Muc2 in ulcerative colitis: a quantitative study.
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Amino Acids↗
Biomedical subjects
J Dekker
Publications and source records attributed to J Dekker.
Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex.
Paired serum and cerebrospinal fluid (CSF) samples from 10 AIDS patients with and 10 without AIDS dementia complex (ADC) were studied, in an attempt to uncover ADC-associated variation in V3 sequences. Sequences were obtained from four of the patients with and eight of those without ADC. Comparison of the sequences using a resampling technique revealed a significant ADC-associated difference occurring at several amino acid positions. Results from serum and CSF sequences were comparable. These differences may indicate that the virus found in ADC and that in non-ADC patients have different biological properties. Comparison of serum versus CSF sequences within samples from both ADC and non-ADC patients, using the same resampling technique, revealed no clear distinctions. In some patients, the sequence populations in serum and CSF were completely distinct, while in others, there was no difference in distribution. These patterns were not associated with ADC.
AIDS Dementia Complex↗
Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population.
Two distinct biological phenotypes of human immunodeficiency virus (HIV) have been described: the non-syncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing (SI) phenotype, with the ability to infect MT-2 cells. The earliest virus population observed following HIV transmission is generally of the NSI phenotype, even after exposure to inocula of mixed NSI/SI phenotype. In this study, the issue of intrapatient selection of virus phenotype following transmission was addressed by studying two cases of accidental transmission. A comparison of the sequences of the V1-V2 and the V3 coding regions of the envelope gene and the p17 region of the gag gene showed that the donor-recipient pairs were tightly clustered in all gene segments, but away from local and published transmission controls. The intrasample variation of the p17 sequence was greater in the recipients and smaller in the donors than that of the V3 region sequence, indicating selection of V3 at transmission. In these transmission cases, the effects of an intravenous inoculation of a small quantity of blood containing predominantly SI V3 sequences (6 of 8 clonal sequences) were compared with those of an intramuscular inoculation of a large quantity of blood containing predominantly NSI viruses (14 of 16 clonal sequences). Both SI and NSI V3 regions were demonstrated to be phenotypic expressions of genetically related viral strains. The inoculation of the predominantly SI virus population resulted in the persistence of an SI virus population in the recipient and a rapid CD4+ T-cell decline. The inoculation of the predominantly NSI population resulted in a selective amplification of SI viruses before seroconversion, followed by a suppression of SI viruses at seroconversion and a rapid decline of CD4+ T-cell numbers. These data suggest that the suppression of SI viruses can be accomplished following the development of HIV-specific immunity and that the ability to suppress SI viruses does not prevent the development of immunodeficiency.
Acquired Immunodeficiency Syndrome↗
Similarity in env and gag genes between genomic RNAs of human immunodeficiency virus type 1 (HIV-1) from mother and infant is unrelated to time of HIV-1 RNA positivity in the child.
Variation in the env (V3 region) and gag (p17 region) genes of genomic RNA of human immunodeficiency virus type 1 was studied in three mother-child pairs. One infant was human immunodeficiency virus type 1 RNA positive at birth (pair 114), one became positive 6 weeks after birth (pair 127), and one became positive 30 months after birth (pair 564). The first two children were born to seropositive mothers, and the last child was infected by breast-feeding following seroconversion of the mother after delivery. In both V3 and p17gag, intrasample variability was much higher in the maternal samples, including the first seropositive sample of the seroconverted mother, than in the infants' samples. Variability was less in p17gag than in V3, except in the postnatally infected child. In all three cases, infection of the child was established by variants representing a minority of the cell-free virus population in the maternal samples. For the two infants born to seropositive mothers, V3 sequences were more similar to the sequence populations of maternal samples collected during pregnancy than to those of samples collected at delivery or thereafter. However, in pair 114 a V3 variant identical to the child's virus was also detected in the sample collected at delivery. In contrast to the V3 region, p17gag sequences of maternal samples of the first trimester of pregnancy and at delivery had comparable resemblance to the child's sequences in pair 114, while in pair 127, similarity to sequences of the sample collected at delivery was higher than that to sequences of the sample from early in pregnancy. In the last pair, V3 and p17gag sequences from a maternal sample collected 18 months prior to the first RNA-positive sample of the child resembled the infant's sequences as much as the sample collected close to the presumed time of infection. Taken together, the evolutionary characteristics for genomic RNA env and gag genes did not point to a particular time of mother-to-child transmission.
Amino Acid Sequence↗
Mucin gene structure and expression: protection vs. adhesion.
The cloning of mucin cDNAs brought about by the application of molecular biology and molecular analyses constitutes a major step in understanding mucin structure and function. Here two classes of mucins are described: epithelium-associated and endothelium/leukocyte-associated mucins, which have thus far been described separately in the literature. The epithelial mucins are generally believed to play a role in cytoprotection. The endothelial and leukocyte class of mucins are adhesion molecules involved in lymphocyte homing and lymphocyte activation or are part of the adhesion cascade that plays a role in the initiation of inflammation. Mucins in general contain many threonine and serine residues, which are extensively O-glycosylated. Due to this profound glycosylation, mucins have a filamentous conformation. By virtue of their extended filamentous, and often negatively charged, structure, mucins can act as a barrier protecting the cell. However, when an opposing cell has specific receptors for mucins, adhesion can override the barrier function. Therefore, mucins may be powerful two-edged swords: they are both protective and adhesive.
Alternative Splicing↗
Reliability of the assessment of impairments, disabilities and handicaps in survey research on speech therapy.
An important aspect to the practice of speech therapy is the diagnostic assessment. This assessment is complementary to the medical diagnosis. The International Classification of Impairments, Disabilities and Handicaps (ICIDH) is regarded as a good starting point for the classification of speech therapy assessments. Based on the ICIDH, a form was developed for the registration of impairments, disabilities and handicaps in survey research on speech therapy. The aim of this study was to evaluate the reliability of the assessment of impairments, disabilities and handicaps based on clinical observations and examinations by speech therapists. On the basis of the percentage of agreement and kappa values it is concluded that the reliability of the assessment of the impairments, disabilities and handicaps was satisfactory to excellent for most of the categories.
Adolescent↗
Intestinal brush border glycohydrolases: structure, function, and development.
The hydrolytic enzymes of the intestinal brush border membrane are essential for the degradation of nutrients to absorbable units. Particularly, the brush border glycohydrolases are responsible for the degradation of di- and oligosaccharides into monosaccharides, and are thus crucial for the energy-intake of humans and other mammals. This review will critically discuss all that is known in the literature about intestinal brush border glycohydrolases. First, we will assess the importance of these enzymes in degradation of dietary carbohydrates. Then, we will closely examine the relevant features of the intestinal epithelium which harbors these glycohydrolases. Each of the glycohydrolytic brush border enzymes will be reviewed with respect to structure, biosynthesis, substrate specificity, hydrolytic mechanism, gene regulation and developmental expression. Finally, intestinal disorders will be discussed that affect the expression of the brush border glycohydrolases. The clinical consequences of these enzyme deficiency disorders will be discussed. Concomitantly, these disorders may provide us with important details regarding the functions and gene expression of these enzymes under specific (pathogenic) circumstances.
Animals↗
Monocyte-macrophage antigen expression on chondrocytes.
OBJECTIVE: To characterize chondrocytes in normal and arthritic joints and compare their phenotype to that of synovial macrophages present in rheumatoid joints. METHODS: Using an immunoperoxidase staining technique, we examined the presence and distribution of a number of leukocyte activation and differentiation antigens on samples of cartilage obtained from resected joints of normal controls and subjects with rheumatoid arthritis or osteoarthritis. RESULTS: Chondrocytes in each group were CD14+, CD68+, Thy-1+, CD11a+, CD18+, MAX.3-, and MAX.24-. Staining was variable for MAX.1 and CD45. HLA-DR and CD71 were expressed only on cells located in the superficial layer of rheumatoid cartilage. We found lower levels of expression of CD14 on chondrocytes in arthritic joints, whereas CD58 was expressed at higher levels. Surface expression of CD14 was confirmed on normal chondrocytes using flow cytometry and further supported by the detection of CD14 mRNA by polymerase chain reaction. CONCLUSION: Our findings demonstrate that chondrocytes express several antigens that are also found on monocytes and macrophages.
Arthritis, Rheumatoid↗
[Role of mucins in inflammatory intestinal diseases].
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Animals↗
Antibody responses to HIV-1 envelope and gag epitopes in HIV-1 seroconverters with rapid versus slow disease progression.
We studied the relationship between the rate of disease progression after HIV-1 seroconversion and the level of IgG antibody response to HIV-1 envelope and core epitopes. This was done by comparing a group of fast-progressing individuals and a group of slow-progressing individuals for serum IgG titers to peptides from the gp120-V3 neutralization domain, to a peptide from the immunodominant gp41 epitope (residues 590 to 607), and to recombinant gp120 and p24. The two groups displayed a large overlap in titers to the envelope epitopes, which precluded their differentiation at most time points after seroconversion. Low responsiveness to envelope antigens was not only found in a few fast-progressors but also in one individual who remained asymptomatic for at least 92 months after seroconversion. The only significant differences between the groups were found in the first months after seroconversion when the responses to the V3 domain and the gp41 epitope were more vigorous in the group of fast-progressors. Furthermore, on evaluating ratios of anti-V3 antibody titers to anti-gp120 antibody titers we found no indication that fast disease progression was associated with a restriction in antibody response to the V3 epitope. We did confirm the finding that fast disease progression is associated with low levels of p24-directed antibodies, both early after seroconversion and at later stages. These data demonstrate that levels of IgG antibodies to envelope epitopes are poor predictors of rapid disease progression and suggest that the role of V3-directed neutralizing antibodies in preventing subversion of the immune system is not decisive in natural HIV-1 infection.
Adult↗
Restriction of lactase gene expression along the proximal-to-distal axis of rat small intestine occurs during postnatal development.
BACKGROUND/AIMS: Developmental changes of lactase activity along the proximal-to-distal axis of the small intestine are poorly understood. A study of delineate lactase gene expression at the cellular level was undertaken. METHODS: The topographical regulation of lactase was studied in conjunction with sucrase-isomaltase in proximal, middle, and distal segments of 0-, 7-, 14-, 16-, 18-, 21-, and 28-day-old and adult rats using in sity hybridization, immunohistochemistry, and ribonuclease protection assays. RESULTS: From 0 to 16 days, lactase messenger RNA (mRNA) and protein were abundant along the total length of the small intestine. However, at weaning, lactase mRNA and protein were no longer detectable in the terminal ileum. After 28 days, zones of reduced lactase expression were found in the duodenum and terminal ileum. These zones demonstrated expression of lactase protein in scattered enterocytes along the villus (patchy expression). In contrast, sucrase-isomaltase was first detected at 16 days, with patchy expression along the total small intestine; at 21 days it was abundant. CONCLUSIONS: Concordant changes in both lactase mRNA and protein detection during development suggest that the horizontal gradient of lactase enzyme expression is dependent on lactase mRNA abundance. Furthermore, zones of patchy lactase expression appear around weaning and flank the area of high lactase expression in the midintestine. Patchy expression is also found for sucrase-isomaltase before weaning.
Animals↗
Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin.
BACKGROUND/AIMS: Human colonic epithelium produces large amounts of mucin. The aim of this study was to examine mucin biosynthesis in the human colon. METHODS: Human colonic mucin was isolated using CsCl density gradients, and polyclonal antiserum was raised. Biosynthesis of colonic mucins was studied by labeling colonic explants with 35S-labeled amino acids or [35S]sulfate and subsequent immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The polyclonal antiserum specifically recognized colonic mucin, primarily reacting with peptide epitopes. Biosynthetic pulse/chase experiments showed a 35S-amino acid-labeled mucin precursor of about 600 kilodaltons, which was converted into a mature, glycosylated, and sulfated mucin and subsequently secreted into the medium. This mature mucin comigrated with isolated colonic mucin with an apparent molecular weight of 550 kilodaltons on SDS-PAGE, whereas gel filtration indicated that the molecular weight is actually much larger. Independent immunoprecipitation with an anti-Muc2 antiserum showed cross-reactivity with the 600-kilodalton precursor. CONCLUSIONS: These results show the biosynthesis of a secretory colonic mucin for the first time. This mucin is synthesized as a precursor protein of approximately 600 kilodaltons, which, after glycosylation, is secreted as a glycoprotein with an apparent molecular weight of 550 kilodaltons on SDS-PAGE. It is very likely that this mucin is Muc2.
Colon↗
Protein sorting versus messenger RNA sorting?
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Animals↗
Negative affect, pain and disability in osteoarthritis patients: the mediating role of muscle weakness.
Negative affect has been shown to be associated with high levels of pain and disability in osteoarthritis (OA) patients. As an explanation of this association, it was hypothesized that muscle weakness is a mediating factor between negative affect, pain and disability. Accordingly, negative affect enhances the patient's tendency to avoid pain-related activities; a low activity level induces muscle weakness, instability of joints and thus pain and disability. This theory leads to the prediction that the association between negative affect, pain and disability is most pronounced in patients with weak muscles. The prediction was tested in a study on patients with OA of the hip and/or knee. Regarding disability (but not pain), the prediction was confirmed. This study indicates that muscle weakness is a mediating factor between negative affect and disability in OA-patients.
Adaptation, Psychological↗
Diagnosis and treatment in physical therapy: an investigation of their relationship.
BACKGROUND AND PURPOSE: The diagnosis made by a physical therapist gives direction to the selection of therapeutic interventions. Therefore, in an investigation, specific relationships between diagnoses and therapeutic interventions are expected. This study was designed to test whether such relationships exist. SUBJECTS AND METHODS: Data on diagnosis, treatment goals, and interventions were gathered on 8,714 patients by 74 physical therapists. The diagnosis and treatment goals were defined in terms of impairments and disabilities. RESULTS: Specific relationships were found to exist between those impairments and disabilities that were chosen as a basis for forming treatment goals and the application of interventions. These relationships are particularly marked at the impairment level. CONCLUSION AND DISCUSSION: It is concluded that the diagnostic categories validly predict which interventions are applied and that the selection of interventions depends on which treatment goals are pursued.
Activities of Daily Living↗
Antigenic variation of the dominant gp41 epitope in Africa.
OBJECTIVE: To determine the value of (combinations of) synthetic peptides representing immunodominant sites on HIV-1/HIV-2 transmembrane proteins for the detection and discrimination between HIV-1 and HIV-2 infection in various populations. DESIGN AND METHODS: Two 24-mer synthetic peptides derived from immunodominant sites on the HIV-1 and HIV-2 transmembrane proteins were used separately, in combination (env 1/2), and in combination with recombinant p24 (p24/env) in enzyme-linked immunosorbent assays. RESULTS: Positive reactions with env-1 were found in 150 out of 150 (100%) samples from Dutch AIDS patients, 60 out of 60 (100%) samples from Dutch homosexual men obtained 1 year after HIV-1-antibody seroconversion, 29 out of 30 (96.7%) samples from these men obtained at the time of HIV-1-antibody seroconversion, 40 out of 41 (97.6%) samples from East Africans with AIDS-related symptoms, and three out of 29 (10.3%) samples from West Africans with HIV-2 infection (including a sample from an individual infected with both HIV-1 and HIV-2). Positive reactions with env-2 in these study populations were 11 out of 150 (7.3%), nine out of 60 (15%), none out of 30 (0%), 25 out of 41 (60.9%) and 29 out of 29 (100%), respectively. In the samples with dual reactivity, true versus cross-reactivity could generally be differentiated on the basis of large differences in optical density values in the respective assays. All samples reacted positively with p24/env; 308 out of 310 (99.3%) were positive in the env 1/2 assay. Four East African samples that had negative or only weakly positive reactions with env-1 showed a noticeably stronger reaction with variant peptides derived from Central African isolate sequences. In all samples from HIV-1-infected Dutch homosexual men, the strongest signal was detected using the env-1 peptide sequence, which is derived from European and American isolates. CONCLUSIONS: Small peptide antigens may permit the detection of strain-specific antibodies, allowing serological characterization of HIV isolates.
Africa↗
Binding of rotavirus by a 46 kD milk-glycoprotein may prevent gastroenteritis.
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Animals↗
Genomic human immunodeficiency virus type 1 RNA variation in mother and child following intra-uterine virus transmission.
In order to study the relationship between virus populations in a human immunodeficiency virus type 1 (HIV-1)-infected mother and her infant, we analysed a 276 bp fragment, including the V3 region, of genomic HIV-1 RNA purified from serum. Samples were collected from the mother 6, 4 and 2 months prior to delivery, during delivery and 10 months after childbirth (samples MA to ME, respectively) and from the infant at birth (cord blood) and the ages of 6 weeks and 9 months. A heterogeneous sequence population was observed in the maternal samples (mean nucleotide variation of 2.4 to 4.2%, range 0 to 8.3%). Until the age of 6 weeks the sequence population in the infant was highly homogeneous (mean nucleotide variation < or = 0.7%, range 0 to 2.5%). At 9 months of age, the infant's virus population showed more heterogeneity (mean nucleotide variation of 1.8%, range 0.4 to 3.6%) and a drift in the consensus sequence was observed. The evolution of the V3 region in the mother was characterized by accumulation of amino acid substitutions diverging from the virus population observed in the infant. The mean nucleotide distance between the maternal sequence populations and the sequence population of the child at birth was 2.8, 2.6, 3.7, 5.2 and 5.3% for the samples MA, MB, MC, MD and ME, respectively. Nearly complete replacement at position 308, previously described as antigenically important, from a proline to a histidine was observed during pregnancy, whereas all clones of the child's virus at birth and at 6 weeks contained a proline at that position. In conclusion, intra-uterine transmission is associated with a homogeneous sequence population in the child at birth, which is more closely related to the sequence population present in the mother during the first and second trimester of pregnancy than to the sequence population at delivery.
Acquired Immunodeficiency Syndrome↗