PubMed Health⌕ Search

Biomedical subjects

Y Sun

Publications and source records attributed to Y Sun.

At least 721 records · Page 40Linked to original sources
PubMed1996

Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.

A patient with Prader-Willi syndrome (PWS) was found to carry a de novo balanced reciprocal translocation, t(15;19)(q12;q13.41), which disrupted the small nuclear ribonucleoprotein N (SNRPN) locus. The translocation chromosome 15 was found to be paternal in origin. Uniparental disomy and abnormal DNA methylation were ruled out. The translocation breakpoint was found to have occurred between exon 0 (second exon) and 1 (third exon) of the SNRPN locus outside of the SmN open reading frame (ORF), which is intact. The transcriptional activities of ZNF127, IPW, PAR-1, and PAR-5 were detected with RT-PCR from fibroblasts of the patient, suggesting that these genes may not play a significant role in the PWS phenotype in this patient. Transcription from the first two exons and last seven exons of the SNRPN gene was also detected with RT-PCR; however, the complete mRNA (10 exons) was not detected. Thus, the PWS phenotype in the patient is likely to be the result of disruption of the SNRPN locus.

Autoantigens↗
PubMed1996

The repertoire of human antibodies to the carbohydrate capsule of Streptococcus pneumoniae 6B.

Antibodies to Streptococcus pneumoniae 6B capsular polysaccharide (PS) induced with a 23-valent PS vaccine among 25 adults were examined. The magnitude of antibody responses among different subjects was highly correlated with the amount of anti-6B antibodies expressing IgG (r = 0.98) and lambda (r = 0.93) isotypes. Most individuals produced one or two dominant IgG antibody clones as identified by their isoelectric points. Two antibody clones with unique amino acid sequences could be readily purified, and the sequences of their light chains match those of A1/A17 V kappa and hslv2046 V lambda genes. Anti-6B antibodies isolated from different subjects used various VL genes and differed in their cross-reactivity with 6A PS. An isoelectric focusing study suggests that some IgG antibodies induced with 6B PS bind 6A PS with lower avidity.

Amino Acid Sequence↗
PubMed1996

The role of the gene 71 product in the life cycle of equine herpesvirus 1.

Equine herpesvirus type 1 (EHV-1) gene 71 encodes a heavily O-glycosylated 192 kDa protein with no identified herpesvirus homologue. Isolation of a deletion mutant in gene 71 (ED71) demonstrated that its protein product is not essential in vitro. To investigate the role of the gene 71 protein in the virus life cycle, ED71 has been characterized in vitro in terms of cellular adsorption, penetration, egress and transmission compared to wild-type and revertant virus. ED71 virions adsorbed to cells less efficiently than wild-type and revertant virus with a consequential effect on virus penetration; virus egress was significantly impaired and the timing of release was also delayed. The percentage of both full and empty capsids accumulating in the nuclei of ED71-infected cells was significantly higher than in wild-type virus-infected cells but the most notable differences were the low number of particles and the low ratio of enveloped to unenveloped capsids in the cytoplasm. The primary mode of transmission of the mutant virus is by direct cell-to-cell spread and the fact that a neutralizing antiserum did not reduce ED71 plaque size, supported the conclusion that deletion of gene 71 impairs the ability of virus to spread via release and readsorption to uninfected cells. Thus, deletion of EHV-1 gene 71 results in a defect in virus maturation and capsid envelopment. Progeny virus is consequently impaired in adsorption/penetration presumably due to the particles lacking the glycoprotein spikes predicted to be encoded by this gene and hence spreads by direct cell-to-cell contact.

Animals↗
PubMed1996

Leukaemia inhibitory factor induced in the sciatic nerve after axotomy is involved in the induction of galanin in sensory neurons.

Dramatic changes occur in neuropeptide expression in sensory and sympathetic neurons following axonal injury. Based on the finding that the cytokine leukemia inhibitory factor (LIF) plays an important role in mediating these changes in sympathetic neurons, its participation in triggering changes in sensory neurons was examined. By the use of transgenic mice in which the LIF gene had been knocked out, LIF was found to contribute to the induction of galanin expression in dorsal root ganglia (DRG) after sciatic nerve lesion. On the other hand, two other neuropeptide changes that occur in DRG under these conditions, the reduction of substance P and induction of neuropeptide Y, were independent of LIF expression. In the sympathetic superior cervical ganglion, transection of the postganglionic nerves close to the ganglion resulted in a rapid induction of LIF mRNA in the ganglion and in the lesioned nerve trunk. In contrast, transection of the sciatic nerve close to or distant from the DRG caused a rapid induction of LIF mRNA in the lesioned nerve, but not in the DRG. DRG were capable of making substantial amounts of LIF mRNA when placed in explant cultures, but, in vivo, only a slight induction was found even when both central and peripheral nerve processes of these sensory neurons were transected. These latter observations suggest that, in contrast to the superior cervical ganglia, the DRG environment inhibits the lesion-induced expression of LIF in vivo and/or explanted DRG produce stimulatory signals not found in vivo. Together with the data on the induction of galanin, these observations provide evidence that LIF, generated at a site at some distance from the ganglion, is involved in triggering part of the cell body reaction in sensory neurons.

Animals↗
PubMed1996

Mechanism of UVB-induced suppression of the immune response to Mycobacterium bovis bacillus Calmette-Guerin: role of cytokines on macrophage function.

Previously we demonstrated that treatment of mice with either UVB radiation or supernatants derived from UVB-irradiated PAM 212 keratinocytes decreased the induction of the delayed-type hypersensitivity (DTH) response to Mycobacterium bovis bacillus Calmette-Guerin (BCG), impaired the clearance of bacteria from their lymphoid organs and also altered macrophage functions. In order to characterize the cytokines involved in these phenomena, UV-irradiated mice were injected with antibodies to interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-beta 1), or tumor necrosis factor-alpha (TNF-alpha). Injection of UVB-irradiated mice with anti-IL-10 immediately after UV irradiation restored the DTH response and reversed the UV-induced inhibition of bacterial clearance. Injection of UV-irradiated mice with anti-TGF-beta only partially restored the DTH response although it allowed a better clearance of BCG than injection of mice with the control antibody. In contrast, injection of anti-TNF-alpha did not affect the UVB-induced suppression of DTH or impaired bacterial clearance. Similarly, the ability of macrophages to phagocytose BCG and kill the intracellular organisms was restored to almost normal levels after injecting UV-irradiated mice with antibodies specific for IL-10 or TGF-beta. Injection of mice with either recombinant IL-10 or TGF-beta mimicked the effect of whole-body UV irradiation on immune function. These results suggest that IL-10 has a major role in UV-induced suppression of both DTH to BCG and impairment in the clearance of bacteria and that TGF-beta has a more significant role in blocking bacterial clearance. Furthermore, these cytokines seem to modulate immune responses by altering macrophage functions in UVB-irradiated mice.

Animals↗
PubMed1996

Complex chromosomal mechanisms lead to APRT loss of heterozygosity in heteroploid cells.

Loss of the wild-type allele of a tumor suppressor gene, or loss of heterozygosity (LOH), is one of the most important mechanisms of carcinogenesis. Adenine phosphoribosyltransferase (APRT) has been used as a surrogate marker for tumor suppressor genes. We have previously shown that APRT deficiency in an APRT heterozygous human cell line, MR12-1, was predominantly caused by the loss of the remaining wild-type allele. Here we report the characterization of the chromosomal pathways leading to LOH in four clones derived from this heteroploid cell line. We performed karyotype analysis, chromosome 16-specific painting, and fluorescence in situ hybridization with an APRT-containing cosmid on these clones and their heteroploid parental cells. Our findings suggest that LOH occurs in tetraploid as well as diploid cells, and that diploid cells with LOH may undergo endoreduplication to attain tetraploidy. Our results also suggest that, in addition to LOH being caused by a single event (such as mitotic recombination or deletion), LOH may be caused by a combination of sequential events, such as mitotic recombination or translocation followed by chromosome loss. The instability of the genomes of the parental cells may have provided a greater diversity of options for genetic evolution. Similar karyotypic evolution may occur at late stages of carcinogenesis in vivo.

Adenine Phosphoribosyltransferase↗
PubMed1996

Ultrasonographic study and long-term follow-up of Takayasu's arteritis.

BACKGROUND AND PURPOSE: Takayasu's arteritis is an inflammatory vasculopathy involving the aorta and its major branches. Little information is available on the natural history and temporal profile of changes in the carotid vessels, the major vessels involved in Takayasu's arteritis. Duplex ultrasonography may provide a reliable and efficient tool for the characterization and follow-up of the brachiocephalic vascular changes in Takayasu's arteritis. METHODS: Sixteen female patients fulfilling the clinical diagnostic criteria for Takayasu's arteritis were studied. Mean age at onset was 23.6 years (SD = 6.0), and mean duration of follow-up was 17.1 years (SD = 11.9). The clinical features were analyzed. Only one patient had had a stroke. They had undergone at least one duplex scanning examination to evaluate the brachiocephalic vessels, including the extracranial carotid, vertebral, and subclavian arteries. Six patients underwent sequential duplex examination and long-term clinical follow-up. RESULTS: All the studied patients had subclavian artery involvement, and 11 (69%) had common carotid artery involvement. The percentage of bilateral concomitant involvement was 100% in the common carotid artery and 33% in the subclavian artery. Homogeneous circumferential intima-media thickening was commonly seen in stenotic common carotid arteries (89%). Four patients had internal carotid artery involvement (all on the left side). In the serial duplex follow-up study, 2 of 6 patients had progressive vascular stenosis with concentric thickening, rather than longitudinal spreading, in the bilateral common carotid arteries. Left-side lesions were more prominent. Most were clinically stationary, despite severe stenosis or occlusion of the common carotid arteries. CONCLUSIONS: The characteristic vascular lesions and progression changes in Takayasu's arteritis detected by duplex ultrasonography are quite different from those seen in ordinary atherosclerosis. Homogeneous circumferential intima-media thickening of the common carotid arteries is a highly specific ultrasonographic finding in patients with Takayasu's arteritis, particularly young women. Sequential duplex scanning showed vascular progression to be unpredictable and unrelated to medication in our patients. Further clinical investigations of vascular progression are warranted, and duplex scanning may provide a simple, safe, and accurate long-term means of follow-up.

Adolescent↗
PubMed1996

Turnover and distribution of intravenously administered mannose-terminated human acid beta-glucosidase in murine and human tissues.

Gaucher disease type 1, the most prevalent lysosomal storage disease, is caused by the defective activity of the lysosomal enzyme, acid beta-glucosidase, or glucocerebrosidase. Infusion of purified acid beta-glucosidase containing alpha-mannosyl-terminated oligosaccharides (alglucerase) is efficacious in reversing hematologic, hepatic, splenic, and bony disease manifestations. The murine tissue distribution and turnover of bolus injections of alglucerase was evaluated by enzymatic activity, quantitative cross-reacting immunologic material analyses, and immunofluorescence studies. Enzyme activity measurements detected distribution to liver, spleen, thymus, kidney, and bone marrow mononuclear cells, but not to lungs and brain. In kidney and thymus, the enzyme was transiently present. In liver and spleen, enzyme activity peaked at about 20 min postinjection followed by a biphasic decrease with t1/2 approximately 40-60 min and approximately 12-14 h. In bone marrow maximal enzyme activity was at 40-60 min with a disappearance t1/2 approximately 60 min. Quantitative cross-reacting immunologic material studies of liver and spleen showed delivery of enzyme with decreased catalytic rate constants whose degradation included denaturation and proteolytic components. By immunofluorescence the human enzyme was distributed primarily to reticuloendothelial cells of the liver and spleen. In autopsy material from a Gaucher disease type 2 patient treated with enzyme, immunohistochemical and activity studies showed distributions similar to those in mice. These studies indicate a complex delivery and intracellular degradation of acid beta-glucosidase with lower intrinsic activity than the administered therapeutic agent.

Animals↗
PubMed1996

Cells expressing angiotensin II receptors in fibrous tissue of rat heart.

OBJECTIVE: Following left coronary artery ligation, markedly increased angiotensin II (AngII) receptor binding appears at the site of myocardial infarction (MI). This is also true for the fibrosed visceral pericardium in rats following pericardiotomy (with or without MI). Cells expressing AngII receptors at these sites remain unknown. In the present study, we sought to identify cells expressing AngII receptors at these sites of fibrosis in the rat heart during both early and late stages of wound healing. METHODS: MI was created by left coronary artery ligation. Sham operation included thoracotomy, pericardiotomy and placement of silk ligature around the left coronary artery without MI. Hearts were collected at postoperative week 1 and 4. In serial sections: autoradiography (125I[Sar1,Ile8]AngII) was used to determine cells expressing AngII receptors; hematoxylin-eosin and alpha smooth muscle actin were used for identification of cell morphology and phenotype, respectively; and picrosirius red for identification of fibrillar collagen. RESULTS: (1) at week 1, necrotic tissue at the site of MI was surrounded by granulation tissue that included macrophages, alpha smooth muscle actin fibroblast-like cells, or myofibroblasts, fibrillar collagen, and new vessels; (2) at week 4, scar tissue had formed and remaining cells were primarily myofibroblasts; (3) pericardial fibrosis was evident at weeks 1 and 4 and contained myofibroblasts, not macrophages or new vessels; (4) at week 1 and 4 myofibroblasts were the predominant cell expressing high-density AngII receptors at the site of MI, while fibroblasts, macrophages and vessels demonstrated low-density AngII receptor binding; and (5) at weeks 1 and 4, myofibroblasts express high-density AngII receptor binding in pericardial fibrosis. CONCLUSION: In a rat model of tissue repair involving either MI or pericardial fibrosis, increased AngII receptor expression is primarily associated with myofibroblasts. This suggests AngII may play a role in mediating the fibrogenic response provided by this wound healing cell at sites of tissue injury in the rat heart.

Angiotensin II↗
PubMed1996

[Synthesis and activities of fragments of inhibin alpha subunit].

For further investigation of inhibin which is available only by laborious isolation, four fragments of inhibin alpha subunit (7-28, 37-65, 1-32, Y-1-32) were prepared by solid phase peptide synthesis using the Fmoc strategy. The effects of these fragments on progesterone production of rat corpus luteal (CL) cells in vitro were examined. The results indicate that these four fragments induced significant decrease of basic progesterone production.

Amino Acid Sequence↗
PubMed1996

Carboxyl-terminal mutations of Gq alpha and Gs alpha that alter the fidelity of receptor activation.

The carboxyl terminus of the G protein alpha subunit is a key determinant of the fidelity of receptor activation. We have previously shown that the Gq alpha subunit (alpha q) can be made to respond to alpha i-coupled receptors by replacing its carboxyl terminus with the corresponding alpha i2, alpha o, alpha z residues. We now extend these findings in three ways: 1) carboxyl-terminal mutations of alpha q/alpha i chimeras show that the critical amino acids are in the -3 and -4 positions, 2) exchange of carboxyl termini between alpha q and alpha z allows activation by receptors appropriate to the carboxyl-terminal residues, and 3) we identify receptors that either do or do not activate the expected carboxyl-terminal chimeras (alpha q/alpha i, alpha q/alpha s, alpha s/alpha q). Replacement of the five carboxyl-terminal amino acids of alpha q with the alpha s sequence permitted an alpha s-coupled receptor (the V2 vasopressin receptor but not the beta 2-adrenergic receptor) to stimulate phospholipase C. Replacement of the five carboxyl-terminal amino acids of alpha z with residues of alpha q permitted certain alpha q-coupled receptors (bombesin and V1a vasopressin receptors but not the oxytocin receptor) to stimulate adenylyl cyclase. Thus, the relative importance of the G alpha carboxyl terminus in permitting coupling to a new receptor depends on the receptor with which it is paired. These studies refine our understanding and provide new tools with which to study the fidelity of receptor/G alpha activation.

Animals↗