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Biomedical subjects

K H Plate

Publications and source records attributed to K H Plate.

68 records · Page 4Linked to original sources
PubMed1991

Cell proliferation in intracranial tumours: selective silver staining of nucleolar organizer regions (AgNORs). Application to surgical and experimental neuro-oncology.

A novel tool in diagnostic and experimental pathology, the AgNOR-technique, which consists of visualization of ribosomal gene activity by selective silver staining, was applied to 144 cytological specimens of human tumours of the nervous system. The number of silver-stained nucleolar organizer regions (AgNORs) was correlated with the biological behaviour of the tumours investigated; low AgNOR number were observed in benign neoplasms such as meningiomas and schwannomas and higher AgNOR numbers in glioblastomas and metastases. The mean AgNOR number per cell was 3.15 in astrocytomas, 4.5 in anaplastic astrocytomas and 5.86 in glioblastoma multiforme. Benign and malignant lesions showed different distribution patterns of AgNORs, with few but centrally located AgNORs in benign, and multiple but scattered AgNORs in malignant tumours. AgNOR number per cell and AgNOR area revealed an inverse relationship (correlation coefficient -0.15, linear regression). In addition to the human tumours, two N-nitroso-N-ethyl-urea (NEU) induced tumors in BD-IX rats a mixed glioma (G-XIII) and a malignant schwannoma (N-XII), were investigated. Twelve G-XIII gliomas revealed homogenous AgNOR-counts (standard error of the mean less than 10%), with absolute values between the values obtained for human glioblastomas and metastases. Seven N-XIII subcutaneously transplanted schwannomas revealed higher AgNOR values than human schwannomas, but lower than experimental gliomas. It is concluded that the AgNOR method, as a technique for visualization of ribosomal gene activity, is valuable for assessing proliferative activity and malignancy in both diagnostic and experimental neuropathology.

Animals↗
PubMed1990

Evaluation of nucleolus organizer regions (NORs) by automatic image analysis: a contribution to standardization.

This study summarizes our experiences with the silver staining of nucleolus organizer regions (AgNORs) in a total of 580 tumours from ten different tissues. In contrast to other investigators, we made use of automatic image analysis for the evaluation of AgNORs. This provided good reproducibility as determined by the standard cumulative means technique and intra-observer (r1) and inter-observer (r2) agreement in 30 benign (r1 = 0.83-0.95, r2 = 0.76-0.92) and 50 malignant tissue samples (r1 = 0.72-0.85, r2 = 0.51-0.78). By using a series of staining times on sections from 30 tissue blocks taken from the ten types of tissue investigated, considerable variation in the argyrophilic staining of NORs in different tissues and in different blocks from one tumour was shown. The mean AgNOR area of resting lymphocytes or connective tissue cells within tissue blocks of the same organ system varied up to four-fold, even though identical staining times had been used. The most suitable silver reaction time which rendered a good diagnostic difference in the AgNOR content of benign and malignant tissue ranged, for example, in the breast cancer specimens, from 23 to 35 min. We therefore conclude that the staining time has to be adjusted to the individual silver-binding characteristics of each tissue block or even each section. The use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory. This, in turn, is most precisely controlled by morphometry.

Humans↗
PubMed1990

Proliferative potential of human brain tumours as assessed by nucleolar organizer regions (AgNORs) and Ki67-immunoreactivity.

Two proliferation markers, silver stained nucleolar organizer regions (AgNOR) and immunoreactivity with Ki-67, were used to assess the proliferative activity in 80 smear preparations from neurosurgically removed intracranial tumours. These included 45 gliomas, 18 meningiomas, 8 metastases and 9 others. We found a remarkably close correlation between the results obtained with both methods. Increasing malignancy, as determined by conventional grading, was paralleled by an increase in the growth fraction and the number of nucleolar organizer regions. Linear regression analysis yielded the following equation: AgNORs/cell = 0.35 x L1 (Ki-67) + 3.24, with a correlation coefficient of rs = 0.53 (Spearman rank correlation test, p less than 0.0001). Thus, both the Ki-67 L1 and the AgNOR technique appear suitable for estimating the proliferative potential in smear preparations of human intracranial neoplasms. The AgNOR technique may be particularly useful for application to stereotaxic biopsies since it can easily be performed on minute tumour samples.

Antigens, Surface↗
PubMed1990

Assessment of histogenesis and proliferative potential in cytologic specimens of human brain tumors. Value of immunocytochemistry and nucleolar organizer regions.

The value of immunocytochemistry and nucleolar organizer regions (NORs) for the histogenetic identification and the estimation of the proliferative potential of brain tumors was assessed by the investigation of imprint smears of 51 neurosurgical tumor specimens. A panel of five monoclonal antibodies was used to cover a broad range of immunohistochemical markers. For the assessment of NORs, a silver staining technique (AgNOR) was used. NORs were enumerated and measured by means of an interactive image analysis system. The immunocytochemical results were similar for the smears and paraffin-embedded sections for 95.6% of the investigations performed and for 76.2% of the cases. Glial fibrillary acidic protein (GFAP) was positive in 9 of 17 tumors of glial origin, but was negative in 9 metastatic tumors. Vimentin was positive in 10 of 10 and fibronectin in 9 of 10 meningiomas investigated. The number of NORs increased steadily with the increasing grade of malignancy. Especially in glioblastomas, the number of NORs per cell exhibited a wide range, which might reflect the heterogeneity of these neoplasms. Metastases revealed a higher number of NORs per cell than did glioblastomas. In the cytologic differential diagnosis of these tumors, an absence of GFAP expression combined with a high NOR count is suggestive of a metastatic tumor.

Adult↗
PubMed1990

[AgNOR cytometry by means of automatic image analysis--a contribution to standardization].

The silver staining of nucleolar organizer regions (AgNORs) was evaluated in a total of 697 tumours from ten different tissues. By means of qualitative light microscopy, type, duration and delay of fixation proved to be influential in determining the AgNOR result. For standardization of the AgNOR technique, staining time series in 30 tissue blocks of the ten types of tissue were evaluated using digital image analysis. The silver incubation time which rendered the most distinct diagnostic difference in the AgNOR content of benign and malignant tissue varied considerably. Accordingly, staining time has to be adjusted to the individual argyrophilia of each tissue block or tissue section, for which the use of internal staining standards such as lymphocytes or connective tissue was found to be mandatory. For routine purposes, the appropriate silver incubation time is achieved if AgNORs are visible as black dots mainly within the nucleoli of proliferating cells.

Autoanalysis↗
PubMed1990

Nucleolar organizer regions in meningiomas. Correlation with histopathologic malignancy grading, DNA cytometry and clinical outcome.

Eighty-one meningiomas (63 grade I, 9 grade II and 9 grade III) and 2 meningeal sarcomas (grade IV) were investigated by a simple one-step silver staining for nucleolar organizer region (NOR)-associated proteins (AgNOR technique) and by DNA cytometry. The number of NORs per cell and the NOR area per cell were correlated with the histopathologic grading, as were the 5c exceeding rate and the 2c deviation index (2cDI) obtained by DNA cytometry. The differences in NOR parameters were only significant (at P less than .001) between grades I and II; P was less than .05 for the 2cDI between grades I and II. No significant differences between grades II and III were found. Among recurrent tumors, the AgNOR technique revealed the proliferative potential in 8 of 11 tumors studied, whereas DNA cytometry failed to recognize malignant features in 8 of 10 tumors investigated.

DNA, Neoplasm↗
PubMed1990

[Prognosis in meningiomas. Relevance of morphologic studies and clinical risk factors].

Since the introduction of the WHO-classification of tumours of the central nervous system in 1979, meningiomas are subdivided in 8 histological types and graded I to IV. The basis for this classification were histopathological investigations combined with clinical follow-up data. Since the introduction of immunocytochemistry as a diagnostic tool in neurooncology, morphological methods have gained renewed interest among neurosurgeons and neurologists. Some of the more recent developments, as well as the classical methods of the neuropathologist, are discussed here, and the results of the impact of morphology on prognosis is discussed on 139 own cases. Beside the histopathological grading, the application of so called proliferative markers as Ki-67 and BUdR seems to be most promising in the prediction of recurrences. Clinical parameters as patients age, preoperative physical status, tumor size and location on the other hand are of particular importance concerning postoperative mortality.

Biomarkers, Tumor↗
PubMed1989

Cystic meningioma with unusual histopathological features.

A parasagittal meningioma of an eighty year old female patient showed by light and electron microscopy cystic architecture (forme humide) as well as nuclear vacuoles (indentations) and cytoplasmic inclusions. The latter are the known pseudopsammoma bodies or hyaline inclusions as demonstrated by light and electron microscopy. Light microcopy on paraffin sections and cytological smear preparations revealed, in addition to the cells of endotheliomatous meningioma and those containing the inclusions a third type with small granular cytoplasmic content. Electron microscopy showed characteristic features of meningioma such as folded double membranes, desmosomes and filaments and thus gave evidence of the meningiomatous nature of the tumor. By immunohistochemistry tumor cells in slightly focal distribution contained vimentin, whereas small clusters of cells with hyaline inclusions were strongly positive for cytokeratin. The dispersed cells of granular cytoplasmic content were positive for fibronectin. These findings, especially of the inclusion containing cytokeratin positive cell clusters may shed new light upon the concept of histogenesis and classification.

Aged↗
PubMedDate not supplied

Retrovirus producer cells encoding antisense VEGF prolong survival of rats with intracranial GS9L gliomas.

With increasing size tumors are continually dependent on a functional blood vessel system to guarantee the supply with oxygen and nutrients. Vascular endothelial growth factor (VEGF) is a key mediator not only of developmental but also of hypoxia-mediated and tumor-induced angiogenesis. Gene therapy using antisense VEGF with the aim to inhibit tumor angiogenesis may be a successful strategy for the treatment of highly vascular and invasive malignant gliomas. We investigated whether retrovirus producer cells encoding antisense VEGF can be used for in vivo gene transfer. The full length mouse VEGF164 cDNA was cloned in a sense and antisense direction into the retroviral expression vector pLEN. pLEN-VEGF (sense) and pLEN-FGEV (antisense) expression vectors were used to transfect the packaging cell line GP + E86 and to establish ecotropic virus producer cell lines. GP + E86:LEN-FGEV (#5) cells showed high expression of antisense VEGF mRNA, whereas GP+ E86:LEN-VEGF (#8) showed high expression of sense VEGF mRNA and active VEGF protein. Co-implantation of GS-9L cells with retrovirus producing cells containing the antisense VEGF construct into the brains of syngeneic rats showed a statistically significant inhibition of tumor growth and prolongation of survival time, while co-implantation of retrovirus producer cells containing the sense VEGF expression vector resulted in an increasing tumor growth and reduced survival time of the rats compared to control animals. Histological analysis of the tumors co-implanted with GP + E86:LEN-FGEV (#5) cells showed the suppression of angiogenesis, high degree of necrosis and no evidence of a significant immune response. Expression of antisense VEGF mRNA in these tumors was confirmed by in situ hybridization analysis. This is the first report demonstrating the potential utility of virus producer cells as in vivo gene transfer vehicles for antisense VEGF gene therapy of malignant gliomas.

Animals↗
PubMedDate not supplied

VEGF in brain tumors.

Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis, vasculogenesis and vascular permeability. In this contribution, molecular and biological properties of VEGF are described. Furthermore, this article focuses on the evidence that angiogenesis in brain tumors is mediated by VEGF. Among the topics discussed are expression patterns of VEGF and its receptors in different brain tumors, possible regulatory mechanism involved in the VEGF-driven tumor angiogenesis and the involvement of VEGF in the genesis of peritumoral edema. Finally, anti-angiogenesis approaches to target VEGF/VEGF receptors are discussed.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Value of immunocytochemistry in aspiration cytology of sacrococcygeal chordoma. A report of two cases.

Two cases of saccrococcygeal chordoma that were diagnosed on the basis of smear preparations are presented. Only one case showed typical physaliferous cells. In both cases the final diagnosis was greatly facilitated by applying peroxidase-antiperoxidase immunocytochemistry techniques to the cytologic specimens. Chordomas coexpress epithelial markers, such as intermediate filaments of the cytokeratin type, epithelial antigens (such as tissue polypeptide and epithelial membrane antigen), intermediate filaments of the vimentin type and S-100 protein. This antigenic spectrum may greatly facilitate the differential diagnosis of chordoma from filum terminale ependymoma, chondroma and chondrosarcoma, metastases of clear cell-type carcinomas and schwannomas, and neurofibromas, even when the only specimens available are from aspiration cytology.

Aged↗
PubMedDate not supplied

Cerebellar primitive neuroectodermal tumor with multipotent differentiation in a family with von Hippel-Lindau disease. Case report.

A family with von Hippel-Lindau disease (vHLD) is presented. Three family members suffered from typical cerebellar hemangioblastomas. Another family member presented with a cerebellar neoplasm of different histology. Detailed histological analysis revealed a primitive neuroectodermal tumor (PNET) with neuronal, glial, myoid and ependymal differentiation. This is apparently the first description of the association of vHLD and a cerebellar PNET with multipotent differentiation.

Adolescent↗