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Left ventricular lead performance in cardiac resynchronization therapy: impact of lead localization and complications.

INTRODUCTION: Cardiac resynchronization therapy (CRT) using left ventricular (LV) pacing from the coronary sinus tributary is increasingly and frequently used in patients with severe congestive heart failure. The present study investigates LV lead performance in different anatomic locations. METHODS: The LV pacing site was defined by bi-plane fluoroscopy. In the left anterior oblique view, the coronary sinus is encircling the mitral ring with the tributaries radiating out like the hands of a watch. Using this clockwise method, Group A had an LV pacing site before 3 o'clock and Group B at or after 3 o'clock. In right anterior oblique view, the LV was divided into three segments: basal, mid-ventricular, and apical. RESULTS: LV lead implantation was successful in all of 120 consecutive patients. Mean follow-up was 16.7 months. Implantation time decreased from mean 190 to 80 minutes during the period (P = 0.01). The mean LV lead stimulation threshold increased initially and stabilized afterwards. The threshold measured at last follow-up was higher than at implantation (2.3 vs 2.7 microJ, P = 0.04). Useful venograms were obtained in 94 patients. No significant difference in thresholds was observed between Groups A and B. Phrenic nerve stimulation was most commonly seen in Group B (8/70 vs 1/24, P = 0.001). CONCLUSION: Implantation of an LV lead for CRT is possible in patients with congestive heart failure and associated with an acceptable low complication rate. LV lead implantation is associated with a learning curve. At mid-term follow-up, LV lead performance is stable and unrelated to the LV implantation site.

Adolescent↗

A period-extender gene, pex, that extends the period of the circadian clock in the cyanobacterium Synechococcus sp. strain PCC 7942.

We cloned the pS1K1 plasmid in the process of apparently "complementing" a circadian clock mutant of cyanobacterium Synechococcus sp. strain PCC 7942, SP22, which has a 22-h period (T. Kondo, N. F. Tsinoremas, S. S. Golden, C. H. Johnson, S. Kutsuna, and M. Ishiura, Science 266:1233-1236, 1994). Sequence analysis revealed that SP22 did not have a mutation in the genomic DNA segment carried on pS1K1, and the sp22 mutation was later found in a recently cloned new clock gene, kaiC. Therefore, the period-extender gene pex that was carried on pS1K1 was a suppressor gene for the sp22 mutation. The pex gene encoded a protein of 148 amino acid residues. No meaningful homologs were found in DNA or protein databases including the Synechocystis genome database. The pex gene was transcribed from 129 and 164 bp upstream of the translation initiation codon as 0.6-kb transcripts. The Pex protein was detected as a fusion protein with a molecular mass of 15 kDa by the epitope tag fusion method using a c-Myc epitope tag. Disruption of the pex gene in wild-type cells shortened the period of the rhythms by 1 h, although it did not affect other properties of the rhythms, whereas its overexpression extended the period by 3 h with a concomitant reduction in the amplitude of the rhythms. In various clock mutants examined, overexpression caused arrhythmicity. Thus, Pex is likely to function as a modifier of the circadian clock in Synechococcus.

Amino Acid Sequence↗

Laparoscopic tubal anastomosis (the one stitch technique): preliminary results.

We report a new laparoscopic technique of tubal anastomosis: the laparoscopic one stitch technique. After preparation and approximation of the two tubal segments, the anastomosis consists of one single suture placed at the '12 o'clock' site of the antimesenteric borders. Four patients have undergone this procedure. Bilateral tubal patency was confirmed in three cases. Hysterosalpingography was not performed on the fourth patient as she was already 1 month pregnant after tubal anastomosis.

Adult↗

[Laparoscopic tubal sterilization reversal: a technic using a single stitch].

We report our laparoscopic technique of tubal sterilization reversal. We perform a simple and atraumatic technique with a single point. After preparation and approximation of the two tubal segments, the anastomosis consists of one single suture placed at the "12 o'clock" site of the antimesenteric border. The feasibility, the advantages and the preliminary results are presented.

Anastomosis, Surgical↗

The place of the clock in pediatric advice: rationales, cultural themes, and impediments to breastfeeding.

This analysis treats the U.S. medical literature as evidence concerning the formal system of knowledge in allopathic medicine. An examination of pediatric advice on breastfeeding reveals the logic of medical reasoning, the use of scientific rationales, and the intrusion of specific cultural themes. The corpus of data includes works of 18 authors published in 36 volumes from 1897 to 1987, 27 volumes being editions of two major pediatric textbooks. All sources advocate breastfeeding but the detailed advice on how to carry out the process actually tends to undermine it. Moreover, the clock has provided the main frame of reference, creating regimentation reminiscent of factory work, segmenting breastfeeding into a series of steps, and emphasizing efficiency in time and motion. Feeding schedules were advocated in former decades as a matter of discipline for the infant, but nowadays they are viewed as biologically innate to normal infants and to breast milk production. The literature manifests responses over the century to behavioral, biochemical and physiological studies; however, except possibly for one textbook, no thorough rethinking has occurred. Sources of the 1980s continue to focus on the tempo of feeding as a major concern. Cultural themes besides the factory model of breastfeeding include the extension of professional advice to family matters, the subordination of lay women to professional expertise, mistrust of women's bodily signals including the let-down reflex in determining the timing of feedings, mistrust of signals from infants as well, and a professional ideal of flexible advice coupled with rigid limits concerning schedules. The literature interweaves the cultural themes with rationales based on physiological studies in support of specific regimens in breastfeeding, and the relegation of control in breastfeeding to medical experts denies the validity of mutual bodily and emotional responses within the mother-infant dyad. Pediatric authorities thus participate in the selection of cultural themes emphasized in motherhood. Although the pediatric literature is not the only influence on physicians and women, it reinforces pressures on women regarding their orientations toward their infants and hence, may be expected to shape our views of infancy, motherhood, and humanity in general. The break from the bindings of schedules has been proclaimed at various points during the century; however, the clock ironically remains the major reference point in most pediatric sources today.

Adult↗

Clocked gene expression in somite formation.

A recent paper describes a striking expression pattern during somite formation for a chick ortholog of the fly hairy gene. Before segmentation, c-hairy1 mRNA oscillates in the presomitic mesoderm such that three distinct spatial patterns are seen. The authors use a series of ingenious manipulations to show that these phases follow each other in time, adding up to a 90-minute periodicity in c-hairy1 expression. The discovery of this clock of gene expression emphasizes the importance of temporally regulated events in the establishment of spatial patterns.

Animals↗

Vertebrate segmentation: snail counts the time until morphogenesis.

During segmentation of vertebrate embryos, unsegmented mesenchymal mesoderm is divided into epithelial segments called somites. This process is governed by oscillating gene expression of the somite clock. A recent paper identifies the transcription factor Snail as a link between the somite clock and the control of somite morphogenesis.

Animals↗

Rates and patterns of gene duplication and loss in the human genome.

Gene duplication has certainly played a major role in structuring vertebrate genomes but the extent and nature of the duplication events involved remains controversial. A recent study identified two major episodes of gene duplication: one episode of putative genome duplication ca. 500 Myr ago and a more recent gene-family expansion attributed to segmental or tandem duplications. We confirm this pattern using methods not reliant on molecular clocks for individual gene families. However, analysis of a simple model of the birth-death process suggests that the apparent recent episode of duplication is an artefact of the birth-death process. We show that a constant-rate birth-death model is appropriate for gene duplication data, allowing us to estimate the rate of gene duplication and loss in the vertebrate genome over the last 200 Myr (0.00115 and 0.00740 Myr(-1) lineage(-1), respectively). Finally, we show that increasing rates of gene loss reduce the impact of a genome-wide duplication event on the distribution of gene duplications through time.

Evolution, Molecular↗

Disruption of segmentation in a short germ insect embryo. I. The location of abnormalities induced by heat shock.

The effect of heat shock (15 min at 48 degrees C) on segmentation has been investigated in the short germ embryo of the locust (Schistocerca gregaria). Prior to formation of the germ anlage and at the disc stage heat shock considerably reduced the survival of eggs but appeared to have little effect upon segmentation. At later stages heat shock had no effect on survival but resulted in disruptions of the segmental pattern. The location of abnormal segments depended upon the stage at heat shock and the number affected depended on its severity. A constant number of normal segments developed between the last segment visible at the time of heat shock and the first abnormal segment. These results are similar to the disruptions observed in amphibian somites following heat shock. However, different parts of the segment pattern varied in their response; the head segments were very rarely affected, and disrupted regions rarely started in the middle abdomen (segments A5 and A6). The results are discussed in relation to two models (the clock and wavefront and progress zone models) that have been proposed as an explanation for the specification of the somite pattern in amphibians.

Animals↗

Genomic and phylogenetic analysis of the human CD1 and HLA class I multicopy genes.

The human CD1 proteins belong to a lipid-glycolipid antigen-presenting gene family and are related in structure and function to the MHC class I molecules. Previous mapping and DNA hybridization studies have shown that five linked genes located within a cluster on human chromosome 1q22-23 encode the CD1 protein family. We have analyzed the complete genomic sequence of the human CD1 gene cluster and found that the five active genes are distributed over 175,600 nucleotides and separated by four expanded intervening genomic regions (IGRs) ranging in length between 20 and 68 kb. The IGRs are composed mostly of retroelements including five full-length L1 PA sequences and various pseudogenes. Some L1 sequences have acted as receptors for other subtypes or families of retroelements. Alu molecular clocks that have evolved during primate history are found distributed within the HLA class I duplicated segments (duplicons) but not within the duplicons of CD1. Phylogeny of the alpha3 domain of the class I-like superfamily of proteins shows that the CD1 cluster is well separated from HLA class I by a number of superfamily members including MIC (PERB11), HFE, Zn-alpha2-GP, FcRn, and MR1. Phylogenetically, the human CD1 sequences are interspersed by CD1 sequences from other mammalian species, whereas the human HLA class I sequences cluster together and are separated from the other mammalian sequences. Genomic and phylogenetic analyses support the view that the human CD1 gene copies were duplicated prior to the evolution of primates and the bulk of the HLA class I genes found in humans. In contrast to the HLA class I genomic structure, the human CD1 duplicons are smaller in size, they lack Alu clocks, and they are interrupted by IGRs at least 4 to 14 times longer than the CD1 genes themselves. The IGRs seem to have been created as "buffer zones" to protect the CD1 genes from disruption by transposable elements.

Antigens, CD1↗

Evolution of influenza virus genes.

The nucleotide sequences of the eight different influenza A virus segments (genes) were compared among 14 different subtypes. These comparisons demonstrate the presence of molecular clocks in the viral genes; they accumulated both silent and amino acid-changing substitutions at approximately constant rates with respect to time during evolution. In addition, comparison of the rates of evolution among the eight viral genes, excluding the P2 gene, revealed a rapid and roughly equal rate of silent substitution for different genes. The P2 gene exception is explained as the result of recombination (reassortment) between distantly related strains. The rate of amino acid-changing substitution differs greatly from gene to gene. The rate of silent substitution was estimated to be 1.1 X 10(-2)/site/year on the average--that is, about 2 X 10(6) times higher than eukaryotic gene equivalents, which is remarkable. Strain A/USSR/90/77 was shown to evolve with a rate that is similar to those of other strains but to behave as if replication was frozen during a certain period (Nakajima et al. 1978). The frozen period was estimated to be 25 yr on the basis of the molecular clock. A similar analysis revealed another example of frozen replication--in this case, apparently for a period of about 9 yr--in a duck strain, A/duck/Ontario/77.

Amino Acid Sequence↗

Nucleotide sequence of the Escherichia coli pyrE gene and of the DNA in front of the protein-coding region.

Orotate phosphoribosyltransferase (EC 2.4.2.10) was purified to electrophoretic homogeneity from a strain of Escherichia coli containing the pyrE gene cloned on a multicopy plasmid. The relative molecular masses (Mr) of the native enzyme and its subunit were estimated by means of gel filtration and electrophoresis in the presence of dodecyl sulfate. The amino acid sequences at the N and C termini, as well as the amino acid composition, were determined. The nucleotide sequence of the structural pyrE gene, including 394 nucleotide residues preceding the beginning of the coding frame, was also established. From the results the following conclusions may be drawn. Orotate phosphoribosyltransferase is a dimeric protein with subunits of Mr 23 326 consisting of 211 amino acid residues. The pyrE gene is transcribed in a counter-clock wise direction from the E. coli chromosome as an mRNA with a considerable leader segment in front of the protein-coding region. This leader contains a structure with features characteristic for a (translated?) rho-independent transcriptional terminator, which is preceded by a cluster of uridylate residues. This indicates that the frequency of pyrE transcription is regulated by an RNA polymerase (UTP) modulated attenuation.

Bacterial Proteins↗

Vertebrate somitogenesis.

In vertebrates, the paraxial mesoderm corresponds to the bilateral strips of mesodermal tissue flanking the notochord and neural tube and which are delimited laterally by the intermediate mesoderm and the lateral plate. The paraxial mesoderm comprises the head or cephalic mesoderm anteriorly and the somitic region throughout the trunk and the tail of the vertebrates. Soon after gastrulation, the somitic region of vertebrates starts to become segmented into paired blocks of mesoderm, termed somites. This process lasts until the number of somites characteristic of the species is reached. The somites later give rise to all skeletal muscles of the body, the axial skeleton, and part of the dermis. In this review I discuss the processes involved in the formation of the paraxial mesoderm and its segmentation into somites in vertebrates.

Animals↗

Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock.

The period (per) locus, which controls biological rhythms in Drosophila, was originally defined by three chemically induced mutations. Flies carrying the pero mutation were arrhythmic, whereas pers and perl mutants had circadian behavioural rhythms with 19-hour and 29-hour periodicities, respectively. Wild-type flies have 24-hour rhythms. Here we compare the per locus DNA sequences of the three mutants with the parental wild-type. The pers and perl mutations lead to amino-acid substitutions, whereas pero introduces an early translation stop (amber). The results indicate that the protein product of per controls biological rhythms. We also report that the abundance of this protein may set the pace of the Drosophila clock. Although circadian rhythms are restored when arrhythmic (per-) Drosophila are transformed with per locus DNA, flies receiving identical transforming DNA segments can produce rhythms with periods that differ by more than 12 hours. Transcription studies reveal a tenfold variation in the level of per RNA among transformed lines. Levels of per RNA are inversely correlated with period length, so that flies with lowest levels of the per product have slow-running biological clocks. On the basis of the combined studies we suggest that perl and pers mutants produce hypoactive and hyperactive per proteins, respectively.

Amino Acid Sequence↗

The human and mouse Period1 genes: five well-conserved E-boxes additively contribute to the enhancement of mPer1 transcription.

The clock gene, Period1, from human and mouse was sequenced and characterized. Both human PERIOD1 (human PER1) and mouse Period1 (mouse Per1) consisted of 23 exons spanning approximately 16 kb, and their structures showed strong similarity to each other. For example, six highly conserved regions were identified in the 5' upstream sequences. These conserved segments exhibited 77-88% identity and possessed several potential regulatory elements including five E-boxes (the binding site of the CLOCK-BMAL1 complex) and four cyclic AMP response elements. Transient transfection assays using a mPer1-luciferase fusion gene revealed that each of the conserved E-boxes additively functions as an enhancer for the transactivation of mPer1 by mCLOCK and mBMAL1.

ARNTL Transcription Factors↗

Focusing X-rays with simple arrays of prism-like structures.

This report discusses the optimization strategy, the theoretical background and first experimental data of a new refractive lens for focusing X-rays. In order to reduce the absorption of X-rays in this transmission lens, optically passive material was removed from the necessarily concave lens shape in a highly regular pattern. The feature dimensions require lens production and replication by deep X-ray lithography, which allows shaping in only one dimension. Consequently such a lens can focus in one direction only, so a crossed lens pair is needed for two-dimensional focusing. The single lens is composed of two large prisms of millimetre size, which touch each other at one of the tips, like an old sand clock. Each large prism contains a highly regular structure of essentially identical prism-like smaller segments. The first lens prototypes focused an X-ray beam with a vertical size of 500 microm and a photon energy of 8 keV to a line with a width of only 2.8 microm. This is only slightly worse than the line width of 1.73 microm expected for its focal length of f = 2.18 m. The photon density enhancement in the focus was 25, but could have been larger as the lens can intercept a beam height of 2.6 mm.

Journal Article↗

[The circuit design of an alarm system for the old solitary man based on daily life].

The system with DS1302 as its clock makes one hour as one basic time unit, and thus there will be 24 monitoring segments in a day. It watches the movements of the aged through the sensors placed in the house-rooms such as bedroom, kitchen, and obtains the data of the movements and activities. Based on the data the MCU (Micro Control Unit) will make an hourly judgment whether the movements and activities are normal ones. When the system makes sure they are abnormal, it will dial out the setting telephone saved in EEPROM, waiting for the other end to pick up phone and then will send the tone alarm out. Once an accident happens, the alarm will be started up immediately by pressing the emergency button of the remote control. When the aged is out, he or she can shift the health mode to the away mode by the remote control, and the system will act as a home security system. In simulation experiments, the system works well at recognizing the data of movements and has a very low mis-alarm ratio. The system provides a viable solution to the social problem of looking after the aged who lives alone.

Activities of Daily Living↗