Treatment of spondyloarthropathies with antibodies against tumour necrosis factor alpha: first clinical and laboratory experiences.
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Antibodies, Monoclonal↗
Biomedical subjects
P Wu
Publications and source records attributed to P Wu.
CYP11B2 expression in rat liver and the effect of spironolactone on hepatic fibrogenesis.
OBJECTIVE: In consideration of the hypothetical possibility that locally produced aldosterone is likely to take an active part in fibrogenesis of the liver, we undertook the present study to investigate the expression of aldosterone synthase gene CYP11B2 in rat liver and the curative effect of spironolactone on fibrosis of the liver. METHODS AND MATERIALS: 160 Wistar rats weighing about 250 g were divided into four groups as follows: model group, spironolactone group, malotilate group and control group. After 2, 4, 6, 8 and 10 weeks, the animals were sacrificed. Morphological examination was based on microscopic and electron microscopic findings. The area of collagen was examined by an Image Analyse System (Leica). By means of reverse transcriptase-polymerase chain reaction and in situ hybridization, the expression of CYP11B2 was detected. RESULTS: The expression of CYP11B2 mRNA, which was localized in the endoplasm of fat-storing cells, was upregulated when fibrogenesis occurred. The grade of fibrosis and the area of collagen in the spironolactone group were less than those in the model group before the 6th week (p < 0.05). After the 6th week, there was no significant difference between the spironolactone group and the model group (p > 0.05). CONCLUSIONS: The expression of CYP11B2 mRNA is upregulated in fibrotic liver. Spironolactone can partly have a fibrogenesis-inhibiting effect in the early stage of CCl(4)-induced hepatic fibrogenesis.
Animals↗
Differential expression of growth hormone messenger ribonucleic acid by somatotropes and gonadotropes in male and cycling female rats.
Past studies have reported the appearance of cells sharing phenotypic characteristics of gonadotropes and GH cells. During diestrus and early proestrus, a subset of somatotropes (40-60%) expressed both GH antigens and gonadotropin (LH-beta, LHbeta, or FSH-beta) messenger RNAs (mRNAs) or GnRH receptors. More recently, we reported that subsets of gonadotropes identified by LHbeta or FSHbeta antigens expressed GH- releasing hormone (GHRH) binding sites. The present studies were designed to learn if these putative multipotential cells also expressed GH mRNA. Biotinylated sense and antisense oligonucleotide probes were developed and cytochemical in situ hybridization tests were optimized for the detection of GH mRNA with GH, LHbeta, and FSHbeta antigens. RNase protection assays were developed with a complementary RNA probe that detected a 380-bp region at the 5' end of the GH mRNA. Both the in situ hybridization and RNase protection assays detected changes in expression of GH mRNA during the estrous cycle with the lowest expression occurring during metestrus and peak expression occurring on the morning of proestrus. Cell counts confirmed the results of the RNase protection assays showing that increases in mRNA levels seen from metestrus to proestrus reflected increased percentages of GH mRNA-bearing cells. In addition, densitometric analyses demonstrated that the higher GH mRNA levels assayed from diestrus to proestrus reflected increased area and density of label per cell. Both types of assays showed sex differences in expression of GH mRNA; male rat cell populations had higher values than female rats in metestrus, diestrus, or estrus. However, percentages of GH cells in male rats were equal to those from proestrous female rats and levels of GH mRNA were lower in male rats than proestrous females. Dual labeling experiments showed that, in male rats and diestrous, proestrous, or estrous females, GH mRNA was expressed in over 70% of GH cells. Expression of GH mRNA was also found in 50-57% of cells with LHbeta or FSHbeta antigens in the same groups. The lowest expression was seen in the metestrous groups (30-40% of GH cells or gonadotropes expressed GH mRNA). Expression of GH mRNA was first increased from metestrus to diestrous largely in GH cells, and slightly in cells with LHbeta antigens. Further increases were seen in GH and LH cells by the morning of proestrus. In contrast, FSH gonadotropes did not show an increased expression of GH mRNA until the morning of proestrus (reaching the same peak reached by LH cells). These data confirm the working hypothesis that a multihormonal cell type develops during diestrus to support both the somatotrope and gonadotrope populations. Collectively, our studies suggest that this multihormonal cell may function to help support the regulatory functions of the gonadotrope during the periovulatory period. In addition, the appearance of significant levels of expression of GH mRNA by male rat gonadotropes suggests that this multihormonal cell may play a role in regulation of the male reproductive system as well.
Animals↗
Effects of lipid-related factors on adipocyte differentiation of bovine stromal-vascular cells in primary culture.
The effects of several factors related to lipids on bovine adipocyte differentiation were investigated in primary culture. Adipocyte differentiation was assessed by development of glycerol-3-phosphate dehydrogenase (GPDH) activity and morphological observation. Addition of triglyceride mixture (Intralipid), caprylic acid and very low-, low- and high-density lipoproteins (VLDL, LDL and HDL) stimulated bovine preadipocyte differentiation in serum-free condition. Especially, VLDL strongly increased both cell protein contents and GPDH activity, suggesting that it stimulated both proliferation and differentiation of bovine preadipocytes. Under Intralipid-induced condition, differentiation of preadipocytes from subcutaneous adipose tissues was more evident than those from omental adipose tissues. However, such depot difference was not observed in medium supplemented with indomethacin, which is a peroxisome proliferator-activated receptor (PPAR) gamma agonist. This suggests that the differentiation capacity of bovine preadipocytes was different between depots and such difference is dependent on the ability to utilize lipids as endogenous PPARgamma ligands. Therefore, lipid metabolites have the stimulatory effects on bovine adipocyte differentiation in vitro, and lipoproteins, especially VLDL, may play an important role in development of bovine adipose tissues in vivo.
Adipocytes↗
4Oth Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
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Anti-Infective Agents↗
[QTLs and epistasis underlying rice (Oryza sativa L.) panicle length in different genetic background and environments].
A double haploid (DH) population and a recombinant inbred (RI) population derived from a cross between a japonica male parent Azucena and indica female parents, IR64 and IR1552 respectively, were used in both field and pot experiments for detecting QTLs and epistasis for rice panicle length in different genetic background and different environments. Panicle length (PL) was measured at maturity. QTLs for PL were detected using single marker analysis and interval mapping. Epistasis effects on the trait were also analyzed. Nine QTLs were detected in DH population, including 5 QTLs detected from field experiment and 4 from pot experiment, among them 3 QTLs mapped on chromosomes 1 and 4 were identified in both field and pot experiments. No significant epistasis effect was detected for PL. Four QTLs were detected in RI population, among them 2 from field condition and 2 from pot experiment. 6 pairs of epistasis loci were detected in RI population. One QTL mapped on chromosome 4 and two pairs of epistatic loci were detected in both field and pot experiments. One QTL on chromosome four was identified in both populations, and one marker locus RG323 on chromosome one was involved in additive effect in DH population, but epistasis effects in RI population.
Chromosome Mapping↗
[Developmental genetic analysis of brown rice thickness of indica rice (Oryza sativa L.)].
Analysis of developmental genetic effects for brown rice thickness (BRT) trait in indica rice (Oryza sativa L.) at four different filling stages was conducted and a developmental genetic model and corresponding statistical approaches for quantitative traits of triploid endosperm in cereal crops was used. The results indicated that the diploid maternal plant, triploid endosperm and cytoplasmic genetic effects were important for BRT trait at all filling stages of rice and those effects were the major effect at initial medium, filling period and mature period respectively. The additive and dominance effects were the major effect alternatively at four filling stages of rice. Significant endosperm and maternal dominance effects for BRT suggest that the utilization of heterosis for BRT is viable. The results of conditional genetic variance components shown that the expression of new quantitative genes in endosperm, cytoplasm and maternal plant for BRT was found at most filling stages of rice. The gene expression was most active at the early filling stages, especially at the second stage (8-14 days after flowering). Near to mature period (22-28 days after flowering), however, the expression of genes decreased sharply and even closed. The phenomena that the genes expressed spasmodically, i.e. the net genetic effects equaled to zero in some filling stages were detected for some genetic effects. Dominance and cytoplasmic correlation coefficients were significant at 0.05 or 0.01 probability level in some filling stages meanwhile there were the most strong relationship between mature period and other periods for BRT.
Genetic Variation↗
[Treatment of superior vena cava syndrome in cancer patients with intravascular stent and local thrombolysis].
OBJECTIVE: To study the therapentic efficacy of using intravascular stent and local thrombolysis for superior vena cava syndrome(SVCS) in cancer patients. METHODS: Among 26 cancer patients with SVCS there were 17 cases of lung cancer with mediastinal lymphnode metastases, 5 cases of malignant mediastinal tumor, 2 cases of non-Hodgkin's lymphomas, 2 cases of esophageal carcinoma with mediastinal lymphnode metastases. Through femoral vein, a catheter with side holes was introduced up to the superior vena cava. Following local dripping of urokinase for 20-40 min, the obstructed region was distended with the inflated balloon and then a self-expanding stent was put in the inflated region. RESULTS: The procedure was successful in 24 patients, but failed in 2 cases because the guide wire could not pass through the obstructed region. In 3 patients with superior vena cava stenosis of 10 cm in length, two stents were used. In the other 21 patients, 1 stent was adequate. Local thrombolytic treatment was given in 24 patients before the angioplastic balloon was inflated. The vena caval pressure at the distal end of the stenotic lesion dropped from 21.23 +/- 1.80 mm Hg before treatment to 5.33 +/- 0.98 mm Hg after treatment. The difference was statistically significant. Collateral veins were no longer filled by contrast after treatment. The caliber of the supericar vena cava restored to normal and its outline was smooth. The symptoms of SVCS subsided after treatment in 2-3 days. CONCLUSION: Intravascular, self-expandable stent combined with local thrombolysis is a micro-invasive and effective method of treatment for cancer patients with superior vena cava syndrome.
Adult↗
Development of novel peptide ligands modulating the enzyme activity of prostate-specific antigen.
Prostate-specific antigen (PSA) is a serine proteinase produced mainly by epithelial cells of the prostate. Measurement of PSA in serum is widely used for diagnosis and monitoring of prostate cancer. The major problem of the PSA determination in early diagnosis is the high false positive rate due to benign prostatic hyperplasia, but the clinical accuracy can be improved by determining the proportions of various molecular forms of PSA. The main biological function of PSA is liquefaction of the seminal gel formed after ejaculation, but PSA has also been suggested to regulate invasiveness and metastatic potential of prostatic tumors. Thus, agents binding to and affecting the function of PSA have the potential to be used for diagnosis and therapy of prostate cancer. We have developed peptides specific for PSA by using cyclic phage display peptide libraries. After deducing the amino acid sequence of the peptides by sequencing the relevant part of phage genome, the peptides were expressed as glutathione-S-transferase (GST) fusion proteins or produced by chemical synthesis. The peptides were shown to bind to PSA specifically as indicated by lack of binding to other related serine proteinases. The binding of the peptides with PSA was strongly inhibited by monoclonal antibodies specific for free PSA and they did not bind to PSA-inhibitor complexes indicating that they bind close to the active site of the enzyme. Most of the peptides enhanced the enzyme activity of PSA against a chromogenic substrate. The affinity of the peptides could be increased by including Zn2+ in the reaction mixture. These results show that peptides that bind to PSA and modulate its enzyme activity can be developed by phage display techniques. These peptides have the potential to be used for targeting of prostatic tumors and diagnostics of prostate cancer.
Humans↗
Effect of anti-P-selectin monoclonal antibody on renal ischemia/reperfusion injury in rats.
OBJECTIVE: To explore the effect of anti-P-selectin monoclonal antibody (mAb) on renal ischemia/reperfusion (I/R) injury in rats. METHODS: Renal function, renal histopathological changes, plasma P-selectin levels and renal P-selectin protein and mRNA expression were studied in a renal I/R injury rat models. Biochemical measurement, ELISA, Immunohistochemistry and Nested RT-PCR were used. RESULTS: Renal function insufficiency and renal histopathological damage were much less in the anti-P-selectin mAb-treated group than the saline-treated group. Plasma P-selectin levels were lower and renal P-selectin protein and mRNA expression were down-regulated in the former group. CONCLUSION: Anti-P-selectin mAb might be an efficient approach for the treatment of renal I/R injury.
Animals↗
[Experimental study on effect of Shenmai injection in improving contractility of fatigue diaphragm in rats].
OBJECTIVE: To study and compare the effects of Shenmai Injection (SMI) and aminophylline on pathogenesis and developing process of diaphragmatic fatigue. METHODS: SMI group, aminophylline group, SMI plus aminophylline group and control group of isolated rat's diaphragmatic muscular strip of equal length were set up, and electric stimulation was applied. Changes of related parameters in the fatigue inducing and recovery process were estimated. RESULTS: During fatigue inducing process, the lowering on maximal rates of relaxation (dR/dtmax) was earlier than that on maximal contraction peak (Pt) and contraction rate (dT/dtmax), and restoring of these parameters were restored later and incompletely. SMI could prolong the time Pt needed for reducing 50%, speed up the restoration of Pt. Although aminophylline could increase Pt, it shortened the fatigue inducing time and postponed the recovery. CONCLUSION: Disturbance in the function of relaxation plays important role in diaphragm fatigue induction. Through strengthening the capability to relax, SMI could improve the function of fatigue diaphragm. Aminophylline would damage the relaxation function together with the increasing contraction of diaphragm simultaneously, and this side-effect could be antagonised partly by SMI.
Aminophylline↗
[Phycobiliprotein and fluorescence immunological assay].
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Algal Proteins↗
[Continuous ethanol fermentation using tapioca starch by immobilized yeast cell without carrier].
A widespread interest has been noted in continuous power ethanol fermentation utilizing systems with immobilized yeast cell through self-flocculating. We studied continuous ethanol fermentation by a naturally flocculent strain of Schizosaccharomyces pombe and the performance of two-stage continuous ethanol fermentation system using suspended-bioreactors(total effective volume 1.5 L) has been established: the high biomass levels achieved allow efficient ethanol conversion(72.7 g/L, average), residual glucose(3.74 g/L) and high productivity(9.7 g/L.h) for 150 g/L glucose concentration in feed(tapioca syrup) with average 90% total conversion of substrate. The system was run steadily during a month research.
Bioreactors↗
A computerized management system for cell bank.
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Cell Line↗
Evidence that the Igkappa gene MAR regulates the probability of premature V-J joining and somatic hypermutation.
The Igkappa gene contains an evolutionarily conserved nuclear matrix association region (MAR) adjacent to the intronic enhancer. To test for the function of this MAR, we created mouse lines with a targeted MAR deletion. In MAR knockout animals, the immune system was normal in nearly all respects, including the distributions of various B cell populations and Ab levels. However, in pro-B cells, enhanced rearrangement was noted on the MAR- allele in heterozygotes. In addition, the efficiencies for targeting and generating somatic mutations were reduced on MAR-deleted alleles. These results provide evidence for the MAR negatively regulating the probability of premature rearrangement and positively regulating the probability of somatic hypermutation.
Alleles↗
Selective, covalent modification of beta-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors.
Microtubules are linear polymers of alpha- and beta-tubulin heterodimers and are the major constituents of mitotic spindles, which are essential for the separation of chromosomes during mitosis. Here we describe a synthetic compound, 2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene (T138067), which covalently and selectively modifies the beta1, beta2, and beta4 isotypes of beta-tubulin at a conserved cysteine residue, thereby disrupting microtubule polymerization. Cells exposed to T138067 become altered in shape, indicating a collapse of the cytoskeleton, and show an increase in chromosomal ploidy. Subsequently, these cells undergo apoptosis. Furthermore, T138067 exhibits cytotoxicity against tumor cell lines that exhibit substantial resistance to vinblastine, paclitaxel, doxorubicin, and actinomycin D. T138067 is also equally efficacious in inhibiting the growth of sensitive and multidrug-resistant human tumor xenografts in athymic nude mice. These observations suggest that T138067 may be clinically useful for the treatment of multidrug-resistant tumors.
Animals↗
A scintillation proximity assay for human interleukin-5 (hIL-5) high-affinity binding in insect cells coexpressing hIL-5 receptor alpha and beta subunits.
The high-affinity receptor for human interleukin-5 (hIL-5) is composed of alpha and beta subunits. A baculovirus expression system was established in Sf9 cells capable of expressing hIL-5 receptor alpha and beta subunits simultaneously. By using wheat germ agglutinin (WGA)-coated scintillation proximity assay (SPA) beads to capture 125I-labeled hIL-5-bound Sf9 cells, a SPA was developed and used to measure hIL-5 high-affinity binding. The hIL-5 receptors expressed in the Sf9 cells represented a single class of high-affinity binding sites with a dissociation constant (Kd) of 0. 24 nM and a density of 2.95 x 10(5) sites/cell. This is the first study in which the high-affinity Kd value similar to that for hIL-5 binding to human eosinophils was achieved using a recombinant expression system. The SPA compared favorably with the filter binding assay with regard to various binding parameters. We also found that several lectins, when coated on SPA beads, were even more effective than WGA-coated SPA beads for capturing the insect cells. We conclude that the baculovirus expression system was highly efficient in producing the high-affinity hIL-5 receptors and that the SPA was a simple and sensitive assay that could be readily adapted into a high-throughput screening format. The SPA described here could be a prototype for binding assays for other multimeric receptors.
Animals↗
Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP).
BACKGROUND: Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate. Continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin (CDDP) allows uniform, high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface for the treatment of peritoneal tumors. This article summarizes the results of 18 patients with peritoneal mesothelioma treated with CHPP. METHODS: From June 1993 through April 1998, 18 patients with primary peritoneal mesothelioma (13 male, 5 female; median age, 51 years) underwent surgical exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at the National Cancer Institute. Seventeen of 18 patients had malignant peritoneal mesothelioma, 13 with associated ascites. One patient had a symptomatic, multiply recurrent, benign, cystic peritoneal mesothelioma. Three patients who had a recurrence after a prolonged progression-free interval (>6 months) after CHPP underwent re-treatment. CHPP parameters included median cisplatin dose of 530 mg (range, 187-816), perfusate volume 6.0 liter (range, 4-9), flow 1.5 liter/min (range, 1-2), intraperitoneal temperature 41 degrees C (range, 38.7-43.2), and central temperature 38.6 degrees C (range, 36.8-39.7). RESULTS: Median follow-up after CHPP is 19 months (range, 2-56) with no operative or treatment-related mortality. Overall operative morbidity was 24% and included two patients with superficial wound infection and one patient each with atrial fibrillation, pancreatitis, fascial dehiscence, ileus, line sepsis, and clostridium difficile colitis. The major treatment-related toxicity was systemic renal toxicity at doses above what was defined as the maximum tolerated dose of cisplatin. Nine of 10 patients had resolution of their ascites postoperatively. Three patients who developed recurrent ascites (27, 22, and 10 months after initial treatment) were re-treated and had resolution of their ascites with ongoing responses at 24, 6, and 4 months after the second perfusion. The median progression-free survival was 26 months, and the overall 2-year survival was 80%. The median overall survival has not been reached. CONCLUSIONS: CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the abdomen and long-term survival, compared with historical controls, can be achieved with aggressive surgical debulking and CHPP. Re-treatment after initial response can result in a second long-term response.
Adolescent↗