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Biomedical subjects

H de Vries

Publications and source records attributed to H de Vries.

At least 55 records · Page 3Linked to original sources

Plasma lactoferrin levels are decreased in end-stage AIDS patients.

The antimicrobial protein lactoferrin (Lf) is present in plasma and in mucosal secretions. Using ELISA we analysed plasma and saliva of HIV-infected patients, patients with AIDS, and healthy controls for the presence of secreted Lf. The plasma Lf levels of AIDS patients (classification C3) were significantly lower (p < 0.001) as compared to asymptomatic and symptomatic HIV infected patients, or controls. In addition, plasma Lf levels closely correlated with neutrophilic granulocyte counts in the HIV-infected patients. Thus, basal plasma Lf levels are likely the result of Lf release by neutrophilic granulocytes. The Candida titres present in the oral cavity were determined in a part of the HIV-infected patient group. As it appeared, the presence of this opportunistic pathogen always coincided with low levels of salivary Lf levels. We conclude that Lf, as part of the nonspecific immune system, might play an important role in the first line of defense against opportunistic microbial infections in AIDS patients.

AIDS-Related Opportunistic Infections↗

The effect of protein restriction on albuminuria in patients with type 2 diabetes mellitus: a randomized trial.

BACKGROUND: A randomized trial was conducted to assess whether protein restriction helps to delay the onset of renal disorders in type 2 diabetic patients. METHODS: Included in the trial were 121 type 2 diabetic patients with microalbuminuria or at least detectable albuminuria, or diabetes of duration > or =5 years. The experimental (39 male/19 female) and control group (35 male/28 female) received counselling on protein restriction and the usual dietary advice, respectively. The outcome measure was albuminuria (mg/24 h). Results. After 6 months in experimental and control groups the change in protein intake was -0.05+/-0.21 and +0.03+/-0.19 g/kg (P = 0.02), and in albuminuria -14% and +11% (P = 0.01), respectively. After 12 months, the differences between the experimental and the control group with respect to both protein intake and albuminuria had decreased. At 6 and 12 months, respectively, albuminuria was 28% (P<0.001) and 18% (P = 0.08) lower in the experimental than the control group. The effect in normoalbuminuric patients did not differ from that in microalbuminuric patients. In the experimental group, blood pressure, HbA1c and body weight decreased; in the control group, such decreases were less or absent. Dose-response analysis showed that a 0.10 g/kg change at 6 months in the intake of protein, of animal protein in particular, was related to an 11.1% change in albuminuria (P<0.005). Combining the intakes at 6 and 12 months suggested a percentage change of 9.1%. CONCLUSIONS: Substantial protein restriction in primary care, type 2 diabetic patients with no nephropathy is barely feasible. However, even a small reduction has a substantial and potentially beneficial effect on albuminuria.

Adult↗

How valid is fasting plasma glucose as a parameter of glycemic control in non-insulin-using patients with type 2 diabetes?

OBJECTIVE: To assess the value of fasting blood glucose as a parameter for glycemic control in type 2 diabetic patients not using insulin. RESEARCH DESIGN AND METHODS: In 1,020 type 2 diabetic patients treated with diet or oral hypoglycemic agents (OHAs), measurements of fasting plasma glucose (FPG) and HbA1c were taken. In 617 patients, the measurement could be repeated after 3 months. Cross-sectional correlation coefficients were calculated for the association between HbA1c and FPG. Receiver-operating characteristic (ROC)-curve analyses were applied to examine the performance of FPG as a diagnostic test for HbA1c. Longitudinally, the change in FPG was compared with the change in HbA1c, with both correlation measures and ROC curve analyses. RESULTS: Correlation coefficients between HbA1c and FPG and between FPG change and HbA1c change were 0.77 and 0.65, respectively. ROC curve analysis showed that HbA1c is difficult to predict from FPG values: 66% of the patients with good HbA1c (< 7.0%) were identified as such by FPG values < 7.8 mmol/l. As a test for HbA1c change, FPG change performed moderately: the highest combined values of sensitivity and specificity (87.7 and 57%, respectively) were reached at a cutoff point of zero in the range of FPG change values. CONCLUSIONS: FPG and HbA1c values that do not correspond are not rare in type 2 diabetic patients on diet or OHA treatment. HbA1c is difficult to predict from FPG values, and even more difficult is the prediction of HbA1c changes from FPG changes.

Blood Glucose↗

Photoreactivity of nifedipine in vitro and in vivo.

Side effects of nitroaromatics used as drugs are often assumed to be caused by incomplete enzymatic reduction of the nitro group. However, photoactivation, although usually not considered as a cause of the toxic effects of nitroaromatics, can play a considerable role. Nifedipine, a nitroaromatic as well, is an important drug used in the treatment of myocardial ischaemia and hypertension. It is extremely sensitive to ultraviolet and visible light up to 450 nm and forms a nitroso derivative in vitro. In the present study it is shown that the nitroso compound is a short-lived intermediate in blood and plasma. It reacts with other constituents to form a stable lactam. In vivo, this lactam proves to be rapidly clear from the blood of rats and is excreted almost quantitatively via the bile. The first photoproduct of nifedipine, nitroso nifedipine, is shown to be converted into the lactam mentioned. Beside the lactam, two other products, which are considered to be derivatives of the lactam, are found. One of these two products is also found in the bile of a rat that was exposed to UVA light after intravenous nifedipine administration. This shows that in an in vivo situation, photoproducts can reach organs other than those exposed to the light. In vitro about 45 to 50% of the original amount of nifedipine is not recovered after exposure of nifedipine to UVA in the presence of bovine serum albumin or after incubation of nitroso nifedipine with bovine serum albumin in the dark. As complex binding of nifedipine of plasma proteins is high, the latter finding may have important implications for the situation in vivo.

Animals↗

Transport of proteolipid protein to the plasma membrane does not depend on glycosphingolipid cotransport in oligodendrocyte cultures.

The possibility that transport of proteolipid protein (PLP) from its site of synthesis to the plasma membrane is dependent on cotransport with (sulfo)galacto-cerebrosides was investigated in primary cultured oligodendrocytes and Chinese hamster ovary (CHO) cells expressing PLP. Sulfation was inhibited by growing oligodendrocytes in the presence of a competitive inhibitor of this process, sodium chlorate. Under these circumstances, sulfatide synthesis was inhibited by 85%. Nevertheless, PLP was still delivered to the plasma membrane in quantitative amounts. Furthermore, when PLP was expressed in CHO cells, which normally synthesize very low amounts of galactosyl ceramide (GalCer) and no sulfatide, PLP was transported to the plasma membrane. Moreover, in CHO cells coexpressing PLP and ceramide galactosyl transferase, PLP cell surface labeling was unaltered. Noting that it has been demonstrated that proteins destined for the apical surface of epithelial cells colocalize with glycolipid-enriched microdomains, we isolated detergent-insoluble membrane complexes from cultured oligodendrocytes. We found, however, that most of the PLP is present in the detergent-soluble fraction and, furthermore, that PLP could not be chased into or out of the insoluble fraction. Taken together, these data make it very likely that in oligodendrocytes PLP transport takes place irrespective of the presence of glycosphingolipids GalCer and sulfatide.

Animals↗

Determinants of specific serum insulin concentrations in a general Caucasian population aged 50 to 74 years (the Hoorn Study).

The aim of this study was to investigate anthropometric and life-style determinants of insulinaemia. Specific fasting serum insulin (FI) was analysed in a general Caucasian population aged 50-74 years, not known to have diabetes mellitus (n = 2226, sample 1). The analysis was repeated some weeks later in a subgroup of sample 1 in which two individual measurements of FI were available (n = 540, sub-sample 2). Specific serum insulin 2 h after ingestion of 75 g glucose (2hI), also measured on two occasions, was analysed in this same subgroup after excluding 59 subjects with fasting plasma glucose >7 mmol l(-1) (n = 481, sub-sample 3). Multiple regression analyses were performed, stratified for sex, with 10log insulin as the dependent variable. All determinants were adjusted for each other. FI was positively associated with BMI and waist-hip ratio (men and women) and inversely associated with intake of fibre (women), moderate alcohol use (men), and current smoking (women). 2hI was positively associated with BMI and waist-hip ratio (men and women), and intake of fat (women). 2hI was inversely associated with physical activity and moderate alcohol use (men and women), and current smoking (men). Family history of diabetes was not associated with insulinaemia. In conclusion, various life-style factors are related to insulinaemia, independent of obesity.

Aged↗

Regulation of oligodendrocyte differentiation: protein kinase C activation prevents differentiation of O2A progenitor cells toward oligodendrocytes.

Oligodendrocytes differentiate on a specific schedule in vivo in order to myelinate axons at the precise time and at the appropriate position. The current study was undertaken to obtain further insight as to how this timed appearance is regulated intracellularly. We observed that exposure of O2A progenitor cells in culture to phorbol 12-myristate 13-acetate (PMA; an activator of protein kinase C, PKC) inhibited their differentiation to oligodendrocytes by suppressing the expression of specific myelin markers at the O4-stage. To positively identify a role of PKC per se in differentiation, the use of a minimal medium with low serum content turned out to be essential. This was demonstrated by showing that the inhibitory effect of PMA on oligodendrocyte differentiation could be completely abolished by a combined action of insulin, triiodothyronine (T3), hydrocortisone and other components of a chemically defined medium (CDM). Furthermore, the PMA-mediated inhibition of oligodendrocyte differentiation could be partially restored by activation of the cAMP signal transduction pathway. The results indicate that PKC plays a crucial role in the differentiation of O2A progenitor cells toward oligodendrocytes: PKC activation prevents differentiation of O2A progenitor cells, whereas differentiation toward oligodendrocytes is dependent on other signaling compounds which may counteract the PKC signal transduction route.

Animals↗

An apical-type trafficking pathway is present in cultured oligodendrocytes but the sphingolipid-enriched myelin membrane is the target of a basolateral-type pathway.

Myelin sheets originate from distinct areas at the oligodendrocyte (OLG) plasma membrane and, as opposed to the latter, myelin membranes are relatively enriched in glycosphingolipids and cholesterol. The OLG plasma membrane can therefore be considered to consist of different membrane domains, as in polarized cells; the myelin sheet is reminiscent of an apical membrane domain and the OLG plasma membrane resembles the basolateral membrane. To reveal the potentially polarized membrane nature of OLG, the trafficking and sorting of two typical markers for apical and basolateral membranes, the viral proteins influenza virus-hemagglutinin (HA) and vesicular stomatitis virus-G protein (VSVG), respectively, were examined. We demonstrate that in OLG, HA and VSVG are differently sorted, which presumably occurs upon their trafficking through the Golgi. HA can be recovered in a Triton X-100-insoluble fraction, indicating an apical raft type of trafficking, whereas VSVG was only present in a Triton X-100-soluble fraction, consistent with its basolateral sorting. Hence, both an apical and a basolateral sorting mechanism appear to operate in OLG. Surprisingly, however, VSVG was found within the myelin sheets surrounding the cells, whereas HA was excluded from this domain. Therefore, despite its raft-like transport, HA does not reach a membrane that shows features typical of an apical membrane. This finding indicates either the uniqueness of the myelin membrane or the requirement of additional regulatory factors, absent in OLG, for apical delivery. These remarkable results emphasize that polarity and regulation of membrane transport in cultured OLG display features that are quite different from those in polarized cells.

Animals↗

Long-term effectiveness of two Dutch work site smoking cessation programs.

This article reports on one of the few experimental studies in Europe to examine work site smoking cessation. The study examined whether a comprehensive intervention (self-help manuals, group courses, a mass media campaign, smoking policies, and a second-year program) is more effective than a minimal intervention (self-help manuals only). Eight work sites participated in the study. The effect of treatment on smoking cessation depended on nicotine dependency levels: Heavy smokers had more success with the comprehensive smoking cessation intervention than with the minimal intervention (with respect to both 14-month quit rate and 6-month prolonged abstinence). For heavy smokers, exposure to mass media exhibitions or to group courses had a beneficial effect on prolonged abstinence. Comprehensive programs may be most appropriate in Dutch work sites with large proportions of heavily addicted smokers.

Adult↗

The dominance of behavioural activation over behavioural inhibition in conduct disordered boys with or without attention deficit hyperactivity disorder.

On the basis of Gray's theory, Quay suggested that conduct disorder (CD) is associated with a Behavioural Activation System (BAS) that dominates over the Behavioural Inhibition System (BIS), whereas attention deficit hyperactivity disorder (ADHD) is characterised by an underactive BIS. Two studies were conducted to test the hypothesis that the dominance of the BAS over the BIS is more pronounced in CD comorbid with ADHD (CD/ADHD) than in CD alone. First of all, a response perseveration task was used, i.e. the door-opening task (Daugherty & Quay, 1991). In this game, the subject chooses either to open the next door or to stop playing; there is a steadily increasing ratio of punished responses to rewarded responses and a large number of doors opened is indicative of response perseveration. As expected, a steady increase in the number of doors opened was found across normal control (NC) boys, CD boys, and CD/ADHD boys (NC < CD < CD/ADHD). Second, the dominance of the BAS over the BIS was examined by observing the social behaviour of the child in interaction with a research assistant who alternately activated the BAS and the BIS while a game was played. The behaviour of the children was analysed according to ethological methods. Group differences in the frequencies of three out of five behavioural categories were in line with the results of the door-opening task (NC < CD < CD/ADHD).

Antisocial Personality Disorder↗

Differential and cell development-dependent localization of myelin mRNAs in oligodendrocytes.

In oligodendrocytes (OLG), the mRNAs for the various myelin proteins localize to different intracellular sites. Whereas the confinement of myelin basic protein (MBP) mRNA to the processes of the cell has been well established, we demonstrate that most other myelin mRNA species are mainly present in the perinuclear region. Using in situ hybridization of cultured rat OLG we found that mRNAs are localized to at least three different locations: 1) to the perinuclear region [myelin-associated glycoprotein (MAG) mRNA]; 2) mainly to the processes (the mRNA for the 14-kDa isoform of MBP); and 3) to both the perinuclear region and the primary processes [2',3'-cyclic nucleotide phosphodiesterase (CNPase) and proteolipid protein (PLP) mRNAs]. Thus, depending on their primary structure, the mRNA species in OLG either remain near the nucleus or localize to primary or secondary processes before their translation. The myelin mRNA localization correlates well with that of the proteins encoded in them, as demonstrated by immunocytochemistry. Since different isoforms of MBP have different locations in transfected HeLa cells (Staugaitis et al.: J Cell Biol 110:1719-1727, 1990), we also have investigated the localization of the various mRNAs in OLG, using exon 2-minus and exon 2-specific probes in situ hybridization. The exon 2-minus MBP mRNAs are transported far into the processes, whereas exon 2-specific mRNA was only detected in the cell body. This suggests that sorting and trafficking of MBP mRNA are regulated by the presence or absence of the exon 2 sequence. Furthermore, during maturation of OLG, exon 2-plus mRNAs disappear, whereas exon 2-minus mRNAs increase. The developmentally regulated expression of exon 2-plus transcripts suggest a role of their protein products in differentiation rather than in myelination.

Animals↗

Carotid artery stenosis is related to blood glucose level in an elderly Caucasian population: the Hoorn Study.

Cross-sectional associations between carotid artery stenosis (CAS) on the one hand, and parameters of glycaemia and specific insulin levels on the other, were investigated in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with insulin or oral hypoglycaemic agents were classified as having known diabetes mellitus (KDM) (n = 66). Using two oral glucose tolerance tests, and based on the World Health Organisation criteria, all other participants were classified as having a normal (NGT) (n = 287), an impaired (IGT) (n = 169) or a diabetic (NDM) (n = 106) glucose tolerance. CAS was defined haemodynamically using duplex scanning. The crude prevalences of only moderate (16-49%) CAS were 6.6%, 7.1%, 5.7% and 12.1% in NGT, IGT, NDM and KDM subjects, respectively. For any severe (> or = 50%) CAS, crude prevalences were 2.8%, 4.7%, 9.4% and 7.6%. The prevalence of any severe CAS was higher in NDM (p < 0.01) and KDM subjects (p = 0.07) than in NGT subjects. The prevalence of a history of stroke or transient ischaemic attack was 1.7%, 1.8%, 2.8% and 1.5% in NGT, IGT, NDM and KDM, respectively. In univariate logistic regression analysis, HbA1c, serum fructosamine, fasting and 2-h post-load glucose were significantly associated with any severe CAS. In multivariate analyses controlling for other risk factors, only HbA1c and 2-h post-load plasma glucose remained significantly associated (odds ratios: 1.29 per % and 1.09 per mmol/l, respectively) in separate models. No association could be shown between either fasting or 2-h post-load specific insulin and any severe CAS in either univariate or multivariate analyses. In conclusion, HbA1c and 2-h post-load plasma glucose are independently associated with any severe CAS, whereas specific insulin is not.

Aged↗

Effects of an employee fitness program on reduced absenteeism.

The effect of participation in an employee fitness program on reduction of absenteeism due to illness on three different worksites (police force, chemical industry, banking) was studied. The study used a longitudinal pretest-posttest design. From 884 subjects, data were collected on absenteeism in the pre-intervention year and on absenteeism in the first year of the fitness program. The subjects were divided into three groups: high participation, low participation, and no participation in the employee fitness program. Results of covariance analyses show that the high participation group had a significant decline in sick days (4.8 days), while the low and no participation groups showed no change in sick days. Even when self-selection in the participation in an employee fitness program seems to be present, there is potentially for a great deal to be gained from participation of this self-selected group in terms of changed sick days.

Absenteeism↗

Photodegradation and photobinding of tiaprofenic acid: in vitro versus in vivo.

The photoreactivity of the photosensitizing nonsteroidal anti-inflammatory drug tiaprofenic acid (TA) and its photoproduct decarboxytiaprofenic acid (DTA) was studied both in the presence and in the absence of bovine serum albumin (BSA). The photoproduct DTA was found to be photostable in buffered aqueous solution at pH 7.4, but photodecomposed when BSA was present in the reaction medium. Both TA and DTA underwent irreversible photobinding to BSA in an almost quantitative way, as evidenced by radioactivity measurements using labeled (3H) compounds. In the case of TA, it has been proven that photobinding is mainly attributable to the phototoreactivity of in situ-generated DTA. The photodegradation and photobinding of TA were also investigated in the epidermis in vivo. Rats were exposed to UVA after application of TA to their shaven dorsal skin. During the initial periods of irradiation, the amount of TA decreased sharply, and the yield of the corresponding photoproduct (DTA) reached a maximum. Prolonged irradiation led to photodegradation of DTA. In vivo photobinding was studied using 3H-TA. Photobinding took place slowly at the beginning, but its rate increased sharply after complete photoconversion of TA, when the photoproduct DTA reached the maximum concentration. Thereafter, the decrease of DTA was more pronounced than that of TA. This indicates that-also in vivo-DTA rather than TA is responsible for the photobinding to biomacromolecules in the viable layer of the epidermis. Overall, the above results suggest that irradiation of TA in buffered aqueous solution, in the presence of proteins, is a reasonable model system to study the photodegradation and photobinding behavior of this drug in vivo. From the qualitative point of view, the main conclusion is that DTA plays a key role both in vivo and in vitro: it is the major photoproduct, it undergoes further photodegradation upon prolonged irradiation, and it appears to be responsible for the photobinding process.

Animals↗

Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study.

We studied the intra-individual variation in plasma glucose, specific serum insulin and serum proinsulin concentrations, measured by two 75-g oral glucose tolerance tests in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population without a history of diabetes mellitus. The intra-individual variation was assessed by the standard deviation of the test-retest differences (SDdif). For subjects with normal (n = 246), impaired glucose tolerance (n = 198), and newly detected diabetes (n = 80) classified at the first test, the following (SDdif/median level of individual average scores) were found: fasting glucose: 0.4/5.4, 0.5/5.9 and 0.7/7.2 mmol/l; 2-h glucose: 1.3/5.6, 1.8/8.5 and 2.3/12.8 mmol/l; fasting insulin: 23/76, 32/89 and 30/116 pmol/l; 2-h insulin: 190/303, 278/553 and 304/626 pmol/l; fasting proinsulin: 4/8, 6/13 and 9/18 pmol/l; 2-h proinsulin: 19/49, 23/84 and 33/90 pmol/l, respectively. In both glucose, proinsulin and insulin concentrations the total intra-individual variation was predominantly determined by biological variation, whereas analytical variation made only a minor contribution. The SDdif can easily be interpreted, as 95% of the random test-retest differences will be less than 2.SDdif, or in terms of percentage, less than (2.SDdif/median level of individual average score) 100. Therefore, for subjects with normal glucose tolerance, 95% of the random test-retest differences will be less than 15% (fasting glucose), 46% (2-h glucose), 61% (fasting insulin), 125% (2-h insulin), 100% (fasting proinsulin) and 78% (2-h proinsulin) of the median value of the individual average scores. No substantial independent association of either age, gender or obesity with the intra-individual variation in glucose, proinsulin, or insulin concentrations was found.

Anthropometry↗

Pros and cons of quitting, self-efficacy, and the stages of change in smoking cessation.

In The Netherlands, 34% of the population smoke, and 70% of these smokers are not planning to quit. The lower percentages in the U.S. population seem to reflect a difference in smoking culture. This study analyzes the pros and cons of quitting and self-efficacy expectation in the 5 stages of change in the Dutch population. The results are compared with the pattern of the pros and cons of smoking and self-efficacy expectations found in U.S. samples. The data show the hypothesized pattern: In the first 2 stages, the expected positive outcomes of quitting discriminated better between the stages than self-efficacy, whereas for later stages, self-efficacy was the better discriminator. This study shows that the stage typology is applicable to the Dutch population and that the pattern of the pros, cons, and self-efficacy is very similar to the pattern found in the U.S. populations.

Adult↗