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Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 451 records · Page 25Linked to original sources
PubMed1996

The chicken FMR1 gene is highly conserved with a CCT 5'-untranslated repeat and encodes an RNA-binding protein.

The transcriptional silencing of the human gene, fragile X mental retardation 1 (FMR1), is due to abnormal methylation in response to an expanded 5'-untranslated CGG trinucleotide repeat and accounts for most cases of fragile X syndrome, a frequent inherited form of mental retardation. Although the encoded fragile X mental retardation protein (FMRP) is known to have properties of a RNA-binding protein, the precise function of FMRP remains to be elucidated. We report the cloning of the chicken homolog of FMR1 and show strong evolutionary conservation, with nucleotide and amino acid identities of 85 and 92%, respectively, between chicken and human. In place of the mammalian CGG trinucleotide repeat, a 99-nt tripartite repetitive element containing a CCT trinucleotide repeat flanked on both sides by dinucleotide repeats was identified. Blocks of highly conserved 3'-untranslated sequence were also found. Within the coding region, two copies each of the highly conserved K homology motif and the Arg-Gly-Gly (RGG) box motif, both ribonucleotide particle family domains implicated in RNA binding, were identified. Chicken FMRP was found to bind RNA in vitro, and this activity correlated with the presence of the carboxy-terminal portion of the protein that includes the RGG motifs.

Animals↗
PubMed1996

Increased stringency of the 1,25-dihydroxyvitamin D3-induced G1 to S phase block in polyploid HL60 cells.

Treatment of mammalian cells with 1,25-dihydroxyvitamin D3 (1,25D3) produces a G1 to S (G1/S) phase cell cycle block. In addition, it has been noted that a smaller proportion of cells accumulates in the G2/M compartment in 1,25D3-treated cultures. Since cyclins have a major influence on the regulation of cell cycle progression, we determined the expression of cyclins A and B as markers of the G2 phase and of cyclin E as the marker of G1/S transition. No increase in the steady-state levels of cyclin A or cyclin B mRNA was detected in the total cell population or in the cyclin B1 protein in the G2/M cell cycle compartment. In contrast, immunodetectable cyclin E protein was increased in cell cultures as a whole and specifically in the G2/M compartment cells. Determination of BrdU incorporation into DNA by flow cytometry showed marked inhibition of DNA replication in cells with DNA content higher than 4C, and autoradiography of 3H-TdR-pulsed cells showed that polynucleated cells did not replicate DNA after 96 h of treatment with 1,25D3 or analogs. Taken together, these experiments show that at least a portion of the G2/M compartment in 1,25D3-arrested cultures of HL60 cells represents G1 cells at a higher ploidy level, which are blocked from entering the high ploidy S phase.

Calcitriol↗
PubMed1996

Rat intercostal nerves as experimental nerve grafts.

In this study, we dissected and measured both sets of intercostal nerves including lengths, diameters, and axon counts in 12 adult rats to provide data applicable to experimental nerve graft research. Dissections showed that total lengths of intercostal nerves from the spinal bifurcation to their last arborizations near the midline ranged from 10 to 89 mm, and diameters ranged from less than 0.1 to 0.5 mm from the thinnest to the thickest part. The segment of easiest dissection was the part between the spinal bifurcation and the lateral cutaneous branch. This part was 4-27 mm (mean, 13.3 mm) long and had an almost constant diameter of 0.18-0.5 mm (mean, 0.32 mm). Counts ranged from 201 to 566 axons/ nerve. The segment proximal to the lateral cutaneous branch was the most convenient part to be harvested as a nerve graft, especially in the 8th to 12th intercostal nerves. These nerves could serve as sources for experimental grafts.

Abdominal Muscles↗
PubMed1996

Magnetic resonance imaging detection of vascular occlusion of a pedicled muscle flap.

Contrast-enhanced magnetic resonance imaging (MRI) can be a highly sensitive monitor of tissue blood perfusion. This technique has been used to assess blood flow through liver, kidney, and certain tumors, but has not been widely applied to the study of skeletal muscle circulation. In our study, we used a novel scanning software to obtain contrast-enhanced T2*-weighted gradient echo MRI images of pedicled quadriceps muscle flaps in rabbits in order to study images of arterial, venous, and arterio-venous occlusion. We administered an intravenous bolus of gadoteridol contrast agent at the initiation of scanning, which produces a decrease in T2*-signal and improves the sensitivity of measuring blood perfusion. Within 30 seconds of MRI scanning, control flaps with intact pedicles exhibited a rapid decrease in T2*-signal intensity, indicating adequate perfusion of blood through muscle tissue; however, occluded pedicled flaps showed no significant change in signal intensity, indicating lack of blood perfusion. Differences in signal intensities as measured by MRI between occluded and control flaps were statistically significant (P < 0.05). Selective vascular occlusion of either artery alone, or both artery and vein were detected within 15 minutes, whereas selective venous occlusion could be detected after 2 hours. We conclude that MRI has the ability to assess skeletal muscle perfusion, and is capable of noninvasively evaluating a cross-section of tissue in both superficial and buried flaps. MRI, therefore, may have the potential for evaluating perfusion in muscle flaps (including buried flaps), and other disorders of muscle circulation such as compartment syndrome.

Animals↗
PubMed1996

New simplified radio-opaque injection technique for visualization of rat arteries.

We have developed a new and simplified injection technique based on a mixture of latex and lead oxide. This injection technique is unique in its possession of both color and radio-opacity. We have developed and refined this methodology in rats, and have demonstrated it to possess superior qualities of injectability. Depiction of small vessels is highly detailed both radiographically and grossly.

Angiography↗
PubMed1996

Application of hemodilution in microsurgical free flap transplantation.

The intra-operative hemodilution and blood auto-transfusion is a blood-saving technique that can be performed when major blood loss is expected. The effects of this technique were studied in 30 microsurgical free flap transplantation patients. Between 400-600 ml blood was collected from the patients before surgery. The patients received dextran, a balanced salt solution, and glucose with the ratio of 3:1 to the collected blood volume, bleeding, and urine before the blood auto-transfusion. There were no significant changes in RBC, HCT, MCV, blood pressure, or heart rate. Of the 30 free flaps, 28 were successful with a 93.3% survival rate. The safety of intra-operative hemodilution and autologous blood transfusion in microsurgery as well as the effect of hemodilution on transplanted flap survival are discussed in this study.

Adult↗
PubMed1996

Effect of anastomosis and geometry of vessel curvature on blood flow velocity and patency in microvessels.

The effect of the geometry of the vessel and the number of anastomoses on the blood flow was studied. Four different shapes of the vessel were constructed by using a 6-cm-long double vein graft model with three anastomoses: (1) an alpha loop, (2) an omega loop, (3) a sigmoid curve, and (4) straight. Blood flow was measured by an ultrasound Doppler flowmeter. The result showed no alternation in blood flow across different geometry and through three patent microanastomoses. However, six out of seven vein grafts were thrombosed at 24 hr postoperative due to vascular kinks. This model demonstrates potential sites of kinking at the dissection end of the femoral artery, the microanastomoses, the side branches of the vein graft, and the adventitial adhesions. This model is recommended to microvascular trainees for the study of kinking and the management of redundant pedicles and vein grafting.

Anastomosis, Surgical↗
PubMed1996

Effect of vein grafting on the survival of microvascularly transplanted muscle flaps.

Since vein grafting is often required during transplantation of free muscle flaps but is associated with a higher failure rate than those flaps transplanted with primary anastomoses, we sought to compare primary repair with the use of vein grafting in an experimental setting. We transplanted the gracilis muscle to the contralateral side in 98 rats using four different methods of vessel repair. In the Control group (n = 28), both femoral vessels were anastomosed primarily. In Experimental Group 1 (n = 25), the femoral artery was anastomosed with an epigastric vein graft and the femoral vein was anastomosed primarily. In Experimental Group 2 (n = 25), the femoral vein was anastomosed with a femoral vein graft and the femoral artery was anastomosed primarily. In Experimental Group 3 (n = 20), both femoral vessels were anastomosed with vein grafts. The Control and Experimental Groups 1-3 survival rates were 89.3, 76.0, 84.0, and 70.0%, respectively; none of the experimental group survival rates was significantly different from that of the control (P < 0.5). This study demonstrates that the use of size-matched, interpositional vein grafts in the arterial or venous pedicle of the rat gracilis muscle flap during transplantation did not significantly decrease flap survival as compared to primary arterial or venous anastomoses. If the observed failure rate persisted with expansion of the study groups to 60-100 animals each, the failure rate of flaps with vein grafts would be significantly lower and comparable to failure rates reported in some clinical series. The large numbers necessary to significantly show this decrease make this model impractical for further studies.

Anastomosis, Surgical↗
PubMed1996

Development of the anti-Ro autoantibody response in a patient with systemic lupus erythematosus.

OBJECTIVE: To characterize the initial events in anti-Ro production by a patient with systemic lupus erythematosus, in whom this autoantibody is developing. METHODS: The immune response to the Ro ribonucleoprotein and other autoantigens were studied by enzyme-linked immunosorbent assay for IgG and IgM, by isoelectric focusing, and by inhibition studies to determine apparent avidity. RESULTS: The patient's sera showed an oligoclonal response to Ro that increased in complexity and affinity with time. IgM anti-Ro appeared shortly before IgG anti-Ro, and disappeared as IgG anti-Ro increased in titer and affinity. IgG antiribosomal P autoantibodies also appeared during the patient's course, but in contrast to anti-Ro, were not preceded by IgM antiribosomal P. CONCLUSION: These data are consistent with the Ro autoantigen being presented and processed in a manner similar to heterologous antigen, and with differences in the mechanisms that lead to the production of IgG anti-Ro autoantibodies as opposed to antiribosomal P autoantibodies.

Adult↗
PubMed1996

Use of internally controlled reverse transcriptase-polymerase chain reaction for absolute quantitation of individual multidrug resistant gene transcripts in tissue samples.

Research into the relative importance of P-glycoprotein (pgp) overexpression, in comparison to other mechanisms of multidrug resistance (mdr) phenotype development, has been hampered by difficulties of measurement in clinical samples. The small size, heterogeneity and often poor quality of clinical specimens renders the quantitation of mdr mRNA species by Northern analysis or RNAse protection difficult. The reverse transcriptase-polymerase chain reaction (RT-PCR) assay has both the sensitivity and specificity to make it suitable for the analysis of mdr mRNA levels in clinical samples. It also has a significant speed advantage over Northern and RNAse protection analysis. Unfortunately the variable nature of the reactions involved have made it difficult to obtain accurate and reproducible quantitative data. To overcome this difficulty we constructed internal RNA standards to each human and rat mdr mRNA species. When included in the RT-PCR reaction these internal standards allow both comparative and absolute quantitation of individual mdr family mRNA levels.

Animals↗
PubMed1996

Effects of SCN substitution for Cl- on tension, [Ca2+]i, and ionic currents in vascular smooth muscle.

Substitution of thiocyanate ions (SCN-) for chloride ions (Cl-) in the extracellular medium of aortic rings and strips causes a biphasic contractile response; initial relaxation followed by sustained contraction. Alterations in these responses are sex-specific, and may elucidate fundamental differences in vascular function between males and females. In order to investigate the role of changes in intracellular Ca2+ ([Ca2+]i) in these changes in tension, we investigated effects of SCN- on [Ca2+]i and ionic currents in vascular smooth muscle cells (VSMC). Extracellular substitution of SCN- for Cl- caused a biphasic change in [Ca2+]i. Initially, [Ca2+]i decreased, reaching a minimum within 1-2 min, subsequently returned to original levels within 4-5 min, and then increased to a higher plateau over the next 10 minutes. This pattern of change in [Ca2+]i is identical to the pattern of tension changes in aortic rings, but it occurs somewhat faster. Partial substitution of SCN- for Cl- elicited increased, but no preceding decrease in [Ca2+]i. In the absence of external Ca2+, anion substitution elicited the decrease in [Ca2+]i but not the subsequent increase. Verapamil (1 microM) blocked the increased [Ca2+]i phase but not the decreased [Ca2+]i phase; whereas, R+ verapamil (up to 5 microM for 20 min), an inactive enantiomer, caused no change. Ionic current measurements obtained using whole cell patch and current clamp techniques revealed two responses to anion substitution: (a) a rapid, transient outward shift in holding current, and (b) a sustained increase in peak current and a hyperpolarizing shift in voltage sensitivity of Ca2+ channels. The calcium channel blocker PN200-110 blocked SCN(-)-enhanced current but had no effect on the changes in holding current. S- verapamil, but not R+ verapamil, reduced SCN(-)-enhanced current. In current clamp mode, SCN- caused an initial hyperpolarization followed by a slow depolarization punctuated by spikes. Thus, SCN- causes changes in vascular smooth muscle [Ca2+]i that could underlie both phases of its effects on tension in isolated aortas and may be explained by the following model: an initial outward shift in current causes hyperpolarization with a consequent decrease in cell excitability, and the somewhat slower increase in Ca2+ channel excitability eventually leads to enhanced calcium influx and tension. These data shed light on possible mechanisms underlying gender-related differences in VSMC physiology.

Acetylcholine↗
PubMed1996

Diurnal pattern of QTc interval: how long is prolonged? Possible relation to circadian triggers of cardiovascular events.

OBJECTIVES: This study sought to evaluate the range and variability of the QT and corrected QT (QTc) intervals over 24 h and to assess their pattern and relation to heart rate variability. BACKGROUND: Recent Holter monitoring data have revealed a high degree of daily variability in the QTc interval. The pattern of this variability and its relation to heart rate variability remain poorly characterized. METHODS: We developed and validated a new method for continuous measurement of QT intervals from three-channel, 24-h Holter recordings. Average RR, QT, QTc and heart rate variability were measured from 5-min segments of data from 21 healthy subjects. RESULTS: Measurement of 6,048 segments showed mean (+/- SD) RR, QT and QTc intervals of 830 +/- 100, 407 +/- 23 and 445 +/- 16 ms, respectively (mean QTc interval for men 434 +/- 12 ms, 457 +/- 10 ms for women, p < 0.0001). The average maximal QTc interval was 495 +/- 21 ms and the average QTc range 95 +/- 20 ms. The maximal QTc interval was > or = 500 ms in 6 subjects and > or = 490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and the high frequency component of heart rate variability were greater during sleep. Both the QTc interval and the variability between hourly minimal and maximal QTc intervals reached their circadian peak shortly after awakening, before declining to daytime levels. CONCLUSIONS: The maximal QTc interval over 24 h in normal subjects is longer than heretofore thought. Both QT and QTc intervals are longer during sleep. The QTc interval and QTc variability reach a peak shortly after awakening, which may reflect increased autonomic instability during early waking hours, and the time of the peak value corresponds in time to the period of reported increased vulnerability to ventricular tachycardia and sudden cardiac death. These findings have implications regarding the definition of QT prolongation and its use in predicting arrhythmias and sudden death.

Adult↗
PubMed1996

delta Opioid extends hypothermic preservation time of the lung.

To test the hypothesis that a delta opioid, DADLE ([D-Ala2, D-Leu5]-enkephalin), could protect tissue from ischemic damage during hypothermic lung preservation, we studied three groups of rats. In group 1 (n = 8), lung function was studied immediately after harvesting. In group 2 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution and preserved for 24 hours. In group 3 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution plus DADLE (1 mg/kg) and preserved for 24 hours. Lung function was studied by using a living rat perfusion model. Venous blood from the host rat perfused the pulmonary artery of the isolated lung. Blood from the isolated lung was returned to the carotid artery of the host rat with a roller pump. Severe pulmonary edema, hemorrhage, and occlusive pulmonary artery resistance occurred in group 2 within 30 minutes of perfusion. Perfusion studies were carried out for more than 60 minutes in groups 1 and 3. Pulmonary blood flow was lower in group 2 than in either group 1 or group 3. Pulmonary vascular resistance was much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway pressure and airway resistance were much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway resistance was also higher in group 3 than in group 1 after 20 minutes of perfusion (p < 0.05). Oxygen tensions from the pulmonary vein of the isolated lung in group 2 were lower than those in groups 1 and 3 (p < 0.05). Alveolar-arterial oxygen difference was much higher in group 2 than in groups 1 and 3 (p < 0.05). Lung tissue wet/dry weight ratio after perfusion was much higher in group 2 than in groups 1 and 3. The results clearly show, for the first time, that DADLE can effectively enhance hypothermic lung preservation in rats.

Airway Resistance↗
PubMed1996

Subtherapeutic erythropoietin and insulin-like growth factor-1 correct the anemia of chronic renal failure in the mouse.

Chronic renal failure (CRF) is associated with a hyporegenerative anemia, which is caused primarily by inadequate production of erythropoietin (EPO) by the diseased kidneys and is responsive to exogenous EPO administration. Little is known about compensatory mechanisms that might supervene in anemia with low levels of EPO. Multiple investigations in vitro suggest an important role for insulin-like growth factor-1 (IGF-1) as well as EPO in erythropoiesis. Recently, both EPO and IGF-1 in vitro have been found to stimulate erythroid colony forming units in the mouse. However, no studies have examined the effect of IGF-1, singly and in combination with EPO, in CRF in vivo. This study examined mice with surgically-induced renal failure of six weeks duration that were treated for three weeks with the combination of subtherapeutic doses of both EPO and IGF-1. The single administration of each cytokine caused no significant change in hemoglobin in all CRF mice. In marked contrast the combined administration of the two cytokines produced a striking rise in hemoglobin, resulting in anemia correction in the majority of animals. The response to the combination therapy was comparable to the maximal response obtained with a single EPO dose (10 U) in a dose-finding study. Although the data are limited to utilizing one dose of each cytokine and one preparation of IGF-1, the large increase in hemoglobin observed with the combination therapy indicates that these two cytokines work in concert to stimulate erythroid precursors in CRF. In addition, untreated CRF mice showed markedly increased serum levels of low molecular weight binding proteins for IGF-1, potentially reducing the bioavailability of IGF-1. These findings taken together suggest that the anemia of CRF may represent both an EPO and a functional IGF-1 deficient state.

Anemia↗
PubMed1996

Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell activation.

We have developed peptide analogs to analyze precise human CD4 substructures involved in MHC class II binding. Forms of the complementarity determining-like regions (CDRs) of the D1 domain of human CD4 were reproduced as synthetic aromatically modified exocyclic (AME) analogs and tested for their ability to block CD4-MHC II interactions and T cell activation. The exocyclic derived from CDR3 (residues 82-89) of human CD4, which specifically associated with CD4 on the T cell surface to create a heteromeric CD4 complex, blocked IL-2 production and antagonized the normal function of the CD4 receptor. The approach of creating novel synthetic antagonistic receptor complexes may represent a new receptor specific pharmaceutical approach to modulate biological function.

Amino Acid Sequence↗
PubMed1996

Identification of betaine as an osmolyte in rat liver macrophages (Kupffer cells).

BACKGROUND & AIMS: Anisosmotic cell volume changes were identified recently as a critical factor in the regulation of eicosanoid formation in stimulated liver macrophages (Kupffer cells). Therefore, the aim of this study was to investigate whether osmolytes are involved in the control of Kupffer cell function. METHODS: Cultured rat liver macrophages (Kupffer cells) were studied with respect to their functional adaptation to hyperosmotic environments. RESULTS: Hyperosmotic exposure of lipopolysaccharide-stimulated Kupffer cells led to sevenfold stimulation of prostaglandin E2 formation caused by a strong induction of cyclooxygenase 2. Hyperosmotic exposure was accompanied by approximately a 10-fold increase of Na(+)-dependent betaine uptake and betaine transporter-messenger RNA levels. Conversely, hypoosmotic exposure decreased betaine uptake and stimulated betaine release from Kupffer cells and the perfused rat liver. Addition of betaine (1 mmol/L) to hyperosmotically exposed Kupffer cells abolished the strong induction of cyclooxygenase 2 and the increase of prostaglandin E2 formation. CONCLUSIONS: This study identifies the use of an osmolyte strategy in liver macrophages. Betaine serves as an osmolyte in Kupffer cells, whose transport is induced in response to increases of ambient osmolarity. Regulation of this transporter as well as betaine availability may represent a novel regulation site for Kupffer cell function.

Animals↗