Biomedical subjects

Z Song

Publications and source records attributed to Z Song.

At least 73 records · Page 4Linked to original sources

PubMed2000

Pig islet xenograft rejection is markedly delayed in macrophage-depleted mice: a study in streptozotocin diabetic animals.

The present study aimed to evaluate the effect of depletion of macrophages and/or natural killer (NK) cells on islet xenograft rejection in the pig-to-mouse model. Five microliters (4,000 to 5,000 IEQ, islet equivalents) of adult pig islets were transplanted under the renal capsule of C57BL/6 mice with streptozotocin-induced diabetes. Macrophages were depleted by injection of liposome-encapsulated dichloromethylene diphosphonate (Lip-Cl2MDP) intraperitoneally (i.p.) at a dose of 100 microl/ 10 g body weight (BW) 2 days before transplantation, and 50 microl/10 g BW weekly thereafter. NK cells were depleted by injection of the monoclonal antibody NK 1.1 (anti-NK 1.1 mAb) i.p. at a dose of 100 microg/mouse 1 day before transplantation, and then 25 microg per week thereafter. Islet graft survival was monitored by daily measurements of blood glucose. Graft survival was 8 +/- 1.2 days in untreated controls, 9 +/- 1.0 days with anti-NK 1.1 mAb alone, 22 +/- 4.9 days with Lip-Cl2MDP alone (P<0.01 vs. controls), and 26 +/- 3.8 days with Lip-Cl2MDP plus anti-NK 1.1 mAb (P<0.01 vs. controls). In the last group, two of six animals were killed with functioning grafts 30 days after transplantation. In untreated controls, rejected xenografts were heavily infiltrated by F4/80+ macrophages and CD3+T cells. In Lip-Cl2MDP-treated groups, the number of F4/80+ macrophages was markedly reduced. On the periphery of xenografts, a small number of CD3+T cells were observed. In conclusion, our results suggest that strategies targeting macrophages may facilitate islet xenograft survival. A role for NK cells cannot be excluded, but appears to be of minor importance.

Animals↗

PubMed2000

Hepatic and extra-hepatic stimulation of glutathione release into plasma by norepinephrine in vivo.

Studies were conducted to determine the effect of norepinephrine (NE) on reduced glutathione (GSH) and oxidized glutathione (GSSG) export from hepatic and extra-hepatic tissues in vivo. Anesthetized Single Comb White Leghorn (SCWL) males were implanted with cannulae in the carotid artery, hepatic vein (HV) and hepatic portal veins (PV), and the left bile duct. In Experiment 1, GSH and GSSG in hepatic and portal venous plasma and bile were determined prior to, during, and following two 20-min infusions of NE (2 and 10 microg/min per kg BW) into the hepatic PV. The lower NE infusion rate increased hepatic venous GSH (indicative of increased GSH export into liver sinusoids) without affecting systemic or hepatic vascular pressures; however, it had no affect on portal venous GSH. The higher NE infusion rate increased GSH in the HV and hepatic PV (indicative of extra hepatic export of glutathione) as well as systemic pressure, hepatic and portal venous pressures, and the transhepatic pressure gradient. Biliary secretion of GSH and GSSG was unaffected by either rate of NE infusion in Experiment 1. In Experiment 2, pretreatment of birds with phentolamine, an alpha-adrenergic receptor blocker (alpha-block), abolished sinusoidal export GSH as well as the ability of NE to stimulate GSH release from hepatic and extra-hepatic tissue. Although HV and PV pressures were lower in alpha-block birds compared with controls, there were no differences in the transhepatic pressure gradient between groups. Plasma GSSG was below the limits of detection in Experiments 1 and 2. The combined results of Experiments 1 and 2 indicate that hepatic export of GSH was independent of changes in systemic or hepatic vascular pressures or changes in the transhepatic pressure gradient. The results of these studies are the first to demonstrate that export of GSH into plasma in vivo is mediated by an alpha-receptor-mediated mechanism in hepatic and extra-hepatic tissues. The findings may be particularly important with regard to antioxidant homeostasis of animals during periods of stress.

Animals↗

PubMed2000

Biliary glutathione secretion in male single comb white leghorn chickens after inhibition of gamma-glutamyl transpeptidase.

The amount of hepatic export of glutathione into bile and the importance of gamma-glutamyl transpeptidase (gammaGT) activity for catabolizing glutathione in the bile duct, have not been reported previously for domestic fowl. Therefore, the primary objective of this study was to establish baseline values of biliary glutathione, and a secondary objective was to investigate the effect of acivicin (AT-125; a gammaGT inhibitor) on biliary glutathione in the chicken. Cannulae were placed in the carotid artery (to measure blood pressure) and into the left bile duct of anesthetized male Single Comb White Leghorn (SCWL) chickens (n = 5; 17 to 18 wk). The right bile duct was clamped between the liver and gall bladder. Bile samples were collected at 15-min intervals into microcentrifuge tubes (on ice) containing serine borate and iodoacetic acid to prevent glutathione oxidation. After two samples were obtained to establish baseline values, retrograde infusion of AT-125 (30 microLmol/kg BW) was given to inhibit gammaGT activity in the biliary tree. Systemic blood pressure of the birds remained above 100 mm Hg throughout each experiment (90 to 120 min). Bile flow did not change significantly during the experiment and ranged between 0.15+/-0.03 and 0.20+/-0.07 mL/15 min per kg BW. Baseline biliary secretion values of reduced glutathione (GSH), oxidized glutathione (GSSG), and total glutathione (TGSH) were 4.6, 5.9, and 17 nmol/min per kg BW. After AT-125 infusion, biliary GSH levels increased from 15 to 31 nmol/min per kg BW, indicating that considerable gammaGT-mediated catabolism of GSH occurred in the biliary tree of SCWL males. These results indicate that considerable turnover of GSH in the livers of domestic chickens is due to biliary excretion and that substantial recovery of GSH occurs through activity of gammaGT in the biliary tree.

Animals↗

PubMed2000

NaDNA-bipyridyl-(ethylenediamine)platinum (II) complex: structure in oriented wet-spun films and fibers.

Complexes of NaDNA with bipyridyl-(ethylenediamine)platinum(II) (abbreviated [(bipy)Pt(en)](2+)) in solid, oriented films, prepared with a wet-spinning method, have been studied using x-ray diffraction, elastic neutron scattering, two-dimensional magic-angle-spinning nuclear magnetic resonance (NMR), infrared (IR) linear dichroism, and IR absorption. All of these experiments indicate that the DNA in this complex is in the B conformation. The neutron diffraction experiments reveal that the rise per residue is 3.31 A, indicating that the [(bipy)Pt(en)](2+) molecular ion causes a small distortion of the B conformation. The neutron data in the direction perpendicular to the helical axis are consistent with a centered orthorhombic unit cell with a=22.65 A and b=32.2 A. The NMR and IR experiments show that the orientation of phosphate groups in the DNA small middle dot[(bipy)Pt(en)](2+) complex is the same as that observed for pure DNA in the B conformation. The IR experiments also show that the [(bipy)Pt(en)](2+) molecular ion stabilizes the B conformation of DNA down to 59% relative humidity, a low water activity. Mechanochemical experiments on wet-spun NaDNA fibers in 68% ethanol with and without [(bipy)Pt(en)](2+) reveal a 9% elongation of the DNA fibers as the complex is formed.

2,2'-Dipyridyl↗

PubMed2000

Biochemical and genetic interactions between Drosophila caspases and the proapoptotic genes rpr, hid, and grim.

In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified. We now show that DCP-1 has a substrate specificity that is remarkably similar to those of human caspase 3 and Caenorhabditis elegans CED-3, suggesting that DCP-1 is a death effector caspase. drICE and DCP-1 have similar yet different enzymatic specificities. Although expression of either in cultured cells induces apoptosis, neither protein was able to induce DNA fragmentation in Drosophila SL2 cells. Ectopic expression of a truncated form of dcp-1 (DeltaN-dcp-1) in the developing Drosophila retina under an eye-specific promoter resulted in a small and rough eye phenotype, whereas expression of the full-length dcp-1 (fl-dcp-1) had little effect. On the other hand, expression of either full-length drICE (fl-drICE) or truncated drICE (DeltaN-drICE) in the retina showed no obvious eye phenotype. Although active DCP-1 protein cleaves full-length DCP-1 and full-length drICE in vitro, GMR-DeltaN-dcp-1 did not enhance the eye phenotype of GMR-fl-dcp-1 or GMR-fl-drICE flies. Significantly, GMR-rpr and GMR-grim, but not GMR-hid, dramatically enhanced the eye phenotype of GMR-fl-dcp-1 flies. These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo.

Animals↗

PubMed2000

[Experimental study on endothelialization of autologous pericardial heart valves in vitro].

OBJECTIVE: To investigate a method of autologous pericardial heart valves (APHV) treatment beneficial to endothelialization. METHODS: Bovine aortic endothelium cells (BAEC) were cultured and seeded in autologous pericardial pieces treated with different methods in vitro. The influence of different treatment on cellular growing, amount of 3H-TdR incorporation and PGI2 releasing, contents of intracellular cAMP was studied by means of transmission electron microscopy, 3H-TdR incorporation experimentation and radioimmunity method. RESULTS: The BAEC seeded in bovine pericardial pieces treated with three different concentrations of GA 10 minutes could alive. In the group with method of treatment with 0.2% GA, the growing of BAEC was best, the cellular density and the amount of 3H-TdR incorporation at different time spots were higher than that of the other groups and it did not enhance the abnormal synthesis of cAMP and PGI2 in BAEC. CONCLUSION: The pericardium treated with 0.2% GA 10 minutes has little toxicity to endothelium cell, which indicates that this method is beneficial to endothelialization of APHV postoperatively.

Animals↗

PubMed2000

An investigation of immunocompetence substances in normal gingival and periodontitis tissue.

OBJECTIVE: To investigate the effects of nitric oxide (NO), endothelin (ET), substance P (SP) and calcitonin gene-related peptide (CGRP) immunocompetence substances and their relationship to chronic periodontitis. METHODS: Immunohistochemical aod histochemical staining methods were used to detect the expression of the NO synthase (NOS), ET, SP and CGRP levels in 20 patients with chronic periodontitis and 20 healthy subjects as control. RESULTS: Quantitative analysis by Quantimat 970 showed that NOS and ET in periodontitis tissue increased significantly (P < 0.01), particularly the content of ET in comparison with healthy subjects. The intergroup expression of SP and CGRP showed no remarkable changes. CONCLUSION: Our results demonstrate that the level of NOS and ET were significantly increased in periodontic tissue, which may diminish the blood supply and influence the periodontal tissue causing tissue damage. Our study suggests that immunocompetence substances NO and ET are closely associated with periodontitis and may play an important role in the disease.

Adult↗

PubMed2000

[Acute mesenteric vein thrombosis: diagnosis and management].

OBJECTIVE: To evaluate the progress in diagnosis and management of acute mesenteric vein thrombosis (AMVT). METHODS: Fifteen patients with AMVT treated from January 1983 to November 1998 were reviewed retrospectively. They were 7 men and 8 women, aged on average 42 years. The duration from onset of symptoms to admission was 24 - 168 hours (mean 84 hours). RESULTS: Six patients were diagnosed before operation, while 9 during laparotomy. Two patients received conservative treatment and the rest underwent surgery. The average length of bowel resection was 300 cm. All the patients received anticoagulation therapy with heparin immediately after operation. Local thrombolytic therapy was given to 4 patients. Four patients died in hospital and two had sequelae of short bowel syndrome. CONCLUSIONS: AMVT is rare but a potentially lethal emergency disease. Early diagnosis, anticoagulation and appropriate surgical approach are essential to improve the prognosis. It is important to keep vigilance for AMVT in the patients in the hypercoagulation status, especially when the symptoms are inconsistent with abdominal signs. Color-US and CT appear to be sensitive in the diagnosis of this condition. Local thrombolytic therapy will be effective. Second-look is a necessarily procedure for reserving the bowel that may be alive. Laparoscopy technique will play an important role in the diagnosis and treatment for AMVT.

Acute Disease↗

PubMed2000

[Primary non-specific ureteritis].

OBJECTIVE: To better understand primary non-specific ureteritis. METHODS: The etiological, clinical, and pathological manifestations, diagnosis, and treatment of 3 cases of primary non-specific ureteritis were discussed. RESULTS: Preoperative diagnosis failed. Uretero-ureterostomy was performed in 2 cases, and ureteroneocystostomy in one. The patients were free from hydronephrosis and ureteral dilatation. CONCLUSIONS: Diagnosis depends on pathological manifestations, differentiation from secondary non-specific ureteritis, ureteral tuberculosis, negative X-ray of ureteral stone and ureteral carcinoma. Surgical intervention is effective with good prognosis.

Adult↗

PubMed2000

[Distinctive infrared spectral features in human breast cancer].

Substantial differences were found in the spectral properties of surgical samples from 20 women patients with histologically normal and cancerous breast tissue. The most striking changes in the spectra were observed in the symmetric and asymmetric stretching bands of phosphodiester groups, which shifted to short wavenumber about 3 cm-1 in nu s PO2-, and to long wavenumber about 2 cm-1 in nu s PO2-. The ratio of A1,173/A1,163 increased and that of A1,025/A1,082 decreased, the intensity of symmetric and asymmetric stretching bands of CH3 decreased and those of CH2 increased in all of breast cancer tissues. Our findings indicated that in breast cancer tissue, the degree of hydrogen-bonding of oxygen atoms in the backbone of nucleic acid increased; the content of glycogen decreased; the degree of hydrogen-bonding of OH groups in serine, tyrosine, and threonine residues of cell proteins decreased; and also there were changes in the packing and the conformational structure of the methylene chains of membrane lipids.

Breast Neoplasms↗

PubMed1999

Multimerin processing by cells with and without pathways for regulated protein secretion.

Multimerin is a massive, soluble, homomultimeric, factor V-binding protein found in platelet alpha-granules and in vascular endothelium. Unlike platelets, endothelial cells contain multimerin within granules that lack the secretory granule membrane protein P-selectin, and in culture, they constitutively secrete most of their synthesized multimerin. To further evaluate multimerin's posttranslational processing and storage, we expressed human endothelial cell prepromultimerin in a variety of cell lines, with and without pathways for regulated secretion. The recombinant multimerin produced by these different cells showed variations in its glycosylation, proteolytic processing, and multimer profile, and human embryonic kidney 293 cells recapitulated multimerin's normal processing for constitutive secretion by human endothelial cells. When multimerin was expressed in a neuroendocrine cell line capable of regulated protein secretion, it was efficiently targeted for regulated secretion. However, the multimerin stored in these cells was proteolyzed more extensively than normally occurs in platelets, suggesting that endoproteases similar to those expressed by megakaryocytes are required to produce platelet-type multimerin. The impact of the tissue-specific differences in multimerin's posttranslational processing on its functions is not yet known. Multimerin's sorting and targeting for regulated secretion may be important for its functions and its association with factor V in secretion granules.

Blood Platelets↗

PubMed1999

Abdominal computed tomography for the diagnosis of intra-abdominal sepsis in critically injured patients: fishing in murky waters.

HYPOTHESIS: Abdominal computed tomographic (ACT) scans are useful in the evaluation of sepsis of unknown origin in patients with major trauma. DESIGN: Prospective case series of consecutive patients. SETTING: Intensive care unit of level I academic trauma center. PATIENTS: Eighty-five critically injured patients admitted to the intensive care unit in 32 months (6% of all intensive care unit admissions) who developed sepsis of unknown origin. INTERVENTIONS: One hundred sixty-one ACT scans. MAIN OUTCOME MEASURES: Sensitivity and specificity of the ACT scans, number of patients subjected to changes in treatment following an ACT scan. RESULTS: Forty-nine patients (58%) had an intraabdominal focus of infection identified on ACT scan. Penetrating trauma and emergent laparotomy were the only independent factors associated with abnormal findings on ACT scan. The sensitivity and specificity of the test were 97.5% and 61.5%, respectively. Overall, 59 patients (69%) benefited from treatment changes after an ACT scan. CONCLUSION: Abdominal computed tomographic scans reliably identify intra-abdominal foci of infection in patients with major trauma evaluated for sepsis of unknown origin.

Abdominal Abscess↗

PubMed1999

Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T-cell immunity.

A murine model of acute hematogenous osteomyelitis was used to study the immune response following Staphylococcus aureus infection and to examine the hypothesis that the bacteria may modify T-cell responses due to the production of bacterial enterotoxins with mitogenic or superantigenic activity. Lymph-node T cell-receptor expression was assessed with use of flow cytometry and reverse transcription-polymerase chain reaction techniques, and increased apoptosis (programmed cell death) in T-cell subsets was monitored. The expression and levels of circulating cytokines and T-cell cytokines within tissues surrounding the damaged area of the proximal tibia were also investigated. Analysis of T-cell receptors in experimental osteomyelitis revealed two distinct patterns of T-cell evolution during the disease. Certain T-cell subsets (Vbeta2, Vbeta3, Vbeta9, and Vbeta10) were activated and expanded during the first 24 hours after infection; they reached maximum levels 6 days after infection, followed by a return to pre-infection levels. In contrast, other T-cell subsets (Vbeta11, Vbeta12, Vbeta13, Vbeta14, and Vbeta16) contracted during the first 24 hours after infection, followed by expansion to a maximum level 9 days after infection. Activation and proliferation of T-cell subsets (notably Vbeta14 T cells) was followed by apoptosis, suggesting that staphylococcal bone infection caused superantigenic-like effects on the mouse immune system. Analysis of cytokine responses in local tissue revealed that the T-cell cytokines interleukin-2 and interferon-gamma showed a late and relatively short activation pattern compared with the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha. The results suggest that Staphylococcus aureus bone infection may undermine the antibacterial immune response through downregulation of T-cell immunity and immune-cytokine production, which could increase the severity of the systemic infection and local osseous destruction that occur with acute hematogenous osteomyelitis.

Acute Disease↗

PubMed1999

HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis.

We have identified a Drosophila homolog of Apaf-1 and ced-4, termed hac-1. Like mammalian APAF-1, HAC-1 can activate caspases in a dATP-dependent manner in vitro. During embryonic development, hac-1 is prominently expressed in regions where cells undergo natural death. Significantly, hac-1 transcription is also rapidly induced upon ionizing irradiation, similar to the proapoptotic gene reaper. Loss of hac-1 function causes reduced cell death, and reducing the dosage of hac-1 suppresses ectopic cell killing upon expression of the dcp-1 procaspase in the retina but has little effect on reaper, hid, and grim-mediated killing. Our data indicate that caspase activation and apoptosis in Drosophila are independently controlled by at least two distinct regulatory pathways that converge at the level of caspase activation.

Amino Acid Sequence↗

PubMed1999

DNA repair and survival in human lens epithelial cells with extended lifespan.

PURPOSE: Ultraviolet-B radiation (290-320 nm) produces cataracts in animals and has been associated with human cataract formation in several epidemiological studies. UVB radiation decreases the long-term cell survival and changes the pattern of protein synthesis in cultured lens epithelial cells. However, the relationship between DNA photoproduct formation and long term cell survival in human lens epithelial cells is not known. In the present work, we used human lens epithelial cells with extended lifespan (HLE B-3 cells) to examine the kinetics of DNA repair and cell survival after UVB exposure. METHODS: Cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts were analyzed by radioimmunoassay. Long-term survival of the cells was determined by measuring their ability form colonies when plated at low density. RESULTS: HLE B-3 cells were repair competent after UVB (302 nm) exposure. Excision repair of the (6-4) photoproduct was more efficient than that of the cyclobutane dimer. Ninety five percent of the (6-4) photoproducts were repaired 24 h after 400 J/m2 UVB exposure, whereas 50% of the cyclobutane dimers were repaired during this time. When cells were split for the clonogenic assay immediately after irradiation, only 10% of the cells formed colonies following 7 days of culture in the serum-containing medium. When cells were split for the clonogenic assay after a 48 hour incubation in serum-containing medium, the colony-forming ability of the irradiated cells increased to 60% following culture in a serum-containing medium. CONCLUSIONS: These results indicate a close correlation between the repair of cyclobutane dimers and the increase in the long-term survival of the cells as measured by their colony-forming ability. The extended lifespan human lens epithelial cells HLE B-3 may be a useful model to investigate the mechanism and regulation of UVB-induced DNA repair in human lens cells.

Cell Survival↗

PubMed1999

Colonic resection in trauma: colostomy versus anastomosis.

OBJECTIVES: The management of colonic trauma is well established for simple injuries with primary repair, and ileocolostomy for right-sided injuries that undergo colonic resection. Segmental colon resection for injuries to the left colon can be managed with either an end colostomy or primary anastomosis. A retrospective review was performed to evaluate the outcome and complications associated with colonic resection for trauma to determine the risk factors associated with anastomotic leakage. METHODS: A retrospective review included patients undergoing colonic resection for trauma. The patients were stratified into colostomy, ileocolostomy, and colocolostomy groups. Patient demographics and colon-related complications were collected. Comparison between the colostomy and colocolostomy groups was performed to determine the difference in outcome. The outcome of right-sided colon injuries managed by either an ileocolonic or colocolonic anastomosis was compared. Analysis was performed to identify the factors associated with an increased risk of anastomotic leakage. RESULTS: One hundred forty patients over a 66-month period were included in the analysis. Overall, 41% (57 of 140) of patients developed a colon-related complication; 28% (39 of 140) of patients developed an abscess. Overall, the anastomotic leak rate was 13% (7 of 56) in the colocolostomy group, 4% (2 of 56) in the ileocolostomy group. Right-sided colon injuries managed with a colocolonic anastomosis had a higher incidence of anastomotic leakage than ileocolonic anastomosis, i.e., 14 versus 4% respectively. Of the seven patients who developed a leak from a colocolonic anastomosis, two patients died (29%). Univariate analysis identified an Abdominal Trauma Index Score > or = 25 (p = 0.03) or hypotension in the emergency department (p = 0.001) to be associated with increased risk of developing an anastomotic leak from a colocolonic anastomosis. CONCLUSION: Colonic injuries that are managed with resection are associated with a high complication rate regardless of whether an anastomosis or colostomy is performed. Colonic resection and anastomosis can be performed safely in the majority of patients with severe colonic injury, including injuries to the left colon. For injuries of the right colon, an ileocolostomy has a lower incidence of leakage than a colocolonic anastomosis. For injuries to the left colon, there remains a role for colostomy specifically in the subgroups of patients with a high ATI or hypotension, because these patients are at greater risk for an anastomotic leak. The role of resection and primary anastomosis versus colostomy in colonic trauma requires further investigation.

Adult↗

PubMed1999

Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response.

Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a poor prognosis. We speculated that a change from this Th2-like response to a Th1-like response might decrease the lung inflammation and thus improve the prognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/c mice intratracheally with P. aeruginosa. In addition, we studied the early immune response leading to different Th responses. Mortality was lower in the C3H/HeN mice (p<0.005), they cleared the bacteria faster (day 3 p<0.01, day 7 p<0.02), had a milder lung inflammation (day 7 p<0.01, day 14 p< or =0.0005) and had a Th1-like IgG subclass switch. At day 3, the C3H/HeN mice produced less NO and TNF-alpha, (p<0.01 and p<0.03) and had the lowest IL-10/IL-12 ratio (p< or =0.05). At day 7, the C3H/HeN mice had the highest IFN-gamma (p<0.02), and the lowest IL-4 (p<0.02) production in the lungs. In conclusion, these results show that the Th1-reacting C3H/HeN mice with chronic P. aeruginosa lung infection have a better disease outcome compared to the Th2-reacting BALB/c mice, indicating that a Th1 response might be beneficial in CF patients with chronic P. aeruginosa lung infection.

Animals↗

PubMed1999

Proteins bound to polyethylene components in patients who have aseptic loosening after total joint arthroplasty. A preliminary report.

BACKGROUND: Immunological responses to proteins that adhere to ultra-high molecular weight polyethylene have not, to our knowledge, been examined previously in patients who have aseptic loosening. In the current study, polyethylene components from forty-nine failed prostheses recovered during revision procedures were examined for the presence of antibodies that were bound to the polyethylene surface or that were reactive with other proteins that were bound to the polyethylene surface. METHODS: The polyethylene components consisted of thirty acetabular cups recovered during revision total hip arthroplasties and nineteen tibial components recovered during revision total knee arthroplasties. After extensive washing, bound proteins were extracted from the polyethylene components with use of 0.1-molar glycine-hydrogen chloride solution followed by four-molar guanidine hydrochloride solution. RESULTS: Sufficient protein for analysis was recovered from forty-two polyethylene components. Polyacrylamide gel electrophoresis demonstrated a minimum of one and a maximum of twelve protein bands, with molecular weights ranging from thirteen to 231 kilodaltons. Immunoblotting revealed the presence of type-I collagen in most (thirty-four) of the forty-two explants, whereas aggrecan proteoglycans were detected in eight samples. Immunoglobulin also was detected in most (thirty-three) extracts, whereas type-II collagen was consistently absent. The presence of autologous antibodies directed against polyethylene-bound proteins in sera drawn at the time of the revision was investigated. Antibodies that were reactive against the ultra-high molecular weight polyethylene-bound proteins were detected in twenty-six of the forty-two patients with use of the Western blot technique. The number of reactive bands ranged from one to six, and the strongest binding was directed against a 103-kilodalton protein. Assays for specificity revealed that these sera autologous antibodies were reactive against the type-I collagen that was present in the explant solutions. CONCLUSIONS: We hypothesize that immunoglobulin complexed with polyethylene may fix complement and that the complement cascade may in turn attract inflammatory cells to the polyethylene surface. Our data support the hypothesis that an immunological response to antigens bound to the polyethylene surface may contribute to aseptic loosening. CLINICAL RELEVANCE: Despite improvements in materials and designs of prostheses, aseptic loosening is the most common complication of total joint replacement, frequently leading to revision operations. We examined the immunological response to proteins that bind to ultra-high molecular weight polyethylene in patients who had aseptic loosening and discovered a high prevalence of antibodies to polyethylene-bound proteins. This immunological response may contribute to an inflammatory reaction in the periprosthetic tissue, ultimately leading to increased bone resorption around the prosthesis.

Antigen-Antibody Complex↗