Search PubMed⌕ Search

Biomedical subjects

L Zheng

Publications and source records attributed to L Zheng.

At least 289 records · Page 16Linked to original sources
PubMed1995

frizzled regulates mirror-symmetric pattern formation in the Drosophila eye.

Coordinated morphogenesis of ommatidia during Drosophila eye development establishes a mirror-image symmetric pattern across the entire eye bisected by an anteroposterior equator. We have investigated the mechanisms by which this pattern formation occurs and our results suggest that morphogenesis is coordinated by a graded signal transmitted bidirectionally from the presumptive equator to the dorsal and ventral poles. This signal is mediated by frizzled, which encodes a cell surface transmembrane protein. Mosaic analysis indicates that frizzled acts non-autonomously in an equatorial to polar direction. It also indicates that relative levels of frizzled in photoreceptor cells R3 and R4 of each ommatidium affect their positional fate choices such that the cell with greater frizzled activity becomes an R3 cell and the cell with less frizzled activity becomes an R4 cell. Moreover, this bias affects the choice an ommatidium makes as to which direction to rotate. Equator-outwards progression of elav expression and expression of the nemo gene in the morphogenetic furrow are regulated by frizzled, which itself is dynamically expressed about the morphogenetic furrow. We propose that frizzled mediates a bidirectional signal emanating from the equator.

Animals↗
PubMed1995

Increased soluble CD14 levels in BAL fluid in pulmonary tuberculosis.

INTRODUCTION: CD14 is a cell surface glycoprotein expressed mainly on mature monocytes and macrophages. Soluble CD14 (sCD14) is present in normal plasma and is found increased in serum of patients with septicemia, polytrauma, and sarcoidosis. In active sarcoidosis, increased levels of sCD14 in BAL supernatant have been demonstrated. STUDY OBJECTIVE: To investigate sCD14 levels in BAL of pulmonary tuberculosis (PTB), another inflammatory disease characterized by granuloma formation. METHODS: BAL was performed in 12 patients with active but untreated PTB and 12 healthy persons. Cytologic and immunocytologic characteristics were determined. sCD14 was measured by a sandwich enzyme-linked immunosorbent assay. RESULTS: The level of sCD14 in patients with PTB was increased compared with controls (mean +/- SEM: 34.4 +/- 9.6 ng/mL vs 11.5 +/- 2.2 ng/mL; p = 0.02). No correlation was found between sCD14 levels and BAL cell differentials or lymphocyte surface markers. CONCLUSION: Similar to sarcoidosis, increased levels of sCD14 are found in BAL supernatant of PTB patients.

Adult↗
PubMed1995

Autocrine feedback death and the regulation of mature T lymphocyte antigen responses.

Antigen-induced T cell death is an important regulatory mechanism in the peripheral immune system. Evidence suggests that this process depends on T cell growth-inducing lymphokines such as IL-2 and occurs in proportion to the degree of T cell receptor occupancy. Strong T cell receptor stimulation leads to the synthesis of death molecules such as Fas ligand and tumor necrosis factor that cause T cell suicide. We propose that T cell death under these circumstances is the culmination of a feedback control mechanism termed propriocidal regulation or autocrine feedback death that regulates the expansion of specific T cell clones under conditions of high lymphokine and antigen load. In a quasi-stochastic system such as the antigen receptor repertoire, feedback information may be essential for the appropriate regulation of peripheral immune responses. Our understanding of this feedback mechanism affords a means to manipulate antigen-specific T cell death in vivo. The application of this approach to the therapy of T cell-medicated immunological diseases is discussed.

Animals↗
PubMed1995

Peptide transporter function and prolidase activities in Caco-2 cells: a lack of coordinated expression.

Peptide transport and prolidase activities were measured to determine whether the expression of these two components of protein nutrition are coordinately regulated; i.e., whether an increase in the peptide transporter function will necessarily lead to a higher prolidase activity, or vice versa. The results indicated that peptide transporter function and prolidase activity respond differently to cell differentiation and feeding schedules. The results also indicated that peptide transport and prolidase activities were different in two Caco-2 cell "clones", with S-K cells transported peptides at higher rates but had lower total prolidase activities, when compared to ATCC cells. These results suggest that the expression of the peptide transporter function and prolidase activity is not coordinated. In addition, both the transporter and the prolidase activities affected the overall transport of Phe when given as the dipeptide Phe-Pro, supporting the notion that intestinal absorption of peptides is an essential component of amino acid absorption. In conclusion, the evidence suggests that the peptide transporter function and prolidase activity are not coordinately expressed by the human intestinal Caco-2 cells.

Basement Membrane↗
PubMed1995

[A study on expression of epidermal growth factor receptor in pleomorphic adenoma of lacrimal gland].

Expression of epidermal growth factor (EGF) receptor was examined in 32 cases of pleomorphic adenoma of lacrimal gland by means of an immunohistochemical method. While normal lacrimal glands were all negative for the antigen, EGF receptor was positive in 10 pleomorphic adenomas and the positive staining was mainly limited in the tumor cells in trabecular or duct-like arrangement or squamous metaplastic epithelium. These data suggest that the expression of EGF receptor be significantly higher in pleomorphic adenoma than in normal lacrimal gland, and also suggest that EGF receptor be expressed in the neoplastic cells which are considered to be of duct origin.

Adenoma, Pleomorphic↗
PubMed1995

Effect of intracerebroventricular injection of somatostatin or GABA on pain threshold and contents of GABA or somatostatin in rat brain.

AIM: To study the interactive influence of somatostatin (Som) and GABA in the brain and its relation to the pain modulation. METHOD: Using radioimmunoassay, amino acid analyzer and measurement of pain threshold. RESULTS: Som 10 micrograms i.c.v. increased the pain threshold (from 4.2 +/- 0.2 to 7.0 +/- 1.1 s) of the rat, but reduced the content of GABA from 2.3 +/- 0.3 to 1.6 +/- 0.4 mumol g-1 in hippocampus and from 2.4 +/- 0.4 to 1.5 +/- 0.2 mmol kg-1 in brain stem. After depletion of the Som in brain by i.c.v. cysteamine (Cys, 600 micrograms), the content of GABA in hippocampus and brain stem was also reduced without modification of the pain threshold. GABA 1500 micrograms i.c.v. had no effect on the pain threshold, however, caused a decrease of Som content from 55 +/- 4 to 37 +/- 5 ng g-1 in hippocampus and from 84 +/- 4 to 55 +/- 6 ng g-1 in brain stem, which was blocked by bicuculline (10 micrograms). After reduced of the GABA content in brain by subcutaneous injection of isoniazid (300 mg kg-1), Som content of the hippocampus and rain stem was markedly elevated. CONCLUSION: Som and GABA inhibited each other, unrelated to their pain modulation.

Animals↗
PubMed1995

[Experimental study on in vivo hematopoietic regulation of interleukin-6 gene therapy].

Interleukin-6 (IL-6), a pleiotropic cytokine, is involved in extensive immune regulation and hematopoietic regulation. We observed the effect of fibroblast mediated human IL-6 gene therapy on hematopoiesis. The platelet counts started to increase at day 4 after implantation of IL-6 highly secreting fibroblast cells and peaked at day 10 and lasted at high level for 22 days. The neutrophil counts were elevated after their implantation, but WBC did not show any remarkable increase. The CFU-GM and CFU-MK in bone marrow and spleen were also increased significantly. The results demonstrated that fibroblasts mediated human IL-6 gene therapy can significantly augment in vivo hematopoietic functions in bone marrow and spleen and elevate the number of nuetrophils and platelets. This study provides a new approach to treat thrombopenia and chemotherapy or radiotherapy-induced hematopoietic suppression.

3T3 Cells↗
PubMed1995

[Trigeminal neuralgia caused by microvascular compression of perforation type].

Of 512 patients of trigeminal neuralgia who had undergone microvascular decompression through a retromastoid craniotomy, 4 were caused by microvascular compression of perforation type. In 3 patients, the perineurium of trigeminal nerve was cut longitudinally, the nerve-tract was separated, the perforating blood vessel was pushed to the distal end, and the vessel was made to leave the nerve sensitive area and then decompression materials were put between the separated nerve-tract. The patients were pain-free and the facial sensation was preserved after operation, and no recurrence occurred in 1 to 3 years after operation. The authors realized that there is a sensitive area near the trigeminal nerve sensory root entry zone. When the blood vessel compresses the sensitive area, trigeminal neuralgia is induced, whereas the vessel decompresses the area, the pain is free. So it is a good evidence for the microvascular compression theory and it is more important than the non-perforation type.

Adult↗
PubMed1995

[Pathologic observations of hepatitis C].

The morphological changes in liver biopsies from 70 patients with a clinical diagnosis of hepatitis C were studied. Sixty-two of the patients had history of blood transfusions. All patients were seropositive for anti-HCV by first and second generation test and/or were seropositive for HCV RNA by PCR method. Clinically, twenty cases diagnosed as acute hepatitis, fifty were chronic including 7 cases with both HBV and HCV infection. The main morphological changes in acute cases being 1. Focal degeneration of liver cells, including large and small droplet fatty changes. 2. Focal necrosis and acidophilic bodies usually being surrounded by T lymphocytes. 3. Sinusoidal inflammatory cell infiltration. 4. Lymphoid aggregation with bile duct epithelial damage was found in 60% of portal tracts. The chronic cases included 17 chronic persistent hepatitis cases (CPH) and 33 chronic active hepatitis cases (CAH). The main histopathologic changes in CAH included dense clusters of lymphocytes (lymphoid aggregates) present in the enlarged portal tracts with bridging necrosis and fibrosis, lobular inflammation including acidophilic bodies, focal necrosis and fatty degeneration. The sinusoidal cells were often hyperplastic. These changes may provide useful diagnostic clues for hepatitis C.

Adult↗
PubMed1995

[Effect of brain somatostatin on electroacupuncture analgesia of rat].

The purpose of this study was to verify the role of somatostatin (Som) of brain in analgesia of electroacupuncture (EA). Intracerebroventricular (icv) injection of Som caused a more marked elevation of pain threshold and of EA analgesic effect, but the activity of Ca(2+)-APTase in hippocampus was significantly decreased; The Som and GABA levels in hippocampus and brain stem were decreased by EA analgesia. The Som in hippocampus and brain stem were obviously depleted by icv injection of cycteamine, but without any change of pain threshold and analgesic effect of EA. These results indicated that the exogenous Som of brain potentiated the analgesic effect of EA, however, the decrease of endogenous of some brain regions took part in the process of EA analgesia.

Acupuncture Analgesia↗
PubMed1995

[Detection of FMR-1 gene expression by RT-PCR].

Fragile X syndrome [FRA(X)] as the most common form of inherited mental retardation in man has an incidence of one per 1250 and is associated with a fragile site at Xq27.3. A gene was identified at the fragile X locus and was designated Fragile X Mental Retardation-1 (FMR-1). FRA(X) resulted from expansion of (CGG)n trinucleotide repeat in 5' untranslated region of the human FMR-1 gene, and was associated with abnormal methylation of a CpG island 250 bp proximal to this (CGG)n repeat. Males with typical FRA(X) showed repression of FMR-1 transcription and absence of FMR-1 protein, which was believed to contribute to the fragile X phenotype. FMR-1 mRNA extracted from leukocytes in normal and clinically suspected males were detected by RT-PCR. The methylation status and CGG expansion were also studied by PCR and Southern blot. Two of 10 clinically suspected males were found devoid of FMR-1 expression and accompanied with hypermethylation of the CpG island and CGG trinucleotide repeat expansion.

CpG Islands↗
PubMed1994

Synthesis, binding properties, and 18F labeling of fluorocarazolol, a high-affinity beta-adrenergic receptor antagonist.

New beta-adrenergic receptor antagonists, 2-(R)-(+)- and 2-(S)-(-)-1-(9H-carbazol-4-yl-oxy)-3-[[1-(fluoromethyl)ethyl]amino ]-2-propanol ((S)- and (R)-fluorocarazolols), were labeled with fluorine-18 at the no-carrier-added level by reductive alkylation of desisopropylcarazolol (4-(2-hydroxy-3-amino-1-propoxy)carbazole) with [18F]fluoroacetone. The latter was prepared by nucleophilic substitution of fluoride on acetol tosylate and may serve as a useful synthetic precursor for other radiotracers. The radiochemical yield of [18F]fluorocarazolol (500-1200 Ci/mmol) from [18F]fluoride was 40 +/- 10% at the end of the 45 min synthesis. Chiral HPLC showed > 99% enantiomeric purity of 2-(S)- and 2-(R)-[18F]fluorocarazolols. The log P of fluorocarazolol was 2.2 at pH 7.4. The in vitro KD values of (S)- and (R)-fluorocarazolol for the beta-adrenergic receptor were measured in a rat heart preparation to be KD = 68 and 1128 pM, respectively. Biodistribution experiments in mice demonstrated specific beta-adrenergic receptor binding of (S)-[18F]fluorocarazolol. (R)-[18F]fluorocarazolol showed no observable specific binding to beta-receptors in vivo. The uptake of (R)-[18F]fluorocarazolol may therefore be used as an estimation of nonspecific binding. Positron emission tomography images of pigs showed receptor-specific uptake of (S)-[18F]fluorocarazolol in the heart and lung. Washout of dissociated ligand from the tissue was observed only after 70 min postinjection. The maximum ratio of specific to nonspecific uptake in pig heart and lung was ca. 10 at 150 min postinjection. Observed levels of fluorocarazolol metabolites in mouse and pig blood were relatively low and remained fairly constant during the period from 10 to 180 min postinjection. These results indicate that (S)-(-)-[18F]fluorocarazolol is of interest for use as a radiopharmaceutical for estimation of beta-adrenergic receptors with positron tomography.

Adrenergic beta-Antagonists↗
PubMed1994

Cloning and expression of phosphatidylcholine-hydrolyzing phospholipase D from Ricinus communis L.

Phosphatidylcholine-hydrolyzing phospholipase D (PLD; EC 3.1.4.4) has been proposed to play an important role in the signal transduction pathways in animals and in various cellular processes in plants. To unravel the structure of PLD and further the investigation of its modes of regulation and cellular function, we have isolated a PLD cDNA from castor bean (Ricinus communis L. var. Hale) by using oligonucleotide probes based on the N-terminal amino acid sequence of purified PLD protein. The nucleotide sequence of the castor bean PLD cDNA clone contains an open reading frame of 2424 bases encoding an 808-amino acid protein of 92,400 daltons. Expression of this PLD cDNA clone in Escherichia coli resulted in the accumulation of a functional PLD able to catalyze hydrolysis and transphosphatidylation reactions, demonstrating that the introduction of this single gene product was sufficient to confer PLD activity and that both the hydrolysis and transphosphatidylation reactions are catalyzed the single PLD protein. Comparison of the deduced protein sequence of the clone to the N-terminal amino acid sequence of purified PLD revealed that the mature PLD protein is preceded by a 30-amino acid leader peptide. Removal of this leader peptide resulted in accumulation of non-functional PLD and also increased PLD degradation in E. coli, suggesting that this leader peptide may be involved in proper folding of PLD. The primary structure of the castor bean PLD exhibits no significant similarities with sequences of other cloned lipolytic enzymes.

Amino Acid Sequence↗
PubMed1994

Catalytic formation of a nitrogenase iron-sulfur cluster.

Biological nitrogen fixation is catalyzed by nitrogenase, an enzyme comprised of two component proteins called the Fe protein and the MoFe protein. Both nitrogenase component proteins contain metalloclusters. The Azotobacter vinelandii nifS gene product (NifS), which is required for full activation of the nitrogenase component proteins, is a pyridoxal phosphate enzyme and is able to catalyze the desulfurization of L-cysteine to yield sulfur and L-alanine (Zheng, L., White, R. H., Cash, V.L., Jack, R.F., and Dean, D.R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2754-2758). An enzyme-bound persulfide that was identified as an intermediate in the cysteine desulfurization reaction catalyzed by NifS has been suggested as a possible S-donor in formation of the iron-sulfide cores of the nitrogenase metalloclusters. In the present work it is shown that NifS is able to effectively catalyze activation of an apo-form of the Fe protein that was prepared by removal of its Fe4S4 cluster using the chelator, alpha,alpha'-dipyridyl. The reconstitution reaction includes apo-Fe protein, NifS, L-cysteine, ferrous ion, dithiothreitol, and MgATP. Reconstitution of the inactive apo-Fe protein catalyzed by NifS results in 80-95% recovery of the original activity and yields an Fe protein having the normal electron paramagnetic resonance spectra properties associated with the Fe protein's Fe4S4 cluster. An altered NifS protein, NifS-Ala325, which lacks the desulfurase activity and is unable to from the NifS-bound persulfide, is not able to catalyze reactivation of the apo-Fe protein. These in vitro results support the proposal that NifS activity provides the inorganic sulfide necessary for in vivo formation of the nitrogenase metalloclusters. Moreover, because NifS has recently been shown to be a member of a highly homologous gene family, it appears that pyridoxal phosphate chemistry might play a general role in iron-sulfur cluster assembly.

Apoproteins↗
PubMed1994

Mechanism for the desulfurization of L-cysteine catalyzed by the nifS gene product.

The nifS gene product (NIFS) is a pyridoxal phosphate binding enzyme that catalyzes the desulfurization of L-cysteine to yield L-alanine and sulfur. In Azotobacter vinelandii this activity is required for the full activation of the nitrogenase component proteins. Because the nitrogenase component proteins, Fe protein and MoFe protein, both contain metalloclusters which are required for their respective activities, it is suggested that NIFS participates in the biosynthesis of the nitrogenase metalloclusters by providing the inorganic sulfur required for Fe-S core formation [Zheng, L., White, R. H., Cash, V. L. Jack, R. F., & Dean, D. R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2754-2758]. In the present study the mechanism for the desulfurization of L-cysteine catalyzed by NIFS was determined in the following ways. First, the substrate analogs, L-allylglycine and vinylglycine, were shown to irreversibly inactivate NIFS by formation of a gamma-methylcystathionyl or cystathionyl residue, respectively, through nucleophilic attack by an active site cysteinyl residue on the corresponding analog-pyridoxal phosphate adduct. Second, this reactive cysteinyl residue, which is required for L-cysteine desulfurization activity, was identified as Cys325 by the specific alkylation of that residue and by site-directed mutagenesis experiments. Third, the formation of an enzyme-bound cysteinyl persulfide was identified as an intermediate in the NIFS-catalyzed reaction. Fourth, evidence was obtained for an enamine intermediate in the formation of L-alanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Allylglycine↗