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Biomedical subjects

H Eriksson

Publications and source records attributed to H Eriksson.

At least 19 recordsLinked to original sources

Bundle-branch block in a general male population: the study of men born 1913.

BACKGROUND: Interest in bundle-branch block has focused primarily on its role as a predictor of mortality and coexisting cardiovascular diseases. Previous studies of prevalence, correlation to cardiovascular disease, and mortality have produced conflicting results. METHODS AND RESULTS: We studied a random-sampled population of 855 men who were 50 years old in 1963 and followed them up for 30 years with repeated examinations. Men who developed bundle-branch block were studied with regard to cumulative incidence, relationship with cardiovascular disease/risk factors, and survival. The prevalence of bundle-branch block increases from 1% at age 50 years to 17% at age 80 years, resulting in a cumulative incidence of 18%. No significant relationship with ischemic heart disease or mortality was found. Men who would develop bundle-branch block had a bigger heart volume at age 50 years and developed diabetes mellitus and congestive heart disease during follow-up more often than control subjects. CONCLUSIONS: Bundle-branch block correlates strongly to age and is common in elderly men. Our results support the theory that bundle-branch block is a marker of a slowly progressing degenerative disease that also affects the myocardium.

Age Factors

Cloning and functional expression of the guinea pig neuropeptide Y Y2 receptor.

Five neuropeptide Y (NPY) receptor subtypes have been cloned in mammals. The degree of sequence conservation differs considerably between subtypes as well as between evolutionary lineages. To shed further light on this, we have cloned the five NPY receptors in the guinea pig. Here, we report the cloning of the guinea pig Y2 receptor. The Y2 receptor is generally highly conserved, with 90-95% identity between different orders of mammals, including the guinea pig. The guinea pig receptor has a divergent cytoplasmic tail, indicating possible differences in regulation of signalling and/or down regulation. COS-7 cells transiently transfected with the gpY2 receptor show saturable 125I-PYY binding with a Kd = 6 pM. In displacement experiments, the gpY2 receptor was similar to the human and rat receptors with the following rank order of potencies: pNPY > pPYY > pNPY13-36 = pNPY22-36 >> [Leu31Pro34]NPY > BIBP3226. Thus, the guinea pig Y2 receptor is well conserved in comparison with human and rat with regard to both amino acid sequence and pharmacological profile.

Amino Acid Sequence

The cloned guinea pig pancreatic polypeptide receptor Y4 resembles more the human Y4 than does the rat Y4.

Pancreatic polypeptide (PP) is involved in gastrointestinal functions and forms, together with neuropeptide Y (NPY) and peptide YY (PYY), the PP-fold family of peptides. The PP-binding receptor subtype Y4 has so far been cloned in human, rat, and mouse, and displays extensive species differences regarding sequence, pharmacology, and distribution. To explore this variability further, we have cloned the Y4 receptor in the guinea pig, which is evolutionarily equally distantly related to both humans and rodents. The guinea pig Y4 receptor is 84% identical to the human Y4 receptor, but only 74-75% identical to the rat and mouse receptors. The two latter are 75-76% identical to human Y4. The guinea pig Y4 receptor bound 125I-hPP with a dissociation constant (Kd) of 29+/-3 pM. The pharmacological profile of guinea pig Y4 has the following rank order of potencies: PP > NPY approximately = PYY approximately = LP-NPY approximately = LP-PYY > NPY2-36 >> [D-Trp32]NPY. Thus, the guinea pig receptor is more similar to the human Y4 than to the rat Y4 both in sequence and pharmacology. This agrees with the greater identity between guinea pig and human PP compared to rat PP. These comparisons suggest that the rodent PPs and Y4 receptors have an accelerated replacement rate.

Amino Acid Sequence

[Pulmonary embolism remains an overlooked diagnosis. Proposed strategy in suspected cases].

The problem of misdiagnosed pulmonary embolism (PE) is reviewed in the light of the introduction of new diagnostic methods such as spiral tomography (helical scanning). Despite new diagnostic methods, the frequency of misdiagnosed PE will not be reduced unless PE is suspected at the right juncture. PE should always be suspected in the presence of 'pulmonary syndromes' and venous thromboembolic risk factors. A strategy for the management of cases of suspected PE is proposed in the article: 1, recognition of the presence of cardiopulmonary disease, 2, determination of the clinical probability of PE; 3, confirmation (or exclusion) of PE; 4, determination of its severity and prognosis; and 5, choice of treatment. A two-part algorithm for use in patients with stable or unstable haemodynamics is also presented.

Diagnosis, Differential

Conditions for the adsorption of proteins on ultrastable zeolite Y and its use in protein purification.

The adsorption of proteins on ultrastable zeolites was investigated. Protein binding to one of these, ultrastable zeolite Y (USY), was studied in detail. Protein binding to USY, with a Si/Al ratio of > 240, was found to be dependent on the pH of the solution, being highest at or just below the pI of the protein. The amount of protein adsorbed on the zeolite was found to be 10 times as much as the estimated binding to the external surface of the USY. We propose an adsorption mechanism involving the formation of a protein layer strongly bound to the USY surface, further protein layers being formed on top of this on the basis of protein-protein interactions. The protein-protein interactions can be disrupted by changing the pH. Ultrastable zeolite Y was used as a new matrix for protein purification. Undesired proteins can be removed from a crude preparation by adsorption on USY, increasing the purity of a specific protein, or the protein can be adsorbed on the zeolite and subsequently eluted through changing the pH. These two means of protein purification are exemplified by the purification of peroxidase from a crude horseradish extract and by the purification of lysozyme from egg white.

Adsorption

Insulin-like growth factor-I in the porcine endometrium and placenta: localization and concentration in relation to steroid influence during early pregnancy.

To initiate the establishment of an epitheliochorial placenta, the developing porcine conceptuses contact the maternal endometrium on its mesometrial side. The porcine conceptuses secrete estrogens which, together with circulating maternal hormones, govern variations in the structure as well as expression and levels of steroid receptors and growth factors during early pregnancy. Mesometrial samples of endometrium or placenta were collected from 15 early pregnant (8-30 days after the onset of estrus) and six cycling (days 1-14) gilts. The variations in tissue morphology and immunohistochemical localization of insulin-like growth factor-I (IGF-I) were related to the tissue levels (by enzyme immunoassay) of receptors for estrogen (ER) and progesterone (PR), as well as mRNA (by solution hybridization) concentrations for the two receptors and IGF-I. IGF-I immunoreactivity was present in samples from all animals, being principally located in maternal epithelium, trophoblast, endothelium and vascular smooth muscle; the latter showing the strongest labeling. The levels of receptor proteins, as well as mRNAs, were highest in the non-pregnant animals at estrus and metestrus. The pregnant animals showed decreasing concentrations to consistently low levels after day 14. Temporal changes in the studied parameters were clearly coincidental with the peak (days 13-14) in conceptus estrogen secretion, e.g. the more uniform IGF-I immunolabeling in the uterine glands (days 8-13) compared with the later stages studied; the conspicuous accumulation and release of secretory vesicles in the endometrial glands (days 8-13), marking the change in secretory quality and quantity, leading to a gradual shift from histotrophic to hemotrophic nutrition of the conceptuses, and finally, the peaking level of IGF-I mRNA in the pregnant endometrium (days 12-13) which decreased considerably thereafter. It is concluded that IGF-I activity in the porcine uterus changes with the early development of the placenta.

Animals

Specific inhibition of the cGMP-inhibited cAMP phosphodiesterase blocks the insulin-like antilipolytic effect of growth hormone in rat adipocytes.

Growth hormone (GH) exerts acute insulin-like effects, such as increased lipogenesis and inhibition of catecholamine-induced lipolysis, in rat adipocytes that have not been exposed to GH during the preceding three hours. We found that OPC3911, a highly specific inhibitor of the cGMP-inhibited cAMP phosphodiesterase, completely blocked the antilipolytic but not the lipogenic effect of GH. This indicates that the antilipolytic effect of GH is mediated through activation of this phosphodiesterase leading to reduction of cAMP levels in the same manner as has been shown for insulin.

3',5'-Cyclic-AMP Phosphodiesterases

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