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PubMed1992

Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure.

In selected patients with cervical intraepithelial neoplasia (CIN), outpatient ablative procedures represent a readily accepted and highly effective treatment modality. The recently introduced loop electrosurgical excision procedure offers a quick and simple alternative to cryotherapy and laser ablation for treating CIN, and has the distinct advantage of allowing both diagnosis and treatment of selected patients at a single visit. This report presents our clinical experience treating 432 patients with CIN using the loop electrosurgical excision procedure on an outpatient basis. Small loop electrodes were used to excise CIN lesions in 275 patients, and large loop electrodes were used in 157. When performed on an outpatient basis under local anesthesia, loop excision was well tolerated by patients with only minimal discomfort. Post-treatment bleeding occurred in less than 2% of the subjects and responded to either recauterization or packing of the cervix. Post-treatment stenosis occurred in less than 1%. The success rate of the loop electrosurgical excision procedure, as defined by absence of cytologic, histologic, or colposcopic lesions 4-48 months after therapy, was 80% for women treated using the small loop electrodes. Ninety percent of all patients treated using the large loop electrodes were free of disease during 6-12 months of follow-up. For women being treated for primary (as opposed to recurrent) disease, the success rate with large loop electrodes was 94%.

Carcinoma in Situ↗

PubMedDate not supplied

[Etiology, occurrence and types of the internal carotid artery loop].

Internal carotid loop was studied in 99 patients out of 1638 cases subjected to angiography. The presence of a loop was arbitrarily accepted when in the tortuous part of the artery one of its segments was situated below the preceding segment. For the spatial analysis of the tortuous part of the artery and its image in the plane of the radiogram a model was used simulating various variants of the course of the internal carotid artery. On the ground of the analysis of the spatial configuration of the arterial loops and the variability of the loop model in the plane of the radiogram six types of the loop were isolated. The loops were found in 9.2% of patients with bilateral angiography and 5.7% of those with unilateral angiography. In adults the loop was present in 5.4% of cases, and in children in 8.9% (statistically significant difference p less than 0.05). It is assumed that the loop in children is a congenital anomaly, while in adulthood besides the congenital etiology an acquired form of the loop is to be taken into account.

Adolescent↗

PubMed1987

Mitochondrial DNA displacement loop structure depends on growth state in bovine cells.

One portion of the mitochondrial genome of mammals contains no structural genes. This so-called displacement loop (D-loop) region includes the two major transcriptional promoters and one of the origins of DNA replication. The D-loop region is often found in a novel triplex structure in which a discrete single-stranded DNA segment is hybridized to one strand of the genome displacing the other strand. The significance of this triplex structure and the possible function of the single-stranded D-loop segment have remained obscure. Here we show that the locations of the major 5' termini of D-loops in growing and nongrowing bovine cells differ by 46 nucleotides. The location of bovine D-loop 5' termini is dependent on the cell cycle but is not directly linked to nuclear DNA replication. The nature of D-loop 5' termini in growing cells is altered by inhibitors of cytoplasmic protein synthesis but not by inhibitors of mitochondrial protein synthesis. Changes in D-loop 5' termini correlate with alterations in transcripts from one of the transcriptional promoters. These findings implicate D-loops in the control of bovine mitochondrial gene expression and suggest mechanisms by which this control might by accomplished.

Animals↗

PubMed1985

Internal auditory canal vascular loops: audiometric and vestibular system findings.

Prominent loops of the anterior inferior cerebellar artery in the cerebellopontine angle are found frequently during anatomic studies of this region. These vascular loops are suspected of causing hearing loss, tinnitus, and vertigo, and surgery has been advocated to separate the vascular loop from the eighth cranial nerve. Previous reports have described pathologic anatomy, surgical approaches, and results of treatment. In this study, we report the results of a uniform battery of audiometric and vestibular system test results administered to fifteen patients with prominent vascular loops in the internal auditory canal diagnosed by pneumo-CT. All patients were tumor suspects before CT because of unilateral (or asymmetric) tinnitus or hearing loss. Hearing losses ranged from mild to profound, and most were of a cochlear type with excellent speech discrimination. Only one-third of the patients had abnormal caloric tests, but spontaneous nystagmus was detected in all but one of the patients by photoelectric nystagmography. The wide range of audiometric and vestibular system test results probably reflects the complex interaction between the vascular loop and eighth cranial nerve, in which the loop exerts pressure on the nerve, and the nerve compromises inner ear circulation. Eighth nerve tumors and vascular loops produce similar symptoms, but a cochlear type of hearing loss with good speech discrimination and normal caloric testing should raise suspicion of a vascular loop. Pneumo-CT is an effective means of diagnosing vascular loops and differentiating them from other lesions of the cerebellopontine angle.

Adult↗

PubMed1993

Observations of the anterior loop of the inferior alveolar canal.

The inferior alveolar nerve may extend beyond the mental foramen as an intraosseous anterior loop. The purpose of this study was to determine if panoramic radiography accurately identifies the anterior loop of the inferior alveolar canal. Adult skulls (n = 25) were radiographed using two panoramic machines both with and without radiopaque markers placed into the inferior alveolar canal and anterior loop. The anterior loop was also measured directly using flexible tubing (2 mm in diameter). Significantly fewer loops were detected in radiographs as compared with anatomic assessment (P < .001). A significant loop (> 2 mm) was identified in 92% to 96% of the direct measurements, whereas radiographs identified only 56% (Panelipse) and 76% (Orthoralix). Analysis of variance demonstrated that the skeletal length of the anterior loop was significantly greater than that measured radiographically (P < .0001). The average length of the anterior loop based on direct measurements was 6.95 mm, whereas radiographic measurements were 3.18 mm (Panelipse) and 3.45 mm (Orthoralix). The difference in detection of anterior loops among the radiographic procedures studied was not significant (P > .05).

Adult↗

PubMed1997

RNA apatamers for yeast ribosomal protein L32 have a conserved purine-rich internal loop.

Two in vitro selection experiments were conducted to determine the RNA sequence requirements for binding ribosomal protein L32 (RPL32) from Saccharomyces cerevisiae. To preserve the wild-type stem-internal loop-stem fold, only a limited portion of the RNA comprising the internal loop region was randomized. Most of the selected RNAs have secondary structures similar to that of the wild-type, and four purines on both sides of the internal loop are highly conserved. Indeed, a pair of 5'-GA-3' dinucleotides is found in all but one of the stem-loop-stem L32 aptamers and these conserved purines may contact the protein directly or form a necessary RNA secondary or tertiary structure. These aptamers have a potential G:U pair bordering the loop adjacent to the conserved GAs, but a cytidine replaces a phylogenetically conserved adenosine at one loop position in many of the selected RNAs. In model RNAs, the cytidine-bearing variant binds protein slightly more strongly than does the wild-type RNA. That the seven-member, 2 + 5 internal loop is important for protein binding is reinforced by the finding that the position, but not the size, of the loop is variable. A minority of the RNA aptamers has three consecutive uridines and may fold into a similar structure, but with the internal loop inverted.

Base Sequence↗

PubMed1997

Identification of interaction partners for the basic-helix-loop-helix protein E47.

Helix-loop-helix proteins constitute a family of transcription factors with the potential to form homo- and hetero-dimers mediated by the helix-loop-helix domain. Oncogenic mutations in such genes can disrupt the equilibrium of protein-protein interactions in the affected cell. In order to assess the biological consequences of such mutations, the full complement of interacting proteins must be known. To identify proteins interacting with the basic-helix-loop-helix domain of the ubiquitously expressed E47 protein, a 'sandwich'-screening procedure was developed which distinguishes between homo- and hetero-oligomers, and specifically excludes the detection of complexes which cannot bind DNA. Nine distinct cDNAs were identified which encode proteins with apparent basic-helix-loop-helix domains, including a novel clone termed eip1 which is distantly related in the basic-helix-loop-helix domain to the Drosophila enhancer-of-split m7 protein. Using epitope-tagging, interaction of E47 basic-helix-loop-helix protein with the eip1 protein encoded by this novel cDNA was confirmed by immunoprecipitation experiments in COS7 cells. Interaction was also observed in the yeast two-hybrid system. Three cDNAs encoding proteins without basic-helix-loop-helix domains were also found to interact in the sandwich-expression screen. Interactions with human PARP and mouse replication factor 1a were confirmed using glutathione transferase-tagged cDNAs. A cDNA encoding part of the nucleolin protein sequence interacted with the E47 basic-helix-loop-helix only when fused to a beta-galactosidase tag.

Amino Acid Sequence↗

PubMed1993

Simulation of lithium transport along the thin segments of Henle's loop.

Although the renal clearance of lithium is widely used as an index of sodium and water delivery to the end of the proximal tubule, micropuncture studies of superficial nephrons suggest that lithium may be reabsorbed additionally in the loop of Henle. In order to examine the possibility of lithium transport in the thin loop segments of deep nephrons, we conducted a computer simulation study using a modification of the mathematical model reported previously. The data for the model were obtained from measurements of osmolality and electrolyte concentrations in systemic plasma and renal papillary interstitial fluid of control and furosemide-treated rats. Papillary interstitium/plasma Li+ concentration ratios were 3.23 and 1.48 in the control and the furosemide group, respectively. Assuming that solute concentration in the renal medulla increases as an exponential function, and applying phenomenological coefficients obtained from hamsters, the transport profiles of Li+ along the thin loop segments were calculated to be very similar to those of Na+. In the control group, about 82% of delivered Li+ was reabsorbed along the entire thin loop segments, with all segments contributing equally. This value may represent the highest possible capacity of the thin loop segments. In the furosemide group, Li+ reabsorption in the thin loop was reduced to 31% of delivered Li+. From these analyses, we conclude that an appreciable amount of lithium may be reabsorbed in the thin loop segments of long-looped nephrons by passive mechanisms. Furosemide inhibits Li+ reabsorption by dissipating the osmotic concentration gradient in the renal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Determinants of helix-loop-helix dimerization affinity. Random mutational analysis of SCL/tal.

Dimerization represents a key regulatory step in the function of basic helix-loop-helix transcriptional factors. In many instances tissue-specific basic helix-loop-helix proteins, such as the hematopoietic factor SCL/tal or the myogenic factor MyoD, interact with ubiquitously expressed basic helix-loop-helix proteins, such as E2A or E2-2. Such dimerization is necessary for high affinity, sequence-specific DNA binding. Previous biochemical and structural studies have shown the helix-loop-helix region to be necessary and sufficient for this interaction. In the present study, we analyzed the relative affinities of various helix-loop-helix interactions using the yeast two-hybrid system. The relative affinities of selected helix-loop-helix species for the partner protein E2-2 were as follows: Id2 > MyoD > SCL/tal. Mutants of SCL/tal with increased affinity for E2-2 were selected from a library of randomly mutated basic helix-loop-helix domains. The amino acid changes in these high affinity versions of SCL/tal introduced residues that resembled those in the corresponding positions of the Id proteins and MyoD. One of the mutants, SCL 12, also contained mutations in highly conserved residues previously thought to be necessary for dimerization. This mutant of SCL demonstrated diminished temperature sensitivity in in vitro interaction assays as compared with the wild type protein. Computational modeling of helix-loop-helix dimers provides an explanation for the increased dimerization affinity of SCL mutant 12.

Amino Acid Sequence↗

PubMed1993

Renal excretory profiles of loop diuretics: consequences for therapeutic application.

In healthy subjects, 24-h natriuresis, kaliuresis, calciuresis, and magnesiuresis increase in response to the first oral dose of a standard (diuretic) formulation of a loop diuretic, such as furosemide 40 mg. However, low-dose formulations of loop diuretics, such as torasemide 2.5 mg, do not elevate 24-h natriuresis after the first dose is administered to normal individuals who are in steady-state habitual sodium balance; these formulations of loop diuretics are consequently labeled as nondiuretic formulations (of diuretic substances). Nondiuretic formulations of loop diuretics do not increase the 24-h urinary outputs of sodium, potassium, calcium, or magnesium after the first dose or in the course of repeated once-daily administration to healthy subjects. The 24-h natriuretic response to the first dose of standard (diuretic) formulations of loop diuretics wanes during repeated once-daily administration to healthy individuals, whereas the kaliuretic response becomes slightly attenuated, and calciuresis and magnesiuresis bear little change. Once-daily treatment with any formulation of a loop diuretic may result in an increase in plasma urate concentration. Nondiuretic formulations of loop diuretics, which are efficacious as once-daily monopharmacotherapy for high blood pressure, should be tried before standard (diuretic) formulations of diuretics are used in the treatment of uncomplicated essential hypertension. When loop diuretics are employed in the treatment of congestive heart failure, the minimal dose compatible with the attainment of clinical objectives should be used.

Diuresis↗

PubMed1986

Thiazides and loop-diuretics therapeutic aspects.

Thiazides and compounds with similar models of action exert their most important renal effects on the cortical-diluting segment of the nephron, most likely from the peritubular side. In contrast, the most important site of action of loop-diuretics is the luminal side of the ascending part of the diluting segment. The different sites of action explain the clinically proven efficacious combination of thiazides and loop-diuretics in severe cardiac failure. Most thiazides and loop-diuretics are eliminated via renal tubular secretion, which leads to decreased renal clearance in patients with chronic heart failure (CHF) as their renal blood flow is decreased even if glomerular filtration rate (GFR) is maintained. A rational approach to enhance the effects of loop-diuretics is to combine them with drugs that increase renal blood flow, thereby increasing the rate of delivery of the drug to its site of action. Dilutional hyponatremia is an important complication of treatment with diuretics. An efficacious treatment of that condition seems to be a combination of loop-diuretics and ACE-inhibitors. Thiazides decrease the urinary excretion of calcium, while loop-diuretics have the opposite effect. The possibility of loop-diuretic induced osteopenia cannot be ruled out, which should be considered when choosing between thiazides and loop-diuretics for the treatment of mild to moderate CHF.

Benzothiadiazines↗

PubMed1995

Bent helix formation between RNA hairpins with complementary loops.

The initial interaction between the ColE1 plasmid specific transcripts RNA I and RNA II, which function as antisense regulators of plasmid replication, comprises a transient complex between complementary loops found within the RNA secondary structures. Multidimensional heteronuclear magnetic resonance spectroscopy was used to characterize complexes formed between model RNA hairpins having seven nucleotide complementary loops. Seven base pairs are formed in the loop-loop helix, with continuous helical stacking of the loop residues on the 3' side of their helical stems. A sharp bend in the loop-loop helix, documented by gel electrophoresis, narrows the major groove and allows bridging of the phosphodiester backbones across the major groove in order to close the hairpin loops at their 5'-ends. The bend is further enhanced by the binding of Rom, a ColE1 encoded protein that regulates replication.

Bacterial Proteins↗

PubMed1983

Studies on the renal receptors of loop diuretics.

The principal renal action of loop diuretics is to inhibit active NaCl transport in the thick ascending limb of the loop of Henle. However, apart from their specific tubular action, kidney function may be affected in other ways. By employing the enantiomeres of the new loop diuretic ozolinone, non-stereospecific increase in renal blood flow and inhibition of tubular secretion of p-aminohippurate and urate were found. In contrast, electrolyte transport in the loop of Henle was inhibited stereospecifically. Perfusion of single loops of rat kidneys in vivo with sugar-specific lectins suggested that a fucose-containing glycoprotein is involved in electrolyte transport in this tubular segment. Loop diuretics might interact with this glycoprotein, leading to inhibition of electrolyte transport. Evidence is presented to suggest that this protein is the Tamm-Horsfall protein. This fucose-containing glycoprotein is localized in the cell membranes of the thick ascending limb of the loop of Henle. It binds furosemide at concentrations very close to those required for inhibition of electrolyte transport in vivo. Furthermore, there is complete agreement between the sodium concentration necessary for stimulation of active transport in isolated thick ascending limbs of the loop of Henle and that necessary for binding of furosemide to the Tamm-Horsfall glycoprotein.

Animals↗

PubMed2000

Five-loop coil occlusion of patent ductus arteriosus prevents recurrence of shunt at follow-up.

Recent reports suggest reopening of the patent ductus arteriosus (PDA) after complete occlusion with three-loop Gianturco coils. We hypothesize that five-loop coils may produce a larger thrombus than three-loop coils, which will result in no or less probability of recanalization of PDA during follow-up. This study is designed to test this hypothesis. Follow-up echocardiographic and Doppler data of 30 patients who underwent five-loop coil occlusion of small to medium-sized PDA during a 33-month period ending December 1998 were examined. Thirty patients had no residual shunt on echo Doppler study on the day following the procedure and were followed for 6 to 30 months (median, 12) after coil implantation. At the last follow-up study, none of the patients had a residual shunt and left atrial size decreased. Careful pulsed, continuous wave, and color Doppler interrogation of left/main pulmonary artery junction and proximal descending aorta did not reveal any evidence for obstruction. The follow-up data suggest that complete occlusion of small- to medium-sized PDAs is feasible with five-loop coils without evidence for recanalization at a mean follow-up of 12 months. Much longer (2 to 5 years) follow-up data may be necessary to confirm these observations. We speculate that a greater degree of thrombosis is produced within the ductus by the five-loop coils, which in turn may be responsible for lack of shunt recurrence. We recommend use of five-loop instead of three-loop coils for transcatheter occlusion of small- to medium-sized PDAs.

Child↗

PubMed2006

Improvement of domain linker prediction by incorporating loop-length-dependent characteristics.

Protein dissection into structural domains that can fold in isolation is an important issue in both functional and structural proteomics. Here, we analyzed inter- and intradomain loop sequences (respectively named domain linker and nonlinker loops) and computed a domain linker likelihood score, which was used for developing a domain boundary prediction protocol. The analysis confirmed our previous results indicating that the amino acid composition in terms of glycine, proline, aspartic acid, asparagine, lysine, and histidine significantly differs between linker and nonlinker loops. However, a detailed examination revealed that the amino acid composition bias actually depends on the loop length. Indeed, significant frequency deviations were observed for glycine, proline, and aspartic acid in short linker and nonlinker loops, whereas deviations were observed for aspartic acid, proline, asparagine, and lysine in long linker and nonlinker loops. Finally, we incorporated this loop-length-dependent amino acid composition bias in a simple linker prediction protocol, which predicted linkers with a 40.6% specificity and a 36.1% sensitivity. These figures are 4.4 and 2.4% higher than those obtained with our former prediction protocol that does not incorporate loop-length-dependent characteristics. This result should have practical significance for experimental protein dissection, since the probability of obtaining a stably folding structural domain by randomly dissecting a protein sequence is estimated to be 12.6%.

Algorithms↗

PubMed1995

Slow conformational exchange in DNA minihairpin loops: a conformational study of the circular dumbbell d .

In recent years various examples of highly stable two-residue hairpin loops (miniloops) in DNA have been encountered. As the detailed structure and stability of miniloops appear to be determined not only by the nature and sequence of the two bases in the loop, but also by the closing base pair, it is desirable to carry out in-depth studies of especially designed small model DNA compounds. Therefore, a circular DNA dumbbell-like molecule is tailored to consist of a stem of three Watson-Crick base pairs, flanked on each side by a minihairpin loop. The resulting circular DNA decamer 5'-d -3' (I) is studied in solution by means of nmr spectroscopy. At a temperature of 269 K the molecule occurs in a 50/50 mixture of two dumbbell structures (denoted L2L2 and L2L4). L2L2 contains three Watson-Crick C-G base pairs and two two-residue loops (H2-family type) in opposite parts of the molecule. On raising the temperature from 269 to 314 K, the L2L4 conformer becomes increasingly dominant (95% at 314 K). This conformer has a partially disrupted closing G-C base pair in the 5'-GTTC-3' loop with only one remaining solvent-accessible hydrogen bond between NH alpha of the cytosine C(1) and O6 of the guanine G(8), whereas the opposite 5'-CTTG-3' loop remains stable. The disruption of the C(1)-G(8) base pair in the L2L4 form is correlated with the presence of a syn orientation for the C(1) base at the 5'-3' loop-stem junction in the 5'-GTTC-3' loop. The two conformers, L2L2 and L2L4, occur in slow equilibrium (2-20 s-1). Moderate line broadening of specific 1H, 13C, and 31P resonances of residues C(1), G(8), T(9), and T(10) at low temperatures, due to chemical exchange between L2L2 and L2L4, show that the interconversion from an anti to syn conformer in residue C(1) has a small local effect on the structure of the dumbbell. T1 relaxation measurements, chemical-shift considerations, and complete band-shape calculations of the exchange process of the G(8) imino proton reveal a possibility for the existence of multiconformational states in the anti-syn equilibrium.

Base Sequence↗

PubMed1988

Identifying lung overdistention during mechanical ventilation by using volume-pressure loops.

We measured the pulmonary mechanics of 23 mechanically ventilated neonates. Airway pressures, inspiratory and expiratory flows were simultaneously measured. Values for respiratory system mechanics were then derived from these data by using a personal computer and a special software program. Volume-pressure (V-P) loops and respiratory system compliance values were determined for representative mechanical breaths. Twelve infants had normal-appearing V-P loops. Eleven had V-P loops characteristic of lung overdistention, showing decreasing changes in volume with progressive increases in pressure. To quantify this visual observation, we determined the change in compliance during the last 20% of inspiration (C20). We then compared this value to the total compliance value for the entire breath (C) using the ratio C20/C. Mean values for C, C20, and C20/C were compared for the two patient groups. Total respiratory system compliance values were similar. C20 values were decreased in those patients with V-P loops showing overdistention. C20/C values were significantly decreased in those patients with V-P loop evidence of overdistention. Patients with V-P loop evidence of overdistention all had C20/C values less than 0.8. Those with normal-appearing V-P loops all had C20/C values greater than 1.0. The C20/C ratio appears to effectively quantitate visual V-P loop evidence of lung overdistention during mechanical ventilation.

Barotrauma↗

PubMed1994

Multiple copy sampling in protein loop modeling: computational efficiency and sensitivity to dihedral angle perturbations.

Multiple copy sampling and the bond scaling-relaxation technique are combined to generate 3-dimensional conformations of protein loop segments. The computational efficiency and sensitivity to initial loop copy dispersion are analyzed. The multicopy loop modeling method requires approximately 20-50% of the computational time required by the single-copy method for the various protein segments tested. An analytical formula is proposed to estimate the computational gain prior to carrying out a multicopy simulation. When 7-residue loops within flexible proteins are modeled, each multicopy simulation can sample a set of loop conformations with initial dispersions up to +/- 15 degrees for backbone and +/- 30 degrees for side-chain rotatable dihedral angles. The dispersions are larger for shorter and smaller for longer and/or surface loops. The degree of convergence of loop copies during a simulation can be used to complement commonly used target functions (such as potential energy) for distinguishing between native and misfolded conformations. Furthermore, this convergence also reflects the conformational flexibility of the modeled protein segment. Application to simultaneously building all 6 hypervariable loops of an antibody is discussed.

Animals↗