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S Tamm

Publications and source records attributed to S Tamm.

At least 19 recordsLinked to original sources

Telomerase activity in melanocytic lesions: A potential marker of tumor biology.

Telomerase activation, being a cardinal requirement for immortalization, is a crucial step in the development of malignancy. With a view toward diagnostic and biological aspects in melanocytic neoplasia, we investigated the relative levels of telomerase activity in 72 nevi and 16 malignant melanomas by means of a modified telomeric repeat amplification protocol (TRAP) assay, including an internal amplification standard. We further compared telomerase activity with the expression of two different proliferation-specific proteins, Ki-67 and repp86, a protein expressed exclusively in the cell cycle phases S, G2, and M. Telomerase activity was associated with the overall growth fraction (Ki-67) but showed a closer correlation with the expression of repp86. Both telomerase activity and proliferation indices discriminated clearly between malignant melanomas and nevi, but not between common and dysplastic nevi. Nonetheless, a portion of nevi exhibited markedly elevated telomerase activity levels without proportionally increased proliferation. This was independent of discernible morphological changes. Clinicopathological correlations showed an association between high telomerase activity and early metastatic spread in melanomas, linking telomerase to tumor biology. Our results provide arguments in favor of an occasional progression from nevi to melanomas and imply that proliferation measurements in combination with telomerase assays may help to elicit early malignant transformation that is undetectable by conventional morphology.

Adolescent↗

Chromosomal location of a Triticum timopheevii--derived powdery mildew resistance gene transferred to common wheat.

A dominant powdery mildew resistance gene introduced from Triticum timopheevii in line 146-155-T of common wheat, Triticum aestivum, was located on chromosome 6B by monosomic analysis. Restriction fragment length polymorphism (RFLP) and microsatellite analyses detected the presence of a T. timopheevii segment, translocated to chromosome 6B, with breakpoints between the loci Xpsr8/Xpsr964 on 6BS and Xpsr154/Xpsr546 on 6BL. The novel powdery mildew resistance gene, which has been designated Pm27, was shown to cosegregate with the microsatellite locus Xpsp3131, which is located on the introgressed T. timopheevii segment. The molecular data confirm the location of Pm27 on the translocated 6B chromosome.

Alleles↗

Molecular basis of artifacts in the detection of telomerase activity and a modified primer for a more robust 'TRAP' assay.

Human somatic cells have essentially no telomerase activity. Telomerase is linked to tumor genesis and is a valuable marker for malignant growth. Extreme paucity of the enzyme neccessitated development of a PCR-based assay, 'telomeric repeat amplification protocol' (TRAP). Unfortunately, this method is not without difficulties. Amplification products are not related to the size of the amplified telomerase products. Furthermore, false positive results can occur, and careful control of reaction conditions is crucial. We analyzed in detail the molecular basis of artifacts. Based on these data, reverse PCR primer was changed and both problems in the TRAP assay were eliminated.

Artifacts↗

A giant nerve net with multi-effector synapses underlying epithelial adhesive strips in the mouth of Beroë (Ctenophora).

We present ultrastructural evidence for the first known example of a giant nerve net in the phylum Ctenophora. The giant fibre system in Beroë underlies paired strips of adherent epithelial cells that run inside the lips. Interlocking actin-lined cell junctions between opposing adhesive strips keep Beroë's large mouth closed while the ctenophore searches for prey. The giant neurons, up to 6-8 microns in diameter, form a continuous lattice-like plexus rich in vesicles, microtubules, and 'presynaptic triads'. A novel feature is that individual giant axons make synaptic contacts with more than one type of effector, i.e. longitudinal muscle fibres and epithelial adhesive cells. Contact of prey with sensory receptors on the lips of Beroë induces rapid disappearance of the actin-lined adhesive cell junctions, and muscular opening of the mouth to ingest prey. Electron microscopy of food-opened mouths shows local thickening of longitudinal muscles and widening of the basal ends of epithelial cells in the adhesive strip, correlated with retraction of the adhesive epithelium into the mesoglea. Addition of 1% Triton X-100 to formaldehyde fixative in the absence of prey also elicits regional thickening of longitudinal muscles at the location of the adhesive strips (visualized by rhodamine-phalloidin staining). The giant neuron system may serve as a final common pathway to rapidly signal disassembly of actin-based junctions between adhesive cells as well as contractions of longitudinal muscles underlying the adhesive strips, thereby enabling Beroë to open its mouth rapidly to engulf prey.

Animals↗

[Conjunctival myxoma. Apropos of an anatomo-clinical case].

In the ocular area, myxoma is a benign and uncommon tumor located essentially in the lids, more rarely in the conjunctiva. We report the case of a 31-year-old male suffering from the recent growth of an epibulbar painless tumefaction located in the temporal conjunctiva. This gelatinous mass was excised and has revealed a conjunctival myxoma. Surgical excision and histopathologic examination of such epibulabar lesions are necessary because they are few malignant tumors, like botryoid rhabdomyosarcoma or fibrosarcoma, which may have a similar clinical aspect.

Adult↗

Ca2+ channels and signalling in cilia and flagella.

Ca(2+) plays a key role in the regulation of ciliary and flagellar movement. This article focuses on the initial steps of this regulation: how and where Ca(2+) enters cilia and flagella to trigger specific changes in axonemal motility. This knowledge is fundamental for understanding the sites, molecular targets and mechanisms of action of Ca(2+) within the cilium of flagellum.

Journal Article↗

[Recurrent episcleritis with hyperemia of the external ear As an early symptom of chronic polychondritis].

A 49-year-old patient with relapsing polychondritis, who presented in the first instance to an eye department, is described. The patient had episcleritis, papilloedema and posterior scleritis. Both auricles were red, swollen and tender under pressure. The patient responded well to systemic steroid therapy for two weeks. Relapsing polychondritis is a rare connective tissue disorder. Early diagnosis is important, as progressive disease may cause lesions of vital organs (lung, heart).

Cartilage Diseases↗

Mechanical properties of ciliary axonemes and membranes as shown by paddle cilia.

Cilia with a distal membrane expansion enclosing a coiled end of the axoneme (paddle cilia or discocilia) have been commonly reported in marine invertebrates. We recently showed that paddle cilia in molluscan veligers are artifacts of non-physiological conditions. Here we investigated the possible mechanisms of formation of paddle cilia under hypotonic conditions; particularly, whether a helical conformational change of doublet microtubules induced by Ca or proton flux is responsible. Typical paddle cilia are induced by hypotonic Ca-free solutions at normal or low pH, showing that axonemal coiling does not require Ca influx or proton efflux. In addition, Triton-demembranated straight axonemes do not coil in high Ca solutions. Most decisively, complete removal of paddle ciliary membranes with detergents, but not mere permeabilization, causes immediate uncoiling and straightening of the axonemes to approximately their original length before hypotonic treatment. These findings and other data show that axonemal coiling in paddles is due to membrane tensile stress acting on an elastic axoneme. Light and electron microscopy of paddles show that axonemes coil uniformly toward the direction of the effective stroke (doublets nos 5-6), even when beating is inhibited by sodium azide or glutaraldehyde before hypotonic treatment. This indicates that axonemes possess an intrinsic asymmetry of stiffness within the beat plane, independent of active microtubule sliding. Paddle cilia thus reveal important mechanical properties of ciliary axonemes and membranes that should be useful for understanding ciliary function.

Animals↗

Dynamic control of cell-cell adhesion and membrane-associated actin during food-induced mouth opening in Beroë.

We used rhodamine-phalloidin and ultrastructural methods to follow dynamic changes in adhesive cell junctions and associated actin filaments during reversible epithelial adhesion in the mouth of the ctenophore Beroë. A cruising Beroë keeps its mouth closed by interdigitated actin-coated appositions between paired strips of cells lining the lips. The mouth opens rapidly (in 0.2-0.3 s) by muscular action to engulf prey (other ctenophores), then re-seals after ingestion. We found that the interlocking surface architecture of the adhesive cells, including the actin-coated junctions, rapidly disappears after food-induced opening of the mouth. In contrast, forcible separation of the lips in the absence of food rips the junctions, still intact, from the surfaces of the cells. The prey-stimulated loss of adhesive cell junctions and associated actin cytoskeleton is one of the most rapid changes in actin-based junctions yet observed. This system provides unique experimental advantages for investigating the dynamic control of reversible cell adhesions and membrane-associated actin filaments.

Actins↗

Age-related changes of the human ciliary muscle. A quantitative morphometric study.

The age-related changes of the ciliary muscle of human eyes (33-87 years) were studied on histological meridional sections. Eighty-five melanoma eyes and 10 eyes of normal donors were investigated. The total area and the length of the muscle, the area of the three main portions and the distance of the inner apex of the muscle to the scleral spur were determined and correlated with age. Total area and length of the muscle show a continuous and significant decrease with age. The area of the longitudinal and reticular portion continuously decreases, whereas the area of the circular portion significantly increases with age. The decrease in area is more pronounced in the longitudinal portion than in the reticular portion of the muscle, which shows an age-related increase in connective tissue. In addition, the distance of the inner apex of the muscle to the scleral spur shortens continuously. Thus, with increasing age the ciliary muscle adopts an anterior-inward position. A similar form is seen in young eyes after ciliary muscle contraction only. There might be a functional relationship between the observed age-changes in the ciliary muscle system and the phenomenon of the so-called 'lens paradox' (steepening of the anterior and posterior curvatures of the disaccommodated lens with age).

Adult↗

Actin pegs and ultrastructure of presumed sensory receptors of Beroë (Ctenophora).

We have investigated the actin content and ultrastructure of two kinds of presumed sensory projections on the lip epidermis of beroid ctenophores. Transmission electron microscopy showed that conical pegs contain a large bundle of densely packed, parallel microfilaments. Rhodamine-phalloidin brightly stained the pegs, confirming that they contain filamentous actin. Epidermal cells with actin pegs also bear a single long cilium with an onion-root structure, previously described as arising from a different type of cell. The actin peg and onion-root cilium project side-by-side, defining a polarized axis of the cell which is shared by neighboring cells. The onion-root body is surrounded by a flattened membrane sac which lies immediately below the plasma membrane. The perimeter of the membrane sac is encircled by aggregates of dense material. An extra layer of dense material is found along the side of the membrane sac facing the peg; this material often makes direct contact with the adjacent actin filament bundle. Cells with actin pegs and onion-root cilia synapse onto adjacent neurites and secretory gland cells, indicating that one or both types of projections are sensory elements. Since the feeding responses of beroids are reported to depend on chemical and tactile stimuli to the lips, the cells bearing pegs and cilia may function as both mechanoreceptors and chemoreceptors, that is, as double sensory receptors.

Actins↗

Ca/Ba/Sr-induced conformational changes of ciliary axonemes.

Macrocilia of the ctenophore Beroë undergo Ca/Ba/Sr-dependent activation of ciliary beating and microtubule sliding disintegration [Tamm, J. Comp. Physiol. A163:23-31, 1988a; Tamm, Cell Motil. Cytoskeleton 11:126-138, 1988b; Tamm, Cell Motil. Cytoskeleton 12:104-112, 1989; Tamm and Tamm, Proc. Natl. Acad. Sci. U.S.A. 86:6987-6991, 1989]. Here we report that detergent-extracted macrocilia show an ATP-independent conformational change in response to high concentrations of Ca, Ba, or Sr ions. When applied locally by iontophoresis, these ions induce a rapid planar curvature of the distal end of the macrociliary shaft, followed by a slower relaxation to the rest position. Tip curling occurs in a direction opposite to the physiological Ca/Ba/Sr response. When applied uniformly in the bath, a threshold concentration of 10(-1) M Sr is required to induce curling of the tip, and the distal ends remain curved. Calmodulin antagonists do not inhibit the tip curling response. Previous workers found that Ca induces changes in the helical shape of isolated doublet microtubules [Miki-Noumura and Kamiya, Exp. Cell Res. 97:451-453, 1976; Miki-Noumura and Kamiya, J. Cell Biol. 81:355-360, 1979; Takasaki and Miki-Noumura, J. Mol. Biol. 158:317-324, 1982] and sperm axonemes [Okuno and Brokaw, Cell Motil. 1:349-362, 1981] and suggested that conformational changes in microtubules may play a role in Ca regulation of ciliary motility. We propose that the Ca/Ba/Sr-induced curling of the macrociliary tip is due to similar helical changes of doublet microtubules, some of which in macrocilia are prevented from sliding by permanent connections (compartmenting lamellae) between adjacent axonemes within the shaft. Although the tip curling response does not appear to be directly relevant to the physiological Ca response of macrocilia, it provides a novel system for investigating Ca-induced conformational changes of microtubules independent of dynein-powered active sliding.

Adenosine Triphosphate↗

Calcium sensitivity extends the length of ATP-reactivated ciliary axonemes.

We use the Ca-dependent activation response of macrocilia of the ctenophore Beroë to map the distribution of Ca sensitivity along axonemes of detergent-extracted ATP-reactivated models. Local iontophoretic application of Ca (or Sr or Ba) to any site along the length of demembranated macrocilia in ATP-Mg solution elicits oscillatory bending. Bending responses are localized to the site of application of these cations and do not propagate. Ca sensitivity for initiating bends is, therefore, distributed along the entire length of the axonemes. Since Ca triggers ATP-dependent microtubule sliding disintegration of macrociliary axonemes, a Ca-sensitive mechanism for activating microtubule sliding extends the length of the axonemes. In contrast, local application of Ca to living dissociated macrociliary cells elicits beating only when applied to the base of the macrocilium, indicating that the effective site of Ca entry is localized to the membrane at the ciliary base. Therefore, the spatial distributions of membrane Ca permeability and axonemal Ca sensors do not coincide.

Actins↗

Extracellular ciliary axonemes associated with the surface of smooth muscle cells of ctenophores.

We describe the first example of bare ciliary axonemes existing outside eukaryotic cells. The axonemes run in longitudinal invaginations of the surface membrane of giant smooth muscle cells in ctenophores. No motility of the surface-associated axonemes has been detected in living muscles. The axonemes are truly extracellular and in direct contact with the extracellular matrix (mesoglea), as shown by the ultrastructural tracer horseradish peroxidase. The axonemes appear partially degraded and disorganized, and individual doublet microtubules are difficult to distinguish. Nevertheless, immunofluorescence microscopy shows that the axonemes retain antigenic sites reacting with mouse monoclonal anti-beta-tubulin. The origin of the extracellular axonemes is unknown: no attached basal bodies (extracellular or intracellular) have been found. The muscle-associated axonemes may play a unique role in smooth muscle function and/or development, and may be related to the evolution of muscle cells in soft-bodied invertebrates that exploit cilia for a wide variety of functions.

Animals↗

Development of macrociliary cells in Beroë. I. Actin bundles and centriole migration.

Differentiation of macrociliary cells on regenerating lips of the ctenophore Beroë was studied by transmission electron microscopy. In this study of early development, we found that basal bodies for macrocilia arise by an acentriolar pathway near the nucleus and Golgi apparatus, in close association with plaques of dense fibrogranular bodies. Procentrioles are often aligned side-by-side in double layers with the cartwheel ends facing outward toward the surrounding plaques of dense granules. Newly formed basal bodies then disband from groups and develop a long striated rootlet at one end. At the same time, an array of microfilaments arises in the basal cytoplasm. The microfilaments are arranged in parallel strands oriented toward the cell surface. The basal body-rootlet units are transported to the apical surface in close association with the assembling actin filament bundle. Microfilaments run parallel to and alongside the striated rootlets, to which they often appear attached. Basal body-rootlet units migrate at the heads of trails of microfilaments, as if they are pushed upwards by elongation of their attached actin filaments. Near the apical surface the actin bundle curves and runs below the cell membrane. Newly arrived basal body-rootlets tilt upwards out of the microfilament bundle to contact the cell membrane and initiate ciliogenesis. The basal bodies tilt parallel to the flat sides of the rootlets, and away from the direction in which the basal feet point. The actin bundle continues to enlarge during ciliogenesis. These results suggest that basal body migration may be driven by the directed assembly of attached actin filaments.

Actins↗

Development of macrociliary cells in Beroë. II. Formation of macrocilia.

Two patterns of macrociliary growth occur in Beroë. Early differentiation described previously (Tamm & Tamm, 1988) leads to the first pattern of ciliogenesis. A tuft of 10-20 single cilia initially grows out from basal bodies that have migrated to the cell surface and are axially aligned. Ciliary membranes then begin to fuse along their length, except at the base, resulting in thicker groups of cilia on each cell. Progressive fusion of ciliary membranes, together with addition and elongation of new axonemes, finally results in mature macrocilia, 5 microns thick and 40 microns long, enclosed by a single membrane distally. The second pattern of ciliogenesis begins with the simultaneous appearance of several hundred ciliary buds on the apical surface. The short cilia possess individual membranes with bulbous tips, and are not axially aligned. Subsequent elongation is accompanied by progressive fusion of neighbouring ciliary membranes, except at the base, leading to flat-topped 'stumps' surrounded by a single membrane distally. Further elongation then proceeds asymmetrically within each stump. Axonemes on the aboral side of the macrocilium stop elongating, while those towards the oral side increase progressively in height, resulting in a slanted profile. Basal feet and central-pair microtubules are now uniformly aligned. Unequal elongation of axonemes on the oral and aboral sides of the macrocilium continues until the macrocilium resembles a lobster's claw, with a long slender shaft projecting from a broad base. Finally, the polarity of unequal growth reverses: the shorter axonemes on the aboral side elongate and almost catch up with the longer ones on the opposite side, resulting in a mature macrocilium of uniform diameter. The unusual membrane architecture of the macrocilium is thus a consequence of selective fusion of the distal regions of originally separate ciliary membranes. The polarized, asymmetrical growth of axonemes on the two sides of the macrocilium illustrates a remarkable control of microtubule elongation at the subcellular level.

Animals↗

Massive actin bundle couples macrocilia to muscles in the ctenophore Beroë.

Macrocilia are thick compound ciliary organelles arising individually from elongated epithelial cells on the lips of beroid ctenophores. A giant wedge-shaped bundle of microfilaments extends 25-30 microns from the base of each macrocilium to the lower end of the cell, terminating at a junction with an underlying smooth muscle cell. The broad end of the microfilament bundle is anchored to the macrocilium by striated rootlet fibers that extend from the basal bodies into the bundle and are linked to the microfilaments by periodic bridges. Fluorescence microscopy of rhodamine-phalloidin stained intact tissue, dissociated macrociliary cells, and Triton/glycerol-isolated bundles shows that the microfilaments contain actin. The microfilaments run generally parallel to the long axis of the bundle but are not highly ordered. Filaments decorated with myosin S1 show a uniform polarity with arrowheads pointing away from the tapered membrane-associated end of the bundle. No variations in bundle length (nor changes in rootlet periodicity) were observed in tissue fixed under conditions of calcium activation. Isolated bundles did not contract in Mg-ATP, even though detached macrocilia underwent reactivated beating and sliding disintegration. Macrocilia are used to bite through food organisms or transport prey into the stomach. The actin filament bundles probably play a supporting role as a structural linker between macrocilia and subepithelial muscle fibers and may serve as intracellular tendons to mechanically coordinate the motor activities of macrocilia and muscles during prey ingestion.

Actins↗

Visualization of changes in ciliary tip configuration caused by sliding displacement of microtubules in macrocilia of the ctenophore Beroë.

Macrocilia from the lips of the ctenophore Beroë consist of multiple rows of ciliary axonemes surrounded by a common membrane, with a giant capping structure at the tip. The cap is formed by extensions of the A and central-pair microtubules, which are bound together by electron-dense material into a pointed projection about 1.5 micron long. The tip undergoes visible changes in configuration during the beat cycle of macrocilia. In the rest position at the end of the effective stroke (+30 degrees total bend angle), there is no displacement between the tips of the axonemes, and the capping structure points straight into the stomach cavity. In the sigmoid arrest position at the end of the recovery stroke (-60 degrees total bend angle), the tip of the macrocilium is hook-shaped and points toward the stomach in the direction of the subsequent effective stroke. This change in tip configuration is caused by sliding displacement of microtubules that are bound together at their distal ends. Electron microscopy and two-dimensional models show that the singlet microtubule cap acts as if it were hinged to the ends of the axonemes and tilted to absorb the microtubule displacement that occurs during the recovery stroke. The straight and hooked shapes of the tip are thought to help the ctenophore ingest prey.

Animals↗