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At least 379 records · Page 21Linked to original sources

PubMed2001

Rationally designed strings of promiscuous CD4(+) T cell epitopes provide help to Haemophilus influenzae type b oligosaccharide: a model for new conjugate vaccines.

The age-related and T cell-independent immunological properties of most capsular polysaccharides limit their use as vaccines, especially in children under 2 years of age. To overcome these limitations, polysaccharide antigens have been successfully conjugated to a variety of carrier proteins, such as diphtheria toxoid or tetanus toxoid (TT) and the diphtheria mutant (CRM197) to produce very successful glycoconjugate vaccines. The increasing demand for new conjugate vaccines requires the availability of additional carriers providing high and long-lasting T helper cell immunity. Here we describe the design and construction of three recombinant carrier proteins (N6, N10, N19) constituted by strings of 6, 10 or 19 human CD4(+) T cell epitopes from various pathogen-derived antigens, including TT and proteins from Plasmodium falciparum, influenza virus and hepatitis B virus. Each of these epitopes is defined as universal in that it binds to many human MHC class II molecules. When conjugated to Haemophilus influenzae type b (Hib) oligosaccharide, these carriers elicit a potent anti-Hib antibody response in mice. In the case of the N19-Hib conjugate, this response is at least as good as that observed with CRM197-Hib, a conjugate vaccine currently used for mass immunization. We also show that some of the universal epitopes constituting the recombinant carriers are specifically recognized by two human in vitro systems, suggesting that T cell memory is provided by the selected epitopes. The data indicate that rationally designed recombinant polyepitope proteins represent excellent candidates for the development and clinical testing of new conjugate vaccines.

Amino Acid Sequence↗

PubMed1994

Cysteine strings, calcium channels and synaptic transmission.

Multidisciplinary studies have led to the discovery and characterization of cysteine string proteins (csps) in both Drosophila and Torpedo. Phenotypic analysis of csp mutants in Drosophila demonstrates a crucial role for csp in synaptic transmission. Expression studies of Torpedo csp (Tcsp) in Xenopus oocytes suggests that the protein has some role in the function of presynaptic Ca2+ channels. However, biochemical purification of Tcsp indicates that is associated with synaptic vesicles rather than with the plasma membrane of presynaptic terminals where Ca2+ channels reside. These results suggest a model in which csps serve as a link by which docked synaptic vesicles could modulate the activity of presynaptic Ca2+ channels.

Animals↗

PubMed1979

Use of circular stapling gun with peranal insertion of anorectal purse-string suture for construction of very low colorectal or colo-anal anastomoses.

A technique is described for construction of the colorectal or colo-anal anastomosis in low rectal resection by using an automatic circular stapling device and inserting the anorectal purse-string suture peranally from below. This method was employed in 4 patients resulting in complete healing in 3 cases and a moderate leak in 1, which, however, eventually healed satisfactorily.

Anal Canal↗

PubMed1990

Complementation of fission yeast cdc2ts and cdc25ts mutants identifies two cell cycle genes from Drosophila: a cdc2 homologue and string.

We have exploited the universality of the molecular mechanisms that control entry into mitosis to clone the Drosophila melanogaster homologues of fission yeast Schizosaccharomyces pombe cell division control (cdc) genes by the complementation of temperature sensitive mutations. The Drosophila genes were expressed in S.pombe as cDNAs from the SP6 promoter. Successful recovery of complementing plasmids required that we first 'adapt' pooled plasmids from a Drosophila embryonic cDNA library for propagation in fission yeast by introducing an ars1-LEU2 DNA fragment into the vector. This library was introduced into S.pombe cdc2 and cdc25 mutants, and plasmids isolated carrying cDNAs that complement these mutations. The gene that encodes the Drosophila cdc2 homologue maps to a single locus in the Drosophila genome at 31E on chromosome 2. It is expressed maternally to provide mRNA in syncytial embryos, and appears to be zygotically expressed in mitotically active regions of the cellularized embryo. We have isolated two different cDNAs that complement cdc25-22. One corresponds to a transcript of string, previously described as the Drosophila homologue of cdc25, and the other to a gene that has not been previously characterized.

Amino Acid Sequence↗

PubMed1982

Evaluating Doppler devices using a moving string test target.

Two moving string test targets have been developed and used to characterize ultrasound Doppler instrumentation. The characteristics investigated were sample volume size and location in space, amplitude sensitivity to Doppler shift, and resolution of Doppler direction. The tests were performed on a combined echo/Doppler instrument and on an annular array system. The procedures can be carried out routinely in the clinical laboratory to ensure that the instrument is working properly or as an aid for correct interpretation of acquired data.

Auscultation↗

PubMed2003

Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain.

Lithium salts are used to treat manic-depressive disorders; however, the mechanism by which lithium produces its therapeutic benefit remains obscure. The action of lithium may involve alterations of proteins important for regulating synaptic function. In this context, we observed recently that lithium at therapeutically relevant concentrations enhanced expression of cysteine string protein (csp) at the level of both mRNA and protein, in cell culture and in rat brain. Several lines of evidence have shown that csps are vital components of the regulated secretory pathway. We were interested whether lithium modulates expression of csp in specific brain regions. To study this issue, we analyzed the effects of chronic lithium administration (21 days) on csp mRNA levels in rat brain using in situ hybridization. Densitometric analysis revealed that lithium upregulated csp mRNA in several brain areas that are important for mood and behavior. This effect may be germane to understanding the beneficial action of lithium in mood disorders.

Animals↗

PubMed2004

Long-term outcome of focal dystonia in string instrumentalists.

This study describes the clinical characteristics and long-term outcome in string instrumentalists with focal task-specific dystonia. We present the results of a follow-up telephone survey of 21 violin and viola players with focal dystonia. Eighteen musicians responded to the questionnaire. Information on long-term outcome was available on average 13.8 years after onset of symptoms. Main complaints were playing-related loss of control and involuntary movements affecting the fingering hand in 16 and the bow arm in 5 patients. In 18 patients (86%), signs of abnormal posture could be detected by watching them play their instrument. Treatment attempts included nerve decompression, physical therapy, retraining, and anticholinergic medication. In selected patients, botulinum toxin injections or splint devices were offered. Only 38% of the performing artists were able to maintain their professional careers, among them none with bow arm dystonia. Focal dystonia may affect the fingering hand or bow arm in violin and viola instrumentalists. Treatment benefit is limited and in more than half of the patients, dystonia leads to the end of their musical career.

Adult↗

PubMed2007

Morphological and functional effects of altered cysteine string protein at the Drosophila larval neuromuscular junction.

The synaptic vesicle-associated cysteine string protein (CSP) is critical for neurotransmitter release at the neuromuscular junction (NMJ) of Drosophila, where the approximately 4% of mutant flies lacking CSP that survive to adulthood exhibit spastic jumping and shaking, temperature-sensitive paralysis, and premature death. Previously, it has been shown that CSP is also required for nerve terminal growth and the prevention of neurodegeneration in Drosophila and mice. At larval csp null mutant NMJs of Drosophila, intracellular recordings from the muscle showed that evoked release is significantly reduced at room temperature. However, it remained unclear whether the reduction in evoked release might be due to a loss of synaptic boutons, loss of synapses, and alterations in trafficking of vesicles to synapses. To resolve these issues, we have examined synaptic structure and function of csp null mutant NMJs at the level of single boutons. csp null mutations proportionally reduce the number of synaptic boutons of both motor neurons (1s and 1b) innervating larval muscles 6 and 7, while the number of synapses per bouton remains normal. However, focal recordings from individual synaptic boutons show that nerve-evoked neurotransmitter release is also impaired in both 1s and 1b boutons. Further, our ultrastructural analyses show that the reduction in evoked release at low stimulation frequencies is not due to a loss of synapses or to alterations in docked vesicles at synapses. Together, these data suggest that CSP promotes synaptic growth and evoked neurotransmitter release by mechanistically independent signaling pathways.

Animals↗

PubMed1994

DNA sequencing with a hexamer string primer and dye-labeled terminators.

A method for fluorescence-based DNA sequencing using a hexamer string primer and dye-labeled terminators is described. Sequencing protocols have been determined that provide an average read length of 393 bases with 99.6% base-calling accuracy for single-stranded M13mp18 DNA, and an average read length of 367 bases with 99.4% base-calling accuracy for double-stranded M13mp19 DNA. The signal intensity is stronger than that obtained with a standard 18-mer primer, while the resolution and length of readable sequence are comparable.

DNA Primers↗

PubMed1999

Pattern formation in the absence of cell proliferation: tissue-specific regulation of cell cycle progression by string (stg) during Drosophila eye development.

During Drosophila eye development, the posterior-to-anterior movement of the morphogenetic furrow coordinates cell cycle progression with the early events of pattern formation. The cdc25 phosphatase string (stg) has been proposed to contribute to the synchronization of retinal precursors anterior to the furrow by driving cells in G(2) through mitosis and into a subsequent G(1). Genetic and molecular analysis of Drop (Dr) mutations suggests that they represent novel cis-regulatory alleles of stg that inactivate expression in eye. Retinal precursors anterior to the furrow lacking stg arrest in G(2) and fail to enter mitosis, while cells within the furrow accumulate high levels of cyclins A and B. Although G(2)-arrested cells initiate normal pattern formation, the absence of stg results in retinal patterning defects due to the recruitment of extra photoreceptor cells. These results demonstrate a requirement for stg in cell cycle regulation and cell fate determination during eye development.

Alleles↗

PubMed1993

Kumacone II: an adapter to aid in the placement of a purse-string suture in very low anterior rectal resection.

We have designed an adapter called the "Kumacone II", being a bottle-shaped rubber device which greatly aids in placing a purse-string suture, even at the lowest level near the anorectal junction of the rectum. When this adapter is used, performing the anastomosis is much less time-consuming and not as much training is needed as for low anterior resection using conventional manual suturing. In a clinical study, the incidence of leakage and incontinence was nil in five out of five patients.

Anal Canal↗

PubMed1983

Influence of diazepam and methylphenidate on identification of rapidly presented letter strings: diazepam enhances visual masking.

The effect of diazepam (0, 5, 10 mg) and methylphenidate (0, 5, 10 mg) on the identification of briefly displayed letter strings composing words was investigated. Each letter was presented for 70 ms. The interstimulus interval (ISI) between two successive letters was 10, 100 or 200 ms. The length of the words (WL) was three, five, seven or nine letters. The dependent variable was the number of correctly identified words. As predicted, strong visual masking effects, the strength of which was dependent on ISI and WL, appeared. In the 10 ms condition, diazepam at both doses, but not methylphenidate, further enhanced masking. It is suggested that the results reflect the effect of GABA on masking, and support certain psychological theories about the inhibitory neuronal pathways that are involved in masking. The human peripheral visual system is a promising model for the experimental assessment and integration of pharmacodynamic, neurophysiological and psychological observations.

Adult↗

PubMed1994

[Intraperitoneal colon anastomosis with laparoscopic purse string suture clamp and Valtrac ring].

In combination with the biofragmentable Valtrac ring a newly developed purse-string suture clamp offers the possibility of performing intraperitoneal anastomoses of the small and large bowel without the need for stapling devices. During this experimental study end-to-end anastomoses of the descending colon were constructed in five pigs. One animal was re-examined on day 1 after the operation and the others were all sacrificed on day 21 after. None of the animals showed any signs of an anastomotic leakage. Little scar tissue was seen macroscopically or histologically in the anastomotic region of the animals sacrificed 3 weeks after the operation. The operative technique presented in this paper might render the so-called assisted laparoscopic procedures for the right hemicolon unnecessary in the future.

Anastomosis, Surgical↗

PubMed1981

Using biofeedback to reduce left arm extensor EMG of string players during musical performance.

Electromyographic (EMG) feedback offers a mechanism for helping musicians reduce specific muscle tension during performance. Nine intermediate to advanced level string players participated in a four-session, pretest/posttest design study to determine (1) if left forearm extensor EMG could be reduced using biofeedback, (2) if reductions in EMG would generalize to a no-feedback condition, and (3) if reductions in EMG would generalize from extensors to flexors. Results indicate that biofeedback did facilitate significant decreases in EMG, that the reductions in EMG did generalize to a no-feedback condition, and that generalization from extensors to flexors did not occur.

Adolescent↗

PubMed1991

Eukaryotic origins: string analysis of 5S ribosomal RNA sequences from some relevant organisms.

Using the PHYLOGEN tree-forming programs, we evaluate the published 5S rRNA sequences in certain of the files in the Berlin DataBank in an attempt to identify the connection between archaebacteria and the eukaryotic protists. These programs are based on methods of string analysis developed by Sankoff and others. Their discriminatory power is derived from their continuous realignment of sequences through repeated assessment of insertions and deletions as well as substitutions. The programs demonstrate that even these small molecules (ca. 120 bases) retain substantial records of evolutionary events that occurred over a billion years ago. The eukaryotes seem to have been derived from ancestors near the common origins of the halobacterial and Methanococcales groups. Identifying what might have been a primordial eukaryote is more difficult because several of the species considered as early derivatives from the common root are isolated species with large genetic differences from each other and from all other extant forms that have been sequenced. The ameboid, flagellated, and ciliated protists seem to have emerged nearly simultaneously from an ancient cluster, but the sarcodinid protozoa have preference as the group of most ancient origin. The euglenozoa and the ciliates are of later derivation. Our ability to tease plausible trees from such small molecules suggests that the mode of analysis rather than the size of the molecule is often a major limitation in the reconstruction of acceptable ancient phylogenics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Purse-string placement for transanal intraluminal circular stapling.

A technique is described that obviates the difficulty in sliding the proximal colon over the intraluminal stapling anvil. The stapler is passed per anus and advanced fully, allowing the colon to be placed over the anvil and tied under direct vision. The stapler is retracted, and only then is the rectal purse-string tied.

Anal Canal↗

PubMed2004

Whole proteome prokaryote phylogeny without sequence alignment: a K-string composition approach.

A systematic way of inferring evolutionary relatedness of microbial organisms from the oligopeptide content, i.e., frequency of amino acid K-strings in their complete proteomes, is proposed. The new method circumvents the ambiguity of choosing the genes for phylogenetic reconstruction and avoids the necessity of aligning sequences of essentially different length and gene content. The only "parameter" in the method is the length K of the oligopeptides, which serves to tune the "resolution power" of the method. The topology of the trees converges with K increasing. Applied to a total of 109 organisms, including 16 Archaea, 87 Bacteria, and 6 Eukarya, it yields an unrooted tree that agrees with the biologists' "tree of life" based on SSU rRNA comparison in a majority of basic branchings, and especially, in all lower taxa.

Algorithms↗

PubMed2001

Cysteine string protein expression in mammary epithelial cells.

Cysteine string protein (Csp) is a secretory vesicle protein previously demonstrated to be required for Ca2+-regulated exocytosis in neurons and endocrine cells. It has been suggested to function by regulating voltage-gated Ca2+ channels or, alternatively, to have a more direct effect on the regulated exocytotic machinery. Here we demonstrate the expression of Csp in mammary epithelial cells and in the KIM-2 mammary cell line. In KIM-2 cells, Csp was found to be associated with a population of small vesicles and showed partial co-distribution with the vesicle protein cellubrevin. KIM-2 cells do not express detectable levels of voltage-gated Ca2+ channels, ruling these out as a site of action. Using the release of transfected growth hormone (GH) as an assay of secretion, we found that GH is secreted in an exclusively constitutive manner from KIM-2 cells. Overexpression of Csp1 inhibits regulated exocytosis in other cell types but has no effect on constitutive GH release by KIM-2 cells. These results suggest that Csp does not have a major function in constitutive exocytosis.

Animals↗