Genomic organization and chromosomal localization of the mouse IKBKAP gene.

The autosomal recessive disorder familial dysautonomia (FD) has recently been demonstrated to be caused by mutations in the IKBKAP gene, so named because an initial report suggested that it encoded an IkappaB kinase complex associated protein (IKAP). Two mutations in IKBKAP have been reported to cause FD. The major mutation is a T-->C transition in the donor splice site of intron 20 and the minor mutation is a missense mutation in exon 19 that disrupts a consensus serine/threonine kinase phosphorylation site. We have characterized the cDNA sequences of the mouse, rat and rabbit IKBKAP-encoded mRNAs and determined the genomic organization and chromosomal location of mouse IKBKAP. There is significant homology in the amino acid sequence of IKAP across species and the serine/threonine kinase phosphorylation site altered in the minor FD mutation of IKAP is conserved. The mouse and human IKBKAP genes exhibit significant conservation of their genomic organization and the intron 20 donor splice site sequence, altered in the major FD mutation, is conserved in the human and mouse genes. Mouse IKBKAP is located on the central portion of chromosome 4 and maps to a region in which there is conserved linkage homology between the human and mouse genomes. The homologies observed in the human and mouse sequences should allow, through the process of homologous recombination, for the generation of mice that bear the IKBKAP mutations present in individuals with FD. The characterization of such mice should provide significant information regarding the pathophysiology of FD.

Familial dysautonomia is caused by mutations of the IKAP gene.

The defective gene DYS, which is responsible for familial dysautonomia (FD) and has been mapped to a 0.5-cM region on chromosome 9q31, has eluded identification. We identified and characterized the RNAs encoded by this region of chromosome 9 in cell lines derived from individuals homozygous for the major FD haplotype, and we observed that the RNA encoding the IkappaB kinase complex-associated protein (IKAP) lacks exon 20 and, as a result of a frameshift, encodes a truncated protein. Sequence analysis reveals a T-->C transition in the donor splice site of intron 20. In individuals bearing a minor FD haplotype, a missense mutation in exon 19 disrupts a consensus serine/threonine kinase phosphorylation site. This mutation results in defective phosphorylation of IKAP. These mutations were observed to be present in a random sample of Ashkenazi Jewish individuals, at approximately the predicted carrier frequency of FD. These findings demonstrate that mutations in the gene encoding IKAP are responsible for FD.

Vitamin and mineral nutritional status and other biochemical data assessed in groups of men from Crevalcore and Montegiorgio (Italy).

The vitamin and mineral nutritional status of 34 elderly (mean age 77.6 +/- 4.7 years) and 39 younger subjects (mean age 41.7 +/- 7.5 years) from Crevalcore and Montegiorgio (the two rural areas of The Seven Countries Study) was studied. Comparisons have been made between centres, between age groups, and with data obtained from similar surveys performed in 1960 and 1970. Levels of thiamin and riboflavin nutritional status were higher in 1991 than in 1970. Plasma retinol values were above levels of deficiency, but vitamin E and beta-carotene tended to be low. The zinc status of the populations, as assessed by leucocyte zinc concentrations, was generally low. A decline in copper intake during the past ten years may be responsible for the low leucocyte copper concentration which was more apparent in the younger subjects. Serum cholesterol was above, and HDL cholesterol below, the European Atherosclerosis Society recommendations.

Dietary studies on two rural Italian population groups of the Seven Countries Study. 1. Food and nutrient intake at the thirty-first year follow-up in 1991.

The food and nutrient intake at the thirty-first follow-up in 1991 of 16 surviving elderly from Crevalcore and Montegiorgio, two Italian rural ares of the Seven Countries Study, are reported. For dietary appraisal the individual weighed record method for 3 and 9 days in three seasons was used. In autumn the dietary history method was also used. Because the number of survivors was small, 15 additional elderly subjects in both areas were surveyed. Then, to detect any change related to age in food intake, 41 younger subjects were assessed with the dietary history method. The results in both areas showed in general a high intra-individual variability and no statistically significant difference in food group and nutrient intake between seasons. Between the two methods for dietary survey no statistically significant difference, in general, was observed (P > 0.05 only for a few items). The diet of the subjects of Crevalcore was characterized by a rather high intake of milk and meat and a low intake of fish and legumes. In Montegiorgio the picture was similar to that of Crevalcore, but at a lower level of intake. In both areas, but particularly in Montegiorgio, these subjects have been abandoning the traditional Mediterranean diet.

Dietary studies on two rural Italian population groups of the Seven Countries Study. 2. Concurrent validation of protein, fat and carbohydrate intake.

On 18 subjects from two rural areas in Italy which were part of the Seven Countries Study (Crevalcore and Montegiorgio), we carried out the concurrent validation of protein, fat, fatty acid and carbohydrate intake in the diet at the thirty-first year follow-up in 1991. The values of the above nutrients obtained using food composition tables from the weighted record method for dietary surveys were compared with the values from chemical analysis of food composites. In both areas for protein, fat and carbohydrate intake the inter-individual variation was large. For protein intake the mean difference was statistically significant but not for fat intake. From 1960 to 1991 protein and fat intake tended to decrease and for protein the means of differences between analysis and calculation were, in general, statistically different. For dietary saturated and polyunsaturated fatty acids, the means of differences were statistically significant in Crevalcore, but this was not the case in Montegiorgio for polyunsaturated fatty acids. The intake of trans fatty acids in both areas was rather low. Available and unavailable carbohydrate intake of both areas showed no statistically significant difference. The mean differences between analysis and calculation for both areas were statistically significant with the exception of cellulose in Crevalcore and sugars in Montegiorgio.

Nutritional status of a group of self-sufficient institutionalized elderly people in Perugia (Italy).

The nutritional status of forty-six self sufficient institutionalized elderly people of Perugia was assessed. The diet of this group is slightly better than that of other groups of elderly people previously examined. As observed in other studies, the diet of the elderly from this region of Italy does not seem to be of the Mediterranean type. The location of subcutaneous fat in elderly men is prevalent in the upper trunk and in women in the arms. The clinical signs of nutritional status among this group of self-sufficient institutionalized elderly people are in general not specific and mostly associated with old age. The pathological conditions observed and the administration of drugs do not appear to substantially influence the nutritional status of this group.

Nutritional status of the elderly V). Dietary and biochemical data and anthropometry of noninstitutionalized elderly in Perugia at the eleventh year follow-up.

The nutritional status of 93 noninstitutionalized elderly of the city of Perugia, mostly of them examined longitudinally, was assessed at the eleventh year follow-up. Diet is still rather rich and unbalanced. Alcohol intake in men is very high. Biological dietary errors have an impact on the nutritional status, particularly for folates, of the individual. But in this regard it is interesting to note that in some cases vitamin and mineral nutriture has improved at this follow-up. In addition the distribution of malnutrition is rather different from that of the previous follow-up. As on previous occasions, no correlation was observed between vitamin intake and corresponding nutritional status (with the exception of riboflavin). Obesity is rather common among women; men present a higher muscular area and hand muscular strength. The clinical evaluation of nutritional status evidences principally changes which are mostly ascribable to old age. Among the pathologies, chronic ischemic heart disease, hypertension, chronic respiratory diseases, osteoarthrosis and diabetes occur most frequently.

[Observations on a population of over-80-year-olds hospitalized in a medical department in the 1985-1986 biennium (1/1/85-12/31/86)]. / Osservazioni su una popolazione di ultraottantenni ricoverati in una divisione di medicina nel biennio 1985-1986 (1.1.85-31.12.86).

542 of 2538 clinical records of admissions to a General Medicine Division in the two-year period 1985-1986 regarding a population of over-eighties have been examined. Personal, clinical, hematochemical and instrumental details were collected, processed and commented, comparing them with the same data obtained in the general population of the same age.

Nutritional status of a group of institutionalized elderly people in Perugia (Italy).

In this group of institutionalized elderly people the anthropometry and body composition situation is much better than that observed in a noninstitutionalized group examined longitudinally on a previous occasion. On the other hand, as expected, indices of physical activity are lower. The diet is in general satisfactory, considering the very low physical activity of those individuals. Only a few foods and nutrients show marginal low intakes (fish, eggs and legumes; lipids, iron, thiamin and vitamin A).

Food and nutrient consumption of two rural Italian population groups followed for twenty years.

The food and nutrient consumption was examined in two rural population groups of 22 middle age men of Italy in connection with a longitudinal study of coronary heart disease. Most of the data were collected with use of the individual weighing method. In the 20 year interval increases and decreases were observed in the consumption of various foods, reflecting the influence of economic and biological factors. In regard to nutrients, in Crevalcore (Bologna) the original high level of some macronutrients and vitamin A progressively decreased. In Montegiorgio (Marche) the original high level of fat intake - in relation to recommended intake - progressively increased, while energy was throughout close to recommended values. The endemic deficit in riboflavin intake progressively decreased, while that for vitamin A remained practically constant.

[Chemical composition and protein value of some baby foods (author's transl)]. / Composizione chimica e qualità proteica di alcuni alimenti omogeneizzati e liofilizzati per la prima infanzia

The determination of lipids, available carbohydrates and unavailable carbohydrates, and of various minerals has been carried out on some baby foods; the value of the protein fraction has been similarly determined by the ultrafiltration method of the enzymic hydrolisate in vitro. Both the total protein content and the essential amino acid availability of the foodstuffs are satisfactory although generally speaking a slight decrease of the protein value has been found in this material as compared to the crude samples, due particularly to the breakdown of sulfur-containing amino acids. This breakdown is due probably to the high temperature reached during the technological processes at industrial level.

[Food protein quality. 4) Effect of technoligical processing on protein quality of baked products for special dietary uses (author's transl)]. / Sulla qualita' delle proteine alimentari. 4) Effetto dei processi tecnologici sulla qualita' proteica di alcuni prodotti da forno per usi dietetici speciali

On samples of biscuits for special dietary use and rusks has been determined the protein quality with the method of enzymatic ultrafiltrate digest (EUD) at various levels of industrial production. The results have shown that the baking over again process has determined a decrease on the velocity of digestion "in vitro" against the raw material with large variations in availability of various essential aminoacids. Particularly decreased is the lysine, the limiting aminoacid of these food products.