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Ectoblastic derivatives (ectodermal and neuroectodermal components) constitute more than 90% of all structures in the murine teratocarcinoma derived from the PCC4-aza-1 line. This tumor was labeled immunocytochemically with fluoresceinated antibodies to A, B and H blood groups. A and B antigens were always noted to be absent from all structures of the three germ layers. With anti-H, however, embryonic and fetal endodermal components, e.g. alimentary or respiratory duct-like structures, gave positive staining. Mesodermal components, i.e. bone and cartilage structures, fibroblasts and myocytes of mature or embryonal type, were negative. Immature and mature ectodermal components, viz. epidermoid cysts or islets, were always positive. Neuroectodermal components, neuroblastic cysts and differentiated neuronal, glial and ependymal elements were always negative. Ectoblastic and/or neuroectoblastic individual cells or cell clusters, observed in the vicinity of positive differentiating ectodermal and neuroectodermal structures, were positive. Similar cells or clusters were negative when located close to negative neuroectodermal components. The undifferentiated, embryonal carcinoma cells and structures were always negative. These observations are compared to the staining patterns of H antigen in murine embryos and adult mice and in human teratocarcinomas. It is suggested that poorly differentiated, morphologically similar ectoblastic and/or neuroectoblastic structures are positive, if they concern ectodermal components, and negative, if they belong to neuroectodermal components, with the exception of some primary sensory cells that are positive. These last cells are also positive in normal fetal and adult tissues. Copyright © 1987 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cerebral astrocytoma has been found in two patients with AIDS related conditions. The fortuity of this unusual association is discussed, insofar as immunosuppression could favour the growth of certain neoplasms. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) of higher eukaryotic cells is a dynamic network of interconnected membrane tubules that pervades almost the entire cytoplasm. On the basis of the morphological changes induced by the disruption of the cytoskeleton or molecular motor proteins, the commonly accepted model has emerged that microtubules and conventional kinesin (kinesin-1) are essential determinants in establishing and maintaining the structure of the ER by active membrane expansion. Surprisingly, very similar ER phenotypes have now been observed when the cytoskeleton-linking ER membrane protein of 63 kDa (CLIMP-63) is mutated, revealing stable attachment of ER membranes to the microtubular cytoskeleton as a novel requirement for ER maintenance. Additional recent findings suggest that ER maintenance also requires ongoing homotypic membrane fusion, possibly controlled by the p97/p47/VICP135 protein complex. Work on other proteins proposed to regulate ER structure, including huntingtin, the EF-hand Ca(2+)-binding protein p22, the vesicle-associated membrane protein-associated protein B and kinectin isoforms further contribute to the new emerging concept that ER shape is not only determined by motor driven processes but by a variety of different mechanisms.

The microtubule-binding 63-kDa cytoskeleton-linking membrane protein (CLIMP-63) is an integral membrane protein that links the endoplasmic reticulum (ER) to microtubules. Here, we tested whether this interaction is regulated by phosphorylation. Metabolic labeling with (32)P showed that CLIMP-63 is a phosphoprotein with increased phosphorylation during mitosis. CLIMP-63 of mitotic cells is unable to bind to microtubules in vitro. Mitotic phosphorylation can be prevented by mutation of serines 3, 17, and 19 in the cytoplasmic domain of CLIMP-63. When these residues are mutated to glutamic acid, and hence mimic mitotic phosphorylation, CLIMP-63 does no longer bind to microtubules in vitro. Overexpression of the phospho-mimicking mitotic form of CLIMP-63 in interphase cells leads to a collapse of the ER around the nucleus, leaving the microtubular network intact. The results suggest that CLIMP-63-mediated stable anchoring of the ER to microtubules is required to maintain the spatial distribution of the ER during interphase and that this interaction is abolished by phosphorylation of CLIMP-63 during mitosis.

The subpellicular microtubules of the trypanosome cytoskeleton are cross-linked to each other and the plasma membrane, creating a cage-like structure. We have isolated, from Trypanosoma brucei, two related low-molecular-weight cytoskeleton-associated proteins (15- and 17-kDa), called CAP15 and CAP17, which are differentially expressed during the life cycle. Immunolabeling shows a corset-like colocalization of both CAPs and tubulin. Western blot and electron microscope analyses show CAP15 and CAP17 labeling on detergent-extracted cytoskeletons. However, the localization of both proteins is restricted to the anterior, microtubule minus, and less dynamic half of the corset. CAP15 and CAP17 share properties of microtubule-associated proteins when expressed in heterologous cells (Chinese hamster ovary and HeLa), colocalization with their microtubules, induction of microtubule bundle formation, cold resistance, and insensitivity to nocodazole. When overexpressed in T. brucei, both CAP15 and CAP17 cover the whole subpellicular corset and induce morphological disorders, cell cycle-based abnormalities, and subsequent asymmetric cytokinesis.

We have previously characterized, in Trypanosoma brucei, a multigene family encoding two developmentally regulated glucose transporters that are 80% identical at the amino-acid level. We report here the characterization of the homologous glucose transporters (TcoHT1 and TcoHT2) in Trypanosoma congolense, an African trypanosome responsible for disease in domestic animals. Both TcoHT isoforms, which are 92.4% identical, are encoded by a single cluster of genes containing two copies of TcoHT1 and three copies of TcoHT2 arranged alternately. Northern blot analysis revealed that TcoHT2 is expressed in all of the adaptive forms, while mRNA encoding TcoHT1 is only present in the metacyclic and bloodstream forms of T. congolense. When transfected with the TcoHT2 gene, Chinese Hamster Ovary cells express a hexose transporter with properties similar to those of the T. congolense procyclic forms (Km D-glucose = 41 microM versus 64 microM). In contrast to TcoHT2, TcoHT1 expressed in the Chinese hamster ovary cells appeared to be a relatively low affinity glucose transporter (Ki D-glucose = 0.8 mM). To determine the region(s) involved in the different apparent affinities for glucose, a chimera analysis was undertaken on the TcoHT isoforms. This study shows that amino-acid residues important for D-glucose recognition are located in the central region (between transmembrane domains 3 and 7) and in the C-terminal intracellular domain of TcoHT2. Site directed mutagenesis identified Ser193 located within transmembrane helix 4 as a key residue in relaxing the apparent affinity of TcoHT1 for glucose.

The authors report an 80-year-old woman who was evaluated for pain in her left leg and ankle. Sixteen years earlier, she had received a diagnosis of monostotic Paget's disease at the same site, based on roentgenographic changes. The lesion was very unusual, with tumor-like lysis of the affected area and fusion of the tibia, fibula, and talus.

Two typical cases of Parsonage-Turner syndrome with reflex sympathetic dystrophy syndrome and adhesive capsulitis of the shoulder are reported. The rarity of this combination is discussed.

A new case of simvastatin-induced acute rhabdomyolysis with heart failure after initiation of treatment with fusidic acid is reported. In most reported instances, statin treatment was initially well tolerated with muscle toxicity developing only after addition of another drug. The mechanism of this muscle toxicity is unelucidated but involvement of a decrease in tissue Co enzyme Q is strongly suspected.

Medullomyoblastoma is a rare tumor of childhood, arising in the cerebellar vermis. In the case reported, the immunohistochemical study (desmin, myosin, myoglobin and actin) and the ultrastructural findings, confirm the presence of rhabdomyoblastic cells associated with a typical medulloblastic component. Differential diagnosis and histogenesis of this tumor are discussed.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease which occurs in immunodepressed subjects and is particularly frequent in AIDS. Some authors having drawn attention to the protean aspect of the disease and claimed that AIDS may lose its basic characteristics and affect the grey matter as well as the white matter, we reviewed a series of 8 patients who had been biopsied and/or autopsied and had been examined at least once by MRI. In this series, contrary to what is regularly observed in toxoplasmic abscesses we did not find any lesion of the grey matter or any mass effect. On the other hand, we confirmed that PLM is not multifocal in all cases and that it course may be interrupted by prolonged remissions. The MRI criteria for PML therefore are reliable, provided multiple T2-weighted slices in coronal plane are performed, clearly showing the anatomy of the white fibres affected. However, it must be borne in mind that HIV-infected patients often have other associated brain pathologies, especially when the immune deficiency increases.

Centriolar area of human cells in culture was stained and observed by coupling immunoperoxidase technique and the use of Rabbit natural antibody. This staining showed a component which appears mainly as granular pericentriolar muffs in continuity with lateral projections similar to the satellites which have been described in conventional electron microscopy.

Numerous factors remain unknown as far as the mechanism of induction of cerebral metastases is concerned. Where as of cancer give metastases more readily than others, especially cerebral metastases, the neoplastic embolus can be either eliminated or remain in place in a state of quiescence. What is the role played by the blood brain barrier from a pathophysiological point of view? Is there a mechanism which prevents central nervous system metastases? What is the importance of individual variation? We attempted to induce cerebral metastases in VX2 carcinoma carrying rabbits to look for an approach to these problems and to create an experimental model of cerebral metastase. The VX2 carcinoma is easily transplantable and its biological characteristics are well known. The VX2 tumor is implanted in the thigh of the rabbits and is used in the experimentation starting two weeks following the take of the graft; the tumor is surgically resected and a solution containing approximatively 50,000 tumor cells for 0,1 ml is prepared. This solution is inoculated via the carotid artery to the same rabbit or to another rabbit of the same breed either or intrathecal way into the brain. Death occurred 6 to 20 days later and was followed by a complete pathological survey. The results were the following: --The inoculation via the carotid artery, even with very highly concentrated solution was never followed by any recognizable brain metastasis. --The inoculation intrathecaly produced only extraparenchymatous metastases where as the direct intracerebral inoculation was followed by the occurence of intracerebral metastases.

A 67 year-old right-handed man presented with an aphasia of acute onset associated to paralysis of vertical eye movements, mild cerebellar right dysmetria and right hemiparesis without hemianopia. CT scan showed two low density areas in the left thalamus and left occipital lobe. Neuropsychological examination revealed a non fluent aphasia with normal repetition, semantic paraphasias, perseverations and good comprehension of verbal and written commands. There was no alexia. Writing was impaired only by motor disturbances. Three weeks after the onset, tetraparesis and impairment of consciousness followed by a locked in syndrome supervened. Death occurred four months after onset. Neuropathological examination showed a left paramedian thalamic infarct involving the ventrolateral, dorso-medial and intralaminar nuclei, sparing the pulvinar. There was an occipital infarct sparing the calcarine scissura and multiple infarctions in the pons and the cerebellum. Broca's and Wernicke's areas were spared. We suggest that the involvement of medial nuclei could be partly responsible of language disturbances in thalamic aphasia.

A patient with a 12-year history of occipital ependymoma was found to have late pleuropulmonary metastases without recurrence of the primary tumor. The pleural metastases were diagnosed by histologic, ultrastructural features and finally by glial fibrillary acidic protein (GFAP) labeling positive reaction. This case is unique because of the long interval between occurrence of the initial tumor and the metastases, and because of the apparent quiescence of the cerebral lesion when the pleuropulmonary metastases were discovered.

Investigations performed by various workers during the last ten years suggest that some forms of mental illness are associated with a variety of immunological reactions. Significant variations in immunoglobulin ratios have been observed in patients with psychotic illness, and cellular and humoral cytotoxic activities against cerebral tissue have been demonstrated in vitro. At the molecular level, several subjects can be proposed for investigation into immunological phenomena in neuropathology. Thus, the neurospecific antigens, which have been isolated by biochemical methods, but the physiological role of which is largely unknown, open news ways to the experimental exploration of psychopathology.

A histological study of lymphocytic infiltration has been undertaken following removal at operation of one hundred human gliomas. This study has been completed with eight cases of tumour recurrence, six attempted autologous grafts, twenty one post-mortems and fourteen explorations of delayed hypersensitivity reactions. About half of the glioma specimens showed lymphocytic infiltration and no reaction was present in the other. Within this series of glioblastomas a correlation existed between the presence of infiltrating lymphocytes and the duration both of pre and post operative tumour evolution. The rejection of autologous grafts seemed to depend directly on the presence of lymphocytic infiltrations associated with the primary tumour. The retarded hypersensitivity reactions obtained after intradermic inoculations of cellular lyophilizates did not seem to be directly related either to the phenomenon of autologous graft rejection or to the presence of lymphocytic infiltrations. The results suggest that there is a complex system represented by two antigenic groups of transplantation type and sensitization type.

This historical study briefly recalls the circumstances of Broca's death, and reports some new data concerning his autopsy, and an analysis of macroscopic, microscopic, and computed tomography appearances of his brain following its discovery by Huard. The authenticity of the origin of the brain was established, and the hypothesis the Broca's death was due to rupture of a vascular malformation or a cerebrovascular accident was confirmed.