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Biomedical subjects

J Korhonen

Publications and source records attributed to J Korhonen.

At least 19 recordsLinked to original sources
PubMed2001

Regional industrial ecology: examples from regional economic systems of forest industry and energy supply in Finland.

Industrial ecology (IE) promotes the development of industrial systems based on recycling of matter and cascading of energy through cooperation. In this paper, the local/regional industrial ecosystem approach is reflected in two examples from Finland. The local forest industry system is based on renewable resources, waste materials and energy utilisation between forestry companies, a saw-mill, a pulp mill, a paper mill and a forest industry power plant. Waste energy from electricity production is used for production of heat and process steam. Regional city energy supply systems in Finland are also to a large extent arranged around power plants that utilise waste energy. The potential of combining the forest industry system with the energy supply systems of cities is considered and the conditions for success in the Finnish case are discussed.

Cities↗
PubMed2001

The autoimmune regulator: a key toward understanding the molecular pathogenesis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune disease with autosomal recessive inheritance. APECED is characterized by the breakdown of tolerance to several organ-specific selfantigens. The symptoms of APECED fall into three main categories: autoimmune polyendocrinopathies, chronic mucocutaneous candidiasis, and ectodermal dystrophies. The gene defective in APECED, AIRE, has been cloned and numerous mutations in this gene have been found in patients with APECED. AIRE is predicted to encode a 545-amino-acid protein containing structural domains characteristic for transcription regulators. The protein has been shown to act as a transcriptional activator in vitro. The AIRE protein is mainly localized to the nucleus, where it can be detected as speckles resembling nuclear bodies. In humans, the expression of AIRE has been observed predominantly in immunologically relevant tissues, especially the thymus. Recently, we have shown in the mouse that Aire is also expressed in various tissues and cell types outside the immune system.

Animals↗
PubMed1999

Role of ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter.

The Tie gene encodes an endothelial cell receptor tyrosine kinase necessary for normal vascular development. The Tie gene promoter targets expression of heterologous genes specifically to endothelial cells in transgenic mice. Here we have characterized the promoter sequences critical for endothelial cell-specific activity in cultured cells and transgenic mice. Progressive deletions and site-directed mutations of the promoter showed that the critical endothelial cell-specific elements are an octamer transcription factor binding site and several Ets binding sites located in two clusters within 300 bp upstream of the major transcription initiation site. Among members of the Ets transcription factor family tested, NERF-2 (a novel transcription factor related to the ets factor ELF-1), which is expressed in endothelial cells, and ETS2 showed the strongest transactivation of the Tie promoter; ETS1 gave lower levels of stimulation and the other Ets factors gave little or no transactivation. Furthermore, the Tie promoter directed the production of high amounts of human growth hormone into the circulation of transgenic mice. The secreted amounts correlated with transgene copy number, being relatively insensitive to the effects of the transgene integration site. These properties suggest that Tie promoter activity is controlled by endothelial cell Ets factors and that it has potential for use in vectors for endothelial cell-specific gene expression.

Animals↗
PubMed1997

Immunoprocedures for detecting human chorionic gonadotropin: clinical aspects and doping control.

The pregnancy hormone human chorionic gonadotropin (hCG) is also present at low concentrations in plasma and urine of men and nonpregnant women. hCG immunoreactivity occurs in various molecular forms: Besides the intact hCG heterodimer, considerable amounts of proteolytically cleaved forms, free subunits, and fragments are found in plasma and urine. Especially in urine, proteolytic fragments constitute a major part of the hCG immunoreactivity. The different forms of hCG cross-react to various degrees in immunoassays and constitute a problem for standardization of specific hCG determinations. After injection of hCG (10,000 IU of Pregnyl; Organon), above-normal concentrations of hCG can be detected in serum and urine for 7-11 days. Most immunoassays for hCG also measure hCG beta. Quantitative hCG determinations are mainly performed on serum samples, and very few commercial hCG determinations have been validated for determination of urine samples. Considerable care must therefore be exercised when utilizing such assays to analyze urines for doping control.

Chorionic Gonadotropin↗
PubMed1997

Disappearance of human chorionic gonadotropin and its alpha- and beta-subunits after term pregnancy.

We have used high-specificity and precision immunofluorometric assays to measure the elimination half-times of human chorionic gonadotropin (hCG), hCG alpha, and hCG beta in serum over 21 days after delivery in six women with term pregnancies. Baseline concentrations and half-times were calculated with the use of a curve-fitting algorithm for multiexponential decay. In contrast to the two-component model, a three-component exponential function with baseline provided a fit for which predicted values could not be distinguished from the observed values by analysis of variance. Median half-times were 3.6, 18.0, and 53.0 h for hCG; 1.0, 23.4, and 194 h for hCG beta; and 0.6, 6.2, and 21.9 h for hCG alpha. The mean ratio of hCG alpha to hCG decreased rapidly from 36.9% to 3.3% on day 3; thereafter it increased to 64.3% 21 days after delivery because of a higher baseline concentration of hCG alpha. hCG beta had the slowest total elimination rate, and the ratio of hCB beta to hCG in serum increased from 0.8% before delivery to 26.7% after 21 days. If the metabolism of hCG and hCG beta is similar in patients with trophoblastic disease, the ratio of hCG beta to hCG must be evaluated with caution in samples taken several days after initiating therapy. We conclude that the disappearance of hCG beta from plasma is slower than previously recognized and that the ratios of hCG beta or hCG alpha to intact hCG vary as a function of postpartum time. Such information may be important in clinical studies of pregnancy disorders.

Adult↗
PubMed1996

Low-dose oral methotrexate with expectant management of ectopic pregnancy.

OBJECTIVE: To investigate recovery times and need for laparoscopy in women with ectopic pregnancy who were treated for 5 days 2.5 mg/day of oral methotrexate or placebo. METHODS: Sixty women with ectopic pregnancy among patients of an outpatient clinic specializing in early pregnancy disorders were selected for medical treatment in a double-blind, placebo-controlled study. The diagnosis was made by transvaginal sonography and serum hCG determinations, either at admission or after repeated examinations. Women were recruited for the study if they had mild symptoms: the hCG increase was less than 50% within 2 days, the diameter of the ectopic pregnancy was less than 40 mm, there were no signs of intra-abdominal bleeding by transvaginal sonography, and there were no secondary reasons for laparoscopy. Either 2.5 mg of methotrexate or placebo was given orally for 5 days. Serum hCG was determined after 2 days, and hCG, red blood cell count, white blood cell count, platelet count, and serum glutamic-oxaloacetic transaminase were measured; transvaginal sonography was performed after 5 and 12 days. Expectant management was continued individually with check-ups at 1-3-week intervals. Laparoscopy was performed if the patient developed abdominal pain or intra-abdominal hemorrhage, as seen by transvaginal sonography. Statistical analysis was by paired or unpaired t test, Mann-Whitney U test, regression analysis, and repeated measures analysis of variance. RESULTS: Seventy-seven percent of the patients recovered without the need for laparoscopy in both groups, and there were no significant differences in recovery times or the need for laparoscopy between groups. CONCLUSION: Oral methotrexate, 2.5 mg for 5 days, does not appear to be more effective than placebo in the treatment of ectopic pregnancy in women eligible for expectant management.

Adult↗
PubMed1996

Failure of creatine kinase to predict ectopic pregnancy.

OBJECTIVE: To investigate serum creatine kinase (CK) levels in pregnant women with ectopic pregnancy (EP), spontaneous abortion, and normal pregnancy with comparable serum hCG concentrations. DESIGN: A retrospective, case-controlled study. SETTING: Helsinki University Central Hospital, Helsinki, Finland. PATIENTS: Forty-four patients with a suspicion of EP of which 15 had laparoscopically confirmed tubal pregnancies; 15 had a spontaneous abortion, a blighted ovum, or a missed abortion; and 14 patients a normal intrauterine pregnancy. INTERVENTIONS: The diagnosis was made by transvaginal sonography and serum hCG determinations either at admission or after repeated examinations. Ectopic pregnancy was confirmed and treated by laparoscopy. MAIN OUTCOME MEASURES: Serum CK and hCG levels. RESULTS: No significant differences in CK levels were observed between the groups by one-way analysis of variance and no correlation was found between serum CK and hCG levels within any group. CONCLUSIONS: Creatine kinase does not appear to be useful in the diagnosis of early EP.

Case-Control Studies↗
PubMed1996

Ectopic pregnancy after in-vitro fertilization is characterized by delayed implantation but a normal increase of serum human chorionic gonadotrophin and its subunits.

We studied the dynamics of serum human chorionic gonadotrophin (HCG) and its free alpha (HCG alpha) and beta (HCG beta) subunits in 49 early pregnancies achieved by in-vitro fertilization (IVF) and embryo transfer. Of the 49 early pregnancies, nine were normal singleton pregnancies, 11 were twin pregnancies, 11 were ectopic, eight ended in a clinical (spontaneous) abortion and 10 ended in a preclinical abortion. The HCG, HCG alpha and HCG beta concentrations in serum were measured on days 12, 19 and 26 after embryo transfer. Most ectopic pregnancies could be distinguished from singleton (and twin) pregnancies on the basis of low HCG concentrations by 12 days after embryo transfer, but clinical abortions could not be distinguished from singleton pregnancies. In general, the measurement of HCG alpha and HCG beta and the molar ratios of the various forms provided only marginal additional value to that obtained from HCG, but on days 19 and 26 after embryo transfer HCG alpha was the most sensitive indicator of a normal pregnancy after IVF and embryo transfer. We conclude that in ectopic pregnancies the concentrations of HCG, HCG alpha and HCG beta increase as expected but 1.5 days later than in normal pregnancies. This appears to be the result of a delay in implantation.

Abortion, Spontaneous↗
PubMed1995

Endothelial-specific gene expression directed by the tie gene promoter in vivo.

The tie gene encodes a receptor tyrosine kinase that is expressed in the endothelium of blood vessels, particularly during embryonic development and angiogenesis in adults. We have cloned and characterized the mouse tie gene and isolated the human and mouse tie promoters. The promoter activities of human and mouse tie were analyzed using luciferase reporter gene constructs in transfected cell lines and beta-galactosidase constructs in transgenic mice. In transfection assays of cultured cells, both human and mouse promoter DNA fragments showed activity that was not restricted to endothelial cells. In contrast, in transgenic mice both promoters directed expression of the reporter gene to endothelial cells undergoing vasculogenesis and angiogenesis. In adult mice, tie promoter activity in lung and many vessels of the kidney was as high as in the vessels of the corresponding embryonic tissues, whereas in the heart, brain and liver, tie promoter activity was downregulated and restricted to coronaries, cusps, capillaries, and arteries. Our results show that the endothelial cell-type specificity of the tie promoter in vivo can be transferred to heterologous genes by using relatively short promoter fragments. The tie promoter, thus, has useful properties for potential gene therapy.

Animals↗
PubMed1995

Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.

We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.) embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous and presumptive lymphatic endothelia, but arterial endothelia were negative. During later stages of development, FLT4 mRNA became restricted to vascular plexuses devoid of red cells, representing developing lymphatic vessels. Only the lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in adult human tissues. Increased expression occurred in lymphatic sinuses in metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels.

Adenocarcinoma↗
PubMed1995

Transvaginal sonography and serum hCG in monitoring of presumed ectopic pregnancies selected for expectant management.

We studied sonographic findings and levels of human chorionic gonadotropin (hCG) in 71 patients with a presumed ectopic pregnancy, recruited for conservative management, to find out whether these parameters may be useful in monitoring treatment. Patients were selected on the basis of decreasing hCG levels, minimal symptoms and an adnexal mass, suggestive of ectopic pregnancy, of < or = 5 cm at transvaginal sonography. In 49 (69%) patients the ectopic pregnancy resolved spontaneously: the adnexal mass resolved significantly more slowly than did hCG levels. In 22 (31%) of the cases laparoscopy was required after an average of 9 days, because of worsening clinical symptoms. The initial size of the ectopic pregnancy did not significantly differ between the two groups, but it increased constantly in the laparoscopy group. The number of patients with free pelvic fluid also increased significantly in the laparoscopy group, whereas blood flow patterns at admission and during follow-up did not differ between the two groups. A decrease in ectopic pregnancy size at day 7 had a sensitivity of 84% and a specificity of 100% in predicting spontaneous resolution. Transvaginal sonography monitoring appears useful in recognizing the ectopic pregnancies most likely to resolve spontaneously without complications.

Adult↗
PubMed1994

Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy.

OBJECTIVE: To study serum hCG dynamics in patients with ectopic pregnancy (EP) selected for expectant management. DESIGN: A prospective observational study. SETTING: Helsinki University Central Hospital, Helsinki, Finland. SUBJECTS: One hundred eighteen patients, who were selected for expectant management among 493 patients with EP. INTERVENTIONS: Patients were examined every 1 to 3 days using transvaginal sonography and serum hCG determinations until hCG values < 10 IU/L (conversion factor to SI unit, 1 IU/L = 2.93 pmol/L) were reached. Laparoscopy was performed if the patient developed abdominal pains or intra-abdominal hemorrhage as revealed by sonography. MAIN OUTCOME MEASURE: Serum hCG level. RESULTS: The median gestational age at the start of follow-up in patients with a spontaneous resolution was 44 days and in patients requiring laparoscopy was 48 days. The success rate for a spontaneous resolution was 88% when the initial hCG level was < 200 IU/L but only 25% at levels > 2,000 IU/L. In the 77 patients with a spontaneous resolution, the initial median hCG concentration was 374 IU/L (range, 20 to 10,762 IU/L) and it decreased to normal in 4 to 67 days (mean, 20 days). In the 41 patients requiring laparoscopy the median initial hCG concentration was 741 IU/L (range, 165 to 14,047 IU/L); a normal level was reached in 3 to 43 days (mean, 12 days) after operation. Follow-up period before operation was 1 to 24 days (mean, 9 days). Laparoscopy was indicated in two thirds of the patients with a serum hCG level > 64% of the initial value after 7 days of follow-up. CONCLUSIONS: Spontaneous resolution of EP correlated with a low and rapidly decreasing hCG level.

Chorionic Gonadotropin↗
PubMed1994

Emergency cesarean section: the effect of delay on umbilical arterial gas balance and Apgar scores.

BACKGROUND: We wanted to conduct a prospective study on the dynamics of emergency cesarean section (ECS) in terms of fetal survival and morbidity. METHODS: The study covered 101 cases of ECS in Helsinki City Hospital, in which the time of alarm, the starting time of the operation, the time of birth, the umbilical arterial gas values, and Apgar scores were known. This group consisted of 60 cases with the operating team in the hospital (group 1) and 41 cases with the team on call (group 2). Means of the parametric variables were compared by the analysis of variance using separate or pooled t-tests after Levene's test of variances. Difference between the rate of adverse outcome (dead or handicapped) in each group was calculated using chi-square test. RESULTS: In group 1, the time between the clinical decision and the time of delivery (mean +/- s.e.mean) was 13.5 +/- 0.7 min, in group 2, 23.6 +/- 0.9 min. The groups did not differ in terms of birthweight, placental weight, Apgar scores, and umbilical arterial gas values, except for pO2. The mean pO2 in group 1 was lower (1.9 +/- 0.1 kPa) than in group 2 (2.5 +/- 0.2 kPa). p = 0.0023. In group 2, one infant was handicapped by hypoxic ischemic encephalopathy and three fetuses had died in utero. The rate of survivors was significantly higher when the operating team was in hospital (p = 0.05). CONCLUSION: The risk of fetal loss is evident when the operating team is on call outside the hospital, at least if the alarm to operation interval exceeds 20 minutes. The present study suggests that 24-hour services of anesthesia and operating theater personnel are crucial for optimal management of emergent situations in the delivery room.

Adult↗
PubMed1994

The mouse tie receptor tyrosine kinase gene: expression during embryonic angiogenesis.

Angiogenesis, the process by which new blood vessels are formed, is essential in reproduction, development, wound repair and oncogenesis. Endothelial receptor tyrosine kinases are likely to play key roles in the intercellular signalling controlling angiogenesis. We have here analysed the expression of the endothelial receptor tyrosine kinase tie during the earliest stages of vascular development. The mouse tie cDNA was isolated and sequenced and the exon structure of the coding region was determined. The part of the tie gene encoding the extracellular domain was found to be organized in exons specifying the characteristic domains of the Tie polypeptide. Early postimplantation mouse tissues were analysed for tie expression by in situ hybridization. No tie mRNA was detected in 7.5 day mouse embryos. In 8.5 day embryos, tie expression was observed in differentiating angioblasts of the head mesenchyme, in the splanchnopleure and dorsal aorta as well as in migrating endothelial cells of the developing heart. A weak tie signal was also obtained from angioblasts in the blood islands of the yolk sac. Furthermore, tie mRNA was prominent in the endocardium of the embryo and in the endothelial cells forming the lung vasculature. Expression of tie persisted in the lung capillaries of adult mice, but was decreased in the endocardium. These results suggest that the tie receptor tyrosine kinase is involved in angiogenesis and/or maintenance of endothelial cell functions.

Amino Acid Sequence↗
PubMed1993

The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells.

The growth factor receptors expressed on endothelial cells are of special interest because of their potential to program endothelial cell growth and differentiation during development and neovascularization in various pathological states, such as wound healing and angiogenesis associated with tumorigenesis. Vascular endothelial growth factor ([VEGF] also known as vascular permeability factor) is a potent mitogen and permeability factor, which has been suggested to play a role in embryonic and tumor angiogenesis. The newly cloned FLT4 receptor tyrosine kinase gene encodes a protein related to the VEGF receptors FLT1 and KDR/FLK-1. We have here studied the expression of FLT4 and the other two members of this receptor family in human fetal tissues by Northern and in situ hybridization. These results were also compared with the sites of expression of VEGF and the related placenta growth factor (PlGF). Our results reveal FLT4 mRNA expression in vascular endothelial cells in developing vessels of several organs. A comparison of FLT4, FLT1 and KDR/FLK-1 receptor mRNA signals shows overlapping, but distinct expression patterns in the tissues studied. Certain endothelia lack one or two of the three receptor mRNAs. These data suggest that the receptor tyrosine kinases encoded by the FLT gene family may have distinct functions in the regulation of the growth/differentiation of blood vessels.

Endothelial Growth Factors↗
PubMed1993

Comparison of the guarding capacities of mouth protectors.

The guarding capacity of seven mouth protectors (Erkoflex 3.0 and 4.0, Erkoloc 3.0, 4.5 and 5.5, TranSheet/Perform and TranSheet/LiteLine) was tested mechanically on 20 plaster models, two or three tests on each mouth protector. Two tests on a plaster model without the protector served as control. An appliance was constructed to simulate the impact of an ice-hockey puck on the teeth, the plaster model was fixed onto the device and the minimum force needed to break the plaster teeth under the protector was recorded. The average total thickness and that of the soft and hard layers of the labial plates of each mouth protector were recorded along with the average thickness of the cervical and incisal hard and soft layers. The results showed that the best protection was achieved with the TranSheet/LiteLine model, followed by TranSheet/Perform and Erkoloc 5.5 and 4.5 mouthgards. All these had a resilient layer against the teeth, and it was shown in stepwise regression analysis that the only property having a statistically significant effect on the guarding capacity was the thickness of this cervical soft layer.

Athletic Injuries↗
PubMed1993

Expression of tie receptor tyrosine kinase in leukemia cell lines.

The tie receptor tyrosine kinase mRNA was originally identified as an amplified product in reverse transcription-polymerase chain reaction analysis of human K562 leukemia cell RNA. In situ hybridization analysis revealed that the corresponding mouse gene is expressed predominantly in endothelial cells. We have explored tie mRNA and protein expression in tumor cell lines. The 4.4 kb tie mRNA was expressed at high levels in five of five human megakaryoblastic leukemia cell lines studied and in two IL-3-dependent mouse myeloid leukemia cell lines, but not in 42 other leukemia cell lines representing various hematopoietic lineages. Increased expression of tie mRNA and protein was observed upon treatment of the megakaryoblastic leukemia cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA), known to enhance megakaryoblastic markers. Among several cell lines from solid tumors, two fibrosarcomas, one rhabdomyosarcoma and one melanoma cell line were positive for tie mRNA. These results suggest that among hematopoietic lineages tie is predominantly expressed in cells with megakaryoblastic properties and that the tie tyrosine kinase is a receptor for a regulatory factor specific for megakaryoblasts, endothelial cells, and occasional tumor cell lines derived from mesenchymal tissues.

3T3 Cells↗