SIOP working committee on psychosocial issues in pediatric oncology

Recognizing the importance of psycho-social issues in the care and cure of the child with cancer, the board of the International Society of Pediatric Oncology (SIOP) in 1991 constituted a Working Committee on Psychosocial Issues in Pediatric Oncology, with Giuseppe Masera as chair and John Spinetta as co-chair. This committee met for the first time in Rhodes, Greece, in October 1991. The committee discussed various psychosocial issues and developed a document on Aims and Recommendations, summarizing the experiences of major centers. This document was approved by the SIOP board, which recommended diffusion of the document to the pediatric oncology community. © 1993 Wiley-Liss, Inc.     

Differential expression and release of LFA-3 and ICAM-1 in human melanoma cell lines

We examined 10 different melanoma cell lines for cellular expression and release of I CAM-1 (CD54) and LFA-3 (CD58) and the influence of cytokines, including IFNa, IFNγ and TNFa. Cellular ICAM-I expression and density varies considerably between the melanoma cell lines. While IFNα has no effect on cellular ICAM-I (cICAM-l) expression, IFNγ and to a lesser extent TNFα can effectively up-regulate cICAM-l. Soluble I CAM-1 (sICAM-1) is detected in the supernatants of all lines tested, release of sICAM-1 correlates with cellular expression. LFA-3 does not much differ in its expression level on melanoma lines, and cytokines have little or no effect on its expression. Soluble LFA-3 is released by only 6 out of 10 lines. Its release can effectively be inhibited by IFNγ in all lines and by TNFa in one, while IFNa has no effect. These data show that expression and release of LFA-3 and ICAM-I differ between melanoma cell lines. This may be of importance for the interaction of melanoma cells with immune effector cells in vivo.     

The monoclonal antibody GZS-1 detects a maturation-associated antigen of human spermatozoa that is also present on the surface of human mononuclear blood cells

A monoclonal antibody (GZS-1) has been generated by fusion of mouse myeloma cells with spleen cells from BALB/c mice immunised with human sperm cells. The antibody was determined to be an IgG₁. The corresponding antigen is present on the whole surface of ejaculated human spermatozoa. It is not detectable on spermatozoa of other mammalian species (rabbit, cat, dog, sheep, boar, bull, horse). In human male genital organs, immunostaining with GZS-1 is observed on sperm cells in the epididymis and the ductus deferens together with the lining epithelium of those organs. No reactivity of sperm cells or germ cell precursors in the testis has been detected. Functional tests using the antibody show a strong inhibitory effect on human sperm in the hamster egg penetration assay. Furthermore, the GZS-1 antigen is detectable on the surface of human lymphocytes and monocytes by immunogold electron microscopy and FACS analysis. By Western blotting of human sperm and seminal plasma performed under reducing conditions immunostaining was detected at 21–25, 31, 51–54, and 62 kDa. The reaction with human lymphocytes shows one major band at 62 kDa and additional bands at 31 and 54 kDa. The results suggest that the monoclonal antibody GZS-1 may recognise an antigen which is secreted from the epithelial cells of the epididymis and binds to ejaculated spermatozoa as a sperm coating antigen. This component may be involved in the capacitation of the sperm and the acrosome reaction. Molecules that are expressed both on sperm and on immunocompetent cells may be relevant for the regulation of immunological processes or for the development of the related immunological tolerance of sperm in the female reproductive tract.     

Congenital varicella syndrome: studies of the virus-specific humoral and cell-mediated immune responses

We describe a three-year-old boy with congenital varicella syndrome. Persistent IgG antibodies to varicella-zoster virus (VZV) were detected in the child's sera for a period of more than three years. Immunological studies performed at three months and at three years of age showed a VZV-specific cellular immune response. The results suggest that intrauterine VZV infections in early pregnancy can induce adequate humoral and cellular immune reactions in the infected foetus.     

Zur Ätiologie der plötzlichen Todesfälle im Säuglingsalter

Zusammenfassung Bei den Obduktionen von insgesamt 69 plötzlichen und unerwarteten Todesfällen im Säuglings- oder Kleinkindesalter fanden sich in 78% Symptome rachitischer Erkrankungen. Die übrigen pathologisch-anatomischen Veränderungen, bestehend aus hochgradiger wäßriger Hirnschwellung und Ödem der Magen- und Darmschleimhaut, wiesen auf vermehrte Gefäßdurchlässigkeit hin.Bestimmungen des Kalium-Calcium-Gehaltes des Herzmuskels solcher an sogenanntem Magen-Darm-Katarrh verstorbener Säuglinge ergaben eine hochsignifikante Verminderung des Calciums und damit eine Veränderung des Kalium-Calcium-Quotienten.In den schwersten Fällen solcher Elektrolytverschiebungen könnte diese Veränderung im Herzmuskel direkt zum Tode an Herzversagen führen.Bei geringeren Elektrolytveränderungen besteht offensichtlich eine langdauernde Elektrolytlabilität, bei welcher jegliche Behinderung der Atemfunktion, sei es durch Infekte der Luftwege, Aspiration von Mageninhalt oder auch mechanische Atemerschwerung, zu irreparabler Hirnschädigung durch Anoxämie oder CO₂-Vermehrung führen kann. Der Tod dürfte dann letzten Endes infolge zentraler Kreislauf-oder Atemlähmung eintreten.Die Grundvoraussetzung für einen erheblichen Prozentsatz plötzlicher und unerwarteter Todesfälle im Säuglings- und Kleinkindesalter dürfte somit die von uns vorgefundene Elektrolytverschiebung sein.Meinem hochverehrten Lehrer, Herrn Professor Dr. A. Werkgartner, zum 70. Geburtstag gewidmet.     

Die Phosphatasen der Darmschleimhaut

Zusammenfassung Die Aktivität der alkalischen und sauren Phosphatase in verschiedenen Darmabschnitten wurde bei verschiedenen Altersklassen der Maus untersucht. Säuglingsmäuse bis zum Alter von 12 Tagen zeigen im Dünndarm ein von allen andern Altersstufen signifikant verschiedenes Verhalten der alkalischen Phosphatase. In der folgenden Lebensperiode bis zum 21.–24. Tag nähert sich die Aktivität der alkalischen Phosphatase in ihrer Verteilung zwischen kardianahen und coecumnahen Darmabschnitten den Verhältnissen beim ausgewachsenen Tier an. Die Aktivität der sauren Phosphatase weist gegenüber der alkalischen geringere Schwankungen auf, doch bestehen auch hier deutliche Altersunterschiede. Im Dickdarm bleibt die Aktivität der alkalischen und sauren Phosphatase während des Wachstums unverändert.Die Befunde sind mit der funktionellen Differenzierung der verschiedenen Darmabschnitte beim heranwachsenden Tier in Zusammenhang zu bringen. Parallelen zur Entwicklung des Menschen werden zur Diskussion gestellt.     

Influence of subchronic administration of oestrone-3-O-sulphamate on oestrone sulphatase activity in liver, spleen and white blood cells of ovariectomized rats

Inhibition of oestrone sulphatase followed by oestrogen removal from tumour cells may be a new form of endocrine therapy of breast cancer in women. We investigated the inhibitory effect of the subchronic administration of oestrone-3-O-sulphamate (EMATE), a steroid sulphatase inhibitor, to ovariectomized rats, to evaluate this method for testing new nonsteroidal inhibitors. EMATE in DMSO was administered both orally and subcutaneously (s.c.) for 7 days at doses of 0.5 and 2.5 mg/kg. In addition the rats were injected s.c. with 0.5 mg oestrone sulphate/kg 26 and 2 h before decapitation under ether anaesthesia. Oestrone sulphatase activity (ESA) was measured radiometrically using [3H]oestrone sulphate as substrate for desulphuration in white blood cells, liver homogenate, microsomes and spleen homogenate. ESA in liver microsomes was found to be nearly 40 times higher than in white blood cells while in spleen ESA was nearly half of that found in liver homogenates and white blood cells. ESA can be inhibited by EMATE down to 50-1.5% of control activity depending on the dose and administration route. The inhibition was in the order, liver homogenate < spleen < liver microsomes < white blood cells, and was more pronounced after s.c. administration of the inhibitor than after oral administration. Ovariectomy was found to be not necessary for oestrone sulphatase-inhibiting studies. Two sequential s.c. injections of oestrone sulphate enhanced the enzyme activities significantly in liver and white blood cells, but not in spleen. In conclusion, white blood cells and liver microsomes of intact female rats can be used for ESA-inhibiting studies. Sulphate-conjugated oestrone can induce oestrone sulphatase in vivo in liver and white blood cells thereby enhancing oestrogen supply in the peripheral organs.     

Analysis of mdm2 and p53 Gene Alterations in Glioblastomas and its Correlation with Clinical Factors

Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.     

Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case–control study

Objective:To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). Methods:A population-based European multi-center case–control study was conducted from 1995 to 1997. Results:After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5–8.0 and 3.4 (95% CI 1.3–9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. Conclusions:A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.