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Biomedical subjects

M A Sleigh

Publications and source records attributed to M A Sleigh.

At least 19 recordsLinked to original sources
PubMed1995

Progress in understanding the phylogeny of flagellates.

Heterotrophic free-living flagellates appear to provide the ancestry for all other eukaryote groups. Not only are the oldest surviving anaerobic eukaryotes flagellated protists, but also there appear to be survivors of a lineage of flagellate forms which could have been close to the sources of the main branches of eukaryote evolution. These 'stem' forms of flagellates developed more complex flagellation with anchoring fibres which became the main components of the cytoskeleton and supported the cytostome; by their phagotrophic activities these flagellates established symbiotic relationships, first with aerobic bacteria to form mitochondria, and later with various forms of prokaryotic and eukaryotic algal cells to form chloroplasts of a variety of types having different pigments, different structure and different food storage patterns. The specific patterns of flagellation, cytoskeleton, cytostome, secreted surface structures and cell aggregation into colonies enable groups of organisms to be recognised, whose most primitive survivors in almost all cases are heterotrophic flagellates. The current view of the phylogeny of eukaryotes suggests that heterotrophic flagellates have provided the origins of all major eukaryote groups, and that the phylogeny of these flagellates is the key to understanding the evolution of all eukaryotes. We anticipate that further rRNA analyses, supported by ultrastructural data, will confirm the central role played by these flagellates in eukaryote evolution.

Animals↗
PubMed1993

Rapid method for cell cycle analysis in a predatory marine dinoflagellate.

Oxyrrhis marina (Dujardin) is a predatory marine dinoflagellate that feeds phagocytically on live phytoplanktonic "prey" cells from the surrounding environment. A rapid method was developed to separate the cell cycle characteristics of these predators from their prey cells in order to study the cell cycle dynamics of this organism. Nuclei from Oxyrrhis were isolated in low salt buffer (PBS) using detergent and mechanical agitation and the DNA stained with Hoechst 33258 in a one step procedure. The method permitted the isolation of nuclei from the Oxyrrhis cells with > 95% efficiency. Discrimination between prey cell nuclei and those of Oxyrrhis was achieved during flow cytometric analysis which yielded routinely G1 CVs of 3-6% for exponentially growing cell populations and 2-3% for stationary phase cells. The method was used to demonstrate the changes in cell cycle dynamics during the exponential and stationary phases of growth. Results indicated that in contrast to most mammalian and phytoplankton cell types Oxyrrhis spent the major portion (ca. 50%) of its cell cycle in G2 + M when actively dividing. Analysis of stationary phase populations also suggests that specific cell cycle control (or restriction) points were present in both G1 and G2 in this species.

Animals↗
PubMed1990

Ciliary adaptations for the propulsion of mucus.

The cilia that propel mucus are specialised for the function in their arrangement, length, some details of structure, beat pattern, beat cycle characteristics, metachronal coordination, local control of beat rate by response to mechanical stimulation and generalised control of beat rate by neurohormones. These features are matched to the properties of the visco-elastic mucus gel that is propelled at the ciliary tips above a low-viscosity periciliary layer whose depth must be regulated within defined limits.

Animals↗
PubMed1989

Adaptations of ciliary systems for the propulsion of water and mucus.

1. The characteristics of ciliary systems are determined by the dominance of viscous effects over inertial effects. 2. The velocity of water propulsion depends on ciliary length, beat frequency, pattern of beating, the arrangement of the cilia and their co-ordination. Beating cilia influence a layer of water only two or three cilium lengths deep, with maximal velocity near the ciliary tip. 3. Mucus is propelled by the tips of short cilia that penetrate the mucus; these cilia are closely spaced on epithelia, and achieve slow propulsion that is relatively independent of load and does not require strong ciliary co-ordination.

Animals↗
PubMed1988

Flagellar root maps allow speculative comparisons of root patterns and of their ontogeny.

A method of mapping the patterns of origin of flagellar roots around basal bodies in two-dimensional diagrams is suggested, making allowance for the varied orientations of members of a pair or quartet of basal bodies in a cell. The method is used to compare flagellar root patterns in a wide range of protistan groups, and appears to demonstrate similarities in many areas. Comparison of such patterns in three published examples shows that during the ontogeny of a basal body it may display first one root pattern and then another, so that the root array of a given basal body is not fixed but changes with the position and role of that basal body in the cell.

Animals↗
PubMed1988

The propulsion of mucus by cilia.

The presence of cilia on epithelia of the respiratory tract was reported more than 150 yr ago, and the two-layer model of mucus transport was put forward more than 50 yr ago. However, it is only in the last 10 yr or so that the motion of mucus-propelling cilia of the mammalian respiratory system has been adequately described, and fluid dynamic studies have developed far enough to allow descriptions of the mechanisms by which ciliary movement is coupled to mucus transport. In this review, scientific developments on the study of cilia and mucus, and interactions between them, are drawn together to further understanding of mucociliary clearance mechanisms of the respiratory tract. The study of the cilia incorporates a discussion of the internal mechanics and biochemistry of the ciliary axoneme, the physical principles of the beat pattern, and the (weak) metachronal coordination of cilia in the lung. Mucus rheology plays a central role in mucociliary transport with the rheologic properties of the mucus determining the effective functioning of this clearance mechanism. Theoretical models provide information on the mechanical principles of the beat pattern as well as providing reliable estimates of the transport rates. Although airflow is not thought to contribute to mucus transport in the normal state, high frequency ventilation and coughing may make significant contributions.

Animals↗
PubMed1984

The effects of serum immunoglobulins on the metachronal coordination of the lateral cilia of Mytilus edulis.

Human IgM and a bovine, IgM-enriched serum fraction isolated from normal adult serum at concentrations of 0.25-1 mg/ml protein induced a pronounced increase in the metachronal wavelength of the lateral (L) cilia of the sea mussel Mytilus edulis without altering their beat frequency. This change in activity was indistinguishable from that induced by 50% adult human or bovine serum. At protein concentrations ranging from 1-9 mg/ml, human IgG or a bovine, IgG-enriched serum fraction had no or little effect on the activity of the L cilia. Similarly, neither monomeric (8S) human IgM (0.25 mg/ml) nor monospecific pentameric IgM (1 mg/ml) isolated from Waldenström's macroglobulinemia patients altered the metachrony of the L cilia. Indirect immunofluorescence demonstrated that both bovine and human IgM became attached almost exclusively to the L cilia, while very little bovine or human IgG was found to associate with these cilia. The results of this study suggest that serum IgM specifically binds to the L cilia of Mytilus in an antigen-antibody manner and agglutinates adjacent cilia into blocks or bundles, thereby increasing the coupling between cilia. As a result, the wavelength of the metachronal coordination is increased. The origin of these ciliary antibodies and their significance to ciliary bioassays used to monitor serum for the detection of cystic fibrosis are discussed.

Animals↗
PubMed1983

Kartagener's syndrome, ciliary defects and ciliary function.

The several genetically-determined structural defects of cilia that cause ineffective mucociliary clearance in Kartagener's syndrome and related diseases (for which the group name Primary Ciliary Dyskinesia is thought most appropriate) are compared with structural defects of flagella of mutant Chlamydomonas, about which biochemical information is also available. This comparison suggests that the effective activity of several or many genes may be essential for formation of each of the major components of the ciliary axoneme, and that Primary Ciliary Dyskinesia may result if a patient is homozygous for ineffective genes at any one of these gene loci. However, the mutants often appear to be "leaky", with incomplete effects; in addition, structural abnormalities of human cilia are relatively common in apparently normal individuals. The relationship of axonemal defects to disorientation of ciliary bases is questioned and the possibility is raised that such disorientation may result from morphogenetic disturbances through infection rather than from genetic origins.

Chlamydomonas↗
PubMed1983

Ciliary function in transport of mucus.

Mucus is propelled by short cilia which rest during each beat cycle. Cilia move from rest by bending sideways and backwards through a recovery stroke in which they keep near the cell surface. This is followed by an effective stroke, in a plane nearly perpendicular to the cell surface, which ends with the cilium bent over in its rest position and with its tip pointing in the direction of propulsion. The cilium moves in a layer of periciliary fluid whose depth is a little less than the ciliary length, so that the overlying mucus is only penetrated by the ciliary tips in the effective stroke. The thickness of the periciliary layer is critical for effective propulsion of mucus. The cilia are coordinated by visco-mechanical interaction between the moving units to produce short oblique metachronal waves which pass across a few ciliated cells before dying away. Many small areas of independently coordinated activity collaborate to propel the overlying mucus. The activity of the cilia can respond to the load of mucus and control of ciliary rate may be exerted indirectly by varying the load rather than by any direct neural mechanism.

Animals↗
PubMed1982

How are different ciliary beat patterns produced?

In this paper, the generation of different patterns of beat is discussed in terms of the internal mechanism of the cilia. A simple classification is proposed for the wide variety of patterns of planar beating. Ctenophore comb plates can show four types of movement: arrest, reverse beating, flagellar beating and forward beating. Other types of cilia show several or all of these beat patterns. Following stimulation of the organism these different beat patterns occur in a definite sequence which is the same in all cases. There is some evidence in each example that change in beating activity from the normal pattern towards the arrest or reversal response is associated with an increase in intraciliary Ca2+ concentration, and it is suggested that the sequence normal ciliary beat leads to symmetrical flagellar beat leads to reverse ciliary beat leads to active arrest represents the response of the axoneme mechanism to progressively increasing levels of intraciliary Ca2+ concentration, different patterns of beat resulting from different patterns of activation of the dynein arms within the axoneme.

Animals↗
PubMed1981

Flagellar beat patterns and their possible evolution.

The roles of flagella and their functioning in unicellular organisms of various groups are described. Water propelled around a cell by the flagellum may cause locomotion of the cell and may bring near to the cell food particles that can be filtered from the water and phagocytosed. For purpose of locomotion alone, a relatively simple flagellar activity is adequate, but the efficient collection of particulate food requires modification of the flagellar activity or of the cell organization or both. The most sophisticated flagellar mechanisms are best explained as having been evolved for the collection of particulate food, although they may occur in groups that are now predominantly or entirely autotrophic. This is consistent with the view that heterotrophic flagellates requiring efficient particle collection for feeding evolved divergent flagellar mechanisms, based upon various structural patterns, and that only later did some of these divergent groups acquire their own particular types of plastid, presumably following phagotrophic uptake of the appropriate type of photosynthetic prokaryote and the establishment of a symbiotic association.

Animals↗
PubMed1981

Serum proteins agglutinate cilia and modify ciliary coordination.

A quantifiable assay is described in which the lateral cilia of the sea mussel Mytilus edulis are used to examine the effects of serum on ciliary function. Human sera and sera from a variety of animals have been found to induce a change in ciliary metachrony. This alteration in activity appears to be brought about by the agglutination of adjacent cilia into blocks, with the effect of increasing the wavelength; the beat frequency remains steady. Parallel studies with the rabbit cilia assay have shown the agglutination of tracheal cilia into clumps by adult bovine serum. The dilution of adult bovine serum lengthens the time before dyskinesia is first observed in both the Mytilus and rabbit assays. Fetal bovine or human cord sera do not cause ciliary dyskinesia or ciliary agglutination. The evidence presented shows that the observed ciliary dyskinesia can be induced by sera from a variety of animals and is not specific to cystic fibrosis; it also suggests that the serum immunoglobulin fraction is responsible for these effects--initial studies implicate IgM.

Adult↗
PubMed1981

Ciliary activity of cultured rabbit tracheal epithelium: beat pattern and metachrony.

The beat pattern of rabbit tracheal cilia has been investigated using high-speed cine photography and scanning electron microscopy, on cultured epithelia of known orientation. The cilia normally rest in the position reached at the end of the effective stroke, the ciliary tips pointing towards the oropharynx. Each beat begins with a recovery (or preparative) stroke in which a bend is propagated up the cilium causing the cilium to rotate backwards in a clockwise sweep, as viewed from above. At the end of its recovery stroke the cilium progresses immediately into the effective (or power) stroke, which is almost planar and in a cephalad direction. The active cilium describes an arc of almost 110 degrees before reaching the rest stage. This beat pattern is not significantly altered over an increase in frequency from 13-29 Hz; the relative duration of the 2 active phases of the beat remain similar over this range. Metachronal waves exist in the form of short erratic areas of coordinated beating which travel only short distances. Within each area, the non-planar recovery strokes initiate an antilaeoplectic wave of activity which recruits inactive cilia to extent the wave. As cilia perform their effective strokes, adjacent cilia in the plane of beating move in an antiplectic sequence. This pattern of coordination is related to the pattern of beat of the cilia and their distribution on the epithelium.

Animals↗
PubMed1979

Freeze substitution for preservation of ciliated surfaces for scanning electron microscopy.

A technique is described for arresting rapid movement of living cells and preserving their fine surface structures for scanning electron microscopy. Rapid freezing is recommended as the method of immobilization and freeze substitution has been employed to fix and dehydrate the specimens; this technique is more reliable than osmium fixation, both in terms of obtaining a much higher proportion of good results and in the improved preservation of detail. Various techniques of substitution have been investigated for best preservation, and the roles of the constituents of the substitution mixture have been discussed.

Alcohols↗