F. Marott Sinex

Identification of a new crosslinking amino acid in elastin

Abstract Recently, Partridge et al . (1963) described the occurrence in elastin of two hitherto unrecognized amino acids for which evidence has now accrued to show their origin from lysine residues in a “pre-elastin” (Partridge et al ., 1964; Miller et al ., 1964). These substances, called desmosine and isodesmosine, are in fact quaternary pyridinium compounds with four side-chain substituents that function in crosslinking of elastin chains (Thomas et al ., 1964). An examination of peptide fractions of elastin selected for enrichment with respect to the desmosines revealed the presence of an additional amino acid, called X 4′ also previously undescribed (Franzblau et al ., 1965). The present communication presents data to show that X 4 can be represented by the formula, N ϵ -(5-amino 5-carboxypentanyl)-lysine.

Biochemistry of Aging The mechanism of aging presents a challenge to modern biochemistry and biology

It should be apparent that while no one really understands all the fundamental mechanisms underlying the aging process, progress is being made, and theories are being advanced which may be tested in the laboratory.

Alzheimer's disease, Down's syndrome, and aging: the genetic approach.

HEN I first heard that adults with Downs syndrome aged prew maturely and died with the stigmata of Alzheimers disease, I was excited because i t seemed to me that if Downs syndrome was due to a trisomy of chromosome 21, then Alzheimers disease in karyotypically normal subjects must be due to some sort of disorder in gene expression on that chromosome. In this paper we will present evidence that Alzheimers disease is an inherited disease, whose penetrance in a particular family is a function of aging.

On the relationship of brain filaments to microtubules.

Abstract— A method has been developed for the isolation of a previously undescribed fibrous protein from rat brain. The newly isolated material consists of bundles of tightly packed 70‐80 Å diameter filaments. Based on studies employing degenerated rat optic nerve, it is proposed that these filaments correspond to the well‐described astrocyte filaments observed in sectioned preparations of mammalian brain. The purified filaments are stable over a wide temperature range, are not disrupted by colchicine, and exhibit limited solubility in the absence of denaturants or detergents. In neutral SDS‐polyacrylamide gel electrophoresis, the filament protein runs as a single band with an apparent molecular weight of 57,000 daltons. This preparation also migrates as a single band in alkaline urea gels, and as a well‐resolved doublet on discontinuous SDS‐urea gels. In all three electrophoretic systems, the filament subunits co‐migrate with rat brain tubulin. Comparative peptide maps of the filament subunits and tubulin indicate a large degree of homology. Our results suggest that microtubules and astrocyte filaments are composed of the same or very similar protein subunits.

Epinephrine-induced cyclic AMP production in skin fibroblasts from patients with dementia of Alzheimer type and controls

Skin biopsies were obtained from six patients with dementia of Alzheimer type (DAT) and from three hospitalized age matched controls. Fibroblasts from these biopsies were grown in culture and compared for their growth characteristics and sensitivity to epinephrine with four cultures from age matched healthy individuals. The growth characteristics were similar in all three groups. The basal levels of cyclic AMP and the epinephrine-induced increase of cyclic AMP levels were also similar in control and DAT cells.

The mortality of adults with down symdrome as a function of age

This study sought to test the hypothesis that adults with Down Syndrome may age faster than the general population by comparing the rate of increase in their mortality with age with that of the general population by the method originally described by Gompertz. The differences were not statistically significant. There is a striking difference in morbidity, the Downs adults being highly vulnerable. Alzheimer populations do not lend themselves readily to this type of analysis.

The interaction of protein with single strands of DNA and RNA

Summary A possible way in which single-stranded polynucleotide might interact with protein is described. Hydrogen bonds between glutamine and asparagine, and pyrimidine and purine, somwhat analogous to Watson-Crick base pairs, are visualized. The model suggests that proteins involved in single-strand interaction would be rich in glutamine and asparagine and that these residues would occur in sequences in which they were separated by two residues of some other amino acid.

Theoretical Mechanisms of in Vitro Senescence

In this chapter we will discuss how somatic mutations might be involved in the senescence of cells in culture and in the intact organism. We will also discuss the possible role that stable phenotypic variations may play in senescence.

Opening Remarks by Chairman

The attendance of this meeting at this early hour testifies to the interest in tritium. Each of you probably has his own special interest in tritium which we hope will be discussed by one or more of our speakers. However, I think a few general remarks about tritium might be in order.

Book Review: Alzheimer's disease research: Ethical and legal issues:

This book on the ethical and legal issues which are raised by research with Alzheimer patients, had its origins in a conference at the Queen Elizabeth Hospital in Toronto in January 1989. The book is about the social contract between physicians who feel compelled to do research on Alzheimers disease by its devastating natureand the victims of the disease who are their subjects. The participating clinical investigators sought the advice and comment of six distinguished ethicists and jurists. Thirty-eight individuals have contributed portions of 20 carefully edited chapters, according to a plan which has avoided at least some of the hazards of multiple authorship. The primary prospective audience is other clinical investigators. The first two chapters set the general framework of the ethical and legal issues about research on patients with Alzheimers disease. In a calm judicious style, general principles are introduced about why research is important and why there are special problems with treating Alzheimer patients fairly and with respect to their rights as human beings.