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Biomedical subjects

W Liao

Publications and source records attributed to W Liao.

At least 73 records · Page 4Linked to original sources

Characterization and functional analysis of the cis-autoproteolysis active center of glycosylasparaginase.

Glycosylasparaginase is an N-terminal nucleophile hydrolase and is activated by intramolecular autoproteolytic processing. This cis-autoproteolysis possesses unique kinetics characterized by a reversible N-O acyl rearrangement step in the processing. Arg-180 and Asp-183, involved in binding of the substrate in the mature enzyme, are also involved in binding of free amino acids in the partially formed substrate pocket on certain mutant precursors. This binding site is sequestered in the wild-type precursor. Binding of free amino acids on mutant precursors can either inhibit or accelerate their processing, depending on the individual mutants and amino acids. The polypeptide sequence at the processing site, which is highly conserved, adopts a special conformation. Asp-151 is essential for maintaining this conformation, possibly by anchoring its side chain into the partially formed substrate pocket through interaction with Arg-180. The reactive nucleophile Thr-152 is activated not only by deprotonation by His-150 but also by interaction with Thr-170, suggesting a His-Thr-Thr active triad for the autoproteolysis.

ATP-Binding Cassette Transporters↗

[Histological and electrophysiologic changes of injury of dorsal root ganglia].

Injury of dorsal root ganglia (DRG) may cause sensory and motor dysfunction. In order to investigate the changes of somato-sensory evoked potential (SEP) and histological characteristics of DRG in different causes and different periods of injury, fifty-two rabbits were chosed to build the models. The rabbits were divided into 4 groups: Control group (n = 4); mechanical compressing group (n = 16); inflammatory injury group (n = 16); and treatment group (2% lidocaine with hydroprednisone was administered locally, n = 16). After one to eight weeks, SEP was determined and samples of DRG were obtained to observe the histological and ultrastructural changes every week. The result showed that the gap junction of microvascular endothelium in DRG had been destroyed by the mechanical compression was the major cause of the vessel permeability increasing. The increasing of endothelial pinocytic vesicles transportation and widening of endothelial gap junction were the main causes of inflammatory irritation of DRG. The local infiltration with 2% lidocaine and hydroprednisone could obviously ameliorate inflammatory injury in DRG.

Animals↗

[Study on dopamine metabolite in cerebrospinal fluid of schizophrenics and epilepsics].

The concentration of dopamine (DA) metabolite-homovanillic acid (HVA) in cerebrospinal fluid (CSF) of 40 patients with schizophrenia 27 with epilepsy and 15 controls without disorders of CNS was reported. The results showed that there were no significant differences in mean levels of HVA among the three groups. It is suggested that both schizophrenia and epilepsy are not abnormal in total level of DA metabolism.

Adult↗

Preliminary observation on the correlation between nm23 expression and Ki-67 antigen with early metastasis of human osteosarcoma.

OBJECTIVES: To detect the nm23 expression in osteosarcoma, analyze the correlation between nm23 expression and early metastasis and to study the relation between nm23 expression with tumor differentiation and cell proliferation, as defined by Ki-67 labeling. METHODS: nm23 oncoprotein expression was measured by immunohistochemical staining using formalin fixed, paraffin embedded sections of 39 surgically resected osteosarcomas and was compared with Ki-67 expression, histological findings and early metastasis. In each sample, the grading of immunoreactivity was recorded as 0, 1+, 2+ according to the percentage of nm23 and Ki-67 labeling cells respectively. RESULTS: The cases with more than 25% positive immunoreactivity of nm23 protein were detected in 48.7% of the total cases. There was no statistical difference between nm23 expression and early metastasis, but the cases with nm23 expression appeared to have a trend to get early metastasis. nm23 expression was significantly correlated with Ki-67 expression, which was associated with differentiation of the tumor cells. CONCLUSION: The role of nm23 as a tumor metastasis suppressor in osteosarcoma is less prominent. Both nm23 and Ki-67 may help predict the possibility of early metastasis in human osteosarcomas.

Adolescent↗

[Determination algorithms in oscillometric blood pressure measurement].

This paper discusses the method of oscillometric blood pressure determination. A new criterion for systolic pressure and diastolic pressure determination has been proposed, which is based on ratio changes of the oscillation amplitude under a wide normalized range. Primary experiment results show the new criterion is effective.

Algorithms↗

Somatosensory- and motor-evoked potentials in a rabbit model of spinal cord ischemia and reperfusion injury.

STUDY DESIGN: Occlusion of the infrarenal abdominal aorta was applied to adult rabbits, which induced spinal cord ischemia, followed by disocclusion and reperfusion. Cortical somatosensory- and motor-evoked potentials were monitored continuously up to 24 hours and correlated to hind limb motor and sensory status. OBJECTIVES: To investigate cortical somatosensory-, and motor-evoked potentials in the rabbit model of spinal cord ischemia and reperfusion injury, especially their changes during reperfusion and their relationship to hind limb motor and sensory function. SUMMARY OF BACKGROUND DATA: Various evoked potentials have been widely studied in neurologic prognosis of spinal cord ischemia. Little information is available from previous studies to correlate cortical somatosensory- and motor-evoked potentials with secondary paraplegia occurring during the reperfusion phase. METHODS: Acute spinal cord ischemia was induced in eight anesthetized rabbits by occlusion of the infrarenal abdominal aorta just beneath left renal artery for 40 minutes. Cortical somatosensory-evoked potentials, elicited by stimulating the posterior tibial nerve and recorded at the skull surface corresponding to sensory projection area, and motor-evoked potentials, elicited by stimulating the skull surface corresponding to the motor projection area and recorded at L4 lamina of the vertebral arch, were monitored immediately before and at different time points during ischemia and reperfusion up to 24 hours after disocclusion. Hind limb motor and sensory functions were evaluated and correlated with cortical somatosensory- and evoked-potentials. RESULTS: Cortical somatosensory-evoked potentials disappeared gradually after the start of occlusion and reappeared during reperfusion. Motor-evoked potentials did not change significantly during occlusion, but deteriorated after disocclusion; they correlated well with hind limb motor and sensory status. CONCLUSIONS: Reperfusion injuries to the spinal cord might occur in the rabbit model after disocclusion. Cortical somatosensory-evoked potentials seemed to be a very sensitive index for spinal cord ischemia, whereas motor-evoked potentials correlated well with the course of reperfusion injuries after disocclusion and reflected long-term follow-up hind limb motor function better than cortical somatosensory-evoked potentials.

Animals↗

Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog.

Canine narcolepsy is a unique experimental model of a human sleep disorder characterized by excessive daytime sleepiness and cataplexy. There is a consensus recognition of an imbalance between cholinergic and catecholaminergic systems in narcolepsy although the underlying mechanisms remain poorly understood. Possible substrates could be an abnormal organization, numbers and/or ratio of cholinergic to catecholaminergic cells in the brain of narcoleptic dogs. Therefore, we sought to characterize the corresponding neuronal populations in normal and narcoleptic dogs (Doberman Pinscher) by using choline acetyltransferase (ChAT), nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH). Cholinergic cell groups were found in an area extending from the central to the gigantocellular tegmental field and the periventricular gray corresponding to the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT), and the parabrachial nucleus. An almost perfect co-localization of ChAT and NADPH-diaphorase was also observed. Catecholaminergic cell groups detected included the ventral tegmental area, the substantia nigra, and the locus coeruleus nucleus (LC). The anatomical distribution of catecholaminergic neurons was unusual in the dog in two important aspects: i) TH- and/or DBH-immunoreactive neurons of the LC were found almost exclusively in the reticular formation and not within the periventricular gray, ii) very few, if any TH-positive neurons were found in the central gray and dorsal raphe. Quantitative analysis did not reveal any significant differences in the organization and the number of cells identified in the LDT, PPT, and LC of normal and narcoleptic dogs. Moreover, the cholinergic to catecholaminergic ratio was found identical in the two groups. In conclusion, the present results do not support the hypothesis that the neurochemical imbalance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations.

Animals↗

Isolation of specific DNA probes for detection of Cryptococcus neoformans.

We report the construction of a genomic library and isolation of repetitive DNA probes from Cr. neoformans that are species- and variety-specific. The inserts of the genomic library were in a range of 0.3-1.8 kb, which were in normal distribution in length. Among 592 clones of the genomic library, there were 400(67.6%) clones inserted repetitive DNA sequence and 192(32.4%) inserted single copy DNA sequence of the Cr. neoformans genome. From the library, three specific probes were identified. Clone pCNIIA6 was serotype A-specific, pCNIIB5 species-specific, and pCNIIIG1 variety-specific (var. neoformans). On the basis of the high specificity and sensitivity of the signals observed by hybridization, we suggest that these probes provide a means for both biotyping and early diagnosis of Cr. neoformans.

Cryptococcus neoformans↗

Small-dose itraconazole pulse therapy in the treatment of onychomycosis.

The aim was to evaluate efficacy and tolerance of a short-schedule treatment regimen using a small dose of itraconazole in pulse intermittently. The open study evaluated the pulse therapy consisting of monthly 1-week cycles of oral itraconazole 200 mg daily for 2-3 consecutive months in 42 patients with onychomycosis. After active therapy, patients were evaluated for a maximum period of 1 year. Twelve of 42 patients were considered as being clinically cured, 17 were markedly improved, 11 were improved and two were failures. A mycological examination at the final visit was performed on all patients. Thirty-five were negative and seven were positive. This short treatment was well tolerated, with no adverse reactions, and may offer a new option for treatment of onychomycosis.

Administration, Oral↗

Contrasting effects of growth hormone and insulin-like growth factor I on the biological activities of endotoxin in the rat.

We previously demonstrated that GH potentiates the biological activities of endotoxin in the rat. In the present study, we wanted to determine if the potentiating effects of GH on the biological activities of endotoxin could be reproduced by insulin-like growth factor I (IGF-I). Endotoxin (5 mg/kg BW) was injected in rats primed with or without GH or IGF-I for 3 days. As expected, endotoxin administration markedly increased circulating tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) and induced organ injury, hypoglycemia, and hyperlipidemia. In GH-primed rats, endotoxin induced a further increase of serum IFN gamma (but not TNF); and five out of six of those rats died within 15 h after giving endotoxin. However, little difference between endotoxin-treated rats with and without IGF-I priming could be seen. Furthermore, IGF-I infusion altered blood glucose, urea, and circulating ICF-I levels more than GH infusion. Therefore, IGF-I does not enhance the biological activities of endotoxin in the rat, suggesting that the enhancement of endotoxin effects by GH is via an IGF-I-independent pathway. Priming rats by GH (but not by IGF-I) induced a further increased response of serum IFN gamma but not TNF to subsequent endotoxin challenge, suggesting that IFN gamma rather than TNF is likely to be involved in this process.

Animals↗

Novel effects of histamine on lipoprotein metabolism: suppression of hepatic low density lipoprotein receptor expression and reduction of plasma high density lipoprotein cholesterol in the rat.

Histamine has been shown to be involved in atherosclerosis and coronary heart disease. Little information is available regarding the effects of histamine on lipoprotein metabolism. In the current study, we investigated the effects of histamine on the expression of hepatic low density lipoprotein (LDL) receptors and on plasma lipoproteins in the rat. Injection of compound 48/80 (C48/80, a histamine releaser) or histamine reduced hepatic LDL receptor expression, but not LDL receptor messenger RNA levels. Oral administration of polymyxin B (an antiendotoxin antibiotic and a histamine releaser) before the injection of C48/80 or histamine did not attenuate their effects. Polymyxin B itself had effects similar to those of C48/80 and histamine on LDL receptors. These results suggest that the effects of histamine are not mediated by the induction of gut-derived endotoxemia. Histamine H2 agonists (dimaprit and impromidine), but not H1 agonists (2-methylhistamine and 2-thiazolylethylamine), also reduced hepatic LDL receptor expression. The suppressive effect of C48/80 on hepatic LDL receptor expression was not attenuated by either the H1 antagonist (chlorpheniramine) or the H2 antagonist (cimetidine). Administration of C48/80 also reduced plasma high density lipoprotein (HDL) cholesterol. The H1 antagonist (chlorpheniramine), but not the H2 antagonist (cimetidine), almost completely reversed the effect of C48/80 on plasma HDL cholesterol. In conclusion, histamine suppresses hepatic LDL receptor expression via a non-H1 receptor-mediated pathway, and histamine reduces plasma HDL cholesterol via an H1 receptor-mediated pathway.

Animals↗

Lipoprotein metabolism in the fat Zucker rat: reduced basal expression but normal regulation of hepatic low density lipoprotein receptors.

Hyperlipoproteinemia is one of the phenotypic characteristics of the fat Zucker rat that carries a mutation in the leptin receptor gene. In the present study, we studied the regulation of hepatic low density lipoprotein (LDL) receptor expression in lean and fat Zucker rats. Compared with lean rats, the fat ones had a pronounced (approximately 60%) reduction in hepatic LDL receptor expression, whereas the levels of receptor messenger RNA (mRNA) were not reduced. Fat rats had increased levels of very low density lipoproteins and high density lipoproteins, but their plasma apo B100 within LDL was reduced. Challenge with 2% dietary cholesterol for 8 days suppressed hepatic LDL receptor expression in lean animals to similar levels as seen in fat ones, whereas the reduction in mRNA levels was much less pronounced. Treatment with ethynylestradiol (5 mg/kg BW per day) for 4 days strongly stimulated hepatic LDL receptor expression in both lean and fat rats; this treatment also increased LDL receptor mRNA levels, but to a lesser extent. In conclusion, the basal expression of hepatic LDL receptors is reduced in fat Zucker rats, but the capacity for the regulation of the receptors remains intact.

Analysis of Variance↗

The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation.

The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.

Amino Acid Sequence↗

[Mutual regulation of proliferation between pulmonary artery endothelial cells and pulmonary smooth muscle cells in vitro].

Vascular endothelial cell are closely related to vascular smooth muscle cells in structure and function. The interactions between them may play important roles in the modulation of function and structure of vascular wall. In the present study, the mitogenic regulations between cultured new bovine pulmonary arterial endothelial cell (PAEC) and pulmonary arterial smooth muscle (PASM) were investigated. When PAECs and PASMs were mixcultured, 3H-TdR incorporation into the mixed cells decreased significantly (P < 0.001 vs control). When PAECs and PASMs were cultured in conditioned medium from PASMs and PAECs respectively or they were cocultured, the proliferation of PAECs was inhibited while that of PASM was stimulated significantly (P < 0.05 vs control). It was also found that the concentration of cAMP increased but cGMP decreased in cocultured PASMs (P < 0.01 vs control), while the concentration of both cAMP and cGMP decreased significantly in cocultured PAECs (P < 0.01 vs control). These findings suggest that PAECs and PASMs may regulate their proliferation each other through the second messenger system.

Animals↗

[The development of a fluid percussion device for brain injury of animals].

This paper discusses a fluid percussion device for brain injury. The injury is produced by striking the cork with a pendulum dropped from a known fall height to produce transient high pressure through a fluid transfer system. Experimental results show the device has the advantages of making a controllable, repeatable, and precise injury, and it can produce different levels of injury on different animals.

Animals↗