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Biomedical subjects

L Kao

Publications and source records attributed to L Kao.

At least 19 recordsLinked to original sources

Comparison of novel and existing methods for detection of linkage disequilibrium using parent-child trios in the GAW12 genetic isolate simulated data.

A novel method for joint detection of association caused by linkage disequilibrium (LD) and estimation of both recombination fraction and linkage disequilibrium parameters was compared to several existing implementations of the transmission/disequilibrium test (TDT) and modifications of the TDT in the simulated genetic isolate data from Genetic Analysis Workshop 12. The first completely genotyped trio of affected child and parents was selected from each family in each replicate so that the TDT tests are valid tests of linkage and association, rather than being only valid as tests for linkage. In general, power to detect LD using the genome-wide scan markers was inadequate in the individual replicate samples, but the power was better when analyzing several SNP markers in candidate gene 1.

Adult↗

Neonatal outcome in severe preeclampsia at 24 to 36 weeks' gestation: does the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter?

OBJECTIVE: Our purpose was to compare neonatal outcome after preterm delivery of infants whose gestation was complicated by the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, partial HELLP syndrome, or severe preeclampsia. STUDY DESIGN: We reviewed the maternal and neonatal charts from 269 consecutive pregnancies complicated by the HELLP syndrome or severe preeclampsia managed at our perinatal center. The HELLP syndrome was defined by previously published laboratory criteria. Viable pregnancies were divided into 3 groups: HELLP syndrome, partial HELLP syndrome (at least 1, but not all 3, features of the HELLP syndrome), and severe preeclampsia (no features of the HELLP syndrome). Results were compared by means of chi2 analysis and Student t test where appropriate. Logistic regression was used to evaluate outcome variables at different gestational ages. RESULTS: There were no significant differences in complications among the 3 groups at each gestational age. There was, as expected, a significant decrease in morbidity and mortality rates with advanced gestational age. CONCLUSIONS: In severe preeclampsia, neonatal morbidity and death are related to gestational age rather than to the presence or absence of the HELLP syndrome. Whether expectant management is safe for women with the HELLP syndrome requires further study.

Adult↗

The clinical utility of serum uric acid measurements in hypertensive diseases of pregnancy.

OBJECTIVE: Our purpose was to evaluate the clinical utility of serum uric acid measurements in the hypertensive diseases of pregnancy. STUDY DESIGN: We performed a nested case-control study to assess the clinical utility of serum uric acid measurements in women with hypertensive diseases of pregnancy. We identified 344 women who had serum uric acid measurements at term and categorized them into five diagnostic groups according to definitions of hypertensive diseases in pregnancy published by the National Working Group on Hypertension in Pregnancy: transient hypertension of pregnancy (n = 69), preeclampsia (n = 130), chronic hypertension (n = 23), chronic hypertension with superimposed preeclampsia (n = 29), and normal (n = 93). We compared the mean uric acid concentration for each group with use of a one-way analysis of variance and Scheffe's post hoc test and calculated the sensitivities and specificities in diagnosing preeclampsia as well as the likelihood ratios for serum uric acid values of 5.5, 6.0, and 6.5 mg/dl. We also examined the correlation between serum uric acid levels and several clinical outcome measures in women with hypertensive diseases of pregnancy. RESULTS: The mean serum uric acid values for women with preeclampsia (6.2 +/- 1.4 mg/dl) and transient hypertension (5.6 +/- 1.7 mg/dl) were significantly higher than those of controls (4.3 +/- 0.8 mg/dl, p < 0.05). The difference in mean serum uric acid values between women with chronic hypertension (4.9 +/- 1.0 mg/dl) and superimposed preeclampsia (5.8 +/- 1.4 mg/dl) were not statistically significant. The likelihood ratio of having preeclampsia with a serum uric acid value of 5.5 mg/dl was 1.41 in gestational hypertension of pregnancy and 2.5 in chronic hypertension. With use of a receiver-operator characteristic curve, we were unable to identify a serum uric acid value that could be used to differentiate various hypertensive diseases of pregnancy. There was a weak correlation between serum uric acid values and several clinical outcome measures of preeclampsia (r = 0.06 to 0.26). CONCLUSION: Although mean serum uric acid values are elevated in women with preeclampsia, the clinical utility of serum uric acid values in differentiating various hypertensive diseases of pregnancy appears to be limited. In the setting of chronic hypertension, however, a serum uric acid level of > or = 5.5 mg/dl could identify women with an increased likelihood of having superimposed preeclampsia.

Case-Control Studies↗

Do twins mature earlier than singletons? Results from a matched cohort study.

OBJECTIVE: Our purpose was to determine whether, as a consequence of advanced maturity, preterm twin infants have a more favorable neonatal outcome than matched singleton infants. STUDY DESIGN: A matched cohort study design was used. Two hundred twenty-four twin infants (112 sets) were matched for gestational age, race, gender, and mode of delivery with singleton infants who were delivered because of refractory preterm labor. Pregnancies with maternal medical disease including preeclampsia, premature rupture of membranes, twin-twin transfusion syndrome, and known fetal anomalies were excluded. Information was obtained by review of maternal and neonatal charts. RESULTS: There was no difference in the incidence of neonatal death (5% vs 7%, p = 0.66), respiratory distress syndrome (38% vs 35%, p = 0.54), grades 3 and 4 intraventricular hemorrhage (5% vs 4%, p = 0.63), grades 2 and 3 necrotizing enterocolitis (4% vs 6%, p = 0.52), and 5-minute Apgar score < or = 6 (21% vs 21%, p = 1.00). Twins had a higher incidence of admission to the Special Care Unit (88% vs 72%, p < 0.001). Results were similar when analysis was limited to presenting twins, nonpresenting twins, and twins concordant with controls for antenatal glucocorticoid exposure. CONCLUSION: Twin infants do not have accelerated maturation and improved neonatal outcome compared with matched singleton infants born at the same gestational age because of preterm labor.

Adult↗

Fetal plasma levels of cellular fibronectin as a measure of fetal endothelial involvement in preeclampsia.

OBJECTIVE: To determine the degree of fetal endothelial involvement in preeclampsia by measuring fetal plasma concentrations of cellular fibronectin. METHODS: In a prospective cohort study, fetal plasma was collected at delivery from the chorionic plate arteries and veins in a convenience sample of 28 pregnancies complicated by preeclampsia and in 28 normal pregnancies. Stored plasma was assayed for cellular fibronectin using a sensitive and specific enzyme immunoassay. On the basis of a desired power of 0.8, alpha of .05, and expected fetal plasma cellular fibronectin values of 4 +/- 2 micrograms/mL, 26 women were required in each group to detect a 40% difference between the groups. Results were compared using the unpaired Student t test, chi 2 analysis with Yates correction, and linear regression. RESULTS: There was no statistically significant difference in fetal plasma concentrations of cellular fibronectin in women with preeclampsia compared with normal pregnant women, either in arteries (3.2 +/- 1.1 and 2.9 +/- 1.5 micrograms/mL; P = .33) or veins (3.3 +/- 1.5 and 2.8 +/- 1.6 micrograms/mL; P = .18). Plasma cellular fibronectin concentrations in fetal arteries correlated significantly with those in fetal veins (r = 0.45, P < .001), but not with those in maternal veins (r = 0.15, P = .27). CONCLUSION: Fetal plasma cellular fibronectin concentrations are similar in preeclamptic and normal pregnancies. We found no evidence that factors responsible for maternal endothelial involvement in preeclampsia are operative in the fetal circulation.

Adult↗

The importance of urinary protein excretion during conservative management of severe preeclampsia.

OBJECTIVES: We determined the natural course of urinary protein excretion during conservative management of severe preeclampsia and investigated whether changes in urinary protein excretion can predict maternal or perinatal outcome. STUDY DESIGN: We reviewed the medical charts of 66 women with severe preeclampsia which was managed conservatively before 32 weeks of gestation and who had at least two 24-hour urinary protein determinations 4 or more days apart after admission. RESULTS: Fifty-nine (89%) of 66 women had an increase in proteinuria during conservative management of severe preeclampsia. The median increase in protein excretion after admission was 660 mg/24 hours (range-4580 to 18,960 mg/24 hours). Patients were divided into two groups. The first group (n = 24) had an increase in 24-hour urinary protein excretion of > or = 2 gm; the second group (n = 42) had a 24-hour urinary protein excretion that decreased (n = 7) or increased by < 2 gm (n = 35). There were no cases of eclampsia or stillbirth in either group. The rate of HELLP (hemolysis, elevated liver enzyme levels, low platelet counts) syndrome, abruptio placentae, cesarean delivery because of fetal distress, 5-minute Apgar scores < or = 6, and the admission-to-delivery intervals were all similar in the two groups. CONCLUSIONS: Proteinuria increases in most women with severe preeclampsia managed conservatively. No differences in maternal or fetal outcomes were found between pregnancies with marked increases in proteinuria and those with modest or no increases.

Adult↗

Dietary consumption and plasma concentrations of vitamin E in pregnancies complicated by preeclampsia.

OBJECTIVE: Vitamin E, a potent antioxidant, has been suggested to play a role in preventing preeclampsia. Our aim was to determine whether consumption and plasma levels of vitamin E are lower in the preeclamptic than in normal women. STUDY DESIGN: A case-control study design was used. We identified 48 women with preeclampsia (late-pregnancy hypertension, proteinuria, and hyperuricemia). Ninety normal women served as the control group. Vitamin E consumption was estimated by use of a previously validated dietary recall questionnaire administered by a single trained research nurse to 42 of the preeclamptic women and all 90 of the control women. Blood was drawn from all women and stored until assayed at -70 degrees C. Plasma vitamin E concentrations were determined by use of high-pressure liquid chromatography. RESULTS: The mean dietary vitamin E consumption was similar for both the preeclamptic and control group (11.74 +/- 9.39 vs 11.34 +/- 7.51 mg/24 hr, p = 0.73). When the analysis also included estimations of vitamin E supplements, the total consumption was found to be higher in those who had preeclampsia than in controls (37.20 +/- 20.54 vs 22.3 +/- 27.24 mg/24 hr, p = 0.003). The mean plasma vitamin E concentration was significantly higher in preeclamptic than in control patients (1.41 +/- 0.39 vs 1.15 +/- 0.32 mg/dl, p < 0.001). Among the preeclamptic patients, those with severe disease associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome (n = 11) had the highest plasma vitamin E concentrations. CONCLUSIONS: We found no evidence that low vitamin E consumption is related to the development of preeclampsia. Higher plasma vitamin E concentrations in preeclamptic patients are speculated to represent a response to oxidative stress.

Adult↗

Plasma and placental calcitonin gene-related peptide in pregnancies complicated by severe preeclampsia.

OBJECTIVE: Our purpose was to determine the concentration of calcitonin gene-related peptide, a potent vasodilator, in maternal plasma, fetal plasma, and placental tissue from pregnancies complicated by severe preeclampsia. STUDY DESIGN: The following groups were studied: severe preeclampsia (group 1, n = 21), normal pregnancies matched for mode of delivery (group 2, n = 21), and nonpregnant women (group 3, n = 17). Maternal venous blood samples were drawn before labor, and fetal venous samples were drawn from the chorionic plate immediately after delivery. Calcitonin gene-related peptide was also quantified in placental tissue samples from 15 patients in group 1 and 15 patients in group 2. Calcitonin gene-related peptide was measured with a sensitive and specific radioimmunoassay. RESULTS: No differences were found between maternal plasma calcitonin gene-related peptide concentrations in groups 1 and 2 (29.8 +/- 4.2 and 30.4 +/- 4.3 pmol/L, respectively). Both had levels similar to those in group 3 (28.5 +/- 5.4 pmol/L). Maternal plasma concentrations in the preeclamptic group were unchanged 3 days post partum (29.1 +/- 3.6 pmol/L). Fetal plasma calcitonin gene-related peptide concentrations were similar in groups 1 and 2 (30.2 +/- 3.9 and 32.2 +/- 8.8 pmol/L, respectively). A significant correlation was found between maternal and fetal calcitonin gene-related peptide concentrations (r = 0.43, p < 0.01). Like plasma levels, calcitonin gene-related peptide levels in the supernatants of placental extracts were not different in preeclamptic and normal pregnancies (108.0 +/- 70.4 and 100.9 +/- 56.1 fmol/gm, respectively). CONCLUSION: On the basis of plasma and placental concentrations, calcitonin gene-related peptide does not seem to play an important role in the pathophysiologic mechanisms of preeclampsia.

Biomarkers↗

Neonatal outcome after preterm delivery for preeclampsia.

OBJECTIVE: Our purpose was to determine whether maternal preeclampsia per se has a beneficial effect on neonatal outcome after delivery before 35 weeks. STUDY DESIGN: A matched cohort study design was used. Two hundred twenty-three infants of strictly defined preeclamptic women were matched for gestational age, race, gender, and mode of delivery with infants of normotensive women with preterm labor and delivery. Pregnancies with multiple gestation, premature rupture of membranes, known fetal anomalies, diabetes, or maternal medical disease were excluded. Information was obtained by review of maternal and neonatal charts. Paired categoric and continuous data were compared by McNemar's test and the Wilcoxon signed-rank test, respectively. RESULTS: There was no difference in the incidence of neonatal death (4.5% vs 4.5%, p = 0.82), respiratory distress syndrome (22.0% vs 22.0%, p = 0.88), grades 3 and 4 intraventricular hemorrhage (2.2% vs 2.2%, p = 0.72), grades 2 and 3 necrotizing enterocolitis (5.8% vs 4.0%, p = 0.48), and culture-proved sepsis (9.0% vs 9.0%, p = 0.85). Results were similar when analysis was limited to infants born at < or = 32 weeks, infants born to mothers with severe preeclampsia, and infants with intrauterine growth restriction. CONCLUSION: Maternal preeclampsia per se does not have a beneficial effect on the postnatal course of infants born at 24 to 35 weeks' gestation.

Betamethasone↗

[Clinical evaluation of cefpodoxime proxetil on the treatment of bacterial infections].

122 patients with bacterial infections of respiratory tract, ear, nose, and throat, urinary tract and skin and soft tissue were treated with cefpodoxime proxetil. In the treatments of patients with clinical efficacy tates of cefpodoxime proxetil for infections in these four systems were 90.0%, 97.5%, 90.0% and 86.4%, respectively. The bacterial clearance rate of gram-positive bacterial was 96.9%, and that of gram-negative bacteria 96.4%. Adverse drug reaction rate was 18.9%.

Adolescent↗

Analysis of dystrophin in fast- and slow-twitch skeletal muscles from mdx and dy2J mice at different ages.

Muscles from mdx, control, and dy2J/dy2J mice at different ages were analyzed for dystrophin in an attempt to relate the chronology of the protein expression with the final phenotypes in regenerated, normal, and dystrophic muscle, respectively. Immunostaining and gold staining of electrophoresis gels were carried out in the investigation. At 5, 25, and 219 days of age, control muscles exhibited dystrophin bands in both the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles. Muscles from the mdx mice at comparable ages (8, 28, and 217 days) never exhibited bands for dystrophin, although titin, nebulin, myosin, and other protein bands were present at intensities comparable to those in control muscles. The dystrophin band was present in both the EDL and SOL from dy2J/dy2J dystrophic mice. As indicated by the present study, the dystrophin deficiency from mdx tissue is not transient. This suggests that dystrophin is not necessary for the success of mdx muscle regeneration.

Age Factors↗

Striatal homogenates from animals chronically treated with haloperidol stimulate dopamine and GABA uptake in cultures of rostral mesencephalic tegmentum.

The effect of pharmacologic denervation of striatal tissue on the production of growth promoting factors was examined in a cell culture system. Relative to saline-treated controls, rats were rendered behaviorally hypersensitive to a subsequent apomorphine challenge by 2 months of chronic treatment with haloperidol. Four days following chronic treatment, the animals were killed and the striata and cerebella were homogenized in Hank's Balanced Salt solution. The supernatants of these crude homogenates were then added to E-13 rostral mesencephalic tegmentum cultures for 6 days. Within 24 h, the haloperidol-treated striatal supernatants induced an overt increase in culture growth relative to all other supernatants. After 6 days, cultures incubated with haloperidol-treated striatal supernatants exhibited a significant increase in dopamine and GABA uptake relative to cultures incubated with all other supernatants. This effect was observed in the presence and absence of glia. The relative degree of this increased uptake was dependent upon the amount of haloperidol-treated striatal supernatant added. Boiling the supernatant removed the growth promoting effect. These results suggest that pharmacologic denervation of striatal tissue leads to a "target-specific" increase in growth promoting activity that may play a role in the pharmacologic and behavioral effects of haloperidol.

Animals↗

Lithium transport in human fibroblasts: relationship to RBC lithium transport and psychiatric diagnoses.

Cultured fibroblasts were prepared from six normal controls, five DSM-III manic patients, and six DSM-III schizophrenic patients. Lithium (Li+) uptake, 24-hour Li+ ratios, and steady-state membrane potential were measured in these cell lines. The uptake of 10 mM Li+ reached maximum at 2 hours, with an intracellular concentration of approximately 15 mM. No significant difference in uptake was found among subject groups. Twenty-four hour Li+ (ratio of intracellular/extracellular Li+) ratios were determined by incubating the cell lines for 24 hours in the presence of 2 mM Li+. No significant difference was observed among groups; nor was there any significant correlation between the fibroblast 24-hour ratios and 24-hour in vitro ratios determined in donor red cells. The relationship between membrane potential and the 24 hour Li+ ratio in fibroblasts was determined. The average potential in these cell lines was -56 mV and was not affected by Li+ treatment. No correlation between the Li+ ratio and membrane potential was found.

Adult↗

Immunological identification of a high molecular weight protein as a candidate for the product of the Duchenne muscular dystrophy gene.

An oligopeptide was synthesized based on translation of the nucleotide sequence of the putative exon region of clone pERT87-25 from the gene for Duchenne muscular dystrophy. Immunization of rabbits with this oligopeptide induced the formation of antibodies directed against a protein present in human, rat, and rabbit skeletal muscle. This protein, which is missing in the skeletal muscle of two patients with Duchenne muscular dystrophy, has a molecular mass of approximately equal to 320-420 kDa and is clearly different from the putative Duchenne muscular dystrophy-related protein nebulin. The data suggest that this 320- to 420-kDa protein is produced by the Duchenne muscular dystrophy gene.

Antigen-Antibody Complex↗

Respiratory burst facilitates the digestion of Escherichia coli killed by polymorphonuclear leukocytes.

We examined factors that may limit degradation of bacterial protein of Escherichia coli S15 killed by polymorphonuclear leukocytes (PMN). Both human and rabbit PMN degraded up to 40% of [14C]amino acid-labeled protein of ingested and killed E. coli in 2 h as determined by loss of acid-precipitable radioactivity. In contrast, equally bactericidal broken-PMN preparations or isolated granules degraded only about 10% of bacterial protein regardless of pH. To determine whether activation of the respiratory burst contributes to digestion, we compared degradation by intact PMN in room air and under N2. Depletion of O2 by N2 flushing had no effect on the bactericidal activity of either human or rabbit PMN but reduced degradation by approximately 50%. Protein degradation during phagocytosis was also reduced in the presence of cyanide or azide, inhibitors of myeloperoxidase (MPO). PMN of two patients with chronic granulomatous disease ingested and killed E. coli S15 as well as did normal PMN but degraded bacterial protein as did normal PMN incubated under N2. The low degradative activity of PMN disrupted by sonication could be raised to nearly the level of intact PMN incubated in room air by preincubation of the PMN with 10(-7) M formyl-methionyl-leucyl-phenylalanine (fMLP) before sonication and by pretreatment of E. coli with MPO. Depletion of O2 or chloride during these preincubations with formyl-methionyl-leucyl-phenylalanine respectively, virtually abolished and markedly diminished stimulation of bacterial protein degradation. We conclude that enhanced MPO-mediated O2 metabolism of intact PMN plays a role in the digestion of killed E. coli.

Animals↗

Environmental modulation of lipopolysaccharide chain length alters the sensitivity of Escherichia coli to the neutrophil bactericidal/permeability-increasing protein.

We have shown previously that the sensitivity of Escherichia coli to the neutrophil bactericidal/permeability-increasing protein (BPI) depends mainly on the polysaccharide chain length of outer membrane lipopolysaccharides (LPS) (J. Weiss, S. Beckerdite-Quagliata, and P. Elsbach, J. Clin. Invest. 65:619-628, 1980). Thus, rough strains of E. coli producing only short-chain LPS are more sensitive to BPI than smooth strains that produce LPS with varied chain lengths. We now show that changes in the bacterial growth environment can modify BPI sensitivity of smooth E. coli as much as 30-fold depending on the bacterial strain and the growth conditions examined. Changes in BPI sensitivity paralleled differences in binding affinity of E. coli for BPI and closely correlated with changes in the chain length of LPS produced under different growth conditions, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No concomitent changes in either the number of LPS molecules per cell or the bacterial protein profile were detected. Rough strains showed little or no growth-dependent variation in BPI sensitivity, further indicating that subtle alterations in bacterial constituents other than LPS do not significantly affect bacterial sensitivity to BPI. Thus, the BPI sensitivity of E. coli can be modulated not only by the genotypic conversion of the LPS phenotype, but also by environmental effects on LPS-polysaccharide formation in wild-type strains.

Antimicrobial Cationic Peptides↗

The role of intramembrane Ca2+ in the hydrolysis of the phospholipids of Escherichia coli by Ca2+-dependent phospholipases.

Ca2+-dependent phospholipases A require Ca2+ concentrations in the millimolar range for optimal activity toward artificial substrates. Because Ca2+-dependent phospholipases A2 degrade the phospholipids of Escherichia coli, treated with the membrane-active antibiotic polymixin B equally well with and without added Ca2+ (Weiss, J., Beckerdite-Quagliata, S., and Elsbach, P. (1979) J. Biol. Chem. 254, 11010-11014), we have examined the possibility that intramembrane Ca2+ can provide the Ca2+ needed for phospholipase action. We studied the effect of Ca2+ depletion on the hydrolysis of the phospholipids of polymixin B-killed E. coli by 1) added pig pancreas phospholipase A2 in E. coli S17 (a phospholipase A-lacking mutant) and 2) endogenous Ca2+-dependent phospholipase A1 in the parent strain E. coli S15. Transfer of E. coli from nutrient broth (Ca2+ concentration approximately 3 X 10(-5) M) to Ca2+-depleted medium (Ca2+ concentration less than 10(-6)M) reduced polymixin B-induced hydrolysis by 50-75%, in parallel with a reduction of bacterial Ca2+ from 19.6 +/- 2.8 to 3.9 +/- 0.6 nmol (mean +/- standard error) per 3 X 10(10) bacteria. The bacterial Ca2+ content was repleted and the sensitivity of the bacterial phospholipids to hydrolysis by both exogenous phospholipase A2 (E. coli S17) and endogenous phospholipase A (E. coli S15) was restored by adding Ca2+ back to the suspensions. Complete restoration occurred at low Ca2+ levels in the reaction mixture (3 X 10(-5) - 10(-4) M) and required time, suggesting that hydrolysis was restored because bacterial Ca2+ stores were gradually replenished and not because extracellular Ca2+ concentrations were raised to levels that were still at least 10X lower than needed for optimal phospholipase A activity. This conclusion is supported by the finding that Ca2+ depletion or addition caused respectively decreased and increased release of lipopolysaccharides by EGTA (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), suggesting that the bacterial Ca2+ pool bound to lipopolysaccharides in the outer membrane shrinks or expands depending on extracellular Ca2+ levels. Thus, the cationic membrane-disruptive polymixin B, thought to compete with Mg2+ and Ca2+ for the same anionic sites on lipopolysaccharides, may liberate the Ca2+ near where the phospholipids are exposed to phospholipase.

Calcium↗