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Biomedical subjects

A Karlsson

Publications and source records attributed to A Karlsson.

At least 217 records · Page 12Linked to original sources

The metabolism of 3'-azido-2',3'-dideoxyguanosine in CEM cells.

When CEM cells were incubated with [3H]-labeled 3'-azido-2',3'-dideoxyguanosine (AzddGuo), the isotope was largely recovered as ribo- and deoxyribonucleotides in the acid soluble fraction of CEM cells, due to extensive catabolism of AzddGuo and recycling of the guanine formed by purine nucleoside phosphorylase. Only 10% was found as the AzddGuo nucleotides, with the diphosphate of AzddGuo as the dominating nucleotide at all time points. Thus nucleoside diphosphate kinase was rate limiting for the formation of AzddGuo triphosphate, responsible for the toxic and antiviral activity of the nucleoside. Inhibition of de novo deoxyribonucleotide synthesis with hydroxyurea increased the phosphorylation of AzddGuo twofold.

Antiviral Agents↗

Anaesthesia effects on in vivo acetylcholine transmission; comparisons of radioenzymatic and HPLC assays.

The effect of general anaesthesia on extracellular levels of acetylcholine (ACh) in the caudate-putamen of freely moving rats was studied by microdialysis. ACh concentrations were determined in the same perfusate samples by radioenzymatic and HPLC/electrochemical procedures in order to compare the assays. The concentration of ACh in perfusate samples was estimated to be 0.30 microM in conscious unrestrained rats. However, when these rats were administered chloral hydrate (400 mg/kg i.p.), the level of ACh was decreased immediately by 50%, attaining a value of 0.06 microM within 20-40 min following the injection. Upon recovery of the righting reflex, ACh levels were once again re-elevated. The levels of choline (Ch), the precursor of ACh, were unaffected by anaesthesia. It was apparent that the level of consciousness (i.e. awake vs. anaesthetized) is an important factor determining ACh overflow. Radioenzymatic and HPLC assays proved to give identical results for the analysis of ACh and Ch.

Acetylcholine↗

(R)- and (S)-5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT): assessment of optical purities and dopaminergic activities.

Racemic 5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT), a potent and selective dopamine (DA) D2-receptor agonist, was resolved into the enantiomers by a new method. The enantiomers of 5-OH DPAT were determined by chiral ion-pair chromatography using N-benzyloxycarbonylglycyl-L-proline as the counter ion. The enantiomeric purity of (R)-5-OH DPAT was found to be greater than 99.7%. The ability of the enantiomers to change the rat brain DOPA levels was evaluated in vivo. The results indicate that (R)-5-OH DPAT is a weakly potent DA D2-receptor antagonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

99mTechnetium dimercaptosuccinic acid scintigraphy in the diagnosis of acute pyelonephritis in rats.

The use of 99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) scintigraphy for the early diagnosis of pyelonephritis has been evaluated in a study performed on adolescent female Sprague-Dawley rats exposed to an ascending Escherichia coli infection. The rats were studied with DMSA scintigraphy either before and 5 days after the infection or 5 and 28 days after the infection. One group of rats received anti-microbial treatment during days 6-11. After the last DMSA scintigraphy the rats were sacrificed and the kidneys prepared for light microscopy study. Kidney morphology was normal and DMSA uptake was high and homogeneous in all control rats. The majority of the rats exposed to E. coli developed inflammatory changes, on light microscopy which extended to various degrees in the renal parenchyma. Five days after the infection the DMSA uptake was consistently reduced, if the inflammatory lesion on light microscopy involved more than 15% of the renal cortex. Twenty-eight days after infection the inflammatory changes were less extensive than at 5 days. The DMSA uptake had usually improved. At this time, however, areas of decreased DMSA uptake could be detected even if the light microscopy changes involved less than 15% of the parenchyma. Microscopical lesions were less frequent and less extensive in the treated than in the untreated rats. The complete return to normal of previously abnormal DMSA uptake was only observed in treated rats. In a few untreated rats cortical scars had formed by day 28. The scars appeared in areas with decreased DMSA uptake at 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Baroreflex-governed sympathetic outflow to muscle vasculature is increased in hypothyroidism.

Microelectrode recording of muscle nerve sympathetic activity (MSA), which is baroreflex-governed and involved in cardiovascular homeostasis, was made in five patients with hypothyroidism and in seven patients with hyperthyroidism prior to treatment and after recovery to euthyroidism. Patients with hypothyroidism had a higher level of MSA when hypothyroid than after recovery (mean +/- SEM 39.3 +/- 7.1 and 26.8 +/- 7.9 bursts/min, respectively, P less than 0.05), whereas hyperthyroidism was not accompanied by a change in the number of sympathetic bursts/min. The response of MSA to manouvres known to influence the neural outflow via baroreceptors and other receptor inputs was not changed with altered thyroid function. The findings provide direct evidence of an increased sympathetic activity in hypothyroidism, but suggest that other physiological properties of MSA are intact in thyroid disease.

Adult↗

Envelope cross-reactivity between human immunodeficiency virus types 1 and 2 detected by different serological methods: correlation between cross-neutralization and reactivity against the main neutralizing site.

A total of 70 human immunodeficiency virus type 1 (HIV-1) and 42 HIV-2 antibody-positive serum samples, collected from groups of individuals in which only one type of HIV prevails, were tested for cross-reactivity against HIV-2 and HIV-1 proteins by Western blot (WB) (immunoblot), radioimmunoprecipitation assay (RIPA), neutralization analysis, and enzyme-linked immunosorbent assay with as antigen synthetic peptides representing selected parts of the envelope (env) glycoproteins. Cross-reactions against the env glycoproteins were observed by WB in 10% (7 of 70) and by RIPA in 40% (28 of 70) of the HIV-1 antibody-positive serum samples and by WB in 29% (12 of 42) and by RIPA in 48% (20 of 42) of the HIV-2 antibody-positive serum samples. Testing by enzyme-linked immunosorbent assay against a 36-amino-acid peptide (Cys-301-Cys-336) of the external glycoprotein of strain HTLV-IIIB of HIV-1 (HIV-1HTLV-IIIB) (known to represent a dominating, linear neutralizing site) showed type-specific reactions in 67% (38 of 57) of HIV-1 antibody-positive serum samples. Type-specific reactions against a homologous 35-amino-acid peptide of strain SBL-6669 of HIV-2 (HIV-2SBL-6669) were found in 75% (30 of 40) of HIV-2 antibody-positive serum samples, and these reactions were correlated to neutralization against HIV-2SBL-6669. Cross-reactions against these peptides were seen in 23% (13 of 57) and 33% (13 of 40) of the HIV-1 and HIV-2 antibody-positive serum samples, respectively. These cross-reactions were correlated to cross-neutralization against HIV-1HTLV-IIIB and HIV-2SBL-6669. Cross-neutralization against one heterotypic virus strain was demonstrated in 16% (9 of 57) of HIV-1 antibody-positive serum samples and in 22% (5 of 22) of HIV-2 antibody-positive serum samples, but no correlation was found between cross-neutralization and env cross-reactivity in WB or RIPA.

Blotting, Western↗

Incubation time of AIDS: progression of disease in a cohort of HIV-infected homo- and bisexual men with known dates of infection.

The time from infection with HIV to symptoms and AIDS is an important parameter in describing the natural course of HIV infection. We here describe disease progression in a group of 389 homo- and bisexual men. Of these 102 had known dates of infection, and during an average follow-up time of 31 months (range 2-108), 28 of these progressed from being symptom-free (CDC group II and III) to having some symptom from CDC group IV; 7 progressed to AIDS. By life-table analysis, the estimated average time from seroconversion to first symptom is approximately 5 years and to AIDS approximately 8 years. Very few patients are diagnosed with AIDS the first 2 years after infection, but after that the risk seems to be 5-10% per year. Increasing use of anti-HIV medication will render studies of this kind difficult in the future.

Acquired Immunodeficiency Syndrome↗

Hydroxyurea increases the phosphorylation of 3'-fluorothymidine and 3'-azidothymidine in CEM cells.

The triphosphates of the nucleoside analogues 3'-azidothymidine and 3'-fluorothymidine inhibit reverse transcriptase and are of therapeutic interest for the treatment of retrovirus infections. At equimolar concentrations 3'-fluorothymidine was more effectively transformed to the triphosphate by human CEM cells than azidothymidine which mainly accumulates as the monophosphate. Hydroxyurea, a drug that inhibits de novo synthesis of deoxyribonucleotides, considerably increased the ability of cells to phosphorylate both analogues. Addition of as little as 50 microM hydroxyurea decreased the amount of dideoxynucleoside required to attain a given intracellular concentration of its triphosphate by an order of magnitude. Hydroxyurea is known to shift the balance of substrate cycles between natural deoxynucleosides and their 5'-phosphates in the direction of synthesis and thereby to increase the import and intracellular phosphorylation of the nucleoside. The present results demonstrate a similar effect for the two analogues and raise the possibility of using this effect in therapy.

Antiviral Agents↗

Determination of (R)- and (S)-propranolol in plasma by high-performance liquid chromatography using N-benzoxycarbonylglycyl-L-proline as chiral selector in the mobile phase.

A normal-phase chromatographic method for the determination of (R)- and (S)-propranolol in plasma is described. The chiral separation is performed by adding an optically active complexing agent, N-benzoxycarbonylglycyl-L-proline, to the mobile phase (dichloromethane). The solid phase is LiChrosorb DIOL. After adjustment of the pH of the plasma, the propranolol enantiomers are extracted into hexane-dichloromethane-n-butanol (72:18:10). The organic phase is evaporated and the residue dissolved in the mobile phase before injection on to the column. Quantifications are performed by using internal standardization, giving a precision of better than 2% (coefficient of variation). The method employs 1-ml plasma samples and has linear calibration graphs (r = 0.999) over the concentration range studied, 9.2-288 nmol/l. injections of sample solutions with a composition different from that of the mobile phase gave system peaks that might affect the shape of the solute peaks. Several possibilities for avoiding these disturbing system peaks in the chromatogram by changing the mobile phase composition are discussed.

Chromatography, High Pressure Liquid↗

Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children.

The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p less than 0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+-ATPase (3%) were all increased in the patients compared with the control children, being 2% (p less than 0.001), 2% (p less than 0.01), and 0.3% (p less than 0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.

Autoantibodies↗

Cross-neutralizing antibodies against HIV-1 (HTLV-IIIB and HTLV-IIIRF) and HIV-2 (SBL-6669 and a new isolate SBL-K135).

A total of 57 HIV-1 antibody-positive sera and 43 HIV-2 antibody-positive sera were all tested for neutralizing capacity against two HIV-1 isolates (HTLV-IIIB and HTLV-IIIRF) and two HIV-2 isolates (SBL-6669 and SBL-K135). SBL-K135 is a new HIV-2 isolate obtained from a patient with clinical AIDS from Guinea-Bissau. Among the HIV-1--positive sera, 84% neutralized any of the HIV-1 isolates, 67% neutralized both HIV-1 isolates, and 35% neutralized any of the HIV-2 isolates. Among the HIV-2--positive sera, 91% neutralized any of the HIV-2 isolates, 67% neutralized both HIV-2 isolates, and 37% neutralized any of the HIV-1 isolates. Thus, neutralizing antibodies in HIV-1-- and HIV-2--positive sera can be cross-reacting, type-specific, or strain-specific. The cross-neutralizing titers were lower than the neutralizing titers against the type-specific viral isolates. The presence of cross-neutralizing antibodies was related to the presence of neutralizing antibodies against both type-specific isolates.

Acquired Immunodeficiency Syndrome↗

Abnormalities of growth in 7- to 18-year-old psychiatric patients.

The growth curves of all nonimmigrant school-age children living in one district of Malmö, Sweden and treated at the Department of Child and Youth Psychiatry during 1983 were investigated. The study group consisted of 40 children. Twenty-five of these children (63%) showed abnormal growth compared to 6 children (15%) with abnormal growth in an age-and sex-matched nonpsychiatric control population (p less than 0.001). A majority of the children with abnormal growth exhibited deviant growth within the first 4 years of life, usually several years before showing any psychiatric symptoms. These results, if borne out by additional studies, may have important clinical applications in the fields of developmental medicine and child psychiatry.

Adolescent↗

A prospective study of immunoglobulin changes in relation to human immunodeficiency virus infection in a cohort of homosexual men.

Changes in IgG levels and patterns in association with human immunodeficiency virus, (HIV) infection were characterized in a prospective investigation by studying serum electrophoresis and antibodies to HIV at least once a year in 144 homo/bisexual (HS) men during a 4-year period. Initially, 25 men (17.4%) were HIV-positive, and this increased to 44 at the end of the study period. HIV-negative men had IgG levels of 11.2 +/- 2.2 g/l. In the 19 HIV seroconverters the mean IgG level rose with time according to the equation IgG = 0.054x + 12.56 (x = months after the last HIV-negative test). Oligoclonal IgG bands were found in three of the 19 seroconverters (16%) prior to conversion and in 2/16 (13%), 5/13 (38%), 7/11 (64%), and 3/8 (38%) 1, 2, 3, and 4 years after conversion, respectively. Of the 25 initially HIV-positive men, five have developed acquired immunodeficiency syndrome (AIDS) during the 4.5 year follow-up. At the first investigation these five men had higher mean IgG levels (16.0 +/- 2.7 g/l) than the 20 men who have remained healthy (14.6 +/- 2.8 g/l), and all five had oligoclonal bands as compared to 9/20 of those who did not develop AIDS. Oligoclonal IgG bands reflect the IgG increase and seem to indicate long-standing HIV infection and a poor prognosis.

AIDS-Related Complex↗

Moclobemide and clomipramine in endogenous depression. A randomized clinical trial.

The purpose of this study was to compare moclobemide and clomipramine in endogenous depression according to the Newcastle II classification. Sixty-two patients were allocated to either 300 mg moclobemide or 150 mg clomipramine, both given in 3 daily doses. Improvements occurred over time but differences between treatments were never statistically significant. Dizziness, tremor and anticholinergic symptoms were significantly more frequent with clomipramine.

Adult↗

Cytogenetic and hematological effects in plastics workers exposed to styrene.

For 20 glass-reinforced plastics workers exposed to styrene and 22 unexposed referents, the frequency and size distribution of micronuclei were determined for lymphocytes stimulated with phytohemagglutinin or pokeweed mitogen, and white blood cell counts were made. Furthermore, chromosome aberrations were scored for 11 of the exposed subjects and 15 of the referents. The mean level of styrene in the breathing zone of the workers was 56 mg/m3. Workers exposed to styrene did not show an increase in any of the cytogenetic end points studied when the effect of age and smoking was allowed for in a multiple regression analysis. A significant 30% increase in the number of peripheral monocytes was observed for the exposed workers. No correlations between the cytogenetic and hematological tests on one hand and the length of exposure time on the other could be detected.

Adolescent↗

Immunoglobulin allotypes are normally distributed in Swedish AIDS patients.

Immunoglobulin allotypes G1m(a), G1m(x), G3m(b) and Km(1) were determined in 83 Swedish AIDS patients. Twenty of the patients had Kaposi's sarcoma and 29 had Pneumocystis carinii pneumonia. The distribution of the Gm and Km allotypes did not significantly differ between these different disease categories and the general Swedish population.

Acquired Immunodeficiency Syndrome↗

Comparison among five mutagenicity assays in workers producing polyurethane foams.

Thirty-two male individuals exposed to isocyanates and amines during the production of plastic foams and 20 male referents were studied by cytogenetic methods (chromosomal aberrations, sister chromatid exchanges and micronuclei in lymphocytes) and by urinary mutagenic assays (thioether concentrations and mutagenic activity with Salmonella TA98 and E. Coli WP2 uvrA). The occupational exposure was monitored by measurements of toluene diisocyanate and N-methylmorpholine in work-room air. The levels were below the current Swedish hygienic standards. Although all parameters, except the sister chromatid exchanges, showed increased mean values for the exposed group compared to the referents, only the urinary thioether concentrations differed significantly. The study was, however, non-conclusive with regard to a genetic effect of the occupational exposure as measured by the cytogenetic parameters. This may be due to the low exposure level. In the micronuclei frequencies there was a significant effect of age. Smoking significantly affected the SCE frequencies, the thioether concentrations and the mutagenic activities in the Salmonella assay. There were statistically significant correlations between the urine specimens collected during one working day and the following morning with regard to the mutagenic activities in the Salmonella and E. coli assays, and in the thioether concentrations as well. The association between the different cytogenetic and urinary mutagenic assays were weak but there were several statistically significant correlation coefficients, indicating that the variables may have a common metabolic background.

Adult↗