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Biomedical subjects

L Min

Publications and source records attributed to L Min.

At least 19 recordsLinked to original sources

Birth weight references for triplets.

OBJECTIVE: The purpose of this study was to formulate growth references that reflect triplet fetal and neonatal populations at each gestational age by combining serial ultrasonographic estimates of fetal weights and measured birth weights. STUDY DESIGN: This historical cohort study was based on 188 pregnancies of live-born triplets of > or =23 weeks' gestation. Ultrasonographic fetal weight measures were modeled as a function of gestational age for each infant. Linear regression models were used to fit the data, and weight percentiles were generated. RESULTS: Well-grown triplets fell substantially below singletons by 30 weeks and twins after 34 weeks. Trichorionic vs monochorionic or dichorionic placentation resulted in 27% higher growth at the 10th %ile, 5% higher growth at the 50th %ile, and 4% higher growth at the 90th %ile by 34 weeks. CONCLUSION: The overall pattern of fetal growth for well-grown triplets does not differ from that of singletons and twins until late gestation, confirming that, in utero, well-grown children have similar growth potentials, regardless of plurality.

Birth Weight↗

Diltiazem overdose haemodynamic response to hyperinsulinaemia-euglycaemia therapy: a case report.

A 59-year-old woman was admitted to the intensive care unit after ingesting 5.76 g of an extended release preparation of diltiazem. The patient was hypotensive and bradycardic and was treated initially with intravenous fluids, adrenaline, noradrenaline, vasopressin and standard insulin doses to maintain the blood glucose levels between 6-10 mmol/L. As the patient remained inotrope dependent the insulin dose was increased to 25 U/hr with an infusion of 50% dextrose to maintain the blood glucose levels between 6-8 mmol/L. Within 30 minutes, the mean arterial pressure increased from 65 mmHg to 80 mmHg and within 60 minutes all vasoactive agents were discontinued. A right heart catheter inserted before the increased dose of insulin revealed that the predominant haemodynamic effect of the hyperinsulinaemia-euglycaemia therapy appeared to be an increase in the peripheral vascular resistance.

Journal Article↗

Mutations of the second extracellular loop of the human lutropin receptor emphasize the importance of receptor activation and de-emphasize the importance of receptor phosphorylation in agonist-induced internalization.

Alanine scanning mutagenesis of the second extracellular loop of the human lutropin receptor (hLHR) showed that mutation of most of the residues present in this region either enhance or impair the internalization of agonist. A more complete analysis of four mutants, two that enhanced internalization (F515A and T521A) and two that impaired internalization (S512A and V519A), showed that the two mutants that impaired internalization also show a decrease in the sensitivity for agonist-induced cAMP accumulation, whereas the two mutants that enhanced internalization show an increase in the sensitivity for agonist-induced cAMP accumulation. None of these mutants had an effect on the agonist-induced phosphorylation of the hLHR, however. We conclude that, in contrast to the prevailing view of the relative importance of receptor phosphorylation in the internalization of G protein-coupled receptors, the phosphorylation of the hLHR is less important than the agonist-induced activation of the hLHR in the process of internalization.

Cell Line↗

Effects of des-aspartate-angiotensin I on angiotensin II-induced incorporation of phenylalanine and thymidine in cultured rat cardiomyocytes and aortic smooth muscle cells.

Des-aspartate-angiotensin I, a pharmacologically active nine-amino acid angiotensin peptide, and losartan, an AT(1) angiotensin receptor antagonist, but not angiotensin-(1-7), another active angiotensin peptide, completely attenuated the angiotensin II-induced incorporation of [3H]phenylalanine in cultured rat cardiomyocytes. The attenuation by des-aspartate-angiotensin I but not that of losartan was inhibited by indomethacin. The data support an earlier suggestion that the nonapeptide attenuates cardiac hypertrophy in rats via an indomethacin-sensitive angiotensin AT(1) receptor subtype. In rat aortic smooth muscle cells, both des-aspartate-angiotensin I and angiotensin-(1-7) had no effect on the angiotensin II-induced [3H]phenylalanine incorporation. However, the two peptides significantly attenuated the angiotensin II-induced [3H]thymidine incorporation in the smooth muscle cells. The attenuation by angiotensin-(1-7) but not by des-aspartate-angiotensin I was inhibited by (D-Ala(7))-angiotensin-(1-7), a specific angiotensin-(1-7) antagonist. Des-aspartate-angiotensin I also attenuated FCS-stimulated [3H]thymidine incorporation. This attenuation was inhibited by the peptide angiotensin receptor antagonist, (Sar(1), Ile(8))-angiotensin II, but not by losartan. These data indicate that des-aspartate-angiotensin I and angiotensin-(1-7) do not participate in the process of protein synthesis in vascular smooth muscle cells and that the nonapeptide and heptapeptide act on different non-AT(1) receptors to mediate their anti-hyperplasic action. Although the exact mechanisms of action remain to be elucidated, the findings indicate that des-aspartate-angiotensin I acts as an agonist on angiotensin AT(1) and non-AT(1) receptor subtypes and induces responses that oppose the actions of angiotensin II.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Production of recombinant salmon calcitonin by amidation of precursor peptide using enzymatic transacylation and photolysis in vitro.

The C terminal amidation is required for full biological activity of salmon calcitonin (sCT). We constructed BL21(DE3)/pGEX-sCT-Ala, an engineering Escherichia coli strain. The soluble fusion protein of GST-sCT-Ala expressed from BL21(DE3)/pGEX-sCT-Ala was purified by affinity chromatography after high density, high expression culture and sonication of bacteria. Following S-sulfonation of the fusion protein, the 33 alanine-extended peptides were released from the fusion protein by cyanogen bromide. The S-sulfonated precursor peptide was transacylated by CPD-Y, o-PNGA as a nucleophile, to produce photosensitive SO(-)(3)-sCT-o-PNGA. After photolysis and folding, the biological activity of sCT was assayed as standard.

Acylation↗

Glucose-dependent insulinotropic peptide signaling pathways in endothelial cells.

Glucose-dependent insulinotropic peptide (GIP) potentiates glucose-induced insulin secretion. In addition, GIP has vasoconstrictive or vasodilatory properties depending on the vascular bed affected. In order to assess whether this effect could be related to differences in GIP receptor expression, several different endothelial cell types were examined for GIP receptor expression. GIP receptor splice variants were detected and varied depending on the endothelial cell type. Furthermore, stimulation of these cells with GIP led to cell type dependent differences in activation of the calcium and cAMP signaling pathways. To our knowledge this is the first physiological characterization of receptors for GIP in endothelial cells.

Alternative Splicing↗

Birth weight references for twins.

OBJECTIVE: We sought to formulate fetal and birth weight references for twins from longitudinal data. STUDY DESIGN: This historic cohort study was based on 1831 pregnancies of twins born alive at >/=28 weeks' gestation from Baltimore, Maryland; Miami, Florida; Charleston, South Carolina; and Ann Arbor, Michigan. RESULTS: When we compared singletons and twins, the percentiles of twins fell substantially below the 10th percentile of singletons by 28 weeks' gestation, below the 50th percentile by 30 weeks' gestation, and below the 90th percentile by 34 weeks' gestation. The difference at the 50th percentile was 147 g (10%) at 30 weeks' gestation, 242 g (14%) at 32 weeks' gestation, 347 g (17%) at 34 weeks' gestation, 450 g (19%) at 36 weeks' gestation, 579 g (22%) at 38 weeks' gestation, and 772 g (27%) at 40 weeks' gestation. CONCLUSION: This new reference demonstrates that, although the overall pattern of fetal growth is slower for twins versus singletons from about 30 weeks' gestation, well-grown twins and singletons do not differ as much as previously believed.

Adult↗

Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors.

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [125I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.

Alkaline Phosphatase↗

Effect of activating and inactivating mutations on the phosphorylation and trafficking of the human lutropin/choriogonadotropin receptor.

The effects of several mutations of the human LH receptor (hLHR) on the phosphorylation, internalization, and turnover of the cell surface receptor were examined. Three gain-of-function mutations associated with Leydig cell hyperplasia (L457R and D578Y) and one associated with Leydig cell adenomas (D578H), one signaling-impaired mutation associated with Leydig cell hypoplasia (I625K), and two laboratory designed signaling-impaired mutations (D405N and Y546F) were used. The signaling-impaired mutations showed a reduction in human CG (hCG)-induced receptor phosphorylation and internalization. Mutation of the phosphorylation sites of these loss-of-function mutants had little or no additional effect on internalization. Cotransfection with G protein-coupled receptor kinase-2 (GRK2) rescued the hCG-induced phosphorylation and internalization of the signaling-impaired mutations but only if the phosphorylation sites were intact. Overexpression of arrestin-3 rescued the rate of internalization regardless of whether or not the phosphorylation sites were intact. Only two of the three constitutively active mutants displayed an increase in basal phosphorylation. Although they all failed to respond to hCG with increased receptor phosphorylation, they all internalized hCG faster than wild-type hLHR (hLHR-wt). Mutation of the phosphorylation sites of these constitutively active mutants lengthened the half-time of internalization of hCG toward that of hLHR-wt. Overexpression of arrestin-3 had little or no effect on the already short half-time of internalization of hCG mediated by these mutants. The data obtained with the signaling-impaired and phosphorylation-deficient mutants of the hLHR support a model whereby receptor phosphorylation and activation play a redundant role in the internalization of hCG. The results obtained with the constitutively active mutants suggest that, when occupied by hCG, these mutants assume a conformation that bypasses many of the steps (i.e. activation, phosphorylation, and/or arrestin binding) involved in internalization.

Arrestins↗

Work and pregnancy: the role of fatigue and the "second shift" on antenatal morbidity.

OBJECTIVE: This study was undertaken to evaluate factors at home and work associated with antenatal morbidity (emergency department visits and hospitalizations) among employed pregnant women. STUDY DESIGN: This prospective study of 213 women included 3 antenatal interviews at about 16, 24, and 30 weeks' gestation with questions on health history, lifestyle, housework, working conditions, and emergency department visits and hospitalizations. Work scores and home scores were formulated from each interview. Fatigue was defined as being very tired or extremely tired at the end of a typical workday. The risk of antenatal morbidity was modeled by means of logistic regression; results are presented as adjusted odds ratios with 95% confidence intervals. RESULTS: The risk of antenatal morbidity, which was greatest during the second trimester, was increased by stress (adjusted odds ratio, 2.45; 95% confidence interval, 1.32-4.57), fatigue (adjusted odds ratio, 3.77; 95% confidence interval, 1.98-7.18), work plus home score (adjusted odds ratio, 1.55; 95% confidence interval, 1.22-1.97), and the interaction of fatigue and work plus home score (adjusted odds ratio, 4.61; 95% confidence interval, 2.02-10.50). CONCLUSIONS: These findings suggest that maternal fatigue contributes significantly to antenatal morbidity.

Adult↗

Effects of des-Asp-angiotensin I on experimentally-induced cardiac hypertrophy in rats.

We studied the effects of des-Asp-angiotensin I, a nine amino acid peptide, on cardiac hypertrophy caused by coarctation of the abdominal aorta in Sprague-Dawley rats. The nonapeptide was effective when given either intravenously or orally. Maximum attenuation was observed with an i.v. dose of 153 pmol/day for 4 days, and an oral dose of 250 nmol/day for 4 days. Three mg p.o. losartan, an angiotensin AT1 receptor antagonist, produced comparable attenuation. However, the attenuation produced by des-Asp-angiotensin I but not by losartan was blunted by 30.4 micromol of indomethacin. The oral efficacy of the nonapeptide was partly due to its low effective i.v. doses which were in the nM range. This range is below the Km of most enzymes including those of the intestinal peptidases (the Km of most enzymes is in the microM range). However, the mechanism of absorption of the peptide from the GIT into the systemic circulation remains to be investigated. The findings demonstrate for the first time, the anti-cardiac hypertrophic action of an angiotensin peptide. Unlike the ACE inhibitors and angiotensin receptor antagonists, the nonapeptide acts as an agonist on an indomethacin-sensitive angiotensin receptor to exert its action.

Angiotensin I↗

An interplay between two EGF-receptor ligands, Vein and Spitz, is required for the formation of a subset of muscle precursors in Drosophila.

Activation of the Drosophila EGF-receptor (DER) is spatially and temporally controlled by the release of its various ligands. DER and its ligand Spitz mediate the formation of specific somatic muscle precursors. We show that a second DER ligand, Vein, complements the activity of Spitz in the development of various somatic muscle precursors. In vn mutant embryos, the DER-dependent muscle precursors do not form in some of the segments. This phenotype is significantly enhanced in embryos carrying only one copy of wild type spitz. Our analysis suggests that Vein activation of DER differs qualitatively from that of Spitz in that it does not lead to the expression of the inhibitory protein Argos, possibly leading to a continuous activation of the DER signaling pathway.

Animals↗

The Drosophila neuregulin homolog Vein mediates inductive interactions between myotubes and their epidermal attachment cells.

Inductive interactions between cells of distinct fates underlie the basis for morphogenesis and organogenesis across species. In the Drosophila embryo, somatic myotubes form specific interactions with their epidermal muscle attachment (EMA) cells. The establishment of these interactions is a first step toward further differentiation of the EMA cells into elongated tendon cells containing an organized array of microtubules and microfilaments. Here we show that the molecular signal for terminal differentiation of tendon cells is the secreted Drosophila neuregulin-like growth factor Vein produced by the myotubes. Although vein mRNA is produced by all of the myotubes, Vein protein is secreted and accumulates specifically at the muscle-tendon cell junctional site. In loss-of-function vein mutant embryos, muscle-dependent differentiation of tendon cells, measured by the level of expression of specific markers (Delilah and beta1 tubulin) is blocked. When Vein is expressed in ectopic ectodermal cells, it induces the ectopic expression of these genes. Our results favor the possibility that the Drosophila EGF receptor DER/Egfr expressed by the EMA cells functions as a receptor for Vein. We show that Vein/Egfr binding activates the Ras pathway in the EMA cells leading to the transcription of the tendon-specific genes, stripe, delilah, and beta1 tubulin. In Egfr1F26 mutant embryos that lack functional Egfr expression, the levels of Delilah and beta1 tubulin are very low. In addition, the ability of ectopic Vein to induce the expression of Delilah and beta1 tubulin depends on the presence of functional Egfrs. Finally, activation of the Egfr signaling pathway by either ectopically secreted Spitz, or activated Ras, leads to the ectopic expression of Delilah. These results suggest that inductive interactions between myotubes and their epidermal muscle attachment cells are initiated by the binding of Vein, to the Egfr on the surface of EMA cells.

Animals↗

Reciprocal signaling between Drosophila epidermal muscle attachment cells and their corresponding muscles.

Directed intercellular interactions between distinct cell types underlie the basis for organogenesis during embryonic development. This paper focuses on the establishment of the final somatic muscle pattern in Drosophila, and on the possible cross-talk between the myotubes and the epidermal muscle attachment cells, occurring while both cell types undergo distinct developmental programs. Our findings suggest that the stripe gene is necessary and sufficient to initiate the developmental program of epidermal muscle attachment cells. In stripe mutant embryos, these cells do not differentiate correctly. Ectopic expression of Stripe in various epidermal cells transforms these cells into muscle-attachment cells expressing an array of epidermal muscle attachment cell-specific markers. Moreover, these ectopic epidermal muscle attachment cells are capable of attracting somatic myotubes from a limited distance, providing that the myotube has not yet been attached to or been influenced by a closer wild-type attachment cell. Analysis of the relationships between muscle binding and differentiation of the epidermal muscle attachment cell was performed in mutant embryos in which loss of muscles, or ectopic muscles were induced. This analysis indicated that, although the initial expression of epidermal muscle-attachment cell-specific genes including stripe and groovin is muscle independent, their continuous expression is maintained only in epidermal muscle attachment cells that are connected to muscles. These results suggest that the binding of a somatic muscle to an epidermal muscle attachment cell triggers a signal affecting gene expression in the attachment cell. Taken together, our results suggest the presence of a reciprocal signaling mechanism between the approaching muscles and the epidermal muscle attachment cells. First the epidermal muscle attachment cells signal the myotubes and induce myotube attraction and adhesion to their target cells. Following this binding, the muscle cells send a reciprocal signal to the epidermal muscle attachment cells inducing their terminal differentiation into tendon-like cells.

Animals↗

[The human SRY gene for prenatal diagnosis].

OBJECTIVE: To establish the method for prenatal sex diagnosis of the fetus carrying sex-linked genetic disorder. METHOD: Human SRY gene was amplified by polymerase chain reaction. A 422-bp male specific fragment was obtained. RESULTS: The fragment was identified in 10 men, but unidentified in 10 women. The diagnostic accordance rate of 20 amniotic fluid samples was 100%, 22 of 47 chorionic villi samples were positive. The rate of positive/negative (22/25) was nearly the sex rate of newborn babies. In the meantime, direct-PCR amplification of blood and amniotic fluid was completed. The fragment was shown from 4 microliters to 0.5 microliters of blood and from 2 ml to 0.5 ml of amniotic fluid. CONCLUSION: The results show that fetal sex determination by PCR will be suitable for clinical prenatal diagnosis of sex-linked genetic disorders.

DNA-Binding Proteins↗

Structural and functional characterization of three human immunoglobulin kappa light chains with different pathological implications.

The structural properties of three immunoglobulins light chains: kappa SCI, responsible for light chain deposition disease (Bellotti, V., Stoppini, M., Merlini, G., Zapponi, M.C., Meloni, M.L., Banfi, G. and Ferri, G. (1991) Biochim. Biophys. Acta 1097, 177-182), k INC responsible for light chain amyloidosis (Ferri, G., Stoppini, M., Iadarola, P., Bellotti, V. and Merlini, G. (1989) Biochim. Biophys. Acta 995, 103-108) and the non-pathogenic kappa MOS were analyzed by fluorescence spectroscopy and circular dichroism. Comparative evaluation of the data shows that SCI and MOS have similar stability under different conditions, while the amyloid k INC behaves as a very unstable protein. As calculated from the GdnHCl curves, the midpoint of unfolding transition was 1.35 M for SCI, 1.20 M for MOS and 0.1 M for INC. Analysis of CD spectra evidences that the three proteins conserve their conformation in the range of pH 4-8. Change in temperature at pH 4.0 produces the premature transition of INC (Tm 40 degrees C) with respect to SCI and MOS (Tm 50 degrees C). At this pH both the pathological SCI and INC light chains aggregate at a temperature of 20 degrees C lower than the normal counterpart. The specific kidney deposition of kappa SCI has been evidenced after injection of the 125I labelled light chain into mice. No deposition was detectable in the case of INC and MOS.

Amino Acid Sequence↗

[Study of transfusion by external jugular vein intubation for bullet wounds complicating shock in the plateau area].

In this experimental study, the model of bullet wounds on both hind legs of dog complicating shock was used. The characteristics of the transfusion by external jugular vein intubation were observed and compared in three groups of dogs: those came from plateau area (n = 30). The result showed that the concentration of heparin which was used to prevent coagulation in the silica gel tube in plateau area should be higher than that in plain area. Other findings were: the inside diameter of the tube which was from 1.5 to 2.0 mm had no relation with the success rate of puncturing and the transfusion rate of the tube with inside diameter of 1.5 was at 160 drops per minute at most.

Animals↗