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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 433 records · Page 24Linked to original sources

Glutathione synthetase deficient human fibroblasts in culture.

Cultured skin fibroblasts from patients with 5-oxoprolinuria caused by hereditary deficiency of glutathione synthetase have decreased levels of the corresponding enzyme as well as of glutathione. Fibroblasts from the same patients accumulated gamma-glutamyl cysteine, but the levels were lower than those of glutathione in control fibroblasts. The uptake of [35S]cystine was equally rapid in control and patient fibroblasts. In the acid-soluble fraction gamma-glutamyl-[35S]cysteine accumulated in fibroblasts from patients but not from controls. Appreciable turnover of gamma-glutamyl cysteine and glutathione in the respective cell strains was observed, the half-lives of these pools being approximately 5 hours. The growth rate of mutant fibroblasts in culture was significantly slower than that of control fibroblasts. There was no significant accumulation of 5-oxoproline in the culture medium.

Cell Division↗

Evaluation of serum gamma-glutamyl transferase as a screening method for excessive alcohol consumption during pregnancy.

Serum gamma-glutamyl transferase was analyzed in 669 pregnant women. They were interviewed with special emphasis on their consumption of alcohol during the first trimester. Thirteen percent admitted a consumption of greater than 30 gm of pure alcohol per day, and 3%, greater than 125 gm per day. One child with a complete fetal alcohol syndrome and one with a partial one were born to mothers with a high consumption of alcohol and elevated serum gamma-glutamyl transferase. The ninety-fifth percentile for serum gamma-glutamyl transferase in women classified as low consumers (less than 30 gm of alcohol per day) was 0.44 mukat/L. With this 95% specificity level used as a cutoff, the sensitivity of the serum gamma-glutamyl transferase test in identifying those who consumed more than 30 gm of alcohol per day was 25%. The conclusion was that screening based on analyses of serum gamma-glutamyl transferase is not to be recommended for routine use in prenatal care.

Adolescent↗

Evolutionary studies on pancreatic colipase.

In this evolutionary study the following criteria have been used to prove the existence of colipase: 1. It restores the activity of human and porcine pancreatic lipase inhibited by bile salt. 2. It cross-reacts with antisera to human and porcine colipases. 3. Its restoration of lipase activity, inhibited by bile salt, in the tributyrin assay system, is prevented by antiserum to colipase. 4. It is a heat-stable, low-molecular-weight protein (molecular weight about 10 000 by gel-filtration). The occurrence of colipase has been verified in the exocrine pancreatic cells from hagfish (Myxine glutinosa), ratfish (Chimaera monstrosa), rayfish (Raja radiata). Greenland shark (Somnius microcephalus) and dogfish (Squalus acanthius). No colipase activity could be found in the gastric juice of crayfish (Pacifastacus leniusculus). These results indicate that colipase envolved in the vertebrates before the organized exocrine pancreatic gland and occurred simultaneously with the bile salts/bile alcohols.

Animals↗

Humoral and cellular immune reactions against tumor cells in patients with urinary bladder carcinoma. Correlation between direct and antibody-dependent cell-mediated cytotoxicity.

Serum IgG fractions from a large and homogeneous group of patients with transitional cell carcinoma of the urinary bladder (TCC) were tested for their capacity to induce antibody-dependent cellular cytotoxicity (ADCC) with lymphocytes from healthy donors against a TCC-derived target cell and one derived from adenocarcinoma of the colon. Both targets have previously been shown to be of comparable susceptibility to cell-mediated lysis in vitro. Some of the IgG preparations showed strong and dose-dependent ADCC against either one or both targets, while others gave weak reactions or none at all. Similar results were obtained with IgG from a matched group of patients with prostatic carcinoma who were used as clinical controls (CC). In parallel experiments, lymphocytes taken from the two donor groups at the same time as the serum samples were tested for their direct cytotoxicity (CMC) against the two targets. CMC gave similar results to ADCC. The differences in cytotoxicity displayed by either IgG or lymphocytes from individual donors were analysed statistically, using nonparametric statistics. To avoid introducing bias due to arbitrary data selection, the entire set of results, comprising both high and low reactors, was included in the statistical assessment. ADCC of the TCC donors' IgG against the TCC target was significantly stronger than against the colon carcinoma and also significantly stronger than that of the control donors. Similarly, the TCC patients' lymphocytes displayed a significantly higher CMC against the TCC target than against the control targets. This was not seen when the lymphocytes from the patients with prostatic carcinoma were tested. When CMC and ADCC of individual donors were compared, a statistically significant correlation between these activities was seen in three of the four donor/target combinations. These results support earlier findings and suggest that a significant fraction of both the disease-related and the 'non-selective' CMC (NK) displayed by cancer patients lymphocytes against allogeneic tumor cells in vitro reflects antibody-dependent reactions.

Aged↗

Antiherpetic activity and mechanism of action of 9-(4-hydroxybutyl)guanine.

9-(4-Hydroxybutyl)guanine was synthesized and tested for antiherpes activity. In cell cultures, different strains of herpes simplex virus type 1 (HSV-1) and type 2(HSV-2) were inhibited by 50% at 2-14 microM of 9-(4-hydroxybutyl)guanine, while a HSV-1 mutant lacking thymidine kinase (HSV-1 TK-) was resistant. Linear competitive inhibition of purified HSV-1-induced thymidine kinase (TK) with thymidine as a variable substrate was observed for 9-(4-hydroxybutyl)guanine with an apparent Ki value of 2.06 microM while the corresponding Ki value for the cellular TK was greater than 250 microM. By using high performance liquid chromatography, the formation of 9-(4-hydroxybutyl)guanine monophosphate by HSV-1 TK was measured and the rate of product formation was found to be about 10% of that found by using thymidine as a substrate. A selective inhibition of HSV-1 DNA synthesis by 9-(4-hydroxybutyl)guanine was observed in infected Vero cells. 9-(4-Hydroxybutyl)guanine had a low cellular toxicity. A weak therapeutic effect on herpes keratitis in rabbits was observed whereas cutaneous HSV-1 infection in guinea pigs and systemic HSV-2 infection in mice were not affected by this compound.

Acyclovir↗

Effect of aphidicolin on DNA synthesis in HSV-1 infected and uninfected Vero cells.

The effect of aphidicolin on DNA synthesis in herpes simplex virus type 1 (HSV-1) infected and uninfected Vero cells was determined by isodensity banding of [32P]-labelled DNA. A 50% inhibition of HSV-1 DNA synthesis was observed at 0.07 microM aphidicolin while 2.1 and 1.3 microM were required to inhibit the cellular DNA synthesis to 50% in infected and uninfected Vero cells, respectively. When the viral DNA synthesis was totally inhibited by 10 microM aphidicolin, the cellular DNA synthesis was inhibited to about 90% in both infected and uninfected cells. Aphidicolin inhibited the cellular DNA synthesis in HSV-1 infected and uninfected Vero cells remaining in the presence of 250 microM foscarnet to the same extent as the DNA synthesis in the absence of foscarnet.

Animals↗

Rehydration using solutions with and without glucose before emergency abdominal surgery in children.

The metabolic effects of six different solutions used for rehydration were studied in 88 children before emergency abdominal surgery. A volume corresponding to 5% of the body weight was given i.v. during 4 h (12.5 ml . kg-1 . h-1) between admission and surgery. The different solutions were: low glucose electrolyte solution (LGE), Rehydrex 2.5%, Rehydrex 5% containing 0.9, 2.5 and 5.0% glucose, respectively, Ringer, Ringer lactate and Ringerdex (30 mmol acetate . l-1). Venous blood samples were drawn before and after rehydration and analysed for glucose, insulin, alanine, 3-hydroxybutyrate (3-HB), non-esterified fatty acids (NEFA), glycerol and base excess. Before rehydration the plasma concentrations of NEFA, glycerol and 3-HB were elevated, while that of alanine was decreased. Plasma levels of NEFA and 3-HB remained unchanged, whereas glucose and insulin decreased after rehydration with glucose-free solutions, i.e. Ringer, Ringer lactate and Ringerdex. With solutions containing glucose the concentrations of NEFA and 3-HB decreased significantly. With Rehydrex 5% hyperglycaemia and hyperinsulinaemia were observed. Rehydration using LGE and especially Rehydrex 2.5% resulted in decreased lipid mobilization and ketonaemia without concomitant marked increase of glucose and insulin. LGE and Rehydrex 2.5% thus appeared to be the most appropriate solutions in a situation where moderate dehydration had to be corrected during a short period of time before emergency abdominal surgery.

Abdomen, Acute↗

Histopathology of benign gingival fibroblastic lesions with special reference to odontogenic fibroma and recurrence rates.

Histopathologic and clinical reexamination of 84 cases diagnosed as peripheral odontogenic fibroma showed 56 cases with no evidence of recurrence, 12 with possible single recurrence and 16 with verified single or multiple recurrences. An effort was made to correlate the histopathologic appearance with the recurrence rate. Three different types of lesions could be identified: fibrous epulis, calcifying fibroblastic granuloma and various types of "fibroma", also showing a high recurrence rate. Our findings show that neither histomorphology nor recurrence rate can be used as a definite criterium to separate neoplasia such as odontogenic fibroma from other gingival fibrous overgrowths.

Adult↗

Serum alpha-fetoprotein--a biochemical indicator of prenatal hypothyroidism.

Serum alpha-fetoprotein (AFP) was analysed at 10-30 days of age in infants with positive TSH screening tests for congenital hypothyroidism. These levels were significantly higher in infants with true positive screening tests than in those with false positive tests; 27 of 43 infants with congenital hypothyroidism had serum AFP levels above the age-related reference range. The postnatal rate of elimination of AFP from serum did not differ in hypothyroid and euthyroid infants, indicating that the difference in serum AFP was due to more extensive synthesis in hypothyroid individuals. The level of serum AFP was inversely correlated with the roentgenological skeletal maturation index. It is postulated that increased serum AFP is caused by prenatal hypothyroidism and that analysis of serum AFP is a valuable tool to identify those infants with congenital hypothyroidism who are at risk of neuropsychological sequelae.

Age Determination by Skeleton↗

Psychological reactions in 102 families with a newborn who has a falsely positive screening test for congenital hypothyroidism.

The potential psychological risks of falsely positive test results in neonatal screenings have not been studied previously. 20 000 newborns were screened for congenital hypothyroidism. Of the 144 positive tests, 137 were false. The families of 102 babies with false positives were explored in reference to their (1) initial parental psychic reactions (emotional reactions and abilities for coping) and (2) residual reactions 6 to 12 months later. 78 families initially exhibited strong emotional reactions. Providing information about a positive screening test is therefore an acute strain to the majority. After a period of 6 to 12 months there was in 18 families persistent insecurity regarding the baby's health. These concerns were linked to the family to the screening and the disease screened for. This may impair the parent-child relation and thus, the child's development. Thus a false positive test appear to trigger in the majority a development of a psychic crisis. 12 families seemed however to have been totally untouched by the potential threat of the information. The crisis is effectively solved by most (consideration must be paid to the integrated psychological support given to all). It is not known whether the 18 risk families actually have been iatrogenically hurt or if their worries brought to attention in connection with the screening merely represent habitual psychic maladjustment. Preparation for parenthood and education about screening principles are beneficial and important. This study demonstrates the importance not only of asking how much worry is elicited but also how this worry is being handled (coping ability) in order to provide a fair estimate as to which families are at risk.

Attitude to Health↗

9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication.

A new compound, 9-(3,4-dihydroxybutyl)guanine, has been synthesized and its antiherpes activity determined. 9-(3,4-Dihydroxybutyl)guanine was selectively phosphorylated by herpes simplex virus thymidine kinase and had a high affinity for this enzyme, with an inhibition constant of 1.5 microM. In cell culture, replication of different strains of herpes simplex virus types 1 and 2 was inhibited to the extent of 50% by 4 to 18 microM (RS)-9-(3,4-dihydroxybutyl)guanine. The (R)-enantiomer of this compound was more inhibitory than the (S)-enantiomer. Herpesvirus DNA synthesis was selectively inhibited by (RS)-9-(3,4-dihydroxybutyl)guanine in infected cells, and a low cellular toxicity was observed. (RS)-9-(3,4-Dihydroxybutyl)guanine had a therapeutic effect when applied topically to guinea pigs with cutaneous herpes simplex type 1 infections and to rabbits with herpes keratitis. Oral treatment of a generalized herpes simplex type 2 infection in mice had a therapeutic effect.

Acyclovir↗

Kinetic analysis in cell culture of the reversal of antiherpes activity of nucleoside analogs by thymidine.

The inhibition of herpes simplex virus type 1 plaque formation by acyclovir, bromovinyldeoxyuridine, 9-(3,4-dihydroxybutyl)guanine, and 9-(4-hydroxybutyl)guanine at different thymidine concentrations was analyzed in Lineweaver-Burk plots. Linear competitive patterns between thymidine and the nucleoside analogs were observed for the inhibition of herpes simplex virus type 1 plaque formation. A new constant, the reversal constant Kr, was introduced to describe the sensitivity in cell culture of an antiviral drug to the reversal of its viral activity by a metabolite (e.g., thymidine).

Animals↗

Identification of thyroxine in human breast milk by gas chromatography-mass spectrometry.

In several previous publications it has been reported that human breast milk contains significant amounts of T4. Great differences in concentrations were found by different authors. In all these publications T4 was assayed by RIA, and it seems probable that the varying results obtained are due to varying specificity of the antibodies used in the assay. Definite demonstration of the presence of T4 in breast milk requires a more specific method than RIA. In the present work we have used combined gas chromatography-mass spectrometry. T4 was isolated from human breast milk by combined anion- and cation-exchange chromatography. The purified material was treated with HCl in methanol and trifluoroacetic acid anhydride and was analyzed by single-ion monitoring of the ions at m/e 983, m/e 870, and m/e 799, major ions in the mass spectrum of the N,O-bis(trifluoroacetyl) methyl ester of T4. Significant peaks confirmed the presence of T4 in human milk. The estimated concentration was less than 10 ng/ml. Attempts were made to quantitate the T4 by selected ion monitoring of the ions at m/e 870 and m/e 822 after addition of monobromotriiodothyronine as internal standard. According to this latter method, the concentration of T4 in four samples of centrifuged breast milk was less than 4 ng/ml. The possible physiological significance of the finding is discussed.

Acetonitriles↗

Demonstration of a direct anti-factor Xa activity in certain heparin-related glycosaminoglycans.

Heparan sulphate/heparin subfractions with high plasma anti-Xa activity have an unusual uronate composition, i.e. high proportions of both glucuronate and sulphated iduronate. These preparations inhibit the amidase activity of factor Xa in an uncompetitive mode and the prothrombin-activation catalyzed by Xa, both in the absence of antithrombin III. Subfractions of low affinity for antithrombin III are equally potent against Xa. The anti-X activity is destroyed by a 3-h periodate oxidation.

Animals↗

A follow-up study of urinary bladder patients tested for tumour-related lymphocyte-mediated cytotoxicity.

A total of 143 patients with transitional cell carcinoma of the urinary bladder were tested for lymphocyte-mediated cytotoxicity against the bladder carcinoma cell line T24. Some of the patients were also tested against MANO (another cell line of transitional cell bladder carcinoma origin), HCV29 (from bladder epithelium, probably transformed in vitro) and/or HT29 (from a colon adenocarcinoma). The patients were divided into a high- or a low-responder group for each cell line. The patients were followed up and the correlation between a high response in the cytotoxicity tests and survival was evaluated using an adaptation of the Mantel-Haenszel statistics. No significant correlation could be demonstrated.

Aged↗