Publications by authors named "Tenhunen A"

Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality.

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Lentiviruses have been used as gene transfer vectors for almost 10 years and their utility has been demonstrated in a variety of different applications. However, their value in cancer gene therapy has not been studied thoroughly. Here we show that VSV-G pseudotyped HIV-1-based lentiviruses are efficient vectors for human tumor cells in vitro and in vivo.

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Lung cancer is a group of diseases that are difficult to cure and new treatment modalities, like gene therapy are actively tested to find alternatives for currently used strategies. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) method is one of the most frequently utilized forms of gene therapy and it has been tested on lung cancer, but no systematic study with comparison of different lung cancer types has been published. In this study, we examined in vitro and in vivo how good targets non-small cell lung cancer (NSCLC) cell lines representing adenocarcinoma, squamous cell lung cancer and large cell lung cancer are for adenovirus-mediated HSV-TK/GCV gene therapy.

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The fusion gene of herpes simplex virus thymidine kinase and green fluorescent protein (TK-GFP) was shown to be a versatile tool for examining the features of thymidine kinase/ganciclovir gene therapy in vitro. In this study, we used viral vectors carrying the fusion gene to characterize the aspects of this gene therapy form in rodent tumor models. Growth of subcutaneous 9L rat tumors transduced ex vivo with TK-GFP gene was prevented when ganciclovir (GCV) treatment was initiated immediately after tumor inoculation.

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Bone morphogenetic protein-4 (BMP4), a member of the transforming growth factor-beta (TGF-beta) family, regulates several developmental processes during animal development. We have now studied the effects of BMP-4 in the metanephric kidney differentiation by using organ culture technique. Human recombinant BMP-4 diminishes the number of ureteric branches and changes the branching pattern.

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Vascular endothelial growth factor (VEGF) is a key regulator of endothelial growth and permeability. However, VEGF may also target nonendothelial cells, as VEGF receptors and responsiveness have been detected for example in monocytes, and high concentrations of VEGF have been reported in human semen. In this work we present evidence that overexpression of VEGF in the testis and epididymis of transgenic mice under the mouse mammary tumor virus (MMTV) LTR promoter causes infertility.

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Outpatient surgery benefits patients only if postoperative sequelae are effectively treated. After laparoscopic tubal ligation (TL) intense pain and consequent postoperative nausea and vomiting (PONV) has been a problem delaying recovery and resulting in hospital admission. Ninety patients were randomised to this double-blind study, the aim being to evaluate the effect of balanced analgesia on postoperative pain and recovery after sterilization.

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Objective: We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone-binding globulin (SHBG) and insulin-like growth factor binding globulin-1 (IGFBP-1) in women with polycystic ovarian disease (PCOD).

Design: Prospective.

Patients: Ten women with PCOD admitted to a University Infertility Clinic.

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Objective: To evaluate expectant management in selected cases of ectopic pregnancy.

Methods: Transvaginal sonography and estimation of serum hCG concentrations were used in the evaluation and follow-up of ectopic pregnancy. Entry criteria for expectant management were: decreasing level of serum hCG, diameter of the ectopic pregnancy less than 4 cm, and no signs of rupture or acute bleeding by vaginal sonography.

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As a conservative nonsurgical treatment of an early ectopic pregnancy, local prostaglandin, parenteral or local methotrexate, local hyperosmolar glucose, and also expectant management have been used successfully in selected cases. The success rate of conservative treatment has been 71%-100% and that of tubal patency after different kinds of conservative treatment 72-93% of patients. In the present study of expectant management in early ectopic pregnancy in patients with decreasing serum hCG levels, spontaneous resolution was observed in 64.

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Ninety-three infertile women with distal tubal occlusion were subjected to salpingostomy in 1982-1984. In 78 of them follow-up data were available for 2-5 years. Second look laparoscopy was performed in 47 patients at a median of 4 months postoperatively.

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Concentrations of LH receptors in ovarian corpora lutea were measured in four women with ultrasonically monitored cycles, [in which luteinized unruptured follicles (LUF) were observed] and in one woman with an LUF observed during laparotomy. LH receptor concentrations were also measured in four control patients with proven fertility. The LH receptor concentrations in cases of LUF syndrome were on average 60% lower (P less than 0.

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Human granulosa-luteal cell production of cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone (P) were studied in response to purified human chorionic gonadotropin (hCG) in cultured cells from hyperstimulated follicles of in vitro fertilized patients. The hCG injection given to the patients 36 hours before laparoscopy caused partial desensitization of adenylate cyclase of these cells to gonadotropins. Preincubation of the cells in hormone free medium for 2 to 3 days significantly increased their cAMP responsiveness to hCG.

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A number of proteins previously thought to be specific for the placenta or pregnancy have been identified in the fluids bathing both the oocyte and the sperm. In many cases their concentrations in follicular fluid and seminal plasma greatly exceeded those in the serum of nonpregnant women or men, and sometimes they even exceeded the levels in pregnancy sera. We report here the occurrence of PP5, PP12, PP14 and PAPP-A in follicular fluid and seminal plasma.

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Placental proteins PP10, PP12, and PP14 and pregnancy-associated plasma protein A (PAPP-A) and relaxin (RX) were studied by the immunoperoxidase method in the uterine mucosa at the time of embryo replacement in 18 women for whom no embryo was available to be replaced. All subjects had received 17 alpha-hydroxyprogesterone caproate at the time of follicle aspiration, which had been performed 36 hours after preovulatory administration of hCG. The time between follicle aspiration and endometrial biopsy varied from 26 to 216 hours.

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The avidin-biotin immunoperoxidase method and antisera against highly purified porcine relaxin were utilized to localize relaxin-like immunoreactivity in biopsied specimens from six preovulatory follicles from four women undergoing laparoscopy for oocyte retrieval in an in vitro fertilization program. By histological criteria, three of the follicles were luteinized and three were not. Relaxin was found in the granulosa cells of those cells which showed histological luteinization, whereas no relaxin was found in the nonluteinized preovulatory follicles.

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In the in vitro fertilization program at Departments I and II of Gynecology and Obstetrics, University of Helsinki, 57 patients were stimulated with clomiphene and hMG. Follicular growth was monitored by ultrasound and serum estradiol measurements. Laparoscopic follicular puncture was performed 36h after hCG injection.

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To elucidate the roles of prostaglandins in peritoneal fluid and sex steroids in patients with endometriosis (N = 29), tubal disorders (N = 15), and unexplained infertility (N = 13), assays were performed using 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (a metabolite of prostacyclin), thromboxane B2 (a metabolite of thromboxane A2), estradiol, and progesterone. Women with normal pelvic anatomy (N = 25) served as controls. Peritoneal fluid 6-keto-PGF1 alpha concentrations in patients with endometriosis (742 +/- 104 pg/ml, mean +/- SE), tubal disorders (987 +/- 211 pg/ml), and unexplained infertility (1659 +/- 770 pg/ml) were higher than those in the control women (515 +/- 77 pg/ml).

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Radioimmunoassay, gel filtration, and immunoperoxidase methods were used to study the occurrence, properties, and concentration of pregnancy-associated plasma protein A (PAPP-A) in the human ovary and in the follicular fluid from 97 hyperstimulated follicles from 29 infertile women participating in an in vitro fertilization program. At the detection level of 15 micrograms/l, PAPP-A was found in 83 of 97 follicular fluids, the levels ranging from undetectable to 483 micrograms/l (median, 130 micrograms/l). In gel filtration, PAPP-A immunoreactivity of follicular fluid eluted in the same volume as placental PAPP-A, and the dose-response curves of follicular fluid PAPP-A and purified PAPP-A were parallel.

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RIA gel filtration, isoelectric focusing; and immunoperoxidase staining were employed to study the occurrence and physicochemical characteristics of placental protein 12 (PP12) in the human ovary, corpus luteum, and preovulatory follicular fluid. Fluid aspirated from 75 follicles from 22 women hyperstimulated for in vitro fertilization contained 6-230 micrograms/liter PP12-like immunoreactive material. The dose-response curves of follicular fluid PP12, amniotic fluid PP12, and purified human placental PP12 were parallel in the PP12 RIA.

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To study peritoneal fluid (PF) prostaglandin (PG) in infertile women, 6-keto-PGF1 alpha (a breakdown product of prostacyclin) and thromboxane B2 (T X B2) (a metabolite of T X A2) were assayed with radio-immunoassays from PF samples collected at laparascopy from patients with endometriosis (n = 29), unexplained infertility (n = 13) and from women with normal pelvic organs (n = 25). The concentrations of 6-keto-PGF1 alpha and T X B2 in PF were increased (p less than 0.05) in endometriosis and unexplained infertility, as compared with the corresponding levels in the controls.

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Placental protein 5 (PP5)-like immunoreactivity was found in 22 of 28 fluids aspirated from hyperstimulated preovulatory follicles of women who participated in an in vitro fertilization program. When detectable, the PP5 levels varied from 7 to 67 micrograms/l, which are of the same order of magnitude as those seen in pregnancy sera. In gel filtration, the PP5-like immunoreactivity of follicular fluid eluted in the same volume as purified human placental PP5; and in radioimmunoassay, this substance gave an inhibition curve which was parallel to that of the PP5 standard.

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