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F Kok

Publications and source records attributed to F Kok.

36 records · Page 2Linked to original sources
PubMed1998

Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: a randomized controlled trial.

A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and investigated whether this response is mediated by an increase in serum triglycerides. Elderly women (> 60 years, n=91) received on separate days four different fat-rich breakfasts (50 energy percent [en%] of fat) and a control breakfast (1.5 en% fat; crossover). The fat-rich breakfasts differed in fatty acid composition: one rich in palmitic acid (21.7 g), one in stearic acid (18.6 g), and the other two in linoleic and linolenic acid-one with a ratio 3:1 (12.5/3.9 g) and the other with a ratio of 15:1 (18.8/1.2 g). At 8 AM before the breakfast (fasting) and at 1 and 3 PM, blood samples were taken, in which FVIIa and serum triglycerides were measured. FVIIa response to the fat-rich meals ranged from 11.6 mU/mL (95% confidence interval: 8.3,14.9) on the stearic meal to 15.9 mU/mL (12.0,19.8) on the linoleic/linolenic 15:1 meal at 1 PM and from 14.9 mU/mL (10.6,19.2) to 21.1 mU/mL (16.6,25.6) for the same meals at 3 PM. The responses did not differ between the fat-rich meals. After the control breakfast, FVIIa decreased, with 6.3 mU/mL (3.9,8.7) at 1 PM and 8.7 mU/mL (6.3,11.1) at 3 PM. The triglyceride response was lower after both linoleic/linolenic rich breakfasts compared with the palmitic and stearic breakfast (P<.05) and was not associated with the FVIIa response at any of the blood sampling occasions. The results of this study show that the response of FVIIa to a fat-rich meal is independent of its fatty acid composition and is not mediated by serum triglycerides.

Aged↗
PubMed1998

Differences between plasma and adipose tissue biomarkers of carotenoids and tocopherols.

Biomarkers of dietary exposure or nutritional status are sought actively to overcome limitations of traditional dietary methodology. We compared plasma and adipose tissue biomarkers for carotenoids and tocopherols. The data consisted of samples from 91 men and 122 women, ages 45-70 years, from the control group of the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC) Study. Pearson correlations between plasma and adipose tissue measurements for beta-carotene, lycopene, and alpha-tocopherol adjusted for smoking status displayed low, although significant, correlations of 0.39, 0.24, and 0.39, respectively. The correlation was further stratified by sex. After being corrected for measurement error using deattenuation factors obtained from a reproducibility study, the stratified correlation coefficients were as high as 0.80 for beta-carotene in men, 0.62 for lycopene in women, and 0.52 for alpha-tocopherol in women. In addition, plasma and adipose tissue measurements from the myocardial infarction (MI) subset of the EURAMIC study population were used to evaluate the odds of MI, adjusting for confounders. We found that the concentration of lycopene in plasma was not positively associated significantly with MI (odds ratio, 1.78; P = 0.26). Adipose tissue lycopene, in contrast to reports elsewhere on the total population, showed an inverse association with MI (odds ratio, 0.62; P = 0.15). These results suggest that plasma and adipose carotenoids represent different markers for nutritional status and cannot be used interchangeably in epidemiological and dietary validation studies.

Adipose Tissue↗
PubMed1997

[Angelman syndrome: a frequently undiagnosed cause of mental retardation and epilepsy. Case report].

The authors describe the case of a typical Angelman syndrome patient. The proband presents developmental delay, mental retardation, macrostomia, wide-spaced teeth, seizures, absent speech, jerky gait, and paroxysms of laughter. The cytogenetic and molecular studies showed a maternal deletion of 15q11q13. These results are in agreement with the clinical diagnosis of Angelman syndrome.

Angelman Syndrome↗
PubMed1996

Predictors of adipose tissue carotenoid and retinol levels in nine countries. The EURAMIC Study.

The adipose tissue carotenoid (alpha-carotene, beta-carotene, and lycopene) and retinol levels and their predictors were determined in 686 male and 339 female middle-aged and elderly subjects from eight European countries and Israel during the years 1991 to 1992. Adipose tissue carotenoid levels in men were 50-76% of those in women, whereas the retinol level in men was 116% of that in women (p < 0.001). When all significant predictors of antioxidant levels were considered in men, waist circumference was shown to be an independent predictor of adipose tissue alpha-carotene, age, waist circumference, and alcohol use were independent predictors of beta-carotene; age, body mass index, and waist circumference were predictors of lycopene; and waist circumference, smoking, and alcohol consumption were predictors of retinol. In the same way, in women waist circumference was shown to be an independent predictor of alpha-carotene level, BMI was a predictor of beta-carotene, smoking was a predictor of retinol, and alcohol consumption was a predictor of lycopene. The observed association of age with beta-carotene was positive, that with lycopene was inverse, and those of body mass index and waist circumference with the antioxidant levels were inverse. Alcohol use was inversely associated with beta-carotene level, and smoking and alcohol use were positively associated with retinol and lycopene levels. Epidemiologic studies on diet-disease relations using adipose tissue levels of carotenoids and retinol should consider gender, body size and composition, smoking, and alcohol consumption as potential confounders in diet-disease relations.

Adipose Tissue↗
PubMed1996

Predictors of adipose tissue tocopherol and toenail selenium levels in nine countries: the EURAMIC study. European Multicentre Case-Control Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast.

OBJECTIVE: To evaluate the levels of adipose tissue alpha-tocopherol, gamma-tocopherol, and toenail selenium and their determinants. DESIGN: Control subjects from multicentre case-control study on antioxidants, myocardial infarction and cancer of the breast. SUBJECTS AND SETTING: 686 male and 339 female middle-aged and elderly subjects from eight European countries and Israel. RESULTS: The antioxidant levels were lower in men than women; adipose tissue alpha-tocophreol level in men was 75% of that in women, gamma-tocopherol 79% and toenail selenium 92%, respectively. In multiple regression analysis adjusting for age and centre waist circumference showed to be the only independent predictor of adipose tissue alpha-tocopherol level and waist/hip (W/H) ratio that of gamma-tocopherol level in men. In women no predictors of adipose tissue alpha-tocopherol or gamma-tocopherol level were found. Smoking and coffee use showed up to be the independent predictors of toenail selenium in men and smoking in women. Age, alcohol use, serum lipids, and reproductive factors were not related to the antioxidant levels. CONCLUSION: The inverse relationships of adipose tissue alpha-tocopherol and gamma-tocopherol levels with central fat distribution should be considered in studies relating the tocopherol levels to the development of chronic diseases in men, and the inverse relationship of toenail selenium with smoking both in men and women, and with coffee consumption in men, should be considered when toenail selenium level is used as a biomarker in epidemiological studies.

Adipose Tissue↗
PubMed1995

Mutational analysis of patients with X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked neurodegenerative disorder characterized by elevated very long chain fatty acid (VLCFA) levels, reduced activity of peroxisomal VLCFA-CoA ligase, and variable phenotypic expression. A putative gene for ALD was recently identified and surprisingly encodes a protein (ALDP) that belongs to a family of transmembrane transporters regulated or activated by ATP (the ABC proteins). We have examined genomic DNA from ALD probands for mutations in the putative ALD gene. We detected large deletions of the carboxyl-terminal portion of the gene in 4 of 112 probands. Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis. SSCP variants were detected in 22 probands and none in 60 X-chromosomes from normal individuals. Mutations were detected in all of the ALD probands. The mutations were distributed throughout the gene and did not correlate with phenotype. Approximately half were non-recurrent missense mutations of which 64% occurred in CpG dinucleotides. There was a cluster of frameshift mutations in a small region of exon 5, including an identical AG deletion in 7 unrelated probands. These data strongly support the supposition that mutations in the putative ALD gene result in ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1995

Altered expression of ALDP in X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disorder with variable phenotypic expression that is characterized by elevated plasma and tissue levels of very long-chain fatty acids. However, the product of the gene defective in ALD (ALDP) is a membrane transporter of the ATP-binding cassette family of proteins and is not related to enzymes known to activate or oxidize fatty acids. We generated an antibody that specifically recognizes the C-terminal 18 amino acids of ALDP and can detect ALDP by indirect immunofluorescence. To better understand the mechanism by which mutations in ALDP lead to disease, we used this antibody to examine the subcellular distribution and relative abundance of ALDP in skin fibroblasts from normal individuals and ALD patients. Punctate immunoreactive material typical of fibroblast peroxisomes was observed in cells from seven normal controls and eight non-ALD patients. Of 35 ALD patients tested, 17 had the childhood-onset cerebral form of the disease, 13 had the milder adult phenotype adrenomyeloneuropathy, 3 had adrenal insufficiency only, and 2 were affected fetuses. More than two-thirds (69%) of all patients studied showed no punctate immunoreactive material. There was no correlation between the immunofluorescence pattern and clinical phenotype. We determined the mutation in the ALD gene in 15 of these patients. Patients with either a deletion or frameshift mutation lacked ALDP immunoreactivity, as expected. Four of 11 patients with missense mutations were also immunonegative, indicating that these mutations affected the stability or localization of ALDP. In the seven immunopositive patients with missense mutations, correlation of the location and nature of the amino acid substitution may provide new insights into the function of this peroxisomal membrane protein. Furthermore, the study of female relatives of immunonegative ALD probands may aid in the assessment of heterozygote status.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1993

Statistical methods in interphase cytogenetics: an experimental approach.

In situ hybridization (ISH) techniques on interphase cells, or interphase cytogenetics, have powerful potential clinical and biological applications, such as detection of minimal residual disease, early relapse, and the study of clonal evolution and expansion in neoplasia. Much attention has been paid to issues related to ISH data acquisition, i.e., the numbers, colors, intensities, and spatial relationships of hybridization signals. The methodology concerning data analysis, which is of prime importance for clinical applications, however, is less well investigated. We have studied the latter for the detection of small monosomic and trisomic cell populations using various mixtures of human female and male cells. With a chromosome X specific probe, the male cells stimulated monosomic subpopulations of 0, 1, 5, 10, 50, 90, 95, 99, and 100%. Analogously, when a (7 + Y) specific probe combination was used, containing a mixture of chromosome No. 7 and Y-specific DNA, the male cells simulated trisomic cell populations. Probes specific for chromosomes Nos. 1, 7, 8, and 9 were used for estimation of ISH artifacts. Three statistical tests, the Kolmogorov-Smirnov test, the multiple-proportion test, and the z'-max test, were applied to the empirical data using the control data as a reference for ISH artifacts. The Kolmogorov-Smirnov test was found to be inferior for discrimination of small monosomic or trisomic cell populations. The other two tests showed that when 400 cells were evaluated, and using selected control probes, monosomy X could be detected at a frequency of 5% aberrant cells, and trisomy 7 + Y at a frequency of 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Aberrations↗
PubMed1992

Mosaicism of trisomy 12 in chronic lymphocytic leukemia detected by non-radioactive in situ hybridization.

Cytogenetic analysis using banding techniques of B-chronic lymphocytic leukemia (CLL) is hampered by the difficult in vitro proliferation of these tumor cells. For detection of specific cytogenetic aberrations these problems can be overcome with non-radioactive in situ hybridization (ISH). ISH may especially be applied for the detection of trisomy 12, which is the most frequent cytogenetic aberration in CLL. Sixty-seven patients with CLL, four normal controls and one lymphoblastoid B-cell line with a trisomy 12 were studied using a chromosome 12 specific probe. To determine the hybridization properties of the CLL cells, all samples were also hybridized with probes specific for chromosomes 1 and 8. All leukemias were analyzed by immunocytochemistry to determine the proportion of tumor cells. Eight cases (11%) showed a trisomy 12. After correction for the number of tumor cells, it was demonstrated that in almost all cases (7 out of 8), the aberration was present in a proportion of the tumor cells (between 30 and 72%). Except for one patient this mosaicism persisted with long-term follow-up. We conclude that the in vivo incidence of trisomy 12 in CLL is approximately 11%, and that trisomy 12 occurs in most instances in only a subpopulation of the leukemic cells. Both findings suggest that trisomy 12 in CLL is a late event.

Chromosomes, Human, Pair 12↗
PubMed1990

In search of a genetic basis for the Rett syndrome.

Rett syndrome is a progressive encephalopathy restricted to the female sex. In the present paper a possible genetic cause for this syndrome is discussed, based on data from the literature as well as our own. Our results are in agreement with others regarding no increase in parental age, or in spontaneous abortions rate among the mothers of affected children and with a normal sex ratio among sibs. We have found no chromosome rearrangement detectable with the methods used and no correlation between fra(X) (p22) and the Rett syndrome. We have observed an alteration in the sequence of replication in one of the two types of late-replicating X-chromosome present in normal women, and suggest that this may signify that genes which are active in the late-replicating X-chromosome are inactivated (or vice-versa) in these patients. This fact could be related to the abnormal phenotype observed in Rett syndrome patients.

Child↗
PubMed1988

[The battered child syndrome: neurologic aspects in 7 cases].

Data on 7 cases of battered child syndrome with neurological complications are reviewed. First symptoms were convulsions and bulged fontanel of undetermined origin. At clinical examination the unexpected presence of retinal hemorrhage in 5/7 patients has been the main criteria to diagnostic definition. CT showed the presence of subdural collections in the majority of the patients. A normal CT, however, does not display the possibility of future problems. Successive CT studies have proved useful. In two cases they demonstrated the appearance of diffuse images of central nervous system destruction some weeks later, and probably related to ischaemic troubles in connection with the aggression mechanisms.

Battered Child Syndrome↗
PubMedDate not supplied

Pediatric multiple sclerosis report of 14 cases.

We present clinical data from 14 multiple sclerosis (MS) patients who have been admitted to our hospital between January 1980 and May 1992, whose age of onset ranged from 2-15 years. Our patients could be classified as having a clinically definite form of the disease. Initial symptoms varied from minor, such as motor or sensory impairment, bladder dysfunction, to the worst clinical presentation, suggesting diffuse encephalopathy. All the patients had a relapsing-remitting course. We report the paraclinical and laboratory examinations that were done in these patients. Over the period 1980 to 1992 these patients had 39 attacks. CSF analysis was performed in the phase of activity of the disease on 23 occasions and was normal in 12. At least one brain CT scan was performed in 9 patients and showed white matter abnormalities in 6. Cranial magnetic resonance imaging was done in 6 patients and were abnormal in 5. Visual evoked potential (EP) was abnormal in 7 of 8 patients; brainstem acoustic EP was abnormal in 4 of 8 patients and somatosensory EP in 4 of 8. MS is not so rare in childhood and although its diagnosis is essentially a clinical one, paraclinical investigations are of great value in the identification of demyelinating disorders in childhood.

Adolescent↗
PubMedDate not supplied

Enterovirus 71 infection and acute neurological disease among children in Brazil (1988-1990).

Surveillance for Enterovirus 71 (EV-71) infection in children up to 15 years of age was carried out in Brazil, from 1988 to 1990. Patients with acute neurological diseases (AND) such as flaccid paralysis, Bell's palsy, acute cerebellar ataxia and Guillain-Barré syndrome were included in the study. EV-71 infection was detected in 24 of 426 children (5.6%) with AND. EV-71 infection was confirmed only by virus isolation in 13 children, by virus isolation and seroconversion in 4, and by seroconversion alone in 7. EV-71 was also isolated from 15 of the 427 household contacts (3.5%) of 165 AND patients. There was some evidence of high infectivity of EV-71: household clusters were detected in the case of 7 of 24 children (29.1%) infected with EV-71 and manifesting AND; EV-71 was isolated from 11/40 household contacts (27.5%) of the infected patients but from only 4/387 household contacts (1.0%) of children in whom it was not possible to demonstrate EV-71 infection. Seven of the 24 children infected with EV-71 exhibited residual motor deficiency when examined 6 months after the disease onset. The relevance of these results for the Plan for Global Eradication of Wild Poliovirus is discussed, as well as the need to increase knowledge about the behaviour of this virus and its possible association with AND.

Acute Disease↗
PubMedDate not supplied

Discontinuing medication in epileptic children: a study of risk factors related to recurrence.

We studied 70 children who had experienced at least two seizures before age 12 years, excluding febrile seizures, neonatal seizures, or seizures occurring during a metabolic, or infectious insult to the central nervous system (CNS) and who had been seizure free for at least 2 years. Twenty children (28.5%) experienced a recurrence, 75% during antiepileptic (AED) drug discontinuation or less than 6 months after discontinuation. Risk factors statistically related to seizure recurrence were greater than 10 seizures before seizure control, an abnormal EEG in the year before AED discontinuation, presence of focal neurologic signs and/or mental retardation, and presence of a mixed seizure pattern. Fourteen children (70%) with recurrence had two or more risk factors, whereas 36 (72%) without recurrence had no risk factor or only one. We conclude that a selected group of epileptic children who remain seizure-free for a period of at least 2 years can have AEDs discontinued based on presence or absence of risk factors.

Anticonvulsants↗
PubMedDate not supplied

Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases.

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

Age of Onset↗
PubMedDate not supplied

[Hypotonic infants and the Prader-Willi Syndrome]

OBJECTIVE: To describe 6 patients with less than 3 years of age that were diagnosed with Prader-Willi syndrome (PWS) due to hypotonia, poor sucking, slight facial anomalies and minor abnormalities of hands and feet. PWS is a neurobehavioural disorder characterized by two distinct phases; in the first, the neonate presents variable degree of hypotonia, feeding problems with none or poor sucking; hypogonadism, characteristic facial features with almond shaped eyes, narrow bifrontal diameter and down-turned corners of the mouth. Neuropsichymotor development is delayed. Hypotonia is non progressive and tends to improve between 8 and 11 months of age. The second phase then starts and is characterized by increasing hyperphagia and obesity, among other features. Unfortunately, most PWS patients are diagnosed only after obesity is installed. METHODS: Methylation, microsatellites analysis and karyotypic studies by traditional and in situ hybridization techniques were done. RESULTS: A deletion of chromosome segment 15q11q13 was disclosed in 4 and maternal disomy in two patients. CONCLUSION: The diagnosis of PWS is generally established after the onset of obesity. So, we suggest that the genetic analysis must be carried out in children with severe hypotonia of unknown cause, poor sucking and some facial features of PWS (small hands and feet, hypogonadism, hypopigmentation, almond eyes and narrow bifrontal diameter). This can allow the early diagnosis and avoid invasive exams necessary for neuromuscular disorder diagnosis like muscle biopsy and electroneuromiography, wich frequently are associated with inconclusives results.

Journal Article↗