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M J van Kroonenburgh

Publications and source records attributed to M J van Kroonenburgh.

34 records · Page 2Linked to original sources

Radioimmunoscintigraphy and immunohistochemistry with melanoma-associated monoclonal antibodies in choroidal melanoma: a comparison of the clinical and immunohistochemical results.

Radioimmunoscintigraphy with monoclonal antibodies (MoAbs) to melanoma associated antigens is a new technique that can be used as an additional test to detect ocular melanomas in clinically difficult cases. Immunoscintigraphy with 99mtechnetium-labelled monoclonal antibody fragments of MoAb 225.28S in 14 patients with melanoma yielded a positive image in only six cases (43%). The expression of high molecular weight melanoma-associated antigen (HMW-MAA) was immunohistochemically assessed in melanoma tissue obtained from these 14 patients to find a possible correlation between the results of immunoscintigraphy and expression of the HMW-MAA. The melanoma tissues were immunohistochemically stained by a sensitive immunoperoxidase procedure with three different monoclonal antibodies to the HMW-MAA: 225.28S, Mel-14, and AMF-6. Expression of the antigen detected by MoAb 225.28S was found in 13 of 14 melanomas; the MoAbMel-14 reacted positively with all 14 melanomas; staining with MoAb AMF-6 was achieved in 10 melanomas. No correlation was found between the immunohistochemical staining results, the conventional histopathological findings, and the immunoscintigraphic results. The immunohistochemical staining results suggest that anti-HMW-MAA MoAbs bind to the melanoma tissue and are therefore potentially suitable for immunoscintigraphy.

Aged↗

Iodine-123-metaiodobenzylguanidine scintigraphy in patients with chemodectomas of the head and neck region.

While studying the uptake of iodine-123-metaiodobenzylguanidine ([123I]MIBG) in chemodectomas, we coincidentally detected catecholamine secreting tumors in 5 out of 14 patients. In three of these cases, a norepinephrine secreting abdominal paraganglioma was subsequently removed. One patient had a norepinephrine secreting chemodectoma and one had a dopamine secreting chemodectoma. Prior to [123I]MIBG imaging and urinary catecholamine measurements, endocrine activity was suspected in only one of these five patients. Apart from these five cases, two other patients showed elevated catecholamine secretion and abnormal abdominal [123I]MIBG concentrations. However, these two patients were not surgically explored, because of normal computed tomography (CT) and magnetic resonance (MRI) studies. We suspect that catecholamine-secreting tumors are more common in patients with chemodectomas than is assumed in the literature, and we therefore recommend urinary catecholamine screening for all patients with chemodectomas. In case of elevated catecholamine secretion, MIBG scintigraphy is indicated.

3-Iodobenzylguanidine↗

[Immunoscintigraphy of choroid melanoma using monoclonal antibodies].

A prospective pilot study on immunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was performed in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma associated antigen were labelled with 740 mBq (20 MCi) of the radionuclide 99mTc and injected intravenously. Images were made with a gamma camera 6 hours after injection. With a double pinhole collimator radioactivity was counted thrice in both eyes 6 hours after injection. In 6 out of 17 patients (35.3%) the melanoma could be imaged with the gamma camera. With the double pinhole collimator a significantly higher activity was measured in the melanomatous eye in 13 out of 17 patients (76.5%). In four patients a false negative result was obtained. Considering these results immunoscintigraphy may be valuable in ocular melanoma diagnostics but its specific value still has to be assessed.

Adult↗

Radioimmunoscintigraphy with melanoma-associated monoclonal antibody fragments in choroidal melanoma.

A prospective pilot study on radioimmunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was carried out in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma-associated antigen were labeled with 740 mBq 99mTc and injected IV; images were made with a gamma camera at 6 h after injection. With a double-pinhole collimator, radioactivity was counted thrice in both eyes at 6 h after injection. In 6 of 16 patients (37.5%), the melanoma could be imaged with the gamma camera. With the double-pinhole collimator, a significantly higher activity was measured in the melanomatous eye in 13 of 16 patients (82.4%). In two patients a false negative result was obtained, and in one patient the difference between the left and right eye was not significant. Considering these results, radioimmunoscintigraphy may be valuable in ocular melanoma diagnostics, but the specificity of MoAb 225.28S needs to be assessed.

Adult↗

Imaging of inflammatory arthritis with technetium-99m-labeled IgG.

The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of [99mTc]albumin and [99mTc]nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with [99mTc]IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

Animals↗

Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies.

Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with 99mTc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo.

Antibodies, Monoclonal↗

Survival of spermatogonial stem cells in the rat after split dose irradiation during LH-RH analogue treatment.

A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2 X 3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival.

Animals↗

A computer model of spermatogenesis in the rat; correlation with flow cytometric data based on autoradiographic cell-cycle properties.

A computer model of rat spermatogenesis was created, based on autoradiographic studies of durations of the phases of the cell cycle (G1, S, G2 and mitotic phases) of each germ-cell type. With this model it is possible to predict and to gain insight into the changes of the DNA content occurring during the normal process of spermatogenesis. The relative proportions of haploid, diploid, S phase and tetraploid germ cells with increasing age of the rats were calculated. Calculated and actual experimental flow cytometry data were compared to test the accuracy of the model, and these show good agreement. The present work demonstrates that single-parameter DNA analysis of testicular cells is primarily a reflection of germ cells in the spermatocyte and spermatid stages of development, and of non-germ cells. The FCM single-parameter DNA analysis of testicular cells is relatively insensitive to changes in the stem cell and spermatogonial stages of germ-cell development.

Animals↗

Effects of danazol on spermatogenesis in adult rats.

Adult male Wistar rats were treated with Danazol (4 mg/day s.c.) for 52 days. The drug produced a marked, rapid drop in serum testosterone concentrations to very low levels and caused a slower decrease in serum FSH, LH and testis weight. Flow cytometric analysis of testicular cell suspensions showed a decline in the absolute numbers of haploid cells (spermatids), tetraploid cells (mainly pachytene spermatocytes) and of cells in the S-phase of the division cycle, suggesting that Danazol inhibited proliferation of spermatogonia and/or primary spermatocytes. Histological counting of the different types of spermatogonia, however, revealed no significant change in their numbers during Danazol treatment. It is concluded that Danazol inhibited spermatogenesis primarily after the preleptotene stage of primary spermatocytes.

Animals↗

Effects of a single injection of a new depot formulation of an LH-releasing hormone agonist on spermatogenesis in adult rats.

Adult male Wistar rats were treated with a single injection (500 micrograms s.c.) of a new biodegradable depot formulation of the LH-releasing hormone (LHRH) analogue [D-Ser(But)6]AzGly10-LH-RH (Zoladex; ICI 118,630) to evaluate its potential for inhibiting spermatogenesis. The drug produced a marked (P less than or equal to 0.05) decrease in serum concentrations of FSH, LH and testosterone with a maximum effect 14 days after treatment. Since striking focal histological changes were seen in the testis after only 1 week, at a time when changes in serum gonadotrophins were minimal, there may be a direct effect of the LHRH analogue on spermatogenesis. Degenerative changes in germ cells as well as Sertoli cells could be observed. Flow-cytometric analysis of testicular cell suspensions showed a significant decline in the absolute numbers of haploid cells (spermatids), tetraploid cells (mainly pachytene spermatocytes) and of the numbers of cells in the S-phase of the cell cycle. This suggests that the drug also inhibits proliferation of spermatogonia and/or primary spermatocytes. Testis weight, serum hormone concentrations, and histological and cytological parameters returned to essentially normal values 52 days after the injection. It is concluded that this new method of administration may have practical and pharmacokinetic advantages for the purpose of reversible inhibition of spermatogenesis.

Animals↗

DNA analysis and sorting of rat testis cells using two-parameter flow cytometry.

By use of two-parameter flow cytometry of rat testis cell suspensions stained with mithramycin for DNA (the peak amplitude of the fluorescence signal versus total fluorescence intensity integrated over time), eight cell compartments could be distinguished without pre-enrichment of the samples. Cells in these compartments were identified by sorting and subsequent microscopic examination.

Animals↗

Side-effects of monoclonal antibody infusions for the diagnosis and treatment of cancer.

This literature review presents an inventory of the nature and incidence of side-effects that arise from the clinical application of monoclonal antibodies (MoAb) for the diagnosis and treatment of cancer. Most side-effects occurred during therapy. Toxic reactions, such as fever, sweating and chills, were more common than immunological skin reactions; they were observed predominantly in association with the elimination of circulating target cells. Dosage and rate of administration of the MoAb appeared to have little influence on the reactions, which disappeared quickly and did not necessitate discontinuation of treatment. Serum sickness, anaphylactic reactions and bronchospasms were not common; the patients reacted quickly to the indicated therapy. Prevention of the side-effects described here, especially during diagnostic applications, was such that they need not form a barrier to the clinical use of MoAb.

Anaphylaxis↗

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF).

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF) was assessed in 161 patients at rest, during maximal exercise, and immediately post-exercise by radionuclide angiography. Fifteen patients had a second examination, giving a total of 176 radionuclide examinations. Additionally, the correlation between post-exercise LVEF and physical validity was investigated. Sixty-one patients (35%) with a recent myocardial infarction (less than 4 weeks), 66 patients (37%) with an old myocardial infarction (greater than 4 weeks), and 21 patients (12%) with valvular lesions were studied. Twenty-eight patients (16%) with an abdominal aneurysm were considered as controls based on history and a normal resting and exercise electrocardiogram (ECG). LVEF and a cumulative regional wall motion (RWM) score for three regions were obtained. LVEF post-exercise was significantly increased compared to LVEF at maximal exercise in all four diagnostic groups. Absolute LVEF values were significantly dependent on the level of exercise. We conclude that immediate post-exercise LVEF should not be used for separating patients with and without coronary artery disease.

Adult↗