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Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 271 records · Page 15Linked to original sources

Calf augmentation using free TRAM flap.

Augmentation of the calf for correction of contour deformities has been most frequently performed utilizing silicone implants. Results of such implants have often been unsatisfactory. We report the case of a 27-year-old woman who chose the use of a transverse rectus abdominis myocutaneous (TRAM) free flap for correction of a left calf contour deformity from childhood polio. This is the first report of calf augmentation with the use of a TRAM free flap and excellent results were obtained.

Adult↗

Cysteine-containing histone H1-like (PL-I) proteins of sperm.

We have determined the presence of cysteine in the protein PL-I from the sperm of the surf clam Spisula solidissima. The existence of cysteine in this histone H1-related protein is responsible for its previously described aggregation behavior. The location of this residue, within the trypsin-resistant domain of the protein, has been established. We have also shown that cysteine is ubiquitously present in the PL-I proteins from the sperm of other bivalve mollusks but is absent from other PL of smaller molecular mass (PL-II, PL-III, PL-IV). We have also found cysteine to be present in the PL-I from a tunicate (Chelysoma productum) but absent in a PL-I from a fish (Mullus barbatus). The possible significance of the unusual occurrence of cysteine in these histone-H1-related proteins is discussed.

Amino Acid Sequence↗

Enhancement of hypothermic heart preservation with fructose 1, 6-diphosphate.

BACKGROUND: We hypothesized that the addition of fructose 1, 6-diphosphate (FDP) to a hypothermic heart preservation solution could improve metabolic recovery because it has several beneficial effects. MATERIALS AND METHODS: Twenty adult Sprague-Dawley rats were used to study hypothermic heart preservation. The hearts were removed under general anesthesia and preserved at 4 degrees C in Euro-Collins solution (30 ml/kg) for 8 h. In the study group (N = 10), FDP (5 mM) was added to the Euro-Collins solution. In the control group (N = 10), no FDP was added. Heart function was studied after preservation using a working heart model. The ability of various concentrations of fructose 1,6-phosphate to passively diffuse through an egg phosphatidylcholine multilamellar vesicle (MLV) membrane bilayer was examined. RESULTS: Cardiac output ranged from 17.0 +/- 1.9 to 24.9 +/- 1.6 ml/min in the study group vs 2.0 +/- 1.0-12.3 +/- 1.7 ml/min for controls, average aortic flow was 10. 8 +/- 1.4 ml/min in the study group vs -1.3 +/- 1.6 ml/min for controls, and maximum LV generated power was 22.8 +/- 1.7 J/min vs 10.1 +/- 1.6 J/min for controls. Coronary flow, left ventricular stroke volume and stroke work, and myocardial oxygen consumption were much higher in the study group than in the control group. Coronary vascular resistance was lower in the study group than in the control group. Electron microscopic study indicated that many myocytes displayed patches of swollen mitochondria in the control group, but was rarely observed in the study group. The addition of 50 mM FDP caused substantial changes in MLV permeability. No dose of sucrose buffers outside the vesicles resulted in a significant changes of MLV permeability. CONCLUSIONS: Our results indicate that the addition of FDP to Euro-Collins solution significantly improves hypothermic rat heart preservation, and FDP appeared to cross the membrane bilayer.

Animals↗

Sequence comparison of the L2 and S10 genes of bluetongue viruses from the United States and the People's Republic of China.

Bluetongue virus (BTV) infection of ruminants is endemic throughout much of the US and China. The S10 and a portion of the L2 gene segments of Chinese prototype strains of BTV serotypes 1, 2, 3, 4, 12, 15, and 16 were sequenced and compared to the same genes of prototype and field strains of BTV from the US. Phylogenetic analysis of the S10 gene segregated the Chinese viruses into a monophyletic group distinct from the US viruses, whereas similar analysis of the L2 gene segregated strains of BTV according to serotype, regardless of geographic origin.

Bluetongue virus↗

Synthesis of the equine estrogen metabolites 2-hydroxyequilin and 2-hydroxyequilenin.

Equilin and equilenin make up approximately 20% of Premarin which is currently the most popular estrogen replacement therapy. Although there are numerous health benefits of estrogen replacement therapy, there are concerns over the link between estrogen replacement therapy and breast and endometrial cancer risk. One potential mechanism of estrogen carcinogenesis involves metabolism of estrogens to 2- and 4-hydroxylated catechols which are further oxidized to electrophilic/redox active o-quinones which have the potential to both initiate and promote the carcinogenic process. In this investigation, we have synthesized potential metabolites of equilin and equilenin, 2-hydroxyequilin and 2-hydroxyequilenin, respectively, as well as their methyl ether metabolites. These compounds were synthesized from commercially available optically pure equilin via a practical and efficient approach; five steps gave 2-methoxyequilin from which 2-hydroxyequilin was prepared by BBr3-catalyzed demethylation in one step. Similarly, treating 2-methoxyequilin with SeO2 followed by demethylation with BBr3 produced 2-hydroxyequilenin. The structures of the catechols as well as those of their methoxy ethers were unambiguously characterized by one-dimensional and two-dimensional NMR experiments, including 1H, 13C, APT, COSY, HMBC, and HMQC as well as mass spectrometry.

Animals↗

The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone.

The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. In this study, we have compared the chemistry of the major catechol metabolite of equilin (4-hydroxyequilin), which is found in several estrogen replacement formulations, to the equilenin catechol (4-hydroxyequilenin). Unlike endogenous catechol estrogens, both equilin and equilenin were primarily converted by rat liver microsomes to 4-hydroxylated rather than 2-hydroxylated o-quinone GSH conjugates. With equilin, a small amount of 2-hydroxyequilin GSH quinoids were detected (4-hydroxyequilin:2-hydroxyequilin ratio of 6:1); however, no peaks corresponding to 2-hydroxyequilenin were observed in incubations with equilenin. These data suggest that unsaturation in the B ring alters the regiochemistry of P450-catalyzed hydroxylation from primarily 2-hydroxylation for endogenous estrogens to 4-hydroxylation for equine estrogens. 4-Hydroxyequilenin-o-quinone reacts with GSH to give two mono-GSH conjugates and one di-adduct. The behavior of 4-hydroxyequilin was found to be more complex than 4-hydroxyequilenin as conjugates resulting from 4-hydroxyequilenin were detected in addition to the 4-hydroxyequilin-GSH adducts. The mechanism of decomposition of 4-hydroxyequilin likely involves isomerization to a quinone methide which readily aromatizes to 4-hydroxyequilenin followed by autoxidation to 4-hydroxyequilenin-o-quinone. Similar results were obtained with 2-hydroxyequilin, although, in contrast to 4-hydroxyequilenin, 2-hydroxyequilenin does not autoxidize and the reaction stops at the catechol. Since 4-hydroxyequilin is converted to 4-hydroxyequilenin and 4-hydroxyequilenin-o-quinone, similar effects were observed for this equine catechol, including consumption of NAD(P)H likely by the 4-hydroxyequilenin-o-quinone, depletion of molecular oxygen by 4-hydroxyequilenin or its semiquinone radical, and alkylation of deoxynucleosides and DNA by 4-hydroxyequilenin quinoids. Finally, preliminary studies conducted with the human breast tumor cell line MCF-7 demonstrated that the cytotoxic effects of the catechol estrogens from estrone, equilin, and 2-hydroxyequilenin were similar, whereas 4-hydroxyequilenin was a much more potent cytotoxin ( approximately 30-fold). These results suggest that the catechol metabolites of equine estrogens have the ability to cause alkylation/redox damage in vivo primarily through formation of 4-hydroxyequilenin quinoids.

Animals↗

Vineland Adaptive Behavior Scale scores as a function of age and initial IQ in 210 autistic children.

Human growth modeling statistics were utilized to examine how Vineland Adaptive Behavior Scale (VABS) scores changed in individuals with autistic disorder as a function of both age and initial IQ. Results revealed that subjects improved with age in all domains. The rate of growth in Communication and Daily Living Skills was related to initial IQ while rate of growth in Social Skills was not. Results should provide hope for parents and further support for the importance of functional social-communication skills in the treatment of autism.

Activities of Daily Living↗

SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein.

Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium-dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells.

Mutation of FMR1 results in fragile X mental retardation. The most common FMR1 mutation is expansion of a CGG repeat tract at the 5' end of FMR1, which leads to cytosine methylation and transcriptional silencing. Both DNA methylation and histone deacetylation have been associated with transcriptional inactivity. The finding that the methyl cytosine-binding protein MeCP2 binds to histone deacetylases and represses transcription in vivo supports a model in which MeCP2 recruits histone deacetylases to methylated DNA, resulting in histone deacetylation, chromatin condensation and transcriptional silencing. Here we demonstrate that the 5' end of FMR1 is associated with acetylated histones H3 and H4 in cells from normal individuals, but acetylation is reduced in cells from fragile X patients. Treatment of fragile X cells with 5-aza-2'-deoxycytidine (5-aza-dC) resulted in reassociation of acetylated histones H3 and H4 with FMR1 and transcriptional reactivation, whereas treatment with trichostatin A (TSA) led to almost complete acetylated histone H4 and little acetylated histone H3 reassociation with FMR1, as well as no detectable transcription. Our results represent the first description of loss of histone acetylation at a specific locus in human disease, and advance understanding of the mechanism of FMR1 transcriptional silencing.

Acetylation↗

A transfecting peptide derived from adenovirus fiber protein.

New strategies to improve the outcome of gene therapy often employ a nonviral gene delivery, which is most likely to fulfil microbiological safety criteria and be retained in the clinical setting. Here we show that efficient gene transfer can be achieved in vitro using as a vector a polyvalent peptide derived from the N-terminal sequence of the human adenovirus fiber protein. The level of transfection is better than that obtained with the two liposomes, DOTAP and DOSPER. Internalization was studied by confocal microscopy using fluorescently marked peptide and DNA. The peptide alone is targeted to the nucleus and concentrated within the nucleolus. Similarly, DNA complexed with peptide also enters the nucleolus, where it is retained for at least 48 h. Peptide I appears to attach to cells by a saturable process, as preincubation of cells with peptide blocks transfection and there is no transfection at 4 degrees C. The peptide contains three domains: a nuclear localization signal of adenovirus fiber protein; a domain containing hydrophobic and polar residues harboring an internalization signal for receptor-mediated endocytosis; and a stretch of lysines. Each of these domains is required for optimum gene transfer. Peptide I may be an interesting alternative to known vectors for gene transfer, for local administration and for ex vivo applications.

Adenoviridae↗

Compartment syndrome of the forearm as the initial symptom of systemic Vibrio vulnificus infection.

Sepsis, cellulitis, and necrotizing fasciitis rarely have been described as causes of compartment syndrome. We report a case in which forearm compartment syndrome presented as the initial symptom of systemic infection. Vibrio vulnificus, the etiologic pathogen of the compartment syndrome, was isolated from wound and blood cultures. The patient was treated with systemic antibiotic treatment and multiple forearm fasciotomies. The infectious process progressed rapidly, however and due to underlying liver insufficiency, the patient died of hepatorenal syndrome. This case illustrates the nature of V. vulnificus infections, which are characterized by shellfish transmission, predilection for soft tissue seeding, and a fulminant course in the compromised host.

Animals↗

Z-plasty closure of the donor defect of the radial forearm free flap.

The radial forearm is a popular free flap site for reconstruction of head and neck defects, because of its abundant, pliable, skin component and an available, extended, vascular pedicle. In addition, vascularized composite flaps, including a segment of radius, can be designed for skeletal stabilization. The donor-site defect can involve various complications, including loss of skin graft, unsatisfactory appearance, numbness, and radial fracture. Recent advances in reducing donor-site defect problems have included the use of rotation skin flaps, local muscle rotation, and soft-tissue expansion; however, each of these has its own limitations. Two cases are presented in which radial forearm donor site defects, measuring less than 4 cm x6 cm, were primarily closed successfully with z-plasties based on the longitudinal skin incision. Each patient has regained preoperative mobility, and prompt primary healing was achieved without complications.

Adult↗

Functional assessment of the shoulder following latissimus dorsi muscle donation in the handicapped.

The latissimus dorsi muscle, one of the largest muscles in the human body, has gained widespread popularity in microsurgical reconstruction. Because the latissimus serves to adduct and medially rotate the upper extremity, caution in its use has been advocated in handicapped and non-ambulatory patients, although a paucity of information exists in the literature. The purpose of this reported project was to determine whether the loss of the latissimus dorsi could be documented objectively or subjectively, either in the preoperative condition or post-harvesting in the handicapped patients. Two paraplegic patients were studied. Results indicate a lack of objective functional deficit; this includes both the nerve-blocked state and the postoperative condition. In addition, both patients failed to demonstrate the need to change any activities of daily living. This evidence suggests that, although careful decisions must be made on a case-by-case basis, the use of the latissimus dorsi muscle is not necessarily contraindicated in this group of patients.

Abdominal Neoplasms↗

Shortening of rat teeth prevents autocannibalization of surgical flaps.

Self-biting in laboratory rats is an irritating problem that can impede progress and affect the credibility of experimental interventions. Autocannibalization frequently complicates the epigastric skin flap model that is often used to evaluate flaps. In one of the authors' studies, the autocannibalization rate of 55.6 percent in nine rats with unprotected skin flaps of the entire abdominal wall necessitated the application of previously reported plastic collars and protective vests to hinder self-biting. Because the use of these devices resulted in distress symptoms in nine of 11 rats with collars and flap congestion in five of five rats with vests, rat incisor teeth shortening was introduced as a stress-free method to prevent chewing. Careful teeth cutting obviated autocannibalization in 19 of 20 rats (p<0.01) during a 5-day follow-up. Rat incisor teeth shortening performed every 3 or 4 days is a simple, inexpensive, and reliable method to prevent autocannibalization in the rat, while maintaining the well-being of the animal.

Animals↗

Quadriceps femoris muscle flap: largest muscle flap model in the rat.

The purpose of this paper is to present a new muscle flap in the rat: the quadriceps femoris muscle flap based on a pedicle consisting of the femoral vessels. In order to establish the anatomic details of this model, seven rats were explored bilaterally, and the regional anatomy of the thigh was examined. The technical aspect of the model was established by the unilateral harvesting of 18 quadriceps femoris muscles. Findings were that this muscle is primarily supplied by a muscular branch originating at the superficial circumflex iliac artery. The average muscle weight was 6 g and the average pedicle length with femoral vessels was 6 mm. Eight of the harvested flaps were transplanted to the contralateral thigh, and the pedicle was anastomosed to the femoral vessels. The other ten flaps were resutured back to their beds. At 72 hr postoperatively, all flaps were viable with the exception of one of the transplanted flaps which was found to be necrotic. The quadriceps femoris muscle flap is technically both a reliable and simple model. With an average weight of 6 g, this flap is by far the largest described in the rat, and offers a convenient model for testing flap-related techniques and outcomes.

Animals↗

Effect of hyperbaric oxygen on microvascular anastomosis healing and patency in the rat.

Recent evidence has shown that changes in blood viscosity and marked increases in both platelet count and fibrinogen concentration occur after exposure to hyperbaric oxygen (HBO). The purpose of the present study was to address whether repeated HBO therapy would increase either hematocrit or platelet count, and to determine if these changes would influence the patency of the microvascular anastomosis, as well as anastomotic healing. Eighty femoral arteries from 40 rats were divided into four groups (n = 10), and arterial anastomoses were performed on normal arteries in the first two groups, and on crushed arteries in the second two groups. One of the normal artery groups and one of the crushed artery groups received repeated HBO treatments for 5 days. Anastomotic patency rates, platelet count, hematocrit, and breaking strength were recorded. Among the results of this study were that: (1) there was no difference in patency rate following HBO treatment in both the normal and crushed artery groups; (2) platelet count was significantly higher following HBO treatment in the groups with the undamaged arteries; (3) breaking strength was significantly increased following HBO treatment in the groups with the crushed arteries. The authors concluded that HBO therapy may be useful in improving the healing of microvascular anastomoses in vessels that have undergone crush injury. Although HBO treatment results in an increased platelet count, this does not influence anastomotic patency.

Anastomosis, Surgical↗

Structures of two new diterpenoid dimers from bulbs of Fritillaria ebeiensis.

Two new ent-kauranoid diterpenoid dimers, fritillebin C (1) and fritillebin D (2), were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu and G.Q. Ji. Their structures were determined to be ent-16beta-hydroxy-kauran-17-yl ent-16beta3-kauran-17-oate (1); ent-16alpha-hydroxy-kauran-17-yl ent-16beta-kauran-17-oate (2) by means of spectral analysis and chemical evidence.

Dimerization↗

Properties of sustained-release tablets prepared by hot-melt extrusion.

The objectives of the present study were to investigate the properties of polyethylene oxide (PEO) as a drug carrier and to study the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets prepared by hot-melt extrusion. During the hot-melt extrusion process, a dry powder blend of drug, polymer, and other adjuvants was fed into the extruder and melted inside the barrel of the machine. The molten mass was extruded through a rod-shaped die and then cut manually into 400-mg tablets. CPM and PEO were shown to be stable under the processing conditions. The molecular weight of the PEO, the drug loading percentage, and the inclusion of polyethylene glycol as a processing aid, were all found to influence the processing conditions and the drug release properties of the extruded tablets. Faster release of CPM from the matrix tablets was observed in acidic medium than in purified water and phosphate buffer (pH 7.4). Drug release from the matrix tablet was controlled by erosion of the PEO matrix and the diffusion of the drug through the swollen gel layer at the surface of the tablets. CPM was dispersed at the molecular level in the PEO matrix at low drug loading level and recrystallization of CPM was observed at high drug loading levels. Hot-melt extrusion was demonstrated to be a viable novel method to prepare sustained-release tablets. PEO was shown to be a suitable polymeric carrier for this process.

Chlorpheniramine↗