Carcinosarcoma in Barrett's oesophagus: A case report with immunohistological examination

A case of a carcinosarcoma which developed in a Barrett's oesophagus is presented. The tumour consisted of an adenocarcinoma and a spindle cell sarcoma. Immunohistological examinations demonstrated vimentin positivity in the sarcomatous portion with a negative reaction for keratin. Immunohistological and histological findings did not rule out the possibility of a double or collision tumour in this case.     

Process of differentiation of cerebellar Purkinje neurons in the chick embryo

Summary The microscopic and ultrastructural differentiation of Purkinje neurons has been studied in 40 chicken embryo cerebella, from the 10th incubation day to hatching, and the transverse diameter of the cell body measured, for each developmental stage, on 30 electron micrographs of sagittally cut Purkinje cells. The developing Purkinje cell bodies, bipolar, at first, given the presence of two processes emerging from the opposite poles of the oval perikaryon, grow progressively in size. After the 12th incubation day, they develop a branched dendritic tree, and, shortly before hatching time, the cells acquire the characteristic flask or pear-shaped configuration. On the 10th incubation day, microtubules are already detectable together with Golgi complexes and a few vesicles of rough endoplasmic reticulum; on the 14th incubation day, RER cisterns are recognizable in the supranuclear cytoplasm, later extending into the whole perikaryon, and attaining their definitive distribution by the 18th incubation day. Pinocytotic and coated vesicles, as well as subsurface cisterns are seen during the whole embryonic life. In the earliest stages of development, three distinct types of junctional contacts between Purkinje cells and surrounding axons are described, and their functional role in relation to synaptogenetic processes is discussed. Beginning with the 16th incubation day, some Purkinje neurons undergo degenerative changes similar to those described in other types of neurons of the central and peripheral nervous system.     

成人小脑髓母细胞瘤的临床及病理研究

目的探讨成人小脑髓母细胞瘤的临床病理特点、组织发生学及影响预后的因素。方法对我院１９７４～１９９５年间２７例成年人（≥１６岁）小脑髓母细胞瘤进行了观察。结果本组年龄１６～５５岁，平均２５．８岁，肿瘤发生于小脑蚓部２１例，小脑半球６例。随访２１例，７例已生存２．５～１７年，１４例死亡。平均生存时间４１．６个月。１年生存率为７１．４％，５年及１０年生存率均１４．３％。组织学类型：经典型１４例，促纤维增生型１３例。结论通过电镜观察及突触素、神经元特异性烯醇化酶和胶质纤维酸性蛋白免疫组化染色观察，证实髓母细胞瘤是具有向神经元及胶质细胞双向分化潜能的原始神经外胚叶肿瘤。影响预后的因素包括年龄、肿瘤部位、治疗手段以及组织学类型     

Distinct signaling pathways of precursor BDNF and mature BDNF in cultured cerebellar granule neurons

Recent studies have focused on a distinctive contrast between bioactivities of precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (matBDNF). In this study, using a proteolytic cleavage-resistant proBDNF mutant (CR-proBDNF), signaling mechanisms underlying the proapoptotic effect of proBDNF and antiapoptotic effect of matBDNF on the low potassium (LK)-inducing cell death of cultured cerebellar granule neurons (CGNs) were analyzed. A time course study demonstrated that unlike matBDNF, CR-proBDNF failed to induce TrkB phosphorylation for up to 360 min. CR-proBDNF did not activate ERK-1, ERK-2 and Akt, which are involved in TrkB-induced cell survival signaling, while matBDNF activated these kinases. On the other hand treatment of CGNs with CR-proBDNF led to a rapid activation of Rac-GTPase and phosphorylation of JNK which are involved in p75^NTR-induced apoptosis. In addition, a JNK-specific inhibitor, SP600125, inhibited the CR-proBDNF-induced apoptosis but did not affect the antiapoptotic effect of matBDNF. CR-proBDNF treatment led to an earlier appearance of active caspase-3. In contrast, matBDNF dramatically postponed the appearance of active caspase-3. Not like other signaling molecules, activation of caspase-3 was conversely regulated by both CR-proBDNF and matBDNF. These results thus suggest that in CGNs proBDNF elicits apoptosis via activation of p75^NTR, Rac-GTPase, JNK, and caspase-3, while matBDNF signals cell survival via activation of TrkB, ERKs and Akt, and deactivation of caspase-3.     

Evidence of vascular differentiation in anaplastic tumours of the thyroid - An immunohistological study

Summary Sixteen cases of anaplastic carcinoma (ACA) and 4 cases of malignant haemangioendothelioma (HAE) of the thyroid were studied by light microscopy and immunohistochemistry.Seven cases of ACA and 3 cases of HAE were characterized by coexpression of immunohistological features of epithelial and vascular endothelial cells.Expression of vimentin was common to all tumours investigated. The present study provides evidence that ACA and HAE are partially closely related tumours showing alternating differentiation. This speaks in favour of a common neoplastic cell with the potential for epithelial and vascular endothelial differentiation.F. Eckert was supported by the Dr. Mildred Scheel-Stiftung/ Deutsche Stiftung für Krebshilfe. U. Schmid was supported by the Krebsliga St. Gallen/Appenzell     

Chromosome DNA imbalances in human astrocytic tumors: A comparative genomic hybridization study of 63 Chinese patients

Astrocytic tumors are the most frequent primary brain neoplasms. They are clinically characterized by wide variations in histology. Analysis of chromosome DNA imbalance may help to advance diagnosis, grading, and classification, and to determine appropriate therapeutic approaches for tumors of astrocytic lineages. Comparative genomic hybridization (CGH) provides comprehensive information about chromosome DNA aberrations, and is an important technique for evaluating the differences at genomic levels among the same or different grade tumors. In this study, 63 astrocytic tumors of Chinese patients were screened by CGH, and the relationship between their chromosome DNA imbalances and the histopathological classification, grading, and clinical features was analyzed. Most tumors showed genomic copy aberrations detected by CGH. The most frequent abnormalities were regional gains in chromosome 1q and 7p; regional losses in chromosome 1p, 2q, 4q, 6p, 10q, 12q, 15q, 19q, and 22q were also frequently observed. The gain of 1q and the loss of 15q were relevant to the histological types and grades of WHO classification. The losses of 4q and 10q correlated with age in the group of anaplastic astrocytoma, which was unreported in the literature. This study confirmed that chromosomal aberrations, such as +1q, −4q, −10q, +7p, and −15q possibly contributed to the pathogenesis of these tumors. Our data was the first report on the chromosomal aberrations of astrocytic tumors of Chinese patients.     

A cerebellar projection onto the pontine nuclei an experimental anatomical study in the cat

Summary Fibres passing from the intracerebellar nuclei to the pontine nuclei proper have been noted only by few students. In the present study this projection is analysed by mapping with the Nauta (1957) and Fink and Heimer (1967) methods the degeneration which occurs in the pontine nuclei following stereotactically placed electrolytic lesions in different parts of the intracerebellar nuclei in the cat. Cerebellopontine fibres come from the lateral cerebellar nucleus (NL) except its ventralmost part, and from the rostral but probably not from the caudal part of the interpositus anterior (NIA) and the interpositus posterior.The fibres end in three fairly well circumscribed regions of the pontine nuclei: a longitudinal column in the paramedian pontine nucleus, a column in the dorsolateral nucleus and one in the dorsal peduncular nucleus. Fibres from the NL as well as the NIA appear to end in all three regions, but the possibility of a more specific distribution cannot be excluded. Parts of the projection areas in the pons appear to be specific to cerebellar afferents, while other parts overlap with terminations of cerebropontine fibres, especially from SmI and SmII.The findings support the conclusions arrived at in recent studies of the cerebral corticopontine projections by P. Brodal (1968a, 1968b, 1971a, 1971 b) that the pontine nuclei are very precisely organized. The general principles in the organization of the corticopontine and cerebellopontine projections appear to be similar.Working in the Anatomical Institute, University of Oslo, with leave of absence from the Laboratory of Normal Anatomy, University of Coimbra, Portugal, with a grant from the Portugese Institute for Higher Culture.     

Somatoiopic studies on cerebellar fastigial cells

Summary The somatotopic inputs into fastigial cells have been studied in relation to cutaneous mechanoreceptors of forelimb and hindlimb. Some fastigial cells were very discriminative, not only in respect of the limb, but also to restricted areas of hairy skin and related toe pads. Others were much less so, forelimb and hindlimb cutaneous receptors evoking similar excitatory-inhibitory responses. In addition, from the contralateral hindlimb, responses were evoked which were comparable with those from the ipsilateral limb.Somatotopic diagrams have been constructed which show in four experiments the sites of fastigial cells in the parasagittal plane of the microelectrode tracks. For each experiment four separate plottings give a comparison of the sizes of responses evoked for forelimb and hindlimb: excitation from nerve volleys; inhibition from nerve volleys; excitation from pad taps; inhibition from pad taps. In this way it is shown that fastigial cells with similar somatotopic relations often occur in clusters, particularly when assessed by their inhibitory responses.Since fastigial inhibition is largely due to Purkyn cells, there is an attempt to correlate the somatotopic relations of Purkyn cells with the somatotopy of fastigial cell inhibition. The excitation of fastigial cells exhibits less somatotopic discrimination, which conforms with the poor somatotopic discrimination of cells of the lateral reticular nucleus.In a final discussion there is consideration of two principal projections from the vermis of the anterior lobe: Purkyn cells inhibiting Deiters neur; Purkyn cells inhibiting fastigial cells which in turn monosynaptically excite Deiters neurones, the inhibition of Deiters neurones being then by disfacilitation. The degree of forelimb-hindlimb convergence in these pathways is reconsidered and is diagrammatically illustrated.     

Electron microscopic,ultracytochemical and immunohistological observations in Crohn's disease of the ileum and colon

Summary Immunohisto- and ultracytochemical studies were carried out on surgical and biopsy specimens from 27 patients suffering from Crohn's disease of the ileum or colon. Control specimens were obtained from 16 patients with nonspecific proctitis or neoplastic disorders of the caecum or rectum. Our results suggest that the initial lesions in Crohn's disease are associated with a typical humoral immune response. In non-ulcerated mucosa a uniform increase of IgA-, IgG- and IgM-cells was found (numbers of IgA-cells: IgG-cells 14.4), whereas disproportional increases of IgG- and IgE-cells were observed in ulcerated mucosa (IgA:IgG 0.7). The IgE-cell multiplication in ulcerated areas suggests the possibility of local hypersensitivity reactions. Macrophages and granulocytes contained IgG, which was also demonstrated in multinucleated giant cells. The granulomas contained extracellular IgG, acid phosphatase and peroxidase. The finding of potentially harmful extracellular lysosomal enzymes may be of pathogenetic significance in view of the hypothesis of Weissmann (1964). Micro-ulcerations of the dome epithelium of hyperplastic Peyer's patches were seen by electron microscopy a finding which can be interpreted as an early lesion through which luminal antigens gain uncontrolled access to Peyer's patches. This could lead to (1.) overstimulation of the local immune system, (2.) disturbance of local immune homeostasis, (3.) imbalanced Ig-production with disproportional increases in IgG and IgE. We were not able to detect Clq or C3 bound to epithelial or vascular basement membranes, and no electron dense deposits were found. Viral particles or bacteria in any of the specimens were not demonstrated by electron microscopy. The type of immune response in Crohn's disease and its pathogenetic significance with remain unclear until more is known about the specificity of the locally produced antibodies.This study was supported by a grant of the Deutsche Forschungsgemeinschaft (Ot 53/4-6)Dedicated to Professor Dr. G. Seifert on the occasion of his 60th birthday     

An HRP and autoradiographic study of cerebellar corticonuclear-nucleocortical reciprocity in the monkey

Summary Combined injections of ³H-leucine and HRP were made into the monkey cerebellar cortex in order to identify any reciprocal connections between the corticonuclear and the nucleocortical pathways. These combined intraaxonal labeling experiments have demonstrated a considerable overlap of orthogradely labeled Purkinje cell axons and terminals with retrogradely labeled HRP-positive neurons in the ventrolateral region of the dentate nucleus following combined injections into the lateral hemisphere, and in the dorsal area of the dentate following combined injections into medial cortical areas of the anterior lobe. There were also areas within the deep cerebellar nuclei where orthogradely labeled corticonuclear terminals did not overlap with retrogradely labeled nucleocortical neurons.     

A computer model of mammalian cerebellar cortex

A computer-simulated model of mammalian cerebellar cortex is described, in which the individual units correspond to 300 μm square regions of the cerebellar cortical sheet. Local properties of these units as well as their pattern of connectivity were derived from anatomical and physiological data. Selection of an appropriate set of parameters produced predicted neuronal firing patterns and excitability changes similar to those obtained from anesthetized cats.The role of Purkinje recurrent collaterals was investigated by varying the strength of Purkinje cell inhibitory coupling to Golgi and basket cells. It is shown that the recurrent collaterals may exert important effects upon the time course of Purkinje cell responses to parallel fiber inputs. For spatially-distributed mossy fiber inputs, a focusing effect of long time course is demonstrated.     

Morphological study of cerebellar transplant cocultivated with cerebral cortical graft in the anterior eye chamber

Summary Morphological organization of Purkinje cells and of molecular layer of the cerebellar cortex cocultivated intraocularly with cerebral cortex for two months was studied. It was found, that while numerous spines on the main dendritic branches of Purkinje cells in single cerebellar grafts were vacant and non-synaptic, dendritic spines of thick Purkinje dendrites in double grafts were covered by large presynaptic bags. The resulting complex synaptic arrangement was strikingly similar although not identical to climbing terminals in normal (in situ) cerebellar cortex. Three distinct types of large presynaptic climbing-fibre like terminals were distinguished: (a) bouton with dense matrix and small round synaptic vesicles, (b) with large round vesicles and (c) containing ovoid synaptic vesicles. The spines of the thin, presumably tertiary dendritic branches were contacted mostly by one parallel axon varicosity, or — as a contrast to normal conditions-by axon terminal, containing ovoid synaptic vesicles. Irrespective of the shape of synaptic vesicles in the presynaptic terminal, all spine-synapses were of asymmetric type; in contrast, synapses on the dendritic shafts were always symmetric.GABA-immunogold reaction has revealed the presence of this inhibitory transmitter in most axon terminals containing ovoid-pleomorphic vesicles within the molecular layer, including those resembling climbing fiber-terminals. This shows a plasticity of the Purkinje cell dendrites to receive non-specific, foreign axons in the absence of specific afferents. Also, the type of synaptic junctions, i.e. whether symmetric or asymmetric, is determined exclusively by the postsynaptic neuron and is independent of the transmitter content of the presynaptic terminal.     

Participation of Golgi neuron processes in the cerebellar glomeruli: An electron microscope study

Summary Synaptic relations, within the cerebellar isles, of Golgi II neuron axons and dendrites have been studied in the cat. Golgi axon endings can be identified with some probability in the outer (cortical) zone of the cerebellar glomeruli in normal material. They can well be recognized in the chronically isolated folium in which mossy fibers have completely degenerated. The Golgi axons are very thin preterminal fibers with small enlargements containing synaptic vesicles and contacting the preterminal intraglomerular parts of the granule cell dendrites as well as their terminal spheroid protrusions. The spheroid protrusions of the granule dendrites are the main postsynaptic loci of the granule neuron having their main synapse with the mossy fiber — generally of central position in the glomerulus — and additional synapses, more often on their outer surface, with the Golgi axons. No significant difference is seen between the two contacts, from which one is known to be excitatory (mossy) and the other inhibitory (Golgi ax.). The Golgi cell has also descending dendrites, known from light microscopy to be engaged in the cerebellar isles. By tracing these dendrites from the cell bodies and using their characteristic short finger-like processes as a criterion for their identification, the synapses between mossy endings and Golgi dendrites could be identified under the EM. They are broad contacts between a dendrite passing along one side of the mossy ending, with several synaptic attachment plaques and with small dendritic processes protruding into invaginations of the mossy ending. — The cerebellar glomerulus is thus a complex synaptic apparatus with two different axonal elements (mossy and Golgi endings) and often two dendritic elements (granule and Golgi dendrites) involved. — The possible functional significance of the Golgi cell is discussed in the light of these findings and the new discoveries by Eccles et al. (1964b, 1966) on its inhibitory nature.     

Lipofuscin in the cerebellar cortex of albino rats: An electron microscopic study

Summary The ultrastructure of autofluorescent, PAS-positive lipofuscin in Purkinje, granule, Golgi epithelial, basket and stellate, microglial and perivascular cells in the cerebellar cortex of senescent rats is described. The membrane-bounded pigment is composed of three elements: 1) electron-lucent homogeneous droplets, 2) a granular matrix and 3) intensely osmiophilic patches. The proportions of these three components vary between cell types and one can grossly differentiate a neuronal and a glial lipofuscin. The lipofuscin granules of stellate and perivscular cells are different from lipofuscin of other cerebellar neurons and glia. It can be concluded from these morphological observations that each cerebellar cell type has its distinct lipofuscin.Supported by the Deutsche Forschungsgemeinschaft La 184/5I would like to thank Mrs. v. Bronewski and Mr. H. Boffin for their technical assistance     

Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy

PurposeCerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects.MethodsPatients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated.ResultsDisease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA–S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments.ConclusionA wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.     

The cerebellar corticonuclear projection from lobule Vb/c of the cat anterior lobe: a combined electrophysiological and autoradiographic study

Summary The present study examines the projection to the cerebellar nuclei of Purkinje cells in particular sagittal zones within the intermediate region of the cerebellar cortex. The boundaries between the zones were delimited electrophysiologically on the basis of their climbing fibre input so that a small volume (10–120 nl) of ³H-leucine could be injected into the centre of a chosen zone. The subsequent uptake and orthograde transport of labelled material by the Purkinje cells was studied autoradiographically. It was found that the smallest injections resulted in injection sites restricted to a single cortical zone and extremely reproducible results could be obtained using such a combined electrophysiological/autoradiographic technique. Larger injections sometimes spread to a neighbouring zone but the resultant terminal labelling within the deep nuclei was invariably consistent with the results obtained from smaller injections. The c₁ and c₃ olivocerebellar zones, which are known to receive climbing fibre input transmitted from the ipsilateral forelimb via a dorsal funiculus spino-olivo-cerebellar pathway (DF-SOCP), were found to project to partially overlapping regions within nucleus interpositus anterior (NIA). No projection to nucleus interpositus posterior (NIP) was demonstrated for either zone. No distinction could be seen between the terminal fields for the medial and lateral halves of the c₁ zone which are, however, known to receive their climbing fibre input from quite separate regions within the inferior olive. The c₂ zone, which was delimited on the basis of its climbing fibre input which is transmitted from both forelimbs via a lateral funiculus SOCP, was found to project exclusively to interpositus posterior. The hemispheral d₁ zone was found to project to the transitional region where interpositus anterior and the dentate nucleus adjoin.     

Saccadic adaptation in lateral medullary and cerebellar infarction

To determine the adaptive capability of saccadic eye movements, and its association with enduring saccadic dysmetria in cerebellar and lateral medullary infarction (LMI), we investigated saccadic accuracy and adaptation in 15 patients with cerebellar or lateral medullary infarction, compared with those of 7 patients with diffuse cerebellar atrophy and 11 normal subjects. Saccade adaptation was elicited by a 37.5% backward target step during the primary saccade in both horizontal directions. Horizontal preadaptive saccadic gains were decreased in patients with cerebellar infarction, and contralesionally in patients with LMI. In contrast, adaptive saccadic gain change was reduced in patients with diffuse cerebellar atrophy and cerebellar infarction. Saccadic hypometria and reduced saccadic adaptability were dissociated in the majority of the patients with cerebellar infarctions; seven of the eight patients with cerebellar infarction showed saccadic hypometria and only three of them showed reduced saccadic adaptation, uni- or bilaterally in two with bilateral infarctions and ipsilesionally in one with unilateral infarction. The most commonly affected structure on MRI was the cerebellar hemisphere in the patients either with saccadic hypometria or with reduced saccadic adaptation. All patients with unilateral LMI exhibited normal saccadic gain adaptation in both directions, including those patients with enduring saccadic ipsipulsion. Our results suggest that the cerebellar hemispheres as well as the dorsal vermis and fastigial nucleus may be involved in the control of saccadic accuracy and adaptation. Reduced saccadic adaptation and persisting dysmetria are not tightly linked to each other in the cerebellar or lateral medullary lesions.     

Morphological changes in the cerebellar cortex of aging Macaca nemestrina

The cerebellar cortices in 4, 10 and 20 year old Macaca nemestrina have been examined for the number of Purkinje (P) and granule cells and the deposition of lipofuscin in P cells in relation to aging. Lipofuscin distribution significantly increased with age in the P cells in these animals. The number of P cells was significantly reduced, while there were no changes in the number of granule cells. It appears from this and other studies that the Purkinje cells are more prone to aging changes than the granule cells of the cerebellum both in lipofuscin formation and cell loss. Although the precise functional significance of these changes in P cells is not clear, their vulnerability may be related to changes in motor function in old age.     

Identification of synapses formed in the cerebellar cortex by purkinje axon collaterals: an electron microscope study

Summary Purkinje axon collaterals and their synaptic terminals can be identified on the basis of three criteria: (1) They are the only myelinated axons of local elements, hence any myelinated axon persisting in chronically isolated folium is a Purkinje axon or its collateral; (2) They are the only known transfolial axons, so that axons and synapses found in the state of secondary degeneration after lesions placed into neighbouring folia of the cerebellar cortex are Purkinje axon collaterals and synapses; (3) The peculiar axonal tubular systems described by Andres (1965) are specific for Purkinje axons and their synaptic endings, which offers an additional clue for their identification. Using these three criteria numerous synapses of Purkinje axon collateral endings have been identified on the large Golgi neurons, both cell bodies and principal dendrites, and on the bodies of basket neurons. No evidence of the termination of Purkinje axon collaterals on other Purkinje cells could be detected.