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Turnover forehead flap combined with composite crus of helix graft for partial nasal reconstruction.

Partial lateral nasal defects challenge the plastic surgeon both technically and aesthetically. Many methods for reconstruction of these defects have been described. We have used a turnover forehead flap in conjunction with composite auricular graft for the reconstruction of nasal defects. The forehead flap is turned over so that the forehead skin serves as internal lining in the nose. The composite auricular graft serves as external nasal lining and provides mechanical support to the ala. The technique was used in seven patients and is presented here with illustrations, selected cases, results, and conclusions concerning patient selection.

Aged↗

Clinical evaluation and computed tomography scan analysis of screw tracts after percutaneous insertion of pedicle screws in the lumbar spine.

STUDY DESIGN: An examination of the accuracy of percutaneous pedicle screw placement in the lumbar spine. Using computed tomography scan analysis after implant removal, the screw tracts could be analyzed regarding the degree and direction of screw dislocation. OBJECTIVES: To investigate the misplacement rate and related clinical complications of percutaneous pedicle screw insertion in the lumbar spine. SUMMARY OF BACKGROUND DATA: The feasibility of the external fixation test has been investigated in several studies. Although pedicle screw misplacement has been reported as one of the main complications, there are no reliable data on the misplacement rate for this difficult surgical procedure. METHODS: In this study, 51 consecutive patients with suspected segmental instability were investigated after external transpedicular screw insertion for the external fixation test. Computed tomography scans of all instrumented pedicles from L2 to S1 were performed after screw removal. The screw tracts were analyzed, and the direction and degree of the pedicle violations were noted. In addition, the screw and pedicle angles were measured. RESULTS: Of 408 percutaneously inserted pedicle screws, only 27 screws (6.6%) were misplaced. There were 19 medial pedicle violations, 6 lateral cortical defects, and only 1 cranial and 1 caudal displacement. With respect to the spinal level, S1 showed the highest misplacement rate, with 11 screw dislocations (12%). After surgery, found two nerve root injuries were found. Only one of the injuries (L4) was related to the malposition of a screw. CONCLUSIONS: This study has shown that percutaneous insertion of pedicle screws in the lumbar spine is a safe and reliable technique. Despite the low misplacement rate of only 6.6%, it should be kept in mind that the surgical procedure is technically demanding and should be performed only by experienced spine surgeons.

Adult↗

Functional assessment of glaucoma.

Several studies have correlated the location of visual field defect on some of these newer tests to location of optic nerve damage with good results. In addition, there is an important and direct relationship between the psychophysical measures of visual function and location of damage. When a given individual had vision loss on more than one test, the same area of the visual field is affected. In addition, as soon as a repeatable defect is identified on perimetry, progression of the defect on later fields occurs within or adjacent to the initially identified area. These findings have significant implications for the care and follow-up of patients with glaucoma. Using these more sensitive tests has improved greatly our detection of early glaucomatous damage. Follow-up testing that concentrates the evaluation to areas already damaged should improve greatly our ability to identify true change from the significant physiologic variability present in glaucoma.

Glaucoma↗

Role of lymphocyte multidrug resistance protein 1 in HIV infection: expression, function, and consequences of inhibition.

The multidrug resistance protein 1 (MRP1) is a drug transporter that protects cells from oxidative stress, which increases HIV-1 replication. The aim of this study was to characterize the expression, function, and role of lymphocyte MRP1 in HIV-1 infection and its modulation by antiretroviral drugs such as the protease inhibitors (PIs). Peripheral blood mononuclear cells (PBMCs) from HIV-positive individuals do not show significant alterations of MRP1 expression despite highly active antiretroviral therapy and HIV plasma viral load levels; however, they exhibit different intracellular MRP1 expression as compared with healthy subjects. By contrast, MRP efflux function is increased in subjects with primary HIV infection and becomes defective in later stages of the infection. PI- and probenecid (PBCD)-mediated inhibition of MRP lowers the in vitro stress-induced response of lymphoid cells by reducing the level of the specific reactive oxygen species superoxide anion and hydrogen peroxide. Finally, the blockade of MRP by PBCD and PIs down-modulates HIV-1 replication by a mechanism independent of inhibition of the HIV-1 protease. Our results are consistent with a model wherein HIV replication is favored by the MRP1-related oxidative stress and inhibition of MRP1 may contribute to the antiviral activity of PIs.

Acquired Immunodeficiency Syndrome↗

A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo.

Mutations in the genes spitz (spi), Star (S), single-minded (sim), pointed (pnt), rhomboid (rho) (all zygotic), and sichel (sic) (maternal), collectively called the spitz group, cause similar pattern alterations in ventral ectodermal derivatives of the Drosophila embryo. The cuticle structures lacking in mutant embryos normally derive from longitudinal strips of the ventro-lateral blastoderm. Defects were found in the median part of the central nervous system in whole-mount embryos stained with anti-HRP (horseradish peroxidase) antibodies. In addition, the nerve cells expressing the even-skipped protein appeared abnormally arranged. These results suggest that groups of cells from the same region, including both epidermal and neural precursor cells, require spitz-group gene activity for normal development. The members of the spitz group differ from one another: sim affects a more median strip of the ventral ectoderm than the other zygotic genes and pnt causes separation rather than deletion of pattern elements. As shown by pole cell transplantations, spi and S are also required for normal development of the female germ line, while sim, rho, and pnt appear to be exclusively zygotically expressed, and the maternal gene sic acts in the germ line autonomously. Some embryos produced by sic-homozygous females differentiate the spitz phenotype, others develop normally or die early. Of all the spitz-group genes, sim appears to have the most specific effect on the embryonic pattern. The significance of the spitz-group phenotypes for the dorso-ventral pattern formation is discussed.

Animals↗

A mutation in the anticodon of a single tRNAala is sufficient to confer auxin resistance in Arabidopsis.

Auxin-resistant mutants have been useful for dissecting the mechanisms that underlie auxin-mediated biological processes. Here we report the isolation and molecular characterization of a novel auxin-resistant mutant in Arabidopsis (Arabidopsis thaliana). Like known mutated AUX/IAA transcription factors, the mutant described here displayed dominant resistance to exogenously supplied auxins (sirtinol, 2,4-dichlorophenoxyacetic acid, indole-3-acetic acid) and a host of pleiotropic phenotypes, including apical hook deformation, defects in lateral root development, reduced stature, and homozygous lethality. This mutant showed the same sensitivity to the ethylene precursor 1-aminocyclopropane carboxylic acid as wild-type plants, and retained the ability to induce IAA19 expression in response to exogenously supplied indole-3-acetic acid. To our surprise, these phenotypes were not caused by a mutation in an AUX/IAA gene, but rather a mutation in a tRNA(ala) gene in which the anticodon was found changed from CGC to CAC. Such a change results in a tRNA that is charged with alanine but recognizes the second most highly used valine codon in Arabidopsis. Therefore, the observed phenotypes are likely the composite of stochastic mutations of many proteins, including downstream effectors.

Anticodon↗

Buried hydrophobic side-chains essential for the folding of the parallel beta-helix domains of the P22 tailspike.

The processive beta-strands and turns of a polypeptide parallel beta-helix represent one of the topologically simplest beta-sheet folds. The three subunits of the tailspike adhesin of phage P22 each contain 13 rungs of a parallel beta-helix followed by an interdigitated section of triple-stranded beta-helix. Long stacks of hydrophobic residues dominate the elongated buried core of these two beta-helix domains and extend into the core of the contiguous triple beta-prism domain. To test whether these side-chain stacks represent essential residues for driving the chain into the correct fold, each of three stacked phenylalanine residues within the buried core were substituted with less bulky amino acids. The mutant chains with alanine in place of phenylalanine were defective in intracellular folding. The chains accumulated exclusively in the aggregated inclusion body state regardless of temperature of folding. These severe folding defects indicate that the stacked phenylalanine residues are essential for correct parallel beta-helix folding. Replacement of the same phenylalanine residues with valine or leucine also impaired folding in vivo, but with less severity. Mutants were also constructed in a second buried stack that extends into the intertwined triple-stranded beta-helix and contiguous beta-prism regions of the protein. These mutants exhibited severe defects in later stages of chain folding or assembly, accumulating as misfolded but soluble multimeric species. The results indicate that the formation of the buried hydrophobic stacks is critical for the correct folding of the parallel beta-helix, triple-stranded beta-helix, and beta-prism domains in the tailspike protein.

Amino Acid Substitution↗

Branching morphogenesis during development of placental villi.

The placenta forms a complex interface between the mother and fetus during development that is designed for efficient nutrient exchange. A large surface area is created by extensive branching morphogenesis of the trophoblast-derived epithelium to create a villous network, called the labyrinth in rodents. These villi are subsequently vascularized with an elaborate capillary network. Morphogenesis begins with selection of a subset of trophoblast cells in the basal layer of the chorion that express the Gcm1 transcription factor. These cells leave the cell cycle and undergo cell shape changes that initiate a process of involution to create primary villi into which fetal blood vessels grow. Much less is known about the regulation of subsequent events in branching, certainly compared with other organs. However, over 60 different mouse mutants have defects during later labyrinth development. Some of these mutant genes encode components of signaling pathways such as the fibroblast growth factor and Wnt pathways that play evolutionarily conserved roles in other branched organs, These mutants represent a still largely untapped resource as most of them have not been studied in detail in relation to placental morphogenesis.

Allantois↗

Use of a double hook plate for treatment of a distal radial fracture in a dog.

Attempted stabilization of open, distal radius and ulnar fractures in a 3-year-old German shepherd dog using intramedullary pins and a Schroeder-Thomas splint resulted in malalignment of the limb and osteomyelitis. A double hook plate was used to rigidly stabilize the distal radial fracture after anatomical realignment. An autogenous cancellous bone graft was used where a lateral architectural defect remained after reduction. Culture of the fracture site showed Staphylococcus sp., which responded to chloramphenicol therapy. Fracture union and resolution of osteomyelitis occurred by 9 weeks after surgery, and the dog had no lameness and a normal muscle mass 22 weeks after surgery. The double hook plate provided rigid internal fixation of the radial fracture, allowed a rapid return to function during osteosynthesis, and minimal interference of antebrachiocarpal joint function occurred.

Animals↗

Alterations in peptidoglycan chemical composition associated with rod-to-sphere transition in a conditional mutant of Klebsiella pneumoniae.

Klebsiella pneumoniae Mir M7 is a spontaneous parentless morphology mutant which grows as cocci at pH 7 and as rods at pH 5.8. This strain has been characterized as defective in lateral wall formation (at pH7). Data suggest that the cell wall is mainly made up of poles of the rods (G. Satta, R. Fontana, P. Canepari, and G. Botta, J. Bacteriol. 137:727--734, 1979). In this work the isolation and the biochemical properties of the peptidoglycan of both Mir M7 rods and cocci and a nonconditional rod-shaped Mir M7 revertant (strain Mir A12) are described. The peptidoglycan of Mir M7 (both rods and cocci) and Mir A12 strains carried covalently bound proteins which could be easily removed by pronase treatment in Mir M7 rods and Mir A12 cells, but not in Mir M7 round cells. However, when the sodium dodecyl sulfate-insoluble residues of Mir M7 cocci were pretreated with ethylenediaminetetraacetic acid (EDTA), pronase digestion removed the covalently bound proteins, and pure peptidoglycan was obtained. EDTA treatment of the rigid layer of Mir M7 cocci removed amounts of Mg2+ and Ca2+, which were 10- and 50-fold higher, respectively, than the amount liberated from the rigid layer of Mir M7 rods and Mir A12 cells. Amino acid composition was qualitatively similar in both strains, but Mir M7 cocci contained a higher amount of alanine and glucosamine. Mir M7 cocci contained approximately 50% less peptidoglycan than rods. Under electron microscopy, the rigid layer of the Mir M7 rods and Mir A12 cells appeared to be rod-shaped and their shape remained unchanged after EDTA and pronase treatment. On the contrary, the Mir M7 cocci rigid layer appeared to be round, and after EDTA treatment it collapsed and lost any definite morphology. In spite of these alterations, the peptidoglycan of Mir M7 cocci still appeared able to determine the shape of the cell and protect it from osmotic shock and mechanical damages. The accumluation of divalent cations appeared necessary for the peptidoglycan to acquire sufficient rigidity for shape determination and cell protection. We concluded that the coccal shape in Mir M7 cells is not due to loss of cell wall rigidity but is a consequence of the formation of a round peptidoglycan molecule. The possibility that the alterations found in the Mir M7 cocci rigid layer may reflect natural differences in the biochemical composition of the septa and lateral wall of normally shaped bacteria is discussed.

Amino Acids↗

Characterization of the Tn5 transposase and inhibitor proteins: a model for the inhibition of transposition.

Tn5 is a composite transposon consisting of two IS50 sequences in inverted orientation with respect to a unique, central region encoding several antibiotic resistances. The IS50R element encodes two proteins in the same reading frame which regulate the transposition reaction: the transposase (Tnp), which is required for transposition, and an inhibitor of transposition (Inh). The inhibitor is a naturally occurring deletion variant of Tnp which lacks the N-terminal 55 amino acids. In this report, we present the purification of both the Tnp and Inh proteins and an analysis of their DNA binding properties. Purified Tnp, but not Inh, was found to bind specifically to the outside end of Tn5. Inh, however, stimulated the binding activity of Tnp to outside-end DNA and was shown to be present with Tnp in these bound complexes. Inh was also found to exist as a dimer in solution. These results indicate that the N-terminal 55 amino acids of Tnp are required for sequence-specific binding. They also suggest that Inh inhibits transposition by forming mixed oligomers with Tnp which still bind to the ends of the transposon but are defective for later stages of the transposition reaction.

Bacterial Proteins↗

Infection of macrophages with lymphotropic human immunodeficiency virus type 1 can be arrested after viral DNA synthesis.

Lymphotropic strains of human immunodeficiency virus type 1 (HIV-1), including HTLV-IIIB, replicate poorly in macrophages. We have shown previously that lymphotropic HIV-1 fuses equally well with T lymphocytes and macrophages (M. J. Potash, M. Zeira, Z.-B. Huang, T. Pearce, E. Eden, H. Gendelman, and D. J. Volsky, Virology 188:864-868, 1992), suggesting that events in the virus life cycle following virus-cell fusion limit virus replication. We report here that HIV-1 DNA is synthesized efficiently in either ADA or HTLV-IIIB infected alveolar macrophages or monocyte-derived macrophages within 24 h of virus infection, as observed by polymerase chain reaction for amplification of viral DNA sequences from the gag gene. Infection by a cloned lymphotropic HIV-1 strain, N1T-A, also leads to viral DNA synthesis. However, circular viral DNA was detected during strain ADA infection but not during HTLV-IIIB or N1T-A infection of monocyte-derived macrophages. These findings indicate that during replication of lymphotropic HIV-1 in macrophages, all steps of the virus life cycle up to and including reverse transcription take place and that defects in later events, including DNA migration to the nucleus, may account for the limited production of viral proteins.

DNA, Viral↗

MR imaging diagnosis of uterovaginal anomalies: current state of the art.

Uterovaginal anomalies are associated with a high incidence of decreased fertility and multiple obstetric problems. These anomalies are caused by alterations in development or fusion of the müllerian ducts. Uterovaginal anomalies are classified into three types: dysgenesis, vertical or lateral fusion defects, and unusual configurations. Systematic analysis of magnetic resonance (MR) images allows accurate morphologic demonstration and classification of uterovaginal anomalies, thereby indicating the appropriate treatment. The following parameters are recorded in MR images: uterine size, external fundal contour, intercornual distance, zonal anatomy, and presence of uterine or vaginal septa. Associated pelvic lesions or renal anomalies are to be reported. MR imaging allows diagnosis of obstructive uterovaginal anomalies; determining the site of obstruction is imperative for planning the proper surgical approach. MR imaging techniques, including planes, sequences, and the application of more recent advances, are discussed. Pelvic phase-array coils and endovaginal coils provide detailed images and can be problem-solving tools in complex anomalies. MR imaging findings associated with a variety of uterovaginal anomalies are shown. The author suggests a five-step approach for diagnosing uterovaginal anomalies with MR imaging.

Female↗

Variability of adjustments to indices in determining patient risk in biochemical screening.

It has long been appreciated that the measurement of biochemical parameters for prenatal screening for neural tube defects, and later aneuploidy, is not as simple as measuring hemoglobin or hematocrit. Early in the game, it was recognized that there are gestational age curves, and that since alpha-fetoprotein (AFP), for example, is a fetal product, its distribution varies as a function of maternal plasma volume, and therefore the weight of the mother. A number of different adjustment factors have been used for AFP and other parameters for years, with varying degrees of consistency and reliability. Here we review a number of adjustments that have been used, and try to give priority to those that have been most effective. Furthermore, laboratories and programs need to be cognizant that with newer parameters being added, the specifics of requirements will vary on a case-by-case parameter basis, and optimal screening can only be achieved with the appropriate adjustments.

Biomarkers↗

Inheritance of Alzheimer's disease: epidemiologic evidence.

The available evidence suggests that there may be two subtypes of AD-- inherited and noninherited. Inherited AD may have certain characteristics, e.g. younger age at onset and some clinical signs or symptoms, which distinguish them from noninherited cases. It is possible that the noninherited type of AD may also have a similar genetic defect as the inherited kind, the only difference being that in one case the defect is inherited from the parents and in the other the defect arises de novo during embryogenesis. An environmental factor operating during embryogenesis may be responsible for causing a genetic defect which later manifests as noninherited AD. Currently, however, there is no precise way to separate these two subtypes. The exact proportion of all cases of AD which are inherited on a genetic basis is not known, but it must be small. The mode of inheritance of genetic AD is not known. It must be emphasized that the subtypes of inherited and noninherited AD are not synonymous with the older categorization of AD into presenile and senile AD.

Aged↗

The epithelium in healing experimental standard lesions in the gastric mucosa of the rat. A light microscopical and scanning electron microscopical study.

In a series of experiments in rats, the movement of the advancing sheet of epithelial cells streaming from a border region into the woind bed of standardized defects in the glandular mucosa of the stomach was studied using the light microscope and the scanning electron microscope (SEM). A very high synthetic activity of mucus in gastric lining cells of the border region (with a typical shift in its reaction product towards a more acidly reacting product showing metachromasia with toluidine blue) was observed histochemically, together with a loss of characteristic features of glandular cells in the border region with an increase in mitotic activity. The SEM images enabled a detailed analysis of the advancing epithelial front in its relation to the border regions. Considerable local differences were noted in the moving pattern of the migrating epithelium, possibly in relation with the nature of the base on which it has to move. The lesion of 3 mm diameter appeared to close usually after 10 days; in some instances, however, small epithelial defects were later found which could easily be traced with the SEM.

Animals↗

The structure of filaments of normal and psoriatic horny cells.

The structure of single filaments of horny cells of normal and psoriatic epidermis was studied in the electron microscopy in situ and in filaments reconstituted from urea extracts by dialysis, against low ionic strength buffer. It was found that both in situ and reconstituted filaments consist of 20 A protofibrils. In filaments of normal horny cells the protofibrils seem to form a rope-like structure while in those of psoriatic horny cells protofibrils appear randomly arranged. The filaments reconstituted from extracts of psoriatic scales range in width from 90 to 500 A, indicating a defect in lateral assembly of protofibrils. Numerous small particles are detectable at high magnification in extracts of both normal and psoriatic horny cells, which are about 20 A wide and 200 A long. These particles are consisted to be the basic structural units from which the protofibrils are formed, by end-to-end junctions.

Callosities↗