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Biomedical subjects

C W Lo

Publications and source records attributed to C W Lo.

88 records · Page 5Linked to original sources

Gap junctional communication compartments in the Drosophila wing disk.

We have examined the gap junctional communication properties of cells in the wing imaginal disk of Drosophila, using intracellular injection of the fluorescent dye tracer Lucifer Yellow. The cell-to-cell passage of Lucifer Yellow is restricted at a boundary line that divides the wing disk into halves. We refer to each half as a "communication compartment" because there is a high level of gap junctional exchange within a compartment and much lower exchange between compartments. Comparison of the positions of the compartments with developmental fate maps suggests that cells in one communication compartment give rise to cuticular structures in the anterior half of the adult dorsal mesothorax, and cells in the other compartment contribute to posterior structures. This communication-restriction line appears to be coincident with the line between the anterior and posterior developmental compartments observed in studies of cell lineage. We propose that gap junctional communication restrictions may play a general role in generating or maintaining developmental compartments.

Animals↗

Breath tests: principles, problems, and promise.

Breath tests rely on the measurement of gases produced in the intestine, absorbed, and expired in the breath. Carbohydrates, such as lactose and sucrose, can be administered in physiologic doses; if malabsorbed, they will be metabolized to hydrogen by colonic bacteria. Since hydrogen is not produced by human metabolic reactions, a rise in breath hydrogen, as measured by gas chromatography, is evidence of carbohydrate malabsorption. Likewise, a rise in breath hydrogen marks the transit time of nonabsorbable carbohydrates such as lactulose through the small intestine into the colon. Simple end-expiratory interval collection into nonsiliconized vacutainer tubes has made these noninvasive tests quite convenient to perform, but various problems, including changes in stool pH, intestinal motility, or metabolic rate, may influence results. Another group of breath tests uses substrates labeled with radioactive or stable isotopes of carbon. Labeled fat substrates such as trioctanoin, tripalmitin, and triolein do not produce the expected rise in labeled breath CO2 if there is fat malabsorption. Bile acid malabsorption and small intestinal bacterial overgrowth can be measured with labeled cholylglycine or cholyltaurine. Labeled drugs such as aminopyrine, methacetin, and phenacetin can be used as an indication of drug metabolism and liver function. Radioactive substrates have been used to trace metabolic pathways and can be measured by scintillation counters. The availability of nonradioactive stable isotopes has made these ideal for use in children and pregnant women, but the cost of substrates and the mass spectrometers to measure them has so far limited their use to research centers. It is hoped that new techniques of processing and measurement will allow further realization of the exciting potential breath analysis has in a growing list of clinical applications.

Bile Acids and Salts↗

"Antral dysmotility". An unrecognized cause of chronic vomiting during infancy.

Ten infants who were less than nine months of age and had chronic nonbilious vomiting were evaluated for gastroesophageal reflux. Upper gastrointestinal series in all showed delayed gastric emptying, a funnel-shaped antrum, absent antral peristalsis, and gastroesophageal reflux. None had evidence of anatomic obstruction in the stomach or duodenum. Manometric studies of the esophagus revealed either normal (4 patients) or elevated (6 patients) lower esophageal sphincter pressures. One-hour esophageal pH probe tests were negative in seven of the ten infants. This obstruction to gastric emptying appears to represent a disorder of antral motility. Medical management, which consisted of small frequent feedings and postural therapy, was successful in six of the infants. The remaining four patients required pyloroplasty. All of the infants are now asymptomatic and gaining weight at either a normal or accelerated rate for their ages. Familiarity with this previously undescribed disorder should prevent the incorrect diagnosis of gastroesophageal reflux secondary to lower esophageal sphincter incompetence and the resulting inappropriate surgical reconstruction.

Chronic Disease↗

Gap junctional communication in the preimplantation mouse embryo.

In this study, we examined cell-to-cell communication via gap junctional channels between the cells of the early mouse embryo from the 2-cell stage to the preimplantation blastocyst stage. The extent of communication was examined by monitoring for the presence of ionic coupling, the transfer of injected fluorescein (molecular weight 330) and the transfer of injected horseradish peroxidase (molecular weight 40,000). In the 2-cell, 4-cell and precompaction 8-cell embryos, cytoplasmic bridges between sister blastomeres were responsible for ionic coupling and the transfer of injected fluorescein as well as the transfer of injected horseradish peroxidase. In contrast, no communication was observed between blastomeres from different sister pairs. Junction-mediated intercellular communication was unequivocably detected for the first time in the embryo at the early compaction stage (late 8-cell embryo). At that stage, ionic coupling was present and fluorescein injected into one cell spread to all eight cells of the embryo. Injected horseradish peroxidase was passed to only one other cell, however, again indicating the presence of cytoplasmic bridges between sister blastomeres. Junctional communication with respect to both ionic coupling and dye transfer was retained between all the cells throughout compaction. At the blastocyst stage, trophoblast cells of the blastocyst were linked by junctional channels to other trophoblast cells as well as to cells of the inner cell mass, as indicated by the spread of injected fluorescein. In addition, the extent of communication between the cells of the inner cell mass was examined in inner cell masses isolated by immunosurgery; both ionic coupling and the complete spread of injected fluorescein were observed.

Animals↗

Gap junctional communication in the post-implantation mouse embryo.

We studied the extent of cell-to-cell communication via junctional channels in in vitro-implanted mouse blastocysts by monitoring ionic coupling and the spread of two injected low molecular weight dyes, fluorescein and Lucifer yellow. In the early attached embryos, both trophoblasts and cells of the inner cell mass (ICM) were ionically coupled to one another. Dye injections in either trophoblasts or ICM cells resulted in spread to the entire embryo. As older and more developed embryos were examined, the spread of injected dye was progressively more limited. In the most developed embryos examined, dye injected into a cell in the ICM region resulted in spread throughout the ICM but not into the surrounding trophoblast cells, while dye injected into a trophoblast cell did not spread to any other cell in the embryo. Simultaneous monitoring of ionic coupling and dye injections in embryos of intermediate stages in this transition revealed that the trophoblast and ICM cells were ionically coupled, even across the apparent boundary where no dye was observed to pass. In the latest stage embryos examined in which no injected dye was observed to move out of the ICM, ionic coupling was still observed between the cells of the ICM and the trophoblasts. Furthermore, in the more developed embryos, dye injected into the ICM region frequently was not transferred to all the cells of the ICM, thus suggesting a further compartmentalization of due spread within the ICM. Our observations that ionic coupling is more extensive than the detectable spread of injected dyes may perhaps reflect a reduced number of junctional channels. With fewer channels less dye would pass between cells, so that, together with continuous quenching, the transfer of injected dye would not be detectable. This partial segregation of cell-to-cell communication as indicated by the limited dye spread may parallel specific differentiation processes, in particular that of giant trophoblast, embryonic ectoderm and extraembryonic endoderm differentiation.

Animals↗

The sedative effect of acupuncture.

Eight patients with diagnosis of anxiety neurosis were treated with acupuncture. Six of them showed good to moderate response while 2 had no change. The endorphin theory in applying acupuncture is discussed.

Acupuncture Therapy↗

Comparative evaluation of hypnotic efficacy of flunitrazepam in psychiatric in-patients.

Flunitrazepam in 2-mg and 4-mg doses was compared with flurazepam 30 mg and nitrazepam 10 mg for hypnotic efficacy in a double-blind, multiple cross-over trial involving 41 psychiatric in-patients. In the vast majority of comparisons involving a number of sleep parameters differences did not reach significance level. Flunitrazepam 4 mg tended to produce the shortest latency time and the longest duration of sleep but also the most side-effects. Nitrazepam 10 mg appeared to have a slight advantage over the other drugs in terms of patient preference. For severe sleep disturbance flunitrazepam 2 mg tended to be the most satisfactory drug in terms of efficacy and paucity of side-effects.

Adult↗

Retroperitoneal actinomycosis with intraperitoneal spread. Stellate pattern on CT.

We report a case of pathologically proved actinomycosis that presented unusual computed tomographic (CT) features: a soft-tissue retroperitoneal mass encasing the adjacent ureter resulting in hydronephrosis and spreading into the intraperitoneal space with a stellate pattern. The role of CT in monitoring the response to antibiotic treatment is also discussed.

Actinomycosis↗

Gap junction communication and the modulation of cardiac neural crest cells.

The analyses of transgenic and knockout mice with perturbations in alpha 1 connexin (Cx43) function have revealed an important role for gap junctions in cardiac development. This likely involves the modulation of cardiac crest migration and function. Studies carried out with these mouse models suggest that clinically there may be a novel category of cardiac defects involving crest perturbations that do not include outflow septation defects, but rather involve more subtle defects in the pulmonary outflow tract.

Animals↗

BMP regulation of the mouse connexin43 promoter in osteoblastic cells and embryos.

We examined BMP regulation of the gap junction gene Gjal (Cx43alpha1) using a series of lacZ reporter constructs containing up to 6.7 kbs of mouse Cx43alpha1 promoter sequence. Using transient transfection assays, we showed that BMP2, BMP4, and GDF5, but not BMP6 or BMP7, can modulate Cx43alpha1 promoter activity in the osteosarcoma cell line ROS17/2.8. Positive regulatory elements were found at the proximal and distal ends of the 6.7 kb promoter fragment, while negative regulatory elements were found in the intervening region. Comparison of Cx43alpha1 promoter sequences from the human vs. mouse showed five regions with significant sequence conservation, two of which contained Smad binding elements in conjunction with a BMP response element. Analysis of a transgenic mouse line containing a Cx43alpha1 promoter driven lacZ reporter construct revealed lacZ expression in the developing joints, an expression pattern similar to that previously reported for Gdf5. LacZ expression was also observed in axial regions of the skeletal anlage, which in situ hybridization analysis confirmed as sites of Gdf5 transcript expression. When the Cx43alpha1 promoter driven lacZ transgene was bred into the brachypodism mouse Gdf5(bpJ)(bp) harboring a Gdf5 loss of function mutation, lacZ expression was extinguished. This was observed in homozygous and heterozygous bp animals, suggesting that Cx43alpha1 promoter regulation by GDF5 is subject to haploinsufficiency. Overall, these observations are consistent with recent studies by others indicating a role for Cx43alpha1 in osteogenesis and osteoblastic function during mouse development.

Amino Acid Motifs↗

Success rates and cost-effectiveness of antibiotic combinations for initial treatment of central-venous-line infections during total parenteral nutrition.

BACKGROUND: Central-venous-line infections can be successfully treated with appropriate antibiotics, thus avoiding the need for catheter removal. Based on our experience, vancomycin, gentamicin, piperacillin, ceftazidime, and amphotericin, alone or in combination, are usually administered, pending sensitivity results. This empirical list, however, has never been verified against actual sensitivity results nor has it been tested for cost or efficacy. METHODS: Medical records of inpatients on hyperalimentation over 1 year were reviewed. Success rate, therapy duration, and drug acquisition cost and charge were assessed for central-venous-line infections. Antibiotics then were paired and evaluated in terms of charge and efficacy against all microorganisms as determined by sensitivity results. RESULTS: In 500 inpatients receiving hyperalimentation for 9,698 patient-days, 8.4 central-venous-line infections/1,000 patient-days occurred. Staphylococcus non-aureus, Candida species, Enterococcus faecium, and Staphylococcus aureus predominantly were isolated. Of the infections, 51 (67%) were sensitive to one or more of the initial antibiotics. A 2-week course of antibiotics successfully treated 50 (66%) catheter infections without line removal. Appropriate initial therapy on average reduced treatment duration by 8 to 10 days and drug charges by $400 to $700. CONCLUSIONS: Amikacin-vancomycin appears to be the most cost-effective selection for presumed central-venous-line infections, pending sensitivity results, followed by valid alternatives. Lower failure rates are well worth the extra cost in pharmaceutical charges.

Adolescent↗