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Biomedical subjects

C F Lam

Publications and source records attributed to C F Lam.

At least 19 recordsLinked to original sources
PubMed1992

A method for the analysis of biological transduction phenomena.

Biological transduction can be defined as the triggering of a cellular response by the binding of molecules of effector substances to specific cellular sites. An example of biological transduction, analyzed in this report, is the triggering of T-cell proliferation by the binding of T-cell growth factor (TCGF) to specific TCGF-binding sites on responsive T-cells. Sigmoidal or S-shaped curves often result when measurements of biological response are plotted as a function of concentration of effector substance. Such curves suggest that effector molecules must bind a critical number of cellular sites, and this critical number of bound complexes must undergo secondary events (cross-linking, association, internalization, second messenger release, etc.) in order to initiate the biological response. The method described here estimates the critical number of cellular sites (R) and the probability of these secondary events (PS/B) as follows: (1) The total number of cellular sites (N) is estimated from binding data, and the probabilities (PB) of effector molecules binding to a site are estimated from response data. (2) The response data are assumed to follow the summed binomial distribution function, which is equated to the incomplete beta function. (3) R and PS/B are estimated by applying nonlinear regression to the incomplete beta function. The T-cell data to which the method was applied gave N = 15,000, R = 5, and PS/B = 7.22 x 10(-4). These results show that the binding of very few TCGF molecules is required for activation of T-cells and that the probability of the secondary events leading to cell proliferation is much smaller than the probability of TCGF binding to T-cells. The method described can be used to analyze any biological transduction experiments where both binding and biological response data are available.

Binding Sites↗
PubMed1991

Effect of refraction on optical microscopic measurement of internal blood-vessel diameter and its correction.

In optical microscopic measurement of internal blood-vessel diameters, the effect of refraction must be taken into account to ensure accuracy of the result. This effect is discussed and an analytical correction formula derived. Phantom blood vessels with known internal and external diameters were used to test the validity of the correction formula. The errors obtained prior to correction were reduced significantly after correction.

Blood Vessels↗
PubMed1991

Diabetes-associated impairment of hepatic insulin receptor tyrosine kinase activity: a study of mechanisms.

Insulin receptor tyrosine kinase activity solubilized from liver of control and streptozotocin diabetic rats was studied using histone H2b and poly-Glu-Tyr (4:1) as phosphoacceptors. Both substrates inhibited autophosphorylation and exogenous kinase activity when added before, but not after, receptor activation with ATP. When H2b was added before ATP, insulin stimulated exogenous kinase activity of diabetic-derived receptors was significantly higher (approximately 50%) than control values at low H2b concentrations, but significantly lower (approximately 50%) than control values at high H2b concentrations, suggesting a decrease in the apparent Km and maximal velocity of the diabetic receptor tyrosine kinase toward H2b. When receptors were allowed to maximally autophosphorylate before the addition of H2b, the maximal H2b kinase activity of diabetic-derived receptors was only approximately 25% lower than that of controls. These effects were not attributable to altered ATP kinetics. Insulin receptor kinase activity toward the substrate poly-Glu-Tyr (4:1) was unaltered by insulinopenic diabetes. Insulin receptor alpha-beta dimers were not detectable in either control or diabetic-derived preparations. We conclude that the impairment of hepatic insulin receptor kinase activity associated with insulinopenic diabetes reflects a decreased ability to maximally activate, which is enhanced when the receptor is activated in the presence of some substrates, e.g. H2b. Impaired signalling by the diabetic-derived receptor appears to be dependent on the type of substrate and its concentration.

Adenosine Triphosphate↗
PubMed1987

Computer-assisted localization of nervous system injuries.

Expert systems to assist in neurological diagnosis require a representation of anatomical relationships. In order to test one representational method, a prototype expert system was developed. It accepts patient signs of neurological dysfunction and identifies the site of nervous system injury. The system's knowledge base is contained in a semantic network which represents nervous system anatomy and the physical signs of injuries. When provided with an individual's physical signs, the network is searched by a simple algorithm; the anatomical locations which best explain the physical signs are the system's output. Medical expert systems which require anatomical reasoning can use a direct representation of spatial relationships to avoid the difficulties of encoding clinical associations in the form of If-Then rules.

Algorithms↗
PubMed1987

Vaginal physiology in postmenopausal women: pH value, transvaginal electropotential difference, and estimated blood flow.

Basal vaginal physiologic study, including pH values in various locations, transvaginal electropotential difference, and blood flow estimation, was done twice in a group of 34 untreated postmenopausal women. Plasma hormone levels (gonadotropins and estrogens) and vaginal cytology were also obtained to confirm the estrogen deficiency state. The pH values in the vaginal fornices were significantly lower than those in the middle portion of the vagina. Sexually active women had significantly lower pH values than sexually inactive women. The transvaginal electropotential difference and estimated blood flow values were lower than those of premenopausal women reported in the literature, indicating impaired vaginal transport mechanism and decreased vaginal blood flow. The close approximation of the data obtained in the two measurements one month apart attests the reproducibility of the methods used.

Blood Flow Velocity↗
PubMed1985

Denaturation behavior of antithrombin in guanidinium chloride. Irreversibility of unfolding caused by aggregation.

The structural stability of the protease inhibitor antithrombin from bovine plasma was examined as a function of the concentration of guanidinium chloride (GdmCl). A biphasic unfolding curve at pH 7.4, with midpoints for the two phases at 0.8 and 2.8 M GdmCl, was measured by far-ultraviolet circular dichroism. Spectroscopic and hydrodynamic analyses suggest that the intermediate state which exists at 1.5 M GdmCl involves a partial unfolding of the antithrombin molecule that exposes regions of the polypeptide chain through which slow, intermolecular association subsequently takes place. The partially unfolded molecule can be reversed to its fully functional state only before the aggregation occurs. Upon return of the aggregated state to dilute buffer, the partially unfolded antithrombin remains aggregated and does not regain the spectroscopic properties, thrombin-inhibitory activity, or heparin affinity of the native inhibitor. This behavior indicates that the loss of the functional properties of the proteins is caused by the macromolecular association. Comparative experiments gave similar results for the human inhibitor. Analyses of bovine antithrombin in 6 M GdmCl indicated that the second transition reflects the total unfolding of the protein to a disulfide-cross-linked random coil. This transition is spectroscopically reversible; however, on further reversal to dilute buffer, the molecules apparently are trapped in the partially unfolded, aggregated, intermediate state. The results are consistent with the existence of two separate domains in antithrombin which unfold at different concentrations of GdmCl but do not support the contention that the thrombin-binding and heparin-binding regions of the protein are located in different domains [Villanueva, G. B., & Allen, N. (1983) J. Biol. Chem. 258, 14048-14053].

Antithrombins↗
PubMed1985

Low-dose oral contraception and blood pressure in women with a past history of elevated blood pressure.

Sixty-one women with a past history of elevated blood pressure (high-risk group) associated with oral contraceptive use (27 patients), unknown etiology (17 patients), or preeclampsia (17 patients) used a low-dose oral contraceptive containing 0.4 mg of norethindrone and 35 micrograms of ethinyl estradiol for 3 to 24 months. The highest blood pressures recorded in the past were 141.0 +/- 14.9 (mean +/- SD) mm Hg systolic and 98.3 +/- 8.0 diastolic. Sixty-one women without a past history of elevated blood pressure (low-risk group), selected from a pool of 616 low-risk patients, were matched with the high-risk group for race, initial age, initial body weight, duration of use, history of smoking, and family history of hypertension. The blood pressures in the high-risk group before and after oral contraceptive therapy were significantly higher than those in the low-risk group. Despite these differences, the mean systolic and diastolic blood pressures in these two groups of women using the low-dose oral contraceptive did not rise when compared with their own baseline blood pressures. Five high-risk patients (8.2%) discontinued therapy because of the redevelopment of hypertension; however, blood pressures at discontinuance were comparable to the previous highest blood pressures.

Adult↗
PubMed1984

Computer modeling of the recombination reaction of rhodopsin.

Various mechanistic schemes for the recombination reaction of rhodopsin were designed and tested using computer modeling and simulation with data from kinetics experiments. The reaction schemes were mathematically modeled by systems of nonlinear first-order ordinary differential equations (ODEs) with unknown rate constants. Each model was fitted to the experimental data by using a modified simplex algorithm for parameter (rate constant) estimation and Gear's method for solving stiff systems of ODEs. The recombination reaction of rhodopsin was best modeled by branched, multistep reaction schemes which included formation of noncovalent complexes, acid-base equilibria, and acid and base-catalyzed dehydration of a Schiff base intermediate. The biochemical bases for these models are discussed.

Animals↗
PubMed1983

The upper and lower bounds of rate constants for general mammillary compartment systems.

The upper and lower bounds of rate constants for general mammillary three and four compartment systems have been derived. It is further proposed that the midpoints of the bounds can be used as initial estimates for parameter estimation. Numerical examples are given demonstrating the closeness of the calculated midpoints to the "known" rate constants of both the three and four compartment systems.

Kinetics↗
PubMed1983

Discriminating somatic evoked potentials using a pairwise procedure.

Generally, investigators use only the magnitude spectra of a signal for processing or for discriminant analysis, with the phase information discarded. However, it is not difficult to generate two different time domain signals having identical magnitude spectra in the frequency domain. Thus the phase information should not be neglected. This paper presents the results of a simulation study of a discriminant analysis procedure for paired variables, e.g. magnitude and phase pairs. The procedure is then applied to discriminating somatic evoked potentials from normal and damaged spinal cords with excellent results.

Animals↗
PubMed1982

Classification of somatic evoked potentials through maximum entropy spectral analysis.

Maximum entropy (ME) spectra are currently considered to be superior to spectra calculated by means of Fast Fourier Transforms (FFT) because the former offer higher resolution. However, in terms of classification of somatic evoked potentials (SEPs), FFT spectra are found to be better than ME spectra. An even better set of parameters for discriminating SEPs is the set of reflection coefficients derived in the process of calculating the ME spectra. They permit separation of SEPs obtained from monkeys with dorsal column lesion from SEPs obtained from normal monkeys, as well as distinguishing between SEPs obtained from large nerve fiber stimulation and SEPs from stimulation of all nerve fibers.

Animals↗
PubMed1980

The effects of low spinal injury on the latencies of cortical evoked responses from forelimb stimulation.

A previous report showed that following spinal cord transaction well below the C7 level in cats, later components of the cortical somatic evoked potential (SEP) (40 msec or longer) produced in response to median or radial nerve stimulation were abnormal (Katz et al., 1977). Evidence presented here shows that early components of the radial nerve SEP are also altered following spinal cord transection. Latencies of both early and late components were increased as higher functional transections of the spinal cord were made. This monotonic increase in latency of the primary components supports the hypothesis that the results may be due to increasing loss of excitatory input. Correlation of latency change with level of injury may serve as a useful diagnostic tool.

Animals↗
PubMed1978

The effects of low spinal injury on somatosensory evoked potentials from forelimb stimulation.

Spinal cord transection below C6 in anesthetized cats results in an alteration in the configuration of the SEP following direct or percutaneous stimulation of the median or radial nerves. The most significant alterations were in components occurring at latencies from 40 to 60 msec. The results of these experiments support the general conclusion that the spinal cord and supraspinal structures act as a functional unit and that the SEP is not solely determined by input over segmental pathways In addition, the alteration in the SEP produced by median nerve stimulation following spinal cord injury below C6 may serve clinically as a monitor of events at the site of injury in cases where an SEP from lower limb stimulation is no longer obtainable.

Animals↗
PubMed1978

Automatic generation of steady state enzyme rate equation and the associated constraint equations.

A computer algorithm is presented to derive initial velocity rate equation for general enzyme raction mechanisms, including sequential as well as complicated random mechanisms. The method is based on the theory of graph and the theory of prime number. In complicated mechanisms, there are many pathways and hence many cycles. The values of the rate constants are constrained according to the principle of detailed balance: the product of rate constants in the clockwise direction of a cycle must equal to the product of the rate constants in the counter-clockwise direction of the same cycle. An algorithm is presented to derive the appropriate constraint equations. These constraint equations are arranged so that when the rate equation is used for estimating rate constants, the resulting rate constants would satisfy the principle of detailed balance automatically.

Computers↗