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Biomedical subjects

J Dekker

Publications and source records attributed to J Dekker.

At least 145 records · Page 8Linked to original sources
PubMed1992

Pain and disability in osteoarthritis: a review of biobehavioral mechanisms.

Pain and disability are cardinal symptoms in osteoarthritis. The literature is reviewed in order to identify causes of these symptoms at the articular, kinesiological, and psychological level. It is concluded that pain and disability are associated with degeneration of cartilage and bone (articular level), with muscle weakness and limitations in joint motion (kinesiological level), and with anxiety, coping style, attentional focus on symptoms, and possibly depression (psychological level). Biobehavioral mechanisms of pain and disability which explain the observed associations are described and the empirical evidence for these mechanisms is evaluated. Methodological and conceptual deficiencies in the research reviewed are pointed out and suggestions for further research are given.

Adaptation, Psychological↗
PubMed1992

Lactase gene expression during early development of rat small intestine.

Expression of lactase messenger (m) RNA and protein in rat small intestine during fetal and postnatal development was analyzed using in situ hybridization and immunohistochemistry. Lactase mRNA was first identified at 18 days of development, and lactase protein was first detected at day 20. Lactase mRNA and protein were present along the entire villus. Lactase mRNA increased, reaching a maximum at day 20. Just before birth a decrease in lactase mRNA was observed. In newborn intestine, lactase mRNA was present only from the base of the villus up to the mid-villus region and was undetectable up to the villus tips. Lactase protein continued to be expressed along the entire villus. These data show that expression of lactase mRNA and protein do not parallel, indicating a posttranscriptional control in fetal development. Lactase gene transcription is initiated late in gestation concomitant with villus formation and is exclusively seen in villus epithelial cells. The restriction after birth of lactase mRNA expression to cells at the villus base suggests the occurrence of a previously unknown step in postnatal differentiation of the enterocyte.

Age Factors↗
PubMed1992

Analysis of human immunodeficiency virus type 1 LTR-LTR junctions in peripheral blood mononuclear cells of infected individuals.

Circularized DNA species containing two long terminal repeat circle junctions were analysed in peripheral blood mononuclear cells of human immunodeficiency virus type 1 (HIV-1)-infected individuals. The circle junction fragments found could be classified into four groups: fragments containing a normal circle junction, fragments with deletions at the circle junction, fragments containing the primer binding site inserted at the circle junction, and fragments containing insertions at the circle junction derived from other regions of the HIV-1 genome.

Base Sequence↗
PubMed1992

Mucin-type glycoproteins.

Considerable advances have been made in recent years in our understanding of the biochemistry of mucin-type glycoproteins. This class of compounds is characterized mainly by a high level of O-linked oligosaccharides. Initially, the glycoproteins were solely known as the major constituents of mucus. Recent studies have shown that mucins from the gastrointestinal tract, lungs, salivary glands, sweat glands, breast, and tumor cells are structurally related to high-molecular-weight glycoproteins, which are produced by epithelial cells as membrane proteins. During mucin synthesis, an orchestrated sequence of events results in giant molecules of Mr 4 to 6 x 10(6), which are stored in mucous granules until secretion. Once secreted, mucin forms a barrier, not only to protect the delicate epithelial cells against the extracellular environment, but also to select substances for binding and uptake by these epithelia. This review is designed to critically examine relations between structure and function of the different compounds categorized as mucin glycoproteins.

Amino Acid Sequence↗
PubMed1991

Rat gastric mucin is synthesized and secreted exclusively as filamentous oligomers.

Oligomeric gastric mucin was isolated from the fundic part of the rat stomach. Previously we have shown by biochemical analysis that this oligomeric mucin consists of disulphide-linked homo-oligomers, which contain no other covalently attached proteins [Dekker, Aelmans & Strous (1991) Biochem. J. 277, 423-427]. Electron-microscopic images of the oligomeric mucin revealed a heterogenous population of long filamentous molecules of 300-3000 nm length. After reduction and carboxymethylation the monomeric mucins displayed a length distribution with a single peak at about 279 nm. Length-distribution analysis of oligomeric molecules with length up to 1000 nm revealed three subpopulations with one, two or three times the length of the monomeric mucin. The oligomers displayed small globular domains of about 15 nm, which were equally spaced along the molecule's length. As the distance between these globular domains was similar to the monomer length, these domains most likely indicate attachment sites of the monomers. These results show that the mucin monomers attached end-to-end in the oligomer. Biosynthesis of the mucin oligomers was studied by labelling of stomach explants in vitro with [35S]methionine, [3H]galactose or [35S]sulphate and subsequent immunoprecipitation of the mucin with a specific antiserum. Analysis by electrophoresis and gel filtration revealed that the oligomerization takes place by formation of disulphide bonds between the 300 kDa mucin precursors. The mucin was exclusively synthesized and secreted as fully glycosylated oligomers, as neither precursor proteins nor monomeric mucin were detected in the culture medium. A model for the biosynthesis of rat gastric mucin is proposed in which the filamentous mucin monomers are linked end-to-end by disulphide bonds.

Animals↗
PubMed1991

The oligomeric structure of rat and human gastric mucins.

Intact oligomeric gastric mucins were isolated from the fundic part of rat and human stomach. Physicochemical properties of the oligomeric mucins from both species, such as buoyant density, molecular mass, proteinase-resistance, amino acid composition and monosaccharide composition were similar. Biochemical analysis showed that the oligomeric mucins from both species consist of disulphide-linked mucin monomers exclusively: no other covalently attached proteins were detected in purified monomeric mucin. Four major differences were found between the monomeric mucins of these species: (1) the human monomer is larger, (2) the proteolytic-digest peptides derived from proteinase-sensitive portions of the polypeptide backbone displayed no sequence similarity, (3) the human mucin was less sulphated compared with rat mucin, and (4) the proteinase-sensitive part of the human mucin was relatively larger. However, analyses of [3H]galactose-labelled mucin from both species on gel filtration revealed that both gastric mucins were exclusively synthesized as oligomers. The results indicate that the oligomeric structures of human and rat gastric mucin are similar and their biosyntheses are not affected by the differences in the subunits.

Amino Acids↗
PubMed1991

Construction and physiological characterization of glyceraldehyde-3-phosphate dehydrogenase overproducing transformants of Aspergillus nidulans.

The construction and characterization of glyceraldehyde-3-phosphate-dehydrogenase (GPD) overproducing transformants of Aspergillus nidulans and their behaviour in acetate-limited continuous cultures and glucose-grown batch cultures are described. The A. nidulans acetamidase deletion strain MH1277 was transformed with the homologous gpdA gene on a vector with the homologous acetamidase-gene (amdS) as a selection marker. Transformant A1 contains about nine integrated copies of the gpdA gene, and shows a proportional gene-dosage GPD production of about 22% of the total soluble cell protein. Compared to the wild-type MH1277, A1 has higher growth yields and reaches higher specific growth rates on both acetate and glucose, which could be due to the key position of GPD in glycolysis and gluconeogenesis.

Acetates↗
PubMed1991

Contribution of antibody response to recombinant HIV-1 gene-encoded products nef, rev, tat, and protease in predicting development of AIDS in HIV-1-infected individuals.

The relation between antibody-response profiles to Escherichia coli-produced HIV-1 nef, rev, tat, and protease proteins and the risk of developing AIDS was studied using stored serum samples taken sequentially from a cohort of 195 initially symptom-free men who were seropositive for antibodies to HIV-1 structural proteins and 72 men who seroconverted for such antibodies. The AIDS attack rates at 39 months follow-up were significantly higher in the men with negative versus positive antibody profiles to nef, tat, and protease, respectively. [Difference (D) between attack rates = 11.279, 5.884, and 8.322, respectively]. No significant difference was found between men with negative versus positive antibody profiles to rev. The above differences between AIDS attack rates were clearly lower than those reported from the same cohort for men who were serum HIV-1 antigen positive versus negative, and for men with low versus normal CD4+ lymphocyte counts, but with respect to nef antibody-response profiles, resembled the difference reported between anti-HIV-1 core antibody-negative versus antibody-positive men. In the subgroup of men without any of the markers previously found to be predictive of progression to AIDS in the cohort (persistent HIV-1 p24 antigenemia, low anti-HIV-1 anti-core antibody reactivity, and low CD4+ cell counts), antibody profiles to nef, rev, tat, and protease did not contribute to the prediction of outcome of infection. When used in combination with persistent HIV-1 p24 antigenemia and low CD4+ cell counts, negative antibody profiles to nef and protease, respectively, were equally sensitive and specific in predicting progression to AIDS, as was low anti-HIV-1 anti-core antibody reactivity.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Covalent oligomerization of rat gastric mucin occurs in the rough endoplasmic reticulum, is N-glycosylation-dependent, and precedes initial O-glycosylation.

Rat gastric mucin undergoes extensive modifications during biosynthesis, including oligomerization, N- and O-glycosylation, and sulfation. We characterized the events in the rough endoplasmic reticulum (RER) and Golgi complex and studied how these steps are interrelated, using specific inhibitors of cellular processes. The mucin precursors oligomerize in the RER by forming intermolecular disulfide bonds. The oligomers comprise a mixture of predominantly di- and trimers of molar ratio 3:2. The oligomerized precursors are transported to the Golgi complex to form mature, oligomeric mucin by extensive O-glycosylation, and sulfation. N-Glycosylation of the precursor is required for efficient oligomerization. Brefeldin A, which inhibits protein transport between RER and Golgi complex, allows oligomerization and concomitantly induces initial O-glycosylation. Oligomerization and egrees from the RER precedes initial O-glycosylation and are therefore independent of the latter process.

Animals↗
PubMed1990

Speed of progression to AIDS and degree of antibody response to accessory gene products of HIV-1.

Antibodies to E. coli-produced HIV-1 nef, rev, tat, vpu, and vpr proteins were measured by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 190 initially symptom-free men who were seropositive for these antibodies at entry into the study. In the men seroconverting for antibodies to structural proteins the levels of nef-, rev-, and tat-specific antibodies, but not of vpu-, and vpr-specific antibodies, within 3 months of seroconversion, appeared to be lower in the five men progressing to AIDS, compared with the men remaining symptom-free during follow-up. Analysis of the prevalence of previously described antibody profiles to these accessory gene products was carried out. In all HIV-1 antibody seroconverters and in those HIV-1 antibody seropositive men with 15 or more months of follow-up who progressed to AIDS, there was a shift from predominantly nef- and vpu-specific antibody negative profiles in the men developing AIDS in the early years of the study to predominantly nef- and vpu-specific antibody positive profiles in men who developed AIDS later. Rev- and tat-specific antibody negative profiles were dominant in men progressing to AIDS throughout follow-up. No vpr-specific antibody profile occurred preferentially in the men progressing to AIDS throughout follow-up. Low antibody reactivity to accessory gene products nef, rev, and tat appears, like low anti-core antibody reactivity, to be associated with progression to AIDS relatively rapidly after infection with HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Resting energy expenditure in women: impact of obesity and body-fat distribution.

Postabsorptive resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were repeatedly assessed with an indirect calorimetric ventilated hood system in a group of 32 healthy premenopausal obese women, body fat percentage 46.4 +/- 0.9 (mean +/- SEM), age 38.5 +/- 0.9 years. RMR and DIT were also measured in a group of 10 healthy premenopausal non-obese women, body fat percentage 31.3 +/- 1.7, age 37.7 +/- 2.4 years. The obese women were subdivided according to the waist-to-hips girth ratio (WHR) into three groups with a different type of body fat distribution: A gluteal-femoral obese group (n = 10), WHR less than 0.79; an intermediate obese group (n = 10), 0.79 less than WHR less than 0.85; and an abdominal obese group (n = 12), WHR greater than 0.85. No significant differences were observed among the obese groups in age, body weight, body fat mass, and fat-free body mass. Body fat distribution was not associated with differences in DIT, pre- and postprandial respiratory quotients and substrate oxidation rates, but the abdominal obese women had significantly higher RMRs adjusted for age, fat mass, and fat-free body mass (6,075 +/- 200 kJ/d) in comparison with the gluteal-femoral obese women (5,502 +/- 205 kJ/d) and in comparison with obese women with an intermediate body fat distribution (5,517 +/- 193 kJ/d), but not in comparison with a non-obese control group, 6,790 +/- 261 kJ/d. It is concluded that within the total group of obese women, the non-abdominal obese can be characterized by relatively reduced resting metabolic rates in comparison with either the abdominal obese or with non-obese women.

Adipose Tissue↗
PubMed1990

Antibody response to viral proteins U (vpu) and R (vpr) in HIV-1-infected individuals.

Antibodies to E. coli-produced HIV-1 vpr and vpu were determined by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 196 initially symptom-free men who were positive for such antibodies at study entry. First detection of vpr- and vpu-specific antibodies always was within 12 months of seroconversion for antibodies to structural proteins. In the combined cohort of 268 men, vpr- and vpu-specific antibodies were found persistently in 26 and 43% of men, respectively. Vpr- and vpu-specific antibodies were transiently detected in 3 and 7%, respectively, and intermittently detected in 18 and 13% of men, respectively. No association was found between the patterns of vpr- or vpu-specific antibody response and clinical outcome. In subjects with different patterns of vpr- and vpu-specific antibody response, no clear temporal relationship existed between the appearance or disappearance of antibodies and the onset of HIV-1-related disease.

Cross-Sectional Studies↗
PubMed1989

Biosynthesis of gastric mucus glycoprotein of the rat.

We have studied the biosynthesis of rat gastric mucin in stomach segments using an antiserum against rat gastric mucin specific for peptide epitopes. Pulse-chase experiments were performed with [35S]methionine, [3H]galactose, and [35S]sulfate to label mucin precursors in different stages of biosynthesis, which were analyzed after immunoprecipitation. The earliest mucin precursor that could be detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was a 300-kDa protein. The occurrence of N-linked "high-mannose" oligosaccharides on this protein was shown by susceptibility to degradation by endo-beta-N-acetylglucosaminidase H. This precursor could be labeled with [35S]methionine and not with [3H]galactose or [35S]sulfate. The 300-kDa precursor was converted into mature mucin after extensive glycosylation and sulfation. The mature mucin but not the 300-kDa precursor was in part secreted into the medium. Specific inhibition of sulfation with sodium chlorate had no effect on rate and amount of mucin secretion. In addition, we show that two core proteins are expressed in rats, slightly varying in Mr among individual animals.

Animals↗
PubMed1989

Isolation and structural analysis of rat gastric mucus glycoprotein suggests a homogeneous protein backbone.

We isolated monomeric gastric mucus glycoprotein from the rat stomach by applying three successive CsCl-density-gradient steps in the continuous presence of guanidinium chloride. The rat gastric mucin was pure as compared with mucin isolated without the chaotropic reagent. In addition, the presence of guanidinium chloride resulted in a better preservation of the protein moiety. The purified mucin was fractionated according to buoyant density and chemically radiolabelled on tyrosine or cysteine residues and digested with specific proteinases. Analysis of mucin fractions of various densities gave identical peptide patterns, suggesting that the fractions contain a common protein backbone. Electron-microscopic images of the individual mucin molecules were recorded using rotary shadowing. They showed large filamentous molecules with a mean length of 208 nm that, after proteolytic digestion, yielded glycopeptides with a mean length of 149 nm. Heterogeneity in buoyant density and electrophoretic mobility is located in this large glycopeptide which remains after proteolytic digestion. Metabolic labelling of the mucin with [35 S]sulphate and [3H]galactose, followed by purification and proteolytic digestion, revealed that this glycopeptide accounts for most of the mass and contains relatively little protein, but probably all the oligosaccharides and sulphate. As this protein part is masked by the oligosaccharides, detailed study by the methods described was not possible. The results indicate that rat gastric mucin is homogeneous in a major part of the protein backbone and that the heterogeneity of the molecule originates most likely from differences in sulphate and/or sugar composition.

Animals↗
PubMed1989

Sulphation causes heterogeneity of gastric mucins.

The synthesis of mucus glycoprotein in rat stomach was studied in stomach segments, which were pulse-labelled with both [3H]galactose and [35S]sulphate and chased for various times. The radioactive glycoproteins were analyzed by CsCl centrifugation and by agarose gel electrophoresis. After a pulse-labelling for 15 min with [3H]galactose, a possible intermediate with an Mr of 200,000 and a buoyant density of 1.60 g/ml could be demonstrated. Following chase periods of 1 and 4 h, [3H]galactose and [35S]sulphate were present in glycoproteins with a mean buoyant density of 1.50 g/ml. This is clearly different from the main density of glycoproteins isolated from mucosal scrapings (1.46 g/ml). Another difference is the high electrophoretic mobility on gel electrophoretic analysis of newly synthesized glycoproteins compared to that of the major portion of the glycoproteins from mucosal scrapings. When sulphation of glycoproteins was inhibited by sodium chlorate, electrophoretic mobility and buoyant density both decreased. Sodium chlorate had no effect on glycoprotein synthesis nor on glycoprotein secretion. We conclude from our data that the heterogeneity in electrophoretic mobility and buoyant density can be attributed to a different degree of sulphation of the same glycoprotein.

Animals↗
PubMed1989

A study suggesting two kinds of information processing of the sexual response.

Genital and subjective sexual arousal in response to sexual imagery was studied. In a previous study subjects who were encouraged to process information on sexual stimuli and sexual responses were more sexually aroused than subjects encouraged to process information on sexual stimuli only. In the present study, the reverse effect was found in subjects who had received further verbal training to differentially process information on sexual stimuli or responses. This suggests two different kinds of processing information on sexual responses. They may result from simple encouragement or verbal training to process sexual information.

Adult↗
PubMed1989

Psychological determinants of sexual arousal: a review.

The literature on the psychological determinants of genital and subjective sexual arousal is reviewed. Various psychological mechanisms are identified and in each instance the available empirical evidence is summarized. Areas requiring further research are indicated and suggestions for methodological improvements are presented.

Arousal↗