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Biomedical subjects

C W Lo

Publications and source records attributed to C W Lo.

At least 55 records · Page 3Linked to original sources
PubMed1994

Posterior ("atypical") atrioventricular junctional reentrant tachycardia.

The aim of this study was to characterize a relatively rare type of atrioventricular (AV) junctional reentrant tachycardia (AVJRT). Posterior AVJRT is a type of AV nodal tachycardia in which the site of earliest atrial activation is posterior to the AV node near the coronary sinus orifice. The mechanism of this tachycardia is not well understood. The characteristics of posterior AVJRT (n = 15) were compared with those of anterior ("common") AVJRT (n = 146) and supraventricular tachycardia using single posterior septal accessory pathways (n = 13). During posterior AVJRT, the AH interval was longer than the retrograde conduction time (His to earliest atrial activity) in 11 cases (73%), indicating that these tachycardias were not fast-slow types of AVJRT. The mean ventriculoatrial (VA) interval in posterior AVJRT (93 +/- 41 ms) was longer than in anterior AVJRT (11 +/- 20 ms; p < 0.005), but was similar to that in tachycardias using accessory pathways (106 +/- 16 ms; p = NS). The site of earliest atrial activation during posterior AVJRT was similar to that in tachycardias using accessory pathways. In all cases of accessory pathway-mediated tachycardia, atrial activation could be advanced by ventricular extrastimuli delivered coincident with the His deflection, but atrial activation was not advanced in any case of posterior AVJRT unless the extrastimulus was delivered > 80 ms before the His deflection. Anterograde conduction was similar in the posterior and anterior AVJRT groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Molecular cloning, expression analysis, and chromosomal localization of mouse Hmg1-containing sequences.

We isolated clones encoding the mouse high-mobility-group (Hmg) chromatin protein, Hmg1, from a 7.5-day mouse embryo cDNA library. The translated amino acid sequence encodes a protein of 24,890 daltons and is identical to previously characterized mouse, rat, and hamster Hmg1. However, comparison of the two mouse Hmg1 cDNA sequences revealed nine sequence alterations. This observation, together with the finding of a complex pattern of hybridizing bands in genomic Southern analysis, suggests that mouse Hmg1 is encoded by a multigene family. The expression of Hmg1 was examined by Northern analysis of RNA isolated from the early mouse embryo and revealed a predominant 1.5-kb transcript in conjunction with low levels of a 2.5-kb transcript. Further analysis of mouse embryos by in situ hybridization showed that Hmg1 transcripts are expressed in high abundance during early mouse embryogenesis. As development progresses, Hmg1 transcript abundance is modulated in a spatially restricted and developmentally regulated manner. Chromosomal localization with recombinant inbred strains revealed that Hmg1-related sequences are widely dispersed in the mouse genome. Here we also report the mapping of six Hmg1 loci to mouse Chromosomes (Chrs) 10, 13, 16, and 17.

Animals↗
PubMed1993

Structure, sequence and expression of the mouse Cx43 gene encoding connexin 43.

Gap junctions, membrane channels that mediate the diffusion of ions and small molecules between cells, are hypothesized to play a role in development and growth regulation. The Cx43 gene (encoding connexin 43) is one member of the gap junction gene family whose transcripts are expressed in a highly regionalized manner during mouse development. We cloned and sequenced Cx43 cDNAs from a 7.5-day mouse embryo cDNA library. These cDNA clones encode the authentic 43-kDa connexin. Analysis of RNA isolated from different regions of the 7.5-day mouse embryo revealed that Cx43 transcripts are differentially expressed, with expression detected in the embryo proper, but not in the extraembryonic region containing the ectoplacental cone. Using one of the newly isolated mouse Cx43 cDNA probes, we screened a mouse genomic DNA library and cloned the Cx43 gene. Restriction mapping and sequencing of the cloned genomic inserts revealed that Cx43 contains two exons and a 10.5-kb intron located in the 5' untranslated region (5'-UTR). We mapped the Cx43 transcription start point (tsp) by RNase protection and primer extension analyses and showed that transcripts expressed in the 7.5-day mouse embryo and in adult tissues are initiated from the same tsp. The DNA sequence immediately upstream from the tsp contains a putative AP1-binding site and a degenerate TATA consensus sequence. A comparison of mouse, rat, human and bovine Cx43s showed that the 3'-UTR has an unexpectedly high degree of sequence homology. This includes conservation of four AUUUA motifs, a sequence associated with transcript instability in immediate early genes.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

Widespread distribution of cells containing human DNA in embryos derived from mouse eggs injected with human chromosome fragments.

The possibility that metaphase chromosomes can serve as a source of genetic material for making transgenic mice was suggested by our previous finding of the incorporation of human satellite DNA into mouse embryos that were injected with microdissected human centromeric fragments. In the present study, we further examined whether this chromosome transfer method can be used to generate transgenic mice containing a portion of human chromosome 4 spanning the Huntington's disease (HD) gene. For this purpose, we used an improved method of metaphase chromosome preparation that may minimize the potential for DNA damage. Using metaphase chromosomes prepared in this manner, chromosome fragments spanning the region of chromosome 4 containing the HD gene were microdissected, retrieved, and injected into fertilized mouse eggs. The injected eggs exhibited good viability and developed with a high efficiency when implanted into foster mothers. To determine whether the human DNA from the injected chromosome fragment had been incorporated into the mouse genome, embryos were harvested at 12.5 days of gestation (dg) and analyzed by in situ hybridization using a human Alu repetitive DNA probe. This analysis showed that most of the embryos contained cells with human Alu repeats. However, all of the embryos were mosaic, and the level of mosaicism was such that we were not able to determine the precise chromosomal origin of the human DNA insert. We discuss the possible basis for the mosaicism and the potential value of such mosaic animals for studying Huntington's disease.

Animals↗
PubMed1992

Restrictions in gap junctional communication in the Drosophila larval epidermis.

We characterized gap junctional communication in the Drosophila larval epidermis by monitoring the pattern of dye spread following the intracellular injection of the fluorescent dye, Lucifer yellow. We found that dye injected into the epidermis spread extensively from cell to cell, but at segment borders and also at boundaries positioned at the lateral aspects of each body segment, dye spread was restricted. The precise position of these boundaries of restricted gap junctional communication was determined by examining the distribution of the fluorescent tracer in thick sections of each dye-injected specimen. These results show that each of the thoracic and abdominal segments is segregated into four domains or communication compartments. We also observed the presence of dye in the procuticle and epicuticle, and examined the possible basis for this dye localization.

Animals↗
PubMed1992

Connexin 43 expression in the mouse embryo: localization of transcripts within developmentally significant domains.

The expression of the gap junction gene, Cx43, during mouse embryogenesis was characterized by an in situ hybridization analysis of mouse embryos from gestation days 4.5 to 12.5. This analysis revealed that Cx43 transcripts are differentially expressed as a function of development beginning at the blastocyst stage. In many regions of the embryo, Cx43 transcripts were found in discrete spatially restricted domains. This was observed in conjunction with the development of the brain, neural tube, prevertebra, limb, and various aspects of organogenesis. In some cases, the differential localization of Cx43 transcripts is associated with developmental processes mediated by inductive interactions, such as that of the eye, otic vesicle, kidney, and the branchial arches. In addition, in the 10.5 day embryo, Cx43 transcripts appear to be distributed as a gradient in regions spanning the midbrain/hindbrain junction, in the telencephalon, and in the limb mesenchyme. Surprisingly, our results also suggest that neural crest and sclerotomal cells, i.e., cells that are presumably migratory, express high levels of Cx43 transcripts. Overall, these results suggest that gap junctions encoded by Cx43 may play a role in various aspects of mouse development, possibly including relaying second messengers emanating from signal transduction pathways that mediate inductive interactions.

Animals↗
PubMed1990

Successful resuscitation and survival following massive overdose of metoprolol.

A 23-year-old female was found unconscious and deteriorated rapidly to cardiac asystole. Prolonged resuscitation was required, and she remained in severe cardiogenic shock, despite high doses of positive inotropic agents. Massive beta-adrenoceptor blocker overdose was suspected (and subsequently confirmed). IV administration of glucagon was followed by prompt haemodynamic improvement and recovery, illustrating the beneficial role of glucagon in overwhelming beta-adrenoceptor blockade.

Adult↗
PubMed1989

Chromosomal recombination and breakage associated with instability in mouse centrometric satellite DNA.

A mouse L cell line containing the centromeric insertion of herpes thymidine kinase genes (tk) was previously shown to undergo a high frequency of DNA rearrangement at the site of tk insertion. Analysis of TK- revertants had demonstrated that DNA rearrangements were usually associated with DNA deletion and were always mediated by intrachromosomal recombinations. In this study, we further analyzed several TK+ subclones to examine the mode of DNA rearrangements in the absence of negative selection pressure. In two clones, LC2-3F and LC2-3E17, rearrangements were accompanied by DNA amplification and were mediated by intrachromosomal recombination. In subclone LC2-3E17-19, we further detected perturbations in the pattern of centromeric heterochromatization. This was associated with chromosome instability, as evidenced by chromosome breakage at the centromere. The analysis of three other sibling clones, LC2-3, LC2-6 and LC2-15, further suggests that reciprocal recombination events may play a role in such centromeric rearrangements. These results suggest that DNA rearrangements in the centromere may be mediated by a number of different mechanisms, and generally do not affect chromosome stability except when accompanied by changes in the pattern of heterochromatization.

Animals↗
PubMed1989

Introduction of human DNA into mouse eggs by injection of dissected chromosome fragments.

A procedure has been developed for introducing exogenous DNA into mouse eggs by injection of chromosome fragments. Chromosome fragments were dissected from human metaphase spreads and microinjected into the pronuclei of fertilized mouse eggs. Many of the injected eggs subsequently exhibited normal pre- and postimplantation development. Embryos obtained from eggs injected with centromeric fragments retained human centromeric DNA as demonstrated by in situ hybridization analysis. From eggs injected with noncentromeric fragments, a mouse was obtained whose tail tissue exhibited the presence of human DNA. This procedure should facilitate incorporation of very large (more than 10 megabases) DNA fragments into cells and embryos without the need for cloned sequences.

Animals↗
PubMed1989

Gap junctional communication in the extraembryonic tissues of the gastrulating mouse embryo.

We characterized gap junctional communication in the extraembryonic tissues of the 7.5-d gastrulating mouse embryo. At this stage of development, the extraembryonic tissues form a large part of the conceptus, and link the embryo proper to the maternal tissue. Using Lucifer yellow injections, cells in most extraembryonic tissues were observed to be very well dye coupled, the only exception being the peripheral regions of the ectoplacental cone. Of particular interest was the fact that no dye coupling was detected between the three major extraembryonic tissues. Thus, the extraembryonic ectoderm (EEC), the extraembryonic endoderm (EEN), and the ectoplacental cone (EPC) corresponded to separate communication compartments, with the EPC being further subdivided into three compartments. Interestingly, the EEN was observed to exhibit a very low level of dye coupling with the adjacent visceral embryonic endoderm (EN), and consistent with the latter dye coupling results was the finding that the EEN was ionically coupled to the EN, but not with any other extraembryonic tissues. However, in the EPC, ionic coupling studies show that the central region was well coupled ionically to the EEC, but only weakly coupled to the peripheral EPC. These findings, in conjunction with our previous study (1988. J. Cell Biol. 107:241-255), demonstrate that the 7.5-d mouse conceptus is subdivided into at least nine major Lucifer yellow-delineated communication compartments, with ionic coupling across some of these compartments effectively unifying the embryo into two large domains corresponding to the embryo proper and the major extraembryonic tissues.

Animals↗
PubMed1989

A comparative evaluation of a minute ventilation sensing and activity sensing adaptive-rate pacemakers during daily activities.

Most studies evaluating the rate response of adaptive-rate pacemakers have been based on treadmill or bicycle exercise. These studies disregard the fact that few pacemaker recipients voluntarily undertake such activities. The rate responses of nine patients (mean age 62 years, range 33-79 years) with implanted minute ventilation sensing (Meta) pacemakers were studied. The indications for pacing were complete heart block (seven patients), sick sinus syndrome (one patient), and five nodal disease (one patient). Significant improvement in maximum distance covered during a 12-minute walking test was observed in the rate adaptive compared to the VVI pacing mode (989 +/- 104 vs 921 +/- 90 m, P less than 0.02). The rate responses of this pacemaker during daily activities were recorded with telemetry during a variety of structured daily activities. The rate responses were also compared to those of an externally attached Activitrax pacemaker in each patient and to a group of ten age and sex matched volunteers. For less strenuous activities such as walking, descending stairs, washing, and bed making, both pacemakers achieved adequate rate responses compared to normal subjects. For more strenuous activities, the Activitrax pacemaker failed to achieve an adequate rate response. For example, the pacing rate achieved on ascending stairs was lower than that achieved on descending stairs (92 +/- 3 vs 102 +/- 3 bpm, P less than 0.02). The direction of rate responses was more appropriate for the Meta pacemaker. Similar to the normal subjects, the maximum rate was reached before the end of an activity with the Activitrax pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1989

Changes in the gastrointestinal tract during enteral or parenteral feeding.

Intestinal adaptation, in terms of increasing intestinal length and weight, usually occurs rapidly after small-bowel resection. However, this response depends on provision of enteral nutrients. If total parenteral nutrition without enteral feeding is prolonged, hypoplasia of the intestinal mucosa results. Adaptation is probably mediated through the presence of luminal nutrients, particularly glutamine, which is preferentially used by the intestine. However, systemic hormonal factors, possibly gastrin, cholecystokinin, and glucagon, also influence intestinal adaptation. Thus, in the management of short-bowel syndromes, enteral nutrition should be added to total parenteral nutrition as soon as possible.

Adaptation, Physiological↗
PubMed1988

Communication compartments in the gastrulating mouse embryo.

We characterized the pattern of gap junctional communication in the 7.5-d mouse embryo (at the primitive streak or gastrulation stage). First we examined the pattern of dye coupling by injecting the fluorescent tracers, Lucifer Yellow or carboxyfluorescein, and monitoring the extent of dye spread. These studies revealed that cells within all three germ layers are well coupled, as the injected dye usually spread rapidly from the site of impalement into the neighboring cells. The dye spread, however, appeared to be restricted at specific regions of the embryo. Further thick section histological analysis revealed little or no dye transfer between germ layers, indicating that each is a separate communication compartment. The pattern of dye movement within the embryonic ectoderm and mesoderm further suggested that cells in each of these germ layers may be subdivided into smaller communication compartments, the most striking of which are a number of "box-like" domains. Such compartments, unlike the restrictions observed between germ layers, are consistently only partially restrictive. In light of these results, we further monitored ionic coupling to determine if some coupling might nevertheless persist between germ layers. For these studies, Lucifer Yellow was coinjected while ionic coupling was monitored. The injected Lucifer Yellow facilitated the identification of the impalement sites, both in the live specimen and in thick sections in the subsequent histological analysis. By using this approach, all three germ layers were shown to be ionically coupled, indicating that gap junctional communication is maintained across the otherwise dye-uncoupled "germ layer compartments." Thus our results demonstrate that partially restrictive communication compartments are associated with the delamination of germ layers in the gastrulating mouse embryo. The spatial distribution of these compartments are consistent with a possible role in the underlying development.

Animals↗
PubMed1988

Organization of chromosomes in the mouse nucleus: analysis by in situ hybridization.

We used in situ hybridization with various biotinylated DNA probes to characterize the distribution of mouse chromosomes in the nucleus. This entailed an examination of plasmid-marked chromosomes from two strains of transgenic mice and also an examination of the distribution of centromeres and total mouse genomic DNA. Our results show that, regardless of the hybridization probes used or the tissue types examined, with sections of mouse tissues embedded in paraffin all chromosomal DNA appeared to be localized to the nuclear periphery. This was observed in tissues fixed with either crosslinking or non-crosslinking fixatives, and submitted to a variety of prehybridization treatments. Further experiments with non-embedded nuclei fractionated from mouse liver revealed a similar distribution of DNA at the telomeric end of chromosome 3, but for centromeric DNA and total mouse genomic DNA, hybridization signals were observed both in the interior and at the periphery of the nucleus. These observations preclude the exclusive localization of chromosomes to the nuclear periphery. However, they indicate that a subset of centromeres are likely to be associated with the nuclear membrane, and that there is such an association at the telomeric end of chromosome 3. Overall, these results are compatible with previous observations of other investigators showing regions of contact between chromosomes and the nuclear membrane.

Animals↗