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X Ye

Publications and source records attributed to X Ye.

At least 163 records · Page 9Linked to original sources
PubMed1997

Adenovirus-mediated in vivo gene transfer rapidly protects ornithine transcarbamylase-deficient mice from an ammonium challenge.

The purpose of this study was to determine the time of onset, duration, and the efficacy of in vivo gene transfer in protecting the ornithine transcarbamylase deficient spf/Y mouse from an acute ammonium challenge. The animals were challenged with ammonia (10 mmol/kg NH4Cl) 1, 2, 7, 14, or 28 d after the administration of a recombinant adenoviral construct deleted in E1 and with a temperature sensitive mutation in E2. Although there was no protection with the control LacZ virus, the ornithine transcarbamylase (OTC)-containing vector provided partial protection from both behavioral symptoms (ataxia, seizures, and abnormal response to sound) and biochemical abnormalities (ammonium, aspartate, alanine, and glutamine) within 24 h and complete protection by 48 h. Mortality was also decreased. Animals receiving the vector 7 and 14 d before the ammonium load were also protected, whereas those treated 28 d before the challenge were not. OTC enzyme activity in liver of untreated spf/Y mice was 5% of control C3H mice. After gene transfer, activity was increased to near control levels through 14 d but had returned to baseline by 28 d. These studies indicate that adenovirus-mediated gene transfer confers a metabolic benefit within 24 h of administration and provides protection against an acute metabolic insult for at least 2 wk.

Adenoviridae↗
PubMed1997

The 139H scrapie agent produces hypothalamic neurotoxicity and pancreatic islet histopathology: electron microscopic studies.

Neuronal degeneration, along with astrocytosis, spongiform vacuolation, and amyloid (PrPSc) formation, have long been regarded as neuropathological hallmarks of transmissible spongiform encephalopathies (TSEs). In animals, these diseases include; scrapie, transmissible mink encephalopathy, chronic wasting disease, bovine and feline spongiform encephalopathies, and in humans; kuru, Creutzfeldt-Jakob disease (CJD), and Gerstmann-Sträussler-Scheinker syndrome (GSS). The abnormal amyloid protein, (PrPSc) is toxic to neurons. Our previous studies showed that hamsters treated with 139H scrapie strain developed obesity, and generalized endocrinopathy, including lesions in hypothalamus, pituitary and pancreas. Histochemical and immunocytochemical studies revealed extensive pathological changes in the islets of Langerhans in 139H-infected hamsters, but not in hamsters infected with 263K scrapie strain. Using routine electron microscopy (EM), we have observed more details of lesions in the beta cells of islets of Langerhans in these animals. Cytoplasmic vacuolation occurred, cytoplasmic organelles were found damaged and disrupted, and membranes were occasionally ruptured. The width of endoplasmic reticulum (ER) lumina were 50-150 nm in controls, whereas in 139H-infected hamsters, they wee occasionally increased up to 4000 nm in diameter. Most beta cells showed degranulation. These EM observations suggest that the cellular death seen in the islets of Langerhans in 139H-infected hamsters is due to necrosis, not apoptosis. Since there were no amyloid deposits found in the islet of Langerhans at the EM level, and there were extremely low scrapie infectivity levels and PrPSc levels in pancreas, it is suggested that the changes noted in pancreas were not a direct toxic effect of PrPSc. Instead, our study suggests that scrapie prion protein PrPSc, acting as a neurotoxicant, alters the hypothalamic neuroendocrine regulation of the pancreas.

Animals↗
PubMed1997

[One-day bowel cleaning for colorectal surgery].

A modified one-day preoperative bowel cleaning was used in patients undergoing surgery for colorectal cancers. It was compared with traditional three-day bowel preparation, 48 patients without obstruction were randomized to two groups, with 24 each. Modified one-day method was used in experimental group, and traditional three-day method was used in control group. No significant changes were found in plasma electrolytes, hemoglobin end hematocrit in both groups. The intraoperative bowel cleaning condition were grade I in all patients. Bowel fluid culture was positive in 30% of the experimental patients, whereas in 70% of the contral patients. Wound infection occurred in one patient in both groups (4.2%). It is suggested that the modified one-day preoperative bowel preparation may alleviate the patients' suffering from diahrrea and homeostatic disturbances, ensure them in good sleep and rest, reduce the nursing work, and result in good bowel cleaning for operation. It is a simple, safe, and effective method for preoperative bowel cleaning.

Adult↗
PubMed1997

Comparative induction of oxidative stress in cultured J774A.1 macrophage cells by chromium picolinate and chromium nicotinate.

The concentration-dependent effects of chromium picolinate and chromium nicotinate were assessed on the enhanced production of reactive oxygen species including superoxide anion and hydroxyl radicals, and lipid peroxidation and DNA fragmentation in cultured macrophage J774A.1 cells. The macrophage cells were incubated with 0-50 micrograms/ml [corrected] concentrations of these chromium (III) salts for 0 and 24 hrs at 37 degrees C. Concentration-dependent effects were observed. Lipid peroxidation increased by 1.3-1.5-fold following treatment of these cells with chromium picolinate while at these same concentrations of chromium nicotinate approximately 1.2-1.8-fold increases in lipid peroxidation were observed. Increases of 1.0-1.5-fold occurred in the production of superoxide anion as determined by cytochrome c reduction following treatment with chromium picolinate while with these same concentrations and conditions only 1.1-1.2-fold increases in cytochrome c reduction were observed following treatment with chromium nicotinate. Approximately 1.2-1.5-fold increases in hydroxyl radical production were observed following treatment of these macrophage cells with increasing concentrations of chromium picolinate and chromium nicotinate. Incubation of the cells with 30-50 micrograms/ml concentrations of chromium picolinate produced 1.2-1.6 fold increases in DNA fragmentation, while under these same conditions with chromium nicotinate 1.2-1.3-fold increases in DNA fragmentation occurred. No significant loss in cell viability was observed with either chromium salt. These results demonstrate that incubation of macrophage J774A.1 cells with these chromium salts induces low levels of oxidative stress as demonstrated by the biochemical assay techniques employed in this study.

Cells, Cultured↗
PubMed1997

Retinal capillary pericyte apoptosis in early human diabetic retinopathy.

OBJECTIVE: To investigate the nature of retinal capillary pericyte dropout in early human diabetic retinopathy. METHODS: In the present study, neural retinas of 12 postmortem eyes from 6 patients (3 diabetic and 3 nondiabetic) were first fixed in buffered formaldehyde and then digested with trypsin. The preparations of trypsin-digested retinal blood vessels were stained with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique and then with perdiodic acid-Schiff technique (PAS), and counter-stained with hematoxylin to evaluate DNA fragmentation of cell nuclei and diabetic changes of retinal capillaries. RESULTS: TUNEL-positive apoptotic pericytes were observed in retinal capillaries in all three diabetic patients in this study. The TUNEL-positive pericytes were presented as darker stained cells with PAS-hematoxylin staining. A few TUNEL-positive retinal capillary endothelial cells were discovered in both eyes of one of the three diabetic patients. Neither TUNEL-positive pericytes nor positive endothelial cells were found in the three nondiabetic patients. A variety of typical diabetic microvascular changes were noticeable with PAS-hematoxylin staining in trypsin-digested retinal preparations from diabetic patients. These changes included thickened capillary walls, microaneurysms, "ghost-cell"-appearance of pericytes, acellular segments of capillaries, and a decreased ratio of retinal capillary pericytes to endothelial cells. All of these changes are characteristics of diabetic retinal microangiopathy. CONCLUSIONS: Retinal capillary pericyte apoptosis is a specific form of cell death which occurs during the early development of diabetic retinopathy. The significant decrease in the ratio of pericytes to endothelial cells and the predominant TUNEL-positive pericytes over endothelial cells suggest that a greater impact of apoptosis-related mechanisms occurs in pericytes than in endothelial cells and, thereby, a greater loss of pericytes takes place in early diabetic retinopathy. Apoptosis, therefore, is an important mechanism of pericyte dropout in the early diabetic retinopathy.

Aged↗
PubMed1996

Sequence preference of 7,12-dimethylbenz[a]anthracene-syn-diol epoxide-DNA binding in the mouse H-ras gene detected by UvrABC nucleases.

We have found that 7,12-dimethylbenz[a]anthracene-syn-diol epoxide (syn-DMBADE)-modified DNA fragments are sensitive to UvrABC incision. The incisions occur mainly seven bases 5' and four bases 3' of a syn-DMBADE-modified adenine or guanine residue. The kinetics of UvrABC incision at different sequences in a DNA fragment are the same, and the extent of UvrABC incision is proportional to the syn-DMBADE concentration. On the basis of these results, we have concluded that UvrABC incision on syn-DMBADE-DNA adducts is independent of DNA sequence and is quantitative. Using the UvrABC incision method, we have analyzed the syn-DMBADE-DNA binding spectrum in several defined DNA fragments, including the first two exons of the mouse H-ras gene. We have found that both guanine and adenine residues in codons 12, 13, and 61 of the H-ras gene are strong syn-DMBADE binding sites. These results suggest that the initial binding of DMBADE may greatly contribute to the frequency of H-ras mutations. Results from dinucleotide binding analysis indicate that the 5'-nearest neighbor displays a greater effect on syn-DMBADE-DNA binding than the 3'-nearest neighbor.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Prolonged metabolic correction in adult ornithine transcarbamylase-deficient mice with adenoviral vectors.

A murine model of ornithine transcarbamylase (OTC) deficiency was used in this study to evaluate the efficacy of recombinant adenoviruses for correcting the metabolic defect in liver. Recombinant adenoviruses deleted in E1 and containing a human OTC cDNA expressed little functional OTC enzyme in vivo and had no observable impact on the underlying metabolic abnormalities of the OTC-deficient mouse (i.e. elevated urinary orotate and serum glutamine). E1-deleted vectors were improved through the use of the strong constitutive promoter from cytomegalovirus driving the normal murine homolog of OTC cDNA and the ablation of E2a with a temperature-sensitive mutation. Infusion of this improved vector into the mouse model was associated with a complete normalization of liver OTC enzyme activity that persisted for at least 2 months with complete but transient correction in serum glutamine and urine orotic acid. These studies illustrate the utility of improved adenoviral vectors in the treatment of liver metabolic disease.

Adenoviridae↗
PubMed1996

Autoimmune diabetes-prone NOD mice express the Lyt2 alpha (Lyt2.1) and Lyt3 alpha (Lyt3.1) alleles of CD8.

Predisposition to Type I insulin-dependent diabetes (IDD) has a strong underlying genetic basis involving class II major histocompatibility complex (MHC) genes as well as several non-MHC genetic systems. In the non-obese diabetic (NOD) mouse, a model for human IDD, genes associated with the appearance of immune cell infiltrates in the pancreatic islets (insulitis) and/or overt IDD have been mapped to chromosomes 1, 3, 6, 11, and 17. A recent report has suggested that CD8+ lymphocytes of the NOD mouse might be deficient in the expression of the CD8 beta molecule, a protein encoded by a gene on chromosome 6. The CD8 beta molecule is a T-cell surface marker, the lack of which could affect selection in the thymus, possibly permitting auto-reactive T-cell clones to populate the peripheral lymphoid tissues. For this reason, we examined the expression of the CD8 molecule by lymphocytes in the NOD mouse. Results indicate that the NOD mouse is not deficient in its transcription of detectable mRNA encoding either the CD8 alpha or beta subunits. However, the NOD mouse expresses the Lyt2 alpha and Lyt3 alpha alleles, suggesting that a portion of chromosome 6 centromeric to the diabetes-susceptibility genetic region is derived from an ancestry common to AKR and, like AKR, the CD8 alpha and CD8 beta 3.1 (but not CD8 beta 3.2) subunits are detected on the cell surface of T lymphocytes of the NOD mouse. Interestingly, though, the CD8 beta 3.1 molecule may not be expressed in the NOD mouse to the same extent as it is expressed in the AKR/J mouse, suggesting the possibility that the NOD mouse possesses a defect somewhere between transcription and cell surface expression of the CD8 beta molecule.

Alleles↗
PubMed1996

Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from high to low glucose levels: a comparative study with retinal capillary endothelial cells.

A number of clinical observations concerning cases of glycemic fluctuation have prompted us to study whether or not a rapid change in blood glucose concentration can aggravate retinal microvascular pathology during the early stage of diabetic retinopathy. We conducted a comparative study of retinal capillary pericytes and endothelial cells in vitro. Both types of cells, either in single culture or in co-culture, were initially incubated in medium with high glucose (20-40 mmol/l), followed by a rapid reduction of glucose to 3.5, 1, or 0.5 mmol/1. This type of reduction of extracellular glucose resulted in depletion of intracellular glucose, occurring much faster in pericytes than in endothelial cells. The abrupt reduction in glucose caused pericyte cell shrinkage and nuclear condensation associated with DNA fragmentation, followed by loss of cell viability. All of these pericyte changes are apoptosis-like characteristics. This apoptotic process was prevented by the addition of cycloheximide, a protein synthesis inhibitor, or by platelet-derived growth factor BB, which is known competent factor for pericyte growth. In analysis of signalling pathways during the abrupt fluctuation of glucose, the occurrence of pericyte apoptosis was an intracellular calcium-dependent, protein kinase C and protein kinase A mediated, and poly (ADP-ribose) synthetase-dependent process. Interestingly, a larger degree of DNA fragmentation was observed with a higher magnitude and a longer duration of pre-existing hyperglycaemia. These results suggest that the magnitude and duration of pre-existing hyperglycaemia prime the apoptotic responsiveness of pericytes. Retinal capillary endothelial cells, after an identical glucose fluctuation treatment did not undergo an apoptotic process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Margination and diapedesis of inflammatory cells in the islets of Langerhans in hamsters infected with the 139H strain of scrapie.

The islets of Langerhans in hamsters infected with the 139H strain of scrapie contain large masses of red blood cells not surrounded by the usual arterial, venous or capillary wall cells. We have referred to these structures as "blood vessel cores" (BVCs). BVCs were almost always centrally located within the islets and surrounded by pancreatic B cells. Margination and diapedesis of inflammatory cells were observed at the BVC walls in 139H-infected hamsters. The cells consisted of the following types: single or clustered lymphocytes; and mixtures of lymphocytes and macrophages or neutrophils. Interaction observed between groups of inflammatory cells and B cells at the BVC walls and inside the islets of Langerhans indicated an inflammatory process. We refer to this interaction as the "linkage-reaction", and to the inflammatory cells as "linkage-inflammatory cells". These phenomena were not observed in other organs (adrenal, uterus, ovary, spleen, liver, kidney, oesophagus, trachea, intestine or pituitary) in 139H-affected hamsters or in the islets of Langerhans of animals infected with other scrapie strains (263K-infected hamsters; 139A-, ME7- and 22L-infected SJL mice). This appears to represent the first clear evidence of an inflammatory reaction in any organ in scrapie-infected animals.

Animals↗
PubMed1996

Histopathological changes in the pituitary glands of female hamsters infected with the 139H strain of scrapie.

Previous studies in hamsters showed that the 139H strain of scrapie injected intracerebrally caused a generalized endocrinopathy and marked hypoglycaemia and hyperinsulinaemia. The low scrapie infectivity levels in the pancreas suggested that the changes noted in that organ were of neuroendocrine origin. In the current study, female weanling Syrian hamsters were inoculated intracerebrally with scrapie strain 139H or 263K, or with homogenate of normal hamster brain. Coronal sections of the pituitary gland were stained with haematoxylin and eosin, Gomori's one-step trichrome, Congo red, thioflavin-S, and antibodies specific for several pituitary hormones. Sections were examined by light microscopy. The hamsters inoculated with scrapie strain 139H showed extensive pituitary vacuolization. Most vacuoles were located in the ventral or ventrolateral parts of the pars distalis. The pituitary glands of 139H-infected hamsters also showed cellular changes, namely, hypertrophy, atrophy and cytoplasmic vesicles. Nuclear changes such as swelling, vesicle formation, chromatin increase, pyknosis, karyorrhexis and karyolysis also occurred. The cellular and nuclear changes were most pronounced in the regions with vacuolation. Hamsters infected with the 263K strain did not show these changes. Immunocytochemical examination suggested that parenchymal cell types which produce different hormones were affected in areas of vacuolation. The changes produced by 139H were not seen in hamsters infected with strain 263K. This study provides the first evidence of cytopathological changes in the pituitary glands of scrapie-infected animals and suggests a relationship between the pituitary changes and the pathological findings in the pancreas and other endocrine organs of 139H-infected hamsters.

Animals↗
PubMed1996

Deep penetration of an alpha-helix into a widened RNA major groove in the HIV-1 rev peptide-RNA aptamer complex.

A combined NMR-molecular dynamics approach has been applied to determine the solution structure of a HIV-1 17-mer rev peptide bound to its 35-mer high affinity RNA aptamer binding site. Complex formation involves adaptive binding with the alpha-helical arginine-rich basic rev peptide targeting a widened RNA major groove centred about adjacent G.A and reversed A.A mismatches. We have also identified a U AU triple in the aptamer complex with the Hoogsteen-paired uracil base sandwiched between two arginine side chains. The intermolecular contacts identified in the aptamer complex readily account for the consequences of peptide and RNA mutations, as well as the results of previous in vitro selection experiments. The details of molecular recognition associated with targeting by rev of its high affinity RNA binding sites open new opportunities for structure-based drug design strategies.

Amino Acid Sequence↗
PubMed1996

Histopathological changes in the islets of Langerhans in hamsters infected with the 139H strain of scrapie: semi-thin section study.

Using histopathological analysis of semi-thin sections stained with toluidine blue, we observed profound pathological changes in the islets of Langerhans of hamsters infected with the scrapie agent (strain 139H). These included cytoplasmic vesicles, nuclear swelling, and vacuolization in the islet cells. Two types of vacuolization were seen. "Localized vacuolization" (LV) has a distinct edge and is restricted or confined within the cell. "Diffuse vacuolization" (DV) has no distinct edge and is scattered within tissues either inside or outside of cells. DV may span intracellular and extracellular regions of the islet tissues. There were abnormal structures which we termed blood vessel cores (BVCs) in the islets of 139H-infected hamsters. BVC is a hollow space filled up with blood cells. Immunocytochemical staining for insulin antibody suggested that BVC was surrounded by the B cells of the islet. In the present study, we observed that many inflammatory cells passed through the blood-tissue barriers using pathways between cell-junction in the lumen of BVC. We also observed many necklace-like hollow spaces between islet cells. They are the pockets of extracellular space. A novel concept of "the accordion effect" was described to explain a function of the extracellular space. Under normal physiological conditions, as the synthesis of insulin increase in B cells, the volume of the B cells will increase while the volume of the extracellular space will decrease. After a synchronized secretory response from the stimulated B cells, the secretory product would move from the intracellular space into the extracellular space, the volume of the B cells would be decreased and the volume of the extracellular space would be increased. Most of the secretory product might be released into the blood stream immediately, causing an insulin releasing peak in the blood stream, whereas the rest would remain in the enlarged extracellular space. As the cycle repeat, the increasing volume of the B cells will squeeze the remaining insulin into the blood stream gradually. Thus, the expandable extracellular space would serve as buffer system and a reservoir to collect and store some secretory products for future use. We refer to this concept as "the accordion effect". The concept of "the accordion effect" may also be true in other endocrine organs such as pituitary gland and adrenal gland.

Animals↗