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Biomedical subjects

J J Zhang

Publications and source records attributed to J J Zhang.

At least 19 recordsLinked to original sources
PubMed2001

Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma.

In response to IFN-gamma, the latent cytoplasmic Stat1 (signal transducer and activator of transcription) proteins translocate into the nucleus and activate transcription. We showed previously that Stat1 recruits a group of nuclear proteins, among them MCM5 (minichromosome maintenance) and MCM3, for transcription activation. MCM5 directly interacts with the transcription activation domain (TAD) of Stat1 and enhances Stat1-mediated transcription activation. In this report, we identified two specific residues (R732, K734) in MCM5 that are required for the direct interaction between Stat1 and MCM5 both in vitro and in vivo. MCM5 containing mutations of R732/K734 did not enhance Stat1-mediated transcription activation in response to IFN-gamma. In addition, it also failed to form complexes with other MCM proteins in vivo, suggesting that these two residues may be important for an interaction domain in MCM5. Furthermore, MCM5 bearing mutations in its ATPase and helicase domains did not enhance Stat1 activity. In vitro binding assays indicate that MCM3 does not interact directly with Stat1, suggesting that the presence of MCM3 in the group of Stat1TAD-interacting proteins is due to the association of MCM3 with MCM5. Finally, gel filtration analyses of nuclear extracts from INF-gamma-treated cells demonstrate that there is a MCM5/3 subcomplex coeluting with Stat1. Together, these results strongly suggest that Stat1 recruits a MCM5/3 subcomplex through direct interaction with MCM5 in the process of IFN-gamma-induced gene activation.

Binding Sites↗
PubMed2001

Synthesis, crystal structure and properties of a new dinuclear manganese(III) complex: a mimic for catalase.

A new dinuclear manganese (III) complex [(ac)Mn(bbml)(2)Mn(ac)] x (BF(4))(2) x 3.5H(2)O (Hbbml=[bis(2-benzimidazolylmethyl)amino]ethanol, Hac=acetic acid) was synthesized and characterized by several physical methods. X-ray structure analysis shows that the complex has a dimeric unit and the two Mn(III) atoms are bridged by the oxygen atoms of the two ligands, forming a bis (micro-alkoxo)dimanganese core. The Mn-Mn distance is 3.2103 A. Electrospray mass spectrometry (ES-MS) experiment shows that the complex cation may easily have lost one or two ac(-) and leave unoccupied coordination site which would favor the coordination and activation of hydrogen peroxide. Furthermore, its catalytic activity for the disproportionation of hydrogen peroxide and the effect of added heterocyclic base were also investigated. The complex has some similarities to manganese catalase in structure and activity.

Binding Sites↗
PubMed2001

Human adrenomedullin gene delivery protects against cardiovascular remodeling and renal injury.

We investigated the potential roles of adrenomedullin (AM) in cardiovascular and renal function by somatic gene delivery. We showed that a single intravenous injection of the human AM gene under the control of cytomegalovirus promoter/enhancer induces a prolonged delay in blood pressure rise for several weeks in spontaneously hypertensive rats, Dahl salt-sensitive, DOCA-salt, and two-kidney one-clip hypertensive rats as compared to their respective controls injected with a reporter gene. Expression of the human AM transcript was identified in the heart, kidney, lung, liver and aorta of the rat after adenovirus-mediated AM gene delivery by RT-PCR followed by Southern blot analysis. Immunoreactive human AM levels were measured in rat plasma and urine following AM gene delivery. AM gene delivery induced significant reduction of left ventricular mass in these hypertensive animal models. It also reduces urinary protein excretion and increases glomerular filtration rate, renal blood flow and urinary cAMP levels. AM gene transfer attenuated cardiomyocyte diameter and interstitial fibrosis in the heart, and reduced glomerular sclerosis, tubular disruption, protein cast accumulation and renal cell proliferation in the kidney. In the rat model with myocardial ischemia/reperfusion injury, AM gene delivery significantly reduced myocardial infarction, apoptosis, and superoxide production. Furthermore, local AM gene delivery significantly inhibited arterial thickening, promoted re-endothelialization and increased vascular cGMP levels in rat artery after balloon angioplasty. Collectively, these results indicate that human AM gene delivery attenuates hypertension, myocardial infarction, renal injury and cardiovascular remodeling in animal models via cAMP and cGMP signaling pathways. These findings provide new insights into the role of AM in cardiovascular and renal function.

Adenoviridae↗
PubMed2001

Uterine transplantation, abdominal trachelectomy, and other reproductive options for cancer patients.

More and more women with cancer issues are now raising fertility concerns as survival improves and childbearing is delayed. Pregnancy is no longer contraindicated in cancer patients including breast and endometrial cancer survivors. In fact, survival in patients treated for breast cancer who subsequently become pregnant is actually higher than that in patients who do not become pregnant. "Therapeutic" abortions are no longer recommended. Assisted reproductive technology (ART) have been associated with ovarian neoplasms, but the association is probably not causal. Neither ART nor hormone replacement is contraindicated in cancer patients. Our institution is very supportive of patients and the difficult decisions cancer survivors face. Using a program of counseling and close collaboration between oncologists, perinatologists, and reproductive endocrinologists, informed patients are offered every possible option, including ART and uterine transplantation, to achieve their family planning objectives.

Breast Neoplasms↗
PubMed2001

[Factors allowing continuous working of female nurses in the People's Republic of China--survey of 15 hospitals in 5 areas].

PURPOSE: Few investigations have been conducted on working, childcare and home education among female nurses (nurses) in the People's Republic of China (P.R. of China). The purpose of this study was to clarify the factors allowing continued working of female nurses. METHODS: The subjects were nurses from 15 hospitals in 3 provinces and 2 autonomous areas. They were surveyed by questionnaire regarding their childcare and home education. In was distributed by the Ministry of Health in the P.R. of China and the data were collected between February and April in 1996. RESULTS: A total of 4,284 (80.0%) questionnaires were collected. 1. About 60% of the nurses began working when they were 15 to 19 years old. The average length of service was 13.9 years. 2. Their professional position correlated directly with their years of service. 3. 4.3% of them had not continued working. 4. The nurses entrust their children to day-care institutions (61.2%) or grandparents (22.3%) during the daytime, and to the father (66.3%) or the grandparents (19.5%) during the night. 5. 17.6% of them have experienced being away from home for more than one month due to their job. 6. 66.8% of the nurses have experienced more than one month official trip, and had children under 14 years old at the time. They entrusted their children to day-care institutions (34.1%), to the father (29.2%) and grandparents (25.3%) during the official trip. CONCLUSIONS: In summary, most nurses are employed when they are young and go on working as nurses. It is possible for them to continue their work after marriage, childbirth, and while they are bringing up their children. The high rate of working woman, sufficient nursery schools and family cooperation in housework can be pointed out as main factors that enable them to continue their work.

Adolescent↗
PubMed2001

[Childcare and home education in families of female nurses in the People's Republic of China--survey of 15 hospitals in 5 areas].

PURPOSE: The purpose of this study was to investigate the actual conditions of childcare and home education among families of female nurses in the P. R. of China. METHODS: The subjects were nurses from 15 hospitals in 3 provinces and 2 autonomous areas. They were surveyed by questionnaire regarding their childcare and home education. It was distributed by the Ministry of Health in the P. R. of China and data were collected between February and April in 1996. RESULTS: A total of 4284 (80.0%) questionnaires were collected. 1. The age of the subjects was between 18 and 62 years old with a mean of 32.9 +/- 9.0 (SD) years 71.4% of them had husbands, whose ages were between 23 and 71 years old, the mean age being 38.3 +/- 8.4 (SD) years. The family types were 63.2% nuclear family and 33.7% extended family, with 3.1% being single. 65.1% of the subjects had children, whose mean number was 1.1 +/- 0.4 (SD). Firstborn children were 49.9% girls and 50.1% boys. 2. The most popular method of infant nutrition was breast-feeding, utilized by 60.1%. The highest rate (67.8%) was in the age group of 25 to 29 years old (P < 0.01). 3. The practice of "swaddling" (wrapping the child so as not to allow movement) was more common in the over 40 year old age group than the under 40 year old group (P < 0.01). Swaddling-practice showed significant differences by area. 4. The rates for children who helped with housework were 50.3% for girls and 46.7% for boys. 5. A number of children between 7 and 18 years old were studying English privately. 6. The greatest expectation of the subjects, for their children aged between 7 and 18 years old, was to study. CONCLUSIONS: 1. Infant nutrition showed significant differences between generations, and swaddling-practice differed with the generation and the area. 2. Although girls help their parents more than boys in Japan, boys and girls equally helped their parents in the P. R. of China. 3. Concerning the topics of private learning and parents expectations, the results were similar to those in Japan.

Adolescent↗
PubMed2000

Human adrenomedullin gene delivery protects against cardiac hypertrophy, fibrosis, and renal damage in hypertensive dahl salt-sensitive rats.

Adrenomedullin (AM) is a potent vasodilator expressed in tissues relevant to cardiac and renal functions. Our previous study showed that delivery of the human AM gene in the form of naked DNA caused a prolonged reduction of blood pressure in genetically hypertensive rats. In this study, we evaluated potential protective effects of adenovirus-mediated AM gene delivery on salt-induced cardiorenal lesions in hypertensive Dahl saltsensitive (DSS) rats. Adenovirus carrying the human AM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM) was generated by homologous recombination of E. coli. Expression of recombinant human AM was detected by a radioimmunoassay in the medium of human embryonic kidney 293 cells transfected with Ad.CMV-hAM. A single intravenous injection of Ad.CMV-hAM caused a significant reduction of systolic blood pressure for 4 weeks in DSS rats compared with control rats with or without injection of adenovirus carrying the green fluorescent protein gene. AM gene delivery significantly reduced left ventricular mass and urinary protein, increased cAMP levels, and enhanced renal function as evidenced by increases in glomerular filtration rate and renal blood flow. Morphological investigations showed that AM gene transfer reduced cardiomyocyte diameter and interstitial fibrosis in the heart as well as glomerular sclerosis, tubular disruption, and protein cast accumulation in the kidney. Expression of human AM mRNA was identified in rat heart, kidney, lung, liver, and aorta, and immunoreactive human AM levels were measured in rat plasma and urine. These results indicate that human AM gene delivery protects against salt-induced hypertension and cardiac and renal lesions in DSS rats via activation of cAMP as a second messenger. These findings provide new insights into the role of AM in salt-induced hypertension and may have implications in therapeutic applications to salt-related cardiovascular and renal diseases.

Adenoviridae↗
PubMed2000

Determination of clopidol residues in chicken tissues by high-performance liquid chromatography-mass spectrometry.

A high-performance liquid chromatographic-mass spectrometric (HPLC-MS) method has been developed for determination of clopidol residues in chicken tissues. Samples are extracted with acetonitrile. The extracts are cleaned up on an alumina column followed by an anion-exchange column. The clopidol is separated on a column (150 cmx4.6 mm) of Intertsil by using acetonitrile-water (20:80) as mobile phase. The clopidol was qualitatively identified by molecule mass and determined quantitatively by selected ion monitoring mode at 190 m/z. The recoveries with RSDs ranged from 91.6+/-10.1 to 97.3+/-5.7 at 0.010 to 10.0 mg/kg by spiking three matrices (chicken muscle, liver, and kidney). The limit of detection was 0.005 mg/kg, and the limit of quantification was 0.010 mg/kg.

Chromatography, High Pressure Liquid↗
PubMed2000

Interlaboratory study of identification and quantitation of multiresidue pyrethroids in agricultural products by gas chromatography-mass spectrometry.

This paper deals with the different GC-MS analytical conditions adopted by four laboratories in an attempt to confirm the accuracy of the GC-electron-capture detection (ECD) analytical results during the international collaborative study for the establishment of the AOAC Official Method 998. 01. What is especially noted is that two laboratories have conducted comparative analysis of the respective 12 blind samples with both methods of GC-ECD and GC-MS, and the analytical results of the two methods turn out to be basically identical. This fully demonstrates that GC-MS is not only an effective confirmation tool in the analysis of the pyrethroid residues but also of sufficient sensitivity regarding the maximum residue limit of determination prescribed by FAO/WHO. Moreover, its selectivity is better than GC-ECD.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

Cambio en las escuelas: Mexican-American parent attitudes toward school health education.

The purpose of this study was to determine the attitudes of Mexican-American (MA) parents of children toward school health education programs in South Texas. The Parent Attitude Scale (PAS) was developed and validated by American Cancer Society (ACS) staff and volunteer health educators. The validated survey was used to question randomly selected parents in the McAllen, Texas, school district regarding their attitudes toward school health education. Of 253 parents contacted, 235 (92.9%) parents were interviewed. Mann-Whitney U-Tests indicated that Mexican-American (MA) parents consider school health education to be more important than non-Mexican-American parents do. MA parents, overall, felt that it was more important that their child has good health habits and more important that their child's teacher provide support to them by teaching good health habits than non-MA parents. MA parents also felt that health was more important relative to other subjects at school than non-MA parents. The data indicate strong support for school health education efforts among MA parents in southern Texas. Such support may grow stronger with appropriate parent-recruitment efforts, including those by the ACS. Mexican-American parents may also represent an untapped resource for social and political support for school health programming.

Adolescent↗
PubMed2000

Kallikrein gene delivery attenuates myocardial infarction and apoptosis after myocardial ischemia and reperfusion.

The tissue kallikrein-kinin system is present in the heart, and kinin has been shown to have cardioprotective effects. In this study, we investigated the potential role of tissue kallikrein in myocardial ischemia/reperfusion injury through adenovirus-mediated human kallikrein gene delivery. One week after gene delivery, the rats were subjected to a 30-minute coronary occlusion followed by a 2-hour reperfusion. Kallikrein gene delivery caused significant decreases in the ratio of infarct size to ischemic area at risk (from 69.6% to 44.5%, n=10 and 8, P<0.01) and in the incidence of ventricular fibrillation (from 64.3% to 16.7%, n=14 and 24, P<0.01) compared with the group injected with control adenovirus. Kallikrein gene delivery also attenuated programmed cell death in the ischemic area compared with the control area as assessed with the terminal deoxynucleotidyl transferase-mediated nick end labeling assay (n=6, P<0.01). Icatibant, a specific bradykinin B(2) receptor antagonist, abolished these kallikrein-mediated beneficial effects. The expression of human tissue kallikrein mRNA was identified in rat heart, kidney, lung, liver, and adrenal gland. After kallikrein gene delivery, cardiac kinin and cGMP levels were significantly elevated compared with the control (29.6+/-12.7 versus 6.1+/-2.1 pg/mg protein, n=7, P<0.01; 1.30+/-0.06 versus 0.86+/-0.09 pmol/mg protein, n=5, P<0.05). These results indicate that kallikrein gene delivery protects against myocardial infarction, ventricular arrhythmias, and apoptosis in ischemia/reperfusion injury via kinin-cGMP signal pathway. The successful application of this technology may have potential therapeutic value in the treatment of coronary artery diseases.

Animals↗
PubMed2000

Facilitatory effect of ritanserin is mediated by dopamine D(1) receptors on olfactory learning in young rats.

The olfactory bulb is critically involved in early olfactory learning. In this study, we examined the effect of intrabulbar infusion of ritanserin, a 5-hydroxytryptamine(2) (5-HT(2)) receptor antagonist on a one-trial aversive olfactory learning in young rats. Ritanserin, a 5-HT(2) receptor antagonist, was continuously infused into the olfactory bulb of postnatal day-11 (PND 11) rat pups during a 30-min training session of pairing citral odor and foot shock. On the following day, the time spent in the part of the apparatus where the odor was present was measured as an index of odor aversion. Consistent with a previous study on olfactory preference learning, 1 nM ritanserin, but not 10 nM, blocked the olfactory aversive learning. We further examined the ability of 10 nM ritanserin to induce olfactory learning in the absence of the unconditioned stimulus foot shock. Pups that received intrabulbar infusion of 10 nM ritanserin in the presence of citral odor developed an aversion to the odor without foot shock. Since ritanserin has been shown to have an affinity for dopamine receptors, we examined the effect of dopamine antagonists on the ritanserin-induced aversive olfactory learning. Co-infusion of the dopamine D(1) receptor antagonist (+/-)-SKF-83566 with ritanserin dose-dependently prevented induced learning. In contrast, the D(2) receptor antagonist spiperone was without effect. These results extend the previous finding on the role of bulbar 5-HT(2) receptors in early olfactory learning and suggest that high concentration of ritanserin facilitates aversive olfactory learning through D(1) receptors in the olfactory bulb.

Animals↗
PubMed2000

[Pharmacokinetics of topically applied in-situ-forming gels of fluconazole in rabbit eyes].

AIM: To study the pharmcokinetics of fluconazole (FCZ) in the aqueous humors and tears of New Zealand white rabbits following topically applied in-situ-forming gels of 0.5% FCZ (ISG-FCZ) and 0.5% FCZ eye drops to rabbit eyes. METHODS: The rabbit tears and aqueous humors were obtained and quantified at different times after topically applying single dose of ISG-FCZ and FCZ eye drops to the rabbit eyes. The drug levels were assayed by megabore capillary gas-liquid chromatography with nitrogen-selective detector. The pharmacokinetic parameters were calculated with nonlinear least square method with computer. RESULTS: FCZ concentrations in rabbit tears within 180 min after applying ISG-FCZ were found to be significantly higher compared with those of FCZ eye drops. The FCZ levels in the aqueous at 10, 30, 60, 90 and 120 min after applying ISG-FCZ are significantly higher compared with FCZ eye drops. The time for arriving peak concentration (Tmax) and the area under concentration (AUC)-time curve as well as the half-life (T1/2) of FCZ in rabbit aqueous humors were markedly higher after application of ISG-FCZ. The peak levels in the aqueous humors showed no difference between the two groups. CONCLUSION: The ISG-FCZ, which upon exposure to physiological conditions will shift the gel phase, can significantly extend FCZ release and increase the precorneal residence time of the drug, thus enhance ocular bioavailability compared with FCZ eye drops.

Acrylic Resins↗
PubMed1999

Evidence for novel caffeine and Ca2+ binding sites on the lobster skeletal ryanodine receptor.

1. The effects of Ca2+, ATP and caffeine on the gating of lobster skeletal muscle ryanodine receptors (RyR) was investigated after reconstitution of the channels into planar phospholipid bilayers and by using [3H]-ryanodine binding studies. 2. The single channel studies reveal that the EC50 (60 microM) for activation of the lobster skeletal RyR by Ca2+ as the sole ligand is higher than for any other isoform of RyR studied. 3. Inactivation of the channel by Ca2+ (EC50 = 1 mM) occurs at concentrations slightly higher than those required to inactivate mammalian skeletal RyR (RyR1) but lower than those required to inactivate mammalian cardiac RyR (RyR2). 4. Lifetime analysis demonstrates that cytosolic Ca2+, as the sole activating ligand, cannot fully open the lobster skeletal RyR (maximum Po approximately 0.2). The mechanism for the increase in open probability (Po) is an increase in both the frequency and the duration of the open events. 5. ATP is a very effective activator of the lobster RyR and can almost fully open the channel in the presence of activating cytosolic [Ca2+]. In the presence of 700 microM Ca2+, 1 mM ATP increased Po to approximately 0.8. 6. Caffeine, often used as a tool to identify the presence of RyR channels, is relatively ineffective and cannot increase Po above the level that can be attained with Ca2+ alone. 7. The results reveal that caffeine increases Po by a different mechanism to that of cytosolic Ca2+ demonstrating that the mechanism for channel activation by caffeine is not 'sensitization' to cytosolic Ca2+. 8. By studying the mechanisms involved in the activation of the lobster RyR we have demonstrated that the channel responds in a unique manner to Ca2+ and to caffeine. The results strongly indicate that these ligand binding sites on the channel are different to those on mammalian isoforms of RyR.

Adenosine Triphosphate↗
PubMed1999

Targeting tumors with iodine-123 labeled deoxyuridine: distribution and DNA binding.

5-lodo-2'-deoxyuridine (IUdR), a thymidine analog, is transported through cell membrane and is incorporated into newly synthesized DNA during the S phase of mitotic cells. In rapidly growing brain tumors such as glioma, radioiodinated IUdR may be an efficient diagnostic as well as therapeutic agent and may provide a means to determine the proliferative activity of the tumor. IUdR was labeled with 123I (t1/2 = 13.3 h, gamma = 159 KeV, 83%) and injected i.v. into nude mice bearing human colorectal carcinoma LS174T. At 3 and 20 h postinjection, tumor uptake was 2.6 +/- 0.9% and 0.5 +/- 0.2%, respectively, of the injected dose per gram of tissue. Radioactivity in other tissues also declined as a function of time, but much more rapidly, yielding tumor-to-blood ratios of 16.4 +/- 2.2 and tumor-to-muscle ratios of 22.2 +/- 7.7 at 20 h postinjection. Of the radioactivity in the tumor, 12.6 +/- 0.9% was bound to DNA at 3 h and 25.2 +/- 2% at 20 h postinjection. A high (7 +/- 1.1% i.d.) uptake in thyroid at 3 h postinjection indicated dehalogenation in vivo.

Animals↗
PubMed1999

The linker domain of Stat1 is required for gamma interferon-driven transcription.

Upon binding of gamma interferon (IFN-gamma) to its receptor, the latent transcription factor Stat1 becomes phosphorylated, dimerizes, and enters the nucleus to activate transcription. In response to IFN-alpha, Stat1 binds to Stat2 in a heterodimer that recruits p48, an IRF family member, to activate transcription. A number of functional domains of the STATs, including a C-terminal transactivation domain, a dimerization domain, and an SH2 domain, are known. However, the highly conserved residues between the DNA binding and SH2 domains (463 to 566), recently christened the linker domain on the basis of crystallographic studies, have remained without a known function. In the present study, we report that KE544-545AA point mutants in Stat1 abolish transcriptional responses to IFN-gamma but not to IFN-alpha. We further show that this mutant Stat1 undergoes normal phosphorylation, nuclear translocation, and DNA binding. Taken together with recent structural evidence, these results suggest that the linker domain acts as a critical contact point during the construction of a Stat1-driven transcriptional complex.

Amino Acid Sequence↗
PubMed1999

Adenovirus-mediated kallikrein gene delivery reduces aortic thickening and stroke-induced death rate in Dahl salt-sensitive rats.

BACKGROUND AND PURPOSE: Kallikrein gene delivery has been shown to attenuate hypertension, cardiac hypertrophy, and renal injury in hypertensive animal models. The aim of this study was to investigate the potential protective effects of kallikrein gene delivery in salt-induced stroke and cerebrovascular disorders. METHODS: Adenovirus harboring the human tissue kallikrein gene (AdCMV-cHK) was delivered intravenously into Dahl salt-sensitive (DS) rats after 4 weeks of high salt loading, and blood pressure was monitored weekly for 9 weeks. RESULTS: A single injection of AdCMV-cHK caused a significant reduction of systolic blood pressure compared with that in control rats, with or without an injection of adenovirus carrying the LacZ (control) gene (AdCMV-LacZ). A maximal blood pressure reduction of 21 mm Hg was observed 2 weeks after gene delivery. The stroke mortality rate of DS rats (AdCMV-LacZ group versus the AdCMV-cHK group) was significantly decreased: 38% versus 9% at 3 weeks and 54% versus 27% at 5 weeks after gene delivery. Kallikrein gene delivery significantly attenuated salt-induced aortic hypertrophy, as evidenced by reduced thickness of the aortic wall. Recombinant human tissue kallikrein was detected in rat serum and urine after gene transfer. Kinin-releasing activities in the brain as well as urinary kinin and cGMP levels were significantly increased in rats receiving the kallikrein gene. CONCLUSIONS: This is the first study to demonstrate the protective effect of kallikrein gene delivery in reducing salt-induced stroke mortality and vascular dysfunction.

Adenoviridae↗