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Biomedical subjects

E Andersson

Publications and source records attributed to E Andersson.

At least 91 records · Page 5Linked to original sources

Biologic activities of retinoic acid and 3,4-didehydroretinoic acid in human keratinocytes are similar and correlate with receptor affinities and transactivation properties.

The biologic activities of retinoic acid and 3,4-didehydroretinoic acid, two endogenous vitamin A derivatives in various tissues, were compared to their affinities for the nuclear retinoic acid receptors and their ability to induce transcriptional activation. Both retinoids were equipotent inducers of differentiation of F9 teratocarcinoma cells. In a morphologic assay, using reconstructed skin, retinoic acid and 3,4-didehydroretinoic acid inhibited keratinization at a concentration of 100 nM. In cultured keratinocytes, a 50% inhibition of the production of the keratinocyte transglutaminase enzyme was achieved with about 20 nM for both retinoids. The in vitro binding to the nuclear retinoic acid receptors alpha, beta, and gamma showed that retinoic acid and 3,4-didehydroretinoic acid had almost equal affinities for the receptors with Kds ranging from 3 to 47 nM. The transcriptional activation resulting from the addition of the two retinoids to cells co-transfected with alpha, beta, or gamma retinoic acid receptor expression vectors and a retinoic acid responsive element linked to the chloramphenicol acetyltransferase reporter gene was similar. Finally, it was demonstrated that retinoic acid did not metabolize to 3,4-didehydroretinoic acid, and a slow conversion of 3,4-didehydroretinoic acid into retinoic acid was not sufficient to explain the biologic effects produced by the former compound. In conclusion, the present study demonstrates that retinoic acid and 3,4-didehydroretinoic acid have the same activity in several different test systems, but their metabolism differs depending on the cell type used.

Cells, Cultured↗

Complete cDNA sequence of a rainbow trout IgM gene and evolution of vertebrate IgM constant domains.

A complete cDNA clone encoding secreted IgM molecules was isolated from a spleen cDNA library of rainbow trout (Oncorhynchus mykiss). It encodes the leader peptide, VH, DH, JH, and the whole constant region of the secreted IgM molecule. We also studied the copy number of the IgM gene and an unusual RNA splicing mechanism which generates membrane IgM lacking the CH4 domain in rainbow trout. Amino acid sequence comparison of IgM protein sequences from this fish and other vertebrates indicates that some domains of IgM have evolved at a relatively constant rate. The evolution of salmonid fish including divergence time is discussed.

Amino Acid Sequence↗

Endothelin contracts human uterine myometrium by a partly dihydropyridine-sensitive mechanism.

The effect of endothelin (ET), a recently discovered 21-amino-acid polypeptide with powerful vasoconstrictor properties, was examined on human uterine myometrial strips in vitro. ET dose-dependently (10(-11)-10(-7) M) increased the contractile force (monitored as contraction amplitude) of the myometrium with significant effects at 10(-8) and 10(-7) M. ET (10(-8) M and up) also increased the basal tone of the myometrium. The calcium channel blocking agents nifedipine (10(-7) M) and diltiazem (10(-6) M) both inhibited the spontaneous tonic contractions of the myometrium. When ET was given in the presence of nifedipine, the tonic contractions were further inhibited, whereas the ET-induced increase in basal tone remained. The same result was obtained with diltiazem (10(-6) M). The results indicate that the contractility of human myometrium may be modulated by ET, and that the effects of ET on the human myometrium are only partly mediated by dihydropyridine-sensitive calcium channels.

Dihydropyridines↗

Leg and foot ulcer prevalence and investigation of the peripheral arterial and venous circulation in a randomised elderly population. An epidemiological survey and clinical investigation.

Five thousand one hundred and forty questionnaires concerning leg ulcers were sent to a randomly selected population aged 65 years and older in Gothenburg in April 1989. The response rate was 89%. Ninety-seven individuals answered affirmatively, that they had leg ulcers, which corresponds to a prevalence of 2.15 +/- 0.42 per cent. These 97 individuals and the same number of controls were asked to come for a medical examination with tests of the peripheral circulation and an interview. Seventy-five (of the 97) were examined. Thirty-five had leg or foot ulcers caused by vascular insufficiency and/or diabetes and the true prevalence was estimated to be 1.02 +/- 0.29 per cent.

Aged↗

A longitudinal follow-up of bacterial vaginosis during pregnancy.

Bacterial vaginosis (BV) has been considered by many investigators to be a risk factor for preterm labor. We have followed vaginal pH and the persistence of clue cells in Papanicolaou stained smears in 119 pregnant women during the course of pregnancy. Of 19 patients with clue cells in their smears during the first trimester, 11 (58%) still had clue cells at the second visit during the third trimester. Of the 100 patients without clue cells during their first trimester, none exhibited clue cells during the third trimester. If the persistence of clue cells is truly a risk factor for adverse pregnancy outcome, screening in the first trimester would identify a risk group of 15%. This risk group diminishes to 9% at the time of the third trimester. Vaginal pH > 4.5 had a recovery sensitivity of 76% and specificity of 83%. If clue cells can be considered as the identifying standard for bacterial vaginosis, the sensitivity and specificity of pH is 89% and 94%, respectively. The establishment of the diagnosis of BV during pregnancy and, in some cases, the treatment of the condition may be important as routine procedures in the antenatal center.

Adult↗

Temperature, but not photoperiod, influences gonadotropin-releasing hormone binding in the pituitary of the three-spined stickleback, Gasterosteus aculeatus.

Gonadotropin-releasing hormone (GnRH) binding characteristics in pituitaries of stickle-backs under different physiological conditions were studied using D-Arg6-Pro9-salmonGnRH-NEt as labeled ligand. Both males and females displayed marked seasonal changes in the capacity of high-affinity GnRH binding sites; there was a high content in the breeding season (summer) (800-1500 pmol/pituitary) and no detectable high affinity (< 150 pmol) binding in late winter-early spring. The binding capacity was lower in postbreeding fish (ca. 400 pmol/pituitary in females, ca. 900 pmol in males) than in breeding fish (females: ca. 1850, males ca. 1400 pmol). GnRH binding sites were also studied in fish exposed to long and short photoperiod in combination with high and low temperature in winter. Only long photoperiod in combination with high temperature stimulated sexual maturation. The capacity of the GnRH binding sites was similar in fish exposed to long (females 1550 pmol, males 1000 pmol) and short (females 1800, males 900) photoperiod in combination with high temperature. In fish exposed to low temperature, binding was nondetectable irrespective of the photoperiod.

Amino Acid Sequence↗

Oral acitretin in psoriasis: drug and vitamin A concentrations in plasma, skin and adipose tissue.

The purpose of the present study was to determine the concentrations of acitretin and its main metabolite, 13-cis acitretin, in epidermis, subcutis and plasma in twelve psoriatic patients treated with 30 mg acitretin orally daily for 6 months. In addition, endogenous concentrations of vitamin A were monitored. Blood samples and biopsies from normal appearing skin were obtained prior to therapy, after 1 and 6 months of treatment and finally 1 month after cessation of therapy. Using a highly sensitive liquid chromatography method concentrations of synthetic retinoids and endogenous retinoid (retinol, 3,4-didehydroretinol) were analysed in hydrolyzed tissue samples and plasma. Steady-state concentration of acitretin in epidermis (17 +/- 9 ng/g) was reached within 1 month of therapy. There was a significant correlation between the individual plasma trough value and the epidermal concentration of acitretin after 1 month of therapy. The acitretin concentrations in subcutis varied from 15 to 1437 ng/g, but the mean values at 1 and 6 months of therapy were similar (177 and 227 ng/g, respectively). After stopping therapy the acitretin level was below the detection limit in both epidermis and serum within 1 month in 9 out of 12 patients. In contrast, only 3 of the patients were negative for acitretin in subcutis biopsies obtained 1 month after stopping therapy. The occurrence of a presumed tissue contaminator with characteristics similar to 13-cis acitretin prevented quantitation of this metabolite in many subcutis samples. The epidermal, subcutis and serum composition of retinol and 3,4-didehydroretinol remained unchanged during therapy, indicating no or only minimal interaction between acitretin and endogenous vitamin A metabolism.

Acitretin↗

The effect of 19-hydroxy prostaglandins on the human myometrium in vitro.

Human semen contains high amounts of different prostaglandins of which the quantitatively dominating compounds are 19-hydroxy PGE and 19-hydroxy PGF. The effect of PGE and PGF on the contractility of the human uterus is well known whereas the corresponding 19-hydroxy derivatives have not previously been examined in detail. In the present investigation 19-hydroxy PGE1 was shown to dose-dependently decrease the frequency and the amplitude of the contractions in human myometrial tissue in vitro. The effect of seminal 19-hydroxy prostaglandins may thus be of importance for sperm transport through the female genital tract.

Alprostadil↗

Evolution of a VH gene family in low vertebrates.

Antibody genes represent one of the most complex receptor gene systems which have evolved in the vertebrate lineage. One of the central questions is how antibody variable region genes diversify the complementarity determining region (CDR) in evolution while they are subject to forces for sequence homogenization operating in multigene families. Information on germ line antibody genes in lower vertebrates is still fragmentary and it would be fruitful to gain insight into this question. We have studied the evolutionary stability of a rainbow trout VH family (RTVH 431) by Southern blot hybridization in various fish species. Comparison of our results with paleontological/zoological evidence suggests that this VH family has been preserved in the genomes of many fish species over a time span of 150 million years. We also show that there exist species-specific residues common to rainbow trout VH genes, which strongly supports the presence of genetic processes for homogenization. These results are compatible with the view that antibody V genes evolve at a fairly constant rate and that the homogenization process (e.g. gene duplication) may be slow enough to allow diversification of CDR by mutation, selection and drift.

Amino Acid Sequence↗

Synthetic retinoids affect differently the epidermal synthesis of 3,4-didehydroretinol.

For unknown reasons, the epidermal concentrations of retinol and its metabolite 3,4-didehydroretinol become characteristically changed during treatment with certain synthetic retinoids. In the present study we investigated [3H]retinol uptake and conversion to 3,4-[3H]didehydroretinol in cultured human skin exposed to six different retinoids. The tissue accumulation of [3H]retinol increased by 50-130% following addition of 1.3 microM of all-trans-retinoic acid, 13-cis-retinoic acid, or 3,4-didehydroretinoic acid (putative metabolites of retinol), and by 13-55% after addition of acitretin, arotenoid Ro 13-7410, or 4-(N-hydroxyphenyl)retinamide. The formation of 3,4-[3H]didehydroretinol was markedly inhibited (minus 80-90%) by the three putative retinol metabolites, moderately inhibited (minus 60-70%) by the aromatic retinoic acid analogues acitretin and arotinoid, and only slightly inhibited (minus 25%) by 4-(N-hydroxyphenyl)retinamide. Addition of citral and ketoconazole, substances known to interfere with the oxidative metabolism of vitamin A, diminished the formation of 3,4-didehydroretinol by 70 and 95%, respectively, but only marginally affected the retinol values. We conclude that the increase in retinol and marked reduction in 3,4-didehydroretinol concentrations in epidermis especially during treatment with 13-cis-retinoic acid are most likely due to diminished conversion of retinol to 3,4-didehydroretinol, but whether or not this reflects feedback inhibition of retinol metabolism or direct inhibition of a specific enzyme remains to be established. Nonetheless, in vitro analysis of 3,4-didehydroretinol biosynthesis appears to be a sensitive means for screening compounds for their ability to interfere with the cutaneous vitamin A metabolism.

Female↗

Location of ulcers on the lower limbs in relation to distal systolic blood pressure indices.

The distal systolic blood pressure indices (AI = ankle/arm and TI = toe/arm) of 100 patients with lower limb ulcers at a dermatology outpatient clinic were correlated to ulcer site. The left limb was more often ulcerated than the right. Most ulcers were situated medially, while ulcers on the anterior and posterior sides were infrequent. An AI below 0.9 and TI below 0.6 is usually considered to indicate arterial insufficiency. Forty-four per cent of the patients had an AI less than 0.9 and 66% a TI less than 0.6. The lowest mean indices in all ulcerated limbs were found in patients with ulcers on the feet, followed by those with ulcers in lateral and posterior positions. A significantly lower TI (p = 0.002) was found in the ulcerated limbs when comparing the patients with one ulcerated and one non-ulcerated leg, but no such difference was found for AI. Thus, the ulcerated and the seemingly healthy limb usually had about the same AI. In all patients, TI decreased significantly with age (p = 0.0001). TI was lower in men, than in women, when the effect of age was eliminated (p = 0.0509).

Adult↗

Bioconversions in aqueous two-phase systems.

Bioconversions involving enzymes and/or microbial cells in aqueous two-phase systems are reviewed. The partitioning of biocatalysts, substrates, and products is discussed in relation to their size. The efficiency of retaining biocatalysts in aqueous two-phase systems is summarized in relation to other methods of recirculating. The influence of phase components on the activity and the stability of enzymatic biocatalysts is exemplified with penicillin acylase and the cellulolytic enzyme system, and the effect of phase components on biocatalytic living cells is exemplified with the production of alpha-amylase with Bacillus sp. Process design costs in bioconversions in aqueous two-phase systems are briefly summarized.

Bacteria↗