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Biomedical subjects

H Eriksson

Publications and source records attributed to H Eriksson.

At least 73 records · Page 4Linked to original sources

Selective cytotoxicity of two rodent T cell lymphomas to rat yolk sac tumours involves a retroviral envelope protein expressed by the lymphoma.

A Gross virus induced rat T cell lymphoma G1-Tc1 and a Moloney virus induced mouse T cell lymphoma YAC-1 are shown to exert a strong cytotoxic activity against rat yolk sac tumours but not to various types of rat, mouse or human normal cells or tumour cell lines including carcinomas, sarcomas, lymphomas and gliomas. Both lymphomas are CD3+, CD4-, CD8- and T-cell receptor (TCR) alpha beta +. The cytotoxicity was not MHC restricted or dependent on the density of MHC class I of the target cells, and the mouse lymphoma killed the rat yolk sac tumour target. The cytotoxic action was fast and up to 80% specific killing was observed in 4-h 51Cr release assays. A rat B cell hybridoma was established from a Wistar/Furth (WF) rat immunized with the syngeneic lymphoma G1-Tc1 producing an immunoglobulin (Ig)G2c monoclonal antibody (MoAb) 1F2. This binds to the lymphomas G1-Tc1 and YAC-1 and also to a murine non-cytolytic Rauscher lymphoma RMA, but not to any other of several rat, mouse or human cell types tested. The 1F2 completely inhibited the killing of rat yolk sac tumours by the two cytolytic lymphomas, but did not interfere with the killing mediated by natural killer (NK) cells or cytolytic lymphokine-activated killer (LAK) cells. Immunochemical analysis of solubilized cell membranes of the lymphoma G1-Tc1 demonstrates that the 1F2 antibody recognizes an epitope on a retroviral gp 70 envelope protein. This indicates that a retroviral protein is involved in the lytic activity of the two lymphomas.

AKR murine leukemia virus↗

The expression of thioredoxin mRNA is increased in the human cervix during pregnancy.

The classic function for thioredoxin is to act as a hydrogen donor for the enzyme ribonucleotide reductase, which is essential for DNA synthesis. In addition, thioredoxin participates in the regulation of different metabolic processes via thiol redox control. These kind of processes involve changes in the activity of different enzymes, receptors or transcription factors via dithiol/disulphide interchange reactions. Thioredoxin is present in the human decidua and trophoblasts. This study was performed to investigate whether thioredoxin mRNA is present in the human cervix, and differently expressed during pregnancy as compared with the non-pregnant state. Cervical biopsies and serum samples were obtained from 28 late pregnant, 41 post-partum and 15 non-pregnant menstruating women. The tissues were analysed for thioredoxin mRNA content using a solution hybridization technique. The thioredoxin mRNA level increased 3-fold at late pregnancy in comparison with the non-pregnant state. No further increase was seen immediately after parturition, either after spontaneous delivery or after pharmacological induction. There was a positive correlation between the cervical thioredoxin mRNA level and the serum oestradiol concentration in the non-pregnant group. We suggest that thioredoxin mRNA in the human cervix is regulated, at least partly, by oestradiol.

Adult↗

Thioredoxin messenger ribonucleic acid is regulated by estradiol in the rat uterus.

Thioredoxin is a major cellular dithiol reductant with a large number of functions in electron transport and thiol redox control of enzymes and transcription factors. To investigate the expression and regulation of thioredoxin in the uterus, 35 rats were ovariectomized (OVX) and treated 14 days after surgery with either growth hormone (GH), dexamethasone (DEX), or estradiol (E2), or combinations of these, for 24 h. Thioredoxin mRNA levels were determined by solution hybridization. The animals receiving E2 or a combination of E2 and DEX showed significantly increased thioredoxin mRNA levels, by 4-fold and 5-fold, respectively, as compared to the OVX control group. The GH or GH+DEX-treated groups did not display any difference in thioredoxin mRNA levels. Thioredoxin mRNA was also measured at different time points in uteri from OVX rats treated with daily E2 injections and was found to be transiently increased, with a maximum 48 h after the initiation of the E2 treatment. In contrast, the thioredoxin mRNA level in the liver of OVX rats was about 10-fold higher than in the uterus but remained unaffected by the different hormone treatments. We conclude that thioredoxin mRNA is expressed in the rat uterus, and up-regulated by E2 in a tissue-specific manner, with a maximum at 48 h after the initiation of hormone treatment.

Animals↗

Recovery and outcome after propofol and isoflurane anesthesia in patients undergoing laparoscopic hysterectomy.

BACKGROUND: Laparoscopic hysterectomy (LH) is expected to provide fast and comfortable recovery, plus an early return to normal daily activities. This study was carried out to compare the outcome after LH in patients anesthetized with isoflurane or propofol. METHODS: Sixty-two patients undergoing LH were randomized to receive either isoflurane-N2O or propofol-N2O anesthesia. The times when the patients could drink, void and walk were recorded. Recovery was also evaluated by the Digit Symbol Substitution Test in the postanesthesia care unit (PACU) 60 and 120 min after the operation. The patients were also given a questionnaire on their further recovery (return to daily activities, pain and nausea) to be filled out at home. RESULTS: Early recovery was significantly (P < 0.05) faster in the isoflurane group (eye opening within 3 min, orientation in 6 min) when compared to the propofol group (eye opening within 7 min, orientation in 14 min), but there was no significant difference in the other parameters of recovery. Most of the patients were discharged from the hospital on the first postoperative day in both groups. Twenty-five percent of the patients, however, stayed two nights in hospital, mainly for social reasons. No difference was found regarding the recovery at home: the patients resumed their normal daily activities on about the sixth postoperative day (median). CONCLUSIONS: It is concluded that both isoflurane and propofol are suitable anesthetics for LH. In this study recovery was not fast enough to make the patients suitable for same-day surgery.

Adult↗

Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective dose-ranging randomized trial. International Multicentre Hirudin Study Group.

The aim of this multicentre, prospective, randomised, dose-ranging study was to compare the safety and efficacy of subcutaneous recombinant hirudin (HBW 023) against intravenous sodium heparin in acute lower limb deep venous thrombosis (DVT). Patients were randomized to treatment with either HBW 023 or heparin for 5 +/- 1 days. HBW 023 was given according to body-weight in three dose groups. Thromboembolic disease was assessed by phlebography and ventilation/perfusion (V/Q) scanning on Day 1 and Day 5 +/- 1. One hundred and fifty-five patients were enrolled, of these 121 were evaluable for efficacy analysis. Significantly fewer patients on HBW 023 developed new V/Q abnormalities during the treatment period, (p = 0.006). There was no difference between the groups in thrombus extension or regression, major bleeding complications or serious adverse events. There were significantly fewer findings of new V/Q mismatch after treatment with HBW 023, and anticoagulant control was superior in these patients.

Adult↗

The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299.

The pharmacological properties of a novel selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist, NAD-299 [(R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrogen (2R,3R)-tartrate monohydrate] were examined in vitro and in vivo and compared with the reference 5-HT1A receptor antagonist, WAY-100635 [N-(2-(1-(4-(2-methoxyphenyl)piperazin-yl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride]. The new compound had high affinity for 5-HT1A receptors in vitro with a Ki value of 0.6 nM. The only other receptors for which NAD-299 had affinity less than 1 microM were alpha-1 and beta adrenoceptors with Ki values of 260 and 340 nM, respectively. Thus, the selectivity of NAD-299 for 5-HT1A receptors was more than 400 times. WAY-100635 had considerably higher affinity than NAD-299 for alpha-1 adrenoceptors (Ki = 45 nM) and dopamine D2 and D3 receptors (Ki = 79 and 67 nM, respectively). Like WAY-100635, NAD-299 competitively blocked 5-HT-induced inhibition of vasoactive intestinal peptide-stimulated cAMP production in GH4ZD10 cells and had no intrinsic activity. Both compounds were therefore 5-HT1A receptor antagonists in vitro and also behaved as such in in vivo experiments. Thus, they competitively antagonized the 8-hydroxy-2-(di-n-propylamino)tetralin-induced 5-HT behavioral effects, hypothermia, corticosterone secretion and inhibition of passive avoidance behavior without causing any actions of their own. The effective dose of NAD-299 varied between 0.03 and 0.35 micromol/kg s.c., depending on the test and the dose of 8-hydroxy-2-(di-n-propylamino)tetralin.

5-Hydroxytryptophan↗

Generation of development environments for the Arden Syntax.

Providing appropriate development environments for specialized languages requires a significant development and maintenance effort. Specialized environments are therefore expensive when compared to their general-language counterparts. The Arden Syntax for Medical Logic Modules (MLM) is a standardized language for representing medical knowledge. We have used PROTEGE-II, a knowledge-engineering environment, to generate a number of experimental development environments for the Arden Syntax. MEDAILLE is the resulting MLM editor, which provides a user-friendly environment that allows users to create and modify MLM definitions. Although MEDAILLE is a generated editor, it has similar functionality, while reducing the programming effort, as compared to other MLM editors developed using traditional programming techniques. We discuss how developers can use PROTEGE-II to generate development environments for other standardized languages and for general programming languages.

Programming Languages↗

Influence of blockers for the estrogen receptor (ER) and type 1 IGF-receptor on the levels of ER, ER mRNA and IGF-I mRNA in the rat uterus.

The effects on the uterine concentration of the estrogen receptor (ER), ER mRNA and IGF-I mRNA were monitored in ovariectomized (OVX) rats treated with blockers for the estrogen receptor (ER) (ICI 182780) or the type 1 IGF receptor (H-1356), alone or in combination with estradiol (E2). The hormone-mediated increase in uterine wet weight after E2 treatment was prevented by a simultaneous injection of ICI 182780. The levels of IGF-I mRNA and ER mRNA increased in rats given estradiol (E2), but not in those also receiving ICI 182780. The level of uterine ER was decreased in all animals that received ICI 182780. H-1356 (H) given as a continuous infusion decreased the estradiol-induced increase in uterine wet weight 24 h after a single E2 injection, but not 48 h after the first (of two) E2 injections. The IGF-I mRNA was increased in the E2 treated group after 24 h, and in both the E2 and H + E2 treated groups after 48 h. The ER mRNA was increased in the E2 treated group after 24 h, but not after 48 h. When H-1356 was given as two single injections and estradiol was or was not administered together with the second injection, the uterine wet weight was not increased as in the group receiving E2 only. The levels of IGF-I mRNA as well as ER mRNA were increased both after E2 and H + E2 treatment. In conclusion, the uterine growth stimulated by E2 was prevented by simultaneous treatment with ICI 182780. In addition a type 1 IGF-receptor blocker, which is an IGF-I analogue inhibiting the autophosphorylation of the receptor, also prevented the hormone-induced uterine growth after 24 h, but not after 48 h, when given as a continuous infusion. The results imply that the growth process stimulated by estradiol utilizes the ER receptor, and also the type 1 IGF-receptor during the first 24 h after E2 treatment.

Animals↗

A new method to study the process of implantation of a human blastocyst in vitro.

OBJECTIVES: To develop a "miniorgan" culture of human endometrium dated according to the LH peak in order to study the process of implantation of a human blastocyst in vitro. DESIGN: Preliminary results of a more extensive study with the same objectives. SETTING: Hospital-based unit of reproductive health and university-related reproductive research laboratories. PATIENTS: Six apparently healthy women with normal regular menstrual cycles providing endometrial material 4, 5 and 6 days after the LH peak. INTERVENTION: One part of the biopsy was used for histologic dating. The other part was incubated in culture medium RPMI-1640 and exposed to the contact with one to three embryos fertilized in vitro. MAIN OUTCOME MEASURE: Biopsy material before and after incubation was studied by morphometric methods in a light microscope. The histologic changes were recorded by photomicrographs. RESULTS: Implantation of an embryo obtained 4 days after IVF penetrated the lining endometrial epithelium of a biopsy obtained 4 days after the LH peak and kept in vitro for 24 hours. The embryo was placed on the lining epithelium of the endometrium within 3 hours after the biopsy was taken. CONCLUSION: A new method to study the process of implantation of a human embryo in vitro has been described, allowing the embryo to penetrate the lining endometrial epithelium in a biopsy obtained at LH +4/+5.

Blastocyst↗

Proteolytic cleavage of MHC class I by complement C1-esterases--an overlooked mechanism?

The complement C1-esterases have been shown to cleave the MHC class I molecules, which are important participants in the activation of T lymphocytes, between the alpha 2- and the alpha 3-domain of the heavy chain. The possible involvement of the C1-esterases in the regulation of peripheral self-tolerance is discussed. It is hypothesized that the C1-esterase-mediated cleavage of the MHC class I molecules either induces: a soluble fragment of the outer two domains of the MHC class I molecule, in association with beta 2-microglobulin, to bind to the T cell receptors and prevent the cells from being activated, or produces a change in the exposure of the alpha 3-domain that remain on the cell surface, acting as mediator of a 'veto signal' that prevents these cells from being activated.

Complement C1s↗

Recovery profile after desflurane with or without ondansetron compared with propofol in patients undergoing outpatient gynecological laparoscopy.

We studied the effect of combining prophylactic ondansetron (4 mg intravenously [IV]) to desflurane-based anesthesia in 90 ASA grade I or 11 women undergoing outpatient gynecological laparoscopy. Recovery after anesthesia, with special focus on postoperative nausea and vomiting (PONV), was assessed. Control groups received a similar desflurane anesthetic (placebo) or a propofol-infusion-based (active control) anesthetic. The study design was randomized, controlled, and double-blind (regarding ondansetron) and single-blind (regarding the anesthetic technique). Early recovery (eye opening, orientation, following commands, sitting) was similar in the three groups. However, overall home readiness (toleration of oral fluids, walking, pain tolerable by oral analgesics, no or only mild nausea) was achieved faster in the desflurane group receiving ondansetron (109 [21-937] min, P < 0.01) and in the propofol group (110 [33-642] min, P < 0.001) when compared to the desflurane only group (372 [45-723] min) (median [range]). The total incidence of PONV in the desflurane-only group was 80% (P < 0.01), compared to 40% and 20% in the desflurane group receiving ondansetron and the propofol group, respectively. The postoperative antiemetic requirements were consistently and significantly (P < 0.01) higher in the desflurane-only group compared to the other two groups. Postoperative sedation, analgesic requirements, and psychomotor recovery (assessed by the Maddox Wing and the Digit Symbol Substitution Tests) were similar in the three groups. Our results suggest that in order to achieve a propofol-like recovery profile in patients with a high likelihood of PONV, desflurane should be combined with a potent antiemetic (e.g., ondansetron).

Adolescent↗

Balanced analgesia improves recovery and outcome after outpatient tubal ligation.

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. The balanced analgesia group received 5 ml of 2% lidocaine gel on the sterilization clips and perioperatively 200 mg of ketoprofen i.v. The lidocaine group received 5 ml of 2% lidocaine gel on the clips and placebo i.v. perioperatively. The placebo group received 5 ml of placebo gel on the clips and placebo i.v. perioperatively. Infusion of propofol and 67% nitrous oxide in oxygen were used for maintenance of anesthesia. Succinylcholine and vecuronium were used for muscle relaxation and 0.1 mg of fentanyl i.v. was given to all patients at induction of anesthesia. Postoperative pain and analgesic requirements, incidence of PONV and need for antiemetic medication were all significantly lower in the balanced analgesia group. Home readiness was consistently achieved 70-90 min sooner in the balanced analgesia group compared to the other groups (P < 0.01 between the balanced analgesia and the placebo group), and the patients were able to return to normal activity sooner (cumulatively 93% of the patients in the balanced analgesia group vs. 60% in the other two groups (P < 0.01 between the balanced analgesia and the other groups) had returned to normal activity on the 2nd postoperative day). It is concluded that in patients undergoing laparoscopic TL the combination of analgesic regimens with different mechanisms of action offer a simple and efficient way of postoperative pain relief, as well as an improvement of quality (i.e. less PONV) and speed of recovery.

Adult↗

Extracorporeal immunoadsorption from whole blood based on the avidin-biotin concept. Evaluation of a new method.

This study of 36 rats with rat colon adenocarcinoma transplants was carried out to investigate the efficacy of a new method of whole blood immunoadsorption (WBIA) in removing biotinylated monoclonal antibodies (MAbs) directly from unseparated blood, in order to increase 'the tumor/normal-tissue uptake ratio', as compared with extracorporeal immunoadsorption (ECIA) of antibodies from plasma. Compared with the ECIA system, the overall volume of the WBIA system (comprising only a pump, an adsorption column, a drop-chamber and tubings) was less (3.6 vs. 6.2 ml), and procedure duration 2 h less. The 17 rats undergoing the WBIA procedure, started 12 h after i.v. injection of 4.0-4.5 MBq 125I-BR96-biotin, manifested neither hemolysis nor any other complication; no signs of organ edema were found at dissection; whole body and blood radioactivity values were reduced by 51% and 89.5%, respectively. The WBIA method was as effective as ECIA, but technically simpler, safer and more reliable.

Adenocarcinoma↗

Is hypertension changing? Blood pressure development in cohorts of 50-year-old men between 1963 and 1993.

OBJECTIVE: To study secular trends in the prevalence and treatment of hypertension in the general population, and the disease course. DESIGN: Health examinations of cohorts of 50-year-old men in 1963, 1973, 1983 and 1993. SETTING: The city of Göteborg, Sweden (about 400,000 inhabitants). PARTICIPANTS: Random population samples of 50-year-old men. MAIN OUTCOME MEASURE: Mean blood pressure (BP) levels in the populations and among treated hypertensives, proportions of hypertensives, and frequency of high BP values (> or = 160/and or 95, and > or = 175/115 mmHg, respectively). RESULTS: The mean population BP decreased from 138.4/89.0 mm to 128.7/84.4 mmHg during the 30-year period (p < 0.0001). Mean BP levels among treated hypertensives decreased from 170/113 to 142/94 mmHg (p < 0.0001), and the proportion of men with high BP values diminished from 3.9 to 0.1%. Also BP levels among normotensives decreased significantly (p < 0.0001). CONCLUSION: The findings could partly be seen as a result of successful case-finding and treatment of hypertension in the region, but alteration of the natural course of hypertension cannot be excluded.

Blood Pressure↗