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Biomedical subjects

H Zhou

Publications and source records attributed to H Zhou.

At least 541 records · Page 30Linked to original sources
PubMed1996

Molecular biology of retinal ganglion cells.

Retinal ganglion cells are the output neurons that encode and transmit information from the eye to the brain. Their diverse physiologic and anatomic properties have been intensively studied and appear to account well for a number of psychophysical phenomena such as lateral inhibition and chromatic opponency. In this paper, we summarize our current view of retinal ganglion cell properties and pose a number of questions regarding underlying molecular mechanisms. As an example of one approach to understanding molecular mechanisms, we describe recent work on several POU domain transcription factors that are expressed in subsets of retinal ganglion cells and that appear to be involved in ganglion cell development.

Animals↗
PubMed1996

Phosphotransfer and CheY-binding domains of the histidine autokinase CheA are joined by a flexible linker.

Multidimensional heteronuclear NMR techniques were applied to study a protein fragment of the histidine autokinase CheA from Escherichia coli. This fragment (CheA1-233) contains the phosphotransfer domain and the CheY-binding domain joined by a linker region. Comparison of chemical shift and NOE cross-peak patterns indicates that the structures of the two domains in CheA1-233 remain nearly the same as in the two individual domain fragments, CheA1-134 and CheA124-257. Relaxation properties of the backbone 15N nuclei were measured to study the rotational correlations of the two domains and properties of the linker region. Dynamics data were analyzed both by an isotropic motional model and an anisotropic motional model. The experimental T1 and T2 values, the derived rotational correlation times, and motional anisotropy are significantly different for the two domains, indicating the two domains reorient independently and the linker region is highly flexible. Dynamics data of CheA1-233 were also compared with those of CheA1-134. Our studies show that flexible domain linkers and extended and flexible terminal polypeptide chains can have significant effects on the motional properties of the adjacent structured regions. These observations suggest a model for the graded regulation of CheA autophosphorylation activity. In this model, the various activity states of the receptor are generated by controlling the access of the mean position of the kinase domain to the phosphotransfer domain. This would then modulate the diffusional encounter rate of the domains and hence activity over a wide and graded range of values.

Amino Acid Sequence↗
PubMed1996

Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor.

4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC50s up to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this "supra-additive" effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.

Aniline Compounds↗
PubMed1996

Expression of parathyroid hormone-related protein in cells of osteoblast lineage.

The expression of parathyroid hormone-related protein (PTHrP) was studied in a range of cell cultures representative of the osteoblast lineage and in rat calvarial sections. Primary newborn rat calvarial cells, a rat preosteoblastic cell line (UMR 201), a mouse stromal cell line (ST 2), a mouse calvaria-derived osteoblastic cell line (KS 4), and rat osteosarcoma cell lines (UMR 106-01 and -06), all expressed PTHrP when examined by reverse transcription polymerase chain reaction (RT-PCR). Using a radioimmunoassay we also demonstrated PTHrP in the conditioned medium of the cultured cells, with the exception of UMR 106-01 and -06 cells. Treatment of UMR 201 cells with all-trans-retinoic acid which induces them to acquire a more differentiated phenotype, also led to a time-dependent decrease in PTHrP mRNA levels as determined by RT-PCR, Northern blot analysis, and in situ hybridization. Decreased PTHrP levels in the conditioned medium of the treated cells was also observed. These results suggested that PTHrP production might be greater in less mature osteoblasts. Examination of the populations obtained from newborn rat calvariae by sequential collagenase digestion revealed that the early digests exhibited low ALP activity, low expression of PTH/PTHrP receptor mRNA, and no adenylate cyclase response to PTHrP(1-34). These populations showed the highest level of mRNA and production of PTHrP. Cells from later digests, the "osteoblast-rich" populations, had reduced PTHrP expression. Immunohistochemistry and in situ hybridization in sections of newborn rat calvariae showed PTHrP expression in cuboidal osteoblasts located adjacent to bone and in spindle-shaped cells in the periosteal region. It is concluded that PTHrP is produced by cells of the osteoblast lineage, supporting the hypothesis that PTHrP may function physiologically as a paracrine factor in bone.

Animals↗
PubMed1996

Computation of neuromagnetic fields using finite-element method and Biot-Savart law.

The finite-element method in combination with the Biot-Savart law is described to compute the magnetic field distribution generated by a dipolar source within a homogeneous volume conductor of an arbitrary shape. In order to calculate the three independent components of the magnetic field outside the volume conductor by means of the Biot-Savart law, the distribution of the current throughout the medium is required. A finite-element mesh is constructed using four-node tetrahedral elements. The potential in each node is computed numerically by the finite-element method using the proper continuity conditions across the boundaries. The gradient of the potential denotes the current density within an element. The components of the magnetic induction are calculated by numerical integration, applying the current density within the tetrahedrons. Simulations are carried out to assess the numerical accuracy for a homogeneous spherical volume conductor. Errors of 3% can be obtained with a locally refined spherical mesh containing about 1000 nodes, for dipoles at any depth and any orientation. A homogeneous realistically shaped model with the shape of the inside of the skull is obtained from magnetic resonance images.

Biomedical Engineering↗
PubMed1996

Prevention and management of related complication due to laparoscopic operation: pneumothorax, pneumomediastinum and subcutaneous emphysema.

Essential prerequisite of laparoscopic operation is establishing and maintaining pneumoperitoneum with a certain pressure. But under certain circumstances CO2-gas insufflating could induce pneumothorax, pneumomediastinum and subcutaneous emphysema during the operation. to probe the mechanism of the above complications. 2 typical cases were reported with attempt to probe the mechanism of the development of such applications. We believe that high intra-abdominal pressure during operation is the primary cause of the complications. The essentials of prevention and management of such complications were proposed.

Adult↗
PubMed1996

Replication of a plasmid lacking the normal site for initiation of one strand.

The origin of replication of the plasmid R1162 contains an initiation site for the synthesis of each DNA strand. When one of these sites (oriL) is deleted, synthesis on the corresponding strand is no longer initiated efficiently in vitro by the R1162-encoded replication proteins, and the plasmid is no longer stably maintained in the cell. However, in vivo the two strands of the plasmid duplex molecule are active at a similar level as templates for DNA synthesis, and newly synthesized copies of each strand are incorporated into daughter molecules at a similar rate. No secondary, strong initiation sites on the delta oriL strand were detected in the region of the origin. The delta oriL plasmid induces the SOS response, and this is important for plasmid maintenance even in a recombination-proficient strain. Our results indicate that an SOS-induced host system can maintain an R1162 derivative lacking one of its initiation sites.

Base Sequence↗
PubMed1996

Development of a complementing cell line and a system for construction of adenovirus vectors with E1 and E2a deleted.

Although adenovirus vectors offer many advantages, it would be desirable to develop vectors with improved expression and decreased toxicity. Toward this objective, an adenovirus vector system with deletion of both the El and E2a regions was developed. A 5.9-kb fragment of the adenovirus type 5 (Ad5) genome containing the E2a gene and its early and late promoters was transfected into 293 cells. A complementing cell line, designated 293-C2, expressed the E2a mRNA and protein and was found to complement the defect in Ad5 viruses with temperature-sensitive or deletion mutations in E2a. A deletion of 1.3 kb removing codons 40 to 471 of the 529 amino acids of E2a was introduced into plasmids for preparation of viruses and vectors. An Ad5 virus with disruption of the El gene and deletion of E2a grew on 293-C2 cells but not on 293 cells. Vectors with E1 and E2a deleted expressing Escherichia coli beta-galactosidase or human alpha1-antitrypsin were prepared and expressed the reporter genes after intravenous injection into mice. This vector system retains sequences in common between the complementing cell line and the vectors, including 3.4 kb upstream and 1.1 kb downstream of the deletion. These vectors have potential advantages of increased capacity for insertion of transgene sequences, elimination of expression of E2a, and possibly reduction in expression of other viral proteins. Although the titers of the vectors with deleted are about 10- to 30-fold below those of vectors with E2a wild-type regions, the former vectors are suitable for detailed studies with animals to evaluate the effects on host immune responses, on duration of expression, and on safety.

Adenoviridae↗
PubMed1996

Mutations in the pore region of ROMK enhance Ba2+ block.

The sequence of the hydrophobic "P" (pore) region of a K(+)-selective channel from the kidney (ROMK2) was altered to match that of the closely related inward rectifier (IRK1) channel by changing two amino acids, leucine (L) 117 and valine (V) 121, to isoleucine (I) and threonine (T), respectively. The mutant channel expressed in Xenopus laevis oocytes had an apparent inhibition constant at zero voltage [Ki(0)] in the presence of Ba2+ of 0.07 +/- 0.01 mM, which was more than 50 times lower than the Ki(0) of the wild-type channel (4.7 +/- 1.0 mM). The increased sensitivity to Ba2+ was accounted for by the point mutation V121T. Single-channel measurements indicated that the increased affinity involved an increase in the on-rate for Ba2+ block and a decrease in the off-rate. Block by Ca+ was also enhanced. The single-channel conductance of the L1171/ V121T mutant was increased by 50%, whereas the degree of inward rectification, ion selectivity, and apparent affinity for K+ were essentially unchanged. When the neutral asparagine residue within the second putative membrane-spanning domain of the ROMK channel was substituted with aspartic acid, the corresponding amino acid in IRK1, the degree of inward rectification was enhanced but Ba2+ block and single-channel inward conductance were unaffected. Thus the site of Ba2+ binding appears to be distinct from the locus of internal Mg2+ block and from at least one of the sites that determines K+ conjuctivity.

Amino Acid Sequence↗
PubMed1996

Antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation of preterm ovine coronary arteries.

The present study was designed to test the hypothesis that betamethasone may potentiate nitric oxide-mediated relaxation of coronary arteries of preterm lambs. Isolated coronary arteries were obtained from lambs delivered at 128 days gestation. The lambs were treated intramuscularly with a single dose of betamethasone or saline 48 h before delivery and were killed after 3 h of ventilation after delivery. Vessel rings were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2, 37 degrees C), and their isometric tension was recorded. The endothelium-dependent relaxation induced by bradykinin and calcium ionophore A23187 was greater in arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. The relaxation was abolished by N omega-nitro-L-arginine. Nitric oxide induced a greater relaxation in vessels from antenatal betamethasone-treated lambs and in vessels preincubated with betamethasone than in vessels from controls. Coronary arteries from control and antenatal betamethasone-treated lambs relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Nitric oxide induced a greater increase in guanosine 3',5'-cyclic monophosphate content in coronary arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. Our data suggest that antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation in coronary arteries from preterm lambs, probably by affecting the activity of soluble guanylate cyclase of vascular smooth muscle cells.

Animals↗
PubMed1996

Antenatal betamethasone therapy augments nitric oxide-mediated relaxation of preterm ovine pulmonary veins.

Antenatal glucocorticoid therapy improves pulmonary function in preterm newborns. We have determined the effect of antenatal glucocorticoid therapy on nitric oxide-mediated relaxation in pulmonary vessels of preterm lambs. Ovine fetuses (126 days gestation; full term = 150 days) were injected with betamethasone (0.5 mg/kg body wt) or saline. After 48 h, lambs were delivered, ventilated for 3 h, and killed. Isolated fourth-generation pulmonary arteries (2-3 mm diameter) and veins (1.5-2 mm diameter) were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to endothelin-1 or U-46619 (in the presence of indomethacin), acetylcholine and bradykinin induced endothelium-dependent nitro-L-arginine-inhibitable relaxation in arteries and veins. The relaxation was greater in veins of betamethasone-treated than in those of control lambs. Veins from lambs without endothelium treated with betamethasone were more sensitive to sodium nitroprusside than veins from controls. For arteries, there was no significant difference in relaxation between different groups. Relaxation induced by 8-bromoguanosine 3',5'-cyclic monophosphate was similar in arteries and veins of different groups. Radioimmunoassay showed that nitric oxide caused a greater increase in guanosine 3',5'-cyclic monophosphate in betamethasone-treated veins than in controls. These data suggest that antenatal betamethasone therapy augments nitric oxide-mediated relaxation of pulmonary veins of preterm lambs, probably by increasing soluble guanylate cyclase activity of vascular smooth muscle.

Animals↗
PubMed1996

Prostaglandins E2 and I2 cause greater relaxations in pulmonary veins than in arteries of newborn lambs.

Prostaglandins E2 (PGE2) and I2 (PGI2) are important vasoactive mediators in pulmonary vessels. The present study was designed to determine whether the responses of pulmonary arteries to these prostanoids are different from those of veins in newborn lambs. Fourth-generation pulmonary arterial and venous rings without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2, 37 degrees C), and their isometric force was measured. During contraction with endothelin-1 or U-46619 (indomethacin was present to eliminate the possible involvement of endogenous cyclooxygenase products), PGE2, PGI2, and carbacyclin (a stable analogue of PGI2) induced greater relaxations in veins than in arteries. In both vessel types, relaxations induced by PGE2 were greater than those induced by PGI2 or carbacyclin. Forskolin, an activator of adenylate cyclase, also induced greater relaxation of veins than of arteries. Relaxation induced by 8-bromoadenosine 3',5' -cyclic monophosphate, an analogue of adenosine 3',5' -cyclic monophosphate (cAMP), was comparable in both vessel types. Radioimmunoassay revealed that the basal and calcium ionophore A-23187-induced releases of PGE2 or 6-ketoprostaglandin F1 alpha (the stable breakdown product of PGI2) were similar between arteries and veins. Measurement of cAMP (in the presence of isobutylmethylxanthine) showed that PGE2 and forskolin induced greater increase in cAMP in veins than in arteries. Our results demonstrate that PGE2 and PGI2 are more potent vasodilators in pulmonary veins than in arteries in newborn lambs. A difference in the activity of adenylate cyclase may contribute to the differential responses to PGE2 and PGI2 between pulmonary arteries and veins. Furthermore, PGE2 appears play an more important role than does PGI2 in modulating pulmonary vascular tone of newborn lambs.

Animals↗
PubMed1996

Generation of glycolaldehyde from guinea pig airway epithelial monolayers exposed to nitrogen dioxide and its effects on sodium pump activity.

Pulmonary injury from nitrogen dioxide (NO2) may in part be related to the generation of aldehydic compounds, which bind with cellular proteins and subsequently impair or inhibit cell function. We examined the generation of aldehydes from guinea pig tracheobronchial epithelial (GPTE) cell monolayers exposed to NO2. With the use of dinitrophenylhydrazine (DNP) to derivatize aldehydic compounds, glycolaldehyde, a two carbon alpha-hydroxyaldehyde, was identified in elevated levels in the basolateral fluid from monolayers exposed to NO2. DNP-glycolaldehyde levels were 81.2 +/- 2.7 and 234.0 +/- 42.6 nM in response to a 1-hr exposure to 1 and 5 ppm NO2, respectively, as compared to an air-control value of 20.3 +/- 6.8 nM. Taking into account dilution and reactivity, cellular glycolaldehyde levels could have reached as high as 3 mM for the 60-min exposure period (i.e., 0.05 mM/min). The effects of exogenous glycolaldehyde on GPTE ouabain-sensitive basolateral 86Rb uptake (an index of Na+,K(+)-ATPase activity) were examined and compared with the actions of NO2 exposure. Bolus addition of glycolaldehyde to the basolateral fluid at concentrations > or = 5 mM led to an inhibition of ouabain-sensitive 86Rb uptake, while lower concentrations had no effect. the effects of exogenous glycolaldehyde differ from NO2 exposure, which led to a sustained elevation of ouabain-sensitive 86Rb uptake with presumed generation of glycolaldehyde at a continuous low level. Glycolaldehyde does not appear to play a significant role in the acute alterations of sodium pump activity, suggesting that the NO2-induced changes in Na+,K(+)-ATPase activity of GPTE monolayers probably are further mediated by other lipid peroxidation products/oxidation processes yet to be identified.

Acetaldehyde↗
PubMed1996

[Studies on Cnidium fruits by stereological method and computer image analysis].

The fruits, pollen grains, vascular bundles, stomata and endosperm cells of 4 Cnidium species were studied and determined by stereological method and computer image analysis technique. Statistical data were presented. In the volume of fruit and the area of vascular bundle, Cnidium dahuricum is the biggest, then C. salinum, C. japonicum and C. monnieri successively. In the volume of pollen grain,C. salinum is the biggest, followed by C. dahuricum, C. japonicum and C. monnieri in succession. In the volume of endosperm cell, C. dahuricum is also the biggest, and then C. japonicum, C. salinum and C. monnieri in order.

Fruit↗
PubMed1996

Effect of emodin on c-myc proto-oncongen expression in cultured rat mesangial cells.

AIM: To explore the possible molecular mechanism of emodin on the inhibition of glomerular mesangial cells (MC). METHODS: In rat MC culture, c-myc mRNA level was detected by dot-blotting as expressed by the dilutions of the total RNA on the visible dots. RESULTS: Low level c-myc mRNA was found in serum-free cultured quiescent MC. Addition of lipopolysaccharide (LPS 10 mg.L-1) induced a higher level expression of c-myc mRNA within 30 min, maximal expression at 2.5 h and persisted for 6 h. This over-expressing of c-myc mRNA was markedly suppressed by emodin (25 mg.L-1), the inhibition of emodin on c-myc mRNA expression was still seen at 6 h, and the greatest suppressive effect was at 2.5 h. CONCLUSION: Emodin participating in its down-regulatory effect of c-myc mRNA over-expression contributes to its inhibitory action on MC.

Animals↗