Biomedical subjects

J Dekker

Publications and source records attributed to J Dekker.

At least 91 records · Page 5Linked to original sources

PubMed1998

Regulation of lactase and sucrase-isomaltase gene expression in the duodenum during childhood.

BACKGROUND: In children, lactase and sucrase-isomaltase are essential intestinal glycohydrolases, and insufficiency of either enzyme causes diarrhea and malnutrition. Little is known about the regulation of lactase and sucrase-isomaltase expression in the duodenum during childhood. In this study, the mechanisms of regulation of duodenal expression of both enzymes were examined in a study population with ages ranging from 1 to 18 years. METHODS: Duodenal biopsy specimens from 60 white children were used to analyze tissue morphology and to quantify lactase and sucrase-isomaltase mRNA and protein. RESULTS: Among healthy subjects, high interindividual variability was noted in both mRNA and protein levels for lactase and sucrase-isomaltase. Lactase mRNA level per subject did not correlate with sucrase-isomaltase mRNA level and thus appeared independent. Both lactase and sucrase-isomaltase protein levels correlated significantly with their respective mRNA levels. For each enzyme, a significant inverse correlation was observed between the degree of villus atrophy and mRNA levels. Aging from 1 to 18 years did not result in significant changes in mRNA or protein levels of either enzyme. Immunostaining patterns within the duodenal epithelium for lactase differed from sucrase-isomaltase in adjacent sections, illustrating independent regulation at the cellular level. CONCLUSIONS: In the duodenum of white children, lactase and sucrase-isomaltase seem primarily regulated at the transcriptional level. The expression of each enzyme in the intestinal epithelium is regulated by an independent mechanism. Lactase and sucrase-isomaltase exhibit stable mRNA and protein levels in healthy children as they grow to adulthood. Mucosal damage affected levels of both enzymes negatively.

Adolescent↗

PubMed1998

Expression of a marker for colonic crypt base cells is correlated with poor prognosis in human colorectal cancer.

BACKGROUND: There is a need for markers in colorectal cancer which will allow subclassification of stage groups into subgroups with high versus low risk of recurrent disease. AIMS: To develop monoclonal antibodies that recognise antigens or immature crypt base cells, on the assumption that in a neoplasm undifferentiated but not the terminally differentiated cells will be responsible for tumour progression. METHODS: Colon crypt cells which were isolated from human colonic mucosa by EDTA/EGTA incubation were studied. By stepwise harvesting, crypt base cell enriched fractions were obtained, and after incubation with antibodies against dominant antigens, used as immunogens. RESULTS: Of one crypt base cell specific antibody (5E9), the reactive epitope appeared to be a non-terminal carbohydrate in the mucin O-glycans of the colon. The epitope did not seem to be colon specific, but was expressed in a variety of other tissues. In colorectal carcinomas, 5E9 immunoreactivity identified a subgroup of patients with a tendency for worse prognosis. CONCLUSION: A mucin associated maturation epitope was identified in colonic crypt base cells, the expression of which in Dukes' stage B3 colorectal carcinoma may be associated with poor prognosis.

Adenocarcinoma↗

PubMed1998

MUC5B is the prominent mucin in human gallbladder and is also expressed in a subset of colonic goblet cells.

To elucidate the roles of human gallbladder mucin (HGBM), such as in gallstone formation and cytoprotection, it is essential to identify HGBM and study its expression. This was performed by metabolic labeling, Western blotting, immunohistochemistry, and RT-PCR. In a large number of individuals, antibodies against purified HGBM and against MUC5B detected a mucin precursor (approximately 470 kDa) in the gallbladder and colon, but not in the small intestine. In the gallbladder, Western blotting using specific anti-MUC5B antibodies showed that this mucin precursor represented an identical mucin, MUC5B. RT-PCR experiments demonstrated a similar tissue distribution pattern of MUC5B mRNA. Immunohistochemistry with anti-HGBM and anti-MUC5B showed staining in gallbladder epithelial cells and colonic goblet cells in the crypt base, but not in the small intestine; double labeling showed that HGBM was located in small granules within goblet cells, colocalizing to MUC2-containing goblet cells. Metabolic labeling demonstrated the secretion of mature MUC5B in the colon. Conclusively, MUC5B is identified as the prominent HGBM and is also expressed and secreted in the colon.

Blotting, Western↗

PubMed1998

Diagnostic assessment and treatment goals in logopedics: impairments, disabilities and handicaps.

This study was aimed to investigate to what extent impairments, disabilities and handicaps are used as diagnostic assessments and treatment goals in logopedics. Traditionally, logopedists are mainly concerned with impairments. These days, increasing attention is demanded for disabilities and handicaps as well. A survey study was carried out on 1,567 patients in logopedic practices in the Netherlands to provide an empirical quantitative description of diagnostic assessments and treatment goals, formulated in terms of impairments, disabilities and handicaps. Results show that logopedists indeed often indicate impairments as diagnostic assessments and as treatment goals, particularly language development impairments and phonetic/phonological articulation impairments. Interestingly, also large numbers of diagnostic assessments and treatment goals were indicated at the level of disabilities and handicaps; the most important being disability in expressing communication and occupational handicap. These results demonstrate that disabilities and handicaps may serve an important function in logopedics, in that they may guide assessment as well as therapy. It is concluded that disabilities and handicaps should be considered in the future development of the profession of logopedics.

Adolescent↗

PubMed1998

Medical and educational fields in logopedics in The Netherlands: a comparison in historical and European perspective.

This study describes differences between medical and educational fields in logopedics practice in The Netherlands. This dichotomy of fields is also found in other Western European countries and may result from the historical development of the profession. The four settings where logopedists work the most (institutional care, private practice, community care and special schools) were studied. One hundred and seventy-two logopedists in 103 practices or departments collected data on 1,761 patients. For each patient a standard registration form was filled in, containing information on (i) patient characteristics, (ii) logopedic diagnostic assessment, and (iii) aspects of treatment. The historical dichotomy into medical and educational fields is still demonstrable in present-day logopedics in The Netherlands. However, the settings within each field also show some differences. Private practice shows a mixture of medical and educational characteristics.

Adolescent↗

PubMed1998

Intestinal carbamoyl phosphate synthase I in human and rat. Expression during development shows species differences and mosaic expression in duodenum of both species.

The clinical importance of carbamoyl phosphate synthase I (CPSI) relates to its capacity to metabolize ammonia, because CPSI deficiencies cause lethal serum ammonia levels. Although some metabolic parameters concerning liver and intestinal CPSI have been reported, the extent to which enterocytes contribute to ammonia conversion remains unclear without a detailed description of its developmental and spatial expression patterns. Therefore, we determined the patterns of enterocytic CPSI mRNA and protein expression in human and rat intestine during embryonic and postnatal development, using in situ hybridization and immunohistochemistry. CPSI protein appeared during human embryogenesis in liver at 31-35 e. d. (embryonic days) before intestine (59 e.d.), whereas in rat CPSI detection in intestine (at 16 e.d.) preceded liver (20 e.d.). During all stages of development there was a good correlation between the expression of CPSI protein and mRNA in the intestinal epithelium. Strikingly, duodenal enterocytes in both species exhibited mosaic CPSI protein expression despite uniform CPSI mRNA expression in the epithelium and the presence of functional mitochondria in all epithelial cells. Unlike rat, CPSI in human embryos was expressed in liver before intestine. Although CPSI was primarily regulated at the transcriptional level, CPSI protein appeared mosaic in the duodenum of both species, possibly due to post-transcriptional regulation.

Adolescent↗

PubMed1998

Clinical experience of rehabilitation therapists with chronic diseases: a quantitative approach.

OBJECTIVES: To provide an overview of the numbers of patients with selected chronic diseases treated by rehabilitation therapists (physical therapists, occupational therapists, exercise therapists and podiatrists). The study was performed to get quantitative information on the degree to which rehabilitation therapists are experienced in the treatment of chronically ill patients. METHODS: Secondary analyses were performed on several databases containing representative data on patients treated by rehabilitation therapists. Rates per 1000 patients in the populations of these rehabilitation therapists and 90% confidence intervals were computed for patients with the following diagnoses: ischaemic heart diseases, stroke, rheumatoid arthritis, osteoarthritis, osteoporosis, multiple sclerosis, Parkinson's disease, epilepsy, headache syndromes, COPD/asthma, diabetes mellitus and chronic back pain (the size of the latter group could only be assessed in physical therapy in primary care). RESULTS: The largest group of chronically ill patients treated by physical therapists in primary care are patients with chronic back pain (82 per 1000). Stroke patients are the most common chronically ill patients treated by physical therapists in institutional care (157 per 1000) and by occupational therapists in institutional (358 per 1000) and noninstitutional care (246 per 1000). These therapists also see a variety of other chronically ill patients. Exercise therapists and podiatrists treat less patients with the selected chronic diseases.

Adult↗

PubMed1998

Outcome of strategy training in stroke patients with apraxia: a phase II study.

OBJECTIVE: Evaluation of a therapy programme for stroke patients with apraxia. The programme is based on teaching patients strategies to compensate for the presence of apraxia. This programme was designed for assessment and treatment by occupational therapists. DESIGN: The outcome was studied in a pre-post test design. Measurements were conducted at baseline and 12 weeks later. SUBJECTS: Thirty-three stroke patients with apraxia were treated at occupational therapy departments n general hospitals, rehabilitation centres and nursing homes. MAIN OUTCOME MEASURES: The following measurements were conducted: an apraxia test, a motor functioning test, observation of activities of daily living (ADL), Barthel Index, and an ADL questionnaire for the therapist and the patient. RESULTS: The patients showed large improvements in ADL functioning on all measures and small improvements on the apraxia test and the motor functioning test. The effect sizes for the disabilities, ranging from 0.92 to 1.06, were large compared to the effect sizes for apraxia (0.34) and motor functioning (0.19). The significant effect of treatment is also seen when individual improvement and subjective improvement are considered. Measured with the Barthel Index for instance, 71% of the patients improved. CONCLUSIONS: These results suggest that the programme seems to be successful in teaching patients compensatory strategies that enable them to function more independently, despite the lasting presence of apraxia.

Activities of Daily Living↗

PubMed1998

Clinical and functional correlates of foot pain in diabetic patients.

PURPOSE: Patients with diabetes mellitus frequently suffer from foot pain. This pain seems to be a neglected area in studies on the diabetic foot. The purpose of this study was to identify clinical variables associated with foot pain in diabetic patients. In addition, the relationships between foot pain and several functional impairments and disabilities were explored. METHOD: The research group consisted of 29 diabetic patients with any symptoms possibly associated with a diabetic foot, who were referred to podiatry. The relationships between several clinical measures and foot pain were analysed by means of Mann-Whitney U-tests. In addition, Spearman rank correlations coefficients were computed to assess the relationships between foot pain and measures of functional health. RESULTS: Diabetic patients suffering from sensory neuropathy experience more severe foot pain. Furthermore, patients with more severe foot pain experience more fatigue, more disabilities in walking and a lower level of affective well-being. CONCLUSION: Based on these findings this paper concludes that foot pain in diabetic patients is an important impairment which deserves further scientific attention.

Adolescent↗

PubMed1998

Pain and disability in patients with osteoarthritis of hip or knee: the relationship with articular, kinesiological, and psychological characteristics.

OBJECTIVE: To determine to what extent articular, kinesiological, and psychological factors each contribute to pain and disability in patients with osteoarthritis (OA), after controlling for other factors. METHODS: Cross sectional study among 200 patients with OA of the hip or knee. Dependent variables include pain (visual analog scale), self-reported disability (questionnaire), and observed disability (performance of standardized tasks). Independent variables include joint degeneration (radiographs), muscle strength (dynamometer), range of joint motion (goniometer), pain coping (behavioral and cognitive strategies), and psychological well being (depression, anxiety, cheerfulness). Multiple regression analysis was used. RESULTS: Pain was found to be associated with muscle weakness and pain coping (p < 0.05). Disability was associated with muscle weakness, range of joint motion, pain, pain coping, and psychological well being (all p < 0.05). Both pain and disability were most strongly associated with kinesiological characteristics and pain coping. CONCLUSION: After controlling for the other characteristics, kinesiological and psychological characteristics in patients with OA are each associated with disability. The association with pain is less clear. Future research on mechanisms underlying these associations is warranted.

Adult↗

PubMed1998

Serological detection of heat shock protein hsp27 in normal and breast cancer patients.

Heat shock protein Mr 27,000 (hsp27) is found in many human breast cancer cells and tissues; its expression is associated with the presence of estrogen receptors, lower cell proliferation, and resistance to certain chemotherapies. The purpose of this study was to assess whether hsp27 may be present in sera from women with primary breast cancer and to know whether autoantibodies to hsp27 may be found in these patients. The study was performed by Western blot analyzing sera from 42 normal premenopausal women, 20 normal postmenopausal women, and 36 breast cancer patients. hsp27 was clearly detected in sera by immunoblotting but only after immunoprecipitation. The mean hsp27 levels in cancer patients were higher than in the control patients; however, 66% of the breast cancer patients showed hsp27 within the normal range, indicating low sensitivity. Moreover, cancer patients with metastatic disease did not show significantly higher hsp27 levels than cancer patients without metastases. Serum hsp27 levels did not correlate with the hsp27 levels in tumor tissues detected by immunohistochemistry. Elevated CA 15-3 levels were not associated with high hsp27 values. Autoantibodies against hsp27 were not detected by immunoblotting in normal sera and in sera from breast cancer patients. As a consequence, serological determination of this biomarker is unlikely to be of utility in the detection and follow-up of breast cancer patients.

Adult↗

PubMed1998

Generation of CMRF-44+ monocyte-derived dendritic cells: insights into phenotype and function.

The CMRF-44 monoclonal antibody (MoAb) recognizes an intermediate stage of blood dendritic cell (DC) differentiation as well as mature CD83+ blood DC. Here we describe the use of the CMRF-44 MoAb to monitor the in vitro development of DC-like cells from peripheral blood mononuclear cells. Neither granulocyte-macrophage colony-stimulating factor (GM-CSF) nor GM-CSF plus tumor necrosis factor-alpha (TNF-alpha) supported the development of CMRF-44+ cells. However, GM-CSF plus interleukin (IL)-4 generated a substantial number of CMRF-44+ cells among the heterogeneous CD14- myeloid cell population, produced after 7 or 10 days of culture. The addition of TNF-alpha to GM-CSF+IL-4 on the fifth day of culture enhanced the generation of CMRF-44+ cells from days 7 to 14. A concentration of 50 U/mL of IL-4 was sufficient to allow the development of CMRF-44+ cells. The presence of GM-CSF was essential, but a wide range of concentrations (50-800 U/mL) was effective for supporting IL-4-induced generation of CMRF-44+ cells. TNF-alpha at concentrations of 20 or 50 ng/mL induced a maximal increase in the number of CMRF-44+ cells. The CMRF-44+ DCs generated in the presence of GM-CSF+IL-4 were large, irregularly shaped cells with variable CD1a expression and have CD83 transcripts but no CD83 surface expression. Additional TNF-alpha treatment induced prominent dendritic processes and surface expression of CD83 on CMRF-44+ DCs. The CMRF-44+ DCs generated in GM-CSF+IL-4 showed higher allostimulatory activity than CMRF-44 cells but were less efficient at processing and presenting soluble antigen to T-lymphocyte lines. TNF-alpha treatment reduced antigen uptake but increased the allostimulatory activity of CMRF-44+ DCs. CMRF-44+ DC differentiation from blood CD14+ monocytes was not radiosensitive and thus does not involve cell division. We conclude that the MoAb CMRF-44 identifies both intermediate and fully mature stages of monocyte-DC differentiation and may be a useful marker in establishing the optimal timing for antigen loading of in vitro-generated monocyte-derived DCs.

Antibodies, Monoclonal↗

PubMed1998

The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial.

OBJECTIVE: To determine the effectiveness of exercise therapy in patients with osteoarthritis (OA) of the hip or knee. METHODS: A randomized single blind, clinical trial was conducted in a primary care setting. Patients with hip or knee OA by American College of Rheumatology criteria were selected. Two intervention groups were compared. Both groups received treatment from the patients' general practitioner, including patient education and medication if necessary. The experimental group also received exercise therapy from a physiotherapist in primary care. The treatment period was 12 weeks. The main outcome measures were pain, medication use (nonsteroidal antiinflammatory drugs, NSAID) and observed disability. RESULTS: A total of 201 patients were randomized. Exercise therapy was associated with a reduction of pain in the past week (difference in change -17.0; 95% CI -23.6, -10.4) and observed disability (-0.19; 95% CI -0.38; -0.01). Effect sizes were medium (0.58) and small (0.28), respectively. No effect of exercise therapy was found for the use of NSAID. Additional beneficial effects (p = 0.05) were found for the use of paracetamol (effect size 0.33), global effect as perceived by the patient (effect size 0.68), and muscle strength of the hip (effect size 0.34). CONCLUSION: After 12 weeks, exercise therapy is effective in reducing pain and disability. The size of the effects is medium and small, respectively.

Aged↗

PubMed1997

Molecular cloning of human MUC3 cDNA reveals a novel 59 amino acid tandem repeat region.

The human MUC3 gene is highly expressed in small intestine and gallbladder. Thus far only 646 basepairs of its cDNA encoding 17 amino acid repeats have been cloned. In order to further clone the human MUC3 cDNA, a human small intestinal cDNA library was constructed and screened with a cDNA probe encompassing the 17 amino acid tandem repeat region of human MUC3. In two subsequent screenings of the library resulting positive clones were used as probes. In total, 27 partial MUC3 cDNA clones were isolated and sequenced that define a semi-unique region and a novel 177 nucleotide tandem repeat region, located upstream of the region encoding the 17 amino acid tandem repeats. The 177 nucleotide repeat region is at least 5 kb in length and encodes 59 amino acid repetitive peptides with a consensus sequence of VSTTPVASSEASTLSTTPVDTSTPVTTSTQASSSPTTAEGTSMPTSTPSEGSTPLTSMP, that is notably different from the 17 amino acid repeat of MUC3 or any other known mucin repeat.

Amino Acid Sequence↗

PubMed1997

Multimerization of the adenovirus DNA-binding protein is the driving force for ATP-independent DNA unwinding during strand displacement synthesis.

In contrast to other replication systems, adenovirus DNA replication does not require a DNA helicase to unwind the double-stranded template. Elongation is dependent on the adenovirus DNA-binding protein (DBP) which has helix-destabilizing properties. DBP binds cooperatively to single-stranded DNA (ssDNA) in a non-sequence-specific manner. The crystal structure of DBP shows that the protein has a C-terminal extension that hooks on to an adjacent monomer which results in the formation of long protein chains. We show that deletion of this C-terminal arm results in a monomeric protein. The mutant binds with a greatly reduced affinity to ssDNA. The deletion mutant still stimulates initiation of DNA replication like the intact DBP. This shows that a high affinity of DBP for ssDNA is not required for initiation. On a single-stranded template, elongation is also observed in the absence of DBP. Addition of DBP or the deletion mutant has no effect on elongation, although both proteins stimulate initiation on this template. Strand displacement synthesis on a double-stranded template is only observed in the presence of DBP. The mutant, however, does not support elongation on a double-stranded template. The unwinding activity of the mutant is highly reduced compared with intact DBP. These data suggest that protein chain formation by DBP and high affinity binding to the displaced strand drive the ATP-independent unwinding of the template during adenovirus DNA replication.

Adenosine Triphosphate↗

PubMed1997

Social deprivation and psychiatric admission rates in Amsterdam.

The main subject of this study was the link between social indicators and the (re)admission rates for, and length of stay in, in-patient mental health care in Amsterdam. In a factor analysis of 15 sociodemographic variables, two principal components analysis factors were distinguished: housing quality and socioeconomic deprivation. The census variables and the factors almost all had high correlations with the crude admission rates as well as the rates standardised for age and sex. In general, the correlations with rates that were also standardised for marital status were significantly lower. This shows that many correlations between indicators and crude rates are determined to a significant extent by the marital status profile of an area. Socioeconomic deprivation is positively correlated with the proportion of readmissions and inversely correlated with average length of stay.

Adolescent↗

PubMed1997

Admission rates for schizophrenia in The Netherlands: an urban/rural comparison.

This article examines admission rates for schizophrenia in terms of degree of urbanization. Patient data was obtained from the Dutch psychiatric register. The scale of urbanization used had five categories and was utilized to establish the degree of urbanization in each municipality (n=647). Admission rates showed a significant positive correlation with the degree of urbanization in the 15-34 years and 35-54 years age groups for both sexes. The average duration of hospitalization and the average number of readmissions showed no association with the degree of urbanization. Taken as a whole, these utilization rates provide evidence of a much higher incidence of schizophrenia in the most urbanized municipalities of The Netherlands.

Adolescent↗

PubMed1997

Biosynthesis of mucins (MUC2-6) along the longitudinal axis of the human gastrointestinal tract.

Little is known about the biosynthesis of mucin molecules in humans. Our aim was to examine the mucin biosynthesis (MUC2-6) along the longitudinal axis of the healthy human gastrointestinal tract. Biopsies of human stomach and small and large intestine were metabolically labeled with 35S-labeled amino acids, [35S]sulfate, or[3H]galactose, immunoprecipitated with antibodies against MUC2-6, and analyzed by reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), MUC5AC [apparent molecular weight (M(r)) 500,000] and MUC6 (apparent M(r) 400,000) were detected in the stomach but not in the small or large intestine, MUC3 (apparent M(r) 550,000) was detected in duodenum and jejunum, MUC2 (apparent M(r)600,000) was detected throughout the small and large intestine, and MUC4 (apparent M(r) > 900,000) was detected predominantly in the large intestine. Interestingly, some individuals displayed double bands of MUC2 and MUC3 precursors, suggesting allelic variation within the respective genes. Between small and large intestine mature secreted MUC2 showed differences in mobility on SDS-PAGE, suggesting differences in glycosylation. Each of the MUC2, MUC3, MUC4, MUC5AC, and MUC6 precursors could be distinguished electrophoretically, and each showed region-specific expression along the gastrointestinal tract.

Digestive System↗