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Biomedical subjects

G de Jong

Publications and source records attributed to G de Jong.

At least 19 recordsLinked to original sources
PubMed2006

Nosocomial outbreak of extended-spectrum beta-lactamase-producing Salmonella isangi in pediatric wards.

Since May 2000, extended-spectrum beta-lactamase-producing (ESBL) Salmonella Isangi were isolated from pediatric patients at a tertiary hospital. A total of 41 patients with positive cultures were reviewed, and the majority presented with gastroenteritis, fever, or both. One ESBL phenotype was noted in all isolates, and clonality was confirmed by pulsed-field gel electrophoresis. This is the first report of Salmonella sp. ESBL resistance in our hospital.

Child, Preschool↗
PubMed2005

Genetic parameters for claw disorders in Dutch dairy cattle and correlations with conformation traits.

Impaired claw health is one of the major problems causing production loss and reduced animal welfare in dairy cattle. In response, the Dutch Animal Health Service (GD) Ltd. initiated this study, in which claws of lactating and near-term cows and heifers in 430 herds were trimmed by hoof trimmers and the health status of the rear claws recorded. Only herds with >75% of the animals having feet trimmed were considered, resulting in records on 21,611 animals. Eight claw disorders were scored: digital dermatitis (DD), interdigital dermatitis/heel horn erosions (IDHE), sole hemorrhage (SH), chronic laminitis (CL), sole ulcer (SU), white line disease (WLD), interdigital hyperplasia (HYP), and interdigital phlegmona (IP). The prevalence varied from 0.6% (IP) to 39.9% (SH). More than 70% of the animals had at least one claw disorder. Conformation traits and locomotion were recorded once during the animal's first lactation by trained classifiers of the Royal Dutch Cattle Syndicate and completely independent of the moment of claw trimming. Heritabilities were estimated using a sire model, and ranged from <0.01 (IP) to 0.10 (DD and HYP). Genetic correlations of incidences of claw disorders with locomotion were variable, ranging from 0.13 (SH) to -0.91 (CL). Genetic correlations with the rear leg conformation traits were lower, ranging from 0.04 (ID with rear leg side view) to -0.69 (IP with rear leg rear view).

Animals↗
PubMed2004

Candida parapsilosis detected in TPN using the BacT/Alert system and characterized by randomly amplified polymorphic DNA.

Candida parapsilosis was detected in environmental swabs and batches of total parenteral nutrition (TPN) products after routine monitoring. The isolates were analysed using randomly amplified polymorphic DNA (RAPD) to determine clonality and establish the most likely source of contamination. Of 20 isolates analysed, 18 were indistinguishable clonally and were found to be associated with particular work stations. The application of regular testing using a system such as the BacT/Alert, and molecular studies for epidemiological analysis, is of benefit to producers of medical products such as TPN to ensure patient safety.

Candida↗
PubMed2004

Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNALeu(UUR) gene.

Screening the mitochondrial DNA of a 64-year-old woman with mitochondrial myopathy revealed 76% of the tRNA(Leu(UUR)) A3302G mutation in muscle. Muscle of her affected son carried 96% mutated mitochondrial DNA. Both patients were biopsied twice, showing isolated complex I deficiency in the son's first biopsy, additional increased (within normal range) complex II + III activities in his second biopsy, combined complex I, II + III deficiency in mothers first biopsy and additional complex IV deficiency in her second biopsy. After a stay in the mountains, the son died of cardiac arrhythmia. The A3302G mutation has been reported before and is associated with mitochondrial myopathy and cardiorespiratory failure. Pathogenesis is explained by abnormal mtRNA processing, which was also reported for the adjacent C3303T mutation associated with cardiomyopathy and/or skeletal myopathy. Our findings suggest that a high mutation load of the A3302G mutation can lead to fatal cardiorespiratory failure, likely triggered by low environmental oxygen pressure and exercise.

Adult↗
PubMed2004

Additive and nonadditive genetic variation in avian personality traits.

Individuals of all vertebrate species differ consistently in their reactions to mildly stressful challenges. These typical reactions, described as personalities or coping strategies, have a clear genetic basis, but the structure of their inheritance in natural populations is almost unknown. We carried out a quantitative genetic analysis of two personality traits (exploration and boldness) and the combination of these two traits (early exploratory behaviour). This study was carried out on the lines resulting from a two-directional artificial selection experiment on early exploratory behaviour (EEB) of great tits (Parus major) originating from a wild population. In analyses using the original lines, reciprocal F(1) and reciprocal first backcross generations, additive, dominance, maternal effects ands sex-dependent expression of exploration, boldness and EEB were estimated. Both additive and dominant genetic effects were important determinants of phenotypic variation in exploratory behaviour and boldness. However, no sex-dependent expression was observed in either of these personality traits. These results are discussed with respect to the maintenance of genetic variation in personality traits, and the expected genetic structure of other behavioural and life history traits in general.

Adaptation, Psychological↗
PubMed2004

Random herd curves in a test-day model for milk, fat, and protein production of dairy cattle in The Netherlands.

With random regression models, genetic parameters of test-day milk production records of dairy cattle can be estimated directly from the data. However, several researchers that used this method have reported unrealistically high variances at the borders of the lactation trajectory and low genetic correlations between beginning and end of lactation. Recently, it has been proposed to include herd-specific regression curves in the random regression model. The objective was to study the effect of including random herd curves on estimated genetic parameters. Genetic parameters were estimated with 2 models; both included random regressions for the additive genetic and permanent environmental effect, whereas the second model also included a random regression effect for herd x 2-yr period of calving. All random regressions were modeled with fourth-order Legendre polynomials. Bayesian techniques with Gibbs sampling were used to estimate all parameters. The data set comprised 857,255 test-day milk, fat, and protein records from lactations 1, 2, and 3 of 43,990 Holstein cows from 544 herds. Genetic variances estimated by the second model were lower in the first 100 d and at the end of the lactation, especially in lactations 2 and 3. Genetic correlations between d 50 and the end of lactation were around 0.25 higher in the second model and were consistent with studies where lactation stages are modeled as different traits. Subsequently, estimated heritabilities for persistency were up to 0.14 lower in the second model. It is suggested to include herd curves in a random regression model when estimating genetic parameters of test-day production traits in dairy cattle.

Animals↗
PubMed2002

Two types of lacunar infarcts: further arguments from a study on prognosis.

BACKGROUND AND PURPOSE: Earlier, we found that lacunar stroke patients with > or =1 asymptomatic lacunar infarcts on CT had leukoaraiosis and hypertension significantly more often than patients without such lesions, and we hypothesized that 2 types of small-vessel disease could be distinguished during life: arteriolosclerosis and microatheromatosis, respectively. Differences in prognosis might sustain this hypothesis of 2 lacunar stroke entities. Therefore, we performed a follow-up in 333 patients with first lacunar stroke, distinguishing those with > or =1 asymptomatic lacunar lesions (LACI+) from those without such lesions (LACI-). METHODS: Cross-sectional follow-up was performed after 785+/-479 days (mean+/-SD) in 104 LACI+ patients and 865+/-545 days in 229 LACI- patients. RESULTS: Mortality at the end of follow-up was 33% in LACI+ and 21% in LACI- patients [odds ratio (OR), 1.74; 95% confidence interval (CI), 1.01 to 3.01]. Stroke recurrence rate was 21% in LACI+ and 11% in LACI- (OR, 2.09; 95% CI, 1.08 to 4.06). Forty percent of LACI+ and 26% of LACI- patients had unfavorable outcome at the end of follow-up (OR, 1.95; 95% CI, 1.17 to 3.26). Kaplan-Meier curves showed less favorable survival in LACI+ (log-rank test, P=0.0218) and survival free of stroke (log-rank test, P=0.0121) than in LACI-. When we restricted the analysis to patients with both silent lesions and leukoaraiosis (n=63) compared with those without (n=196), differences were even more pronounced. CONCLUSIONS: Prognosis for mortality, recurrent stroke, and overall functional outcome in lacunar stroke patients with > or =1 silent lacunar lesions is more unfavorable than in patients without such lesions. These findings sustain the idea of 2 lacunar stroke entities.

Arteriosclerosis↗
PubMed2002

Genotype x environment interaction for protein yield in Dutch dairy cattle as quantified by different models.

Variance components and breeding values for protein yield were estimated with REML without and with correction for heterogeneity of variances. Three different sire models were applied, which all accounted for genotype x environment (G x E) interaction. The first model included a sire x herd-year-season subclass (HYS) interaction. The second model divided all records in four different types of management groups, based on estimated HYS subclass effect. The third model, the reaction norm model, performed a random linear regression on the estimated HYS effect. For comparison, a standard model that did not take G x E interaction into account was also applied. Data consisted of 102,899 305-d first-lactation protein records of Holstein Friesians of 1,000 ofthe largest Dutch dairy herds. All animals calved in 1997, 1998, or 1999. Estimated breeding values (EBV) for 2,150 bulls with at least five daughters were calculated. The interaction model detected an interaction variance of 2.5% of the phenotypic variance. The EBV showed a correlation of 1.00 with those of the standard model without interaction. The model with the division in groups showed correlations between groups ranging from 0.73 to 0.86. The EBV showed correlations from 0.84 to 0.91 with the EBV of the standard model. The reaction norm model calculated EBV that had a correlation of 1.00 with the EBV of the standard model. The reaction norm model was not able to detect significant variance of the slope for the protein data corrected for heterogeneity of variances.

Analysis of Variance↗
PubMed2001

A flow cytometry technique for measuring chromosome-mediated gene transfer.

BACKGROUND: Using artificial chromosome expression systems (ACes), we have developed a unique and rapid screening technique to quantify delivery of foreign DNA into cells in vitro. Delivery was measured within 24 h after transfection, using flow cytometry to detect the transfer of ACes labeled with thymidine analogue. This technique can be used to optimize delivery parameters of ACes and heterologous DNA into cells and eventually tissue. METHOD: Chinese hamster ovary (CHO) cells carrying artificial chromosomes were grown in media supplemented with iododeoxyuridine (IdUrd). The 60-mb artificial chromosome was purified by flow cytometry sorting and transfected into Chinese hamster lung fibroblast cells (V79-4) or mouse connective tissue cells [LM(tk-)] using LipofectAMINE 2000trade mark, a cationic lipid, and Superfecttrade mark, a cationic dendrimer. The cells were incubated with an FITC-conjugated anti-bromodeoxyuridine (BrdUrd) antibody and analyzed by flow cytometry. IdUrd-incorporated artificial chromosome expressing green fluorescent protein (GFP) was transfected into V79-4 cells. Delivery was measured at 24 h and GFP expression was detected at 48 h. RESULTS: The delivery of intact artificial chromosomes into V79-4 and LMtk- cells was detected within 2 h and up to 48 h post-transfection. Maximum delivery rates of 20% and 14% were observed using LipofectAMINE 2000 and Superfect, respectively. Flow cytometry data correlated with microscopic observations. IdUrd incorporation resulted in less quenching after staining with Hoechst 33258 and chromomycin A3 than BrdUrd incorporation. The fluorescence intensity of the FITC-conjugated anti-BrdUrd antibody was greater with IdUrd-incorporated chromosomes than with BrdUrd-incorporated chromosomes. CONCLUSION: The results indicate that IdUrd-labeled artificial chromosomes can be detected 24 h after transfection. This efficient, sensitive, high-throughput detection technique is being used to evaluate and optimize other transfer technologies (e.g., electroporation and sonoporation), different delivery reagents, and protocols in a variety of cells in vitro. This work represents the first step in utilizing artificial chromosomes as nonviral vectors for gene therapy.

Animals↗
PubMed2001

Radiation induced apoptosis in ataxia telangiectasia homozygote, heterozygote and normal cells.

Recent reports suggest that the radiation-induced, p53-dependent, apoptotic response is aberrant in ataxia telangiectasia (AT) cells. We investigated the possibility that an aberrant apoptotic response to ionizing radiation may also be the characteristic of AT heterozygotes and may facilitate in discriminating AT heterozygotes from the general population. Log phase, Epstein Barr virus (EBV) transformed lymphoblastoid cell lines and primary lymphocytes from three AT families were irradiated and the apoptotic response at 30h post radiation was measured by flow cytometry using TUNEL and hypodiploid methods. Our results show that the apoptotic response of AT homozygote (ATM-/-), AT heterozygote (ATM+/-) and normal cells (ATM+/+) to ionizing radiation, measured by the hypodiploid and TUNEL methods using flow cytometry, is dose and time dependent. Furthermore, this response is paradoxical in that ATM (-/-) lymphoblastoid cells were characterized by a reduced post radiation apoptotic response compared to their normal counterparts. Heterozygote (ATM+/-) lymphoblastoid cells displayed an intermediate response to ionizing radiation. In contrast, primary, non-transformed AT cells exhibited the same apoptotic response as their normal counterparts. Our results thus indicate that pre-radiation, EBV-transformed, lymphoblastoid cell lines from individual families may be useful in discriminating ATM status, but patient-derived, primary AT homozygous, heterozygous and normal primary cultured lymphocytes cannot be discriminated by this assay.

Apoptosis↗
PubMed2001

Efficient in-vitro transfer of a 60-Mb mammalian artificial chromosome into murine and hamster cells using cationic lipids and dendrimers.

Non-integrating artificial chromosomes represent a potentially promising approach to ex-vivo and in-vivo gene therapy applications. These large vectors require an efficient means for delivery to target cells. We have evaluated a panel of twenty-one commercially available transfection agents for their ability to mediate the in-vitro transfer of a 60-Mb murine artificial chromosome consisting of mouse major satellite DNA and a payload including a marker gene (hygromycin B) and a reporter gene (lacZ). A rapid screening procedure utilizing iododeoxyuridine-incorporated artificial chromosomes facilitated the assessment of different transfection conditions. The results were confirmed by cytogenetic analysis of positively transfected clones. By transfecting both hamster lung fibroblast cells (V79-4) and murine connective tissue cells [L-M(TK-)], the best results were obtained using either Superfect (cationic dendrimer) or LipofectAMINE 2000 (cationic lipid) with protocols adapted for metaphase chromosome preparation. Transfection efficiencies of 10(-4)-10(-2) (0.01-1%) were routinely observed, and recipient cells were able to maintain expression of the reporter gene over the total length of the experiment. This represents a significant advance over our previous attempts at mass-transfection of artificial chromosomes using microcell fusion, where we routinely achieved efficiencies at least two orders of magnitudes less than reported here. These data are particularly noteworthy given that lipid-mediated gene transfer typically involves transfecting millions of plasmids (1 microg of DNA from a 5 kb plasmid is approximately 1.2 x 10(11) copies) to each cell whereas the much larger artificial chromosomes comprise only a one-to-one ratio, yet achieve transfection efficiencies of (10(-2)-10(-1)), that is, comparable to our results. These data suggest that artificial chromosomes containing therapeutic genes can be successfully delivered to target cells in vitro using well-established transfection agents.

Animals↗
PubMed2000

Defects of blastogenesis: counseling dilemmas in two families.

Three patients are described with defects of blastogenesis and predominantly midline defects. Two were sibs of whom the firstborn were female cephalothoracopagus-conjoined twins with multiple predominantly midline defects initially thought to be a sporadic occurrence. A subsequent brother presented with severe hydrocephalus, rhombencephalosynapsis, conotruncal defect, ambiguous genitalia, and unilateral pre-axial polydactyly; an autosomal recessive defect is postulated in this case. Patient 3 had hydrocephalus, small cerebellum, cleft lip and palate, and a large sacrococcygeal teratoma, the better differentiated part of which included ovarian tissue with primordial follicles. The latter may occur in incomplete twinning as a defect of blastogenesis. The mother had had a previous termination of a fetus with hydrocephalus from a different relationship. Counseling was difficult since no examinations were done on the previous fetus and no further investigations of this family could be obtained, but a genetic origin is suspected. Most defects of blastogenesis are sporadic; however, some cases have a genetic cause and ultrasound examinations should be offered in subsequent pregnancies.

Abnormalities, Multiple↗
PubMed2000

Maintenance of genetic variation in phenotypic plasticity: the role of environmental variation.

We study genetic variation in phenotypic plasticity maintained by a balance between mutation and weak stabilizing selection. We consider linear reaction norms allowing for spatial and/or temporal variation in the environments of development and selection. We show that the overall genetic variation maintained does not depend on whether the trait is plastic or not. The genetic variances in height and slope of a linear reaction norm, and their covariance, are predicted to decrease with the variation in the environment. Non-pleiotropic loci influencing either height or slope are expected to decrease the genetic variance in slope relative to that in height. Decrease in the ratio of genetic variance in slope to genetic variance in height with increasing variation in the environment presents a test for the presence of loci that only influence the slope, and not the height. We use data on Drosophila to test the theory. In seven of eight pair-wise comparisons genetic variation in reaction norm is higher in a less variable environment than in a more variable environment, which is in accord with the model's predictions.

Alleles↗
PubMed2000

Genetic variance in temperature dependent adult size deriving from physiological genetic variation at temperature boundaries.

An increase in genetic variation in body size has often been observed under stress; an increase in dominance variance and interaction variance as well as in additive genetic variance has been reported. The increase in genetic variation must be caused by physiological mechanisms that are specific to adverse environments. A model is proposed to explain the occurrence of an increase in genetic variation in body size in Drosophila at extreme temperatures. The model has parameters specific to the low- and high-temperature regions of the viable range. Additive genetic variation in the boundary temperatures leads to a marked increase in additive genetic variation in development rate and body size at extreme temperatures. Additive genetic variation in the temperature sensitivity in the low- and high-temperature regions adds non-additive genetic variation. Development rate shows patterns in additive genetic variation that differ from the patterns of genetic variation in body size; therefore, the genetic correlation between development rate and body size changes sign repeatedly as a function of temperature. The existence of dominance in the genetic variation in the boundary temperatures or in the low- and high-temperature sensitivities leads to a higher total genetic variance due to higher dominance and interaction variance, for both development rate and body size.

Animals↗
PubMed2000

Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas.

Colorectal adenomas are macroscopically visible morphological changes of the mucosa that can develop focal carcinoma in the absence of surgical intervention. The successive molecular changes proposed to occur at different stages in the adenoma-carcinoma sequence were primarily based on DNA studies of exophytic, polypoid-type adenomas. Not all colorectal lesions, however, display an exophytic phenotype and a presumed distinct colorectal neoplasm, the nonpolypoid adenoma, was subsequently described as a precursor of colorectal cancer. The low incidence of KRAS mutations in nonpolypoid colorectal adenomas reported previously suggested a different genetic basis for the transformation process in these lesions. We have pursued the identification of genetic changes in benign sporadic nonpolypoid colorectal adenomas in a selected Swedish patient group with no family history of colorectal cancer. Mutation screening of the adenomatous polyposis coli (APC), KRAS, and TP53 genes was conducted using the protein truncation test, heteroduplex-single-strand conformation polymorphism analysis, and denaturing gradient gel electrophoresis on PCR-amplified fragments. Fourteen mutations in the APC gene were characterized in 10/20 samples. Mutations in the KRAS and TP53 genes were identified in 3/57 and 4/51 adenomas, respectively. The mutation frequencies and distribution of mutations in APC correlate with published data on exophytic adenomas. The low mutation frequency of the TP53 gene is consistent with the benign nature of the research material. KRAS activation (an early event in polypoid colorectal adenomas) apparently does not play a significant role in nonpolypoid adenoma development but may result in the development of a polypoid configuration. Genes Chromosomes Cancer 27:202-208, 2000.

Adenoma↗
PubMed1999

Genetic variability in sensitivity to population density affects the dynamics of simple ecological models.

Many 1-dimensional discrete time ecological models contain a sensitivity parameter that does not affect the dynamic complexity of these models. We show that genetic variability in this parameter can have a strong effect on population dynamics. We incorporate ecological dynamics in two different population genetic models with one locus and two alleles. The first is the classical model of a randomly mating population in Hardy-Weinberg equilibrium, and the second is a model of differential selection in males and females. In populations in Hardy-Weinberg equilibrium, variability in the sensitivity parameter can be maintained by overdominance. In this case, the dynamics of the polymorphic population tend to be much simpler than those of monomorphic populations. In the model with different selection in males and females, polymorphisms can be maintained in various ways, e.g., by opposing directional selection in males and females. Polymorphism in the sensitivity parameter tends to simplify population dynamics in the model with different selection in males and females as well. A number of interesting dynamic effects can be observed, e.g., multiple attractors with complicated basins of attraction. Then the final state of the system after a successful invasion by mutant alleles may depend on the mutation rate and on the distribution of mutational steps. In addition, there are situations in which genetic variability destabilizes a stable population dynamic equilibrium in the monomorphic model. There is an analogy between genetic variability and variability imposed by the environment. If differences in sensitivity are caused by the environment, dynamic effects similar to those in the genetic models can be observed. In addition, source-sink structures that are known to occur in spatially structured models can be seen in the genetic model if one of the genotypes is inviable. The results suggest that combining ecological and population genetic models can lead to a number of new insights. More work is needed, e.g., with fertility models, in which fitnesses are not assigned to individuals, but to mating pairs.

Alleles↗