Search PubMed⌕ Search

Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 343 records · Page 19Linked to original sources
PubMed1998

Truncation of Sp1 transcription factor by myeloblastin in undifferentiated HL60 cells.

When HL60 cells are exposed to 1,25-dihydroxyvitamin D3 (1,25D3), they undergo changes approximating the phenotype of the monocyte. Little is known, however, about the regulation and the mechanisms of this transition. It was previously noted that DNA binding by the Sp1 transcription factor in nuclear extracts of HL60 cells is profoundly altered when these cells are induced to differentiate by 1,25D3. In the present study, we show that in untreated HL60 cells only a truncated, approximately 30-kDa Sp1 fragment, encompassing the C-terminal region, binds to the GC element-containing DNA. Full-length 105-kDa Sp1 protein cannot be detected in these cells, although reverse transriptase-polymerase chain reaction reveals the presence of both 5' and 3' ends of Sp1 mRNA. Following treatment with 10(7) M 1,25D3 for 96 hr or in cells made resistant to 1,25D3 or to 1-beta-D-arabinocytosine, the Sp1 protein can be demonstrated. After an exposure to purified myeloblastin, a serine protease, purified recombinant Sp1 protein and extracts of 1,25D3-treated cells show a pattern of DNA binding similar to the pattern seen using extracts of untreated HL60 cells, indicating that the Sp1 protein is a target for myeloblastin. Because myeloblastin is present in naive HL60 cells and is downregulated during their differentiation, inhibition of proteolysis of these transcription factors seems to provide a mechanism through which differentiating HL60 cells can acquire a new repertoire of gene expression, perhaps for the maintenance of the differentiated phenotype.

Binding, Competitive↗
PubMed1998

Results of termino-lateral neurorrhaphy to original and adjacent nerves.

In this comprehensive investigation, we studied three different neurorrhaphy models in an attempt to elucidate the potential of termino-lateral nerve repair to original and adjacent nerves. In experimental group 1, the peroneal nerve was sectioned and then attached to the posterior tibial nerve in a termino-lateral fashion. In experiment group 2, the motor nerves to the gastrocnemius muscle were sectioned and then attached to the posterior tibial nerve in a termino-lateral fashion. In experimental group 3, the obturator nerve (L2-4) was sectioned and attached to the sciatic nerve (L4-6) in a termino-lateral fashion. For the control in each group, the same type of nerve used in each respective group was transected without repair. Experimental groups 1 and 2 showed viable axons in the peroneal nerve distal to the neurorrhaphy site. Experimental group 3 showed no viable axons at these sites. No regeneration was observed in the transected nerve without repair in all three control groups. This study suggests that termino-lateral neurorrhaphy is a viable means of repairing damaged nerves if the distal segment of the sectioned nerve is reattached to its original trunk distal to its original branch point. However, the results from experimental group 3 demonstrate that termino-lateral neurorrhaphy cannot be used to repair nerves when the donor and recipient nerves originate from different spinal cord levels.

Anastomosis, Surgical↗
PubMed1998

Rat tail replantation as a training model for microvascular procedures of digit replantation.

In this study we sought to evaluate the potential of rat tail replantation as a tool for very-small-vessel microvascular anastomoses. We used 10 adult Sprague-Dawley rats. The tail was completely amputated 2.0-cm distal to the base of the tail. Then the tail was replanted with anastomoses of two superficial dorsal veins from both sides and one artery. All 10 replanted tails were pink, viable, and normal-appearing at all daily inspections performed from the first to the fourteenth postoperative days. This model can provide a training tool for the acquisition of superior microvascular surgical technique for the repair of very small vessels that stimulate digital replantation.

Amputation, Traumatic↗
PubMed1998

Quantitative measurements of cerebral blood flow in rats using the FAIR technique: correlation with previous iodoantipyrine autoradiographic studies.

Flow-sensitive alternating inversion recovery (FAIR) is a recently introduced MRI technique for assessment of perfusion that uses blood water as an endogenous contrast agent. To characterize the FAIR signal dependency on spin tagging time (inversion time (TI)) and to validate FAIR for cerebral blood flow (CBF) quantification, studies were conducted on the rat brain at 9.4 T using a conventional gradient-recalled echo sequence. The T1 of cerebral cortex and blood was found to be 1.9 and 2.2 s, respectively, and was used for CBF calculations. At short TIs (<0.8 s), the FAIR signal originates largely from vascular components with fast flows, resulting in an overestimation of CBF. For TI > 1.5 s, the CBF calculated from FAIR is independent of the spin tagging time, suggesting that the observed FAIR signal originates predominantly from tissue/capillary components. CBF values measured by FAIR with TI of 2.0 s were found to be in good agreement with those measured by the iodoantipyrine technique with autoradiography in rats under the same conditions of anesthesia and arterial pCO2. The measured pCO2 index on the parietal cortex using the FAIR technique was 6.07 ml/100 g/min per mmHg, which compares well with the pCO2 index measured by other techniques. The FAIR technique was also able to detect the regional reduction in CBF produced by middle cerebral artery occlusion in rats.

Animals↗
PubMed1998

A new heart failure model in rat by an end-to-side femoral vessel anastomosis.

OBJECTIVE: The aim of this study was to develop a new shunting procedure for producing heart failure in the rat incorporating microvascular techniques and avoiding an abdominal operation. METHOD: We performed an end-to-side anastomosis between the femoral vein and the femoral artery just proximal to their trifurcation into the saphenous, epigastric, and distal femoral vessels. RESULTS: Of the 15 rats which underwent this procedure, six died within 48 h. The nine surviving animals were sacrificed and examined six weeks following surgery. All nine had developed cardiac hypertrophy and cardiac failure. CONCLUSION: This model provides a relatively simple and reproducible means of creating high output heart failure and cardiac hypertrophy in the rat without necessitating abdominal surgery.

Anastomosis, Surgical↗
PubMed1998

Blood pressure at age 3-24 years in a rural community in Anhui, China.

PURPOSE: This community-based study in Anhui, China examined the sex-specific pattern of blood pressure (BP) and its major determinants between age 3 and 24 years. METHODS: BP, height, weight, and related covariates were obtained from all eligible subjects by consistent methods. A generalized additive model was used to explore independent relations between BP and covariates. The sample for analyses included a total of 14,277 subjects (7244 males and 7033 females). RESULTS: Systolic blood pressure (SBP) increased linearly with age to an apparent plateau around the age of 15 years in girls and 20 years in boys. Diastolic blood pressure (DBP) essentially paralleled SBP. Until the age of 10, both SBP and DBP were similar in boys and girls; thereafter, values for boys surpassed those for girls with an average difference of 9 mmHg and 4 mmHg for SBP and DBP, respectively, at 20 years of age. This sex difference appeared to persist into early adulthood. The independent relation between BP and each of the three major determinants (age, height, and weight) was nonlinear over the age range studied. Sex-specific regression models with linear terms for age, height and weight were developed for each of four age groups (3-9, 10-14, 15-19, 20-24 years). The 5th, 10th, 90th, and 95th percentiles based on the percentage of predicted values can serve as the cutoffs for low, normal-low, normal-high, and high BP. The predicted values were derived from the above regression models that take into account an individual's sex, age, height, and weight. CONCLUSIONS: This analysis provided important basis for classification of hypertension status and subsequent investigation of environmental risk factors in this population.

Adolescent↗
PubMed1998

Function of hexameric RNA in packaging of bacteriophage phi 29 DNA in vitro.

A cyclic hexamer of the 120-base prohead RNA (pRNA) is needed for efficient in vitro packaging of the B. subtilis bacteriophage phi 29 genome. This capacity of pRNA to form higher multimers by intermolecular base pairing of identical subunits represents a new RNA structural motif. Dimers of pRNA are likely intermediates in formation of the cyclic hexamer. A three-dimensional model of the pRNA hexamer is presented.

Bacillus Phages↗
PubMed1998

Alkylation of 2'-deoxynucleosides and DNA by the Premarin metabolite 4-hydroxyequilenin semiquinone radical.

Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and continues to be one of the most widely dispensed prescriptions in the United States. In addition to endogenous estrogens, Premarin contains unsaturated estrogens including equilenin. We synthesized the catechol metabolite of equilenin, 4-hydroxyequilenin (4-OHEN), and found that the semiquinone radical of 4-OHEN reacted with 2'-deoxynucleosides generating very unusual adducts. 2'-Deoxyguanosine (dG), 2'-deoxyadenosine (dA), or 2'-deoxycytosine (dC) all gave four isomers, but no product was observed for thymidine under similar physiological conditions. The structures of these adducts were determined by electrospray mass spectrometry and NMR experiments including 1H, 13C, DQF-COSY, ROESY, HOHAHA, HMQC, and HMBC. The spectral data show that dG forms a cyclic adduct with the 4-OHEN producing 2-N1,3-N2-deoxyguanosyl-1,3-dihydroxy-5,7,9(10)-estratriene-4,17-d ione. Similarly, reaction with dA produced 1-N6,3-C2-deoxyadenosyl-2,3-dihydroxy-5,7,9(10)-estratriene-4,17-d ione, and incubations with dC resulted in 1-N3,3-N4-deoxycytosyl-2,3-dihydroxy-5,7,9(10)-estratriene-4,17-di one. We found that care needed to be taken during the isolation of the dA adducts in particular, as any exposure to acidic environments caused hydrolysis of the sugar moiety leaving alkylated adenine. In mixtures of the deoxynucleosides treated with 4-OHEN, reaction occurred primarily with dG followed by dC and dA. With DNA significant apurinic sites were produced as 4-OHEN-adenine adducts were detected in the ethanol wash prior to hydrolysis. When the DNA was hydrolyzed to deoxynucleosides and analyzed by electrospray mass spectrometry, only one isomer of 4-OHEN-dG and one isomer of 4-OHEN-dC were observed. Our data suggest that several different types of DNA lesions could be expected from 4-OHEN including apurinic sites and bulky stable adducts, in addition to the published oxidized damage to DNA caused by 4-OHEN. The production of these semiquinone radical-derived DNA adducts could play a role in the carcinogenic effects of Premarin estrogens.

Alkylation↗
PubMed1998

Inhibition of glutathione S-transferase activity by the quinoid metabolites of equine estrogens.

The risk factors for women developing breast and endometrium cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy (ERT) in particular has been correlated with a slight increased cancer risk, although the numerous benefits of ERT may negate this harmful side effect. Equilenin and equilin are equine estrogens which make up between 30% and 45% of the most widely prescribed estrogen replacement formulation, Premarin (Wyeth-Ayerst). In this study we have synthesized the catechol metabolites of equilenin [4-hydroxyequilenin (4-OHEN)] and equilin [4-hydroxyequilin (4-OHEQ)] and examined how changing unsaturation in the B ring affects the formation of o-quinone GSH conjugates and the ability of the o-quinones and/or GSH conjugates to inhibit glutathione S-transferase (GST). Interestingly, both 4-OHEN and 4-OHEQ autoxidized to o-quinones without the need of oxidative enzyme catalysis. 4-OHEN-o-quinone reacts with GSH to give two mono-GSH conjugates and one diadduct. The behavior of 4-OHEQ was found to be more complex than 4-OHEN as conjugates resulting from 4-OHEN were detected in addition to the 4-OHEQ GSH adducts. Both 4-OHEN and 4-OHEQ were found to be potent inhibitors of GST-catalyzed conjugation of GSH with 1-chloro-2,4-dinitrobenzene. In contrast, the endogenous catechol estrogens, 4-hydroxyestrone (4-OHE) and 2-hydroxyestrone (2-OHE), were without effect unless tyrosinase was present to convert the catechols to o-quinones. Scavengers of reactive oxygen species and metal chelators had no effect on GST inhibition by catechol estrogens with the exception of the catalase which protected GST activity. Kinetic studies showed that 4-OHEN was a potent irreversible inactivator of GST. Preincubation of the enzyme with 4-OHEN showed a time-dependent increase in inhibitory effect, and gel filtration did not restore GST activity confirming the irreversible nature of the enzyme inactivation. Analysis of the Kitz-Wilson plot gave a dissociation constant of the reversible enzyme-inhibitor complex (Ki = 620 microM) and a rate constant of conversion of the reversible enzyme-inhibitor complex to the irreversibly inhibited enzyme (k2 = 7.3 x 10(-)3 s-1). These data suggest that 4-OHEN is an irreversible inactivator with relatively low affinity for GST; however, once formed the 4-OHEN enzyme complex is rapidly converted to the irreversibly inhibited enzyme. The inhibition mechanism likely involves oxidation of the catechol estrogens to o-quinones and covalent modification and/or oxidation of critical amino acid residues on GST. In addition, hydrogen peroxide generated through redox cycling of the o-quinone and/or semiquinone radical and GSH could cause oxidative damage to GST.

Animals↗
PubMed1998

The equine estrogen metabolite 4-hydroxyequilenin causes DNA single-strand breaks and oxidation of DNA bases in vitro.

Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and continues to be one of the most widely dispensed prescriptions in North America. In addition to endogenous estrogens, Premarin contains unsaturated equine estrogens, including equilenin [1,3,5(10),6,8-estrapentaen-3-ol-17-one]. In previous work, we showed that the equilenin metabolite 4-hydroxyequilenin (4-OHEN) can be autoxidized to 4-OHEN-o-quinone which readily entered into a redox couple with the semiquinone radical catalyzed by NAD(P)H, P450 reductase, or quinone reductase, resulting in generation of reactive oxygen species [Shen, L., Pisha, E., Huang, Z., Pezzuto, J. M., Krol, E., Alam, Z., van Breemen, R. B., and Bolton, J. L. (1997) Carcinogenesis 18, 1093-1101]. As oxidative damage to DNA by reactive oxygen species generated by redox active compounds has been proposed to lead to tumor formation, we investigated whether 4-OHEN could cause DNA damage. We treated lambda phage DNA with 4-OHEN and found that extensive single-strand breaks could be obtained with increasing concentrations of 4-OHEN as well as increasing incubation times. If scavengers of reactive oxygen species are included in the incubations, DNA could be completely protected from 4-OHEN-mediated damage. In contrast, NADH and CuCl2 enhanced the ability of 4-OHEN to cause DNA single-strand breaks presumably due to redox cycling between 4-OHEN and the semiquinone radical generating hydrogen peroxide and ultimately copper peroxide complexes. We also confirmed that 4-OHEN could oxidize DNA bases since hydrolysis of 4-OHEN-treated calf thymus DNA and HPLC separation with electrospray MS detection revealed oxidized deoxynucleosides, including 8-oxodeoxyguanosine and 8-oxodeoxyadenosine. Our data suggest that DNA single-strand breaks and oxidation of DNA bases by 4-OHEN could contribute to the carcinogenic mechanism(s) of equine estrogens.

Animals↗
PubMed1998

Limited proteolysis as a probe for arrested conformational maturation of delta F508 CFTR.

Deletion of phenylalanine 508 (delta F508) in the cystic fibrosis transmembrane-conductance regulator (CFTR) prevents the otherwise functional protein from reaching the plasma membrane and is the leading cause of cystic fibrosis. Indirect evidence suggests that the mutant protein, delta F508 CFTR, is misfolded. We address this issue directly, using comparative limited proteolysis of CFTR at steady steady state and during biosynthesis in the native microsomal environment. Distinct protease susceptibilities suggest that cytosolic domain conformations of wild type and delta F508 CFTR differ, not only near F508, but globally. Moreover, delta F508 CFTR proteolytic cleavage patterns were indistinguishable from those of the early folding intermediate of wild type CFTR. The results suggest that the delta F508 mutation causes the accumulation of a form of the protein that resembles an intermediate in the biogenesis of the wild type CFTR, rather than induces the production of non-native variant.

Animals↗
PubMed1998

Effect of cryopreservation on survival of composite tissue grafts.

The problems in cryopreserving complex tissues remain poorly understood. In the present study, the viability of cryopreserved complex tissue, including skin and muscle flaps, and tail, was compared to simple artery and vein grafts in a rat model. Forty-four grafts, including the femoral artery (n = 15), femoral vein (n = 9), gracilis muscle flap (n = 8), groin cutaneous flap (n = 9), and tail (n = 3) were cryopreserved at -196 degrees C for 1 to 2 weeks, and then microvascularly transferred to analogous sites in inbred recipient animals. Three to 60 days post-transplant, all cryopreserved femoral arteries and veins were patent. Host groin cutaneous flaps with cryopreserved vessels grafted into the arterial pedicle survived with no complications However, severe endothelial-cell damage with extensive sloughing in the grafts was demonstrated at 30 min and 1 week following reperfusion, using factor VIII immunologic stain. Reendothelialization was evident at 2 months postoperatively. All cryopreserved composite tissue underwent early pedicle thrombosis The muscle and cutaneous tissue also showed gross and microscopic edema, with extensive red-cell extravasation within 30 min of reperfusion Cryopreservation thus can maintain the functional integrity of simple vessel grafts, but these grafts survive only as a conduit, given the severe endothelial-cell damage The failure of transferred complex cryopreserved tissue may reflect a combination of cellular or architectural damage to the capillary bed from ice formation during the freezing process and from reperfusion injury.

Animals↗
PubMed1998

Effect of hyperbaric oxygen on survival of the composite ear graft in rats.

In this study the authors set out to determine whether postoperative hyperbaric oxygen (HBO) therapy increases the survival rate of the composite graft in the rat ear model. A composite graft (1 x 0.5 cm2) that included skin, subcutaneous tissue, and cartilage was created from the left ear, and was transferred onto the posterior auricular site of the right ear. The animals were divided into two groups: a control group (N = 10) and an experimental group receiving HBO (N = 10). The experimental group was given HBO immediately following reattachment for 4 hours, and then for 6 hours each day for 5 days (2 atm). The results showed the average ear flap survival area in the experimental group was 82%, and it was 26.5% in the control group (p < 0.01). Histology demonstrated the existence of neovascularization in the experimental group. We have concluded that postoperative HBO therapy increases the survival of the rat ear composite graft, and that the effect of this therapy is influenced by the magnitude (size and thickness) of the graft.

Animals↗
PubMed1998

Delayed treatment with aminoguanidine decreases focal cerebral ischemic damage and enhances neurologic recovery in rats.

Delayed treatment with aminoguanidine (AG), a relatively selective inhibitor of inducible nitric oxide synthase, ameliorates brain damage produced by occlusion of the rat's middle cerebral artery (MCA). We investigated whether the protection exerted by AG is dose-dependent and whether it is associated with improved neurologic outcome. We also studied the effect of the timing of administration of AG relative to the induction of cerebral ischemia. Halothane-anesthetized spontaneously hypertensive rats underwent permanent MCA occlusion distal to the lenticulostriate branches. Neurologic deficits were assessed daily by the postural reflex test and beam balance test. Infarct volume was determined in thionin- stained sections 96 hours after ischemia and values corrected for swelling. Treatment with AG (intraperitoneally, twice daily), starting 24 hours after MCA occlusion, decreased neocortical infarct volume in comparison to vehicle-treated rats. After correction for swelling, the decrease was 8 +/- 12% at 50 mg/kg (n = 8; P > .05; analysis of variance), 25 +/- 13% at 100 mg/kg (n = 7; P < .05), 30 +/- 16% at 200 mg/kg (n = 7; P < .05) and 32 +/- 9% at 400 mg/kg (n = 5; P < .05). Twenty-four hours after induction of ischemia neurologic deficits scores did not differ between treated and untreated rats (P > .05). However, from 48 to 96 hours after ischemia, neurologic deficits improved significantly in rats treated with AG (100 to 400 mg/kg) compared to rats in which vehicle was administered (P < .05). The decrease in neocortical infarct volume was greatest when AG (100 mg/ kg; twice daily) was administered 12 (26 +/- 17%; n = 9) or 24 hours (25 +/- 13, n = 7) after MCA occlusion. The findings show that AG decreases ischemic brain damage dose-dependently and improves neurologic recovery. Delayed treatment with AG may be a therapeutic strategy to selectively target the evolution of ischemic damage that occurs in the post-ischemic period.

Animals↗
PubMed1998

Ambulatory blood pressure and Holter monitoring of emergency physicians before, during, and after a night shift.

BACKGROUND: Occupational stress may affect measured hemodynamic and electrocardiographic variables. Data describing the physiologic effects of work on the emergency physician (EP) are sparse. OBJECTIVE: To determine whether blood pressure (BP) and heart rate variability (HRV) of the EP are affected during a night shift in the ED. METHODS: This prospective study evaluated BP and HRV in attending EPs at an urban academic medical center for a 24-hour period during which a night shift was scheduled. Participants were fitted with an oscillometric ambulatory BP device and a Holter monitor at 1500 hours on the day of a night shift. The monitors were worn continuously before, during, and after a night shift (2300-0700) in the ED and were removed at 1500. Systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), heart rate (HR), measures of HRV, and occurrence of cardiac dysrhythmias were evaluated. Comparisons were made for ED and non-ED awake periods and non-ED sleep periods. RESULTS: Twelve participants completed the study. Eight (67%) subjects were men and 4 (33%) were women. Age ranged from 28 to 40 years (mean 34.1+/-4.1). Results were analyzed using repeated-measures ANOVA. An elevation of mean DBP (5.5 mm Hg+/-4.37; p < 0.05; 95% CI 1-10) during night shift activity was seen. A trend toward elevation of SBP, MAP, and HR was discernible. HRV measures indicated a significant relative increase in sympathetic vs parasympathetic tone and an increase in HR of prework and work compared with postwork. Dysrhythmias observed included sinus tachycardia, sinus bradycardia, sinus pause, atrial premature beats, atrial couplets and triplets, supraventricular tachycardia, and premature ventricular contractions. CONCLUSIONS: The elevation of DBP during a night shift suggests that these patterns of BP variability are activity- or stress-related rather than a result of a true diurnal variation. HRV analysis suggests that sympathetic tone is heightened both before work and during work. The implications of such findings to the health of the EP warrant further investigation.

Adult↗