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S Autio

Publications and source records attributed to S Autio.

At least 19 recordsLinked to original sources
PubMed1992

Blood dolichol in lysosomal diseases.

Highly elevated serum total dolichol (free dolichol + dolichyl ester) concentrations have recently been found in two lysosomal storage diseases, aspartylglucosaminuria (AGU) and mannosidosis. The present study demonstrates that the increase of serum dolichol in AGU patients is caused by an increase of serum free dolichol. In 15 patients the mean serum level of free dolichol (227 +/- 16 ng/mL) was 1.9 times higher (p < 0.001) than that in healthy controls (120 +/- 6 ng/mL), while the amounts of dolichol fatty acid esters were similar in the patients and controls (110 +/- 9 vs. 118 +/- 6 ng/mL). In contrast, 10 patients with neuronal ceroid-lipofuscinosis (NCL) (three with infantile, four with juvenile, and three with variant late infantile NCL) had significantly (p < 0.01) lower mean serum levels of both free (79 +/- 5 ng/mL) and total (159 +/- 6 ng/mL) dolichol than age-adjusted healthy controls (free, 100 +/- 6 ng/mL; total, 206 +/- 14 ng/mL). Decreased blood dolichol has not been reported earlier for any other disease. We conclude that the increased serum free dolichol in AGU reflects disturbed lysosomal function and that the decreased free and esterified dolichols in NCLs speak against their presumed primary lysosomal nature.

Adolescent↗
PubMed1992

Autophagy, cathepsin L transport, and acidification in cultured rat fibroblasts.

The mechanisms of enzyme delivery to and acidification of early autophagic vacuoles in cultured fibroblasts were elucidated by cryoimmunoelectron microscopic methods. The cation-independent mannose-6-phosphate receptor (MPR) was used as a marker of the pre-lysosomal compartment, and cathepsin L and an acidotropic amine (3-(2,4-dinitroanilino)-3'-amino-N-methyl-dipropylamine (DAMP), a cytochemical probe for low-pH organelles) as markers of both pre-lysosomal and lysosomal compartments. In addition, cationized ferritin was used as an endocytic marker. In ultrastructural double labeling experiments, the bulk of all the antigens was found in vesicles containing tightly packed membrane material. These vesicles also contained small amounts of endocytosed ferritin and probably correspond to the MPR-enriched pre-lysosomal compartment. Some immunolabeling was also visible in the trans-Golgi network. In addition, cathepsin L, DAMP, and large amounts of ferritin were found in smaller vesicles which can be classified as mature lysosomes. Early autophagic vacuoles were defined as vesicles containing recognizable cytoplasm. MPR, cathepsin L, and DAMP, but not ferritin, were detected in the early vacuoles. Inhibition of the acidification in the early vacuoles by monensin did not prevent the delivery of MPR and cathepsin L. The presence of MPR in the vacuoles suggests that cathepsin L is not delivered to early autophagic vacuoles solely by fusion with mature, MPR-deficient lysosomes. Furthermore, although lysosomes were loaded with endocytosed ferritin, it was not detected in autophagic vacuoles. Either the trans-Golgi network or the MPR-enriched pre-lysosomes may be the main source of enzymes and acidification machinery for the autophagic vacuoles in fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serum lipids and lipoproteins during therapeutic amenorrhea induced by lynestrenol and depot-medroxyprogesterone acetate.

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were determined in mentally handicapped subjects (n = 87). 33 women were on lynestrenol 5-10 mg for therapeutic amenorrhea (TA). 18 of them were randomly allocated to continue on lynestrenol and 15 were switched to intramuscular administration of medroxyprogesterone (DMPA). The switch to DMPA resulted in significant increases in HDL-C (33%), Apo A1 (12%), as well as in the HDL-C/LDL-C (48%) and Apo A1/Apo B (22%) ratios. The concentrations of HDL-C and Apo A1 were significantly greater in patients receiving DMPA, than in patients continuing with lynestrenol therapy. The amenorrhea incidence, however, did not differ between the two therapy groups. It is concluded that therapy with DMPA may be associated with smaller atherosclerosis risk than with peroral lynestrenol, because of its weaker effect on HDL-C and A1 levels.

Adult↗
PubMed1990

Elevated levels of serum dolichol in aspartylglucosaminuria.

Slightly elevated serum dolichol levels have so far been demonstrated only in alcoholics. We now report two diseases with exceptionally high serum dolichol levels. They are autosomal, recessively inherited lysosomal storage diseases, aspartylglucosaminuria (AGU) and mannosidosis. In 16 patients with AGU the mean serum level of total dolichols (457 +/- 43 ng/ml) was more than two-fold when compared to healthy controls (170 +/- 4 ng/ml). In two patients with mannosidosis the levels were almost two-fold. The percentage distribution of the dolichol homologues with 18, 19 or 20 isoprene units did not differ between the patients and controls. The inclusion of an additional control group excluded the possible influence of mental retardation and imparied moving ability on the results. Elevated serum dolichols in patients with lysosomal storage diseases may reflect a disturbance in lysosomal function and serve as a diagnostic marker. The biochemical mechanisms leading to this phenomenon remain to be established.

Acetylglucosamine↗
PubMed1988

Pyrazole is different from acetone and ethanol as an inducer of the polysubstrate monooxygenase system in mice: evidence that pyrazole-inducible P450Coh is distinct from acetone-inducible P450ac.

The induction of liver microsomal monooxygenase activities elicited by pyrazole, ethanol, and acetone, all shown to be inducers of rat P450j and rabbit P450LM3a, has been compared in inbred strains of DBA/2N, AKR/J, and Balb/c mouse. Pyrazole strongly increases coumarin 7-hydroxylase (COH) activity in DBA/2N but much less in other strains. The effect of pyrazole on aniline p-hydroxylase and ethanol oxidase activities is also strain dependent: an increase was seen only in the DBA/2N strain. Ethanol and acetone were unable to induce COH, whereas aniline p-hydroxylase and ethanol oxidase were elevated about 1.4- to 3.3-fold in all strains. No strain difference could be detected in aniline p-hydroxylase or ethanol oxidase inducibility. There was a strong correlation between aniline p-hydroxylase and ethanol oxidase activities in every strain, whereas no positive correlation could be found between COH and aniline p-hydroxylase activities. Immunoinhibition experiments showed that a polyclonal antibody against purified pyrazole-inducible COH (P450Coh) blocked about 90% of COH activity, but only about 10% of aniline p-hydroxylase or ethanol oxidase in mouse liver microsomes. Monoclonal antibody 1-91-3 (raised against rat acetone-inducible P450ac) did not inhibit COH, whereas aniline p-hydroxylase was blocked 46-76% and ethanol oxidase 25-70%, depending on the source of microsomes. In immunoblots, anti-P450Coh recognized only its own antigen but not the P450ac, whereas monoclonal antibody 1-98-1 against P450ac detected P450ac and a corresponding form in the D2 mouse liver, but not the P450Coh. The purified P450ac and P450Coh had molecular masses of 52 and 50 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These antigens were expressed differentially in response to pyrazole, ethanol, and acetone: P450Coh was increased only after pyrazole treatment, but 1-98-1-detectable protein was elevated in D2 mouse liver microsomes by ethanol and acetone, but not by pyrazole. We conclude that mouse P450Coh and rat P450ac are not corresponding forms of the same isozyme, and that a P450ac-like protein, responsible for most of aniline p-hydroxylation and ethanol oxidation, is present in the D2 mouse liver. These two P450 isozymes are also dissimilarly expressed in the mouse liver in response to inducer administration.

Acetone↗
PubMed1988

Clinical features in a de novo interstitial deletion 15q13 to q15.

A boy with several dysmorphic features and suffering from mental and motor retardation was found to have a de novo interstitial deletion of chromosome 15, involving bands q13 to q15. His clinical picture is described and compared with the clinical features reported in other deletions of this chromosome, located or extending distally from the region associated with Prader-Willi syndrome.

Child↗
PubMed1988

Peroral lynestrenol and arterial disease in mentally retarded women. A case-control study based on autopsy findings.

Autopsy findings from 170 non-smoking and mentally retarded women aged 12-51 years were analysed for any epidemiological association between the use of peroral lynestrenol for inducing therapeutic amenorrhea (TA) and arterial disease. Eighty-six women had received lynestrenol continuously for an average of 81 months (range 2-220 months) and the other 84 had not. After exclusion of 6 cases with known risk factors (diabetes, hypertension) predisposing to arterial disease, pathological arterial changes were found in 16 patients, 10 of them belonging to the TA group and 5 to the non-lynestrenol group. The incidence of arterial disease at autopsy at the age of 35 or more was 8/19 in TA patients and 1/15 in non-lynestrenol patients (p = 0.078). The benefits of prolonged TA induced by lynestrenol in this group of patients must be weighed very carefully against the possible risks involved.

Adolescent↗
PubMed1987

Pyrazole as a modifier of liver microsomal monooxygenase in DBA/2N and AKR/J mice.

Effects of pyrazole on liver microsomal monooxygenase was studied in two inbred strains of mice, DBA/2N (D2) and AKR/J (AKR). A selective effect on microsomal monooxygenase was found. In the D2 mouse pyrazole strongly increases the coumarin 7-hydroxylase (CoH) and 7-ethoxycoumarin O-deethylase (ECDE) activities while on the total cytochrome P-450 (P-450) content and ethylmorphine N-demethylase (EMDM) and benzo(a)pyrene hydroxylase (AHH) activities the effect is biphasic (increased with lower doses and decreased with higher). For AKR the effect of pyrazole is different from the D2. The increase of CoH and ECDE is weaker and no biphasic effect for the other three parameters can be seen. Instead only a decrease takes place. The optimal dose of pyrazole for the induction of CoH in the D2 mice is 200 mg/kg once a day during three days. The effect of pyrazole is strongest in animals (D2) of 4-10 weeks old. For young animals (2 weeks old) no effect except of a weak decrease in AHH can be seen. Also for old animals the effect is weak. Recovery of the monooxygenase after pyrazole induction takes place in about 120 hr except for the total P-450 content which is still below normal. No sex dependence in the effect of pyrazole on CoH was found.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1987

Prevalence of the fragile X syndrome in four birth cohorts of children of school age.

The prevalence of the fragile X syndrome among 12,882 children (6594 boys and 6288 girls) born during the years 1969-1972 in Kuopio province in eastern central Finland has been studied retrospectively. Mentally retarded children were selected from normal schools by using school achievement tests and from registers of mentally retarded individuals. In the present study fragile X syndrome was found in 6/111 mentally retarded children (5.4%), in 4/61 boys and in 2/50 girls, respectively. It was not detected in the control group of 85 healthy children. The corrected prevalence of fragile X syndrome among boys in four successive birth cohorts was estimated to be 1 in 1210 or 0.8/1000, and that among girls, 1 in 2418 or 0.4/1000. The overall prevalence was calculated to be 1 in 1612 or 0.6/1000 children.

Child↗
PubMed1987

Chromosomal aberrations in 85 mentally retarded patients examined by high resolution banding.

Eighty-five mentally retarded patients had their chromosomes examined by using the high resolution banding techniques. Fifty-nine of them had multiple congenital anomalies and/or dysmorphic features. Twenty-six had mental retardation but no major anomalies; they were primarily suspected of having the fragile X syndrome. This suspicion was first excluded. Fifteen patients were found to have a chromosome aberration, interpreted as clinically significant. Eleven of them had been examined earlier by conventional methods. The aberrations found were divided into three groups: (I) those detectable with an accuracy of ca. 300-400 bands (N = 4), (II) those detectable with an accuracy of ca. 400-550 bands (N = 6) and (III) those detectable with an accuracy of ca. 550-850 bands (N = 5). The aberrations are described and discussed.

Adolescent↗
PubMed1986

Frequency of rare fragile sites among mentally subnormal schoolchildren.

The frequency of rare fragile sites was studied among 240 children in special schools for subnormal intelligence (IQ 52-85). 1/130 boys studied (0.8%) had the fragile site at Xq27.3 while it was not found in any girl (0/110). In two children an autosomal rare fragile site at 2q11.2 (2/240, 0.8%) was seen. In addition a constitutional chromosome abnormality was found in a further seven children (7/240, 2.9%).

Adolescent↗
PubMed1985

Partial trisomy 12q: clinical and cytogenetic observations.

High resolution chromosome banding showed a male infant with profound mental retardation, hypertonia and multiple congenital anomalies to have the karyotype 46,XY,-der (2),t(2;12)(q37.3;q24.13)pat. Most of the clinical findings were compatible with those of the previously described cases with partial trisomy 12q. Some of the clinical features seem to disappear with increasing age.

Child↗
PubMed1984

Metabolism of collagen in aspartylglycosaminuria: urinary excretion of hydroxyproline.

Aspartylglycosaminuria (AGU) is a lysosomal storage disorder of glycoprotein degradation characterized by severe mental retardation and connective tissue alterations. We have previously described low collagen production in skin fibroblast cultures from AGU patients. In the present work we showed that the urinary excretion of hydroxyproline (total, non-dialysable and free hydroxyproline as indicators of collagen metabolism) was reduced in young AGU patients in comparison with age-matched controls. In adult patients no significant difference was detected. The results support the view that reduced collagen production is associated with the connective tissue abnormalities in this disorder.

Acetylglucosamine↗
PubMed1984

Abnormal collagen fibrils in aspartylglycosaminuria. Altered dermal ultrastructure in a glycoprotein storage disorder.

Patients with aspartylglycosaminuria, a lysosomal storage disorder of glycoprotein degradation, express connective tissue signs that refer to impaired mechanical properties of the tissue. We studied the ultrastructure of the dermis of patients with aspartylglycosaminuria to detect possible alterations in the connective tissue matrix, alterations that could explain the clinical findings. The organization of fiber bundles was studied by light microscopy and scanning electron microscopy, and diameters and volume densities of individual collagen fibrils were measured. The histologic organization of the dermis in patients with aspartylglycosaminuria was normal. However, by scanning electron microscopy a looser organization and more irregular orientation of the fiber bundles were detected. Transmission electron microscopy revealed a strikingly abnormal variation in the diameters of individual collagen fibrils (from 20 to 160 nm) in all layers of the dermis, with slight irregularity of shape especially in the thickest fibrils. Occasional giant fibrils (greater than 200 nm) were observed. The distribution of the ruthenium red-positive material around the fibrils was normal. Ultrastructural changes similar to these have been found in the collagen fibrils of some patients with Ehlers-Danlos syndrome as well as certain other disorders affecting dermal connective tissue. Altered collagen fibril formation offers an explanation for the connective tissue lesions in aspartylglycosaminuria.

Acetylglucosamine↗