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Biomedical subjects

M Tikkanen

Publications and source records attributed to M Tikkanen.

10 recordsLinked to original sources
PubMed1995

Lack of association of apolipoprotein E allele epsilon 4 with late-onset Alzheimer's disease among Finnish centenarians.

No association between Alzheimer's disease (AD) and apolipoprotein E type epsilon 4 (ApoE epsilon 4) phenotype was found among centenarians in Finland (N = 179). The data are based on ascertainment of all centenarians in Finland in 1991. All examinations were conducted during 1991. The diagnoses of dementia and AD were based on clinical grounds, conforming to DSM-III-R and NINCDS-ADRDA criteria. The percentage of ApoE epsilon 4 alleles among the centenarians was 8.7% (31 of 358 alleles). This is significantly lower than percentages found in younger Finnish populations. Thirty (16.8%) of the 179 centenarians were epsilon 4 allele carriers. One hundred fifty-one (84.4%) of the centenarians were women. Twenty-eight (18.5%) of the women had at least one epsilon 4 allele, as did two (7.1%) of the men. The prevalence of clinically diagnosed AD was 26.8%; 44% of the subjects were cognitively normal, 23% had signs of cognitive decline or at most mild dementia (with no differential diagnosis), and 6% had a dementia clinically diagnosed as being due to some cause other than AD. For AD cases versus cognitively normal subjects, the odds ratio associated with being a carrier of the epsilon 4 allele was 1.34 (p = 0.64; 95% CI = [0.5, 3.3]). Among women, the odds ratio was 0.99 (p = 1.0; 95% CI = [0.4, 2.6]). There were fewer, but not significantly so, epsilon 4 carriers among subjects with cognitive decline or at most mild dementia (12.2%) than there were among the cognitively normal subjects (16.5%). The AD patients had no evidence of difficulty standing on a flat stationary surface unless the surface suddenly moved.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗
PubMed1995

Apolipoprotein E polymorphism and dietary plasma cholesterol response.

All studies have demonstrated a strong association between plasma cholesterol and apoE phenotypes in the following order: E4/E4 > E4/E3 > E3/E3 > E3/E2. It has been thought possible that the apoE gene might be involved in the modulation of dietary plasma cholesterol responses, perhaps explaining the differences in cholesterol concentrations. Some dietary intervention studies have suggested that apoE4 individuals react to dietary change with exaggerated cholesterol responses. In one study, apoE4/E4 individuals responded by increased cholesterol reductions during low fat intake, and by increased cholesterol elevations during switchback to high fat diet. Plausible mechanisms have been postulated which could explain such differences. However, other studies have reported no differences in plasma lipid responses among apoE phenotypes. The studies cannot be directly compared because of different designs and study populations with differing apoE allele frequencies. Thus the possible role of genetic variation in the apoE gene in the modulation of dietary plasma lipid responses remains to be confirmed in prospective dietary studies, involving diets both rich and poor in fat and cholesterol.

Apolipoproteins E↗
PubMed1985

The recognition domain for the low density lipoprotein cellular receptor is expressed once on each lipoprotein particle.

The stoichiometry of binding of monoclonal antibodies and Fab fragments to LDL was assessed. Increasing amounts of two [125I]-labelled antibodies which define epitopes at or near the LDL-receptor recognition domains of apoB were incubated with fixed amounts of LDL and antibody-LDL complexes were separated from free antibodies by heparin-MnCl2 precipitation. Saturation kinetics were obtained and data were analyzed according to Scatchard. One antibody or Fab fragment was bound per LDL particle. Homogeneity of binding was indicated by straight Scatchard lines and by the binding of virtually all LDL particles by an antibody affinity chromatographic column.

Antibodies, Monoclonal↗
PubMed1984

Evolution of low density lipoprotein structure probed with monoclonal antibodies.

To assess the relationship of apoB structures in different species of animals, the expressions of apoB epitopes in the sera or plasmas of 23 different mammalian species and one marsupial, and on the low density lipoprotein (LDL) from three species of apes, six species of monkeys, and eight non-primates were measured in competitive radioimmunoassays. The abilities of the sera or LDL to compete with 125I-labeled human LDL for binding to seven monoclonal antihuman LDL antibodies immobilized on microtiter plates were determined. LDL of apes bound to most antibodies, while monkey LDL bound to two or three antibodies. Other mammalian LDL bound only weakly to two of the antibodies or to none. The two monoclonal antibodies binding the LDL of more species were those antibodies which also inhibited the binding to and degradation of LDL by human fibroblasts. The rank order of binding of the LDL of a given species to the antibodies correlated with the rank order inhibition of binding and degradation of 125I-labeled human LDL in the human fibroblast system. This suggests that epitopes spatially located near the recognition site of apoB for cellular receptors have a greater tendency to be conserved.

Animals↗
PubMed1981

Pituitary function in prolactinoma. Effect of surgery and postoperative bromocriptine therapy.

Forty-five women and fifteen men with prolactinomas have been treated surgically. Patients with large tumours received pituitary irradiation and postoperative hyperprolactinaemia was treated with bromocriptine. The patients have been followed-up for 6-36 months following the operation. The tumours were larger and the levels of production higher in men as compared with women. All women had amenorrhoea. Galactorrhoea was present in forty-three women but not in the men. After surgery serum prolactin levels fell significantly in all women but remained above normal in thirty-six; prolactin remained high in twelve men. Bromocriptine effectively decreased the postoperative hyperprolactinaemia. The surgical complications were oculomotor nerve paresis in one woman and one man. After surgery six (23%) women developed impaired GH secretion, six (15%) impaired thyroid function, eight (18%) impaired cortisol secretion and five (17%) impaired LH secretion in isolation or combination which had not been present preoperatively. Three patients relapsed. Fifteen women menstruated after surgery and ten began to do so during the subsequent bromocriptine treatment. Thus, menstruation was restored in all six women with microadenomas in sixteen of twenty patients with intrasellar macroadenomas and three of nineteen patients with suprasellar adenomas. The preoperative LH-reserve proved to be an important prognostic indicator. Nine patients, i.e. 50% of patients desiring fertility became pregnant. In the men gonadal function deteriorated in four patients and did not improve in any without testosterone treatment.

Adenoma↗