Search PubMed⌕ Search

Biomedical subjects

J E Van Dijk

Publications and source records attributed to J E Van Dijk.

15 recordsLinked to original sources

The effect of cervical X-irradiation on activity index of thyrocytes and plasma TSH: a pre-clinical model for radiation-induced thyroid damage.

Because radiotherapy in the head and neck region is necessary in the treatment of childhood cancer, possibilities to prevent damage to the thyroid gland must be explored. We developed a model in which radiation-induced effects can be investigated in a way that these effects can be quantified, using thyroid dysmorphology and plasma TSH. Thirty-five Wistar rats, 5 weeks old, were X-irradiated on the cervical region, with a single dose varying from 0 to 20 Gy. After 6 weeks, TSH, T4 and T3 were determined, and thyroid glands were processed for histological examination by two independent pathologists. A histological classification scale was developed, using follicular size, colloid density and cell height of thyrocytes to measure hyperplasia and hypertrophy. By the sum of these scores, a cell-activity index was calculated, which was related to plasma TSH concentration. Numbers of PAS-positive droplets and epithelial desquamation were also counted. Inter-observer reliability was assessed. Good to very good reliability was found for scores of follicular size, colloid density and cell height. Significant increase of cell-activity index was found after 10, 15 and 20 Gy. The plasma TSH concentration was positively correlated to the cell-activity index, increasing with radiation-doses up to 15 Gy. The number of desquamated cells was significantly increased after radiation doses >10 Gy, with moderate reliability. In conclusion, this model using cell-activity index of thyrocytes together with plasma thyrotropin concentrations and desquamation of cells can be used for interpretation and future (pre-clinical) studies of prevention of radiation-induced thyroid damage.

Animals↗

Immunohistochemical evaluation of versican, in relation to chondroitin sulphate, in canine mammary tumours.

The expression of increased amounts of versican, a chondroitin sulphate proteoglycan, in neoplastic tissues may play a role in promoting tumour cell proliferation and migration. This study investigated the immunolocalization of versican in normal and neoplastic canine mammary tissues, using antibodies 12C5 and 2B1, against different epitopes of the protein core of versican. Antibody CS56, recognising chondroitin sulphate (CS), was used to investigate the relation between versican and CS, which accumulates in canine mammary tumours. We found enhanced versican expression in both benign and malignant tumours, appearing in three main patterns: in periductal tissues, probably in association with basement membranes of ducts; in peripheral invasive areas of malignant tumours; and in spindle cell proliferations and myxoid areas of complex and mixed tumours. The 12C5 and 2B1 immunoreactivities co-localised in all types of tumours, and could be improved by chondroitinase digestion. The only exception was the abundant extracellular matrix (ECM) of spindle cell proliferations, particularly in myxoid areas of complex and mixed tumours, which displayed intense and diffuse 12C5 immunoreactivity and patchy or absent 2B1 and CS56 immunoreactivities; versican immunoreactivity could not be enhanced by chondroitinase digestion. The results indicate that versican is one of the extracellular matrix components characteristic of canine mammary tumours. It appears likely that in complex and mixed tumours versican exists in at least two forms, one of them lacking the CS attachment domain and the 2B1 epitope. Furthermore, the enhanced versican expression in the invasive areas of malignant tumours indicates the involvement of this proteoglycan in tumour cell invasion.

Animals↗

Vestibular schwannoma: negative growth and audiovestibular features.

At the University Medical Center Utrecht, non-operative management was used for 44 patients with a unilateral vestibular schwannoma between 1990 and 1997. During that period, consecutive tumor sizes were determined by magnetic resonance imaging. Three of the 44 patients showed an average decrease in tumor size of 16.7% according to American Academy of Otolaryngology-Head and Neck Surgery standards. This study describes the initial vestibular status and audiometric changes measured over up to 10 years in these three patients. Vestibular function was determined once, by means of the bithermal caloric test, the torsion test, the saccade test, the smooth pursuit test, and the registration of spontaneous nystagmus. The three patients had severe vestibular paresis on the affected side. Pure-tone and speech audiometry were performed at regular intervals. Although the size of their tumors decreased, their hearing gradually deteriorated, just as it does in the majority of patients with a growing or stable vestibular schwannoma. The observations presented here suggest that the development of symptoms in a vestibular schwannoma does not differentiate between patients with a stable, growing or shrinking tumor. The development of symptoms may be the result of the same pathogenetic mechanism.

Adult↗

Behavioral and physiological effects of biotechnology procedures used for gene targeting in mice.

The effects of gene-targeting procedures on the behavior and physiological development of (chimeric) mice have been investigated. We used six groups of mice, each of them undergoing specific aspects of the biotechnological procedure, including electroporation, microinjection, and/or blastocyst culture. Changes in behavior and physiological development of the progeny (age 4-30 weeks) were investigated. Besides increased body weights, no significant difference between the six treatment groups and untreated C57BL/6 controls could be attributed to the biotechnology procedures. Therefore, we conclude that these procedures per se do not induce significant discomfort for the offspring. Differences in behavior, observed for the two groups of chimeric mice [one derived from electroporated embryonic stem (ES) cells and the other from nonelectroporated ES cells] when compared to the other (nonchimeric) groups, are, at least partly, due to the genetic background of the 129/Ola strain from which the ES cells are derived rather than to the biotechnological manipulations of the ES cells and/or blastocysts. The occurrence of hermaphrodites (8%) and some other gross pathologies observed in both groups of chimeric animals seem to indicate that developmental problems may occur when cells from different origin are simultaneously contributing to the development of one individual. This implies that during the production of gene-targeted mice, health and welfare of chimeric animals must be carefully monitored.

Age Factors↗

Assessment of vestibular schwannoma growth: application of a new measuring protocol to the results of a longitudinal study.

This study pertains to a group of 44 patients with unilateral vestibular schwannoma who did not undergo surgery. Prospectively, the dimensions of the tumor were depicted at regular intervals by means of magnetic resonance imaging and then judged independently by an otolaryngologist and a neuroradiologist. Retrospectively, the size of the tumor was quantified by measuring the maximum surface of the lesion in the axial plane. The retrospective surface measurements confirmed the assessments made in the prospective part of the study: growth in 18% of the patients and shrinkage in 7%; 75% remained unchanged. This approach is a pragmatic means to determine whether the size of a tumor has changed over the course of time.

Adult↗

Indicators of erythrocyte formation and degradation in rats with either vitamin A or iron deficiency.

Vitamin A deficiency produces anemia and altered iron status. In this study with rats we tested two hypotheses regarding vitamin A deficiency: (1) that it impairs erythropoiesis, leading to an increased red cell turnover, and (2) that it inhibits the glycosylation of transferrin. Erythropoietic activity was assessed indirectly by determining the myeloid:erythroid ratio in bone marrow smears, the number of erythroid colonies in the red pulp of spleen, the blood reticulocyte index, and zinc protoporphyrin and plasma transferrin receptor concentrations. Transferrin glycosylation was assessed by measuring the sialic acid content of transferrin. The effects of vitamin A deficiency were compared with those of iron deficiency. Iron deficiency produced anemia and low iron levels in organs. Vitamin A deficiency produced low levels of plasma and hepatic retinol, and it induced decreased plasma total iron-binding capacity and raised iron levels in tibia and spleen. Short- but not long-term iron deficiency reduced the number of erythroid colonies in spleen; vitamin A deficiency had no influence. Neither iron nor vitamin A deficiency influenced the myeloid:erythroid ratio in bone marrow smears and the blood reticulocyte production. Plasma transferrin receptor and erythrocyte zinc protoporphyrin concentrations were not affected by vitamin A deficiency but increased with iron deficiency. Vitamin A deficiency did not stimulate erythrocyte breakdown, as indicated by unaltered plasma lactate dehydrogenase activity and reduced plasma total bilirubin levels. Both vitamin A and iron deficiencies raised the proportion of multiple sialylated transferrins in plasma. Thus, we have not found evidence that vitamin A deficiency affects erythropoiesis and erythrocyte turnover. The iron accumulation in spleen and bone marrow may be related to reduced iron transport due to inhibition of transferrin synthesis rather than inhibition of transferrin sialylation.

Journal Article↗

Acoustic neuroma: deterioration of speech discrimination related to thresholds in pure-tone audiometry.

Pure-tone and speech audiometry were performed in 231 patients with a unilateral acoustic neuroma. Tumor sizes were obtained through imaging. Audiometric parameters, such as the mean pure-tone thresholds, the maximum discrimination, the slope of the speech audiogram, the roll-over index and the difference between the speech reception threshold and the Fletcher index, were studied and compared with data in the literature. Results showed that patients with an acoustic neuroma have worse speech discrimination than can be expected from the pure-tone audiogram. However, the results presented here indicate that hearing impairments nowadays are not as severe as those described in earlier studies. More patients with a unilateral acoustic neuroma are detected, including even those with a minor hearing impairment. The roll-over index is not characteristic for patients with an acoustic neuroma.

Adult↗

Electronystagmographic changes in patients with unilateral vestibular schwannomas in relation to tumor progression and central compensation.

Vestibular function was studied in a group of 121 patients with unilateral vestibular schwannomas who were referred to University Hospital Utrecht between 1986 and 1996. Testing included the caloric test, torsion test, saccade test, smooth pursuit test and the registration of spontaneous nystagmus. Each patient's symptoms were taken from a chart review. The size of the tumor was expressed as the maximum extrameatal diameter in the axial plane parallel to the petrous ridge as seen in magnetic resonance imaging or computed tomography. Large tumors were significantly more often accompanied by a more severe paresis on caloric testing, a smaller gain on torsion testing, spontaneous nystagmus, an abnormal saccade test and an abnormal smooth pursuit test. The presence of spontaneous nystagmus was significantly more frequently combined with an abnormal smooth pursuit and saccade test. There was a significant correlation between the slow component's velocity of the spontaneous nystagmus and the size and progression of tumor. However, a specific relation between tumor size and central vestibular compensation could not be demonstrated.

Caloric Tests↗

Thyrotrophin receptors in normal and neoplastic (primary and metastatic) canine thyroid tissue.

Thyrotrophin (TSH) is the conditional growth factor of thyroid epithelial cells. Abnormalities in TSH-receptor binding such as a low receptor number or low binding affinity may be a marker of thyroid carcinoma or metastases, or may exhibit a relationship with the functional variability of such tissues. The dog was used as a model to characterize TSH-receptor binding in normal thyroid tissues, naturally occurring thyroid neoplasms and distant metastases. In normal dog thyroid tissues, specific 125I-labelled TSH binding ranged from 2.7 to 15.5%, and low cross-reactivity with bovine LH (0.023%) was observed. One class of TSH-binding sites was found in eight normal thyroid tissues and 22 thyroid carcinomas; two normal thyroid tissues and one tumour exhibited two classes of binding sites. The concentration of binding sites was lower in the five carcinomas with reduced pertechnetate uptake (0.09 pmol/mg protein) than in the five thyroid neoplasms with increased uptake (0.19 pmol/mg) (P = 0.055). Compared with the original carcinoma tissues, TSH binding revealed a reduced binding affinity in eight out of eleven metastases. Two metastases showed a complete absence of TSH binding, suggesting that they were not dependent on TSH for growth. We conclude that one class of TSH-binding site is predominant in normal dog thyroid tissues and dog thyroid carcinomas. TSH could therefore contribute, at least in theory, to further growth of primary dog thyroid carcinomas. Secondly, assays measuring TSH binding may not be able to discriminate between malignant and benign dog thyroid tumours. TSH receptor number or affinity may be related to the functional variability of thyroid neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gastrointestinal food allergy and its role in large domestic animals.

The significance of food allergy as a primary cause for gastrointestinal disturbances in domestic animals, especially calves and piglets, is discussed. The immunological backgrounds and pathogenesis are described in some detail. The clinical and pathological manifestations in animals are related to those in man. Diagnostic possibilities, therapy and prevention, as far as known in animals, are mentioned and, based on human experiences, further extensions are proposed.

Allergens↗

[ A case of avian tuberculosis with exudative characteristics in a horse (author's transl)].

A case of avian tuberculosis in a horse, with fatal course, is reported. The animal was imported from Poland and became ill after some weeks, in the beginning showing non-specific symptoms which became more severe until death supervened. Post-mortem examination showed a generalised form of tuberculosis. The most important lesions were seen in the lungs, liver, kidneys, spleen, intestinal tract, bones, bone marrow, and the internal lymph nodes. Beside chronic proliferative tuberculosis of the organs, many exudative foci were found with remarkably abundant acid fast bacilli. Mixed lesions were seen, too. Mycobacterium avium was isolated in microbiological examination. The pathogenesis of the infection, the predisposing factors leading to this generalised and open form of tuberculosis and the increasing importance of avian tuberculosis for animals and man are discussed.

Animals↗

Perilesional IL-2 treatment of a VX2 head-and-neck cancer model can induce a systemic anti-tumour activity.

BACKGROUND: Head-and-neck cancer is associated with impaired cell-mediated immune reactivity. A rabbit model with VX2 Squamous Cell Carcinoma transplanted into both auricles was used to test the effects of a regimen for local Interleukin 2 (IL-2) therapy, optimal in murine tumour models. MATERIALS AND METHODS: Peri-tumoural IL-2 treatment started when one of the tumours exceeded 2 cm2 and consisted of 100,000 or 300,000 Chiron Units IL-2 or only solvent during 5 consecutive days. RESULTS: In 4 out of 12 (33%) rabbits the treated primary tumours regressed completely, simultaneously with the non-treated contra-lateral tumours. Also metastases in draining lymph nodes of both treated and untreated primary tumours regressed in three of these animals. Tumour cells injected in the cured animals were rejected. The histology of the regressing tumours in cured cases showed an active granulomatous reaction with a histiocytic response, splitting up of tumour islands, and fibrinoid obstruction of blood vessels. CONCLUSION: These findings showed local and systemic therapeutic effects of this local IL-2 regimen in a VX2 head-and-neck cancer model.

Animals↗