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Biomedical subjects

Y Zhang

Publications and source records attributed to Y Zhang.

At least 325 records · Page 18Linked to original sources
PubMed2002

Radiation exposure from diagnostic and therapeutic treatments and risk of breast cancer.

An association between low-dose diagnostic X-ray exposure or therapeutic radiation treatment and breast cancer risk has not been established. To further investigate the issue, we analysed data from a case-control study of breast cancer in Connecticut in 1994-1997. A total of 1217 subjects (608 breast cancer cases and 609 controls), 30-80 years old, participated in the study. A standardized, structured questionnaire was used to collect information through in-person interviews on diagnostic or therapeutic radiation and other breast cancer risk factors. An odds ratio (OR) of 1.7 (95% confidence interval (CI) 0.8-3.6) was observed for postmenopausal women with therapeutic radiation treatment for skin problems such as ringworm and acne, and an OR of 2.5 (95% CI 1.0-6.8) for those who reported having been treated six or more times. Radiation treatment received at younger ages seems to carry a higher risk. In earlier studies therapeutic radiation for skin problems has been associated with an increased risk of breast cancer. Therefore, it is possible that scattered radiation from these treatments could increase the risk of breast cancer. Radiation exposure from diagnostic X-rays was not associated with a significantly increased risk of breast cancer in this study.

Adult↗
PubMed2002

Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1).

Sin3 is an evolutionarily conserved corepressor that exists in different complexes with the histone deacetylases HDAC1 and HDAC2. Sin3-HDAC complexes are believed to deacetylate nucleosomes in the vicinity of Sin3-regulated promoters, resulting in a repressed chromatin structure. We have previously found that a human Sin3-HDAC complex includes HDAC1 and HDAC2, the histone-binding proteins RbAp46 and RbAp48, and two novel polypeptides SAP30 and SAP18. SAP30 is a specific component of Sin3 complexes since it is absent in other HDAC1/2-containing complexes such as NuRD. SAP30 mediates interactions with different polypeptides providing specificity to Sin3 complexes. We have identified p33ING1b, a negative growth regulator involved in the p53 pathway, as a SAP30-associated protein. Two distinct Sin3-p33ING1b-containing complexes were isolated, one of which associates with the subunits of the Brg1-based Swi/Snf chromatin remodeling complex. The N terminus of p33ING1b, which is divergent among a family of ING1 polypeptides, associates with the Sin3 complex through direct interaction with SAP30. The N-terminal domain of p33 is present in several uncharacterized human proteins. We show that overexpression of p33ING1b suppresses cell growth in a manner dependent on the intact Sin3-HDAC-interacting domain.

Amino Acid Sequence↗
PubMed2002

Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition?

OBJECTIVE: To test the hypothesis that, when measured in the long axis, left ventricular systolic function is abnormal in patients with diastolic heart failure. DESIGN: A case-control study. SETTING: University teaching hospital (tertiary referral centre). PATIENTS: 68 patients with heart failure, 29 with a left ventricular ejection fraction (LVEF) of > 0.45 and diastolic dysfunction (diastolic heart failure), 39 with an LVEF of </= 0.45 (systolic heart failure), and 105 normal subjects, including 33 age matched controls. METHODS: LVEF was measured by cross sectional Simpson's method, and mitral annular amplitudes and velocities by M mode and tissue Doppler echocardiography, respectively, along with mitral Doppler inflow velocities. Results were compared between the three groups. MAIN OUTCOME MEASURES: Peak systolic mitral annular velocity and amplitude between the different groups. RESULTS: The mitral annular peak mean velocity and amplitude in systole were lower in the patients with diastolic heart failure (mean (SEM), 4.8 (0.2) cm/s) than in the age matched normal controls (6.1 (0.14) cm/s), but higher than those with systolic heart failure (2.8 (0.13) cm/s) (all p < 0.001). Similar changes were seen the mitral annular amplitude during systole. Peak early diastolic velocity and amplitude were also significantly reduced in the group with diastolic heart failure. Left ventricular hypertrophy was evident in over 95% patients in both diastolic and systolic heart failure groups, with a comparable left ventricular mass index. CONCLUSIONS: In patients with diastolic heart failure and evidence of left ventricular hypertrophy, there is systolic left ventricular impairment as measured by myocardial Doppler imaging of the longitudinal axis. Thus subtle abnormalities of systolic function are present in patients with heart failure and a normal left ventricular ejection fraction, and there appears to be a continuum of systolic function between those with truly normal, mildly impaired (labelled diastolic heart failure), and obviously abnormal left ventricular systolic function. Isolated diastolic dysfunction is uncommon.

Adult↗
PubMed2002

Determinants of erythropoietin release in response to short-term hypobaric hypoxia.

We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P < 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes > or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.

Acute Disease↗
PubMed2002

Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1.

11beta-Hydroxylase (hCYP11B1) and aldosterone synthase (hCYP11B2) are closely related isozymes with distinct roles in cortisol and aldosterone production respectively. Aldosterone synthase catalyzes the final step in aldosterone biosynthesis and is expressed only in the zona glomerulosa of the normal adrenal. 11beta-Hydroxylase catalyzes the final reaction in the production of cortisol and is expressed at higher levels in the zona fasciculata. The mechanisms causing differential expression of these genes are not well defined. Herein, we demonstrate contrasting roles for the orphan receptor steroidogenic factor-1 (SF-1) in the regulation of human (h) CYP11B1 and hCYP11B2. Human NCI-H295R (H295R) or mouse Y-1 cells were transiently transfected with luciferase reporter constructs containing 5'-flanking regions of hCYP11B1, hCYP11B2, human 17alpha-hydroxylase (hCYP17), human cholesterol side-chain cleavage (hCYP11A1) or mouse (m) cyp11b2 (mcyp11b2). Co-transfection of vectors encoding SF-1 increased expression of hCYP11B1, hCYP11A1 and hCYP17 constructs, but inhibited hCYP11B2 reporter activity. Murine, bovine and human SF-1 were unable to increase transcription of hCYP11B2 in H295R cells. Both hCYP11B2 and mcyp11b2 promoter constructs were inhibited similarly by human SF-1. In mouse Y-1 cells, reporter expression of hCYP11B2 and mcyp11b2 was very low compared with hCYP11B1 constructs, suggesting that this adrenal cell model may not be appropriate for studies of CYP11B2. Electrophoretic mobility shift assay demonstrated that SF-1 interacted with an element from both hCYP11B1 and hCYP11B2. However, mutation of this element, termed Ad4, did not prevent agonist stimulation of hCYP11B2 by angiotensin II or forskolin but blocked activity of hCYP11B1. In some, but not all, reports of genetic linkage analysis, a naturally occurring single nucleotide polymorphism within the Ad4 element of hCYP11B2 (-344C/T) has been associated with cardiovascular disease. Herein, we have demonstrated that this polymorphism influenced binding of SF-1 in electrophoretic mobility shift assays, with the C allele binding SF-1 more strongly than the T allele. However, when hCYP11B2 constructs containing these alleles were transfected into H295R cells, there was no difference in agonist-stimulated expression or the response of either reporter construct to co-expression with human SF-1. Taken together, these data suggest that SF-1 and the Ad4 element are not major regulators of adrenal hCYP11B2 gene expression. Thus far, hCYP11B2 is the first steroid hydroxylase gene which is not positively regulated by SF-1.

Animals↗
PubMed2002

Peripheral but not central leptin prevents the immunosuppression associated with hypoleptinemia in rats.

Leptin is a peripheral immunoenhancing reagent that directly activates splenic lymphocytes in mice. We found that a 48 h fast in rats resulted in a decrease in serum leptin that was accompanied by a lower delayed-type hypersensitivity (DTH) response. Peripheral leptin replacement completely restored this response in fasted animals. We employed a recombinant adeno-associated virus (rAAV) system to deliver leptin gene directly into rat brain to assess the effect of sustained long-term central expression of leptin on immune responses. The rAAV-leptin rats had elevated central leptin over the 60 day duration of the experiment, whereas body fat and circulating leptin fell to near zero levels. The DTH response was significantly reduced by 10-20% in rats receiving rAAV-leptin compared with the control rats, and the difference was maintained for over 50 h. When the rats undergoing rAAV-leptin gene therapy were given either murine recombinant leptin or PBS s.c., rats receiving leptin had a 17% higher DTH response than rats receiving PBS. The isolated splenocytes from the former group also proliferated 34% more in vitro in response to the mitogen concanavalin A as compared with the latter group. These results suggest that peripheral leptin has a dominant role in maintaining T-cell-mediated immune responses in rats, and central leptin is unable to compensate for the immunosuppression associated with peripheral hypoleptinemia. Furthermore, preservation of normal cell-mediated immune responses does not require fat tissue as along as serum leptin levels are maintained.

Animals↗
PubMed2002

One-step, highly efficient site-directed mutagenesis by toxic protein selection.

A fast and efficient site-directed mutagenesis method has been developed, using the newly constructed plasmid pTPS19, which expresses the toxic CcdB protein originally encoded by the E. coli F plasmid. Once the target gene is cloned into pTPS19, desired mutations can be introduced with two primers. The first contains the desired mutation, and the second is designed to create a +1 frame shift in the ccdB gene to inactivate the CcdB protein. The mutants can be directly selected on LB plates containing IPTG, through which the toxic CcdB protein is induced, thereby eliminating cells carrying wild-type parental plasmids. Based on stringent selection through the toxic CcdB protein, mutagenesis efficiency of 90%-100% was reached even after one round of transformation.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Contribution of calcium and other dietary components to global variations in bone mineral density in young adults.

A research project on comparative international studies of osteoporosis using isotope techniques was organized by the International Atomic Energy Agency (IAEA) with the participation of 12 countries (Brazil, Canada, Chile, China, Croatia, Hungary, Philippines, Russia, Singapore, South Africa, Turkey, and the United Kingdom). Participating centers in 11 countries (all but the UK) made measurements and collected data on men and women aged 15 to 49 years. In addition to studies of bone mineral density (BMD) at the femoral neck and lumbar spine using DEXA, anthropometric, lifestyle, and nutritional data were also collected. The results of the nutritional studies are reviewed in this paper. Overall, about 8% of the observed variability in spine BMD could be attributed to nutritional factors in men and women; in men, no such relationship could be determined. No single nutritional component (not even calcium) stood out as being of particular importance across all participating centers.

Absorptiometry, Photon↗
PubMed2002

Diagnosis and treatment of epithelial salivary gland tumours in children and adolescents.

In a series of 2,871 epithelial salivary gland neoplasms managed in the Peking University School of Stomatology between 1974 and 1999, 86 arose in children <16 years of age (52 parotid, 12 submandibular gland, 2 sublingual gland, and 20 minor salivary gland). Considerable delay was encountered in diagnosis (benign 24 months and malignant 16 months). In this group of children, 46 tumours (53%) proved to be malignant, with an incidence in the parotid, submandibular, sublingual, and minor salivary glands of 31/52 (60%), 2/12, 0/2, and 13/20 (65%), respectively. Sixty-six of 86 neoplasms (77%) occurred in children between 10 and 16 years of age. Only six neoplasms were encountered in children of 5 years or younger, four of which were high-grade malignant tumours. Benign tumours were successfully treated by local excision with only one recurrence. Of 46 malignant neoplasms, 8 were treated palliatively; of the remainder 8 were lost to follow-up and 2 patients died of their disease.

Adenoma↗
PubMed2002

Non-linear transform-based robust adaptive latency change estimation of evoked potentials.

OBJECTIVES: To improve the latency change estimation of evoked potentials (EP) under the lower order alpha-stable noise conditions by proposing and analyzing a new adaptive EP latency change detection algorithm (referred to as the NLST). METHODS: The NLST algorithm is based on the fractional lower order moment and the nonlinear transform for the error function. The computer simulation and data analysis verify the robustness of the new algorithm. RESULTS: The theoretical analysis shows that the iteration equation of the NLST transforms the lower order alpha-stable process en (k) into a second order moment process by a nonlinear transform. The simulations and the data analysis showed the robustness of the NLST under the lower order alpha-stable noise conditions. CONCLUSIONS: The new algorithm is robust under the lower order alpha-stable noise conditions, and it also provides a better performance than the DLMS, DLMP and SDA algorithms without the need to estimate the alpha value of the EP signals and noises.

Algorithms↗
PubMed2001

Effect of acute binge cocaine on levels of extracellular dopamine in the caudate putamen and nucleus accumbens in male C57BL/6J and 129/J mice.

Levels of dopamine, both basal and after binge-pattern cocaine administration, were measured in the caudate putamen and nucleus accumbens of C57BL/6J and 129/J mice by in vivo microdialysis. Six-week old males were surgically implanted with a CMA guide cannula into the caudate putamen or nucleus accumbens. After 4 days recovery, dialysis probes were lowered into the caudate putamen or the nucleus accumbens and mice were placed in individual microdialysis chambers. The next morning experiments were carried out on freely moving animals. Experimental animals received 1-day binge cocaine administration (15 mg/kgx3, i.p. at hourly intervals) while control animals received saline in the same pattern. Dialysates were collected every 20 min and dopamine content was determined by HPLC with electrochemical detection. Basal levels of dopamine in the dialysate of the caudate putamen were 4.2+/-0.2 nM in C57BL/6J mice and 5.0+/-0.3 nM in 129/J mice. In the nucleus accumbens, basal levels of dopamine were 0.65+/-0.04 nM in the C57BL/6J mice and 0.75+/-0.03 nM in 129/J mice, with no significant differences between strains in either region. Binge cocaine administration significantly increased mean dopamine levels in the caudate putamen in the C57BL/6J mice (with a 3-h mean of 6.80 nM) and in the 129J mice (9.94 nM). In this region, 129/J mice had significantly higher levels of cocaine-induced dopamine than did C57BL/6J mice. In the nucleus accumbens, administration of cocaine also significantly increased dopamine levels in both strains (1.32 nM in C57BL/6J and 1.43 nM in 129/J), but with no difference between strains.

Animals↗
PubMed2001

Identification of two novel human dynein light chain genes, DNLC2A and DNLC2B, and their expression changes in hepatocellular carcinoma tissues from 68 Chinese patients.

Two full-length cDNAs, DNLC2A and DNLC2B, were cloned and characterized. Their open reading frames respectively encode 96 amino acids which are most closely homologous to roadblock/LC7, one member of an ancient dynein light chain protein family, conserved in nematode, fruit fly, mouse and rat. The DNLC2A was expressed in 12 of 16 human tissues examined, with especially strong expression in heart, liver and brain, whereas there was weak expression in lung, prostate, testis, small intestine and colon. The expression of DNLC2B was generally high compared with that of DNLC2A except in liver. Northern blotting and/or semi-quantitative RT-PCR analysis examined the expression changes of DNLC2A and DNLC2B in 68 hepatocellular carcinoma tissue samples. It was revealed that DNLC2A was up-regulated (45 out of the 68 cases) while DNLC2B was down-regulated (44 out of 68 cases), compared with their adjacent tumor-free liver tissues. Interestingly, among the total 68 liver cancer samples tested, DNLC2A was up-regulated while DNLC2B was down-regulated in 28 cases; DNLC2A was up-regulated while no obvious change was observed for DNLC2B in 10 cases; no obvious change was observed for DNLC2A while DNLC2B was down-regulated in 14 cases. Although the underlying mechanism is not clear to date, the apparent up-regulation of DNLC2A and down-regulation of DNLC2B suggest that these genes might be involved in tumor progression. On the other hand, the different expression changes of the two homologous genes indicate that hepatocellular carcinomas are caused by different pathological mechanisms. In addition, DNLC2A was assigned to human chromosome 20q12-q13.11 near the marker D20S106 by radiation hybrid mapping.

Adult↗
PubMed2001

[Expression of type I and type II 5alpha-reductase isoenzymes in prostate cancer tissues].

OBJECTIVE: To study the relative tissue distribution and expression pattern of type I and type type II 5alpha-reductase isozymes in prostate cancer tissues. METHODS: Immunohistochemistry and RT-PCR method were used to investigate qualitatively and semi-quantitatively the expression of type I and type II 5alpha-reductases in prostate tissues from 15 normal persons and 15 patients with prostate cancer. RESULTS: Two isozymes were detected in both normal and cancerous prostate tissues with the two methods. Both 5alpha-reductases were mainly localized in the cytoplasm, and higher degree of staining was observed in epithelial cells than in stroma. Significantly higher level of type I 5alpha-reduetase expression was observed in cancerous tissue than in normal tissue. The expression level of type I 5alpha-reduetase was positively correlated with the tumor stage and grade, and serum PSA concentration. The expression of type II 5alpha-reductase was very weak in prostate cancer tissue. CONCLUSION: The type I 5alpha-reductase, not type II, is involved in the pathogenesis of protate cancer. Selective type I 5alpha-reductase inhibitors or dual inhibitors of both type human 5alpha-reductase isoforms can be used in the treatment of prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

The neuroprotective actions of FK506 binding protein ligands: neuronal survival is triggered by de novo RNA synthesis, but is independent of inhibition of JNK and calcineurin.

The immunosuppressant FK506 displays substantial neuroprotective and neuroregenerative effects. It is not fully understood to which extent these effects depend on the inhibition of the calcineurin phosphatase (PP2B). The present study has re-addressed this issue using Lie120, a novel highly specific inhibitor of calcineurin, which does not block the enzymatic activity of FKBPs or cyclophilins, respectively. We have determined the effect of FK506 (10-500 nM), V-10,367 (a FK506 derivative which does not block calcineurin; 1-5 microM) and Lie120 (a novel specific inhibitor of calcineurin, 0.1-5 microM) on the cellular survival and the pro-degenerative JNK activity of PC12 and Neuro2A cells following application of 200 microM H(2)O(2). FK506 and V-10,367, but not Lie120, protected both cell lines against H(2)O(2)-mediated death, whereas an increase in JNK1 activity was blocked by FK506 and Lie120, but not by V-10,367. Co-incubation of FK506 and V-10,367 with the mRNA synthesis inhibitor actinomycin D abolished the protective effect of FK506 and V-10,367. This antagonization was effective when actinomycin D was applied 30 min or 1 h, but not 2 or 4 h, after H(2)O(2) suggesting that FKBP-ligands confer their neuroprotection by rapid de novo synthesis of (functionally) anti-apoptotic proteins. The search for the corresponding effector genes revealed that the expression of FKBP25, FKBP38 and FKBP52 (analysis by reverse transcription-polymerase chain reaction (RT-PCR) did not change following H(2)O(2) or FK506, and this was also true for the expression of apoptosis-related genes caspase 3, bax, bcl-2 and bcl-xL (analysis by Multiplex-PCR). Summarizing, neuronal protection by FKBP-ligands is not mediated either by calcineurin or by JNK1 in this experimental set-up, whereas the FK506 mediated inhibition of JNK1 is realized by the inhibition of calcineurin, an effective activator of JNK1 in neurons.

Animals↗
PubMed2001

Vaccination of mice with a cocktail DNA vaccine induces a Th1-type immune response and partial protection against Schistosoma japonicum infection.

Several defined vaccine candidate antigens of Schistosoma japonicum have shown promise in large animal vaccination experiments. However, vaccination of mice in the laboratory with either single recombinant antigens or DNA encoding forms of the individual antigens has so far failed to induce significant protection against S. japonicum cercarial challenge infection as judged by worm reduction, although specific antibodies were generated. This is in contrast to the results achieved using radiation-attenuated vaccines which are highly protective. Even in large animal vaccination experiments, the protection levels obtained with single defined antigens were far below those achieved using the attenuated vaccines. One possible interpretation is that the immune responses induced by single antigen vaccination may not be strong enough to combat the challenging infection. We, therefore, carried out mouse vaccination experiments using a cocktail DNA vaccine comprising four DNA plasmids encoding four different S. japonicum antigens, Sj62, Sj28, Sj23 and Sj14-3-3, respectively. We, also investigated whether co-injection of the mouse IL-12 encoding plasmid with the cocktail DNA vaccine was able to enhance the Th1 responses and hence the protective immunity. Three intramuscular injections of the cocktail DNA vaccine induced a significant Th1-type cellular response with high level of IFN-gamma production by splenocytes upon in vitro stimulation with recombinant antigens. Importantly, significant IgG antibody responses were also induced against crude worm antigens. In two out of three experiments, significant resistance (34-37 and 44-45%, respectively) was demonstrated while another experiment did not show any protection against S. japonicum cercarial challenge infection. Co-injection of the IL-12 encoding DNA did not further enhance these responses, nor the level of resistance, compared with the cocktail DNA alone.

Animals↗