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Biomedical subjects

Z Sun

Publications and source records attributed to Z Sun.

At least 145 records · Page 8Linked to original sources
PubMed1999

Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide.

Pyrazinamide (PZA) is an important antituberculosis drug. Unlike most antibacterial agents, PZA, despite its remarkable in vivo activity, has no activity against Mycobacterium tuberculosis in vitro except at an acidic pH. M. tuberculosis is uniquely susceptible to PZA, but other mycobacteria as well as nonmycobacteria are intrinsically resistant. The role of acidic pH in PZA action and the basis for the unique PZA susceptibility of M. tuberculosis are unknown. We found that in M. tuberculosis, acidic pH enhanced the intracellular accumulation of pyrazinoic acid (POA), the active derivative of PZA, after conversion of PZA by pyrazinamidase. In contrast, at neutral or alkaline pH, POA was mainly found outside M. tuberculosis cells. PZA-resistant M. tuberculosis complex organisms did not convert PZA into POA. Unlike M. tuberculosis, intrinsically PZA-resistant M. smegmatis converted PZA into POA, but it did not accumulate POA even at an acidic pH, due to a very active POA efflux mechanism. We propose that a deficient POA efflux mechanism underlies the unique susceptibility of M. tuberculosis to PZA and that the natural PZA resistance of M. smegmatis is due to a highly active efflux pump. These findings may have implications with regard to the design of new antimycobacterial drugs.

Amidohydrolases↗
PubMed1999

Dimeric RFX proteins contribute to the activity and lineage specificity of the interleukin-5 receptor alpha promoter through activation and repression domains.

Interleukin-5 (IL-5) plays a central role in the differentiation, proliferation, and functional activation of eosinophils. The specific action of IL-5 on eosinophils and hematopoietically related basophils is regulated by the restricted expression of IL-5 receptor alpha (IL-5Ralpha), a subunit of high-affinity IL-5R, on these cells. We have previously identified an enhancer-like cis element in the IL-5Ralpha promoter that is important for both full promoter function and lineage-specific activity. Here, we demonstrate by yeast one-hybrid screening that RFX2 protein specifically binds to this cis element. RFX2 belongs to the RFX DNA-binding protein family, the biological role of which remains obscure. Using an electrophoretic mobility shift assay, we further show that RFX1, RFX2, and RFX3 homodimers and heterodimers specifically bind to the cis element of the IL-5Ralpha promoter. The mRNA expression of RFX1, RFX2, and RFX3 was detected ubiquitously, but in transient-transfection assays, multimerized RFX binding sites in front of a basal promoter efficiently functioned in a tissue- and lineage-specific manner. To further investigate RFX functions on transcription, full-length and deletion mutants of RFX1 were targeted to DNA through fusion to the GAL4 DNA binding domain. Tissue- and lineage-specific transcriptional activation with the full-length RFX1 fusion plasmid on a reporter controlled by GAL4 binding sites was observed. Distinct activation and repression domains within the RFX1 protein were further mapped. Our findings suggest that RFX proteins are transcription factors that contribute to the activity and lineage specificity of the IL-5Ralpha promoter by directly binding to a target cis element and cooperating with other tissue- and lineage-specific cofactors.

Animals↗
PubMed1999

AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells.

Mechanical induction of growth factor synthesis may mediate adaptive responses of smooth muscle cells (SMC) to increases in physical load. We previously demonstrated that cyclic mechanical stretch induces expression of the SMC, fibroblast, and epithelial cell mitogen heparin-binding epidermal growth factor-like growth factor (HB-EGF) in bladder SMC, an observation that suggests that this growth factor may be involved in compensatory bladder hypertrophy. In the present study we provide evidence that the activator protein-1 (AP-1) transcription factor plays a critical role in this mechanoinduction process. Rat bladder SMC were transiently transfected with a series of 5' deletion mutants of a promoter-reporter construct containing 1. 7 kb of the mouse HB-EGF promoter that was previously shown to be stretch responsive. The stretch-mediated increase in promoter activity was completely ablated with deletion of nucleotide positions -1301 to -881. Binding of AP-1, as evaluated by electrophoretic mobility shift assay, to a synthetic oligonucleotide containing an AP-1 binding site increased in response to stretch, and binding was inhibited by excess unlabeled DNA corresponding to nucleotides -993 to -973 from the HB-EGF promoter, a region that contains a previously recognized composite AP-1/Ets site. Stretch-induced promoter activity was significantly inhibited by site-directed mutagenesis of the AP-1 or Ets components of this site. Consistent with the promoter and gel-shift studies, curcumin, an inhibitor of AP-1 activation, suppressed the HB-EGF mRNA induction after stretch. Stretch also specifically increased mRNA levels for matrix metalloproteinase (MMP)-1, the promoter of which contains a functional AP-1 element, but not for MMP-2, the promoter of which does not contain an AP-1 element. The stretch response of the MMP-1 gene was also completely inhibited by curcumin. Collectively, these findings indicate that AP-1-mediated transcription plays an important role in the regulation of gene expression in bladder muscle in response to mechanical forces.

Animals↗
PubMed1999

Treatment with lexipafant ameliorates the severity of pancreatic microvascular endothelial barrier dysfunction in rats with acute hemorrhagic pancreatitis.

CONCLUSION: Treatment with lexipafant reduced the severity of pancreatitis-associated endothelial barrier compromise, also associated with a decrease in systemic concentrations of interleukin (IL) 1. Thus, the present findings imply that platelet-activating factor (PAF) may play an important role in the pathogenesis of pancreatic endothelial dysfunction by signaling and triggering the production and release of certain cytokines. BACKGROUND: Pancreatic capillary endothelial barrier dysfunction is an initial and characteristic feature of acute pancreatic injury and pancreatitis. PAF, a proinflammatory mediator and an intercellular signaling substance, has been considered to be involved in the inflammatory reaction and the systemic endothelial dysfunction of acute pancreatitis. METHODS: The development of pancreatic capillary endothelial barrier dysfunction was monitored by tissue edema and exudation of plasma albumin into the interstitium, 3 and 12 h after induction of acute pancreatitis by intraductal infusion of 5% sodium taurodeoxycholate in rats. Pancreatic leukocyte recruitment was reflected by measuring myeloperoxidase activity. Serum levels of IL-1 beta and IL-6 were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Pretreatment with lexipafant, a potent PAF receptor antagonist, significantly reduced the pancreatitis-induced increase in pancreatic endothelial barrier dysfunction, pancreatic leukocyte recruitment and serum levels of IL-1 beta, although a difference persisted between animals with sham operation and pancreatitis.

Acute Disease↗
PubMed1999

Human apolipoprotein A-I kinetics within triglyceride-rich lipoproteins and high density lipoproteins.

Stable isotope methodology was used to determine the kinetic behavior of apolipoprotein (apo) A-I within the triglyceride-rich lipoprotein (TRL) fraction and to compare TRL apoA-I kinetics with that of apoA-I in high density lipoprotein (HDL) and TRL apoB-48. Eight subjects (5 males and 3 females) over the age of 40 were placed on a baseline average American diet and after 6 weeks received a primed-constant infusion of [5,5,5-(2)H(3)]-l-leucine for 15 h while consuming small hourly meals of identical composition. HDL and TRL apoA-I and TRL apoB-48 tracer/tracee enrichment curves were obtained by gas chromatography;-mass spectrometry. Data were fitted to a compartmental model to determine the fractional secretion rates of apoA-I and apoB-48 within each lipoprotein fraction. Mean plasma apoA-I levels in TRL and HDL fractions were 0. 204 +/- 0.057 and 134 +/- 15 mg/dl, respectively. The mean fractional catabolic rate (FCR) of TRL apoA-I was 0.250 +/- 0.069 and HDL apoA-I was 0.239 +/- 0.054 pools/day, with mean estimated residence times (RT) of 4.27 and 4.37 days, respectively. The mean TRL apoB-48 FCR was 5.2 +/- 2.0 pools/day and the estimated mean RT was 5.1 +/- 1.8 h. Our results indicate that apoA-I is catabolized at a slower rate than apoB-48 within TRL, and that apoA-I within TRL and HDL fractions are catabolized at similar rates.

Adult↗
PubMed1999

Increased tail artery vascular responsiveness to angiotensin II in cold-treated rats.

Chronic exposure of rats to cold for 1-3 weeks results in a mild form of hypertension. The renin-angiotensin system (RAS) has been implicated in this model of cold-induced hypertension. Previously we have characterized the vascular responsiveness in cold-acclimated animals, using aortic tissue, and recent studies have focused on the thermoregulatory responses of angiotensin II (AngII), utilizing the tail artery of the rat. Therefore in the current study we evaluated the vascular responsiveness of cold-treated rats to AngII in both aorta and tail artery at 2 and 4 weeks of cold exposure (5+/-2 degrees C). Systolic blood pressures were significantly elevated in cold-treated animals compared with control animals at both 2 and 4 weeks of cold exposure. At both of these time points body weights were reduced and ventricular weights were increased in cold-treated animals. After 2 weeks of cold exposure the vascular responsiveness of the aorta to AngII was significantly lower than that of controls. This vascular responsiveness to AngII was elevated and returned to control levels after 5 weeks of cold exposure. However, this pattern was not observed in the tail artery. The vascular responsiveness of tail artery rings from cold-treated rats to AngII was significantly greater than that of control animals during both 2 and 5 weeks of exposure to cold. The vascular contractile responses of both the aorta and tail artery to KCI in the cold-treated animals was not different from that of the control animals maintained at ambient room temperature, suggesting that the vascular smooth muscle contractile components were not altered by the cold exposure. Thus, the in vitro vascular reactivity to the receptor-mediated vasoconstrictor AngII was decreased in the sparsely innervated aorta and increased in the more densely innervated tail artery of the cold-treated animals when compared with controls. These results suggest that the increased responsiveness of AngII on the smooth muscle of the tail artery may play a role in adaptation to the cold and the maintenance of cold-induced hypertension.

Angiotensin II↗
PubMed1999

[The effect of hydroxycamptothecin and topotecan to SKOV3 and CAOV3 in vitro].

OBJECTIVE: To examine the effect of hydroxycamptothecin (HCPT) and topotecan, two kinds of derivative of camptothecin, to two ovarian cancer cell lines, SKOV3 and CAOV3. METHODS: Methyl thiazolyl tetrazolium (MTT) was used to establish the dose-effect curves. The ability of these two drugs to induce apoptosis of the two cell lines was determined by the method of terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA Ladder. The morphological changes of the cells were observed by electronic microscope. Expression of c-myc, bcl-2, and fas was estimated by the immunohistochemical staining. RESULTS: The inhibition of HCPT and topotecan to the growth of SKOV3 and CAOV3 was dose-dependent. 50% inhibiting concentration (IC50) of HCPT and topotecan to SKOV3 was 72 ng/ml and 160 ng/ml, respectively; IC10 of HCPT and topotecan to CAOV3 was 141 ng/ml and 12 ng/ml, respectively. The inhibition of HCPT and topotecan to clone forming rate of two cell lines was significant. The growing curves of SKOV3 and CAOV3 treated by HCPT and topotecan were significantly lower than controls. HCPT and topotecan of 5 ng/ml can elongate the double time of SKOV3 for 49.00 and 1.75 times, respectively. They can elongate the double time of CAOV3 for 2.77 and 1.94 times, respectively. After treated by HCPT or topotecan, SKOV3 generated DNA Ladder. Positive rates of TUNEL of SKOV3 and CAOV3 were elevated by HCPT and topotecan notably. HCPT and topotecan did not affect the expression of c-myc, bcl-2, fas of SKOV3 and CAOV3. Observed by electronic microscope, heterochromatin of SKOV3 and CAOV3 coagulated after treated by HCPT. Micro villi of SKOV3 and CAOV3 were damaged, and some vacuoles appeared in the cytoplasm. CONCLUSIONS: HCPT and topotecan can inhibit growth of SKOV3 and CAOV3 significantly. HCPT and topotecan can induce apoptosis of SKOV3 and CAOV3.

Antineoplastic Agents↗
PubMed1999

[Effect of Panax notoginseng saponin on Ca2+, CaM in craniocerebral injury].

OBJECTIVE: To explore the change of nerve cell Ca(2+)-overload, Ca(2+)-CaM and the effect of Panax Notoginseng saponin (PNS) on it in craniocerebral injury. METHODS: Blood and brain contents of Ca2+, CaM were examined by radio-immunoassay (RIA) and atomic absorption spectrometry(AAS), and effect of PNS on these parameters was observed in craniocerebral injury rabbits. RESULTS: The levels of Ca2+ and CaM in blood and those in brain were significantly positively correlated. PNS could reduce Ca2+ and CaM contents in blood and in cerebral tissue. CONCLUSION: PNS could block the Ca(2+)-overload and Ca(2+)-CaM complex production in nerve cell after cranial cerebral injury, thereby to protect the injured brain in a certain degree. Blood CaM level is an objective index for assessment of Ca(2+)-overload in nerve cell.

Animals↗
PubMed1999

[Dose-effect of inhaled nitric oxide on pulmonary hypertension in inhaled injury in rabbits].

OBJECTIVE: To explore the relation of dose-response of NO inhalation in treatment of pulmonary hypertension in rabbits with smoke inhalation injury. METHODS: The effect of various concentrations (1, 5, 10, 20, 30, 40, 50 and 60) x 10(-6) of NO on pulmonary hypertension after smoke inhalation injury was studied with right heart catheterization in 15 rabbits. RESULTS: Mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), pulmonary minute vessel pressure (Pmv), and pulmonary vascular resistance (PVR) were not changed remarkably (P > 0.05) after inhalation of (1 or 5) x 10(-6) NO. mPAP, PCWP, and Pmv were lowered significantly after inhalation of (10, 20, 30, 40, 50 and 60) x 10(-6) NO (P < 0.05, P < 0.01). Major vascular relaxation occurred when NO concentration was at 30 x 10(-6), and PVR did not further decrease along with the increase of NO concentration. CONCLUSION: The concentration of inhaled NO should not exceed 30 x 10(-6) for the treatment of pulmonary hypertension in early stage of smoke inhalation.

Administration, Inhalation↗
PubMed1999

[Extracorporeal shock wave lithotripsy in situ for middle ureteral stones].

OBJECTIVE: To report the experience with in situ ESWL for patients with middle ureteral stones. METHODS: 52 patients suffering from stones with an average 11 mm (range 5 - 20 mm) in dimension were treated using modified Puigvert technique in prone position via the entry route of lateral abdomen. The patients received 3,000 - 5,000 shocks per session at the power setting ranged from 2 to 7. RESULTS: The stone free rate at 3 months was achieved in 96% patients retreatment was performed in 30% patients. The therapeutic results were calculated as efficiency quotient being 74%. No severe complications occurred in all patients. CONCLUSIONS: In situ ESWL for middle ureteral stone is safe and effective and may serve as the first line therapy.

Adult↗
PubMed1999

[In vitro adherence of bacteria to intraocular lenses of different materials].

OBJECTIVE: To compare the in vitro adherence of different bacteria onto the surface of various intraocular lenses (IOLs). METHOD: Electron microscopic and bacterial culture quantitative methods were used to study the adherence of Staphylococcus (S) epidermidis, Staphylococcus aureus and Pseudomonas (P) aeruginosa onto the surface of PMMA and other three foldable IOL materials (HEMA, ACRY, SI). RESULTS: S. Epidermidis: HEMA < ACRY < SI < PMMA; S. aureus: HEMA was the least and PMMA was the most, no significant difference between ACRY and SI IOLs; P. aeruginosa: HEMA was the least while no significant difference among PMMA, SI and ACRY IOLs (P > 0.05). CONCLUSION: The foldable IOLs have the potent ability to reduce the infectious endophthalmitis after surgery of extraction of cataract with IOL implantation.

Acrylic Resins↗
PubMed1999

[Effect of bFGF, IGF-I and their synergy on the mitogenesis of bovine lens epithelial cells].

OBJECTIVE: To assess the effect of basic fibroblast growth factor (bFGF), insulin like growth factor-I (IGF-I) and their synergy on the mitosis of bovine lens epithelial cells (BLECs). METHODS: BLECs were cultured in vitro. The fourth passage cells were inoculated into 24 well tissue culture plates, treated with different concentrations of bFGF, IGF-I, and bFGF + 20 microg/L IGF-I for 20 hours, (3)H-thymidine was added for 16 hours, then the radioactivity was determined by liquid scintillation counting. RESULTS: Either bFGF (1 - 100 microg/L) or IGF-I (20 - 100 microg/L) increases mitosis of BLEC significantly, and 20 microg/L IGF-I may increase bFGF induced mitogenesis. CONCLUSION: Growth factor and their synergic effect may play an important role in lens epithelial cell proliferation.

Animals↗
PubMed1999

[Synthetic assessment of health impact of cerebrovascular diseases on potential health days of life lost].

OBJECTIVE: To assess synthetically the impact on population health caused by cerebrovascular diseases. METHODS: Incidence, duration of disease, disabilities and deaths of cerebrovascular diseases were analyzed with potential health days of life lost (PHDLL) as an indicator in urban areas of Changsha, Hunan Province. RESULTS: The PHDLL caused by cerebrovascular disease totaled 2 624.94 days per thousand of population, 33.01% of them attributed to deaths and 53.44% to chronic disability. CONCLUSION: Hemorrhagic cerebrovascular disease mainly lead to death and ischemic one caused chronic disability.

Adolescent↗
PubMed1999

[A clinico-pathological and etiological study of Binswanger's Disease].

OBJECTIVE: To study the pathology, incidence and etiology of Binswanger's disease. METHODS: Autopsied brains from 9 cases of Binswanger's disease and 13 cases of non-demented elderly individuals were studied by clinico-pathological, immunohistochemical and micrometer methods. RESULTS: The lesions of Binswanger's disease were mainly located in the subcortical white matter, periventrical regions, brainstem and cerebellum. The pathological changes were demyelination, lacunar infarction, gliosis and dilatation of perivascular space (Virchow-Robin space, VR space, P < 0.01). The wall thickness of deeply penetrating arteries in the white matter was significantly increased (P < 0.01). CONCLUSION: Binswanger's disease is not a rare entity. The findings of this study suggest that arteriosclerosis is a primary factor in the pathogenesis of Binswanger's disease.

Aged↗
PubMed1999

[Pathomorphological and amyloid beta-protein immunohistochemical findings in autopsied brains of Alzheimer's disease].

OBJECTIVE: To study the incidence and neuropathological features of Alzheimer's disease in Chinese and the significance of silver and amyloid beta-protein staining for the pathological diagnosis of Alzheimer's disease. METHODS: Among 445 autopsy cases above 60 years in age (including 60) collected from 1982-1998 in the Department of Pathology, Beijing Hospital, totally 29 cases were diagnosed as Alzheimer's disease pathologically (6.5%), accompanying with a history of mental deterioration and the histological changes in certain areas of the brain fulfilling the Khachaturian or Mirra criteria. Tissue blocks were taken from 6 standard regions of the brains for Bodian, Bielschowsky and amyloid beta-protein immunostaining. Senile plaques and neurofibrillary tangles were quantified. RESULTS: Four main types of senile plaques were noticed and the result by amyloid beta-protein immunostaining was considered more sensitive than that of the silver impregnation staining. The former one enabled to demonstrate all the 4 types of senile plaques, while silver impregnation staining could only demonstrate clearly the primitive and neuritic plaques, but not the small diffuse and burn-out plaques. The senile plaques were noticed to be focused in the hippocampus, superior temporal gyrus and middle frontal gyrus while the neurofibrillary tangles, were mainly obtained in the hippocampus, temporal cortex and amygdaloid. Cerebral amyloid angiopathy was found in 25 out of 29 Alzheimer's disease cases. CONCLUSIONS: Alzheimer's disease may be the main cause of dementia among the elders in Chinese and immunostaining for amyloid beta-protein pretreated with formic acid may set a high value on the pathological diagnosis of Alzheimer's disease.

Aged↗
PubMed1999

[Research on quality of life of stroke patients and linear model of its impact factors].

The present study reviewed the investigation of 278 stroke patients of Changsha city population in 1994. The result showed that patients of stroke might have different quality of life during the process of their illness. Multiple regression model indicated that major factors on the chronic stroke patients were type of stroke, age, home nursing time, labor-losing days, occupations. The study provides reference source for prevention of stroke and improvement of quality of life.

Adult↗