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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 397 records · Page 22Linked to original sources
PubMed1986

Identification of the stable free radical tyrosine residue in ribonucleotide reductase.

The small subunit of iron-dependent ribonucleotide reductases contains a stable organic free radical, which is essential for enzyme activity and which is localized to a tyrosine residue. Tyrosine-122 in the B2 subunit of Escherichia coli ribonucleotide reductase has been changed into a phenylalanine. The mutation was introduced with oligonucleotide-directed mutagenesis in an M13 recombinant and verified by DNA sequencing. Purified native and mutant B2 protein were found to have the same size, iron content and iron-related absorption spectrum. The sole difference observed is that the mutant protein lacks tyrosyl radical and enzymatic activity. These results identify Tyr122 of E. coli protein B2 as the tyrosyl radical residue. An expression vector was constructed for manipulation and expression of ribonucleotide reductase subunits. It contains the entire nrd operon with its own promoter in a 2.3-kb fragment from pBR322. Both the B1 and the B2 subunits were expressed at a 25-35 times higher level as compared to the host strain.

Coliphages↗
PubMed1986

A new method for intraoral patch testing.

Intraoral patch testing was performed in 3 subjects, 2 of whom were contact sensitive to nickel. Maxillary acrylic plates carrying test pieces containing 66% nickel were applied for 48 h, and readings were performed 24 h after removal. Few if any clinical signs were detected, but biopsies from the mucosal contact sites showed lichenoid reactions. Biopsies from control sites showed no or slight non-specific inflammatory reactions.

Adult↗
PubMed1986

In vitro activation of amphibian dermal melanocytes by nicotine.

Epidemiologic investigations have shown that nicotine could be a factor causing oral melanin pigmentation in man. Nicotine was therefore tested on amphibian skin melanocytes. Cell reactions were registered by spectrophotometry, in vitro light microscopy, photomicrography and light and electron microscopy. It was found that dermal melanocytes in the toad Bufo bufo and the frog Rana arvalis were activated by nicotine and that this activation was not mediated via beta-adrenergic receptors in melanocytes.

Animals↗
PubMed1986

Children with inborn errors of phenylalanine metabolism: prognosis and phenylalanine tolerance.

Twenty-three children, who were detected by neonatal PKU screening, were followed for 8-18 years in one paediatric centre. Dietary treatment was started if the blood phenylalanine level exceeded 0.72 mmol/l. All 23 infants were initially given a low phenylalanine diet. The growth and development rates of the children did not differ significantly from those in a reference population, although one child had mild mental retardation and another had a short attention span. Fourteen children were still on a strict phenylalanine-restricted diet on their last follow-up (at 8-18 years of age). In nine children who were initially put on a low phenylalanine diet, it was possible to normalize the diet between 1/2 and 10 years of age, while maintaining the blood phenylalanine levels between 0.25 and 0.72 mmol/l. It seems likely that those of our patients who markedly increased their phenylalanine tolerance during childhood had a regulatory mutation of the phenylalanine hydroxylase system. A continuous reevaluation of each child treated with a low phenylalanine diet reduces the use of unnecessarily restricted diets.

Adolescent↗
PubMed1986

Maternal TSH-receptor antibodies and TSH antibodies in screening for congenital hypothyroidism.

Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyperthyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.

Congenital Hypothyroidism↗
PubMed1986

Acyclic guanosine analogs as substrates for varicella-zoster virus thymidine kinase.

This study was performed to obtain information on the enzymatic background to the antiviral activity of acyclic guanosine analogs. Five acyclic guanosine analogs, the (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, 9-[(2-hydroxyethoxy)methyl]guanine, and 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine, were compared in enzyme kinetic experiments using purified varicella-zoster virus and human placenta mitochondrial thymidine kinase (TK). All analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by varicella-zoster virus TK, but only low affinities and phosphorylation rates were observed. No affinity for the mitochondrial TK was observed for any of the analogs.

Guanosine↗
PubMed1986

Mode of action, toxicity, pharmacokinetics, and efficacy of some new antiherpesvirus guanosine analogs related to buciclovir.

9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine (3HM-HBG), (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine ([+/-]2HM-HBG), and cis-9-(4-hydroxy-2-butenyl)guanine (2EN-HBG), new acyclic guanosine analogs structurally related to buciclovir (BCV [(R)-9-(3,4-dihydroxybutyl)guanine]), were evaluated in parallel with buciclovir as anti-herpes simplex virus (HSV) agents. In cell cultures, replication of different strains of HSV type 1 (HSV-1) and HSV-2 was inhibited at nontoxic drug concentrations. The concentrations giving 50% inhibition of plaque formation were, however, dependent on virus strain and cell type. In most cell types, the order of activity against HSV-1 strains was 3HM-HBG greater than (+/-)2HM-HBG greater than BCV greater than 2EN-HBG, whereas the drugs showed an approximately equivalent activity against HSV-2 strains in different cells. The cytotoxic effects of the drugs were also cell type dependent, the order of activity being BCV greater than 3HM-HBG = (+/-)2HM-HBG greater than 2EN-HBG. At growth-inhibitory concentrations, the guanosine analogs BCV, 3HM-HBG, and (+/-)2HM-HBG showed clastogenic effects in human lymphocytes, mainly because of the induction of chromatid breaks. When evaluated for their anti-HSV effects in systemic HSV-1 infections in mice, the order of activity was BCV = 3HM-HBG greater than (+/-)2HM-HBG greater than 2EN-HBG, and in mice infected systemically with HSV-2, only BCV and 3HM-HBG showed efficacy. The differences between efficacy in vitro and in vivo could be explained in part by differences in kinetics of the drugs in mouse plasma, as the more efficacious drugs, BCV and 3HM-HBG, showed lower clearances and longer half-lives than the less efficacious ones, (+/-)2HM-HBG and 2EN-HBG. When used topically against a cutaneous HSV-1 infection in guinea pigs, 3HM-HBG showed an effect equivalent to that of BCV, whereas (+/-)2HM-HBG and 2EN-HBG were inactive. Mechanistically, the guanosine analogs were characterized by a high affinity for the viral thymidine kinase and a low affinity fo a cellular thymidine kinase and by their inhibition of viral DNA synthesis in infected cells.

Acyclovir↗
PubMed1986

Regional variations of iodine nutrition and thyroid function during the neonatal period in Europe.

In order to evaluate further the possibility that transient hypothyroidism and hyperthyrotropinemia in newborn infants could result from a state of relative iodine deficiency, the urinary concentration of iodine, used as an index of the dietary intake of iodine was determined in casual urine samples collected in 1,076 full-term infants aged 3-6 days in 16 cities in 10 different European countries and in Toronto, Canada. In addition, the results obtained by programs of systematic neonatal screening for congenital hypothyroidism in the same areas were compared. There were marked regional differences in iodine nutrition during the neonatal period in Europe (median urinary iodine: 16.2 micrograms/dl in Rotterdam, the Netherlands, and 1.1 micrograms/dl in Freiburg, FRG. A low iodine supply in newborn populations was accompanied by, and probably explained, an elevated frequency of transient disorders of thyroid function in young infants. Iodine prophylaxis is urgently needed in some European countries not only for the prevention of goiter, but mostly for the prevention of impairment of thyroid function during the critical period of brain development.

Canada↗
PubMed1986

Methods for production and detection of monoclonal antibodies against surface components of adhesive implanting mouse blastocysts.

Monoclonal antibodies against mouse blastocysts in the adhesion stage of implantation were obtained by intrasplenic immunization with blastocysts either injected into the spleen after irradiation or transferred after drying on a piece of nitrocellulose paper. About 10 blastocysts were deposited at each of 4 immunizations before the spleen cells were used for hybridoma production. The supernatants obtained were examined for anti-blastocyst antibodies in indirect immunofluorescence labelling of native blastocysts and with ABC-immunoperoxidase staining either of blastocysts attached to nitrocellulose paper or of methanol-fixed blastocysts. Further, sections of paraffin-embedded blastocysts were used for detection of antigens.

Animals↗
PubMed1986

Inhibition of herpes simplex virus-induced DNA polymerases and cellular DNA polymerase alpha by triphosphates of acyclic guanosine analogs.

The triphosphates of the antiherpes acyclic guanosine analogs (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine [BCVTP and (S)-DHBGTP], 9-(4-hydroxybutyl)guanine (HBGTP), and 9-(2-hydroxyethoxymethyl)guanine (ACVTP) were investigated for their effects on partially purified DNA polymerases of herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) as well as cellular DNA polymerase alpha of calf thymus and Vero cells. The triphosphates of the four analogs were all competitive inhibitors when dGTP was the variable substrate with both the viral and the cellular DNA polymerases with activated calf thymus DNA or poly(dC)oligo(dG)12-18 as template. No inhibition was observed with deoxythymidine 5'-triphosphate as substrate and poly(dA)oligo(dT)12-18 as template. All analogs were preferential inhibitors of the viral DNA polymerases. Ordering the compounds according to their decreasing binding affinities, as reflected by their increasing inhibition constants for the viral DNA polymerases, gave ACVTP greater than HBGTP greater than BCVTP greater than (S)-DHBGTP. The DNA polymerase from the HSV-1 mutant, CI(101)P2C5, resistant to ACV, showed a stronger decrease in sensitivity for ACVTP and HBGTP than for BCVTP compared to the effects on DNA polymerase from the wild-type strain CI(101). The analogs were not able to support DNA synthesis in the absence of the competing substrate dGTP. A decrease in the ability of calf thymus DNA to serve as primer template for HSV-2 DNA polymerase was observed after preincubation with the triphosphates of the acyclic guanosine analogs. The analogs showed a progressive inhibition of the HSV-2 DNA polymerase activity with incubation time, and the inhibition could be reversed by high concentrations of dGTP both with and without addition of fresh enzyme or fresh template. However, no reversion was obtained when fresh enzyme or template was added if dGTP was omitted. The data indicate that these analogs inhibited the DNA polymerases by a similar mechanism and that the inhibition was reversible.

Acyclovir↗
PubMed1986

Serum thymidine kinase in transplant patients: its relation to cytomegalovirus activity, renal transplant rejection and its use for monitoring of antiviral therapy.

Twenty patients, cadaveric renal transplant recipients, were retrospectively analysed for serum levels of deoxythymidine kinase. Special reference was made to the thymidine kinase level in relation to rejection, and viral infection. Seven of the patients experienced clinically suspected cytomegalovirus infection. All these patients had elevated levels of serum thymidine kinase during the period of clinical disease. Usually the thymidine kinase level parallelled the severity of the disease. All patients with irreversible rejection had increased levels of serum thymidine kinase, but normally not as high, as seen in patients with severe cytomegalovirus infection. There was also some correlation between clinically suspected rejection, that lead to rejection treatment, and moderate increase in thymidine kinase. However, not all rejection episodes were accompanied by a thymidine kinase increase. Serum thymidine kinase was analysed and compared in patients with self-healing cytomegalovirus disease, and those treated with phosphonoformate. A rapid decline in thymidine kinase level was found in connection with successful antiviral therapy, when compared to the decline in untreated patients. Some bone marrow transplanted patients were also included in this analysis.

Adult↗
PubMed1986

Characterization of the humoral immune response in Plasmodium falciparum malaria. III. Factors influencing the coexpression of antibody isotypes (IgM and IgG-1 to 4).

Isotypes (IgM and IgG-1 to 4) of anti-P. falciparum antibodies were investigated in sera of malarial patients or immune donors by enzyme linked immunosorbent assay (ELISA) and two indirect immunofluorescence assays (IFAs), one staining intra-erythrocytic parasites of all stages and the other a restricted number of parasite antigens deposited in the membrane of infected erythrocytes by invading merozoites (Perlmann & Wahlgren, 1983; Perlmann et al., 1984, Wahlgren et al., 1985a). There was no correlation in overall antibody titres between the two IFAs. Antibodies of both IgM and all four IgG isotypes were detected in both assays. With the IFA for intracellular parasites a brilliant fluorescence was obtained with antibodies of all isotypes. However IgG-2 antibodies often gave staining restricted to the surface of schizonts. The incidence and reactivity in individual sera of antibodies of the different isotypes did not relate to the immune status of the donors (acute infection or clinically immune) but related well to the degree of malarial exposure as reflected by the overall antibody titres. This, in all three assays, high titred sera frequently contained antibodies of all isotypes while low titred sera usually only contained antibodies of IgM, IgG-1 and IgG-3 isotype. On average, the overall expression of antibodies of different isotypes in individual sera appears to reflect a sequential downstream (5' to 3') activation of the corresponding Igh-C genes in P. falciparum specific B-cell clones.

Adolescent↗
PubMed1986

Changes in lung volume and lung-thorax compliance during cardiac surgery in children 11 days to 4 years of age.

To examine the effects of cardiac surgery and cardiopulmonary bypass (CPB) on the lung, functional residual capacity (FRC) and lung-thorax compliance were measured at four stages during open heart surgery in 15 children. The patients were anesthetized with fentanyl/droperidol and N2O/O2, paralyzed, and ventilated with volume-controlled mechanical ventilation at 20-30 breaths/min. FRC was measured by tracer gas washout. Static lung-thorax compliance (CLT) was calculated as tidal volume divided by the airway pressure difference between the end of the postinspiratory pause and the end of the expiration, and also from the increase in FRC caused by adding 5 cmH2O of PEEP (CLT[FRC]). Before skin incision, both FRC and compliance were closely correlated with weight and length. During this stage, FRC was 21 +/- 5 ml/kg, CLT 0.90 +/- 0.21, and CLT(FRC) 1.28 +/- 0.35 ml X cmH2O-1 X kg-1 X PEEP 5 increased FRC by 34 +/- 9%. In patients with intact pleural cavities throughout the operation (n = 10), FRC increased by 4 +/- 2 ml/kg when the sternum was retracted (P less than 0.01). During CPB, FRC decreased by 4 +/- 3 ml/kg (P less than 0.01), and FRC at the end of surgery was 5 +/- 4 ml/kg less than before skin incision (P less than 0.01). In these ten children, there was a 13% and 6% decrease in mean CLT and CLT(FRC), respectively, during the operation (P less than 0.05) and mean CLT(FRC) was at least 40% greater than CLT during all four stages (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1985

Fish physiology and metal pollution: results and experiences from laboratory and field studies.

Physiological methods, previously used as health indicators in laboratory investigations on fish exposed to toxicants, have been applied to feral fish living in metal-polluted waters. A background to the use of a physiological approach for detecting early-arising effects of toxic chemicals on fish is given, together with a description of the clinical parameters used and their physiological relevance. The results and experiences from the field application show that certain clinical methods may be very useful in detecting and diagnosing sublethal disturbances in natural fish populations in polluted areas. Furthermore, the results indicate a good agreement between metal-induced physiological effects detected in fish exposed under natural field conditions and those found in laboratory experiments.

Animals↗
PubMed1985

Ophthalmological, psychometric and therapeutic investigation in two sisters with hereditary glutathione synthetase deficiency (5-oxoprolinuria).

Two sisters with hereditary glutathione synthetase deficiency (5-oxoprolinuria) were investigated. Assays of erythrocyte enzyme levels in relatives revealed additional clinically healthy carriers. The girls had chronic metabolic acidosis, which was corrected by substitution with bicarbonate. They had an increased rate of hemolysis which was well compensated. Their granulocyte function was normal when tested in vitro. In both girls mental retardation developed progressively without additional clinical neurological symptoms. Their electroretinograms were abnormal indicating disturbed retinal electrophysiological function. Therapeutic trials were performed with oral administration of glutathione (Tathion), mercaptopropionylglycine (Thiola) and vitamin E. None of these compounds had an effect on the urinary excretion of 5-oxoproline, acid-base balance, pathological electroretinograms or the clinical condition. Initially, Thiola therapy increased the low levels of glutathione in patient erythrocytes but after several months of treatment the concentration of glutathione declined to pretreatment levels. There was no indication that orally administered glutathione, mercaptopropionylglycine or vitamin E had a beneficial effect in the doses used. Nevertheless, vitamin E administration has been continued in addition to the correction of acidosis with sodium bicarbonate.

Adolescent↗
PubMed1985

Survival curves of glutathione synthetase deficient human fibroblasts: correlation between radiosensitivity in hypoxia and glutathione synthetase activity.

The role of intracellular non-protein bound sulphydryl compounds (NPSH), and in particular that of glutathione (GSH), in the response of cells to ionizing radiation under different O2 concentrations has been assessed using cell strains deficient in glutathione synthetase and exhibiting different NPSH levels. The cell strains used originated from patients with 5-oxoprolinuria and from their relatives (heterozygotes and proficient homozygotes). No correlation has been found between NPSH and GSH concentrations and radiosensitivity under oxic, aerobic and hypoxic conditions. However, a highly significant correlation has been observed between radiosensitivity under hypoxic conditions (and therefore the oxygen enhancement ratio) and the glutathione synthetase activity, suggesting that synthesis of GSH is required after irradiation. In order to explain our results we postulated, beside radical processes, the existence of a GSH-dependent enzymatic repair mechanism for N2 type damage. Hypoxic radio-sensitivity measured with survival curves would result from the interaction of both competition and biochemical repair processes.

Cell Survival↗
PubMed1985

Measurement of functional residual capacity by sulfur hexafluoride washout.

Measurement of functional residual capacity (FRC) by the open-circuit multiple breath tracer gas washout technique is an established method. A system based upon washout of sulfur hexafluoride (SF6) during mechanical ventilation is described. The central unit in the system is a sensitive and rapid-response infrared SF6 analyzer. SF6 is washed in until the alveolar concentration of SF6 is 0.5%, a concentration so low that the supply of other gases is hardly influenced. During washout, the flow of SF6 from the lungs is calculated by a computer every 10 ms from signals representing expiratory flow and SF6 concentration. The total volume of SF6, washed out, is calculated by integration of SF6 flow. Since the alveolar concentration at the end of washin is known, the lung volume may be obtained. The measurement procedure is highly automated and the result is presented by the computer immediately after washout. Accurate and reproducible results in model lung tests were obtained during air and N2O/O2 ventilation. Comparison with body plethysmography (FRCBOX) in eight sitting healthy subjects gave the following: FRCSF6 = 7 ml + 0.98 X FRCBOX, r = 0.99. Comparison with nitrogen washout (FRCN2) in five postoperative patients gave the following: FRCSF6 = 59 ml + 0.97 X FRCN2, r = 0.97. FRCSF6 during N2O/O2 ventilation was the same as during air/O2 ventilation in a group of paralyzed patients. The measurement system has not been tested in patients with obstructive lung disease.

Adolescent↗