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Biomedical subjects

L Kwong

Publications and source records attributed to L Kwong.

8 recordsLinked to original sources

Alterations in postnatal intestinal function during chronic hypoxemia.

Growth failure is a major complication of chronic hypoxemia, as seen in infants and children with cyanotic congenital heart disease. To determine whether chronic hypoxemia during infancy affects the gastrointestinal tract, we examined small intestinal growth and digestive enzyme activities in chronically hypoxemic newborn lambs and in age-matched controls. Chronic hypoxemia was produced by placing an inflatable occluder around the main pulmonary artery and performing a balloon atrial septostomy. Aortic oxygen saturation was reduced to 60-74% for 2 wk, after which the small intestine was removed for analysis. During chronic hypoxemia, somatic growth rate was decreased to 60% of control (hypoxemic, 135 +/- 20 versus control, 216 +/- 26 g/d, p less than 0.02). No differences in caloric intake were found (hypoxemic, 129 +/- 4 versus control, 128 +/- 4 kcal/kg/d). Chronic hypoxemia did not alter small intestinal growth, as measured by jejuno-ileal weight, jejuno-ileal length, mucosal weight, or mucosal protein or DNA contents. However, sp act of lactase, the principal disaccharidase of the infant lamb intestine, were significantly decreased (hypoxemic, 0.08 +/- 0.01 versus control, 0.146 +/- 0.03 units of enzyme activity/mg DNA, p less than 0.05), as were the total small intestinal contents of lactase (hypoxemic, 61.7 +/- 7.0 versus control, 120.6 +/- 21.7 units of enzyme activity, p less than 0.01). There also were decreases in specific and total activities of other digestive enzymes such as maltase, amino-oligopeptidase, and alkaline phosphatase in hypoxemic intestine that did not achieve statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A possible role for DIF-2 in the formation of stalk cells during Dictyostelium development.

The differentiation inducing factor (DIF) is essential for stalk cell formation in monolayers of Dictyostelium discoideum and is necessary for the expression of several prestalk cell-specific genes. DIF activity has been fractionated into a major species, designated DIF-1, and several minor species, including DIF-2. Although DIF-1 is an excellent inducer of stalk cell formation from vegetative cells, it is a poor inducer of stalk cell formation from prestalk cells. In contrast, DIF-2 is more active for the conversion of prestalk cells into stalk cells, than for the conversion of vegetative cells to stalk cells. The same results were obtained regardless of whether chemically synthesized or naturally occurring components were utilized. In addition, stalk cell formation was three- to fourfold higher when vegetative cells were incubated with DIF-1 for a suboptimal period and then subsequently incubated with DIF-2, than when cells were incubated with DIF-2 first and then subsequently with DIF-1. These results indicate a distinct role for DIF-2 during stalk cell formation and suggest the possibility that DIF-1 and DIF-2 act sequentially.

Cell Differentiation

Plasma apolipoprotein E, high density lipoprotein1 (HDL1) and urinary mevalonate excretion in pancreatectomized diabetic dogs: effects of insulin and lovastatin.

Hypercholesterolemia and increased concentrations of an apolipoprotein E (apoE)-containing HDL subclass, high density lipoprotein1 (HDL1) have been observed in streptozocin-alloxan diabetic dogs consuming normal amounts of dietary cholesterol. The aim of this study was to characterize the response of HDL1 and its targeting ligand, apoE, to insulin and HMG-CoA reductase inhibitor treatment in pancreatectomized diabetic dogs. Following induction of diabetes, plasma total cholesterol, HDL1, and apoE concentrations were all increased. Urinary mevalonate excretion, an index of cholesterol synthesis in humans, was 6-fold that of nondiabetic controls. Lipoprotein fractionation by Pevikon block electrophoresis and gel filtration chromatography showed that the increased cholesterol and apoE were associated with alpha 2-migrating particles corresponding to HDL1. Insulin treatment, resulting in near normal fasting blood glucose concentrations in the group as a whole (average 5.1 mM, 92 mg/dl), led to variable reductions in apoE, total plasma cholesterol, and HDL1. Uncorrected dyslipidemia during intensified insulin treatment appeared to be related to failure to achieve euglycemia. Despite unremitting hyperglycemia, treatment with lovastatin resulted in pronounced decreases in plasma cholesterol, HDL1 and apoE to concentrations below those observed in nondiabetic animals. Mevalonate excretion also fell, but remained twice normal. Thus neither modality corrected all of the abnormalities in canine diabetic dyslipidemia. Since apoE-containing HDL1 may mediate cholesterol traffic between the periphery and the liver (reverse cholesterol transport), the present observations suggest that increased cholesterol synthesis is accompanied by parallel abnormalities in cholesterol flux through the reverse transport pathway in the canine model.

Animals

A Dictyostelium morphogen that is essential for stalk cell formation is generated by a subpopulation of prestalk cells.

The stalk cell differentiation inducing factor (DIF) has the properties required of a morphogen responsible for pattern regulation during the pseudoplasmodial stage of Dictyostelium development. It induces prestalk cell formation and inhibits prespore cell formation, but there is as yet no strong evidence for a morphogenetic gradient of DIF. We have measured DIF accumulation by monolayers of isolated prestalk and prespore cells in an attempt to provide evidence for such a gradient. DIF is accumulated in the largest quantities by a subpopulation of prestalk cells that specifically express the DIF-inducible genes pDd56 and pDd26. Since it has been shown recently that cells that express pDd56 are localized in the central core of the prestalk cell region of the pseudoplasmodia, our current results suggest a morphogenetic gradient generated by this region.

Blotting, Northern

Studies on the accumulation of the differentiation-inducing factor (DIF) in high-cell-density monolayers of Dictyostelium discoideum.

A number of factors that have been shown to influence cell type determination in Dictyostelium discoideum were assessed for their effects on the accumulation of the stalk cell differentiation-inducing factor (DIF) in high-cell-density monolayers of strain V12-M2. DIF accumulation is markedly enhanced by low pH, butyrate, and the proton pump inhibitor diethylstilbestrol (DES), conditions that induce stalk cell formation in low-cell-density monolayers in the absence of added DIF. These results are discussed in relation to a model for cell type determination recently proposed by (J.D. Gross, M.J. Peacey, and R. Pogge Von Strandmann (1988, Differentiation, 38: 91-98). DIF accumulates in high-cell-density monolayers after the cells have become independent of cyclic AMP for stalk cell formation. This accumulation is greatly enhanced by the addition of cyclic AMP. This result may explain why cyclic AMP stimulates stalk cell formation in low-density monolayers in the presence of suboptimal levels of DIF, following preincubation in the presence of saturating levels of cyclic AMP (L. Kwong, A. Sobolewski, and G. Weeks, 1988, Differentiation 37, 1-6). Adenosine has no effect on DIF accumulation in high-cell-density monolayers.

Butyrates

Stalk cell formation in monolayers of Dictyostelium discoideum V12-M2.

Stalk cell formation in low-cell-density monolayers of Dictyostelium discoideum, strain V12-M2, occurs following the sequential addition of cyclic AMP and the differentiation-inducing factor (DIF). Both cyclic AMP and DIF are essential for the appearance of the prestalk-specific isozyme alkaline phosphatase-II, which suggests that both factors are necessary for prestalk cell formation. The available evidence suggests that the cyclic AMP requirement for stalk cell formation is mediated through the cell surface cyclic AMP receptor. However, stalk cell formation is inhibited by caffeine and this inhibition is reversed by the cell-permeable analogue 8-Br-cyclic AMP, which suggests in addition a possible involvement for elevated intracellular cyclic AMP concentrations in stalk cell formation. During in vivo development cells first become independent of cyclic AMP at the tipped aggregate stage, but the acquisition of cyclic AMP independence is advanced by several hours when cells are incubated in the presence of cyclic AMP for 2 hours. Cells do not become independent of DIF until the culmination stage of development, which suggests the possibility that DIF is required for the conversion of prestalk cells to stalk cells. There is an absolute requirement for DIF for stalk cell formation in low-density monolayers of prestalk cells but only part of population exhibits a requirement for cyclic AMP, which suggests that the prestalk cell population consists of two distinct cell types. Stalk cell formation from prespore cells is totally dependent on both cyclic AMP and DIF.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation

Stalk cell formation in monolayers from isolated prestalk and prespore cells of Dictyostelium discoideum: evidence for two populations of prestalk cells.

Cells from the pseudoplasmodial stage of Dictyostelium discoideum differentiation were dispersed and separated on Percoll gradients into prestalk and prespore cells. The requirements for stalk cell formation in low-density monolayers from the two cell types were determined. The isolated prespore cells required both the Differentiation Inducing Factor (DIF) and cyclic AMP for stalk cell formation. In contrast, only part of the isolated prestalk cell population required both cyclic AMP and DIF, the remainder requiring DIF alone, suggesting the possibility that there were two populations of prestalk cells, one independent of cyclic AMP and one dependent on cyclic AMP for stalk cell formation. The finding that part of the prestalk cell population required only a brief incubation in the presence of DIF to induce stalk cell formation, whilst the remainder required a considerably longer incubation in the presence of both DIF and cyclic AMP was consistent with this idea. In addition, stalk cell formation from cyclic-AMP-dependent prestalk cells was relatively more sensitive to caffeine inhibition than stalk cell formation from cyclic-AMP-independent prestalk cells. The latter cells were enriched in the most anterior portion of the migrating pseudoplasmodium, indicating that there is spatial segregation of the two prestalk cell populations. The conversion of prespore cells to stalk cells took longer and was more sensitive to caffeine when compared to stalk cell formation from cyclic-AMP-dependent prestalk cells.

Caffeine

Incidence of motile, curved anaerobic rods (Mobiluncus species) in vaginal secretions.

Aerobic and anaerobic cultures as well as a Gram stain and wet mount preparation were made of vaginal swabs taken from various groups of women including those with vaginal discharge. The bacteria commonly found in cultures were lactobacilli, coryneforms, Staphylococcus epidermidis and facultative streptococci. Anaerobes were isolated from 75% (475 of 632) of specimens. The incidence of Trichomonas vaginalis, Candida species, Gardnerella vaginalis and Mobiluncus species in the five groups of women varied from 2.2-5.1%, 11.5-35.7%, 23.3-36.7% and 20.0-34.8% respectively. Except for Candida species, differences in the prevalence of these organisms between the groups of women were not significant. The isolation rates of Candida species in women attending the antenatal clinic and staff health clinic were significantly higher than women in the other groups. Mobiluncus species were found to occur either with T. vaginalis, Candida species or G. vaginalis alone or with any two or with all three or in the absence of these organisms. However, the incidence of Mobiluncus species was significantly higher in women colonized with G. vaginalis (112 of 185, or 60.5%) compared with women not infected (47 of 477, or 9.8%). Also, Mobiluncus species occurred in large numbers when found in the presence of G. vaginalis. When found without G. vaginalis, Mobiluncus species occurred in much smaller numbers. As with G. vaginalis, Mobiluncus species also occurred concomitantly with certain anaerobes, mainly Bacteroides species and peptostreptococci.

Animals