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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 415 records · Page 23Linked to original sources

Gas exchange in the partially atelectatic lung.

An 11-month-old girl was anaesthetised for resection of a coarctation of the aorta. The child took part in a research project in which functional residual capacity (FRC) and alveolar deadspace were being monitored on-line. Initial measurements during controlled ventilation showed an unexpectedly low PaO2 and an alveolar deadspace more than double the normal value. After manual hyperventilation and tracheal suction, FRC increased by 25% and PaO2 and the alveolar deadspace fraction reverted towards normal values for an infant. We therefore had strong grounds for suspecting atelectasis, although the shunt through the atelectatic lung was, in theory, too small to account for the increase in alveolar deadspace. We also noted that the shape of the expired CO2 trace was improved after hyperinflation, as was the time needed to wash out SF6 (the tracer gas used to measure FRC) from the lung. From these observations, we conclude that atelectasis may be associated with more widespread disturbances of gas exchange than is generally realised, perhaps because of distension of adjacent lung regions.

Anesthesia, General↗

Sulphur amino-acid degradation in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria).

The role of a low intracellular glutathione concentration in sulphur amino-acid degradation was investigated in two sisters (10 and 13 years old) with glutathione-synthetase deficiency, by determination of the urinary excretion of sulphur amino-acids and their main degradation products. The urinary excretion of total sulphur and inorganic sulphate was normal, indicating adequate dietary intake of sulphur amino-acids and normal oxidation to inorganic sulfate. Decreased excretion of N-acetylcysteine was found in the younger sister, which could be due to a reduced intracellular availability of cyst(e)ine. Increased excretion of mercaptolactate was found in the older sister, probably featuring a more catabolic condition in this subject. She also had an increased excretion of thiosulphate. Low excretion of thiocyanate was observed in both subjects, probably a consequence of a reduced dietary intake of thiocyanate or its precursors. Neither glutathione nor gamma-glutamylcysteine were detectable in urine. The excretion of cysteinylglycine was clearly reduced, reflecting that this dipeptide mainly is a degradation product of glutathione.

Acetylcysteine↗

Antiherpes effects and pharmacokinetic properties of 9-(4-hydroxybutyl) guanine and the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine.

Three acyclic guanosine analogs with similar structures, the (R) and (S) forms of 9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine, were compared for antiherpes activity in vivo and in vitro. The three guanosine analogs were viral thymidine kinase-dependent inhibitors of virus multiplication. In cell cultures, (S)-9-(3,4-dihydroxybutyl)guanine was the least active of these three drugs against a variety of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains. This was also the case for a certain HSV-1 or HSV-2 strain in different cell lines. In cell cultures, (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine had similar antiherpes activities. However, in vivo in cutaneous HSV-1 infections in guinea pigs treated topically and in systemic HSV-2 infections in mice treated orally or intraperitoneally, only (R)-9-(3,4-dihydroxybutyl)guanine had a therapeutic effect. The extremely short half-life in plasma and the high clearance of 9-(4-hydroxybutyl)guanine as compared with those of (R)-9-(3,4-dihydroxybutyl)guanine probably made 9-(4-hydroxybutyl)guanine inefficacious when given intraperitoneally or orally to mice infected with herpesvirus. On the other hand, no kinetic differences between (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine were observed in penetration through guinea pig skin ex vivo, and no preferential metabolism of 9-(4-hydroxybutyl)guanine in skin was noted. We deduced that high thymidine levels in guinea pig skin preferentially antagonize the antiviral effect of 9-(4-hydroxybutyl) guanine in cutaneous HSV-1 infections.

Acyclovir↗

Immunohistochemical localisation of tissue plasminogen activator and urokinase in the vessel wall.

Immunoreactive plasminogen activators were studied in tissue sections using a peroxidase method and monospecific antibodies to tissue plasminogen activator produced by a melanoma. Tissue plasminogen activator reactivity was found in skin melanomas and in endothelial and smooth muscle cells of arteries and veins. Vessels of the umbilical cord showed higher reactivity than peripheral vessels. Only faint antiurokinase reactivity was found. By means of the fibrin slide technique, fibrinolytic activity could be shown in peripheral vessel walls but not in the umbilical cord, which suggests that immunoreactivity of tissue plasminogen activator bound to an inhibitor can also be demonstrated. This method may be a useful tool in further studies of tissue plasminogen activator in physiological as well as pathological processes.

Arteries↗

Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis.

Filter paper blood samples taken routinely from 100 239 newborn infants were radioimmunoassayed five years later for plasma thyrotrophin concentrations. In 32 cases (0.03%) these were found to be raised. Thirty one of these children were traced and subjected to follow up examination by a paediatrician and a psychologist. Of the 31 children, 15 were found to have been receiving treatment for congenital hypothyroidism since a median of 5 months of age (diagnosed group). Of the 16 others, seven children were found to have raised serum thyrotrophin concentrations and were classified as hypothyroid (undiagnosed group). The remaining nine children were euthyroid. Children in the diagnosed group had a mean Griffiths developmental quotient of 87 (control value 103; p less than 0.01), and five out of 13 showed impaired neurological development. Of the remainder, those in the undiagnosed group had a mean developmental quotient of 100 and those in the euthyroid group a mean developmental quotient of 107. In this study achieving a detection rate of congenital hypothyroidism of one in 3000 in a neonatal screening programme resulted in overdiagnosis of about a quarter of patients considered to have true positive findings. This was outweighed, however, by the early identification of all infants with the disease.

Child, Preschool↗

Differential sensitivity of pinna reflex and esophageal temperature to clonidine in mice depleted of central noradrenaline by DSP-4.

Mice injected with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, had marked depletions of central noradrenaline and an attenuated post-decapitation reflex. DSP-4-treated mice exhibited an increased sensitivity to the alpha 2-adrenoceptor agonist clonidine as measured by inhibition of the pinna reflex, but normal sensitivity as measured by hypothermia. This differential sensitivity may reflect the presence of supersensitive postsynaptic alpha 2-adrenoceptors in some, but not all, CNS regions after DSP-4 treatment.

Amines↗

The bisphosphonates HEBP and AHPrBP but not AHBP inhibit mineral mobilization and lysosomal enzyme release from mouse calvarial bones in tissue culture.

The effect of 3 bisphosphonates, 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP), 3-amino-1-hydroxy-propylidene-1, 1-bisphosphonate (AHPrBP) and azacycloheptylidene-2, 2-bisphosphonate (AHBP), on the release of minerals (40Ca, 45Ca, Pi) and enzymes from cultured mouse calvaria was investigated in an organ culture system. HEBP and AHPrBP reduced PTH-stimulated mobilization of calcium and inorganic phosphate without affecting the release of lactate dehydrogenase. In contrast, no significant effect by AHBP on mineral mobilization and lysosomal enzyme release could be registered. In parallel with inhibited mineral mobilization, HEBP and AHPrBP inhibited the release of the lysosomal enzyme beta-glucuronidase. A possible cellular mechanism of action of bisphosphonates is discussed in the light of these data.

Animals↗

On the structure of bovine articular cartilage high density proteoglycans. Isolation of the keratan sulfate and chondroitin sulfate side chains.

The structure of adult bovine articular cartilage high density proteoglycans (PG-I) was studied by degradation with Pronase, chondroitinase ABC, and alkaline borohydride treatments and fractionation and analysis of the products. The keratan sulfate (KS) peptides were rich in glutamic acid, proline, and serine and had a low glycine content. The chondroitin sulfate (CS) peptides had a high content of serine, glycine, and glutamic acid and a much lower proline content than the KS peptides. The data indicate that the KS and CS chains occur in more distinct regions of the protein core(s) than in bovine nasal cartilage PG. After alkaline borohydride treatment there was an almost quantitative conversion of xylose to xylitol and galactosaminitol was the only hexosaminitol detected in KS fractions. The results obtained indicated that the alkali-labile bonds linking the CS and KS chains are the same as those reported to occur in other cartilage PGs. The Mr of the KS chains calculated from the glucosamine and galactosaminitol contents gave values of 6,000-7,000, although gel chromatography and light scattering measurements indicated considerable heterogeneity. The KS and CS chains were quantitatively precipitated by cetylpyridinium chloride and the KS and a portion (15%) of the CS chains were found to be soluble in 1% cetylpyridinium chloride. The abnormal solubility properties of the CS chains in the presence of 1% cetylpyridinium chloride is thought to be due to their low sulfate content. The molecular weight of the remainder of the CS chains, based on the ratio of xylitol to galactosamine, varied from 6,500 to 16,000. The low Mr CS chains were rich in 6-sulfated disaccharides whereas the higher Mr chains had a higher content of 4-sulfated disaccharides. The ratio of galactose to xylitol also varied with Mr. These results indicate similarities in the structure of the adult bovine articular cartilage PG-Is to other cartilage high density PGs. The heterogeneities observed in the composition of the KS and CS chains, and their occurrence in relatively distinct regions of the protein core(s) indicate, however, that there is still much to be learned about the structure of these complex macromolecules.

Amino Acids↗

Biochemical and hematological studies on perch, Perca fluviatilis, from the cadmium-contaminated river Emån.

In a field investigation, biochemical and hematological parameters were measured in perch, Perca fluviatilis, living in the cadmium-contaminated river Emån in the southeast of Sweden. The number of lymphocytes was 45-100% higher in perch from the contaminated area than in the reference perch, indicating a stimulated immune defense. In addition, the cadmium-loaded fish suffered from a slight anemia and a disturbed carbohydrate metabolism and blood plasma ion composition. The observed effects suggest that cadmium affects fish in the environment similar to what has been observed in laboratory studied. However, the weaker response may imply that the perch in the field stimulation have been adapted and thus acquired an increased resistance to cadmium.

Animals↗

Physiological effects of an additional stressor on fish exposed to a simulated heavy-metal-containing effluent from a sulfide ore smeltery.

Perches (Perca fluviatilis), kept in slightly hypotonic brackish water, were exposed to dilutions of a simulated heavy-metal-containing effluent from a sulfide ore smeltery . Biochemical and hematological effects of the effluent, as well as the metal residues in liver and muscle tissues, were investigated after 12 and 27 days of exposure. The metal analyses revealed no significant uptake of metals in liver and muscle during the experiment. In spite of this, the exposed fish showed several physiological effects. Some of these, e.g., anemia, hypocalcemia, increased muscle water content, and reduced liver size, were of a transient nature, while others, such as disturbed chloride balance and hyperglycemia, seemed to be more persistent. At the end of the experiment (29-33 days of exposure), the physiological response to stress treatment (asphyxia) and a subsequent recovery were studied in exposed and unexposed fish. This stress investigation indicates that an additional stressor may strengthen the toxic effects of the heavy-metal-containing effluent. Furthermore, the secondary stress responses were more pronounced and the ability to recover from them seemed to be impaired in exposed fish as compared to unexposed fish.

Anemia↗

Nucleic acid hybridization, a method to determine effects of antiviral compounds on herpes simplex virus type 1 DNA synthesis.

An application of the nucleic acid hybridization technique to screen effects of antiherpes compounds on herpes simplex virus type 1 (HSV-1) DNA synthesis is described. Whole cells are applied to nitrocellulose filters, their DNA is denatured and fixed to the filter. The resulting DNA spots are hybridized to cloned nick-translated HSV-1 DNA and the amount of hybridization is monitored by autoradiography or scintillation counting. Six antiherpes compounds: bromovinyldeoxyuridine, acyclovir, (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine and forscarnet, were evaluated for their effects on HSV-1 DNA synthesis. The most active compounds were bromovinyldeoxyuridine and acyclovir, with mean 50% inhibition values (IC50) for four different HSV-1 strains of 0.3 microM and 0.8 microM, respectively. The (R)-enantiomer of the new antiherpes compound 9-(3,4-dihydroxybutyl)guanine was found to be more active than the (S)-enantiomer, with mean IC50s of 6.5 and 14 microM, respectively, while mean IC50s of 2.5 and 68 microM were obtained for 9-(4-hydroxybutyl)guanine and foscarnet, respectively.

Antiviral Agents↗

The odontogenic keratocyst: a benign cystic tumor?

Three hundred nineteen odontogenic keratocysts from 255 patients (167 males and 88 females, a 2:1 ratio) were histologically and clinically examined. The cysts sometimes occurred as multiple or recurrent lesions or in association with Gorlin's syndrome. The rate of recurrence for the total population was 27%. The 116 patients who were tentatively diagnosed as having keratocyst prior to surgery had a recurrence rate of 26%. There was no direct correlation between a large number of different histopathologic parameters and the propensity of a lesion to recur. Based on these data, a theory for the growth mechanism of these lesions is presented, and it is that the odontogenic keratocyst should be regarded as a benign cystic neoplasm and treated accordingly.

Adolescent↗

Phosphorylation of four acyclic guanosine analogs by herpes simplex virus type 2 thymidine kinase.

Four acyclic guanosine analogs, the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, and acyclovir were compared in enzyme kinetic experiments, using purified herpes simplex virus type 2 thymidine kinase. All four analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by the viral thymidine kinase, but different affinities and relative rates of phosphorylation were observed.

Guanosine↗