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Biomedical subjects

L C Kao

Publications and source records attributed to L C Kao.

At least 37 records · Page 2Linked to original sources
PubMed1989

Short-term variability of pulmonary function tests in infants with bronchopulmonary dysplasia.

We determined the short-term variability of pulmonary function in infants recovering from bronchopulmonary dysplasia. Sixteen infants with birth weight of 1,231 +/- 929 grams (mean +/- SD) and gestational age of 29 +/- 4 weeks were studied twice at 17 +/- 8 weeks postnatally at intervals of 4 to 8 days during a period of clinical stability. The infants were still on supplemental oxygen but were off diuretics and bronchodilators. We used a modification of the rapid thoracic compression method to measure forced expiratory flow (Vmax FRC) and the time constant (tau) of expiratory flow at functional residual capacity. Thoracic gas volume (TGV), mean and total airway resistance (RawM and RawT), and mean and total specific airway conductance (SGawM and SGawT) were measured in a whole body pressure plethysmograph. An esophageal balloon was used to measure dynamic pulmonary compliance (Cdyn). Variabilities were defined as the standard deviation of percent changes between the first and second tests. They were 30% for VmaxFRC, 23% for tau, 12% for TGV, 20% for RawM, 35% for RawT, 25% for SGawM, 72% for SGawT, and 23% for Cdyn. All these tests are useful in assessing pulmonary function of infants with BPD; however, their variability must be taken into account when interpreting short-term changes.

Bronchopulmonary Dysplasia↗
PubMed1989

Effects of inhaled metaproterenol and atropine on the pulmonary mechanics of infants with bronchopulmonary dysplasia.

We evaluated the individual and combined effects of an inhaled beta-adrenergic agent (metaproterenol) and an inhaled anticholinergic agent (atropine) on the pulmonary function of infants with bronchopulmonary dysplasia. In this randomized, double-blind study we studied 15 infants at a mean postnatal age of 15.8 weeks (range 4-28 weeks). On 4 successive days, pulmonary function tests were measured before and after a single treatment with one of the following four aerosols: placebo, metaproterenol, atropine, and combined metaproterenol and atropine. Following treatment with metaproterenol, atropine, and combined metaproterenol and atropine, airway resistance and maximal expiratory flow at functional residual capacity improved significantly when compared with baseline. Pulmonary function values returned toward baseline by 3 hours after the treatments. We found no significant differences between the effects of metaproterenol and atropine and were unable to show any synergy of the two agents.

Administration, Inhalation↗
PubMed1989

Effects of 8-bromo-cAMP on expression of endocrine functions by cultured human trophoblast cells. Regulation of specific mRNAs.

There is little information on the molecular events underlying the effects of cAMP on human chorionic gonadotropin (hCG) and particularly steroidal hormone production in normal trophoblasts. We examined the effects of 8-bromo-cAMP on mRNAs encoding two components of the cholesterol side-chain cleavage system, cytochrome P-450scc and adrenodoxin, and the alpha- and beta-subunits of hCG in cultured cytotrophoblasts. cAMP caused an increase in all of these mRNAs within 24 h, whereas actin mRNA declined. alpha-hCG mRNA increased first, followed by adrenodoxin, beta-hCG and cytochrome P-450scc mRNAs. The effects of 8-bromo-cAMP on alpha- and beta-hCG, adrenodoxin, and cytochrome P-450scc mRNAs, in cytotrophoblasts and JEG-3 choriocarcinoma cells, required the catalytic unit of protein kinases since H-7, a kinase inhibitor, blocked the increase in the mRNAs and prevented the stimulation of hCG and progesterone secretion. 8-Bromo-cAMP promoted a rapid increase in alpha-hCG mRNA in cytotrophoblasts in the presence of cycloheximide, an inhibitor of protein synthesis. In cytotrophoblasts, cycloheximide reduced basal and 8-bromo-cAMP-stimulated adrenodoxin mRNA abundance. In contrast, basal and cAMP-stimulated adrenodoxin mRNA was augmented by cycloheximide in JEG-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Environmental factors and Parkinson's disease: a case-control study in China.

We studied the role of environment in the development of Parkinson's disease (PD) in China, where industrialization is relatively recent and the population geographically stable. Using a case-control method, we investigated the relationship between PD and exposure to the following factors before disease onset: place of residence, source of drinking water, environmental and occupational exposure to various agricultural and industrial processes. Occupational or residential exposure to industrial chemicals, printing plants, or quarries was associated with an increased risk of developing PD. In contrast, living in villages and exposure to the common accompaniments of village life, wheat growing and pig raising, were associated with a decreased risk for PD. PD cases and controls did not differ with respect to other factors investigated. These findings are consistent with the hypothesis that environmental exposure to certain industrial chemicals may be related to the development of PD.

Adult↗
PubMed1989

Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts.

Trophoblast implantation, vascular remodeling, and maintenance of intervillous blood flow may depend on the regulated production of proteolytic enzymes such as plasminogen activator (PA). Since the functional activity of plasminogen activators is determined not only by the quantity of protease but also by levels of specific plasminogen activator inhibitors (PAI), we examined trophoblasts both in vitro and in vivo for the presence of two PAIs, PAI-1 and PAI-2. Cytotrophoblasts were isolated from first trimester or term placentae, cultured, and immunocytochemically stained using specific anti-PAI antibodies. The antiserum against PAI-1 demonstrated prominent cell-surface staining and some cytoplasmic staining. The antiserum generated against PAI-2 revealed a cytoplasmic localization, with some trophoblasts staining intensely, whereas others had no apparent reactivity. We also found that cultured cytotrophoblasts contain the mRNAs for PAI-1 and PAI-2. Immunohistochemical analysis of tissue sections from 8-, 16-, and 40-week implantation sites using antisera against PAI-1 demonstrated weak staining of villous syncytiotrophoblasts but prominent cytoplasmic staining of trophoblasts invading the decidua and myometrium. Antisera against PAI-2 stained the cytoplasm of villous syncytiotrophoblasts, but no staining was evident in villous cytotrophoblasts or in invading trophoblasts. We conclude that 1) human trophoblasts can express both PAI-1 and PAI-2 in vitro and in vivo and 2) prominent PAI-1 immunostaining defines invading trophoblasts, whereas PAI-2 is the predominant PAI accumulated in villous syncytiotrophoblasts. Thus, the various trophoblast forms have distinctive patterns of PAI expression.

Cells, Cultured↗
PubMed1989

Control of the steroidogenic machinery of the human trophoblast by cyclic AMP.

Human cytotrophoblasts express adenylate cyclase activity and possess membrane-bound regulatory proteins that bind guanine nucleotides (G proteins). Stimulation of the cyclase by forskolin or addition of 8-bromo-cAMP augments progesterone secretion by cultured cytotrophoblasts at least in part, by promoting accumulation of components of the cholesterol side-chain cleavage system. This is the consequence of increased synthesis of the proteins participating in steroidogenesis as a result of the 8-bromo-cAMP-provoked increase in their respective mRNAs. We propose that progesterone synthesis by cytotrophoblasts is up-regulated by cyclic AMP, which acts to increase expression of genes encoding the steroidogenic machinery. Paracrine or autocrine factors may initiate this cascade by stimulating the cytotrophoblast adenylate cyclase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells.

Adrenodoxin is an iron-sulfur protein serving as an electron transport intermediate for two mitochondrial steroidogenic cytochromes P450. We have cloned and sequenced three human adrenal adrenodoxin cDNAs. The longest 5'-untranslated region was 131 bases long, and the coding sequences, identical in all three clones, predict a preprotein of 180 amino acids. The 3'-untranslated regions were 235, 596, and 776 bases long due to the presence of alternate polyadenylation sites. RNA transfer blots showed multiple size species of adrenodoxin mRNA consistent with finding multiple polyadenylation sites. Similar sized cross-hybridizing RNA species are found abundantly in the adrenal and testis and to a lesser degree in RNA from human fetal brain, spleen, placenta, kidney, liver, and intestine, as well as in cultured fibroblasts, suggesting the same or a very similar iron-sulfur protein is found in mitochondria of nonsteroidogenic tissues. JEG-3 cells, a transformed progesterone-producing line of trophoblastic origin, accumulate mRNAs for cytochrome P450scc (the mitochondrial cholesterol side-chain cleavage enzyme), adrenodoxin, and the fos oncogene when stimulated with 8-bromo-cyclic AMP. Addition of actinomycin D to such cultures blocked cAMP-induced accumulation of mRNAs for cytochrome P450scc and adrenodoxin. Addition of cycloheximide or puromycin to such cultures substantially reduced basal levels and markedly attenuated the cAMP-induced accumulation of cytochrome P450scc mRNA, but augmented the accumulation of adrenodoxin and fos mRNAs in additive and multiplicative fashions, respectively. These data indicate that the cAMP-induced synthesis of the steroidogenic machinery is not wholly dependent on cycloheximide-sensitive protein mediators.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

The human villous cytotrophoblast: interactions with extracellular matrix proteins, endocrine function, and cytoplasmic differentiation in the absence of syncytium formation.

Human syncytiotrophoblasts are derived from villous cytotrophoblasts by cell fusion. Coincident with this morphologic transformation, trophoblasts acquire specific endocrine functions, including elaboration of chorionic gonadotropin (hCG). We wondered if syncytia formation was a prerequisite for biochemical differentiation or simply was one part of the differentiation program. By growing purified human cytotrophoblasts under serum-free conditions and manipulating the culture surface, we were able to disassociate morphologic from biochemical differentiation. We have shown previously (Endocrinology 1986, 118:1567) that human cytotrophoblasts grown in the presence of fetal calf serum flatten out, aggregate, and form functional syncytiotrophoblasts in vitro over 24-96 hr. Here we demonstrate that when grown in the absence of serum, the cells do not undergo these morphologic changes, but remain as individual spherical cells. If the culture surface was precoated with fibronectin or a variety of collagens, but not albumin, the cells regained their ability to flatten, aggregate, and form syncytia. Attachment to and syncytia formation on fibronectin was blocked by the addition of the R-G-D-S-containing peptide, Gly-Arg-Gly-Asp-Ser-Pro. Attachment to and syncytia formation on type I collagen was blocked by anti-human fibronectin F(ab')2 fragments, while association with type IV collagen was not affected by this antibody, suggesting that fibronectin mediates trophoblast association with type I collagen, but not type IV. Although syncytia formation did not occur when cytotrophoblasts were cultured under serum-free conditions in the absence of ECM proteins, biochemical differentiation was not affected. These cells secreted hCG at the same rate under serum-free conditions whether they were plated on plastic only--which prevented syncytia formation--or fibronectin, laminin or, type IV collagen--which allowed syncytia formation to occur. Furthermore, cytoplasmic differentiation in the absence of syncytia formation was confirmed by performing transmission electron microscopy on cytotrophoblasts grown under serum-free conditions in the presence of 8-bromo-cAMP. We conclude that syncytia formation is not a prerequisite for biochemical differentiation, but simply part of the trophoblast differentiation program.

Cell Adhesion↗
PubMed1988

Improving pulmonary function does not decrease oxygen consumption in infants with bronchopulmonary dysplasia.

To determine whether the high oxygen consumption VO2 in infants with bronchopulmonary dysplasia (BPD) is caused by increased mechanical power of breathing, and if improvement of pulmonary mechanics would reduce mechanical power of breathing and VO2 we gave 16 infants with oxygen-dependent BPD at 19.5 +/- 10.7 (mean +/- SD) weeks of age placebo, theophylline, and orally administered diuretics or theophylline plus diuretics. Pulmonary mechanics, mechanical power of breathing, and VO2 were measured at the beginning and end of each study period. In the placebo group, all infants had elevated VO2 (7.4 +/- 1.4 mL/kg/min) and carbon dioxide production (6.6 +/- 1.2 mL/kg/min), increased airway resistance (59 +/- 30 cm H2O/L/sec), decreased dynamic compliance (0.073 +/- 0.024 mL/cm H2O/cm), increase respiratory rate (52 +/- 11), and increased mechanical power of breathing (2.22 +/- 1.05 kg.cm/kg/min). Treatment with theophylline, diuretics, and theophylline plus diuretics resulted in a significant improvement in pulmonary mechanics and mechanical power of breathing, but not in VO2. These results suggest that the increased VO2 in infants with BPD is not secondary to increased mechanical power of breathing.

Bronchopulmonary Dysplasia↗
PubMed1988

High-density lipoprotein subclass distribution in premature newborns before and after the onset of enteral feeding.

Changes in high-density lipoprotein (HDL) subclass distribution were evaluated in a group of premature infants during the early postnatal period to ascertain whether enteral feeding brought about a rapid shift from neonatal to adult-like distributions. All infants were fed a combination of breast milk and formula. Cord blood of premature infants had a predominance of large, less dense (HDL2b)gge and a paucity of intermediate-sized (HDL3a)gge particles. Lack of a peak in the (HDL3a)gge is a characteristic feature for cord blood, whereas a prominent (HDL3a)gge peak is characteristic of adult plasma. After the start of enteral feeding, blood was obtained at two time-points: 6-14 days (sample A) and 17-32 days (sample B) postdelivery. With the onset of feeding, triglyceride increased significantly from an average of 34 mg/dl in cord blood to 120 mg/dl in sample B, and cholesterol increased from 86 to 112 mg/dl in the same period. Increases in plasma lipid concentrations were paralleled by a redistribution of subclasses such that three components of almost equal intensity were evident in sample B; these consisted of (HDL2b)gge, (HDL2a2)gge, and (HDL3b)gge. A paucity of (HDL3a)gge particles persisted even after onset of enteral feeding; thus, increases in plasma triglyceride and cholesterol per se are not sufficient to induce the adult-like distribution. It is suggested that development of the normal adult HDL subclass pattern is complex and is probably related to the development and interaction of several factors, including plasma enzymes involved in lipid hydrolysis and esterification, lipid exchange proteins, and hormonal status.

Age Factors↗
PubMed1987

Regulation of urokinase-type plasminogen activator production by cultured human cytotrophoblasts.

Cultured human cytotrophoblasts synthesize and secrete urokinase-type plasminogen activator (uPA) during the first 24 h of culture, but secretion declines during the subsequent day. In contrast, synthesis and secretion of fibronectin increases during the 2 days of culture. The levels of uPA mRNA parallel the changes in synthesis and secretion of uPA. Treatment of cytotrophoblasts with 8-bromo-cAMP (1.5 mM) transiently raises uPA mRNA levels and uPA secretion. This treatment reduces fibronectin mRNA levels and causes a sustained increase in beta chorionic gonadotropin mRNA content and chorionic gonadotropin secretion. We conclude that a cAMP-mediated process up-regulates uPA expression in cytotrophoblasts. However, the stimulatory effect of the cyclic nucleotide analog on uPA is transient.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

The effect of bilateral kainic acid-induced lateral habenula lesions on dopamine-mediated behaviors.

Bilateral kainic acid-induced lateral habenula lesions produced dose specific alterations in dopamine mediated behaviors in the rat. Intermediate doses of apomorphine and amphetamine produced potentiated stereotypic responsiveness while higher doses produced a behavioral response similar to that observed in sham-operated and virgin controls. Autoreceptor specific doses of apomorphine and its associated behavioral hypoactivity was unaffected by lesions. Animals with lesions did not exhibit the response potentiation normally induced by chronic haloperidol treatment.

Animals↗
PubMed1987

Oral theophylline and diuretics improve pulmonary mechanics in infants with bronchopulmonary dysplasia.

We studied the effects of orally administered theophylline and diuretics (chlorothiazide and spironolactone) on pulmonary mechanics in 16 infants with bronchopulmonary dysplasia. Their gestational age (mean +/- SD) was 28.5 +/- 3.4 weeks, and postnatal age at the time of study 19.5 +/- 10.7 weeks. The infants were randomized to two groups. Group 1 received successively placebo, theophylline, and theophylline plus diuretics; Group 2 received theophylline, placebo, and placebo plus diuretics on successive 4-day periods. Pulmonary function was measured before beginning the study (baseline) and at the end of each 4-day period. No significant changes in pulmonary function were noted after treatment with placebo. After treatment with theophylline, dynamic compliance (Cdyn) increased from baseline (mean +/- SD) 0.075 +/- 0.017 to 0.091 +/- 0.028 mL/cm H2O/cm (P less than 0.01), airway resistance (Raw) decreased from 67.19 +/- 36.71 to 41.44 +/- 22.50 cm H2O/L/sec (P less than 0.001), maximal expiratory flow at functional residual capacity (VmaxFRC) increased from 0.261 +/- 0.240 to 0.357 +/- 0.299 thoracic gas volume (TGV)/sec (P less than 0.01), and time constant decreased from 0.312 +/- 0.224 to 0.275 +/- 0.247 sec (P less than 0.02). After treatment with combined placebo and diuretics, Cdyn increased to 0.103 +/- 0.023 mL/cm H2O/cm (P less than 0.05), Raw decreased to 31.76 +/- 24.90 cm H2O/L/sec (P less than 0.001), VmaxFRC increased to 0.638 +/- 0.595 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.141 sec (P less than 0.05). After treatment with combined theophylline and diuretics, Cdyn increased to 0.118 +/- 0.017 mL/cm H2O/cm (P less than 0.001), Raw decreased to 35.98 +/- 25.85 cm H2O/L/sec (P less than 0.02), VmaxFRC increased to 0.479 +/- 0.377 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.137 sec (P less than 0.01). We conclude that theophylline and diuretics have additive effects on the improvement of pulmonary function in infants with bronchopulmonary dysplasia.

Administration, Oral↗
PubMed1987

Environmental factors in the etiology of Parkinson's disease.

Parkinson's disease (PD) has been proposed to result from the interaction of aging and environment in susceptible individuals. Defective metabolism of debrisoquine, inherited as an autosomal recessive, has been associated with this susceptibility. In 35 PD patients and 19 age-matched controls, no significant differences in debrisoquine metabolism were found, although a trend to impaired metabolism was noted in patients with disease onset less than or equal to 40. Foci of PD patients were associated with rural living and well water drinking, or rural living coupled with market gardening or wood pulp mills. In a questionnaire survey, patients with PD onset less than or equal to age 47 were significantly more likely to have lived in rural areas and to have drunk well water than those with onset greater than or equal to age 54 (p less than or equal to 0.01). Because of population mobility in North America, a case-control study designed to test environmental, occupational, dietary and other proposed risk factors for PD was conducted in China, where the population is more stationary and the environment more stable. No significant differences in incidences of head trauma, smoking or childhood measles were found between patients and controls.

Adult↗
PubMed1987

Effects of dopamine antagonists and apomorphine on regional energy metabolism in rat CNS.

Alterations in 2-[14C]deoxyglucose uptake were studied in 154 brain regions from animals acutely challenged with a dopamine (DA) agonist or antagonist. Doses of apomorphine inducing locomotion and stereotypic behavior produced increased uptake in the subthalamic nucleus, the substantia nigra reticulata, and the ventroanterior and ventrolateral nuclei of the thalamus while decreased uptake was observed in the lateral habenula and several midline thalamic nuclei. The six centrally active DA antagonists studied produced uniform increases in uptake in the lateral habenula and the anterior regions of both the n. accumbens and striatum whereas decreased uptake was observed in the mesencephalic reticular formation and the reticular nucleus of the thalamus. Low doses of apomorphine that produced behavioral hypoactivity resulted in a pattern of metabolic alterations that resembled those associated with DA antagonists more closely than metabolic alterations seen with DA agonists. These results suggest that unique alterations in neuronal activity in several brain regions, including the traditional dopaminergic projection areas, are associated with the expression of specific DA-mediated behaviors.

Animals↗
PubMed1987

8-Bromo-adenosine 3',5'-monophosphate regulates expression of chorionic gonadotropin and fibronectin in human cytotrophoblasts.

Addition of 8-bromo-cAMP to primary cultures of human placental cytotrophoblasts results in significant alterations in the synthesis of secreted proteins, as detected by labeling with pulses of [35S]methionine. Using immunoprecipitation techniques, we demonstrated that exposure to 8-bromo-cAMP prevented the de novo synthesis and secretion of the extracellular matrix component fibronectin, but enhanced the production of hCG subunits. The effects of the cyclic nucleotide on synthesis and secretion of these proteins were evident within 24 h. 8-Bromo-cAMP increased the cellular content of mRNA encoding the hCG alpha- and beta-subunits and prevented the increase in fibronectin mRNA, as determined by blot hybridization analysis using specific cDNA probes. These findings demonstrate that cyclic nucleotides regulate the synthesis of several specific proteins in cultured human trophoblast by regulating levels of the mRNAs encoding the proteins. The actions of cyclic nucleotides in this regard may be essential for the normal expression of trophoblast endocrine function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

The effect of antimuscarinic agents on haloperidol induced behavioral hypersensitivity.

Varying doses of scopolamine, trihexyphenidyl and benztropine were administered to rats or guinea-pigs by themselves or in combination with 0.5 mg/kg haloperidol for 24 days. All animals were then challenged with 0.75 mg/kg apomorphine and assessed for stereotypic behavior following a 96 h drug free interval. Animals treated with haloperidol alone exhibited behavioral hypersensitivity to apomorphine challenge. Animals treated with both an antimuscarinic agent and haloperidol exhibited a significant reduction in behavioral responsiveness relative to animals treated with only haloperidol. This reduction was directly proportional to the antimuscarinic dose administered. A non-significant trend toward hyposensitivity was observed in animals who had been treated with antimuscarinic agents alone. These results suggest that the development of behavioral hypersensitivity may reflect CNS alterations in cholinergic as well as dopaminergic activity.

Animals↗