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Biomedical subjects

J M Aerts

Publications and source records attributed to J M Aerts.

At least 19 recordsLinked to original sources

Effect of energy restriction and re-alimentation in Belgian Blue double-muscled beef cows on digestibility and metabolites.

Four groups of five non-lactating and non-pregnant Belgian Blue double-muscled (BBDM) cows were used to investigate the effect of energy level (E) on digestion, and blood and urine metabolites. The energy levels of the groups, applied indoors during a 140-day restriction period, were 100%, 90%, 80% or 70% of their energy requirements (E100, E90, E80, E70) respectively. Afterwards, animals grazed on the same swards for 203 days (re-alimentation period). Balance trials were conducted at the end of the restriction period (BT1) and at the end of the re-alimentation period (BT2). Blood was sampled at the end of these trials. Diets consisted of maize silage and straw (80/20 on a dry matter basis) and a mineral-vitamin premix, fed at the appropriate E during BT1, or maize silage and a mineral-vitamin premix, fed at 125% of the maintenance requirements, during BT2. Significant increases of the digestibility coefficients were found during BT1 when E decreased, resulting in a better net energy capture of 7% for E70 compared with E100 (p < 0.05). Slightly, but non-significantly higher digestibility coefficients were observed for decreasing E during BT2. Plasma concentrations of glucose and creatinine did not differ between treatments during BT1, while differences were found for triacylglycerols and alpha-amino nitrogen. A tendency for a linear increase was observed for non-esterified fatty acids with decreasing E. Differences in blood metabolite concentrations disappeared in BT2. Urinary creatinine excretion was not affected by E, while body nitrogen loss increased linearly with energy restriction in BT1. No differences were found during BT2, suggesting that non-lactating and non-pregnant BBDM cows are able to adapt to a cyclic change of body weight and body reserves. These data show that restricted cows mobilized body fat as well as body protein. It is concluded that the qualitative aspects of metabolism during energy restriction are comparable in double-muscled cows with those in non-double-muscled animals, although the magnitude of the effects may be different.

Adaptation, Physiological↗

Plasma chitotriosidase and CCL18: early biochemical surrogate markers in type B Niemann-Pick disease.

Type B Niemann-Pick disease (NPD) is a nonneuronopathic lysosomal storage disorder which is characterized by accumulation of sphingomyelin-laden macrophages. The availability of plasma markers for storage cells may be of great value in facilitating therapeutic decisions. Given the similarity of the storage cells in NPD and Gaucher disease, we studied Gaucher plasma markers (chitotriosidase and CCL18) in two siblings homozygous for the R228C mutation in acid sphingomyelinase (ASM) and a type B course of NPD. The older sibling, first examined at the age of 9 months, showed marked hepatosplenomegaly and pulmonary involvement. The younger sibling has mild asymptomatic hepatosplenomgaly at the age of 5 months. Analysis of plasma specimens revealed markedly increased levels of chitotriosidase and CCL18 in the older sibling. In the younger child also, plasma chitotriosidase and CCL18 were clearly elevated above normal values almost immediately after birth and rapidly increased further. Histochemistry confirmed production of CCL18 by foam cells. In conclusion, plasma chitotriosidase and CCL18 may also serve as markers for the formation of pathological lipid-laden macrophages in type B NPD, in analogy to Gaucher disease. The availability of sensitive plasma surrogate markers may be of great value for monitoring the efficacy of enzyme supplementation therapy that is currently being developed.

Bone Marrow Cells↗

Quantification of the heat exchange of chicken eggs.

In the incubation process of domestic avian eggs, the development of the embryo is mainly influenced by the physical microenvironment around the egg. Only small spatiotemporal deviations in the optimal incubator air temperature are allowed to optimize hatchability and hatchling quality. The temperature of the embryo depends on 3 factors: (1) the air temperature, (2) the exchange of heat between the egg and its microenvironment and (3) the time-variable heat production of the embryo. Theoretical estimates on the heat exchange between an egg and its physical microenvironment are approximated using equations that assume an approximate spherical shape for eggs. The objective of this research was to determine the heat transfer between the eggshell and its microenvironment and then compare this value to various theoretical estimates. By using experimental data, the overall and the convective heat transfer coefficients were determined as a function of heat production, air humidity, air speed, and air temperature. Heat transfer was not affected by air humidity but solely by air temperature, embryonic heat generation, and air speed and flow around eggs. Also, heat transfer in forced-air incubators occurs mainly by convective heat loss, which is dependent on the speed of airflow. A vertical airflow is more efficient than a horizontal airflow in transferring heat from the egg. We showed that describing an egg as a sphere underestimated convective heat transfer by 33% and was, therefore, too simplistic to accurately assess actual heat transfer from real eggs.

Air Movements↗

Computer-assisted image analysis to quantify daily growth rates of broiler chickens.

1. The objective was to investigate the possibility of detecting daily body weight changes of broiler chickens with computer-assisted image analysis. 2. The experiment included 50 broiler chickens reared under commercial conditions. Ten out of 50 chickens were randomly selected and video recorded (upper view) 18 times during the 42-d growing period. The number of surface and periphery pixels from the images was used to derive a relationship between body dimension and live weight. 3. The relative error in weight estimation, expressed in terms of the standard deviation of the residuals from image surface data was 10%, while it was found to be 15% for the image periphery data. 4. Image-processing systems could be developed to assist the farmer in making important management and marketing decisions.

Animals↗

Do heavy broiler chickens visit automatic weighing systems less than lighter birds?

1. In previous studies it was found that automatic broiler weighing systems can have accuracy problems. Researchers reported poor agreement between automatic and manual mean weighing used as a reference. The difference was observed especially after 4 to 5 weeks and this was explained by assuming that heavier birds visited the weighing system less at the end of the growing period. 2. Our study tested this hypothesis under practical production conditions. 3. In total, 193,536 digital images of broilers on and in the neighbourhood of the platforms were collected over three growing periods of 6 weeks. The area (upper view) of the broilers was calculated using image analysis techniques. 4. The hypothesis that the weighing system was used less frequently by heavier animals was confirmed. More specifically, statistical differences between the area of broilers on and in the neighbourhood of the weighing system could be demonstrated for week 5.

Animals↗

Recursive prediction of broiler growth response to feed intake by using a time-variant parameter estimation method.

The objective of this study was to explore whether time-variant parameter estimation procedures allow modeling and predicting the dynamic growth response of broiler chickens to feed intake in real time. A recursive linear model was used that estimated the model parameters every 24 h based on a fixed number of actual and past measurements (i.e., time window). Based on 48 datasets, it was concluded that the mean relative prediction error (MRPE) of the recursive linear modeling approach had a minimum for a window size of 5 d. Weight of the birds could be predicted during the growth process 3 to 7 d ahead with a mean relative prediction error of 5% or less. In comparison with the prediction results of three static empirical growth models (one linear and two nonlinear models), the recursive modeling technique had a similar accuracy to the nonlinear empirical models (MRPE of 1.4% to 2.3% vs. 1.1% to 2.8%), but it was less accurate for larger prediction horizons (2 to 7 d). The compact recursive linear model was more accurate than the static linear growth model for prediction horizons of one up to 4 d, depending on the feeding strategy. Since such recursive modeling approach allows the prediction of broiler growth without any prior knowledge of the system and takes into account the time-variant (nonlinear) nature of the growth process based on only a small window of measured information, it is suitable for real-time integration in process management.

Animal Nutritional Physiological Phenomena↗

Quantification and control of the spatiotemporal gradients of air speed and air temperature in an incubator.

Around the optimal incubator air temperature only small spatiotemporal deviations are allowed. However, air speed and air temperature are not uniformly distributed in the total volume of the incubator due to obstruction of the eggs and egg trays. The objectives of this research were (1) to quantify the spatiotemporal gradients in temperature and velocity and (2) to develop and validate a control algorithm to increase the uniformity in temperature during the entire incubation process. To improve the uniformity of air temperature, the airflow pattern and the air quality need to be controlled more optimally. These data show that the air temperature between the eggs at a certain position in a large incubator is the result of (1) the mean air temperature of the incubator; (2) the exchange of heat between the egg and its micro-environment, which is affected by the air speed at that certain position; (3) the time-variable heat production of the embryo; and (4) the heat influx or efflux as a result from the movement of hot or cold air in the incubator toward that position, which is affected by the airflow pattern. This implies that the airflow pattern needs to be controlled in a more optimal way. To maximize the uniformity of air temperature, an active and adaptive control of the three-dimensional (3-D) airflow pattern has been developed and tested. It was found to improve the spatiotemporal temperature distribution. The chance of having a temperature reading in the interval from 37.5 to 38.1 degrees C increased by 3% compared to normal operating conditions.

Air Movements↗

Active control of the growth trajectory of broiler chickens based on online animal responses.

The objective of the research reported here was to control the growth trajectory of broiler chickens during the production process based on an adaptive compact dynamic process model. More specifically, the daily feed supply was calculated, based on a model-based control algorithm, with the aim of following a previously defined target growth trajectory as close as possible. For the modeling of the dynamic growth response of broiler chickens to the control input, feed supply, an online parameter estimation was used. The developed control algorithm was able to grow the birds according to different target trajectories ranging from restricted (final BW of 1,800 g and 1,945 g in experiments 1 and 3, respectively) to compensatory growth trajectories (final BW of 2,400 g and 2,100 g in experiments 2 and 4, respectively). The mean relative error (MRE) between the different predefined target growth trajectories and the realized growth trajectories ranged from 3.7% to 6.0%. With a few exceptions, the numerical values of feed conversion ratio and mortality after wk 1 were lower and the values of uniformity index were higher in the controlled groups compared with animals fed ad libitum. As a conclusion, it can be stated that integration of dynamic data-based modeling approaches with new hardware and sensing techniques to measure information from the animals should make it possible to control broiler growth trajectories.

Algorithms↗

Inhibition of substrate synthesis as a strategy for glycolipid lysosomal storage disease therapy.

The glycosphingolipid (GSL) lysosomal storage diseases are caused by mutations in the genes encoding the glycohydrolases that catabolize GSLs within lysosomes. In these diseases the substrate for the defective enzyme accumulates in the lysosome and the stored GSL leads to cellular dysfunction and disease. The diseases frequently have a progressive neurodegenerative course. The therapeutic options for treating these diseases are relatively limited, and for the majority there are no effective therapies. The problem is further compounded by difficulties in delivering therapeutic agents to the brain. Most research effort to date has focused on strategies for augmenting enzyme levels to compensate for the underlying defect. These include bone marrow transplantation (BMT), enzyme replacement and gene therapy. An alternative strategy that we have been exploring is substrate deprivation. This approach aims to balance the rate of GSL synthesis with the impaired rate of GSL breakdown. The imino sugar N-butyldeoxynojirimycin (NB-DNJ) inhibits the first step in GSL biosynthesis and has been used to evaluate this approach. Studies in an asymptomatic mouse model of Tay-Sachs disease have shown that substrate deprivation prevents GSL storage in the CNS. In a severe neurodegenerative mouse model of Sandhoff disease, substrate deprivation delayed the onset of symptoms and disease progression and significantly increased life expectancy. Combining NB-DNJ and BMT was found to be synergistic in the Sandhoff mouse model. A clinical trial in type I Gaucher disease has been undertaken and has shown beneficial effects. Efficacy was demonstrated on the basis of significant decreases in liver and spleen volumes, gradual but significant improvement in haematological parameters and disease activity markers, together with diminished GSL biosynthesis and storage as determined by independent biochemical assays. Further trials in type I Gaucher disease are in progress; studies are planned in patients with GSL storage in the CNS.

Animals↗

Clinically relevant therapeutic endpoints in type I Gaucher disease.

The introduction of enzyme supplementation therapy for Gaucher disease has had a great impact on the lives of many patients. Organomegaly, cytopenia and bone disease have been shown to improve in response to treatment, resulting in an improvement in quality of life. However, the assessment of organ system involvement is not always done in such a way that the relationship with clinically relevant endpoints is clear. The lack of adequately validated methods of assessment, especially for bone disease, has hindered the establishment of treatment goals and guidelines for treatment optimization.

Biomarkers↗

[Fabry's disease; towards a treatment].

Fabry's disease, deficiency of the enzyme alpha-galactosidase A, is an X-linked lysosomal storage disorder. Clinical symptoms are caused by continuous deposition of specific glycolipids in endothelial cells, neural cells, skin and cornea. These depositions give rise to skin (angiokeratoma) and eye abnormalities (cornea verticillata), acroparaesthesias and anhidrosis and later in life cause renal insufficiency and cardiovascular complications. Hemizygous males suffer from Fabry's disease, whereas female carriers (heterozygotes) are usually asymptomatic. Recently, an atypical presentation of Fabry's disease was described in males who only presented with cardiac involvement. Therefore, the actual number of Fabry patients in the Netherlands could be higher than the predicted 300. Diagnosis in males can be established by measuring alpha-galactosidase enzyme activity in plasma, leukocytes or fibroblasts. Apart from kidney transplantation only symptomatic therapy is available today. Enzyme supplementation therapy (as shown in Gaucher's disease) and substrate deprivation are possible ways of treatment in the future.

Cardiomyopathy, Hypertrophic↗

Identification of a novel acidic mammalian chitinase distinct from chitotriosidase.

Chitinases are ubiquitous chitin-fragmenting hydrolases. Recently we discovered the first human chitinase, named chitotriosidase, that is specifically expressed by phagocytes. We here report the identification, purification, and subsequent cloning of a second mammalian chitinase. This enzyme is characterized by an acidic isoelectric point and therefore named acidic mammalian chitinase (AMCase). In rodents and man the enzyme is relatively abundant in the gastrointestinal tract and is found to a lesser extent in the lung. Like chitotriosidase, AMCase is synthesized as a 50-kDa protein containing a 39-kDa N-terminal catalytic domain, a hinge region, and a C-terminal chitin-binding domain. In contrast to chitotriosidase, the enzyme is extremely acid stable and shows a distinct second pH optimum around pH 2. AMCase is capable of cleaving artificial chitin-like substrates as well as crab shell chitin and chitin as present in the fungal cell wall. Our study has revealed the existence of a chitinolytic enzyme in the gastrointestinal tract and lung that may play a role in digestion and/or defense.

Amino Acid Sequence↗

Modelling the static and dynamic responses of total heat production of broiler chickens to step changes in air temperature and light intensity.

1. The objective of this work was to explore the possibilities of modelling the static and dynamic responses of total heat production of broiler chickens to step changes in temperature and light intensity (light-dark alterations) using compact dynamic model structures. 2. Seventy-seven experiments were performed in an open-circuit respiration chamber to measure the dynamic response of heat production to step variations in temperature and light (on/off). The animal responses were modelled using transfer function model structures. 3. It was demonstrated that the complex process of the dynamic response of heat production of broiler chickens to step changes in air temperature and light-dark alterations can be modelled assuming 1st order dynamics. The coefficient of determination between measured and simulated heat production was on average 0.83 for responses to air temperature and 0.93 for responses to light-dark alterations.

Animals↗

Activation of mononuclear cells by interleukin-12: an in vivo study in chimpanzees.

Interleukin (IL)-12 is considered a central regulator of host resistance against a variety of pathogens. Therefore, IL-12 has been advocated as a potential therapeutic agent in infections. To determine the in vivo effects of IL-12 on mononuclear cells involved in the host immune response, four chimpanzees received an intravenous injection of recombinant IL-12 (1 microgram/kg). IL-12 induced a sustained decrease in lymphocyte counts, with decreases in CD3+/CD4+ and CD3+/CD8+ cells, while monocyte counts showed a transient increase. IL-12 injection resulted in a shift toward a Th1-mediated immune response as indicated by increased interferon-gamma production during whole-blood stimulation, while not influencing IL-4 production. IL-12-induced activation of NK cells and phagocytes, as indicated by increased NK cell cytotoxicity and increased plasma levels of granzymes A and B and of chitotriosidase activity. These data support the hypothesis that IL-12 may serve as a useful therapeutic agent in infections where a cell-mediated response is protective.

Animals↗

Sphingomyelinase treatment of rat hepatocytes inhibits cell-swelling-stimulated glycogen synthesis by causing cell shrinkage.

Breakdown of plasma-membrane sphingomyelin caused by TNF-alpha is known to inhibit glucose metabolism and insulin signalling in muscle and fat cells. In hepatocytes, conversion of glucose to glycogen is strongly activated by amino acid-induced cell swelling. In order to find out whether breakdown of plasma-membrane sphingomyelin also inhibits this insulin-independent process, the effect of addition of sphingomyelinase was studied in rat hepatocytes. Sphingomyelinase (but not ceramide) inhibited glycogen synthesis, caused cell shrinkage, decreased the activity of glycogen synthase a, but had no effect on phosphorylase a. Cell integrity was not affected by sphingomyelinase addition as gluconeogenesis and the intracellular concentration of ATP were unchanged. As a control, glycogen synthesis was studied in HepG2 cells. In these cells, the basal rate of glycogen production was high, could not be stimulated by amino acids, nor be inhibited by sphingomyelinase. Regarding the mechanism responsible for the inhibition of glycogen synthase a, sphingomyelinase did not affect amino acid-induced, PtdIns 3-kinase-dependent, phosphorylation of p70S6 kinase, but caused an increase in intracellular chloride, which is known to inhibit glycogen synthase phosphatase. It is concluded that the decrease in cell volume, following the breakdown of sphingomyelin in the plasma membrane of the hepatocyte, may contribute to the abnormal metabolism of glucose when TNF-alpha levels are high.

Adenosine Triphosphate↗

Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages.

Atherosclerosis is initiated by the infiltration of monocytes into the subendothelial space of the vessel wall and subsequent lipid accumulation of the activated macrophages. The molecular mechanisms involved in the anomalous behavior of macrophages in atherogenesis have only partially been disclosed. Chitotriosidase and human cartilage gp-39 (HC gp-39) are members of the chitinase family of proteins and are expressed in lipid-laden macrophages accumulated in various organs during Gaucher disease. In addition, as shown in this study, chitotriosidase and HC gp-39 can be induced with distinct kinetics in cultured macrophages. We investigated the expression of these chitinase-like genes in the human atherosclerotic vessel wall by in situ hybridizations on atherosclerotic specimens derived from femoral artery (4 specimens), aorta (4 specimens), iliac artery (3 specimens), carotid artery (4 specimens), and coronary artery (1 specimen), as well as 5 specimens derived from apparently normal vascular tissue. We show for the first time that chitotriosidase and HC gp-39 expression was strongly upregulated in distinct subsets of macrophages in the atherosclerotic plaque. The expression patterns of chitotriosidase and HC gp-39 were compared and shown to be different from the patterns observed for the extracellular matrix protein osteopontin and the macrophage marker tartrate-resistant acid phosphatase. Our data emphasize the remarkable phenotypic variation among macrophages present in the atherosclerotic lesion. Furthermore, chitotriosidase enzyme activity was shown to be elevated up to 55-fold in extracts of atherosclerotic tissue. Although a function for chitotriosidase and HC gp-39 has not been identified, we hypothesize a role in cell migration and tissue remodeling during atherogenesis.

Acid Phosphatase↗

Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase.

The existence of a non-lysosomal glucosylceramidase in human cells has been documented (van Weely, S., Brandsma, M., Strijland, A., Tager, J. M., and Aerts, J. M. F. G. (1993) Biochim. Biophys. Acta 1181, 55-62). Hypothetically, the activity of this enzyme, which is localized near the cell surface, may influence ceramide-mediated signaling processes. To obtain insight in the physiological importance of the non-lysosomal glucosylceramidase, the availability of specific inhibitors would be helpful. Here we report on the generation of hydrophobic deoxynojirimycin (DNM) derivatives that potently inhibit the enzyme. The inhibitors were designed on the basis of the known features of the non-lysosomal glucosylceramidase and consist of a DNM moiety, an N-alkyl spacer, and a large hydrophobic group that promotes insertion in membranes. In particular, N-(5-adamantane-1-yl-methoxy)pentyl)-DNM is a very powerful inhibitor of the non-lysosomal glucosylceramidase at nanomolar concentrations. At such concentrations, the lysosomal glucocerebrosidase and alpha-glucosidase, the glucosylceramide synthase, and the N-linked glycan-trimming alpha-glucosidases of the endoplasmic reticulum are not affected.

1-Deoxynojirimycin↗