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M H Nathanson

Publications and source records attributed to M H Nathanson.

80 records · Page 5Linked to original sources
PubMed1989

Plasma kinetics of complement component C4: comparison of three models.

Plasma C4 kinetics were studied in members of a kindred with hereditary incomplete C4 deficiency and in control subjects. Test subjects received iodine 125-labeled C4 intravenously, and plasma disappearance curves for 125I-C4 were plotted. By nonlinear least-squares analysis, we fit two-, three-, and four-exponential models of plasma disappearance to the plasma curves of each subject. Goodness of fit was significantly better for all subjects with the three-exponential versus the two-exponential model (p less than 0.0005). No further improvement in curve fit was accomplished by using a four-exponential model (p greater than 0.5). Metabolic rates and extravascular/plasma ratios calculated from the two- and three-exponential models were significantly different. As judged by extravascular/plasma ratio, the two-exponential model underestimated the amount of extravascular C4. Furthermore, the two-exponential model significantly over-estimated catabolic and synthetic rates. Hence, our results show that C4 kinetics are not optimally described by a conventional, two-exponential model. A possible explanation for our findings is that in previous studies of C4 metabolism, the analysis of plasma radioactivity disappearance curves was done by inspection, whereas we used least-squares analysis, a method that determines the number of exponentials with greater reliability.

Complement C4↗
PubMed1987

Metabolism of C4 and linkage analysis in a kindred with hereditary incomplete C4 deficiency.

We studied a kindred in which C4 deficiency had been discovered. Unlike families with total absence of C4, in this kindred C4 deficiency was found to be incomplete, autosomal dominant, not caused by null alleles, and not associated with a high incidence of systemic lupus erythematosus. The deficient state was caused by hyposynthesis of C4, not by hypercatabolism. The locus for incomplete C4 deficiency was not closely linked to the major histocompatibility complex. The abnormal autosomal dominant allele is, apparently, rare, and how it causes decreased synthesis of C4 is unknown.

Adult↗
PubMed1987

Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs.

The quantity and distribution of body iron normally vary little over time. This homeostasis is maintained primarily through control of intestinal iron absorption, but the mechanism of this regulation is unclear. Modern techniques for computer simulation and numerical analysis now make it possible to study the kinetics of iron absorption in vivo. We used a physiologically based mathematical model of iron metabolism to analyze tracer iron kinetics in normal and iron-deficient beagles. The model provides characteristic information about both intestinal and systemic iron exchange, thus permitting formulation of an hypothesis that may explain the regulation of iron absorption under these conditions. The results indicate that control of iron absorption is a function of independent expression of iron requirements by each tissue, including the intestinal mucosa. This hypothesis is consistent with other in vivo and in vitro observations in iron deficiency and may have implications for understanding the mechanism of the altered iron absorption in other disorders of iron metabolism.

Animals↗
PubMed1985

Iron absorption in normal and iron-deficient beagle dogs: mucosal iron kinetics.

Absorption of dietary iron requires uptake of iron by the brush border of the intestinal epithelial cells, intracellular transport, and transfer to the systemic circulation. In iron-deficiency anemia, iron absorption is greatly increased, but the individual steps responsible for this increase have not been identified. We have developed a method to evaluate the rate constants for each of these steps, and we report here our results in beagle dogs a) under normal conditions and b) after phlebotomy to produce iron-deficiency anemia. Simultaneous administration of oral 59Fe3+-citrate and intravenous 55Fe-transferrin was used to investigate the kinetics of mucosal iron transport. Plasma levels of both isotopes and the whole-body excretion pattern of 59Fe were monitored sequentially, and the fractional mucosal transport rates were estimated by nonlinear least-squares fit of a physiologically based mathematical model to these data. Under normal conditions the fractional rate of mucosal iron uptake from the intestinal lumen was rate limiting, being less than 1% of the fractional rate of either iron incorporation into the mucosal storage pool or transfer of iron from the mucosa to the plasma. After induction of iron-deficiency anemia, the fractional mucosal iron uptake rate increased sixfold (P less than 0.005), while the rate of incorporation into the mucosal storage pool decreased ninefold (P less than 0.02); in contrast, the fractional rate of iron transfer to the plasma did not change. These results indicate that the enhanced iron absorption in iron-deficiency anemia is attributable to an increase in mucosal iron available for transfer to the plasma, leading in turn to a net increase in iron absorption, despite a normal fractional transfer rate.

Anemia, Hypochromic↗
PubMed1985

Multiple-objective criteria for optimal experimental design: application to ferrokinetics.

Optimal experimental design is used to predict the experimental conditions that will allow the "best" estimates of model parameters. A variety of criteria must be considered before an optimal design is chosen. Maximizing the determinant of the information matrix (D optimality), which tends to produce the most precise simultaneous estimates of all parameters, is commonly considered as the primary criterion. To complement this criterion, we present another whose effect is to reduce the interaction among the parameter estimates so that changes in any one parameter can be more distinct. This new criterion consists of maximizing the determinant of an appropriately scaled information matrix (M optimality). These criteria are applied jointly in a multiple-objective function. To illustrate the use of these concepts, we develop an optimal experimental design of blood sampling schedules using a detailed ferrokinetic model.

Humans↗
PubMed1984

A model of intestinal iron absorption and plasma iron kinetics: optimal parameter estimates for normal dogs.

A multicompartment model describing the physiological processes of intestinal iron absorption has been developed. The model accounts for uptake by the intestinal mucosa of iron in the lumen, followed by either iron incorporation into a mucosal storage pool (presumably ferritin) or direct iron transfer to the plasma. To enable analysis of iron absorption from noninvasive measurements, plasma iron kinetics were also analyzed. The model was validated in studies of three beagle dogs given oral 59Fe-citrate and intravenous 55Fe-transferrin simultaneously. Model parameters were estimated from the best (least-squares) fit of the model outputs to the tracer iron activity in venous blood samples and in the whole body. The parameter values show that both incorporation of iron into the mucosal storage pool and transfer of iron from the mucosa to the plasma occur at rates approximately 100 times greater than mucosal uptake of iron from the gut lumen. Further, release of iron from mucosal storage, while measurable, occurs at a slow rate. The study demonstrates the practicality of this noninvasive approach for the simultaneous study of iron absorption and plasma iron kinetics.

Animals↗
PubMedDate not supplied

Endocrine and paracrine calcium signaling in bile duct cells.

Bile duct cells play an important role in maintaining, modifying and augmenting bile flow. It is well established that cyclic AMP (cAMP) is an important second messenger for secretion in these cells, but less is known about cytosolic Ca2+ (Ca2+i). Here we review evidence that ATP and acetylcholine (ACh) are Ca2+i agonists for bile duct cells, and that these agonists increase Ca2+i through inositol 1,4,5-trisphosphate (InsP3). We also review data suggesting that hepatocytes have the ability to secrete ATP, so that they may serve as a paracrine source for this signaling molecule in vivo. Finally, we compare the effects of cAMP and Ca2+i on secretion, both in isolated bile duct units and isolated hepatocyte couplets. Implications and future directions for studying the role of Ca2+i in bile ductular secretion are discussed.

Acetylcholine↗