acetate (PMA) leads to development of mature macrophages. NB4 cells are derived from the bone marrow of an acute promyelocytic leukemia (APL) patient in relapse, have a translocated RA receptor-alpha, and are converted into nondividing granulocytes by 13-trans-RA treatment. When HL-60 or NB4 were cultured in the presence of 13-trans-RA, IL-1 beta mRNA and protein levels were increased. In the more mature THP-1 cells which are induced to macrophage-like cells by 13-trans-RA treatment, RA was unable to induce any IL-1 beta expression, implying that the effect of 13-trans-RA is associated with granulocytic differentiation. Moreover, PMA and 13-trans-RA had a strong synergistic effect in the induction of IL-1 beta gene expression. Nuclear run-off analysis indicated that the increased IL-1 beta gene expression was due to an enhanced rate of transcription. When the cells were transfected with an IL-1 beta-X-CAT reporter plasmid containing the -2982/-2748 promoter segment of the IL-1 beta gene conferring responsiveness to PMA, both NB4 and HL-60 cells responded with increased CAT activity when stimulated with 13-trans-RA alone. In contrast to PMA, 13-trans-RA was unable to increase AP-1 enhancer activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Renal biopsy findings and clinicopathologic correlations in nephropathia epidemica.

A series of 126 adult patients with a serologically confirmed diagnosis of nephropathia epidemica (NE) were studied during the acute phase of the disease. In 86 cases, renal biopsy was performed. The severity of renal failure correlated slightly with blood inflammatory parameters and the degree of hematuria but not with the amount of proteinuria. The degree of hematuria correlated inversely with the level of thrombocytopenia. The most common histopathologic lesion was acute tubulointerstitial nephritis. Interstitial edema and inflammatory cell infiltrations were most usually present, followed by tubular epithelial and luminal alterations. Slight glomerular mesangial changes were present in 25% of the biopsy specimens. Except for hemorrhage in the outer renal medulla, the histologic lesions were relatively mild and unspecific. Interstitial hemorrhage should remind a pathologist of the possibility of NE. Tubular, interstitial and glomerular histologic damage were but vascular lesions were not associated with the clinical severity of renal failure. Glomerular alterations did not relate to the amount of urine protein excretion. Correlations, however, were so weak that in clinical work renal biopsy is usually not indicated for determination of the severity of renal failure in NE. Intrinsic renal events are probably important in the development of renal failure in NE.

Acute Kidney Injury↗
PubMed1993

Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients.

We have examined the mononuclear cell fraction from 35 individuals, 18 with hematologic malignancies and 17 healthy controls for the presence of cell surface-associated plasminogen activator (PA) activity. PA activity was found on the cell surface of 10 out of 12 samples from patients with acute leukemia. In addition to active urokinase (uPA) found on the cell surface in four out of five acute myeloid leukemia patients, tissue-type PA activity was detected in the same samples (3 of 5). Two out of four samples from acute lymphoid leukemia displayed only uPA activity and three out of three samples from biphenotypic leukemia were also clearly uPA-positive. Plasmin activity was not detected in any of the samples. PA activity was not found on the surface of mononuclear cells from either patients with chronic lymphoid leukemia or healthy controls and, in this respect, the cell surface-bound uPA activity behaved as a marker for acute leukemia. The finding of PA activity on the cell surface in acute leukemia suggests that there may be continuous generation of plasmin with consequent consumption of plasma plasmin inhibitors.

Bone Marrow↗
PubMed1993

Persistence of plasmin-mediated pro-urokinase activation on the surface of human monocytoid leukemia cells in vitro.

Human leukemia cell lines, unlike those from adherent tumors, have been shown to continuously activate the pro-urokinase (pro-u-PA) they produce. In the present study we found that, in normal cell-culture conditions in 10% FCS the plasminogen activation cascade works continuously on monocytoid leukemia cells, which expressed plasmin activity and active u-PA on their cell surface. This plasmin catalyzed the conversion of the produced pro-u-PA to active 2-chain urokinase (tcu-PA), and was derived from bovine serum plasminogen by the activity of cell-bound tcu-PA. Plasmin generation was abolished and pro-u-PA accumulated in cell cultures that were grown for several days, either in the presence of serum thoroughly depleted of plasminogen, or in the presence of 1 mM tranexamic acid. Plasmin generated on the cell surface was found to be present in 2 enzymatically active fragments, of M(r) 85,000 and M(r) 50,000, which were slowly released into the growth medium. These fragments could activate pro-u-PA in serum-free growth medium. Most of the bound plasmin could be washed off cells with 10 mM tranexamic acid, but complete removal of plasmin from the cell surface required washing of the cells with acid-glycine pH 3.0.

Animals↗
PubMed1993

Binding of tissue-type plasminogen activator to human melanoma cells.

We have shown (Bizik et al., Cell Regul 1:895-905, 1990) that tPA can activate plasminogen on the surface of human melanoma cells in the presence of alpha 2-macroglobulin (alpha 2M) secretion. In the present study, we investigated the binding of tPA on the surface of Bowes melanoma cells, selected since they lacked production of PAI-1 and alpha 2M. Elution of tPA from the cell layers indicated that polylysine (5 micrograms/ml) and tranexamic acid (10 mM), an analog of lysine, were the most efficient agents for disrupting the interaction between tPA and cell surface component(s). Using a panel of monoclonal antibodies against individual domains of tPA revealed that an antibody directed to the kringle-2 domain of tPA interfered most significantly with cell-surface plasmin generation. As tPA is a glycoprotein, interactions between the tPA sugar moieties and cell surface were also tested by the use of a series of monosaccharides. N-acetyl-D-glucosamine (100 mM) was the most potent sugar to release tPA from melanoma cells, but the results indicated that the oligosaccharides of tPA play only a supportive role in the binding of tPA to the cell surface. Quantitative comparison of the cell surface localized tPA, which was eluted by tranexamic acid, with the total cellular tPA showed that cell surface bound tPA could represent up to 10%. We conclude that tPA interacts with the melanoma cell surface in a similar manner as has been described for binding of tPA to fibrin and to the putative endothelial cell surface receptor.

Antibodies, Monoclonal↗
PubMed1993

Identification of human type D retrovirus as a contaminant in a neuroblastoma cell line.

In this report we describe a type D virus isolated from a human neuroblastoma cell line (Paju). The viral RNA was isolated, partially molecularly cloned and sequenced. Our clones were shown to be identical to a human D-type retrovirus previously isolated from a human lymphoblastoid cell line. However, we obtained no evidence for the virus in earlier passage of the Paju cell line and therefore we must consider this isolate a laboratory contamination. contamination.

Adolescent↗
PubMed1993

Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker.

Ezrin, a widespread protein present in actin-containing cell-surface structures, is a substrate of some protein tyrosine kinases. Based on its primary and secondary structure similarities with talin and band 4.1 it has been suggested that this protein could play a role in linking the cytoskeleton to the plasma membrane (Gould, K.L., A. Bretscher, F.S. Esch, and T. Hunter. 1989. EMBO (Eur. Mol. Biol. Organ.), J. 8:4133-4142; Turunen, O., R. Winqvist, R. Pakkanen, K.-H. Grzeschik, T. Wahlström, and A. Vaheri. 1989. J. Biol. Chem. 264:16727-16732). To test this hypothesis, we transiently expressed the complete human ezrin cDNA, or truncated cDNAs encoding the amino- and carboxy-terminal domains of the protein, in CV-1 cells. Protein epitope tagging was used to unambiguously determine the subcellular distribution of the protein encoded by the transfected cDNA. We show that this protein is concentrated underneath the dorsal plasma membrane in all actin-containing structures and is partially detergent insoluble. The amino-terminal domain displays the same localization but is readily extractable by nonionic detergent. The carboxy-terminal domain colocalizes with microvillar actin filaments as well as with stress fibers and remains associated with actin filaments after detergent extraction, and with disorganized actin structures after cytochalasin D treatment. Our results clearly demonstrate that ezrin interacts with membrane-associated components via its amino-terminal domain, and with the cytoskeleton via its carboxy-terminal domain. The amino-terminal domain could include the main determinant that restricts the entire protein to the cortical cytoskeleton in contact with the dorsal plasma membrane and its specialized microdomains such as microvilli, microspikes and lamellipodia.

Amino Acid Sequence↗
PubMed1993

Susceptibility of human cells to Puumala virus infection.

Nephropathia epidemica involves several organs including kidney, lung, liver and brain. To investigate the susceptibility of putative target cells to the agent responsible, Puumala virus, we screened established human cell lines of lung (WI-38, A-427, CCD-11Lu), kidney (A-704), liver (Hep G2), pharynx (Detroit 562), submaxillary gland (A-253) and neural (SK-N-MC, SH-SY5Y) origin as well as primary human kidney glomerular cells, endothelial cells and peripheral blood monocytes/macrophages. Propagation of the Sotkamo strain of Puumala virus was also tested in the primary kidney, spleen and lung cells of bank voles (the natural host of the virus). All of the primary cells and most of the established cell lines expressed viral protein, synthesized viral RNA and secreted infectious virus, except the neural SK-N-MC and SH-SY5Y cells. None of the tested cell types except the primary bank vole kidney cells could propagate the virus as efficiently as the Vero E6 cells. The observed host cell range is wide and consistent with a multiorgan involvement of Puumala virus. No cytopathic effects were seen in any of the infected cell cultures.

Animals↗
PubMed1993

Clinical spectrum of neurological herpes simplex infection.

All cases of neurological infections virologically verified as due to herpes simplex virus (HSV) during a 2-year period in the Helsinki University Hospital area were studied. Altogether 10 cases were divided clinically into two forms: encephalitis 5 cases, polyradiculomyelitis, meningitis and miscellaneous 5 cases. All the cases of encephalitis were treated with acyclovir. None of the severe cases of herpes radiculomyelitis received this drug, because of lack of a rapid virological diagnosis. Besides encephalitis HSV was associated with other types of severe diseases and those need attention for proper therapy.

Acyclovir↗
PubMed1993

Proteolytic activity in leg ulcer exudate.

Twenty-five leg ulcer exudate samples from 17 patients with chronic non-healing venous leg ulcer were analyzed for proteolytic activity using radial caseinolysis procedures and zymographic analysis, and for fibronectin fragmentation using immunoblotting technology. Caseinolytic activity was detected in 21 of the 25 samples. A minority of them were inhibited (3 were totally, 6 partially inhibited) by aprotinin, a serine proteinase inhibitor, suggesting that proteinase(s) other than plasmin were also responsible for the caseinolysis. In zymographic analysis, 23 of the 25 samples showed positive reactions for enzyme activities comigrating with plasmin and urokinase-type plasminogen activator. Fibronectin fragmentation, another sign of proteolytic activity, was seen in all but 2 ulcers. No correlation was seen between bacterial infection or inflammatory cells and the above parameters in the wound fluid. Acute wound fluid collected from the donor sites of patients undergoing split skin grafting was used as a control. In the control specimens no proteolytic activity was found during the days following operation. These results show that there is proteolytic activity in the chronic ulcer exudate and support the possibility that the proteolytic activity and consequent fibronectin fragmentation may be related to the retarded epithelization and ulcer healing.

Adult↗
PubMed1993

Puumala virus antibody and immunoglobulin G avidity assays based on a recombinant nucleocapsid antigen.

Puumala virus is the causative agent of nephropathia epidemica (NE), a hantavirus infection which occurs widely in northern and central Europe and is generally diagnosed by the indirect immunofluorescence (IF) method. We have now expressed the Puumala virus Sotkamo strain nucleocapsid (N) protein-coding S genome segment as a beta-galactosidase fusion protein in Escherichia coli by using the pEX2 expression vector. The recombinant protein was purified by cutting the protein band from an agarose gel, melting the agarose, and removing the protein by freezing, incubation on ice, and centrifugation. The recovery was about 1 to 5 mg/200 ml of bacterial suspension, sufficient for coating 100 to 500 enzyme immunoassay microtiter plates. In a study of 312 IF-positive and 233 IF-negative serum samples from NE patients, the recombinant-N-protein enzyme immunoassay detected immunoglobulin G antibodies to Puumala virus with 97.8% sensitivity and 98.5% specificity compared with the IF test results. In addition, an immunoglobulin G avidity enzyme immunoassay was developed and used successfully to diagnose acute NE from a single serum sample. The results demonstrate that the bioengineered antigen is suitable for use in routine diagnostic assays for Puumala virus immunity and recent infection.

Adolescent↗
PubMed1993

Distribution and lateral mobility of the urokinase-receptor complex at the cell surface.

Pro-urokinase (pro-uPA) and activated uPA are confined to focal adhesions and cell-cell contacts. We studied the distribution of the uPA receptor (uPAR) on human fibroblasts (HES) and rhabdomyosarcoma (RD) cells by immunofluorescence and immunoelectron microscopy. Two monoclonal antibodies (MAb) utilized were against uPAR: MAb R4, which reacts with occupied and unoccupied uPAR, was concentrated at focal adhesions; MAb R3 reacting with unoccupied receptor stained cell surfaces diffusely. MAb R4 stained cell-cell contacts, tips of microspikes, and co-localized with vinculin. Of the matrix and integrin components tested, alpha v beta 3 integrin was found at focal adhesions but more centrally than uPAR. Since uPAR is anchored to the plasma membrane through a GPI lipid, we studied its mobility by antibody-induced clustering. This revealed that unoccupied uPAR was relatively mobile; MAb R3 redistributed it to clusters. In contrast, uPAR R4 and uPA antibodies at the focal contact sites remained mostly within focal contacts. Addition of exogenous uPA resulted in loss of R3 staining and increase of uPA in focal adhesions. These results suggest that occupancy of the receptor with uPA is associated with localization to cell contact sites and restricted lateral mobility.

Antibodies, Monoclonal↗
PubMed1993

Human spumaretrovirus in the etiology of sudden hearing loss.

The etiology of sudden sensorineural hearing loss, so called sudden deafness, has for long puzzled researchers. Recently we have studied the possibility that a hitherto relatively unknown retrovirus group consisting of human spumaretroviridae (HSRV) might be the causative agent of sudden deafness. During the last 3 months we have screened about 30 cases of sudden deafness. In 4 of them antibodies against HSRV were detected. Three of them had suffered from a flu-like condition about 2 weeks before the onset of hearing loss. In 2 cases the hearing of both ears was involved, in 1 case a relapsing hearing loss was observed, and 1 case developed a Meniere-like symptomatology with a fluctuant hearing loss. Vertigo was present in 3 patients and all suffered from tinnitus. Full recovery of hearing was observed in 4 of 6 affected ears whereas 2 ears became practically deaf with poor speech discrimination. At present it seems likely that a significant part of sudden deafness is caused by HSRV infection. The course of infection follows the spontaneous course of sudden deafness described by many authors. We encourage otologic units to screen for HSRV when assessing the etiology of sudden deafness.

Adult↗
PubMed1993

Retinoids increase urokinase-type plasminogen activator production by human retinal pigment epithelial cells in culture.

PURPOSE: To examine the effect of two retinoids, all-trans-retinoic acid (tretinoin) and all-trans-9-(4-methoxy-2,3,6- trimethylphenyl)-3,7-dimethyl- 2,4,6,8-nonatetraenoic acid (acitretin) on the production of plasminogen activators and plasminogen activator inhibitors by human retinal pigment epithelial cells in culture. METHODS: Cultures of human retinal pigment epithelial cells were incubated with either of the retinoids at a concentration of 1 microM for 24-72 hours. The media were assayed using solid-phase immunocapture assays and zymography. RESULTS: Both retinoids caused a twofold to sevenfold increase in urokinase-type plasminogen activator in the medium. The effect was seen after 24 hours in culture and was further augmented up to 72 hours. No significant amounts of tissue-type plasminogen activator were detected. The plasminogen activator inhibitor activity was unaffected by the retinoids. Proliferation and morphology of retinal pigment epithelial cells were also unaffected by the retinoids in incubations for up to 72 hours. CONCLUSIONS: Retinoids profoundly affect the extracellular proteolysis of retinal pigment epithelial cells in culture. This effect may be related to the differentiation-inducing activity of retinoids seen in other cell types, often connected with changes in extracellular proteolysis. It is possible that retinoids may modulate dedifferentiation, proliferation, and migration of retinal pigment epithelial cells seen in vitro, as well as in the pathogenesis of retinal disease.

Acitretin↗
PubMed1992

Heparin binding to the urokinase kringle domain.

The binding of urokinase to immobilized heparin and dextran sulfate was studied using activity assays of the bound urokinase. The markedly higher binding observed with high M(r) urokinase compared to low M(r) urokinase indicated a role for the amino-terminal fragment (ATF). This was confirmed by the use of inactive truncated urokinase and monoclonal antibodies specific for the ATF in competition assays of urokinase binding. Antibody competition assays suggested a site in the kringle domain, and a synthetic decapeptide Arg-52-Trp-62 from the kringle sequence (kringle numbering convention) was competitive in assays of urokinase binding to dextran sulfate and heparin. Heparin binding to the urokinase kringle was unambiguously demonstrated via 1H NMR spectroscopy at 500 MHz. Effective equilibrium association constants (K(a)*) were determined for the interaction of isolated kringle fragment and low M(r) heparin at pH 7.2. The binding was strong in salt-free 2H2O (K(a)* approximately 57 mM-1) and remained significant in 0.15 M NaCl (K(a)* approximately 12 mM-1), supporting a potential physiological role for the interaction. This is the first demonstration of a function for the kringle domain of urokinase, and it suggests that while the classical kringle structure has specificity for lysine binding, there may also exist a class of kringles with affinity for polyanion binding.

Amino Acid Sequence↗