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Biomedical subjects

Y He

Publications and source records attributed to Y He.

At least 235 records · Page 13Linked to original sources

Effect of 6-OHDA injection on the AMPA glutamate receptor subunits in the substantia nigra of Sprague-Dawley rats.

Parkinson's disease (PD) is characterized by the destruction of dopaminergic cells in the substantia nigra (SN). The cause of the cell death and the development of Parkinsonism is however unknown. There are increasing evidences to suggest the involvement of glutamate mediated by its receptors. Using immunohistochemistry and cell counting, the present study investigated whether the numbers of neurons immunostained with glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR1, GluR2/3 and GluR4 in the SN of rats would change after the injection of 6-hydroxydopamine (6-OHDA) into the SN. The results showed that the numbers of GluR1 positive cells were significantly decreased in the substantia nigra pars compacta (SNc), pars reticulata (SNr) and pars lateralis (SNl) from 3 days (13.7%) to 3 months (40.3%) and of GluR2/3 cells, from 1 week (17.6%) to 3 months (19.1%) after 6-OHDA injection, compared to those in the contralateral non-injected side. There was, however, no significant difference in the number of GluR4 positive cells between the injected and non-injected SN. The results were discussed.

Animals↗

Regulation of a calcium-dependent tyrosine kinase in vascular smooth muscle cells by angiotensin II and platelet-derived growth factor. Dependence on calcium and the actin cytoskeleton.

A novel, p125FAK homologue, CADTK, has been detected in neural, epithelial, or hematopoietic cells but not in fibroblasts. We now demonstrate CADTK expression in a mesenchymal cell, rat aortic smooth muscle cells (RSMC). Angiotensin II (Ang II) or platelet-derived growth factor (PDGF-BB and PDGF-AA) markedly stimulated CADTK tyrosine phosphorylation in RSMC but did not affect p125FAK phosphorylation. The PDGF-depedent CADTK tyrosine phosphorylation was slower and more prolonged than that of Ang II, correlating well with the differential effects of these agonists on cytosolic calcium ([Ca2+]i) signaling. An intracellular calcium chelator inhibited both the rapid and sustained activation of CADTK by Ang II and PDGF. Extracellular calcium chelation inhibited the PDGF-stimulated increase in CADTK tyrosine phosphorylation as well as the sustained (but not the early) activation by Ang II. In contrast, p125FAK tyrosine phosphorylation was maximal in quiescent, adherent RSMC and was not affected by incubation with EGTA. Depletion of protein kinase C activity partially inhibited both the Ang II- and PDGF-induced CADTK tyrosine phosphorylation. Additional results confirm a relation between CADTK and the cytoskeleton. First, the tyrosine phosphorylation of paxilin correlated with activation of CADTK; this increase was inhibited by EGTA. Second, cytochalasin D blocked the PDGF- or Ang II-stimulated tyrosine phosphorylation of CADTK, suggesting a role for the cytoskeleton in agonist-dependent CADTK activation. Third, immunofluorescence analysis of CADTK localization demonstrated actin-like cytoskeleton staining extending into focal contacts. These results suggest that in mesenchymal cells, CADTK is localized to and activated by an actin cytoskeleton-dependent mechanism; a mechanism that is regulated in a calcium and protein kinase C-dependent manner independently of p125FAK.

Angiotensin II↗

Analysis of titanium dental implants after failure of osseointegration: combined histological, electron microscopy, and X-ray photoelectron spectroscopy approach.

A multitechnique approach has been used to characterize the surface of nonosseointegrated titanium implants and the surrounding biological tissues. Five pure titanium dental implants were used as reference, and 25 removed implants were studied. Surface and in-depth chemical compositions of the implants (from a total of 16 patients) were investigated by X-ray photoelectron spectroscopy (XPS). Histological slides of the surrounding tissues were examined by light microscopy, XPS, and electron microprobe analysis. None of the failed implants presented the regular surface composition and depth profile of the TiO2 overlayer; foreign elements (Ca, Na, P, Si, Cl, Zn, Pb, and Al) were observed on some implants. Fibrosis, lymphocytic and plasmocytic infiltrates, and granulomatous lesions were detected in the surrounding tissues. XPS and electron microprobe analysis indicated the presence of Zn, Fe, Sn, and Ti in the tissues. As a possible scenario for implant failure, we propose and discuss a oxidoreduction mechanism, leading to a partial dissolution or the complete dissociation of the protective titanium dioxide overlayer and to ion diffusion through the surrounding tissues.

Connective Tissue↗

Synaptic distribution of GluR2 in hippocampal GABAergic interneurons and pyramidal cells: a double-label immunogold analysis.

GluR2 is the regulatory subunit in the AMPA family of glutamate receptors (GluRs) in that its presence inhibits calcium flux and dominates the current/ voltage characteristics of AMPA receptors. Studies from other laboratories have shown that GABAergic interneurons have a lower ratio of GluR2/GluR1 mRNA than pyramidal cells as well as possessing AMPA receptors that have a higher relative permeability to calcium. We hypothesized that such differences might be related to differences in the subunit stoichiometry at the AMPA synapses in each cell class, and used a GluR2-specific monoclonal antibody in a double-label immunogold protocol with anti-GABA and anti-CaM kinase II to compare the GluR2 representation at asymmetric synapses in GABA neurons to that of pyramidal cells in rat CA1. Virtually all CA1 pyramidal cells as well as the majority of GABAergic interneurons were GluR2 positive. EM immunogold labeling also showed that GABAergic interneurons had distinctive ultrastructural features and contained GluR2 in both their soma and their dendrites, as did the spines and shafts of pyramidal cells. GluR2 immunoreactivity was frequently preferentially located at asymmetric synapses on both pyramidal cell spines and shafts as well as the dendritic processes and soma of GABAergic interneurons. However, the labeled synapses on GABAergic neurons had a significantly lower number of immunogold particles than those on pyramidal cells. In fact, 90% of the labeled asymmetric synapses on GABAergic cells had one to three gold particles, whereas greater than 70% of the labeled asymmetric synapses on pyramidal cells had four or more gold particles associated with the synapse. These data suggest that while both cell classes contain GluR2, they differ in the relative representation of GluR2 at their AMPA synapses, such that GABAergic neurons might possess AMPA receptors with higher calcium permeability on average than pyramidal cells. Such differences in subunit representation at AMPA-receptor-mediated synapses would not only lead to differences in calcium permeability and functional characteristics across these two cell classes, but might also be relevant to the hippocampal patterns of selective vulnerability with respect to excitotoxicity and neurodegeneration.

Animals↗

Differential localisation of the metabotropic glutamate receptor mGluR1a and the ionotropic glutamate receptor GluR2/3 in neurons of the human cerebral cortex.

Specimens of human cerebral cortex were obtained during neurosurgical operations and studied by immunocytochemistry and electron microscopy, using antibodies to the metabotropic glutamate receptor subunit mGluR1a and the ionotropic glutamate receptor GluR2/3. A small number of non-pyramidal neuronal cell bodies were labelled for mGluR1a. Double immunolabelling with mGluR1a and GluR2/3 showed that most pyramidal cell bodies were labelled for GluR2/3 but not for mGluR1a. Despite the non-colocalisation of these two receptor subtypes in cell bodies, however, many dendrites and dendritic spines were double-labelled for mGluR1a and GluR2/3 at electron microscopy. As there is evidence that most neurons positive for GluR2/3 are pyramidal cells, this suggests that mGluR1a is present in dendrites of pyramidal neurons, despite absent or low levels of immunoreactivity in their cell bodies.

Adolescent↗

Immunofluorescence study of a muscle biopsy from a 1-year-old patient with Walker-Warburg syndrome.

A previous study of two patients with Walker-Warburg syndrome (WWS) showed a severe deficiency of the extracellular matrix protein laminin beta2 chain and alpha-sarcoglycan (adhalin) in skeletal muscle fibers. More recently, however, other researchers have shown that in their WWS patients the expression of the laminin beta2 chain and alpha-sarcoglycan was normal. Here we describe a 1-year-old boy affected with WWS. We performed immunohistochemical studies on a muscle biopsy from this patient using monoclonal antibodies against dystrophin, dystrophin-associated glycoproteins and several proteins of the extracellular matrix. We confirm previously reports as far as the diminished expression of laminin beta2 chain and alpha-sarcoglycan is concerned. The expression of some other laminins was unusual, whereas the expression of collagen IV and VI was normal. These results suggest that complex syndromes like WWS are quite heterogeneous, although they might represent variant expressions of a single pathological entity.

Biopsy↗

Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.

BACKGROUND: The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority. RESULTS: The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified. CONCLUSIONS: The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.

Animals↗

The cultural context of caregiving: a comparison of Alzheimer's caregivers in Shanghai, China and San Diego, California.

BACKGROUND: Systematic comparisons of the psychological and physical responses of caregivers of Alzheimer's disease (AD) patients in the US and China have not been previously reported. METHODS: Informal caregivers of community dwelling AD patients in Shanghai, China and demographically-matched non-caregiving Chinese controls were compared with a sample of American caregivers residing in San Diego, California and demographically-matched American controls. RESULTS: Despite some demographic discrepancies, caregivers from both China and the US were similar. Caregivers from both cultures reported more depressive symptoms and more physical symptoms when compared with non-caregivers. Both groups of caregivers reported that patients required similar amounts of care and help with activities of daily living (ADLs). However, Shanghai caregivers reported less access to emotional support when compared with the San Diego sample. A conceptual model, guided by the stress process model of Pearlin et al. (1990), was used to explore multivariate relationships between caregiver characteristics and the physical and psychological health of our sample of AD caregivers in Shanghai, China. Results from a path analytical procedure revealed that the relationships among these variables and health outcome did not differ significantly from those observed in the US sample. CONCLUSIONS: Although elderly family members are venerated in the stereotypical Chinese family unit, and informal caregiving of disabled family members is socially mandated, the negative health consequences of caregiving appear to be similar to those observed among caregivers in the US.

Aged↗

Identification of proteinase 3 as the major caseinolytic activity in acute human wound fluid.

Wound fluid contains several proteinases that are important in the repair process. In this study, we analyzed caseinolytic activity in wound fluid obtained from acute (burn) wounds. Caseinolytic activity in wound fluid increased markedly 2 d after injury and appeared on casein zymographs as a series of bands or a smear ranging from 30 to 100 kDa. Most of the enzyme activity was inhibited by the synthetic human neutrophil elastase inhibitor MDL 27,367 but not by the naturally occurring inhibitor of elastase, human secretory leukoproteinase inhibitor. Fractionation of wound fluid indicated that a single enzyme accounted for approximately 80% of the caseinolytic activity. This enzyme degraded the elastase substrate methoxysuccinyl-ala-ala-pro-val-p-nitroanilide at a slow rate. The above findings suggested that the enzyme responsible for caseinolytic activity might be proteinase 3, an elastase-related enzyme whose physiologic functions are poorly understood. Consistent with the above possibility, we found that monoclonal antibodies against proteinase 3 removed caseinolytic activity from wound fluid, and that purified proteinase 3 had a similar caseinolytic profile and inhibitor sensitivity to burn fluid.

Antibodies, Monoclonal↗

A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation.

Vascular endothelial growth factor (VEGF) is a potent secreted factor that promotes angiogenesis and maintains the integrity of the endothelium. Levels of VEGF are increased in many tumors and are elevated in women with pre-eclampsia, a serious disease of pregnancy. Here we show by in situ hybridization that the trophoblast contains the mRNA encoding a soluble version of the VEGF receptor known as Flt-1 (sFlt-1: initially described by Kendall and Thomas, PNAS 90:10705-10709). Binding assays and Western blotting of villus-conditioned media confirmed the production of sFlt-1. Serum from pregnant women was found to contain a VEGF-binding protein that was not present in serum from men or nonpregnant women. As determined by heparin affinity, column fractionation, and cross-linking, this protein was identical to sFlt-1. Taken together, these results show that the placenta secretes sFlt-1, which would be expected to be a VEGF antagonist. This is the first report of production of the sFlt-1 receptor in vivo, and it reveals a new mechanism for naturally regulating this potent angiogenic agent. The presence of such an antagonist suggests that regulation of VEGF action is essential to successful pregnancy. This has important implications for the activity of VEGF locally and systemically in other conditions.

Blotting, Western↗

Group psychoeducation of relatives of schizophrenic patients: two-year experiences.

In order to assess the feasibility and acceptability of group psychosocial education for the relatives of schizophrenics in the community, a 2-year project was carried out in two cities: Jinan and Shanghai, China. The completed sample included 682 cases in the experimental group and 366 cases in the control group. The experimental group received group psychotherapy including 14 lectures and five group discussions with conventional services, and the control group had conventional services only. The annual relapse rate in the experimental group was much lower than that in the control group (17.6 and 23.2%, P < 0.01) and the rate of regular work in the experimental group was higher than that in the control group (37.5 and 30.0%, P < 0.05). At the end of the second year, the relatives in the experimental group had less care burden, better mental and physical health status and more knowledge of caring for schizophrenics than those in the control group. This approach was well accepted by both mental health workers and relatives of schizophrenics and the rate of drop-out was 18.4% only during the 2-year period.

Adult↗

PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.

Classical congenital muscular dystrophy with merosin deficiency is caused by mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the introns flanking the 64 LAMA2 exons was carried out and, based on these sequences, oligonucleotide primers were designed to amplify the coding region of each exon separately. By PCR-SSCP analysis, we identified eight new mutations in nine families originating from various countries. All induced a premature truncation of the protein, either in the short arm or in the globular C-terminal domain. A 2 bp deletion in exon 13, 2098delAG, was found in three French non-consanguineous families and a nonsense mutation of exon 20, Cys967stop, in two other non-consanguineous families originating from Italy. Determination of rare intragenic polymorphisms permitted us to show evidence of founder effects for these two mutations suggesting a remote degree of consanguinity between the families. Other, more frequent polymorphisms, G to A 1905 (exon 12), A to G 2848 (exon 19), A to G 5551 (exon 37), and G to A 6286 (exon 42), were used as intragenic markers for prenatal diagnosis. This study provides valuable methods for determining the molecular defects in LAMA2 causing merosin deficient congenital muscular dystrophy.

Child↗

Regulation of leptin promoter function by Sp1, C/EBP, and a novel factor.

Leptin is a hormone produced in adipose cells that regulates energy expenditure, food intake, and adiposity. To understand leptin's transcriptional regulation, we are studying its promoter. Four conserved and functional regions were identified. Mutations in the C/EBP and TATA motifs each caused an approximately 10-fold decrease in promoter activity. The C/EBP motif bound recombinant C/EBP alpha and mediated trans-activation by C/EBP alpha, -beta, and -delta. Mutation of a consensus Sp1 site reduced promoter activity 2.5-fold and abolished binding of Sp1. Mutation of a fourth factor-binding site, denoted LP1, abolished protein binding and reduced promoter activity 2-fold. Factor binding to the LP1 motif was observed with adipocyte, but not with nonadipocyte extracts. Adipocytes from fa/fa Zucker rats transcribed the reporter plasmids more efficiently than did control adipocytes. No effect on the transient expression of leptin was noted upon treatment with a thiazolidinedione, BRL49653, or upon cotransfection with peroxisome proliferator-activated receptor-gamma/retinoid X receptor-alpha or sterol response element-binding protein-1. Mutations of the Sp1, LP1, and C/EBP sites in pairwise combinations diminished promoter activity to the extent predicted assuming these motifs contribute independently to leptin promoter function. Our identification of motifs regulating leptin transcription is an important step in the elucidation of the mechanisms underlying hormonal and metabolic regulation of this gene.

Adipocytes↗

[Determination of cyanide in whole blood by completely differential spectrophotometry].

This paper introduced a method for the determination of cyanide in whole blood by completely differential spectrophotometry with pyridine-pyrazolone method after stabilization by addition of silver sulfate and separation by distillation. The analytical results showed a precision 5.4% (n = 6) for the determination of 0.068 microgram.ml-1 CN- in whole blood. The average recovery was 97.4%. This method was successfully used for the determination of cyanide in whole blood of non-smokers and smokers.

Cyanides↗

[The evaluation of computer cytological test with colposcopy for the diagnosis of cervical lesions].

OBJECTIVE: To assess the value of computer cytological test (CCT) with colposcopy for the diagnosis of early cervical diseases. METHODS: 3,016 cervical pap smears have been done in our hospital from March 15, 1995 to March 15, 1996. The CCT smears were analyzed first, then cytologist made the final reports, cervical biopsies under the guidance of colposcopy were taken in 56 cases with abnormal findings. RESULT: We found 375 (12.4%) abnormal pap smears out of 3,016 cases, in which cervical squamous cancer 5 cases, endometrium adenocarcinoma 1 case. The low grade squamous intraepithelial lesion (LSIL) and human papilloma virus (HPV) infection most frequently happened at the younger patients. There are 59 cases (2.0%) of LSIL, among which HPV infection accounted 79.7%. We use CCT for primary selection, its sensitivity is 98.9% specificity is 90.9%. CONCLUSION: Sexually transmitted diseases is closely related to cervical early disease. CCT should be done in the younger women, especially high-risk patients. Positive cases of CCT must be examined by colposcopy and pathological biopsy, this is the best way to diagnosis cervical disease.

Adolescent↗

[Relationship between health status and work ability among elderly Al exposed workers].

In this study, health status and work ability of 80 elderly male workers exposed to aluminum (Al) were assessed by physiological and neurobehaviral tests. The results showed that workers with cardiovascular or respiratory diseases had lower work ability index(WAI). Vital capacity and musculoskeletal function index(MSFI) were correlated closely with work ability. Mental performance capacity decreased with the increasing of age, and mental performance score was associated with work ability. It is suggested that vital capacity and MSFI may serve as index reflecting physical work ability of Al-exposed workers. Simple reaction time, visual memory, manual dexterity and pursuit aiming may reflect mental work ability.

Adult↗

[Identification and determination of Shenbaiye].

This study was amied at the method of identifying and determining Shenbaiye so that a ground can be provided for the quality requirements. Three Chinese materia medica (Radix Sophorae flavescentis, I; Cortex Phellodendri, II; Rhizoma Atractylodis, III) of Shenbaiye were identified by means of TLC successfully. The method in detail and the chromatogram were presented. The determination of I in Shenbiaye was carried out by solid phase cleaned-up and separated through neutral alumine column (10 x 1 cm i.d.) eluting with chloroform. This eluent was extracted with sulphuric acid (0.01 mol/L) and the excess of acids was titrated with sodium hydroxide (0.02 mol/L) using the methyl red as an indicator. The total alkaloid content of I was calculated as matrine of I in Shenbaiye. This method was established with a precision of 1.10% (n = 5) and the recoveries of 97.59 +/- 1.28% (n = 8). The results of determination of samples were reported.

Alkaloids↗