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The effect of thermomechanical treatments on grain size and precipitate evolution as well as their impact on the shape memory properties of cold-drawn Fe41–Ni28–Co17–Al11.5–Ti2.5–B0.05(at. %) wires were studied. Cold drawing produces a strong {hkl} < 111 > /{hkl} < 001 > texture in this alloy. Different thermal treatments promote the evolution of specific recrystallisation textures as well as grain growth, while ageing at 600 °C to 650 °C leads to the formation of γ’ precipitates. Variation in size and distribution of the precipitates via ageing significantly affect the functional properties. A maximum transformation strain of 1.3% without fracture was obtained on sample tested on heating–cooling experiments.

Fe–Mn–Al–Ni superelastic alloy is a potential candidate for diverse engineering applications due to its outstanding properties and low material costs. Recent studies suggest that slight changes in the chemical composition severely affect superelastic response, phase stability and grain growth kinetics. In this paper, we found that the Al stabilizes the parent α phase at high temperature and promotes the formation of β precipitation at lower temperature. An alloy with a 3:1 ratio between Al and Ni produces homogeneously distributed β precipitates with high phase fraction in the alpha matrix after quenching from 1200 °C. The presence of these precipitates stabilizes the α phase, lowers the martensitic transformation temperature and gives the alloy a fully-reversible stress-induced martensitic transformation behaviour without the need to apply an aging step. In alloys with lower Al content the β precipitation produced during quenching is severely restricted and pseudoelasticity is impaired.

The Fe–12Mn–1C Hadfield steel is an abrasion-resistant alloy of high technological relevance for mining and heavy machinery. This composition is susceptible to pearlite formation which is detrimental for the material’s ductility. Although its spread use, the study of pearlite formation has been preserved to laboratory conditions which cannot be transferred to industrial practices. This manuscript provides updated information about this phenomenon by constructing the time–temperature-transformation diagram of the alloy between 400 and 600 °C. The pearlitic reaction occurs above 450 °C and begins on the grain boundaries. Only 7 min is needed for the transformation to start at 550 °C, and a maximum pearlite fraction of 35% is reached after 150 min at this temperature. Results are compared with the Fe–12Mn–0.8C composition mostly found in literature. The discussion comprises the effects of carbon and manganese content on the pearlitic reaction with the support of thermodynamics calculations.

Mechanical alloying of Cu-16 at.%Al and Cu-30 at.%Al was performed using both a planetary and a horizontal milling devices. The starting powders were high-purity Cu and Al. The different stages of milling were identified and characterized as initial, intermediate, final, and completion. The obtained microstructures were investigated by scanning electron microscopy and transmission electron microscopy. The evolution of the microstructure was studied considering the particle size variation. A decrease in the particle size was found as the Al content increases. The evolution of the nanostructure was studied considering the grain size variation. No marked changes on the nanostructure were detected during milling regardless either the type of mill used or composition selected. Mean grain sizes’ values found were between 10 nm and 26 nm for each stage of milling. Power consumption of the milling process was calculated at laboratory scale to analyze the chances of a potential scaling up of the milling process. Starting aggregation state, microstructure and dominant phase changes, and evolution of mechanical alloying stages were considered. Performance of milling was compared to traditional high-temperature methods to compare the advantages and disadvantages of both synthesis methods.

The present paper presents results about cyclic behaviour and the evolution of the dislocation structure of reduced activation ferritic–martensitic steels and commercial martensitic steels AISI 410 and 420. The variation of the free dislocation density within subgrains and subgrain size was mainly analysed during the cyclic softening of EUROFER 97 steel. From the analysis of the flow stress components, the friction and back stresses, and the information of the evolution of the dislocation structure, it could be concluded that the softening of tempered martensitic steels at 20°C is produced by the contribution of the friction stress and aided later by the back stress.

MxA is an antiviral protein exclusively induced by type I interferons (IFN) and some viruses, and MxA gene expression is one of the most appropriate markers for measuring the biologic activity of exogenous IFN.

To define the factors related to ALS outcome in a population-based, prospective survey.

The occurrence and the distribution of GAGs have been studied histochemically in 224 human cerebral tumors by means of Alcian blue techniques. In the normal peritumoral gray matter the alcianophilia is stronger than in the white matter and demonstrated the presence of HA and CS. In the glioma group the alcianophilia, due to HA and CS, is mainly related to the presence of infiltrated cortex. In the other tumors, GAGs are histochemically disclosed in relation to collagen, reticulin, mesodermic areas, etc. The vessels of every tumor show a positive staining for HA, CS, and HS. The histochemical findings are consistent with the biochemical ones as reported in Part I, even though the significance of GAGs in cerebral tumors remains unknown.

Leptomeningeal dissemination of pituitary adenoma is a very rare occurrence. The present report describes the case of a 28 year old man with a nonfunctioning pituitary adenoma which was operated on and irradiated. Eight years later, the patient developed Cushing's syndrome and multiple leptomeningeal masses were revealed by brain CT and MNR. The diagnosis was ACTH-cell adenoma, without malignant histological signs.

60 cases of chronic spinal muscular atrophy (CSMA) were followed-up for a period varying from 5 to 40 years. The neuromuscular impairment was evaluated by Norris’ ALS score, both at the time of last examination and retrospectively at the time of diagnosis. Age at onset of symptoms was the most important factor in the progression of the neuromuscular damage. Monomelic or asymmetric location of symptoms at the time of diagnosis and duration of the disease were not significantly correlated to the worsening of ALS score.

The problem of differentiation of medulloblastoma is considered. In this regard 43 medulloblastomas, showing cells with glial or neuronal features by routine histologic methods, were studied. The investigation was carried out by means of the immunohistochemical demonstration of the glial fibrillary acidic protein (GFAP) and the neuron-specific enolase (NSE). In most cases, GFAP-positive cells are preexisting astrocytes; in two cases they correspond to the transitional cells of the subependymal layer. NSE was demonstrated in areas filled with cells with neuroblastic features. The relationship between medulloblastoma with neuron-differentiation and cerebellar neuroblastoma is discussed.

A 45-year-old patient suffering from chronic renal insufficiency developed dermatopolymyositis. Since the patient did not respond to treatment with high doses of prednisone and immunoglobulin, concomitant cyclosporine A was added. Four months later, worsening signs of bilateral pyramidal disorder and an altered state of consciousness appeared. Serial computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple alterations of the cerebral white matter. Cyclosporine was then discontinued. One month later, exitus occurred. Microscopic examination of the brain showed diffuse tumescence; histological examination revealed perivascular and diffuse lymphomonocyte infiltrations, areas of demyelination, astrocytes with bizarre nuclei, and oligodendrocytes with enlarged nuclei due to hyperchromatic inclusion. Morphological examination confirmed the presence of intranuclear icosahedral viral bodies. Progressive multifocal leukoencephalopathy was diagnosed. The literature contains only one report of an analogous case observed during a course of cyclosporine treatment for Wegener's granulomatosis.

The effects of collagenase on the immunohistochemical demonstrability of laminin, fibronectin and Factor VIII/RAg in human nervous tissue have been studied. The influence of this, and other proteolytic enzymes such as pepsin and trypsin, has been investigated in relation to different fixatives. Collagenase gave better results with Carnoy fixed material than after formalin fixation; unlike trypsin and pepsin, it did not produce tissue digestion.

Brain tumors containing undifferentiated cells were selected from a series of 504 childhood brain tumors; 117 were analyzed. Most tumors were medulloblastomas, followed by cerebral neuroblastomas, pineocytomas-blastomas, ependymoblastomas, and polar spongioblastomas. Of each oncotype, the main histological features were evaluated, including differentiation and the most important prognostic factors. The terminology and different tumor entities are discussed in light of the recent PNET system. The usefulness of its application is evaluated in relation to prognosis.

Gliomas induced in the rat by transplacental administration of ethylnitrosourea (ENU) are intensely immunoreactive for vimentin and scarcely for glial fibrillary acidic protein (GFAP). Since tumoral transformation takes place during the late fetal and early postnatal period, the sequential expression of the two glial antigens has been investigated in this age period in ENU-treated and control rats. Immunohistochemical and immunoelectron microscopical methods have been employed. Vimentin was widely expressed starting from embryonal day 14 (E 14) in the processes of radial glia; as long as radial glia was present, vimentin decorated it. GFAP was, at earliest, observed at E 20 and expressed by glial cells with a stellate, i.e., mature shape. No GFAP-positive radial process was observed. No difference was found between ENU-treated and control rats. Since ENU is most effective in producing tumors when administered at the 16–17th day of fetal life, vimentin-positive radial glia is a candidate target of ENU. The similarity of intermediate filament pattern between radial glia in the late fetal life and tumors induced by transplacental ENU suggests that radial glia might be the cell of origin.

Fisher 344 rats born from mothers treated with ethylnitrosourea (ENU) 50 mg/kg intravenously were injured at the 1 st and 2nd month of extrauterine life by a transcranial stab. The wound affected cerebral cortex, white matter and basal ganglia. The animals were killed 15 and 45 days and 5 months after injury and cell reaction was studied histogically and immunohistochemically. Bromodeoxyuridine (BrdUrd) was administered 1 h before sacrifice and the labeled cells were evaluated. In ENU-treated rats injured at 1 month of age only minor differences were found in comparison with injured controls. In ENU rats injured at 2 months of age and killed 15 days later, a higher number of BrdUrdlabeled cells was found in comparison with controls; 45 days after injury the cell reaction acquired the aspect of a microtumor, however, no microtumor unrelated with the needle track was present. In ENU rats killed 5 months after the injury, there was no difference between injured and not injured ENU-treated rats, as far as the aspect and the number of tumors were concerned. The tumor phenotype was, thus, anticipated by the cell response to trauma in ENU rats. The interpretation is that the additional cell division, in response to trauma, anticipate not only the phenotypic, but also the cell kinetics changes, as indicated by BrdUrd labeling.

Neo-vascularization and endothelial hyperplasia have been shown to be very active in malignant gliomas. In this contribution the vascularization of the cortex infiltrated by malignant gliomas is morphometrically studied and the endothelial proliferations are immunohistochemically investigated and reconstructed by a three-dimensional computer-assisted procedure. Vessel density increases after tumor infiltration in some cases only. The diameter of vessels increases and so does the number of nuclei/vessel after the complete invasion of the cortex when vascular glomeruli develop. In completely infiltrated cortex with development of glomeruli and circumscribed necroses, vessel density is very low. No neoformation of vessels takes place before the complete infiltration of the cortex by the tumor. The hyperplastic formations, usually arranged parallel to the deep or outer cortical layers, take origin from the radially penetrating vessels from the meninges and their lateral branching. The hyperplasia deforms the vascular network, making it often inadequate to supply tumor cells. Immunohistochemically, the cells composing the hyperplastic structures are variably positive for factor VIII/RAg and, at a lesser extent, for a-smooth muscle actin. The poorness of the vascular network in many instances of completely infiltrated cortex is responsible for the development of circumscribed necroses.

The immunohistochemical distribution of laminin in 70 cases of primary and secondary brain tumors has been studied. The sections were fixed in Carnoy, embedded in paraffin, and treated with collagenase before applying the specific immune serum. In normal neural tissue and in gliomas, the distribution of laminin overlaps with that of basement membrane, as is known from observations on ultrastructure in the literature. The overlapping was observed also in neurinomas, papillomas of the choroid plexus, ependymomas, and meningiomas. Problems arise in the interpretation of the results in the other oncotypes. In hemangiopericytomas and hemangioblastomas, laminin demonstrates a basement membrane around the vessels only; it is absent around stromal cells. In desmoplastic medulloblastomas, laminin forms a network among the tumor celis. In primary lymphomas, concentric rings of laminin are evidenced around some vessels. In discussing the results, the ultrastructural distribution of basement membranes is taken into account.

GAG electrophoretic pattern and concentration have been studied in 38 human cerebral tumors and in specimens of normal nervous tissue. Gray matter had higher total GAG concentration and higher CA to HA ratio than white matter. In both, DS was present in very small amount whereas HS represented 15% of GAGs. All benign gliomas displayed the same electrophoretic pattern and contained more GAGs than normal nervous tissue. Dermatan sulfate was detected in malignant gliomas, as well as in other oncotypes, due to their mesodermic component. Ependymomas were particularly rich in HS and meningiomas were poor in HA.

The reproliferation of glioblastomas after radiation and chemotherapy has been studied in 25 tumors by means of whole mount histological preparations. The tumors have been subdivided into four groups according to the radiation dose and the distance from the end of radiation. After 4,000 rad vessel proliferations and mitoses stop, while vessel degenerations and astrocytes with deformed nuclei appear. Six months after 6,000 rad have been delivered, repopulation phenomena are clearly evident and are mainly represented by mitoses both in parenchyma and in the vessel walls, circumscribed necroses with pseudopalisadings, proliferations of formerly degenerated vessels, etc.

Experimental cerebral tumors have been induced by transplacental ENU. The morphologic study of the brains of treated rats revealed that cellular hyperplasias appear at the 30th day of extrauterine life in the paraventricular white matter, i.e., before the already known “early neoplastic proliferations”. Cytofluorimetric investigations failed to demonstrate differences between treated and control rats during the 1st month. On the contrary, adenylate cyclase activity is very high in that period. The duration of the latency period is discussed.

The application of BCNU, CCNU and MeCCNU has been shown to greatly reduce the number of tumors induced in rats by transplacentally administered ENU and to inhibit the full development of tumor proliferation. Moreover, no neurinomas appeared after treatment with CCNU. The application of GCNU proved to be much less effective.

In a case of congenital paramyotonia a muscle biopsy was performed and studied morphologically, histochemically and ultrastructurally. A clearcut pattern of changes has been observed with ATPase and oxidative enzymes. On electron microscopy special changes known as “tubular aggregates” were found. The relationship between the two findings, as well as the significance of such alterations in the range of periodic paralyses and myotonic phenomena, are discussed.

Summary Neoplasms of the third ventricle are lesions arising within the ventricular cavity, often free but more often pedunculated. True third ventricle tumours are surgically removable. In a consecutive surgical series of 580 intracranial tumours the authors operated on 27 lesions of the third ventricle, 7 of which were benign gliomas. The histological diagnosis was polar spongioblastoma in 5 cases and fibrillar subependymal astrocytoma in 2 cases. The dominant clinical features were a slowly progressive or intermittently increased intracranial pressure syndrome, and mental and visual disturbances. CT and CSF contrastographic studies provided the essential diagnostic data for the therapeutic plan. CT scans at follow-up studies confirmed the successful removal of the lesions. A right trans-ventricular approach was employed in all cases. Depending on the size and position of the lesion, removal was performed through the foramen of Monro or through a sub-choroidal approach. In two patients a ventriculo-atrial shunt was necessary in spite of tumour removal. No surgical mortality occurred and patients are well at a follow-up time of from 2 to 6 years.

Summary The pathological effects of radio- and chemotherapy have been studied in 31 malignant gliomas. The brains have been examined by means of the complete study technique. Many histological features have been related to surgery, localization, preoperative duration, postoperative survival, irradiation, and chemotherapy. No specific alterations have been found, but some positive correlations have been established: decrease of mitoses, occurrence of macrophages and vessel degeneration after radiation, increase of monstrous cells after chemotherapy.

Summary A case of primary diffuse leptomeningeal gliomatosis with anaplastic features, diagnosed during life and confirmed at autopsy, is presented. The clinical, radiological and pathological features are compared with those of the very few cases reported in the literature. Early papilloedema and hydrocephalus were followed by spinal and cranial nerve palsies. The NMR images and the tissue biopsy turned out to be useful for reaching an in vivo diagnosis.

Summary The pathological effects of radio- and chemotherapy on the normal nervous tissue have been studied in 42 brains with malignant gliomas. The brains have been examined by means of the complete study technique. In seven cases the picture of delayed radionecrosis has been found. Apart from this, many histological features have been related to post-operative survival, radiation dose, interval between radiation and death, chemotherapy, steroids, size and activity of the tumour. Some alterations, such as peritumoural necroses, macrophage areas, vessel wall degenerations etc. result from radiotherapy. The relations and pathogenesis are discussed.

Bcl-2proto-oncogene prevents apoptosis in many conditions. First detected in lymphomas, it has been also described in non-lymphoid tissues. The immunohistochemical distribution of bcl-2 protein in 100 neuroepithelial tumors is presented. Bcl-2 was positive in some neurons of normal nervous tissue, in reactive astrocytes and variably in all neuroepitelial tumors. The reaction product was either diffuse or granular, due to bcl-2 protein localization on cytoplasmic, nuclear and mitochondrial membranes. The positivity was high in medulloblastomas and in astrocytic tumors. In the latter, the strongest staining was found in cells retaining the astrocytic aspect. Oligodendroglial cells were minimally stained.

The occurrence, distribution and concentration of GAGs in ENU and MNU experimental brain tumors induced in the rat are reported. GAGs have been histochemically studied by Alcian Blue methods; they have been quantified and qualitatively evaluated by electrophoresis of brain extracts. The pattern of GAGs in normal rats is consistent with the data of the literature. No GAG accumulation precedes the tumor development. Early neoplastic proliferations, oligodendroglial and mixed glial microtumors are strongly alcian-positive; the alcianophilia spares clusters of cells developing a cytoplasm. In large tumors, GAGs are histochemically demonstrable in the honey-comb areas of oligodendrogliomas and in peripheral infiltration areas of polymorphic gliomas.

Medulloblastoma is a highly malignant cerebellar tumor of children and, less frequently, of adults, with a tendency to early recurrence and dissemination through the cerebrospinal fluid. The prognosis has improved significantly in recent decades, in parallel with the improvement in neurosurgical techniques and the use of postoperative radiotherapy. An overview is given of the prognostic role of clinical and pathological features of individual cases as reported in the literature. Apart from the presence or absence of metastases at diagnosis and the radiotherapy modality, none of the factors studied was generally thought to have a definite significant prognostic role. The extent of surgical excision seems to influence survival more in pediatric cases than in adults. Ongoing cytogenetic studies and molecular biology investigations are aimed at better categorization of medulloblastomas and individualized postoperative treatment.

The distribution of vimentin (VIM) has been histochemically investigated in 53 cerebral tumors and compared in gliomas to that of glial fibrillary acidic protein (GFAP). In gliomas VIM is less positive than GFAP, but shows the same distribution. It cannot be considered as indicating immaturity of glial tumor cells. VIM is also positive in glial processes of cerebellar pilocytic astrocytomas, in Schwann cells of neurinomas and in endothelial cells of all oncotypes. In medulloblastomas, VIM decorates reactive glia cells. A diffuse positive reaction has been observed in meningiomas. In hemangioblastomas, besides intervascular and endothelial cells, groups of polygonal cells are intensely positive for both VIM and GFAP. The interpretatiên of VIM in cerebral tumors is largely based on the distribution patterns of this intermediate filament in the developing CNS of rodents.

GFAP, Factor VIII/RAg, laminin, and fibronectin were immunohistochemically investigated in 15 glioblastomas and 15 gliosarcomas. GFAP was found variably positive in the glial areas. F VIII/RAg characterizes the endothelial cells and in gliosarcomas suggests the origin of the sarcomatous component from the endothelial proliferations. Laminin separates the two components and characterizes the inner and the outer basement membranes in the vessels. It is multiplied and thickened in endothelial proliferations, while it is often fragmented in the larger vessel wall proliferations. Our observations confirm that gliosarcoma represents the last stage of a process which starts with the endothelial hyperplasia of glioblastoma.

Experimental cerebral tumors have been induced by transplacental ENU. A systematic diachronic study of the brains has been performed starting from the 15th day of extrauterine life. The tumoral lesions firstly appear as “early stage proliferations” or oligodendroglial foci and develop as glial micro-and macrotumors or as isomorphic and polymorphic oligodendrogliomas respectively.

Summary Tumours of the nervous system have been induced by transplacental ENU. Until the fourth month of life the tumoural lesions appear as mixed glial proliferations or oligodendroglial foci. From the fourth month on they develop as glial micro- and macrotumours or as isomorphic and polymorphic oligodendrogliomas.

Abstract: Ependymoma is a rare tumor entity. It affects children and adults and has four preferential locations: supra- and infra-tentorial, spinal, and conus-cauda-filum. For statistical reasons, therefore, it is difficult to identify prognostic factors in series from single institutions because of the limited number of cases. The problem is complicated by the existence of some variants and by the difficulty in recognizing the anaplastic variant, because the common criteria used for recognizing malignancy in gliomas are not completely reliable in ependymomas. Apart from age and location, many parameters have been considered for prognostic purposes, including extension of surgical removal and radiotherapy. Among histological factors, the number of mitoses, labelling indices of proliferation markers, and cell density turned out to be good parameters for prognostic purposes. An overview is given of the contributions in the literature, including our own, on this problem.

We describe a protocol for the ultrastructural detection of DNA-incorporated bromodeoxyuridine (BUdR) in resin embedded tissue by means of post-embedding immunogold labeling. The paraventricular zone of rat embryos brains was dissected, fixed either in paraformaldehyde or glutaraldehyde, and embedded in LR White. BUdR gold labeling was only found when thin sections were pretreated with 4 N HCl. Other DNA denaturing agents, such as Na ethoxide, formamide, formic acid, heat or HCl at lower concentrations were ineffective. Very little difference in the degree of labeling was found depending on the fixation. This method can be applied to investigate the fine structure of replicating cells in other in vivo conditions, such as human tumors.

The usefulness of 1-naphthol as substrate for horseradish peroxidase (HRP) in immunohistochemistry was studied using the peroxidase-antiperoxidase (PAP) and avidin-biotin-complex (ABC) methods in the demonstration of glial fibrillary acidic protein (GFAP), vimentin, carbonic anhydrase C (CA.C), and factor VIII-related antigen (FVIII/RAg) in central nervous tissue and cerebral tumors. In the presence of ammonium carbonate, 1-naphthol is oxidized by HRP and hydrogen peroxide, producing a fine gray-violet precipitate. The oxidation product of 1-naphthol proved capable of binding a great number of basic dyes. For each stain the final reaction product had a characteristic color that was different from the spontaneous color of the dye and from the color displayed by nuclei. The final color obtained with this procedure was alcohol resistant and could be mounted in solvent-based mounting media. The results obtained with the 1-nappthol basic dye (1-NBD) method were compared with those obtained using the diaminobenzidine (DAB) reaction in the demonstration of GFAP-positive astrocytes. The DAB reaction produced a more intense staining but also a coarser precipitate than the 1-NBD reaction. The 1-NBD procedure showed more morphological detail of fine structures and did not obscure nuclei and mitosis. The very low toxicity of 1-naphthol compared with DAB (a suspected carcinogen) is an important advantage of the 1-NBD method, as is its high specificity and sensitivity.

Proliferating cell nuclear antigen (PCNA)/cyclin is currently often investigated immunohistochemically in tumors as a marker of cell proliferation, but many problems remain open concerning its reliability as a prognostic factor. PCNA has been studied in a series of 123 brain tumors using the monoclonal antibody PC10. A clear intra-and inter-tumor variability of PCNA-positive nuclei has been found, but taking into account the tumor areas with the highest number of positive nuclei, a positive correlation between this number and the histological malignancy of tumors has been demonstrated. The staining intensity of nuclei was variable; very-intensely positive nuclei, counted separately, are hypothesized to represent nuclei in S-phase of the cell cycle. In ependymomas the investigation included a quantitative statistical analysis. The number of PCNA-positive nuclei correlated with cell density and mitotic index, but only very intensely positive nuclei showed a significant statistical correlation with survival. In spite of the many possibilities of wrong interpretation of PCNA expression, the most important of which is its deregulation, the method is useful in the practice for prognostic purposes. Its important advantages are the possibility of a retrospective application and a visual analysis of the proliferation potential of tumors.

Abstract: We report a meningioma with very extensive surrounding oedema. This finding, along with the age of the patient and other clinical features, made correct diagnosis difficult. The pathophysiology of oedema in general and its exceptional extent in this case are discussed.

A patient, suffering from an oat-cell bronchial carcinoma, presented with complex partial seizures, complete loss of recent memory, mild disorientation and confabulation. There was no complaint of anxiety. The rest of the neurological examination and four computed tomographic scans of the head were normal. Repeated EEG recordings were abnormal. Antiepileptic and antipsychotic treatment led to full remission within 10 days. Post-mortem examination of the brain revealed no pathological changes.

A method of doubling the output-voltage swing and to increasing the slew rate of an operational amplifier is described. Two practical circuits and experimental results are given.