PubMed Health⌕ Search

Biomedical subjects

R R Kohn

Publications and source records attributed to R R Kohn.

At least 19 recordsLinked to original sources
PubMed1986

Relation between complications of type I diabetes mellitus and collagen-linked fluorescence.

Nonenzymatically glycosylated proteins gradually form fluorescent cross-linked protein adducts--a process termed "browning." The rate of this reaction increases with the glucose concentration. Assaying for the presence of browning products in long-lived proteins should therefore provide information on long-term metabolic control. We measured collagen-linked fluorescence typical for nonenzymatic browning in skin-biopsy specimens from 41 subjects with longstanding Type I diabetes and from 25 controls. Fluorescence correlated with age and (weakly) with the duration of diabetes. Mean age-adjusted fluorescence values were twice as high in diabetic subjects as in control subjects (P less than 0.0001) and increased with the severity of retinopathy, nephropathy, and arterial and joint stiffness. The correlation was significant for retinopathy (r = 0.42; P less than 0.01), arterial stiffness (r = 0.41; P less than 0.01), joint stiffness (r = 0.34; P less than 0.05), and the sum of all complications (r = 0.47; P less than 0.01). Fluorescence also correlated with systolic (r = 0.42; P less than 0.01) and diastolic (r = 0.36; P less than 0.05) blood pressures. If one can assume that the fluorescence results from a browning product of glucose, our data suggest that there is an overall correlation between the severity of diabetic complications and cumulative glycemia over many years.

Adult↗
PubMed1984

Accelerated age-related browning of human collagen in diabetes mellitus.

The nonenzymatic glycosylation reaction that is accelerated in diabetes is the first step of the Maillard or nonenzymatic browning reaction that occurs in stored food. The glucose-protein adduct rearranges and dehydrates to form brown and fluorescent pigments, which can act as crosslinks, resulting in decreased protein solubility and altered mechanical properties. Evidence suggesting that this process occurs in vivo has been found in lens crystallins. The observation that nonenzymatic glycosylation and insolubility increases in collagen with age and diabetes led us to investigate the possible browning of human collagen. Insoluble human dura mater collagen was digested with collagenase. Absorbance at 350 nm and fluorescence at 440 nm (excitation at 370 nm) of the solubilized material was measured. A linear increase in the amounts of yellow and fluorescent material was observed with age. Samples obtained at autopsy from three type I diabetics and a young type II diabetic showed increased fluorescence and had absorbance values that corresponded to the amount of chromophore found in nondiabetics twice their age (P less than 0.025). The collagen adducts from aged and diabetic individuals had absorption and fluorescence spectra identical to those of collagen samples that underwent nonenzymatic browning with glucose in vitro. The structure of these collagen adducts is unknown. However, their likely occurrence throughout the body could explain the correlation between arterial stiffening, decreased joint mobility, and the severity of microvascular complications in type I diabetics.

Adult↗
PubMed1984

Collagen aging in vitro by nonenzymatic glycosylation and browning.

Aging and diabetes mellitus are associated with cross-linking and nonenzymatic glycosylation of collagen. Incubation of tendon fibers with reducing sugars results in increased breaking time in urea similar to that seen in aging, and in nonenzymatic glycosylation and browning. Effect of a sugar is proportional to the amount of sugar available in the open chain form. The increase in breaking time correlates with the appearance of chromophores characteristic of crosslinked browning products. Collagen altered by nonenzymatic browning may play a role in some age-like major complications of diabetes.

Aging↗
PubMed1983

Human collagen digestion: I. Nature of the digestion kinetics as a function of age and structure.

The digestion of human collagen by bacterial collagenase was studied in order to relate collagen structure to the digestion kinetics. The digestion was shown to be first order in collagen and in collagenase on given material from run to run. There was no product inhibition and no enzyme deactivation. However, the rate changed with age, and also within a run as a function of conversion. It was shown that the normalized time (time X enzyme concentration), to reach a given amount of digestion can be plotted as a linear function of the sample age, from 20 to 70 years. The digestion broke down into two regions. The first was a rapid first order region which amounted to about 10% of the collagen. The second region could be graphed as a second order plot to obtain a straight line. This implied that the rate of digestion was functionally second order in collagen; first order in concentration and first order in conversion of collagen.

Adult↗
PubMed1983

Human collagen digestion: II. Theoretical model and application to data.

A kinetic mechanism for the digestion of collagen by bacterial collagenase has been proposed which is consistent with experimental data. Arguments are presented justifying the application of a homogeneous approach to the digestion of insoluble collagen. The mechanism takes account of increased kinetic blockages with aging and enzyme complexity. It is shown to be applicable to collagen from various tissues, including relatively impure preparations. However, the mechanism is not applicable to collagen from the immature period of the lifespan. Kinetic blockages are shown to increase three- to four-fold from age 20 to 70 years, within the main helical region of the collagen molecule. There is no increase of kinetic blockages in the N-terminal region of the molecule over this age range.

Adult↗
PubMed1983

Effects of age and diabetes mellitus on cyanogen bromide digestion of human dura mater collagen.

To extend previous studies on the apparent acceleration of collagen aging in diabetes mellitus, dura collagen from human adults of different ages, with and without diabetes, was processed to yield soluble and insoluble fractions. Insoluble fractions were cleaved by cyanogen bromide. Release of peptides from insoluble collagen by cyanogen bromide decreased markedly with age and was much less from the collagen of diabetics than from nondiabetics of similar ages. The acrylamide gel profiles of peptides released were similar, but not identical, for samples of different ages and for samples from diabetics. It was concluded that age-dependent and diabetes-dependent cross-linking was widespread throughout helical regions of collagen molecules and that collagen throughout the body is altered in diabetes. Analyses of fragments of insoluble collagen are required to gain information on the chemistry of the cross-links that form with aging and diabetes.

Adult↗
PubMed1982

Cause of death in very old people.

According to the Vital Statistics, white women have a modal life span of 85 to 90 years, with most individuals dying at around the same age from either ischemic heart disease, cerebrovascular disease, pneumonia, or accidents, or at earlier ages from malignant neoplasms. White men die earlier than women, and nonwhite populations contain two or more subpopulations that die earlier than white populations. Major causes of death listed in Vital Statistics show similar patterns in the aged for all populations. A review of autopsy findings in 200 persons older than 85 years yielded a very different pattern. No acceptable cause of death, other than complications of the aging syndrome, was identified in at least 30% of the cases. Vital Statistics for the aged is misleading because diagnoses are not definitive. Physicians accept causes of death in the aged that would not be acceptable in younger persons, and the role of aging processes themselves as cause of death are not appreciated. Aging is characterized by a universal progressive decline in physiological function to the point where life cannot be maintained in the face of otherwise trivial tissue injury. It is proposed that senescence be viewed as a disease and be accepted as a cause of death.

Age Factors↗
PubMed1981

Effects of age and diabetes mellitus on the solubility and nonenzymatic glucosylation of human skin collagen.

Collagen from human skin was fractionated into neutral salt-soluble, acid-soluble, pepsin-released, and insoluble fractions. No age-related changes were observed in the proportion of collagen extracted by neutral salt. A significant age-related decrease in the proportion of acid-soluble collagen was found. A highly significant (P less than 0.001) age-related decrease in the amount of collagen released by pepsin digestion was observed, with a concomitant age-related increase in the fraction of insoluble collagen. The amount of ketoamine-linked glucose bound to this insoluble collagen also increased significantly with age. Skin collagen from three juvenile onset diabetics (JOD) and one young maturity onset diabetic (MOD) appeared to have undergone accelerated aging. JOD and the young MOD had significantly less collagen released by pepsin digestion and significantly more insoluble collagen than would be predicted by their ages. The collagen released by pepsin digestion of the diabetic samples had more high molecular weight components than similar fractions obtained from age-matched nondiabetic controls. There was also more ketoamine-linked glucose bound to the insoluble collagen of JOD than to that fraction from comparably aged control subjects. The apparent acceleration of collagen aging in diabetes mellitus may play a role in complications of diabetes that occur in collagen-rich tissues.

Adolescent↗
PubMed1980

Glucosylation of human collagen in aging and diabetes mellitus.

Several of the characteristic complications of diabetes mellitus resemble age-like changes in collagen-rich tissues. It has been reported that increased glucosylation of hemoglobin and serum proteins occurs in diabetes. Glucosylation of insoluble human tendon collagen, a protein with little or no turnover was determined by a thiobarbituric acid method in 23 subjects as a function of age and the presence or absence of diabetes. Amounts of glucose and collagen solubilized by collagenase digestion of the samples were also determined. Glucosylation of collagen was found to increase with age and was markedly increased in juvenile onset diabetes. There appeared to be a limit to the amount of glucosylation that could occur, and older individuals with maturity-onset diabetes demonstrated glucosylation within that limit. The glucose nonenzymatically bound to human collagen may indicate the level of long-term control of the diabetes, and may play a role in the alteration of collagenous tissue properties that occurs in both aging and diabetes.

Adolescent↗