Biomedical subjects

C Z Chen

Publications and source records attributed to C Z Chen.

At least 19 recordsLinked to original sources

PubMed2005

Insights into biological functions across species: examining the role of Rab proteins in YIP1 family function.

The YIP1 family comprises an evolutionarily conserved group of membrane proteins, which share the ability to bind di-prenylated Rab proteins. The biochemical capability of YIP1 family proteins suggests a possible role in the cycle of physical localization of Rab proteins between their cognate membranes and the cytosol. YIP1 is essential for viability in yeast and a deletion of YIP1 can be rescued with the human homologue YIP1A. We have made use of this evolutionary conservation of function to generate a series of mutant alleles of YIP1 to investigate the biological role of Yip1p. Our findings indicate evidence for the participation of Yip1p in both Rab and COPII protein function; at present, we are not able to distinguish between the models that these roles represent, i.e. independent or dependent activities of Yip1p.

ADP-Ribosylation Factors↗

PubMed2004

Effect of cardiopulmonary bypass on leukocyte activation: changes in membrane-bound elastase on neutrophils.

BACKGROUND: Neutrophil elastase is known to be released from the activated leukocytes as a result of cardiopulmonary bypass (CPB). However, its biological effect on organ injury is questionable because it is quickly bound by natural proteinase inhibitors (PIs). Recently, membrane-bound elastase (MBE) was found to be able to resist the PIs' process and, thus, is biologically more active. This paper studies the effect of CPB on the kinetic change of MBE and its possible link to postoperative inflammation and organ function. METHOD: Ten consecutive patients undergoing elective coronary artery bypass grafting (CABG) surgery with CPB were recruited into the study. Blood samples were taken before sternotomy, after aortic declamping, at the end of CPB, three and six hours after CPB and on the first postoperative day. MBE was determined by substrate assay from isolated neutrophils. Inflammation and organ function markers methods. RESULTS: MBE slightly increased after aortic declamping, while it significantly increased and reached its peak at the end of CPB; it returned to its preoperative level on the first postoperative day. In contrast to lung sequestration of neutrophils, there was no transpulmonary gradient of MBE between left and right atria after aortic declamping. Neither MBE nor total MBE activity was positively correlated with postoperative inflammation markers such as blood lactate and C-reactive protein and organ function markers such as creatine phosphokinase and alanine aminotransferase. CONCLUSIONS: CPB induces increased MBE expression on neutrophils with its peak at the end of CPB. Lack of association between neutrophil MBE and clinical markers suggests that multiple systems might be involved in the post-CPB inflammatory reaction and organ dysfunction.

Aged↗

PubMed2000

Analysis of the interactions of human ribonuclease inhibitor with angiogenin and ribonuclease A by mutagenesis: importance of inhibitor residues inside versus outside the C-terminal "hot spot".

Ribonuclease inhibitor (RI) binds diverse mammalian RNases with extraordinary avidity. Here, we have investigated the structural basis for this tight binding and broad specificity by mutational analysis of the complexes of RI with angiogenin (Ang) and RNase A (K(D)=0.5 fM and 43 fM, respectively). Both crystal structures are known; the interfaces are large, and the ligands dock similarly, although few of the specific interactions formed are analogous. Our previous mutagenesis studies focused primarily on one contact region, containing RI 434-438 and the enzymatic active site. Many single-residue replacements produced extensive losses of binding energy (2.3-5.9 kcal/mol), suggesting that this region constitutes a "hot spot" in both cases. We have now explored the roles of most of the remaining RI residues that interact with Ang and/or RNase A. One major cluster in each complex lies in a Trp-rich area of RI, containing Trp261, Trp263, Trp318, and Trp375. Although the energy losses from individual replacements in this portion of the Ang complex were small-to-moderate (0-1.5 kcal/mol), the changes from multiple substitutions were much greater than additive, and the binding energy provided by this region is estimated to be approximately 6 kcal/mol (30 % of total). Effects of replacing combinations of hot spot components had also been found to be superadditive, and this negative cooperativity is now shown to extend to the neighboring contact residue RI Ser460. The overall contribution of the hot spot, taking superadditivity into account, is then approximately 14-15 kcal/mol. The hot spot and Trp-rich regions, although spatially well separated, are themselves functionally linked. No other parts of the RI-Ang interface appear to be energetically important. Binding of RNase A is more sensitive to substitutions throughout the interface, with free energy losses>/=1 kcal/mol produced by nearly all replacements examined, so that the sum of losses greatly exceeds the binding energy of the complex. This discrepancy can be explained, in part, by positive cooperativity, as evident from the subadditive effects observed when combinations of residues in either the hot spot or Trp-rich region are replaced. These findings suggest that the binding energy may be more widely distributed in the RNase A complex than in the Ang complex.

Amino Acid Motifs↗

PubMed2000

Quaternary ammonium functionalized poly(propylene imine) dendrimers as effective antimicrobials: structure-activity studies.

Quaternary ammonium functionalized poly(propyleneimine) dendrimers were synthesized and their antibacterial properties were evaluated using a bioluminescence method. These quaternary ammonium dendrimers are very potent biocides. The antibacterial properties depend on the size of the dendrimer, the length of hydrophobic chains in the quaternary ammonium groups, and the counteranion. Since these dendrimers are well characterized and monodisperse, they also serve as an effective system to study the structure-activity relationship. The antimicrobial properties of these dendrimer biocides have a parabolic dependence on molecular weight, which is different from the bell-shaped molecular weight dependence of conventional polymer biocides. The dependence on the hydrophobic chain of the quaternary ammonium structure is similar to conventional polymer biocides, and shows a parabolic relationship with dendrimer biocides carrying C10 hydrophobes the most potent. The antimicrobial properties of these novel biocides with bromide anions are more potent than those with chloride anions. Biocides derived from hyperbranched polymers were also synthesized and found to possess somewhat lower effectiveness.

Anti-Bacterial Agents↗

PubMed1999

Superadditive and subadditive effects of "hot spot" mutations within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A.

Previous single-site mutagenesis studies on the complexes of ribonuclease inhibitor (RI) with angiogenin (Ang) and RNase A suggested that in both cases a substantial fraction of the binding energy is concentrated within one small part of the crystallographically observed interface, involving RI residues 434-438. Such energetic "hot spots" are common in protein-protein complexes, but their physical meaning is generally unclear. Here we have investigated this question by examining the detailed interactions within the RI.ligand hot spots and the extent to which they function independently. The effects of Phe versus Ala substitutions show that the key residue Tyr434 interacts with both ligands primarily through its phenyl ring; for Tyr437, the OH group forms the important contacts with RNase A, whereas the phenyl group interacts with Ang. Kinetic characterization of complexes containing multiple substitutions reveals striking, but distinctive, cooperativity in the interactions of RI with the two ligands. The losses in binding energy for the RNase complex associated with replacements of Tyr434 and Asp435, and Tyr434 and Tyr437, are markedly less than additive (i.e., by 2.4 and 1.3 kcal/mol, respectively). In contrast, the energetic effects of the 434 and 435, and 434 and 437, substitution pairs on binding of Ang are fully additive and 2.5 kcal/mol beyond additive, respectively. Superadditivities (0.9-2.4 kcal/mol) are also observed for several multisite replacements involving these inhibitor residues and two Ang residues, Arg5 and Lys40, from this part of the interface. Consequently, the decreases in binding energy for some triple-variant complexes are as large as 8.5-10.1 kcal/mol (compared to a total DeltaG of -21.0 kcal/mol for the wild-type complex). Potential explanations for these functional couplings, many of which occur over distances of >13 A and are not mediated by direct or triangulated contacts, are proposed. These findings show that the basis for the generation of hot spots can be complex, and that these sites can assume significantly more (as with Ang) or less (as with RNase) importance than indicated from the effects of single-site mutations.

Alanine↗

PubMed1999

Intestinal atrophy has a greater impact on nitrogen metabolism than liver by-pass in piglets fed identical diets via gastric, central venous or portal venous routes.

Whole-body nitrogen metabolism is altered during parenteral feeding as a result of gut atrophy and/or lack of splanchnic first-pass metabolism. We developed in vivo models to describe the metabolic and physiologic effects of first-pass metabolism by the small intestine/liver, liver or non-splanchnic tissues. Fifteen 2- to 4-d-old piglets were fed identical diets continuously for 8 d via gastric (IG), portal (IP) or central venous (IV) catheters. Despite similar weight gain, IV and IP pigs had higher nitrogen output and hence lower nitrogen retention (80%) compared with IG pigs (87%) (P = 0.002). Body protein content was also higher in IG pigs (583 mg/g dry matter) compared with IV (550) and IP pigs (534) (P = 0.003). Despite similar intestinal lengths, total small intestinal and mucosal weights were approximately 40% lower in IV and IP pigs than in IG pigs. Free urea cycle amino acids were altered in plasma and mucosa, suggesting that limited arginine synthesis by an atrophied gut may have limited protein deposition. Although villous atrophy was observed in the duodena and jejuna of IV and IP pigs, reduced crypt depth was observed only in IV pigs. Crypt depth was similar in all four gut sections from IG and IP pigs, suggesting that nutrient flux through the liver affects gut growth. Overall, metabolic responses to IV (non-splanchnic) and IP (liver) feeding were similar as a result of gut atrophy, whereas responses to IG (small intestine + liver) and IP (liver) feeding were different, suggesting that small intestinal atrophy affects nitrogen metabolism to a greater extent than liver by-pass.

Amino Acids↗

PubMed1998

Clinical trials of type I and in vitro studies of type II immunoadsorbents for systemic lupus erythematosus therapy.

A highly selective immunoadsorbent was prepared by immobilization of DNA on carbonized resin beads (Type I) for the removal of the pathogenic antibodies of systemic lupus erythematosus (SLE) patients. Thirty cases of clinical trials of this SLE therapy were performed at 12 hospitals in China. The levels of anti-DNA antibodies after whole blood perfusion were decreased 40-70%. Almost all the symptoms were relieved, and some patients were freed from medicine administration. A new immunoadsorbent was prepared using aminated cellulose beads (Type II) having a higher DNA immobilization capacity of 0.6 mg/ml than the 0.4 mg/ml capacity for Type I. Stationary adsorption tests with the sera of SLE patients showed that the Type II immunoadsorbent could remove 60% of the pathogenic antibodies, which is much higher than the 30% for the Type I adsorbent.

Adult↗

PubMed1998

Threonine requirement of neonatal piglets receiving total parenteral nutrition is considerably lower than that of piglets receiving an identical diet intragastrically.

Evidence is accumulating that the amino acid requirements for neonates receiving total parenteral nutrition (TPN) are significantly different than those for oral feeding and need to be determined. The parenteral threonine requirement was determined in 3-d-old male Yorkshire piglets (n = 25) by examining the effect of varying dietary threonine intakes [0.05-0.6 g/(kg.d)] on phenylalanine oxidation. The diet included adequate energy, total amino acids and phenylalanine, with excess tyrosine. Phenylalanine kinetics were determined from a primed, continuous intravenous infusion of L-[1-14C]phenylalanine. Phenylalanine oxidation, estimated from the rate of 14CO2 released in expired air during isotope infusion, decreased (P < 0.05) as threonine intake increased from 0.05 to 0.15 g/(kg.d) and was low and constant for threonine intakes >0.15 g/(kg.d). Using breakpoint analysis with 95% confidence interval (CI), mean requirement and safe level of parenteral threonine intake were estimated to be 0.19 and 0.21 g/(kg. d), respectively (equivalent to 13 and 14 mg/g amino acids, respectively). To compare these data with those of orally fed controls, we then repeated the experiment by infusing identical diets intragastrically to piglets (n = 25); the varying dietary threonine intakes were 0.1-1.2 g/(kg.d). Employing identical kinetics and analyses, the mean requirement and safe level of oral threonine intake were estimated to be 0.42 and 0.51 g/(kg.d), respectively (equivalent to 28 and 34 mg/g amino acids, respectively). These data demonstrate that the threonine requirement of neonates during TPN is approximately 45% of the mean oral requirement.

Administration, Oral↗

PubMed1998

Heat-aggregated human IgG as immunosorbent for rheumatoid arthritis.

In order to selectively remove pathogenic rheumatoid factors (RF) from plasma of rheumatoid arthritis (RA) patients, a new immunosorbent was developed by immobilizing heat-aggregated human IgG (HAH IgG) on epichlorohydrin-activated agar gel. Different parameters influencing ligand coupling were studied, i.e., ligand concentration, reaction time, temperature and pH. The maximum amount of HAH IgG immobilized on the carrier was 2.7 mg/ml. Adsorption capacity was evaluated by ELISA technique. After incubation of 3.0 ml of RA plasma with 1.0 ml of the adsorbent, the RF IgM, IgG, and IgA were removed by 88%, 74%, and 50%, respectively. The decrease of total immunoglobulins and albumin were less than 7% and 9%. In vitro, perfusion of 10.0 ml plasma at 37 degrees C through 3.0 ml of adsorbent, at a flow rate of 5.0 ml/min for 60 min, resulted in the removal of 49% of RF IgM, 72% of RF IgG and 58% of RF IgA. No leakage of ligand and no decline in adsorption capacity and mechanical strength were observed after steam-sterilization.

Arthritis, Rheumatoid↗

PubMed1997

Site-specific mutagenesis reveals differences in the structural bases for tight binding of RNase inhibitor to angiogenin and RNase A.

RNase inhibitor (RI) binds with extraordinary affinity (Ki approximately 10(-13)-10(-16) M) to diverse proteins in the pancreatic RNase superfamily. In the present study, the structural basis for the recognition of two RI ligands, human angiogenin (Ang) and bovine RNase A, has been investigated by site-specific mutagenesis of human RI and Ang. The RI residues examined were those that appear to form strong contacts with RNase A in the crystal structure of the porcine RI x RNase A complex [Kobe, B. & Deisenhofer, J. (1995) Nature (London) 374, 183-186] that would not be replicated in the Ang complex. Ala substitutions of five of these residues (Glu-287, Lys-320, Glu-401, Cys-408, and Arg-457) were found to have little or no effect on binding of RNase A. In contrast, replacements of Tyr-434, Asp-435, and Tyr-437 and deletion of the C-terminal residue Ser-460 substantially weakened affinity for RNase A: the losses of binding energy associated with the mutations were 5.9, 3.6, 2.6, and 3.5 kcal/mol, respectively. Thus these four residues, which are neighbors in the tertiary structure, appear to constitute a "hot spot" for the RNase A interaction. However, only one of them, Asp-435, was equally important for binding of Ang; the Ki increases produced by mutations of the others were 20- to 93-fold smaller for Ang than for RNase A. Consequently, Tyr-434 plays a significant but lesser role in the Ang complex, whereas Tyr-437 and Ser-460 make only minor contributions. Ala mutations of four Ang residues (His-8, Gln-12, Asn-68, and Glu-108) that correspond to RI contacts on RNase A produced no major changes in affinity for RI. These findings indicate that RI uses largely different interactions to achieve its extremely tight binding of RNase A and Ang.

Animals↗

PubMed1997

Pulsed brachytherapy as a substitute for continuous low dose rate: an in vitro study with human carcinoma cells.

PURPOSE: Pulsed dose rate (PDR) brachytherapy as a substitute for continuous low dose rate (CLDR) has the potential to be a useful option in brachytherapy. However, the frequency and duration of pulses that will produce results practically equivalent to CLDR is still an open and important question. This study was designed to compare the survival of human tumor cells, cultured in vitro, and exposed to continuous or pulsed irradiation where the pulse frequency was varied. METHODS AND MATERIALS: Three different human carcinoma cells, derived from cervical and breast cancers, were exposed to CLDR gamma rays, or to pulsed irradiations with the same overall dose rate. Pulsed regimens used were 3.8 min every hour, 7.6 min every 2 h, 11.4 min every 3 h, 15.2 min every 4 h, 22.8 min every 6 h, and 45.6 min every 12 h. For each comparison between CLDR and PDR, the overall dose and the overall time were the same. Experimental design was such that significant differences in biological effectiveness, if present, would be detected. RESULTS: For the cell lines investigated, hourly pulses resulted in cell survival indistinguishable from CLDR. However, as the pulse interval was increased, cell survival progressively decreased compared with CLDR, and the pulsed regimes were no longer equivalent to continuous low dose rate. CONCLUSIONS: This study provides some evidence to support the suggestion that a 10-min pulse, repeated every 1 to 2 h, would be functionally equivalent to a continuous low dose rate irradiation, at least in terms of early responding endpoints. Longer intervals between pulses might result in loss of equivalence in some cases.

Brachytherapy↗

PubMed1997

[Studies on improving the ability of learning and memories of yangshoudan].

OBJECTIVE: To observe the effects of Yangshoudan(YSD) on the ability of learning and memories in experimental animals. METHODS: The tests of darkness-avoidance response in normal young mice and rats, aged mice, as well as in model mice with dysmnesia induced by anisodine, model rats with dysmnesia induced by scopolamine hydrobromide and with orientation disturbance induced by pentobarbital sodium. RESULTS: In normal young mice and rats, the error times in five minutes in learning and memories tests was reduced (P < 0.01-0.05) by YSD, while in dysmnesia groups the error times in five minutes also reduced (P < 0.01-0.05) and the incubation period of memories could be shortened by YSD. In orientation disturbance mice, the averages and percentages of correct response times increased by YSD. CONCLUSIONS: YSD could improve the memory ability both in normal and dysmnesia which either induced by drugs or due to age. This indicates primarily that YSD has the effects of improving the ability of learning and memories and of antidementia.

Animals↗

PubMed1997

Retrograde flush and cold storage for twenty-two to twenty-five hours lung preservation with and without prostaglandin E1.

BACKGROUND: Our previous study showed that retrograde flush through the left atrium is better than antegrade flush in 6-hour lung preservation. Whether it is feasible in long-term lung preservation is not clear. Several studies suggested that prostaglandin E1 may not be necessary in retrograde flush because of the low vascular resistance on the venous side. This study evaluates the effects of retrograde flush and prostaglandin E1 in 24-hour lung preservation. METHODS: Canine donor lungs were retrograde flushed with University of Wisconsin solution. Group A (n = 7) was pretreated with prostaglandin E1. No prostaglandin E1 was used in group B (n = 7). After flush and cold storage at 4 degrees C for 22 to 25 hours, left lung allotransplantation was performed. Measurements were taken before transplantation (baseline), and at 10, 30, 60, and 120 minutes after transplantation while the right pulmonary artery was occluded. RESULTS: After 120 minutes of reperfusion, the oxygen tension and carbon dioxide tension were 643 +/- 24 and 37 +/- 3 mm Hg in group A and 600 +/- 29 and 37 +/- 3 mm Hg in group B, respectively (p = NS). Pulmonary artery pressure (group A vs group B) was 20 +/- 1 versus 28 +/- 2 mm Hg (p < 0.01); right atrium pressure: 4 +/- 1 versus 8 +/- 1 mm Hg (p < 0.01); left pulmonary vascular resistance: 1109 +/- 51 versus 1525 +/- 133 dyne.sec.cm-5 (p < 0.05); airway resistance: 22 +/- 1 versus 24 +/- 1 cm H2O/L/sec (p = NS); lung dynamic compliance: 30 +/- 1 versus 26 +/- 1 cc/cm (p < 0.05) respectively. As compared with the baseline (19 +/- 1), airway resistance was significantly increased after 2 hours of reperfusion in group B (p < 0.05). Electron microscopy revealed that type I pneumocytes, capillary endothelial cells, and epithelial cells of bronchi were well preserved and the contents of lamellar bodies of type II pneumocyte were reduced. CONCLUSIONS: Canine lung was well preserved by retrograde flush and cold storage with University of Wisconsin solution after 24 hours preservation. Pretreatment of prostaglandin E1 is helpful in reducing pulmonary vascular resistance and airway resistance and improving lung dynamic compliance.

Adenosine↗

PubMed1996

Retrograde versus antegrade flush in canine left lung preservation for six hours.

BACKGROUND: Retrograde flush through the left atrium is now used by some investigators in clinical lung preservation. However, to date there are no studies which compare its result with that of routine antegrade flush. METHODS: Mongrel dogs were divided into two groups: antegrade group (n = 7) and retrograde group (n = 8). After flush and 6 hours of cold storage in Euro-Collins solution, the left lung was transplanted in weight matched recipients, and their right pulmonary artery was then clamped at 10-, 30-, 60-, and 120-minute intervals for 10 minutes to test the lung function. The ultrastructure of lungs in both groups were also studied. RESULTS: Results showed the following (antegrade group versus retrograde group): the wet/dry ratio of the transplanted lung was 7.14 +/- 0.15 versus 6.33 +/- 0.20 (p < 0.01); the arterial oxygen tension (mm Hg) was 389 +/- 42 versus 534 +/- 23 (p < 0.05) and 370 +/- 51 versus 580 +/- 37 (p < 0.01) at 60 and 120 minutes, respectively. The peak airway pressure (cm H2O) was 23.4 +/- 0.8 versus 20.6 +/- 0.6 (p < 0.05) and 23.7 +/- 0.6 versus 21.3 +/- 0.8 (p < 0.05) at 10 and 60 minutes, respectively. Electron microscopic studies showed that at the end of preservation, type I and type II pneumocytes and capillaries were normal in both groups. Occluded capillaries with red blood cells were found in the antegrade group. After reperfusion, damaged epithelium and thicker air-blood barrier were found in the antegrade group. CONCLUSIONS: Retrograde flush offers a better lung preservation with less edema, decreased airway resistance, and improved oxygenation as compared with the antegrade group in 6 hours lung preservation.

Airway Resistance↗

PubMed1995

Improved 4- and 6-hour myocardial preservation by hypoxic preconditioning.

BACKGROUND: A brief hypoxic episode can precondition myocardium against a subsequent ischemic-reperfusion injury. The present study sought to determine whether intracellular ionic alterations, induced expression of heat-shock proteins (hsps), and/or catalase are involved in the cellular mechanisms by which hypoxic preconditioning can preserve postischemic function in a model of prolonged hypothermic storage. METHODS AND RESULTS: Two groups of isolated working rat hearts were studied: control (CON) and hypoxically preconditioned (HP) hearts. Hearts were arrested at 4 degrees C with St Thomas' cardioplegic solution and immersion-stored for either a 4- or 6-hour period. Myocardial function (ie, heart rate, aortic flow, coronary flow, developed pressure, and its first derivative dP/dtmax) was determined at baseline, after preconditioning, and during reperfusion. At similar time points, myocardial [Na+]i, [K+]i, [Mg2+]i, and [Ca2+]i were measured using an atomic absorption spectrophotometer, and the induction of hsp 70 and catalase mRNAs was assayed using Northern blot analysis. After 4 and 6 hours of hypothermic storage, aortic flow, dP/dtmax, and [K+]i were increased, whereas [Na+]i and [Ca2+]i were decreased significantly in the HP group compared with the CON group. Steady state mRNA levels of catalase and hsp 70 were increased from baseline levels only in the HP group, with a peak (2.8- and 2.4-fold versus baseline) after 4 hours of storage. CONCLUSIONS: Our results indicate that intracellular ionic alterations and upregulation of catalase and hsp 70 gene expression may contribute to the mechanisms underlying hypoxic preconditioning, leading to improved postischemic function during prolonged hypothermic storage of hearts.

Animals↗

PubMed1995

Hypoxic preconditioning enhances functional recovery after prolonged cardioplegic arrest.

The purpose of this study was to assess the ability of hypoxic preconditioning to improve myocardial salvage after prolonged hypothermic cardioplegic arrest. Isolated working rat hearts were arrested at 4 degrees C with St. Thomas' Hospital cardioplegic solution and immersion stored for 4 or 6 hours. Two groups were studied, control and hypoxically preconditioned (HP) hearts. After 4 hours' preservation, aortic flow, coronary flow, and the first derivative of aortic pressure were 8.7 +/- 1.6 mL/min, 17.8 +/- 1.6 mL/min, and 2,064 +/- 123 mm Hg/s, respectively, in control hearts (n = 11) and 25.7 +/- 2.5 mL/min, 27.1 +/- 2.5 mL/min, and 2,655 +/- 93 mm Hg/s, respectively, in HP hearts (n = 11) (p < 0.05). After 6 hours' preservation, aortic flow, coronary flow, and the first derivative of aortic pressure were 3.5 +/- 1.2 mL/min, 18.8 +/- 0.4 mL/min, and 1,622 +/- 226 mm Hg/s, respectively, in control hearts (n = 6) and 21.5 +/- 3.2 mL/min, 25.5 +/- 2.3 mL/min, and 2,439 +/- 239 mm Hg/s, respectively, in HP hearts (n = 6) (p < 0.05). After 6 hours' preservation, adenine nucleotides and creatine phosphate levels were not significantly different between the two groups, but lactate dehydrogenase release was significantly increased (p < 0.05) in control versus HP hearts (4.66 +/- 0.58 IU/L versus 1.98 +/- 0.28 IU/L). We conclude that hypoxic preconditioning reduces cellular necrosis and preserves myocardial function after prolonged hypothermic cardioplegic arrest.

Adenine Nucleotides↗

PubMed1995

Clinical trials of immunoadsorbent in systemic lupus erythematosus therapy.

Five patients with systemic lupus erythematosus (SLE) were perfused through an extracorporeal shunt filled with DNA-immunoadsorbent (DNA immobilized on carbonized resin beads). High concentrations of anti-DNA antibodies (36.4-67.0%) (binding percentage with 125I-DNA) in the serum of SLE patients were reduced to 13.8-53.0%, respectively. The highest removal percentage was 62.1%. Although the decline levels varied, the symptoms of patients, i.e., long-term severe joint pain, severe edema, hydropericardium, and ascites were all relieved considerably. The immunoadsorbent showed satisfactory blood compatibility.

Antibodies, Antinuclear↗

PubMed1994

Radiopotentiation of human brain tumor cells by the spermine analog N1,N14-bis(ethyl)homospermine.

PURPOSE: To determine whether the cytotoxicity produced by radiation can be increased by the spermine analog N1,N14-bis(ethyl)homospermine (BE-4-4-4). METHODS AND MATERIALS: Two human tumor cell lines, SF-126 and U-251 MG, were either treated with 0.1 or 0.4 microM BE-4-4-4 for 3 or 4 days, or with 0.2 microM BE-4-4-4 for 4 days. At the end of BE-4-4-4 treatment, cells were irradiated and assayed immediately. Polyamine levels, cell survival, and cell number were determined. RESULTS: In SF-126 cells, treatment with 0.2 microM BE-4-4-4 for 4 days killed about 50% of the cells and also increased the cytotoxicity of radiation. The dose enhancement ratio was approximately 1.3:1.5, which is similar to that reported for alpha-difluoromethylornithine. Polyamine levels were partially depleted, and growth was inhibited to about 60% of control levels. Pretreatment of cells with either 0.1 or 0.4 microM BE-4-4-4 for 3 or 4 days produced less of an increase in radiation-induced cytotoxicity, even though these exposures killed 30-40% or 60-90% of the cells, respectively. Similar treatment with 0.1-0.4 microM BE-4-4-4 in U-251 MG cells had minimal effects on cytotoxicity and growth inhibition, while treatment with 1.0 microM and 2.0 microM BE-4-4-4 for 4 days produced more than a 50% depletion in polyamine levels and partial inhibition in growth, but failed to demonstrate radiopotentiation. CONCLUSION: The cytotoxic polyamine analog BE-4-4-4 can increase the cytotoxicity caused by radiation in at least one cell line. The amount of potentiation depends on the concentration of the analog, with the most occurring at the intermediate concentration. Because we did not observe potentiation in both cell lines, and because of the dose dependence seen in SF-126 cells, the clinical efficacy produced by combined BE-4-4-4 and radiation protocols may be limited.

Brain Neoplasms↗