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Biomedical subjects

L L Hsu

Publications and source records attributed to L L Hsu.

At least 19 recordsLinked to original sources
PubMed2007

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Age Factors↗
PubMed2003

Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3.

Accumulation of transition metals has been suggested to be responsible for the deteriorated nigrostriatal dopaminergic system in Parkinson's patients. In the present study, the mechanism underlying the zinc-induced neurotoxicity was investigated in the nigrostriatal dopaminergic system in vivo. Our 6-methoxy-8-paratoluene sulfonamide quinoline fluorescence study showed zinc translocation in the infused nigral cells after intranigral infusion of zinc. Furthermore, lipid peroxidation in the zinc-infused substantia nigra was consistently elevated 4 h to 7 d after the infusion. At the same time, an abrupt increase in cytosolic cytochrome c content in the infused substantia nigra was observed 4 h after zinc infusion and gradually decreased to basal levels 7 d after infusion. Both TUNEL-positive neurons and DNA fragmentation, indicatives of apoptosis, were detected in the zinc-infused substantia nigra. Furthermore, striatal dopamine content was reduced 7 d after the infusion. In attempt to prevent zinc-induced neurotoxicity, vitamin D3 was systemically administered. Zinc-induced increases in lipid peroxidation and cytosolic cytochrome c in the infused substantia nigra were prevented by this treatment. Moreover, zinc-induced reduction in striatal dopamine content was attenuated after vitamin D3 treatment. Our in vivo data suggest that zinc-induced oxidative stress may result in apoptosis followed by reduced dopaminergic function in the nigrostriatal dopaminergic system. Furthermore, vitamin D3 prevented zinc-induced oxidative injuries in the rat brain.

Animals↗
PubMed2001

Silent infarcts in children with sickle cell anemia and abnormal cerebral artery velocity.

BACKGROUND: A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infarction as seen on magnetic resonance imaging (MRI). OBJECTIVES: To determine if transfusion therapy affects the rate at which silent infarcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler (TCD) ultrasonography. STUDY DESIGN: Children with elevated TCD ultrasonographic velocity were randomized to receive long-term transfusion therapy or standard care. Magnetic resonance imaging of the brain was obtained at randomization, annually, and with clinical neurologic events. The risk for new silent lesions and/or stroke was compared for each treatment arm. RESULTS: Among the 37% of subjects with silent infarcts, those receiving standard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy. For subjects receiving standard care, those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality. CONCLUSIONS: Transfusion therapy lowers the risk for new silent infarct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infarct. However, those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality. The finding of a silent infarct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen. Similarly, elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infarct or stroke.

Anemia, Sickle Cell↗
PubMed2001

Joint effects of alcohol consumption and cigarette smoking on atherogenic lipid and lipoprotein profiles: results from a study of Chinese male population in Taiwan.

BACKGROUND: The present study examines the effect of joint exposure to cigarette smoking and alcohol intake on serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglyceride (TG) among Chinese male adults in Taiwan. METHODS: A sample of 3311 men aged 20-59 years who reported having stable smoking and drinking behaviors during the period between January 1995 and December 1996 was selected from a periodic health checkup population. Serum lipids and lipoprotein cholesterol fractions were measured on fasting blood samples taken from participants. Statistical methods of analysis of variance and analysis of covariance were conducted to examine the associations of different smoking-drinking behavioral patterns with lipid and lipoprotein levels. RESULTS: In the observed population, the percentages of men who had stable cigarette smoking and alcohol consumption behaviors were 39.5% (1,307/3,311) and 27.0% (895/3,311), respectively. Mean values of TC and TG increased significantly and monotonically with increasing levels of cigarette smoking and alcohol consumption. In addition, alcohol intake was significantly associated with increased HDL-C and reduced LDL-C levels in a dose-dependent manner. More interestingly, the effect of alcohol consumption on LDL-C (negative) and TG (positive) levels was substantially greater for heavy smoker (>20 cigarettes/day) than for light smokers (< or = 20 cigarettes/day) and non-smokers, while alcohol intake exerted a strong positive influence on HDL-C concentration regardless of levels of cigarette smoking. CONCLUSIONS: In this Chinese male population, cigarette smoking and alcohol consumption were confirmed to have similar effects on lipid and lipoprotein levels as in Caucasians. More interestingly, a significance of joint exposure to smoking and drinking in predicting lipid and lipoprotein levels was evident. These data indicate the importance of multifactorial interventions to obtain more favorable lipid and lipoprotein levels in the population.

Adult↗
PubMed2001

Prevalence and clustering of cardiovascular risk factors among healthy adults in a Chinese population: the MJ Health Screening Center Study in Taiwan.

OBJECTIVE: To gain insight into the prevalence and clustering of multiple cardiovascular risk factors in a healthy Chinese adult population in Taiwan. DESIGN: A cross-sectional study was carried out in 1996. SUBJECTS: A total of 46,603 subjects (23,485 men and 23,118 women) who were aged 20--59 y and attended a private health screening center for health examination of their own volition. MEASUREMENTS: Multiple cardiovascular risk factors including cigarette smoking, overweight (23 kg/m(2)< or =body mass index (BMI)<25 kg/m(2)) and obesity (BMI> or =25 kg/m(2)), lipid disorder (a ratio of total cholesterol level to the level of high density lipoprotein cholesterol>5 or use of lipid-lowering drugs), hypertension (systolic blood pressure> or =140 mmHg or diastolic blood pressure> or =90 mmHg or use of anti-hypertensive medications), and diabetes mellitus (fasting serum plasma glucose level> or =126 mg/dl or use of anti-diabetic medications) were determined. RESULTS: In comparison to women, men had a higher prevalence of current smoking (42.1 vs 5.6%), overweight (25.1 vs 17.1%) and obesity (33.1 vs 21.5%), lipid disorder (45.1 vs 19.6%), hypertension (17.4 vs 13.2%), as well as diabetes mellitus (4.1 vs 3.4%). The prevalence of men or women having two or more of the cardiovascular risk factors of interest was 54.3 and 21.7%, respectively. With advancing age, the prevalence of risk factors became greater for both genders. More importantly, the clustering of risk factors increased monotonically with increasing BMI levels for men and women. CONCLUSIONS: The prevalence and clustering of cardiovascular risk factors are commonplace in this healthy Chinese adult population. Considering the significant association between clustering of risk factors under study and BMI levels, this study gives an indication that population-based multifactorial interventions may work out favorably for specific groups.

Adult↗
PubMed1996

Hepatomegaly in neuroblastoma stage 4s: criteria for treatment of the vulnerable neonate.

Infants with neuroblastoma (NBL) frequently present as stage 4s and overall, such patients have a good prognosis. However, not all survive, and neonates with hepatomegaly are particularly at risk. We therefore reviewed our 4s experience, the objective being to identify lethal patterns of disease progression. The specific aims of this work were (1) to develop a semiquantitative scoring system based on the severity of signs and symptoms that alone or in combination presaged a fatal outcome, and (2) to determine if early intervention could reverse life-threatening disease. Thirty-five patients were seen over a period of 50 years. The signs and symptoms of organ distress caused by hepatomegaly occurred in the lungs, kidneys, gastrointestinal tract (GI), the inferior vena cava (IVC), and the liver. A scoring scale reflecting organ compromise was developed, the scores ranging from 0 (0 compromise) to 10 (all 5 systems showing evidence of impairment). Scores were derived for 32 of 35 patients; 13 were 4 weeks old or under (neonates) when first seen, and 19 were aged 1-12 months (infants). Neonates were more likely than infants to develop increasing symptomatology (50% versus 25%) and were more likely to die when a score of 2 or more developed. None of the 6 neonates who did so survived despite treatment, compared with three of four infants. Early intervention is recommended: (1) for 4s neonates who develop a score of 1 and (2) for older infants with a score > or = 2.

Hepatomegaly↗
PubMed1994

Fluctuations in microvascular blood flow parameters caused by hemodynamic mechanisms.

We have developed a mathematical model of microvascular network blood flow in which the nonlinear flow properties of blood and the nonuniform axial distribution of red blood cells in each vessel, as well as disproportionate cell partitioning at bifurcations, are all accounted for. The movements of red blood cells in the network are tracked; hence, the model is able to simulate temporal variations in local flow parameters in the network due to hemodynamic mechanisms. The model was applied to four rat mesenteric networks for which the topology, boundary conditions, blood velocity, and discharge hematocrit (Hctd) had been measured for each branch. Temporal variations in Hctd and blood velocity after simulation convergence were predicted. In some cases of the three vessels connected to a node, Hctd of one vessel fluctuates in a simple periodic form, Hctd of the second one oscillates in a more complex periodic form, whereas the Hctd of the third one does not oscillate at all. These variations were obtained with constant flow boundary conditions and, therefore, are due to hemodynamic factors alone. The temporal variations in flow parameters predicted by the model simulations are caused by hemorheological mechanisms and would be superimposed on variations caused by other mechanisms (e.g., vasomotion). The frequencies of the predicted fluctuations in blood velocity are in qualitative agreement with observed in vivo variations in dual-slit velocity in the arterioles of the cremaster muscle of anesthetized Golden hamster.

Animals↗
PubMed1992

Isolation and expression of a gene which encodes a wall-associated proteinase of Coccidioides immitis.

A chymotrypsinlike serine proteinase of Coccidioides immitis with an estimated molecular size of 34 kDa has been shown by immunoelectron microscopy to be associated with the walls of the parasitic cells of this human respiratory pathogen. The proteinase has been suggested to play a role in spherule development. We report the isolation of a 1.2-kb cDNA from an expression library of C. immitis constructed in the lambda ZAP II phage vector. The cDNA is suggested to encode the 34-kDa protein. We demonstrate identity between segments of the deduced amino acid sequence of the open reading frame of the 1.2-kb cDNA and three distinct sequences obtained from cyanogen bromide cleavage peptides of the purified proteinase. The occurrence of N-glycosyl linkage sites in the deduced sequence of 309 amino acids of the open reading frame (ORF) correlates with our identification of such linkage sites in the native glycosylated proteinase. A protein encoded by an 800-bp fragment of the 1.2-kb cDNA, which was produced by transformed Escherichia coli XL1-Blue, was recognized by the anti-34-kDa protein antibody in a Western blot (immunoblot). Northern (RNA) hybridization of total poly(A)-containing RNA of C. immitis with the labeled 1.2-kb cDNA clone revealed a single band of approximately 1.75 kb. Partial homology was demonstrated between the deduced amino acid sequence of the ORF (927 bp) and reported sequences of alpha-chymotrypsin and chymotrypsinogens. Expression of the proteinase gene was examined by Northern dot blot analysis of total RNA from different stages of parasitic cell development in C. immitis. Maximum levels of specific mRNA were detected during early endospore wall differentiation. The 34-kDa proteinase appears to be concentrated in walls of the parasitic cells at stages of active growth. We suggest that the enzyme may participate in wall plasticization and/or intussusception or in cell wall turnover.

Amino Acid Sequence↗
PubMed1991

Coccidioides immitis fractions which are antigenic for immune T lymphocytes.

The principal mechanism of resistance to coccidioidomycosis in experimental animals has been reported to be T-cell-mediated immunity. We have generated a Coccidioides immitis antigen-specific murine T-cell line to identify specific macromolecules capable of eliciting an immune mouse T-cell proliferative response. The murine T cells were stimulated in vitro with a soluble conidial wall fraction (SCWF), which has been previously characterized by humoral and cellular immunoassays. The SCWF was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred to a nitrocellulose membrane, and the stained blot was cut into seven pieces based on the molecular size of the SCWF components. The nitrocellulose membrane strips were converted into antigen-bearing particles and tested in a T-cell proliferation assay. Antigenic components of the SCWF in the molecular size range of 43 to 66 kDa were identified as the most immunoreactive. In a parallel study, we used a cDNA expression library derived from mRNA of the mycelial phase of C. immitis, which was constructed in lambda gt11 to identify clones that encoded T-cell-reactive fusion proteins (FPs). The cDNA library was screened by using anti-SCWF rabbit serum, and the FPs expressed in Escherichia coli were isolated and tested for T-cell response in the same manner as the SCWF components. The nucleotide sequence of a 0.2-kb cDNA insert encoding a protein which elicited vigorous T-cell response was determined. The isolated cDNA insert hybridized to a single 1.9-kb mRNA band in a Northern blot of the total RNA fraction of the mycelial phase of C. immitis. Antibody with affinity for the T-cell-reactive FP was isolated from anti-SCWF rabbit serum by solid-phase immunoadsorption. The FP-specific antibody reacted with a 47-kDa polypeptide in Western blots (immunoblots) of the SCWF. The same antibody preparation was used for immunoelectron microscopy to show that the FP was localized in the walls of arthroconidia and spherules of C. immitis. Attempts to clone and sequence the entire gene which encodes the T-cell-reactive protein are under way. The results of this study should lead to the determination of the complete structure of an important T-cell-stimulating antigen of C. immitis.

Amino Acid Sequence↗
PubMed1987

Chronic bombesin treatment increased the [3H]spiperone binding, glutamate decarboxylase and choline acetyltransferase activity in the rat brain.

The effects of chronic bombesin (BBS) on [3H]spiperone (SPD) binding activity, choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and glutamate decarboxylase (GAD) were investigated in the rat brain corpus striatum (CS). The chronic i.p. administration of BBS to rats increased: (1) the specific [3H]SPD binding to the striatal Pm (plasma membrane) (16%, P less than 0.03 and 34%, P less than 0.008 at 5 micrograms/kg respectively), (2) the specific GAD activity in the CS by 52% (5 micrograms/kg, n.s.) and 46% (10 micrograms/kg, P less than 0.05) respectively, (3) the specific ChAT activity in the CS by 54% (10 micrograms/kg, P less than 0.002), and (4) the specific AChE activity by 23% (10 micrograms/kg, P less than 0.02) after 14 days. It increased only: (1) the specific [3H]SPD binding by 29% (P less than 0.001, at 10 micrograms/kg) and (2) the specific GAD activity by 23% (P less than 0.015, 10 micrograms/kg), after 7 days. Neither ChAT nor AChE activity was affected after 7 days treatment of BBS at 10 micrograms/kg. In vitro study showed that BBS at 0.2 microM did not affect any of the neurochemical parameters examined in the CS. Thus, the changes in brain chemistry caused by chronic BBS were not due to direct effects of BBS but may be mediated through its metabolites or CCK release. Data indicate that the central effects of peripherally administered BBS are dependent on both the duration and the dosage of the drug treatment and that the dopaminergic and GABAergic systems seem to be more vulnerable to chronic BBS than the cholinergic system in the rat brain CS.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1987

Monoclonal antibodies to a brain dopamine binding protein: production, specificity, and immunohistochemistry.

A dopamine binding protein (DABP) has been purified from the rat brain synaptic membrane to homogeneity by affinity chromatography and gel electrophoresis. The monoclonal antibodies against the DABP were produced by the mouse-mouse hybridoma technique and characterized for their specificity to dopamine receptors by displacement of dopamine receptor binding. These monoclonal antibodies have been used to localize DABP in rat brain by immunohistochemistry. A specific linear structure of reaction product was seen in both caudate nucleus and cerebral cortex. This finding suggests that the DABP is present in the cerebral cortex and caudate nucleus as a membranous component of the neurons or their processes.

Animals↗
PubMed1987

Cyclophosphamide: effects of paternal exposure on the brain chemistry of the F1 progeny.

The effects of acute and chronic cyclophosphamide (CP) exposure to male rats on several neurotransmitter enzymes have been examined in various brain regions of the F1 progeny at 90 d old. The acute postmeiotic CP exposure to male rats induced significant biphasic changes in the choline acetyltransferase (ChAT) activity in various brain regions of F1 progeny; significant decreases in the cerebellar acetylcholinesterase (AChE) activity of the male (47%) and the female (14%) F1 progeny, and moderate decrease (26%) in the hippocampal AChE activity in the female F1 progeny; and a moderate increase (29%) in the temporo-cortical glutamic acid decarboxylase (GAD) activity of the female F1 rats. The chronic CP-exposed male rats resulted in a slight but significant decrease (16%) in the temporo-cortical ChAT activity in the female F1 progeny; a marked increase (51%) in the hypothalamic AChE activity in the male F1 progeny; and a marked decrease (32%) in cerebellar GAD activity and a slight increase (13%) in the striatal GAD activity in the female F1 progeny. These enzymatic changes in the adult brain of F1 progeny of CP-treated males may be associated with the behavioral abnormalities observed previously. Results suggest that these neurochemical parameters may be useful markers for analysis of the potential neurotoxicity of CP.

Acetylcholinesterase↗
PubMed1986

Lactational ethanol exposure: brain enzymes and [3H]spiroperidol binding.

Long-Evans lactating rats were fed 27% calories as ethanol in a liquid diet to determine whether alcohol received through the milk would alter normal brain development in the offspring. On days 16, 21 and 30, brains of the female offspring were removed, corpus striatum dissected and assayed for choline acetyltransferase activity, glutamic acid decarboxylase activity and [3H]spiroperidol binding activity. At day 16, there were no differences among the three treatment groups for the enzyme activities assayed. At day 21, glutamic acid decarboxylase activity in the pairfed group was higher than in ET and CT groups. Choline acetyltransferase activity in PF group was higher when compared to ad libitum controls and [3H]spiroperidol binding was not affected. At 30 days of age, animals exposed to ethanol had higher choline acetyltransferase activity and [3H]spiroperidol binding activity when compared to pairfed and ad libitum controls; and higher glutamic acid decarboxylase activity when compared to ad libitum controls. Data from the present study suggest that ethanol exposure during the brain growth spurt has a toxic effect on the late development of dopaminergic, cholinergic and GABAergic systems in the corpus striatum. These results may be related to the clinical symptoms of hyperactivity and problems with motor control in children exposed to alcohol during the third trimester and during lactation.

Animals↗
PubMed1986

Multiple forms of aryl acylamidase in regional tissues of developing rat brain.

The specific activities of two forms of aryl acylamidase (AAA) were examined in 7 regions of the developing rat brain, plus the remainder of the brain and the whole brain. AAA-1 activity peaked at 15 days old in all brain regions studied except the whole brain where it peaked at 22 days of age. AAA-2 activity peaked between 15 and 29 days old in most brain regions studied except corpus striatum and hippocampus where the AAA-2 activity peaked before 15 days old. In all areas and at all time periods, with the exception of CS after 15 days of age, AAA-2 activity was much higher than that of AAA-1. The developmental pattern of AAA-1 is generally the same in the different brain regions while that of AAA-2 shows more regional specificity. These results indicate that neither AAA-1 nor AAA-2 may be associated with amine N-acetyltransferase in the brain which has an entirely different developmental pattern.

Aging↗
PubMed1985

Effects of phospholipids on the specific binding of [3H]spiroperidol to the cholate extract of rat brain synaptic membranes.

Effects of phospholipids including PC, PE, PI, and PS on the specific [3H]SPD binding to the solubilized dopamine receptors were examined in the cholate extracts of the cortical and striatal synaptic membranes (P2M) of the rat brain. PC and PS, but not PE or PI, at 0.4 mM greatly enhanced the specific [3H]SPD binding to the cholate extracts of both cortical and striatal P2M fractions. PC and PS did not enhance the specific [3H]DA binding to the same cholate extracts. The enhancing effects of PC and PS were temperature-dependent and in a dose-response manner peaking at 0.4 mM and 0.2 mM respectively. Such temperature dependence indicated that the PC effects were not due to trapping of [3H]SPD by PC but represented a possible DAR-PC complex formation that allowed higher binding for the ligand. Failure of natural cerebellar P2M in enhancing the [3H]SPD binding to the cholate extract supports the notion that fluidity of the phospholipids is required for the binding or the formation of the DAR-PC (or PS) complex. Scatchard analysis of the [3H]SPD binding to the cholate extract in the absence or presence of PC or PS indicated that the PC or PS enhancement of the ligand binding may be mainly due to an increase in the number of binding sites since both PC and PS significantly increased the Bmax but not the Kd of the binding.

Animals↗
PubMed1985

Ethylene dibromide: effects of paternal exposure on the neurotransmitter enzymes in the developing brain of F1 progeny.

The effects of ethylene dibromide (EDB) exposure to male rats on several neurotransmitter enzymes have been examined in various brain regions of the F1 progeny, from 7 to 90 days of age. The choline acetyltransferase activity was significantly increased at 21 days old, in most brain regions studied in the F1 progeny of the EDB-treated males, but not at 7, 14 or 90 days old. The acetylcholinesterase activity was altered in different brain regions of the F1 progeny of the EDB-exposed males at both 14 and 21 days old but not at 7 or 90 days old. Glutamic acid decarboxylase activity was increased in corpus striatum but decreased in frontal cortex only at 21 days of age. These neurochemical changes in the developing brain of F1 progeny of EDB-treated males at low doses may be associated with behavioral abnormalities observed early in their development.

Acetylcholinesterase↗
PubMed1984

A brain synaptic dopamine-binding protein: isolation and partial characterization.

A dopamine-binding protein (DABP) has been purified from the rat brain cortex to homogeneity. Solubilization of the DABP from the synaptosomal membranes (P2M) by cholic acid, subsequent agarose gel filtration of the cholic acid extract to separate phospholipids from the DABP, and lastly DA affinity chromatography successfully resulted in a purified DABP with approximately 0.006% yield in protein concentration and 0.03% yield in specific [3H]-DA binding. The specific [3H]-DA binding of the purified DABP was 117 fmol/mg protein/10 min with a 4.6-fold purification compared with the whole homogenate. The purified DABP had an Rf value of 0.67 on native disk polyacrylamide gel and it gave one single polypeptide subunit on the SDS gel with an Rf value of 0.63. The apparent molecular weight of this single subunit was estimated to be 34.5 kilodaltons. The elution patterns from either DA- or ADTN-affinity (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene-affinity) columns indicated that this DABP had higher affinity for DA agonists than for DA antagonists. Photoaffinity labeling of [3H]-DA to this DABP in the P2M fraction and the specific [3H]-DA to the purified DABP demonstrated a nanomolar range affinity corresponding to either D2 or D3 receptors. These data suggested that the purified DABP could be related to either D2 or D3 receptors in the brain.

Animals↗