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Biomedical subjects

J Wei

Publications and source records attributed to J Wei.

At least 163 records · Page 9Linked to original sources

Increased expression of M2 muscarinic receptor mRNA and binding sites in the rostral ventrolateral medulla of spontaneously hypertensive rats.

A significant body of evidence suggests that the development and maintenance of elevated blood pressure in the spontaneously hypertensive rat (SHR), a genetic model for essential hypertension, is due at least partly to a central hyper-cholinergic state. For example, this strain responds with an exaggerated pressor response to pharmacological stimulation of central muscarinic receptors in certain brain regions compared to normotensive Wistar Kyoto rats (WKY). At least part of the enhanced response to central muscarinic receptor stimulation in SHR is due to the altered expression of post-synaptic receptors. In the present study, the reverse transcriptase-polymerase chain reaction and autoradiographic techniques were used to estimate the relative levels of mRNA and density of receptor binding sites for the five subtypes of muscarinic receptors within the rostral ventrolateral medulla (RVL) of SHR and WKY. Adult (12-week-old) SHR exhibited an increase in the levels of both M2 muscarinic mRNA, and M2 receptor binding sites in RVL compared to age-matched normotensive WKY. Similarly, 4-week-old pre-hypertensive SHR exhibited increased levels of M2 mRNA in whole medulla oblongata, and an increase in the number of binding sites for M2 receptors in the RVL. Since the RVL is known to integrate tonic cholinergic sympathoexcitatory input, these results suggest that the increased expression of M2 muscarinic receptors in this region represents one neurochemical correlate for the maintenance of excessive central efferent sympathetic nervous activity in the SHR. Since the neurochemical change precedes the development of hypertension, the altered medullary M2 receptor expression may play a role as an initiating or predisposing factor for the development of hypertension in SHR.

Animals↗

Monoclonal antibodies specific to the acute lymphoblastic leukemia t(1;19)-associated E2A/pbx1 chimeric protein: characterization and diagnostic utility.

Nonrandom chromosomal abnormalities are found in most human malignancies, particularly leukemias and lymphomas. A characteristic t(1;19) (q23;p13.3) chromosomal translocation is detected in 5% of childhood acute lymphoblastic leukemia (ALL) cases. This translocation results in the formation of a fusion gene, which leads to the expression of an oncogenic E2A/pbx1 protein. Breakpoints in the E2A gene almost invariably occur within a single intron, and the identical portion of PBX1 is joined consistently to exon 13 of E2A in fusion mRNA. In this article, we report the development of monoclonal antibodies against E2A/pbx1 fusion protein using a specific peptide that corresponds to the junction region of the protein. The obtained antibodies recognize specifically the chimeric E2A/pbx1 fusion protein and lack cross-reactivities with E2A and pbx1. Immunohistochemical staining and flow cytometric studies show that these antibodies can distinguish t(1;19)-positive from t(1;19)-negative leukemic cells. These results indicate that the obtained E2A/pbx1-specific monoclonal antibodies might prove to be valuable diagnostic reagents and important tools for elucidating the mechanisms involved in oncogenesis and progression of t(1;19)-positive childhood ALL.

Amino Acid Sequence↗

Is the polymorphic microsatellite repeat of the dopamine beta-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia?

Six allelic fragments were typed by a polymerase chain reaction process with a pair of primers specific for a sequence containing the polymorphic (GT)n repeat, a microsatellite repeat, in the human dopamine beta-hydroxylase (DBH) gene. Their frequencies in unrelated patients with schizophrenia were 0.003 (A1), 0.114 (A2), 0.343 (A3), 0.526 (A4), 0.006 (A5), and 0.009 (A6), and in unrelated control subjects, 0.012 (A1), 0.086 (A2), 0.309 (A3), 0.574 (A4), 0.006 (A5), and 0.012 (A6). Kruskal-Wallis analysis revealed significant differences among the three groups, the drug-free and drug-treated patients, and the control subjects, in serum DBH activity of the subjects whose genotype was A2/A3 (H = 6.0, p < .05) or A3/A3 (H = 9.8, p < .01), in serum homovanillic acid concentration of those whose genotype was A3/A4 (H = 7.7, p < .025), and in serum tyrosine concentration of those whose genotype was A4/A4 (H = 8.3, p < .02). Mann-Whitney U test showed that in the subjects carrying the A3/A4 genotype, serum noradrenaline concentration of drug-treated patients was significantly higher than that of control subjects (N = 58, p < .02). These results suggest that genotypic polymorphism of the human DBH is likely to be associated with biochemical variability of the catecholamine pathway in schizophrenia.

Adult↗

Integrin signaling in leukocytes: lessons from the alpha6beta1 integrin.

The adhesive interactions of leukocytes with basement membrane components and other extracellular matrix (ECM) proteins are mediated largely by the integrin family of receptors. These interactions can be regulated by various effector molecules including chemokines, growth factors, and other cell surface proteins by a mechanism termed inside-out signaling of integrin function. On engagement by their ligands, integrins activate a wide range of signaling pathways that regulate a broad array of leukocyte functions such as chemotaxis, cytokine responsiveness, phagocytosis, and gene expression. This review highlights recent advances in the understanding of integrin signaling in leukocytes with an emphasis on our own work on the alpha6beta1 integrin, the major laminin receptor expressed by these cells.

Animals↗

Possible control of dopamine beta-hydroxylase via a codominant mechanism associated with the polymorphic (GT)n repeat at its gene locus in healthy individuals.

Six allelic fragments were typed by a PCR-based process with a pair of primers specific for a sequence containing the polymorphic (GT)n repeat at the human dopamine beta-hydroxylase (DBH) locus in 125 unrelated healthy individuals. Their frequencies among these individuals were 0.012 (A1), 0.08 (A2), 0.344 (A3), 0.548 (A4), 0.004 (A5) and 0.012 (A6); the two major alleles, A3 and A4, made up nearly 90% of the alleles. These individuals were divided into four groups according to the genotype they possessed, i.e. A3/A3, A4/A4, A3/A4 and others (mixed group). Kruskal-Wallis analysis revealed a significant difference in serum DBH activity among these four genetic groups (H = 32.7, P < 0.0001). The homozygotic genotypes, A3/A3 and A4/A4, were associated with low and high DBH activity, respectively, and the heterozygotic genotype, A3/A4, seemed to play a role in keeping the DBH activity at a moderate level. The present work suggests that the human DBH is likely to be controlled via a codominant mechanism associated with the dinucleotide repeat polymorphism at its gene locus.

Alleles↗

Possible association of catecholamine turnover with the polymorphic (TCAT)n repeat in the first intron of the human tyrosine hydroxylase gene.

Five allelic fragments were typed by a PCR-based process with a pair of primers specific for the polymorphic sequence due to (TCAT)n tetranucleotide repeat, a microsatellite repeat, in the first intron of the human tyrosine hydroxylase gene, i.e. A1, A2, A3, A4 and A5. Comparisons of some neurochemical parameters of the catecholamine pathway were then made between the unrelated individuals genotypically classified into six subgroups, five homozygotic and one heterozygotic. Among the six subgroups, the individuals with the A2/A2 genotype had the highest levels of serum noradrenaline and those with the A4/A4 genotype had the lowest, and the individuals with the A1/A1 genotype had the highest levels of serum homovanillic acid. These findings suggest that polymorphism of the (TCAT)n repeat in the first intron of the human tyrosine hydroxylase gene may be associated with catecholamine turnover. Possibly, the two alleles, A2 and A4, may be related to the high and low excitabilities of the noradrenergic nerves, respectively, and the allele, A1, may be associated with the up-regulation of dopamine turnover.

Adult↗

A monoclonal antibody shows discrete cellular and subcellular localizations of mGluR1 alpha metabotropic glutamate receptors.

The metabotropic glutamate receptor, mGluR1 alpha, is postsynaptic in excitatory synapses in many populations of neurons and mediates long-term responses. The present study defines the distribution of this receptor using a new, highly specific monoclonal antibody to mGluR1 alpha. Overall distribution of immunostaining was similar to that described previously with polyclonal antibodies, including prominent staining in the olfactory bulb, interneurons of the CA1 hippocampus stratum oriens/alveus, globus pallidus, thalamus, Purkinje cells and in cells of the outer dorsal cochlear nucleus and with little or low staining in principal cells of the cerebral cortex and hippocampus. Interestingly, the well-known association of mGluR1 alpha receptors with neocortical interneurons was even more prevalent than previously noted with polyclonal antibodies. Ultrastructural studies in the hippocampus and cerebellum showed dense immunoperoxidase staining in postsynaptic membranes and densities and in perisynaptic and extrasynaptic membranes, as well as substantial cytoplasmic staining associated with organelles, especially the endoplasmic reticulum.

Animals↗

Hydroxyl radical formation in hyperglycemic rats during middle cerebral artery occlusion/reperfusion.

Preexisting hyperglycemia is associated with enhanced reperfusion injury in the postischemic rat brain. The goal of this study was to evaluate whether the hyperglycemic exacerbation of brain injury is associated with enhanced generation of hydroxyl radicals in rats subjected to middle cerebral artery occlusion (2 h), followed by reperfusion (2 h). Magnetic resonance images revealed the exacerbation of focal brain injury in hyperglycemic rats. The salicylate trapping method was used in conjunction with microdialysis to continuously estimate hydroxyl radical production by measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA) during ischemia/reperfusion. In normoglycemic rats, from a mean baseline level of 130 nmol/l, 2,3-DHBA levels surged to peak levels of 194 nmol/l 45 min into ischemia and to 197 nmol/l 15-30 min into the reperfusion period, returning to baseline by 2 h into reperfusion. A similar temporal profile was observed in hyperglycemic rats, except that absolute 2,3-DHBA levels were higher (165 nmol/l at baseline, 317 nmol/l peak during ischemia, 333 nmol/l peak during reperfusion), and levels remained significantly high (p < .05) throughout the reperfusion period. These results suggest that hydroxyl radical is an important contributor to the exacerbation of neuronal and cerebrovascular injury after focal ischemia/reperfusion in hyperglycemic rats.

Animals↗

Responses of plasma fibronectin to the changes of dietary protein levels in rats.

In this study, the plasma fibronectin was evaluated as a nutritional marker in protein- and protein-energy malnourished rats in comparison with plasma prealbumin, albumin, and total protein. The plasma fibronectin was determined by nephelometric assay based on the interaction of an antigen and antibody. The rats were subjected to three diets, containing 20, 5, and 0% casein, respectively, for 5 wk except in the last 2 wk, the rats on the 0% casein diet were re-fed on a 20% casein diet. The results showed that in the rats on a 5% casein diet (protein malnourished), the plasma fibronectin concentration rose significantly in the early stage and normalized thereafter. In the rats subjected to a 0% casein diet (protein-energy malnourished), the plasma fibronectin concentration did not decline quickly in response to protein depletion, compared with the plasma prealbumin, albumin, and total protein concentrations. Following the re-feeding of a 20% casein diet in the last 2 wk, the plasma fibronectin concentration was restored earlier than other plasma protein concentrations. No significant change in plasma fibronectin concentration was found in the rats receiving a 20% casein diet (control) over the 5 wk feeding period. It is concluded that plasma fibronectin may not be a suitable marker for protein or protein-energy malnutrition, though it is a sensitive index for nutritional rehabilitation.

Animals↗

Perfusion deficit parallels exacerbation of cerebral ischemia/reperfusion injury in hyperglycemic rats.

Magnetic resonance imaging (MRI) techniques were used to determine the effect of preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury and the level of cerebral perfusion. Middle cerebral artery occlusion (MCAO) was induced by a suture insertion technique. Forty one rats were divided into hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or 2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6 brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated using gradient echo (GE) bolus tracking and steady-state spin echo (SE) imaging techniques, respectively. Brain injury correlated with the perfusion level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by 37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We conclude that preexisting hyperglycemia increases acute postischemic MRI-measurable brain cellular injury in proportion to an associated increased microvascular ischemia.

Animals↗

NG-nitro-L-arginine methyl ester modifies the input function measured by dynamic susceptibility contrast magnetic resonance imaging.

In rat brain dynamic susceptibility contrast magnetic resonance (MR) images, vessels visible on the same scan plane as the brain tissue were used to measure the characteristics of the input function of the MR contrast agent gadopentetate dimeglumine. MR images were acquired 30 and 60 minutes after intravenous injections of 3 mg/kg and 15 mg/kg NG-Nitro-L-arginine methyl ester (L-NAME) (n = 9). The time of arrival (TOA) and the mean transit time corrected for TOA of the input function were increased by 3 mg/kg or 15 mg/kg L-NAME. The area of the input function was increased by 15 mg/kg L-NAME. In two animals, similar modifications of the input function induced by 20 mg/kg L-NAME were reversed by infusion of sodium nitroprusside. In two other animals, MABP was increased by phenylephrine to a similar extent as in L-NAME experiments, but did not induce the same modifications of the input function, showing that the action of L-NAME on the input function was not simply caused by an effect on MABP. These results show that the input function can be significantly altered by manipulations widely used in cerebrovascular studies. These input function changes have important implications for calculation of cerebral blood flow.

Animals↗

[Maturation of bone marrow megakaryocyte in patients with chronic idiopathic thrombocytopenic purpura].

Colony formation units of megakaryocyte of twenty four patients with idopathic thromboeytopentic purpura (CITP) were observed by plasma clot cultures in vitro. We observed the maturation degree of megakarycyte and the effect of recombinant interferon alpha-2a (rIFN-alpha-2a) on megakaryocyte colony growth and maturation. The results showed that the number of CFU-MK of the patients with CITP was greater than that of the control group, while the patients with normal number of megakaryocytes on bone marrow smears had less BFU-MK and total clonies than the controls had. Through image analysis, we found that the black level of the positive cells of GP II a and GMP-140, the diameter and the area of megakaryocyte of patients with CITP were lower or smaller than those of the control group. These evidenced the block of megakaryocytopoiesis and megakarycyte maturation. The growth of MK colonies of marrow of patients with CITP was inhibited by r-IFN-alpha-2a.

Adolescent↗

[Chemical constituents of seeds of Camellia sinensis var. assamica].

Five compounds were isolated from the acid-hydrolytic products of n-butanol extract and ethanol extract of the seeds of Camellia sinensis var. assamica. Their structures were elucidated by chemical and spectroscopic analyses as octacosane, three new acyl-sapogenins: 22-O-angeloyl theasapogenol B, 22-O-angeloyl theasapogenol E and 22-O-angeloyl theasapogenol A, and naringenin respectively.

Drugs, Chinese Herbal↗

[Effect of extremely low frequency (correction of frenquency) magnetic field on brain ischemic reaction in rats].

The effect of extremely low frequency magnetic field (ELMF, 15 Hz, 18 mT) on ischemic brain produced by ligation of general carotid artery in left side was studied in rats. The results showed that the degree of brain blood vessel dilation was higher in magnetic field group than that in control group at the 1st, 3rd and 6th hour after ligation and the extent of damage of neurocyte was apparently lighter in magnetic field group than that in control group at the 3rd and 6th hour after ischemia. It indicates that ELMF stimulation improves the brain blood circulation after brain ischemia and alleviates the brain ischemic reaction.

Animals↗

Comparison of effects of 5 and 20 Hz magnetic field on brain responses.

Effects of 5 and 20 Hz magnetic field (MF) on brain response were compared in 22 normal subjects during selective response (SRP) and selective mental arithmetic (SMA). It was found that significant changes in event-related potentials and EEG power spectra were induced by 5 Hz MF, but changes induced by 20 Hz MF were only in EEG coherence during SMA. The features of brain response changes suggest that the brain is in a more well being state after 5 Hz MF stimulation.

Brain↗

[Determination of composition of electronic material by fundamental parameter method of XRF].

The fundamental parameters (FP) method of XRF in determination of the composition of electronic ceramic materials is studied. The fundamental parameters needed in calculation are developed by math calculation and the program is developed in C language. The method can also be used in determination of the composition of alloy. Some samples are analysed by this method and the relative derivation is less than 3%.

English Abstract↗

In situ hybridization analysis of Girk2 expression in the developing central nervous system in normal and weaver mice.

A mutation in the gene Girk2 that encodes an inwardly rectifying potassium channel is the genetic defect causing the behavioral and pathologic abnormalities of the weaver mutant mouse. Of the pathologic abnormalities, the best studied is the neuronal degeneration that occurs in the cerebellar cortex and in the midbrain dopaminergic neurons. A detailed characterization of the topographic and temporal expression of Girk2 is fundamental to elucidate the mechanisms underlying neurodegeneration in these mutant mice. In this study we utilized in situ hybridization to determine the expression of Girk2 mRNA during prenatal and postnatal development in the murine central nervous system (CNS). Girk2 expression was seen in multiple regions of embryonic CNS including the cerebellum and midbrain. During postnatal development, the highest expression was seen in the cerebellum, midbrain and hippocampus. However, since the developing cerebellum undergoes significant neuronal loss due to the degeneration of granule cell precursors, Girk2 mRNA expression in this area decreases progressively.

Animals↗

Diverse cell death pathways result from a single missense mutation in weaver mouse.

Neuronal death affects selectively granule cell precursors of the cerebellum and the dopaminergic neurons of midbrain in the weaver mutant mouse. The weaver phenotype is associated with a missense mutation in the gene coding for the GIRK2 potassium channel, which results in chronic depolarization. Using DNA gel electrophoresis, electron microscopy (EM), the in situ end-labeling (ISEL) technique at the light and EM level, and immunohistochemistry for apoptosis-related proteins c-Jun and proliferating cell nuclear antigen (PCNA), we have investigated the mechanisms of cell death in cerebellum and substantia nigra. Between postnatal day P1 and P21, in the external germinal layer of the cerebellum, most degenerating granule cell precursors were found to aggregate to form clusters. Degenerating cells exhibited strong nuclear staining for ISEL, c-Jun, and PCNA and had a typical apoptotic morphology by EM. Increased c-Jun and ISEL staining were also occasionally seen in Purkinje cells. Between P14 and P21, when dopaminergic neurons start to degenerate, staining for ISEL, c-Jun, and PCNA in weaver substantia nigra was the same as in controls. By EM, however, we found only in weaver mice numerous dopaminergic cells that showed extensive vacuolar and autophagic changes of cytoplasm, preservation of membrane and organelle integrity, and absence of chromatin condensation or DNA fragmentation by EM-ISEL. The combination of vacuolar and autophagic changes identifies a novel type of non-necrotic, nonapoptotic cell death. After biochemical analysis of DNA, a clear-cut laddering, suggestive of oligonucleosomal fragmentation, was present in samples from weaver cerebellum. Cell death diversity appears to be influenced by specific features of target cells. These findings may be relevant for understanding the mechanisms of cell death in neurodegenerative diseases.

Animals↗