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Biomedical subjects

K H Norwich

Publications and source records attributed to K H Norwich.

At least 19 recordsLinked to original sources

Sites of infusion and sampling for measurement of rates of production in steady state.

When labeled and unlabeled (endogenously produced) substances enter an organism through different ports of entry, the anatomical location of these entry sites must be taken into account explicitly in calculating rates of appearance. All traditional formulas that are used for calculating rates of appearance are based on the assumption that labeled and unlabeled substances enter by means of the same port. These formulas are, therefore, not in general valid for metabolites such as lactate, where the entry ports differ. In such cases, specific activity will not be uniform throughout the organism even when the labeled and unlabeled substances are both in steady state. One cannot speak of the (unique) specific activity, because none exists. It is useful in these cases to define a distributed specific activity, which is the ratio of the concentration of labeled substance at one anatomical site to the concentration of unlabeled substance at another. We can then show that the rate of appearance for the double steady state (steady tracer infusion method) is given, approximately, as the ratio of the rate of infusion of the labeled substance to a particular distributed specific activity.

Animals

On the fundamental nature of perception.

The process of recognition or isolation of one or several entities from among many possible entities is termed intellego perception. It is shown that not only are many of our everyday percepts of this type, but perception of microscopic events using the methods of quantum mechanics are also intellego in nature. Information theory seems to be a natural language in which to express perceptual activity of this type. It is argued that the biological organism quantifies its sensations using an information theoretical measure. This, in turn, sets the stage for a mathematical theory of sensory perception.

Humans

An informational approach to sensory adaptation.

Concepts from information theory can enhance our understanding of perceptual processes by providing a unified picture of the process of perception. A single equation is shown to embrace adaptation phenomena, stimulus-response relations, and differential thresholds. Sensory adaptation is regarded as representing a gain in information by the receptor. It is calculated that for constant stimuli in the form of step inputs, insects and arachnids obtain approximately the same amount of information per stimulus from their respective environments as do human beings.

Adaptation, Physiological

Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production.

To understand the relationships among 1) the dose of 25-hydroxyvitamin D [25(OH)D] in vivo, 2) the activity of 1-hydroxylase in renal mitochondria, and 3) the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 [25(OH)D3]. We followed the metabolism of intracardially administered [25-hydroxy-26,27-methyl-3H]cholecalciferol [25(OH)[3H]D3] for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-[26,27-methyl-3H]cholecalciferol [1,25(OH)2[3H]D3] as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2[3H]D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2[3H]D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

An informational approach to reaction times.

Simple reaction time is the minimum time required to respond to a signal such as a steady light or tone. Such a reaction time is taken to be the time required for transmission of a fixed quantity of information. delta H, from stimulus to subject. That is, information summation replaces energy summation. This information is calculated from consideration of the quantum nature of the stimulus. The theoretically derived equation for reaction time is fitted to experimental data. Piéron's empirical law for reaction time is obtained as an approximation from a proposed informational equation. The exponent in Piéron's law is found to be the same as the exponent in the power law of sensation. Threshold appears to be the smallest stimulus capable of transmitting the quantity of information delta H.

Humans

Automatic speech recognition--can it improve the man-machine interface in medical expert systems?

Computer-aided medical diagnosis has existed for two decades, but has not yet attained widespread acceptance among physicians. It is proposed that automatic speech recognition may be a significant factor in the eventual acceptance of the technology by the medical profession. The current state-of-the-art of automatic speech recognition is briefly surveyed, and problems with the technology are discussed. A potential natural language interface with DIAG, an expert system for aiding in dermatologic diagnosis, is described. A system that has been developed for accepting input of body parts in freestyle format is presented as a prototype for a natural language interface with an automatic speech recognition device.

Diagnosis, Computer-Assisted

Secretory patterns of glucoregulatory hormones in prehepatic circulation of dogs.

The temporal organization of patterns of secretion of insulin, glucagon, and somatostatin was studied in basal conditions in normal or pancreatectomized dogs fitted with an indwelling hepatic portal catheter. Portal and peripheral blood samples were collected at a 7.5- or 15-min frequency, which covered the medium range of the ultradian period. The raw data were studied using spectral analyses employing fast Fourier transformation (FFT) techniques. The results indicate that in normal dogs: 1) endogenous physiological periodicities, statistically significant at a level of alpha = 0.05 (i.e., 95% confidence interval), were found to exist for the three pancreatic hormones in portal blood between 0.54 and 1.78 h/cycle and in peripheral blood between 0.59 and 1.84 h/cycle; 2) the portal levels of the hormones are significantly higher than peripheral ones; and, 3) whereas pancreatic hormones oscillated, glucose was found to maintain a steady level. In pancreatectomized dogs, no regular rhythm was detected. Thus, whereas endogenous periodicities exist for the secretion of pancreatic hormones in the normal dog, in the pancreatectomized dog the extrapancreatic glucagon and somatostatin are secreted in nonperiodic, randomly occurring pulses.

Animals

A computer program for simulating a distributed metabolic system. Distribution volumes in a simulated organism.

A metabolite or hormone is distributed with non-uniform concentration throughout some volume within an intact organism. Various methods involving radioactive tracers are used to estimate the total mass of the metabolite and its volume of distribution. The calculations of mass and volume are based on very simple models, and cannot usually be validated by measurements on the real animal. Hence we have developed a computer program for simulating a metabolic system with convective and diffusive transport. The tracer experiments can be simulated by solving the differential equations for convective diffusion by finite element methods. Thus the total metabolic mass and distribution volume can be both 'measured' and calculated by all the standard techniques. In this way some mathematical methods currently in general use can be seen to be patently incorrect, and others quite acceptable. The concept of a metabolic doublet was introduced, by analogy with an electrical dipole.

Biological Transport

An approach to measuring the in vivo transformation of glycerol to a very low density lipoprotein triglyceride.

This paper describes a new method which permits measurement of the steady-state rate of transformation of serum glycerol to a very low density lipoprotein (VLDL) triglyceride in vivo in dogs. Although the turnover of glycerol and the turnover of VLDL triglyceride glycerol have both been previously measured, the rate of transformation of the former into the latter has not. While there is considerable dog-to-dog variation in the absolute turnover and transformation rates, the relationship between the various rates is quite constant. Thus, 13% of the serum glycerol which normal fasting dogs utilize is converted to VLDL triglyceride. The remaining 87% is converted to other products. Also, 28% of VLDL triglyceride glycerol in these dogs is derived from serum glycerol. The balance, 72%, is derived from other sources. The procedure described here can be used to quantitate the contribution of glycerol to VLDL in a number of conditions in which glycerol and (or) VLDL triglyceride metabolism is altered, thereby providing another way to gain insight into the metabolism of VLDL. Even more generally, the principles developed here can be applied to estimate the transformation of other precursors to other products in vivo.

Animals

A new approach to the measurement of glycerol turnover.

These studies describe a new method, using a single bolus injection of labelled glycerol, to measure glycerol turnover. In a series of experiments utilizing single animals, this new approach was compared with the previously used method of constant tracer infusion. The two gave identical results. In the bolus method, once the time of maximum glycerol specific activity had been established, glycerol turnover could be calculated using very few additional data points obtained over a very short time span. This simplification was possible because the decay of glycerol specific activity was found to conform to a straight line on a plot of the logarithm of the specific activity versus the logarithm of the time. This new approach should simplify the measurement of glycerol turnover and should permit the determination of the rate of glycerol transformation to other end products.

Animals

Experimental validation of measurements of glucose turnover in nonsteady state.

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.

Animals

The development of a glucose clamp.

A reliable control system was developed for clamping (i.e., holding at a steady level) the concentration of blood glucose in the hyperglycemic region of a normal nonanesthetized dog. The system is based upon, and hence largely validates, a mathematical model of the canine glucoregulatory mechanism which was assembled from the results of experiments in which radioisotopes were used. The operation of the clamp, however, does not require the use of radioisotopes. The glucose clamp is a tool which may be applicable clinically in the measurement of glucose turnover and in the laboratory in the study of the effects of glucose turnover of variable insulin with constant glucose levels.

Animals