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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 36 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. Restriction fragment polymorphisms of the TNF-β gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. We studied this TNF polymorphism in a sample of diabetic families. In all IDDM-associated haplotypes (n= 129) the 5.5-kb allele was more frequent than in haplotypes found only in healthy family members (n=112) (58.1% versus 40.2%, P〈0.01). Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes-A24,B39,DR4 and A2,B56,DR4-had the 5.5-kb TNF fragment. Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. The distribution of various combinations of TNF alleles in IDDM probands (n= 63) did not differ from that expected according to the Hardy-Weinberg distribution. Our results indicate that the 10.5-kb allele of TNF-β gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. Alternatively, there may be heterogeneity in pathogenetic effector mechanisms.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 305-310 
    ISSN: 1432-0428
    Keywords: Diabetes ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the effect of diabetes on the lipid composition of the lungs and of the pulmonary artery, 43 streptozotocin diabetic rats and 43 control rats were examined. Triglyceride deposits were observed by a histochemical method in the branches of the pulmonary artery in 10 diabetic rats but in none of the controls. In the pulmonary tissue of the diabetic rats the total lipid content was not different from that of control animals, but the relative amount of phospholipids was decreased (p〈0.001), and that of non-esterified fatty acids (p〈0.001) and triglycerides (p〈0.05) increased as compared to the control rats. These results indicate abnormalities in the lipid metabolism of the pulmonary artery and lungs during insulin deficiency.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; incidence ; epidemiology ; time trends ; Finland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Central Drug Registry in Finland ascertained 5,920 incident cases of Type 1 (insulin-dependent) diabetes mellitus diagnosed under the age of 15 years, during 1965–1984. The incidence was higher for males 29.2/100,000 (95% confidence intervals 28.2–30.2/100,000) than for females 26.1/100,000 (25.1–27.1/100,000). A non-linear increase in incidence with age was confirmed, with peaks at ages 2,9 and 14 years in males and at 3,5–6 and 11 years in females. A significant temporal variation in incidence was found, adjusting for age and sex. During 1965 to 1984 the incidence rose by about 57% or by 2.4% annually. However, a non-linear curve with two incidence peaks in 1978 and 1983 would better describe the temporal pattern than a linear trend. There was no significant difference in the temporal variation between males and females. The changes in diabetes risk appeared to affect proportionally all age groups under 15 years. Two possible mechanisms were explored: a calendar period effect vs a birth cohort effect. The calendar time period effect was significant alone and also when adjusted for the birth cohort effect. One the contrary, the birth cohort effect was not significant, when adjusted for the calendar period effect. In conclusion, over the past two decades, the incidence of childhood Type 1 diabetes in Finland has increased by about 57%. The pattern of change was a steady rising background incidence superimposed by sudden outbreaks suggesting environmental causative factors.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Mumps ; mumps antibodies ; mumps-measlesrubella vaccination ; Type 1 (insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A nationwide mumps-measles-rubella vaccination was introduced in 1982 in Finland to children aged 1.5 to 6 years and since then mumps has virtually disappeared in the country. We investigated whether this rapid epidemiological change had any impact on antibody activity against mumps virus in Type 1 (insulin-dependent) diabetic children or on the incidence of Type 1 diabetes in Finland. Two case-control series were collected before (series I and II) and three series after (series III–V) the introduction of the vaccination. IgA class mumps antibody levels were significantly higher in Type 1 diabetic children than in matched control children in the first two but not in the three later series. IgG class antibody levels were similar in patients and control subjects in the first two series but significantly lower in patients than in control subjects in the three later series. The overall incidence of Type 1 diabetes in 0–14-year-old children increased until 1987 but remained about the same during 1988–1990. In 5–9-year-old children no further increase in Type 1 diabetes was seen since 1985, whereas in 0–4-year-old children the incidence continued to rise until 1990. The results suggest that the elimination of natural mumps by mumps-measles-rubella vaccination may have decreased the risk for Type 1 diabetes in Finland; a possible causal relationship is substantiated by the observed concomitant decrease in mumps antibody levels in diabetic children. However, further studies are required to determine if the vaccine virus, like natural mumps, could trigger the clinical onset of Type 1 diabetes in young children.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Infant feeding ; dairy products ; cow's milk protein antibodies ; IDDM ; childhood ; islet cell antibodies ; insulin autoantibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide “Childhood Diabetes in Finland” study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Preclinical IDDM ; islet cell antibodies ; early insulin response ; glucose elimination rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5–69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6–12 months. Seventeen siblings (29.8%) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P〈0.05) and had higher initial ICA levels (P〈0.01). In addition they had a lower FPIR in the first IVGTT (P〈0.001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P〈0.05 or less), a lower glucose elimination rate from the third test onwards (P〈0.01 or less) and higher IAA levels at 3 years (P〈0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P〈0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P〈0.05) and IAA levels up to 3 years (P〈0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. 388-393 
    ISSN: 1432-0428
    Keywords: Key words Preclinical IDDM, islet cell antibodies, early insulin response, glucose elimination rate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5–69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6–12 months. Seventeen siblings (29.8 %) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P〈0.05) and had higher initial ICA levels (P〈0.01). In addition they had a lower FPIR in the first IVGTT (P〈0 .001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P〈0.05 or less), a lower glucose elimination rate from the third test onwards (P〈0.01 or less) and higher IAA levels at 3 years (P〈0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P〈0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P〈0.05) and IAA levels up to 3 years (P〈0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate. [Diabetologia (1994) 37: 388-393]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Adipose tissue ; catecholamines ; diabetes ; exercise ; free fatty acids ; glycerol ; lipolysis ; rat ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Diabetes ; insulin ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of insulin on the triglyceride deposits found in the pulmonary artery branches of streptozotocin-diabetic rats was investigated by treating the animals for two, five, nine or 14 days with insulin (3–8 units/day). Histochemical analysis showed that the triglyceride deposits in the pulmonary artery developed within three to four days after the induction of diabetes, but were not present in any animals five days from the initiation of insulin therapy. Plasma triglycerides, non-esterified fatty acids, phospholipid and total cholesterol concentrations were within the normal range within two days of the inception of insulin therapy and random plasma glucose levels were normal within five days. Analysis of lung lipids showed that after 14 days of insulin treatment the decreased content of phospholipids and the increased content of non-esterified fatty acids found in diabetic rats were also normalized. These findings suggest that insulin has an important role in the regulation of lipid metabolism in the pulmonary artery and lung tissue in the diabetic state.
    Type of Medium: Electronic Resource
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