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Biomedical subjects

L Zhou

Publications and source records attributed to L Zhou.

At least 487 records · Page 27Linked to original sources
PubMed1995

Cellulases and hemicellulases of the anaerobic fungus Piromyces constitute a multiprotein cellulose-binding complex and are encoded by multigene families.

More than 80% of the extracellular Avicelase, endoglucanase, xylanase and mannanase activities of the anaerobic fungus Piromyces were associated with a cellulose-binding complex. The complex was composed of at least 10 polypeptides ranging in size from 190 kDa to 50 kDa, and contained numerous endoglucanases, xylanases and mannanases. Multiple genes encoding each of these activities were isolated from an expressing cDNA library.

Anaerobiosis↗
PubMed1995

Suppression of NF kappa B activation and NF kappa B-dependent gene expression by tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase.

Tepoxalin, a dual inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5LO) with cytokine modifying activity, is also a potent inhibitor of the transcription factor, nuclear factor kappa B (NF kappa B). NF kappa B is a pleiotropic activator that is involved in the regulation of many genes whose products participate in immune or inflammatory responses. Tepoxalin inhibited in a dose related manner NF kappa B activation by PMA + ionomycin or H2O2 in Jurkat and HeLa cells. TNF-alpha-induced NF kappa B was also inhibited by tepoxalin in HeLa cells, while relatively less marked inhibition was observed in Jurkat cells. Activation of NF kappa B in several monocytic cell lines was also suppressed by tepoxalin. However AP-1 stimulation under the same conditions was not affected by tepoxalin. Other CO, LO inhibitors such as naproxen or zileuton did not inhibit NF kappa B activities. This inhibitory activity of tepoxalin was further illustrated by its suppression of NF kappa B regulated genes such as IL-6 in PMA stimulated human PBL and c-myc in IL-2 dependent T cell lines. Tepoxalin also blocked PMA + ionomycin-induced I kappa B degradation in a time-dependent fashion. The possible mechanism of tepoxalin in NF kappa B activation and its potential clinical application are discussed.

Animals↗
PubMed1995

The immunostimulatory compound 7-allyl-8-oxoguanosine (loxoribine) induces a distinct subset of murine cytokines.

C8- and N7, C8-substituted guanine ribonucleosides comprise a class of molecules with potent immunostimulatory activity for a variety of humoral and cellular immune responses. Although it has been suggested that the immunostimulatory activity may be partially mediated by cytokine production, to date there has been no systematic evaluation of the spectrum of cytokines elicited by these nucleosides. In this study, we examine the cytokines produced by murine spleen cells in response to the di-substituted guanosine analog loxoribine (7-allyl-8-oxoguanosine). First, the levels of cytokine mRNA in spleens from vehicle- or loxoribine-treated mice were compared using PCR analysis with a panel of cytokine-specific primers. Enhancement of IL-1 alpha, TNF-alpha, TNF-beta, IL-6, IFN-alpha, and IFN-gamma mRNA was seen in the spleens of loxoribine-treated mice. IL-12 mRNA responses were more complex, with an increase in the p40 chain and a decrease in the p35 chain. In contrast, no increase was seen for mRNA levels of IL-2, IL-3, IL-4, IL-5, IL-7, or GM-CSF. ELISA assays on the supernatants of loxoribine-treated spleen cells demonstrated that IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were all produced in a dose-dependent fashion with TNF-alpha produced first, followed by IL-6 and IFN-gamma, and last by IL-1 alpha. IFN-alpha beta activity rose as quickly as TNF-alpha, leveling off at 8 to 12 hr, and was supplanted by a later-occurring surge of IFN-gamma production. IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were also detected in the sera of mice injected with loxoribine. When antibodies against the relevant cytokines were tested, only anti-IFN-alpha beta inhibited NK activity or lymphocyte proliferation and, in both cases, activity was partially restored by the addition of exogenous IFN-alpha beta. Taken together, these data indicate that loxoribine induces the production of a selective cohort of cytokines all of which have been shown to have immunostimulatory activity. However, only IFN-alpha beta appears to play a role in the enhancement of NK activity and lymphocyte proliferation.

Animals↗
PubMed1995

Characterization of recombinant soluble human transforming growth factor-beta receptor type II (rhTGF-beta sRII).

Recombinant human transforming growth factor soluble receptor Type II (rhTGF-beta sRII) corresponding to the 159 amino acid extracellular domain of hTGF-beta RII has been expressed in insect cells using the baculovirus expression system or in a mouse myeloma cell line. N-terminal sequence analysis of the purified protein revealed the removal of the 23 amino acid signal peptide. In SDS-PAGE, the rhTGF-beta sRII resolves into multiple bands due to N-linked glycosylation. Recombinant hTGF-beta sRII is a TGF-beta antagonist and will inhibit the biological activities of TGF-beta 1, TGF-beta 3, and TGF-beta 5 on TGF-beta-responsive cell lines, such as murine HT-2 or human TF-1 with an ED50 of approximately 0.3 micrograms/mL. However, hTGF-beta sRII does not inhibit TGF-beta 2 bioactivities in these cell lines, suggesting that hTGF-beta RII has low affinity for TGF-beta 2. Polyclonal antibodies to hTGF-beta sRII have been produced in goats and purified on Protein-G affinity columns. This antibody can inhibit TGF-beta 1,2,3,5-dependent bioactivities on human cell lines such as TF-1. Additionally, this antibody has species cross-reactivity and will also inhibit TGF-beta-dependent bioactivities on murine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Polarography as a tool in peptide and protein analysis: studies on metal-chelating substances induced by cadmium in the algae Pheodactylum tricornutum and the graminae Agrostis capillaris.

Methods to determine characteristics and quantities of metal-binding substances are needed in order to identify phytochemical systems for use in agriculture and waste treatment. A metal-binding polypeptide (phytochelatin) was prepared by liquid chromatography from the algae Pheodactylum tricornutum and roots of the graminae Agrostis capillaris after exposure to cadmium. Polarographic (voltammetric) analysis indicated binding of cadmium by the polypeptide at different stabilities. No catalytic hydrogen peak at -1.7 V appeared in the polarogram of plant and algae metal-binding substance, but did appear in the polarogram of the metal-chelating protein metallothionein. In all polarograms, two significant peaks were detected. One at approximately -520 mV probably represents the reduction of single cadmium-sulfur bonds, and one at -930 mV the reduction of cadmium-thiolate complexes. A dose-response relationship between cadmium concentration and peak current at -930 mV was observed after exposure of roots of Agrostis at 5 and 10 microM.

Cadmium↗
PubMed1995

Characterization of IS1167, a new insertion sequence in Streptococcus pneumoniae.

A new insertion sequence in Streptococcus pneumoniae was identified as a 1435-bp segment of the genome containing 24-bp terminal inverted repeats and flanked by 8-bp direct repeats. A copy of the element, named IS1167, adjacent to the comAB genes was sequenced; seven additional copies were found in the genome of strain CP1200 and relatives descended from strain R36A. Among 22 independent pneumococcal isolates, 11 contained copies of elements hybridizing to IS1167 in nine distinct restriction fragment patterns, with 3-12 copies each. The bulk of the element was occupied by two overlapping open reading frames, encoding basic proteins which together exhibited strong similarity to the full length of the putative transposase of the staphylococcal transposable element, IS1181, as well as significant similarity to those of seven additional known or putative insertion sequences related to the mycobacterial element, IS1096.

Amino Acid Sequence↗
PubMed1995

HMB45: a specific marker for melanoma metastases in the central nervous system?

The monoclonal antibody HMB45 is used to detect an epitope specific for melanocytes, malignant melanomas and melanoma metastases. Using the PAP method, we observed consistent expression of HMB45 in 19 metastases of melanotic and amelanotic malignant melanomas of the central nervous system, while metastases of 32 adenocarcinomas, 10 squamous cell and 8 small cell carcinomas were negative except for 2 cases of breast cancer. Differential diagnosis between cancer and melanoma metastases can be made using cytokeratins as an additional immunocytochemical marker protein. Ten meningeomas and 5 pineocytomas were also negative. Even though it is not absolutely specific, we consider the HMB45 immunoreaction diagnostic for a metastasis of a malignant melanoma if the tumour is cytokeratin negative and HMB45 positive in a large number of tumour cells.

Antigens, Neoplasm↗
PubMed1995

An efficient route to N6 deoxyadenosine adducts of diol epoxides of carcinogenic polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons are metabolized to a wide variety of oxidized derivatives, including highly reactive diol epoxides which alkylate DNA. The reaction lacks regio- or stereospecificity but occurs primarily at the exocyclic amino groups of deoxyguanosine and deoxyadenosine. An efficient route to N6 adducts of deoxyadenosine is described using as examples those arising from trans opening of the anti-tetrahydrodiol epoxides of naphthalene, benzo[a]pyrene, and benzo[c]phenanthrene. The adducts were synthesized in 50-92% yields by reaction of 6-fluoropurine 2'-deoxyriboside with aminotriols formed by trans opening of racemic dihydrodiol epoxides using liquid NH3. The diastereomeric adducts were separated by HPLC and their absolute configurations were assigned by circular dichroism. 1H NMR studies revealed significant differences in conformation of the tetrahydroaromatic ring between the sterically unrestricted naphthalene derivative and the sterically congested derivatives of benzo[a]pyrene and benzo[c]phenanthrene. These differences may have a bearing on the higher carcinogenicity shown by the latter hydrocarbons. Undecadeoxyoligonucleotides bearing regio- and stereochemically defined adenine N6-anti-trans-benzo[a]pyrene adducts have been prepared.

Base Sequence↗
PubMed1995

The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15.

To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins. IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors. These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein.

Amino Acid Sequence↗
PubMed1995

Mechanism research of cryoanalgesia.

The sciatic nerves of rabbits were frozen at different temperatures (-20 degrees C, -60 degrees C, -100 degrees C, -140 degrees C, and -180 degrees C). The morphology and function of the frozen nerves were examined with light microscopy (hematoxylin and eosinophilin stain and a histochemical thiocholine method) and electron microscopy. The function of the nerve after freezing was assessed using short latency somatosensory evoked potentials, sensory conduction velocity, and electromyogram at various intervals after freezing. There were no changes in morphology or function of nerves cryolesioned at -20 degrees C. The nerve fibers cryolesioned at -60 degrees C showed signs of freezing degeneration and lost their conductive function although, these nerves all recovered. Approximately half of nerve fibers cryolesioned at -100 degrees C showed Wallerian degeneration, and although the time to remyelination was delayed, nerve regeneration was still complete. At -140 degrees C and -180 degrees C the nerve fibers showed immediate necrosis, with destruction of basal membranes and proliferation of collagen fibers. The results explained the mechanism of cryoanalgesia. Our study demonstrates that cryo-temperatures lower than -140 degrees C will cause permanent alterations in nerve morphology and function, whereas warmer temperatures do not result in permanent nerve damage and are therefore not likely to provide long-term analgesia to patients.

Analgesia↗
PubMed1995

Electron-affinic radiosensitizers possessing NPSH-reactive side chains: cytotoxicity and radiosensitizing activity towards hypoxic EMT6 cells in vitro.

A new class of dual-function nitroazole derivatives that are composed of electron-affinic nitroazole rings and a thiol-reactive alpha, beta-unsaturated carbonyl side chain were synthesized to evaluate their physico-chemical properties, reactivity with glutathione (GSH), and cytotoxicity and radiosensitizing activity towards EMT6/KU cells in vitro. Among this class of nitroazole compounds, 2-nitroimidazole-derivative (1), 3-nitro-1,2,4-triazole derivative (2), and 2-methyl-4-nitroimidazole derivative (3) with a common side-chain structure of trans CH2CH = CHCO2CH3 readily reacted with GSH in phosphate-buffer solution (pH 7.2, 310 K). These compounds showed higher cytotoxicities to both aerobic and hypoxic EMT6/KU cells than the corresponding alpha, beta-saturated counterparts (6-8) with a side-chain structure of CH2CH2CH2CO2CH2CH3. The hypoxic cytotoxicity of 1 and 2 with similar electron affinities to that of misonidazole (9) was potentiated by the combined effects of depletion of non-protein thiols (NPSH) by the alpha, beta-unsaturated carbonyl side chains and bioreduction of the nitroazole rings. The sensitizer enhancement ratios in vitro (SERvitro) of 1 (2.80 +/- 0.20) and 2 (2.63 +/- 0.27) at a dose of 1.0 mmol dm-3 are comparable with the oxygen enhancement ratio (OER = 2.90 +/- 0.10) and are significantly larger than those of their respective counterparts 6 (1.28 +/- 0.06) and 7 (1.22 +/- 0.09). A less electron-affinic compound, 3, also gave a large SERvitro = 1.80 +/- 0.18, whereas the counterpart 8 was not effective (1.10) in radiosensitizing hypoxic cells. Compounds 1-3 not only altered the slope, but also reduced the shoulder of the dose-survival curve. These 'dual-function' nitroazole radiosensitizers show much lower levels of in vitro radiosensitization, as measured by the C1-6, than the previously reported 'anomalous' radiosensitizers such as 5-substituted 4-nitroimidazole radiosensitizers.

Azoles↗
PubMed1995

Aspirin inhibits secretagogue-stimulated and postprandial pancreatic exocrine secretion in conscious rats.

The effect of salicylate and nonsalicylate antiinflammatory drugs and prostaglandins (PGs) on pancreatic exocrine secretion are controversial. We studied the effect of aspirin (ASA) on secretin- and cholecystokinin (CCK)- or meal-stimulated pancreatic secretion. The interrelation between ASA, PG, and pancreatic exocrine secretion was also investigated. Conscious rats with chronic duodenal, pancreatic, and biliary cannulas received secretin (5 pmol/kg/h, i.v.) and CCK (56 pmol/kg/h) or a meal with administration of cimetidine (20 mg/kg/h, i.v.), ASA (1.2, 12, or 60 mumol/h, i.v.), Salicylic acid (SA) (1.2, 12, or 60 mumol/h, i.v.), prostaglandin E2 (PGE2) (10 micrograms/kg/h), or indomethacin (2 mg/kg) was given, respectively. Pancreatic flow volume, bicarbonate, and protein were determined every 15 min. An inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) (36 micrograms/kg/h) and an activator, phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate, TPA) (100 ng/kg/h) were used for evaluation of the role of protein kinase C on basal and secretagogue-stimulated pancreatic secretion. ASA, but not SA inhibited the secretin- and CCK-stimulated pancreatic secretion including volume, bicarbonate, and protein in a dose-dependent manner without affecting basal pancreatic secretion. ASA and indomethacin suppressed meal-stimulated pancreatic secretion up to 83.8%. PGE2 significantly inhibited the secretin- and CCK-stimulated pancreatic secretion which was further suppressed by the concomitant ASA infusion. Modulation of protein kinase C failed to affect pancreatic secretion. The data indicate that ASA inhibits both secretin- and CCK-stimulated pancreatic secretion by a mechanism independent of prostaglandin biosynthesis inhibition.

Animals↗
PubMed1995

Effect of endogenous insulin on pancreatic exocrine secretion in perfused dog pancreas.

Canine pancreas was perfused with an intraarterial infusion of Krebs-Ringer bicarbonate solution containing 5% dog red blood cells, 0.1% bovine serum albumin, and 3% dextran at 15 ml/min, while portal effluent was continuously collected. Pancreatic juice was obtained in 15-min samples via main pancreatic duct cannulation. After a 1-h basal period, secretin and cholecystokinin-8 (CCK), at doses of 2.5 ng.min-1 each, were simultaneously infused for 10 min, with background infusion of a normal rabbit serum (NRS) or an antiinsulin serum (Anti-I) in 5 ml each via a sidearm of the intraarterial catheter. The infusion of secretin and CCK resulted in a significant increase in pancreatic bicarbonate and protein secretion during the infusion of NRS, whereas the pancreatic secretory response of bicarbonate and protein was profoundly suppressed by the infusion of Anti-I in six pancreata so studied. This suppression by Anti-I coincided with significant increases in somatostatin and pancreatic polypeptide levels in portal venous effluent. In three additional pancreata, simultaneous infusions of Anti-I with antisomatostatin (5 ml) and antipancreatic polypeptide (5 ml) serum failed to inhibit the pancreatic exocrine secretion. These results indicate that secretin- and CCK-stimulated pancreatic secretion of bicarbonate and protein depends heavily on local action of insulin. The suppression by Anti-I of pancreatic secretion is mediated, in part, by local releases of somatostatin and pancreatic polypeptide. Thus, the insuloacinar axis plays an important regulatory role in pancreatic exocrine secretion in the dog, and it involves at least three islet hormones including insulin, somatostatin, and pancreatic polypeptide.

Animals↗
PubMed1995

Antiproteinuric effect of a thromboxane receptor antagonist, S-1452, on rat diabetic nephropathy and murine lupus nephritis.

To shed light on the role of thromboxane A2 (TXA2) in renal injury, we evaluated the effects of S-1452, a TXA2 receptor antagonist, on rats with streptozotocin (STZ)-induced diabetic nephropathy and murine lupus nephritis. In STZ diabetes rats (n = 6), urinary protein excretion significantly increased from 8 weeks and was about 5 times as much as that in normal rats at 10 weeks after induction of diabetes. In S-1452-treated rats (n = 6), increase in urinary protein was rarely observed and was significantly inhibited at 8 and 10 weeks after induction of diabetes. In (NZB x NZW)F1 mice, no proteinuria was detected in vehicle controls (n = 20) and S-1452-treated mice (n = 20) from 0 to 8 weeks after initiation of S-1452 treatment. Proteinuria was observed in 3, 7 and 8 mice in the control group, and 0, 2 and 5 mice in the S-1452 group at 12, 16 and 20 weeks after initiation of S-1452 treatment, respectively. Proteinuria developed more slowly in S-1452-treated mice than in vehicle controls. In conclusion, TXA2 receptor antagonist, S-1452, suppresses the progression of renal injury.

Acetylglucosaminidase↗
PubMed1995

Uptake of radiolabeled and colloidal gold-labeled chyle chylomicrons and chylomicron remnants by rat platelets in vitro.

This study examined the uptake of chyle chylomicrons (CMs) and chylomicron remnants (CMRs) by rat platelets in vitro. CMs and CMRs were doubly labeled with [3H]arachidonate ([3H]-20:4) and [14C]cholesterol and were incubated with platelets for up to 4 hours. A significant uptake (binding and/or internalization) of CMs by the platelets occurred, as indicated by the parallel increase of [3H]20:4 and [14C]cholesterol in platelets with incubation time. Addition of unlabeled CMs, VLDLs, LDLs, and HDLs decreased the uptake of labeled CMs. The competition experiments suggested that there is both a saturable binding and a nonspecific uptake of CMs. During incubation with CMs, the proportion of [3H]20:4 in phospholipids decreased and that in 1,2-x-diacylglycerol increased. The data indicated that a phospholipase C-mediated degradation of phosphatidylcholine and phosphatidylethanolamine occurred, whereas [3H]20:4 in triglyceride and 14C in cholesterol ester did not change. Electron microscopic studies after incubation with colloidal gold-labeled CMs (CM-Au's) demonstrated an accumulation of CM-Au particles in the open canalicular system of the platelets. Some CM-Au particles were localized in cytoplasmic vacuoles that were not stained by ruthenium red. Some CM-Au's or free gold particles were in vacuoles that showed acid phosphatase activity, indicating that some true endocytosis of CM occurred. The uptake of [3H]-20:4- and [14C]cholesterol-labeled CMRs was low compared with the uptake of CMs. After incubation with colloidal gold-labeled CMRs (CMR-Au's), only a few platelets contained CMR-Au in their open canalicular systems, and no CMR-Au particles were seen in the cytoplasm or in acid phosphatase-positive vacuoles. Rat platelets can thus interact with CMs by a process that leads to a sequestration in the open canalicular system and endocytosis and a net degradation of CM phospholipids. The conversion of CMs to CMRs counteracts this interaction.

Animals↗
PubMed1995

Enhanced collagen synthesis and transcription by peak E, a contaminant of L-tryptophan preparations associated with the eosinophilia myalgia syndrome epidemic.

The pathogenesis of the eosinophilia myalgia syndrome (EMS) remains unclear. Several abnormal constituents have been found in the L-tryptophan lots responsible for the illness, particularly, 1,1-ethylidenebis[L-tryptophan], also called peak E or EBT, and 3-phenylamino-alanine or peak 5. However, the role of these contaminants in the pathogenesis of EMS and in the development of fibrosis is unknown. We now report that peak E, a dimer of L-tryptophan, is a potent stimulus for human dermal fibroblast DNA and collagen synthesis. Peak E (0.1-1.0 microM) increased DNA synthesis up to four-fold (P = 0.0001) in a dose-dependent manner (r = 0.987). When added to monolayer cultures for 2 to 24 h, peak E (0.5 to 100 microM) caused a progressive, more than threefold increase in alpha 1(I) procollagen mRNA levels and collagenous protein. No increase in procollagen mRNA levels was found after the addition of another major L-tryptophan contaminant, peak 5, or with L-tryptophan itself. Transient transfection with a 2.5-kb alpha 1(I) procollagen promoter-luciferase construct showed that peak E causes a twofold upregulation of promoter activity (P = 0.022). Contraction of collagen gels, consisting of human dermal fibroblasts incorporated into a type I collagen lattice, was enhanced two-fold by exposure to peak E (P = 0.001). We conclude that a major constituent of contaminated batches of L-tryptophan, peak E, is a potent stimulus for fibroblast activation and collagen synthesis. This stimulatory action of peak E may provide a direct mechanism for the development of fibrosis in EMS.

Cells, Cultured↗
PubMed1995

[A randomized crossover comparison of azasetron and granisetron in the prophylaxis of emesis induced by chemotherapy including cisplatin].

The clinical application of 5-HT3 receptor antagonists has enabled continuation of the course of chemotherapy including cisplatin, which induces strong nausea and vomiting, and to prevent the delay of curative treatment for cancer patients receiving neoadjuvant chemotherapy. However, with the development of basic research on the mechanisms of vomiting, each 5-HT3 receptor antagonist has appeared to have different pharmacological actions and, subsequently, the difference in the clinical efficacy of each drug has been reported in Europe and USA. In freshly advanced head and neck carcinoma cases, a randomised crossover study was performed to compare the efficacy and safety profile of a single intravenous dose for 7 days of azasetron (10 mg/day) or granisetron (3 mg/day) in the prophylaxis of nausea and vomiting induced by multi-drug chemotherapy including cisplatin (50 mg/m2 or 60 mg/m2). Anti-emetic effects were evaluated by the protective rates for nausea and vomiting for 7 days following the start of cisplatin administration. Both 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute and delayed emesis induced by chemotherapy, whereas the efficacies of azasetron on day 3 and 4 were superior to those of granisetron. No adverse effect of either drug was observed in this study.

Aged↗