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At least 667 records · Page 37Linked to original sources
PubMed2004

Olmsted syndrome--a rare syndrome with oral manifestations.

Olmsted syndrome is a rare, congenital condition characterized by severe palmo-planter keratosis, periorificial keratosis, and hypotrichosis. Though orofacial keratosis is one of the consistent findings of Olmsted syndrome, it has never been reported in the dental literature. We report a case of Olmsted syndrome in an eight-year-old boy who presented with massive and crippling palmoplanter keratosis and bilateral oral lesions in the form of keratotic plaques at the corners of the mouth, as well as on the dorsum of the tongue.

Child↗
PubMed2001

NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100.

Processing of the nf(kappa)b2 gene product p100 to generate p52 is an important step in NF-kappaB regulation. We show that this step is negatively regulated by a processing-inhibitory domain (PID) within p100 and positively regulated by the NF-kappaB-inducing kinase (NIK). While the PID suppresses the constitutive processing of p100, NIK induces p100 processing by stimulating site-specific phosphorylation and ubiquitination of this precursor protein. Further, a natural mutation of the gene encoding NIK in alymphoplasia (aly) mice cripples the function of NIK in p100 processing, causing a severe defect in p52 production. These data suggest that NIK is a specific kinase regulating p100 processing and explain why the aly and nf(kappa)b2 knockout mice exhibit similar immune deficiencies.

Animals↗
PubMed2006

Vitamin D insufficiency in male osteoporosis.

Osteoporosis is an important public health issue among men, affecting up to 20% of all men in the United States >50 years of age. The social and economic costs of male osteoporosis are profound but can be minimized by a preventive approach, including early identification and treatment of men at risk for this potentially crippling disease. As part of this preventive approach, clinicians should screen susceptible patients for vitamin D deficiency, a commonly occurring, highly correctable risk factor for osteoporosis. Appropriate detection of vitamin D deficiency in men at risk for osteoporosis and adequate correction of this deficiency will significantly reduce morbidity and mortality associated with male osteoporosis.

Calcifediol↗
PubMed2001

[Is there still a place for conservative treatment of distal radius fractures in the adult?].

Contrary to Colles'opinion which pretended the fracture of the distal radius would heal without sequellae, many studies devoted to this problem showed that complications will affect one third of the cases (malunion, nerve compression, dystrophy, tendon rupture). It is important for the surgeon to know well the different fracture types, the general condition of his patient as well as his osteoarticular state to make the good choice of treatment. Our study shows that the nonoperative treatment will be chosen for any fracture type as far as it concerns an old or crippled patient, especially if there is an osteoporosis. On the contrary, for a young and active patient with a good bone quality, non operative treatment will be chosen as far as the fracture will be reducible and stable. If it is not, an osteosynthesis has to be done. Many studies already published tend to demonstrate that there is a correlation between anatomical and functional results. However, concerning elderly, this correlation tend to disappear with time.

Adult↗
PubMed2000

Conditionally replicative adenoviral vectors for cancer gene therapy.

During the past century, many attempts have been made to exploit the ability of some viruses to infect and destroy cancer cells. Crippled, non-replicative viruses have been used as vectors to transfer genes into tumours. Both strategies have serious limitations. The time is now ripe, however, for full convergence of these two research tracks. On the one hand, the intratumoral propagation of replicative viruses would overcome the low levels of gene transfer achieved by current viral vectors. On the other hand, the versatility provided by vectors encoding foreign genes, which are limited in their uses only by our ingenuity, would overcome the physiological barriers to robust propagation of the viral progeny in the tumour. This empowering synthesis will provide truly new opportunities that might realise the promises of gene transfer for the therapy of cancer.

Adenoviridae↗
PubMed2002

New uses of bisphosphonates: osteogenesis imperfecta.

Osteogenesis imperfecta is a heterogeneous group of inherited disorders chiefly affecting type I collagen, resulting in bone fragility responsible for a host of recurrent fractures. Limb and spine deformities, growth failure and restricted mobility are the end-result in severe cases. Cyclical intermittent intravenous infusions of pamidronate, a potent inhibitor of bone resorption, have yielded substantial improvement in chronic pain, bone mineral density, fracture rate and mobility without significant side effects. The role of growth hormone and bone marrow transplantation in the treatment of osteogenesis imperfecta is still unresolved. Newer, theoretically more potent bisphosphonates are currently being tested in this potentially crippling condition.

Bone Density↗
PubMed2003

Septic arthritis.

This chapter describes a rational approach to septic arthritis based on sound principles of pathology and therapeutics. Early diagnosis and prompt treatment are essential if normal function of the infected joint is to be restored. In any acute joint disease, infection must be suspected, and if present, detected. It is important to identify causative bacteria in order to administer the correct antibiotic. The clinical features are different in neonates, children and adults. Diagnosis is not usually difficult and may be aided by diagnostic ultrasound and arthrocentesis. Both antibiotics and joint lavage are essential parts of management. Successful outcome is based on effective treatment and results in normal joint function. Ineffective or delayed treatment may be crippling.

Animals↗
PubMed1986

Vestibular nerve section and saccus decompression: an evaluation of long-term results.

The 1972 AAOO committee (Alford, 1972) guidelines brought some uniformity into the evaluation of therapy for Menière's Disease. We have adhered to its recommendations in this long-term follow-up report of 21 saccus decompressions and 29 vestibular nerve sections performed on 46 patients between 1968 and 1977. Comparisons between these and other groups have been possible with regard to: control of vertigo; hearing; tinnitus; and development of hydrops in the contralateral ear. All the vestibular nerve section group have enjoyed sustained relief from vertigo. Class D results (recurrent vertigo) account for 14 per cent of the saccus decompression group at one year and 29 per cent at eight to 10-year follow-up. Hearing levels in both groups deteriorated in parallel as time progressed but tinnitus became less noticeable. Nineteen per cent of the long-term review patients showed evidence of developing cochlear hydrops in the contralateral ear. Conservative surgical procedures should be employed whilst any useful hearing exists, though the emphasis remains on controlling vertigo. Saccus decompression, despite its controversial therapeutic basis, will remain the first-line surgical procedure for many otologists. However, in the fit young Menière's cripple or saccus decompression failure with serviceable hearing, vestibular nerve section remains the treatment of choice.

Adult↗
PubMed1987

A technique of tongue reconstruction following near-total glossectomy.

Total glossectomy is the most crippling of all oral cavity resections. Speech problems are unavoidable and post-operative aspiration is often severe. Two patients are presented who have had tongue reconstructions following near-total glossectomies. In each case a quilted, split-skin grafted pectoralis major muscle flap was used. The speech and swallowing results of these two patients are compared with two patients who underwent a hemiglossectomy and total glossectomy respectively without tongue reconstruction. Only if the suprahyoid and extrinsic tongue muscles are preserved can an active oral phase of swallowing and usable speech be regained by tongue reconstruction.

Carcinoma, Squamous Cell↗
PubMed1994

Transfection of mu MDR 1 inhibits Na(+)-independent Cl-/-HCO3 exchange in Chinese hamster ovary cells.

We have used single-cell photometry to measure intracellular pH (pHi) for several MDR cell lines constructed by stably transfecting LR73 chinese hamster ovary fibroblasts with mutant and wild type murine MDR 1 genes. In addition, plasma membrane electrical potential (delta psi) has been measured for the same cells by the K+/valinomycin null point titration method using the ratiometric styryl probe di-4-ANEPPS. Both the untransfected, parental cell line and a cell line expressing substantial mutant MDR 1 protein (K432R/K1074R) that is unable to confer the MDR phenotype are found to have delta psi > or = -40 (+/- 5) mV and pHi < or = 7.16 (+/- 0.03) units. In contrast, MDR cell lines constructed by transfecting wild type mu MDR 1 cDNA are found to exhibit delta psi from 15 to 19 mV lower and pHi from 0.13 to 0.34 units higher. A cell line that overexpresses crippled MDR protein (S941F) that is not resistant to colchicine or doxorubicin, but which is resistant to vinblastine [Gros, P., Dhir, R., Croop, J., & Talbot, F. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 7289-7293], exhibits elevated pHi and slightly elevated delta psi, relative to LR73. Northern and western blot analyses confirm the substantial overexpression of the mu MDR genes and proteins in these lines, as well as the mild overexpression of endogenous hamster p-GP mRNA in some lines. In general agreement with previous studies that examined myeloma cells overexpressing hu MDR 1 protein [Roepe, P.D., Wei, L.-Y., Cruz, J., & Carlson, D. (1993) Biochemistry 32, 11042-11056] we find that overexpression of wild type mu MDR 1 protein inhibits Cl(-)- and -HCO3-dependent pHi homeostasis. Via single-cell photometry studies we now conclude that this is due to inhibition of Na(+)-independent Cl-/-HCO3 exchange (strict anion exchange or AE). As concluded previously for other MDR cells, decreased AE activity is not due to decreased expression of the exchanger; in fact, again similar to previous work [Roepe et al. (1993) Biochemistry 32, 11042-11056], we find increased levels of AE mRNA in some MDR cell lines. Models that may explain these data that are also consistent with the known physiology of cells that endogenously express MDR protein are suggested. These data are consistent with a model for MDR protein function wherein overexpression of the protein decreases delta psi and/or elevates pHi via Cl(-)- and -HCO3-dependent mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

A Cdc42 mutant specifically activated by intersectin.

The Rho family GTPase Cdc42 functions as a molecular switch and controls many fundamental cellular processes such as cytoskeletal regulation, cell polarity, and vesicular trafficking. Guanine nucleotide exchange factors of the Dbl family activate Cdc42 and other Rho GTPases by catalyzing the removal of bound GDP, allowing for GTP loading, and subsequent effector recognition ultimately leading to downstream signaling events. Analysis of existing structural data reveals that the Dbl exchange factor intersectin engages a strictly conserved GTPase residue of Cdc42 (tyrosine 32) in a unique mode with respect to all other visualized exchange factor-Rho GTPase interfaces. To investigate this differential binding architecture, we analyzed the role of tyrosine 32 of Cdc42 in binding, and stimulation by Dbl family exchange factors. Deletion of the hydroxyl side chain of tyrosine 32 substantially increases the affinity of Cdc42 for intersectin, yet severely cripples interaction with Dbs, a normally potent exchange factor of Cdc42. Moreover, Cdc42(Y32F) is exclusively activated by intersectin, while virtually unresponsive to other Cdc42-activating exchange factors in vitro and in vivo. Further, the structural determinants unique to intersectin, which permit selective recognition and concomitant stimulation of Cdc42(Y32F), have been defined. Cdc42 and other individual Rho GTPases receive input stimulatory signals from a multitude of Dbl exchange factors, and therefore, Cdc42(Y32F) could act as a valuable reagent for understanding the specific influence of ITSN on Cdc42-mediated signaling phenomena.

Adaptor Proteins, Vesicular Transport↗
PubMed2006

Conserved Asp327 of walker B motif in the N-terminal nucleotide binding domain (NBD-1) of Cdr1p of Candida albicans has acquired a new role in ATP hydrolysis.

The Walker A and B motifs of nucleotide binding domains (NBDs) of Cdr1p though almost identical to all ABC transporters, has unique substitutions. We have shown in the past that Trp326 of Walker B and Cys193 of Walker A motifs of N-terminal NBD of Cdr1p have distinct roles in ATP binding and hydrolysis, respectively. In the present study, we have examined the role of a well conserved Asp327 in the Walker B motif of the N-terminal NBD, which is preceded (Trp326) and followed (Asn328) by atypical amino acid substitutions and compared it with its equivalent well conserved Asp1026 of the C-terminal NBD of Cdr1p. We observed that the removal of the negative charge by D327N, D327A, D1026N, D1026A, and D327N/D1026N substitutions, resulted in Cdr1p mutant variants that were severely impaired in ATPase activity and drug efflux. Importantly, all of the mutant variants showed characteristics similar to those of the wild type with respect to cell surface expression and photoaffinity drug analogue [125I] IAAP and [3H] azidopine labeling. Although the Cdr1p D327N mutant variant showed comparable binding with [alpha-32P] 8-azido ATP, Cdr1p D1026N and Cdr1p D327N/D1026N mutant variants were crippled in nucleotide binding. That the two conserved carboxylate residues Asp327 and Asp1026 are functionally different was further evident from the pH profile of ATPase activity. The Cdr1p D327N mutant variant showed approximately 40% enhancement of its residual ATPase activity at acidic pH, whereas no such pH effect was seen with the Cdr1p D1026N mutant variant. Our experimental data suggest that Asp327 of N-terminal NBD has acquired a new role to act as a catalytic base in ATP hydrolysis, a role normally conserved for Glu present adjacent to the conserved Asp in the Walker B motif of all the non-fungal transporters.

Amino Acid Sequence↗
PubMed1999

The role of water in the catalytic efficiency of triosephosphate isomerase.

The structural basis for the effect of the S96P mutation in chicken triosephosphate isomerase (cTIM) has been analyzed using a combination of X-ray crystallography and Fourier transform infrared spectroscopy. The X-ray structure is that of the enzyme complexed with phosphoglycolohydroxamate (PGH), an intermediate analogue, solved at a resolution of 1.9 A. The S96P mutation was identified as a second-site reverent when catalytically crippled mutants, E165D and H95N, were subjected to random mutagenesis. The presence of the second mutation leads to enhanced activity over the single mutation. However, the effect of the S96P mutation alone is to decrease the catalytic efficiency of the enzyme. The crystal structures of the S96P double mutants show that this bulky proline side chain alters the water structure within the active-site cavity (E165D; ref 1) and prevents nonproductive binding conformations of the substrate (H95N; ref 2). Comparison of the S96P single mutant structure with those of the wild-type cTIM, those of the single mutants (E165D and H95N), and those of the double mutants (E165D/S96P and H95N/S96P) begins to address the role of the conserved serine residue at this position. The results indicate that the residue positions the catalytic base E165 optimally for polarization of the substrate carbonyl, thereby aiding in proton abstraction. In addition, this residue is involved in positioning critical water molecules, thereby affecting the way in which water structure influences activity.

Animals↗
PubMed2001

Early and multiple Ac transpositions in rice suitable for efficient insertional mutagenesis.

A GFP excision assay was developed to monitor the excision of Ac introduced into rice by Agrobacterium-mediated transformation. The presence of a strong double enhancer element of the CaMV 35S promoter adjacent to the Ac promoter induced very early excision, directly after transformation into the plant cell, exemplified by the absence of Ac in the T-DNA loci. Excision fingerprint analysis and characterization of transposition events from related regenerants revealed an inverse correlation between the number of excision events and transposed Ac copies, with single early excisions after transformation generating Ac amplification. New transpositions were generated at a frequency of 15-50% in different lines, yielding genotypes bearing multiple insertions, many of which were inherited in the progeny. The sequence of DNA flanking Ac in three representative lines provided a database of insertion tagged sites suitable for the identification of mutants of sequenced genes that can be examined for phenotypes in a reverse genetics strategy to elucidate gene function. Remarkably, two-thirds of Ac tagged sites showing homology to sequences in public databases were in predicted genes. A clear preference of transposon insertions in genes that are either predicted by protein coding capacity or by similarity to ESTs suggests that the efficiency of recovering knockout mutants of genes could be about three times higher than random. Linked Ac transposition, suitable for targeted tagging, was documented by segregation analysis of a crippled Ac element and by recovery of a set of six insertions in a contiguous sequence of 70 kb from chromosome 6 of rice.

Base Sequence↗
PubMed2003

Utilization of implantable defibrillators in Africa.

Sub-Saharan Africa is dominated by diseases of poverty. HIV/AIDS affects 28.5 out of a total of 600 million in the region. South Africa is the only country in sub-Saharan Africa in which implantable cardiovertor defibrillators (ICDs) are implanted (0.8/million in 2001). Only 3 of the 35 new ICDs were implanted in state-funded public hospitals. The pacemaker implantation rate for South Africa was 41/million in 2001. Approximately 20% of the population consume 56% of the health care expenditure, mainly funded by Medical Insurance. A tax-funded state health care system serves the rest of the population, but is concentrated on improving sanitation and primary health care. Diversion of funds from academic tertiary hospitals has reduced specialised services, particularly cardiology and cardiac surgery, and has resulted in an exodus of skilled personnel to the private sector. In the rest of sub-Saharan Africa, tertiary health care is mainly privately funded. Cardiology and cardiac surgery is not widely available. Many countries are crippled by debt and chronic local conflicts. Only one state hospital (Groote Schuur, Cape Town) provides an electrophysiology (EP) service including catheter ablation and ICD implantation, and training in EP, by two electrophysiologists. EP services are available privately in 3 centres. No EP service exists in the rest of sub-Saharan Africa.

Africa↗
PubMed2000

Is psoriasis a T-cell disease?

The etiology and pathogenesis of psoriasis--one of the most common chronic, inflammatory, hyperproliferative skin disorders of man--have long fascinated dermatologists, pathologists and biologists alike. Here, we have a model disease that offers to study neuroectodermal-mesenchymal interactions in the widest sense possible. Epithelial, endothelial, and hematopoietic cells as well as neurons projecting into the skin apparently all interact with each other to generate the characteristic psoriatic lesion. For decades, the ongoing controversy on the molecular nature, choreography and hierarchy of these complex interactions e.g. between epidermal keratinocytes, T cells, neurotrophils, endothelial cells and sensory nerves has served as a driving force propelling investigative dermatology to ever new horizons. This debate has not only been at the heart of our quest to develop more effective forms of therapy for this socially crippling disease, but it also has profoundly influenced how we view the skin as a whole: the numerous competing theories on the pathogenesis of psoriasis published so far also are reflections on the evolution of mainstream thought in skin biology over the last decades. These days, conventional wisdom infatuated with a T-cell-centered approach to inflammatory skin diseases-- portrays psoriasis as an autoimmune disease, where misguided T lymphocyte activities cause secondary epithelial abnormalities. And yet, as this CONTROVERSIES feature reminds us, some authoritative "pockets of academic resistance" are still quite alive, and interpret psoriasis e.g. as a genetically determined, abnormal epithelial response pattern to infectious and/or physicochemical skin insults. Weighing the corresponding lines of argumentation is not only an intriguing, clinically relevant intellectual exercise, but also serves as a wonderful instrument for questioning our own views of the skin universe and its patterns of deviation from a state of homeostasis.

Animals↗
PubMed2002

Cytolethal distending toxin of Actinobacillus actinomycetemcomitans. Occurrence and association with periodontal disease.

The cytolethal distending toxin (Cdt) of Actinobacillus actinomycetemcomitans, a periodontal pathogen, is a newly described cytotoxin with immunosuppressive properties, capable of causing cell cycle arrest of lymphocytes. The objectives of this study were to investigate the occurrence of A. actinomycetemcomitans with the cdt genotype in the subgingival plaque of periodontitis patients and to determine the association of this bacterial genotype with periodontal disease. A total of 146 subgingival plaque samples from periodontitis patients were assayed by the PCR method using oligonucleotide primers targeting the cdt operon of A. actinomycetemcomitans. Primers targeting the leukotoxin gene A (ltxA) of A. actinomycetemcomitans was used to determine the occurrence of the bacteria in the plaque samples at baseline. At baseline, A. actinomycetemcomitans was detected in 106 out of 146 (73%) diseased sites studied. Among the 106 diseased sites found to harbor A. actinomycetemcomitans, 13 sites were positive for the bacteria with the cdt genotype (12%). Out of the 13 positive sites, 10 sites were obtained from patients diagnosed with aggressive periodontitis (77%). Thus, A. actinomycetemcomitans with the cdt genetic subtype has low occurrence in the subgingival plaque of periodontitis patients. However, a strong association was observed between the presence of the bacteria and aggressive forms of periodontitis. Thus, the cytotoxic and immunosuppressive properties of A. actinomycetemcomitans Cdt may function to cripple the host immunity and contribute to the pathogenesis of aggressive periodontitis.

Adult↗
PubMed2004

Capturing attention when attention blinks.

Four experiments addressed the question of whether attention may be captured when the visual system is in the midst of an attentional blink (AB). Participants identified 2 target letters embedded among distractor letters in a rapid serial visual presentation sequence. In some trials, a square frame was inserted between the targets; as the only geometric object in the sequence, it constituted a singleton. Capture effects obtained when the AB was most severe and when it was over were compared. There were 3 main results. First, capture occurred even when the AB was crippling, suggesting that a singleton exogenously engaged attention even when processing of a previous target was continuing apace. Second, when the singleton contained the key target feature, capture effects were clearly manifest. Third, even when the singleton did not possess the key target feature, it still succeeded in capturing attention, although the effects were both feeble and fleeting.

Attention↗