L Viinikka's research while affiliated with University of Oulu and other places
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Publications (224)
To study the production of prostacyclin (PGI2) and thromboxane A2 (TxA2) in endometriosis in vitro, samples of endometriotic tissue taken during operation from 6 women were superfused for 4.5 hours in 95% 02/5% CO2 at 37°C and the stable metabolites of PGI2 (= 6-keto-PGF1α), and TxA2 (= TxB2) were measured by radioimmunoassays from the superfusates...
Objective: Labetalol reduces blood pressure primarily by blocking alpha-and beta-receptors, but other mechanisms of action may also be possible. We studied the effects of labetalol on the synthesis of vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin-1 (ET-1) by cultured human umbilical vein endothelial cells (HUVECs). We also studie...
Prostacyclin (PGI(2)) and thromboxane A(2) (TxA(2)) may take part in lung pathology; high concentrations of PGI(2) may protect newborn rabbits against hyperoxic lung injury, and TxA(2) may participate in the development of bronchopulmonary dysplasia (BPD). Aims: To examine in small preterm infants, the relationship between pulmonary PGI(2) and TxA(...
To evaluate in a randomised blind study the effect on puncture site lesions of two different incision devices used to obtain blood samples from preterm infants by repeated heel sticks.
The neonatal intensive care unit at the Hospital for Children and Adolescents and Laboratory, Helsinki University Central Hospital.
A total of 100 preterm infants (b...
Vascular endothelial cells are one of the main targets of tumor necrosis factor α (TNF-α) action. We studied whether these cells are capable of producing TNF-α after stimulation with proinflammatory cytokines and bacterial lipopolysaccharide (LPS).
Human umbilical vein endothelial cells (HUVECs) were incubated with interferon-γ (IFNγ) interlukin β...
Tamoxifen protects against myocardial infarction through mechanisms that are poorly understood. We studied the effects of tamoxifen and another antiestrogen, toremifene, on the production of vasoconstrictive endothelin-1 and of vasodilatory nitric oxide in 44 postmenopausal patients with breast cancer. These started treatment, in randomized order,...
To determine whether transdermal hormone replacement therapy modifies the ability of plasma or serum to regulate the synthesis of prostacyclin and that of endothelin-1 by cultured human umbilical vein endothelial cells.
Prospective, randomized study.
Department of Obstetrics and Gynecology, Helsinki University Central Hospital.
Thirteen postmenopau...
Tamoxifen and toremifene are two mostly used antiestrogens in the treatment of breast cancer. To compare their effect on bone in postmenopausal breast cancer patients we measured the urinary output of two bone resorption markers, pyridinoline (Pyr) and deoxypyridinoline (Dpyr) as well as bone density (BMD) in 30 breast cancer patients using either...
To determine whether human vascular endothelial cells produce tumor necrosis factor-alpha (TNF-alpha) after stimulation with proinflammatory cytokines and bacterial lipopolysaccharides (LPS).
Prospective, in vitro repeated-measurements analysis of cellular responses.
Research laboratory in an academic medical center.
Human umbilical vein endothelia...
Endothelial cell damage is characteristic for respiratory distress syndrome and development of chronic lung disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen that takes part in the growth and repair of vascular endothelial cells. We measured VEGF in 189 tracheal aspirate samples (TAF), and in 24 plasma samples from 44 int...
To study the plasma levels of homocysteine in preeclampsia and relate them to insulin sensitivity.
In association with a 3-hour intravenous glucose-tolerance test (glucose 0.3 g/kg at 0 and 0.03 IU insulin 20 minutes later), we measured plasma levels of homocysteine, vitamin B12, and folic acid in 22 women with preeclampsia and 16 controls between...
To clarify production of nitric oxide with pre-eclampsia.
Production of nitric oxide and elimination of its metabolites, nitrite and nitrate, determines ultimately the level of those metabolites in plasma of subjects whose diets lack them. We measured simultaneously plasma levels and renal clearance of nitrite and nitrate in 20 women with preeclamp...
Unlabelled:
The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron...
Severe perinatal aspiration of meconium is frequently complicated by unsuccessful neonatal adaptation with associated pulmonary hypertension. This vascular complication is supposedly related to pulmonary release of vasoconstrictory agents, including metabolites of arachidonic acid. Thus, to investigate the role of prostanoids on these meconium-indu...
We undertook this study to evaluate a recently introduced ELISA kit for determining serum transferrin receptor (TfR) concentration (TfR, Ramco Laboratories, Inc.), to produce reference values for healthy adults, and to compare the results with another commercially available reagent system. The mean (SD) recovery of added TfR was 88% (6%). In diluti...
It is well documented that postmenopausal estrogen/progestin therapy (HRT) protects women against cardiovascular disorders. However, the mechanism(s) by which this protection is mediated remains largely unresolved, because beneficial effects of estrogen on the blood lipid profile account for only 20-30% of the overall protection. Growing evidence s...
Optimal vascular homeostasis requires efficient control of both proliferation and elimination of vascular endothelial cells. Programmed cell death, or apoptosis, is the main mechanism controlling cell elimination, and it is an essential component of vascular formation. Human vascular endothelial cells die in vitro, if prevented from obligatory surv...
Oral postmenopausal hormone replacement therapy (HRT) decreases the risk of cardiovascular disorders, but the mechanisms of this protection are largely unknown. We compared the long-term effects of sequential oral HRT and transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as vasoconstrictive endothelin- and thromboxane A2, all of...
Endothelial cell damage is characteristic for respiratory distress syndrome and development of bronchopulmonary dysplasia (BPD). Vascular endothelial growth factor (VEGF) is an endothelial mitogen that takes part in growth, maintenance, and repair of vascular endothelial cells. We measured VEGF in tracheal aspirate fluid (TAF) from 29 intubated pre...
Cerebrospinal fluid (CSF) amino acid neurotransmitter concentrations in 23 patients with acute encephalitis were compared with those in patients with acute brain infarction, multiple sclerosis and controls. The concentration of glutamate was significantly higher in encephalitis (5.2+/-6.7 micromol/l) and stroke patients (9.6+/-14.2 micromol/l) than...
Women with prior preeclampsia are characterized by hyperinsulinemia and a 2- to 3-fold excess risk of hypertension and ischemic heart disease in later life. We therefore studied whether these women present changes in pituitary, ovarian, and endothelial factors that could also affect the risk of vascular disorders. Twenty-two women with prior preecl...
Objectives: Vasodilatory nitric oxide (NO) is evidently a factor in pregnancy physiology and perhaps also in preeclampsia. Human umbilical vein endothelial cells (HUVECs) express the calcium-dependent NO synthase (NOS), whereas the scanty data on the expression of the inducible isoform of NOS (iNOS) are discrepant. We have previously shown that HUV...
Objective: Oral postmenopausal hormone replacement therapy (HRT) decreases the risk of cardiovascular disorders, but the mechanisms of this protection are largely unknown. We compared the long-term effects of sequential oral HRT and transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as vasoconstrictive endothelin-1 and thromboxan...
Cultured human umbilical vein endothelial cells (HUVECs) are a widely used model to study the regulation of endothelial production of vasoactive substances such as endothelin-1 (ET-1) and prostacyclin (PGI2) in human. As even short term culturing is known to affect the function of many cell types, we studied whether there are differences in the pro...
Hereditary tyrosinaemia type 1 is a rare but serious metabolic disorder with an autosomal recessive mode of inheritance. We describe the prenatal diagnosis of an affected fetus performed by DNA-mutation analysis and a subsequent pregnancy with a healthy child in the same family. © 1997 John Wiley & Sons, Ltd.
To study the relationship between endothelin-1 (ET-1) in the airways and respiratory distress in preterm infants.
ET-1 was determined in 60 tracheal aspirates from 11 preterm intubated infants (gestational age 28.0 +/- 2.5 weeks) during the first week of life.
The concentration of ET-1 of the aspirates was 6 to 2760 pg/mL (median 293 pg/mL). Negati...
Both cell-matrix and cell-cell interactions are important regulators of the function of most human cells. In this study we investigated how these interactions controlled the production of vasodilators nitric oxide (NO), and prostacyclin (PGI2), in freshly isolated human umbilical vein endothelial cells (HUVECs). On the reconstituted extracellular m...
Long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase is one of three enzyme activities of the mitochondrial trifunctional protein. We report the clinical findings of 13 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. At presentation the patients had had hypoglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during...
To elucidate the mechanism of cardiovascular protection of hormone replacement therapy (HRT) by comparing the effect of oral and transdermal HRTs on the production of antiaggregatory, vasodilatory prostacyclin, and its endogenous antagonist, thromboxane A2.
Oral estradiol (2.0 mg/d) plus norethisterone acetate (1.0 mg/d) (n = 13) or transdermal est...
Nitric oxide (NO) is an important intra- and intercellular mediator. Although NO can be measured using many different chemical methods, the compound is challenging for a clinical chemistry laboratory, since its half-life in vivo in humans is only a few seconds. Most of the NO is oxidized to nitrite/nitrate, and the concentrations of these anions ha...
To elucidate the mechanisms by which estrogens protect against occlusive vascular disorders, we studied the effect of 17 beta-estradiol on the production of prostacyclin (PGI2) and nitric oxide (NO) in primary cultures of human umbilical vein endothelial cells (HUVECs).
To study the effect of 17 beta-estradiol on PGI2 production, HUVECs were incuba...
To determine if hormone replacement therapy (HRT) modifies the ability of plasma or serum to regulate the synthesis of vasodilatory prostacyclin and that of vasoconstrictive endothelin-1 by cultured human umbilical vein endothelial cells.
Plasma and serum collected before and during the sixth treatment cycle of HRT from 13 healthy postmenopausal wo...
To explore the mechanism(s) by which antiestrogens may protect against the development of cardiovascular disorders, we measured the production of vasodilatory, antiaggregatory prostacyclin (PGI2) and that of vasoconstrictive, proaggregatory thromboxane A2 (TxA2) before and after 6 months' use of antiestrogens in postmenopausal patients after operat...
To study the effect of hirudin on endothelial cell prostacyclin (PGI2) and endothelin-1 (ET-1) production, we cultured human umbilical vein endothelial cells (HUVECs), stimulated them with 0.00001-10 kU/l of hirudin for 12-24 hours, and measured by radioimmunoassays the concentrations of 6-ketoprostaglandinF1 alfa (6-keto, a metabolite of PGI2) and...
Nitric oxide is an important vasodilator, and in this study we studied whether the calcium-dependent nitric oxide production capacity of human umbilical vein endothelial cells was affected by preeclampsia.
Human umbilical vein endothelial cells were isolated from 11 preeclamptic and 10 normotensive pregnancies. The maximal calcium ionophore A23187-...
We studied 20 hirsute patients with high levels of serum testosterone (T), calculated free T, androstenedione, and dehydroepiandrosterone sulfate and 19 age-matched nonhirsute normoandrogenic control women. The bone mineral density (BMD) in the lumbar spine, femoral neck, and trochanter major region in hirsute patients was higher than that in the c...
We studied 20 hirsute patients with high levels of serum testosterone (T), calculated free T, androstenedione, and dehydroepiandrosterone sulfate and 19 age-matched nonhirsute normoandrogenic control women. The bone mineral density (BMD) in the lumbar spine, femoral neck, and trochanter major region in hirsute patients was higher than that in the c...
Hormone replacement therapy (HRT) protects against cardiovascular disorders, but the mechanisms of this action are poorly understood. We assessed the plasma levels of vasoconstrictive endothelin-1 (ET-1) in 26 healthy postmenopausal women before and during HRT. The women were randomized to receive either continuous transdermal (estradiol 50 ug/24 h...
To compare the effects of a 30-minute standardized submaximal exercise test on the urinary excretion of the metabolites of prostacyclin and thromboxane A2 in healthy pregnant and nonpregnant women.
Time-fixed urine samples were collected before, during, and after the exercise test from nine pregnant and six nonpregnant women, and the samples were a...
The exact mechanisms by which estrogens protect against occlusive vascular disorders are not known. One possibility could be an effect on vascular endothelial vasoactive compounds, such as vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin (ET-1). Here we report on the effect of 17 beta-estradiol on the synthesis of PGI2 and ET-1 in c...
To determine if hyperinsulinemia, hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein (HDL) cholesterol are present in women with pregnancy-induced hypertension or preeclampsia.
Serum concentrations of insulin, uric acid, total and lipoprotein cholesterol, triglyceride, and apolipoproteins A-I and B were measured in 31 wo...
Thirty-five children with acute lymphoblastic leukemia were monitored weekly during the first 12 weeks of chemotherapy. The transferrin receptor (TfR) concentration was 2.8 +/- 0.2 mg/l (mean +/- S.E.M.) at diagnosis, decreased up to 3 weeks, and then increased reaching a maximal level at 8 weeks. The mean values for reticulocyte counts followed a...
The initial depression of erythropoiesis followed by a rapid stimulation of erythropoiesis in children with newly diagnosed ALL may serve as a model to study TfR and Epo as indicators of erythropoiesis. We studied weekly the blood hemoglobin and reticulocyte counts, TfR and Epo from 35 children with newly diagnosed ALL during 12 weeks from diagnosi...
Kivivuori SM, Järvenpää AL, Salmenperä L, Viinikka L, Siimes MA. Erythropoiesis of very low-birth-weight infants dependent on prenatal growth rate and protein status. Acta Paediatr 1994; 83:13–18. Stockholm. ISSN 0803–5253
This study investigated erythropoiesis in very low-birth-weight infants with special reference to the role of protein status in...
To study whether balance between antiaggregatory, vasodilatory prostacyclin (PGI2) and proaggregatory, vasoconstrictory thromboxane A2 (TXA2) could be affected by dietary manipulation, 18 pre-eclamptic women were treated in randomized order between 31 and 36 weeks of gestation either with primrose oil (n = 7), with fish oil (n = 5), or with placebo...
To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants.
Placebo controlled prospective study.
Departments of Obstetrics and Gynaecology, University of Helsinki, University of Oulu...
A recently introduced test measures the concentration of transferrin receptor (TfR) in serum, which increases shortly after the onset of iron deficiency. In adults this increase reflects the degree to which tissue iron availability is impaired. We developed a fluoroimmunoassay to quantify TfR. The purpose of this study was to evaluate the role of T...
To study the effect of strenuous physical exercise on the balance between vasodilatory and antiaggregatory prostacyclin (PGI2) and its endogenous antagonist thromboxane A2 (TxA2), we measured the urinary output of two metabolites of PGI2 (6-keto-prostaglandin F1 alfa, 6-keto, and 2,3-dinor-6-keto), as well as two metabolites of TxA2 (thromboxane B2...
To find out whether the tendency toward poor outcome in lupus pregnancies could be explained by changes in prostacyclin/thromboxane production, to relate these changes to the presence of antiphospholipid antibodies, and to study the potential benefits of low-dose aspirin.
We followed the urinary output of prostacyclin metabolites (6-keto-prostaglan...
We evaluated the effects of marathon running on bone metabolism in 23 noncompetitive athletes (15 women, 8 men, age range 23–55 years). The volunteers were studied 10 days before, immediately after, and 1, 3, and 5 days after the run. Serum osteocalcin levels were decreased on average by 20% (from 4.9 to 3.9 g/liter, P=0.005) in men and by 10% (fro...
Desogestrel is a strong progestogen with low androgenicity which has so far been used only in oral contraceptives. We studied the feasibility of administering desogestrel in combination with oestradiol as hormone replacement therapy (HRT). Thirty women received a sequential combination containing 1.5 mg micronised oestradiol (24 days) and 0.15 mg d...
Prostacyclin (PGI2), a powerful vasodilatory prostanoid, and endothelin-1 (ET-1), a potent vasoconstrictive peptide, are produced by vascular endothelial cells. We show that human serum (10%) caused a 3.2-fold stimulation both in PGI2 and ET-1 synthesis in human endothelial cells cultured from umbilical veins, and human plasma (10%) stimulated prod...
All pregnancy-associated tissues are capable of producing prostaglandins including PGI2 and TXA2. In normal pregnancy there is a dominance of PGI2 over TXA2 which may contribute to the maternal circulatory adaptation to pregnancy. Furthermore, both fetoplacental PGI2 and TXA2 production are important regulators of the fetal blood supply. It has bee...
The data presented in this review clearly show that many different cytokines regulate the synthesis of PGI2 in vascular EC (Tables 1 & 2). Since these agents are synthesized, stored, and/or released from platelets, leukocytes and cells present in the vascular wall (Fig.), they are to be found at sites of vascular injury and may, through their effec...
To see if changes in prostacyclin and thromboxane A2 (TXA2) production during early pregnancy in women with habitual abortion is a pregnancy-induced change, we compared the production of these prostanoids in habitual aborters and in healthy controls in nonpregnant state and related it to luteal function.
Comparison between patients (n = 16) with a...
Objective To see if changes in prostacyclin and thromboxane A 2 (TXA 2 ) production during early pregnancy in women with habitual abortion is a pregnancy-induced change, we compared the production of these prostanoids in habitual aborters and in healthy controls in nonpregnant state and related it to luteal function. Design Comparison between patie...
We studied the role of smooth muscle-relaxing prostacyclin and its endogenous antagonist, thromboxane A2, in preterm labor by assessing the urinary output of the breakdown products of prostacyclin (6-keto-prostaglandin F1 alpha and 2,3-dinor-6-keto-prostaglandin F1 alpha) and those of thromboxane A2 (thromboxane B2, 2,3-dinor-thromboxane B2).
Thirt...
Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1...
This minireview deals with the presence of epidermal growth factor (EGF) in human tear fluid. It explains the occurrence of EGF in tear fluid, the origin of EGF and its dependency on tear fluid dynamics. The alterations in tear fluid EGF concentrations that occur during diseases of the ocular surface are described and discussed in the context of th...
Gestational choriocarcinoma metastasizes rapidly, in which process the vasoactive prostanoids may be significant. We therefore compared the urinary excretion of prostacyclin and thromboxane A2 (TxA2) metabolites in 19 women with gestational choriocarcinoma and 20 healthy age-matched women by assessing spot urine samples for 6-keto-prostaglandin F1...
The concentration of epidermal growth factor (EGF) in tear fluid (TF) was recently shown to decrease with increasing tear fluid flow (TFF). The purpose of the present study was to clarify the effects of ocular surface disease on the TF EGF concentrations. Tear fluid samples (n = 243) were collected from diseased eyes by means of blunted glass capil...
To evaluate the significance of vasoactive prostanoids in habitual abortion, we measured urinary excretion of prostacyclin metabolites (6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and of thromboxane A2 metabolites (TxB2 and 2,3-dinor-TxB2) during 25 pregnancies in 22 women with recurrent spontaneous abortion (RSA). The control group were 16...
Prostacyclin (PGI2) is an antithrombotic and vasodilatory factor, which is produced mainly by the vascular endothelium. Little is known about how this process is regulated. We investigated the effect of human milk on PGI2 synthesis by human vascular endothelial cells by measuring its stable metabolite, 6-keto-prostaglandin F1 alpha, by RIA. Human m...
To study the source of immunoreactive epidermal growth factor (ir-EGF) released by thrombin formation we removed 99.9% of the leukocytes normally present in platelet-rich plasma and induced coagulation with 30 mM of Ca2+. The absence of leukocytes did not reduce the amount of ir-EGF released; thus platelets are most likely the only source of the ir...
Human serum stimulated the synthesis of a vasoconstrictive peptide, endothelin-1 (ET-1), and a vasodilatory prostanoid, prostacyclin (PGI2), by cultured human umbilical vein endothelial cells in a concentration- and time-dependent manner. Incubation in 20% concentration of the serum for 24 h stimulated ET-1 synthesis almost six-fold while PGI2 prod...
To clarify the variation of mouse epidermal growth factor production during the 24-h and female reproductive cycles, we measured its concentrations in the plasma, submandibular salivary gland, urine, kidneys and liver of adult male and female mice during consecutive 12-h dark and 12-h light periods, different stages of pregnancy, and lactation. The...
Medical 'oophorectomy' by GnRH agonist or danazol is an effective treatment for endometriosis. Since increased bone loss is a potential risk of hypoestrogenism, we compared the effect of nafarelin and danazol treatment on bone metabolism. Twelve patients with laparoscopically confirmed endometriosis received nafarelin (400 micrograms day intranasal...
To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kid...
Prostacyclin (PGI2) is an antithrombotic factor, which may prevent the initiation and the complications of arteriosclerosis. The most important site of PGI2 production is the vascular endothelium, but little is known about how this process is regulated. In this connection, there is special interest in the roles of various growth factors released fr...
Serum levels of CA-125 and squamous cell carcinoma-associated antigen (SCC) were measured in 30 patients with squamous cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of...
Arachidonic acid is metabolized in endothelial cells to antiaggregatory, vasodilatory prostacyclin (PGI2), and in platelets to aggregatory, vasoconstrictory thromboxane A2 (TxA2). The balance of these two prostanoids is supposed to be involved with thrombogenesis and atherogenesis. Acetylsalicylic acid (ASA) inhibits irreversibly the key enzyme of...
To eludicate hormonal regulation of epidermal growth factor (EGF) concentration we studied the effects in adult female mice of ovariectomy and postovariectomy treatments with testosterone plus estradiol on the EGF concentrations in submandibular salivary gland (SMG), plasma, kidneys and urine. In the tissues, we also studied the location of EGF imm...
To study the role of vasodilatory prostacyclin and vasoconstrictory thromboxane A2 in climacteric vascular instabilities, overnight urine samples were collected from sixteen women suffering from hot flushes and sweating before, during and after the six months' cyclic estradiol-desogestrel therapy as well as from ten non-climacteric control women. T...
We studied the effect of ovarian cancer and its chemotherapy on the urinary excretion of prostacyclin (PGI2) and thromboxane A2 (TxA2) hydration and metabolic products. In six patients we measured 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha (PGI2 products) and thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (TxA2 products) by HPLC followed by radioi...
We examined the effect of short- and long-term exercise on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TXA2) synthesis in type I (insulin-dependent) diabetic patients and healthy control subjects. PGI2 synthesis was assessed by determining the urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha and TX synthesis by...
The prognostic value of cerebrospinal fluid (CSF) and serum neuron-specific enolase and brain-type creatine kinase isozyme (CK-BB) measurements was studied in 75 consecutive victims of out-of-hospital cardiac arrest. All patients with a CSF neuron-specific enolase level of more than 24 ng/mL 24 hours after cardiac arrest remained unconscious and di...
We investigated the molecular nature of the epidermal growth factor immunoreactivity (ir-EGF) in serum and platelets of normal subjects. In serum, ir-EGF appeared and increased during spontaneous blood coagulation, reaching a plateau in 2 h. The mean plateau measured by time-resolved immunofluorometric assay was 778 pg/mL [130 pmol/L; range, 465-13...
Testosterone is known to increase epidermal growth factor (EGF) concentrations in mouse plasma and submandibular salivary gland. We tested in adult sialoadenectomized (sx) and sham-operated female and male mice our hypothesis that female sex steroids also affect EGF concentrations in fluids and tissues. In 10-day treatment estradiol-17 beta increas...
Decreased fetoplacental prostacyclin (PGI2) production has been shown in preeclampsia, and increased pulmonary PGI2 synthesis has been demonstrated in experimental hypoxia. We measured the urinary excretion of the main metabolites of PGI2, 6-keto-prostaglandin F1 alpha (6-keto) and 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3-dinor), during the fir...
Epidermal growth factor (EGF) is a mitogenic polypeptide, which was first isolated from mouse submaxillary gland. Since EGF also stimulates the growth of corneal epithelial cells and only preliminary data exist on its presence in tear fluid, we studied the occurrence of human EGF (hEGF) in the tear fluid of 36 healthy persons (31 women and 5 men fr...
In adult male and female mice we compared the epidermal growth factor (EGF) concentrations after gonadectomy and studied the effects of postgonadectomy treatments with estradiol and progesterone. In gonadectomized mice the mean concentration of EGF in the submandibular salivary gland (SMG) was (7-fold) higher in the females than the males. In the k...
Among the unsettled questions in the physiology of human epidermal growth factor (EGF) are (1) does EGF circulate in the blood and (2) what is the source of the abundant urinary immunoreactive EGF (irEGF). Therefore, we monitored the concentration of irEGF by an ultrasensitive assay in blood plasma from 5 healthy subjects every 20 min overnight car...
To study the production of antiaggregatory prostacyclin (PGI2) and proaggregatory thromboxane (TxA2) by ovarian tumors, we incubated pieces of benign and malignant ovarian tissue in vitro, and measured by radioimmunoassay the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (a hydration product of PGI2) and thromboxane B2 (TxB2) (a hydr...
The long-term patency of the internal mammary artery (IMA) in coronary artery surgery has been superior to that of other grafts. We tested the IMAs as free grafts in an experimental study with 8 dogs. The right IMA was dissected free as a naked artery without surrounding tissue, and the left IMA was dissected with surrounding tissue using electroca...
Epidermal growth factor (EGF) stimulated prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells, as measured by radioimmunoassay of its stable metabolite 6-keto-prostaglandin F1 alpha. This effect of EGF was dose-dependent, the lowest stimulatory concentration of EGF was 1.0 ng/ml and 100 ng/ml caused a 2.7 +/- 0.3 (mean...
Cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) were measured in 22 patients with probable Alzheimer's disease and in 35 patients with multi-infarct dementia, and in 15 controls. CSF NSE in patients with Alzheimer's disease did not differ from those in controls. In patients with multi-infarct dementia without recent vascular event...