[Retrospect and prospect of cardiovascular pathology].
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Animals↗
Biomedical subjects
T Wang
Publications and source records attributed to T Wang.
[The relationship between the phenotype of tumor infiltrating cells and the prognosis in laryngeal cancer].
By using the method of immunohistochemical avidin-biotin-peroxidase complex (ABC), toluidine blue and HE staining, the infiltrated grade and dispersed feature about the T-lymphocytes, B-Lymphocytes, macrophages, langerhans cells, mast cells and eosinophils of peritumoral stroma were investigated in 82 cases with laryngeal carcinoma. A stepwise logistic regression analysis of eight clinicopathologic variables and the density of six kinds of tumor infiltrating cells in the study were analyzed with the clinical outcome of the patients. The results showed that T-lymphocytes was the major infiltrated cells. The other cells such as macrophages, langerhans cells, mast cells and eosinophils were also to be found in local infiltration, but the B-cell was scanty. All these cells except B-cell had significant effect on the 5-year survival rate of the patients. By the multivariate analysis, the peritumoral infiltrated eosinophils was the most influential variable affecting clinical outcome, followed by the peritumoral infiltrated T-lymphocytes and the tumor histologic grade. We concluded that tumor infiltrating cells played a critical role in local host antitumor immune reaction.
Adult↗
[Removal of petrous bone cholesteatoma and obliteration with adipose tissue].
Three cases of petrous bone cholesteatoma removed through translabyrinthine-cochlear approach with the surgical defect obliterated by using adipose tissue covered with superficial temporalis fasia flap were reported. The average follow-up period was two years without any sign of recurrence. The etiology, diagnosis and methods of surgical treatment were discussed.
Adipose Tissue↗
[Pathologic observations of hepatitis C].
The morphological changes in liver biopsies from 70 patients with a clinical diagnosis of hepatitis C were studied. Sixty-two of the patients had history of blood transfusions. All patients were seropositive for anti-HCV by first and second generation test and/or were seropositive for HCV RNA by PCR method. Clinically, twenty cases diagnosed as acute hepatitis, fifty were chronic including 7 cases with both HBV and HCV infection. The main morphological changes in acute cases being 1. Focal degeneration of liver cells, including large and small droplet fatty changes. 2. Focal necrosis and acidophilic bodies usually being surrounded by T lymphocytes. 3. Sinusoidal inflammatory cell infiltration. 4. Lymphoid aggregation with bile duct epithelial damage was found in 60% of portal tracts. The chronic cases included 17 chronic persistent hepatitis cases (CPH) and 33 chronic active hepatitis cases (CAH). The main histopathologic changes in CAH included dense clusters of lymphocytes (lymphoid aggregates) present in the enlarged portal tracts with bridging necrosis and fibrosis, lobular inflammation including acidophilic bodies, focal necrosis and fatty degeneration. The sinusoidal cells were often hyperplastic. These changes may provide useful diagnostic clues for hepatitis C.
Adult↗
[Clinical study of laryngeal and laryngopharyngeal cancers with ultra-weak chemiluminescence analysis].
Ultra-weak luminescence of serum in 30 normal persons and 40 patients (12 laryngeal cancers, 18 laryngopharyngeal cancers, and 10 benign tumour patients) was studied using SHG-1 type photobiological photometer. The results showed that the intensity in malignant tumour group was higher than that of the benign group, which in turn was higher than that of the normal group with significant statistical differences (P < 0.05). The study implied that ultra-weak luminescence test is of value in diagnosis of laryngeal and laryngopharyngeal cancers.
Adult↗
N-methyl-D-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies.
The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-D-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 microM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 microM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA.
3,4-Dihydroxyphenylacetic Acid↗
Neurotrophin 3 potentiates neuronal activity and inhibits gamma-aminobutyratergic synaptic transmission in cortical neurons.
Neurotrophins have traditionally been regarded as slowly acting signals essential for neuronal survival and differentiation. However, brain-derived neurotrophic factor and neurotrophin 3 (NT-3) have recently been reported to exert an acute potentiation of synaptic activity at the amphibian neuromuscular junction. Little is known about the role of neurotrophins on functional synapses in the central nervous system. Here we show that NT-3 rapidly increased the frequency of spontaneous action potentials, and it synchronized excitatory synaptic activities in developing cortical neurons. Moreover, the inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA) subtype A receptors was found to be reduced by NT-3. Thus, the excitatory effects of NT-3 on spontaneous action potentials were attributable to a reduction of GABAergic transmission. Our findings, together with previous reports of rapid regulation of central nervous system neurotrophin expression by neuronal activity and of the role of GABAergic transmission in cortical plasticity, suggest a mechanism for modulation of synaptic transmission and activity-dependent synaptic modulation in cortical neurons.
Amphibians↗
Transforming growth factor beta 1 promotes spontaneous transformation of cultured rat liver epithelial cells.
The neoplastic transformation of cultured rat liver epithelial cells by various means has consistently been associated with the development of resistance to the mito-inhibitory effect of transforming growth factor beta (TGF-beta), suggesting that such phenotype plays a mechanistic role during the transformation of these cells. We have studied the induction of the "TGF-beta-resistant" phenotype in a clonal strain of early passage WB-F344 normal cultured rat liver epithelial cells, the proliferation of which was markedly inhibited by TGF-beta. The control WB cells in continuous culture slowly developed TGF-beta resistance. However, when the same cells were exposed to step-wise increases of TGF-beta concentration in their culture medium, the development of TGF-beta resistance was accelerated. Cells which had been grown in medium containing 1 ng/ml TGF-beta developed colony-forming capacity in soft agar containing epidermal growth factor. Cells which were grown in media containing 5 and 10 ng/ml TGF-beta demonstrated a low level of colony-forming efficiency in soft agar medium without added epidermal growth factor and tumorigenicity in isogeneic rats. These TGF-beta-resistant cells also exhibited progressively increasing levels of expression of the c-fos and and myc mRNA, and increased resistance to the cytotoxicity of Adriamycin and melphalan. The latter phenomenon was accompanied by an increase in the mdr-1 mRNA expression, cellular glutathione level, and glutathione S-transferase activity. The results suggest that chronic exposure to high concentration of TGF-beta promotes the spontaneous neoplastic transformation of cultured rat liver epithelial cells, and that this process may represent one of the mechanisms of cellular adaptation for induction of the multidrug-resistant phenotype during the carcinogenesis of epithelial cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Hemolytically inactive C4B complement allotype caused by a proline to leucine mutation in the C5-binding site.
The fourth component of complement (C4) is encoded by two highly homologous genes, C4A and C4B. Only one hemolytically inactive C4A allotype (C4A6) has been reported. No hemolytically inactive C4B allotype has been described. We report the first hemolytically inactive (hi) allotype of C4B, C4B*1 (hi). This unique variant was first recognized by hemolytic overlay assays and confirmed to segregate in the affected pedigree with the major histocompatibility complex haplotype A28,B35,CW4,DR6, C4A3,C4B1(hi), BFF,C2C. By single strand conformational polymorphism, we detected only a migration variant in exon 12 caused by a C to T transition in the second base of codon 459. This mutation results in a leucine substitution for proline (P459L) 1 residue downstream of a residue known to contribute to the C5-binding site. Allele-specific oligonucleotide analysis of samples demonstrated cosegregation of the mutation with the hemolytically inactive allotype in the affected pedigree. Site-directed mutagenesis and expression studies showed that the P459L mutation causes loss of hemolytic function. C4B*1(hi) is the first example of a circulating C4B protein lacking detectable hemolytic activity and the P459L mutation expands our knowledge of the C5-binding site of C4.
Base Sequence↗
The POX1 gene encoding peroxisomal acyl-CoA oxidase in Saccharomyces cerevisiae is under the control of multiple regulatory elements.
Transcription of POX1, the gene encoding peroxisomal acyl-CoA oxidase in the yeast Saccharomyces cerevisiae, is controlled by the carbon source given for cell growth. The gene is repressed in glucose, derepressed in glycerol, and induced in oleate. This regulation is controlled by cis-acting elements in the 5' region of the gene, which bind regulatory proteins. By deletion analysis and DNA band shift assays, we have characterized three such elements in the POX1 upstream sequence, two upstream repression sequences and an upstream activating sequence. Each was able to regulate the transcription of a heterologous gene construct iso-1-cytochrome-c (CYC1)/lacZ.
Acyl-CoA Oxidase↗
The cellular DNA polymerase alpha-primase is required for papillomavirus DNA replication and associates with the viral E1 helicase.
Persistent infection by papillomaviruses involves the maintenance of viral DNA as a nuclear plasmid, the replication of which requires host DNA polymerases. The role of the cellular DNA polymerase alpha-primase holoenzyme was probed by using soluble extracts from rodent cells that replicate bovine papilloma virus 1 and human papilloma virus 6b DNA in the presence of the viral E1 helicase and the E2 transcription factor. Monoclonal antibodies directed against the catalytic 180-kDa subunit of polymerase alpha inhibit DNA synthesis in this system. Addition of purified human polymerase alpha-primase holoenzyme to neutralized extracts restores their DNA synthetic activity. The amino-terminal 424 amino acids of E1 forms a specific protein complex with the p180 polymerase subunit. Immune complexes can be isolated with antibodies directed against E1 that contain a DNA polymerase activity. Moreover, this polymerase activity can be neutralized by anti-polymerase alpha antibodies. Permissivity barriers were not encountered in this in vitro system, as bovine E1 can interface with the murine and human replication apparatus. Although the large tumor antigens encoded by simian virus 40 and polyoma share limited primary sequence homology with the papillomavirus E1 proteins, the organization of functional motifs at the level of primary protein structure is remarkably similar. In addition to their origin-specific DNA-binding activity, each of these helicases may function to help recruit the cellular polymerase alpha-primase complex to the viral replication origin.
Animals↗
Efficacy and toxicity of ifosfamide stereoisomers in an in vivo rat mammary carcinoma model.
Ifosfamide (IFF) is a nitrogen mustard with significant activity against a number of tumors. Since it is a chiral molecule, it has been suggested that enantioselective metabolism could result in different efficacy and toxicity profiles for (R)- and (S)-ifosfamide. Both experimental animal and clinical data suggest that N-dechloroethyl metabolites of (S)-IFF are more significantly associated with neurological toxicity, which may limit therapeutic use of IFF. We have used purified ifosfamide enantiomers to examine the pharmacokinetics; spectrum of toxicity including lethality, weight loss, and myelosuppression; and antitumor effects of the mixture compared to each of the purified enantiomers. In the MatB mammary carcinoma grown in female Fischer rats we demonstrated that the antitumor efficacy appears to be the same for (R)-IFF and (S)-IFF, while the (R)-IFF has greater myelotoxicity. Pharmacokinetic analysis of plasma concentration-time confirms that the (R)-IFF is metabolized to a greater extent than (S)-IFF via the activation pathway. These data suggest that purified (R)-IFF may be an effective way to delivery active cytotoxic drug while limiting the generation of neurotoxic metabolites.
Animals↗
Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12.
Transforming growth factor-beta (TGF-beta) family members bind to receptors that consist of heteromeric serine-threonine kinase subunits (type I and type II). In a yeast genetic screen, the immunophilin FKBP-12, a target of the macrolides FK506 and rapamycin, interacted with the type I receptor for TGF-beta and with other type I receptors. Deletion, point mutation, and co-immunoprecipitation studies further demonstrated the specificity of the interaction. Excess FK506 competed with type I receptors for binding to FKBP-12, which suggests that these receptors share or overlap the macrolide binding site on FKBP-12, and therefore they may represent its natural ligand. The specific interaction between the type I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor-mediated signaling.
Binding, Competitive↗
Enhanced functional preservation of cold-stored rat heart by a nucleoside transport inhibitor.
This study investigates the hypothesis that inhibition of nucleoside transport during hypothermic storage elevates tissue adenosine (ADO) content and improves the function of the isolated rat heart. The hearts, flushed with a cardioplegic solution containing varying concentrations (0-100 nM) of a nucleoside transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI), were immersion-stored at 0 degrees C for 9 hr. Function was assessed after 30 min of working reperfusion. Function of unstored fresh hearts served as controls and poststorage recovery is reported as percentage of control function. Poststorage heart rate in all groups returned to control level after reperfusion. Recovery of other functional parameters in the no-NBTI group was as follows: aortic flow (AF), 56.2 +/- 4.6%; coronary flow (CF), 53.9 +/- 3.2%; cardiac output (CO), 55.5 +/- 4.0%; systolic pressure, 81.6 +/- 2.5%; work, 47.0 +/- 4.2%; and coronary vascular resistance (CVR), 157.1 +/- 7.8% of control. NBTI improved functional recovery in a dose-dependent fashion; the maximal improvement was seen at a dose of 5 nM, in which the recovery was: AF, 78.1 +/- 3.4%; CF, 73.5 +/- 4.4%; CO, 76.7 +/- 3.6%; work, 70.7 +/- 5.0%; and CVR, 127.5 +/- 4.5% of control (P < 0.05 vs. no-NBTI). The ADO A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (0.1 microM) blocked the effects of 5 nM NBTI; the recovery of AF, CF, CO, work, and CVR decreased to 62.8 +/- 8.0%, 58.3 +/- 5.0%, 61.5 +/- 3.9%, 54.4 +/- 4.5%, and 163.8 +/- 12.7% of control, respectively (P < 0.05 vs. 5 nM NBTI). Tissue ADO content in 5 nM NBTI hearts at the end of storage was 0.075 +/- 0.025 mumol/g dry wt, which was significantly elevated from 0.016 +/- 0.004 mumol/g dry wt in no-NBTI hearts. Purine release during initial reperfusion was delayed in 5 nM NBTI hearts, indicating the inhibition of nucleoside transport by NBTI. But NBTI treatment did not improve end-storage or end-reperfusion myocardial ATP. In conclusion, the addition of NBTI to cardioplegic solution enhanced tissue ADO and improved poststorage function of the hypothermically stored rat heart. The effect is ADO A1-receptor mediated without invoking energy conservation.
Adenosine↗
Magnetic-field-induced metal-insulator transition in two dimensions.
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Journal Article↗
A transforming growth factor beta type I receptor that signals to activate gene expression.
Transforming growth factor beta (TGF-beta) is a multifunctional factor that regulates many aspects of cellular functions. TGF-beta signals through a heteromeric complex of the type I and type II TGF-beta receptors. However, the molecular mechanism of signal transduction by this receptor complex remains unresolved. The type II receptor belongs to a transmembrane receptor serine-threonine kinase family. A new member of this receptor family (R4) was identified and shown to be a functional TGF-beta type I receptor on the basis of its ability to restore a TGF-beta-induced gene response in mutant cell lines lacking endogenous type I receptor. Both ligand binding and signaling of the R4 protein were dependent on the presence of a functional type II receptor. The type I receptor has an intrinsic serine-threonine kinase activity, which was essential for signal transduction.
Animals↗
Phenylketonuria in China: identification and characterization of three novel nucleotide substitutions in the human phenylalanine hydroxylase gene.
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China↗
Antifreeze glycoproteins from antarctic notothenioid fishes fail to protect the rat cardiac explant during hypothermic and freezing preservation.
The antarctic notothenioid fishes avoid freezing through the action of circulating antifreeze glycoproteins (AFGPs). This study investigated whether AFGPs could serve as cryoprotectants for the isolated rat heart under three different storage conditions. (1) Hearts were flushed with 15 mg AFGP/ml cardioplegic solution (CP) and stored for 9 h at 0 degrees C. This AFGP concentration has been reported to protect pig oocytes during hypothermic storage. (2) Hearts were flushed with 10 mg AFGP/ml CP-14 and stored frozen at -1.4 degrees C for 3 h. At this concentration the AFGPs significantly reduce the solution freezing point and also change the crystal morphology from dendritic to spicular. (3) Hearts were flushed with 10 micrograms AFGP/ml CP-15 and stored frozen at -1.4 degrees C for 5 h. At this low concentration the AFGPs have a strong inhibitory effect on ice recrystallization, but have little effect on the freezing point and less apparent effect on the crystal habit. After hypothermic or freezing storage, the functional viability was assessed by determining cardiac output (CO) during working reperfusion. No difference in CO was found between AFGP-treated and untreated hearts after 9 h of 0 degree C storage. CO in hearts frozen in CP-14 without AFGPs recovered to 50% of the freshly perfused control hearts. Hearts frozen in the presence of high concentrations of AFGPs (10 mg/ml CP-14) failed to beat upon thawing and reperfusion, although their tissue ice content was less than that found in hearts without AFGP treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗