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S Partanen

Publications and source records attributed to S Partanen.

At least 19 recordsLinked to original sources

Alkaline fixation-resistant acid phosphatases in human tissues: histochemical evidence for a new type of acid phosphatase in endothelial, endometrial and neuronal sites.

The effect of pH during formalin fixation on acid phosphatases in human tissues was studied. Lysosomal-type acid phosphatase was sensitive to alkaline fixation, being completely inactive after fixation at pH 9.0. Prostatic and tartrate-resistant osteoclastic/macrophagic types were alkaline fixation-resistant, as was an acid phosphatase localized in endothelium, endometrial stromal cells and intestinal nerves. The latter activity was further separable into fluoride- and tartrate-sensitive beta-glycerophosphatase and fluoride-sensitive, tartrate-resistant alpha-naphthyl phosphatase. The activities appeared to represent either different, tightly associated enzymes or separate activity centres of a single enzyme. Alkaline fixation-resistant alpha-naphthyl phosphatase at endothelial, endometrial and neuronal sites was also well demonstrated in unfixed or neutral formalin-fixed sections as tartrate-resistant activity similar to classical tartrate-resistant acid phosphatase, but these phosphatases appear to be antigenically different. Alkaline fixation-resistant acid phosphatase showed a restricted tissue distribution both in endothelium (mainly in vessels of abdominal organs) and at neuronal sites (only in intestinal nerves). Alkaline fixation-resistant acid phosphatase appears to represent a previously unknown or uncharacterized enzyme activity whose chemical properties could not be classified as any previously known type of acid or other phosphatases.

Acid Phosphatase↗

Structural determinants for ligand binding and catalysis of triosephosphate isomerase.

The crystal structure of leishmania triosephosphate isomerase (TIM) complexed with 2-(N-formyl-N-hydroxy)-aminoethyl phosphonate (IPP) highlights the importance of Asn11 for binding and catalysis. IPP is an analogue of the substrate D-glyceraldehyde-3-phosphate, and it is observed to bind with its aldehyde oxygen in an oxyanion hole formed by ND2 of Asn11 and NE2 of His95. Comparison of the mode of binding of IPP and the transition state analogue phosphoglycolohydroxamate (PGH) suggests that the Glu167 side chain, as well as the triose part of the substrate, adopt different conformations as the catalysed reaction proceeds. Comparison of the TIM-IPP and the TIM-PGH structures with other liganded and unliganded structures also highlights the conformational flexibility of the ligand and the active site, as well as the conserved mode of ligand binding.

Aminoethylphosphonic Acid↗

Protein tyrosine phosphatase activity in human endometrium.

Protein tyrosine phosphatase (PTP) activity was demonstrated in human endometrium by a histochemical method using phosphotyrosine as substrate. For comparative purposes, non-specific acid phosphatase (AcP) activity was also examined. Protein tyrosine phosphatase activity was very low in proliferative and atrophic endometrium, but its activity was increased 9-fold in glandular epithelium during the secretory phase, and 48-fold in predecidual endometrium, induced by a progestagen-releasing intrauterine device, compared with the proliferative endometrium. Thus, PTP activity appeared to be progesterone-induced. Endometrial PTP appeared to be cellular rather than secretory in origin; its activity was inhibited by vanadate, and its histochemical properties were different from those of lysosomal AcP, but similar to those of prostatic-type AcP. Endometrial PTP may functionally counteract the effects of protein tyrosine kinases (PTKs) associated with growth factor receptors and cellular oncoproteins. Cyclic endometrial proliferation and differentiation are thought to be regulated by the autocrine and paracrine pathways by growth factors such as epidermal growth factor, insulin-like growth factor I and platelet-derived growth factors, and their receptors. However, cessation of proliferation could not be explained by the amounts of these growth factors present or their receptors, in that no constant changes at the interface of the late proliferative and early secretory phases were found. Down-regulation of stimulatory-signalling pathways of PTKs by endometrial PTP induced by progesterone may explain the decrease observed in proliferative activity of glandular cells in cyclic endometrium.

Acid Phosphatase↗

Histochemically demonstrable acid phosphotyrosine phosphatase activity in human tissues.

A histochemical method for the demonstration of activity of acid phosphatase(s) hydrolyzing o-phospho-L-tyrosine at pH 6.2 is described. Due to the instability of ordinary acid phosphatase incubation media containing phosphotyrosine and lead salt, the latter was dissolved in citrate solution (possibly forming a chelate) to obtain a stable incubation mixture. Localization of enzyme activity at the cellular level was good. Phosphotyrosine is known to be hydrolyzed at slightly acid pH by prostatic, macrophagic, and low-molecular weight cytoplasmic acid phosphatases and phosphotyrosyl protein phosphatases. These enzymes have been suggested or are established to be involved in cellular regulation by dephosphorylation of tyrosyl residues of proteins formed by various protein tyrosine kinases. An unexpected finding from various tissues was that the widely distributed lysosomal acid phosphatase did not contribute to the histochemical reaction, possibly due to poor hydrolysis of phosphotyrosine by lysosomal-type acid phosphatase. Various human tissues were studied for their acid phosphotyrosine phosphatase activities, which were then quantitated photometrically. Highest activity was found in the prostate glands, seminal vesicle epithelium, endometrial secretory glands, alveolar macrophages, stratum granulosum of the skin, and lymph nodes. The contribution of various enzymes hydrolyzing phosphotyrosine to histochemically detected activity in different tissues is discussed here.

Humans↗

Sequential appearance of relaxin, prolactin and IGFBP-1 during growth and differentiation of the human endometrium.

Relaxin (RLX) is a product of the human corpus luteum, pregnancy decidua and placenta, prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) are products of the cyclic endometrium and of the pregnancy decidua. All three proteins are thought to function interdependently in endometrium/decidua as local factors within the uterus without reaching the systemic circulation. In this study, the avidin-biotin immunoperoxidase method for immunolocalization with monoclonal or polyclonal antibodies has been applied to serial sections of endometria obtained from patients at different stages of the menstrual cycle and in early and late gestation. This allowed the cellular localization of the three proteins to be followed simultaneously through the reproductive stages from cyclic endometrium to term gestational decidua. The production, as opposed to sequestration of RLX from an ovarian source was demonstrated by the application in parallel of an antibody to the processed hormone and its connecting peptide. RLX was shown localized to the glandular and luminal epithelia in the proliferative and secretory phases. The decidualized stromal cells also immunostained for RLX in the late secretory phase and in early and late pregnancy. PRL was localized first to the glandular epithelium and then stroma, appearing after RLX, IGFBP-1 appeared later in the secretory phase and predominantly in the decidualized stromal cells confirming previous studies. In contrast, all three proteins were immunostained in early pregnancy and increased to term gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗

Comparison of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin, with or without dihydroergotamine, in abdominal hysterectomy.

The effects of administration of low-molecular-weight heparin (enoxaparin 20 mg) once a day, of unfractionated heparin (5000 IU twice a day, and of unfractionated heparin (2500 IU) plus dihydroergotamine (0.5 mg) twice a day were assessed in 100 patients undergoing abdominal hysterectomy. The test medications were given subcutaneously 2 hours before operation and for 3 days thereafter. There were no thromboembolic complications. Intraoperative blood loss, wound haematomas and blood loss via drains during four days after operation were similar in the three groups. None of the 37 patients receiving enoxaparin experienced major postoperative bleeding. Six out of 31 patients receiving unfractionated heparin without dihydroergotamine and two out of 32 patients receiving dihydroergotamine in addition experienced major bleeding necessitating re-operation and/or blood transfusion, (P < 0.05). Enoxaparin caused less major bleeding than unfractionated heparin with or without dihydroergotamine in patients undergoing hysterectomy.

Dihydroergotamine↗

Insulin-like growth factor binding proteins in human breast cancer tissue.

Breast tumor cell lines have been shown to secrete at least five distinct insulin-like growth factor (IGF) binding proteins (IGFBP), the secretion being related to the estrogen receptor (ER) content. In this study we investigated IGFBP mRNA expression and IGFBP content in relation to ER content in human breast tumors. Tissue specimens from 47 breast cancers were studied. In five cases the adjacent histologically normal tissue was also analyzed. IGFBP content in tissue homogenates was studied by Western ligand blot analysis, using [125I] IGF-I as a label, and IGFBP mRNA expression by reverse transcriptase polymerase chain reaction. The results show that human breast tumors express mRNAs encoding IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5. The pattern of IGFBPs in different tumors varies. No correlation exists between ER content and IGFBPs with molecular weights 24,000 Mr, 28,000 Mr, 34,000 Mr or 43,000 Mr, whereas the 49,000 Mr IGFBP was more abundant in ER negative tumors (P less than 0.05). The IGFBP content was significantly (P less than 0.05) higher in five tumors than in their adjacent normal tissues suggesting that increased content of IGFBPs is a feature typically associated with the malignant transformation of breast tissue.

Blotting, Western↗

Decidual transformation of human extrauterine mesenchymal cells is associated with the appearance of insulin-like growth factor-binding protein-1.

Human extrauterine decidual cells were studied for the presence of insulin-like growth factor-binding protein-1 (IGFBP-1) by using an avidin-biotin complex immunoperoxidase method with a purified monoclonal antibody 6303 against IGFBP-1. It is well established that human decidua expresses mRNA for IGFBP-1 and synthesizes and secretes this protein. We now describe, for the first time, that cells morphologically similar to uterine decidual cells found beneath the peritoneal mesothelium in inguinal hernia and in the cervical mucosa during normal pregnancy and in the mesenchymal tissue of the Fallopian tubes and ovaries at term react with the monoclonal antibody for IGFBP-1 equally to endometrial decidual cells. These results imply that the extrauterine mesenchymal cells, which have undergone decidual transformation, are not only morphologically but also functionally, similar to their counterparts in the uterus. Secondly, the data suggest that IGFBP-1 expression is associated with a special type(s) of cells and a certain stage of differentiation rather than special organs in the body.

Carrier Proteins↗

Binding of epidermal growth factor and insulin-like growth-factor I in renal carcinoma and adjacent normal kidney tissue.

The binding of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) to cell membranes was determined in 14 renal cancers and in 13 normal kidney tissues adjacent to the tumors. The soluble 34K IGF binding protein (34K IGF-BP) content and the phosphotyrosyl-protein phosphatase activity in renal cancer tissue and adjacent normal tissue were also determined. The specific EGF receptor binding in renal cancers was 12.7 +/- 2.5% (mean +/- SEM) as compared to 2.6 +/- 0.2% (mean +/- SEM) in normal tissues (p less than 0.01). Phosphotyrosyl-protein phosphatase activity in renal cancer tissue was less than half of that observed in normal renal tissue (p less than 0.01). The highest IGF-I binding was observed in 5 renal cancers although no consistent differences between IGF-I binding to tumor and normal tissues were observed. Both EGF and IGF binding to kidney tissue were higher than binding to gastro-intestinal tissue irrespective of whether normal or malignant tissues were compared. All normal kidney tissues and 7 of 8 kidney tumors contained measurable amounts of 34K IGF-BP as determined by RIA and the cross-linking technique. In 2 tumor tissue samples the 34K IGF-BP content was increased 8- and 15-fold over that seen in adjacent normal kidney tissue, whereas in the 6 other renal cancers the 34K IGF-BP was similar to that observed in normal kidney tissue.

Adenocarcinoma↗

Effect of haem arginate on colony formation by haematopoietic progenitors in vitro.

The effect of haem arginate, a new stable haem compound, was studied on colony formation by erythroid (CFU-E, BFU-E) and granulocyte-macrophage (CFU-GM) progenitors from the bone marrow of 12 healthy persons. At the concentration of 10 mumol/l haem arginate significantly (p less than 0.05) increased and at the concentration of 200 mumol/l significantly decreased (p less than 0.005) the colony formation of CFU-E. A similar, though not significant, trend was seen in the BFU-E colony growth, while the CFU-GM colony formation was not influenced at any concentration between 1 and 200 mumol/l. We conclude that the stimulation of erythropoiesis in vitro is seen at lower concentrations with haem arginate than with former haemin preparations.

Arginine↗

Spontaneous erythroid colony formation in the differential diagnosis of erythrocytosis.

Erythroid colony formation in vitro was studied in 80 patients with erythrocytosis. 43 of the patients had polycythaemia vera (PV), 18 patients had secondary erythrocytosis, 6 had normal red cell mass, and 13 patients were regarded as unclassified. Spontaneous erythroid colony formation, in the absence of exogenous erythropoietin in the cultures, was discovered in all patients with PV, whereas no patient with secondary erythrocytosis or with normal red cell mass showed this phenomenon. 8 of the 13 patients with unclassified erythrocytosis spontaneously formed erythroid colonies. 7 patient with unclassified erythrocytosis have been followed for 5 yr. 3 of the 4 patients with spontaneous colony growth but none of the 3 without it can now be classified as PV. Thus, spontaneous erythroid colony formation indicates PV even in early and atypical cases. Therefore, the culture of erythroid progenitors is very useful in the differential diagnosis of problematic cases with erythrocytosis.

Adult↗

Colony formation by megakaryocyte progenitors in myelodysplatic syndromes.

In vitro megakaryocytic colony formation by progenitors from the bone marrow was studied in 40 myelodysplastic syndrome patients. Megakaryocytic colonies were decreased in number or absent in 30 patients; only 10 showed normal colony growth. The growth correlated to some extent with the FAB-class. Patients with normal colony formation had either RA or RARS, but also in these two FAB-types half of the patients showed reduced megakaryocytic colony formation. Only 1 out of 15 patients with RAEB or RAEBt had normal megakaryocyte growth. The patients with CMML did not show any megakaryocytic colonies. The growth of erythroid colonies was normal in 3 patients and reduced or absent in the others. All 3 with normal erythroid colony formation also showed normal megakaryocyte growth, and all patients with normal megakaryocyte colony formation also had normal granulocyte-macrophage colony growth. Granulocyte-macrophage colony and cluster formation was normal in 17 patients. Defective formation of megakaryocytic, erythroid, and granulocyte-macrophage colonies was seen in 22 patients, compatible with a defect in a pluripotent stem cell. Megakaryocytic colony formation had no obvious correlation with any specific chromosome abnormality, and the distribution of the growth patterns was almost similar in patients with a normal and those with an abnormal karyotype.

Adult↗

Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer.

Levels of epidermal growth factor receptor (EGF-R) and insulin-like growth factor receptor (IGF-R) in breast cancer tissue were evaluated. The binding of growth factors was compared to the content of estrogen receptors (ER) and progesterone receptors (PgR). EGF-R correlated negatively to the ER and PgR (Kendall correlation, P less than 0.001), whereas the IGF-R correlated positively to ER and PgR (analysis of variance, P less than 0.001). In contrast, no correlation was found between EGF-R and IGF-R. IGF-R binding was higher in tumor tissues than in adjacent normal tissues (Wilcoxon rank test, P less than 0.001), whereas the EGF-R binding in normal tissue did not differ from that in cancer tissue. The degree of differentiation in ductal breast cancer correlated to EGF-R (chi 2 test, P = 0.018), but not to IGF-R. The bindings of both growth factors were the same in metastases and primary breast tumors. Our results show that EGF-R and IGF-R are present in normal breast tissue and breast cancer tissue. The growth factor receptors are related to steroid receptor content and their presence is associated with malignant transformation of breast cells and dedifferentiation of breast cancer.

Adult↗

Megakaryocytic colony formation in polycythaemia vera and secondary erythrocytosis.

Megakaryocytic colony formation by progenitor cells of 18 patients with polycythaemia vera, seven with secondary erythrocytosis and four with erythrocytosis of unexplained origin was studied in vitro by the methyl cellulose culture assay. Fourteen of the 18 patients with polycythaemia vera showed spontaneous megakaryocytic colony formation, i.e. colony growth with normal human plasma as the only source of colony stimulation. None of the patients with secondary erythrocytosis or erythrocytosis of unknown origin or of the normal controls grew colonies in the presence of normal human plasma only. When the plasma of a patient with aplastic anaemia was used instead of normal human plasma and phytohaemagglutinin stimulated leucocyte conditioned medium (PHA-LCM) was added to the culture medium, two of the patients with polycythaemia vera and one with secondary erythrocytosis formed slightly increased numbers of megakaryocytic colonies, while the rest of the patients showed normal colony formation. All of the patients with polycythaemia vera but none of those with secondary erythrocytosis or erythrocytosis of unknown origin showed spontaneous erythroid colony growth. The present study shows that most patients with polycythaemia vera form spontaneous megakaryocytic colonies in vitro. This phenomenon has recently also been demonstrated in essential thrombocythaemia and it is apparently analogous to spontaneous erythroid colony growth seen in all myeloproliferative disorders.

Adult↗

Mechanism of anaemia in rheumatoid arthritis: demonstration of raised interleukin 1 beta concentrations in anaemic patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukaemia (HEL) cells in vitro.

The pathogenesis of the anaemia associated with rheumatoid disease is unclear. It has previously been shown that the degree of the anaemia correlates with the severity of the inflammatory disease and that serum from patients with arthritis inhibits erythropoiesis. This study was designed to examine whether interleukin 1 could be a mediator of the anaemia in rheumatoid arthritis. Radioimmunoassay of interleukin 1 beta in serum showed that patients with rheumatoid arthritis and associated anaemia had significantly higher interleukin 1 beta concentrations than patients with rheumatoid arthritis without anaemia. Pure recombinant human interleukin 1 alpha and interleukin 1 beta, in concentration ranges similar to those found in the arthritic patients, markedly suppressed the colony formation of the erythroid, but not the granulocyte-macrophage progenitor cells in cultures of normal bone marrow. Natural human interleukin 1 and recombinant interleukin 1 beta, but not interleukin 1 alpha, suppressed in a dose dependent manner the proliferation of the human erythroleukaemia cell line (HEL) in cultures, suggesting that the interleukin 1 effect is a direct one. The results show that interleukin 1 is a humoral inhibitor of erythropoiesis and suggests that interleukin 1 is involved in the development of anaemia in association with rheumatoid arthritis.

Adult↗

Erythroid colony formation and effect of hemin in vitro in hereditary sideroblastic anemias.

Colony formation by erythroid burst-forming units (BFU-E) and erythroid colony-forming units (CFU-E) and the effect of hemin on colony growth was studied in vitro in three Finnish families with hereditary sideroblastic anemia (HSA). Defective activity of heme synthase has been demonstrated in family A and that of delta-aminolevulinic acid synthase in family B. No biochemical defect has been recognized so far in family C. CFU-E colony growth was defective in seven of the eight persons studied. The formation of BFU-E colonies was normal in family A and increased in family C, whereas of the two members of family B one showed normal and one decreased BFU-E colony growth. Hemin in 30-120 microM concentration increased significantly both BFU-E (p less than 0.01) and CFU-E (p less than 0.005) colony formation in family C. No effect was seen in family A, and in family B the only effect was normalization of the decreased BFU-E colony growth by the highest hemin concentration in one person. This study indicates that differences exist between families with HSA in erythroid colony formation and in response to hemin in vitro, but the low number of investigated members in each family does not permit a conclusive evaluation of the impact of the carrier versus patient status or of sex on the results.

Adult↗