PubMed Health⌕ Search

Biomedical subjects

B Sikorska

Publications and source records attributed to B Sikorska.

At least 19 recordsLinked to original sources

GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.

Deletions of 1p occur in approximately 30% of meningiomas. Based on loss of heterozygosity (LOH) analysis, two regions on 1p have been suspected to be carriers of tumor suppressor genes. We chose the GADD45A and EPB41 genes as tumor suppressor candidates based on their function and chromosomal localization. We analyzed 19 cases of meningioma with LOH of 1p by means of sequencing of the GADD45A gene and Western blotting of the GADD45a protein. Twenty cases of meningioma without 1p LOH were also analyzed by Western blotting to find out if changes of the GADD45a protein expression occurred. Nineteen samples with 1p LOH (12 grade I; 7 grade II, WHO classification) and 20 samples without 1p LOH (18 grade I; 2 grade II) were also analyzed by means of real-time polymerase chain reaction to find abnormalities in EPB41 mRNA levels in meningioma. LOH analysis was performed using seven microsatellite markers: D1S508 (1p36.2), D1S199 (1p36.1) D1S2734 (1p36.1), D1S2720 (1p34), D1S197 (1p32), D1S162 (1p32), D1S429 (1p11). LOH analysis confirmed previously described localization of putative tumor suppressor genes on 1p and involvement in meningioma pathogenesis (1p36 and 1p32). The open reading frame of GADD45A and intron splicing sites showed neither mutations nor polymorphisms. GADD45a protein molecular weight and expression level were unaltered in meningiomas with and without 1p LOH. We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. EPB41 gene expression was unchanged in all analyzed meningiomas. This suggests that involvement of the EPB41 gene (4.1R protein) in meningioma pathogenesis should be reconsidered.

Blood Proteins↗

Ultrastructural pathology of prion diseases revisited: brain biopsy studies.

We report here a detailed ultrastructural comparison of brain biopsies from 13 cases of Creutzfeldt-Jakob disease (CJD) and from one case of fatal familial insomnia (FFI). The latter disease has not heretofore benefited from ultrastructural study. In particular, we searched for tubulovesicular structures (TVS), 35-nm particles regarded as the only disease-specific structures at the level of thin-section electron microscopy. Our material consisted of brain biopsies obtained by open surgery from one FFI case from a new French family, one case of variant CJD (vCJD), nine cases of sporadic CJD (sCJD), two cases of iatrogenic (human growth hormone) CJD and one case of hereditary CJD (Val203Iso). The ultrastructural picture of the cerebral cortex of the FFI patient was virtually indistinguishable from that of CJD. TVS were found, albeit only after prolonged search. Typical spongiform change was observed, consisting of intracellular membrane-bound vacuoles containing secondary chambers (vacuoles within vacuoles) and amorphous material. Neuronal degeneration was widespread: some processes contained degenerating mitochondria and lysosomal electron-dense bodies and these met the criteria for neuroaxonal dystrophy. Other processes contained branching cisterns; still others were filled with electron-dense masses and amorphous vesicles. The overall ultrastructural appearance of variant CJD was similar to that of FFI cerebral cortex, except for a much higher number of cellular processes containing TVS. We detected TVS in the majority of sCJD cases that, in addition to typical spongiform change and robust astrocytic reaction, showed widespread neuritic and synaptic degeneration and autophagic vacuoles. We conclude that TVS are readily found in FFI, vCJD and sCJD and that widespread neuritic degeneration is a part of ultrastructural pathology in prion diseases.

Adult↗

Molecular heterogeneity of meningioma with INI1 mutation.

BACKGROUND: INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported. AIMS: To analyse the INI1 gene in meningioma. METHODS: Exons 1, 4, 5, and 9 of the INI1 gene were analysed by the polymerase chain reaction and direct sequencing in 80 meningiomas. For all cases, western blotting of the INI1 protein was performed. RESULTS: Only one of the 80 samples showed a cytosine insertion in codon 376. This mutation changed the open reading frame in almost the whole exon 9 and resulted in a longer hSNF5 protein. Complex analysis of the above described tumour sample by western blotting, DNA sequencing, and loss of heterozygosity (LOH) analysis showed that this particular meningioma consisted of heterogeneic cellular components. One of these components had a mutated INI1 gene, whereas in the other component INI1 was intact. CONCLUSIONS: INI1 mutation is a rare event in the molecular pathology of meningiomas. It is possible for the INI1 gene to be mutated in only a proportion of meningioma cells.

Amino Acid Sequence↗

Prognostic significance of apoptosis in laryngeal cancer. A quantitative immunomorphological study.

The main purpose of the study was to investigate the prognostic significance of apoptosis of cancer cells and to examine the relationship between apoptosis and morphological markers of the host immune response in laryngeal cancer. Apoptotic tumour cells, detected by the TUNEL technique, expression of HLA DR (an antigen belonging to human leukocyte-associated antigens class II) in cancer cells, the number of tumour infiltrating T cells (CD45RO+ cells), B cells (CD20+ cells), macrophages (CD68+ cells) and mast cells as well as the mitotic index were investigated in 28 laryngeal cancers. Sections were studied morphometrically using image analysis. Significant inverse correlations between the number of apoptotic tumour cells and HLA DR-positive tumour cells as well as between the number of apoptotic tumour cells and the number of CD45RO+ cells at the tumour periphery were observed. Analysis of survival showed that patients with high rates of apoptosis had significantly worse prognosis as compared to patients with low apoptotic rates. Differences in HLA DR expression and numbers of CD45RO+ cells were also found between groups of patients with high and low numbers of apoptotic cells. Whether these findings are due to immunosuppressive effects of apoptosis needs further investigation.

Antigens, CD↗

[Pregnancy in patients with end-stage renal failure on maintenance dialysis: case reports].

Pregnancy in women with end-stage renal failure on maintenance dialysis is rare, and the chance of successful delivery is relatively low. In this paper we present two cases of women who conceived just prior to initiation of renal replacement therapy and the pregnancy was terminated successfully already on chronic dialysis treatment. The special attention was paid on the necessity of multi-disciplinary collaboration and the need for changes in regular dialysis schedule as the conditions crucial for successful delivery. In summary, the review of current literature dealing with mentioned problem was done.

Adult↗

HLA-DR expression is a significant prognostic factor in laryngeal cancer. A morphometric study.

HLA-DR antigen expression in tumour cells was investigated in 68 laryngeal carcinomas. The tissue sections were studied by a morphometric method using a computer image analysis system. Although the highest number of HLA-DR-positive cells was observed in the groups with the lowest clinical stage, these differences did not reach statistical significance. Analysis of survival showed a significantly different survival time of patients classified as HLA-DR positive (10% and more HLA-DR+tumour cells) compared to those classified as HLA-DR negative. There were no significant differences in survival times between patients with glottic and extraglottic cancers, or between patients with various grades of histological malignancy.

Carcinoma, Squamous Cell↗

Quantitative analysis of HLA DR expression and lymphocytic infiltrate in laryngeal cancer including clinical and morphological correlations.

HLA DR antigen expression in tumor cells and lymphocytic infiltrates at the tumour periphery were investigated in 68 laryngeal carcinomas. The tissue sections were studied by a quantitative method using computer image analysis system. The highest number of CD45RO+ cells was observed in the groups of the lowest clinical stage. There were statistically significant differences between the groups in the number of T cells, whereas no differences were found in HLA DR+ cancer cell number, B cell number or mitosis count. Statistical analysis revealed a significant correlation between T-cell number at the periphery of the tumour and the number of cancer cells showing HLA DR expression. The results of the analysis, using Cox proportional hazard model with selected factors, showed that only HLA DR expression in cancer cells had a significant effect on survival, whereas the number of CD45RO+ and CD20+ cells, histological grade and mitosis count did not contribute further to prognostic information. To our knowledge, this is the first time that HLA DR expression and its correlation with lymphocytic infiltration have been shown by a quantitative method in laryngeal cancer.

Carcinoma, Squamous Cell↗

Glomerular and interstitial renal findings in patients with liver cirrhosis with normal renal function. The histomorphometric study.

Seventeen kidney autopsy tissue sections from patients with cirrhosis of the liver were quantitatively examined and compared with fifteen cases of normal controls. The study was limited only to cases with normal renal function and without macroscopic renal changes. Morphometric investigations were performed by means of a computer image analysis system. The study revealed that total glomerular area, total number of glomerular cells per total glomerular area, mesangium (percentage of total glomerular area), and number of sclerotic glomeruli (percentage of total glomeruli) were significantly increased in cirrhotic patients. There was no significant increase in relative interstitial volume and in total glomerular cell per unit of glomerular area in comparison with controls. The results indicate that, despite the lack of renal clinical and laboratory manifestation, cirrhosis of the liver can be accompanied by a variety of glomerular disorders. These abnormalities consist of an enlargement of the glomeruli, an increase in glomerular cellularity proportional to the increase in glomerular size, thickening in mesangial matrix, and increased glomerulo-sclerotic lesions.

Adult↗

Chronic granulomatous disease of childhood: gastric manifestation and response to salazosulfapyridine therapy.

The case history of a 10-year-old boy with chronic granulomatous disease (CGD) and gastric obstruction is presented. First abdominal symptoms occurred at 4 years of age when antral narrowing was detected. Due to unresponsiveness to antibiotic and steroid treatment, salazosulfapyridine therapy was initiated. Objective remission was observed within 3 months and salazosulfapyridine was withdrawn after a further 6 months of therapy. At 6 years of age clinical and radiological recurrence of gastric obstruction was observed. Salazosulfapyridine was reinstated and continued as maintenance therapy. The child has been well for more than 4 years. Salazosulfapyridine therapy can be recommended as safe conservative treatment of gastric obstruction in CGD.

Child↗

[Chest X-ray films in particular types of transposition of the great arteries (author's transl)].

The article has been based on the study of 46 cases of transposition of the great arteries including children aged one day to one year. No symptoms of interventricular septal defect were discovered in X-ray films, nor was it possible to define the type of transposition. The author also discussed the narrowing of the base of the heart. The shape of the base may be due not only to the small thymus shadown, but also to the position of the aortal arch in the central plane of the body.

Age Factors↗