Choroid plexus carcinoma. Cytologic identification of malignant cells in ascitic fluid

Abdominal deposits of a choroid plexus carcinoma in a patient with a ventriculoperitoneal shunt were cytologically diagnosed by examination of ascitic fluid after regression of the primary tumor. The morphology of the malignant cells in ascitic fluid was more similar to that of mesothelial cells than to the appearance of cells from this lesion in cerebrospinal fluid.     

TARG1 protects against toxic DNA ADP-ribosylation

ADP-ribosylation is a modification that targets a variety of macromolecules and regulates a diverse array of important cellular processes. ADP-ribosylation is catalysed by ADP-ribosyltransferases and reversed by ADP-ribosylhydrolases. Recently, an ADP-ribosyltransferase toxin termed ‘DarT’ from bacteria, which is distantly related to human PARPs, was shown to modify thymidine in single-stranded DNA in a sequence specific manner. The antitoxin of DarT is the macrodomain containing ADP-ribosylhydrolase DarG, which shares striking structural homology with the human ADP-ribosylhydrolase TARG1. Here, we show that TARG1, like DarG, can reverse thymidine-linked DNA ADP-ribosylation. We find that TARG1-deficient human cells are extremely sensitive to DNA ADP-ribosylation. Furthermore, we also demonstrate the first detection of reversible ADP-ribosylation on genomic DNA in vivo from human cells. Collectively, our results elucidate the impact of DNA ADP-ribosylation in human cells and provides a molecular toolkit for future studies into this largely unknown facet of ADP-ribosylation.     

The choroid plexus removes beta-amyloid from brain cerebrospinal fluid

beta-Amyloid (Abeta) concentration in the cerebrospinal fluid (CSF) of the brain may be regulated by the choroid plexus, which forms a barrier between blood and brain CSF. Abeta uptake from CSF was determined as its volume of distribution (V(D)) into isolated rat choroid plexus tissue. The V(D) of [125I]Abeta1-40 was corrected by subtraction of the V(D) of [14C]sucrose, a marker for extracellular space and diffusion. Abeta uptake into choroid plexus was time and temperature dependent. Uptake of [125I]Abeta was saturable. Abeta uptake was not affected by addition of transthyretin or apolipoprotein E3. In studies with primary culture monolayers of choroidal epithelial cells in Transwells, Abeta permeability across cells, corrected by [(14)C]sucrose, was greater from the CSF-facing membrane than from the blood-facing membrane. Similarly, cellular accumulation of [125I]Abeta was concentrative from both directions and was greater from the CSF-facing membrane, suggesting a bias for efflux. Overall, these results suggest the choroid plexus selectively cleanses Abeta from the CSF by an undetermined mechanism(s), potentially reducing Abeta from normal brains and the brains of Alzheimer's disease patients.     

Choroid plexus and paraphysis in lower vertebrates

Cytoarchitecture of the choroid plexus of the third ventricle and the paraphysis was investigated in some lower vertebrates to compare the histologic characteristics of these organs. Both epithelia are similar in appearance in the same class. Minor microscopic variations exist in the different classes of vertebrates, but do not provide a fundamental distinction between the two organs. The epithelia, moreover, have similar staining properties, contain mucicarmine- and PAS-reactive materials, and are derived from a common neuroepithelium. Tubules are identified in the choroid plexus and in the paraphysis; all are similarly formed by simple folding of epithelium on the surface into the stroma. The paraphyses in all vertebrates studied contain villi similar to those seen in the choroid plexus. Cilia are identified in both choroidal and paraphyseal epithelia, and are not an indication of degree of epithelial differentiation. Many types of epithelium are noted in both organs during histologic differentiation as well as in the mature stage. Functionally, the choroid plexus is active in both secretion and absorption. Accumulation of particulate material within the epithelial cytoplasm may indicate phagocytic as well as absorptive activity of cells. Based on a common neuroepithelial origin and similar histochemical properties, we conclude that the paraphysis is a modified choroid plexus. The velum transversum is an arbitrary boundary between diencephalon and telencephalon, and is itself formed of choroid plexus. The medial telencephalic ventricle is the rostral portion of the third ventricle. All neuroepithelial infoldings at the rostral end of the diencephalic roof including the velum transversum are intraventricular choroid plexuses; the neuroepithelial outpouchings in this region are the extraventricular choroid plexuses (paraphysis) of the diencephalon.     

Choroid plexus papilloma. Report of a case with cytologic differential diagnosis.

The cytopathologic features of choroid plexus papilloma observed in the ventricular fluid of a 9-month-old boy are reported and compared with other pediatric central nervous system neoplasms. The cytologic features of choroid plexus papilloma are similar to those of normal choroid plexus and may be difficult to distinguish from those of a well-differentiated papillary ependymoma. However, the cell clusters are distinct from those associated with choroid plexus carcinoma and primitive neuroectodermal tumors.     

Choroid plexus carcinoma. Report of a case with cytopathologic differential diagnosis

The cytopathologic features of choroid plexus carcinoma in the cerebrospinal fluid of a 13-month-old male infant were reviewed and compared with those of other small-cell malignant neoplasms of childhood and young adulthood involving the central nervous system. The cytologic features of the choroid plexus carcinoma (tight spatial clusters and isolated anaplastic cells with striking nuclear lobulation) were distinct from those of lymphoma, leukemia, neuroblastoma, ependymoma and pineal germinoma. However, the cells had a striking resemblance to those of anaplastic ependymoma and metastatic adenocarcinoma.     

Role of transthyretin in thyroxine transfer from cerebrospinal fluid to brain and choroid plexus

The transport of 125I-labeled thyroxine (T4) from the cerebrospinal fluid (CSF) into brain and choroid plexus (CP) was measured in anesthetized rabbit [0.5 mg/kg medetomidine (Domitor) and 10 mg/kg pentobarbitonal sodium (Sagatal) iv] using the ventriculocisternal (V-C) perfusion technique. 125I-labeled T4 contained in artificial CSF was continually perfused into the lateral ventricles for up to 4 h and recovered from the cisterna magna. The %recovery of 125I-labeled T4 from the aCSF was 47.2+/-5.6% (n=10), indicating removal of 125I-labeled T4 from the CSF. The recovery increased to 53.2+/-6.3% (n=4) and 57.8+/-14.8% (n=3), in the presence of 100 and 200 microM unlabeled-T4, respectively (P<0.05), indicating a saturable component to T4 removal from CSF. There was a large accumulation of 125I-labeled T4 in the CP, and this was reduced by 80% in the presence of 200 microM unlabeled T4, showing saturation. In the presence of the thyroid-binding protein transthyretin (TTR), more 125I-labeled T4 was recovered from CSF, indicating that the binding protein acted to retain T4 in CSF. However, 125I-labeled T4 uptake into the ependymal region (ER) of the frontal cortex also increased by 13 times compared with control conditions. Elevation was also seen in the hippocampus (HC) and brain stem. Uptake was significantly inhibited by the presence of endocytosis inhibitors nocodazole and monensin by >50%. These data suggest that the distribution of T4 from CSF into brain and CP is carrier mediated, TTR dependent, and via RME. These results support a role for TTR in the distribution of T4 from CSF into brain sites around the ventricular system, indicating those areas involved in neurogenesis (ER and HC).     

Choroid plexus trophic factors in the developing and adult brain

The choroid plexus (CP), localized in brain ventricles, is the major source of cerebrospinal fluid (CSF) and participates in the blood-CSF barrier. It is essential for brain immunosurveillance and the clearance of toxics, and for brain development and activity. Indeed, the CP secretes a large variety of trophic factors in the CSF that impact the entire brain. These factors are mainly implicated in neurogenesis, but also in the maintenance of brain functions and the vasculature. In this mini-review, we provide an overview of the various trophic factors secreted by the CP in the CSF, and describe their roles in the developing, adult and diseased brain.     

Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid.

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A ('angiotensin-converting enzyme') and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.     

Expression of the E.coli ada gene in yeast protects against the toxic and mutagenic effects of N-methyl-N''-nitro-N-nitrosoguanidine.

The E.coli ada gene protein coding region has been ligated into an extrachromosomally replicating yeast expression vector downstream of the yeast alcohol dehydrogenase gene promoter region to produce pADH06C. The yeast strains SX46A, 7799-4B and VV-6 are deficient in endogenous O6-alkylguanine-DNA-alkyltransferase and transformation of these strains with this shuttle vector resulted in the expression of 1730, 1260 and 374 fmoles ada-encoded ATase/mg protein in stationary phase yeast: transformation with the parent vector had no effect on endogenous ATase activity which remained less than 2 fm/mg. In comparison with parent vector transformed yeast, all of the pADH06C-transformed strains showed an increase in the resistance to the toxic effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, 7799-4B and VV-6 were more resistant to the mutagenic effects of this agent. These results indicate that the toxic and mutagenic effects of MNNG in yeast are mediated, at least in part, by DNA lesions than can be repaired by the E.coli ada gene product.