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At least 181 records · Page 10Linked to original sources

A 'first loop' linear epitope accessible on native hepatitis B surface antigen that persists in the face of 'second loop' immune escape.

Murine monoclonal antibodies (mAbs) were raised following immunization with native mutant hepatitis B surface antigen (HBsAg) purified from human sera. A set of antibodies binding to a linear epitope carried between residues 121 and 129 of the s region was demonstrated. These antibodies were shown by cross-competition assays to bind to a single epitope whose antigenicity was influenced by the TTP motif lying between residues 125 and 127. This first loop epitope remained accessible on the surface of HBsAg in spite of major second loop mutations abrogating the normal a conformational epitopes. The mAb and its binding region in the first loop are important diagnostically and may represent an importance immunological target, one that is stable in the face of immunologically driven escape.

Animals↗

Autocrine stimulation in colorectal carcinoma (CRC): positive autocrine loops in human colorectal carcinoma and applicable significance of blocking the loops.

Many tumors co-express growth factors and their receptors; thus, the concept of autocrine secretion was proposed to explain the unrestrained growth of the malignant cells. Autocrine stimulation refers to positive autocrine secretion, which functions to stimulate cell growth. Many of the positive autocrine loops have been demonstrated in human colorectal carcinoma (CRC), which are considered to play an important role in the initiation and progression of the cancer. These autocrine loops provide information for prognostic markers and targets for biological therapies of CRC. Interruption of the autocrine loops could potentially inhibit malignant cell growth. The field is encouraging but further research is needed.

Autocrine Communication↗

Caloric irrigators: air, open-loop water and closed-loop water.

Selective stimulation of the semicircular canal system of one ear by establishing a temperature gradient is still widely used in the clinic in the caloric test. The results obtained are noted for their imprecision and variability. This is, in part, due to a lack of uniformly applied standardized test protocols, as well as difficulties in applying a precise stimulus. The relative merit of the three types of irrigation are reviewed. Whilst some authors argue that both the closed-loop and air irrigators produce even more variability of response than open water systems, the present author believes that intratest replication studies indicate that the closed-loop irrigation stimulus is the least variable and best tolerated by the patient. In perhaps one-fifth of patients, response to the first irrigation is much stronger than subsequent stimulus applications. It is suggested that there may therefore be a case for routinely performing five irrigations in the bithermal caloric test, including a replication of the first irrigation. It is assumed that psychological factors, especially anxiety, may explain the phenomenon of enhanced initial response, and some of the variability of caloric test responses in general. Use of the closed-loop irrigator is advocated for ease of use, reduced routine maintenance and to minimize patient distress, thereby reducing anxiety and result variability.

Air↗

A comparative evaluation of open loop and closed loop drug administration strategies in the treatment of AIDS.

In recent years, many researchers in the field of biomedical sciences have made successful use of mathematical models to study, in a quantitative way, a multitude of phenomena such as those found in disease dynamics, control of physiological systems, optimization of drug therapy, economics of the preventive medicine and many other applications. The availability of good dynamic models have been providing means for simulation and design of novel control strategies in the context of biological events. This work concerns a particular model related to HIV infection dynamics which is used to allow a comparative evaluation of schemes for treatment of AIDS patients. The mathematical model adopted in this work was proposed by Nowak & Bangham, 1996 and describes the dynamics of viral concentration in terms of interaction with CD4 cells and the cytotoxic T lymphocytes, which are responsible for the defense of the organism. Two conceptually distinct techniques for drug therapy are analyzed: Open Loop Treatment, where a priori fixed dosage is prescribed and Closed Loop Treatment, where the doses are adjusted according to results obtained by laboratory analysis. Simulation results show that the Closed Loop Scheme can achieve improved quality of the treatment in terms of reduction in the viral load and quantity of administered drugs, but with the inconvenience related to the necessity of frequent and periodic laboratory analysis.

Acquired Immunodeficiency Syndrome↗

Closed-loop estimation of the open-loop carotid sinus baroreflex transfer function for the use of animal experiments in space.

In order to develop effective counter measures to cardiovascular maladaptation associated with space flight, it is essential to know how dynamic characteristics of blood pressure regulation are altered in space. The open-loop transfer characteristics of the carotid sinus baroreflex can be divided into the neural arc and peripheral arc transfer functions (Ikeda et al. 1996). The neural arc transfer function represents the dynamic input-output characteristics from arterial pressure (AP) to efferent sympathetic nerve activity (SNA), while the peripheral arc transfer function represents those from SNA to AP. Although AP perturbation according to a white noise sequence can be used to estimate the transfer functions under baroreflex closed-loop conditions (Kwanda et al. 1997), arterial catheter implantation necessary to perturb AP limits the applicability of this method to freely moving animal experiments. To overcome this problem, we explored the closed-loop system identification method using electrical stimulation. We used aortic depressor nerve (ADN) stimulation and rapid pacing (RP) of the heart to perturb the arterial baroreflex system.

Algorithms↗

Study of a human excluded jejunal loop (Thiry-Vella loop).

A case of a human jejunal loop excluded from the intestinal transit was studied. The loop was located in the retrosternal space as the first step of esophageal transit reconstruction, after an unsuccessful esophagocoloplasty performed in order to treat a caustic stenosis of the esophagus. The motility, secretion of electrolytes and the absorption of glucose and alanine by the loop were determined.

Adult↗

Molecular recognition in helix-loop-helix and helix-loop-helix-leucine zipper domains. Design of repertoires and selection of high affinity ligands for natural proteins.

Helix-loop-helix (HLH) and helix-loop-helix-leucine zipper (HLHZip) are dimerization domains that mediate selective pairing among members of a large transcription factor family involved in cell fate determination. To investigate the molecular rules underlying recognition specificity and to isolate molecules interfering with cell proliferation and differentiation control, we assembled two molecular repertoires obtained by directed randomization of the binding surface in these two domains. For this strategy we selected the Heb HLH and Max Zip regions as molecular scaffolds for the randomization process and displayed the two resulting molecular repertoires on lambda phage capsids. By affinity selection, many domains were isolated that bound to the proteins Mad, Rox, MyoD, and Id2 with different levels of affinity. Although several residues along an extended surface within each domain appeared to contribute to dimerization, some key residues critically involved in molecular recognition could be identified. Furthermore, a number of charged residues appeared to act as switch points facilitating partner exchange. By successfully selecting ligands for four of four HLH or HLHZip proteins, we have shown that the repertoires assembled are rather general and possibly contain elements that bind with sufficient affinity to any natural HLH or HLHZip molecule. Thus they represent a valuable source of ligands that could be used as reagents for molecular dissection of functional regulatory pathways.

Amino Acid Sequence↗

Cycloleucine fluxes during rat vasa recta and loop microinfusions in vivo and loop microperfusions in vitro.

Amino acids are apparently recycled between loops of Henle and vasa recta in rat papilla in vivo. To examine this process in the absence of metabolism, we performed continuous microinfusions of rat renal papillary ascending thin limbs (ATLs) and vasa recta in vivo, and microperflusions of isolated rat renal papillary descending thin limbs (DTLs) and ATLs in vitro using the nonmetabolizable, synthetic, neutral amino acid cycloleucine. Like naturally occurring amino acids, approximately = 25% of radiolabeled cycloleucine microinfused into ATLs in vivo was reabsorbed by a process that was not saturable or inhibitable. Also, like naturally occurring amino acids, approximately = 47% (relative to inulin) of radiolabeled cycloleucine microinfused into ascending vasa recta in vivo was transferred directly into ipsilateral tubular structures (probably DTLs) by a saturable and inhibitable process. In DTLs perfused in vitro, unidirectional bath-to-lumen fluxes (Jbl) tended to exceed unidirectional lumen-to-bath fluxes (Jlb), whereas in ATLs perfused in vitro Jlb tended to exceed Jbl, but the differences were not statistically significant. Moreover, none of the unidirectional fluxes was saturable or inhibitable, an observation compatible with apparent reabsorption from ATLs in vivo but incompatible with apparent movement from vasa recta to DTLs in vivo. These in vitro observations are like those made previously for the naturally occurring neutral amino acid L-alanine. The lack of saturation and inhibition, like the previous data on L-alanine, suggest that transepithelial movement of amino acids in thin limbs of Henle's loop may occur via a paracellular route and that regulation of amino acid movement in vivo may involve vasa recta, not DTLs. They also suggest that cycloleucine is a good nonmetabolizable surrogate for the study of neutral amino acid transport in the kidney.

Alanine↗

Open-loop and closed-loop control of posture: a random-walk analysis of center-of-pressure trajectories.

A new conceptual and theoretical framework for studying the human postural control system is introduced. Mathematical techniques from statistical mechanics are developed and applied to the analysis and interpretation of stabilograms. This work was based on the assumption that the act of maintaining an erect posture could be viewed, in part, as a stochastic process. Twenty-five healthy young subjects were studied under quite-standing conditions. Center-of-pressure (COP) trajectories were analyzed as one-dimensional and two-dimensional random walks. This novel approach led to the extraction of repeatable, physiologically meaningful parameters from stabilograms. It is shown that although individual stabilograms for a single subject were highly variable and random in appearance, a consistent, subject-specific pattern emerged with the generation of averaged stabilogram-diffusion plots (mean square COP displacement vs time interval). In addition, significant inter-subject differences were found in the calculated results. This suggests that the steady-state behavior of the control mechanisms involved in maintaining erect posture can be quite variable even amongst a population of age-matched, anthropometrically similar, healthy individuals. These posturographic analyses also demonstrated that COP trajectories could be modelled as fractional Brownian motion and that at least two control systems-a short-term mechanism and a long-term mechanism-were operating during quit standing. More specifically, the present results suggest that over short-term intervals open-loop control schemes are utilized by the postural control system, whereas over long-term intervals closed-loop control mechanisms are called into play. This work strongly supports the position that much can be learned about the functional organization of the postural control system by studying the steady-state behavior of the human body during periods of undisturbed stance.

Adult↗

Securing the loop--historic review of the methods used for creating a loop colostomy.

Loop transverse colostomy is a procedure that has been traditionally employed on a temporary basis for a number of indications, but, with improvement of intestinal suturing and stapling techniques, the applicability of this modality has become quite limited. This paper addresses the issue of securing the loop and traces the history of the development of this method to decompress the bowel, to divert the fecal stream, and to defunctionalize the distal colon.

Colostomy↗

Comparison of the Lippes Loop D and tapered Lippes Loop D intrauterine devices.

The tapered Lippes Loop D (LLD) is compared to the standard LLD to evaluate efficacy and termination events. The tapered device was designed with the intention of lowering the expulsion rate below the rate for women with standard Lippes Loops. The two devices were randomly assigned to 989 women in two studies. Expulsion rates for the tapered device were lower at six months (p less than 0.10) and at 12 months (p less than 0.05). When the women were divided into groups by uterine measurement, the differences continued to be significant for women with larger uteri but not for those with smaller uteri. Comparison of other pertinent event rates showed no significant differences. Analysis of the data indicates that the tapered LLD represents an improvement in expulsion rates over the standard LLD.

Female↗

Temporary inhibition of papain by hairpin loop mutants of chicken cystatin. Distorted binding of the loops results in cleavage of the Gly(9)-Ala10 bond.

Temporary inhibition of the cysteine proteinases papain and cathepsin L was observed with several hairpin loop mutants of recombinant chicken cystatin at enzyme concentrations above nanomolar. Kinetic modelling of inhibition data, gel electrophoresis and amino acid sequencing revealed that reappearance of papain activity is due to selective cleavage of the Gly(9)-Ala10 bond in the N-terminal binding area of the chicken cystatin variants, resulting in truncated inhibitors of lower affinity. Cleavage of the same bond by contaminating papaya proteinase IV was ruled out by previous purification of papain and suitable control experiments. According to the proposed kinetic model, cleavage occurs within the enzyme-inhibitor complex with first order rate constants ktemp of 2.3 x 10(-3) up to 5 x 10(-1) s-1. A similar ktemp/Km ratio was found for all mutants (0.7 x 10(6)-2.1 x 10(6) s-1.M-1); it is almost identical with the kcat/Km ratio of the peptide substrate Z-Phe-Arg-NHMec. These results suggest that distorted contacts of one of the hairpin loops affect binding of the N-terminal contact area in a way that covalent interaction of the Gly(9)-Ala10 bond with the active-site Cys residue of papain can occur and the bond is cleaved in a substrate-like manner.

Alanine↗

Modeling loop structures in proteins and nucleic acids: an RNA stem-loop.

We have used a novel modeling technique, based on combining information from several preexisting structures, to generate a three-dimensional (3D) model for the RNA stem-loop responsible for translational repression of the MS2 RNA bacteriophage replicase. Specific features of the model have been tested experimentally by chemical and enzymatic structural probes; results from these experiments have been used to "improve" the model by fixing initial assumptions. The new model and chemical modification data are in part consistent, and further predictions are being tested. The modeling algorithm has a wide range of potential applications, particularly to loop regions in proteins and nucleic acids.

Algorithms↗

The majority of the nucleotides in the top loop of the genomic 3' terminal stem loop structure are cis-acting in a West Nile virus infectious clone.

The flavivirus genome RNA terminates with a conserved 3' stem loop (SL) structure that was shown to be essential for virus replication. A stretch of conserved nts is located in the top loop (TL) of this structure. Mutation of the TL nts (5' ACAGUGC 3') in a WNV infectious clone indicated that 3 of the 7 TL nts (5' ACAGUGC 3') are critical for virus replication. Mutation of 3 of the other nts reduced the efficiency of virus replication. The four 5' TL nts are conserved in both mosquito- and tick-borne flavivirus genomes, while the TL 3' C is conserved in mosquito-borne viruses. The conservation of two or three G-C base pairs in the TL flanking sequences suggests that a stable stem is necessary for precise presentation of the TL sequence. The TL may participate in RNA as well as protein interactions.

Animals↗

Comparison of titanium loop and supramid loop lens implants: 100 patients.

One-hundred patients having intracapsular cataract extraction with intraocular lens implantation are compared with 139 patients having routine intracapsular cataract extraction. All patients were operated on by one surgeon, utilizing one technique, and, where implantation was performed, utilizing one style of lens from one manufacturer. Follow-up period was 6 to 28 months. Seventy-four percent of the implant patients achieved VA greater than or equal to 20/40, compared to 84.2% of the routine cataract patients. Of patients receiving Supramid/Prolene-supported lenses, 84.7% had VA greater than or equal to 20/40. Those patients with titanium-supported loops have a much higher incidence of CME resulting in decreased VA, indicating that this type of lens should not be used. Dislocation of intraocular lenses was the same, whether or not the loops were sutured.

Aged↗

Simplified non-looping functional loop technique for HDR brachytherapy.

The loop technique has been employed in interstitial implantation of head and neck cancers for decades. However, cable-driven afterloading sources may be unable to negotiate the curve of the loop. The technique allows separate afterloading of each catheter ensuring a good dose distribution to the surface of the implanted structure.

Brachytherapy↗

Bimodal loop-loop interactions increase the affinity of RNA aptamers for HIV-1 RNA structures.

Multiple loop-loop interactions between adjacent RNA hairpins regulate gene expression in different organisms. To demonstrate that such natural interactions could be mimicked for generating RNA ligands that are able to recognize simultaneously at least two structured RNA targets, a double kissing complex model was designed. The target consisted of two HIV-1 transactivating responsive (TAR) RNA variants, BRU and MAL, connected by a non-nucleotidic linker. The double ligand was generated by combining the corresponding hairpin aptamers, R06BRU and R06MAL, identified previously by in vitro selection [Ducongé, F., and Toulmé, J. J (1999) RNA 5, 1605-1614]. The resulting interaction was analyzed by thermal denaturation monitored by UV spectroscopy, electrophoretic mobility shift assays (EMSAs), and surface plasmon resonance (SPR) experiments. The bimodal complex was characterized by a binding equilibrium constant increased by at least 1 order of magnitude compared to that of the complexes between the individual parent hairpins. This resulted from a slower dissociation rate. We then made use of such a strategy for targeting two structured functional motifs of the folded 5' untranslated region (5'UTR) of HIV-1. Two bivalent RNA ligands were designed that targeted simultaneously the TAR and dimerization initiation site (DIS) hairpins or the TAR and poly(A) ones. The results show that these ligands also displayed enhanced affinity for their target compared to the individual molecules. The work reported here suggests that bimodal structured RNA ligands might provide a way of increasing the affinity of aptamers for folded RNA targets.

Base Pairing↗