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Biomedical subjects

Y Liang

Publications and source records attributed to Y Liang.

At least 289 records · Page 16Linked to original sources

Glucose metabolism and insulin release in mouse beta HC9 cells, as model for wild-type pancreatic beta-cells.

Glucose metabolism and its relationship with glucose-induced insulin release were studied in beta HC9 and beta TC3 cells to identify and characterize key factors controlling the intermediary metabolism of glucose and glucose-induced insulin release. The beta HC9 cell line, derived from pancreatic islets with beta-cell hyperplasia, is characterized by a normal concentration-dependency curve for glucose-stimulated insulin release, whereas the beta TC3 cell line, derived from pancreatic beta-cell tumors, shows a marked leftward shift of this curve. Maximum velocity and the Michaelis-Menten constant of glucose uptake in beta HC9 and beta TC3 cells were similar, even though GLUT-2 expression in these two cell lines differed. In both cell lines, the kinetic characteristics of glucose usage, glucose oxidation, and glucose-induced oxygen consumption were similar to those of glucose phosphorylation, indicating that the kinetics of glucose metabolism from the glucose phosphorylation step in the cytosol to the mitochondrial process of oxidative phosphorylation are determined by the glucose-phosphorylating enzyme, that is, by glucokinase in beta HC9 cells and by hexokinase in beta TC3 cells. Thus beta HC9 cells provide an opportunity for the quantitative analysis of glucose metabolism, the associated generation of coupling factors, and other essential beta-cell functions involved in glucose sensing and insulin secretion.

Animals↗

Differential regulation of kallikrein, kininogen, and kallikrein-binding protein in arterial hypertensive rats.

This study was designed to determine whether the kallikrein-kinin system exerts a protective action in hypertension induced by chronic inhibition of nitric oxide synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats, while controls received regular tap water. Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively. There was no significant change in hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher than in controls, whereas renal beta-actin mRNA levels were similar between groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP were consistent with their protein levels. Immunoreactive total kininogen and low-Mr kininogen levels in sera and tissue kallikrein levels in kidney were significantly higher in the L-NAME-treated group, whereas KBP levels in the circulation were lower compared with controls. Systolic blood pressure was increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2-receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4 mmHg, P < 0.05). This difference was confirmed by direct measurement of mean blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin significantly decreased MBP of L-NAME-treated rats, and this effect was blunted in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg, P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis may have a protective role against the cardiovascular effects induced by chronic inhibition of nitric oxide synthesis.

Animals↗

[Protective effect of verapamil on light-induced rat retinopathy].

OBJECTIVE: In order to search for simple and effective medicine to protect light-induced retinopathy. METHOD: We used verapamil as a protective agent. We measured the contents of the end product of lipid peroxidation, malondialdehyde (MDA), in the rat retinas immediately, 4 days, 15 days and 30 days after the damage in the damaged group and protective group, and observed their histopathologic structures and the integrity of the outer blood-retinal barrier. RESULTS: The results showed that the content of MDA in the normal retina was 0.36 +/- 0.07 nmol/mg, while in the damaged group the MDA levels at different times were 0.52 +/- 0.03 nmol/mg, 0.70 +/- 0.20 nmol/mg, 0.52+/- 0.07 nmol/mg, and 0.47 +/- 0.03 nmol/mg respectively, being significantly different from that of the normal group. In the protective group, the MDA levels at different times were 0.40 +/- 0.04 nmol/mg, 0.49 +/- 0.03 nmol/mg, 0.40 +/- 0.05 nmol/mg and 0.39 +/- 0.08 nmol/mg respectively, being significantly different from that in the damaged group at the corresponding times. In the damaged group, the histologic study showed that the retinal structures were damaged in various degrees at 4 days and most severely at 15 days after light exposure and the outer blood-retinal barrier was also damaged, while in the protective group no significant pathologic changes of retina were seen. CONCLUSION: Verapamil is an effective protective medicine for light-induced retinopathy.

Animals↗

MR evaluation of the brain in central diabetes insipidus.

OBJECTIVE: To evaluate the role of magnetic resonance (MR) imaging in determining the cause of central diabetes insipidus (CDI) by using MR imaging to describe the findings in the hypothalamic-pituitary area in patients with CDI. METHODS: Thirty-one cases of clinically proved CDI were prospectively studied. A control study was also conducted in 200 normal subjects. MR imaging was performed on a 1.0 T superconductive unit with T1-weighted images obtained in the sagittal, coronal and axial planes. RESULTS: Hypothalamic-pituitary masses or structural changes were identified in 26 cases and normal structures in 5. The normal high signal intensity of the posterior pituitary lobe was absent in 29 cases, but remained unchanged in 2. In the control group, the frequency of the high signal of the posterior lobe was 93%. CONCLUSIONS: The absence of the normal high signal in the posterior pituitary lobe is closely related to the loss of hypothalamic-pituitary function. MR imaging is very sensitive in demonstrating the changes in this area in CDI and it can provide an accurate diagnosis when combined with the clinical information.

Adolescent↗

[A pathological study of goat multiple organ failure model].

We succeeded in replication a standardized goat model of multiple organ failure (MOF). In the experimentation, the animals were monitored and supported with facilities pertaining to a human intensive care unit, with constant infusion of LPS into portal vein following trauma and hemorrhagic shock. The main organs of MOF goats were observated by the light microscopy and electronmicroscopy, including the lungs, hearts, livers, kidneys, intestines and spleens. The results showed that there were some areas of spotty and mass necrosis in the organ parenchyma with inflammatory cell infiltration. Our studies suggested that once the clinical multiple organ failure, severe pathological changs occur in organs.

Animals↗

[Clinical analysis of diagnosis and treatment of 44 cases with intraspinal lipoma].

44 cases of intraspinal lipoma were confirmed by pathologic examination. We excised the lipomas totally or partly. After surgery, 8 cases improved greatly, 19 cases improved, 18 not improved. CT scan and MRI are the key methods for diagnosis of intraspinal lipoma, most of intraspinal lipomas are adherent to the spine and root of nerves tightly and difficult to be dissected. So it's not easy to excise the lipoma entirely. But if we use microsurgery we can get better results.

Adolescent↗

[An experimental study of pathomorphology in the iris and ciliary body after intraocular lens implantation].

OBJECTIVE: To study the pathological changes and morphological features in the iris and ciliary body after lens extraction and intraocular lens (IOL) implantation in rabbits and discuss the mechanism of postoperative intraocular inflammatory response. METHODS: 27 adult pigmented rabbits were divided into three groups, (1) extracapsular lens extraction and IOL implantation. (2) simple extracapsular lens extraction, and (3) the control group without surgical intervention. The iris and ciliary body in every eye were taken on the 1st, 7th and 14th days after surgery, their pathological changes were observed with light microscopy, and the number of inflammatory cells were counted. The data were analyzed by using analysis of variance of SAS software. RESULTS: The pathological changes might be divided into three stages: (1) acute inflammation and exudative changes in the early stage (on the 1st day postoperatively), (2) subacute inflammation and granuloma formation in the middle stage (on the 7th day postoperatively, and (3) chronic inflammation and fibrosis in the late stage (on the 14th day postoperatively). CONCLUSION: The inflammatory cells in the iris and ciliary body are significantly higher in eyes with IOL implantation than that in eyes with simple extracapsular lens extraction (P < 0.01). Besides macrophages, there are many lymphocytes, eosinophils and plasma cells in the iris and ciliary body, suggesting that an active immune response exist in the inflammation.

Animals↗

[An experimental study of cytology in the aqueous humor of rabbit eyes after intraocular lens implantation].

OBJECTIVE: The study was designed to count the number of white blood cells and observe their subset distribution in the aqueous humor after extracapsular lens extraction and intraocular lens (IOL) implantation in capsular bag in rabbits and to discuss the mechanism of postoperative intraocular inflammatory response. METHODS: 27 adult pigmented rabbits were divided into three groups: (1) The IOL was placed in the capsular bag after extracapsular lens extraction; (2) The extracapsular lens extraction; and (3) The control group without any surgical intervention. Aqueous humor samples were aspirated on the postoperative 1, 3, 7 and 14 days, and the total number of white blood cells in the aqueous humor and their subset distribution were counted. The data were analyzed by using analysis of variance of SAS software. RESULTS: There was a significantly higher number of inflammatory cells in the IOL implanted eyes than that in the eyes with only extracapsular lens extraction. CONCLUSIONS: In the early postoperative stage, there was a marked increase in the number of white blood cells and polymorphonuclear leukocytes in the IOL group, that is probably related to the mechanical ocular tissue damage and the breakdown of the blood-aqueous barrier induced by the operative procedures. There were a significant increase in the macrophages, eosinophiles, and lymphocytes in the IOL group, that suggests that an active immune response exist in the anterior ocular inflammation after IOL implantation.

Animals↗

[Determination of puerarin in gegen ginlian tablets by RP-HPLC].

A quantitative method was developed for the determination of puerarin in Gegen Qinglian Tablets by reversed phase HPLC. Chromatographic conditions included column ODS-C18, column temperature: 35 C, UV detector: 250 nm, mobile phase: EtOH-H2O (23:77), flow rate: 1 ml/min. The number of theoretical plates calculated for puerarin peak was no less than 2000. The standard curve was linear in the concentration range of 5-80 micrograms/ml, and the correlation coefficient was 0.9999. The average recovery and the relative standard deviation were 97.6% and 1.8% respectivily.

Chromatography, High Pressure Liquid↗

Failure to detect missense mutations in the S182 gene in a series of late-onset Alzheimer's disease cases.

The possibility of an interaction of multiple genes has been speculated in pathogenesis of Alzheimer's disease (AD). Because we have recently cloned a novel gene S182 bearing five different missense mutations which segregate with early-onset familial AD, we sought the frequency of these mutations in familial and sporadic late-onset AD to clarify the incidence of these mutations in the disease. The current study showed lack of these mutations in 118 independent subjects affected with late-onset Alzheimer's disease.

Aged↗

Irreversible binding kinetics of Bacillus thuringiensis CryIA delta-endotoxins to gypsy moth brush border membrane vesicles is directly correlated to toxicity.

To examine the binding of Bacillus thuringiensis delta-endotoxins, CryIAa, CryIAb, and CryIAc, to Lymantria dispar (gypsy moth) brush border membrane vesicles (BBMV), saturation kinetic analyses were conducted according to a two-step interaction scheme [formula: see text] for delta-endotoxin binding to BBMV, rather than the one-step reversible binding presented in prior reports. The order of toxicity of the delta-endotoxins, as measured by the dose required for a 50% inhibition of weight gain (ID50), was CryIAa (77.3 ng) > CryIAb (157 ng) > CryIAc (187 ng). While both the maximum extent of binding, Bmax, and the half-maximum insertion rate concentration, K1/2, was observed to be indirectly related to toxicity, the rate constant of irreversible binding, k2, was found to be directly correlated to toxicity.

Animals↗

Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction.

BACKGROUND: The reported frequency of active coronary lesions (plaque rupture and coronary thrombosis) in sudden death due to coronary artery atherosclerosis (sudden coronary death) has varied from < 20% to > 80% of cases in previous series. In hearts lacking an active coronary lesion, sudden death has usually been attributed to a healed myocardial infarction. The purpose of the present study was to determine the frequency of active and inactive coronary lesions and myocardial infarction in individuals with sudden coronary death. METHODS AND RESULTS: The hearts of persons who died as a result of sudden coronary death underwent perfusion-fixation and postmortem angiography. An active coronary lesion was defined as a disrupted plaque, luminal fibrin/platelet thrombus, or both. We defined an inactive lesion as having a cross-sectional luminal stenosis of > or = 75% with neither plaque disruption nor luminal thrombus. Ninety hearts were examined (from 72 men and 18 women; mean age at the time of death, 51 +/- 10 years). Acute myocardial infarction was present in 19 (21% [acute myocardial infarction only in 9, both acute and healed myocardial infarction in 10]), healed myocardial infarction only in 37 (41%), and no myocardial infarction in 34 (38%). Active coronary lesions were identified in 51 (57%): acute thrombi plus disrupted plaques in 27, acute thrombi only in 21, and disrupted plaques only in 3. In hearts with acute myocardial infarction, active coronary lesions were significantly more prevalent than in hearts with only healed myocardial infarction or hearts lacking an acute or a healed myocardial infarction (89%, 46%, and 50%, respectively; P < .005). Hearts without acute or healed myocardial infarction and without active lesions were similar to hearts with active lesions with respect to heart weight and severity of epicardial coronary disease. CONCLUSIONS: Acute changes in coronary plaque morphology (thrombus, plaque disruption, or both) were found in 57% of cases of sudden coronary death. In hearts with myocardial scars and no acute infarction, active coronary lesions were identified in 46% of cases. Neither myocardial infarction (acute or healed) nor an active coronary lesion was present in 19% of hearts.

Coronary Angiography↗

Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.

We report the cloning of a novel gene (E5-1) encoded on chromosome 1 which has substantial nucleotide and amino-acid sequence similarity to the S182 gene on chromosome 14q24.3. Mutations, including three new missense mutations in the S182 gene, are associated with the AD3 subtype of early-onset familial Alzheimer's disease (AD). Both the E5-1 and the S182 proteins are predicted to be integral membrane proteins with seven membrane-spanning domains, and a large exposed loop between the sixth and seventh transmembrane domains. Analysis of the nucleotide sequence of the open reading frame (ORF) of the E5-1 gene led to the discovery of two missense substitutions at conserved amino-acid residues in affected members of pedigrees with a form of familial AD that has a later age of onset than the AD3 subtype (50-70 years versus 30-60 years for AD3). These observations imply that the E5-1 gene on chromosome 1 and the S182 gene on chromosome 14q24.3 are members of a family of genes (presenilins) with related functions, and indicates that mutations in conserved residues of E5-1 could also play a role in the genesis of AD. Our results also indicate that still other AD susceptibility genes exist.

Alzheimer Disease↗

Variable effects of maturity-onset-diabetes-of-youth (MODY)-associated glucokinase mutations on substrate interactions and stability of the enzyme.

Mutations in the human glucokinase (GK) gene are thought to cause maturity-onset diabetes of youth (MODY) by leading to the production of enzymes with reduced catalytic activities and increased glucose Km values. However, in some cases the diabetic phenotype is more severe than might be predicted from these apparent kinetic effects alone. To determine whether these mutations might also effect other characteristics of the enzyme, nine MODY-associated mutants were expressed as fusion proteins with Schistosoma japonicum glutathione S-transferase (GST) and compared with three wild-type human GK isoforms that were also expressed in the same manner. Three GST-GK isoforms (liver 1, liver 2 and islet) were kinetically indistinguishable from each other and from purified rat liver GK. Noteworthy is a glucose-induced fit effect for the interaction of trinitrophenyl (TNP)-ATP with GST-GK, whereby glucose significantly increased the affinity of TNP-ATP binding to GST-GK without changing the stoichiometry of binding. The nine MODY-associated mutations studied either showed diminished catalytic activity, substrate affinities, allosteric regulation, or stability of the fusion enzyme. We conclude that: (1) Gly261 and Lys414 are important for ATP binding; (2) Val203 may be essential for a glucose-induced fit effect; and (3) the stability of fusion protein may be significantly reduced when Glu300 is replaced by Lys. These results suggest that, in addition to effects on the Km and Vmax. of GK, a decrease in the ATP-binding affinity or stability of the mutated enzyme may also contribute to a reduction of GK activity in individuals with GK-MODY. In the B-cell this would have the effect of blunting glucose-stimulated insulin release, thereby contributing to the diabetic phenotype.

Adenosine Triphosphate↗

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.

Alzheimer Disease↗

The morphogenesis of a Chinese strain of HIV-1 forming inclusion bodies in Jurkat-tat III cells.

A rapid/high replicative strain of human immunodeficiency virus type 1 (HIV-1) (BC9101) was isolated directly in the Jurkat-tat III cell line from a Chinese patient with AIDS. The thin-section electron microscopy was performed and revealed high efficiency of replication of BC9101 with some unusual biological properties. Many vacuoles, most of them filled with HIV particles, were found close to the nucleus. Double-cored virions and double budding were frequently observed in the vacuoles and at the vacuolar membrane. Virus particles matured by budding both into intracytoplasmic vacuoles and through the plasma membrane. Inclusion bodies of varying sizes, some consisting of thousands of HIV particles, were found in the cytoplasm. All the illustrated features describing formation of inclusion bodies were compatible with the observation that HIV particles were assembled at and budded from the cytoplasmic vacuole membrane. They were then released from the membrane into the vacuoles, and subsequently, the maturation occurred. Some of the vacuoles accumulated to such a high number of mature virus particles that inclusion bodies were formed. During the disintegration of the cells, the inclusion bodies surrounded by the vacuolar membrane were released from the cells. The nucleotide sequence of the vpu gene of BC9101 was investigated and indicated that the unusual biological properties may due to the lack of a start codon for translation of the vpu protein.

Acquired Immunodeficiency Syndrome↗

Cloning and characterization of the promoter region of the mouse mu opioid receptor gene.

Opioid compounds have potent analgesic and euphoric properties. They act with specific cell-membrane receptors which have been pharmacologically defined into three major classes, mu, kappa and delta. These receptors are highly regulated with respect to their gene expression, resulting in a temporally and spatially specific pattern of distribution for each receptor. To characterize the promoter sequence of the mu opioid receptor (MOR) gene, a mouse genomic DNA library was screened under high stringency with a rat MOR (MOR-1) cDNA probe and genomic sequences for the mouse MOR gene were isolated. From one genomic clone, a 2.3-kb EcoRI fragment, which hybridized to the 5'-end of the rat MOR-1 cDNA probe, was subcloned and sequenced. This fragment contains 1.3 kb of sequence upstream of the initiation codon, extends downstream through exon 1 and includes a portion of intron 1. Primer extension analysis using mouse brain poly (A)+ RNA identified a transcription initiation site 793 bp upstream from the translation start site. Chimeric constructs of mouse MOR deletion fragments fused to a luciferase reporter gene were transfected into a human neuroblastoma cell line, SK-N-SH, which constitutively expresses endogenous MOR. These transient expression studies indicated that the 0.2-kb region upstream from the transcription initiation site possesses a functional promoter, which directs the expression of the reporter gene in vitro and may possess promoter activity for the mouse MOR gene in vivo.

Animals↗

Evaluation of PAPNET system for rescreening of negative cervical smears.

We rescreened 2,238 cervicovaginal smears conventionally prepared with Papanicolaou stain by PAPNET system. The slides screened manually as negative, were sent to PAPNET system. The image tapes were reviewed on a high-resolution monitor, and categorized as negative, unsatisfactory, and atypical. All atypical cases were rescreened manually. Abnormal cases were reviewed by a cytopathologist. Two-thousand one hundred and two (94%) cases rescreened by PAPNET were negative. Nine of 45 unsatisfactory cases by PAPNET were unsatisfactory by manual review. Ninety-one (4.0%) cases by PAPNET were atypical. On manual rescreening, 86 of 91 were negative, 20% showing benign cellular changes; five of 91 were atypical, the atypia, however, not exceeding low-grade category. The detection rate by PAPNET method was 0.2% (five of 2,238 cases). We conclude: 1) In a cytology laboratory with good quality control, PAPNET rescreening does not significantly increase the detection rate. 2) For cytology laboratories without in-house rescreening, PAPNET offers an alternative at a price. 3) The PAPNET system also offers a tool by which a laboratory can occasionally monitor its performance. 4) The cost benefit analysis of the system requires further study and scrutiny.

Female↗