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Biomedical subjects

C van den Bos

Publications and source records attributed to C van den Bos.

At least 19 recordsLinked to original sources

No adverse effect of vincristine on handwriting in children after completion of therapy.

BACKGROUND: Long-term writing difficulties in children after treatment with vincristine for acute lymphoblastic leukemia, Wilms tumor, B non-Hodgkin lymphoma, and malignant mesenchymal tumors, were investigated. PROCEDURE: Handwriting of 33 survivors and 33 controls matched for age, sex, and grade, was assessed with the BHK-scale. The examiner was blinded for whether a child was a case or a control. RESULTS: No significant difference in writing speed was found. Mean difference in number of letters produced during 5 min was 6.4 (+/-67.1, range -103 to +169). No significant difference was found in quality of writing scores; mean difference in points was 1.5 (+/-7.7, range -19 to +22). Cumulative vincristine dose, age at diagnosis or time since completion of treatment did not affect writing speed or quality. CONCLUSION: Chemotherapy, including vincristine, does not lead to long-term problems in speed or quality of writing in children treated for cancer.

Antineoplastic Agents, Phytogenic↗

[A boy with acute cerebellar ataxia without opsoclonus caused by neuroblastoma].

A 2-year-old boy presented with acute cerebellar ataxia without opsoclonus. The ataxia was assumed to be post-viral. After a period of years a neuroblastoma was detected. Treatment with a curative intent was successful and consisted of metaiodobenzylguanidine I 131, chemotherapy, tumour resection, chemotherapy again and follow-up treatment with isotretinoin after irradiation. In the literature, 5 other children have been described with acute cerebellar ataxia without opsoclonus in whom neuroblastoma was detected eventually. The mean age of these children at initial presentation was 26 months. The mean time between initial presentation and diagnosis ofneuroblastoma or ganglioneuroblastoma was 12 months. Urine concentrations of catecholamine metabolites were normal in 5 of the 6 total children; concentrations were elevated in 1 child. The tumour was located paravertebrally in 5 of the 6 children. Ataxia resolved following resection of the neuroblastoma in all patients. Each child with prolonged or recurrent acute cerebellar ataxia should be extensively investigated for the presence of neuroblastoma, even in the absence of opsoclonus.

Acute Disease↗

Decreasing the number of MOPP courses reduces gonadal damage in survivors of childhood Hodgkin disease.

BACKGROUND: Children treated for Hodgkin disease are at risk for gonadal damage. Since most children were treated with radiotherapy (RT) in combination with chemotherapy, the presumed detrimental effect of MOPP (mustine, vincristine, procarbazine, and prednisone) (in contrast to schemes with less or without alkylating agents) could not be discerned completely from the effects of RT. PROCEDURES: Children with Hodgkins disease treated without RT were included in sequential protocols containing six courses of MOPP (n = 24), six courses of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (n = 17), or three courses of MOPP/ABVD (n = 35). Of these 76 patients, 48, who had completed treatment and had reached puberty, were investigated for gonadal damage. RESULTS: Of the male patients, 81% of MOPP treated patients had increased follicular stimulating hormone (FSH) values, in 23% luteinizing hormone (LH) values were abnormal. In ABVD treated patients, no elevated levels of FSH or LH were noted. In 30% of patients treated with MOPP/ABVD, FSH values were abnormal, but no abnormal LH values were found. Median testicular volume per group decreased in relation to a higher number of MOPP courses. Sperm analysis revealed azoospermia in nearly all MOPP treated patients. In ABVD and MOPP/ABVD treated patients both oligospermia and azoospermia were noted. The number of sperm samples were too less to make any sound conclusions. Menarche occurred in all females, however in some at a relatively later age. One female patient treated with MOPP/ABVD had a normal pregnancy. CONCLUSIONS: Limitation of MOPP therapy to three courses, in children treated without any RT, results in less gonadal damage as compared with six MOPP courses. From our data, MOPP damages Sertoli cells and may also damage Leydig cells as suggested by the higher LH values in conjunction with normal testosterone levels.

Adolescent↗

Quality of life, self-esteem and worries in young adult survivors of childhood cancer.

This study assessed quality of life, self-esteem and worries in young adult survivors of childhood cancer compared to a group of young adults with no history of cancer. The impact of demographic, medical and treatment factors and self-esteem on survivors' quality of life and worries was studied. Participants were 400 long-term survivors (LTS) of childhood cancer (age range 16-49 years, 45% female) who had completed treatment an average of 16 years previously and 560 persons (age range 16-53 years, 55% female) with no history of cancer. All participants completed the MOS-24 (Medical Outcome Study Scale), a Worry questionnaire consisting of three scales (cancer-specific concerns, general health concerns, present and future concerns), and the Rosenberg Self-Esteem Scale. Small to moderate differences were found in mean MOS-24 scores between the LTS group and controls (range effect sizes -0.36-0.22). No significant difference was found in the mean self-esteem scores between LTS and controls. Female LTS had more cancer-specific concerns than male LTS. In several related areas of general health, self-image and dying, the LTS group reported less worries than controls, but LTS worried significantly more about their fertility, getting/changing a job and obtaining insurance's. Multiple linear regression analysis revealed that female gender, unemployment, severe late effects/health problems and a low self-esteem were predictors of worse quality of life in survivors. In addition, age at follow-up, unemployment, years since completion of therapy and a low self-esteem were associated with a higher degree of survivors' worries. Quality of life and the level of self-esteem in LTS of childhood cancer is not different from their peers. Although many LTS worried not more or even less about health issues than their peers, they often are concerned about some present and future concerns. The investigated factors could explain poor quality of life and worries only to a limited extent. Further research exploring determinants and indices of quality of life and worries in LTS is warranted.

Adolescent↗

Frequent adverse events after treatment for childhood-onset differentiated thyroid carcinoma: a single institute experience.

Since the mortality rate for childhood differentiated thyroid carcinoma is nearly zero, the focus must be to minimise morbidity following treatment. Our aim was to analyse early and late adverse events. Twenty-five of 26 children treated between 1962 and 2002 were evaluated. Median follow-up was 14.2 years (range 0.9-39.4 years). All underwent total thyroidectomy, 15 (60%) with lymph node dissection and 15 (60%) with adjuvant radio-iodide therapy. Mortality was zero. Seven developed recurrent disease, two developed a third recurrence. Twenty-one (84%) had > or =1 adverse event. Eight had permanent hypoparathyroidism (PH), six permanent recurrent nerve paralysis (PRNP) and two Horner's syndrome. Risk factors for PH and PRNP were total thyroidectomy with lymph node dissection (RR: 6.45, P = 0.015) and recurrent nerve tumour encasement (RR: 8.00, P = 0.001), respectively. Other adverse events were fatigue (n = 5), scar problems (n = 4) and chronic myeloid leukaemia (n = 1). These results emphasise the need to improve treatment strategies.

Adenocarcinoma, Follicular↗

Screening for late effects in survivors of childhood cancer: growth hormone deficiency from a pediatric oncologist's point of view.

At the Emma Kinderziekenhuis/Academic Medical Center in Amsterdam, survivors of childhood cancer are screened annually or biennially for the occurrence of late treatment effects. The screening procedures are based on previously used treatment modalities. The data gathered at the outpatient clinic are registered in the database PLEKsys. Evaluation of the data concerning over 1000 cancer survivors screened since the start of the clinic once more illustrated the relation between cranial irradiation and the development of central endocrine abnormalities. Surprisingly, at least a proportion of the growth hormone (GH)-deficient cancer survivors were registered as not being on a replacement therapy regimen. The reasons for survivors not to be on replacement therapy are currently being evaluated. The late-effects outpatient clinic and the PLEKsys database provide a platform for additional research in fields including endocrinology, which should be aimed at improving the care for and the health status of the survivors of childhood cancer.

Child↗

No excess fatigue in young adult survivors of childhood cancer.

Clinical reports suggest that many survivors of childhood cancer experience fatigue as a long-term effect of their treatment. To investigate this issue further, we assessed the level of fatigue in young adult survivors of childhood cancer. We compared the results with a group of young adults with no history of cancer. The impact of demographic, medical and treatment factors and depressive symptoms on survivors' fatigue was studied. Participants were 416 long-term survivors of childhood cancer (age range 16-49 years, 48% of whom were female) who had completed treatment an average of 15 years previously and 1026 persons (age range 16-53 years, 55% female) with no history of cancer. All participants completed the Multidimensional Fatigue Inventory (MFI-20), a self-report instrument consisting of five scales (general fatigue, physical fatigue, mental fatigue, reduced activity, reduced motivation) and the Center for Epidemiologic Studies Depression Scale (CES-D). Small differences were found in the mean scores for the different dimensions of fatigue between the long-term survivors and controls (range effect sizes -0.34 to 0.34). Women experienced more fatigue than men. Logistic regression revealed that being female and unemployed were the only demographic characteristics explaining the various dimensions of fatigue. With regard to medical and treatment factors, diagnosis and severe late effects/health problems were associated with fatigue. Finally, depression was significantly associated with fatigue on all subscales. Our clinical practice suggests a difference in fatigue in young adult childhood cancer survivors and their peers. This could not be confirmed in this study using the MFI-20. The well known correlation between fatigue and depression was confirmed in our study. Further research is needed to clarify the undoubtedly complex somatic and psychological mechanisms responsible for the development, maintenance and treatment of fatigue in childhood cancer survivors.

Adolescent↗

[Children with fever peaks and bone and joint pain: systemic juvenile idiopathic arthritis or acute lymphoblastic leukemia after all?].

In two 3-year-old infants, a girl and a boy, systemic juvenile idiopathic arthritis was suspected because of daily fever peaks, signs of polyarthritis and general malaise. Drug treatment was unsuccessful, and after extensive laboratory investigation acute lymphoblastic leukaemia (ALL) was diagnosed and treated adequately. ALL is the most common malignancy in childhood. About one-third of the patients present with joint or bone pain and fever. In this group of children, it can be difficult to identify ALL because it may mimic the clinical picture of systemic juvenile idiopathic arthritis and because of the possibility of a normal blood count at presentation. ALL should always be considered in the differential diagnosis in children with musculoskeletal pain and fever, even in the face of a normal blood count. In any case, a bone-marrow examination should be done before steroid treatment is given.

Arthralgia↗

Mutation at the CK2 phosphorylation site on Cdc28 affects kinase activity and cell size in Saccharomyces cerevisiae.

We have recently reported that protein kinase CK2 phosphorylates both in vivo and in vitro residue serine-46 of the cell cycle regulating protein Cdc28 of budding yeast Saccharomyces cerevisiae, confirming a previous observation that the same site is phosphorylated in Cdc2/Cdk1, the human homolog of Cdc28. In addition, S. cerevisiae in which serine-46 of Cdc28 has been mutated to alanine show a decrease of 33% in both cell volume and protein content, providing the genetic evidence that CK2 is involved in the regulation of budding yeast cell division cycle, and suggesting that this regulation may be brought about in G1 phase of the mammalian cell cycle. Here, we extended this observation reporting that the mutation of serine-46 of Cdc28 to glutamic acid doubles, at least in vitro, the H1-kinase activity of the Cdc28/cyclin A complex. Since this mutation has only little effects on the cell size of the cells, we hypothesize multiple roles of yeast CK2 in regulating the G1 transition in budding yeast.

Alanine↗

Phosphorylation of Cdc28 and regulation of cell size by the protein kinase CKII in Saccharomyces cerevisiae.

The CDK (cyclin-dependent kinase) family of enzymes is required for the G(1)-to-S-phase and G(2)-to-M-phase transitions during the cell-division cycle of eukaryotes. We have shown previously that the protein kinase CKII catalyses the phosphorylation of Ser-39 in Cdc2 during the G(1) phase of the HeLa cell-division cycle [Russo, Vandenberg, Yu, Bae, Franza and Marshak (1992) J. Biol. Chem. 267, 20317-20325]. To identify a functional role for this phosphorylation, we have studied the homologous enzymes in the budding yeast Saccharomyces cerevisiae. The S. cerevisiae homologue of Cdc2, Cdc28, contains a consensus CKII site (Ser-46), which is homologous with that of human Cdc2. Using in vitro kinase assays, metabolic labelling, peptide mapping and phosphoamino acid analysis, we demonstrate that this site is phosphorylated in Cdc28 in vivo as well in vitro. In addition, S. cerevisiae cells in which Ser-46 has been mutated to alanine show a decrease in both cell volume and protein content of 33%, and this effect is most pronounced in the stationary phase. Because cell size in S. cerevisiae is regulated primarily at the G(1) stage, we suggest that CKII contributes to the regulation of the cell cycle in budding yeast by phosphorylation of Cdc28 as a checkpoint for G(1) progression.

Amino Acid Sequence↗

The development of a new information model for a pediatric cancer registry on late treatment sequelae in The Netherlands.

Worldwide, the need is felt for life time follow up of survivors of childhood cancer and for the establishment of registries of the late effects of pediatric oncology treatments. There is however little consensus about how this all should take place. For example, agreement on the nature of this follow up and the type of data to be collected in view of the earlier diagnosis and treatment of the patient is lacking. In a close collaboration between the 'Late Effects Study Group' (consisting of the Pediatric Oncology department of the Emma Children's Hospital and the department of Medical Oncology at the Academic Medical Center), the Netherlands Cancer institute/Antoni van Leeuwenhoek Hospital, and the department of Medical Informatics of the University of Amsterdam, consensus was reached on a new dataset on adverse late effects of pediatric oncology treatment. This dataset was used in developing an information model for the design of a computerized documentation system, PLEKsys. PLEKsys covers both standardized documentation of all relevant data items for evaluating late effects and review facilities on individual patient basis and on patient cohorts. We will install PLEKsys at all Dutch pediatric oncology centers and use the information model as a starting point in developing a National Pediatric Oncology Follow up Registry. A national programme encompassing all Dutch pediatric oncology centers has already been set up to co-ordinate the construction of this national registry.

Child↗

S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14.

Changes in cytosolic calcium concentrations regulate a wide variety of cellular processes, and calcium-binding proteins are the key molecules in signal transduction, differentiation, and cell cycle control. S100A12, a recently described member of the S100 protein family, has been shown to be coexpressed in granulocytes and monocytes together with two other S100 proteins, MRP8 (S100A8) and MRP14 (S100A9), and a functional relationship between these three S100 proteins has been suggested. Using Western blotting, calcium overlays, intracellular flow cytometry, and cytospin preparations, we demonstrate that S100A12 expression in leukocytes is specifically restricted to granulocytes and that S100A12 represents one of the major calcium-binding proteins in these cells. S100A12, MRP8, and MRP14 translocate simultaneously from the cytosol to cytoskeletal and membrane structures in a calcium-dependent manner. However, no evidence for direct protein-protein interactions of S100A12 with either MRP8 or MRP14 or the heterodimer was found by chemical cross-linking, density gradient centrifugation, mass spectrometric measurements, or yeast two hybrid detection. Thus, S100A12 acts individually during calcium-dependent signaling, independent of MRP8, MRP14, and the heterodimer MRP8/MRP14. This granulocyte-specific signal transduction pathway may offer attractive targets for therapeutic intervention with exaggerated granulocyte activity in pathological states.

Antigens, Differentiation↗

Transplantation of human umbilical cord blood cells in macrophage-depleted SCID mice: evidence for accessory cell involvement in expansion of immature CD34+CD38- cells.

In vivo expansion and multilineage outgrowth of human immature hematopoietic cell subsets from umbilical cord blood (UCB) were studied by transplantation into hereditary immunodeficient (SCID) mice. The mice were preconditioned with Cl2MDP-liposomes to deplete macrophages and 3.5 Gy total body irradiation (TBI). As measured by immunophenotyping, this procedure resulted in high levels of human CD45(+) cells in SCID mouse bone marrow (BM) 5 weeks after transplantation, similar to the levels of human cells observed in NOD/SCID mice preconditioned with TBI. Grafts containing approximately 10(7) unfractionated cells, approximately 10(5) purified CD34+ cells, or 5 x 10(3) purified CD34+CD38- cells yielded equivalent numbers of human CD45+ cells in the SCID mouse BM, which contained human CD34+ cells, monocytes, granulocytes, erythroid cells, and B lymphocytes at different stages of maturation. Low numbers of human GpA+ erythroid cells and CD41+ platelets were observed in the peripheral blood of engrafted mice. CD34+CD38+ cells (5 x 10(4)/mouse) failed to engraft, whereas CD34- cells (10(7)/mouse) displayed only low levels of chimerism, mainly due to mature T lymphocytes. Transplantation of graded numbers of UCB cells resulted in a proportional increase of the percentages of CD45+ and CD34+ cells produced in SCID mouse BM. In contrast, the number of immature, CD34+CD38- cells produced in vivo showed a second-order relation to CD34+ graft size, and mice engrafted with purified CD34+CD38- grafts produced 10-fold fewer CD34+ cells without detectable CD34+CD38- cells than mice transplanted with equivalent numbers of unfractionated or purified CD34+ cells. These results indicate that SCID repopulating CD34+CD38- cells require CD34+CD38+ accessory cell support for survival and expansion of immature cells, but not for production of mature multilineage progeny in SCID mouse BM. These accessory cells are present in the purified, nonrepopulating CD34+CD38+ subset as was directly proven by the ability of this fraction to restore the maintenance and expansion of immature CD34+CD38- cells in vivo when cotransplanted with purified CD34+CD38- grafts. The possibility to distinguish between maintenance and outgrowth of immature repopulating cells in SCID mice will facilitate further studies on the regulatory functions of accessory cells, growth factors, and other stimuli. Such information will be essential to design efficient stem cell expansion procedures for clinical use.

ADP-ribosyl Cyclase↗

Copurification of P6, MRP8, and MRP14 from human granulocytes and separation of individual proteins.

A method is described for purification of P6, MRP8, and MRP14, three calcium-binding proteins assigned to the S100 protein family. The purification procedure included preparation of human granulocytes, ammonium sulfate precipitation, and anion-exchange chromatography and resulted in the copurification of P6, MRP8, and MRP14. Individual proteins were separated by either preparative isoelectric focusing or preparative SDS-PAGE. The procedure was carried out in the course of 4 days and yielded several milligrams of essentially pure P6, MRP8, and MRP14 in either native or denatured form.

Amino Acid Sequence↗

p21(cip1) rescues human mesenchymal stem cells from apoptosis induced by low-density culture.

Mammalian cells are programmed to undergo programmed cell death in response to a variety of conditions. We demonstrate that human mesenchymal stem cells (hMSCs) undergo programmed cell death upon seeding at low density. Under these conditions, we observed an increased proportion of cells in S-phase and a decreased proportion of cells in G1-phase. This indicated that a change in control of G1-S-phase transition in response to low-density seeding had occurred and, therefore, we measured the level of cyclin-dependent kinase inhibitory proteins governing this transition. Human MSCs cultured at low density exhibited lowered levels of both the p21 and p27 cyclin-dependent kinase inhibitors, and these protein levels appear to be regulated at a post-transcriptional level. Conversely, overexpression of the p21 cell cycle-dependent kinase inhibitor but not that of p27 protected hMSCs from programmed cell death upon culture at low density. Furthermore, p21 and p27 are expressed differentially during endochondrial bone development. The loss of p21 in hypertrophic chondrocytes correlates with the onset of apoptosis during endochondrial ossification. We suggest that p21 and p27 play a central role in skeletal development.

Apoptosis↗