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Biomedical subjects

E Ruoslahti

Publications and source records attributed to E Ruoslahti.

At least 271 records · Page 15Linked to original sources
PubMed1980

Direct tissue visualization of normal cross-reacting antigen in neoplastic granulocytes.

Normal cross-reacting antigen, a glycoprotein that shares some antigenic determinants with carcinoembryonic antigen, was consistently demonstrated by tissue immunoperoxidase staining in the cytoplasm of both non-neoplastic and neoplastic neutrophilic granulocytes. It was absent in lymphoid cells, but occasional cells of the macrophage/histiocyte series showed variable staining. Malignant cells from patients who had non-Hodgkin or Hodgkin lymphomas were negative for normal cross-reacting antigen. These findings were in contrast to the findings of specific normal cross-reacting antigen positivity in neoplastic granulocytes from three patients who had acute granulocytic leukemia, three who had chronic granulocytic leukemia, and one who had a granulocytic sarcoma. Similar normal cross-reacting antigen positivity was also seen in granulocytes from two patients who had granulocyte dysplasia. It is suggested that direct tissue visualization of normal cross-reacting antigen using immunoperoxidase technics may be of value in the classification and diagnosis of hematologic malignancies, and may provide an additional marker for cells of the granulocytic series.

Antigens, Neoplasm↗
PubMed1980

Alpha fetoprotein levels in neonatal hyperbilirubinaemia.

Serum alpha fetoprotein (AFP) levels were studied in 15 neonatally hyperbilirubinaemic children and 15 controls matched for sex and gestational age. All children were born between 38 and 40 weeks of gestation. During the first seven weeks of postnatal life hyperbilirubinaemic children had serum AFP concentrations over twice as high as controls. At the age of 5-7 days the mean (+/- S.E.M.) serum AFP values were 52.4 +/- 5.8 mg/l for hyperbilirubinaemic children and 24.8 +/- 4.3 mg/l for controls (p less than 0.001). At 20-25 days of age they were 7.28 +/- 1.10 and 2.75 +/- 0.45 mg/l, respectively (p less than 0.001), and at 40-49 days 1.39 +/- 0.21 and 0.46 +/- 0.07 mg/l (p less than 0.001). However, no correlation was found between serum bilirubin and AFP concentrations in hyperbilirubinaemic children.

Age Factors↗
PubMed1980

Human chromosome 11 is syntenic with human specific fibronectin production in human x mouse cell hybrids.

Evidence is presented indicating that human chromosome 11 carries a structural locus for fibronectin (FN). A panel of cell hybrids of FN fiber-producing normal human diploid cells fused with mouse A9 cells were immunofluorescence stained with species-specific, affinity purified antibodies to human FN (AHFN); similar anti-mouse FN antibodies (AMFN); and the nonspecies-specific anti-FN antiserum (AFN) which was used in an earlier study of this same hybrid panel (Eun and Klinger, 1980). All hybrids that had the human 11 produced extracellular fibers that fluoresced brightly when reacted with the AHFN and AFN. All other human chromosomes could be eliminated as being related to FN production, suggesting that the 11 caries a structural FN locus. This agrees with our earlier study in which a nonspecies-specific antiserum was used and with the preliminary report of Smith et al. (1979), who used a different cell system. The apparent discrepancy between these results and those of Owerbach et al. (1978), who reported synteny of FN with the human No. 8, was partly resolved in that one of their FN positive hybrids was found to react with our AMFN but not with the AHFN, suggesting that some other as yet undefined mechanism may be operating in their hybrids which were made with mouse LM/TK- cells. The parental mouse A9 cells of our hybrids do not produce FN fibers, although a radioimmunoassay detects a small amount of mouse FN secreted into the medium. The fibers of some of our AHFN positive hybrids also react weakly with AMFN, but none react only with AMFN. This suggests that fibers produced by these hybrids bind some mouse as well as human FN. Why this is not so in all the producers is not clear.

Animals↗
PubMed1980

Differences in the nuclear proteins of normal and malignant liver cells.

Immunological tests and 2-dimensional gel electrophoresis revealed differences between the nuclear proteins from normal and malignant liver cells. Immunization of rabbits with a nuclear nonhistone protein fraction isolated from normal mouse liver resulted in antisera that in immunofluorescence gave nuclear staining in sections of normal liver, but did not stain nuclei of a transplantable mouse hepatoma. Antisera prepared against a nuclear protein fraction from the hepatoma allowed immunofluorescent staining of hepatoma nuclei but did not stain nuclei from normal liver. Nuclei in liver regeneration after injury caused by administration of carbon tetrachloride stained with antiserum against normal nuclei but not with antisera against hepatoma nuclei. Neither antiserum stained nuclei in fetal liver cells. The presence of differing sets of nuclear proteins in the normal and malignant liver cells was indicated by 2-dimensional gel electrophoresis. Approximately 300 polypeptides were resolved by this technique. Most of these were quantitatively different in the normal and hepatoma nonhistone protein preparations. Several qualitative differences also seemed to be present. Nonhistone proteins from regenerating liver shared some polypeptides with hepatoma that were absent in normal liver. Nuclear proteins characteristic of malignant tissues may provide clues toward the understanding of gene regulation in malignant cells, and some of them could become useful tumor markers.

Animals↗
PubMed1980

Molecular interactions of fibronectin.

Fibronectin mediates attachment of cells to surfaces in vitro, and its abundance in basement membrane structures suggests that it serves a similar function in vivo. The cell attachment promoting activity of fibronectin depends on its capacity to interact with a number of other macromolecules. These include collagen, fibrin(ogen), glycosaminoglycans, and as yet unidentified receptors on the surfaces of various mammalian and avian cells and on the surfaces of Staphylococci. Denatured collagens bind more avidly to fibronectin than the native forms. Of the latter, type III is the most active one. The collagen-binding is inhibited by fibrinogen and vice versa, indicating that the same (or overlapping) binding site are responsible for the binding of fibronectin to collagen and fibrinogen. The binding site for collagen in fibronectin can be localized in a homogeneous fragment with a molecular weight of 30,000. This binding site is distinct from the one interacting with cell surfaces, since the cell attachment promoting activity is found associated with collagen-nonbinding fragments of fibronectin. These same fragments also bind to Staphylococci, suggesting that the cell surface receptor in these bacteria may be similar to that of eukaryotic cells. Glycosaminoglycans bind to collagen-fibronectin complexes resulting in a complex more stable to disruption with urea than complexes of any two of the components. This phenomenon may be important in the formation of the fibronectin-containing, adhesive, extracellular matrix, and its significance to the apparent disturbances that many malignant cells have in forming such a matrix in particular, warrants further study.

Cell Adhesion↗
PubMed1979

Binding of bilirubin by bovine and human alpha-fetoprotein.

alpha-Fetoprotein, a fetal protein associated with certain tumors, was found to bind bilirubin. Addition of human or bovine alpha-fetoprotein to bilirubin solutions enhanced the light absorbance of bilirubin and shifted its maximum. Bovine alpha-fetoprotein caused a marked shift towards shorter wavelengths, while human alpha-fetoprotein gave a slight red shift. The spectral changes were used to study the characteristics of the binding of bilirubin by bovine alpha-fetoprotein. These studies indicated the presence of one binding site/molecule of alpha-fetoprotein with an association constant of about 1.1 . 10(6) M-1. A difference between the spectral changes brought about by alpha-fetoprotein and albumin allowed comparison of their relative affinities for bilirubin. The spectrum approximated the average between the spectra induced by the two proteins when the ratio of bovine alpha-fetoprotein to bovine albumin was 6.3 : 1, and of the human proteins 21 : 1, respectively. These results show that alpha-fetoprotein from two species binds bilirubin with an affinity somewhat lower than that of albumin. Binding of bilirubin by alpha-fetoprotein is in agreement with the recent demonstration of structural homology between alpha-fetoprotein and albumin. Whether alpha-fetoprotein plays a role in the metabolism of bilirubin or other degradation products of heme remains to be investigated.

Animals↗
PubMed1979

Increase in fibronectin in the deep dermis of involved skin in progressive systemic sclerosis.

The distribution and amount of fibronectin in both involved and uninvolved skin from scleroderma patients and controls were compared by indirect immunofluorescence. A marked increase in fibronectin was found in the deep dermis of involved scleroderma skin, while the subepidermal papillary regions of all specimens revealed little variation in fibronectin content. The districution of the accumulated fibronectin appeared to parallel that of the accumulated collagen in the involved reticular dermis.

Adult↗
PubMed1979

Distribution of fetal bovine serum fibronectin and endogenous rat cell fibronectin in extracellular matrix.

Normal rat kidney cells were cultured in medium supplemented with normal fetal bovine serum (FBS) or FBS depleted of fibronectin. The cell surface fibronectin of these cultures was visualized by indirect immunofluorescence using species-specific antisera for either rat fibronectin or bovine fibronectin. Anti-rat-fibronectin revealed fibrillar structures on the cells grown in either normal medium or fibronectin-depleted medium. Anti-bovine fibronectin revealed similar fibrillar networks, but only on the cells grown in medium containing bovine fibronectin. Staining in each case was abolished by absorption with the homologous antigen. It appears that exogenous fibronectin was incorporated into the same structures as endogenous fibronectin. This finding suggests that circulating fibronectin may serve as a building block for the assembly of extracellular matrix, possibly by cells which are incapable of synthesizing it.

Animals↗
PubMed1979

Immunofluorescent localization of fibronectin in the human kidney.

Fibronectin is a glycoprotein shown previously to be present on the surfaces of cells, connective tissue matrices, and in extracellular fluids. Its distribution in the human kidney was evaluated by immunofluorescence methods studying 65 renal biopsies with a variety of pathologic disorders. Fibronectin was found in the mesangium of the normal kidney and increased proportionately in the disease states characterized by mesangial expansion. It was visualized in glomerular capillary loops in some biopsies with membranoproliferative glomerulonephritis, diffuse proliferative glomerulonephritis, and membranous nephropathy. Additionally, fibronectin was detected in glomerular crescents, diabetic nodules, vascular thrombi, glomerular sclerosis, and variably in the interstitium.

Fibronectins↗
PubMed1979

Differential expression of alpha-fetoprotein and gamma-glutamyltranspeptidase in chemical and spontaneous hepatocarcinogenesis.

The expression of two markers of fetal liver, alpha-fetoprotein (AFP) and gamma-glutamyltranspeptidase (GGT), was studied in chemical and spontaneous hepatocarcinogenesis in mice. Serum AFP concentration increased within 3 weeks 3 weeks from the commencement of feeding of o-aminoazotuluene. This early elevation subsided about 3 months after the beginning of the administration of the carcinogen. A new, sustained elevation of the serum AFP level followed at 5 to 6 months accompanied by the appearance of liver tumors. In immunofluorescence, some small oval cells and scattered adult-type hepatocytes contained AFP during the early stage of chemical carcinogenesis. During the later phase, AFP was detected in a few of the nodular areas, in solitary hepatocytes, and in groups of carcinoma cells. GGT activity in the liver increased within 1 week after the carcinogen regimen was started, preceding the early increase of AFP production. At the final stage, the chemically induced hepatomas contained about 80 times more GGT than did normal liver. In histochemical staining, proliferating oval cells and small areas of hepatocytes stained for GGT during the early weeks, and later most nodules, small areas of nonnodular parenchyma, and carcinomas contained GGT. During spontaneous carcinogenesis in male C3HeB/FeJ mice, premalignant lesions, accompanied by a slight increase of serum AFP, precede the appearance of liver tumors. No cells staining for AFP were detected during this early stage. Once overt liver cancers had developed, AFP was readily detectable in the tumors and was localized to some but not all carcinoma cells. The corresponding serum AFP levels were highly elevated. In contrast to the high levels of GGT found during chemical carcinogenesis, no elevation of GGT was found in livers at various stages of spontaneous carcinogenesis, including cancers in eight individual mice. These results indicate that the production of AFP and GGT is not turned on as a single "genetic package," and that these two markers differ in their behaviour in liver carcinogenesis.

Animals↗
PubMed1978

Developmental changes in carbohydrate moiety of human alpha-fetoprotein.

Human AFP purified from fetal serum and amniotic fluid was separated into three different variants by chromatography on concanavalin A insolubilized on Sepharose (Con A--Sepharose). The three variants were indistinguishable in immunodiffusion and radioimmunoassay. Sera from patients with yolk-sac tumor and amniotic fluid from early pregnancy were found to contain a high proportion (15-45%) of AFP which does not bind to Con A, while AFP in fetal and newborn sera, and in amniotic fluid from late pregnancy, contained less (2-6%) of this variant. The use of a large excess of Con A--Sepharose and the fact that the non-bound AFP consistently eluted as non-bound in rechromatography showed that this AFP is non-reactive with Con A. Fractionation of radiolabelled AFP from cord serum in a mixture with amniotic fluid verified the difference in the amount of the Con-A nonreactive variant in AFP from these two sources. These results suggest that AFP synthesized by the yolk-sac tissue and by the liver are glycosylated differently. The variant may prove to be diagnostically useful.

Amniotic Fluid↗