Development of a novel drug-delivery system using bacteriophage MS2 capsids.
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Animals↗
Biomedical subjects
M Wu
Publications and source records attributed to M Wu.
Activities of bay Y 3118, levofloxacin, and ofloxacin alone or in combination with ethambutol against Mycobacterium avium complex in vitro, in human macrophages, and in beige mice.
Levofloxacin, ofloxacin, and Bay Y 3118 are new fluoroquinolones with variable in vitro bacteriostatic and bactericidal activities against the Mycobacterium avium complex (MAC). The potential therapeutic activities of these agents both alone and combined with ethambutol were evaluated in a human macrophage test system and in the beige mouse animal test system with MAC strain 101. Bay Y 3118 at a human-equivalent dose of 30 mg/kg/day for 4 weeks caused a significant reduction in mortality compared with that in untreated controls (P = 0.02). Bay Y 3118 also caused significant reductions in the number of MAC organisms in the blood, liver tissue, and spleen tissue compared with those in untreated controls. Levofloxacin at a human-equivalent dose of 200 mg/kg/day was associated with a significant reduction in mortality (10 versus 39%); however, treatment with either levofloxacin or ofloxacin (200 mg/kg/day) did not result in significant reductions in the numbers of MAC organisms in blood, liver, and spleen compared with those in untreated controls. When Bay Y 3118 was combined with ethambutol, there was no enhancement in therapeutic activity except in the spleen in terms of CFU per gram (reductions of 89% compared with the untreated control, 63% compared with Bay Y 3118 alone, and 72.5% compared with ethambutol alone). Levofloxacin in combination with ethambutol was more active than either drug alone in the reduction of organisms in blood, liver, and spleen. Bay Y 3118 was the most active fluoroquinolone for monotherapy of MAC infection in beige mice, and the combination of ethambutol plus either levofloxacin or ofloxacin was at least additive. In summary, this study demonstrates that quinolones, although active, are inhibitory against MAC in vivo and that there is little correlation between the activity of quinolones in vitro and the activity in mice.
Animals↗
Chemotactic Preferences and Strain Variation in the Response of Phytophthora sojae Zoospores to Host Isoflavones.
The zoospores of Phytophthora sojae are chemotactically attracted to the isoflavones genistein and daidzein that are released by soybean roots. In this study we have examined the response of P. sojae zoospores to a wide range of compounds having some structural similarity to genistein and daidzein, including isoflavones, flavones, chalcones, stilbenes, benzoins, benzoates, benzophenones, acetophenones, and coumarins. Of 59 compounds examined, 43 elicited some response. A comparison of the chemotactic responses elicited by the various compounds revealed a primary role for the phenolic 4(prm1)- and 7-hydroxyl groups on the isoflavone structure. A few compounds acted as repellents, notably methylated flavones with a hydrophobic B ring. The chemotactic response to many of the analogs was markedly different among different strains of P. sojae.
Journal Article↗
Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells.
Treatment of WEHI 231 immature B-lymphoma cells with an antibody against their surface immunoglobulin (anti-Ig) induces apoptosis and has been studied extensively as a model of B-cell tolerance. Anti-Ig treatment of exponentially growing WEHI 231 cells results in an early transient increase in c-myc expression that is followed by a decline to below basal levels; this decrease in c-myc expression immediately precedes the induction of cell death. Here we have modulated NF-kappaB/Rel factor activity, which regulates the rate of c-myc gene transcription, to determine whether the increase or decrease in c-Myc-levels mediates apoptosis in WEHI 231 cells. Addition of the serine/threonine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), which blocks the normally rapid turnover of the specific inhibitor of NF-kappaB/Rel IkappaBalpha in these cells, caused a drop in Rel-related factor binding. TPCK treatment resulted in decreased c-myc expression, preventing the usual increase seen following anti-Ig treatment. Whereas inhibition of the induction of c-myc expression mediated by anti-Ig failed to block apoptosis, reduction of c-myc expression in exponentially growing WEHI 231 cells induced apoptosis even in the absence of anti-Ig treatment. In WEHI 231 clones ectopically expressing c-Myc, apoptosis induced by treatment with TPCK or anti-Ig was significantly diminished and cells continued to proliferate. Furthermore, apoptosis of WEHI 231 cells ensued following enhanced expression of Mad1, which has been found to reduce functional c-Myc levels. These results indicate that the decline in c-myc expression resulting from the drop in NF-kappaB/Rel binding leads to activation of apoptosis of WEHI 231 B cells.
Animals↗
Nitrogen dioxide causes pulmonary arterial relaxation via thiol nitrosation and NO formation.
Micromolar concentrations of nitrogen dioxide (NO2), a key metabolite of nitric oxide (NO) and peroxynitrite (ONOO-), were observed to cause a prolonged relaxation of isolated endothelium-removed rings of bovine pulmonary arteries (BPA) precontracted with 30 mM potassium. Relaxation to NO2 was markedly inhibited by 1 microM hemoglobin (Hb), 10 microM methylene blue (MB), and 10 microM LY-83583. The response to NO2 was enhanced in the presence of 1 mM reduced glutathione (GSH) or cysteine. The addition of NO2 to Krebs bicarbonate buffer (under 95% N2-5% CO2) containing 1 mM GSH or BPA resulted in an increase in NO formation (measured in head space gas). Relaxation to NO2 and NO formation were markedly decreased after GSH depletion by pretreatment of BPA with diethyl maleate. A high-performance liquid chromatography analysis of the products formed immediately after the addition of NO2 to GSH detected a previously isolated (but not identified) potent relaxing agent formed by a reaction of GSH with ONOO-, and this material comigrated with a synthetic product thought to be S-nitro-GSH (GSNO2). Nanomolar concentrations of GSNO2 caused a potent dose-dependent relaxation that was inhibited by Hb, MB, and LY-83583. Therefore NO2 appears to cause a prolonged guanosine 3',5'-cyclic monophosphate-mediated relaxation in BPA via thiol nitration and a subsequent time-dependent release of NO. Thus NO2 (and ONOO-) may function in a tissue hormonelike regulatory role in inflammatory processes in which large amounts of these species are produced.
Animals↗
Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling.
Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation.
Adult↗
An antidiabetic thiazolidinedione potentiates insulin stimulation of glycogen synthase in rat adipose tissues.
Thiazolidinedione derivatives are a novel class of insulin-sensitizing agents that have demonstrated effective antidiabetic activity in vivo. Here, the effects of the potent thiazolidinedione derivative, AD-5075, on the rate-limiting enzyme of glycogen synthesis, glycogen synthase, were investigated in cultured rat adipose tissue. Short term preincubation of adipose tissue with AD-5075 potentiated acute insulin stimulation of I-form glycogen synthase activity in a concentration-dependent (EC50 approximately, 61nM) and time-dependent (t1/2 approximately, 2.3 h) manner. The thiazolidinedione derivative increased the responsiveness of I-form glycogen synthase activity to insulin stimulation at both maximal and submaximal insulin concentrations. In contrast, it had no effect on total glycogen synthase activity. Isoproterenol inhibited acute insulin activation of I-form glycogen synthase activity in a dose-dependent manner; maximal inhibition was attained at a concentration of 3 nM. AD-5075 antagonized isoproterenol inhibition of insulin's action. The concentration of glycogenolytic agent required to attain maximal inhibition was increased an order of magnitude in tissue treated with the antidiabetic agent. Short term preincubation of adipose tissue under hyperglycemic conditions (15 or 25 mM glucose) decreased insulin-stimulated I-form glycogen synthase activity. Concurrent treatment of the tissue with AD-5075 abrogated this glucose toxicity-induced inhibition of insulin action. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, blocked insulin activation of glycogen synthase in a dose-dependent manner. Half-maximal inhibition was observed at approximately 0.3 microM, and maximal inhibition occurred at 1.0 microM. AD-5075 did not antagonize wortmannin's inhibitory action. These results indicate that thiazolidinediones can act directly on adipose tissues to augment an important metabolic effect of insulin and counteract the inhibitory effects of catecholamines or hyperglycemia. As insulin stimulation of glycogen synthase remains wortmannin inhibitable in the presence of AD-5075, the effects of thiazolidinediones on insulin signal transduction may be phosphatidylinositol 3-kinase-dependent.
Adipose Tissue↗
Confocal microscopy analysis of living Xenopus eggs and the mechanism of cortical rotation.
The dorsoventral body axis in amphibian embryos is established by a rotation of the outer cortex relative to the inner cytoplasmic core. This cortical rotation depends on microtubules and is correlated with a parallel array of microtubules just inside the vegetal cortex. Since the parallel array moves with the inner cytoplasm and most of its microtubules are oriented with their plus ends facing the direction of cortical movement, it has been suggested that plus end-directed motor molecules attached to the cortex drive the rotation by moving along microtubules of the parallel array. Using an inverted confocal microscope to examine living eggs, however, we found that rotation movements precede the formation of a detectable parallel array at the vegetal pole, that the parallel array consists of multiple layers of microtubules at depths ranging from 4 to 8 microns inside the plasma membrane and that the velocity of rotation is immobilized eggs increases with depth in this region. These findings suggest that (1) early cytoplasmic movements are due to something other than the fully formed parallel array and (2) the motor molecules responsible for the bulk of the rotation movement are not restricted to a monolayer at the subcortical interface but may be distributed throughout the parallel array, perhaps causing microtubules to slide along other microtubules by a mechanism similar to that seen in cilia and eukaryotic flagella.
Animals↗
Experimental and clinical study on hepatobiliary surgery in China.
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Animals↗
[Uterine papillary serous carcinoma--one kind of special type of uterine endometrial carcinoma].
OBJECTIVE: To study the clinico-pathologic features of uterine papillary serous carcinoma and point out the complete difference between the two kinds of endometrial carcinoma. METHODS: One hundred and ten cases of endometrial carcinoma who received treatment in the our hospital from May 1, 1982 to April 30, 1994 were analyzed retrospectively. RESULTS: Of them, 10 cases (9.1%) of uterine papillary serous carcinoma (UPSC) were found. The age in average was 67.2 years old, which is nearly 10 years older than those with ordinary endometrial cancer (P < 0.01). The occurrence of UPSC was revealed no relationship with the relative factors of occurrence of endometrial carcinoma. The study shows that tumor has very marked tendency of lymph node metastasis, much worse grade, much deeper myometrial invasion and much earlier extrauterine disease. CONCLUSIONS: UPSC is a special pathologic type of endometrial carcinoma with completely different clinico-pathologic behavior. The surgical staging is necessary for the patients with UPSC to get comprehensive stage because the clinical stage is usually not correct enough.
Aged↗
[Metabolism and utilization of calcium derived from hydrolysed oyster shell in rats].
Experimental rats modeled on calcium deficiency were fed with calcium derived from hydrolysed oyster shell, calcium carbonate and calcium chloride respectively, equivalent to 45 mg a day, for four weeks to study their bioavailability. Calcium contents in the blood, urine, feces and bone of rats were determined with atomic absorption spectrometry and EDTA complex titration, and their bone density was measured with densitometry. Results showed proportions of calcium absorption and retention were 67.3% +/- 16.7% and 64.6% +/- 17.5%, respectively, in rats fed with calcium from hydrolysed oyster, and their femur calcium content and bone density (BMC/BW) 131.2 +/- 1.48 mg/g and 0.318 +/- 0.034 g/cm2, respectively, significantly higher than those in the rats fed with calcium carbonate. There were no significant difference in blood calcium contents, weight gains and feed intake between those three groups of rats. It suggests that calcium derived from hydrolysed oyster shell may be absorbed and utilized more easily than calcium carbonate.
Animals↗
Selection of novel analogs of thalidomide with enhanced tumor necrosis factor alpha inhibitory activity.
BACKGROUND: Tumor necrosis factor alpha (TNF alpha) is thought to mediate both protective and detrimental manifestations of the inflammatory response. Recently, thalidomide (alpha-N-phthalimidoglutarimide) was shown to partially inhibit monocyte TNF alpha production (by 50-70%) both in vivo and in vitro. More efficient inhibition of TNF alpha may, however, be necessary to rescue the host from more acute and extensive toxicities of TNF alpha-mediated inflammation. MATERIALS AND METHODS: Three structural analogues of thalidomide were selected for study based on increased activity against TNF alpha production. The parent drug and the analogs were tested in vitro in human peripheral blood mononuclear cell cultures for their effects on lipopolysaccharide (LPS) induced cytokine protein and mRNA production using ELISAs and Northern blot hybridization. The in vitro effects of the drugs were then confirmed in vivo in a mouse model of LPS induced lethality. RESULTS: The new compounds (two esters and one amide) showed increased inhibition of TNF alpha production by LPS-stimulated human monocytes, relative to the parent drug thalidomide. The analogs and the parent drug enhanced the production of interleukin 10 (IL-10), but had little effect on IL-6 and IL-1 beta protein and mRNA production. When tested in vivo, the amide analog protected 80% of LPS-treated mice against death from endotoxin induced shock. CONCLUSIONS: Analogs of thalidomide designed to better inhibit TNF alpha production in vitro have correspondingly greater efficacy in vivo. These finding may have therapeutic implication for the treatment of human diseases characterized by acute and extensive TNF alpha production such as tuberculous meningitis or toxic shock.
Animals↗
[Population genetics of short tandem repeat locus HUMTH01].
The distributions of genotypes and allele frequencies for the short tandem repeat locus HUMTH01 in Chinese and German populations were studied by amplified fragment length polymorphism analysis. The PCR amplification products with different primers were compared by coelectrophoresis and the population data from different laboratories were evaluated. Based on the allele frequencies of HUMTH01, the genetic distances among 25 populations were computed and a phylogenetic tree was constructed accordingly. Some new implications for population genetics were obtained from this phylogenetic tree.
Chromosome Mapping↗
Responses of bat inferior collicular and auditory cortical neurons to pulsatile amplitude modulated sound pulses.
Under free field stimulation conditions, this study examined the responses of inferior collicular and cortical neurons of the big brown bat, Eptesicus fuscus, to pulsatile amplitude modulated sound pulses by means of temporally patterned pulse trains. When the pulse trains were delivered at different pulse repetition rates between 1 and 100 pps, inferior collicular neurons can follow pulse repetition at a higher rate than can auditory cortical neurons. 85% of 40 inferior collicular neurons studied always discharged impulses to each presented pulse delivered at repetition rates of up to 40 pps and 20% of these neurons could follow the repetition rate throughout the entire range of repetition rates tested. In contrast, only 60% of 56 auditory cortical neurons could follow a repetition rate up to 10 pps. At higher repetition rates, they only discharged impulses to the first pulse of each pulse train. According to variation in number of impulses, filtering properties of responses of inferior collicular and auditory cortical neurons to pulse repetition rate can be described as low-pass, high-pass, or band-pass. Most (63%) inferior collicular neurons behaved like band-pass filters to pulse repetition rate while most auditory cortical neurons behaved like all-pass (52%) or low-pass (37%) filters. Possible mechanisms underlying the different filtering properties between the inferior collicular and auditory cortical neurons are discussed.
Acoustic Stimulation↗
A study of polymorphism of antithrombin III at the level of both protein and DNA in a Chinese population.
The protein and DNA polymorphisms of human antithrombin III (ATIII) were studied by isoelectric focusing (IEF) and PCR techniques in a Chinese population sample (n = 51). Products of two alleles within the coding region of the ATIII locus were observed by IEF. The allele frequencies were: ATIII*1 = 0.9608, ATIII*2 = 0.0392. The PCR analysis of the fragment length polymorphism (FLP) for the ATIII 5' locus disclosed two alleles. Their frequencies were: ATIII5'*1 = 0.4118, ATIII 5'*2 = 0.5882. An association analysis between these two ATIII polymorphisms revealed the incompatibility between the ATIII 5'FLP and the ATIII IEF variants, indicating that the ATIII 5' FLP is not responsible for ATIII variants.
Antithrombin III↗
[Detection of stromelysin mRNA expression in human hepatocellular carcinoma by in situ hybridization].
For the propose of detecting the significance of stromelysin (of matrix metalloproteinase family) mRNA expression in the invasion and metastasis process of liver cell carcinoma, 19 cases of human hepatocellular carcinoma (HCC) and their surrounding tissues were studied by in situ hybridization techniques. Nine cases of the HCC tissues were positive while all the tumor surrounding tissues were negative. The stromelysin expression levels were higher in those HCC complicated with portal tumor emboli or in those classified pathologically in II-IV degree. It is considered that portal cancer emboli is a characteristic event for intrahepatic and extrahepatic metastasis of HCC, and matrix metalloproteinase may be of importance for the tumor invasion and metastasis.
Adult↗
[Subcellular localization of blood group substances ABH in human gastrointestinal tracts].
Authers investigated subcellular localization of ABH substances in normal human stomach, duodenum and transverse colon by post-embedding immunogold method using monoclonal antibodies specific for A, B and H antigens. The immunoreactivity was usually restricted to the following organelles: mucigen granules of epithelical cells of gastric mucosa, zymogenic granules of chief cells of the gastric gland, both mucigen granules and Golgi cisternae of neck mucous cells of the gastric gland and of epithelial cells of the duodenum mucosa as well as the Brunner's gland. ABH antigens were also visualized in microvilli of absorptive cells and mucigan granules of goblet cells of the transverse colon. The results suggested that ABH substances in those cells were produced in Golgi cisternae and were transfered to secreting granules, then were secreted with mucus. The mosaic distribution of ABH substances in cells and the effect of embedding resins on ABH antigens and the ultrastructure of cells were discussed.
ABO Blood-Group System↗
[Simultaneous phenotyping of proteins with various pHs by complex IEF and its application in forensic haemogenetics].
We have developed a new technique of complex isoelectric focusing (IEF) by which various proteins with different pHs can be detected out in polyacrylamide gels containing ampholytes with different pH ranges at the same time. The success of phenotyping 12 human proteins by this technique proved it was reliable and efficient. The cumulative Epp and the cumulative Dp reached 0.9 and 0.9999 respectively. It provides a new approach to analysis of genetic markers in the field of forensic haemogenetics.
Blood Proteins↗