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At least 235 records · Page 13Linked to original sources
PubMed1997

Fish mapping of a translocation breakpoint at 6q21 (or q22) in a patient with heterotaxia.

Heterotaxia is a congenital lateralization defect of visceral organs. As several single-genes that act on the formation of left-right asymmetry during embryogenesis have been identified in animals, a defect in the similar system may play a role in heterotaxia in man. We previously reported a Japanese girl with heterotaxia associated with a de novo balanced translocation (6;18)(q21 or q22;q21.3 or q22). In the present study, based on a hypothesis that one of the putative situs-determining genes is disrupted at a breakpoint of the translocation, we first isolated a yeast artificial chromosome (YAC) clone covering a breakpoint, 6q21 (or q22) of the translocation. Then, using STSs mapped on the YAC, we isolated bacterial artificial chromosome (BAC) clones spanning the breakpoint. FISH analysis using the BAC clones as probes revealed that the breakpoint is confined to a segment between two STS loci, WI-4066 and the CHLC.GATA6B06.192, within a genetic distance of 1.4 cM. The human connexin43 gene was not disrupted in our patient, although mutations of this gene have been reported in patients with complex heart disease and heterotaxia. The molecular localization of the translocation breakpoint in our patient may contribute to the positional cloning of a putative heterotaxia gene.

Blotting, Southern↗
PubMed2005

Essential role of obscurin in cardiac myofibrillogenesis and hypertrophic response: evidence from small interfering RNA-mediated gene silencing.

Obscurin is a recently identified giant multidomain muscle protein (approximately 800 kDa) whose structural and regulatory functions remain to be defined. The goal of this study was to examine the effect of obscurin gene silencing induced by RNA interference on the dynamics of myofibrillogenesis and hypertrophic response to phenylephrine in cultured rat cardiomyocytes. We found that that the adenoviral transfection of short interfering RNA (siRNA) constructs targeting the first coding exon of obscurin sequence resulted in progressive depletion of cellular obscurin. Confocal microscopy demonstrated that downregulation of obscurin expression led to the impaired assembly of new myofibrillar clusters and considerable aberrations of the normal structure of the contractile apparatus. While the establishment of the initial periodic pattern of alpha-actinin localization remained mainly unaffected in siRNA-transfected cells, obscurin depletion did cause the defective lateral alignment of myofibrillar bundles, leading to their abnormal bifurcation, dispersal and multiple branching. Bending of immature myofibrils, apparently associated with the loss of their rigidity, a modified titin pattern, the absence of well-formed A-bands in newly formed contractile structures as documented by a diffuse localization of sarcomeric myosin labeling, and an occasional irregular periodicity of sarcomere spacing were typical of obscurin siRNA-treated cells. These results suggest that obscurin is indispensable for spatial positioning of contractile proteins and for the structural integration and stabilization of myofibrils, especially at the stage of myosin filament incorporation and A-band assembly. This demonstrates a vital role for obscurin in myofibrillogenesis and hypertrophic growth.

Actinin↗
PubMed1976

Sacral agenesis. Analysis of 22 cases.

Sacral agenesis is a rare congenital anomaly of the spine and is usually associated with urologic abnormalities. Twenty-two patients are reviewed. Twenty-one had other congenital and developmental abnormalities in addition to sacral agenesis. Physical examination showed flattening of the buttocks, loss of the gluteal cleft, widely spaced buttock dimples, and a palpable sacral defect. Lateral views of the spine are essential when anteroposterior views suggest an absence of sacral segments. Seven patients had a significant familial history of diabetes mellitus. All patients with involvement of more than one sacral segment had neurogenic bladder dysfunction with incontinence. The degree of neurologic deficit could not be predicted from the radiologic appearance of the sacrum.

Abnormalities, Multiple↗
PubMed1983

Homicide of an aggressive adolescent boy with right temporal lesion: a case report.

The case is reported of a 14-year-old male who killed an 8-year-old child following an alleged insult. The subject had been known to be aggressive throughout his school career. He had suffered one nocturnal seizure at the age of 13, but he never was amnesic for any of his fights. There was a history of possible hypoxic birth trauma. Neuropsychiatric investigation revealed developmental lags in speech and other psychosocial skills and, on computer tomography, a circumscribed lesion (cystic defect) lateral to the right nucleus amygdalae.

Adolescent↗
PubMed2007

Cilia-driven leftward flow determines laterality in Xenopus.

Determination of the vertebrate left-right body axis during embryogenesis results in asymmetric development and placement of most inner organs. Although the asymmetric Nodal cascade is conserved in all vertebrates, the mechanism of symmetry breakage has remained controversial. In mammalian and fish embryos, a cilia-driven leftward flow of extracellular fluid is required for initiation of the Nodal cascade. This flow is localized at the posterior notochord ("node") and Kupffer's vesicle, respectively. In frog and chick embryos, however, molecular asymmetries are required earlier, from cleavage stages through gastrulation. The validity of a cilia-based mechanism for all vertebrates therefore has been questioned. Here we show that a cilia-driven leftward flow precedes asymmetric nodal expression in the frog Xenopus. Motile monocilia emerged on the gastrocoel roof plate during neurulation and lengthened and polarized from an initially central position to the posterior pole of cells. Concomitantly, a robust leftward fluid flow developed from stage 15 onward, significantly before asymmetric nodal transcription started in the left-lateral-plate mesoderm at stage 19. Injection of 1.5% methylcellulose into the archenteron prevented leftward flow and resulted in laterality defects, demonstrating that the flow itself was required for asymmetric gene expression and organ placement.

Animals↗
PubMed2005

Zebrafish scl functions independently in hematopoietic and endothelial development.

The SCL transcription factor is critically important for vertebrate hematopoiesis and angiogenesis, and has been postulated to induce hemangioblasts, bipotential precursors for blood and endothelial cells. To investigate the function of scl during zebrafish hematopoietic and endothelial development, we utilized site-directed, anti-sense morpholinos to inhibit scl mRNA. Knockdown of scl resulted in a loss of primitive and definitive hematopoietic cell lineages. However, the expression of early hematopoietic genes, gata2 and lmo2, was unaffected, suggesting that hematopoietic cells were present but unable to further differentiate. Using gene expression analysis and visualization of vessel formation in live animals harboring an lmo2 promoter-green fluorescent protein reporter transgene (Tg(lmo2:EGFP)), we show that angioblasts were specified normally in the absence of scl, but later defects in angiogenesis were evident. While scl was not required for angioblast specification, forced expression of exogenous scl caused an expansion of both hematopoietic and endothelial gene expression, and a loss of somitic tissue. In cloche and spadetail mutants, forced expression of scl resulted in an expansion of hematopoietic but not endothelial tissue. Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development.

Animals↗
PubMed1994

The AO system for primary mandibular reconstruction.

We reviewed the records of 27 patients who underwent primary mandibular reconstruction with AO plates to investigate the outcome and complications of this procedure. Immediate soft-tissue flap coverage was required in 26 patients. Early complications were seen in 44% of the patients, with the highest incidence after irradiation (P = 0.02). Late complications were mostly related to tumor recurrence (12). Late complications not associated with recurrence were persistent pain (2), minor infections (3), plate exposure (3), and plate fracture (1). Good to excellent cosmetic results were obtained in all but 1 patient. Full mastication was not possible for any of our patients, and therefore function was not fully restored. Speech and deglutition were mostly influenced by the amount of soft-tissue resection. Mean follow-up was 20 months (range 3 to 52). At last evaluation, 12 patients were alive and free of disease, and 15 were dead of disease or other causes. Our results show that primary mandibular reconstruction with rigid plates is a safe, effective, and reliable technique to restore mandibular continuity and cosmesis. For lateral defects, this method is a viable alternative to free vascularized osseocutaneous flaps.

Adult↗
PubMed2002

Horizontal space misrepresentation in unilateral brain damage. I. Visual and proprioceptive-motor influences in left unilateral neglect.

Patients with unilateral neglect can misperceive horizontal distances in the contralesional space as being shorter than equivalent ipsilesional ones. We evaluated the visual and motor-proprioceptive components of space misrepresentation through a distance reproduction task performed both with and without visual guidance. Four groups of right brain damaged patients (neglect with hemianopia (N+H+), neglect with inferior quandrantanopia (N+Q+), neglect without hemianopia (N+H-) and patients without neglect or hemianopia (N-H-)) and one group of healthy controls (C) performed the line bisection task and reproduced horizontal distances either by setting the endpoints or by doubling the length of a line in the contralesional or ipsilesional space. The doubling length task was administered in three different conditions: (a) visuomotor (the patient draws the line in free vision); (b) visual (by sight the patient guides the examiner drawing the line); (c) proprioceptive-motor (the patient is blindfolded and manually inspects and extends the horizontal distance subtended by the line). Compared to C and N-H- patients, only N+H+ patients exhibited a significant ipsilesional shift in line bisection. N+H+ patients showed the most severe contralesional-overextension/ipsilesional-underextension asymmetry in the endpoint, visuomotor and visual line extension task. In the proprioceptive-motor condition no asymmetry was found and N+H- showed greater overextension on both sides of space. In N+H-, brain damage was mainly centered in central-frontal cortex and basal ganglia. These findings re-emphasize the relevance of damage to visual retinotopically organized representations of space in the genesis of horizontal space misrepresentation of neglect patients and suggest the possible association of a non-lateralized defective processing of proprioceptive-motor information with unilateral neglect.

Adult↗
PubMed2001

Promontofixation for the treatment of prolapse.

Genital prolapse is a common problem in women. The wide variety of surgical techniques used to treat this problem demonstrate how difficult it is to manage. Laparoscopic surgery offers a new approach. It allows a good view of the anterior and posterior compartments so that a global approach for the prolapse is possible by the same surgical route. Traditional promontofixation can be combined with a new approach to the posterior compartment. Laparoscopic promontofixation through installation of an intervesicouterine prosthesis for the treatment of hysterocele and cystocele is associated with paravaginal repair of lateral defects and a Burch anterior colposuspension for urinary stress incontinence. When combined with laparoscopic treatment of rectocele by myorrhaphy and reinforcement of the fascia by means of a prosthesis, it provides a complete range of treatment for all types of feminine prolapse. After 20 years of experience through laparotomy, promontofixation using a triangle has been carried out by laparoscopy at the authors' center since 1991 in an attempt to eliminate the cystocele by solidly anchoring the uterus and bladder floor to the promontory. This laparoscopic technique follows the usual steps for pelvic prolapse repair: 1. Total or subtotal hysterectomy or suspension of the uterus is performed in such a way that it returns to normal physiologic position, and a solid subvesical floor is created. 2. The physiologic axis of the vagina is restored by creating a strong, low posterior point of support and by performing culdoplasty. 3. Evident or latent stress incontinence is treated. It would be pointless to treat the hysterocele on its own because, once the prolapse has been cured, the subvesical mass will disappear and allow urinary incontinence to appear. 4. Reconstruction of the posterior rectovaginal support structures seems to be mandatory and is carried out in almost all cases. The first phase of the laparoscopic approach to pelvic prolapse allowed the authors to explore the technical aspects. Several approaches are possible by laparoscopy. Herein, the authors report 8 years of technical research and assessment. This experience confirms the tremendous potential of laparoscopic surgery for the treatment of all aspects of this pathology by the same route. Stress incontinence, cystocele, hysterocele, rectocele, or enterocele can be treated. The operative time is longer than with the open route, and the surgeon must be highly experienced. Based on their experience, the authors are discovering new concepts. More data are required before a conclusion can be drawn concerning this promising new approach.

Culdoscopy↗
PubMed1996

Prospective study of the quality of life of cancer patients after intraoral tumor surgery.

PURPOSE: The aim of this prospective study was to determine the quality of life of patients with oral cancer after intraoral ablative surgery. PATIENTS AND METHODS: Eighty-five consecutive patients with squamous cell carcinoma of the floor of the mouth were enrolled in the study. Reconstruction of intraoral soft tissues was accomplished by local tissue (67.8%), jejunal grafts (16.9%), and cutaneous and myocutaneous flaps (15.3%). Soft tissue resections were combined with resections of the alveolar process of the mandible in 35.0% and mandibular discontinuity resections in 31.7% of the cases. A self-administered, standard questionnaire consisting of 22 visual analog scale items with a maximum index value of 154 was used to determine the physical functional status, the psychological status, and social functioning of cancer patients (Functional Living Index--Cancer). The questionnaire was administered preoperatively and 3, 6, and 12 months postoperatively. RESULTS: The Functional Living Index score increased significantly toward the end of the first postoperative year because of an increase in all three factors of the scale. All modes of soft tissue reconstruction achieved nearly equal levels of life quality in patients with median or lateral defects at the end of the observation period. Only patients with large bilateral defects exhibited lower preoperative and postoperative values because of extensive loss of functionally important soft tissue. Patients with discontinuity resections of the mandible took longer to regain the same level of life quality as patients without bone resections. Persistence of dysphagia, reflux of liquids, limitations to liquid food, and sleep disorders had a significant negative effect on the score. CONCLUSIONS: It is concluded that rehabilitation of oral cancer patients is particularly difficult in the case of large soft tissue defects and is not always accomplished completely even with primary microsurgical tissue repair.

Activities of Daily Living↗
PubMed1997

Processing and analyzing the mouse temporal bone to identify gross, cellular and subcellular pathology.

A technique has been developed for preparing the mouse temporal bone for histopathological examination: first, as a whole mount to detect any gross malformations of the bony or membranous labyrinths; second, in dissected segments to localize damage in the different sensory organs and to quantify sensory- and supporting-cell losses; and finally, in semi-thick and thin sections to identify and characterize subcellular pathology. Examples are given of the successful application of this technique to mice with very different inner-ear problems, including those with an abnormally short cochlear spiral, a defective lateral semicircular canal, abnormal otoliths over the saccular macula, an increased susceptibility to noise damage and those which lack fibroblast growth factor receptor 3.

Animals↗
PubMed2002

Isolation and characterization of a Japanese flounder clonal line, reversed, which exhibits reversal of metamorphic left-right asymmetry.

We have isolated a clonal line reversed (rev) of homozygous Japanese flounder through gynogenesis. The homozygous offspring gynogenetically produced from rev exhibited reversal of organization of the metamorphic L/R asymmetry such as the direction of eye-migration at a high frequency (20-30%). The molecular analysis using a left-specific marker pitx2 revealed that the embryonic L/R axis was ambiguously established: in more than half of rev embryos, pitx2 was expressed bilaterally in the lateral plate mesoderm (LPM). Previous studies in other animals demonstrated that ectopic pitx2 expression in the LPM could cause laterality defects of the visceral organs. Likewise, our results using rev imply that bilateral pitx2 expression could lead to randomization of the visceral organs. Coincidence of ectopic pitx2 expression and reversal of the direction of eye-migration in the population of rev offspring suggests that the rev locus is critical in specification of both the metamorphic and the visceral L/R asymmetries. However, reversal of the sidedness of the orientation of the visceral organs was not always accompanied by reversal of the direction of metamorphic eye-migration, suggesting that different mechanisms should be involved downstream of the rev locus in directing these two phases of asymmetric morphogenesis in the Japanese flounder.

Amino Acid Sequence↗
PubMed2000

Left-right axis malformations in man and mouse.

The study of left-right axis malformations in man and mouse has greatly advanced understanding of the mechanisms regulating vertebrate left-right axis formation. Recently, the roles of the TGF-beta family, Sonic hedgehog and fibroblast growth factor signaling, homeobox genes, and cilia in left-right axis determination have been more clearly defined. The identification of genes and environmental factors affecting left-right axis formation has important implications for understanding human laterality defects.

Animals↗
PubMed1998

Pitx2 determines left-right asymmetry of internal organs in vertebrates.

The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin. The gene Pitx2 is expressed in the left lateral plate mesoderm and, subsequently, in the left heart and gut of mouse, chick and Xenopus embryos. Misexpression of Shh and Nodal induces Pitx2 expression, whereas inhibition of activin signalling blocks it. Misexpression of Pitx2 alters the relative position of organs and the direction of body rotation in chick and Xenopus embryos. Changes in Pitx2 expression are evident in mouse mutants with laterality defects. Thus, Pitx2 seems to serve as a critical downstream transcription target that mediates left-right asymmetry in vertebrates.

Activin Receptors, Type II↗
PubMed1997

Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice.

The development of characteristic visceral asymmetries along the left-right (LR) axis in an initially bilaterally symmetrical embryo is an essential feature of vertebrate patterning. The allelic mouse mutations inversus viscerum (iv) and legless (lgl) produce LR inversion, or situs inversus, in half of live-born homozygotes. This suggests that the iv gene product drives correct LR determination, and in its absence this process is randomized. These mutations provide tools for studying the development of LR-handed asymmetry and provide mouse models of human lateralization defects. At the molecular level, the normally LR asymmetric expression patterns of nodal and lefty are randomized in iv/iv embryos, suggesting that iv functions early in the genetic hierarchy of LR specification. Here we report the positional cloning of an axonemal dynein heavy-chain gene, left/right-dynein (lrd), that is mutated in both lgl and iv. lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development. Our findings indicate that dynein, a microtubule-based motor, is involved in the determination of LR-handed asymmetry and provide insight into the early molecular mechanisms of this process.

Amino Acid Sequence↗
PubMed1998

Rigid fixation in mandibular reconstruction.

A primary goal of mandibular reconstruction is to preserve form and function. Free vascularized bone remains the gold standard for mandibular reconstruction of the anterior defect. While lateral mandibular defects need for vascularized bone remain controversial, free bone flaps provide the most reliable bone stock readily available for dental implantation. Mandibular alignment remains critical for recreating the 3-dimensional relationships of mandibular projection, occlusion, and condylar placement. Depending on the defect, a variety of techniques can be used to maintain mandibular alignment. These include prefabrication of the plate, placement of an internal fixation device, and intermaxillary fixation. Fixation techniques in this day and age generally rely on plates and screws. Miniplates are popular among some reconstructive surgeons while others prefer larger reconstruction plates that can span the entire defect. Bony contouring is critical since keeping bone surfaces in contact allows for improved bone healing. Condylar reconstruction this critical, when the ramus and condylar head are resected, require reconstruction to maintain the entire solid arch. A variety of these techniques are discussed. While the challenge remains reconstituting a solid arch, a variety of techniques can be employed. These techniques including fixation technique, bony contour, mandibular alignment, and condylar reconstruction will be discussed.

Bone Plates↗
PubMed2001

[Morphologic assessment for diagnosing urogynaecologic disorders].

Morphologic assessment for diagnosing urogynecologic disorders is done as part of the gynecologic examination and urogenital ultrasound with the equipment available in the gynecologist's office. Evaluation of the pelvic floor by separate palpation of both sides, assessment of contractility, testing of speculum elevation, and ultrasound examination of voluntary motor function by elevation of the bladder neck during muscle contraction provide adequate information on the pelvic floor status for initiating pelvic floor re-education and/or conditioning. In assessing prolapse, differentiation of a lateral defect from a central defect of the anterior compartment is an important prerequisite for surgical decision-making in stress urinary incontinence (colposuspension versus TVT-plasty) and urogenital prolapse (abdominal versus vaginal access). Introitus or perineal ultrasound allow for reliable assessment of the topography of the bladder neck and will also demonstrate morphologic changes of the urethra, the periurethral tissue, and the bladder. - Radiographic examinations (e. g., excretory urography, double-balloon urethrography, micturition cystourethrography, retro- and antegrade depiction of fistulae) are not part of the basic diagnostic work-up and should only be performed in the framework of specific urogynecologic assessment. These procedures are indicated for assessing the upper urinary tract, for confirming the diagnosis of urethral diverticulae, and for clarifying extraurethral urinary incontinence. - Magnetic resonance imaging allows for the detailed morphologic assessment of the levator ani muscle, the endopelvic fascia, and the urethra. However, since normal values for comparison have not yet been established and the examination is complicated and expensive, the use of MRI is still restricted to scientific investigations.

Endosonography↗
PubMed1990

[Magnetic resonance tomography of the shoulder. Possibilities of over interpretation of normal findings].

In order to test the criteria for abnormalities of the shoulder as seen on MR, 30 normal shoulders were examined. The examination included T1, proton and T2-weighted SE sequences and T2*-weighted FE sequences, using transverse, oblique coronary and oblique sagittal planes. In 57% there was increased signal intensity in the tendon of the rotator cuff; this might have been interpreted as a rupture of the cuff or tendinitis. Anatomical examination suggests that the finding is due to a normal layer between the long head of the biceps and the tendon joint complex. The anterior glenoid labrum could not be clearly delineated in 57% and the posterior labrum in 5%. In two cases there was a superior, postero-lateral defect in the head of the humerus. The currently accepted criteria for the MRT diagnosis of shoulder abnormalities need to be critically re-evaluated.

Adolescent↗