Search PubMed⌕ Search

Biomedical subjects

O Simell

Publications and source records attributed to O Simell.

At least 145 records · Page 8Linked to original sources
PubMed1996

Correlation of toddlers' serum lipoprotein(a) concentration with parental values and grandparents' coronary heart disease: the STRIP baby study.

The correlation between lipoprotein(a) (Lp(a)) concentrations in children aged 7-24 months and their family members was determined and the association between the Lp(a) values of the children and a family history of coronary heart disease (CHD) was assessed. The Lp(a) values of the children correlated strongly with midparent Lp(a) values as early as at 7 months of age (r = 0.54 to 0.59, p < 0.0001). This correlation was stronger than the correlation of serum total cholesterol and total cholesterol corrected for Lp(a)-cholesterol between children and parents. None of the parents had CHD. The median Lp(a) concentration of the parents with a family history of CHD was significantly higher than that of parents with no such history (111 vs 87 mg/1, p = 0.024). However, the children's Lp(a) levels were not associated with CHD in their grandparents. The genetic dependence of the Lp(a) concentration is already evident in infancy. The Lp(a) concentration in young parents, but not in their 24-month-old children, is associated with CHD in grandparents. This may be explained by a dilution of the genetic influence on Lp(a) over two generations.

Adult↗
PubMed1996

Mucosa-associated (beta 7-integrinhigh) lymphocytes accumulate early in the pancreas of NOD mice and show aberrant recirculation behavior.

The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) becomes expressed on islet vessels of NOD mice early during lymphocyte accumulation in islets. Because MAdCAM-1 preferentially mediates the homing of mucosal lymphocytes, islet-associated MAdCAM-1 could favor the accumulation of mucosal lymphocytes in pancreatic islets. Therefore, we investigated the relative frequency of islet-infiltrating lymphocytes with a mucosal phenotype (alpha 4/beta 7-integrinhigh and L-selectinlow) at early and advanced stages of insulitis. We found that until the age of 12 weeks, lymphocytes with a mucosal phenotype were particularly frequent in the pancreas (percentage of beta 7-integrinhigh-lymphocytes was 48% at 8 weeks and 73% at 12 weeks), whereas in diabetic mice older than 16 weeks, their relative number was smaller (26% of pancreas-infiltrating lymphocytes). To define the origin and homing behavior of beta 7-integrinhigh-lymphocytes before their accumulation in pancreatic islets in NOD mice, we sought for such lymphocytes in different lymphoid organs and studied their recirculation. We found that compared with lymphocytes in several other strains, in NOD mice such lymphocytes were most frequent in nonmucosal lymphoid tissues (peripheral and pancreatic lymph nodes, spleen) from an early age. When injected to blood circulation, mucosal beta 7high-lymphocytes failed to home efficiently back to mucosal lymphoid tissue in NOD mice but homed aberrantly to nonmucosal lymphoid tissues. After adoptive transfer of diabetogenic splenocytes, the first lymphocytes accumulating in the pancreas were predominantly beta 7-integrinhigh. We conclude that mucosa-associated lymphocytes are involved in the early phases of islet-inflammation in NOD mice and that the aberrant homing behavior of lymphocytes expressing high levels of beta 7-integrin may associate with their accumulation in pancreatic islets early during insulitis.

Aging↗
PubMed1996

Apolipoprotein E polymorphism and serum lipids in a randomized, prospective trial of an infant diet with reduced saturated fat and cholesterol.

BACKGROUND: The inherited apolipoprotein E (apoE) phenotype may determine effectiveness of dietary atherosclerosis prevention. This study analyzes the effects of apoE phenotypes on changes in serum lipid concentrations in a 6-month prospective, randomized trial of a low-saturated-fat, low-cholesterol diet in infancy. PATIENTS AND METHODS: One thousand sixty-two healthy infants were randomized to intervention and control groups at the age of 7 months. Counseling was provided to the intervention families when the children's ages were 7, 8, and 10 months. Dietary goals were the child's intake of energy ad libitum, fat at 30% to 35% of energy, cholesterol at less than 200 mg/d, and saturated, monounsaturated, and polyunsaturated fatty acids at a 1:1:1 ratio. Control families consumed an unrestricted diet. The apoE phenotype of 846 of the infants was determined; serum lipid and lipoprotein concentrations were measured at 7 and 13 months of age; and nutrient intakes were analyzed using 3-day food records at 8 and 13 months of age. RESULTS: At 7 months of age, serum cholesterol concentration was higher in apoE4-positive infants (E2/E4, E3/E4, and homozygous E4) than in apoE4-negative infants (159 +/- 31 mg/dL [4.10 +/- 0.81 mmol/L] vs 150 +/- 29 mg/dL [3.89 +/- 0.74 mmol/L]). The high-density lipoprotein cholesterol concentration was slightly lower in apoE4-positive infants than in apoE4-negative infants (34 +/- 8 mg/dL [0.88 +/- 0.20 mmol/L] vs 35 +/- 7 mg/dL [0.91 +/- 0.19 mmol/L]). Between 7 and 13 months of age, the serum cholesterol concentration in infants in the intervention group was unchanged, apoB concentration increased slightly, and apoA1 concentration decreased. In the control infants, serum cholesterol concentration increased 9 +/- 25 mg/dL (0.24 +/- 0.65 mmol/L), apoB concentration increased markedly, and apoA1 concentration was stable. Changes in serum lipid and apo concentrations that resulted from the dietary intervention were independent of the apoE phenotype. CONCLUSIONS: The apoE phenotype influenced serum cholesterol concentration markedly by 7 months of age. Between the ages of 7 and 13 months, a reduced saturated fat and cholesterol diet effectively prevented the age-associated increases in serum cholesterol and non-high-density cholesterol concentrations that were obvious in the control infants. The effects of the diet occurred in the infants independently of the apoE phenotype.

Analysis of Variance↗
PubMed1995

Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol.

Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed, but dietary interventions have been limited by fears of diet-induced growth failure. We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomised study. Every 1-3 months, families in the intervention group received dietary advice aimed at adequate energy supply, with low fat intake (30-35% energy, polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1, and cholesterol intake < 200 mg daily). Infants in control families consumed an unrestricted diet. 3-day food records were collected at ages 8 and 13 months. Growth was carefully monitored. Between 7 and 13 months serum cholesterol and non-high-density-lipoprotein cholesterol concentrations did not change significantly in the intervention group (mean change -0.03 [SD 0.72] mmol/L and 0.01 [0.67] mmol/L) but increased substantially in the control group (0.24 [0.64] mmol/L and 0.23 [0.60] mmol/L; p for difference in mean changes between groups < 0.001). Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months (4065 [796] vs 4370 [748] kJ, p = 0.033, and 9.3 [3.5] vs 14.5 [4.8] g, p < 0.001, respectively), and intake of polyunsaturated fat was higher (5.8 [2.2] vs 4.4 [1.4] g, p < 0.001). Growth did not differ between the groups and was as expected for children at this age. Serum cholesterol concentrations fell significantly in parents of intervention-group infants. The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets, with no effect on the children's growth.

Cholesterol↗
PubMed1995

Serum insulin profiles in consecutive children 2 years after the diagnosis of IDDM.

We studied associations of 24-h serum insulin profiles with insulin dose, age, gender, haemoglobin A1c (HbA1c) and C-peptide values, as well as blood glucose profiles in 77 consecutive children-nine aged 2-4, 14 aged 5-8, 26 aged 9-12, and 28 aged 13-17 years--2 years after the onset of insulin-dependent diabetes mellitus (IDDM). Mean weight-based insulin doses in the four age groups were similar (0.7 +/- 0.2 U.kg-1.day-1 in all); body surface-area-based doses differed. Insulin doses correlated significantly with the 24-h mean and area-under-the-curve (AUC) values, and with mean values at 03.00 hours of serum insulin in the children aged 5-8 and 13-17 years. The mean insulin concentrations of the age groups (95% confidence intervals) increased with age [6.1 (3.8, 9.7), 7.6 (5.9, 9.8), 10.4 (8.6, 12.4), and 14.0 (11.6, 16.8) mU/l; p < 0.0002]. The 24-h mean of serum insulin together with HbA1c concentration predicted 32% of the variation of mean blood glucose concentrations. Of children aged less than 9 years, 50% had insulin values less than 5 mU/l (healthy subjects' lower reference limit), and 14% were of less than 2 mU/l (detection limit of the assay) at 03.00 hours. At 07.00 hours, 82% had insulin values of less than 5 mU/l, and 36% were of less than 2 mU/l, respectively. Some young children had night-time hypoglycaemia with simultaneous hypoinsulinaemia. Insulin profiles correlated poorly with the HbA1c and peak C-peptide values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Effect of alloxan on the endocrine function of human fetal islet-like cell clusters--an in vitro study.

We studied the effects of alloxan on insulin and glucagon secretion, islet insulin content, and morphology of human fetal islet-like cell clusters (ICCs). ICCs were derived after collagenase digestion and culture of pancreata from two fetuses. Culture medium (RPMI 1640) containing either 2.0 (low) or 11.1 (high) mM glucose was used during the alloxan exposure. Alloxan exposure lasted for 5 min at room temperature, with final concentrations of 0.3, 1, 3, 10, 30 and 100 mM. Medium samples were collected for hormone assays on days 0, 1, 2, 3, 6, and 10 and islet insulin contents were measured on day 10 after alloxan treatment. Electron microscopy of ICCs was done 24 h after the drug exposure. Control ICCs steadily increased their insulin secretion during the whole study period. Alloxan concentrations above 0.3 mM significantly (p < 0.01) decreased insulin secretion at the low glucose concentration. High glucose protected beta cells from alloxan toxicity. There was no difference in islet insulin contents between alloxan-treated and control cultures. Glucagon secretion by glucose media was not affected by alloxan exposure. All islet cells including beta cells remained intact in electron microscopy. The results suggest a block in insulin secretion by alloxan, but beta cells appear to recover at least partly in their insulin-secreting capacity.

Alloxan↗
PubMed1995

Short-term and long-term initial stay in hospital of children with insulin-dependent diabetes: adjustment of families after two years.

A randomized prospective trial on the effect of the length of initial hospital stay (23 +/- 4 days and 9 +/- 3 days) in 61 consecutive children with newly diagnosed diabetes was carried out. Since the metabolic outcome was similar in the treatment groups for the first two years, we analyzed the adjustment and subjective well-being of families to the diabetes after a two-year follow-up period. A semi-structured interview by a psychologist who was blinded to the initial treatment length and medical history of the child showed that 74% of the families in the short-term and 58% in the long-term treatment groups had good overall psychosocial ability to function (ns); there were no unusual fears in 37% and 15% of the families (ns), respectively. After short-term treatment, families needed slightly but not significantly less time to be confident about the management of diabetes in the family. These findings show that the short-term initial hospital stay does not unfavorably affect the adjustment of the family to diabetes and should probably be preferred over the long-term initial hospital stay.

Adolescent↗
PubMed1995

Effect of weaning on serum lipoprotein(a) concentration: the STRIP baby study.

Risk for coronary heart disease is increased in adult Caucasians with high serum lipoprotein(a) [Lp(a)] concentration. In adults the concentration is mainly regulated by genetic factors. Our previous study suggests that breast milk has a beneficial effect on serum Lp(a) concentration in infants. Now we analyzed the influence of weaning by measuring serum Lp(a) and cholesterol in 414 infants at 7, 13, 24, and 36 mo of age. At 7 mo the infants received, in addition to solid food, only breast milk (n = 148), breast milk and formula (n = 74), or formula only (n = 191). Median (range) serum Lp(a) concentrations were then 25 (< or = 12-743) mg/L, 35 (< or = 12-1188) mg/L, and 45 (< or = 12-577) mg/L in the three feeding groups, respectively (p = 0.0013). Breast milk and formula were changed to cow's milk in all infants before 12 mo of age. At 13 mo serum Lp(a) concentration had increased more in infants who were weaned from breast milk than in those who had been fed both breast milk and formula, or formula only (median increases 37, 26, and 20 mg/L, respectively; p = 0.0062). Thus the serum Lp(a) concentration was similar in all feeding groups at 13 mo. This finding was also observed at 24 and 36 mo. The increase in serum Lp(a) concentration was independent of the baseline Lp(a) level, apolipoprotein E phenotype, gender, and weight gain of the infants between 7 and 13 mo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients.

Lysinuric protein intolerance is an autosomal recessive disease caused by defective transport of cationic amino acids. Of the 38 lysinuric protein intolerance patients diagnosed in Finland since 1965, four pediatric patients have died. We describe the clinical courses and autopsy findings for these patients. All patients developed acute respiratory insufficiency. In addition to pulmonary hemorrhages, three of the patients had pulmonary alveolar proteinosis and one had cholesterol granulomas. Three patients had a clinically obvious renal insufficiency, but all four showed histologic signs of immune complex-mediated glomerulonephritis. The patients also developed hepatic insufficiency with fatty degeneration or cirrhosis. All patients showed anemia, thrombocytopenia, and a severe bleeding tendency. The bone marrow of three patients was hypercellular, but the amount of megakaryocytes was decreased in two cases. Amyloid was present in the lymph nodes and the spleen. Bone specimens showed osteoporosis. We conclude that pediatric patients with lysinuric protein intolerance are predisposed to develop pulmonary alveolar proteinosis and glomerulonephritis. They are also at risk of protein malnutrition in the active growth phase, probably due to higher requirements for total nitrogen and amino acids.

Adolescent↗
PubMed1994

Individualized dietary counselling of families: serum cholesterol concentration and growth of children aged 7-13 months.

We studied the effect of a change in dietary fat composition on serum total and high-density lipoprotein cholesterol and growth in healthy infants between 7 and 13 months of age. The intervention families (n = 22) received individualized dietary counselling when the infant was 7, 8 and 10 months of age. The intervention diet was designed to have a fat content of 35-45 E% of total energy intake in infants aged 7-12 months and 30-35 E% after 12 months of age. The ratio of saturated to monounsaturated to polyunsaturated fatty acids was designed to be 1:1:1. The children in the control group (n = 23) were given no specific advice on the fat composition of the diet. Intake of polyunsaturated fatty acids was significantly higher in the intervention group than in the controls (5.9 E% versus 3.6 E%, p < 0.05). Serum total cholesterol concentration decreased significantly in the intervention group during the study from 4.16 +/- 0.41 mmol/l to 3.86 +/- 0.48 mmol/l (p < 0.05). The infants of both groups grew like average Finnish children. Modification of dietary fat composition, as widely recommended for adults and older children to prevent coronary heart disease, decreases cholesterol values in infants without affecting their normal growth.

Cholesterol↗
PubMed1994

Sonography in the detection of achilles tendon xanthomata in children with familial hypercholesterolaemia.

Patients with heterozygous familial hypercholesterolaemia (FH) are at high risk for the development of coronary artery disease. Achilles tendon xanthomata are often the first clinical manifestation of FH, but are seldom palpable earlier than during the third decade. Twenty-one FH children aged 3-18 years underwent high-frequency ultrasound examination of the achilles tendon. Hypoechoic infiltration of the normal tendon structure was demonstrated in 8 of 21 (38%) of the FH children. The findings were similar in boys and girls. Control subjects (n = 68) aged 1-25 years had no sonographically detectable tendon abnormalities. The thickness of the achilles tendon of the FH children was (mean +/- SD) 7.1 +/- 1.5 mm (range 5-10 mm). The respective values for the controls were 5.8 +/- 1.0 mm (3-7 mm. We conclude that ultrasound examination sensitively detects cholesterol accumulation in the achilles tendon of FH children before tendon xanthomata are clinically evident.

Achilles Tendon↗
PubMed1994

Plasma membrane clustering of system y+ (CAT-1) amino acid transporter as detected by immunohistochemistry.

Transport of cationic amino acids in fully differentiated mammalian cells is mediated primarily by system y1+ [cationic amino acid transporter (CAT)-1 gene product]. Antibodies, prepared against synthetic peptide sequences predicted to be extracellular loops of the CAT-1 transporter protein, detected the transporter on the surface of cultured cells. In human fibroblasts, porcine pulmonary artery endothelial cells, and cultured rat hepatoma cells, the CAT-1 transporter protein was clustered in an apparent random pattern throughout the plasma membrane. In contrast, labeling of the fibroblasts with antibodies against the epidermal growth factor receptor or the GLUT-1 glucose transporter demonstrated a uniform staining pattern covering the entire cell surface. The CAT-1 antibody labeling was specific, as demonstrated by peptide inhibition and the lack of staining by preimmune serum. Furthermore, hepatocytes did not exhibit specific antibody binding consistent with the lack of system y1+ activity. Disruption of the microtubule assembly resulted in a reversible loss of the CAT-1 transporter clusters and a more generalized labeling of the cell body. The data demonstrate the existence of microdomains within the plasma membrane that contain the CAT-1 transporter protein.

Amino Acid Sequence↗
PubMed1994

Flow rate and composition of whole saliva in rural and urban Tanzania with special reference to diet, age, and gender.

The association of flow rate and biochemical and microbiological characteristics of saliva with diet was studied in 83 12-year-old children and in 127 adults (84 in the age group 35-44 years, 43 in the age group 65-74 years) living in rural and urban communities in Tanzania. No significant differences were observed between the salivary flow rates of the rural and urban subjects. The mean salivary flow rates were slightly lower in women than in men and significantly lower in the 12-year-old children than in the two older age groups (p < 0.05). The buffer effect was higher in the rural than the urban population. Further, it was lower in women than in men (p < 0.001). Salivary protein, IgG, and sialic acid concentrations were significantly higher in the rural than in the urban population, whereas amylase activity and IgA concentrations were lower. Microbiological studies showed mutans streptococci in 97% of the rural and in 91% of the urban subjects (n.s.). Lactobacilli grew significantly less often in the rural than urban samples (p < 0.01). Analyses of 24-hour dietary recalls showed that the rural and urban diets differed. The proteins in the rural diet were largely of plant origin, while in the urban diet animal proteins dominated. The rural diet contained also less sucrose but more fibre (mainly from grain) than the urban diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Serum levels of oncofetal markers CA 125, CA 19-9, and alpha-fetoprotein in children with hereditary tyrosinemia type I.

Hereditary tyrosinemia type I (HTT-I) is an inherited metabolic disorder with severe liver disease and a high risk for hepatic malignancy. Patients with HTT-I are monitored with repeated analyses of serum amino acids, urine succinylacetone, and serum alpha-fetoprotein (AFP). Oncofetal markers CA 125 and CA 19-9 are elevated in serum of patients with various gastrointestinal diseases and malignancy. To study the biology of oncofetal antigens in tyrosinemia and to assess the possible usefulness of these markers in HTT-I, we studied serum concentrations of CA 125 (n = 160) and CA 19-9 (n = 188), together with AFP (n = 337), in serial samples from 10 patients. At early stages of the disease, most children with an acute type of disease had a remarkably elevated serum CA 125 concentration (153-1560 IU/L) that normalized gradually after the institution of therapy. Serum CA 125 levels may thus reflect acute metabolic imbalance in fulminant HTT-I. The patients with a chronic type of disease showed CA 125 levels within the normal range at diagnosis that slowly increased as the liver condition worsened. These concentrations, however, never reached values seen in acute HTT-I. Serum concentration CA 19-9 in HTT-I was mostly normal. Serum AFP levels fluctuated in all patients and positively correlated with tests for metabolic state and biliary function. A distinct increase in the serum AFP level was recorded in association with the detection of massive hepatocellular carcinoma and also preceded metabolic imbalance leading to porphyria crises.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Abnormal pulmonary macrophages in lysinuric protein intolerance. Ultrastructural, morphometric, and x-ray microanalytic study.

Pediatric patients with lysinuric protein intolerance are predisposed to develop alveolar hemorrhage and pulmonary alveolar proteinosis. We evaluated the ultrastructural features of pulmonary alveolar proteinosis and the potential abnormality of pulmonary macrophages in lysinuric protein intolerance. Lung tissue specimens obtained at autopsy were examined by transmission electron microscopy. Pulmonary macrophages from bronchoalveolar lavages were studied by electron microscopy, morphometry, and x-ray microanalysis and compared with control cells. The macrophages of patients with lysinuric protein intolerance contained significantly more multilamellar structures than did control cells and showed electron-dense material identified to contain excess iron. The predisposition to develop alveolar proteinosis and the abnormal ultrastructure of pulmonary macrophages suggest altered phospholipid metabolism in patients with lysinuric protein intolerance. The marked intramacrophageal accumulations of iron might indicate altered iron metabolism or subclinical hemorrhages in lung tissue.

Adult↗
PubMed1993

Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes.

BACKGROUND: Epidemiologic studies have implicated the ingestion of cow's milk in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). Moreover, in a recent study, 100 percent of patients with new-onset IDDM had antibodies against bovine serum albumin (BSA), with a majority directed against a 17-amino-acid BSA peptide (ABBOS). Cellular immune mechanisms are thought to be the principal mediators of pancreatic beta-cell destruction in IDDM. METHODS: We measured the responses of peripheral-blood mononuclear cells to BSA and ABBOS or serum IgG anti-BSA antibodies (by particle-concentration fluorescence immunoassay) in 71 patients with IDDM, 55 subjects at various degrees of risk for IDDM, 36 patients with other autoimmune disorders (chronic autoimmune thyroiditis, rheumatoid arthritis, and systemic lupus erythematosus), and 48 normal subjects. RESULTS: The responses of peripheral-blood mononuclear cells to BSA or ABBOS were positive in 2 of 24 patients with new-onset IDDM, 1 of 25 first-degree relatives of patients with IDDM who were negative for islet-cell antibodies, 2 of 30 first-degree relatives of patients with IDDM who were positive for islet-cell antibodies, 1 of 28 patients with established IDDM, and 1 of 29 normal subjects. Similarly, anti-BSA antibodies were not detected significantly more often in patients with new-onset IDDM (3 of 31, 10 percent) than in normal subjects (1 of 37, 3 percent; P = 0.32). However, many patients with autoimmune disease and subjects at increased risk for IDDM had anti-BSA antibodies (frequency, 10 to 31 percent). CONCLUSIONS: Anti-BSA antibodies may reflect a general defect in the process of immunologic tolerance associated with a predisposition to autoimmunity rather than immunity specific to beta cells. The absence of cellular immunity to BSA and ABBOS in IDDM does not support a role for this antigen in the pathogenesis of the disorder.

Adult↗
PubMed1993

Repeated fluorodeoxyglucose positron emission tomography of the brain in infants with suspected hypoxic-ischaemic brain injury.

Positron emission tomography (PET) permits the study of cerebral metabolism in vivo. We performed repeated PET studies with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for estimation of neurological prognosis in infants with suspected hypoxic-ischaemic brain injury. Fourteen infants (gestational age 35.3 +/- 4.67 weeks) were examined during the neonatal period (at age 38.4 +/- 2.7 weeks) and again at the age of 3.5 +/- 0.7 months; one further infant was studied only once at the age of 2.5 months. All children also underwent ultrasound examinations. Electroencephalography and computed tomography or magnetic resonance imaging were performed according to their clinical condition and their neurological development has been followed. FDG accumulated most actively in the subcortical areas (thalami, brainstem and cerebellum) and the sensorimotor cortex during the neonatal period. The repeated PET study showed that the uptake of FDG was markedly high and increased in all brain sections of infants with normal development (n = 11), whereas those with delayed development (n = 4) had significantly lower values (P < or = 0.005).

Brain Ischemia↗