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Biomedical subjects

J van Dijk

Publications and source records attributed to J van Dijk.

At least 19 recordsLinked to original sources
PubMed2007

State-of-the-art dosimetric methods for internal and external exposures: conclusions of a EURADOS action.

In radiation protection dosimetry the quantity of interest is the effective dose (E); the dose limit to an adult worker applies to the sum of the relevant doses from external exposures and the relevant committed effective doses from intakes of radionuclides, during the same period of time. A EURADOS study was carried out to investigate how the results from personal dosemeters for external radiation, from workplace monitoring and from monitoring of internal exposures can be combined into a consistent system of individual monitoring. The integration of dosimetric methods and data for external and internal radiation require the complete characterisation of the occupational exposure present at the workplace, and the availability of adequate equipment and tools for the assessment of effective dose. To evaluate the capability of services to accomplish this approach, a European Dosimetry Network has been established among 28 European countries through the respective contact-persons and their dosimetric facilities which collaborated with EURADOS providing relevant data about performance and legal aspects. The information collected was presented as a monograph in Radiation Protection Dosimetry in 2004. The more relevant conclusions of this study are presented here.

Algorithms↗
PubMed2006

Prevalence of acquired undescended testis in 6-year, 9-year and 13-year-old Dutch schoolboys.

OBJECTIVE: To investigate the prevalence of acquired undescended testis (UDT) in Dutch schoolboys. DESIGN AND PARTICIPANTS: As a part of routine school medical examinations, during a 2-year period (2001-3), testis position was determined in 6-year, 9-year and 13-year-old schoolboys. Before the examination, a parent questionnaire was sent inquiring both about the position of the testes and whether the child had been admitted earlier to hospital for orchidopexy. In 6-year and 13-year olds, a physical examination was performed by the school medical officer; in 9-year olds, a school nurse interview was held. Each boy for whom there was any doubt of the scrotal position was referred to the hospital for examination of both testes. SETTING: Institution for Youth Health Care "Noordkennemerland" and Medical Centre Alkmaar, Alkmaar, the Netherlands. RESULTS: Testis position was determined in 2042 boys aged 6, 1038 aged 9 and 353 aged 13. Of these, 47, 53 and 8 boys, respectively, were referred to the hospital and seen for further evaluation. The diagnosis of acquired UDT was made in 25 boys aged 6, 23 aged 9 and four aged 13. In 33 boys, a congenital UDT was diagnosed; 32 (97%) had already been diagnosed and treated at an early age. CONCLUSIONS: The prevalence of acquired UDT for 6-year, 9-year and 13-year olds was, respectively, 1.2% (25/2042), 2.2% (23/1038) and 1.1% (4/353). In addition, congenital UDT is treated during the early years of life and, in contrast with popular belief, screening programmes for detecting UDT in the early years are successful.

Adolescent↗
PubMed2006

Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during coronary artery surgery.

BACKGROUND: Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG. METHODS: Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU.kg(-1).h(-1)) normoglycemic (plasma glucose between 3.0 and 6.0 mmol.liter(-1)) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD). RESULTS: There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol.liter(-1). In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group. CONCLUSION: A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.

Adrenocorticotropic Hormone↗
PubMed2000

Variation in semicarbazide-sensitive amine oxidase activity in plasma and tissues of mammals.

Semicarbazide-sensitive amine oxidase (SSAO) (E.C. 1.4.3.6) is a group of enzymes with as yet poorly understood function which is widely present in nature. The variation in methodology for determination of activity, differences in substrates used and in nomenclature have made it difficult to compare SSAO in different species and tissues. Since SSAO is implicated in the pathophysiology of diabetes mellitus and congestive heart failure, our aim was to analyse the importance and abundance of SSAO in human plasma and tissues compared to other mammals. In plasma of ten different mammals, Vmax values were found to vary more than 10,000-fold, while KM differed much less; in human plasma SSAO activity is relatively low. In some species more than one SSAO entity was present in plasma. SSAO activity was ubiquitous in tissues of human, rat and pig, but varied considerably, both between species and between tissues. In human tissues, SSAO activity is higher than in tissues from rat and pig. Relative to monoamine oxidase-B there is also wide variation in SSAO, with much higher relative activities in human than in rat and pig tissues. We conclude that in plasma, SSAO activity is highest in ruminants, while in tissues, SSAO activity is more prominently present in human than in rat and pig.

Amine Oxidase (Copper-Containing)↗
PubMed2000

A vaccine strategy utilizing a combination of three different chimeric vectors which share specific vaccine antigens.

A large number of recombinant of viral and bacterial systems have been engineered as vectors to express foreign genes for vaccination and/or gene therapy. A common problem is the immune response to the vector itself. The presence of anti-vector immune responses may preclude sufficient 'priming' or immunogenicity if pre-existing immune responses are present, or they may impair optimal 'boosting' upon repeated immunization or delivery with the same vector. To circumvent this problem we developed a strategy using different chimeric vectors which share only the expression of common specific antigens desired for immunization. This approach not only has the advantage of avoiding increased anti-vector responses, but allows the use of combinations of vectors which could subsequently present the same or related antigen differently to the immune system as well as at alternative sites to induce the optimal type of immunity against the pathogen of interest.

Animals↗
PubMed1999

Apc1638T: a mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development.

The adenomatous polyposis coli (APC) gene is considered as the true gatekeeper of colonic epithelial proliferation: It is mutated in the majority of colorectal tumors, and mutations occur at early stages of tumor development in mouse and man. These mutant proteins lack most of the seven 20-amino-acid repeats and all SAMP motifs that have been associated with down-regulation of intracellular beta-catenin levels. In addition, they lack the carboxy-terminal domains that bind to DLG, EB1, and microtubulin. APC also appears to be essential in development because homozygosity for mouse Apc mutations invariably results in early embryonic lethality. Here, we describe the generation of a mouse model carrying a targeted mutation at codon 1638 of the mouse Apc gene, Apc1638T, resulting in a truncated Apc protein encompassing three of the seven 20 amino acid repeats and one SAMP motif, but missing all of the carboxy-terminal domains thought to be associated with tumorigenesis. Surprisingly, homozygosity for the Apc1638T mutation is compatible with postnatal life. However, homozygous mutant animals are characterized by growth retardation, a reduced postnatal viability on the B6 genetic background, the absence of preputial glands, and the formation of nipple-associated cysts. Most importantly, Apc1638T/1638T animals that survive to adulthood are tumor free. Although the full complement of Apc1638T is sufficient for proper beta-catenin signaling, dosage reductions of the truncated protein result in increasingly severe defects in beta-catenin regulation. The SAMP motif retained in Apc1638T also appears to be important for this function as shown by analysis of the Apc1572T protein in which its targeted deletion results in a further reduction in the ability of properly controlling beta-catenin/Tcf signaling. These results indicate that the association with DLG, EB1, and microtubulin is less critical for the maintenance of homeostasis by APC than has been suggested previously, and that proper beta-catenin regulation by APC appears to be required for normal embryonic development and tumor suppression.

Adenomatous Polyposis Coli Protein↗
PubMed1997

Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial.

PURPOSE: The objective of this study was to determine whether the thermal dose delivered during hyperthermia treatments and other thermal factors correlate with outcome after combined radiation and hyperthermia of breast carcinoma recurrences. Data were from the combined hyperthermia and radiation treatment arms of four Phase III trials, which when pooled together, demonstrated a positive effect of hyperthermia. METHODS AND MATERIALS: Four Phase III trials addressing the question of whether hyperthermia could improve the local response of superficial recurrent breast cancer to radiation therapy were combined into a single analysis. Thermal dosimetry data were collected from 120 of the 148 breast cancer recurrence patients who received hyperthermia. The data were analyzed for correlations between thermal parameters as well as important clinical parameters and outcome (complete response rate, local disease free survival, time to local failure, and overall survival). RESULTS: Five thermal parameters were tested, all associated with the low regions of the measured temperature distributions. Max(TDmin) and Sum(TDmin) were associated with complete response where TDmin is the minimum thermal dose measured by any of the tumor temperature sensors during a treatment: Max(TDmin) is the maximum of TDmin over a series of treatments. Using a categorical relationship with a cutoff of 10 min for Sum(TDmin), the complete response rate was 77% for Sum(TDmin) > 10 min and 43% for Sum(TDmin) < or = 10 min (p = 0.022, adjusted for study center and significant clinical factors). The overall complete response rate for hyperthermia and radiation was 61% compared to 41% for radiation alone. Either Max(TDmin) or Sum(TDmin) were also associated with local disease free survival, time to local failure and overall survival. CONCLUSIONS: An earlier report of this trial demonstrated a significant benefit when hyperthermia was added to radiation in the treatment of breast cancer recurrences. The analysis of thermal factors demonstrates that parameters representative of the low end of the measured temperature distributions are associated with initial complete response rate, local disease-free survival, time to local failure and overall survival.

Breast Neoplasms↗
PubMed1997

Vimentin- and desmin-positive cells in the moulting budgerigar (Melopsittacus undulatus) skin.

The distribution of vimentin- and desmin-positive cells in the budgerigar (Melopsittacus undulatus) dermis was investigated by means of immunohistochemical reactivity with the commercially available (Euro-Diagnostics) polyclonal antibodies. The staining pattern for vimentin in the paraffin sections was generally comparable to that in other animal species with regard to endothelial cells, vascular wall cells, muscle cells and fibroblasts. The modified Schwann cells in the inner core of the Herbst corpuscles reacted distinctly with anti-vimentin and anti-desmin. Some connective tissue cells in the superficial dermal layer, in the feather papilla and along the pulp core inside of the regenerating feathers were particularly well stained with anti-vimentin. Fibroblast-like cells of the regenerating feathers, particularly at the base of the pulp, also reacted strongly with anti-desmin. The findings were discussed with regard to references.

Animals↗
PubMed1995

Determination of semicarbazide-sensitive amine oxidase activity in human plasma by high-performance liquid chromatography with fluorimetric detection.

We report here a simple and sensitive method for the measurement of semicarbazide-sensitive amine oxidase (SSAO) activity in human plasma. Benzaldehyde, generated during a 1-h incubation of plasma with benzylamine, is derivatized with the specific aldehyde reagent dimedone after prior deproteinization. Quantitation of the derivatization product is done by automated injection onto an isocratic high-performance liquid chromatographic system with fluorimetric detection. The assay shows good linearity and reproducibility (intra-assay C.V. 7%). Detection limit is 25 mU/l (= pmol/ml/min). In 51 healthy controls (age 49 +/- 13 yr, 20 males) the measured SSAO activity was 352 +/- 102 mU/l (mean +/- S.D.). A large number of samples (70-80) can easily be processed in one day by one technician.

Adult↗
PubMed1995

Eicosanoid production by rat cerebral endothelial cells: stimulation by lipopolysaccharide, interleukin-1 and interleukin-6.

The capacity of rat cerebral endothelial cells (RCEC) to form eicosanoids was determined after incubation with 14C-labelled arachidonic acid. Prostaglandin E2 (PGE2) was the main metabolite formed by RCEC and was responsible for 54% of the total amount of eicosanoids produced. In contrast, in primary cultures of rat aorta endothelial cells, 32% of the amount of prostaglandins was 6-keto-PGF1 alpha). RCEC treated with 50 ng/ml LPS for 24 h responded with an augmented PGE2 synthesis and 6-keto-PGF1 alpha of 3.4-fold and 2.2-fold, respectively. Cultures treated with IL-1 beta (50 ng/ml) for 3 h showed a stimulation of the release of PGE2 and 6-keto-PGF1 alpha of 2.5- and 4.5-fold, respectively, and 2.0-fold and 2.3-fold, respectively, after IL-6 (50 ng/ml) incubation for 3 h. PGE2 is the main eicosanoid formed by RCEC in response to inflammatory agents, suggesting an important role of the cerebral endothelial cells in the transduction of an inflammatory response in the central nervous system.

Animals↗
PubMed1994

Therapeutic effects of monoclonal antibody G250, interferons and tumor necrosis factor, in mice with renal-cell carcinoma xenografts.

Because renal-cell carcinoma (RCC) is considered relatively resistant to radio- and chemotherapy, RCC patients may benefit from new treatment modalities, e.g. immunotherapy. In vitro and in vivo studies suggest that combinations of cytokines such as interferon gamma or interferon alpha (IFN-gamma, IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) may act synergistically. In this study we tested whether a monoclonal antibody (MAb) G250, reactive with a RCC-associated antigen, showed anti-tumor effects in vivo in nude mice with established s.c. human RCC xenografts, and also whether this MAb could enhance the anti-tumor effect of combinations of IFNs and TNF-alpha. Treatment with combinations of IFN-alpha/TNF-alpha or IFN-gamma/TNF-alpha, or with MAb G250 alone, resulted in a significant inhibition of tumor growth. Treatment with MAb G250, in combination with IFN-gamma/TNF-alpha, did not result in an improve anti-tumor effect as compared to that of either treatment alone. In contrast, MAb G250 combined with IFN-alpha/TNF-alpha resulted in a significantly enhanced anti-tumor response. In one experiment, 3 out of 10 mice showed complete tumor regression, with no recurrence after 90 days. Large numbers of infiltrating macrophages were found surrounding viable and necrotic tumor tissue after treatment with G250 combined with IFN-alpha/TNF-alpha. These results suggest that combination therapy, consisting of IFN-alpha, TNF-alpha and MAbs, may have therapeutic value in the treatment of RCC.

Animals↗
PubMed1993

Isolated profundaplasty in critical limb ischaemia--still of any use?

Because of the improved quality of peripheral bypass surgery, the role of isolated profundaplasty in revascularisation of the critically ischaemic limb has become very limited. This retrospective study of 72 isolated profundaplasties performed for critical limb ischaemia revealed a clinical improvement 1 year postoperatively of 39% in the period 1978-1983 and of only 9% between 1984-1990. In the total period, patient survival after 1 year was 81% and limb salvage 60%. Clinical, haemodynamic and arteriographic parameters were analysed for their predictive value of clinical success. The presence of tissue necrosis or ulceration (clinical stage IV) affected clinical outcome negatively (p < 0.05). Risk factors and indicators for arteriosclerotic disease, age of the patient and ankle-brachial systolic pressure index (ABI) had no significant predictive value. Evaluation of the preoperative arteriographies revealed that only the aspect of the profunda femoris artery beyond its orifice was of significance: there was a strong relationship between the absence of obstructive disease in this part of the artery and clinical improvement (p < 0.005). These two significant parameters may be guidelines when considering an isolated profundaplasty as an alternative in the treatment of critical limb ischaemia. However, in the presence of other treatment possibilities nowadays, especially bypass surgery, the procedure appears to offer a very poor success rate.

Aged↗
PubMed1991

Localization of monoclonal antibody G250 and bispecific monoclonal antibody CD3/G250 in human renal-cell carcinoma xenografts: relative effects of size and affinity.

A study was made of the relative effects of size and binding strength of various forms of the monoclonal antibody (MAb) G250, reacting with primary and metastatic human renal-cell carcinoma (RCC), on the localization in human RCC xenografts in nude mice. Preferential tumor localization was demonstrated after injection of 125I-labelled intact IgG, with increasing tumor/non-tumor ratios in time. Approximately 27.4% of the injected dose/gram (%ID/g) was localized in the xenograft 24 hr post-injection. A control MAb did not preferentially localize in xenografts. With F(ab')2 fragments, higher tumor/blood ratios were obtained, although a lower percentage of injected dose per gram was bound to the tumor, 24 and 48 hr post-injection. Using a bispecific MAb CD3/G250 F(ab')2 fragment, which reacts with CD3 on human T lymphocytes and binds monovalently to RCC, an enhanced accumulation in tumor tissue was also observed. The %ID/g tumor obtained with bispecific CD3/G250 F(ab')2 was comparable with %ID/g tumor found with G250 F(ab')2. The 10-fold lower binding affinity to RCC compared with intact IgG or F(ab')2 had only marginal effects on %ID/g tumor. These results show that MAb G250 preferentially localizes to RCC xenografts. Because injection of F(ab')2 fragments resulted in higher tumor/non-tumor ratios, G250 F(ab')2 may therefore be more suitable for diagnostic evaluation of RCC in patients. The tumor uptake is more dependent on size than on affinity. Furthermore, the data obtained with bispecific MAb CD3/G250 F(ab')2 support the hypothesis that this bispecific MAb may be able to target cytotoxic T lymphocytes to RCC in humans to mediate destruction of RCC.

Animals↗
PubMed1990

Determination of urinary norepinephrine and epinephrine by liquid chromatography with fluorescence detection and pre-column derivatization.

We assayed norepinephrine and epinephrine by utilizing solvent extraction, fluorescence derivatization, and "high-performance" liquid chromatography. A 100-microL aliquot of urine was extracted twice according to Smedes et al. (J Chromatogr 1982;231:25-39) and subsequently incubated with 1,2-diphenylethylenediamine. A 100-microL aliquot of the resulting mixture was injected into a reversed-phase column, and norepinephrine and epinephrine were detected fluorometrically. The within-day CV was 3.0-4.0% and the between-day CV 3.4-7.1% for normal and high concentrations of both analytes. At low concentrations (15-40 nmol/L) these CVs were 4.2-6.8% and 6.8-9.2%, respectively. The detection limit of the assay was less than 0.4 nmol/L for each analyte. We discuss the critical steps for extraction, derivatization, and chromatography. The present method combines the qualities of high precision, specificity, and sensitivity.

Chromatography, High Pressure Liquid↗
PubMed1989

Induction of tumor-cell lysis by bi-specific monoclonal antibodies recognizing renal-cell carcinoma and CD3 antigen.

Bi-specific monoclonal antibodies (MAbs) were developed by somatic hybridization of 2 mouse hybridomas, one producing MAb against the G250 renal-cell carcinoma (RCC)-associated antigen and the other against the T-cell antigen CD3 (OKT3). The dual specificity of the hybrid MAb produced by these so-called quadromas was analyzed by immunohistochemistry on tissue sections and by cytotoxicity assays with relevant target and effector cells. The bi-specific MAb could induce TCR alpha beta/CD3+ and TCR gamma delta/CD3+ cloned lymphocytes to kill RCC cells. A noteworthy finding was that the TCR alpha beta and gamma delta lymphocyte clones showed different triggering abilities. The specificity of target-cell lysis by the cytotoxic T cells (CTL) was dictated by the specificity of the G250 MAb. Control bi-specific MAb, recognizing a cell-surface structure not involved in T-cell activation, did not induce lysis. Several IgG subclass switch variants of the G250 hybridoma, i.e., IgG1, 2a, 2b and IgE, were used for somatic hybridization with the OKT3 hybridoma (IgG2a). Except for IgE, all IgG subclass combinations could equally induce cytolysis. Induction of cytolysis was inhibited only by excess OKT3 MAb. Comparison of 2 bi-specific MAb preparations of the same combination (IgG2a/1), produced by 2 quadromas derived from the same parental hybridomas after identical purification procedures, produced different amounts of bispecific MAb.

Animals↗
PubMed1988

An automatic prompting instrument to increase task-related responding in low-functioning individuals.

The present study was aimed at developing and assessing an automatic prompting instrument with three multihandicapped students who showed breaks in performance. The effects of the instrument were compared with the effects of manual prompting with simple tasks involving locomotion. The results indicated that manual and instrument prompting were both successful in reducing the amount of time spent in breaks. The effects of the instrument were replicated within subjects. The same effects were still visible during a follow-up assessment. The reliability and durability of those effects as well as the practical implications of automatic prompting are discussed.

Activities of Daily Living↗