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Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 109 records · Page 6Linked to original sources

Proteomic detection of changes in protein synthesis induced by NGX6 transfected in human nasopharyngeal carcinoma cells.

In the previous study, we cloned a new gene, named NGX6, related to nasopharyngeal carcinoma (NPC) at 9p. To study its function in the pathogenesis of NPC, we have investigated changes in protein synthesis between NPC cell line HNE1 and that transfected with the gene. Using high-resolution two-dimensional electrophoresis, we found that 22 protein spots showed variations that were significant and reproducible. Analysis of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searches identified seven proteins that were upregulated and seven proteins that were downregulated. These proteins included Fas, zinc-finger protein (ZNF), RAB, and Ah receptor-interacting protein (AIP). The functional implications of the identified proteins are discussed.

Down-Regulation↗

Synergistic protective effect of caspase inhibitors and bFGF against brain injury induced by transient focal ischaemia.

We tested the hypothesis that combined use of trophic factors and caspase inhibitors increases brain resistance to ischaemia in mice. Intracerebroventricular administration of bFGF (>10 ng) 30 min after MCA occlusion decreased infarct size and neurological deficit in a dose-dependent manner following 2 h ischemia and reperfusion (20 h). Combined administration of the subthreshold doses of bFGF (3 ng) and caspase inhibitors (z-VAD.FMK, 27 ng or z-DEVD.FMK, 80 mg) reduced infarct volume by 60%, and reduced neurological deficit. Treatment with a subthreshold dose of bFGF (3 ng) extended the therapeutic window for z-DEVD.FMK (480 ng) from 1 to 3 h after reperfusion. Caspase-3 activity in the ischaemic brain was increased 30 min and 2 h after reperfusion but, was significantly reduced in bFGF-treated animals by 29 and 16%, respectively. Caspase-3 activity was not reduced by a direct bFGF effect because addition of bFGF (10 nM - 2 microM) did not decrease recombinant caspase-3 activity, in vitro. Our data show that combining caspase inhibitors and bFGF lengthens the treatment window for the second treatment, plus lowers the dosage requirements for neuroprotection. These findings are important because low doses of caspase inhibitors or bFGF reduce the possibility of side effects plus extend the short treatment window for ischaemic stroke.

Amino Acid Chloromethyl Ketones↗

Growth of infants during the first 18 months of life in urban and rural areas of southern China.

OBJECTIVE: Observe the growth pattern of infants from birth to 18 months. METHODOLOGY: A prospective study was conducted from 1994 to 1996 in urban and township-rural areas of Guangdong Province, southern China, recruiting 568 and 257 newborn infants, respectively. Anthropometric data was collected at birth, 1.5, 4, 5, 6, 8, 10, 12, 15, and 18 months. RESULTS: The urban infants at birth had Z-scores of weight for age (WAZ), height for age (HAZ) and weight for height (WHZ) below the National Center for Health Statistics (NCHS) median (P < 0.01). However, from 1.5 to 4 months, the WAZ and WHZ scores were above (P < 0.01), but by 7 months fell and remained at - 0.7 to - 0.8 SD below the NCHS median (P < 0.01). HAZ scores improved after birth, were at the NCHS median to 8 months (P = NS), and then decreased to 0.2-0.4 SD below the NCHS median (P < 0.01). Compared with the urban infants, the township-rural infants were lighter and shorter throughout the first 18 months of life, and from 8 months of age, were - 1 SD or more below the NCHS median. CONCLUSIONS: Growth retardation was found in this sample of Chinese infants. The magnitude of growth retardation was greater for infants in the township-rural area compared with those in the urban area.

Age Distribution↗

Hypothalamically induced emotional behavior and immunological changes in the cat.

Numerous animal studies on the correlation between stress and immunity have been performed but few such studies have been made concerning the relationship between various kinds of stress-related emotional behavior and immunological changes. Electrical stimulation of the hypothalamus in cats elicits various emotional behaviors such as restlessness, defensive attack, defensive retreat and quiet biting attack. We examined changes in the lymphocyte proliferative responses and plasma cortisol level which accompanied such emotional behavior. A significant increase in plasma cortisol was observed in the restlessness, defensive attack and defensive retreat groups, but not in the quiet biting attack or non-response (control) groups. A significant increase in the lymphocyte proliferative responses to phytohemagglutinin (PHA) was observed in the restlessness and defensive attack groups but not in the defensive retreat, quiet biting attack or non-response groups. These results suggest that various kinds of emotional behavior appear to be differentially correlated with the lymphocyte proliferative responses, while also being differentially correlated with the plasma cortisol concentration. Because the changes in lymphocyte responses and plasma cortisol did not always completely correlate with one another, the changes in the lymphocyte responses are not considered to be influenced by plasma cortisol alone.

Animals↗

Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells.

Isoliquiritigenin, which is possibly a principal anti-tumor constituent of licorice, a traditional Chinese herb, was examined for apoptosis-inducing activity in human gastric cancer MGC-803 cells. Typical morphological and biochemical features of apoptosis including cell shrinkage, chromatin condensation, DNA ladder formation, and appearance of apoptotic peaks (subG(1)) were observed in MGC-803 cells with isoliquiritigenin treatment. Using Fluo-3 and Rh123 as fluorescent probes, respectively, it was found that the intracellular free calcium concentration increased and the mitochondrial transmembrane potential (Deltapsi(m)) decreased in a dose-dependent manner in apoptotic cells. These results suggest that isoliquiritigenin induced apoptosis of MGC-803 cells through calcium- and Deltapsi(m)-dependent pathways, indicating that it is potentially useful as a natural anti-cancer agent.

Antineoplastic Agents, Phytogenic↗

Plexus avulsion and spinal cord injury increase the serum concentration of S-100 protein: an experimental study in rats.

The possibility of using the presence of the glial-cell-derived protein S-100 in serum as a marker for neuronal damage caused by spinal cord injury and plexus avulsion injury was investigated in 144 adult rats. After a spinal cord injury had been induced at the thoracic level or a plexus avulsion injury at the lumbar level, blood samples were taken and analysed for S-100 protein by a monoclonal two-site immunoluminometric assay. The two types of neurotrauma changed the kinetics of serum S-100 in different ways. After spinal cord injury it rapidly increased and within 72 hours had reached a concentration about 5 times that of the control animals. Three peak concentrations occurred at 3, 12, and 72 hours, respectively, and differed significantly from those of the control group (p < 0.05). After six days the values had returned to normal. After lumbar plexus injury alone there was no significant increase in the concentration of S-100. These results suggest that the concentration of S-100 protein in serum may be used as an early diagnostic tool for detecting neuronal damage caused by spinal cord injury or plexus avulsion associated with damage to the root entry zone.

Animals↗

Photogeneration of singlet oxygen (1O2) and free radicals (Sen*-, O2*-) by tetra-brominated hypocrellin B derivative.

To improve photodynamic activity of the parent hypocrellin B (HB), a tetra-brominated HB derivative (compound 1) was synthesized in high yield. Compared with HB, compound 1 has enhanced red absorption and high molar extinction coefficients. The photodynamic action of compound 1, especially the generation mechanism and efficiencies of active species (Sens*-, O2*- and 1O2) were studied using electron paramagnetic resonance (EPR) and spectrophotometric methods. In the deoxygenated DMSO solution of compound 1, the semiquinone anion radical of compound 1 is photogenerated via the self-electron transfer between the excited and ground state species. The presence of electron donor significantly promotes the reduction of compound 1. When oxygen is present, superoxide anion radical (O2*-) is formed via the electron transfer from Sens*- to the ground state molecular oxygen. The efficiencies of Sens*- and O2*- generation by compound 1 are about three and two times as much as that of HB, respectively. Singlet oxygen (1O2) can be produced via the energy transfer from triplet compound 1 to ground state oxygen molecules. The quantum yield of singlet oxygen (1O2) is 0.54 in CHCl3 similar to that of HB. Furthermore, it was found that the accumulation of Sens*- would replace that of O2*- or 1O2 with the depletion of oxygen in the sealed system.

Benzoquinones↗

Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study.

BACKGROUND: A high calcium intake, mainly from dairy products, may increase prostate cancer risk by lowering concentrations of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a hormone thought to protect against prostate cancer. The results of epidemiologic studies of this hypothesis are inconclusive. OBJECTIVE: We investigated the association between dairy product and calcium intakes and prostate cancer risk in the Physicians' Health Study, a cohort of male US physicians. DESIGN: At baseline, the men answered abbreviated dietary questionnaires. During 11 y of follow-up, we documented 1012 incident cases of prostate cancer among 20885 men. We estimated dairy calcium intake on the basis of consumption of 5 major dairy products and used logistic regression to estimate relative risk. RESULTS: At baseline, men who consumed >600 mg Ca/d from skim milk had lower plasma 1,25(OH)(2)D(3) concentrations than did those consuming < or =150 mg Ca/d [71 compared with 85 pmol/L (30.06 compared with 35.64 pg/mL); P = 0.005]. Compared with men consuming < or =0.5 daily servings of dairy products, those consuming >2.5 servings had a multivariate relative risk of prostate cancer of 1.34 (95% CI: 1.04, 1.71) after adjustment for baseline age, body mass index, smoking, exercise, and randomized treatment assignment in the original placebo-controlled trial. Compared with men consuming < or =150 mg Ca/d from dairy products, men consuming >600 mg/d had a 32% higher risk of prostate cancer (95% CI: 1.08, 1.63). CONCLUSIONS: These results support the hypothesis that dairy products and calcium are associated with a greater risk of prostate cancer.

Calcium, Dietary↗

Automated identification of Fos expression.

The concentration of Fos, a protein encoded by the immediate-early gene c-fos, provides a measure of synaptic activity that may not parallel the electrical activity of neurons. Such a measure is important for the difficult problem of identifying dynamic properties of neuronal circuitries activated by a variety of stimuli and behaviours. We employ two-stage statistical pattern recognition to identify cellular nuclei that express Fos in two-dimensional sections of rat forebrain after administration of antipsychotic drugs. In stage one, we distinguish dark-stained candidate nuclei from image background by a thresholding algorithm and record size and shape measurements of these objects. In stage two, we compare performance of linear and quadratic discriminants, nearest-neighbour and artificial neural network classifiers that employ functions of these measurements to label candidate objects as either Fos nuclei, two touching Fos nuclei or irrelevant background material. New images of neighbouring brain tissue serve as test sets to assess generalizability of the best derived classification rule, as determined by lowest cross-validation misclassification rate. Three experts, two internal and one external, compare manual and automated results for accuracy assessment. Analyses of a subset of images on two separate occasions provide quantitative measures of inter- and intra-expert consistency. We conclude that our automated procedure yields results that compare favourably with those of the experts and thus has potential to remove much of the tedium, subjectivity and irreproducibility of current Fos identification methods in digital microscopy.

Journal Article↗

Red and black rice decrease atherosclerotic plaque formation and increase antioxidant status in rabbits.

The influence of white, red and black rice consumption on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in rabbits. Male rabbits (n = 36) were divided into five groups. They were fed a normal laboratory purified diet (normal group, n = 6), a high cholesterol (0.5 g/100 g) diet (HC group, n = 6), a high cholesterol diet with 30 g/100 g white rice (WR group, n = 8), 30 g/100 g red rice (RR group, n = 8), or 30 g/100 g black rice (BR group, n = 8) for 10 wk. Blood samples were collected for lipid measurements and aorta were removed for assessment of atherosclerotic plaques at the end of the protocol. The oxidant and antioxidant status of blood, erythrocytes, liver and aorta was evaluated. The area of atherosclerotic plaque was 50% lower in rabbits fed the red or black rice diets than in those fed the white rice diet. Compared with the HC and WR groups, serum HDL cholesterol and apolipoprotein (apo) A-I concentration were greater (P < 0.05) in the RR and BR groups. Liver reactive oxygen species (ROS) and aortic malondialdehyde (MDA) were significantly lower, and the liver total antioxidative capacity (TAC) and erythrocyte superoxide dismutase (SOD) activity were significantly higher in the RR and BR groups compared with the HC and WR groups. Red or black rice consumption reduced or retarded the progression of atherosclerotic plaque development induced by dietary cholesterol. The enhanced serum HDL cholesterol and apo A-I concentrations, and the increased antioxidant and decreased oxidative status may be mechanisms of the antiatherogenic effect of red or black rice.

Analysis of Variance↗

Regulation of zygotic gene activation in the preimplantation mouse embryo: global activation and repression of gene expression.

Superimposed on the activation of the embryonic genome in the preimplantation mouse embryo is the formation of a transcriptionally repressive state during the two-cell stage. This repression appears mediated at the level of chromatin structure, because it is reversed by inducing histone hyperacetylation or inhibiting the second round of DNA replication. We report that of more than 200 amplicons analyzed by mRNA differential display, about 45% of them are repressed between the two-cell and four-cell stages. This repression is scored as either a decrease in amplicon expression that occurs between the two-cell and four-cell stages or on the ability of either trichostatin A (an inhibitor of histone deacetylases) or aphidicolin (an inhibitor of replicative DNA polymerases) to increase the level of amplicon expression. Results of this study also indicate that about 16% of the amplicons analyzed likely are novel genes whose sequence doesn't correspond to sequences in the current databases, whereas about 20% of the sequences expressed during this transition likely are repetitive sequences. Lastly, inducing histone hyperacetylation in the two-cell embryos inhibits cleavage to the four-cell stage. These results suggest that genome activation is global and relatively promiscuous and that a function of the transcriptionally repressive state is to dictate the appropriate profile of gene expression that is compatible with further development.

Acetylation↗

Adaptive intrapatient dose escalation of cisplatin in patients with advanced head and neck cancer.

The purpose of this study was to explore the feasibility and toxicity of intrapatient dose adjustment using predefined levels of exposure to cisplatin, with the ultimate goal to further improve the antitumor activity of the treatment. The primary parameter for adaptive dosing was the level of platinum DNA adducts in peripheral white blood cells (WBC) and the secondary parameter the area under the curve (AUC) of unbound platinum in plasma, which were determined during the applied courses. Target levels had been defined in a previously performed pharmacologic study. The concept of adaptive dosing was tested in 16 patients with locally advanced head and neck (H/N) cancer who would receive six weekly courses of cisplatin at a starting dose level of 80 mg/m(2), which was previously investigated in a phase II study. Forty-seven percent of patients received a dose increase varying from 10 to 40%. Only two patients had exposure levels significantly below the defined target levels for DNA adducts and AUC. The majority of patients reached the defined target levels by modest dose increases of 10-20% during course 2. Relevant but reversible ototoxicity (temporary grade 3 in two patients) and renal toxicity (temporary grade 2 in two other patients) were observed. The pattern and severity of the toxicity was comparable to that encountered in the previous phase II study in H/N cancer patients. We conclude that the strategy of intrapatient dose adjustment for cisplatin is practically feasible in a research setting even when a short turn around time of 1 week is the limit for reporting results. Although in some patients the dose increase that had to be applied to reach target levels was substantial (up to 40%), this approach in H/N cancer patients is not expected to improve the response rate significantly, because these significantly underdosed patients represented only a small percentage of the investigated population. The great majority of patients needed only limited (10-20%) dose increases which very likely will not improve the response rate to a clinically significant extent. The outlined concept is currently being explored in other tumor types and schedules of cisplatin.

Adult↗

Antitumor effect of the idiotypic cascade induced by an antibody encapsulated in poly(d,l-lactide-co-glycolide) microspheres.

A major difficulty encountered during development of antibody vaccines is their weak immunogenicity. In this study, a monoclonal antibody CS20.5 to human breast cancer antigen CA15.3 was coencapsulated in poly(d,l-lactide-co-glycolide) microspheres with monophosphoryl lipid A. The antitumor effect of this formulation was investigated in a murine model. The induced Ab2 biologically mimics antigen as it competed with CA15.3 for the same idiotope on Ab1. Ab3 induction was also observed. After five sequential administrations of encapsulated antibody, mice showed statistically significant tumor regression. These results indicate that this formulation may serve as a potential treatment for breast cancer.

Animals↗

Smoking cessation in China: findings from the 1996 national prevalence survey.

OBJECTIVES: To describe patterns of smoking and smoking cessation in China within the context of the stages of change model, using data from the 1996 national prevalence survey. DESIGN: A cross sectional survey was carried out using the 145 preselected disease surveillance points, which provide a representative sample for the entire country. A standardised questionnaire on smoking was interviewer administered. SETTING: The country of China. SUBJECTS: 122,220 people aged 15-69 years. MAINTENANCE MEASURES: Smoking cessation patterns, as defined by smoking status (current or former) and stage of change (precontemplation, contemplation, and action). RESULTS: The sample included 45,995 ever smokers of whom 4336 had quit. About 72% of current smokers reported not intending to give up their smoking behaviour, and about 16% of current smokers said they intended to do so, but have not taken any action. Of all ever smokers, the percentage of former smokers was 9.5%, and 12% of current smokers had quit at least once, but relapsed by the time of the survey. The patterns were similar in men and women with regard to the stated intent to quit. Among males, the percentage of former smokers increased with age but the percentage intending to quit was constant at about 15% across age strata. The most common reason for quitting was illness. Participants with a university education were more likely to have made an attempt to quit. CONCLUSIONS: The percentage of smokers contemplating quitting was low in China in 1996. The study shows that smokers in China must be mobilised to contemplate quitting and then to take action.

Adolescent↗

Simulated microgravity enhances vasoconstrictor responsiveness of rat basilar artery.

Recently, hypertrophy and increased myogenic tone of brain vessels have been observed in rats after simulated microgravity. It is expected that simulated microgravity may also induce hyperreactivity of brain vessels. To test this hypothesis, Sprague-Dawley rats were subjected to a 4-wk tail-suspended hindlimb unloading (TS) to simulate the cardiovascular deconditioning effect of microgravity. After 4 wk, the vasoreactivity of isolated basilar arterial rings from TS rats to both receptor- and non-receptor-mediated vasoconstrictors, such as KCl, arginine vasopressin, or 5-hydroxytryptamine (5-HT), and vasodilators such as ACh, thrombin, adenosine, or sodium nitroprusside were examined and compared with those from simultaneous control (Cn) rats. In the first part of this study, it was found that the maximal isometric contractile responsiveness evoked by vasoconstrictors such as KCl, arginine vasopressin, or 5-HT was enhanced in basilar arterial rings from TS rats, whereas vasodilatory responsiveness to vasodilators showed no significant difference between TS and Cn rats. In the second part of this study, it was found that removal of the endothelium had no effects on the contractile responsiveness to 5-HT in basilar arterial rings from TS rats but enhanced markedly the responsiveness in basilar arterial rings from Cn rats to an extent comparable with that of TS rats. Application of tetraethylammonium also had no effects on the contractile response to 5-HT in basilar arterial rings from TS but significantly increased the responsiveness of basilar arterial rings from Cn rats with endothelium intact. These results showed that 4-wk simulated microgravity enhanced the vascular contractile responsiveness of basilar arterial rings to both receptor- and non-receptor-mediated vasoconstrictors, and the enhancement of 5-HT-induced contraction in TS rat basilar arteries was due to an impairment of endothelium-dependent mechanism. These results suggest that endothelium-derived hyperpolarizing factors are responsible for this endothelium-dependent attenuating modulatory mechanism in contractile responsiveness of rat basilar arteries to 5-HT.

Animals↗

Green tea and its catechins inhibit breast cancer xenografts.

Investigators have shown that green tea may decrease the risk of cancer. It is widely accepted that the main active component of green tea is epigallocatechin-3-gallate (EGCG). In this study, we examined the effect of green tea on breast cancer growth and endothelial cells in in vitro assays and in animal models. Furthermore, we compared the potency of the different catechin components of green tea extract (GTE), including EGCG. Our data showed that mixed GTE and its individual catechin components were effective in inhibiting breast cancer and endothelial cell proliferation. In mouse experiments, GTE suppressed xenograft size and decreased the tumor vessel density. Our results demonstrated the value of all catechins and argued for the use of a mixed GTE as a botanical dietary supplement, rather than purified EGCG, in future clinical trials.

Animals↗

Novel promoter polymorphism in insulin-like growth factor-binding protein-3: correlation with serum levels and interaction with known regulators.

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is a major determinant of circulating levels of the IGFs and is clinically useful for the evaluation of GH deficiency and for predicting the response to GH treatment. Recent studies provide evidence that the circulating level of IGFBP-3 is inversely related to the risk of several common cancers, and that antiproliferative agents such as antiestrogens and retinoids act in part by up-regulating IGFBP-3 gene (IGFBP3) expression. Although approximately 50% of the substantial interindividual variability in circulating IGFBP-3 levels is known to have a genetic basis, the specific loci involved are unknown. Direct sequencing of genomic DNA specimens from a multiethnic population identified several single nucleotide polymorphisms in the promoter region of IGFBP3. For the most common single nucleotide polymorphism (nucleotide -202) found to be in Hardy-Weinberg equilibrium, genotype was highly correlated to circulating level of IGFBP-3 in 478 men from the Physicians' Health Study. In vitro, we documented significantly higher promoter activity of the A allele at the -202 locus compared with the C allele, consistent with the relationship observed between genotype and circulating IGFBP-3 (AA > AC > CC). A positive correlation was observed between circulating retinol levels and circulating IGFBP-3 levels; subset analysis by genotype showed that this relationship was only present among individuals carrying an A allele at -202 (AA > AC > CC). Tall individuals or individuals with a body mass index of 27 or greater had levels of circulating IGFBP-3 that were significantly higher when they possessed at least one A allele (AA > AC > CC). The IGFBP3 promoter region deserves investigation as a locus where polymorphic variation occurs frequently and may influence GH responsiveness, somatic growth, and possibly cancer risk.

Aging↗

Association of plasma antibodies against the inducible Hsp70 with hypertension and harsh working conditions.

Autoantibodies against certain stress or heat shock proteins (Hsps) may play a role in the pathogenesis and/ or prognosis of some diseases. Using immunoblotting with human recombinant Hsps and univariate and multivariate logistic regression models, we have investigated the presence of antibodies against Hsp70, the inducible member of the 70-kDa family of heat shock proteins, and analyzed its possible association with hypertension and working conditions. Plasma and serum were collected from 764 steel mill workers from 6 work sites exposed to (1) severe noise; (2) severe noise and dust; (3) noise, dust, and heat; (4) noise and heat; (5) severe noise and heat; and (6) office conditions (control). Workers with prolonged exposure to stresses such as noise, dust, and high temperature and a combination of these in the workplace had a high incidence (26.6% to 40.2%) of antibodies to Hsp70 compared to the lowest incidence (18.6%) of antibodies to Hsp70 in the control group of office workers. Moreover, there was a statistical association of antibodies against Hsp70 with hypertension. The statistical correlation between the presence of antibodies to Hsp70 and hypertension is higher in the group of workers with blood pressure of 160/95 mmHg than in the 140/90-mmHg group after excluding possible effects of the workplace stresses. These results suggest that harsh workplace conditions can increase the production of antibodies against Hsp70 and that the presence of antibodies to this stress protein may be associated with hypertension. The precise mechanism for the elevation of antibodies against Hsps by environmental and workplace stresses and their relation to hypertension remains to be established.

Autoantibodies↗