Spindle-cell glioblastoma or gliosarcoma?

'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

Immunoregulatory Factor Released From a Cell Line Derived From Human Decidual Tissue

ABSTRACT: The culture supernatant of the TTK-1 cell line, established from human decidual tissue, was found to contain a factor that strongly suppressed the mixed lymphocyte reaction (MLR). The mechanism of the MLR-suppressive activity as well as the biochemical characterization of this factor was analyzed. The TTK-1 supernatant suppressed the MLR much more strongly than the culture supernatants of the three other malignant cell lines examined. The molecular weight of this factor was estimated to be between 43 kilodaltons (kd) and 67 kd by gel filtration chromatography. The TTK-1 supernatant also suppressed the proliferation of the interleukin 2 (IL-2)-dependent T cell lines, but did not suppress that of the IL-2-independent T cell lines, suggesting that the TTK-1 supernatant inhibited the action of IL-2 and subsequently suppressed the MLR. The fact that the TTK-1 cell line originated from human decidual tissue might imply the important role of this factor in immunological fetomaternal balance.     

The high prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma

BACKGROUND: Although many histopathologic factors in squamous cell carcinoma of the tongue predict the prognosis, the major predictive factors have not been identified clearly. This study analyzed the prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma. METHODS: The clinicopathologic features of 124 consecutive patients seen between January 1985 and December 1999 with previously untreated squamous cell carcinoma of the tongue were reviewed. Their mean age was 58.5 years (range: 23-90) and the male-female ratio was 1.8: 1 (79 men and 45 women). There were 41, 40, 30, and 13 cases at stage I to stage IV, respectively. The clinicopathologic factors, especially the histologic grade at the deep invasive front (invasive front grade, IFG), were analyzed to determine factors predicting prognosis. RESULTS: The 5-year disease-free survival rate of the patients treated with curative aim only was 66.7%. Clinicopathologic factors significantly associated with the prognosis were T classification, tumor size, stage classification, tumor depth, macroscopic appearance, cervical lymph node metastasis (nodal metastasis), microvascular invasion, and IFG. In a multivariate analysis, patients with tumor depth >/=4 mm, IFG >/=8 points, and nodal metastasis had a reduced disease-free survival and IFG >/=11 points had a predictive value for nodal metastasis (odds ratio: 7.34; P = 0.0019). CONCLUSION: This study found that a high IFG malignancy score had a high prognostic value for squamous cell carcinoma of the tongue.     

Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by inter-facial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatial implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamne frr at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-β-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Angiolipoma of the buccal mucosa: a possible role of mast cell-derived VEGF in its enhanced vascularity

A case of angiolipoma occurring in the buccal mucosa of a 69-year-old male is described. The patient had noticed a painless mass in his buccal mucosa for 2 years. The surgically removed tumor, measuring 9 mm in diameter, was mainly located in the submucosal layer with focal expansion into the muscle layer. Histologically, the tumor was well-demarcated and composed of proliferations of mature fat cells and fibrous connective tissue containing many small blood vessels, which were evenly distributed. There was diffuse infiltration of a large number of mast cells, which were immunopositive for vascular endothelial growth factor (VEGF) especially around blood vessels, suggesting that VEGF produced by mast cells in angiolipomas plays an important role in the vascular proliferation in this particular tumor.     

Morphology of corticotectal cells in the primary visual cortex of hooded rats

In primary visual cortex of hooded rats, pyramidal cells in layer V may be classified as long, medium, or short, on the basis of the layer in which the apical dendrite terminates. The present study determines which of these types of pyramidal cells project to the superior colliculus. Two different strategies were used to label corticotectal cells with horseradish peroxidase (HRP). In the first set of experiments, a large number of corticotectal cells were labeled by retrograde transport following injection of HRP into the superior colliculus. In the second set of experiments, single unit recording was used to identify corticotectal cells physiologically by antidromic activation from the superior colliculus. These cells were then impaled and labeled by intracellular iontophoresis of HRP. The results from both techniques suggest that only long pyramidal cells send an axon to the superior colliculus. These cells are distinguished by an apical dendrite that extends into layer I. We conclude that in hooded rats corticotectal cells in primary visual cortex are the long pyramids in layer V.     

Golgi study on brain of macular mutant mouse as a model of Menkes kinky hair disease

Summary This study was undertaken to elucidate, using the Golgi method, the neuropathological change in the brain of the macular mutant mouse, whose hemizygote (Ml/y) is considered to be a model of Menkes kinky hair disease (MKHD). The hemizygote mice gradually lost weight after 10 days of age and died with emaciation and seizure around day 15. The normal littermate (+/y) was well developed. In the cerebrum, the arborization of pyramidal neurons in the layer V of the Ml/y was the same as that in the +/y on day 10. However, development of arborization in the Ml/y was delayed in comparison with that in the +/y on days 12 and 14. Purkinje cells with several somal sprouts were observed in the cerebellum in both the Ml/y and +/y on day 7. The somal sprouts in the +/y had regressed gradually by day 12, while they were still in the anterior and middle lobes of the Ml/y on day 14. Additionally, the trunks of Ml/y stem dendrites became thicker and a cactus formation was recognized on the branching portion of the dendrites on day 14. Arborization of these abnormal Purkinje cells was distinctly poor compared with that in the +/y. These results suggest that the growth of the neurons is delayed in the Ml/y and simultaneously their cytoskeletal developments are disturbed, especially in the Purkinje cells. There is a close similarity in many respects to the neuropathological change in MKHD.     

pp60c-src encoded by the proto-oncogene c-src is a product of sensory neurons

The advent of recombinant DNA technology has led to the identification in the DNA of normal animal cells of over 30 proto-oncogenes that are homologous to retroviral transforming genes. One of these encodes a protein kinase (pp60c-src) of unknown function, that is preferentially synthesized in brain and neural retina. Here the expression of pp60c-src in the peripheral nervous system was examined in sensory neurons from chick dorsal root ganglia with antisera raised against the transforming protein of Rous sarcoma virus (pp60v-src) expressed in Escherichia coli carrying the cloned v-src gene. This antiserum recognizes pp60c-src specifically in normal chicken cells. Western immunoblotting showed that dorsal root ganglia of stage 30 (day 6.5) chick embryos contained elevated levels of pp60c-src. Immunoperoxidase staining of neuron-enriched cultures prepared from chick dorsal root ganglia showed pp60c-src immunoreactivity in cells with neuronal morphology; flat, fibroblastic cells contained no detectable immunoreactivity. Indirect double immunofluorescence with pp60src antibodies and monoclonal antibodies against the 200-kD subunit of neurofilament protein confirmed that the cells expressing pp60c-src were neurons. Ninety-six percent of the neurofilament-positive cells were immunoreactive with pp60src antibodies, and conversely, all pp60c-src-positive cells were immunoreactive with neurofilament antibodies. pp60c-src immunofluorescence appeared to be distributed over the cell body, processes, and growth cones. These results clearly demonstrate that pp60c-src is a product of neurons and is expressed in sensory neurons in culture.