Radiologic-pathologic correlation polymicrogyria.
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Adult↗
Biomedical subjects
M M Smith
Publications and source records attributed to M M Smith.
Choristomas of the seventh and eighth cranial nerves.
Choristomas, masses of normal tissues in aberrant locations, contain smooth muscle fibers and fibrous tissues. We describe the MR imaging features of two choristomas located in the internal auditory canals and arising from the facial and vestibulocochlear nerves. Both lesions enhanced with contrast material. In one case, enhancement was seen in the geniculate ganglion and greater superficial petrosal nerve. In the other, a medial component enhanced less than the lateral component did.
Adult↗
Influence of the adenovirus 5 E1A oncogene on chromatin remodelling.
In the eukaryotic nucleus, compaction of DNA into chromatin can limit the access of trans-acting factors, providing an additional level of regulation to processes such as transcription, replication, and repair. Recent studies have suggested that the protein products of the adenovirus 5 E1A oncogene can influence SWI-SNF and histone acetylase activities, two cellular processes that facilitate transcription in the context of chromatin. This review focuses on the unexpected effects of E1A on cellular processes that remodel chromatin in relation to its transcriptional and transforming activities.
Acetylation↗
[Animal models used for the evaluation of anti-osteoarthritis drugs].
Naturally occurring osteoarthritis occurs in a variety of animal species including mice, guinea pigs, dogs and cynomolgus macaques and some of these animals have been used to evaluate the ability of anti-osteoarthritis drugs to reduce synovial inflammation and preserve cartilage integrity. However, the genetically determined animal models of osteoarthritis require the establishment of colonies which may take several years to develop and may be influenced by the strain of animal used and ill-defined environmental factors. On the other hand, the injection of irritants or enzymes into joints, or destabilization by surgical means, can rapidly and reproducibly lead to joint arthropathy and has therefore been more widely used. Although small animals, particularly rats and rabbits, have been the favoured target species, large animals such as dogs and sheep offer many advantages including the opportunity to undertake topographical analysis of joint cartilage and serial aspiration of synovial fluid. Meniscectomy is a common orthopaedic procedure which, in man and animals, is known to lead to osteoarthritis. In the past we have used this technique to induce osteoarthritis in pure bred dogs but more recently we have employed pure bred Merino sheep, which were matched for age, sex and weight. Using this ovine model we have been able to monitor the early and intermediate stages of cartilage metabolism, as well as identify key proteinases responsible for the loss of proteoglycans from these tissues in osteoarthritis. The effects of anti-osteoarthritis drugs on inflammatory mediators and cartilage metabolism has been successfully studied using the ovine model of osteoarthritis.
Animals↗
Elevated suicide levels associated with legalized gambling.
There has been no systematic, large-scale statistical investigation of the link between gambling and suicide, despite the suggestion of such a link from small-scale case studies. This article examines whether gamblers or those associated with them are prone to suicide and whether gaming communities experience atypically high suicide rates. Las Vegas, the premier U.S. gambling setting, displays the highest levels of suicide in the nation, both for residents of Las Vegas and for visitors to that setting. In general, visitors to and residents of major gaming communities experience significantly elevated suicide levels. In Atlantic City, abnormally high suicide levels for visitors and residents appeared only after gambling casinos were opened. The findings do not seem to result merely because gaming settings attract suicidal individuals.
Adult↗
Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4.
Repression of yeast a cell-specific genes by the global repressor Ssn6/Tup1 has been linked to a specific organization of chromatin. We report here that Tup1 directly interacts with the amino-terminal tails of histones H3 and H4, providing a molecular basis for this connection. This interaction appears to be required for Tup1 function because amino-terminal mutations in H3 and H4 that weaken interactions with Tup1 cause derepression of both a cell-specific and DNA damage-inducible genes. Moreover, the Tup1 histone-binding domain coincides with the previously defined Tup1 repression domain. Tup1/histone interactions are negatively influenced by high levels of histone acetylation, suggesting a mechanism whereby the organization of chromatin may be modulated in response to changing environmental signals.
Acetylation↗
Prosthodontic appliance for repair of an oronasal fistula in a cat.
A 4.5-month-old Himalayan cat was evaluated because of a cleft secondary palate. Multiple surgical procedures failed to provide soft-tissue coverage of the defect. A 3-cm silastic nasal septal button was trimmed and placed in the oronasal fistula. This prosthodontic appliance provided obturation of the defect without the need for removal or cleaning. Food accumulation between the appliance and oral mucosa was minimal, avoiding the need for appliance manipulation. The owner reported clinical signs related to oronasal fistula or appliance complications were not evident 12 months after placement.
Animals↗
Use of a modified toggle pin for repair of coxofemoral luxation in dogs with multiple orthopedic injuries: 14 cases (1986-1994).
OBJECTIVE: To develop modifications of the toggle pin procedure for use as a ligament of the head of the femur (LHF) prosthesis and to assess outcomes when used for coxofemoral luxation (CFL) in dogs with multiple orthopedic injuries. DESIGN: Retrospective case series. SAMPLE POPULATION: 14 dogs with CFL as a component of orthopedic polytrauma. PROCEDURE: Modifications to previous descriptions of the technique for use of a toggle pin for LHF prosthesis included deletion of the osteotomy of the greater trochanter in 12 of 16 joints with CFL, drilling of the femoral tunnel from a distal-to-proximal direction, deletion of a second femoral bone tunnel for suture placement, and use of a 2-hole polypropylene button to secure the LHF prosthetic suture. RESULTS: Mean age at time of injury, weight, and duration between injury and definitive surgery was 4.1 +/- 1.1 years, 19.7 +/- 2.8 kg, and 5.8 +/- 2.7 days, respectively. Weightbearing began 3.0 +/- 0.4 days after surgery. Mean postoperative follow-up period for dogs with maintained coxofemoral reduction of longer than 1 month (n = 13) was 19.5 +/- 6.1 months. Owners reported good or excellent clinical results, which were confirmed by semiquantitative assessment methods. Radiographic signs of degenerative joint disease were minimal. There was no significant difference between hind limbs when comparing mid-thigh limb circumference at the time of follow-up examination. CLINICAL IMPLICATIONS: A modified toggle pin procedure for LHF prosthesis can maintain coxofemoral reduction and allow early weightbearing in dogs with coxofemoral luxation as a component of multiple orthopedic injuries.
Accidents, Traffic↗
Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation.
Expression of the adenovirus E1A243 oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G1 phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A243, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A243 in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A243. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells.
Adenovirus E1A Proteins↗
A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission.
The histone proteins are essential for the assembly and function of th e eukaryotic chromosome. Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The mutant requires two amino acid substitutions in histone H4: a lethal Thr-to-Ile change at position 82, which lies within one of the DNA-binding surfaces of the protein, and a substitution of Ala to Val at position 89 that is an intragenic suppressor. Genetic and biochemical evidence shows that the mutant histone H4 is temperature sensitive for function but not for synthesis, deposition, or stability. The chromatin structure of 2 micrometer circle minichromosomes is temperature sensitive in vivo, consistent with a defect in H4-DNA interactions. The mutant also has defects in transcription, displaying weak Spt- phenotypes. At the restrictive temperature, mutant cells arrest in the cell cycle at nuclear division, with a large bud, a single nucleus with 2C DNA content, and a short bipolar spindle. At semipermissive temperatures, the frequency of chromosome loss is elevated 60-fold in the mutant while DNA recombination frequencies are unaffected. High-copy CSE4, encoding an H3 variant related to the mammalian CENP-A kinetochore antigen, was found to suppress the temperature sensitivity of the mutant without suppressing the Spt- transcription defect. These genetic, biochemical, and phenotypic results indicate that this novel histone H4 mutant defines one or more chromatin-dependent steps in chromosome segregation.
Chromatin↗
Radiation-induced cerebral osteogenic sarcoma.
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Brain Neoplasms↗
Image-guided spine surgery.
Conventional imaging techniques are of limited usefulness in spinal navigation, due to their lack of a "three-dimensional perspective." An interactive image-guided approach has been developed that provides a three-dimensional image-space representation of surgical space, using a specially designed referencing system and computer workstation. The system is described and results from laboratory tests and clinical cases are reported. It is concluded that interactive image-guided stereotaxis can be a valuable tool in spinal localization because of its degree of precision and the increased margin of safety it can offer.
Bone Screws↗
CT in adult supraglottitis.
We describe the CT appearance of supraglottitis and its complications in three adults. The most common CT findings were thickening of the epiglottis, aryepiglottic folds, false and true vocal cords, obliteration of the preepiglottic fa, thickening of the platysma muscle, and reticulation of the subcutaneous fat. Multiple loculated fluid-density collections consistent with abscesses were seen in one patient. Although the diagnosis of supraglottitis is generally made on the basis of the patient's history and by direct endoscopy, CT may be used to confirm the diagnosis when an adequate laryngoscopic examination cannot be performed. CT is also useful in evaluating the complications of this disorder.
Adult↗
Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis.
The pathogenesis of neurological dysfunction associated with human immunodeficiency (HIV)-1 infection is uncertain. However, the presence of macrophage infiltrates in the central nervous system is a key feature of HIV encephalitis and is correlated with HIV-associated dementia. Moreover, it has been demonstrated that HIV-infected monocyte/macrophages can produce toxic substances that may play a critical role in the development of HIV-associated dementia. However, the exact mechanisms responsible for HIV infection and leukocyte recruitment to the central nervous system remain speculative. Similar to HIV-infected patients, simian immunodeficiency virus (SIV)-infected macaque monkeys develop immunosuppression and acquired immune deficiency syndrome (AIDS)-related inflammatory disorders, including AIDS encephalitis. In this study, we demonstrate that encephalitic brain from SIV-infected animals has elevated immunohistochemical expression of the C-C chemokines, macrophage inflammatory protein-1 alpha and -beta, RANTES, and monocyte chemotactic protein-3, and the C-X-C chemokine interferon-inducible protein-10. These findings suggest that one or all of of these chemokines could be involved in leukocyte recruitment to the brain in SIV-infected macaque monkeys.
AIDS Dementia Complex↗
Cyclic AMP signaling is required for function of the N-terminal and CR1 domains of adenovirus E1A in Saccharomyces cerevisiae.
We have constructed yeast vectors in which derivatives of the adenovirus E1A gene are expressed from the GAL1 promoter. Cells expressing E1A289 grow poorly and accumulate cells with a 1C DNA content. Using a series of E1A deletion mutants, we have identified three regions within the E1A protein that are necessary for the G1 growth phenotype; each deletion partially relieves the growth defect. These deletions span residues 4-25, 38-60 and 140-186, which fall within the N-terminal, CR1 and CR3 domains of E1A respectively. Expression of the first 82 residues of E1A, spanning just the N-terminal and CR1 domains, strongly inhibits yeast cell growth in G1 showing that these domains can function independently of other domains of E1A. Using this strong growth inhibition, we isolated a yeast mutant in the net1 gene that conferred resistance to the expression of E1A1-82. The mutant was insensitive to expression of both E1A1-82 and full length E1A, but remained sensitive to the toxicity caused by over-expression of a Gal4p-VP16 fusion. Finally, we found that the function of E1A in yeast depends on the cyclic AMP signaling pathway, providing a striking parallel with the action of E1A at the c-fos promoter in mammalian cells. These results suggest that a genetic analysis of the yeast model system will provide relevant new insights into mechanisms of gene regulation by E1A proteins.
Adenovirus E2 Proteins↗
Histone H4 and the maintenance of genome integrity.
The normal progression of Saccharomyces cerevisiae through nuclear division requires the function of the amino-terminal domain of histone H4. Mutations that delete the domain, or alter 4 conserved lysine residues within the domain, cause a marked delay during the G2+M phases of the cell cycle. Site-directed mutagenesis of single and multiple lysine residues failed to map this phenotype to any particular site; the defect was only observed when all four lysines were mutated. Starting with a quadruple lysine-to-glutamine substitution allele, the insertion of a tripeptide containing a single extra lysine residue suppressed the G2+M cell cycle defect. Thus, the amino-terminal domain of histone H4 has novel genetic functions that depend on the presence of lysine per se, and not a specific primary peptide sequence. To determine the nature of this function, we examined H4 mutants that were also defective for G2/M checkpoint pathways. Disruption of the mitotic spindle checkpoint pathway had no effect on the phenotype of the histone amino-terminal domain mutant. However, disruption of RAD9, which is part of the pathway that monitors DNA integrity, caused precocious progression of the H4 mutant through nuclear division and increased cell death. These results indicate that the lysine-dependent function of histone H4 is required for the maintenance of genome integrity, and that DNA damage resulting from the loss of this function activates the RAD9-dependent G2/M checkpoint pathway.
Amino Acid Sequence↗
Control and elimination of tuberculosis in Australia.
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Australia↗
Evaluation of three fixation techniques for repair of mandibular fractures in dogs.
Bilateral midbody hemimandibular osteotomies were performed between premolars 3 and 4 in 18 adult dogs. Hemimandibles were repaired by use of monocortically applied bone plates (n = 6), an interdental fixator composed of an Erich arch bar and acrylic (n = 6), or a type I external skeletal fixator (n = 6). At the immediate postoperative evaluation, hemimandibles stabilized with interdental fixators had an osteotomy gap distance (mean +/- SEM, 1.6 +/- 0.2 mm) that was significantly (P < 0.05) greater than for hemimandibles stabilized with external skeletal fixators (1.2 +/- 0.3 mm). Osteotomy gap distance of hemimandibles stabilized with external skeletal fixators (1.5 +/- 0.2 mm) was significantly (P < 0.05) greater at weeks 4 (1.1 +/- 0.2 mm) and 8 (0.8 +/- 0.3 mm) after surgery than the osteotomy gap distance of hemimandibles stabilized by application of bone plates. By week 16, significant differences in osteotomy gap distance were not detected between groups. Immediately after surgery, mandibular alignment measurements were not significantly different for dogs with bone plates (0.3 +/- 0.1 mm), interdental fixators (0.3 +/- 0.1 mm), and external skeletal fixators (0.9 +/- 0.5 mm). Mandibular alignment scores were not significantly different between treatment groups during the remaining postoperative period. Occlusal measurements were not significantly different between evaluations performed before surgery and 16 weeks after surgery, regardless of treatment group. Radiographic evidence of healing in hemimandibles stabilized with external skeletal fixators was significantly (P < 0.05) less at 4 and 8 weeks, compared with hemimandibles stabilized with bone plates and interdental fixators; however, radiographic evidence of bone healing was not significantly different between fixation groups at 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗