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Biomedical subjects

O Hernell

Publications and source records attributed to O Hernell.

At least 55 records · Page 3Linked to original sources
PubMed1998

Digestion of ceramide by human milk bile salt-stimulated lipase.

BACKGROUND: There is a renewed interest in metabolism of sphingolipids because of their role in signal transduction. Sphingomyelin is the dominating phospholipid in human milk but its metabolism and possible function in the gastrointestinal tract of breast fed infants is unknown. We explored whether bile salt-stimulated milk lipase has a role in sphingolipid metabolism. METHODS: In vitro assays of sphingomyelinase and ceramidase activities, using radiolabeled substrates, human milk samples and purified native and recombinant variants of bile salt-stimulated milk lipase with or without known activators or inhibitors. RESULTS: Human whey and purified lipase catalysed hydrolysis of palmitoyl-labeled ceramide with the highest rate around pH 8.5-9.0. 1 mg of lipase hydrolysed 0.7 micromol ceramide in one hour at pH 8.5 in presence of 4 mM bile salt. The activity of whey was inhibited by antibodies towards human bile salt-stimulated milk lipase, indicating that this lipase accounted for virtually all ceramidase activity in the milk. In contrast, bile salt-stimulated milk lipase showed no activity against sphingomyelin. However we give evidence of a separate, hitherto unknown, acid sphingomyelinase in human milk. Under the used in vitro conditions this sphingomyelinase could account for hydrolysis of half of milk sphingomyelin in one hour. CONCLUSIONS: Human milk bile salt-stimulated milk lipase hydrolyses ceramide and may thus have a role in sphingomyelin digestion, but only after initial hydrolysis to ceramide and phosphorylcholine. Part of the latter could be carried out in the stomach by the acid milk sphingomyelinase now described. We speculate that these two milk enzymes may be of importance for optimal use of human milk sphingolipids.

Amidohydrolases↗
PubMed1997

Naturally occurring variants of human milk bile salt-stimulated lipase.

Analysis of milk samples from a number of lactating women revealed molecular variants of bile salt-stimulated lipase (BSSL) of both lower and higher molecular mass than that commonly occurring. In contrast to previous observations, we report on individuals having only a variant of lower mass, both one of lower and one of common mass, or both one of lower and one of higher mass of the lipase. From two individuals we purified the lower molecular mass BSSL variant and characterized it. The amount of lipase in the milk of these two individuals was considerably less than average (mean of 10 women with BSSL of the most common molecular mass). The BSSL variant of lower mass showed the same bile salt activation, pH dependency, temperature stability as those most commonly occurring. We could localize the difference in mass to the large O-glycosylated repeat sequence close to the C-terminus of the protein. With respect to all characteristics studied, the BSSL variant of higher mass was also similar to that most commonly ocurring. Again, the difference in mass could be localized to the repeat region of the protein. Hence, it appears as if the repeat region, normally carrying 16 repeats of 11 amino acids each, varies in size between individuals.

Amino Acids↗
PubMed1997

Nutrient intake and weight development in children during chemotherapy for malignant disease.

The aim of the study was to assess the actual daily oral intake of energy, protein, fat and carbohydrate in relation to current recommendations in children with malignant disease during chemotherapy and to follow their weight development. Dietary information was collected for 21 consecutive days via 7-day recording in 14 children, aged 5-16 years. The number of days with loss of appetite, vomiting, and the number of days on anti-emetic drugs were also recorded. The average daily energy intake decreased from 91% of the recommendation of the Swedish Nutrition Recommendations (SNR), before chemotherapy to 69% after start of chemotherapy. During days spent at home, the energy intake increased to 77% of SNR. Twenty-two per cent of the total energy intake during the hospital days came from sucrose. On average, the children experienced loss of appetite on 50% of the days, vomiting on 12%, and received anti-emetic drugs on 38%. On admission, the average SD score for body weight for the whole group was -0.09. The mean weight reduction after 1 week was 0.19 SD (P = 0.05) compared to the admission weight. The weight reduction 6 weeks (n = 10) and 3 months (n = 13) after the start of chemotherapy was 0.10 SD and 0.37 SD (P = 0.04), respectively.

Adolescent↗
PubMed1997

Endurance running performance in relation to cardiovascular risk indicators in adolescents.

We evaluated endurance running performance and body mass index (BMI) in relation to biochemical cardiovascular disease (CVD) risk indicators (s-lipids, s-insulin, s-ferritin), and blood pressure in 14- and 17-year-old healthy Swedish adolescents (n = 879), also considering current dietary intake and physical activity. Endurance running performance was assessed using a 3 km running test and height, body weight, waist and hip circumference, and skinfolds were measured at clinical examination. Physical activity and dietary intake were evaluated using self-reported 7-day-records. The results showed that high endurance running performance was related to a favourable CVD risk indicator profile. Multiple regression analyses including running time, BMI, physical activity, dietary fat and iron intake, and age as independent and s-lipids, s-insulin, and s-ferritin as dependent variables revealed that, in both boys and girls, low BMI was associated to a favourable s-lipid profile and lower s-insulin values and, in boys but not in girls, also to lower s-ferritin values. There were, however, no independent associations between level of physical activity or endurance running performance on the one side and s-lipids, s-insulin, or s-ferritin values on the other. High dietary fat intake was associated to s-lipids in a non-atherogenic direction; in boys to higher HDL-C and in girls to lower TG. In conclusion the study showed that body mass seems to be the most important factor explaining the differences in s-lipid and s-insulin values between adolescents with different level of physical performance capacity. An interesting finding was, that s-ferritin, being a proposed risk factor for CVD, in the older boys related to body mass in a similar way as s-lipids and s-insulin.

Adolescent↗
PubMed1997

Prognostic impact of bone marrow karyotype in childhood acute lymphoblastic leukaemia: Swedish experiences 1986-91.

The prognostic value of cytogenetic classification in acute lymphoblastic leukaemia (ALL) was evaluated in Swedish children below 16 years of age (n = 372) diagnosed between 1986 and 1991. A bone marrow karyotype was obtained in 281 cases, of which 149 (53%) showed clonal abnormalities. Event-free survival (p-EFS) was 0.64-0.69 in patients with diploid and pseudodiploid karyotype. Patients with massive hyperdiploidy (> 50 chromosomes) had the best outcome (p-EFS = 0.76) and those with hypodiploidy (< 46 chromosomes) had the worst (p-EFS = 0.33). White blood cell count and age were the strongest predictors of outcome. The karyotype reached borderline significance. The diagnostic karyotype was also a predictor of outcome after relapse, with hyperdiploid patients doing better than the others. The presence of a structural chromosomal abnormality did not constitute a negative prognostic factor when intensive chemotherapy was given.

Adolescent↗
PubMed1997

Three variants of parathyroid hormone-related protein messenger RNA are expressed in human mammary gland.

PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.

Adult↗
PubMed1996

Visual acuity and erythrocyte docosahexaenoic acid status in breast-fed and formula-fed term infants during the first four months of life.

It has been recognized that preterm infants have a more rapid development of visual acuity if fed human milk or a formula enriched with the long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) compared to a standard formula devoid of LCPUFA. Few studies have addressed whether the same is also true in term infants. The aim of the present study was to follow visual acuity and fatty acid composition in red blood cells (RBC) for the first 4 mon of life in 17 breast-fed and 16 formula-fed term infants. The formula used did not contain LCPUFA, but contained 1.7 wt% alpha-linolenic acid, and the linoleic/alpha-linolenic acid ratio was 8.5. The increase in visual acuity measured by Teller acuity cards developed more rapidly in breast-fed infants compared to formula-fed infants (P < 0.001). This was parallelled by a decrease in DHA of RBC in formula-fed infants, and with a significantly lower level at two and four months as compared to breast-fed infants. The content of DHA in milk from the breast-feeding mothers was high compared to other Western countries. The difference in visual acuity between the two feeding groups could be due to differences in DHA status as reflected by the RBC levels, but other explanations are possible. Intervention studies are required to verify if development of visual acuity in term formula-fed infants is dependent on the DHA level of formula.

Breast Feeding↗
PubMed1996

Insulin resistance syndrome in adolescents.

To explore whether the so-called insulin resistance syndrome can be identified in adolescents, serum insulin level was measured in 842 healthy Swedish adolescents (462 boys and 380 girls) and the values were related to current serum lipoprotein and apolipoprotein values (triglyceride [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C), low-density lipoprotein cholesterol [LDL-C], apolipoprotein [apo] A-I, apo B, and lipoprotein(a)), blood pressure (BP), and anthropometric measurements and previous physical growth. Mean serum insulin values were higher in 14-year-olds as compared with 17-year-olds and were highest in midpuberty. Adolescents with a high serum insulin had a higher attained height and weight during infancy and childhood. Obesity (body mass index [BMI] > 30 kg/m2) was found in 1% of both boys and girls, and hypertensive BP levels were found in 3% of the boys and 1% of the girls. Controlling for age, serum insulin correlated positively with BMI (r = .36 and .25 in boys and girls, respectively), TG (r = .32 and .14), LDL-C (r = .17 and .24), and apoB (r = .23 and .23) and negatively with HDL-C (r = -.13 and -.21). High serum insulin, TG, LDL-C, and BP and low HDL-C clustered in adolescents with high BMI. In conclusion, the findings of this study indicate that features typical of the insulin resistance syndrome are already present in adolescents.

Adolescent↗
PubMed1996

Carboxylic ester hydrolase and amylase in ischemic pancreatitis in the guinea pig.

The observation that an elevated level of pancreatic carboxylic ester hydrolase (CEH) in serum is a more sensitive and specific marker of acute pancreatitis than is elevated serum amylase activity prompted us to explore whether these findings could be confirmed in an experimental model and, if so, to find the explanation behind this difference. We therefore developed a model for ischemic pancreatitis in the guinea pig and a sandwich enzyme-linked immunosorbent assay for determination of CEH in this species. There was a strong correlation between duration of ischemia and severity of pancreatic inflammation and between severity of inflammation and serum CEH level. In contrast, serum amylase was elevated only in animals with the most severe grade of inflammation. Amylase was, however, increased in urine in animals with mild inflammation, but the level did not increase with severity of inflammation. Only one of 31 animals had detectable CEH in urine. In animals with intermediate serum CEH levels the serum and biliary concentrations correlated, indicating that CEH may be cleared by the liver. Amylase was detectable in bile only in animals with high serum levels. The results confirm our observations made in previous clinical studies. A likely explanation for differences in serum levels of CEH and amylase is clearance from the circulation at different rates and, at least partly, via different routes, e.g., the liver and kidney, respectively.

Amylases↗
PubMed1996

Cardiovascular risk indicators cluster in girls from families of low socio-economic status.

We evaluated tobacco use, physical activity, dietary intake and cardiovascular risk indicators (s-lipids, s-insulin, s-ferritin, anthropometric measurements, blood pressure, physical fitness) in healthy 14- and 17-year-old Swedish adolescents in relation to socio-economic status (SES) of their parents. Girls reported more smoking than boys (14-year-olds 10 and 3%, 17-year-olds 27 and 18%, girls and boys, respectively). Daily smoking was associated to low SES of the family, but was most strongly associated to smoking in peers (OR = 58.7). Tobacco use was considerably higher among adolescents attending vocational programs at secondary high school as compared with theoretical programs. Daily smokers had a more unfavourable serum lipid profile compared with non-smokers. Adolescents from families with a low educational level of the mother had a higher relative dietary fat intake. Boys and girls from families of low SES had higher body mass index (BMI), and girls, but not boys, also had lower physical fitness. Clustering of high BMI, low physical fitness and daily smoking was more pronounced in girls from families of low SES. In conclusion, our study shows that in both boys and girls low SES and educational level of the parents are related to an unfavourable cardiovascular risk profile in Swedish adolescents. Furthermore, smoking in adolescents is more related to smoking in peers than to smoking in parents, implying that preventive efforts should focus on peer groups.

Adolescent↗
PubMed1996

Nucleotides in human milk: sources and metabolism by the newborn infant.

Ribonucleotides in human milk have been claimed to have several effects in recipient infants. It is, however, not known whether the nucleotides found in human milk result from degradation of nucleic acids or are actively secreted as a response to a nutritional demand of the infant. Furthermore, little is known of the newborn infant's endogenous capacity to digest nucleic acids to absorbable products. We therefore analyzed human milk, during established lactation, with respect to the concentration of nucleic acid and ribonucleotide metabolites. Expressed as nucleotide equivalents, 68 +/- 55 mumol/L were present as nucleic acid, 84 +/- 25 mumol/L as nucleotides, and 10 +/- 2 mumol/L as nucleosides. The nucleotide/nucleoside profile showed a substantial predominance for pyrimidines and uric acid. This specific profile could, at least to some extent, result from limited catalysis during storage of the milk in the breast, because enzymes capable of degrading nucleotides were found in the milk. To evaluate the endogenous capability of newborn infants to metabolize RNA and nucleotides, fetal small intestine was analyzed for relevant digestive enzymes. Such intestine, from a fetus of 22-wk gestation, digested RNA to cytidine, uridine, and uric acid in vitro. Furthermore, a fetal small intestinal homogenate generated a net increase in pyrimidines and purines when incubated with human milk, whereas when incubated with infant formula, devoid of nucleic acids, it did not.

Animals↗
PubMed1995

Recombinant human-milk bile-salt-stimulated lipase. Functional properties are retained in the absence of glycosylation and the unique proline-rich repeats.

Human milk bile-salt-stimulated lipase ensures efficient utilization of milk lipid in breast-fed infants. The N-terminal two-thirds of the peptide chain is highly conserved and shows striking similarities to typical esterases. In contrast, the remaining C-terminal part consists of a unique sequence of 16 proline-rich O-glycosylated repeats of 11 residues each. Recently we could show, using recombinant lipase variants, that neither these repeats nor the single N-linked sugar chain are essential for catalytic efficiency. In the present study, we report on the lack of importance of glycosylation and the unique repeats for other important functional properties, i.e. bile-salt activation, heparin binding, heat stability, stability at low pH and resistance to proteolytic inactivation. Compared to native enzyme, recombinant full-length lipase produced in two mammalian cell lines differed slightly in glycosylation pattern with no effects on the functional properties. Moreover, a variant lacking all repeats and the C-terminal tail following the last repeat exhibited the same functional characteristics as purified native milk enzyme. Thus, the structural basis for all the typical and functionally important properties reside in the N-terminal conserved part, in spite of the fact that none of these properties are shared by typical esterases. We could however, demonstrate that the C-terminal repeats are responsible for the unusual behaviour of the enzyme in size-exclusion chromatography, resulting in a considerably higher than expected apparent molecular mass.

Animals↗
PubMed1995

Serum lipid values in adolescents are related to family history, infant feeding, and physical growth.

Total serum cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein (a) (Lp(a)) were analysed in 879 14- and 17-year-old healthy adolescents (477 boys and 402 girls), and related to family history of cardiovascular disease, early feeding, weight and length at birth, and physical growth during infancy and childhood. Mean TC was significantly higher in girls than in boys (4.4 and 4.2 mmol/l, respectively, both age-groups together). High TC values ( > 5.2 mmol/l) were more prevalent in girls than in boys: 14% and 17% compared to 6% and 12% in 14- and 17-year-old girls and boys, respectively. Mean TC and LDL-C values were lower during mid-puberty in both boys and girls while, in boys but not in girls, mean HDL-C values decreased and TG values increased successively with increasing pubertal stage. Girls who were taking oral contraceptives had higher mean values of TC (4.91/4.39 mmol/l), TG (1.32/0.83 mmol/l), and apo B (0.89/0.73 g/l). Boys with a family history of early deaths ( < 55 years) from myocardial infarction and girls with a family history of cerebral haemorrhage/thrombosis in fathers had higher mean values of TC (4.55/4.17 and 5.03/4.40 mmol/l, for boys and girls, respectively), LDL-C (2.84/2.47 and 3.08/2.56 mmol/l), and apo B (0.73/0.70 and 0.86/0.73 g/l). Adolescents with short duration of breast feeding ( < 6 months), or early introduction of infant formula, had higher mean values of TC (4.29/4.14 mmol/l) and apo B (0.72/0.68 g/l). There were no significant correlations between serum lipid values and body weight or length at birth, but adolescents with high LDL-C (upper quartile) seemed to have lower attained heights during infancy and childhood. In conclusion, this study shows that serum lipids in adolescence are primarily related to age and sex but also to early determinants like family history of cardiovascular diseases, infant feeding, and early physical growth.

Adolescent↗
PubMed1995

Sex differences in iron stores of adolescents: what is normal?

We evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school-based cross-sectional study were analyzed for serum ferritin (SF), serum iron, total iron-binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7-day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14- and 17-year-olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values < 12 micrograms/L. Of the 17-year-old boys, 7% compared to 1% of the 17-year-old girls had SF values > 100 micrograms/L. Forty-one percent of cases with SF values > 12 micrograms/L had serum iron values < 15 microM, and 22% had transferrin saturation values < 16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (< 12 micrograms/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut-off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.

Adolescent↗