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Biomedical subjects

J France

Publications and source records attributed to J France.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparison of mathematical models to describe disappearance curves obtained using the polyester bag technique for incubating feeds in the rumen.

Different nonlinear models were evaluated as candidates to describe ruminal degradation kinetics of forages from data obtained by the incubation of the feeds in the rumen using polyester bags. Nine models were used: segmented model with three straight lines (Mod0); simple Mitscherlich or exponential (Mod1); inverse polynomial (Mod2); compartmental model with two exponential terms (Mod3); generalized Mitscherlich (Mod4); generalized Michaelis-Menten (Mod5); logistic (Mod6); Gompertz (Mod7); and generalized Von Bertalanffy (Mod8). All these models can be represented in the general form D = W + S0 x phi(t), where D is in situ disappearance at incubation time t, W and S0 are positive scalars, and phi is a positive monotonically increasing function unique to each of the models studied. Based on first principles, a general formula for calculating the extent of degradation of feeds in the rumen has been derived that is applicable to all the models. The disappearance curves of different feed components (DM, N, and NDF) of 87 Mediterranean forages (i.e., a total of 261 curves) were fitted to all the models. A comparative study was carried out based on the mathematical, statistical, and biological characteristics of the models. Flexible models that can accommodate both diminishing returns and sigmoidal behavior were more appropriate in describing the curves. A discrete-lag parameter was introduced into Mod0, Mod1, and Mod2 to describe the initial stage of the disappearance curve, and this parameter considerably improved the fit of experimental data. Based on statistical criteria, models Mod1, Mod4, Mod5, and Mod8 were better than the others for most statistical tests and disappearance curves, but differences among these four models were not consistent. The estimates of degradation parameters to quantify the rate (half-life, fractional degradation rate), and extent (undegradable fraction, effective degradability) of ruminal degradation of feeds were also used as a means to discriminate between models, although in most cases all of the models gave similar values of the degradation parameters. In particular, when the extent of degradation was calculated for each forage and feed component, differences between the estimates obtained with the different models were of little nutritional significance for the animal.

Animal Feed↗
PubMed1999

Vascular sources of phenylalanine, tyrosine, lysine, and methionine for casein synthesis in lactating goats.

The contribution to casein biosynthesis of peptides derived from blood was examined in late lactation goats (254 to 295 d in milk). Ratios of mammary uptake of free amino acids (AA) in blood to output of AA in milk protein and ratios of the enrichments of Phe, Tyr, Met, and Lys at isotopic plateau in secreted milk casein to the free AA in arterial and mammary vein blood were monitored during the last 5 h of a 30-h continuous i.v. infusion of [1-13C]Phe, [2H4]Tyr, [5-13CH3]Met, and [2-15N]Lys on two occasions: before (control) and on d 6 of an i.v. infusion of Phe (6 g/d). During the control, uptakes of free Phe and Met were less than their output in milk. This result was comparable with the labeling kinetic results, suggesting that vascular peptides contributed 5 to 11% of Phe and 8 to 18% of Met. Free Tyr and Lys uptakes during the control were sufficient for milk output; however, the labeling kinetics indicated that 13 to 25% of the Tyr and 4 to 13% of the Lys were derived from peptides. Infusion of Phe increased the uptake of free AA but reduced the contribution of peptides toward Phe (0 to 3%) and Tyr (8 to 14%) supply for casein synthesis. Whole body hydroxylation of Phe to Tyr increased from 10 to 18% with the infusion of Phe; within the mammary gland, this conversion was lower (3 to 5%). Results suggest that the mammary utilization of peptides containing Phe and Tyr appears to depend on the supply of free AA in blood.

Animals↗
PubMed1998

Down-regulation of the transporter for antigen presentation, proteasome subunits, and class I major histocompatibility complex in tumor cell lines.

Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In this study, reverse transcription-PCR was used to assess the expression in human tumor cell lines of mRNA for multiple components of the class I MHC antigen-processing pathway, including several proteasome subunits that have been implicated in antigen processing but have not been previously examined in this context (e.g., low molecular weight polypeptide proteasome subunit (LMP) 10, proteasome activator (PA) 28alpha, and PA28beta). Deficiencies in the expression of antigen-processing genes were demonstrated in 9 of 27 cell lines, representing a variety of histological types. In some cases, virtually complete deficiencies were observed in the expression of the four genes encoded within the MHC (TAP1, TAP2, LMP2, and LMP7), as well as LMP10, which is encoded outside the MHC. Combined deficiencies of these gene products were common, and marked deficiency of LMP10 was found in five of the nine cell lines with deficits. The existence of deficiencies in the expression of genes at dispersed loci suggested that the basis for the deficiencies was a regulatory mechanism, as opposed to mutation or deletion of these genes. Furthermore, most of the deficiencies were reversed by treatment with IFN-gamma. In contrast to such extreme deficiencies, we found unaltered or only partially decreased expression of PA28alpha and PA28beta in tumor cell lines. Thus, tumors may evade immune surveillance by simultaneously down-regulating multiple components of the MHC-I antigen-processing pathway, thereby altering the processing and presentation of tumor antigens. Expression of essential proteasome subunits, however, may still be maintained.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Alternative models for analyses of liver and mammary transorgan metabolite extraction data.

Alternative models for analyses of liver and mammary transorgan data were formulated and fitted to liver and mammary data sets respectively. The models considered metabolite inputs to and effluxes from an extracellular pool. In general, fits were greatly improved over previous efforts using other models (Miller et al. 1991a; Hanigan et al. 1992; Wray-Cahen et al. 1997). Errors of prediction were generally less than 15% for liver and less than 20% for mammary glands. With the possible exception of glutamine for the udder, all metabolites exhibited linear responses to extracellular concentrations within the observed ranges of inputs. However, prediction biases were evident for beta-hydroxybutyrate, acetate, and propionate by liver and for arginine, histidine, citrulline and glycerol by mammary tissue. These biases were hypothesized to be caused by the existence of additional regulatory complexity. With the exception of histidine, parameter estimates for essential amino acid removal by liver were 2-3-fold lower than for mammary gland. Infusion of an amino acid mixture into the mesenteric vein did not alter parameter estimates for removal of amino acids by the liver. Treatment of cows with bovine somatotropin resulted in changes in mammary parameter estimates for aspartate, glutamate, leucine, phenylalanine, glucose, and glycerol.

Amino Acids↗
PubMed1998

Application of a mechanistic model of bovine milk protein synthesis to examine the use of isotope labeling methods.

Two types of models of bovine milk protein synthesis were used to simulate collection and analysis of data from infusion experiments involving isotope-labeled amino acids (AA). Analytical solutions to a system of ordinary differential equations that describe isotope enrichment curves of each AA pool within the mammary gland were derived and are presented. Numerical solutions from a dynamic mechanistic model suggest that normal experimental procedures can affect the shape of enrichment curves and, therefore, results derived from them. Simulation results suggest that standard methods utilizing in vivo isotope kinetics may be of limited value to characterize the metabolism of the bovine mammary gland, especially AA metabolism and milk protein synthesis and secretion. The results clearly demonstrate the flexibility of such models for the testing of many hypotheses and possible experimental protocols.

Animals↗
PubMed1998

Application of a mechanistic model to study competitive inhibition of amino acid uptake by the lactating bovine mammary gland.

A mathematical model is used to describe uptake by a countertransport system and subsequent flow of three amino acids (AA), Phe, Val, and Met, from arterial blood to milk protein in the mammary gland of a lactating cow. The model suggests that total uptake of all AA is higher than net uptake and that a large proportion of the incoming AA is released from the cell directly back to blood. The model is used to predict which of the three AA is limiting the rate of milk protein synthesis and the response to increased arterial concentration of the first-limiting AA. Simulations are performed to predict possible outcomes of several experimental protocols to AA infusion, which might be used to test in vivo the responsiveness of the bovine mammary gland to an altered arterial concentration of AA. Of the three AA considered, arterial Met concentration appears to be first-limiting. The infusion profile that gives the greatest response in milk protein synthesis rate alters the arterial profile of AA such that it is identical to that of proteins originating in the mammary gland. Model construction can be simplified by acknowledging normal biological constraints.

Amino Acids↗
PubMed1998

Different mathematical approaches to estimating microbial protein supply in ruminants.

Many of the amino acids that are available for absorption in ruminants are derived from microbial protein that has been synthesized in the reticulorumen. This paper focuses on the prediction of the microbial protein supply and evaluates different approaches to represent mathematically the process of microbial protein synthesis. In current protein evaluation systems for ruminants, the microbial protein supply is predicted using empirical equations that relate microbial protein production to the amounts of ruminally available energy and nitrogen. In contrast, mechanistic models of rumen function endeavor to describe quantitatively the microbial protein production that is based on underlying identifiable processes. A brief description is presented of two culture techniques used to examine microbial ecosystems, namely, batch culture and chemostat culture. The mathematical equations describing these cultures are helpful in understanding key parameters of microbial production for inclusion in models, including specific growth rate, growth yield, and substrate affinity. The availability of carbohydrates is a primary determinant of microbial protein production in the rumen, and the adequacy of mathematical representations of this relationship in empirical and mechanistic models is assessed. The representation of substrate utilization for nongrowth processes and the relationship between microbial protein production and the availability of various nitrogen sources are discussed. A variable part of the synthesized microbial protein does not reach the duodenum but is degraded in the rumen, and its representation is examined. The prediction of microbial protein supply should be based on a sound representation of the underlying mechanisms, including the interactions among microbes and between microbial activity and substrate degradation.

Animals↗
PubMed1997

Causes of inaccurate prediction of volatile fatty acids by simulation models of rumen function in lactating cows.

Extant mechanistic models of rumen functions are unable to predict the molar proportion of volatile fatty acids (VFA) accurately. In order to make these models useful in investigating theories on nutrient flows that go beyond the rumen, the representations adopted need to be improved. This theoretical study was directed at identifying what parts of a rumen model may be responsible for the inaccurate VFA prediction. For five distinct parts of a model, not involving the description of the microbiological metabolism, the hypothesis was tested that their inappropriate description can be a probable cause of inaccurate VFA prediction. These five parts were: (1) the input functions of feed ingestion; (2) the representation of insoluble, degradable substrate of roughage and concentrate origin; (3) the kinetics of VFA absorption from the rumen; (4) the VFA coefficients that describe the stoichiometry of the conversion of fermented substrate into VFA; and (5) the representation of the rumen particle dynamics. Every hypothesis was tested by modifying the model description and simulating it to steady state. Observations required were derived from digestion trials with lactating dairy cows. Simulation results demonstrated that the predicted molar proportion of rumen VFA concentrations is particularly influenced by VFA absorption kinetics and VFA coefficients. Although the description of particle dynamics also had a large influence with certain choices of its parameterization, it is probably a less important cause of inaccurate predication when rumen feed degradation (apparent from rumen outflow) is predicted well. In conclusion, to obtain improved predictions of the molar proportions of rumen VFA, further work is required on the representation of VFA absorption kinetics and of VFA coefficients of fermentation stoichiometry.

Animals↗
PubMed1997

Model of milk protein synthesis. A mechanistic model of milk protein synthesis in the lactating bovine mammary gland.

A model of amino acid (AA) uptake and metabolism by the mammary gland (udder) of a high producing dairy cow in mid-lactation is presented. Two cell types, milk-secreting alveolar epithelial cells, and constitutive stromal cells are represented separately. Solution of the model at steady state, with appropriate assumptions, allows calculation of amino acid (AA) pool sizes in tissue bound AA and milk protein bound AA, and concentrations of intracellular free AA. Bidirectional flux rates of amino acids between each of these pools is also estimated. The flow of two amino acids, phenylalanine (Phe) and tyrosine (Tyr), is described using uptake kinetics of the L-system AA transporter. Model results suggest that AA uptake capacity of the alveolar cells, and the amount/activity of protein translation components limit the rate of milk protein synthesis in the high-producing dairy cow. A considerable amount of experimental work is necessary to provide data, if a comprehensive quantitative understanding of milk protein synthesis is to be achieved.

Amino Acids↗
PubMed1997

Conformational control of cyclosporin through substitution of the N-5 position. A new class of cyclosporin antagonists.

Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represent a new class of cyclosporin antagonists. 1H NMR (DMSO-d6) studies have shown that the compounds exist in a single, all trans conformation. A comparison of this NMR data with X-ray crystallographic analysis of a CypA/CsA derivative complex demonstrates that the solution structure does not correspond to the bioactive conformation.

Cyclosporine↗
PubMed1997

Description of a model integrating protein and energy metabolism in preruminant calves.

This paper describes the development of a mechanistic model integrating protein and energy metabolism in preruminant calves of 80-240 kg live weight. The objectives of the model are to gain insight into the partitioning of nutrients in the body of growing calves and to provide a tool for the development of feeding strategies for calves in this weight range. The model simulates the partitioning of nutrients from ingestion through intermediary metabolism to growth, consisting of accretions of protein, fat, ash and water. The model contains 10 state variables, comprising fatty acids, glucose, acetyl-CoA and amino acids as metabolite pools, and fat, ash and protein in muscle, hide, bone and viscera as body constituent pools. Turnover of protein and fat is represented. The model also includes a routine to check possible dietary amino acid imbalance and can be used to predict amino acid requirements on a theoretical basis. The model is based on two experiments, specifically designed for this purpose. Simulations of protein and fat accretion rates over a wide range of nutrient input suggest that the model is sound. In can be used as a research tool and for the development of feeding strategies for preruminant calves.

Animals↗
PubMed1997

Evaluation of a model integrating protein and energy metabolism in preruminant calves.

In a companion paper, a mechanistic model is described, integrating protein and energy metabolism in preruminant calves of 80-240 kg live weight. The model simulates the partitioning of nutrients from ingestion through intermediary metabolism to growth, consisting of accretions of protein, fat, ash and water. The model also includes a routine to check possible dietary amino acid imbalance and can be used to predict amino acid requirements. This paper describes a sensitivity and behavioral analysis of the model, as well as tests against independent data. Increasing the carbohydrate:fat ratio at equal gross energy intakes leads to higher simulated protein- and lower simulated fat-deposition rates. Simulation of two experiments, not used for the development of the model, showed that rates of gain of live weight, protein and fat were predicted satisfactorily. The representation of protein turnover enables the investigation of the quantitative importance of hide, bone and visceral protein in protein and energy metabolism. The model is highly sensitive to 25% changes in kinetic parameters describing muscle protein synthesis and amino acid oxidation. Comparing simulated with experimentally derived amino acid requirements shows agreement for most amino acids for calves of approximately 90 kg live weight. For calves of approximately 230 kg live weight, however, lower requirements for lysine and for methionine+cystine are suggested by the model. More attention has to be paid to the inevitable oxidative losses of amino acids. It is concluded that the model provides a useful tool for the development of feeding strategies for preruminant calves in this weight range.

Amino Acids↗
PubMed1997

Risk for hypertension and pain sensitivity in women.

To evaluate the possible negative association between risk for hypertension and pain sensitivity by in women 24 healthy young adult women with a parental history of hypertension and 24 without a parental history of hypertension participated in 2 laboratory sessions in which electric shock and the cold-pressor test were administered To assess the possible role of stress-induced analgesia in blood pressure-related hypoalgesia, the sessions were identical with the exception of the fact that participants were exposed to a stressful 20-min videogame before the pain stimuli on one occasion and a nonstressful control task on the other. Women with a parental history of hypertension and high blood pressure reactivity to the videogame displayed a reduced sensitivity to electric shock on both days, suggesting that risk for hypertension is associated with reduced sensitivity to at least some pain stimuli in women. Blood pressure reactivity to stress-associated baroreceptor stimulation was not implicated as a mediator of decreased pain perception. However, other analyses revealed an effect of family history on shock pain only among women who report relatively high anxiety, suggesting that other aspects of the stress response may be involved in this phenomenon.

Journal Article↗
PubMed1997

A model to describe growth patterns of the mammary gland during pregnancy and lactation.

Extensive proliferation and death of cells in the mammary gland occur during pregnancy and lactation. In this study, a mechanistic model was developed that yielded a single equation to describe the pattern of mammary growth of mammals throughout pregnancy and lactation. The model contains a single pool, which is the cell population of the mammary gland; one influx, representing cell proliferation; and one efflux, representing cell death. The parameters of the equation lend themselves to direct physiological interpretation. The model fitted data on mammary gland DNA adequately and can be related to current knowledge on factors and inhibitors of mammary gland growth. A unique definition of the parameters of the model can be difficult because of the high degree of variation among animals, an improper number of observations, or timing, as indicated by analyses of simulated data. The model can also be applied to the study of the entire lactation curve. The widely applied gamma equation and the equation that was developed in this study were compared using weekly production data from dairy cows. The new model performed well, particularly when a sharp peak in milk production occurred. The model has the advantage of providing, for the first time, a simple biological description of the lactation curve that can be used to discriminate changes in lactational performance that are associated with experimental treatments.

Animals↗
PubMed1996

Microbial biotransformation products of cyclosporin A.

In order to mimic the human metabolic pathway of cyclosporin A (CyA) a total of 28 bacterial and 72 fungal strains was screened for their ability to transform CyA. Among 3 bacteria and 11 fungi, which produced the main human metabolite OL-17 [eta HyMeBmt1]CyA, Actinoplanes sp. (ATCC 53771) achieved the best transformation rate (5.4%). Furthermore, the two N-demethylated minor products [Leu4]CyA (3.2%) and [Leu9]CyA (4.7%) were isolated, both known as minor natural metabolites and the first one also as a human biotransformation product. Microbial conversion of CyA using the actinomycete Sebekia benihana (NRRL 11111) yielded [gamma HyMeLeu4]CyA (35%), [gamma HyLeu4]CyA (4.5%) and [gamma HyMeLeu4, gamma HyMeLeu6]CyA (8.6%). The structures of these derivatives correspond with those of the human metabolic pathway. The related compounds [Nva2]CyA (CyG) and [D-MeSer3]CyA were similarly converted to the corresponding 4-gamma-hydroxylated analogues. None of the biotransformation products showed a better immunosuppressive effect than CyA, although in various cases the cyclophilin binding affinity was comparable to that of CyA.

Bacteria↗
PubMed1996

A simple but flexible growth function.

The functional form W(t) = Wf - (Wf - Wo) exp[-k infinite (t - T) + 2c(root of t - root of T)] where Wf, Wo, k infinite, c and T are constants, is derived as a growth equation and evaluated using commonly applied growth functions such as the Gompertz, logistic, monomolecular and Richards. Further evaluation is made with reference to sets of observations on growth in a number of animal species ranging from mice to horses. The new function provides a flexible growth equation capable of describing sigmoidal and diminishing returns behaviour. It appears adept at describing sigmoidal patterns exhibiting faster early growth and a fairly low but variable point of inflexion, and can therefore be perceived as a generalised Gompertz equation. The function also has the ability to describe a wide range of hyperbolic shapes when there is no point of inflexion. The analysis described suggests that this simple equation is a worthwhile addition to the corpus of growth functions.

Animals↗