In control of its fate: gene regulation in Toxoplasma gondii.

The intracellular protozoan parasite Toxoplasma gondii is an important opportunistic pathogen in animals and man. In parallel to its clinical significance, T. gondii is also receiving considerable attention as an attractive model organism for intracellular parasitism. Regulation of gene expression at various levels underlies the intricate interplay between the parasite and its host cell, as well as the interconversions between different life-stages. In this article we will discuss some of what is currently known about gene organization and gene regulation in T. gondii as well as some of the tools available to dissect the parasite at a molecular level.

[Comparison of the relative bioavailability and pharmacokinetics of estrone after oral administration of esterified estrogens in a tablet formulation and an aqueous suspension]. / Vergleichende Untersuchung zur relativen Bioverfügbarkeit und Pharmakokinetik von Estron nach oraler Gabe von veresterten Estrogenen als Drageeformulierung und als wässrige Suspension.

In a two-way crossover study in 18 young female volunteers aged from 22 to 38 years the relative bioavailability and pharmacokinetics of esterified estrogens were investigated after single administration of a sugar-coated tablet formulation (Femavit 1.25) in comparison to a single dose of an oral suspension. The content of active ingredients was in both cases 1.25 mg esterified estrogens. As marker compound the dominating active compound estrone (CAS 53-16-7) was chosen. Estrone in serum was measured using a validated radioimmuno assay. The administration of the test and reference preparation was performed on either day 3-7 of two subsequent menstruation cycles in order to obtain low endogenous hormone levels. The relative bioavailability of estrone from the test preparation, based on the total AUC (AUC under the baseline + AUC over the baseline), was 99.2% (90%-confidence interval 91.8-107.1%) und therefore fulfilled the bioequivalence criterion. After deduction of the baseline-AUC a relative bioavailability of the sugar-coated formulation of 113.9% was found, with a broad 90% confidence interval of 72.5-178.9%, due to a higher variability. The absolute Cmax values were similar (255 pg/ml after tablet administration and 279 pg/ml after suspension), bioequivalence also in regard to Cmax was proven. The value of tmax was 4 h for both preparations.

[Transmission electron microscopic studies of the organization of the ependymocytes in the central canal of the spinal cord of Cercopithecus nigroviridis (Pocock 1907), (Platyrrhina, Cercopithecoidea)]. / Transmissionselektronenmikroskopische Untersuchungen zur Organisation der Ependymocyten im Zentralkanal des Rückenmarks von Cercopithecus nigroviridis (Pocock 1907), (Platyrrhina, Cercopithecoidea).

The ependyma of the central canal of the spinal cord of the monkey Cercopithecus nigroviridis was examined by transmission electron microscopy. In the lumbar region and in the filum terminale, many cytoplasmatic protrusions are visible. They are irregular in size and shape and display many microvilli. They are extending into the lumen of the central canal. The basal parts of the ependymocytes occasionally have a very close association with the ependymal blood vessels. The pericapillary space, the pericapillary structures like pericytes and collagen fibrils, and the basal lamina are absent. Opposite branches of the ependymocytes growing together could be observed in the central canal, eventually forming a cytoplasmic unit. Cytoplasmatic extensions of the ependymocytes bridge the lumen of the central canal and melt into each another. Lacunae, such as described by LEONHARDT (1980) in the apical cytoplasm of the ependyma in the rabbit, do also exist in the ependyma coating the central canal of the spinal cord of the monkey Cercopithecus nigroviridis. Some of these lacunae have direct contact to the luminar surface of the central canal, others are separated. Cilia and short microvilli are coating the lacunae. Adjacent ependymal cells form complex interdigitations with each other. Close to their surface on the central canal, there are numerous zonulae adhaerentes. Profiles of the granular and agranular endoplasmatic reticulum are in very close contact to the fine filaments of the zonulae.

Preliminary electron microscopic observations on ependymal cells in the caudal segment of the filum terminale and the ampulla caudalis of Macaca fascicularis and Cercopithecus griseoviridis (primates, Cercopithecidae).

In a previous paper, the concept of the terminal organ (TO) of the subcommissural complex was forwarded. Functionally this complex is a neuro (glio-) hemal organ which serves to discharge the Reissner's secretory material into the systemic circulation. The TO is characterized by structural specializations that make feasible the discharge and chemical decomposition of the secretory material stowed in the massa caudalis (MC). The TO is probably not only the ampulla caudalis (AC); it may comprise even parts of the filum terminale next to the AC. The boundary of the TO is uncertain as yet. It cannot be precluded that the AC, which itself varies in shape and size, is just a receptaculum massae caudalis. The material of the MC escapes from the AC either through apertures of the wall of the AC or of the filum terminale (Neuropori caudalis, slit-shaped gaps). It is also likely that the secretory material becomes chemically decomposed in the AC and is intra- (trans-) cellularly discharged. In this connexion, certain ependymal cells may be of significance. These cells exhibit large, tongue-shaped central projections (temporarily developed?) which bear a considerable number of long microvilli. The significance of these cells probably lies in the enlargement of the cell surface bathing in the CSF which contains the MC. These cells are most abundant in the area of the TO; single, isolated cells of the same type occur in other areas of the ependyma of some primates. This would indicate that the TO does not contain special types of cells not found in other parts of the ependyma, but that the TO differs from other ependymal regions in the density of peculiar cell types.

[Comparative scanning and transmission electron microscopy studies of the ependyma of the central canal in the spinal cord of primates. I. Electron optical image of the ependyma in the central canal of the spinal cord of the callithrix monkey (Callithrix jacchus, Linné 1758)]. / Vergleichende raster- und transmissionselektronen-mikroskopische Untersuchungen am Ependym des Zentralkanals im Rückenmark von Primaten. I. Das elektronenotische Bild des Ependyms im Zentralkanal des Rückenmarks des Weissbüscheläffchens (Callithrix jacchus, Linné 1758).

The ependyma lining the central canal of the spinal cord of adult males and females monkey, Callithrix jacchus, was examined by scanning and transmission electron microscopy. The cross section of the lumen of the central canal are round, oval, or triangular. Light and dark ependymal cells, depending on the density of the cytoplasm, were found. The light ependymal cells are fewer than the dark cells. The ependyma cytoplasm contained numerous mitochondria, filamentous structures, one or more well-developed Golgi-complexes, vesicles of the smooth endoplasmic reticulum, ribosomes, lysosomes, multivesicular bodies, profiles of the rough endoplasmic reticulum, large osmophilic bodies, and microtubules. The nuclei of the ependyma cells usually have a simple, regular round or oval shape. They occupy a relatively large portion of the cell volume and lie in the central or mediobasal position. Some of the nuclei show deep invaginations into the karyoplasm. Most of the mitochondria occupy mainly the supranuclear portion of the apical cytoplasm. There are of the crista-typ. Ribosomes occur free in the cytoplasm, but some attached to the profiles of the rough endoplasmic reticulum or being arranged as polysomes. The filamentous structures are generally prominent cytoplasmic components and are distributed at the apical, lateral, or basal region of the ependymocytes. They are grouped into bundles and arranged in parallel arrays. Some of these bundles reach the plasmamembrane at the free lumina of the central canal, others take contact to the filamentous structures of the zonulae adherentes of the junctional complex below the free surface. The granular endoplasmic reticulum shows specializations. There profiles surrounding granular substances and widely distributed granulations in connection with the nuclear envelope. The functional significance of the deposition of these granulations is still unknown. The luminal surface of the ependymocytes bears many microvilli and cilia. The cilia are regularly arranged in cranio-caudal direction. Each cilium has the typical (9 + 2)-subfibres. The intercellular space at the surface of the ependymal layer shows a single zonula adherens or zonulae adherentes in the row. Tight junctions and gap junctions were not found in the material examined. Cell processes of liquor contacting neurons between adjacent ependyma cells, protruding into the lumen of the central canal, could be observed. The termination of these neurons contains accumulations of mitochondria in the central part, large amounts of vesicles, and small dense bodies. They have short microvilli and some stereocilia at the free surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Preliminary electronmicroscopical observations on the ampulla caudalis and the discharge of the material of Reissner's fibre into the capillary system of the terminal part of the tail of Ammocoetes (Agnathi).

The discharge of the material of the Reissner's fibre (RF) and the massa caudalis (MC) into the "meningeal spaces" has until now not been studied in detail and with the aid of the electron-microscope. It was generally assumed that the material of the MC disintegrates in the "meningeal spaces", but the nature and function of those spaces have not been established. The CNS of Ammocoetes ist encompassed by the meninx primitiva, which is the meningeal tissue of the lower vertebrates; the meninx does not differentiate during ontogeny into the pia mater and the arachnoides. In contrast, the meninx primitiva of mammals is the anlage in the ontogenetical sense of the leptomeninges in adult individuals. The results presented in this paper are valid for Ammocoetes only; Petromyzon and Myxine must be studied anew from a perspective which may be the result of our study. Of particular interest would be an anatomical analysis of these caudalmost structures of the CNS (Ampulla caudalis [AC], MC, neuropori, lacunae etc.) in Branchiostoma. The diameter of the RF of Ammocoetes is approximately 1.7 micron; this is not different from the diameter of the RF in adult individuals. In the AC the RF divides into several smaller fibres which eventually disintegrate and form the amorphous MC. In sagittal sections, the fibrillary structure of the RF is distinct. In cross sections the small fibres may appear as globules. The terminal part of the RF is very often coiled. The ependyma of the caudal part of the canalis centralis (CC) ist not remarkable; liquor contacting neurons are frequently found with their dendrites touching the RF. Liquor contacting neurons are never found in the ependyma of the AC. The ependymal cells of the dorsal part of the AC possess neither kinocilia or microvilli. The disappearance of these organelles begins in the dorsal part of the caudalmost segment of the CC. Most surprising is the distribution of the attachment devices which are probably desmosomes. In the ependyma of the caudal part of the spinal cord the attachment devices are typically situated; in the ependyma of the AC these devices are absent. We use the general term "attachment devices" until the nature of these devices has been clearly determined. In the caudalmost part of the spinal cord as well as in the AC, the intercellular spaces between the ependymal cells communicate, forming a 3-dimensional labyrinth. If there are no attachment devices between the proximal parts of the ependymal cells, the intercellular spaces may provide a passageway between the CC and the loose tissue of the meninx primitiva.(ABSTRACT TRUNCATED AT 400 WORDS)

[Reissner's fiber in the central canal of primate spinal cord]. / Der Reissnersche Faden im Zentralkanal des Rückenmarks von Primaten.

The Reissner's fibre (RF) in the canalis centralis of the spinal cord was studied with the aid of transmission and scanning electron microscope in Tupaia, Cebus, Sarmiri, Macaca, Alouatta, Ateles, Callithrix and Callicebus. The RF of the primates is structurally not different from the corresponding structure of other chordates. The diameter of the RF is slightly increasing in the canalis direction. The increase of the diameter varies between 2 and 5 micron. It is assumed that the increase is brought about by the inclusion of cell debris into the fibre. Material which definitely does not belong to the RF is found in the cerebrospinal fluid (CSF) of the canalis centralis and occasionally it adheres to the surface of the fibre. This material appears either as amorphous flocculent substances, the granulation of which differs in both density and size of the granula or as vesicles. If the material makes contact with the RF, a membrane-like structure may appear which is a condensation restricted to the area of the contact between material of different viscosity and granulation. The origin of this variable material is still not clarified. According to our observations, it is probably sequestrated material from ependymal cells. It is not a secretion as sometimes assumed since the intracellular processes of the synthesis of the secretion have not been observed.

Electron microscopic study of the origin and formation of Reissner's fiber in the subcommissural organ of Cebus apella (Primates, Platyrrhini).

Two kinds of secretion are formed in cells of the subcommissural organ (SCO) of Cebus apella. The "light secretion" is found in saccules originating from the endoplasmic reticulum. This secretion is stored in the peripheral portion of the cells and is not involved in formation of Reissner's fiber (RF). In close association with the Golgi complex, electron-dense granules are developed, containing a finely granular substance. These granules accumulate beneath the apical plasmalemma of the cell. Their content is discharged into the third ventricle, where it occurs in the form of a thin layer of secretion. This material appears to constitute the RF at the level of the entrance to the mesencephalic aqueduct.

Apical protuberances of supporting cells in the regio olfactoria of the mole, Talpa europaea, Linnaeus, 1758 (Insectivora, Talpidae).

The regio olfactoria of the mole, Talpa europaea, was studied by scanning and transmission electron microscopy. Peculiar structural differentiations, i.e. ovoid-shaped, balloon-like protuberances were found on the surface of the supporting cells. The apical portion of these protuberances contained finely dispersed granular material, whereas in their central part vesicular extensions of the smooth endoplasmic reticulum were observed.