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PubMed2004

Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis.

The cysteinyl leukotrienes (cys-LTs), leukotriene (LT) C(4), LTD(4), and LTE(4), are smooth muscle constrictors that signal via the CysLT(1) receptor. Here we report that the cys-LTs play an important role in chronic pulmonary inflammation with fibrosis induced by bleomycin in mice. Targeted disruption of LTC(4) synthase, the pivotal enzyme for cys-LT biosynthesis, protected significantly against alveolar septal thickening by macrophages and fibroblasts and collagen deposition. In contrast, targeted disruption of the CysLT(1) receptor significantly increased both the concentration of cys-LTs in the bronchoalveolar lavage fluid and the magnitude of septal thickening as defined by morphology, digital image analysis, and deposition of reticular fibers. These findings change our understanding of the pathobiology mediated by the cys-LTs by revealing their role in chronic inflammation with fibrosis, likely via the CysLT(2) receptor, and by uncovering a dual role for the CysLT(1) receptor, namely proinflammatory acute constriction of smooth muscle and antiinflammatory counteraction of chronic injury.

Animals↗

PubMed2005

Three-year follow-up of posterior capsule opacification with two different silicone intraocular lenses.

PURPOSE: To compare posterior capsule opacification (PCO) after cataract surgery with implantation of two silicone intraocular lenses (IOLs) with different designs. METHODS: We carried out a prospective, clinical study of 116 patients randomized to standardized phacoemulsification with implantation of CeeOn Edge (n = 57) or SI40NB (n = 59) IOLs. The follow-up period was 3 years. To evaluate PCO morphologically, digital images were obtained and analysed using evaluation of posterior capsule opacification computer software (epco). The neodymium:YAG (Nd:YAG) capsulotomy rate was recorded. RESULTS: At 2 and 3 years, the eyes with SI40NB IOLs had significantly more PCO than those with the CeeOn Edge IOLs (p = 0.00014 and p = 0.002). Nine Nd:YAG capsulotomies were performed in the SI40NB group and none in the CeeOn Edge group. This difference was statistically significant (p = 0.003). In some patients a regression of PCO was noticed and confirmed using epco. Statistically less PCO was noted when the capsulorhexis rim was placed so that it covered all 360 degrees of the optic of the IOL. CONCLUSIONS: A clinically and statistically significant difference in PCO development between CeeOn Edge and SI40NB IOLs at 2 and 3 years postoperatively was found. These findings support earlier studies indicating that a sharp edge of the optic is a more important factor in IOL design than IOL material in the prevention of PCO.

Aged↗

PubMed2004

A dual role for Hox genes in limb anterior-posterior asymmetry.

Anterior-to-posterior patterning, the process whereby our digits are differently shaped, is a key aspect of limb development. It depends on the localized expression in posterior limb bud of Sonic hedgehog (Shh) and the morphogenetic potential of its diffusing product. By using an inversion of and a large deficiency in the mouse HoxD cluster, we found that a perturbation in the early collinear expression of Hoxd11, Hoxd12, and Hoxd13 in limb buds led to a loss of asymmetry. Ectopic Hox gene expression triggered abnormal Shh transcription, which in turn induced symmetrical expression of Hox genes in digits, thereby generating double posterior limbs. We conclude that early posterior restriction of Hox gene products sets up an anterior-posterior prepattern, which determines the localized activation of Shh. This signal is subsequently translated into digit morphological asymmetry by promoting the late expression of Hoxd genes, two collinear processes relying on opposite genomic topographies, upstream and downstream Shh signaling.

Animals↗

PubMed2006

Form and function of ON-OFF amacrine cells in the amphibian retina.

ON-OFF amacrine cells were studied with whole cell recording techniques and intracellular staining methods using intact retina-eyecup preparations of the tiger salamander (Ambystoma tigrinum) and the mudpuppy (Necturus maculosus). Morphological characterization of these cells included three-dimensional reconstruction methods based on serial optical sections obtained with a confocal microscope. Some cells had their detailed morphology digitized with a computer-assisted tracing system and converted to compartmental models for computer simulations. The dendrites of ON-OFF amacrine cells have spines and numerous varicosities. Physiological recordings confirmed that ON-OFF amacrine cells generate both large- and small-amplitude impulses attributed, respectively, to somatic and dendritic generation sites. Using a multichannel model for impulse generation, computer simulations were carried out to evaluate how impulses are likely to propagate throughout these structures. We conclude that the ON-OFF amacrine cell is organized with multifocal dendritic impulse generating sites and that both dendritic and somatic impulse activity contribute to the functional repertoire of these interneurons: locally generated dendritic impulses can provide regional activation, while somatic impulse activity results in rapid activation of the entire dendritic tree.

Amacrine Cells↗

PubMed1993

Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud.

In this work we have attempted to characterize the programmed cell death process in the chick embryonic interdigital tissue. Interdigital cell death is a prominent phenomenon during limb development and has the role of sculpturing the digits. Morphological changes in the regressing interdigital tissue studied by light, transmission and scanning electron microscopy were correlated with the occurrence of internucleosomal DNA fragmentation, evaluated using agarose gels. Programming of the cell death process was also analyzed by testing the chondrogenic potential of the interdigital mesenchyme, in high density cultures. Our results reveal a progressive loss of the chondrogenic potential of the interdigital mesenchyme, detectable 36 hours before the onset of the degenerative process. Internucleosomal DNA fragmentation was only detected concomitant with the appearance of cells dying with the morphology of apoptosis, but unspecific DNA fragmentation was also present at the same time. This unspecific DNA fragmentation was explained by a precocious activation of the phagocytic removal of the dying cells, confirmed in the tissue sections. From our observations it is suggested that programming of cell death involves changes before endonuclease activation. Further, cell surface changes involved in the phagocytic uptake of the dying cells appear to be as precocious as endonuclease activation.

Animals↗

PubMedDate not supplied

From normal morphology and function to the breast pathophysiology.

At present mammography is the only method validated by trials performed over several decades; however it is burdened by some limitations which at times make its integration with other diagnostic imaging procedures necessary. These procedures are able to enhance the organ morphology (digital galactography) or the organ function (US, color-Doppler US, MRI, PET, scintigraphy). Among the methods of "functional" support, an emerging role is played by nuclear medicine with the use of specific radiopharmaceuticals for breast scintigraphy, PET and-lymphoscintigraphy of sentinel lymph node.

Breast Neoplasms↗

PubMed2001

[The experimental study of intratemporal facial nerve regeneration in chitin chamber].

OBJECTIVE: To investigate the feasibility of intratemporal facial nerve regeneration in a chitin chamber. METHODS: A left 6 mm intratemporal facial nerve gap was created in adult white rabbit, and a total of 48 animals were used. The proximal and distal stumps were bridged with chitin chamber (experimental group) and silicone chamber (control group). Regeneration of the nerve was assessed by gross observation, nerve electrophysiological test, histological examination and digital morphological analysis in both groups. RESULTS: 1. Three months after implantation, the proximal transected neural stump was connected with the distal stump in the chitin chamber. Five months after operation, the regenerated nerve exhibited a more nature fascicular organization and the chitin tubes were completely absorbed. 2. Nerve evoked potentials showed better conduction ability in the chitin chamber. There were no significant difference in electrophysiological indices between the two chamber groups. 3. Most of the regenerated nerve fibers were myelinated nerve fibers, and axons and myelins had similar histograms between the experimental and control groups. 4. Five months after operation, the mean percentage of recovery of the regenerated nerve fiber area, axonal area and axonal number were more than 71% in the experimental group. There was no significant difference between the control and experimental groups. CONCLUSION: These results suggested that intratemporal facial nerve could regenerate effectively within the chitin chamber in rabbits and such kind of chamber may be clinically useful.

Animals↗

PubMed2006

[Roles of the BMP family in pattern formation of the vertebrate limb].

In the process of limb development, various signaling molecules are produced in the organizing center of the limb bud. These molecules regulate pattern formation and the morphogenesis of the limb. Members of the bone morphogenetic protein (BMP) family and their receptors are expressed in the limb bud in spatiotemporal specific patterns. BMP signaling regulates chondrogenesis of limb mesenchyme, and promotes apoptosis of the interdigital soft tissue. Recently, this signaling was found to be involved in establishment of dorsoventral polarity of the limb bud and in regulation of limb growth via maintenance of the apical ectodermal ridge. BMPs also regulate digit morphology. In these events, BMPs work together with other signaling molecules, but they sometimes act as negative regulators of these other molecules so that limb morphogenesis can proceed normally.

Animals↗

PubMed1987

[Histophysiology of the uterine isthmus].

The uterine isthmus is morphologically defined as a topographic zone between the uterine corpus and the cervix, in very close association with the vasomusculary afferences. Architecturally isthmus corresponds to the connective-muscular function which is different by its thickness (from 2 mm to 10 mm) and by its morphology (digited, undulating sharp and regular). Histologically isthmus is made up by collagen fibers myometrial muscle cells, irregularly directed. The relationship of these two components reveal their functional synergy between the predominance of the connective tissue and the weakners of the muscle cells. The specific function of the isthmus and its autonomy depend: of the type and direction of the collagen fibers, and the quantity and arrangement the muscle cells, of the biochemical modifications and the variability of the ground substance moreover of the relations with the nervovascular endings. The isthmus incontinence is associated with these structural anomalies (muscular components, elastic fibers defects, connective tissue pathology, activity of the nerve endings, enzymatic troubles under hormonal control).

Collagen↗

PubMed2001

Morphological diversity in digital skin microstructure of didelphid marsupials.

The purpose of this study was to investigate how didelphid marsupials have diversified in morphology of their claws and digital pads as they evolved different foraging preferences such as terrestrial, aquatic, and arboreal feeding behaviours. Both arboreal and more terrestrial didelphids have papillary ridges on the digital pads of the fore and hindfoot. In contrast, the papillary ridges on the pedal digital skin of the water opossum Chironectes minimus have been replaced by nonoverlapping, thickened epidermal scales. Chironectes also differs from the other didelphids studied in having finger tips with reduced claws and digital pads that are covered with raised epidermal scales having projecting, finger-like cones arranged radially around the perimeter of each scale. The reduced claws and unusual digit skin microstructure of Chironectes likely improve this animal's ability to recognise and identify live animal prey under water using only its sense of touch.

Animals↗

PubMedDate not supplied

Quantitative evaluation of equine deep digital flexor tendon morphology using magnetic resonance imaging.

Injury of the distal aspect of the deep digital flexor tendon (DDFT) is a recognized cause of lameness, but diagnosis is difficult. This study aimed to improve understanding of DDFT morphology and pathology using retrospective evaluation of magnetic resonance (MR) images. We hypothesized that: (1) The distal aspect of the DDFT in normal horses would have a repeatable proximal/distal pattern and symmetry between limbs and between lobes; (2) DDFT dimensions would be related to bodyweight, navicular bone dimensions and hoof size; (3) this symmetry and pattern would be lost in DDFT injury; and (4) DDFT size would increase with injury. MR images of 64 live horse limbs, 26 with no identified DDFT lesion and 38 with identified DDFT abnormalities, and 19 normal cadaver limbs were analyzed. Using standardized transverse images, measurements of DDFT cross-sectional area, medial-lateral (ML) width and dorsal-palmar depth were obtained at six preselected sites. A uniform distal to proximal shape pattern was identified in all horses. The flattened crescent shape at the insertion changed to a deeper bilobed shape more proximally, with the mid-navicular area having the greatest cross-sectional area. Strong ML (P < 0.0006) and left/right symmetry (P < 0.02) were observed. In addition, there was a strong association between DDFT cross-sectional area and horse weight (P = 0.005) and between DDFT and navicular bone ML width (P = 0.004). Symmetry between sides or between lobes was lost at sites with a unilateral lesion and correlation between horse weight and DDFT cross-sectional area was lost in the presence of lesions. DDFTs with core lesions had a consistent increase in cross-sectional area overall, but other lesion types had no significant increase in size. The shape and symmetry seen in normal tendons could be related to the mechanical demands placed upon individual lobes. The limited increase in cross-sectional area with injury may be explained by the restrictive structures of the hoof, possibly explaining the ongoing pain seen in such lesions.

Animals↗

PubMed1989

A study of capillary morphology in the digits of patients with acquired clubbing.

We sought to determine the capillary morphology in patients with clubbing to compare it with that in subjects without clubbing. Subjects were placed in the clubbed or nonclubbed groups on the basis of caliper measurements of their index fingers. In each subject, photomicrographs of eight fingers were done focusing on the dorsal skin just proximal to the base of the nail. Each photomicrograph was randomly graded with respect to the presence and extent of plexus formation, the presence of arborized loops, and the presence of splayed loops. Comparison of the plexus score, presence of arborized loops, and presence of splayed loops were significantly different between the clubbed and nonclubbed groups (p less than 0.001 in all three analyses). Only a plexus score of 2 or greater demonstrated a useful degree of sensitivity and specificity (89 and 90%, respectively). We concluded that a significant difference in the morphologic features of the capillaries existed between nonclubbed subjects and those with acquired clubbing.

Adult↗

PubMed1997

Initial investigation of mathematical morphology for the digital extraction of the skeletal characteristics of trabecular bone.

OBJECTIVE: To develop a filter utilizing mathematical theory to extract the skeletal patterns of trabecular bone. METHODS: Studies of morphology in the extraction of patterns of calcification in mammograms provided the theoretical framework. Using these studies as a basis, a morphological filter was applied to extract skeletal patterns from digital images of trabecular bone. Sequential images (subset) were combined in a structured fashion to create an aggregate (sumset) which compared with the original images, skeleton and line skeleton images. RESULTS: Binary images of the skeletal patterns in continuous, round and mesh-like forms were obtained from the original images by processing with the skeleton operation using a disc-shaped single structuring element. The line skeleton operation using line structuring elements with constant directions allowed the extraction of linear and discontinuous patterns. Both the skeleton and line skeleton operations extracted binary subset images which depicted skeletal patterns correlating with the operation sequence. CONCLUSIONS: Modification of the morphological filter enhanced the extraction of skeletal characteristics of trabecular bone. A morphological filter may be a useful adjunct in computer-aided structural analysis of bone.

Bone Density↗

PubMed1988

Growth factor- and phorbol ester-induced changes in cell morphology analyzed by digital image processing.

We have developed the computer-aided image processing analysis to visualize and quantitate the cell motility and morphological changes in living cultured cells. The effect of growth factors on cell motility and morphology has been analyzed by this method. Insulin, insulin-like growth factor-I (IGF-I), and epidermal growth factor (EGF) elicited membrane rufflings in rat embryo fibroblast 3Y1 cells as well as in human epidermoid carcinoma KB cells. Insulin and IGF-I also induced ruffling membranes in Balb/c-3T3 cells. The quantitative analysis by the programmed trace mode of the AVEC system has shown that the motion of the membrane rufflings was observed within 2 min, reached the maximum level within 4-8 min, and rapidly decreased within 10-15 min after the addition of these growth factors. The analysis also revealed the temperature- and growth factor concentration-dependent changes in the motion of membrane rufflings elicited by these growth factors. 12-O-Tetradecanoylphorbol-13-acetate, one of the well-known tumor promoters, rapidly induced cell rounding in Balb/c-3T3 cells. This change of cell morphology could be also quantified by the trace mode analysis. The fluorescent phalloidin staining experiment indicated that these growth factor- or phorbol ester-induced morphological changes were accompanied by the reorganization of filamentous actin. Furthermore, we were able to visualize actin stress fibers in living EBTr cells by enhancing the video image and to follow the reduction of stress fibers induced by cytochalasin B without any fixation or fluorescent probes.

Actins↗

PubMedDate not supplied

Fundus morphology assessed by digital image analysis in children with fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) is associated with anomalies of the eye ground. The aim of this study was to evaluate the development of fundus morphology in children with FAS from early childhood to adolescence. METHODS: Funds photographs were evaluated by digital image analysis in 16 children with FAS. Age at the baseline study was between 0.25 and 14 years, and the median follow-up period was 7 years (range: 0.5 to 12). Sixteen sex- and age-matched healthy children were used as controls. RESULTS: Children with FAS had a smaller optic disc area, lower frequency of excavations, greater tortuosity of retinal vessels, and a smaller number of vascular branching points compared with the controls. There were no significant differences in the funds abnormalities between the first and last examinations. CONCLUSION: No interval change of retinal funds morphology was found at follow up, suggesting that the ocular abnormalities associated with FAS remain unchanged during childhood.

Adolescent↗

PubMed1975

Regeneration of digits and forelimbs in the Kenyan reed frog Hyperolius viridiflavus ferniquei.

Newly metamorphosed individuals of the Kenyan reed frog, Hyperolius viridiflavus ferniquei, are able completely to regenerate amputated digits, including the morphologically complex digital pad. The sequence of morphological events is very similar to that seen in the typical epimorphic regeneration of amphibian extremities. Amputated forearms typically produce hypomorphic spike regenerates. Despite the lack of underlying hand and digital structures, an apical "digital" pad commonly differentiates.

Animals↗

PubMed1998

Identification of clustered microcalcifications on digitized mammograms using morphology and topography-based computer-aided detection schemes. A preliminary experiment.

RATIONALE AND OBJECTIVES: A mathematical morphology-based computer-aided detection (CAD) scheme for the identification of clustered microcalcifications was developed and tested. The potential for improving either sensitivity or specificity by combining the results with those previously reported was investigated. METHODS: The CAD scheme presented here is based on mathematical morphology and a series of simple rule-based criteria for the identification of clustered microcalcifications. A database of 105 digitized mammograms was used for training and rule setting of the scheme. A test set of 191 digitized mammograms was used to evaluate its performance. The same test set had been used to evaluate a multilayer, topography-based scheme. The results obtained by the two schemes were then combined using logical OR and AND operations. RESULTS: The morphology-based and topography-based CAD schemes performed at sensitivities of 82.9% and 89.5%, with false-positive detection rates of 1.3 and 0.4 per image, respectively. A logical OR operation resulted in 95.4% sensitivity. An AND operation achieved 76.2% sensitivity, with no false identifications on 93% of images. CONCLUSIONS: By combining the results of the morphology-based and the topography-based schemes, either sensitivity or specificity can be improved.

Algorithms↗

PubMed1994

Improving detection of coronary morphological features from digital angiograms. Effect of stenosis-stabilized display.

BACKGROUND: We have developed a digital display method that stabilizes the motion of a stenosis in sequential frames of a coronary angiogram, allowing it to be scrutinized at high display frame rates. The purpose of this study was to determine whether this technique improves visual detection of low-contrast luminal morphological features. METHODS AND RESULTS: An observer detection study was conducted using computer-simulated arterial segments containing known target features, inserted into clinical digital coronary angiograms. Four observers performed a forced-choice detection of a simulated filling defect in each of 320 angiograms using the conventional and stenosis-stabilized dynamic displays (at 7.5, 15, and 32 frames per second) and a single-frame static display (total of 8960 detections). In a second simulated clinical task, three observers detected a bridging stenotic lumen in 600 angiograms using the two displays (3600 detections). In a third experiment, two angiographers rated the likelihood of intraluminal thrombus in 89 right coronary digital angiograms by consensus reading with both dynamic displays. Detectability of the simulated filling defect was similar for both dynamic display methods at 7.5 frames per second (averaging twice that for static images). As display rate was increased to 32 frames per second, detectability for the conventional display declined, whereas the stabilized display detectability increased for all observers (P < .05). On average, stabilization allowed detection of filling defects equivalent to a 71% increase in feature contrast. Response time for the conventional display averaged 12.9 +/- 4.7 seconds. For the stenosis-stabilized display, response time fell with increased frame rate (P < .05) to 4.9 +/- 1.2 seconds at 32 Hz, similar to the time for static images (4.6 +/- 0.8 seconds). The detectability of the bridging stenotic lumen was increased by 62% with the stabilization compared with conventional dynamic display (P < .00001). Consensus reading of coronary angiograms showed differences between the two dynamic display methods (kappa = 0.11) that may be explained by an improvement in observer uncertainty. A rating of definite for thrombus present or absent was more frequent with the stabilized display (39% versus 15%, P < .0001). CONCLUSIONS: These data suggest that stabilized display of coronary angiograms significantly increases detectability, reduces the time required for detection, and improves observer uncertainty for the presence of small luminal morphological features. The method of angiographic display may thus have an impact on clinical coronary angiographic interpretation.

Coronary Angiography↗