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L Sipos

Publications and source records attributed to L Sipos.

At least 19 recordsLinked to original sources
PubMed2001

Mutations in Drosophila heat shock cognate 4 are enhancers of Polycomb.

The homeotic genes controlling segment identity in Drosophila are repressed by the Polycomb group of genes (PcG) and are activated by genes of the trithorax group (trxG). An F(1) screen for dominant enhancers of Polycomb yielded a point mutation in the heat shock cognate gene, hsc4, along with mutations corresponding to several known PcG loci. The new mutation is a more potent enhancer of Polycomb phenotypes than an apparent null allele of hsc4 is, although even the null allele occasionally displays homeotic phenotypes associated with the PcG. Previous biochemical results had suggested that HSC4 might interact with BRAHMA, a trxG member. Further analyses now show that there is no physical or genetic interaction between HSC4 and the Brahma complex. HSC4 might be needed for the proper folding of a component of the Polycomb repression complex, or it may be a functional member of that complex.

Alleles↗
PubMed2001

The Trithorax-mimic allele of Enhancer of zeste renders active domains of target genes accessible to polycomb-group-dependent silencing in Drosophila melanogaster.

Two antagonistic groups of genes, the trithorax- and the Polycomb-group, are proposed to maintain the appropriate active or inactive state of homeotic genes set up earlier by transiently expressed segmentation genes. Although some details about the mechanism of maintenance are available, it is still unclear how the initially active or inactive chromatin domains are recognized by either the trithorax-group or the Polycomb-group proteins. We describe an unusual dominant allele of a Polycomb-group gene, Enhancer of zeste, which mimics the phenotype of loss-of-function mutations in trithorax-group genes. This mutation, named E(z)(Trithorax mimic) [E(z)(Trm)], contains a single-amino-acid substitution in the conserved SET domain. The strong dominant trithorax-like phenotypes elicited by this E(z) allele suggest that the mutated arginine-741 plays a critical role in distinguishing between active and inactive chromatin domains of the homeotic gene complexes. We have examined the modification of E(z)(Trm) phenotypes by mutant alleles of PcG and trxG genes and other mutations that alter the phosphorylation of nuclear proteins, covalent modifications of histones, or histone dosage. These data implicate some trxG genes in transcriptional repression as well as activation and provide genetic evidence for involvement of histone modifications in PcG/trxG-dependent transcriptional regulation.

Acetylation↗
PubMed1999

Preoperative history and postoperative survival of supratentorial low-grade astrocytomas.

The preoperative history and postoperative course of histologically verified 348 low-grade and 383 anaplastic astrocytomas have been reviewed. In 71.2 and 48.0% of patients epilepsy was the initial symptom of a suspected astrocytoma, and the history was longer than 3 years in 28.1 and 19.5% of cases, respectively. Before the advent of CT, angiography was performed because of a suspected tumour 2-9 years before surgery in 34 cases. The second angiography years later demonstrated the tumour which in 18 cases at surgery proved to be low-grade astrocytoma or anaplastic astrocytoma in 16 cases. During the last 10 years CT or MRI demonstrated a low-density lesion in 21 patients years before surgery. Operation was postponed for different reasons. Ten tumours appeared at 'delayed' surgery as low-grade, but 11 as anaplastic astrocytoma. In the same period 29 further patients were operated on after a history of seizures, longer than 3 years. Histology showed anaplastic astrocytoma in 10 cases also. Malignant transformation occurred nearly in half of the patients during the observation period. This strongly suggests that dedifferentiation is a spontaneous process, an intrinsic feature of astrocytomas and does not depend on any kind of external stimulus. Another 51 patients' surgery was performed following a shorter (1-24 months) history of epilepsy. The 5-year survival rate was 44 and 39.5% Median survival times (53.5 and 51 months) did not show a significant difference between the two groups, but the total survival, including second survivals after reoperation displayed a significant difference (57.5 vs 67.5 months) in favour of patients with a shorter history of seizures. These experiences confirm the difficulties in decision of the time of surgery. Considering the frequent malignant transformation among patients with a long history of seizures, followed by a relatively shorter survival, it may be supposed that an early radical removal in suitable cases might prevent the late dedifferentiation and recurrence.

Adolescent↗
PubMed1998

[The role and importance of CT-guided stereotaxic brain biopsy in neurosurgery. Experiences with 523 cases].

Between 1989 and 1996, 523 stereotactic biopsies of different intracranial lesions were performed at our institution. In 96.3% of the cases accurate histological diagnosis was made. In 59 cases the drainage of the abscess or cyst was carried out. In 48 cases the lesion was axial, in 27 parasellar, 7 pineal and 37 infratentorial. In the rest of the cases the lesion was in the supratentorial hemispheres. Transient neurological deficits were observed in 3.4% of the cases and craniotomy with haematoma evacuation had to be carried out in one case following the biopsy. There was no mortality associated with the interventions in our material. Our experience supports that CT guided biopsy is a safe and efficient method for obtaining histological diagnosis in different intracranial lesions and showed to be very useful in planning te appropriate treatment for each patient.

Biopsy↗
PubMed1998

Apoptosis and p53 expression in human gliomas.

Twenty-five human gliomas of different histological grade and type were studied for p53 expression by immunohistochemistry and for apoptosis using ApopTag method. p53 expression (percentage of positive cells) was highest in anaplastic astrocytomas, followed by low grade astrocytomas and surprisingly in glioblastomas. Granular cytoplasmic p53 positivity appeared in 4/5 low grade oligodendroglioma and in 2/5 low grade mixed oligoastrocytomas. The means of apoptosis index in the different tumor types ranged between 0.8 and 11.5 with the highest values in anaplastic astrocytoma and glioblastomas. Although the number of cases per group were relatively low and the individual vales showed differences it seems that p53 expression is related to the biological aggressiveness of gliomas. It is also suggested that high level of apoptosis in malignant glioma could represent a p53 independent pathway.

Adult↗
PubMed1998

Chromatin domain boundaries in the Bithorax complex.

Eukaryotic chromosomes are thought to be organized into a series of discrete higher-order chromatin domains. This organization is believed to be important not only in the compaction of the chromatin fibre, but also in the utilization of genetic information. Critical to this model are the domain boundaries that delimit and segregate the chromosomes into units of independent gene activity. In Drosophila, such domain boundaries have been identified through two different approaches. On the one hand, elements like scs/scs' and the reiterated binding site for the SU(HW) protein have been characterized through their activity of impeding enhancer-promoter interactions when intercalated between them. Their role of chromatin insulators can protect transgenes from genomic position effects, thereby establishing independent functional domains within the chromosome. On the other hand, domain boundaries of the Bithorax complex (BX-C) like Fab-7 and Mcp have been identified through mutational analysis. Mcp and Fab-7, however, may represent a specific class of boundary elements; instead of separating adjacent domains that contain separate structural genes. Mcp and Fab-7 delimit adjacent cis-regulatory domains, each of which interacts independently with their target promoters. In this article, we review the genetic and molecular characteristics of the domain boundaries of the BX-C. We describe how Fab-7 functions to confine activating as well as repressive signals to the flanking regulatory domains. Although the mechanisms by which Fab-7 works as a domain boundary remain an open issue, we provide preliminary evidence that Fab-7 is not a mere insulator like scs or the reiterated binding site for the SU(HW) protein.

Animals↗
PubMed1998

Transvection in the Drosophila Abd-B domain: extensive upstream sequences are involved in anchoring distant cis-regulatory regions to the promoter.

The Abd-B gene, one of the three homeotic genes in the Drosophila bithorax complex (BX-C), is required for the proper identity of the fifth through the eighth abdominal segments (corresponding to parasegments 10-14) of the fruitfly. The morphological difference between these four segments is due to the differential expression of Abd-B, which is achieved by the action of the parasegment-specific cis-regulatory regions infra-abdominal-5 (iab-5), -6, -7 and -8. The dominant gain-of-function mutation Frontabdominal-7 (Fab-7) removes a boundary separating two of these cis-regulatory regions, iab-6 and iab-7. As a consequence of the Fab-7 deletion, the parasegment 12- (PS12-) specific iab-7 is ectopically activated in PS11. This results in the transformation of the sixth abdominal segment (A6) into the seventh (A7) in Fab-7 flies. Here we report that point mutations of the Abd-B gene in trans suppress the Fab-7 phenotype in a pairing-dependent manner and thus represent a type of transvection. We show that the observed suppression is the result of trans-regulation of the defective Abd-B gene by the ectopically activated iab-7. Unlike previously demonstrated cases of trans-regulation in the Abd-B locus, trans-suppression of Fab-7 is sensitive to heterozygosity for chromosomal rearrangements that disturb homologous pairing at the nearby Ubx locus. However, in contrast to Ubx, the transvection we observed in the Abd-B locus is insensitive to the allelic status of zeste. Analysis of different deletion alleles of Abd-B that enhance trans-regulation suggests that an extensive upstream region, different from the sequences required for transcription initiation, mediates interactions between the iab cis-regulatory regions and the proximal Abd-B promoter. Moreover, we find that the amount of DNA deleted in the upstream region is roughly proportional to the strength of trans-interaction, suggesting that this region consists of numerous discrete elements that cooperate in tethering the iab regulatory domains to Abd-B. Possible implications of the tethering complex for the regulation of Abd-B are discussed. In addition, we present evidence that the tenacity of trans-interactions in the Abd-B gene may vary, depending upon the tissue and stage of development.

Abdomen↗
PubMed1997

Re-operations of supratentorial anaplastic astrocytomas.

Results of re-operations of 99 adult patients with recurrent supratentorial lobar glioblastomas (60 patients) and anaplastic astrocytomas (39 patients) have been reviewed. In all cases both surgical interventions were performed at the same institute. Age of patients with glioblastoma varied between 19 and 64 and with anaplastic astrocytoma between 21 and 68 years, with a mean value of 48 and 36 years, respectively. The median interval between the first and second operations was 47 weeks for patients with glioblastoma and 83 weeks with anaplastic astrocytoma. The mortality rate of the re-operations was 3%. Following re-operation radio- and/or chemotherapy was applied in most of the cases. Median survival time after re-operation was 18.5 weeks in patients with glioblastoma and 55 weeks with anaplastic astrocytoma. Survival curves were calculated according to Kaplan-Meier method and for statistical evaluation the generalized Wilcoxon test and multiple linear regression method were used. Histologically lower grade tumour at the first operation and longer interval between the two operations proved to influence positively and dedifferentiation of the primary tumour negatively the survival time.

Adult↗
PubMed1996

[Diagnostic and therapeutic possibilities in adult malignant gliomas].

Despite of the recent advances in diagnostic and therapeutic techniques the outcome of patients with malignant gliomas remains poor. The most widely used classifications and management of supratentorial gliomas are reviewed focusing on the chemotherapeutic possibilities. More accurate diagnosis and new therapeutic approaches will be available with the results of immunological studies. With the help of genetical experiments the development and malignant transformation of the gliomas will come to light. The gene therapy seems to be promising even in case of malignant glioma.

Adult↗
PubMed1996

Aneurysm of the internal auditory artery: our experience and review of the literature.

The aneurysms of the internal auditory artery (IAA) situated distal from anterior inferior cerebellar artery (AICA)-IAA junction, are extremely rare lesions. A case of distal aneurysm if IAA is presented causing subarachnoid haemorrhage (SAH) and complete ipsilateral deafness. After the neurosurgical treatment the hearing of the patient definitely improved. The literature of distal aneurysms of AICA is reviewed focusing on the clinical features of these malformations, causing cerebello-pontine angel (CPA) symptoms with or without SAH.

Aneurysm, Ruptured↗
PubMed1994

Mcp and Fab-7: molecular analysis of putative boundaries of cis-regulatory domains in the bithorax complex of Drosophila melanogaster.

A very large cis-regulatory region of approximately 300 kb is responsible for the complex patterns of expression of the three homeotic genes of the bithorax complex Ubx, abd-A and Abd-B. This region can be subdivided in nine parasegment-specific regulatory subunits. Recent genetic and molecular analysis has revealed the existence of two novel cis-regulatory elements Mcp and Fab-7. Mcp is located between iab-4 and iab-5, the parasegment-specific regulatory subunits which direct Abd-B in parasegments 9 and 10. Similarly, Fab-7 is located between iab-6 and iab-7, the parasegment 11 and 12-specific regulatory units. Mcp and Fab-7 appear to function as domain boundaries that separate adjacent cis-regulatory units. We report the analysis of two new Mcp mutant deletions (McpH27 and McpB116) that allow us to localize sequences essential for boundary function to a approximately 0.4 kb DNA segment. These essential sequences closely coincide to a approximately 0.3 kb nuclease hypersensitive region in chromatin. We also show that sequences contributing to the Fab-7 boundary appear to be spread over a larger stretch of DNA, but like Mcp have an unusual chromatin structure.

Animals↗
PubMed1994

Slit-ventricle syndrome in shunt operated children.

Chronic intracranial hypotension is considered as a frequent complication in shunted hydrocephalus, besides obstruction and shunt-infections. In the last twenty years 32 cases of slit-ventricle were diagnosed among the more than one thousand operations on hydrocephalic children at the Paediatric Department of the National Institute of Neurosurgery, Budapest, Hungary. Most of them have been operated on in infancy. Time from the first operation to the development of slit-ventricle ranged from one to twelve years, the mean was 6.5 years. Seven patients were symptomless (22%), while 25 patients (78%) had more or less severe slit-ventricle syndrome with headache (25 cases), nausea/vomiting (23 cases), altered consciousness (21 cases), brainstem signs (12 cases), and epileptic fits (2 cases). Ten patients with moderate clinical signs improved under conservative treatment. In 15 cases an anti-siphon device (ASD) was implanted. In five of them the clinical result was good, but in the remaining 10 cases typical hypertensive signs were seen. In these cases low flow rate valves were implanted instead of the middle flow rate valve and ASD. In one case the intracranial hypertension persisted, so a middle flow rate shunt system was "reimplanted" and finally the patient improved. In this study the experiences with these 32 cases will be analysed and discussed. The authors stress the primary use of combined valves to avoid the slit-ventricle syndrome.

Cerebrospinal Fluid Shunts↗
PubMed1993

Predicting the topology of eukaryotic membrane proteins.

We show that the so-called 'positive inside' rule, i.e. the observation that positively charged amino acids tend to be more prevalent in cytoplasmic than in extra-cytoplasmic segments in transmembrane proteins [von Heijne, G. (1986) EMBO J. 5, 3021-3027], seems to hold for all polar segments in multi-spanning eukaryotic membrane proteins irrespective of their position in the sequence and hence can be used in conjunction with hydrophobicity analysis to predict their transmembrane topology. Further, as suggested by others, we confirm that the net charge difference across the first transmembrane segment correlates well with its orientation [Hartmann, E., Rapoport, T. A. and Lodish H. F. (1989) Proc. Natl Acad. Sci. USA 86, 5786-5790], and that the overall amino-acid composition of long polar segments can also be used to predict their cytoplasmic or extra-cytoplasmic location [Nakashima, H. and Nishikawa, K. (1992) FEBS Lett. 303, 141-146]. We present an approach to the topology prediction problem for eukaryotic membrane proteins based on a combination of these methods.

Aspartic Acid↗
PubMed1993

Multiple intracranial melanoma metastases treated with surgery and radiosurgery with long term control. A case report.

A case of malignant melanoma with multiplex brain metastases is described, where both surgical and radiosurgical treatment was applied. Due to CNS manifestations the patient was operated on in two sessions. First the symptomatic large tumor was removed, and the other, small lesion which could not be reached from the same approach was operated later. The primary skin lesion was discovered and removed between the two operations. A CT scan three months after the second operation revealed recurrence at the site of the first operation, and the appearance of two new tumors. The intracranial neoplasms were treated in one session by stereotactic radiosurgery using a linear accelerator. Six months after this treatment a new skin lesion was removed and the patient received DTIC therapy. Successive CT scans after the irradiation showed a steady regression of the radiosurgically treated tumors, and more than one year after the irradiation no tumor could be detected on the CT scans.

Adult↗
PubMed1993

Pathological characteristics of surgically removed craniopharyngiomas: analysis of 131 cases.

Pathological specimens of 131 surgically removed craniopharyngiomas were obtained from the registry of the National Institute of Neurosurgery, Budapest between 1977 and 1991. The cases were reviewed statistically with reference to their gross and microscopic features and clinical characteristics. Macroscopically, 34% of the tumours were cystic, 23% solid and 43% mixed. Histologically, 38% of the cases belonged to the adamantinous group, 26% were squamous epithelial type, 15% were combined, that is expressing the characteristics of both. In 21% of the cases the surgically removed samples did not contain enough material for correct histopathologic classification. There was no recurrence in the group with the squamous epithelial type tumours, while 59% of the adamantinous, and 36% of the combined craniopharyngiomas recurred. The 5-year survival proportion was 73% at the squamous epithelial, 60% in the adamantinous, and 55% at the combined histological types.

Adolescent↗
PubMed1992

Characterization of human gliomas by a monoclonal antibody both on tissue culture and paraffin-embedded sections.

A monoclonal antibody designated OITIC3-11 was produced against GFAP positive human glioblastoma multiforme tumour cells. The specificity of the monoclonal antibody was tested on different types of human brain tumours and on normal adult brain both on tissue cultures and paraffin-embedded sections. The OITIC3-11 monoclonal antibody reacted with 16 of 18 malignant and 1 of 6 benign gliomas but did not react with meningioma, pituitary adenoma, metastatic brain tumours and normal adult brain tissue.

Animals↗