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Biomedical subjects

A Vaheri

Publications and source records attributed to A Vaheri.

At least 289 records · Page 16Linked to original sources

Plasminogen and tissue-type plasminogen activator bind to immobilized fibronectin.

Fibronectin immobilized onto polystyrene surface was found to bind plasminogen and tissue-type plasminogen activator (t-PA) but only slightly the urokinase type as determined using mono- and polyclonal antibodies against the activators. Of the defined fibronectin fragments tested, the Mr 120,000-140,000 fragment was found to bind both plasminogen and t-PA. Proteolytically modified plasminogen (Lys-plasminogen) bound considerably better than the native form (Glu-plasminogen). Experiments with 125I-plasminogen yielded Kd = 9.1 X 10(-8) M for the binding to immobilized fibronectin. The partially or completely inactive single-chain form of t-PA (pro-t-PA) bound considerably better than the activated two-chain form. Lysine at greater than 3 mM inhibited the binding of plasminogen. The interaction was independent of calcium ions. CaCl2 (greater than 0.5 mM) and NaCl (greater than 0.2 M) inhibited the binding of pro-t-PA and of t-PA. Fibronectin-bound t-PA retained its ability to activate plasminogen. The observed interactions may operate in directional proteolysis localizing plasminogen and plasminogen activator to degrade fibronectin-containing extracellular matrix including fibrin clots.

Epitopes↗

Mr 75,000 protein, a tumor marker in renal adenocarcinoma, reacting with antibodies to a synthetic peptide based on a cloned human endogenous retroviral nucleotide sequence.

Using a rabbit antiserum to a synthetic undecapeptide deduced from a cloned human retroviral gag-gene-related DNA sequence, we found a specific immunohistochemical reaction in all of 42 tested renal cell adenocarcinomas (RCC), while none of 17 similarly tested Wilms' tumors and 65 carcinomas at other sites were positive. The RCC included two cases that presented with distant metastases. It had not been possible to establish the origin of these until immunohistochemical staining revealed this typical reaction. Subsequent renal angiography disclosed the primary. In immunoblotting the antiserum detected an Mr 75,000 protein in RCC tissue, and this reaction was blocked by the undecapeptide. The usefulness of this protein as a tumor marker for RCC is discussed.

Adenocarcinoma↗

Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) comprises a variety of clinically similar diseases of viral etiology that are endemic to and sporadically epidemic throughout the Eurasian continent and Japan. Although HFRS has not been reported in North America, viruses that are antigenically similar to HFRS agents were recently isolated from rodents in the United States. Examination and comparison of eight representative isolates from endemic disease areas and from regions with no known associated HFRS indicate that these viruses represent a new and unique group that constitutes a separate genus in the Bunyaviridae family of animal viruses.

Animals↗

Fibronectin in formation and degradation of the pericellular matrix.

Fibronectin is a large multifunctional glycoprotein present both in soluble form in plasma and other body fluids and in an insoluble form in interstitial connective tissues and in association with most basement membranes. The protein seems to provide a link between circulating body fluids, cell surfaces and the extracellular matrix. At sites of injury, fibronectin, covalently cross-linked to the fibrin clot, may provide a growth substratum for the invading cells and appears through its multiple interactions with other matrix components and cell surfaces to be involved in the organization of the matrix that will replace the clot. Fibronectin deposition may serve as a useful early marker for connective tissue formation in pathological processes and its fragmentation may serve as an indicator of pathological conditions involving proteolytic events.

Animals↗

Evidence for p15 cleavage site in myc-specific proteins of avian MC29 and OK10 viruses.

Myc-related proteins were precipitated from MC29 virus-transformed cells (PR-2) and from OK10 virus-transformed cells (9C) by anti-gag and anti-myc sera. Immunoprecipitates were cleaved with the avian retroviral protease p15 and the cleavage products analyzed in SDS-PAGE. Cleavage fragments of p110gag-myc (product of MC29 virus) and p58myc (product of OK10 virus) showed the presence of a p15 cleavage site within the myc-specific region. The site is missing in deletion mutants of MC29 virus.

Animals↗

Urokinase-type plasminogen activator and its inhibitor secreted by cultured human monocyte-macrophages.

Human blood monocytes in culture differentiate to macrophagelike cells within 1 week. Coinciding with this morphological transition the cells started releasing increasing amounts of the serine proteinase plasminogen activator (PA; Mr 56,000) of the urokinase (u-PA) type and the proteinase inhibitor alpha-2-macroglobulin (alpha 2M). Unlike the cell-associated PA activity, which was also readily detected in fresh monocytes, the activity secreted into the serum-free culture medium could be measured only after treatment of the samples with sodium dodecyl sulphate. Heat or acid treatment of the medium was not sufficient to reveal the PA activity, suggesting that, apart from alpha 2M, another PA-inhibiting substance was present in the culture medium. The inhibitor (Mr 65,000) was found to be synthesized by macrophages and specifically inhibited u-PA activity but not tissue-type PA (t-PA) or plasmin activity. Dexamethasone decreased the secretion of PA by differentiated macrophages without affecting the production of alpha 2M or the PA inhibitor. Dexamethasone also inhibited the morphological differentiation of the cells when added to the monocyte-phase cells.

Cell Adhesion↗

Kinetics of specific IgA, IgD, IgE, IgG, and IgM antibody responses in rubella.

Rubella-specific IgD and IgE antibodies were determined with a solid-phase enzyme immunoassay using enzyme-labeled heavy-chain specific anti-immuno-globulins, and the antibody responses in rubella infection were compared to IgM, IgA, and IgG antibodies. IgD and IgE antibodies increased rapidly after the onset of infection, remained at a high level for at least 2 months, and declined slightly by 6 months. In comparison, the IgM antibodies decreased more rapidly, whereas the IgG antibodies persisted longer at a steady level. By 6 months the mean levels of the different antibodies had declined from their maximal mean levels as follows: IgM, 52%; IgA, 42%; IgE, 35%; IgD, 29%; and IgG, 8%. Thus IgD and IgE antibodies, in spite of their known short half lives, persisted longer than IgM and IgA antibodies, which limits their diagnostic value. The IgA antibody responses were found too variable to substitute for IgM antibody determination in diagnosis of a recent rubella virus infection from a single serum specimen. Comparison of maternal and cord blood sera indicated that, in addition to IgG antibodies, rubella-specific IgD antibodies were found to cross the placenta.

Adult↗

Endoneurial fibrosis following nerve transection. An immunohistological study of collagen types and fibronectin in the rat.

Indirect immunofluorescent techniques with antibodies to type I, III, and V collagens and fibronectin were used to study rat sciatic nerve tributaries after transection with intact contralateral nerves as controls. Codistribution of type I and III collagens characterized the epineurium of normal nerve. In the perineurium, however, type I collagen was absent, but type III and V collagens and fibronectin were detected. Type I and III collagens were codistributed in the endoneurial stroma where a homogeneous staining by antibodies to fibronectin was also observed. During the 4-week observation period after transection the perineurium reacted by slight thickening which was most clearly demonstrated by staining with antibodies to fibronectin and to type V collagen. A widening of the type I-negative cleft also occurred. Endoneurial, type V collagen-positive cuffs around the nerve fibers became disorganized, and a concomitant increase of the stroma containing type I and III collagens and fibronectin was observed. The codistribution of the fibrous collagen types appeared similar in normal epineurium and endoneurium. Type V collagen was located in the perineurium and in endoneurial cuffs surrounding the nerve fibers. The present data indicate that collagen accumulation takes place in the perineurium and endoneurium of transected nerve. The cell type responsible for the synthesis of the connective tissue material is discussed.

Animals↗

Chronic mumps virus encephalitis. Mumps antibody levels in cerebrospinal fluid.

To study the outcome of mumps virus encephalitis 47 patients were contacted 1-15 years after the acute encephalitis associated with mumps virus infection. Twenty-three patients experienced clinical sequelae such as difficulties in memory and learning, focal motor or sensory signs, and loss of hearing and visual acuity. Lumbar puncture was performed on 8 patients. Antibodies to mumps virus were detected in 6 cerebrospinal fluid (CSF) specimens using enzyme immunoassay and in 3 patients an abnormal serum/CSF antibody ratio was observed 11, 26 and 58 (controls greater than 85); 14.3, 1.4 and 6.1 years after the acute encephalitis, respectively. Antibodies to other microbes were either undetectable in the CSF or the serum/CSF ratios were normal. The clinical sequelae in about half of the patients and the signs of intrathecal mumps antibody production are suggestive of a chronic process in the central nervous system after encephalitis associated with mumps virus infection.

Adult↗

Antibodies to human T lymphotropic virus type III demonstrated by a dot immunobinding assay.

A dot immunobinding (DIB) technique was applied to the demonstration of antibodies to human T-lymphotropic virus type III (HTLV-III). By this technique IgG antibodies to HTLV-III were demonstrated in six of six Swedish patients with acquired immune deficiency syndrome and in 37 of 39 (95%) Swedish homosexual men with persistent generalized lymphadenopathy but in none of 50 Swedish healthy blood donors. Findings obtained by this method showed complete concordance with those obtained by an enzyme-linked immunosorbent assay. All sera positive by DIB were also positive by Western blotting. The DIB assay is simple and well suited for screening of sera for HTLV-III antibodies.

Acquired Immunodeficiency Syndrome↗

Selective reactivity of antibodies to human immunoglobulins G, M, and A with rubella virus proteins.

Proteins of purified rubella virus were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and immunoblotted with human sera and immunoglobulin class heavy-chain-specific peroxidase conjugates. The levels of rubella antibodies in these sera were predetermined by the radial hemolysis test, the density gradient centrifugation method for immunoglobulin M (IgM) antibodies, and IgG-, IgM-, and IgA-specific enzyme immunoassays. In immunoblotting, rubella-specific IgG antibodies reacted with both envelope glycoproteins (E1 and E2) and the capsid protein (C). In contrast, rubella IgM antibodies reacted predominantly with E1, whereas the specific reactivity of IgA antibodies was directed mainly to the capsid protein. Purified IgM rheumatoid factor added to IgG-positive, IgM-negative serum did not give false-positive reactivity in the immunoblotting test as it did in solid-phase enzyme immunoassays. The immunoglobulin class-specific reactivities with the different viral proteins are expected to have diagnostic applications.

Antibodies, Viral↗

Altered white cell count, protein concentration and oligoclonal IgG bands in the cerebrospinal fluid of many patients with acute psychiatric disorders.

In a prospective study, an abnormal white cell count and/or elevated protein concentration in the cerebrospinal fluid (CSF) was observed in 14/54 patients (26%) with acute psychiatric disorders, but in none of the 46 control subjects (p less than 0.001). In addition, electrophoretic analysis of immunoglobulin G (IgG) showed an oligoclonal pattern in the CSF of 22 psychiatric patients (41%). No such pattern could be detected in the control group (p less than 0.001). These findings reinforce the value of lumbar puncture and CSF analysis in acute psychiatric disorders.

Acute Disease↗

Extracellular matrix and epithelial differentiation of Wilms' tumor.

Different histologic types of 82 Wilms' tumors were graded on the basis of the histologic pattern. Representative tumors of each group were analyzed by the immunoperoxidase method for evaluation of the histogenesis of Wilms' tumor and the value of antibodies against extracellular matrix (ECM) components (collagens I and III, laminin, fibronectin) in differential diagnosis of different types of Wilms' tumors. The tubules of classic Wilms' tumor expressed laminin, which could be seen also in and around some blastemal cells. Blastema and tubules were negative for interstitial collagens, but Type I and III collagen were prominent in the fibrovascular stroma. The monomorphous tubular, psammomatous and rosetting tumors expressed laminin, but no interstitial collagens. In sarcomas, only the blastemal variant of spindle-cell sarcomas was negative for interstitial collagens, which were abundantly seen in all other sarcomas. While spindle-cell sarcomas were devoid of laminin, the highly malignant rhabdoid and clear-cell sarcomas expressed laminin in a characteristic dotted fashion. Staining for fibronectin gave varying results and had therefore only a limited value in distinguishing different types of Wilms' tumors. However, the antibodies against interstitial collagens and against the basement membrane glycoprotein laminin turned out to be a useful adjunct in differential diagnosis and classification, especially of sarcomatoid Wilms' tumors. The basement membrane of normal nephrons is similar to that in tubules of triphasic Wilms' tumor, but the ECM of blastemas is different. This transformed phenotype might represent a maturation arrest of the blastemal cell when compared with the expression of proteins during normal nephrogenesis.

Adenocarcinoma↗

Immune functions in homosexual men with antibodies to HTLV-III in Finland.

The occurrence of HTLV-III antibodies in a voluntary group of 175 homosexual men in a low risk AIDS area was studied, and the findings were correlated to clinical, virological, immunological and lifestyle parameters. Fifteen of 175 men had HTLV-III antibodies; two of these had AIDS, five had LAS and two had enlarged lymph nodes. In the HTLV-III antibody negative group, no signs of AIDS or pre-AIDS were seen during a 10 month follow-up. In HTLV-III antibody positive individuals, low TH/TS ratio was mainly due to decreased number of TH cells. Most HTLV-III antibody positive cases had low responses to a specific antigen, PPD, while responses to the mitogens PHA and PWM were only slightly affected. In HTLV-III antibody negative cases, 13% had a low TH/TS ratio, mostly due to elevation of TS cells. In this group, mitogen and antigen responses were normal or only slightly affected. The results reinforce the causal relationship between HTLV-III and AIDS and suggest that the cells primarily affected by the virus infection are TH cells, responsible for antigen specific responses. Longitudinal studies are required to find out, what is the relationship of immune response to the development of clinical AIDS in HTLV-III infected individuals.

Acquired Immunodeficiency Syndrome↗

Renal cell adenocarcinoma and retrovirus p30-related antigen excreted to urine.

The authors have previously demonstrated in syncytiotrophoblastic cells of human placenta, hydatidiform and destructive moles, and choriocarcinoma antigens reacting with antibodies to the endogenous feline retrovirus RD114 p30 and human T cell leukemia-lymphoma virus p19 proteins. The authors now report that a monoclonal IgG1 antibody (HPS-1), recognizing both syncytiotrophoblasts and RD114 p30, also reacts with an antigen in the tumor cell cytoplasm of all 27 renal cell adenocarcinomas studied. Positively stained antigenic material was also seen in the lumen of normal tubuli of tumor kidneys, suggesting its excretion into urine. None of 10 normal kidneys, 17 Wilms' tumors, 5 transitional cell carcinomas of the renal pelvis, 5 similar tumors of the urinary bladder, 20 adenocarcinomas of the cervix uteri, 20 adenocarcinomas of the corpus uteri, or 20 adenocarcinomas of the colon showed any positive staining. All 3 renal oncocytomas studied gave a positive staining reaction. In RD114 p30 radioimmunoassay antigenic activity was detected in the urine of renal cell adenocarcinoma patients in amounts up to 1.93 ng/mg protein, but not in the serum. After nephrectomy, a decline of the excreted antigen was observed, the preoperative values being 0.16 to 1.93 ng/mg protein and the postoperative ones ranging from immeasurable to 0.58 ng/mg protein. The patients with measurable postoperative urine values had clinically detectable distant metastases. The p30-related antigen may provide a marker for renal cell adenocarcinoma.

Antibodies, Monoclonal↗