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Biomedical subjects

R Yang

Publications and source records attributed to R Yang.

At least 217 records · Page 12Linked to original sources
PubMed1995

Protection against endotoxic shock by bactericidal/permeability-increasing protein in rats.

Bactericidal/permeability-increasing protein (BPI) is a neutrophil primary granule protein that inhibits effects of LPS in vitro. The current study examined the effects of BPI on hemodynamics, mortality, and circulating endotoxin and cytokines in conscious rats with endotoxic shock. Catheters were implanted into the right femoral artery and vein. 1 d later, human recombinant BPI (10 mg/kg) or vehicle was intravenously injected immediately, 30 min, or 2 h after intravenous injection of LPS (7.5 mg/kg). Mean arterial pressure (MAP) and heart rate were monitored and blood was collected before and after injection. BPI given immediately or 30 min after LPS prevented the LPS-induced reduction in MAP at 4-8 h and markedly reduced mortality. BPI given 2 h after LPS injection had no protective effect. BPI treated immediately after LPS reduced the circulating levels of endotoxin and IL-6 but increased the circulating levels of TNF. We propose that BPI exerts its protective effect through a TNF-independent mechanism, by inhibiting endotoxin-stimulated production of IL-6.

Animals↗
PubMed1995

Using oligonucleotide probe arrays to access genetic diversity.

As the Human Genome Project and related efforts identify and determine the DNA sequences of human genes, it is important that highly reliable and efficient mechanisms are found to access individual genetic variation. It is only through a greater understanding of genetic diversity that the true benefit of the Human Genome Project will be realized. One approach, hybridization to high-density arrays of oligonucleotides, is a fast and effective means of accessing this genetic variation. Light-directed chemical synthesis has been used to generate miniaturized, high-density arrays of oligonucleotide probes. Application-specific oligonucleotide probe array designs have been developed for the rapid screening of characterized genes. Dedicated instrumentation and software have been developed for array hybridization, fluorescence detection and data acquisition and analysis. In a specific and challenging application, oligonucleotide probe arrays have been used to screen the reverse transcriptase and protease genes of the highly polymorphic HIV-1 genome to explore genetic diversity and detect mutations conferring resistance to antiviral drugs. Results from this application strongly suggest that oligonucleotide probe arrays will be a powerful tool for rapid investigations in sequence checking, pathogen detection, expression monitoring and DNA molecular recognition.

Base Sequence↗
PubMed1995

Developmental activity variations of DNA polymerase alpha, delta, epsilon in mouse forebrains and spleens.

The levels of DNA polymerase alpha, delta, epsilon were examined in the neonatal mouse forebrains and spleens. The levels of DNA polymerase alpha were determined by the difference of polymerase activity in the absence and the presence of alpha specific inhibitor, BuPdGTP, or its monoclonal antibody. The levels of DNA polymerase delta were determined in H.A fractions after separating it from the other two enzymes. The levels of DNA polymerase epsilon were identified in H.A fractions by the use of alpha-monoclonal antibody or BuPdGTP. Results showed that in the mouse forebrain DNA polymerase alpha, delta, epsilon activities are the highest before birth, decline sharply following birth and are very low on the 8th day and hardly detectable on the 17th day; as for the mouse spleen, however, DNA polymerase alpha, delta, epsilon activities are the lowest at birth, increase rapidly after birth and reach their maxima on the 8th day and then decline gradually but remain in higher levels. These results not only prove that DNA polymerase alpha and delta take part in cell DNA replication but also suggest that DNA polymerase epsilon is involved in DNA replication.

Animals↗
PubMed1995

[Study on the reversing effect of tripiperaquine on human multidrug resistant leukemic cell line K562/A02].

K562/A02 is a Cell line with multi-drug resistance established in our laboratory bey long term induction with adriamycin. In this paper, reversal of MDR in K562/A02 cell line by tripiperaquine is reported. The cytotoxicity and intracellular concentration of daunorubicin (DNR) in K562/A02 were measured by MTT colorimetric assay and spectrofluorimetry. The results showed that the sensitivity of K562/A02 to DNR was greatly enhanced by tripiperaquine at 10 micrograms/ml, with an 11-fold increase in cytotoxic activity. The intracellular concentration of DNR in K562/A02 was significantly increased after coincubation with 20 mumol/L tripiperaquine for 3 hours. Our results suggest that tripiperaquine might be used in clinical trial to reverse MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Absence of WAF1 mutations in a variety of human malignancies.

A newly cloned gene named wild-type p53-activated fragment 1 (WAF1; also known as p21, Pic-1, Cip-1, or SDI1) is directly regulated by p53 and can itself suppress tumor cell growth in culture. Induction of expression of WAF1 may be an important means by which cells with DNA injury arrest their growth to repair DNA or undergo apoptosis. Based on the hypothesis that mutations of this gene may play a role in carcinogenesis, we have studied 351 DNAs from 14 kinds of malignancies, as well as 36 human transformed cell lines, for alterations of WAF1 gene by single-strand conformation polymorphism analysis of polymerase chain reaction amplification of the DNA coding region of the WAF1 gene. No abnormal band shifts of WAF1 were noted in any of the samples or cell lines, but three major variants in exons 2 and 3 of the gene were found that are consistent with the existence of two different DNA polymorphisms. Sequence analysis of the amplified products producing these three variants in each exon from normal DNAs confirmed the presence of the polymorphisms in the WAF1 gene. Of 290 selected tumor samples previously evaluated for p53 mutations by single-strand conformation polymorphism, 90% had no detectable p53 alterations. In summary, mutations within the coding portion of the WAF1 gene were undetectable in a large series of human tumors, many of which had a normal p53 gene. This suggests that WAF1 alterations are generally caused indirectly, through p53 mutations rather than through intragenic mutation of the WAF1 itself.

Base Sequence↗
PubMed1994

Heterologous expression of the cytotoxin restriction in Aspergillus nidulans and Aspergillus niger.

The cDNA clone of restrictocin was placed under the control of the glucoamylase promoter from Aspergillus awamori and was transformed into Aspergillus nidulans and Aspergillus niger. Site-specific changes were introduced into cDNA constructs and these were transformed into A. nidulans. The secretion signal sequence was deleted from one form of the gene and three mutations introduced single amino acid substitutions into the protein. Culture conditions were optimized for maximum expression levels of restrictocin. The activities of the expressed proteins were characterized with an in vitro rabbit reticulocyte assay. Protein synthesis in this assay was inhibited 50% by 2.5 ng/ml wild-type restrictocin, 3.5 ng/ml E95G, 30 ng/ml E95C, and 600 ng/ml H136L. Toxic effects of restrictocin were observed in the A. nidulans expression system with reduced levels of cellular protein and messenger RNA upon induction of restrictocin expression as well as the formation of the alpha-fragment product of ribosomal RNA cleavage. Toxic effects were most highly pronounced in strains expressing restrictocin without the signal sequence, less so in strains expressing native restrictocin, and absent in strains expressing H136L restrictocin.

Allergens↗
PubMed1994

Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction.

One feature of enteric mucosal immunity is oral tolerance (OT), a state of diminished systemic immune responsiveness to an antigen induced by previous oral feeding of that antigen. Because OT induction requires an interaction between the intestinal and systemic immune systems, the authors plan to use it as a method in experimental small bowel transplantation (SBT) to evaluate the ability of the intestinal allograft to cooperate immunologically with the host. Two different methods have been used in experimental SBT to establish graft venous drainage: anastomosis of the graft mesenteric vein to the recipient portal vein or to the inferior vena cava. This experiment was designed to examine the role of the intestinal venous drainage routes in OT induction. Rats with a surgically created mesenterico-caval shunt (MCS) and their sham controls received an immunization protocol to induce OT to ovalbumin. The results showed that OT was readily induced in the sham animals, but not in the animals with MCS. These results indicate that intestinal venous drainage through the liver plays a central role in OT induction. Therefore, future analyses of OT in allogeneic SBT will require an animal model with portal venous drainage of the intestinal graft.

Administration, Oral↗
PubMed1994

Lack of graft-versus-host disease after fetal intestine transplantation.

Clinical small bowel transplantation has often been complicated by lethal graft-versus-host disease (GVHD), attributed to the numerous allogeneic immunocompetent lymphocytes contained in the graft. Because the fetal immune system is relatively immature, the authors hypothesized that the risk of GVHD after small bowel transplantation might be diminished by using the fetal intestine as the donor organ. This experiment tested this hypotheses in a rat model. Jejunoileal segments harvested from Lewis (LEW) rat fetuses were transplanted subcutaneously into adult recipients of either syngeneic LEW or semiallogeneic LEW x Brown-Norway F1 (LBNF1) strains. The recipients had follow-up for 21 days after transplantation to assess the growth of the intestinal grafts ("neogut") and evaluate for GVHD. Growth of the intestinal grafts was observed in 65% (53 of 82) of the recipients, with a neogut weight of 4.5 +/- 3.7 g and length of 2.8 +/- 2.1 cm. No significant difference in graft survival rate or neogut weight and length was found between the LEW and LBNF1 recipients. Histopathologic examination of the neogut showed a mature intestinal architecture similar to that of normal adult rat intestine, with well-developed enteric lymphoid tissues including Peyer's patches. However, no clinical or histopathologic evidence of GVHD was found in any of the LBNF1 recipients. These results are consistent with the author's hypothesis and suggest that the use of fetal donor intestine for small bowel transplantation might have some immunologic advantages over the adult (immunologically mature) donor intestine.

Animals↗
PubMed1994

Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hydroxyl radicals generated in vivo kill neurons in the rat spinal cord: electrophysiological, histological, and neurochemical results.

We have used microdialysis to establish an experimental model to characterize mechanisms whereby released substances cause secondary damage in spinal cord injury. We use this model here to characterize damaging effects of the hydroxyl radical (OH.) in vivo in the spinal cord. OH. was generated in vivo by pumping H2O2 and FeCl2/EDTA through parallel microdialysis fibers inserted into the spinal cord. These agents mixed in the tissue to produce OH. by Fenton's reaction. Two types of control experiments were also conducted, one administering only 5 mM H2O2 and the other only 0.5 mM FeCl2/0.82 mM EDTA. During administration of these chemicals, electrical conduction was recorded as one test for deterioration. OH. blocked conduction completely in 2.5-5 h and Fe2+/EDTA partly blocked conduction, but H2O2 alone did not cause detectable blockage. Histological examination supported the hypothesis that neurons were killed by OH., as Fe2+/EDTA and H2O2 alone did not destroy significant numbers of neurons. OH., H2O2, and Fe2+ all caused gradual increases in extracellular amino acid levels. These results are consistent with Fe(2+)-catalyzed free radical generation playing a role in tissue damage upon spinal cord injury.

Animals↗
PubMed1994

Protection against rat endotoxic shock by p55 tumor necrosis factor (TNF) receptor immunoadhesin: comparison with anti-TNF monoclonal antibody.

The protective efficacy of a p55 tumor necrosis factor receptor immunoadhesin (TNFR-IgG) was compared with that of an anti-TNF monoclonal antibody (MAb) in a rat endotoxic shock model. TNFR-IgG (5 mg/kg), given 30 min before endotoxin (LPS), attenuated LPS induction of hypotension and tachycardia and eliminated LPS induction of serum TNF activity. In contrast, anti-TNF MAb (5 mg/kg) had little effect on LPS-induced hemodynamic changes and neutralized only partially the excessive serum TNF activity. The 6-day survival was 1 of 10 controls; 6 of 11, 5 of 7, and 8 of 9 rats receiving 0.2, 1.0, or 5.0 mg/kg TNFR-IgG, respectively; and 3 of 8 rats receiving 5 mg/kg anti-TNF MAb. These results indicate that TNFR-IgG is more potent than anti-TNF MAb at neutralizing excessive TNF activity in vivo.

Animals↗
PubMed1994

Analysis of the pediocin AcH gene cluster from plasmid pSMB74 and its expression in a pediocin-negative Pediococcus acidilactici strain.

The 3,500-bp pap operon in the 8,877-bp plasmid pSMB74 contains a cluster of four genes, papABCD, of which papA encodes prepediocin (A. M. Motlagh, M. Bukhtiyarova, and B. Ray, Lett. Appl. Microbiol. 18:305-312, 1994). The cluster without the promoter was cloned in the shuttle vector pHPS9. An Escherichia coli strain and a pediocin-sensitive Pediococcus acidilactici strain transformed with the recombinant plasmid, pMBR1.0, produced pediocin AcH. Deletion analysis by introducing mutations in the four genes in pMBR1.0 revealed that only papA and papD were required for pediocin AcH production and that the gene product of papD has both translocation and processing functions. In the transformed minicells of E. coli chi 925 the proteins of the pap cluster were synthesized, indicating no polar effect due to deletion.

Bacteriocins↗
PubMed1994

[Pingyangmycin-induced chromosome damage in lymphocytes of laryngeal cancer patients].

Lymphocytes from 28 untreated laryngeal cancer patients and 23 healthy controls were cultured in vitro and exposured to pingyangmycin (bleomycin A5), a clastogen. The lymphocytes were arrested in metaphase and analyzed. The total chromosome aberration rate, mean chromatid break rate per cell and cell aberration rate were 1.98% +/- 0.05%, 0.57% +/- 0.35%, and 42.8% +/- 12% respectively for laryngeal cancer patients. However, for healthy controls these values were 0.94% +/- 0.04%, 0.28% +/- 0.12%, and 27% +/- 12% respectively. Statistical analysis showed there are significant differences between the two groups. The data indicate that under our experimental conditions chromatid break rate 0.40 can be considered to be a borderline value, 0.80 hypersensitive value. For any individual, if the chromatid break rate is 0.40 or more, one should be ranked as having cancer risk. If 0.80 or more, then, highly cancer risk.

Adult↗
PubMed1994

[Effects of beta-endorphin on blood pressure and heart rate in rats].

The present work was undertake to investigate the mechanism of changes of blood pressure and heart rate induced by beta-endorphin (beta-End) after microinjection into the Nucleus Amygdaloideus Centralis (AC) of anaesthetized rats. The results were as follows: (1) beta-End (100, 250 pg/microliters) injected into AC decreased both blood pressure and heart rate. (2) Both these effects could be antagonized by naloxone and beta-End anti-serum. (3) The effects of beta-End could also be reversed by phentolamine and propranolol. The results showed that the cardiovascular effects on beta-End were mediated by opioid receptors and through the intervention of adrenergic neurons.

Amygdala↗
PubMed1993

(2,3)-alpha-Methylenepenams: synthesis and in vitro activity.

A series of alpha-methylene penicillins was synthesized and SAR were studied. The alpha-isomers were found to be chemically reactive and biologically active in contrast to the beta-isomers. In addition, the alpha-isomers have broader spectrum of in vitro activity than the corresponding penicillins. Generally, the alpha-isomers are more active against gram-negative bacteria than the corresponding penicillins, but slightly weaker in potency towards gram-positive organisms.

Anti-Bacterial Agents↗
PubMed1993

Changes of hepatoma echo patterns with tumor growth. A study of the microanatomic basis in a rat model.

OBJECTIVES: The echo patterns of human hepatoma vary considerably as the tumors grow. This sonographic study investigates the microanatomic basis of the echo-pattern changes in an animal model. METHODS: ACI rats (n = 35) with intrahepatically implanted Morris hepatoma 3924A were imaged with 10-MHz ultrasound from days 7 to 28 after tumor implantation. The sonograms were precisely correlated with the histologic sections and microangiograms obtained from the same section plane. RESULTS: Small hepatomas (size = 6.6 +/- 1.6 mm) without necrosis demonstrated a low-echo pattern. Medium-sized tumors (size = 11.7 +/- 3.3 mm) had a low-echo periphery and a high-echo center. The low-echo periphery corresponded to viable tumor and the high-echo core corresponded to central coagulation necrosis. Large tumors (size = 20.9 +/- 7.5 mm) with extensive necrosis revealed an irregular mixed-echo pattern. CONCLUSIONS: The trend of increasing echogenicity of the hepatomas with tumor growth is due to the progression of coagulation necrosis.

Animals↗
PubMed1993

Liver cancer ablation with extracorporeal high-intensity focused ultrasound.

Recent animal studies have demonstrated the capacity of high-intensity focused ultrasound (HIFU) to extracorporeally ablate selective tissue targets in the liver without requiring surgical exposure of the liver or insertion of instruments into the liver. The potential value of HIFU as a noninvasive local treatment for human hepatic cancers has attracted considerable interest. This report reviews the current status of HIFU research and sets forth questions for future study.

Animals↗