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Biomedical subjects

Y Chu

Publications and source records attributed to Y Chu.

At least 37 records · Page 2Linked to original sources
PubMed2001

NO-dependent vasorelaxation is impaired after gene transfer of inducible NO-synthase.

Proinflammatory stimuli produce expression of inducible NO-synthase (iNOS) within blood vessels and are associated with impaired endothelium-dependent relaxation. Gene transfer of iNOS was used to test the hypothesis that expression of iNOS in blood vessels produces impairment of NO-dependent relaxation as well as contraction. An adenoviral vector containing cDNA for murine iNOS, AdCMViNOS, and a control virus, AdCMVBglII, were used for gene transfer to rabbit carotid arteries in vitro and in vivo. After gene transfer of iNOS in vitro, contractile responses to KCl, phenylephrine, and U46619 were impaired. Relaxation in response to acetylcholine, ADP, A23187, and nitroprusside was also impaired. For example, maximum relaxation of vessels to acetylcholine (10 micromol/L) was 78+/-4% (mean+/-SE) after AdBglII (10(10.5) plaque-forming units) and 34+/-5% after AdiNOS (10(10.5) plaque-forming units, P<0.05). NO-independent relaxation in response to 8-bromo-cGMP and papaverine was not impaired after AdiNOS. Contraction and relaxation were improved in carotid arteries expressing iNOS by aminoguanidine and L-N-iminoethyl lysine, inhibitors of iNOS. After intraluminal gene transfer of iNOS in vivo, contraction of vessels in vitro was normal, but responses to acetylcholine were impaired. In summary, the major finding is that NO-dependent relaxation is impaired in arteries after gene transfer of iNOS in vitro and in vivo. Thus, expression of iNOS per se impairs NO-dependent relaxation.

Adenoviridae↗
PubMed2001

Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment.

Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the entorhinal cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II entorhinal cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 +/- 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p < 0.0003) and mild or moderate Alzheimer's disease (46.06%; p < 0.0017) displayed significant losses of layer II entorhinal cortex neurons relative to those with no cognitive impairment but not relative to each other (p > 0.33). There was also significant atrophy of layer II entorhinal cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II entorhinal cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.

Aged↗
PubMed2001

An experimental study on drugs for improving blood circulation and removing blood stasis in treating mild chronic hepatic damage.

Large and small doses of drugs for improving blood circulation and removing blood stasis were used in model rats to treat mild chronic hepatic damage induced by carbon tetrachloride (CCl4). The results show that large dose of Dang Gui ([symbol: see text] Radix Angelicae Sinensis) and Dan Shen ([symbol: see text] Radix Salviae Miltiorrhizae) (drugs for regulating blood flow) and small dose of Yu Jin ([symbol: see text] Radix Curcumae) and Niu Xi ([symbol: see text] Radix Achyranthis Bidentatae) (drugs for activating blood flow) can significantly elevate the activity of SOD (P < 0.05) and/or lower the T/K ratio, markedly reduce the MDA content (P < 0.05 or P < 0.01) and significantly decrease the activities of ALT and AST (P < 0.05 or P < 0.01), demonstrating that these drugs are effective in combating oxygen free radicals (OFR) in chronic liver damage. On the contrary, large dose of Tu Bie Chong ([symbol: see text] Eupolyphaga seu Steleophaga) and E Zhu ([symbol: see text] Rhizoma Curcumae) (drugs for removing blood stasis) tend to increase the ALT and AST (P < 0.05) activities. The results suggest that the synergism of elevation of the SOD activity and reduction of T/K ratio contributes to the action of drugs for improving blood circulation and removing blood stasis in combating the liver damage induced by CCl4.

Alanine Transaminase↗
PubMed2001

[Immunorelated pancytopenia].

OBJECTIVE: A report of a group of patients with pancytopenia which might be related to abnormal immunity. METHODS: The clinical and laboratory features of 29 patients with positive bone marrow mononuclear cell (BMMNC) Coombs tests were analyzed. RESULTS: Most of these cases were pancytopenia with normal or decreased bone marrow cellularities and increased normoblasts. They were all found to have negative results of conventional hemolysis tests and hematopoietic nutrient determination and had no evidence of malignant clonal hematopoiesis. However, all of them showed positive BMMNC-Coombs test and good response to corticosteroids. CONCLUSION: Immunorelated pancytopenia might be caused by abnormal immunity (especially autoantibody) mediated destruction or abnormal function of blood cells. It is beneficial to differentiate immunorelated pancytopenia from aplastic anemia or myelodysplastic syndromes.

Adolescent↗
PubMed2001

[Sequential intensified immunosuppressive therapy combining with hematopoietic growth factors in the treatment of severe aplastic anemia].

OBJECTIVE: To explore more effective regimen for reducing early mortality of severe aplastic anemia (SAA) and improving therapeutic effectiveness. METHODS: Antilymphocyte globulin/antithymocyte globulin (ALG/ATG) and cyclosporine A (CsA) (sequential intensified immunosuppressive therapy, SIIST), with or without hematopoietic growth factors (HGFs) were administered to 73 SAA patients in a prospective randomized clinical trial to test the effectiveness of the addition of HGFs for the patients. RESULTS: The response rate of SIIST with HGFs group was significantly higher than that of SIIST alone group (89.2% vs 63.9%), with lower rates of early infection (24.3% vs 55.3%) and mortality (4.0% vs 16.7%), shorter duration of cytopenia and blood transfusion dependence and faster recovery of bone marrow hematopoiesis. The addition of HGFs to SIIST was tolerated well in all patients. There was no difference in the treatment outcome of the two groups with GM-CSF plus Epo or G-CSF plus Epo. CONCLUSION: The use of HGFs in combination with SIIST could reduce early infection and mortality rates and, therefore, improve the response rates in SAA patients.

Adolescent↗
PubMed2001

[Study on the transformation from myelodysplastic syndromes into acute leukemias].

OBJECTIVE: To study the patterns of transformation from myelodysplastic syndromes (MDS) into acute leukemias (AL). METHODS: Leukemic transformation of MDS patients was dynamically followed up and the clinical manifestations, peripheral blood and bone marrow pictures, karyotypes, immunophenotypes, response to treatment and prognosis of post MDS acute leukemia (postMDS-AL) were observed. RESULTS: During the past eight year and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia with a median interval of 5 (1 - 21) months. There were no significant differences among the rates of leukemia from RA, RAEB and RAEB-t groups. The transformation was developed either gradually or rapidly. There were five parameters related to the leukemic transformation: under 40 years of age, pancytopenia, more than 0.15 blasts in bone marrow, at least two types of abnormal karyotype and combined chemotherapy. All of the 21 post MDS-AL were acute myeloid leukemia (AML); and most of them were M(2), M(4) and M(5). Two (9.52%) post MDS-AML developed extramedullary infiltration. Leukopenia was found in 47.62% of patients. Two third of the patients, whose bone marrows were generally hypercellular, showed neutropenias. After evolving into AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD(33) (49.83 +/- 24.50)%, CD(13) (36.38 +/- 33.84)%, monocytic antigen CD(14) (38.50 +/- 24.60)%, and stem cell marker CD(34) (34.67 +/- 30.59)% were found on bone marrow mononuclear cells of post MDS-AML cases. In some cases, lymphoid antigens, such as CD(5), CD(7), CD(9) and CD(19) were coexisted with myeloid antigens. A low complete remission rate (31.25%) and short survival duration with median survival of 6 (1 - 28) months were found in patients with post MDS-AML treated by induction therapy. CONCLUSION: MDS was at high risk of evolving into AML, either gradually or rapidly. Patients with post MDS-AML had specific biologic features and worse prognoses.

Acute Disease↗
PubMed2000

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.

Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Gene transfer of calcitonin gene-related peptide prevents vasoconstriction after subarachnoid hemorrhage.

We sought to determine whether adenovirus-mediated gene transfer in vivo of calcitonin gene-related peptide (CGRP), a potent vasodilator, ameliorates cerebral vasoconstriction after experimental subarachnoid hemorrhage (SAH). Arterial blood was injected into the cisterna magna of rabbits to mimic SAH 5 days after injection of AdRSVCGRP (8x10(8) pfu), AdRSVbetagal (control virus), or vehicle. After injection of AdRSVCGRP, there was a 400-fold increase in CGRP in cerebrospinal fluid. Contraction of the basilar artery to serotonin in vitro was greater in rabbits after SAH than after injection of artificial cerebrospinal fluid (P<0.001). Contraction to serotonin was less in rabbits with SAH after AdRSVCGRP than after AdRSVbetagal or vehicle (P:<0.02). Basal diameter of the basilar artery before SAH (measured with digital subtraction angiogram) was 13% greater in rabbits treated with AdRSVCGRP than in rabbits treated with vehicle or AdRSVbetagal (P:<0.005). In rabbits treated with vehicle or AdRSVbetagal, arterial diameter after SAH was 25+/-3% smaller than before SAH (P<0.0005). In rabbits treated with AdRSVCGRP, arterial diameter was similar before and after SAH and was reduced by 19+/-3% (P<0.01) after intracisternal injection of CGRP-(8-37) (0.5 nmol/kg), a CGRP(1) receptor antagonist. To determine whether gene transfer of CGRP after SAH may prevent cerebral vasoconstriction, we constructed a virus with a cytomegalovirus (CMV) promoter, which results in rapid expression of the transgene product. Treatment of rabbits with AdCMVCGRP after experimental SAH prevented constriction of the basilar artery 2 days after SAH. Thus, gene transfer of CGRP prevents cerebral vasoconstriction in vivo after experimental SAH.

Adenoviridae↗
PubMed2000

Deterin, a new inhibitor of apoptosis from Drosophila melanogaster.

Deterin, a new apoptosis inhibitor from Drosophila melanogaster, possesses an unusual structure of only a single baculovirus inhibitor of apoptosis (IAP)-type repeat and no RING finger motif. The biochemical actions of deterin are demonstrated in SF9 and S2 cell transfection assays, in which the expressed protein acts in the cytoplasm to inhibit or deter cells from apoptosis otherwise induced by the caspase-dependent apoptosis activator reaper or by cytotoxicants. A loss of function phenotype for deterin of cell death was indicated by transfections with either a dominant negative deterin mutant or with inhibitory RNA (RNAi) for deterin. The dominant negative C-terminal fragment that antagonized antiapoptotic activity of deterin did not affect antiapoptotic activity of DIAP1 or p35. Both the baculovirus IAP-type repeat (BIR) domain and the alpha-helical C-terminal domain are necessary in both SF9 and S2 cells for deterin to manifest its activity to prevent cell death. The approximately 650-base deterin transcript is present in embryos, third instar larvae, and late stage nurse cells of adult females. The deterin transcript is distributed throughout early stage embryos, whereas in later stage embryos it becomes progressively restricted to the central nervous system and gonads. Whereas the nematode survivin-type IAP has thus far been implicated only as a mitotic regulator, Drosophila deterin constitutes the first invertebrate member of the survivin-type IAP group to exhibit apoptosis-inhibitory activity.

Amino Acid Sequence↗
PubMed2000

Obtaining maximal optic nerve length during enucleation procedures.

OBJECTIVE: To determine optimal scissor blade design and surgical approach to facilitate obtaining a long optic nerve segment during enucleation procedures. METHODS: Two hundred mock enucleations were performed with the use of a human child skull model and a silicone sphere to simulate an eye. Temporal and nasal approaches with scissor blades with noncurved, mildly curved, or strongly curved blades were tested. RESULTS: Longer optic nerve segments were obtained with mildly curved scissor blades from both temporal and nasal surgical approaches. Strongly curved scissor blades uniformly produced smaller specimens. CONCLUSIONS: Mildly curved scissors should be used for enucleation when a long optic nerve specimen is desired. Strongly curved scissors should be avoided.

Eye Enucleation↗
PubMed2000

Gene therapy of hypertensive vascular injury.

Hypertension and vascular injury usually require prolonged treatment, and compliance is a key to efficacy for pharmacologically-based antihypertensive therapy. Gene therapy has the potential to be long lasting, with few side effects. Recent studies have provided promising results, in which hypertension can be treated by either augmentation of vasodilation or inhibition of vasoconstriction through gene transfer in experimental models. Gene transfer is also becoming useful for the study of mechanisms of physiologic and pathophysiologic conditions, including hypertension. In this mini-review, we summarize some recent studies in this area of research, and suggest some areas where progress is needed to advance the research toward gene therapy.

Gene Transfer Techniques↗
PubMed2000

Stress and micromotion in the taper lock joint of a modular segmental bone replacement prosthesis.

The stress distribution within the components and the micromotion of the interface significantly influence the long-term function of the taper lock joint in a modular segmental bone replacement prosthesis. Bending-induced gap opening between the cone and the sleeve can lead to an inflow of biological fluids, and thus accelerate implant corrosion. Local areas of high stress can also accelerate the corrosive processes and initiate local yielding, which may lead to a fracture in one of the components. In this study, a 3-D finite element (FE) model of a modular segmental bone replacement prosthesis was developed to study the interface micromotion and component stress distribution under the maximum loads applied during gait for a taper lock joint with multiple material combinations. Bending was the main cause of the local high stresses and interface separation within the taper joint. For Ti6A14V components, cortical bone bridging and ingrowth across the taper lock gap reduced the peak stress by 45% and reduced the contact interface separation by 55%. Such tissue formation around the taper lock joint could also form a closed capsule to restrict the migration of potential wear particles and thus prevent the biologic process of bone resorption induced by metal debris.

Bone and Bones↗
PubMed2000

Supplementation with L-histidine during dietary zinc repletion improves short-term memory in zinc-restricted young adult male rats.

Zinc, an essential dietary element, modulates neurotransmission in brain regions associated with cognition. Cognitive dysfunction has been reported in offspring of female rats fed zinc-restricted diets during gestation and/or lactation. Studies on the cognitive effects of zinc restriction during young adulthood are limited. After a 3-wk period of dietary zinc restriction, male rats (71-75 d old) were repleted with zinc chloride alone, or zinc chloride supplemented with L-histidine, and short-term memory was measured using the Morris water maze. During restriction, zinc-restricted rats demonstrated significantly longer (86.0%) retrieval latencies than nonrestricted controls, and significantly lower liver (25.5%), bone (32.5%) and hippocampal (3.2%) zinc concentrations. During subsequent repletion, rats repleted with zinc chloride supplemented with L-histidine improved their retrieval latencies to the extent that they were no longer significantly different from controls by repletion d 3. This was associated with a return of hippocampal zinc concentrations to control values by repletion d 3. The mean retrieval escape latencies of the zinc chloride-repleted rats remained significantly prolonged (75.0%). Collectively, these data indicate the following: 1) feeding a zinc-restricted diet for 3 wk impairs short-term memory in young adult male rats, and 2) repletion with dietary zinc supplemented with L-histidine improves short-term memory function more efficiently than dietary zinc chloride alone. The latter point suggests that dietary zinc supplemented with L-histidine is more bioavailable to the brain than zinc provided as zinc chloride alone. These findings are important in that they highlight the importance of both dietary zinc formulation and the use of functional assessments in determining zinc nutriture.

Analysis of Variance↗
PubMed2000

Interference of the simian virus 40 origin of replication by the cytomegalovirus immediate early gene enhancer: evidence for competition of active regulatory chromatin conformation in a single domain.

Replication origins are often found closely associated with transcription regulatory elements in both prokaryotic and eukaryotic cells. To examine the relationship between these two elements, we studied the effect of a strong promoter-enhancer on simian virus 40 (SV40) DNA replication. The human cytomegalovirus (CMV) immediate early gene enhancer-promoter was found to exert a strong inhibitory effect on SV40 origin-based plasmid replication in Cos-1 cells in a position- and dose-dependent manner. Deletion analysis indicated that the effect was exerted by sequences located in the enhancer portion of the CMV sequence, thus excluding the mechanism of origin occlusion by transcription. Insertion of extra copies of the SV40 origin only partially alleviated the inhibition. Analysis of nuclease-sensitive cleavage sites of chromatin containing the transfected plasmids indicate that the chromatin was cleaved at one of the regulatory sites in the plasmids containing more than one regulatory site, suggesting that only one nuclease-hypersensitive site existed per chromatin. A positive correlation was found between the degree of inhibition of DNA replication and the decrease of P1 cleavage frequency at the SV40 origin. The CMV enhancer was also found to exhibit an inhibitory effect on the CMV enhancer-promoter driving chloramphenicol acetyltransferase expression in a dose-dependent manner. Together these results suggest that inhibition of SV40 origin-based DNA replication by the CMV enhancer is due to intramolecular competition for the formation of active chromatin structure.

Animals↗
PubMed2000

Role of inwardly rectifying K(+) channels in K(+)-induced cerebral vasodilatation in vivo.

We tested whether activation of inwardly rectifying K(+) (Kir) channels, Na(+)-K(+)-ATPase, or nitric oxide synthase (NOS) play a role in K(+)-induced dilatation of the rat basilar artery in vivo. When cerebrospinal fluid [K(+)] was elevated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dependent vasodilator response was elicited (change in diameter = 9 +/- 1, 27 +/- 4, 35 +/- 4, 43 +/- 12, and 47 +/- 16%, respectively). Responses to K(+) were inhibited by approximately 50% by the Kir channel inhibitor BaCl(2) (30 and 100 microM). In contrast, neither ouabain (1-100 microM, a Na(+)-K(+)-ATPase inhibitor) nor N(G)-nitro-L-arginine (30 microM, a NOS inhibitor) had any effect on K(+)-induced vasodilatation. These concentrations of K(+) also hyperpolarized smooth muscle in isolated segments of basilar artery, and these hyperpolarizations were virtually abolished by 30 microM BaCl(2). RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K(+)-induced dilatation of the basilar artery in vivo appears to partly involve hyperpolarization mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na(+)-K(+)-ATPase, or NOS.

Acetylcholine↗
PubMed2000

[Nitrogen dynamics in different organs of Calamagrostis angustifolia and Carex lasiocarpa in Sanjiang plain].

The dynamics of nitrogen content and storage in different organs of Calamagrostis angustifolia and Carex lasiocarpa which are dominant vegetation in swamp wetland were determined, and the utilization rate of nitrogen and its nutrient limitation in the region were analyzed. The results showed that the aboveground and underground biomass might be described by p = gamma + alpha t + beta t2 and p = a0 + b0t, respectively. The content of total N, NH4(+)-N and NO3(-)-N varied widely with different organs because of the effects of soil water, nutrient content, atmospheric temperature, vegetable feature and selective absorption to nitrogen, etc. The content of NO3(-)-N in different organs varied less than that of NH4(+)-N, and NH4(+)-N/NO3(-)-N was < 1. The N:P content less than 14 in two vegetations showed that it was N but not P was the limitation nutrient to the growth of vegetation in this region, moreover, the limitation was less in July than in August. This conclusion was also drawn from the analysis of the NH4(+)-N and NO3(-)-N content in soil.

Biomass↗