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At least 1,297 records · Page 72Linked to original sources
PubMed1997

Synaptic body movements in the sensory cells of lateral line organs in the urodele amphibian Ambystoma mexicanum.

Examination of the neuromasts in the tail of the living juvenile axolotl Ambystoma mexicanum with interference contrast (Nomarski) microscopy shows that their cellular structures can be identified in considerable detail. Microscopy was performed with a 40 x water immersion objective or with a 100 x objective in a tail insertion chamber. Thus the sensory hair bundles can be seen and their orientation can be determined. Large spheres in the basal part of the sensory cells were predicted to be synaptic bodies. Subsequent examination in the transmission electron microscope of the cells observed in the light microscope confirmed this notion. Inspection during periods of several hours reveals definite movements of the synaptic bodies.

Ambystoma mexicanum↗
PubMed1997

Basilar membrane velocity noise.

Basilar membrane (BM) noise, measured as a velocity signal under the quiet acoustic condition, was investigated in the guinea pig. The cochleas of anesthetized young healthy guinea pigs were surgically exposed and a hole was made on the lateral wall of the scala tympani of the first cochlear turn for visualization of the BM and measurement of the BM velocity with a laser interferometer. The amplitude and frequency of the BM velocity noise were analyzed by a spectrum analyzer under different conditions. The spectrum of the BM velocity noise was a band limited function with a peak velocity at the topographic best frequency of the measured location on the BM. The peak velocity ranged to about 8 microm/s and depended on the physiological condition of the cochlea. Saline blockage of the external auditory canal or the middle ear did not change the BM noise. BM noise was much smaller, or was not evident, when the cochlear sensitivity decreased. The suppression tuning curve of the BM velocity noise indicates that the maximum suppression caused by an acoustic pure tone occurred at the best frequency location. A low sound level wide band acoustic noise given to the external ear canal produced a spectrum function having the same frequency and amplitude response as the BM noise. Electrical stimulation of the crossed olivocochlear bundle significantly depresses the BM velocity noise. These data demonstrate that the BM noise is a representation of internal rather than external noise. The amplitude and frequency of the BM noise reflect the usual cochlear sensitivity and frequency selectivity. Since the organ of Corti in the sensitive cochlea is a highly sensitive and tuned mechanical system, the internal (to the animal) noise responsible for the BM noise may originate from mechanical vibrations remote from the cochlea and propagated to the ear, or may be caused by Brownian motion of cellular structures in the cochlea.

Acoustic Stimulation↗
PubMed1999

Distortion product otoacoustic emissions and outer hair cell defects in the hyt/hyt mutant mouse.

Thyroid hormone plays an important role in hearing development. Hereditary hypothyroidism is frequently associated with sensorineural hearing loss as identified in both animal models and human patients. Building upon our original demonstration of congenital deafness and hair cell abnormality in a hyt/hyt mouse model which carries an autosomal recessive mutation causing hereditary hypothyroidism, we investigated the functional capacity of the outer hair cell (OHC) system in these animals using distortion product otoacoustic emissions (DPOAEs). In particular, the amplitude and detection features of DPOAEs were correlated with measures of the auditory brainstem response (ABR) as well as the cellular structure and ultrastructure of the organ of Corti. Input-output (I/O) functions for the 2f(2)-f(1) DPOAEs were obtained for frequencies from 2 to 18 kHz. The thresholds were significantly higher and amplitudes were significantly lower in the homozygous mice (hyt/hyt) than in both heterozygous mice (hyt/+) and wild-type controls at DPOAE frequencies recorded above 6 kHz. Hearing thresholds were significantly elevated in the mutant compared to control mice. In addition, morphological studies revealed consistent inner ear defects in hyt/hyt animals including distortion of the tectorial membrane, dysplasia of the tunnel of Corti and distinct OHC abnormalities. The most striking histopathological finding was a contiguous membrane along the apices of all of the OHC stereocilia. Such ultrastructural changes in the stereocilia of the OHC may limit the deflection of the stereocilia and therefore affect an active cochlear function that produces otoacoustic emissions as well as cause a failure to evoke the normal action potentials in the auditory nerve. From both functional and morphologic evaluations, it was concluded that the OHC system is the most susceptible to the developmental effects of congenital hypothyroidism in the hyt/hyt mouse. The normal OHCs with well-developed ciliary bundles are crucial to maintain the activity of biological mechanisms within the cochlea.

Animals↗
PubMed2001

Morphological and functional differentiation of human thyroid cells in collagen gel culture.

OBJECTIVE: Cultured human thyroid cells in collagen gel culture were examined on cell morphology and the production of thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4) which are components of functional differentiation. METHODS: Thyroid cells obtained from normal human thyroid tissues (four cases), follicular adenoma tissues (three cases), papillary carcinoma tissues (three cases), and follicular carcinoma tissue (one case), were cultured in collagen gel. Then these cultured cells were observed on cellular morphology and production of Tg, T3 and T4. Moreover, changes in morphological characteristics and production of Tg, T3 and T4 induced by addition of thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) to medium in collagen gel culture were determined. RESULTS: Normal and tumor cells in collagen gel culture formed colonies and follicles with Tg production, similar to in vivo-like three-dimensional cellular structures and functions. Normal thyroid cells stimulated TSH induced more Tg and produced morphological changes, i.e. enlarged follicular lumens and increased the height of follicular cells, but did not promote cell proliferation. Reversely, normal thyroid cells stimulated with EGF promoted cell proliferation, but did not change morphological findings and did not increase production of Tg, T3 and T4. CONCLUSIONS: These findings suggest that collagen gel culture is useful for observing the effects of stimulation by cell growth factor on the morphological and functional differentiation of human thyroid cells.

Cell Differentiation↗
PubMed2001

Ultrastructural study of rat hippocampus after chronic administration of aluminum L-glutamate: an acceleration of the aging process.

An ultrastructural study of rat hippocampus was performed on young (group 1) and old (group 4) rats receiving daily subcutaneous injections of aluminum L-glutamate and on old untreated rats (group 5). Young controls were treated with sodium L-glutamate (group 2) and physiological saline (group 3). Group 1 showed vacuolated astrocytes with numerous lipofuscin deposits, mitochondrial swelling, a thinning of the myelin sheath, and many multivesicular bodies invading the cytoplasm. Cellular structure did not appear to be affected in groups 2 and 3. Group 4 showed swollen mitochondria, a demyelination process in axonal regions, sizable perivascular oedema with vessel retraction and gliofilament bundles. In this group, lipofuscin deposits in astrocytes were associated with multivesicular bodies that thinned the myelin sheath to the breaking point; however, no excitotoxic glutamate-induced effects were observed. In group 5, extreme cytoplasmic vacuolation was observed, with massive mitochondrial swelling, considerable thinning of the myelin sheath (at times to the breaking point), sizable vacuolar degeneration and gliofilament bundles. These results indicate that ultrastructural alterations in the hippocampus, such as cell vacuolization, massive mitochondrial swelling and the demyelination process, occur with aging and independently of aluminum intoxication. Similar alterations were observed in aluminum L-glutamate-intoxicated young rats, but not in controls. These results are consistent with aluminum-induced acceleration of the aging process.

Aging↗
PubMedDate not supplied

Dietary vitamin E and T cell-mediated function in the elderly: effectiveness and mechanism of action.

One of the most dramatic and consequence-bearing age-related phenomena is the decline of the immune function with old age. Age-related T cell-mediated immunity dysfunction has been implicated in the etiology of many of the chronic degenerative diseases of the elderly, including arthritis, cancer, autoimmune diseases and increased susceptibility to infectious diseases. T cells from aged individuals are impaired in their response to mitogens and in their cytokine production. In recent years, several studies have emphasized the importance of intracellular anti-oxidant levels for preserving the immune function. Recent progress in understanding the mechanisms of action of anti-oxidants on cellular metabolism, have shown that anti-oxidants may modulate signal transduction and gene expression in immune cells. Vitamin E is widely recognized as a major lipid-soluble chain-breaking anti-oxidant in the biological membrane, where it scavenges free radicals, inhibiting the initiation and chain propagation of lipid peroxidation and protecting cellular structures against oxidative stress damage. Experimental studies have provided evidences for a role of vitamin E in protecting the immune system of elderly subjects. This article reviews the studies concerning the effect of both vitamin E deficiency and supplementation on T cell-mediated immune function in aging. Following a chronological pathway, the present article will also discuss the knowledge regarding the underlying mechanism of action of vitamin E.

Aged↗
PubMed2002

Peroxynitrite signaling: receptor tyrosine kinases and activation of stress-responsive pathways.

Peroxynitrite, generated for example in inflammatory processes, is capable of nitrating and oxidizing biomolecules, implying a considerable impact on the integrity of cellular structures. Cells respond to stressful conditions by the activation of signaling pathways, including receptor tyrosine kinase-dependent pathways such as mitogen-activated protein kinases and the phosphoinositide-3-kinase/Akt pathway. Peroxynitrite affects signaling pathways by nitration as well as by oxidation: while nitration of tyrosine residues by peroxynitrite modulates signaling processes relying on tyrosine phosphorylation and dephosphorylation, oxidation of phosphotyrosine phosphatases may lead to an alteration in the tyrosine phosphorylation/dephosphorylation balance. The flavanol (-)-epicatechin is a potent inhibitor of tyrosine nitration and may be employed as a tool to distinguish signaling effects due to tyrosine nitration from those that are due to oxidation reactions.

Animals↗
PubMed1998

Generation of superoxide anion by mitochondria and impairment of their functions during anoxia and reoxygenation in vitro.

A small portion of the oxygen consumed by aerobic cells is converted to superoxide anion at the level of the mitochondrial respiratory chain. If produced in excess, this harmful radical is considered to impair cellular structures and functions. Damage at the level of mitochondria have been reported after ischemia and reperfusion of organs. However, the complexity of the in vivo system prevents from understanding and describing precise mechanisms and locations of mitochondrial impairment. An in vitro model of isolated-mitochondria anoxia-reoxygenation is used to investigate superoxide anion generation together with specific damage at the level of mitochondrial oxidative phosphorylation. Superoxide anion is detected by electron paramagnetic resonance spin trapping with POBN-ethanol. Mitochondrial respiratory parameters are calculated from oxygen consumption traces recorded with a Clark electrode. Respiring mitochondria produce superoxide anion in unstressed conditions, however, the production is raised during postanoxic reoxygenation. Several respiratory parameters are impaired after reoxygenation, as shown by decreases of phosphorylating and uncoupled respiration rates and of ADP/O ratio and by increase of resting respiration. Partial protection of mitochondrial function by POBN suggests that functional damage is related and secondary to superoxide anion production by the mitochondria in vitro.

Adenosine Diphosphate↗
PubMed1997

Surface vesicles: a possible function in commensal relations of Bacteroides fragilis.

Surface vesicles (SV) defined by electron microscopy as outer membrane (OM) extrusions were detected in Bacteroides fragilis strains from distinct sources. A partial identity between SV and OM electrophoretic protein profiles, in addition to the microscopic analysis, may suggest the designation of OMSV. Sialidase activity, a virulence determinant, was associated with these sub-cellular structures in all the strains, but in an inverse relation to the vesicle quantity per cell. A commensal strain, previously defined as avirulent in an animal model, presented the lowest vesicle-associated sialidase activity and the greatest SV expression as opposed to what happened with clinical and environmental strains. These results seem to suggest that these surface components have a function in commensal stages of B. fragilis.

Bacterial Outer Membrane Proteins↗
PubMed2003

Self-organisation and forces in the microtubule cytoskeleton.

Modern microscopy techniques allow us to observe specifically tagged proteins in live cells. We can now see directly that many cellular structures, for example mitotic spindles, are in fact dynamic assemblies. Their apparent stability results from out-of-equilibrium stochastic interactions at the molecular level. Recent studies have shown that the spindles can form even after centrosomes are destroyed, and that they can even form around DNA-coated beads devoid of kinetochores. Moreover, conditions have been produced in which microtubule asters interact even in the absence of chromatin. Together, these observations suggest that the spindle can be experimentally deconstructed, and that its defining characteristics can be studied in a simplified context, in the absence of the full division machinery.

Animals↗
PubMed2003

Gene selection in microarray data: the elephant, the blind men and our algorithms.

Gene expression array data provide shadows of intricate cellular processes. Learning how to make the most of the information present in expression arrays has become a discipline in itself. In recent years, there has been an explosion of methods that analyze gene expression arrays to produce long lists of genes that express differentially in distinct cellular states. These lists will have to be organized, and the algorithms that produced them combined, if we wish to piece together the rich cellular structures probed by this high-throughput technology. Researchers will have to understand the benefits and limitations of the many existing methods to produce the combination of algorithms that best suits their gene expression experiments.

Algorithms↗
PubMed2002

Calponin h1 induced a flattened morphology and suppressed the growth of human fibrosarcoma HT1080 cells.

Calponin h1 (CNh1) is an actin-binding protein that is expressed mainly in smooth muscle cells and is known to regulate smooth muscle contraction. Recently, re-expression of CNh1 in leiomyosarcoma cell lines is reported to suppress cell proliferation and tumorigenicity. However, little is known about the associated cellular structural and functional changes. Since CNh1 is also detected in normal fibroblasts, we hypothesised that CNh1 would also inhibit cell proliferation of the fibrosarcoma cells, HT1080, in which CNh1 is suppressed. An expression vector of human CNh1 complementary DNA was transfected into human HT1080 cells by a calcium-phosphate precipitation method. CNh1-transfected cells exhibited a flattened morphology with organised actin filaments, a significant decrease in cell motility and enhancement in adhesion to fibronectin in association with an increase in integrin alpha5beta1 expression. Anchorage-independent growth and tumorigenicity in nude mice were suppressed in the CNh1-transfected cells. Our results suggest that CNh1 may have a role as a tumour suppressor in human fibrosarcoma by influencing cytoskeletal activities.

Animals↗
PubMed1997

Cell polarity: par for the polar course.

The nematode PAR-1 gene is required for asymmetric cell divisions during development. Recently identified mammalian Par-1 homologues are kinases that phosphorylate microtubule-associated proteins; their overexpression disrupts the microtubule cytoskeleton, and alters cellular structure and organization.

Animals↗
PubMed1998

Fluorescent speckle microscopy, a method to visualize the dynamics of protein assemblies in living cells.

Fluorescence microscopic visualization of fluorophore-conjugated proteins that have been microinjected or expressed in living cells and have incorporated into cellular structures has yielded much information about protein localization and dynamics [1]. This approach has, however, been limited by high background fluorescence and the difficulty of detecting movement of fluorescent structures because of uniform labeling. These problems have been partially alleviated by the use of more cumbersome methods such as three-dimensional confocal microscopy, laser photobleaching and photoactivation of fluorescence [2]. We report here a method called fluorescent speckle microscopy (FSM) that uses a very low concentration of fluorescent subunits, conventional wide-field fluorescence light microscopy and digital imaging with a low-noise, cooled charged coupled device (CCD) camera. A unique feature of this method is that it reveals the assembly dynamics, movement and turnover of protein assemblies throughout the image field of view at diffraction-limited resolution. We found that FSM also significantly reduces out-of-focus fluorescence and greatly improves visibility of fluorescently labeled structures and their dynamics in thick regions of living cells. Our initial applications include the measurement of microtubule movements in mitotic spindles and actin retrograde flow in migrating cells.

Animals↗
PubMed2000

Speckle microscopy: when less is more.

Fluorescent speckle microscopy is a new and simplified method for generating fiduciary marks on cellular structures. It promises to become the method of choice for studying polymer movement and dynamics in vivo.

Actin Cytoskeleton↗
PubMed1998

Discovering the poles in yeast.

How cells generate and orientate polarized growth is of fundamental importance to understanding cell morphogenesis. The budding yeast Saccharomyces cerevisiae and the distantly related fission yeast Schizosaccharomyces pombe have both been used for genetic analysis of cell morphogenesis. Generation and maintenance of their cell shape require the formation of polarized growth sites and the correct localization of these growth sites on the cell surface with respect to other cellular structures. In this review, the authors discuss and compare the mechanisms used by the two yeasts to achieve polarized growth.

Cell Polarity↗
PubMed2002

Lessons from constitutively active mutants of G protein-coupled receptors.

In the past decade, the concept of constitutive activity has profoundly modified our understanding of G protein-coupled-receptors (GPCRs). Here, we review the contribution of constitutively active mutants (CAMs) to our understanding of three aspects of GPCR physiopathology: (1) GPCR activation is a complex mechanism involving both the release of inactive state conformational constraints, mimicked by most CAMs, and the creation of new interactions that stabilize the active state and are mimicked by a restricted set of CAMs; (2) GPCR phosphorylation, internalization and desensitization processes are activated by receptor conformations, which partly overlap those activating G protein; (3) natural CAMs, mostly affecting GPCRs of the endocrine system, are found in several hereditary and acquired diseases, including cancers. One major remaining question is how CAMs recapitulate the different structural modifications of the agonist-induced active conformation(s) of the wild-type receptor. This characterization is a prerequisite for further use of CAMs as ligand-free models of active GPCRs in structural, cellular and physiological studies.

Amino Acid Sequence↗
PubMed1995

The heterogeneity of vesicular acetylcholine storage in cholinergic nerve terminals.

The vesicular hypothesis of quantal acetylcholine release describes the process by which discrete packages (or quanta) of the transmitter are released from nerve terminals through the exocytosis of the content of synaptic vesicles. However, cholinergic synaptic vesicles can no longer be vaguely regarded as simple membrane bound 'sacks' of the transmitter. Modern molecular, biochemical, morphological and electrophysiological research has revealed them to be complex cellular structures with a heterogeneous mixture of functions. Thus, not all synaptic vesicle populations are formed under the same circumstances and there are variations in the releasability of synaptic vesicle populations. This review briefly outlines some of the experimental research that has lead to our current thinking on the heterogeneity of vesicular acetylcholine storage in cholinergic nerve terminals. In addition, a model for vesicular acetylcholine storage and release is presented that attempts to accommodate many of the modern ideas concerning cholinergic synaptic vesicle function and interaction.

Acetylcholine↗