Importance of protection of cold-stored small intestine against oxygen free-radical-induced injury during the initial period of reperfusion.
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Adenosine↗
Biomedical subjects
S C Sun
Publications and source records attributed to S C Sun.
Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury?
After crystalloid cardioplegic arrest, cardiac-derived thromboxane A2 may be an important initiating mediator of no-reflow and hemodynamic deterioration during reperfusion because of its potent vasoactive properties. Although previous studies have already documented the increased release of cardiac thromboxane A2 after ischemia, none have studied the effects of cardiac thromboxane A2 on hemodynamics. We therefore tested the ability of cardiac thromboxane A2 to mediate deterioration of coronary flow and functional recovery during reperfusion after global ischemia. Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548. In eight of 15 hearts in each group, preischemic and postischemic aortic flow, coronary flow, cardiac output, heart rate, and stroke work were determined. In the remaining seven hearts in each group, preischemic and postischemic coronary effluent levels of the stable hydrolysis product of thromboxane A2 and thromboxane B2 were determined with radioimmunoassay through the use of nonrecirculating perfusate. At the completion of the experiment, water content was determined by wet weight/dry weight calculations. In a separate group (n = 7) preischemic myocardial water content was determined. Within the group protected by cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly decreased (p < 0.05) compared with preischemic values (aortic flow, 50.8 +/- 2.7 versus 29.4 +/- 3.3 ml/min; coronary flow, 13.2 +/- 1.3 versus 8.5 +/- 1.3 ml/min; cardiac output, 64.0 +/- 3.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.5 +/- 0.7 versus 7.1 +/- 0.8 cm H2O.ml). In relation to the group with cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly greater (p < 0.05) in the group with the receptor antagonist (aortic flow: 49.5 +/- 2.4 versus 29.4 +/- 3.3 ml/min; coronary flow; 12.4 +/- 1.2 versus 8.5 +/- 1.3 ml/min; cardiac output, 62.0 +/- 2.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.6 +/- 0.8 versus 7.1 +/- 0.8 cm H2O.ml). Overall, postischemic coronary effluent thromboxane B2 levels were greater than preischemic values (105.6 +/- 12.4 versus 69.6 +/- 9.8, p < 0.05) and treatment with the receptor antagonist did not significantly affect postischemic thromboxane B2 levels (92.0 +/- 7.3 versus 82.3 +/- 15.5, p = not significant). Neither ischemia nor treatment with the receptor antagonist significantly affected heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Cecropia immunoresponsive factor, an insect immunoresponsive factor with DNA-binding properties similar to nuclear-factor kappa B.
The immune genes in Hyalophora cecropia contain an upstream sequence that is homologous to the binding site of the mammalian nuclear-factor kappa B (NF-kappa B). These genes are strongly induced by bacteria, lipopolysaccharides and 4 beta-phorbol 12-myristate 13-acetate. Induction of the immune genes involves the activation of a DNA-binding protein complex that we have named Cecropia immunoresponsive factor (CIF). CIF specifically recognizes the kappa B-like DNA sequences in the promoter regions of the Cecropia immune genes. The DNA binding activity of CIF correlates well with the transcriptional induction of the immune genes. Competition assays show that CIF has a DNA binding specificity similar to mammalian NF-kappa B. The two factors also share other characteristics, including the pattern of induction and the migration on the native gel.
Animals↗
Improved distribution of antegrade cardioplegic solution with simultaneous coronary sinus occlusion following acute coronary artery occlusion.
This study was designed to evaluate the distribution of cardioplegic solution infused antegradely with simultaneous coronary sinus occlusion. After 1 hr LAD occlusion, sheep were placed on cardiopulmonary bypass. Hearts were arrested with 300 ml of cold cardioplegia and replenished with two additional doses. In group I (n = 10), antegrade cardioplegia (ACP) was given alone; in group II (n = 9), ACP was given in combination with simultaneous coronary sinus occlusion. Microspheres were infused into the cardioplegic line to determine the antegrade distribution of the solution, while a different microsphere was injected into the anterior interventricular vein to detect the venous backflow of the solution. The data showed that myocardium distal to LAD occlusion in group II received more antegrade (0.17 +/- 0.02 versus 0.06 +/- 0.02 ml/g/min, P less than 0.01, in subendocardium; and 0.15 +/- 0.03 versus 0.09 +/- 0.02 ml/g/min, P = NS, in subepicardium) and retrograde (2181 +/- 455 versus 0 counts/g/min, P less than 0.01, in subendocardium; and 2,146 +/- 527 versus 0 counts/g/min, P less than 0.01, in subepicardium) distribution of cardioplegic solution in comparison to group I. We therefore conclude that simultaneous coronary sinus occlusion significantly improves the distribution of antegrade cardioplegic solution to the regionally occluded myocardium by increasing collateral flow as well as venous backflow.
Animals↗
Superoxide dismutase: enhanced small intestinal preservation.
Injury from oxygen free radicals has been suggested to be of greater significance in the preservation of small intestine than of other organs. To determine if using the free radical scavenger, superoxide dismutase (SOD), with University of Wisconsin (UW) solution would improve preservation of small intestine, acute and chronic studies were conducted. Thirty-centimeter segments of small intestine from Lewis rats were flushed with and stored in Collins, UW, or SOD-modified (8000 U/ml) UW solution at 4 degrees C for 18 hr. For the acute study, small intestine segments were subsequently reperfused using support rats. The support rats in the UW/SOD group also received SOD (1750 U, iv) at the onset of reperfusion of small intestine. After 2 hr of reperfusion, maltose absorption and weight gain of small intestine were determined. For the chronic study, small intestine segments were transplanted as isografts. SOD (1750 U, iv) was also given to recipients prior to reperfusion of grafts in the UW/SOD group. Long-term effects were determined by recipient survival for at least 17 days. Results showed the small intestine in the UW/SOD group had the best recovery of mucosal absorption (256 +/- 39 versus 202 +/- 21 in the Collins group, P less than 0.01), the least percentage weight gain (19 +/- 3% versus 25 +/- 5% in the UW group and 38 +/- 5% in the Collins group, P less than 0.01), and the best 17-day survival rate (9/12 versus 2/9 in the UW group, P less than 0.025, and 0/8 in the Collins group, P less than 0.01) among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine↗
Use of hot wire anemometry to measure velocity of the limb during human movement.
Hot film anemometry, x-configuration probes were used in two experiments to evaluate their effectiveness at measurement of limb velocity. Data from tests with a probe attached to the end of a pendulum establish that the hot films measure velocity in the swing phase within 0.098 ms-1. The kinetic energy per unit mass of the pendulum was predicted within +/- 0.005 m2 s-2, from the measured velocity. In gait experiments with one human subject at speeds greater than 0.25 ms-1, the hot film anemometer and a video system predicted speeds within 0.083 ms-1. The hot film data are electronic signals that are easily stored and processed. The results from these experiments demonstrate that hot film anemometry is an effective and efficient method for direct measurement and analysis of the limb velocity.
Biophysical Phenomena↗
Affinity purification and characterization of CIF, an insect immunoresponsive factor with NF-kappa B-like properties.
1. A rapid DNA affinity purification procedure was worked out for the purification of the Cecropia Immunoresponsive Factor (CIF) from the pupae of Hyalophora cecropia. 2. CIF consists of a single polypeptide chain of 65 kDa and is present as a homodimer under native conditions. 3. CIF binds to the kappa B-like sequences upstream of the H. cecropia immune genes with the following order of affinity: attacin kappa B greater than lysozyme kappa B greater than cecropin A kappa B greater than cecropin B kappa B. 4. The purified CIF also strongly binds to the kappa B sequences from both the immunoglobulin kappa light chain gene and the MHC class I gene. 5. The DNA binding of CIF can be inhibited by antisera directed against NF-kappa B-related proteins. 6. The cytoplasmic factor Cl, co-purified from the affinity column, contains two polypeptide chains, one of which has the same molecular weight as CIF.
Animals↗
I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding.
The active nuclear form of the NF-kappa B transcription factor complex is composed of two DNA binding subunits, NF-kappa B p65 and NF-kappa B p50, both of which share extensive N-terminal sequence homology with the v-rel oncogene product. The NF-kappa B p65 subunit provides the transactivation activity in this complex and serves as an intracellular receptor for a cytoplasmic inhibitor of NF-kappa B, termed I kappa B. In contrast, NF-kappa B p50 alone fails to stimulate kappa B-directed transcription, and based on prior in vitro studies, is not directly regulated by I kappa B. To investigate the molecular basis for the critical regulatory interaction between NF-kappa B and I kappa B/MAD-3, a series of human NF-kappa B p65 mutants was identified that functionally segregated DNA binding, I kappa B-mediated inhibition, and I kappa B-induced nuclear exclusion of this transcription factor. Results from in vivo expression studies performed with these NF-kappa B p65 mutants revealed the following: 1) I kappa B/MAD-3 completely inhibits NF-kappa B p65-dependent transcriptional activation mediated through the human immunodeficiency virus type 1 kappa B enhancer in human T lymphocytes, 2) the binding of I kappa B/MAD-3 to NF-kappa B p65 is sufficient to retarget NF-kappa B p65 from the nucleus to the cytoplasm, 3) selective deletion of the functional nuclear localization signal present in the Rel homology domain of NF-kappa B p65 disrupts its ability to engage I kappa B/MAD-3, and 4) the unique C-terminus of NF-kappa B p65 attenuates its own nuclear localization and contains sequences that are required for I kappa B-mediated inhibition of NF-kappa B p65 DNA binding activity. Together, these findings suggest that the nuclear localization signal and transactivation domain of NF-kappa B p65 constitute a bipartite system that is critically involved in the inhibitory function of I kappa B/MAD-3. Unexpectedly, our in vivo studies also demonstrate that I kappa B/MAD-3 binds directly to NF-kappa B p50. This interaction is functional as it leads to retargeting of NF-kappa B p50 from the nucleus to the cytoplasm. However, no loss of DNA binding activity is observed, presumably reflecting the unique C-terminal domain that is distinct from that present in NF-kappa B p65.
Animals↗
[Comparative study of brain tumors treated at China Medical University, China and Kyushu University, Japan].
We have re-examined histopathological specimens of brain tumors extirpated at China Medical University from May, 1990 to June, 1992. During the last 2 years, about 400 cases of brain tumors were operated and 349 cases were histopathologically diagnosed and classified by one of the authors (T. I). The most common tumor was meningioma, 97 cases, followed by gliomas, 87 case and neurinoma, 71 cases. The sex and age distributions of these three tumor types were compared to those of Kyushu University Hospital, Japan. The most striking difference was age of meningioma and neurinoma patients, and Chinese patients were 10 years younger than Japanese patients. The incidence of 30th age group of meningioma was 25% in China and 10% in Japan. Thirty percent of neurinoma patients were operated at 30th and 40th age in China and Japan, respectively. The sex and ages of astrocytoma patients were almost the same frequencies in China and Japan. Among 22 cases of congenital tumors, 11 cases of epidermoid tumor in cerebello-pontine cistern was included. Cerebral tuberculoma, although rarely encountered in Japan, was 2 cases in China.
Adolescent↗
Improved recovery of heart transplants by combined use of oxygen-derived free radical scavengers and energy enhancement.
Oxygen free radical injury during reperfusion of ischemically stored heart transplants may further impair the ability of the transplanted heart to reuse substrate for recovery. We compared the effects of oxygen free radical scavengers, superoxide dismutase and catalase, either alone or combined with glucose-insulin-potassium, in an improved model of the heterotopically transplanted rat heart. Group 1 hearts (n = 8) received no preservation before transplantation and were transplanted immediately. Hearts in four other groups (n = 8 for each group) underwent cold storage (4 degrees to 6 degrees C) for 3 1/2 hours before transplantation. Five minutes before reperfusion of the transplanted hearts, recipient rats received one of the following intravenous treatments: saline (group 2), glucose-insulin-potassium (group 3), superoxide dismutase/catalase (group 4), and superoxide dismutase/catalase plus glucose-insulin-potassium (group 5). Left ventricular end-diastolic pressure, rate of rise of left ventricular pressure, myocardial blood flow, coronary resistance, and tissue adenosine triphosphate content of the heart transplants were assessed during or at the end of 2 hours of reperfusion. Hearts treated with superoxide dismutase/catalase alone showed improvement of end-diastolic pressure and myocardial blood flow. The use of glucose-insulin-potassium alone did not facilitate the recovery of transplanted hearts. In contrast, the combined use of superoxide dismutase/catalase plus glucose-insulin-potassium resulted in a superior recovery of all functional and hemodynamic parameters. These results indicate that free radical scavengers in the presence of glucose-insulin-potassium significantly improve functional recovery in the setting of heart transplantation.
Animals↗
An electrophysiological correlate of protein kinase C isozyme distribution in cultured cerebellar neurons.
Protein kinase C (PKC) is a family of at least seven closely related molecules (isozymes) that vary in terms of their requirements for activation and their distribution among cells of the brain. A striking example of this differential distribution is seen in the cerebellum, where Purkinje cells express PKC-I, an isozyme that is strongly activated by both phorbol ester (PE), and low doses of cis-unsaturated fatty acid (c-UFA), while granule cells predominantly express PKC-II, an isozyme that is strongly activated by PE but not c-UFA. Both Purkinje and granule cells have large, easily recorded voltage-gated K currents. These currents are attenuated by PKC activators in several other varieties of neuron. We hypothesized that the effects of these two PKC activators would be predicted by the distribution of the relevant PKC isozyme, and that the delayed outward rectifier current, IK, would be attenuated by both PE and c-UFA in Purkinje cells, but only by PE in granule cells. This hypothesis was confirmed in perforated-patch recordings. The attenuation produced by both activators could be blocked by application of a specific PKC inhibitor, RO-31-8220, and could not be mimicked by inert forms of PE or c-UFA. To our knowledge, this study represents the first report of an electrophysiological correlate of PKC isozyme distribution.
Animals↗
Improved small intestinal preservation with additional use of superoxide dismutase to University of Wisconsin solution.
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Adenosine↗
[CT findings in "fresh" cerebral paragonimiasis].
There are few reports on CT findings in "fresh" cerebral paragonimiasis. We have experienced four cases of "fresh" cerebral paragonimiasis examined by CT scan. Three patients were children aged 7, 9, and 14 years, and one was an adult aged 25 years. Three patients were examined by CT scan 2 to 6 months after the onset of high grade fever, convulsion and focal deficit signs, and a patient was examined one month after his progressive visual disturbance. The unique CT findings are multilocular cystic lesions in temporo-occipital or in temporo-parietal lobes with extensive brain edema. Two cases were also associated with "soap-bubble" calcifications. The cysts were more dense than CSF and enhanced by contrast media. The histopathological specimen showed that the eggs of paragonimus were in the abscess cavity, of which the wall was composed with highly vascular gliomesenchymal capsule and numerous cell infiltration. Three patients underwent craniotomy for removal of abscess and decompression. Bitionol were administered and all patients recovered well. We also discussed the differential diagnosis of cerebral parasitic granulomas.
Adolescent↗
Organization and expression of the immunoresponsive lysozyme gene in the giant silk moth, Hyalophora cecropia.
Lysozyme is one of the antibacterial proteins that are produced by the giant silk moth Hyalophora cecropia in response to bacterial infection or injury. As an essential step toward the understanding of the mechanisms involved in the immune response, we have isolated and characterized the lysozyme gene from Cecropia. The complete nucleotide sequence of the gene as well as the immediate flanking sequences have been determined. The gene includes three exons. Its first intron contains a repetitive sequence. In the evolutionary aspect, the Cecropia lysozyme gene and two vertebrate lysozyme genes have been found to maintain a similar organization pattern of exons. The lysozyme gene has been found to be strongly induced by lipopolysaccharides and a phorbol ester as well as bacteria. In the induction by bacteria, the lysozyme transcript appears at about 2 h, reaches to the maximum level at about 24 h, and then declines. Comparison of the 5'-flanking sequences with several other genes involved in the immune response of H. cecropia and Drosophila melanogaster revealed a kappa B-like consensus sequence. This sequence is specifically recognized by a nuclear protein from the induced pupa.
Amino Acid Sequence↗
Structure and expression of the attacin genes in Hyalophora cecropia.
To study the regulation of the immune genes in insects, we have cloned and sequenced the attacin gene locus of the giant silk moth Hyalophora cecropia. The locus contains one acidic and one basic attacin gene as well as two pseudogenes, which are remnants of basic attacin genes. A small insertion element was found within the locus. The two functional attacin genes are transcribed in opposite directions and have two introns inserted at homologous positions. A common sequence, GGGGATTCCT, is found at nucleotide position -48 in the acidic gene and at nucleotide position -58 in the basic gene. Interestingly, this decanucleotide is similar to the consensus of the NF-k B-binding site. Expression studies revealed that both attacins are strongly induced by phorbol 12-myristate 13-acetate, lipopolysaccharide and bacteria. However, only the acidic attacin gene showed a clear response to injury.
Animals↗
The dynamics of antegrade cardioplegia with simultaneous coronary sinus occlusion. Effects on aortic root infusion pressure, coronary sinus pressure, and myocardial cooling.
It has been suggested that antegrade cardioplegia with coronary sinus occlusion improves homogeneous myocardial cooling and reduces myocardial injury in the presence of coronary artery occlusion. Little data are available on the exact relationships among the basic elements or this intervention, including antegrade infusion rate, aortic root pressure, the degree of coronary sinus occlusion, coronary sinus pressure, and myocardial cooling. The purpose of this study was to determine these relationships and to provide some basic guidelines for better understanding of this intervention. Twenty-two sheep were placed on cardiopulmonary bypass, the distal left anterior descending artery was occluded, and the proximal coronary sinus was snared. Sixteen combinations of infusion rate (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade cardioplegia, yielding 96 measurements. Myocardial temperatures in the occluded and nonoccluded regions, aortic root infusion pressure, and coronary sinus pressure were measured during each infusion of cardioplegic solution. Coronary sinus occlusion was then released, and the whole heart was reperfused for 30 minutes for another infusion of cardioplegic solution and measurements. Results showed good degrees of linearity between infusion rate and aortic root infusion pressure for all coronary sinus occlusion and noninfusion groups (p less than 0.01). A positive effect of coronary sinus occlusion on aortic root infusion pressure was observed. The graded increases in infusion rate with various degrees of coronary sinus occlusion were constantly associated with elevation of coronary sinus pressure (p less than 0.01). It was also noted that myocardial temperatures in the region of the occluded left anterior descending artery were significantly lower in coronary sinus occlusion groups than in nonocclusion groups (p less than 0.01 or 0.05). Myocardial temperature in the nonoccluded region decreased significantly with the stepwise increases in infusion rate (p less than 0.01), but not with the increases in coronary sinus occlusion (not significant). Based on this and previous studies, we recommend that the induced coronary sinus pressure be safely maintained in the range of 25 to 35 mm Hg and that further studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total coronary sinus occlusion for the intervention of antegrade cardioplegia plus coronary sinus occlusion.
Animals↗
Hemolin: an insect-immune protein belonging to the immunoglobulin superfamily.
Insects have an efficient defense system against infections. Their antibacterial immune proteins have been well characterized. However, the molecular mechanisms by which insects recognize foreignness are not yet known. Data are presented showing that hemolin (previously named P4), a bacteria-inducible hemolymph protein of the giant silk moth Hyalophora cecropia, belongs to the immunoglobulin superfamily. Functional analyses indicate that hemolin is one of the first hemolymph components to bind to the bacterial surface, taking part in a protein complex formation that is likely to initiate the immune response.
Amino Acid Sequence↗
Cardioplegia for the immature myocardium. A comparative study in the neonatal rabbit.
This study examined the effect of hypothermia (15 degrees C) alone or combined with various cardioplegic solutions on functional recovery of the neonatal heart after 120 minutes of global ischemia in an isolated working rabbit heart model. Control hearts were preserved with hypothermia alone, and groups 1 to 6 were given different hyperkalemic crystalloid cardioplegic solutions. Each cardioplegic solution differed in Na+ and Ca++ content. Aortic flow, coronary flow, cardiac output, heart rate, peak systolic pressure, and stroke work were measured before ischemia and after 35 and 45 minutes of reperfusion. There were no statistical differences in hemodynamic recovery in the six groups in which cardioplegia was used. However, hearts preserved with multidose hyperkalemic cardioplegia showed significantly better recovery of cardiac output (86% versus 75%; p less than 0.05), coronary flow (88% versus 72%; p less than 0.05), and stroke work (86% versus 75%; p less than 0.05) than those preserved with hypothermia alone. These results suggest that hypothermic hyperkalemic cardioplegia improves preservation of the neonatal rabbit heart but that variations in Ca++ and Na+ content appear not to provide further myocardial protection.
Age Factors↗