Educational pathways of childhood cancer survivors-a parental cohort.

PURPOSE: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients. METHODS: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings. RESULTS: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii). CONCLUSIONS: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed. IMPLICATIONS FOR CANCER SURVIVORS: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.

Improved 2D nano-LC/MS for proteomics applications: a comparative analysis using yeast proteome.

The most commonly used method for protein identification with two-dimensional (2D) online liquid chromatography-mass spectrometry (LC/MS) involves the elution of digest peptides from a strong cation exchange column by an injected salt step gradient of increasing salt concentration followed by reversed phase separation. However, in this approach ion exchange chromatography does not perform to its fullest extent, primarily because the injected volume of salt solution is not optimized to the SCX column. To improve the performance of strong cation exchange chromatography, we developed a new method for 2D online nano-LC/MS that replaces the injected salt step gradient with an optimized semicontinuous pumped salt gradient. The viability of this method is demonstrated in the results of a comparative analysis of a complex tryptic digest of the yeast proteome using the injected salt solution method and the semicontinuous pump salt method. The semicontinuous pump salt method compares favorably with the commonly used injection method and also with an offline 2D-LC method.

Technical considerations for microstructural analysis of human trabecular bone from specimens excised from various skeletal sites.

The purpose of this study was to test the effect of repositioning, systematic displacements of the region of interest (ROI), and acquisition parameters (scan mode and integration time) on quantitative analysis of human trabecular bone microstructure at various skeletal sites, using microcomputed tomographic (microCT) technology. We investigated 28 cylindrical specimens of human trabecular bone (length 14 mm, diameter 8 mm) from four skeletal sites (femoral neck, greater trochanter, second lumbar vertebra, and distal radius). These specimens were selected from over 200 microCT measurements, in order to cover a large range of bone volume fraction (BV/TV) observed at each site. Cylindrical ROIs (length 6 mm, diameter 6 mm) were examined twice at an isotropic resolution of 26 microm, 8 weeks apart. In addition, comparative analyses were performed for displacements of the volumes of interest (VOIs) by 1, 2, 3, and 4 mm (83.4%, 66.6%, 50%, and 33.3% overlap), respectively. Eventually, comparative measurements were obtained at different resolution scan modes and integration times. The results show that microCT measurements are highly reproducible (range of the root mean square coefficient variation % (RMS CV%) = 0.64% to 1.29% for BV/TV at different sites). Displacements of the VOI of up to 4 mm generally led to non significant systematic differences in mean values of < 10%. When comparing various combinations of resolution scan modes and integration times, the use of an integration time of 100 ms was found to be preferable for determining microstructural parameters from human samples with this microCT scanner.

HIV type 1 V3 serotyping of Tanzanian samples: probable reasons for mismatching with genetic subtyping.

HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.

PIP: HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Findings are reported from a study conducted to determine whether HIV-1 serotyping could be effectively used to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. The HIV-1 genetic subtypes of 86 people with AIDS in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were then compared with V3 serotyping results obtained by analysis with tests manufactured by Behring and the Pettenkofer Institute, tests conducted by St. Mary's Hospital Medical School, tests conducted by Georg-Speyer-Haus, and tests conducted by Universite Francois Rabelais. The following HIV-1 genetic subtypes were identified: 25 cases of A (29%), 47 of C (55%), 13 of D (15%), and 1 of G (1%). The sensitivity and specificity of the serotyping assays varied considerably. These data indicate that HIV-1 serotyping is not accurate enough to predict genetic subtypes in Tanzania. This conclusion was reached based upon the highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. The serotyping results instead reflect the frequency distribution of V3 serotypes.

S-Acylation and plasma membrane targeting of the farnesylated carboxyl-terminal peptide of N-ras in mammalian fibroblasts.

We have used a series of fluorescent lipid-modified peptides, based on the farnesylated C-terminal sequence of mature N-ras [-GCMGLPC(farnesyl)-OCH3], to investigate the membrane-anchoring properties of this region of the protein and its reversible modification by S-acylation in cultured mammalian fibroblasts. The farnesylated peptide associates with lipid bilayers (large unilamellar phospholipid vesicles) with high affinity but in a rapidly reversible manner. Additional S-palmitoylation of the peptide suppresses its ability to desorb from, and hence to diffuse between, lipid bilayers on physiologically significant time scales. NBD-labeled derivatives of the farnesylated N-ras C-terminal heptapeptide, when incubated with CV-1 cells in culture, are taken up by the cells and reversibly S-acylated in a manner similar to that observed previously for the parent protein. The S-acylation process is highly specific for modification of a cysteine rather than a serine residue but tolerates replacement of the peptide-linked farnesyl moiety by other hydrophobic groups. Fluorescence microscopy reveals that in CV-1 cells the S-acylated form of the peptide is localized preferentially to the plasma membrane, as has been observed for N-ras itself. This plasma membrane localization is unaffected by either reduced temperature (15 degrees C) or exposure to brefeldin A, treatments which inhibit various trafficking steps within the secretory pathway. These results suggest that in mammalian cells the plasma membrane localization of mature N-ras is maintained by a 'kinetic trapping' mechanism based on S-acylation of the protein at the level of the plasma membrane itself.

Synthesis of characteristic lipopeptides of the human N-Ras protein and their evaluation as possible inhibitors of protein farnesyl transferase.

Lipopeptides carrying a farnesyl thioether or a palmitic acid thioester and a farnesyl thioether were prepared from S-farnesyl cysteine methyl ester by N-terminal extension of the peptide chain employing the base labile Fmoc blocking group of the palladium(0) sensitive Aloc urethane. By means of this technique a lipohexapeptide representing the completely functionalized, i.e. palmitoylated and farnesylated C-terminus of the human N-Ras protein, was prepared. If acid labile blocking functions like the Boc group were used, upon deprotection an undesired addition of the acid to the double bonds of the farnesyl residue occurred. Therefore, acid labile blocking groups should not be employed in the synthesis of farnesylated lipopeptides. The lipopeptide methyl esters which carry only a farnesyl group do not inhibit protein farnesyl transferase, whereas palmitoylated peptides are weak inhibitors of this enzyme.

-CA-125 antigen as a prognostic factor for survival in patients with epithelial ovarian carcinoma of FIGO stage I--preliminary results-. / CA 125 als Prognosefaktor für das Uberleben bei Patientinnen mit epithelialen Ovarialkarzinomen des FIGO-Stadium I--preliminäre Ergebnisse.

The tumour marker CA 125 has proved useful in monitoring the course of disease and in indicating responsiveness to therapy in patients suffering from epithelial ovarian cancer. Due to its poor sensitivity, however, attempts to improve early detection by screening with this tumour marker have been unsuccessful to date. This study was performed to evaluate whether there was a relation between pre-operative CA 125 levels and the survival of patients with epithelial ovarian cancer FIGO stage I. If such a relation exists, CA 125 may be an effective variable in singling out those subsets of patients with stage I disease for whom adjuvant chemotherapy would bring an additional therapeutic benefit. Our results suggest CA 125 may be a significant prognostic factor. With a 5-year survival of 43%, marker-positive ovarian cancer carries a poor prognosis. Since the question as the whether follow-up treatment is required in this early, potentially curable stage of disease, is contingent upon numerous factors and since an individualised therapeutic regimen may lead to increased survival rates, the prognostic influence of CA 125 and its relationship to other prognostic factors should be evaluated by multivariate analysis.

[Intrapulmonary sarcoid, presenting as tumor or as multiple pulmonary nodules with and without cavities (author's transl)]. / Vorkommen von Kavernen und metastasenähnlichen Lungenherden bei Sarkoidose.

Eight cases of nodular, partially cavitary intrapulmonary--mainly acute--sarcoid mimicking metastatic disease or cavitary disease of other etiology are presented to point out the fact that sarcoid can occur in this form. Almost all these patients were young and asymptomatic with the lesions discovered incidentally on the chest films taken for other reasons. The pulmonary nodules and cavities present differential diagnostic problems; with the concomitant--or previous--presence of hilar or mediastinal lymph-adenopathy and the finding of unsharp borders of the nodules somewhat supporting the diagnosis of sarcoid.

[Hemangioma of the renal pelvis (author's transl)]. / Hämangiom des Nierenbeckens.

A cavernous hemangioma of the renal pelvis preoperatively diagnosed by angiography is reported. The pathologic-anatomical findings are included.

[Semi-deep radiotherapy under high-kilovoltage conditions]. / Halbtiefentherapie unter Hartstrahltherapiebedingungen

The semi-deep radiotherapy, performed by high-kilovoltage technique, fills a gap between superficial and megavolttherapy, as it renders possible an irradiation in focal depth of 2--4 cm, while largely preserving the deep underlying tissue. Besides which, every form of radiotherapy can be used, as under conventinal conditions. A further advantage exists in the markedly greater skin tolerance and in the low bone absorption of high-kilovoltage radiation, so that much higher focal doses can be achieved. This means that--in superficial processes--the high-voltage technique can replace the much more expensive therapy with accelerated electrons. The RT 305 equipment for high-voltage technique can be especially recommended for the following indications: 1. Skin and limph node metastases as well as tumors and metastases which are not situated deeper than 5 cm below the skin surface. Hereby, thean be exposed up to 8000 R, by small or medium cone. At the same time, in comparison to conventional X-ray therapy, the deep tissue is largely preserved. 2. Postoperative radiotherapy of tumors situated right under the skin. 3. Radiotherapy of inoperable breast cancer. 4. Irradiation of relapses on pre-exposed skin. 5. We assume that the high-voltage technique is also suitable for primary radiotherapy of larynx carcinomas, although we have no personal experience of this. 6. The palliative irradiation of deep tumors with the RT 305, due to its preservation of the skin and the relatively low bone absorption, can be performed more easily than with conventional X-ray therapy. The method of choice, however, is the megavolt-therapy. 7. Degenerative diseases and arthroses.