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Biomedical subjects

S Andersson

Publications and source records attributed to S Andersson.

At least 199 records · Page 11Linked to original sources

Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases. IX. Influence of the cross-linking reagent on the retentive and enantioselective properties of chiral sorbents based on bovine serum albumin.

Three modifications of silica-bound, cross-linked bovine serum albumin (BSA) were evaluated as chiral sorbents for use in the liquid chromatographic separation of enantiomers. Glutaraldehyde, formaldehyde and di-(N-succinimidyl) carbonate were used as bifunctional reagents for the immobilization of BSA. The sorbents all contain the same loading of BSA (14.4 +/- 0.1%, w/w) and differ only with respect to the cross-linker used for immobilization. Despite their apparent similarity, the sorbents show very different chromatographic properties, not only with respect to retention of analyte enantiomers (k' and alpha), but also with respect to column efficiency (affecting Rs values). The data obtained indicate that the chemical structure of the cross-linking reagent affects to a large extent the accessibility of important chiral binding sites. Although the data obtained are difficult to interpret in any detail, certain generalizations concerning the different behaviour of the sorbents can be made.

Albendazole↗

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.

Animals↗

Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase.

The enzyme steroid 5 alpha-reductase catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone, and impairment of this reaction causes a form of male pseudohermaphroditism in which genetic males differentiate predominantly as phenotypic females. We previously isolated cDNA clones that encode a human steroid 5 alpha-reductase enzyme. Here, we report molecular and genetic studies demonstrating that the gene encoding this cDNA is normal in subjects with the genetic disease steroid 5 alpha-reductase deficiency. We further show that in contrast to the major steroid 5 alpha-reductase in the prostate and cultured skin fibroblasts, the cDNA-encoded enzyme exhibits a neutral to basic pH optima and is much less sensitive to inhibition by the 4-aza steroid, finasteride (MK-906). The results provide genetic, biochemical, and pharmacological support for the existence of at least two steroid 5 alpha-reductase isozymes in man.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Cost-effectiveness analysis of treatment with liposomal amphotericin B versus conventional amphotericin B in organ or bone marrow transplant recipients with systemic mycoses.

Economic appraisal of pharmaceuticals is becoming increasingly important. In a retrospective study of patient records from 58 organ or bone marrow-transplanted patients with systemic mycoses, the cost-effectiveness of treatment with a liposomal amphotericin B formulation was compared with that of conventional amphotericin B. Treatment with liposomal amphotericin B results in fewer adverse reactions, increased life expectancy and higher costs than treatment with conventional amphotericin B. Pricing liposomal amphotericin B at about SKE6000 per patient treatment day will result in an additional cost per life-year gained of about SEK150 000 relative to that using conventional amphotericin B for patients receiving kidney, kidney and pancreas, or pancreas transplants. For liver and bone marrow transplant (BMT) recipients the marginal cost-effectiveness ratio was about SEK195 000 and SEK150 000 per life-year gained. Compared with alternative use of resources in society and health care, use of liposomal amphotericin B rather than conventional amphotericin treatment can be considered cost-effective at the price assumed.

Adult↗

Clinical and immunological follow-up of previously hospitalized HIV-2 seropositive patients in Bissau, Guinea-Bissau.

A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency.

Acquired Immunodeficiency Syndrome↗

Acupuncture and occlusal splint therapy in the treatment of craniomandibular disorders. Part I. A comparative study.

One hundred and ten patients, 23 males and 87 females, participated in a comparative study of the effect of acupuncture and occlusal splint therapy. All the patients exhibited signs and symptoms of craniomandibular disorders (CMD) and had had pain for more than six months. The participants were randomly assigned to three groups; acupuncture treatment, occlusal splint therapy or control. The patients were evaluated before and immediately after treatment/control time. Ten different subjective and/or clinical assessment variables were used in the evaluation of the treatment effects. Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged. In this short-term study, acupuncture gave better subjective results (p < 0.001) than the occlusal splint therapy.

Acetaminophen↗

Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism.

The conversion of testosterone into dihydrotestosterone by steroid 5 alpha-reductase is a key reaction in androgen action, and is essential both for the formation of the male phenotype during embryogenesis and for androgen-mediated growth of tissues such as the prostate. Single gene defects that impair this conversion lead to pseudohermaphroditism in which 46X,Y males have male internal urogenital tracts, but female external genitalia. We have described the isolation of a human 5 alpha-reductase complementary DNA from prostate. Subsequent cloning and genetic studies showed that this gene (designated 5 alpha-reductase 1) was normal in patients with 5 alpha-reductase deficiency. We report here the isolation of a second 5 alpha-reductase cDNA by expression cloning and the polymerase chain reaction. The biochemical and pharmacological properties of this cDNA-encoded enzyme (designated 5 alpha-reductase 2) are consistent with it being the major isozyme in genital tissue. A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5 alpha-reductase deficiency. These results verify the existence of at least two 5 alpha-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Evolution of the dec-1 eggshell locus in Drosophila. I. Restriction site mapping and limited sequence comparison in the melanogaster species subgroup.

We have analyzed approximately 18 kb of DNA in and upstream of the defective chorion-1 (dec-1) locus of the eight known species of the melanogaster species subgroup of Drosophila. The restriction maps of D. simulans, D. mauritiana, D. sechellia, D. erecta, and D. orena are shown to have basically the restriction map of D. melanogaster, whereas the maps of D. teissieri and D. yakuba were more difficult to align. However, the basic amount of DNA and sequence arrangement appear to have been conserved in these species. A small deletion of varying length (65-200 bp) is found in a repeated sequence of the central transcribed region of D. melanogaster, D. simulans, and D. erecta. Restriction site mapping indicated that the dec-1 gene is highly conserved in the melanogaster species subgroup. However, sequence comparison revealed that the amount of nucleotide and amino acid substitution in the repeated region is much larger than in the 5' translated region. The 5' flanking region showed noticeable restriction site polymorphisms between species. Based on calculations from the restriction maps a dendrogram was derived that supports earlier published phylogenetic relationships within the melanogaster species subgroup except that the erecta-orena pair is placed closer to the melanogaster complex than to D. teissieri and D. yakuba.

Amino Acid Sequence↗

HIV-2 infection in hospitalized patients in Bissau, Guinea-Bissau.

During 11 months in 1989-1990, 1009 consecutive hospitalized adult patients admitted to the medical wards of the National Hospital in Bissau were interviewed, examined clinically, and tested for antibodies to HIV-1 and HIV-2. The prevalence of HIV-2 infection was 20.4% (206 out of 1009) and of HIV-2-associated AIDS 4.4% (44 out of 1009). HIV-2 infection was more frequent in women (25%, 110 out of 440) than in men (16.9%, 96 out of 569). HIV-1 infection was diagnosed in one patient only, and one patient (with AIDS) had reactivity to both HIV-1 and HIV-2. Among HIV-2-seropositive patients, AIDS was demonstrated in 21.3% and AIDS-related symptoms (not fulfilling the AIDS criteria) in 19.4%. The frequency of AIDS-associated symptoms was significantly higher in HIV-2-seropositive patients than in seronegative patients. The clinical profile of the HIV-2-associated AIDS cases was very similar to that described in HIV-1-associated AIDS cases in Africa. Seven out of 51 patients fulfilling the clinical criteria for AIDS were HIV-seronegative. The World Health Organization (WHO) clinical case definition for AIDS in Africa had a specificity of 99% and a positive predictive value of 86%. Tuberculosis was more common in HIV-2-seropositive patients (6.3%) than in HIV-2-seronegative patients (2.2%). A history of blood transfusion was a significant risk factor for HIV-2 infection. HIV-2 infection and AIDS are public health problems in Guinea-Bissau.

Acquired Immunodeficiency Syndrome↗

Generation of free radicals in lipid emulsion used in parenteral nutrition.

Lipid emulsions used in parenteral nutrition are prone to peroxidation that may be an important feature of oxygen-associated tissue damage. Incubation of lipid emulsion [Intralipid (IL)] with H2O2 and FeCl2 increased lipid peroxidation, measurable as increased production of pentane, from 0.39 +/- 0.33 to 0.99 +/- 0.18 microM (p less than 0.0001). Malondialdehyde was increased from 0.010 +/- 0.005 mM to 0.380 +/- 0.025 mM (p less than 0.001). Superoxide dismutase and catalase (each 100 U/mL) or vitamin C (10 mM) inhibited pentane and malondialdehyde production (p less than 0.0001). Incubation of human erythrocytes in the presence of FeCl2 caused 11.0 +/- 3.2% hemolysis (control 0.95 +/- 0.14%). Addition of 0.44% IL increased hemolysis to 66.5 +/- 3.4%, whereas further addition of vitamin E or C significantly inhibited hemolysis to 16.4 +/- 8.1 and 38.9 +/- 7.1%, respectively (p less than 0.0001). IL was administered i.v. to eight preterm infants. It increased 3- to 28-fold (p less than 0.001) the amount of pentane in expired breath. Partly, this increase was due to pentane dissolved in IL as a result of lipid peroxidation during storage. After discontinuing IL infusion, the elimination of pentane was nonexponential, consisting of a rapid and a slow component. According to our results, IL undergoes peroxidation causing free-radical-dependent damage to human cells. We propose that the adverse effects of parenteral IL are partially caused by free oxygen radicals generated by lipid peroxidation.

Fat Emulsions, Intravenous↗

Expression of cytochrome P-450(17) alpha, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase, and steroid 5 alpha-reductase in rat H540 Leydig tumor cells.

The rat H540 Leydig tumor cell is established as a model for acute lutropin action on the initial step of steroidogenesis, namely the conversion of cholesterol to pregnenolone. Herein, we demonstrate that H540 cells express high levels of three steroid-metabolizing enzymes which are involved in the further processing of pregnenolone in the endoplasmic reticulum of the steroidogenic cell. In particular, in addition to expressing 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) and 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta-HSD), H540 cells also showed high levels of steroid 5 alpha-reductase mRNA and activity. The H540 cells therefore exhibit similarity to Leydig cells from sexually immature animals which also demonstrate high 5 alpha-reductase activity. Thus, after 3 beta-HSD-catalyzed formation from pregnenolone, progesterone was efficiently converted to 5 alpha-pregnan-3,20-dione (5 alpha-dihydroprogesterone) and subsequent metabolism to the corresponding 17 alpha-hydroxylated derivative and 5 alpha-androstan-3,17-dione in a reaction catalyzed by P-450(17) alpha. H540 cells have apparently very low 17-ketosteroid reductase activity and, therefore, a principal end-product of the steroidogenic pathway in these cells was 5 alpha-androstan-3,17-dione. H540 cells maintained in primary culture under serum-free conditions accumulated demonstrable levels of mRNA species for P-540 17 alpha (1.7 kb), 3 beta-HSD (1.6 kb) and 5 alpha-reductase (2.7 kb). This finding suggests that the H540 tumor cell model will not only be of utility in the study of acute lutropin action but also in the elucidation of mechanisms involved in the regulation of expression of various families of microsomal steroid-metabolizing enzymes.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗