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Biomedical subjects

F Meng

Publications and source records attributed to F Meng.

At least 73 records · Page 4Linked to original sources

Hybridization dominance of kinetics in recombinant ATH-1376 obtained via protoplast fusion between Aspergillus niger and Trichoderma reesei.

Comparisons of the kinetics of mycelium growth, cellulase biosynthesis, and the degradation of filter paper to accumulate reducing-sugar by the filtrates of cultures were carried out among the recombinant strain ATH-1376 and its two parents, Aspergillus niger AMS11 and Trichoderma reesei QM9414. The results showed that both the specific mycelium growth rate and the cellulase biosynthesis rate of the recombinant were dramatically dominant over those of the two parents. In addition, the negative correlation between the specific mycelium growth rate and the cellulase biosynthesis rate of the recombinant ATH-1376 was much lower than those of its parents. In terms of the amount of reducing-sugar accumulated from the hydrolysis of filter paper by culture filtrates, there were great differences among the three different treatments, i.e., fermentation filtrate of single parental strain, mixture of the fermentation filtrates from two parental strains with different ratios (v:v), and filtrate from the mixed culture of the two parental strains. Out of these, the second approach, particularly with the ratio of 1:1, was best for the accumulation of reducing sugar. Within various tested periods of enzymic hydrolysis, the amounts of reducing-sugar produced by the recombinant were 1.19 to 2.26 times as much as the maximum amounts produced in parallel by the mixture of filtrates (1:1) from separate fermentations of the two parental strains. These results suggested that constructing the engineered strains with hybridization dominance of these two typical genera of far-heredity could be effective to overcome the great deficiencies of routine mixculture, single-strain fermentation, or double fed-batch fermentations.

Aspergillus niger↗

Moving from the orphanin FQ receptor to an opioid receptor using four point mutations.

It is unclear how receptor/ligand families that are evolutionarily closely related achieve functional separation. To address this question, we focus here on the newly discovered Orphanin FQ, a peptide homologous to the opioid peptide Dynorphin, and its receptor, the Orphanin FQ receptor, which is highly homologous to the opioid receptors. In spite of this high degree of homology in terms of both ligands and receptors, there is little direct cross-talk between the Orphanin FQ system and the endogenous opioid system. Thus, the opioid peptides show either relatively low affinity or no affinity toward the Orphanin FQ receptor; conversely, Orphanin FQ has no affinity toward any of the opioid receptors. We sought to investigate the molecular basis of such discrimination by attempting to reverse it and endowing the Orphanin FQ receptor with the ability to bind opioids. We report that by mutating as few as four amino acids, we can produce a receptor that recognizes pro-Dynorphin products with very high affinity and yet still binds Orphanin FQ as well as the wild-type receptor. This suggests that the Orphanin FQ receptor has developed features that specifically exclude the opioids and that these features are distinct from those required for the high affinity binding of its own endogenous ligand.

Analgesics↗

INDEPTH Wide-Angle Reflection Observation of P-Wave-to-S-Wave Conversion from Crustal Bright Spots in Tibet

Three-component wide-angle seismic data acquired in southern Tibet during Project INDEPTH show strong P-to-S converted reflections from reflectors that are aligned at a depth of approximately 15 kilometers beneath the northern Yadong-Gulu rift. These converted reflections are locally higher in amplitude than the corresponding P-wave reflections. Modeling of reflection mode conversion as a function of incidence angle indicates that this condition obtains for a reflector that is a solid over fluid interface; it is not typical of a solid-solid interface. The likely candidates for a fluid trapped within the crystalline crust of southern Tibet are granitic magma and water (brine).

Journal Article↗

Mapping the receptor domains critical for the binding selectivity of delta-opioid receptor ligands.

While a good deal has been learned about determinants of high affinity ligand/receptor interactions in G-protein-coupled receptors, less is known about mechanisms of ligand selectivity. The opioid receptors offer an excellent opportunity to study the mechanisms whereby structurally very similar receptors discriminate between different but structurally highly related ligands. In the current study, we use a series of chimeric constructs between the delta-opioid receptor and either the mu- or the kappa-opioid receptors to investigate the structural basis of binding selectivity of multiple classes of delta-opioid receptor selective ligands. Our results demonstrate that a region containing the sixth transmembrane domain (TM6) and the third extracellular loop (EL3) in the delta-opioid receptor is absolutely critical for delta-opioid receptor selectivity. The introduction of this region into the kappa-opioid receptor is sufficient to impart a delta profile for delta-opioid receptor selective alkaloids such as naltrindole and naltriben. In order to locate the amino acid residues that may be involved in ligand selectivity in TM6 and EL3 of the delta-opioid receptor, several mutations were introduced into that region. These mutations showed differential effects on peptide and alkaloid ligands. In addition, none of the individual mutations alone could account for the changes exhibited by the chimeric receptors. We conclude that the selectivity of most delta-opioid ligands is achieved through their interaction with many different residues in the TM6/EL3 region. Our results also support a view that the extracellular domains of peptide receptors may provide the basis of a sorting mechanism for ligand selectivity.

Binding, Competitive↗

A chimeric analysis of the opioid receptor domains critical for the binding selectivity of mu opioid ligands.

The mu opioid receptor plays a key role in mediating the physiological, pharmacological, and behavioral effects of endogenous opioids and of opiate drugs such as morphine and heroin. This study examines the structural features critical to the selective binding of mu ligands to the mu receptor as opposed to the other two highly homologous opioid receptors, delta and kappa. We use a series of chimeric constructs between the mu and either the delta or the kappa receptors to investigate the structural bases of binding selectivity of multiple classes of mu-selective ligands. Our results demonstrate that a region comprising the sixth transmembrane domain and the third extracellular loop is critical for the mu/kappa discrimination by all mu-selective ligands. This region is also critical for mu/delta discrimination by the mu antagonists. However, mu agonists, particularly the peptides, exhibit more complex interactions, often relying on the N-terminal region surrounding the first extracellular loop for mu/delta discrimination. Thus, the same mu peptide ligand depends on different parts of the receptor to discriminate between mu and delta receptors on the one hand and mu and kappa on the other. In general, antagonists show the most consistent discrimination mechanisms regardless of construct, whereas agonists, particularly peptides, achieve selectivity by interacting with numerous domains of the receptors.

Animals↗

Cloning and characterization of multiple opioid receptors.

Over the course of 1 to 2 years, the field has moved swiftly to investigate the functional and structural properties of the newly cloned opioid receptors. Achieving a better understanding of these macromolecules is likely to have profound implications for drug design aimed at the production of better analgesic drugs, for a more fundamental understanding of mechanisms of action of drugs of abuse, and for a more comprehensive knowledge base regarding the biology of opioid peptides in particular, and neuroactive peptides in general.

Animals↗

An attempt on using the method of R-Q double-factor analysis to identify and group fusants.

A subsequent numeric taxonomy method for identifying and grouping the fusants was explored on the basis of characterization of the protein profiles of the fusants. By these two means, several typical excellent candidates of recombinants could be searched out quickly. Among the fusants from a definite fusion-cross, the different sister-strains were regarded as the samples of observation (n = N), the positions of the all bands of protein profiles as the objects (p = P), and the photometer-scanning area of the specific band as the experimental value (X) (zero was taken when the specific band of a certain strain was absent). The genetic multirelationships among the inter- and intra-sister-strains in terms of the positions and contents of the protein bands after fusion recombination occurred from this definite fusion-cross could therefore be determined on the same orientational factor-plate by using the computer program of the R-Q double-factor method to analyze this data matrix (Xnxp). These sister-strains could then be identified and grouped from the deduced heredity relationship between the fusants and parents.

Aspergillus niger↗

[Vaginal bleeding patterns and the regularity in use of Norplant].

OBJECTIVES: To understand vaginal bleeding patterns and the regularity in use of Norplant, and find out the main cause of termination that Norplant users can not bear. METHODS: A total of 306 menstrual diaries of Norplant users for 5 years were analyzed. The analysis of bleeding patterns was carried out by using the reference period approach and followed the guidelings published by WHO. RESULTS: The total number of vaginal bleeding days and the number of spotting days in the first reference periods were 36.6 days and 21.5 days, respectively. They were decreased obviously in the third reference period. The number of bleeding days was not obviously changed. The percentage of irregular bleeding was predominent in all of the bleeding patterns, 43.1%-57.6% usually. The percentage of prolonged bleeding was 13.4%-31.0%, secondly. The percentage of "normal" was only 33%. The number of bleeding days and the percentage of prolonged bleeding were more in bleeding termination group than in continuation group. The percentage of irregular bleeding was lower. CONCLUSIONS: During the initial stage of use of Norplant the total number of vaginal bleeding days was increased, but decreased obviously after 6 months. This change was influenced by the number of spotting days. Irregular bleeding and prolonged bleeding were main types of the disturbance of menstrual cycles after use of Norplant, The main cause of termination was prolonged bleeding.

Adult↗

Spontaneous malignant transformation of fibrous dysplasia.

OBJECTIVE: To evaluate the clinical and radiological findings in diagnosing spontaneous malignant transformation of fibrous dysplasia. METHODS: Fifteen cases of sarcomatous transformation proved by operation and pathological examinations were found in a group of 356 patients with fibrous dysplasia, and their radiological manifestations were retrospectively studied. The 15 cases included 8 osteosarcomas, 5 fibrosarcomas and 2 chondrosarcomas. All the 15 patients were known to have long-standing fibrous dysplasia, but no radiation therapy was ever received. Eleven patients had polyostotic fibrous dysplasia and 4 had monostotic type. RESULTS: Malignant transformation most frequently occurs in the cystic expansive lesion of the long tubular bone. Pains, swelling and late appearance of a bony mass are the main clinical manifestations. The early radiological features of sarcomatous transformation in fibrous dysplasia are moth-eaten or cystic areas of osteolysis located in the involved bone. The cortical destruction and gradual formation of a soft tissue mass that contains tumor-bone are highly suspicious of osteosarcomatous transformation, while ring-like and spotty calcification in the tumor matrix is indicative of chondrosarcoma. Fibrosarcoma usually shows simple osteolytic destruction. CONCLUSIONS: According to the clinical radiological findings, patients of sarcomatous transformation can be detected in the early stage. These radiological findings may be used as a clue for differentiating various kinds of sarcomatous transformation.

Adult↗

Primary astroglial cultures derived from several rat brain regions differentially express mu, delta and kappa opioid receptor mRNA.

The existence of opioid receptors within glial cell membranes has been proposed by several laboratories based on biochemical and radioligand binding data. The recent cloning of the mu, delta and kappa receptors has enabled us to directly examine the issue of opioid receptor expression in rat brain astroglia by using solution hybridization/ribonuclease protection assays to analyze the total RNA obtained from primary cultures of cortical, striatal, cerebellar, hippocampal and hypothalamic astrocytes. The results indicate that all five glial cultures expressed mu, delta and kappa receptor mRNA. The rank order of receptor mRNA abundance, expressed collectively across all five cultures, was determined to be delta > or = kappa >> mu. An analysis of the glial distribution profile for each receptor type revealed that mu receptor mRNA levels were the most abundantly expressed in cortical cultures, while the greatest levels of delta receptor mRNA were found in the cortical and hypothalamic cultures, and significant kappa receptor mRNA levels were produced by the cortical, hypothalamic and cerebellar cultures. Furthermore, the five glial cultures each expressed different levels of total opioid receptor (mu + delta + kappa) mRNA. The rank order of total opioid receptor mRNA expression across different astroglial cultures was found to be cortex > hypothalamus > cerebellum = hippocampus > striatum. An analysis of the relative expression profiles for mu, delta and kappa receptor mRNA within each culture revealed that all cultures manifested relatively high levels of delta and kappa receptor mRNA, but relatively low levels of mu receptor mRNA. Generally, cortical, hippocampal and hypothalamic cultures were characterized by comparable levels of delta and kappa receptor mRNA, and little, if any, mu receptor mRNA. However, striatal cultures were characterized by a high level of delta receptor mRNA which was approximately twice and four times that of the kappa and mu receptor mRNA, respectively. In contrast, cerebellar cultures expressed predominantly kappa receptor mRNA at a level which was almost twice that of the delta receptor mRNA, and expressed very little mu receptor mRNA. These data show that primary astroglial cultures not only express mu, delta and kappa receptor mRNAs, but they do so in a manner dependent upon receptor type and brain region. This suggests a regional heterogeneity of astrocytes with respect to opioid receptor expression, a characteristic previously described only for neurons. Furthermore, it suggests the existence of an additional anatomical component in CNS opioid systems.

Animals↗

Brain enzyme activities after intracerebroventricular injection of streptozotocin in rats receiving acetyl-L-carnitine.

Intracerebroventricular (i.c.v.) injection of streptozotocin has been introduced as a means to inhibit glucose utilization in the rat brain, and to induce changes in neurotransmitter systems and behavior which resemble those seen in Alzheimer's disease. In this study, enzyme activities previously investigated in Alzheimer's disease (peptidases, dehydrogenases and acetyltransferases) were measured in the septum and hippocampus of control and streptozotocin-treated rats. Streptozotocin-treated rats receiving acetyl-L-carnitine were also included in the experiments, to assess possible neuroprotective effects of this substance. All enzyme activities in the septum were affected by streptozotocin, with the exception of choline acetyltransferase activity. By contrast, choline acetyltransferase activity was the only enzyme activity affected in the hippocampus. The weight of the septum was reduced in streptozotocin-treated animals. These findings indicate that i.c.v. injection of streptozotocin causes septal damage and enzymatic changes that do not closely resemble those seen in Alzheimer's disease, which are more specific. Acetyl-L-carnitine partly prevented this damage, as reflected by an attenuation of the streptozotocin-induced decrease in hippocampal choline acetyltransferase activity. This finding indicates that streptozotocin-treated rats may be valuable to test possible neuroprotective effects of drugs.

Acetylcarnitine↗

Sequence analysis of anti-AChR antibodies in experimental autoimmune myasthenia gravis.

Autoantibodies directed against the acetylcholine receptor (AChR) lead to AChR loss and muscular weakness in myasthenia gravis and its experimental model, experimental autoimmune myasthenia gravis (EAMG). The role of different anti-AChR sequences and specificities in the pathogenesis of EAMG was investigated by sequencing a panel of 19 mouse mAbs, previously elicited against Torpedo and human AChR, that bound to at least four different epitope regions. The pathogenicity of eight mAbs that cross-reacted with mouse or rat AChR was tested. EAMG was induced by four mAbs against the main immunogenic region (MIR). Sequence analysis of different anti-AChR specificities showed a large diversity of H and L chain sequences. Highly homologous H chain sequences (> 90%) were found among some mAbs with similar specificities, whereas highly homologous L chain sequences were not restricted to Abs of a particular fine specificity. Sharing of a highly homologous VH gene or an identical DJH region was observed among three of four pathogenic anti-MIR mAbs, obtained by immunization with AChRs from different species. The VH genes of these three pathogenic mAbs were closely related to PC7183 germline genes indicating that some pathogenic Abs may already be present in the germline repertoire.

Amino Acid Sequence↗

A chimeric study of the molecular basis of affinity and selectivity of the kappa and the delta opioid receptors. Potential role of extracellular domains.

Within the large family of G-protein-coupled receptors, a picture is emerging which contrasts the binding of small ligands and the binding of peptides to the seven-helix configuration of the proteins. Because of its unique richness in both peptide and non-peptide ligands, the opioid receptor family offers several advantages for achieving a better understanding of similarities and differences in ligand/receptor interactions across different classes of agonists and antagonists. Since multiple, naturally occurring, ligands interact with the multiple receptors with varying degrees of selectivity, this family is also an excellent model for examining the structural basis of selectivity. Thus, the molecular basis of binding affinity and selectivity of the kappa and the delta opioid receptors was investigated by the construction of four kappa/delta chimeric receptors. The pharmacological profiles of these chimeras as well as those of the wild type kappa and delta receptors were determined by their binding with several different categories of opioid ligands. A linear model was used to deduce the relative contribution of each corresponding pairs of kappa-delta receptor segments to the binding of a given ligand. The results show that the kappa and delta receptors bind the same opioid core differently and achieve their selectivity through different mechanisms. In addition, the interaction of a peptide ligand with a receptor appears to be different from that of a small ligand. Furthermore, these results point to a particularly important role of the second extracellular loop and the top half of transmembrane domain 4 in the binding of prodynorphin products. Together, the results suggest that these peptide receptors can be bound and activated via multiple binding pockets as a function of their own topography and the nature of the interacting ligand.

Amino Acid Sequence↗

Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L-carnitine.

Treatment of rats with i.c.v. injected streptozotocin (STREP) may provide a relevant model of neurodegeneration that is induced by a decrease in the central metabolism of glucose. Acetyl-L-carnitine (ALCAR) enhances the utilization of alternative energy sources and by such a mechanism of action ALCAR could antagonize the effects of STREP treatment. In this study the effects of chronic treatment with ALCAR were evaluated on spatial discrimination learning in the Morris task and choline acetyltransferase (ChAT) activity of middle-aged STREP-treated rats. Chronic treatment with ALCAR attenuated both the STREP-induced impairment in spatial bias and the decrease in hippocampal ChAT activity. These findings indicate that ALCAR treatment has a neuroprotective effect, although further studies are needed to characterize the mechanism of action of ALCAR in this model.

Acetylcarnitine↗

Integrin alpha 5 during early development of Xenopus laevis.

The full length sequence of the Xenopus integrin alpha 5 subunit is reported. Analysis of cloned cDNA fragments reveals that alternative polyadenylation of alpha 5 mRNA occurs in the embryo. Furthermore, a variant form of the alpha 5 mRNA is expressed which encodes an integrin alpha 5 subunit with a truncated cytoplasmic domain. Integrin alpha 5 mRNA and protein are expressed in oocytes, eggs and throughout development. Spatial expression of alpha 5 mRNAs is first detected by whole mount in situ hybridization in presumptive neural crest cells and in the somitic mesoderm from the midgastrula stage onwards. In contrast, the alpha 5 protein is present on newly formed plasma membranes beginning at first cleavage. During neurulation, the integrin alpha 5 subunit disappears from the outer layer of the ectoderm, the notochord and the neural tube and accumulates in the sensorial layer of the ectoderm, the somites and the neural crest cells. These results provide evidence for the position specific regulation of alpha subunit expression in early vertebrate embryos.

Amino Acid Sequence↗

Effectiveness of Norplant implants through seven years: a large-scale study in China.

The effectiveness of Norplant implants over a seven year period of continuous use was studied in a multicenter trial. Pregnancy rates were 0.4 per 100 in both year six and year seven. More than 3,600 women completed 6 years and more than 2,400 women completed 7 years. Pregnancy rates increased with weight (p < .05) and decreased with age, but in years 6 and 7 combined, the pregnancy rate neither reached nor exceeded 1 per 100 woman years in any 5 year age group or in any 10 kg weight group.

Adult↗

Immunocytochemistry of Kaposi's sarcoma-like tumor cells from pigtailed macaques with simian AIDS.

Some macaques infected with SRV-2 developed SAIDS and RF, a Kaposi's sarcoma (KS)-like tumor. We investigated the immunophenotypic markers of this SAIDS-associated retroperitoneal fibromatosis (RF). RF tumor is characterized by proliferation of spindle cells accompanying inflammatory cell infiltrates, fibroblasts, and endothelial cells. RF spindle cells in tumor tissues revealed several immunobiologic characteristics similar to vascular smooth-muscle cells or myofibroblasts based on positive immunoreactivity of smooth-muscle alpha-actin and desmin. The majority of cultured RF spindle cells also expressed specific markers for vascular smooth muscle. These results suggest that the RF spindle cells are derived from vascular smooth-muscle cells. Furthermore, RF tissues and cells were persistently infected with SRV-2, which may play an important role in viral etiology of AIDS-associated neoplasm in this macaque model.

Animals↗

[Stability of angesin solution].

Chemical kinetics of ethyl acetate extract from the roots of Angelica sinensis in aguerus solution (angesin solution) was studied by isothermal acceleration test. The useful life (t0.9) calculated for angesin solution is one year.

Drug Stability↗