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PubMed1985

Efficacy of spinal manipulation/mobilization therapy. A meta-analysis.

A quantitative review (meta-analysis) was undertaken to synthesize existing evidence on the efficacy of joint mobilization and manipulation and expose consumers of rehabilitation research to the methods and procedures of quantitative reviewing. Potentially relevant studies were obtained through a computer-assisted bibliographic search of the Index Medicus data base and through examination of references contained in retrieved studies. A total of 57 titles were potentially relevant to manipulation/mobilization, but only nine met the prespecified criteria for inclusion in the quantitative review. Data analysis indicated that studies not employing random assignment were more likely to produce results supporting the use of manipulation/mobilization therapies. The effects in favor of manipulation and mobilization were greater when manual therapy was provided in conjunction with other forms of treatment and were also greater when the treatment effects were measured immediately following therapy. In addition, hypotheses tests appearing in journals published in the United States showed manipulation/mobilization less effective in comparison with reports appearing in English language journals published outside the United States. The results provided only limited empirical support for spinal mobilization and manipulation when used to treat pain, flexibility limitations, and impairment in physical activity.

Back Pain↗

PubMed2002

Impact of incorporating the 2C5 crystal structure into comparative models of cytochrome P450 2D6.

Cytochrome P450 2D6 (CYP2D6) metabolizes approximately one third of the drugs in current clinical use. To gain insight into its structure and function, we have produced four different sets of comparative models of 2D6: one based on the structures of P450s from four different microorganisms (P450 terp, P450 eryF, P450 cam, and P450 BM3), another on the only mammalian P450 (2C5) structure available, and the other two based on alternative amino acid sequence alignments of 2D6 with all five of these structures. Principal component analysis suggests that inclusion of the 2C5 crystal structure has a profound effect on the modeling process, altering the general topology of the active site, and that the models produced differ significantly from all of the templates. The four models of 2D6 were also used in conjunction with molecular docking to produce complexes with the substrates codeine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); this identified Glu 216 [in the F-helix; substrate recognition site (SRS) 2] as a key determinant in the binding of the basic moiety of the substrate. Our studies suggest that both Asp 301 and Glu 216 are required for metabolism of basic substrates. Furthermore, they suggest that Asp 301 (I-helix, SRS-4), a residue thought from mutagenesis studies to bind directly to the basic moiety of substrates, may play a key role in positioning the B'-C loop (SRS-1) and that the loss of activity on mutating Asp 301 may therefore be the result of an indirect effect (movement of the B'-C loop) on replacing this residue.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1987

The role of aromatic side chain residues in micelle binding by pancreatic colipase. Fluorescence studies of the porcine and equine proteins.

Fluorescence techniques have been employed to study the interaction of porcine and equine colipase with pure taurodeoxycholate and mixed micelles. Nitrotyrosine-55 of porcine colipase is obtained by modification with tetranitromethane (low excess, in the presence of taurodeoxycholate) of the protein followed by gel filtration and ion-exchange chromatography. Verification of the residue modified was obtained by h.p.l.c. peptide purification and sequence analysis. Reduction and quantitative reaction with dansyl chloride yields a fluorescent derivative that is twice as active in conjunction with lipase as is native colipase and that exhibits a strong emission band at 550 nm. Addition of micellar concentrations of taurodeoxycholate causes a 4.3-fold increase in the emission maximum as well as a 70 nm blue shift to 480 nm. Inclusion of oleic acid to form a mixed micelle reduces these spectral effects. Scatchard analysis of the data yield a Kd of 6.8 X 10(-4) M and a single colipase-binding site for taurodeoxycholate micelles. The data, by analogy to a phospholipase system, are consistent with a direct insertion of dansyl-NH-tyrosine-55 into the micelle. The presence of a single tryptophan residue (Trp-52) in equine colipase provides an intrinsic fluorescent probe for studying protein-micelle interaction. The emission maximum of horse colipase at 345 nm indicates a solvent-accessible tryptophan residue which becomes less so on binding of micelles. A blue shift of 8 nm and a 2-fold increase in amplitude is indicative of a more hydrophobic environment for tryptophan induced by taurodeoxycholate micelles. There is also a decrease in KSV for acrylamide quenching in the presence of micelles, which further supports a loss of solvent accessibility. The most dramatic pH effects are observed with KI quenching, and may indicate the presence of negative charges near Trp-52.

Acrylamide↗

PubMed2006

Orthodontic retention: a systematic review.

OBJECTIVE: To evaluate the effectiveness of different retention strategies used to maintain tooth position after treatment by orthodontic appliances. DATA SOURCES: The search strategy was carried out according to the standard Cochrane systematic review methodology. The following databases were searched for randomized clinical trials (RCT) or controlled clinical trials (CCT): Cochrane Oral Health Group Trials Register, Cochrane Clinical Trials Register, MEDLINE and EMBASE. No language restrictions were applied. Authors of trials were contacted to identify unpublished trials. Inclusion and exclusion criteria were applied when considering the studies to be included and a quality assessment made for each paper. DATA SELECTION: The primary outcome was the amount of relapse. Secondary outcomes were survival of retainers, adverse effects on oral health and patient satisfaction. DATA EXTRACTION: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two reviewers. Five studies (2 RCTs and 3 CCTs) fulfilled the inclusion criteria. DATA SYNTHESIS: There was evidence, based on data from one trial, that there was a statistically significant increase in stability in both the mandibular (P<0.001) and maxillary anterior segments (P<0.001) when the CSF (circumferential supracrestal fiberotomy) was used in conjunction with a Hawley retainer, compared with a Hawley retainer alone. However, this evidence may be unreliable due to flaws in the study design. There was also weak, unreliable evidence that teeth settle quicker with a Hawley retainer than with a clear overlay retainer after 3 months. CONCLUSIONS: There is currently insufficient evidence on which to base the clinical practice of orthodontic retention.

Humans↗

PubMed1986

Conjunctivitis, tracheitis, and pneumonia associated with herpesvirus infection in green sea turtles.

Fourteen juvenile (15- to 20-month-old) green sea turtles (Chelonia mydas), representative of a group of sea turtles with clinical signs of respiratory tract disease, were euthanatized and submitted for necropsy. Macroscopically, lesions included periglottal necrosis, tracheitis with intraluminal caseous and laminated necrotic debris, and severe pneumonia. Several turtles had caseous conjunctival exudate covering the eyes. Microscopically, the turtles had fibrinonecrotic inflammation around the glottal opening, tracheitis, and severe bronchopneumonia and interstitial pneumonia. In multifocal areas, periglottal and tracheal epithelial cells adjacent to areas of necrosis had hypertrophic nuclei with amphophilic intranuclear inclusions. A mixed population of primarily gram-negative microorganisms was isolated from the tracheal and glottal lesions. Attempts at viral isolation in cultures of green sea turtle kidney cells resulted in the development of cytopathic effects characterized by giant cell formation and development of intranuclear inclusions. Using electron microscopy, intranuclear viral particles (88 to 99 nm in diameter) were seen in inclusion-containing tracheal and glottal epithelial cells and infected green sea turtle kidney cells; particles were consistently seen enveloping from nuclear membranes, and mature particles (132 to 147 nm) were found in the cytoplasm. On the basis of size, conformation, location, and presence of an envelope, the particles most closely resembled those of herpes-viruses.

Animals↗

PubMed2005

Inhibited cell growth and protein functional changes from an editing-defective tRNA synthetase.

The genetic code is established in aminoacylation reactions catalyzed by aminoacyl-tRNA synthetases. Many aminoacyl-tRNA synthetases require an additional domain for editing, to correct errors made by the catalytic domain. A nonfunctional editing domain results in an ambiguous genetic code, where a single codon is not translated as a specific amino acid but rather as a statistical distribution of amino acids. Here, wide-ranging consequences of genetic code ambiguity in Escherichia coli were investigated with an editing-defective isoleucyl-tRNA synthetase. Ambiguity retarded cell growth at most temperatures in rich and minimal media. These growth rate differences were seen regardless of the carbon source. Inclusion of an amino acid analogue that is misactivated (and not cleared) diminished growth rate by up to 100-fold relative to an isogenic strain with normal editing function. Experiments with target-specific antibiotics for ribosomes, DNA replication, and cell wall biosynthesis, in conjunction with measurements of mutation frequencies, were consistent with global changes in protein function caused by errors of translation and not editing-induced mutational errors. Thus, a single defective editing domain caused translationally generated global effects on protein functions that, in turn, provide powerful selective pressures for maintenance of editing by aminoacyl-tRNA synthetases.

Amino Acyl-tRNA Synthetases↗

PubMed1996

Relative prognostic importance of histologic invasion of the laryngeal framework by hypopharyngeal cancer.

This study assessed the relative prognostic importance of histologic invasion of the laryngeal framework by hypopharyngeal cancer. The laryngeal specimens and medical records of 55 patients found to have primary hypopharyngeal cancer between 1962 and 1988 were reviewed. Full 3-year follow-up information was obtained for 51 patients. The overall 3-year survival rate was 43% A(22/51). The 3-year survival rate was 55% (17/31) without histologic invasion versus 25% (5/20) with invasion (p < .05). To assess how invasion affected survival rates in conjunction with clinical predictors, we divided the cohort into two groups (mild versus severe illness) based on the presence or absence of anemia and comorbidity. Only in the group with mild illness did histologic invasion provide additional prognostic information. These results demonstrate that the inclusion of clinical variables in predictions of prognosis can strikingly alter the prognostic importance of invasion of the laryngeal framework.

Anemia↗

PubMed2006

Phylogenetic analysis of the evolution of the niche in lizards of the Anolis sagrei group.

Recent advances in ecological niche modeling (ENM) algorithms, in conjunction with increasing availability of geographic information system (GIS) data, allow species' niches to be predicted over broad geographic areas using environmental characteristics associated with point localities for a given species. Consequently, the examination of how niches evolve is now possible using a regionally inclusive multivariate approach to characterize the environmental requirements of a species. Initial work that uses this approach has suggested that niche evolution is characterized by conservatism: the more closely related species are, the more similar are their niches. We applied a phylogenetic approach to examine niche evolution during the radiation of Cuban trunk-ground anoles (Anolis sagrei group), which has produced 15 species in Cuba. We modeled the niche of 11 species within this group using the WhyWhere ENM algorithm and examined the evolution of the niche using a phylogeny based on approximately 1500 base pairs of mitochondrial DNA. No general relationship exists between phylogenetic similarity and niche similarity. Examination of species pairs indicates some examples in which closely related species display niche conservatism and some in which they exhibit highly divergent niches. In addition, some distantly related species exhibit significant niche similarity. Comparisons also revealed a specialist-generalist sister species pair in which the niche of one species is nested within, and much narrower than, the niche of another closely related species.

Algorithms↗

PubMed1982

Biology of Chlamydia.

The genus Chlamydia consists of two species, Chlamydia trachomatis and C. psittaci. The former includes (a) the trachoma/inclusion conjunctivitis (TRIC) agents, subdivided into the serotypes A-K; (b) the lymphogranuloma venereum (LGV) agents, subdivided into the serogroups (L 1-3); and (c) the mouse penumonitis agent. The major characteristics differentiating the two species are sulfonamide susceptibility and the formation of distinct inclusion granula in host cells, in the case of C. trachomatis, whereas C. psittaci is resistant to sulfonamides and forms less dense inclusions. Chlamydiae are characterized by a special growth cycle. The infective form of Chlamydia is the elementary body (EB), which stimulates its own phagocytosis by the host cell, an event followed by the EB's transformation into the reticulate body (RB). The RB forms small buds which subdivide by simple fission to produce several RB within the host cell cytoplasm. The growth cycle is completed by transformation of the RB into the infective EB from before liberation of the latter from the host cell. The chlamydiae are deficient in independent energy metabolism. Thus, their supply of ATP and essential building blocks must be obtained from the host cell cytoplasm. The TRIC agents have neuraminidase localized to the surface structures. Receptors of the microbe are temperature-sensitive, whereas the host cell is trypsin-sensitive.

Anti-Bacterial Agents↗

PubMed1988

Ultrastructural alterations in caudate nucleus in aged cats.

These studies provide information on the changes in the ultrastructure in the caudate nucleus of aged cats. The major finding was that there was a decrease in the density of synapses in caudate neuropil. This decrease occurred in animals after 3 years of age and remained relatively constant in older animals. In conjunction with this change a population of unusually long synapses also occurred. These larger synaptic appositions were associated with enlarged spine heads. The caudate also showed a number of qualitative ultrastructural alterations. Many neurons contained accumulations of lipofuscin or lipopigment granules in aged animals. These inclusions occurred in both soma and dendrites of neurons and all types of glial cells. A unique configuration of collapsed agranular cisterns also was observed in aged animals. The present results indicate that decreases in synaptic density may be one morphological event underlying functional alterations observed in caudate neurons in aged cats.

Aging↗

PubMed2003

Quantitative assessment of inter-clinician variability of target volume delineation for medulloblastoma: quality assurance for the SIOP PNET 4 trial protocol.

BACKGROUND AND PURPOSE: To assess inter-clinician variability amongst specialist paediatric radiation oncologists in delineating clinical target volumes for treating medulloblastoma as a quality assurance exercise prior to the introduction of the SIOP PNET 4 trial protocol of conformal radiotherapy to the posterior fossa and tumour bed. PATIENTS AND METHODS: Participants from 17 UK centres attended an educational meeting and then completed a clinical planning exercise to outline: (1) the whole posterior fossa and (2) the tumour bed. Quantitative analysis of the volumes, lengths, spatial positioning and axial planes for each individual was carried out and variation between individuals analysed. RESULTS: Outlining of the posterior fossa was reasonably consistent, although most variation was seen in defining the superior border of the tentorium. A major difference was the decision whether or not to include the post-surgical meningocoele in the clinical target volume (CTV). The CTV for the tumour bed was under treated by all participants due to lack of inclusion of pre-operative tumour extent. CONCLUSIONS: This exercise demonstrated several ambiguities in the draft protocol and highlighted particular areas of inter-clinician variation. Consequently the protocol was revised and improved to take account of these findings. We recommend that planning exercises, in conjunction with education and training, should be implemented before the start of any new radiotherapy trial. In the future, the use of image transfer will allow prospective peer review of target volumes before treatment commences. These measures are essential to ensure that alterations in clinical practice are achieved in a uniform way.

Cerebellar Neoplasms↗

PubMed2000

Effectiveness of interventions to prevent work-related eye injuries.

OBJECTIVE: The objective of this review was to describe the effectiveness of interventions designed to prevent work-related eye injuries in construction, manufacturing, and agricultural industries. Two types of interventions were of interest: (1) effectiveness of different types of eye protection and/or environmental controls in the workplace, and (2) evaluation of behavioral interventions focused on increasing the use of eye protection among at-risk workers. METHODS: Cochrane Collaboration search strategies were used to identify reports of the effectiveness of interventions designed to prevent eye injuries. To be included, a measurable outcome (change in eye injury rates, use of eye protection or costs for eye injury care) had to be reported. Studies that focused on exposures to lasers, radiation or microwaves were not included. RESULTS: Seven reports met inclusion criteria-all from industrial settings. None of the studies was a controlled trial and only one involved a comparison group. CONCLUSIONS: Although there is some evidence that policy changes are effective in changing behaviors and reducing eye injuries in manufacturing settings either in conjunction with a broader program focused on eye safety or by policy alone, there is limited scientific literature about the effectiveness of eye injury prevention interventions. There is a need for systematic evaluation of interventions designed to prevent eye injuries and to change the overall safety culture.

Accident Prevention↗

PubMed1977

[Reiter's syndrome in children. Ultramicroscopic study of the synovial membrane].

The clinical picture of a 12 year-old boy with Reiter's syndrome, manifested by conjunctivitis, keratitis, polyarthritis and urethritis, is presented and compared with the other 26 boys and girls with this syndrome that have been reported elsewhere. Light microscopy and inmunofluorescence studies of synovial membrane showed nonspecific changes. However, with the electron-microscope two types of cellular inclusions were seen in both, synovial cells and macrophages. Such changes were similar to those described in adults with Reiter's syndrome.

Anti-Bacterial Agents↗

PubMed2006

Immunogenicity and protective efficacy of a recombinant filamentous haemagglutinin from Bordetella pertussis.

Bordetella pertussis is the causative agent of whooping cough, a major childhood pathogen; acellular vaccines consisting of purified B. pertussis antigens such as filamentous haemagglutinin (FHA) are commonly used to prevent pertussis. Despite the importance of FHA in B. pertussis pathogenesis and its inclusion in most acellular vaccines, the functional importance of individual domains in the induction of protective immunity is largely unknown. In this study, we have purified a recombinant FHA protein from Escherichia coli consisting of a 42 kDa maltose binding domain of E. coli and the 43 kDa type I immunodominant domain of FHA. The fusion protein (Mal85) was purified from E. coli cell lysates via affinity chromatography with an amylose column. Mal85 was then delivered to BALB/c mice intranasally encapsulated in liposomes, formulated with Protollin(TM) or in conjunction with an immunostimulatory CpG oligonucleotide. Mice were also vaccinated intraperitoneally with alum-adsorbed Mal85. Sera from all treatment groups showed strong IgG responses to Mal85 and recognized native FHA. Specific salivary IgA was induced in mice vaccinated with Mal85 in liposomes, Protollin(TM) and delivered with CpG. Vaccination with Mal85 encapsulated in liposomes or formulated with Protollin(TM) provided protection against aerosol challenge with B. pertussis in BALB/c mice. These data indicate that the type I domain of FHA is a protective antigen in mice and may serve as a candidate for inclusion in new acellular pertussis vaccines.

Adhesins, Bacterial↗

PubMed1996

Microbiologic, radiographic, and anatomic study of the nasolacrimal duct apparatus in the rabbit (Oryctolagus cuniculus).

This study was motivated by the sporadic observation of epiphora in two male rabbits. The epiphora was unilateral and not associated with conjunctivitis or Pasteurella infection. To characterize the cause of epiphora, we studied 15 specific-pathogen-free New Zealand White rabbits. This study group was composed of the two affected males, four unaffected males, and nine unaffected females. Clinical evaluation consisted of bacterial culture of conjunctival specimens, examination of conjunctival scrapings for chlamydial inclusions, culture and cytologic examination of specimens from the nasolacrimal duct, plain and contrast radiography, latex casting, histologic examination, and the Schirmer tear test. Important differences found in the rabbits with epiphora included an opalescent, gritty, nasolacrimal duct flush fluid and marked unilateral dilatation of the duct proximal to a dorsal flexure at the caudal limit of the incisor tooth root. The flush solution from one affected rabbit cleared with ether, suggesting the presence of triglycerides or cholesterol. The organisms most commonly isolated from the conjunctiva were Moraxella sp., Oligella urethralis, Staphylococcus aureus, coagulase-negative Staphylococcus sp., and Streptococcus viridans. The organisms most commonly isolated from the nasolacrimal duct flush fluid were Moraxella sp., S. viridans, and Neisseria sp. Culture of the nasolacrimal duct flush fluid yielded microorganisms more consistently than did culture of the conjunctival specimens. All microorganisms isolated from affected rabbits also were isolated from unaffected rabbits. There was no apparent contribution of microorganisms to the development of epiphora, and Schirmer tear test results for affected animals were within the range seen in unaffected animals. Occlusion of the nasolacrimal duct was presumed to be attributable to fat droplets. This study augments the existing literature and represents the first report of anomalous nasolacrimal duct anatomic features in the rabbit.

Animals↗

PubMed1992

Malignant rhabdoid tumor of soft tissues: a cytopathological and immunohistochemical study.

We describe the cytopathological and immunohistochemical features of a primary malignant rhabdoid tumor (MRT) located in the left forehead region of an 8-mo-old female. The cardinal characteristics are hyaline cytoplasmic inclusions, rounded or bean-shaped nucleus, vesicular chromatin, central prominent nucleolus, and poorly defined cytoplasmic profile. Both the cytoplasm and the hyaline inclusion are vimentin and keratin positive, but negative with desmin, S-100 protein, neuron-specific enolase, (NSE) myoglobin, leukocyte common antigen (LCA), and alpha-1-antichymotrypsin. This immunohistochemical pattern, although not exclusive to MRT, is fairly typical of MRT, and when it is assessed in conjunction with cytopathological findings and clinical data permits a confident diagnosis of MRT. We emphasize the utility of immunohistochemical techniques in making the differential diagnosis of MRT against other childhood round-cell tumors.

Biopsy, Needle↗

PubMed1988

On the utility of 13C-n.m.r. spectroscopy in the identification of the primary structures of manno-oligosaccharides and glycopeptides.

The utility of 13C-n.m.r. spectroscopy in the identification of the primary structures of mannose-containing glycans is investigated. Unlike 1H resonances where the chemical shifts reflect multiple short- and long-range effects, the chemical shifts of 13C resonances are dependent largely upon short-range effects classified as glycosylation (linkage) and substitution effects. These effects are parametized for glycans composed of mannose and encoded in a FORTRAN algorithm. Applications of this program to "unknown" sets of experimental chemical shifts for the resonances of anomeric carbons gave the following conclusions. (1) This program can be used to produce a sub-set of possible structures inclusive of the "known" structure. (2) For other than simple oligosaccharides, it is unlikely that a single structure is consistent with the data for anomeric carbons alone, even when the linkage composition of the glycan has been assessed from other spectral data. (3) When used in conjunction with other chemical techniques, this program can provide a powerful tool for primary analysis of the structure of mannose-containing glycans.

Algorithms↗

PubMed2003

Hodgkin's disease in HIV.

The outcome of patients with HIV-HD has improved with better, combined antineoplastic and antiretroviral approaches. New and effective antiretroviral drugs (ie, protease inhibitors), in conjunction with nucleoside analogs, improve the control of the underlying HIV infection when used during treatment of HD with chemotherapy. In fact, the possibility of reducing viral load to undetectable levels and increasing the CD4+ cell count reduces the risk of OIs during antineoplastic treatment. The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HD may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival. Finally, more effective antineoplastic regimens--such as high-dose chemotherapy with autologous stem cell transplantation (which is required in the case of HIV-HD, due to its aggressiveness)--should be considered to improve the response rate and disease-free survival of these patients.

Antineoplastic Combined Chemotherapy Protocols↗