Biomedical subjects
Publications and source records attributed to M Debiec-Rychter.
An aberrant leukemic clone with a 46,X,i(Xq) karyotype appeared at the first relapse of the disease in a case of acute myeloblastic leukemia (AML). The DNA replication pattern displayed asynchronous late termination within the homologous arms of the isochromosome in all investigated metaphases. The origin of asynchrony in the isochromosome's DNA replication pattern is discussed.
The proliferative capacities of the PHA-stimulated bone marrow and peripheral blood lymphocytes were studied in children with newly diagnosed acute lymphoblastic leukemia by means of BrdU-Hoechst-Giemsa technique. The investigations were carried out at the following times: before treatment; during the first 72 h of the therapy, and after the remission induction. In patients with large amount of blasts, subpopulations of lymphocytes reacting either quickly or slowly could be distinguished. Some of the latter showed the recovery of proliferative capacities during the therapy. The problem whether the entire failure in proliferation of lymphocytes was due to the dilution of lymphocyte population by non-PHA-responsive blasts, due to the proliferation of long-lived leukemic cells or other factors, is discussed.
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We report here ultrastructural and immunohistochemical studies of neuroblastic differentiation in the retrospective (n = 17) and prospective (n = 26) series of primitive neuroectodermal tumors (PNETs). By electron microscopy, neuritelike structures containing parallel-oriented microtubules, adhesive plaque junctions, and pleomorphic dense-core vesicles were found in the majority of tumor specimens while synaptic specializations were very rare. By immunohistochemistry, synaptophysin appeared to be the most reliable marker for neuroblastic differentiation present in the most reliable marker for neuroblastic differentiation present in the majority of tumors, while 200 kDa neurofilament protein was immunovisualized in a lower proportion of tumors. Glial fibrillary acidic protein (GFAP) was expressed in both reactive astrocytes and in a small proportion of otherwise typical neoplastic cells. We conclude that the majority of PNETs revealed diverse differentiation and that electron microscopy is still the most reliable tool for its detection followed by immunohistochemistry for synaptophysin.
The aim of this report was to evaluate the prognostic value of allele loss of the WT1 gene in children with sporadic Wilms' tumour. Allele loss of the WT1 gene was evaluated using microsatellite polymorphisms in the 3' untranslated region of WT1 in a radioactive PCR assay. The study comprised 66 children (30 girls and 36 boys), aged from 2 days to 13 years, treated for Wilms' tumour according to the SIOP-09 and PGGL scheme. We have used DNA isolated from the neoplastic versus normal kidney tissue from the paraffin embedded sections using microdissection procedure. Loss of heterozygosity (LOH) of the WT1 gene was found in 12 children (19.6%), 5 cases were non-informative. No significant correlation could be found between the LOH of WT1 gene and sex and age. Significantly more frequent occurrence of LOH in tumor in low stage of advancement and low degree of malignancy was found. However, no significant effect of LOH of WT1 gene was observed on frequency of recurrences, metastasis and deaths. Study of allele loss of the WT1 gene may be recommended in difficult cases as an additional factor useful for the diagnosis and in the assignment of the tumour to the appropriate risk group.
Male ACI/seg rats of different postnatal ages were injected, i.p., with 150 mg/kg bromodeoxyuridine one hour before being sacrificed. The incorporation of this compound into the DNA of prostate epithelium was detected immunohistochemically. The labeling indices in prostate epithelium were 16.8, 26.5 and 13.7%, in 3, 11 and 17 days old rats, respectively. It decreased gradually thereafter to 1.8% in 60 days old rats. The mRNA of N-acetyltransferase 1 was detected by a non-isotopic in situ hybridization method using a mixture of specific digoxigenin-11-dUTP-labeled oligodeoxynucleotide probes. The mRNA of N-acetyltransferase 1 was detected during the entire postnatal period. It was not detected in the stromal or endothelial cells. The coincidence of N-acetyltransferase expression in actively proliferating prostate epithelial cells during the postnatal period suggest that the prostate tissue may be particularly sensitive during this period to the carcinogenesis by aromatic and heterocyclic amines.
BACKGROUND: The goal of the presented studies as a retrospective reliability assessment of classical banding cytogenetic studies and of prognosing epicrises in a group of 14 cases, affected with additional marker chromosomes. MATERIAL AND METHODS: Having collected the study material from peripheral blood, by means of trophoblast biopsy or amniocentesis, cytogenetic preparations were obtained, allowing for pre- or postnatal evaluation of the karyotype. A panel of auxiliary cytogenetic techniques accompanied the routine CTG protocol. RESULTS: In a group of 6875 persons with recommendations to pre- or postnatal cytogenetic diagnostics, 14 (0.2%) cases of ESACs were diagnosed. In 5 cases of DA/DAPI(+) inv dup (15) as observed. A presence of polymorphic interstitial RHG(+) band was found within the marker chromosome. The measured size of that band allowed associating it with either the presence or the absence of pathological signs. In 9 cases of ESACs, DA/DAPI(-), the application of banding techniques (NOR and CBG) allowed to discover bisatellite heterochromatic ESACs in 6 cases (2 non-mosaic and 4 mosaic). In three other mosaic and non-satellite cases of ESACs, a 'genetic inactivity' of the marker chromosome was observed in one case, while a 'genetic activity' was ascertained in two cases. The 'activity' of marker chromosomes was studied by means of replication banding techniques. CONCLUSIONS: At the time of the outburst of molecular techniques, still up-to-date is the use of classical banding techniques and of the replication techniques, allowing DNA replication kinetics studies at the level of single band.
An unusual posterior fossa neoplasm in a 26-year-old woman with short history of the cerebellar symptoms is presented. CT and MR images showed the tumor within the cerebellopontine angle, suspected as meningioma. At surgery, the tumor was dura-attached and did not infiltrate the arachnoid. Histologically, the neoplasm was a small blue cell tumor with solid and microcystic pattern, consistent with primitive neuroectodermal tumor (PNET). Immunohistochemically the cells were strongly positive for NCAM and GFAP. Fluorescence in situ hybridization (FISH) was performed with the cosmids G9 and F7 (flanking EWSR1/22q12 region) DNA probes and dual-color spectrum-orange LSI HER-2/neu (17q11.2)/spectrum green CEP17 (17p11.1-q11.1) DNA probe. The presence of isochromosome 17q within neoplastic cells was found. The tumor was classified as a medulloblastoma. We demonstrate the utility of a multidisciplinary approach to nervous system tumor diagnosis. The clinical features together with histological, immunohistochemical, and characteristic molecular alteration allowed classification of the presented case.
Embryonal tumors, the most common group of malignant brain tumors in childhood, are heterogeneous and have been associated with a large number of genetic abnormalities. The aim of this study was to comprehensively analyze loss of heterozygosity (LOH) on regions harboring suppressor genes (PTCH2, PTCH1, APC, PTEN, DMBT1, SUFU, AXIN1, hSNF5/INI1) and to study chromosomal regions in which deletions have been described most frequently (1p, 1q, 11p, 16p, 17p). Twenty-nine children (17 male and 12 female), aged from 1 year 13 years were included in this study. There were 24 medulloblastomas (MB) and 5 supratentorial primitive neuroectodermal tumors (sPNET). Tissue samples from 29 primary and 11 recurrent tumors were analyzed according to the LOH standard procedures, which were extended to include fluorescence in situ hybridization for detection of isochromosome 17q (i(17q)) and direct sequencing ofTP53 exon 4. LOH on 17p was found in 15 out of 29 tumors. FISH analysis identified the presence of i(17q) in 16 tumors. Comparison of LOH analysis and the FISH data indicated that alterations of 17p were related to be the introduction of an i(17q) formation. LOH on 10q and 9q was observed in 4 and 2 cases, respectively, and was associated with alterations of chromosome 17. These results indicated a connection between alterations of PTCH/SHH genes and abnormalities of chromosome 17. A deleted region on 22q, covering the hSNF5/INI1 locus, was observed in 3 tumors. Progression of the molecular changes occurred in 1 case of recurrent medulloblastoma. LOH on 10q and 17p was found in both primary and recurrent tumor, while losses on 11p, 16p, and 16q occurred only in the recurrent tumor. No evidence of alteration in TP53 exon 4 was identified.
The karyotypes and selected isoenzymes of five cell lines, HU 961b, HU 1922, HU 609, HCV-29 and HU 1703 He, were characterized. These cell lines were derived either from histologically normal human urothelial cells or from transitional cell carcinoma (TCC) of the urinary bladder. They displayed different life span in vitro and transplantability in nude mice, as well as a unique isoenzyme and chromosomal pattern. In addition, various chromosomes were involved in the formation of marker chromosomes in these cell lines. Since there was a lack of consistency in chromosomal changes in the cell lines with TCC origin, the cause of malignancy could not be attributed to the abnormality of specific chromosomes.
Human benign hyperplastic prostate (BHP) tissues were implanted subcutaneously in male Beige nude mice for up to 16 weeks. The implants maintained the normal histological appearance of BPH without signs of atrophy for up to 6 weeks. Their epithelium expressed proliferating cell nuclear antigen (PCNA), demonstrating that these cells actively underwent cell division. Thereafter the tissues gradually became atrophic, and some tissues maintained for 16 weeks completely lost recognizable prostatic epithelium. The glandular epithelium tended to undergo squamous cell metaplasia associated with atrophy. The epithelial linings of the implants consistently expressed prostate-specific antigen and prostate acid phosphatase as demonstrated by immunohistochemistry, except in areas of severe atrophy and squamous metaplasia. The nuclei of the implants hybridized with a human-specific DNA probe. Continuous feeding of the mice with dihydrotestosterone or hydrocortisone did not change significantly the morphology or the proliferation index of the epithelial cells within the glandular alveoli of implanted tissues or of normal mouse prostates.
Human benign hyperplastic prostate (BHP) tissues were implanted subcutaneously in male Beige nude mice for up to 16 weeks. The implants maintained the normal histological appearance of BPH without signs of atrophy for up to 6 weeks. Thereafter the tissues gradually became atrophic, with the tendency to undergo squamous cell metaplasia, but some tissues still maintained normal epithelium at 16 weeks. The epithelial linings of the implants consistently expressed prostate-specific antigen and prostate acid phosphatase, as demonstrated by immunohistochemistry, except in areas of severe atrophy and squamous metaplasia. Continued feeding of the mice with dihydrotestosterone or hydrocortisone did not change significantly the morphology or the proliferation index of the epithelial cells within implants or host prostates.
The present study determined the influence of implantation sites, androgens, and the graft's fibrovascular elements on the maintenance of epithelial elements of human benign hyperplastic prostate tissue (BPH) in the nude mouse. BPH fragments prepared from fresh surgical specimens were implanted subcutaneously (s.c.), intraperitoneally (i.p.), or under the renal capsules (r.c.) into male Beige nude mice, which had been implanted s.c. with a Silastic tube filled with 4-dihydrotestosterone (DHT) or cholesterol. Two weeks later the BPH tissues were removed from the mouse and examined microscopically. The implants from all three sites maintained a comparable morphology, with epithelial and/or angio-leiomyomatous stromal hyperplastic appearance, without striking signs of atrophy, irrespective of supplementation with DHT. Expression of proliferating cell nuclear antigen in the implants was comparable, indicating that there was no significant influence of implantation site on the proliferative ability of either epithelia or the stromal fibroblasts. The PCNA-positive cells in the implants, including the vascular and myofibrous elements, hybridized in situ to a human-specific repeated-sequence DNA probe, indicating that these proliferating cells were of human origin. Our data suggest that during the early phases of the adaptation and maintenance of BPH implants, survival of epithelial cells is actively supported by fibro-vascular mesenchymal elements of the prostate grafts in a manner apparently unaffected by DHT supplements.