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M Novak

Publications and source records attributed to M Novak.

142 records · Page 8Linked to original sources

Immunological characterization of the region of tau protein that is bound to Alzheimer paired helical filaments.

Tau protein is known to be present in the paired helical filaments (PHFs) of Alzheimer brains. This study investigated the fragments of tau protein that remain bound to pronase-treated PHFs and conditions that lead to the release of these tau fragments from the core structure of the PHF. Antibody 423 reacted with PHFs and with fetal rat tau but not with adult rat tau, pig tau, or recombinant human tau. Three other antibodies that react with the tubulin binding region of tau only reacted with PHFs after they were disrupted with formic acid or guanidine. Other antibodies that recognize tau sequences C terminal to the tubulin binding region also recognized pronase-treated PHFs. Antibodies SMI34 and T3P that recognize phosphorylated epitopes were reactive with pronase-treated PHFs. Tau fragments from the PHF were solubilized by acid or guanidine treatment. These findings suggest that the fragments of tau that are bound to PHFs and protected from pronase digestion include sequences from the tubulin binding region to the C terminus of tau. In addition, some of these sequences appear to be conformationally or post-translationally modified.

Alzheimer Disease

A clue to the basic defect in cystic fibrosis from cloning the CF antigen gene.

The metabolic basis of the autosomal recessive disease cystic fibrosis (CF) remains unidentified. Elevated levels of a serum protein in CF homozygotes and obligate heterozygotes have been described. As heterozygotes are clinically unaffected, any consistently observed abnormality in these individuals is a likely pointer to the aetiology of the disease. The gene for this serum protein, called cystic fibrosis (CF) antigen, has been mapped to chromosome 1. It is not the gene that is mutant in CF because this has since been assigned to chromosome 7 by cosegregation of the disease with closely linked DNA markers in CF families. CF antigen is a product of normal and leukaemic granulocytes and is inducible in the promyelocytic cell line HL60 (M.N., J.D., C. Hayward, F. Northrop, D.J.H.B., J. Walker, V. van H. and D.S.S., manuscript in preparation). We have isolated cDNA clones for this protein from a library constructed with messenger RNA from chronic myeloid leukaemia (CML) cells. The complete nucleotide sequence was obtained from the cDNA clone and by primer extension of mRNA. We have confirmed that the gene encoding CF antigen is on chromosome 1 and have localized it to a particular region. RNA blot analysis shows a 550-bp major transcript in CML cells and in induced HL60. The amino-acid sequence predicted from the nucleotide sequence shows significant homology with intestinal and brain calcium-binding proteins. Abnormal accumulation of such a protein in CF is a clue which must be pursued now that evidence is gathering that the basic defect in CF is in pathways controlling chloride channel activity.

Amino Acid Sequence

L-carnitine supplementation of a soybean-based formula in early infancy: plasma and urine levels of carnitine and acylcarnitines.

The absence of carnitine in the diet of normal infants results in marked reduction of plasma carnitine levels. In order to evaluate the effects of L-carnitine supplementation of soybean formula, plasma and urine levels of free carnitine and acylcarnitine were compared in infants receiving carnitine-free soybean protein-based formula and the same formula supplemented with 50 and 250 nmol/ml L-carnitine. In infants receiving soybean formula with 50 nmol/ml L-carnitine, the plasma levels of free carnitine were not significantly different from those in infants receiving formula with 250 nmol/ml L-carnitine; however, urine levels of free carnitine were significantly increased when the infants received formula with 250 nmol/ml L-carnitine. In normal full-term infants, supplementation of soybean formula with 50 nmol/ml L-carnitine was sufficient to maintain normal plasma levels that were comparable to breast-fed infants.

Acetylcarnitine

Biography after the end of metaphysics: a critique of epigenetic evolution.

This article places Erik Erikson's model of ego development against the ground of modern culture. It finds that this model fails to see the relationship between individual crises and the modern postmetaphysical world view, where the meaning of life is in question. The article suggests that Erikson's description of crisis and ego integration remains sound, but that this process should be tied to the specific problems associated with living in modern society. The article ends by returning to Erikson's original insight: that we need to locate the life cycle in the social-cultural setting in which it unfolds. This will make the study of biography at once a psychological analysis and a cultural critique.

Biological Evolution