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J Szymas

Publications and source records attributed to J Szymas.

At least 19 recordsLinked to original sources

Online Internet-based robotic telepathology in the diagnosis of neuro-oncology cases: a teleneuropathology feasibility study.

This feasibility study examined the diagnostic accuracy of Internet-based dynamic-robotic telepathology using neuropathology cases. Randomly, 83 cases were selected from the routine diagnostic workload of the Neurosurgical Pathology Laboratory in Poznan, Poland. Telepathology diagnoses were compared with conventional paraffin section diagnosis. The neuropathologists, operating a robotically controlled motorized microscope over the Internet from 3 different Polish cities, individually reviewed the cases using computer workstations. Viewing times ranged from 2 minutes 54 seconds to 32 minutes 12 seconds per case. The mean diagnostic accuracy for telepathology diagnosis was 95%, with 2 of 3 observers achieving 100% diagnostic accuracy. Image quality was judged to be sufficient for correct evaluation, and the viewing times required to establish a final diagnosis by remote video microscopy were acceptable. Generally, user acceptance of robotic telepathology was high.

Adolescent↗

Patterns of chromosomal imbalances in invasive breast cancer.

Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.

Adult↗

Chromosomal imbalances in brain metastases of solid tumors.

Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.

Brain Neoplasms↗

Teleeducation and telepathology for open and distance education.

Our experience in creating and using telepathology system and multimedia database for education is described. This program packet currently works in the Department of Pathology of University Medical School in Poznan. It is used for self-education, tests, services and for the examinations in pathology, i.e., for dental students and for medical students in terms of self-education and individual examination services. The system is implemented on microcomputers compatible with IBM PC and works in the network system Netware 5.1. Some modules are available through the Internet. The program packet described here accomplishes the TELEMIC system for telepathology, ASSISTANT, which is the administrator for the databases, and EXAMINATOR, which is the executive program. The realization of multi-user module allows students to work on several working areas, on random be chosen different sets of problems contemporary. The possibility to work in the exercise mode will image files and questions is an attractive way for self-education. The standard format of the notation files enables to elaborate the results by commercial statistic packets in order to estimate the scale of answers and to find correlation between the obtained results. The method of multi-criterion grading excludes unlimited mutual compensation of the criteria, differentiates the importance of particular courses and introduces the quality criteria. The packet is part of the integrated management information system of the department of pathology. Applications for other telepathological systems are presented.

Computer-Assisted Instruction↗

Olfactory neuroblastoma: detection of genomic imbalances by comparative genomic hybridization.

Olfactory neuroblastoma (esthesioneuroblastoma) is a very rare tumour of the olfactory mucosa. Morphological features and cytogenetic studies strongly suggest a neuro-ectodermal origin. Up to now, cytogenetic studies are inconsistent. Some of them have proposed that the tumour belongs to the pPNET family. In the present study we describe genomic imbalances in olfactory neuroblastoma in a 46-year-old woman by using the molecular cytogenetic technique--comparative genomic hybridization (CGH)--in order to define the spectrum of genetic abnormalities in the tumour. The anatomical location and morphological findings were the basis for the diagnosis of esthesionearoblastoma. Immunohistochemical reactions for NSE, synaptophysin, chromogranin A, HNK-1/Leu-7 and S-100 revealed a characteristic immunophenotype. The CGH analysis showed multiple changes including DNA overrepresentations of chromosomes 4, 8, 11 and 14, partial DNA gains of the long arms of chromosomes 1 and 17, deletions of the entire chromosomes 16, 18, 19 and X, and partial losses of chromosomes 5q and 17p. This study represents an early utilisation of the CGH technique in olfactory neuroblastoma and demonstrates that the tumour carries complex chromosomal aberrations.

Biomarkers, Tumor↗

Determination of endogenous serum proteins in normal and oedematous brain tissue of cat by rocket and crossed immunoelectrophoresis.

A quantitative method for determination of endogenous serum proteins has been established and tested in an experimental model of peritumoural brain oedema in cats. Rocket and crossed immunoelectrophoresis were applied for determination of total serum proteins, albumin, IgG and haemoglobin in blood and brain homogenates. Modifications such as the use of non-ionic detergents and of antisera with different specificity were established for each antigen under investigation. The content of total serum proteins, albumin and IgG was substantially higher in tumour and peritumoural brain tissue than in the non-oedematous brain. The measurement of haemoglobin allowed the calculation of blood volume and, in consequence, the differentiation between intra- and extravascular serum proteins. The results are in line with earlier measurements obtained by different analytical methods and demonstrate that the present technique provides a reliable approach for the quantitative assessment of serum protein extravasation.

Animals↗

Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia.

Transient forebrain ischemia of 30 min duration was produced in anaesthetized rats by four-vessel occlusion. After survival periods of 3 h to three days brains were perfusion-fixed and sections through the mid-dorsal hippocampus were processed for conventional staining and immunohistochemical analysis. Neuronal damage in the hilus was manifested 3-8 h after ischemia; neurons in the CA1 and CA2 sector suffered delayed neuronal death after 48-72 h whereas the dentate gyrus and the CA3 sector were normal. Vasogenic edema formation was visualized using antibodies against rat serum-proteins, serum albumin and immunoglobulins. By 3 h after ischemia, only faint and diffuse serum-staining was detected. At 8 h survival, weak astrocytic-staining was present. After 24-72 h CA1-CA2 exhibited massive serum extravasation. The molecular layer of the dentate gyrus showed edema formation in the absence of granule cell damage. The glial reaction was studied using antibodies against glial fibrillary acidic protein, vimentin and S-100 protein. Glial fibrillary acidic protein and S-100 protein-staining increased in areas with either edema or neuronal damage. In contrast, changes in vimentin were only detected in areas with neuronal necrosis. The observations demonstrate that following 30 min of ischemia neuronal damage is accompanied by changes in blood-brain barrier function and reactive glial alterations. The dissociation between neuronal necrosis and astroglial hypertrophy and hyperplasia reflects differences in cellular responsiveness which constitute inherent features of postischemic hippocampal injury.

Animals↗

[Detection of Leu-M1 immunoreactivity in brain tissue and brain tumors].

Immunohistochemical investigations were made of 170 tumours of the central nervous system, using anti-Leu-M1, with electron microscopy being used on 22 of them. At least focal Leu-M1 positive reactivity was established from 10 in 24 astrocytomas, four in 22 oligodendrogliomas, and 9 in 15 ependymomas. Unambiguous Leu-M1 positivity was recorded from 54% of Grade I gliomas and 20% of Grade II gliomas. Other malignant primary tumours of neuroepithelial origin as well as all meningiomas and neurinomas proved to be Leu-M1 negative. However, severe immunopositivity was exhibited in all cases by reactive cerebral tissue adjacent to tumours. Three of four carcinoma metastases were Leu-M1 positive. Investigations, using electron microscopy, have clearly shown that MMA positivity in reactive brain is associated primarily with extracellular space and with plasma membranes of gliocytes. No products of immune reaction were identified, on the other hand, not even ultrastructurally, from neoplastically dedifferentiated cells of anaplastic neuroepithelial tumours. This is likely to suggest that neoplastically transformed gliocytes are no longer capable of expressing lacto-N-fucopentose III. It has proved helpful in distinguishing between the benign and malignant nature of a tumour. More observations along those lines might contribute to more knowledge on dedifferentiation of gliocytes. Also, in electron microscopy, MMA positivity of carcinomas proved to be associated with glycocalyceal material.

Antigens, Differentiation, Myelomonocytic↗

Quantitative analysis of experimental peritumoral edema in cats.

Cat brain tumors were produced by stereotactical xenotransplantation of rat glioma clone F98 into the internal capsule of the left hemisphere. Two to four weeks after implantation, the tissue content of water, sodium, potassium, calcium, magnesium, serum albumin, serum immunoglobulin, and hemoglobin was measured in samples taken from the tumor, from peritumoral white and gray matter, and from homotopic regions of the opposite hemisphere. Extravasated serum protein content was determined by subtracting intravascular from total tissue protein, using the hemoglobin content as a marker of blood volume. The development of brain tumors was accompanied by severe vasogenic brain edema, which was clearly confined to the ipsilateral white matter. The increase of water was paralleled by an increase of sodium, calcium, and serum proteins. Potassium and magnesium content remained constant. The calculated sodium and calcium content of edema fluid approximated that of blood serum. The content of blood proteins was about 50% lower, but the ratio of albumin/immunoglobulin was the same as in blood. It is concluded that peritumoral edema is a combination of plasma ultrafiltrate and whole plasma extravasation with different modes of formation. Implications for the pathophysiology and therapy of peritumoral edema are discussed.

Animals↗

Experimental transplantation gliomas in the adult cat brain. 1. Experimental model and neuropathology.

Tumours were produced in the adult cat brain by injection of the rapidly growing anaplastic rat glioma clone F98 in order to study their neuropathology, pathophysiology, regional biochemistry and magnetic reasonance imaging. We report here the neuropathological behaviour of cell suspensions in the basal ganglia and the left cerebral hemisphere one, two, three, four and six weeks after stereotactic implantation with respect to tumour growth, immunological tumour regression and alterations of the blood-brain barrier with associated vasogenic brain oedema. Injected cell suspensions produce consistently growing tumours during the first, second and third weeks. Tumour sizes varied according to the survival time and were only slightly dependent on the inoculated cell number, i.e., 3 and 6 x 10(6) tumour cells, respectively. Immunohistochemistry with respect to proteins of the cytoskeleton and other cell markers showed positive tumour cell immunoreactions for vimentin and S 100, but not for GFAP, Leu-7, Leu-M1 and MBP. While leucocyte infiltration is apparent after only one week, major tumour regression phenomena develop after three weeks in conjunction with severe lymphocytic reactions of the host, resulting in complete tumour rejection with scar gliosis after four and six weeks, respectively. This transplantation glioma model is accompanied by vasogenic brain oedema both within the tumour area and in the homolateral hemisphere. Immunohistochemistry of serum proteins, i.e. total serum protein, albumin and IgG reveals impairment of the blood-brain barrier after one week, reaching its maximum after two and three weeks. The oedematous changes decrease dramatically after four and six weeks, when most of the serum proteins are reabsorbed by cellular activities in the tumour scar. The vasogenic brain oedema in this xenogeneic glioma transplantation model may be enhanced by the immunological reactions in the brain.

Animals↗

Experimental transplantation gliomas in the adult cat brain. 2. Pathophysiology and magnetic resonance imaging.

In adult cats experimental brain tumours were produced by stereotactical xenotransplantation of the rat glioma clone F 98 into the internal capsule of the left hemisphere. Two to four weeks after transplantation tumours and peritumoural oedema were investigated by magnetic resonance imaging (MRI), electrophysiological recording and analysis of tissue content of water, electrolytes and extravasated serum proteins. Spherical tumours with a diameter of about 10 mm developed at the injection site and were surrounded by massive white matter oedema. Water content in peritumoural white matter increased from 2.63 +/- 0.17 to 3.65 +/- 0.19 ml/g d.w. (means +/- SD), sodium from 187 +/- 11 to 351 +/- 55 mueq/g d.w. and calcium from 7.4 +/- 1.1 to 13.3 +/- 1.3 +/- 1.3 mueq/g d.w. Potassium and magnesium did not change. Oedema development was associated with the extravasation of 18.0 +/- 16.8 mg/g d.w. albumin and 15.8 +/- 12.2 mg/g d.w. immunoglobulin. The calculated electrolyte content of oedema fluid approximated that of plasma but the serum protein content was about 40% lower. The ratio of low (albumin) to high (immunoglobulin) molecular weight proteins was the same in blood and oedema fluid. It is, therefore, concluded that peritumoural oedema consist of two components, a whole plasma extravasate and a protein-free ultrafiltrate. Peritumoural oedema could be clearly detected by MRI but differentiation between tumour and oedema was only possible after contrast enhancement with gadolinium-DTPA. The ratios of the intensities of the MR signal correlated linearly with the water content within white matter. MRI, in consequence, allows quantification of oedema provided a reference area with normal water content is present.

Animals↗

Medulloblastoma: histological evaluation and prognosis. A clinical, immunohistochemical and electron microscopic study.

Eighty-four cases of medulloblastoma were examined immunohistochemically and 12 by electron microscopy to assess differentiation in these tumors. Based upon the largest series of medulloblastoma studied to date, we demonstrated glial fibrillary acidic protein (GFAP) positivity, in 25% (21/84) of these tumors showing glial differentiation. GFAP-positive cells were seen more frequently in the desmoplastic variant of medulloblastoma (7/10). Under electron microscopy, the major part of the 12 tumors studied appeared primitive and undifferentiated. In 7 cases, groups of cells were found with primitive neuronal and/or glial features. GFAP positivity was confirmed at light microscopy level in all cases where cells showed glial differentiation in the form of glial-like filaments in cytoplasma. However, a follow-up questionnaire study of those patients who had received only surgical treatment revealed no difference in mean survival time between GFAP-positive and GFAP-negative medulloblastoma.

Adolescent↗

Differential expression of glial- and neuronal-associated antigens in human tumors of the central and peripheral nervous system.

The immunoreactivity of a panel of poly- and monoclonal antibodies raised against different glial and neuronal antigens was investigated in paraffin-embedded specimens of 116 human tumors of the central and peripheral nervous system. We used antibodies against the HNK-1 epitope, which is shared between natural killer cells and the nervous system, glial fibrillary acidic protein (GFAP), vimentin, neurofilaments, S-100 protein, neuron-specific enolase (NSE) and myelin basic protein (MBP). HNK-1 immunoreactivity was detectable in nearly all neuroectodermal tumors. Especially in those derived from the neuroepithelium, which include the various types of gliomas, we observed a strong staining with this antibody. The only exceptions were the choroid plexus papillomas and individual ependymomas. In tumors derived from the neural crest HNK-1 reactivity was more variable and less intense. In other tumors of the nervous system HNK-1 was not detectable, except for two out of four malignant lymphomas. In addition to its reactivity with human lymphocytes HNK-1, therefore, seems to be a useful 'marker' for neurogenic tumors in general. GFAP expression was prominent in all astrocytomas and the astrocytic cells within mixed gliomas and gangliogliomas. Immunoreactivity was more variable in glioblastomas and ependymomas, while only isolated GFAP-positive cells were present in oligodendrogliomas, medulloblastomas, one plexus papilloma, and some neurinomas. Vimentin immunoreactivity was found in tumor cells of nearly all tumors of the central nervous system with the exception of oligodendrogliomas, most plexus papillomas, neuronal tumors and most medulloblastomas.

Antibodies, Monoclonal↗

[Significance of immunohistochemistry in neuro-oncology. I. Demonstration of glial fibrillary acid protein (GFAP) in extracranial metastases from primary brain tumors].

8 cases were studied to determine whether immunohistochemical investigation with anti-GFAP could contribute to confirming a primary brain tumor origin for an extracranial metastasis. The materials studied consisted of 3 glioblastomas, 3 anaplastic astrocytomas, and 2 medulloblastomas, along with their extracranial metastases. GFAP could be immunohistochemically demonstrated in all 6 primary glial tumors as well as in the metastases of the 3 astrocytomas and of 2 glioblastomas. The medulloblastomas and their metastases were immunohistochemically GFAP-negative. GFAP is thus a marker for extracranial metastases of astrocytomas and glioblastomas. A negative result however does not exclude the possibility that a metastasis is of glial origin as shown by the GFAP-negative metastasis of the one glioblastoma.

Adult↗

Effect of dexamethasone on glial fibrillary acidic protein in peritumorous edema of cats: a morphometric study.

In 54 cats experimental brain tumors were produced by xenotransplantation of the blastomatous glial cell clone RG2 into the internal capsule of the left hemisphere. Fifteen of these animals were treated with dexamethasone for 1 week and four animals for 2 h. The occurrence of glial fibrillary acidic (GFA) protein in tumor and peritumoral edema was studied by immunocytochemistry at intervals ranging between 3 and 35 days after implantation. High concentrations of GFA protein were present in giant and many of the larger tumor cells but not in small tumor cells. In peritumorous white matter it appeared in reactive astrocytes, where it reached its maximum 2 weeks after implantation. At this time, morphometric evaluation of GFA protein-positive areas revealed an increase from 0.095 +/- 0.035% to 5.17 +/- 1.42%. Application of dexamethasone for 1 week reduced this area to 1.67 +/- 0.57% (P less than 0.001). The results obtained demonstrate that the development of peritumorous edema is associated with considerable stimulation of GFA protein production which is inhibited by dexamethasone. Production of GFA protein by reactive astrocytes, in consequence, does not seem to be involved in the resolution process of peritumoral edema under dexamethasone therapy.

Animals↗