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K C Gatter

Publications and source records attributed to K C Gatter.

303 records · Page 17Linked to original sources

An electron microscopic study of the types and proportions of neurons in the cortex of the motor and visual areas of the cat and rat.

The neuronal cell somata in the cortex of the motor and visual areas of the cat and rat have been studied with the electron microscope. It has been possible to recognize the cell types which have been identified in the corresponding functional areas of the cortex of the monkey: pyramidal, large and small non-pyramidal. The large non-pyramidal or stellate cell has abundant endoplasmic reticulum and mitochondria and receives numerous asymmetric and symmetric synapses; the small non-pyramidal or stellate has a small amount of cytoplasm and few synapses of both asymmetric and symmetric nature. The proportions of these types of neurons are of the same order of magnitude in the different functional areas and in the different species: approximately two-thirds are pyramidal, slightly less than one-third are small stellate, and less than 10 per cent are large stellate. There is the same mean number of synapses upon the pyramidal and small stellate cell in the visual and motor areas of the rat and cat, but this number is less in the monkey being 50 per cent less in the visual cortex and 25 per cent less in the motor area.

Animals↗

The intrinsic connections of the cortex of area 4 of the monkey.

The intrinsic connections of area 4 of the monkey have been investigated with axonal degeneration methods after the placement of microelectrode lesions within the cortex. The fibre degeneration is restricted to within a few millimetres of the damage and is asymmetrically distributed in the form of an ellipse with its long axis anteroposteriorly. The same pattern is found in all topographic subdivisions of the motor cortex. There are two distinct zones of degeneration, dense fine terminal degeneration for 200 to 300 micrometer all around the lesion, and a moderate degree of fibre terminal degeneration for a further 2 to 3 mm. The intrinsic connections are disposed predominantly in a horizontal or oblique direction and within the laminae of origin, but there are fibres passing between adjoining laminae and between layers III and V and VI. Two horizontal plexuses of degenerating fibres are present, at the boundary layers II and III and at the level of the Betz cells, and these fibres arise within the cortex. The afferent and efferent fibres of the cortex are arranged strictly perpendicular to the surface. The extent and pattern of the intrinsic connections of area 4 are very similar to those of area 17 of the visual cortex.

Animals↗

An electron microscopic study of the termination of intracortical axons upon Betz cells in area 4 of the monkey.

After small lesions within the cortex of area 4 of the monkey degenerating axon terminals have been seen with the electron microscopy to contact the cell bodies, proximal parts of the apical dendrites and initial segments of Betz cells 0.5 to 2.5 mm from the damage. The degenerating axon terminals make symmetrical synapses which are presumed to be inhibitory in function. The degenerating terminals are probably from the axons of the basket cells described in Golgi-impregnated material, and which correspond to the large stellate cell recognized in electron microscopic studies.

Animals↗

An immunoelectron microscopic study of human placenta using three monoclonal antibodies.

An immunoelectron microscopic technique was used to analyse the distribution in term human placentae at the ultrastructural level of three antigens recognized by recently developed monoclonal antibodies. Two of the antigens (recognized by NDOG-1 and NDOG-2) were present only on the outer villous membrane of the syncytiotrophoblast. The other (HLA-A, B, C) was absent from syncytiotrophoblast and present on some capillary endothelial cells and on Hofbauer cells in the villous stroma.

Antibodies, Monoclonal↗

Transferrin receptor on endothelium of brain capillaries.

The blood/brain barrier prevents the passive diffusion of proteins and metabolites from cerebral blood vessels into tissue spaces around neuronal and glial cells. To provide nutrients for these cells, transport mechanisms must exist and indeed have been demonstrated for metabolites. We now show that monoclonal antibodies against rat and human transferrin receptors label blood capillaries in the brain but not in other tissues. In the rat this labelling occurs after injection of antibody into the blood, thus the receptors seem to be accessible at the endothelial surface. It is possible that transferrin receptors are expressed on these cells to allow transport of transferrin (and thus iron) into brain tissues.

Animals↗

Squamous cell head and neck cancer: evidence of angiogenic regeneration during radiotherapy.

BACKGROUND AND PURPOSE: Intra-tumoural neoangiogenesis is an essential process for tumour progression. Although intensification of angiogenic pathways during cytotoxic therapy has been reported by a few experimental studies, the role of angiogenesis in response to radiotherapy is unclear. We recently reported an adverse effect of intense angiogenesis in the radiotherapy outcome of squamous cell head and neck cancer (SCHNC). In the present study we investigated the radiotherapy-induced changes in the microvessel density (MVD) and in the expression of the angiogenic factor thymidine phosphorylase (TP) in SCHNC. PATIENTS AND METHODS: Twenty-four patients with SCHNC underwent a biopsy of the primary lesion immediately before and after delivery of 20Gy of conventionally fractionated radiotherapy. The MVD and the expression of TP was assessed with immunohistochemistry. RESULTS: The irradiated samples were composed of cancer cell islets or bands, immersed within avascular degenerated tissue. In tumours that did not reach complete response after the end of radiotherapy, these viable cancer tissue areas had a significantly higher MVD (p=0.006) and increased percentage of cancer cells with nuclear TP expression (p=0.0004) than the MVD and the TP expression noted in specimens before radiotherapy. TP expression in these islets was directly related to the MVD (p=0.004, r=0.56). CONCLUSION: The present study supports the idea that intensified angiogenic growth (angiogenic regeneration) during radiotherapy is associated with failure of radiotherapy.

Carcinoma, Squamous Cell↗

Assessment of vascular maturation in lung and breast carcinomas using a novel basement membrane component, LH39.

LH39, is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly- formed vessels of several pathological conditions including cancer. We examined the ratio of mature/immature vessels in 50 breast and 81 lung carcinomas and correlated the vascular maturation index (VMI) to different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the percentage fraction of mature vessels (LH39 positive)/total number of vessels (CD31 positive). VMI in breast carcinomas ranged from 0-47% (median 8.75%), which was significantly lower than that observed in the normal breast cases (range 54%-70%; median 68%). The median VMI in the non-small cell lung carcinomas was 46% (range 15%-90%). There was a significant inverse correlation between high tumor VMI and absence of nodal involvement in both breast and lung tumors examined (p=0.01). Thymidine phosphorylase (TP) expression, but not vascular endothelial growth factor (VEGF) expression, was related to a low VMI showing an intense vascular remodeling in TP expressing cases. Thus, assessment of vessel maturation might be complementary to microvessel number to aid the identification of patients who might benefit from specific antiangiogenic therapies or vascular targeting treatment.

Antibodies, Monoclonal↗

C-erbB-2 oncoprotein expression in operable non-small cell lung cancer.

Although c-erbB-2 oncoprotein immunohistochemical expression has been thoroughly studied in a variety of human tumors, its prognostic significance remains unclear. Moreover, differences in assessment criteria further complicate the evaluation of c-erbB-2 as a prognostic marker. In the present study we examined the expression of c-erbB-2 protein in 107 patients suffering from operable (T 1,2-N0, 1 staged) non-small cell lung cancer (30 adenocarcinomas and 69 squamous cell carcinomas) treated with surgery alone. A 3-7 year of follow up (median 45 months) was available for all patients. Paraffin embedded sections were stained with the NCL-CB11 monoclonal antibody using the immunoperoxidase technique. Analysis was based on cytoplasmic reactivity as membrane staining was impossible to assess against this background. Strong positive cytoplasmic staining was identified in 20/107 (19%) of cases, weak in 30/107 (20%) and negative in 57/107 (53%). Results were correlated with patient variables (age,sex) and tumor parameters (T,N-stage, grade, histology, Ki67 proliferation index, p53 and EGFR expression). C-erbB-2 expression was not related to any of these factors. Although c-erbB-2 defined a worse prognosis, univariate analysis of survival did not confirm any statistically significant difference between the c-erbB-2 staining groups (p=0.5). T,N-stage were the only statistically significant prognostic variables. Any contribution of c-erbB-2 to the development of tumour aggressive behaviour in non-small cell lung cancer requires assessment in the specific subgroups of patients.

Adenocarcinoma↗

Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis.

Tumour angiogenesis is an important prognostic factor in non-small cell lung cancer. Recently, EGFR and c-erbB-2 protein was found to regulate cell adhesion and the invasive growth of cancer through its association with the cadherin-catenin complex. The role of c-erbB-2 protein in cell migration has been also reported. In this study we investigate the combined role of tumoral neoangiogenesis and c-erbB-2/EGFR expression in the metastatic behaviour and prognosis of operable non-small cell lung cancer. 107 tumour samples from patients suffering from operable non small cell lung cancer were examined. EGFR and c-erbB-2 were not correlated with each other. C-erbB-2 expression was associated with low angiogenesis, approaching statistical significance in adenocarcinomas (p = 0.08). The absence of expression of both c-erbB-2 and EGFR oncogenes in tumours with high angiogenesis, was most frequently observed in node negative cases (p = 0.04). C-erbB-2 overexpression defined a subgroup of node negative patients with low angiogenesis and prognosis similar to patients with tumours bearing high angiogenesis. These findings support the hypothesis that expression of the erb genes is a mechanism activated in non-small cell lung cancer to enable cancer cell migration. This pathway seems to be activated mainly in tumours with poor vasculature presumably lading to an unfavourable intratumoral nutritional and oxygen ambience.

Aged↗

Focal expression of thymidine phosphorylase associates with CD31 positive lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer.

Platelet-derived endothelial cell growth factor (PDECGF) also called thymidine phosphorylaze (TP) has been shown to have considerable angiogenic activity. 141 cases of early stage non-small cell lung cancer were stained for TP and vascular grade using the P-GF.44C and JC70 MoAbs, respectively. The early steps of TP activation could be identified in 27 cases, where one or two foci of cancer cell TP overexpression occurred within a general pattern of negative/weak staining. Thirty-three foci of overexpression were analyzed for the local microvessel density in the adjacent stroma, assessed by microvessel counting (MC) and Chalkley Score (CS) comparatively with the remaining TP negative tumor areas. The degree of local inflammatory (lymphocyte and macrophage) infiltration was also assessed. A statistically significant increase of mean MC and mean CS was observed in areas of TP overexpression in both low and high angiogenesis cases. Overall, the mean MC in overexpressing areas, assessed in 250x fields, was 20.4 +/- 12.8 vs. 13.6 +/- 9.5 in areas with no TP expression (p = 0.0001). The mean CS was 5.7 +/- 3.3 and 4.0 +/- 2.1, respectively (p = 0.0003). Ten out of 19 (54%) cases with low lymphocytic infiltration showed marked stromal lymphocytic infiltration in the area of focal TP overexpression (p = 0.01). The present study provides further evidence of a direct association of TP and the process of angiogenesis in non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

Bcl-2 and p53 expression in stage I endometrial carcinoma.

The role of p53 and bcl-2 apoptosis related proteins in the pathogenesis of endometrial cancer remains unclear. We immunohistochemically examined 133 surgically removed tumour specimens from patients with stage I endometrial cancer for p53 oncoprotein nuclear expression and bcl-2 cytoplasmic reactivity. 114/133 (86%) cases were of the endometrioid histological sub-type. A cut-off point of 10% of cells with strong reactivity was used for positivity. Positive p53 expression was observed in 12/133 (9%) and positive bcl-2 in 40/133 (30%) cases. p53 expression was not related to bcl-2 expression. No association of p53 and bcl-2 with depth of myometrial invasion, vascular invasion or histological grade was observed. However, continuous variable analysis revealed a trend of low grade cases to have a higher percentage of bcl-2 positive cells (16.3 + 27% vs. 7.8 + 16%; p = 0.09, unpaired two tailed t-test). Interestingly, a statistically significant association of p53 positivity with age was also observed (p = 0.03). A strong association of high grade with depth of myometrial invasion (p = 0.006) and vascular invasion (p = 0.0001) was also noticed. In addition, the presence of adenomyosis was also associated with low grade (p = 0.01) and absence of vascular invasion (p = 0.02). We conclude that although loss of bcl-2 protein expression and p53 mutant protein nuclear accumulation are early events in the endometrial cancer progression, histological grade and vascular invasion remain the most important factors defining local invasive behaviour of endometrial cancer.

Adult↗