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Biomedical subjects

G Lu

Publications and source records attributed to G Lu.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Studies of microsatellite instability in Chinese gastric cancer tissues].

OBJECTIVE: To identify the microsatellite instability(MSI) rates in Chinese gastric cancer samples. METHODS: 29 microsatellite markers were selected to examine 42 paired gastric cancer tissues for MSI on all chromosomes except Y. RESULTS: The total frequency of MSI in all 42 gastric cancers was 33.9% with higher rates at loci of D3S1577, D3S1067,D8S279,D9S257, D1S248, D7S520 and D2S147,and the highest rate at D3S1577 and D3S1067(51.35%). MSI varied with different pathological types. The frequencies of MSI were signi- ficantly higher in poorly differentiated tumors and signet cell types, compared with well differentiated tumors(P=0.0026 and 0.0013 by chi-square test),and no difference was noted between poorly differentiated and signet cell types. CONCLUSION: MSI may play an important role in Chinese gastric cancer, particularly the poorly differentiated adenocarcinomas. The data presented here further support the previous hypothesis that pathologically distinct subtypes of gastric cancer undergo different genetic pathways during tumorigenesis.

Adult↗
PubMed1998

Influence of myocardial infarction, coronary artery bypass surgery, and stroke on cognitive impairment in late life.

Relations between cognitive test scores in later life and prior myocardial infarction (MI), coronary artery bypass graft surgery (CABG), and stroke were examined for this study. Subjects were 3,734 Japanese-American men (80% of surviving Honolulu Heart Program cohort) aged 71 to 93 years at the time of cognitive testing. Impairment was defined as scoring below the 16th percentile on a validated cognitive assessment scale. Prior MI, stroke, and CABG were established using hospital surveillance, history, and record review. After adjustment for age, years of education, and years of childhood spent in Japan, men with prior stroke were significantly more likely than others to have poor cognitive performance (odds ratio 4.4, 95% confidence limits 3.0 to 6.7). History of > 1 stroke was associated with an odds ratio of 50 (95% confidence limits 10.5 to 238.3). There was no significant association between cognitive performance and > or = 1 prior MI or history of CABG. Time between events and cognitive function testing did not affect results. Analyses support a significant association between clinical stroke and persistent cognitive impairment, but fail to implicate CABG or MI.

Aged↗
PubMed1998

Effect of motilin and erythromycin on calcium-activated potassium channels in rabbit colonic myocytes.

BACKGROUND & AIMS: Motilin and erythromycin are prokinetic agents that act on the same receptor in gastrointestinal smooth muscle to cause contraction. Both agonists may also cause an increase in outward current. The aim of this study was to determine whether motilin and erythromycin activate calcium-activated potassium (KCa) channels. METHODS: Freshly dispersed longitudinal smooth muscle cells of the rabbit colon were used to measure whole-cell outward current and single-channel activity using patch clamp recording methods. RESULTS: Erythromycin and motilin increased a calcium-dependent outward potassium current and increased the open probability of KCa channels of cell- attached patches. CONCLUSIONS: Erythromycin and motilin activate KCa channels via an intracellular second messenger system. This effect may modulate the increase in contractility caused by these agonists.

Animals↗
PubMed1998

Antibody responses to bee melittin (Api m 4) and hornet antigen 5 (Dol m 5) in mice treated with the dominant T-cell epitope peptides.

BACKGROUND: Mice treated with the dominant T-cell epitope peptides of allergens were reported to have reduced peptide or allergen-specific T-cell responses on subsequent immunization, but the extent of reduction of allergen-specific antibodies is not clear. OBJECTIVE: This study was done to compare the extent of reduction of T-cell and antibody responses in peptide-treated mice. Two allergens were tested. Bee melittin (Api m 4), an allergen of 26 amino acid residues, has a single dominant T- or B-cell epitope. Hornet antigen 5 (Dol m 5), an allergen of 204 amino acid residues, has multiple dominant T- or B-cell epitopes. METHODS: Mice were treated with T-cell peptides of Api m 4 or Dol m 5 and then immunized biweekly with their respective allergen with alum adjuvant. T-cell peptides tested were residues 7-19 of Api m 4 and residues 41-60, 141-160, and 176-195 of Dol m 5. T-cell responses at week 9 or 11 were assayed by proliferation of spleen cell cultures. Antibody responses of different isotypes were measured biweekly by ELISA. RESULTS: Partial reduction of 30% to 50% of T-cell responses to peptide or allergen was observed in bee and hornet peptide-treated mice. About 65% reduction of Api m 4-specific antibody response was observed early in the immune response but gradually subsided to about 40% late in the response. Partial reduction of about 40% of Dol m 5-specific antibody response was only observed early in the immune response. CONCLUSION: Peptide treatment is partially effective in the reduction of T-cell responses of univalent or multivalent allergens. It is also partially effective in the reduction of antibody response of a univalent allergen, but it is poorly effective for a multivalent allergen.

Adjuvants, Immunologic↗
PubMed1998

Structure of double-shelled rice dwarf virus.

Rice dwarf virus (RDV), a member of the Reoviridae family, is a double-stranded RNA virus. Infection of rice plants with RDV reduces crop production significantly and can pose a major economic threat to Southeast Asia. A 25-A three-dimensional structure of the 700-A-diameter RDV capsid has been determined by 400-kV electron cryomicroscopy and computer reconstruction. The structure revealed two distinctive icosahedral shells: a T=13l outer icosahedral shell composed of 260 trimeric clusters of P8 (46 kDa) and an inner T=1 icosahedral shell of 60 dimers of P3 (114 kDa). Sequence and structural comparisons were made between the RDV outer shell trimer and the two crystal conformations (REF and HEX) of the VP7 trimer of bluetongue virus, an animal analog of RDV. The low-resolution structural match of the RDV outer shell trimer to the HEX conformation of VP7 trimer has led to the proposal that P8 consists of an upper domain of beta-sandwich motif and a lower domain of alpha helices. The less well fit REF conformation of VP7 to the RDV trimer may be due to the differences between VP7 and P8 in the sequence of the hinge region that connects the two domains. The additional mass density and the absence of a known signaling peptide on the surface of the RDV outer shell trimer may be responsible for the different interactions between plants and animal reoviruses.

Amino Acid Sequence↗
PubMed1998

Effect of nitric oxide on calcium-activated potassium channels in colonic smooth muscle of rabbits.

Nitric oxide (NO) hyperpolarizes intestinal smooth muscle cells. This study was designed to determine the mechanism whereby NO activates KCa channels of circular smooth muscle of the rabbit colon. Transmural biopsies of the rabbit colon were stained for NADPH-diaphorase. Freshly dispersed circular smooth muscle cells were studied in the whole cell configuration, as well as in on-cell and excised inside-out patch recording configurations, while KCa current and the activity of KCa channels, respectively, were monitored. NADPH-diaphorase-positive nerve fibers were found in both muscle layers. NO (1%) increased whole cell net outward current by 79% and hyperpolarized resting membrane voltage from -59 to -73 mV (n = 8 cells, P < 0.01). In the on-cell patch recording configuration. NO (0.5% or 1%) in the bath increased NPo of KCa channels; charybdotoxin (125 nM) in the pipette solution blocked this effect. In the excised inside-out patch recording configuration, NO (1%) had no effect on NPo of KCa channels. In the on-cell patch recording configuration, methylene blue (1 microM) or cystamine (5 mM) in the bath solution decreased the effect of NO (1%) on NPo of KCa channels. NPo was increased by 8-bromo-cGMP (8-BrcGMP; 1 mM), a cGMP analog, and zaprinast (100 microM), an inhibitor of cGMP phosphodiesterase. These data suggest that NO increased whole cell outward K+ current by activating KCa channels through a cGMP pathway.

Animals↗
PubMed1998

Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular smooth muscle cells.

Oleic acid and angiotensin II (Ang II) are elevated and may interact to accelerate vascular disease in obese hypertensive patients. We studied the effects of oleic acid and Ang II on growth responses of rat aortic smooth muscle cells (VSMCs). Oleic acid (50 micromol/L) raised thymidine incorporation by 50% at 24 hours and cell number by 55% at 6 days (P<.05). Ang II (10(-11) to 10(-6) mol/L) did not significantly increase thymidine incorporation or VSMC number. Combining Ang II and 50 micromol/L oleic acid doubled thymidine incorporation and VSMC number. Losartan, an angiotensin type 1 (AT1) receptor antagonist, blocked the synergistic interaction between Ang II and oleic acid, whereas the AT2 receptor antagonist PD 123319 did not. Protein kinase C inhibition and downregulation, as well as inhibition of extracellular signal-regulated kinase (ERK) activation by PD 98059, eliminated the rise of thymidine incorporation in response to oleic acid and the synergistic interaction with Ang II. However, the response to 10% fetal bovine serum was unaffected. An antisense oligodeoxynucleotide to ERK-1 and ERK-2 reduced ERK protein expression and activation by 83% and 75%, respectively. Antisense prevented the rise of thymidine incorporation in response to oleic acid and the synergy with Ang II. Antisense reduced but did not prevent increased thymidine incorporation in response to serum. The data indicate that oleic acid and Ang II exert a synergistic mitogenic effect in VSMCs and suggest an important role for the AT1 receptor, PKC, and ERK in this synergy. The observations raise the possibility that a synergistic mitogenic interaction between oleic acid and Ang II accelerates vascular remodeling in obese hypertensive patients.

Angiotensin II↗
PubMed1998

Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells.

Obese hypertensive patients with cardiovascular risk factor clustering have increased plasma nonesterified fatty acid levels and are at high risk for atherosclerotic events. Our previous studies demonstrated that oleic acid induces a mitogenic response in rat aortic smooth muscle cells (RASMCs) through protein kinase C (PKC)- and extracellular signal-regulated kinase (ERK)-dependent pathways. In the present study we investigated the possibility that the generation of reactive oxygen species (ROS) constitutes a critical component of the oleic acid-induced mitogenic signaling pathway in RASMCs. We studied the effect(s) of oleic acid on the generation of ROS using the oxidant-sensitive fluoroprobe 2',7'-dichlorofluorescin diacetate. Relative fluorescence intensity and fluorescent images were obtained with laser confocal scanning microscopy from 1 to 5 minutes, since preliminary studies demonstrated that the peak fluorescence intensity occurred within 5 minutes. Oleic acid (100 micromol/L) induced a time-dependent increase of cell fluorescence that was >8-fold of that seen in control cells at 5 minutes. This was blocked by catalase, which suggests that H2O2 was the principal ROS. The oleic acid-induced increases in H2O2 were blocked when PKC was inhibited with the use of bisindolylmaleimide and when PKC activity was downregulated by exposing RASMCs to phorbol 12-myristate 13-acetate for 24 hours. Stearic and elaidic acids, which are weak PKC activators, did not significantly increase H2O2 production. The increase of H2O2 in response to oleic acid was inhibited by the antioxidant N-acetylcysteine. N-Acetylcysteine also completely blocked ERK activation and the increase of thymidine incorporation in response to oleic acid. The data suggest that generation of H2O2 in RASMCs exposed to oleic acid is PKC dependent. Moreover, H2O2 production emerges as a critical intermediary event in the oleic acid-mediated mitogenic signaling pathway between the activation of PKC and ERK. These observations raise the possibility that the elevated plasma nonesterified fatty acids, including oleic acid, in obese hypertensive patients contribute to vascular growth and remodeling by a PKC-dependent mechanism to generate ROS that subsequently activate ERK.

Acetylcysteine↗
PubMed1998

[Heart function and clinical observations of patients with severe congestive heart failure treated with milrinone].

To evaluate the clinical effects of milrinone in patients with severe heart failure, heart function and clinical observations were performed on 25 patients with severe congestive heart failure treated with domestic intravenous milrinone for 15 days. Results showed that the total response rate to milrinone was 96% while 60% of them had significant improvement. Heart function and diameter of left atrial, left ventricle, and right ventricle were measured by pulsed Doppler and M-mode echocardiographg before and after the treatment. The systolic function of the left ventricle (such as SV, CO, EF, FS, IVST, PLVWT) was significantly improved. The diastolic function of the left ventricle (such as E peak, A peak, IRT) was also improved. Diameter of left atrial, left ventricle, and right ventricle was significantly reduced. The heart rate and blood pressure remained unchanged. No obvious side-effect was found in our observation. The domestic intravenous milrinone is a drug of choice for the management of patients with severe congestive heart failure.

Adult↗
PubMed1998

[Effects of plendil on serum oxygen free radicals and insulin resistance in patients with essential hypertension].

To evaluate the effects of plendia on oxygen free radicals and insulin resistance in patients with essential hypertension, thirty non-obesive moderate hypertensive patients were treated with plendil for 30 days. Antihypertensive effect and effects on serum lipid peroxide (LPO), superoxide dismutase (SOD), insulin sensitivity index (ISI) were studied. Results showed: 1. SOD activity and ISI decreased but contents of LPO and insulin increased in the treatment group. After a course of plendil therapy the above mentioned parameters fell to normal ranges. 2. Plendil had obvious antihypertensive effect but with no significant changes in heart rate. 3. Plendil had no significant effect on fasting blood glucose and lipids. Plendia was an effective and safe drug for treatment of essential hypertension. It also had the effects of antioxidation which improved the sensitivity to insulin.

Calcium Channel Blockers↗
PubMed1998

[Surgical treatment of sacral tumor].

From 1990 to 1996, 21 patients with sacral tumor were surgically, including 8 cases with giant tumor of bone, 7 cases of spinal cord tumor, each 2 cases of neurofibroma and adenoma, 1 case of myeloma and 1 case of lipoma with low grade of malignancy. A total of 22 operations involving one for recurrent tumors in 21 cases were performed. Sacral resection and curettage plus resection were the surgical ways. 19 patients were followed up with an average period of 2.5 years. 15 patients showed good results, 3 patients occurred urinary incontinence and constipation, one of 3 cases occurred weakness of ankles and feet. Authors conclude that surgery should be advised and actively adopted for sacral tumors.

Adult↗
PubMed1998

[Effect of xueling on relating substances of renal hypertension in rats].

Xueling(p.o.) obviously reduces the aldosterone content of renal hypertension rats, but not affecting markedly the endothelin, atrial natriuretic factor, calcitonin gene-related peptide, thromboxane B2 and 6-keto-prostaglandin F1 alpha. The content reduction of aldosterone is one of the mechanisms to lower blood pressure.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin.

Previous studies established that fetal rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. Whereas brain-derived neurotrophic factor (BDNF) or phorbol 12-myristate-13-acetate (PMA) induces NPY production in rat cultures, only PMA does so in human cultures. We addressed these questions: 1) Do soluble products of rat or human astrocytes (conditioned medium; rCM and hCM, respectively) enhance the functional expression of cultured NPY neurons and if so, do they enhance the expression of somatostatin (SRIF) neurons as well? 2) Is the NPY-enhancing activity (EA) in the CM species specific? rCM enhanced (approximately 2-fold) both basal and BDNF-stimulated production of NPY and coculture of rat aggregates and astrocytes did not prevent this NPY-EA. Likewise, the hCM enhanced (approximately 2.5-fold) basal and PMA-stimulated production of NPY by human aggregates. Moreover, the hCM enhanced NPY production by rat aggregates and rCM enhanced NPY production by human aggregates. In addition, rCM and hCM each enhanced BDNF-, forskolin-, or PMA-stimulated NPY production by rat aggregates. Under each of the above conditions, the rCM/hCM suppressed (approximately 50%) production of SRIF by rat aggregates. In summary, secretory products of rat and human astrocytes exert opposite effects on the functional expression of NPY and SRIF neurons in culture: enhancement of NPY and suppression of SRIF. By the criteria evaluated in this study, these astrocyte-derived activities do not exhibit species specificity.

Animals↗
PubMed1997

The heterologous interactions among plant 14-3-3 proteins and identification of regions that are important for dimerization.

The 14-3-3 proteins constitute a family of dimeric proteins that are involved in many cellular functions. At least two mammalian 14-3-3 proteins can form heterodimers and the approximate regions important for dimerization have been identified. In this study, we demonstrate that eight Arabidopsis and one maize 14-3-3 protein can dimerize with each other and with themselves. Native gel Western analysis of Arabidopsis cell extract also suggests the presence of 14-3-3 heterodimers in vivo. Finally, we identified the domains of one 14-3-3 protein that are sufficient for homodimerization and heterodimerization. These data support the hypothesis that evolutionarily divergent 14-3-3 proteins can interact with each other to form diverse molecular modulators or adapters in signaling pathways.

14-3-3 Proteins↗
PubMed1997

Novel tetramer assembly of pyruvate decarboxylase from brewer's yeast observed in a new crystal form.

A new crystal form of thiamine diphosphate dependent pyruvate decarboxylase from Saccharomyces cerevisiae has been obtained in the presence of the activator pyruvamide. The crystallographic structure analysis reveals differences in the domain packing in the enzyme subunit and a novel assembly of the subunits in the tetramer, when compared to the structure of native PDC. The orientation of the beta domains in the subunit differs by a 6.3 degrees and 8.3 degrees rotation, respectively, whereas the subunit-subunit interface in the dimer, formed by the alpha and gamma domains, is essentially maintained. In the tetramer, one of the dimers rotates relative to the second dimer by approximately 30 degrees creating a new dimer-dimer interface.

Crystallization↗
PubMed1997

Importance of the dimer-dimer interface for allosteric signal transduction and AMP cooperativity of pig kidney fructose-1,6-bisphosphatase. Site-specific mutagenesis studies of Glu-192 and Asp-187 residues on the 190's loop.

The role of the 190's loop of fructose-1,6-bisphosphatase (Fru-1, 6-P2ase) in the allosteric regulation of Fru-1,6-P2ase has been investigated through kinetic studies on three mutant enzymes, Glu-192 --> Ala, Glu-192 --> Gln, and Asp-187 --> Ala. AMP is an allosteric inhibitor, which binds to the regulatory sites and induces the R- to T-state transition; for wild-type Fru-1,6-P2ase AMP inhibition is cooperative with a Hill coefficient of 2.0. The replacement of Asp-187, which forms an interaction across the C1:C2 monomer-monomer interface, with alanine did not change the catalytic efficiency, and it had no effect on the cooperativity of AMP inhibition; however, the apparent dissociation constant for AMP increased more than 4-fold as compared to the value for the wild-type enzyme. The replacement of Glu-192, which forms interactions across the C1:C4 dimer-dimer interface, with Ala and Gln lowered kcat from 21 s-1 for wild-type enzyme to 15 s-1 and 13 s-1, respectively, for the mutant enzymes, while their respective Km values were not changed. However, these replacements did have dramatic effects on AMP inhibition; first, cooperative AMP inhibition was lost; second, the AMP inhibition was biphasic, which can be interpreted as due to AMP binding to two classes of binding sites. The high affinity class of sites corresponds to the regulatory sites, while the low affinity class of sites may be the active sites. The results reported here, combined with the structural and kinetic results from the Lys-42 --> Ala enzyme, strongly suggest that the C1:C4 dimer-dimer interface, rather than the C1:C2 monomer-monomer interface, is critical for the propagation of the allosteric signal between the AMP sites on different subunits; in addition, cooperative AMP inhibition is essential for the enzyme to be fully inhibited by the binding of AMP to the allosteric site.

Adenosine Monophosphate↗
PubMed1997

Structure of Semliki Forest virus core protein.

Alphaviruses are enveloped, insect-borne viruses, which contains a positive-sense RNA genome. The protein capsid is surrounded by a lipid membrane, which is penetrated by glycoprotein spikes. The structure of the Sindbis virus (SINV) (the type virus) core protein (SCP) was previously determined and found to have a chymotrypsin-like structure. SCP is a serine proteinase which cleaves itself from a polyprotein. Semliki Forest virus (SFV) is among the most distantly related alphaviruses to SINV. Similar to SCP, autocatalysis is inhibited in SFCP after cleavage of the polyprotein by leaving the carboxy-terminal tryptophan in the specificity pocket. The structures of two different crystal forms (I and II) of SFV core protein (SFCP) have been determined to 3.0 A and 3.3 A resolution, respectively. The SFCP monomer backbone structure is very similar to that of SCP. The dimeric association between monomers, A and B, found in two different crystal forms of SCP is also present in both crystal forms of SFCP. However, a third monomer, C, occurs in SFCP crystal form I. While monomers A and B make a tail-to-tail dimer contact, monomers B and C make a head-to-head dimer contact. A hydrophobic pocket on the surface of the capsid protein, the proposed site of binding of the E2 glycoprotein, has large conformational differences with respect to SCP and, in contrast to SCP, is found devoid of bound peptide. In particular, Tyr184 is pointing out of the hydrophobic pocket in SFCP, whereas the equivalent tyrosine in SCP is pointing into the pocket. The conformation of Tyr184, found in SFCP, is consistent with its availability for iodination, as observed in the homologous SINV cores. This suggests, by comparison with SCP, that E2 binding to cores causes major conformational changes, including the burial of Tyr184, which would stabilize the intact virus on budding from an infected cell. The head-to-tail contacts found in the pentameric and hexameric associations within the virion utilize in the same monomer surface regions as found in the crystalline dimer interfaces.

Amino Acid Sequence↗