Search PubMed⌕ Search

Biomedical subjects

O Simell

Publications and source records attributed to O Simell.

At least 19 recordsLinked to original sources
PubMed1992

Mumps and Coxsackie B3 virus infection of human fetal pancreatic islet-like cell clusters.

Islet-like cell clusters (ICCs) prepared from human fetal pancreases were infected with mumps or coxsackie B3 virus. Double-labeled antibody technique showed that the viruses infected both insulin-secreting and other pancreatic cells and that secretion of immunoreactive insulin into the culture medium of the mumps virus-infected cells had already ceased on day 7. The mumps virus-infected ICC clusters produced virus for 14 days, and the mumps virus antigen was detected in the ICCs through the whole 22-day observation period. The coxsackie B3 virus-infected ICCs contained cells highly positive for viral antigen during the first 2 days after infection, and the infectious virus was detected in the culture medium for 22 days. This in vitro model indicates that mumps and coxsackie B3 viruses infect human fetal pancreatic endocrine cells and are able to alter beta-cell function. Coxsackie B3 virus infection in ICCs is lytical and seems to lead to rapid cell destruction, but long-lasting, restricted mumps virus infection in human fetal pancreatic ICCs offers an interesting model to study the effects of viral infection in the endocrine pancreas and beta cell.

Cells, Cultured↗
PubMed1992

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.

Antigens, CD↗
PubMed1991

Randomised prospective study of short-term and long-term initial stay in hospital by children with diabetes mellitus.

To assess how an isolated change in the pattern of care influences outcome of care and hospital use, a randomised prospective 2-year study was done in which 31 of 61 consecutive children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) were admitted to hospital at disease onset for about a week and compared with the other 30 children who were admitted for about 4 weeks. Insulin treatment and education about diabetes were similar in the two groups. Duration of initial stay in hospital had no effect on metabolic control during the 2 years but time since diagnosis was significant with respect to effect on haemoglobin A1 (p = 0.001), haemoglobin A1c (p = 0.004), and insulin dose (p less than 0.001). At 2 years, 45% of the children in the short-term group and 29% in the long-term group were C-peptide positive (p = NS); C-peptide positivity correlated with age. A change in the pattern of care of children with IDDM, led to a pronounced decrease in hospital use by this patient group. Irrespective of the length of initial stay in hospital, equally good metabolic control was obtained in both groups for 2 years.

Adolescent↗
PubMed1991

Lack of glucose-induced functional maturation during long-term culture of human fetal islet cells.

To investigate the long-term effects of glucose on the function of human fetal islets we cultured islet-like cell clusters (ICC) obtained from 12 human fetuses with a mean age of 16.1 weeks in media containing 2.8, 11.1 or 16.7 mM glucose. On the 8th day of culture, the ICC that had been maintained in 16.7 mM glucose contained 60% less insulin than the ICC cultured in 2.8 mM glucose. However, insulin release was similar in both groups, and was not affected by a 24-h incubation in high vs. low glucose. Also (pro) insulin biosynthesis was not significantly affected. During a 24-day culture period, the total release of insulin and glucagon was similar in all glucose concentrations. The ICC released about 75% of their insulin content but only 15% of their glucagon content during the last 48 h of the 24-day culture period, again regardless of glucose concentration in media. Insulin release was insensitive to acute glucose and leucine challenges in perifusion experiments after culture for 1, 5, 8 or 16 days in 11.1 mM glucose, whereas glucagon was always a potent stimulus. In conclusion, the function of cultured young human fetal islet cells is remarkably independent of glucose, even during prolonged exposure. Moreover, the primary role of glucagon in fetal life may be that of a paracrine stimulator of beta-cell function.

Arginine↗
PubMed1991

Children in sauna: hormonal adjustments to intensive short thermal stress.

Hormonal response to Finnish sauna bath was investigated in 20 prepubertal children (age 5-10 years). Blood leukocyte count, plasma potassium, serum aldosterone, growth hormone and prolactin concentrations increased; plasma volume, plasma sodium, catecholamines, serum antidiuretic hormone, atrial natriuretic peptide (ANP), cortisol, and thyrotropin concentrations remained unchanged during sauna bath. One hour after sauna, serum thyrotropin, atrial natriuretic peptide and blood glucose concentrations decreased, whereas the rest of the hormones remained unchanged. Our results implicate that maintenance of homeothermia resulted in moderate hormonal changes in children during Finnish sauna bath which indicate similar adequate hormonal thermoregulatory adjustment as previously documented in adults.

Catecholamines↗
PubMed1990

Tuberous sclerosis and infantile spasms.

The short- and long-term outcome and special problems of 24 children with infantile spasms and tuberous sclerosis (TS) was studied. The diagnosis of TS is frequently missed: white spots on the skin have to be carefully looked for. In the present study, these spots were always found, and calcifications or hypodense areas of the brain were revealed by CT scans before one year of age. In addition to epilepsy, manifestations of TS included: giant cell astrocytoma, iridic heterotopia, cardiac rhabdomyoma, brain cysts, polycystic kidneys with severe arterial hypertension, retinal phakomas, angiofibroma and white spots on the skin. Long-term outcome was poor. None of the children had normal intelligence and all but one had epilepsy, which was often intractable. Behavioural problems were common. The prognosis, in terms of later intelligence, epilepsy and behavioural problems, was worse than in those with 'idiopathic' infantile spasms or in those with simultaneous neurological disorders. An early diagnosis of TS in patients with infantile spasms clarifies the prognosis and avoids some of the hazards of ACTH therapy. TS children have a high relapse rate after ACTH therapy, so prolonged courses may be indicated.

Adolescent↗
PubMed1989

Hormonal background of the hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants.

We studied the hormonal background of the fluid derangements and arterial hypertension associated with adrenocorticotrophic hormone (ACTH) treatment for infantile spasms in ten infants aged 5-22 months. They received a 6 week course of (carboxymethyl-cellulose-)ACTH: 80 IU at 0800 hours daily in weeks 1-3, then tapering, and termination at the end of week 6. The infants showed large, variable increases in 24 h urine cortisol during treatment. The mean plasma cortisol concentration (24 h after ACTH injection) was not significantly increased, but was correlated with the relative dose of ACTH. The mean plasma aldosterone concentration decreased. No significant change occurred in plasma renin activity (PRA), or in the concentrations of renin substrate (RS) or arginine vasopressin (AVP). Seven infants developed arterial hypertension, which was severe in three. This severe hypertension was associated with the highest relative ACTH doses and the highest plasma RS and cortisol concentrations. In the group as a whole, systolic blood pressure correlated with plasma RS and cortisol concentrations, but not with the other parameters. At the end of treatment urine and plasma cortisol dropped below the pretreatment levels and stayed low for greater than 2 weeks. There was a sharp peak in PRA and plasma aldosterone concentration, and a decrease in plasma RS. Plasma AVP levels dropped markedly. The mean body weight increased sharply and urine flow decreased. Mean plasma electrolyte levels remained unaltered. The danger at termination of ACTH treatment appears to be associated with a sudden transition from hypercortisolism to hypocortisolism, activation of the renin-angiotensin-aldosterone axis, and suppression of AVP secretion.

Adrenocorticotropic Hormone↗
PubMed1989

Comparison of ornithine metabolism in hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome, lysinuric protein intolerance and gyrate atrophy fibroblasts.

We measured L-ornithine oxidation in cultured skin fibroblasts from seven patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome (McKusick 23897), and compared it with oxidation by ornithine aminotransferase deficient gyrate atrophy (McKusick 25887) cells and lysinuric protein intolerance (McKusick 22270) cells in which there is an ornithine transport abnormality at the plasma membrane. Net uptake of ornithine is not abnormal in intact HHH cells. Ornithine oxidation was depressed in HHH and gyrate atrophy cells but not in lysinuric protein intolerance cells; the latter finding suggests there is no significant mitochondrial defect in lysinuric protein intolerance cells. Since HHH cells have intact ornithine aminotransferase, impaired oxidation is compatible with deficient penetration of ornithine into mitochondria in this disease. We could not demonstrate a gene dosage effect in oxidation values.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Lysinuric protein intolerance mutation is not expressed in the plasma membrane of erythrocytes.

We measured mediated fluxes of L-lysine and L-ornithine across the plasma membrane of erythrocytes from control subjects and patients homozygous for the lysinuric protein intolerance (LPI) mutation. We found no differences in net uptake or efflux of cationic amino acids in control and LPI cells, contrary to our findings in cultured skin fibroblasts. We conclude that expression of the LPI (y+) transport system for cationic amino acids varies between tissues and that measurements of fluxes in erythrocytes cannot be used for diagnosis of LPI.

Adult↗
PubMed1988

Venous thrombosis associated with lupus anticoagulant and anticardiolipin antibodies.

We describe deep vein thrombosis associated with lupus anticoagulant and anticardiolipin antibodies in three children aged 10 to 14 years. One of them also had arterial thromboses. None of the patients had systemic lupus erythematosus when the thrombosis first occurred, but one fulfilled the criteria for systemic lupus erythematosus 3 years later. At presentation all had symptoms suggestive of pulmonary embolism and evidence of an autoimmune disease: Addison's disease in one, anti-DNA or antinuclear antibodies in all three, and a positive Coombs' test in two. Two of the three gave a false-positive test for syphilis. In the patient with systemic lupus erythematosus recurrent thrombocytopenia and severe haemolytic anaemia necessitated splenectomy. A child should be tested for lupus anticoagulant or anticardiolipin antibody if venous or arterial occlusion occurs without a known predisposing cause, or if there is pulmonary embolism or symptoms or laboratory findings suggestive of a connective tissue disease.

Adolescent↗
PubMed1988

Morphology, yield and functional integrity of islet-like cell clusters in tissue culture of human fetal pancreata obtained after different means of abortion.

Morphology, yield and function were studied in cultured islet-like cell clusters (ICC) from 140 human fetal pancreata obtained after abortions of different types performed at 11-23 weeks of gestation (12 by hysterotomy, 75 by mechanical dilation and extraction, and 53 induced with prostaglandin). After collagenase digestion and culture in medium supplemented with 10% human serum, up to 2000 free-floating ICC were formed from a single pancreas. Randomly scattered insulin- and glucagon-immunoreactive cells were found in the medullary part of the ICC. More than 100 ICC developed in 100% of the hysterotomies and 87% of the mechanical abortions, but in only 53% of the prostaglandin-induced abortions. Insulin and glucagon levels in the culture medium decreased rapidly during the first 7 days of culture, but then remained stable for at least 31 days. The hysterotomy-derived ICC responded to 10 mmol/l theophylline plus 20 mmol/l glucose by a 12.2 +/- 3.1 (SEM, N = 7) fold increase in insulin release, as compared with a 5.4 +/- 0.9 fold response of the prostaglandin ICC (N = 16; P less than 0.02). Despite the low proportion of B-cells, (pro)insulin biosynthesis accounted for 10% of the total protein biosynthesis in low (2 mmol/l) glucose. In conclusion, the yield and viability of the ICC were clearly better, if prostaglandin had not been used for the induction of the abortion.

Abortion, Induced↗
PubMed1988

Effects of growth hormone and insulin-like growth factor I on endocrine function of human fetal islet-like cell clusters during long-term tissue culture.

The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Culture Techniques↗
PubMed1988

Maturation of insulin response to glucose during human fetal and neonatal development. Studies with perifusion of pancreatic isletlike cell clusters.

The insulin release in response to glucose was studied in perifused isletlike cell clusters (ICCs) obtained from human fetal or neonatal pancreases at various stages of development: 12-15 gestational wk (n = 7), 17-20 wk (n = 13), 22.5 wk (n = 2, 1 diabetic pregnancy), and 26-44 wk (n = 6, postnatal samples). The ICCs were stimulated with 20 mM glucose and subsequently with 10 mM theophylline plus 20 mM glucose as a viability test. Insulin release increased to a detectable level (greater than 0.1 pg.ICC-1.min-1) during glucose stimulation in four of seven of the youngest fetuses. At 17-20 wk the basal rate of insulin release had increased by at least 15-fold above the detection limit (1.5 pg.ICC-1.min-1), and glucose promoted a sustained monophasic response that was on the average 1.6-fold higher than the basal level. The response was significant (P less than .05) in 9 of 13 experiments. With postnatal ICC (gestational age 26-44 wk), an early-phase peak response was observed in 5 of 6 experiments. The mean rates of insulin release after 5-12 min of glucose stimulation were 4.8 pg.ICC-1.min-1 in newborn infants and 2.1 pg.ICC-1.min-1 in 17- to 20-wk fetuses. The corresponding mean relative insulin responses (stimulated to basal) were 3.3-fold (range 1.1-7.5) and 1.6-fold (1.0-3.4), respectively (P less than .05, Mann-Whitney U test). The results suggest that the human fetal pancreas is already responsive to glucose during the first half of gestation, but the biphasic insulin release does not start to mature until the postnatal phase.

Cells, Cultured↗
PubMed1987

Food and guar decrease absorption of trimethoprim.

Absorption of trimethoprim suspension 3 mg/kg has been studied in 12 healthy adult volunteers when given alone, with food or with food and guar, using a randomised Latin-squares study design. Serum and urine trimethoprim concentrations were followed for 24 h. The mean peak serum concentration was higher when fasting subjects were treated (mean: 2.35, 1.84 and 1.97 micrograms/ml for the fasting, food and food + guar groups, respectively; ANOVA p less than 0.001 for the difference between fasting and non-fasting values). The times of the peak serum concentrations did not differ. Food ingestion decreased the area under the curve by 22.2%, as did food + guar. For maximal efficacy trimethoprim should be administered between meals.

Absorption↗
PubMed1987

The effect of ACTH therapy on serum dehydroepiandrosterone, androstenedione, testosterone and 5 alpha-dihydrotestosterone in infants.

Serum concentrations of dehydroepiandrosterone (DHEA), androstenedione, testosterone, 5 alpha-dihydrotestosterone and cortisol were measured in 10 infants (age 5-22 months) before, during and after 6-weeks of ACTH therapy for infantile spasms. During therapy, their mean DHEA concentrations increased 2.3-fold, androstenedione 12.3-fold, testosterone 2.7-fold, 5 alpha-dihydrotesterone 2.5-fold and cortisol 2.9-fold compared to pre-therapy values. Serum dehydroepiandrosterone sulphate (DHEA-S) concentrations were also increased during ACTH therapy above the normal prepubertal range. Three days after the cessation of ACTH treatment, all androgens had returned to the pre-therapy level. We conclude: At least in pharmacologic doses ACTH alone stimulates adrenal androgen secretion in infants, excluding the necessity of a separate adrenal androgen stimulating hormone.

Adrenocorticotropic Hormone↗