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PubMed2005

A behavior systems view of the organization of multiple responses during a partially or continuously reinforced interfood clock.

We examined how a 50% Pavlovian partial reinforcement (PRF) schedule, versus a 100% continuous reinforcement (CRF) schedule, altered the asymptotic amount and distribution of focal and general search behavior in rats during 48-sec trials with and without a four-segment interfood clock (S1-S2-S3-S4-US). Under CRF, but not PRF, average asymptotic focal search (nosing in the feeder) increased across the last two clock segments (S3 and S4), and more for the clock group than the no-clock group. Locomotor general search peaked in the second clock segment (S2) for the CRF-clock and CRF-no-clock groups and in S3 for the PRF-clock groups. Furthermore, the ratio of general search to maximum focal search was higher for the PRF-clock group than for the CRF-clock group. This pattern of results supports the view that predictable reward presentations temporally organize search states and related responses between food presentations. The relative expression of these responses varies with the predictability and proximity of reward and is more sharply defined in the presence of a clock.

Animals↗
PubMed2005

Retinal nerve fiber layer thickness in the fellow eyes of normal-tension glaucoma patients with unilateral visual field defect.

PURPOSE: To quantitatively evaluate retinal nerve fiber layer (RNFL) thickness in the fellow eyes of normal-tension glaucoma (NTG) patients with unilateral visual field defect. DESIGN: Observational case-control study. METHODS: Twenty-nine NTG patients with unilateral visual field defect were enrolled in this study. All 29 fellow eyes showed normal visual field. Thirty-one normal eyes of 31 subjects served as controls. The RNFL thickness around the optic disk was determined using Fast RNFL thickness (3.4) of optical coherence tomography. Average and segmental (4 quadrants and 12 clock- hours) RNFL thickness measurements were compared among the three groups. RESULTS: RNFL thicknesses were significantly different among the three groups in the average, superior quadrant (11 and 12 clock-hour segments), and inferior quadrant (6 clock-hour segment) (P = .00, one-way ANOVA and Tukey's tests). CONCLUSIONS: RNFL thickness reductions are already present in the fellow eyes of NTG patients with unilateral visual field defect.

Case-Control Studies↗
PubMed1997

Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis.

We have identified and characterized c-hairy1, an avian homolog of the Drosophila segmentation gene, hairy. c-hairy1 is strongly expressed in the presomitic mesoderm, where its mRNA exhibits cyclic waves of expression whose temporal periodicity corresponds to the formation time of one somite (90 min). The apparent movement of these waves is due to coordinated pulses of c-hairy1 expression, not to cell displacement along the anteroposterior axis, nor to propagation of an activating signal. Rather, the rhythmic c-hairy mRNA expression is an autonomous property of the paraxial mesoderm. These results provide molecular evidence for a developmental clock linked to segmentation and somitogenesis of the paraxial mesoderm, and support the possibility that segmentation mechanisms used by invertebrates and vertebrates have been conserved.

Animals↗
PubMed2003

Evolution of segmentation: rolling back the clock.

Recent work has revealed striking similarities in the genetic mechanisms underpinning somitogenesis in zebrafish and segmentation in the spider. Could this mean that the bilaterian common ancestor was segmented after all?

Animals↗
PubMed2004

Increasing scans per examination improves the reproducibility on retinal nerve fiber layer measurements by optical coherence tomography.

PURPOSE: To investigate whether increasing the number of scans per examination would improve the reproducibility of retinal nerve fiber layer (RNFL) measurements by optical coherence tomography (OCT) in healthy and glaucomatous eyes. METHODS: A total of 28 eyes of 28 healthy subjects and 20 eyes of 20 patients with primary chronic open-angle glaucoma were recruited. OCT RNFL assessments were obtained in one randomly selected eye. Each subject underwent seven scans on five separate occasions within a 1-month period. RESULTS: In the healthy group, the intervisit mean coefficient of variations (COV's) for the average RNFL thickness (100 sampling points) and the quadrant RNFL measurements (25 sampling points) were similar in a series of three, five, and seven scans per examination (p > 0.05), but COV's for the two clock-hour segment measurements (seven sampling points, superotemporal and inferotemporal) were significantly lower in a series of five and seven scans per examination than that of three scans per examinations (p < 0.01). In the glaucoma groups, COV's for the two quadrant (superior and inferior) and five clock-hour segment RNFL measurements (superior, superotemporal, temporal, inferotemporal, and superonasal) were significantly lower in a series of five and seven scans per examination than that of three scans per examination (p < 0.01). There was no statistical difference in the COV's between a series of five scans and that of seven scans per examination in all OCT RNFL thickness parameters in healthy and glaucomatous eyes (p > 0.05). Similar results were observed with intravisit COV comparisons. CONCLUSION: Increasing the number of scans per examination may improve the reproducibility of quadrant and clock-hour segment OCT RNFL measurements in healthy and glaucomatous eyes. A series of five scans per examination is recommended for OCT RNFL measurements.

Adult↗
PubMed1999

[Segmentation in vertebrates: a molecular clock linked to periodic somite formation].

In the vertebrate embryo, somites constitute the basis of the segmental body pattern. They give rise to the axial skeleton, the dermis of the back and all striated muscles of the body. In the chick embryo, a pair of somites buds off, in a highly coordinated fashion, every 90 minutes, from the cranial end of the presomitic mesoderm (PSM) while new mesenchymal cells enter the paraxial mesoderm as a consequence of gastrulation. The processes leading to the segmentation of the somite are not yet understood. We have identified and characterised c-hairy1, an avian homologue of the Drosophila segmentation gene, hairy. c-hairy1 is strongly expressed in the presomitic mesoderm where its mRNA exhibits a cyclic posterior-to-anterior wave of expression whose periodicity corresponds to the formation time of one somite (90 min). Fate mapping of the rostral half of the PSM using the quail-chick chimera technique supports a model of cryptic segmentation within the presomitic mesoderm, and indicates that c-hairy1 expression dynamics are not due to massive cell displacement. Analysis of in vitro cultures of isolated presomitic mesoderm demonstrates that rhythmic c-hairy1 mRNA production and degradation is an autonomous property of the paraxial mesoderm. Rather than resulting from the caudal-to-rostral propagation of an activating signal, it arises from pulses of c-hairy1 expression that are coordinated in time and space. Blocking protein synthesis does not alter the propagation of c-hairy1 expression, indicating that negative autoregulation of c-hairy1 expression is unlikely to control its periodic expression. Most of the segmentation models proposed for somite formation rely on the existence of an internal clock coordinating the cells to segment together to form a somite. These results provide the first molecular evidence of a developmental clock linked to segmentation and somitogenesis of the paraxial mesoderm, and support the possibility that segmentation mechanisms used by invertebrates and vertebrates have been conserved.

Animals↗
PubMed2001

A molecular clock involved in somite segmentation.

Somites are transient embryonic structures that are formed from the unsegmented presomitic mesoderm (PSM) in a highly regulated process called somitogenesis. Somite, formation can be considered as the result of several sequential processes: generation of a basic metameric pattern, specification of the antero-posterior identity of each somite, and, finally, formation of the somitic border. Evidence for the existence of a molecular clock or oscillator linked to somitogenesis has been provided by the discovery of the rhythmic and dynamic expression in the PSM of c-hairy1 and lunatic fringe, two genes potentially related to the Notch signaling pathway. These oscillating expression patterns suggest that an important role of the molecular clock could reside in the temporal control of periodic Notch activation, ultimately resulting in the regular array of the somites. We discuss both the importance of the Notch signaling pathway in the molecular events of somitogenesis and its relationship with the molecular clock, and, finally, in that context we review a number of other genes known to play a role in somitogenesis.

Animals↗
PubMed1988

Postradiation segmental myoclonus selectively inhibited by REM sleep (sleep-wake myoclonus).

A 46-year-old male patient was irradiated following left orchiectomy for seminoma. Three months after radiation, segmental myoclonus appeared involving all skeletal muscle groups up to the level of D10, the area of radiation. Urodynamic testing showed the presence of segmental myoclonus in the urethral sphincter. An around-the-clock 'continuous segmental myoclonus' during sleep and wakefulness with a frequency of 1 c/s and an amplitude of 400 microV selectively inhibited by REM sleep was not found in the literature. This continuous segmental myoclonus caused by a radiation myelopathy at D10-D11 was followed up for 2 years. It was partially controlled by carbamazepine.

Carbamazepine↗
PubMed1998

Segmental denervation and reinnervation of the iris sphincter as shown by infrared videographic transillumination.

OBJECTIVE: This study aimed to analyze the denervation and reinnervation history of individual segments of the iris sphincter in patients with Adie's syndrome. DESIGN: The irises of these patients were retroilluminated by shining an infrared-rich light through the lower eyelid and sclera and viewing the transilluminated iris from the front with an infrared-sensitive video camera. The irises of the same group of patients also were videotaped through a slit-lamp camera using routine frontal illumination. Both of these techniques also were used to examine a series of normal subjects. PARTICIPANTS: A total of 61 patients with Adie's syndrome or Adie's-like denervation of the iris sphincter (from surgery, trauma, or radiation) and 10 normal subjects were studied. MAIN OUTCOME MEASURES: Slit-lamp examination results of the segmental movement of the iris were compared to the infrared transillumination pattern of the iris sphincter before and during the light reflex, before and during the near-vision reaction, before and during eye movement, and before and after the application of dilute pilocarpine and 1% pilocarpine. RESULTS: Whenever an iris sphincter segment contracted, it also became denser by using these techniques. Reinnervated iris segments failed to contract to light but did contract and became denser with a near effort or with eye movement. Segments supersensitive to pilocarpine became denser than adjacent segments without supersensitivity, but atrophic-appearing segments looked translucent and thin, failing to become denser, even with 1% pilocarpine. CONCLUSIONS: The innervational history and current status of each clock-hour segment of the iris sphincter can be determined using this technique of videographic infrared transillumination, and the progression and pattern of iris denervation and reinnervation can be determined in patients with Adie's pupil. A miotic Adie's pupil that is "tonic," even in darkness, was found to be associated with a dense pattern of infrared transillumination in sphincter segments, which the authors interpret as being associated with a rich reinnervation from accommodative fibers. Segments that become densely reinnervated appear to lose their cholinergic supersensitivity.

Adie Syndrome↗
PubMed2004

A Notch feeling of somite segmentation and beyond.

Vertebrate segmentation is manifested during embryonic development as serially repeated units termed somites that give rise to vertebrae, ribs, skeletal muscle and dermis. Many theoretical models including the "clock and wavefront" model have been proposed. There is compelling genetic evidence showing that Notch-Delta signaling is indispensable for somitogenesis. Notch receptor and its target genes, Hairy/E(spl) homologues, are known to be crucial for the ticking of the segmentation clock. Through the work done in mouse, chick, Xenopus and zebrafish, an oscillator operated by cyclical transcriptional activation and delayed negative feedback regulation is emerging as the fundamental mechanism underlying the segmentation clock. Ubiquitin-dependent protein degradation and probably other posttranslational regulations are also required. Fgf8 and Wnt3a gradients are important in positioning somite boundaries and, probably, in coordinating tail growth and segmentation. The circadian clock is another biochemical oscillator, which, similar to the segmentation clock, is operated with a negative transcription-regulated feedback mechanism. While the circadian clock uses a more complicated network of pathways to achieve homeostasis, it appears that the segmentation clock exploits the Notch pathway to achieve both signal generation and synchronization. We also discuss mathematical modeling and future directions in the end.

Animals↗
PubMed2003

Evaluation of the glaucomatous damage on retinal nerve fiber layer thickness measured by optical coherence tomography.

PURPOSE: To evaluate the relationship between visual field and retinal nerve fiber layer (RNFL) thickness measured by optical coherent tomography (OCT) and to assess the diagnostic ability of OCT to distinguish between early glaucomatous or glaucoma-suspect eyes from normal eyes. DESIGN: Retrospective, non-randomized, cross-sectional study. METHODS: A total of 160 eyes of 120 normal Japanese adults, 23 eyes of 16 patients with ocular hypertension, 38 eyes of 35 glaucoma-suspect patients, and 237 glaucomatous eyes of 140 glaucoma patients were enrolled in the study. The glaucoma group included 89 early glaucomatous eyes. Thickness of the RNFL around the optic disk was determined with three 3.4-mm diameter circle OCT scans. Average and segmental RNFL thickness values were compared among all groups. The correlation between mean deviation and RNFL thickness in glaucomatous eyes was also analyzed. Receiver operating characteristic (ROC) curve area was calculated to discriminate normal eyes from early glaucomatous or glaucoma-suspect eyes. RESULTS: A significant relationship existed between the mean deviation and RNFL thickness in all parameters excluding the 3-o'clock area. The average RNFL thickness had the strongest correlation in all parameters (r = -0.729, P <.001). Retinal nerve fiber layer thickness at the 7-o'clock inferotemporal segment had the widest areas under the ROC curves in all parameters for early glaucomatous eyes (0.873). CONCLUSIONS: Measurement of RNFL thickness by OCT is useful in detecting early RNFL damage. Furthermore, OCT measurements of RNFL thickness may provide clinically relevant information in monitoring glaucomatous changes.

Cross-Sectional Studies↗
PubMed2005

Retinal nerve fiber layer thickness measured by optical coherence tomography and its correlation with visual field defects in early glaucoma.

BACKGROUND AND PURPOSE: To study the relationship between retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and visual field defects in early glaucomatous eyes and to study the diagnostic ability of OCT in distinguishing early glaucomatous eyes from normal eyes. METHODS: We studied 68 eyes from primary open-angle glaucoma patients with early visual field defect (mean deviation > -6 dB), and 94 normal eyes from healthy age- and gender- matched individuals. All participants underwent 3.4-mm diameter circular OCT scans and Humphrey 30-2 mode visual field testing. The average and segmental RNFL thickness values were compared between the 2 groups. The correlation between the mean deviation in the visual field examination and RNFL thickness was evaluated. The area under the receiver operating characteristic (ROC) curve was used to distinguish normal eyes from early glaucomatous eyes. RESULTS: There was a significant difference in RNFL thickness between the 2 groups based on the following parameters: average thickness; superior, inferior, and nasal quadrant thickness; and 1-7, 11, 12 o'clock hour segment thickness (p < 0.05). In the glaucoma group, superior and inferior quadrant thicknesses and average RNFL thickness significantly correlated with the visual field index (superior quadrant thickness, r = 0.36; inferior quadrant thickness, r = 0.32; average RNLF thickness, r = 0.35; p < 0.05). The average RNFL and inferior quadrant thickness of early glaucomatous eyes had the widest areas under the ROC curves (0.812 and 0.793, respectively). CONCLUSIONS: Measurement of average and inferior quadrant RNFL thickness by OCT is useful in detecting early glaucomatous change.

Adult↗
PubMed2006

Optical coherence tomography measurement of retinal nerve fiber layer after acute primary angle closure with normal visual field.

PURPOSE: To detect retinal nerve fiber layer (RNFL) thickness after a single acute primary angle closure (APAC) attack with normal visual field. DESIGN: Prospective, observational case study. METHODS: Twenty-eight patients who had a single unilateral APAC attack associated with normal visual fields at three months after remission and 28 single eyes from normal controls were enrolled. Duration of APAC attack was 5.9 +/- 2.7 hours. Comparisons of average RNFL thickness and RNFL thickness in four quadrants and in 12-o'clock-hour segments of the attacked eyes, unaffected fellow eyes, and normal controls were made using fast RNFL thickness (3.4) of Stratus optical coherence tomography. RESULTS: Significant differences were demonstrated comparing the inferior-quadrant RNFL thicknesses for the attacked eyes with those of the normal controls (P = .02) and fellow eyes (P = .02) using one-way analysis of variance with Tukey's tests. CONCLUSIONS: Inferior region RNFL thickness was significantly decreased in the attacked eyes after an APAC episode associated with normal visual field.

Acute Disease↗
PubMed2006

A clock and wavefront mechanism for somite formation.

Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. In this article, we develop a mathematical formulation of a new version of the Clock and Wavefront model proposed by Pourquié and co-workers (Dubrulle, J., McGrew, M.J., Pourquié, O., 2001. FGF signalling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106, 219-232). Dynamic expression of FGF8 in the presomitic mesoderm constitutes the wavefront of determination which sweeps along the body axis interacting as it moves with the segmentation clock to gate cells into somites. We also show that the model can mimic the anomalies formed when progression of the wavefront is disturbed and make some experimental predictions that can be used to test the hypotheses underlying the model.

Animals↗
PubMed2002

Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling.

A molecular oscillator regulates the pace of vertebrate segmentation. Here, we show that the oscillator (clock) controls cyclic initiation of transcription in the unsegmented presomitic mesoderm (PSM). We identify an evolutionarily conserved 2.3 kb region in the murine Lunatic fringe (Lfng) promoter that drives periodic expression in the PSM. This region includes conserved blocks required for enhancing and repressing cyclic Lfng transcription, and to prevent continued expression in formed somites. We also show that dynamic expression in the cycling PSM is lost in the total absence of Notch signaling, and that Notch signaling acts directly via CBF1/RBP-Jkappa binding sites to regulate Lfng. These results are consistent with a model in which oscillatory Notch signaling underlies the segmentation clock and directly activates and indirectly represses Lfng expression.

Animals↗
PubMed2006

Dact1 presomitic mesoderm expression oscillates in phase with Axin2 in the somitogenesis clock of mice.

During segmentation (somitogenesis) in vertebrate embryos, somites form in a rostral-to-caudal sequence according to a species-specific rhythm called the somitogenesis clock. The expression of genes participating in somitogenesis oscillates in the presomitic mesoderm (PSM) in time with this clock. We previously reported that the Dact1 gene (aka Dpr1/Frd1/ThyEx3), which encodes a Dishevelled-binding intracellular regulator of Wnt signaling, is prominently expressed in the PSM as well as in a caudal-rostral gradient across the somites of mouse embryos. This observation led us to examine whether Dact1 expression oscillates in the PSM. We have found that Dact1 PSM expression does indeed oscillate in time with the somitogenesis clock. Consistent with its known signaling functions and with the "clock and wavefront" model of signal regulation during somitogenesis, the oscillation of Dact1 occurs in phase with the Wnt signaling component Axin2, and out of phase with the Notch signaling component Lfng.

Animals↗
PubMed1999

Notch around the clock.

The establishment of a segmental pattern within the vertebrate body plan is achieved during embryogenesis by the somitogenesis process. Two molecular systems have been implicated in this phenomenon: a molecular clock linked to vertebrate segmentation and the Notch signalling pathway. Rhythmic expression of the Lunatic Fringe gene in the presomitic mesoderm has now provided a link between these two systems.

Animals↗