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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 361 records · Page 20Linked to original sources
PubMed2001

Analysis of trace amino acid neurotransmitters in hypothalamus of rats after exhausting exercise using microdialysis.

A simple but effective coupling of microdialysis and capillary electrophoresis with laser induced fluorescence detection technique was applied to analysis of amino acid neurotransmitters in the hypothalamus of rats after acute exhausting exercise. The separation of amino acids was achieved using an uncoated fused-silica capillary (57 cm x 75 microm I.D.) with a buffer of 10 mM disodium tetraborate at pH 10 and an applied voltage of 12.5 kV. The detection limit was 10(-10) M for each amino acid. It is sufficiently sensitive and rapid for the determination of amino acids in a 5-microl Microdialysate. In comparison to pre-exercise, a significant increase in the levels of six hypothalamic amino acids (arginine, glycine, lysine, glutamic acid, alanine, gamma-amino-n-butyric acid) was found after exercise. These results demonstrate that the increase of metabolic amino acids in the hypothalamus of rats can be induced by exhausting exercise and suggests that amino acid neurotransmitters may play functional roles in the central effects of exercise.

Amino Acids↗
PubMed2001

Molecular cloning and characterization of a novel calcium/calmodulin-dependent protein kinase II inhibitor from human dendritic cells.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a widely distributed protein kinase that regulates numerous physiological functions. Inhibitors of CaMKII are useful tools for investigating the CaMKII functions. Here we identified a novel CaMKII inhibitor protein (CaM-KIIN) from the human dendritic cell cDNA library by large-scale random sequencing. Human CaM-KIIN contains 79 amino acids, which shares 98% identity and 98% positives with rat CaMKII inhibitor protein beta and 65% identity and 78% positives with rat CaMKII inhibitor alpha. Human CaM-KIIN mRNA expression was detectable in various tissues and cell lines by Northern blot and RT-PCR. To investigate its biological functions, full-length human CaM-KIIN was overexpressed in colon adenocarcinoma LoVo cells. When expressed in LoVo cells, it could inhibit cell proliferation, block cell growth, and decrease the viable cell number. These results characterize a potential cellular inhibitor protein of CaMKII that plays an important role in the regulation of cell growth.

Adenocarcinoma↗
PubMed2001

[Treatment of dyskinetic disorders with tremor by lesioning and DBS of Vim].

OBJECTIVE: To explore the effect of stereotactic operation in treatment of dyskinetic disorders with tremor as the main symptom and to study the value of anatomic location and microelectrode functional location. METHODS: Surgiplan system and microelectrode direction technique were used to locate the Vim, and then target lesioning and deep brain simulation (DBS) were performed in 22 patients with dyskinetic disorders with tremor. After the operation, a follow-up was conducted for 6 approximately 12 months. RESULTS: After the operation, tremor disappeared in 21 patients and hypermyotonia was improved in 13 cases. During the follow-up tremor completely disappeared in 18 patients, including 3 cases treated with DBS, was markedly alleviated in 3 cases and was slightly improved in one case. Typical cell firing at tremor was recorded in 17 cases during the operation. CONCLUSION: The surgiplan system and microelectrode recording technique play an important role in location of Vim. Accurate location is crucial for success of operation. The curative effect of DBS is similar as lesioning operation.

Adult↗
PubMed2001

Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors.

1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared, some showed not only low IC(50) values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring.

Enzyme Inhibitors↗
PubMed2001

The highly lipophilic DNA topoisomerase I inhibitor DB-67 displays elevated lactone levels in human blood and potent anticancer activity.

The novel silatecan 7-t-butyldimethylsilyl-10-hydroxycamptothecin (DB-67) is 25- to 50-times more lipophilic than camptothecin and readily incorporates into lipid bilayers. Using the method of fluorescence anisotropy titration, we determined that DB-67 bound to small unilamellar vesicles composed of dilaurylphosphatidylcholine (DLPC) with an association constant (K value) of 5000 M(-1). This association constant is significantly higher than the K(DLPC) value observed for camptothecin (K(DLPC) value of 110 M(-1)). Using HPLC methods, we demonstrated that the presence of liposomal membranes readily stabilize the lactone form of DB-67. At drug and lipid concentrations of 10 microM and 0.3 mM, respectively, the lactone form of DB-67 persisted in liposome suspension after 3 h of incubation at 37 degrees C. Thus an advantage of a liposomal formulation of DB-67 is that the presence of lipid bilayers assists with stabilizing the key pharmacophore of the agent. The highly lipophilic character of DB-67, in combination with its 10-hydroxy moiety (which functions to enhance lactone stability in the presence of human serum albumin), results in DB-67 having superior stability in human blood with a percent lactone at equilibrium value of 30 [Cancer Res. 59 (1999) 4898; J. Med. Chem. 43 (2000) 3970]. Potent cytotoxicities against a broad range of cancer cells were observed for DB-67, indicating that DB-67 is of comparable potency to camptothecin. The impressive human blood stability and cytotoxicity profiles for DB-67 indicate it is an excellent candidate for comprehensive in vivo pharmacological and efficacy studies. Based on these promising attributes, DB-67 is currently being developed under the NCI RAID program. Due to its potent anti-topoisomerase I activity and its intrinsic blood stability, DB-67 appears as an attractive novel camptothecin for clinical development.

Anisotropy↗
PubMed2001

[Study of delayed encephalopathy after acute carbon monoxide poisoning by clinical characteristic, CT and MRI features].

OBJECTIVE: To explore the diagnosis value of CT and MRI in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). METHODS: The clinical, CT and MRI data of 20 patients with DEACMP were analysed. RESULTS: The main clinical manifestations of the disease were intellectual disturbances and personality disorders. CT scan in DEACMP showed that some characteristic changes (such as diffuse low density) was observed within bilateral cerebral white matter, prominently within bilateral or unilateral globus pallidus or basal ganglia areas. The MRI showed that brain lesions in DEACMP were bilateral symmetric punctate, spotty or confluent foci within periventricular white matter and centrum semioval, which showed high signal intensity in T2-weighted and low signal intensity in T1-weighted. The chronic ischemia changes were found in the globus pallidus or basal ganglia areas. Cerebral cortex lesions were observed occasionally. CONCLUSIONS: The diagnosis of DEACMP mainly depends on case history, clinical features and neuroradiological presence. MRI is more valuable in the diagnosis and the differential diagnosis than CT.

Adolescent↗
PubMed2001

Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection: complex formation as a means for cardioprotective signaling.

An essential role for protein kinase C epsilon (PKCepsilon) has been shown in multiple forms of cardioprotection; however, there is a distinct paucity of information concerning the signaling architecture that is responsible for the manifestation of a protective phenotype. We and others have recently shown that signal transduction may proceed via the formation of signaling complexes (Circ Res. 2001;88:59-62). In order to understand if the assembly of multiprotein complexes is the manner by which signaling is conducted in cardioprotection, we designed a series of experiments to characterize the associations of Src tyrosine kinase with PKCepsilon in a conscious rabbit model of nitric oxide (NO)-induced late preconditioning. Our data demonstrate that PKCepsilon and Src can form functional signaling modules in vitro: PKCepsilon interacts with Src; the association with PKCepsilon activates Src; and adult cardiac cells receiving recombinant adenoviruses encoding PKCepsilon exhibit increased Src activity. Furthermore, our results show that NO-induced late preconditioning involved PKCepsilon-Src module formation and enhanced the enzymatic activity of PKCepsilon-associated Src. Inhibition of PKC blocked cardioprotection, module formation, and PKCepsilon-associated Src activity, providing direct evidence for a functional role of the PKCepsilon-Src module in the orchestration of NO-induced cardioprotection in conscious rabbits.

Animals↗
PubMed2001

Parkin gene causing benign autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is an early-onset parkinsonism caused by exonic deletions or point mutations in the parkingene. The relationship between the type of the genetic defect and the clinical presentation, the response to therapy, and the evolution have not been yet determined. The authors describe a single-basepair deletion at nucleotide 202 in exon 2 of the parkin gene in a kindred with a benign clinical course.

Adolescent↗
PubMed2001

[Resection of neoplasm in fourth ventricle and at the back of pons through cerebellomedullary fissure approach].

OBJECTIVE: To investigate the advantage of cerebellomedullary fissure approach to resect the space occupying lesion in the fourth ventricle region and at the back of pons and to discuss the microsurgical skills. METHODS: The craniotomy is through the posterior fossa. To maximize the width of exposure, a long skin incision is made from the occipital protuberance down to the C4-5 level, and a free occipital bone flap is turned. The tonsils of cerebellum are reached by opening the tonsillovermian fissure and then moved upward so as to expose the operating field. Neoplasm in the fourth ventricle and at the back of pons was resected. RESULTS: Among the 23 cases, total resection was achieved in 20, and subtotal resection in 3. CONCLUSION: The cerebellomedullary fissure approach can provide a panoramic view between the two lateral recesses and from the obex to the aqueduct without excision of neural tissue. During the operation, the inferior vermis is not incised. The vessels and nervous tissue are extracted at a minimum extent. Such a procedure is much safer.

Adolescent↗
PubMed2001

Pro-apoptotic cleavage products of Bcl-xL form cytochrome c-conducting pores in pure lipid membranes.

During apoptotic cell death, cells usually release apoptogenic proteins such as cytochrome c from the mitochondrial intermembrane space. If Bcl-2 family proteins induce such release by increasing outer mitochondrial membrane permeability, then the pro-apoptotic, but not anti-apoptotic activity of these proteins should correlate with their permeabilization of membranes to cytochrome c. Here, we tested this hypothesis using pro-survival full-length Bcl-x(L) and pro-death Bcl-x(L) cleavage products (DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L)). Unlike Bcl-x(L), DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L) caused the release of cytochrome c from mitochondria in vivo and in vitro. Recombinant DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L), as well as Bcl-x(L), cleaved in situ by caspase 3-possessed intrinsic pore-forming activity as demonstrated by their ability to efficiently permeabilize pure lipid vesicles. Furthermore, only DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L), but not Bcl-x(L), formed pores large enough to release cytochrome c and to destabilize planar lipid bilayer membranes through reduction of pore line tension. Because Bcl-x(L) and its C-terminal cleavage products bound similarly to lipid membranes and formed oligomers of the same size, neither lipid affinity nor protein-protein interactions appear to be solely responsible for the increased membrane-perturbing activity elicited by Bcl-x(L) cleavage. Taken together, these data are consistent with the hypothesis that Bax-like proteins oligomerize to form lipid-containing pores in the outer mitochondrial membrane, thereby releasing intermembrane apoptogenic factors into the cytosol.

Animals↗
PubMed2001

FADD-deficient T cells exhibit a disaccord in regulation of the cell cycle machinery.

FADD is an adapter protein that was originally isolated as a transducer of apoptotic signals for death domain-containing receptors. However, FADD-deficient mice are embryonic lethal and FADD(-/-) T cells developed from FADD(-/-) embryonic stem cells in the RAG-1(-/-) hosts lack the full potential to proliferate when stimulated through their T-cell receptor complex, suggesting that FADD protein might play a dualistic role in mediating not only cell death signaling but other non-apoptotic cellular pathways as well. Here we show that a substantial number of freshly isolated FADD(-/-) peripheral T cells are cycling but are defective in their co-stimulatory response when stimulated. Analysis of several cell cycle proteins shows normal down-regulation of p27 inhibitor but increased levels of p21, decreased levels of cyclin D2, and constitutive activation of several cyclin-dependent kinases in activated T cells. These data suggest that FADD is involved in the regulation of cell cycle machinery in T lymphocytes.

Animals↗
PubMed2001

Phosphorylation of chloride-ATPase reconstituted from Aplysia gut.

The present study was primarily done to compare cation-ATPase phosphorylation kinetics with an anion-ATPase's phosphorylation kinetics because of the paucity of information in this area. Utilizing a proteolipsomal preparation containing Cl(-)-ATPase from Aplysia gut, it was demonstrated that phosphorylation of this P-type ATPase was absolutely dependent upon Mg(2+). In organic phosphate concentrations directly (P(i)) enhanced phosphoprotein formation in the presence of increasing concentrations of Mg(2+). It was also shown that the calculated rate constant for E(1)-P formation was 26/sec. This approximated E(1)-P rate constant values for other electrogenic, uniport P-type ATPases, and therefore it was concluded from the results that the anion-ATPase phosphorylation kinetics did not greatly differ from cation-ATPase phosphorylation kinetics.

Adenosine Triphosphatases↗
PubMed2001

Effects of surface type and relative humidity on the production and concentration of nitrous acid in a model indoor environment.

A nested chamber design was constructed for the purpose of studying parameters that affect indoor air chemistry. Experiments were conducted in this system to investigate the effects of three surface types (Teflon, wallpaper, and carpet) and two levels of relative humidity (50% and 70% RH) on the formation of gas-phase nitrous acid (HONO) through the heterogeneous reaction of nitrogen dioxide (NO2) with sorbed water vapor. The results of this investigation show that, compared with Teflon surfaces, carpet made of synthetic fibers increased the NO2 surface removal rate by nearly an order of magnitude and resulted in higher peak HONO concentrations. The results also suggest that the capacity of a surface to sorb water will determine if HONO is released from that surface after the NO2 source has been turned off and the heterogeneous reaction between NO2 and sorbed water is no longer significant. Vinyl-coated wallpaper was found to release HONO for prolonged periods of time after the NO2 source was turned off at both 50% and 70% RH whereas Teflon was found to do so only at 70% RH. The results of this investigation also demonstrate the utility of the nested chamber design in investigating indoor air chemistry.

Air Pollution, Indoor↗
PubMed2001

Naturally processed HLA class II peptides reveal highly conserved immunogenic flanking region sequence preferences that reflect antigen processing rather than peptide-MHC interactions.

MHC class II heterodimers bind peptides 12-20 aa in length. The peptide flanking residues (PFRs) of these ligands extend from a central binding core consisting of nine amino acids. Increasing evidence suggests that the PFRs can alter the immunogenicity of T cell epitopes. We have previously noted that eluted peptide pool sequence data derived from an MHC class II Ag reflect patterns of enrichment not only in the core binding region but also in the PFRS: We sought to distinguish whether these enrichments reflect cellular processes or direct MHC-peptide interactions. Using the multiple sclerosis-associated allele HLA-DR2, pool sequence data from naturally processed ligands were compared with the patterns of enrichment obtained by binding semicombinatorial peptide libraries to empty HLA-DR2 molecules. Naturally processed ligands revealed patterns of enrichment reflecting both the binding motif of HLA-DR2 (position (P)1, aliphatic; P4, bulky hydrophobic; and P6, polar) as well as the nonbound flanking regions, including acidic residues at the N terminus and basic residues at the C terminus. These PFR enrichments were independent of MHC-peptide interactions. Further studies revealed similar patterns in nine other HLA alleles, with the C-terminal basic residues being as highly conserved as the previously described N-terminal prolines of MHC class II ligands. There is evidence that addition of C-terminal basic PFRs to known peptide epitopes is able to enhance both processing as well as T cell activation. Recognition of these allele-transcending patterns in the PFRs may prove useful in epitope identification and vaccine design.

Amino Acid Motifs↗
PubMed2001

Immunocytochemical analysis of cholinergic amacrine cells in the tiger salamander retina.

Cholinergic amacrine cells in the tiger salamander retina were observed for the first time by using antibodies against choline acetyltransferase (ChAT). ChAT-immunoreactive cells were present in the inner nuclear layer (INL) and in the ganglion cell layer (GCL), and the somas of the former population (average diameter = 15.13 microm) were slightly smaller than those of the latter population (average diameter = 16.42 microm). The processes of these cells form two distinct narrow bands in the inner plexiform layer (IPL), one located near 0.2 inner plexiform units (IU) and the other near 0.65-0.7 IU. Soma size, cell density and spatial distribution of ChAT-positive cells were quantitatively analyzed. Our results suggest that cholinergic amacrine cells in the salamander retina are very similar to their counter parts in other species, and they can be used as a model system for studying cholinergic functions in the visual system.

Acetylcholine↗
PubMed2001

Cloning and characterization of Siglec-10, a novel sialic acid binding member of the Ig superfamily, from human dendritic cells.

The Siglecs (sialic acid-binding Ig-like lectins) are a subfamily of I-type lectins, which specifically recognize sialic acids. Nine members of the family have been identified thus far. We have obtained a novel cDNA clone from a human dendritic cell cDNA library encoding a protein with sequence and structural features of the Siglec family, hence designated as Siglec-10. The full-length Siglec-10 cDNA encodes a type 1 transmembrane protein containing four extracellular immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs. The N-terminal V-set Ig domain has most of the amino acid residues typical of the Siglecs. Siglec-10 shows the closest homology to Siglec-5 and Siglec-3/CD33. Various cells and cell lines including monocytes and dendritic cells express Siglec-10. High levels of mRNA expression were seen in peripheral blood leukocytes, spleen, and liver. When expressed on COS-7 cells, Siglec-10 was able to bind human red blood cells and soluble sialoglycoconjugates in a sialic acid-dependent manner. The identification of Siglec-10 as a new Siglec family member and its expression profile, together with its sialic acid-dependent binding capacity, suggest that it may be involved in cell-cell recognition by interacting with sialylated ligands expressed on specific cell populations.

Amino Acid Motifs↗