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Biomedical subjects

P Yang

Publications and source records attributed to P Yang.

At least 271 records · Page 15Linked to original sources

Acute myocardial infarction, reperfusion injury, and intravenous magnesium therapy: basic concepts and clinical implications.

The concept of reperfusion-induced injury has aroused special interest during the past decade as thrombolysis and direct angioplasty were introduced for early restoration of coronary blood flow in patients with acute myocardial infarction. There is experimental and clinical evidence that oxygen-derived free radicals (oxyradical hypothesis), activation of the complement system (complement hypothesis), and disturbance in calcium homeostasis (calcium hypothesis), may account for the development of reperfusion injury. Data from numerous animal experiments and clinical trials suggest that magnesium, a physiologic calcium blocker, may be efficacious for reduction of reperfusion injury. Despite encouraging results from previous clinical trials that revealed beneficial effects of intravenous magnesium therapy with respect to mortality, left ventricular function, and infarct size, a recently published large-scale trial (ISIS-4) provided conflicting data and caused major controversy. Further clinical trials, well-designed and carefully conducted, should elucidate the beneficial effects of magnesium in acute myocardial infarction, especially in conjunction with new and aggressive reperfusion techniques.

Calcium Channel Blockers↗

Molecular cloning and characterization of the CER2 gene of Arabidopsis thaliana.

Plants with defects in the synthesis of their epicuticular wax layer, eceriferum mutants (cer), are readily detected by the naked eye as bright green glossy plants when compared with the more glaucous normal plants. In a previous report, evidence was presented for the isolation of three lines from the Arabidopsis thaliana transformant collection (BRL5, BRL7 and BRL9) which failed to complement the cer2 mutant isolated previously. The analysis of the chemical composition of the epicuticular wax of these mutants suggests that the cer2 mutant of Arabidopsis is defective in very long chain fatty acid elongation. This paper reports the molecular cloning of the CER2 gene of Arabidopsis through the isolation of plant DNA flanking the site of T-DNA insertion as well as the characterization of the two independent T-DNA insertion mutant alleles, BRL5 and BRL9, of this gene. In the mutant line BRL5, T-DNA was found to be inserted in the second exon of the CER2 gene whereas in BRL9, T-DNA is inserted in the only intron of this gene. Nucleotide sequence analysis suggests that the ORF encodes a 47.3 kDa polypeptide. High levels of CER2 transcripts were detected in stems and flowers. The predicted amino acid sequence of the CER2 gene product reveals little homology with known protein sequences. In accordance with structural characterization of the T-DNA insertion mutants, no evidence of transcripts derived from the CER2 gene was found in either BRL5 or BRL9.

Amino Acid Sequence↗

Solitary fibrous tumor of the soft tissue. An immunohistochemical and ultrastructural study.

Solitary fibrous tumor is a rare spindle cell neoplasm of adults that usually arises in the pleura, recently reported in other locations. The authors describe three cases of solitary fibrous tumors in adults that occurred as circumscribed masses in the somatic soft tissue, including the arm, back, and abdomen. Histologically, they were characterized by a proliferation of spindle cells separated by thick bands of collagen and prominent vascularity often showing a hemangiopericytoma-like pattern. The spindle cells, having low mitotic figures and little nuclear atypicality, exhibited a variety of growth patterns, including storiform, fascicular and herringbone, and nuclear palisading. Vimentin and CD34 immunoreactivities were observed in many spindle cells of all tumors. They had ultrastructural features of fibroblast and myofibroblast in two cases examined. Solitary fibrous tumors seem to represent distinct mesenchymal neoplasms that require us to identify their unusual location other than the pleura and be familiar with their histologic appearances for arriving at the correct diagnosis.

Aged↗

Myofibroblastic tumor of soft tissue displaying desmin-positive and actin-negative immunophenotypes.

Myofibroblasts have ultrastructural and functional characteristics intermediate between fibroblasts and smooth muscle cells. Previous studies indicated that most myofibroblasts express actin and vimentin but not desmin immunophenotypes. Two benign intramuscular myofibroblastic tumors which displayed a desmin-positive and actin-negative immunophenotype are reported. The tumors occurred on the back of a 45 year old man who had neurofibromatosis 1 and the thigh of a 37 year old man without neurofibromatosis. Both tumors were encapsulated and composed of short intersecting bundles of spindle cells in a collagenous background. Although the tumors were cellular, nuclear pleomorphism was minimal and mitotic figures were rare. Characteristically, most tumor cells were immunoreactive strongly for desmin and vimentin but gave negative staining for muscle-specific actin, alpha-smooth muscle actin, alpha-sarcomeric actin, myosin, S-100 protein, cytokeratins, and CD34. On electron microscopy, the tumor cells were characterized by short spindle-indented nuclei, abundant cytoplasmic intermediate filaments, prominent plasmalemmal pinocytosis and frequent cell coverage by basal lamina. Aggregation of thin myofilaments with focal condensations was identified occasionally. Although the tumors showed distinct morphological and immunohistochemical features enabling delimitation from other soft tissue lesions, they may overlap histologically with myofibroblastoma of the breast, lymph node and soft tissue, low grade malignant nerve sheath tumor, leiomyosarcoma, cellular schwannoma, inflammatory fibrosarcoma and nodular fasciitis.

Actins↗

A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission.

The histone proteins are essential for the assembly and function of th e eukaryotic chromosome. Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The mutant requires two amino acid substitutions in histone H4: a lethal Thr-to-Ile change at position 82, which lies within one of the DNA-binding surfaces of the protein, and a substitution of Ala to Val at position 89 that is an intragenic suppressor. Genetic and biochemical evidence shows that the mutant histone H4 is temperature sensitive for function but not for synthesis, deposition, or stability. The chromatin structure of 2 micrometer circle minichromosomes is temperature sensitive in vivo, consistent with a defect in H4-DNA interactions. The mutant also has defects in transcription, displaying weak Spt- phenotypes. At the restrictive temperature, mutant cells arrest in the cell cycle at nuclear division, with a large bud, a single nucleus with 2C DNA content, and a short bipolar spindle. At semipermissive temperatures, the frequency of chromosome loss is elevated 60-fold in the mutant while DNA recombination frequencies are unaffected. High-copy CSE4, encoding an H3 variant related to the mammalian CENP-A kinetochore antigen, was found to suppress the temperature sensitivity of the mutant without suppressing the Spt- transcription defect. These genetic, biochemical, and phenotypic results indicate that this novel histone H4 mutant defines one or more chromatin-dependent steps in chromosome segregation.

Chromatin↗

Conformational alteration of Oct-1 upon DNA binding dictates selectivity in differential interactions with related transcriptional coactivators.

VP16 (termed VP16-H here) of herpes simplex virus (HSV) belongs to a family of related regulatory proteins which includes VP16-B of bovine herpesvirus (BHV). We show that VP16-B, while also being a powerful transactivator of transcription dependent on Oct-1 binding sites in its target promoters, has virtually no activity on a defined VP16-H-responsive, octamer-containing target promoter. While Oct-1 binds equally well to the VP16-B-responsive and -nonresponsive sites, VP16-B interacts with Oct-1 only when Oct-1 is bound to the BHV octamer site and not when it is bound to the HSV site. We show from the analysis of chimeric proteins that the ability of VP16-B to discriminate between the Oct-1 forms depends on features of its N-terminal region. We also show from an analysis of chimeric DNA motifs that sequences that lie 3' to the POU domain-contacting region of the HSV octamer site play a role in making it unresponsive to VP16-B. Finally, we show by high-resolution hydroxyl radical footprint analysis that the conformation of Oct-l is different on the two sites. These results augment our previous report on an allosteric effect of DNA signals on the conformation of bound proteins and indicate that different conformations of the same DNA binding protein can be recognized selectively by related members of interacting regulatory proteins. The possible implications of our observations for selective gene regulation by Oct-1, a ubiquitous transcription factor, and other multimember transcription families are discussed.

Animals↗

Autoantibodies and immunoglobulins in collagenous colitis.

BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown. Autoimmunity has been suggested, but no serological findings have supported such a theory. AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38 matched healthy controls was analysed for autoantibodies--that is, antinuclear antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and microsomal antigen, together with antibodies to endomysium, gliadin, and cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and complement factors C3 and C4 were also determined. RESULTS: In patients with collagenous colitis the mean value of IgM was significantly increased 2.5 g/l (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p = 0.002). Antinuclear antibodies occurred in nine of 38 patients compared with three of 38 controls, this difference was not statistically significant (p = 0.11). The results of all other immunoglobulins, complement factors, and specific antibodies showed no statistical difference between patients and controls. CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is found in this study, although the findings of a positive ANA-titre in some patients and an increased IgM level might give some support for this hypothesis.

Adult↗

Effects of TNF-alpha on [Ca2+]i and contractility in isolated adult rabbit ventricular myocytes.

The mechanism of the acute negative inotropic effect of tumor necrosis factor-alpha (TNF-alpha) was studied in enzymatically isolated adult rabbit ventricular myocytes. In cells loaded with fura 2 acetoxymethyl ester (AM) and paced intermittently at 0.2 Hz, TNF-alpha at doses < or = 10,000 U/ml caused a significant reduction in active cell shortening at 20 min, without reducing the amplitude of the accompanying intracellular Ca2+ concentration ([Ca2+]i) transient. Similar results were obtained in cells loaded with indo 1-AM and paced continuously at 0.2 Hz during exposure to TNF-alpha (10,000 U/ml). The effect of TNF-alpha on cell shortening could be prevented by the nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME) but not its inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). The NO scavenger hemoglobin also attenuated the effects of TNF-alpha. TNF-alpha also caused a significant increase in diastolic cell length without any change in diastolic [Ca2+]i. The effect on cell length was prevented by L-NAME but not D-NAME. In cells loaded with the pH indicator seminaphthorhodafluor-AM, TNF-alpha did not alter pH sufficiently to account for the negative inotropic effect. These data suggest that high doses of TNF-alpha can acutely induce NO synthesis in isolated myocytes and reduce contractility by decreasing myofilament [Ca2+]i responsiveness. The mechanism of this altered myofilament [Ca2+]i response is unknown but does not appear to be pH mediated.

Animals↗

Perinuclear antineutrophil cytoplasmic antibody in pouchitis after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: It has been shown that perinuclear antineutrophil cytoplasmic antibody (P-ANCA) may be associated with pouchitis after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: P-ANCA was studied with the indirect immunofluorescence technique in 76 UC patients after IPAA. Twenty-eight patients had had pouchitis, whereas 48 patients did not. RESULTS: P-ANCA was found in 49 of 76 (64.5%) UC patients after IPAA. In patients who had had pouchitis attacks within 1 year of serum sampling (group 1) 12 of 12 (100%) patients had positive P-ANCA. In patients who had had pouchitis attacks 1 or several years before the serum sampling (group 2) 9 of 16 (56.3%) patients had positive P-ANCA. In patients who had not yet had a pouchitis attack (group 3) 28 of 48 (58.3%) were positive. The occurrence of P-ANCA in group 1 was significantly higher than in group 2 (p = 0.01) or group 3 (p = 0.005). No statistically significant difference was found between the occurrence of P-ANCA in group 2 and group 3. Furthermore, we found that the titres of P-ANCA in the pouchitis patients were associated with the observation time since the first pouchitis attack to the time of serum sampling (r = -0.43, p = 0.02) and a pouchitis relapse index (average pouchitis attacks per year, r = 0.47, p = 0.03). CONCLUSIONS: P-ANCA was found in UC patients after proctocolectomy with IPAA. Patients with recent (< or = 12 months) or ongoing pouchitis are all P-ANCA-positive. Pouchitis patients with higher P-ANCA titres are more prone to have frequent relapses.

Adult↗

Macrophages in the retina of normal Lewis rats and their dynamics after injection of lipopolysaccharide.

PURPOSE: To investigate the density, distribution, and morphology of macrophages (bone marrow-derived microglia) and major histocompatibility complex (MHC) class II-positive cells in the retina of Lewis rats and the dynamics of these cells after systemic lipopolysaccharide (LPS) injection. METHODS: Immunohistochemistry was carried out using monoclonal antibodies specific to monocytes and macrophages (ED1, ED2) and MHC class II-positive cells (OX-6) on whole-mounts of the retina obtained from Lewis rats before and at different time points after footpad injection of 200 micrograms of LPS. RESULTS: The inner layers of the normal retina contained a network of macrophages, whereby ED1 and ED2 staining revealed similar results. Macrophages were either dendritiform or pleiomorphic in morphology, with the former predominant. The density of positive cells was higher at the peripheral part and the periequatorial part (271 +/- 10 cells/mm2 and 267 +/- 9 cells/mm2, respectively) than at the posterior part (196 +/- 11 cells/mm2; P < 0.0001 in both cases). Lipopolysaccharide injection induced an early adherence of monocytes to retinal blood vessels, followed by a massive influx of the macrophages into the retina. The ED1-ED2 positive cells showed a variety of morphologic appearances: large round cells, pleiomorphic cells, and dendritiform cells. Pleiomorphic cells were striking at 48 hours, whereas dendritiform cells were predominant in the whole retina at 72 hours and thereafter. On day 14, the dendritiform cell numbers returned to approximately preinjection levels. Major histocompatibility class II-positive cells could not be found in the normal retina, nor after LPS injection. CONCLUSIONS: The network of MHC class II-negative microglia in the retina were studied. These cells may play an important role in immunoregulation and stability of the immunologic microenvironment within the retina. Systemic LPS injection was followed by a massive influx of macrophages into the retina. The absence of MHC class II-positive cells in the retina after LPS challenge may be an important protective mechanism against possible autoimmune damage.

Animals↗

[Eyebrow reconstruction by a scalp island flap based on the frontal branch of the superficial temporal artery].

The author studied the course and measured the length of the frontal branch of the superficial temporal artery in 30 normal subjects. 19 eyebrows were reconstructed in 11 burned patients using the scalp island flap based on the frontal branch of the superficial temporal artery. The results were satisfactory. The reconstructed eyebrows looked natural with wooly hair of the frontal hairline. This method can be used not only in male patients but also in female or pediatric patients.

Adult↗

Hepatobiliary complications of parenteral nutrition.

Total parenteral nutrition (TPN) has become an important tool in the management of acutely ill patients and in patients unable to tolerate oral nutrition. Although the benefits of this treatment are obvious, there are various hepatobiliary complications associated with use of TPN. We review the spectrum of liver and biliary abnormalities associated with use of TPN, as well as discuss the management of these complications in both adults and infants.

Biliary Tract Diseases↗

Immunohistochemical studies of macrophages and MHC class II-positive cells in the iris and ciliary body of Lewis rats.

PURPOSE: To investigate the density, distribution and morphology of macrophages and MHC class II-positive dendritic cells in the iris and ciliary body of lewis rats. METHODS: Immunohistochemistry was performed using monoclonal antibodies specific to monocytes and macrophages (ED1, ED2) and MHC class II-positive cells (OX6) on wholemounts of the iris-ciliary body complex isolated form normal lewis rats. RESULTS: A well developed network of macrophages was present in the iris and ciliary body of normal lewis rats. These cells, morphologically displaying dendritiform or pleiomorphic appearance, were more densely arranged in mid-iris (950 +/- 189 cells/mm2) than in iris base (482 +/- 78 cells/mm2) and pupil margin (595 +/- 92 cells/mm2). A similar network of MHC class II-positive cells with a cell density 452 +/- 78 cells/mm2 was almost uniformly distributed in the iris of normal lewis rats. CONCLUSIONS: A network of macrophages and MHC class II-positive cells was established in the iris and ciliary body of normal lewis rats. These cells may be involved biologically in the generation of anterior chamber associated immune deviation-inducing signal within the anterior chamber and the transferring of this signal from the eye to the spleen, and pathophysiologically in the pathogenesis of uveoretinitis.

Animals↗

[Cluster epithelial cells in nasal secretions of allergic rhinitis and its relation to eosinophils].

The cytology of nasal secretions in 20 patients with allergic rhinitis and 15 patients with chronic maxillary sinusitis was investigated with transmission electron microscope to study the ultrastructure of the cluster epithelial cells in nasal secretions of allergic rhinitis. The results showed that the cluster epithelial cells were predominant cellular element in allergic nasal secretions. The number of cluster cells correlated positively with the number of eosinophils and the levels of eosinophilic cationic protein. It is suggested that the exfoliation of cluster nasal epithelial cellular elements may be caused by eosinophic cationic protein with resultant hyperreactivity of nasal mucosa.

Adolescent↗

[Changes of the cornea induced by lipopolysaccharide in Lewis rats].

PURPOSE: To investigate changes of the cornea induced by lipopolysaccharide (LPS). METHODS: Immunohistochemical study using monoclonal antibodies to monocytes, macrophages (ED1, ED2) and MHC class II antigen (OX6) was performed on the corneal wholemounts obtained from normal lewis rats and those after LPS injection. RESULTS: Macrophages were noted to be present in whole cornea with a gradually decreased cell density from limbus to central part in normal lewis rats. However, major histocompatibility complex class II antigen (MHC class II)-positive cells were only distributed at limbus. Footpad injection of LPS induced an increase of monocytes and macrophages in whole cornea and a dramatical changes of these cells morphologically. MHC class II-positive cells were only and shortly noted on the surface of the cornea endothelium at early stage after LPS injection. CONCLUSION: LPS-induced increase of macrophages in the cornea may be an important defense mechanism in response to LPS challenge. On the other hand, the absence of MHC class II-positive cells both in the normal and in the inflamed cornea may be contributed to the stability of immunological microenvironment within this tissue.

Animals↗

Arterial oxygen saturation in Tibetan and Han infants born in Lhasa, Tibet.

BACKGROUND: Reduced oxygen availability at high altitude is associated with increased neonatal and infant mortality. We hypothesized that native Tibetan infants, whose ancestors have inhabited the Himalayan Plateau for approximately 25,000 years, are better able to maintain adequate oxygenation at high altitude than Han infants, whose ancestors moved to Tibet from lowland areas of China after the Chinese military entered Tibet in 1951. METHODS: We compared arterial oxygen saturation, signs of hypoxemia, and other indexes of neonatal wellbeing at birth and during the first four months of life in 15 Tibetan infants and 15 Han infants at 3658 m above sea level in Lhasa, Tibet. The Han mothers had migrated from lowland China about two years previously. A pulse oximeter was placed on each infant's foot to provide measurements of arterial oxygen saturation distal to the ductus arteriosus. RESULTS: The two groups had similar gestational ages (about 38.9 weeks) and Apgar scores. The Han infants had lower birth weights (2773 +/- 92 g) than the Tibetan infants (3067 +/- 107 g), higher concentrations of cord-blood hemoglobin (18.6 +/- 0.8 g per deciliter, vs. 16.7 +/- 0.4 in the Tibetans), and higher hematocrit values (58.5 +/- 2.4 percent, vs. 51.4 +/- 1.2 percent in the Tibetans). In both groups, arterial oxygen saturation was highest in the first two days after birth and was lower when the infants were asleep than when they were awake. Oxygen saturation values were lower in the Han than in the Tibetan infants at all times and under all conditions during all activities. The values declined in the Han infants from 92 +/- 3 percent while they were awake and 90 +/- 5 percent during quiet sleep at birth to 85 +/- 4 percent while awake and 76 +/- 5 percent during quiet sleep at four months of age. In the Tibetan infants, oxygen saturation values averaged 94 +/- 2 percent while they were awake and 94 +/- 3 percent during quiet sleep at birth and 88 +/- 2 percent while awake and 86 +/- 5 percent during quiet sleep at four months. Han infants had clinical signs of hypoxemia--such as cyanosis during sleep and while feeding--more frequently than Tibetans. CONCLUSIONS: In Lhasa, Tibet, we found that Tibetan newborns had higher arterial oxygen saturation at birth and during the first four months of life than Han newborns. Genetic adaptations may permit adequate oxygenation and confer resistance to the syndrome of pulmonary hypertension and right-heart failure (subacute infantile mountain sickness).

Altitude↗

Activation of mitogen-activated protein kinase cascades by p21-activated protein kinases in cell-free extracts of Xenopus oocytes.

In the evolutionarily distant yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, genetic evidence suggests that activation of pheromone-induced mitogen-activated protein kinase (MAPK) cascades involves the function of the p21cdc42/racl-activated protein kinases (PAKs) Ste20 and Shk1, respectively. In this report, we show that purified Ste20 and Shk1 were each capable of inducing p42MAPK activation in cell-free extracts of Xenopus laevis oocytes, while a mammalian Ste20/Shk1-related protein kinase, p65pak (Pak1), did not induce activation of p42MAPK. In contrast to p42MAPK, activation of JNK/SAPK in Xenopus oocyte extracts was induced by both the yeast Ste20 and Shk1 kinases, as well as by mammalian Pak1. Our results demonstrate that MAPK cascades that are responsive to PAKs are conserved in higher eukaryotes and suggest that distinct PAKs may regulate distinct MAPK modules.

Animals↗