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K Liu

Publications and source records attributed to K Liu.

At least 145 records · Page 8Linked to original sources
PubMed2000

[Experiment research on the mechanism of skin contracture after expansion].

OBJECTIVE: The aim of this study is to observe the repairing process of skin chronic injury due to expansion and explore the mechanism of skin contracture after expansion. METHODS: 20 dogs used in this study were divided randomly into four groups. Skin samples were collected from the back of dogs when expansion finished and 3 months, 6 months, 1 year after expansion. Normal skim from the other side on the back of dogs was used as control group. The dermal ultrastructure was observed by electriscope. The expression of alpha-SMA in dermis at different stage has been analyzed by immunohistochemistry, and the concentration of intracellular free Ca2+ in the fibroblast has been measured by Fura-2 fluorescen indicator. Meanwhile we constructed a 3-dimension system in vitro to analyze the afgfect of different cell density and collagen concentration to fibroblast contracture. RESULTS: (1) The microfilment in fibroblast was fragile, and the features of myofibroblast was absent, the collagen fibers were returned to reticular arrangement along with time. One after expansion few of the collagen remained irregular in arrangement and aparse. (2) After expansion the concentration of Ca2+ increased significantly. (3) In 3-D culture system the density of fibroblasts positively corresponded to fibroblast contracture and the collagen concentration negatively corresponded to it. CONCLUSION: After expansion the dog skin has a structure between scar tissue and thoroughly regeneration skin. Dermal fibroblast is the dynamic source of the skin contracture, meanwhile the density of fibroblast and collagen concentration are two essential factors during skin contracture.

Actins↗
PubMed2000

[Purification of hsp70 and its immunoprotective effect against mouse hepatoma].

OBJECTIVE: To purify hsp70 protein and observe its anti-tumor effect on mouse H22 hepatoma. METHODS: Cytosolic hsp70 protein of heat treated H22 cells was purified successively by chromatographic procedures, including DEAE 52-cellulose, ConA-sepharose 4B and ADP-argarose chromatography. The molecular weight and the identity of the purified hsp70 protein were confirmed by SDS-PAGE and Western blot. Tumorigenicity of H22 hepatoma was examined in purified hsp70-treated C3H mice. RESULTS: A sharp stained protein band with a molecular weight of about 70 kD was obtained and shown to be hsp70 as confirmed by Western blot. In C3H mice challenged with H22 hepatoma, tumor developed in 6 of 6 mice while in hsp70 pretreated mice, none of the 6 H22 challenged mice developed tumor. Nevertheless, C57BL/6 mice pretreated with hsp70 or RPMI 1640 all developed tumor upon challenge with EL-4 lymphoma. CONCLUSION: The results suggest that the immunoprotective effect of hsp70 protein is due not to hsp70 per se, but rather to the specific antigenic peptides it carries.

Animals↗
PubMed2000

[Studies on the chemical constituents of Viscum coloratum].

Four compounds were isolated from Viscum coloratum (Kom.) Nakai by means of both solvent extraction and chromatographic separation methods. These constituents were identified through spectral analysis of IR, 1H-NMR. 13C-NMR and MS. They are syringin, oleanolic acid, beta-acetylamyrin and homoeriodictyol-7-beta-D-glucoside. It is the first separation from freshly collected Viscum colortum (Kom.) Nakai, which parasitizing on pear tree.

Glucosides↗
PubMed1999

Structure of a triple helical DNA with a triplex-duplex junction.

Extended purine sequences on a DNA strand can lead to the formation of triplex DNA in which the third strand runs parallel to the purine strand. Triplex DNA structures have been proposed to play a role in gene expression and recombination and also have potential application as antisense inhibitors of gene expression. Triplex structures have been studied in solution by NMR, but have hitherto resisted attempts at crystallization. Here, we report a novel design of DNA sequences, which allows the first crystallographic study of DNA segment containing triplexes and its junction with a duplex. In the 1.8 A resolution structure, the sugar-phosphate backbone of the third strand is parallel to the purine-rich strand. The bases of the third strand associate with the Watson and Crick duplex via Hoogsteen-type interactions, resulting in three consecutive C(+).GC, BU.ABU (BU = 5-bromouracil), and C(+).GC triplets. The overall conformation of the DNA triplex has some similarity to the B-form, but is distinct from both A- and B-forms. There are large changes in the phosphate backbone torsion angles (particularly gamma) of the purine strand, probably due to the electrostatic interactions between the phosphate groups and the protonated cytosine. These changes narrow the minor groove width of the purine-Hoogsteen strands and may represent sequence-specific structural variations of the DNA triplex.

Base Pairing↗
PubMed1999

Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women.

CONTEXT: Three major coronary risk factors-serum cholesterol level, blood pressure, and smoking-increase incidence of coronary heart disease (CHD) and related end points. In previous investigations, risks for low-risk reference groups were estimated statistically because samples contained too few such people to measure risk. OBJECTIVE: To measure long-term mortality rates for individuals with favorable levels for all 3 major risk factors, compared with others. DESIGN: Two prospective studies, involving 5 cohorts based on age and sex, that enrolled persons with a range of risk factors. Low risk was defined as serum cholesterol level less than 5.17 mmol/L (<200 mg/dL), blood pressure less than orequal to 120/80 mm Hg, and no current cigarette smoking. All persons with a history of diabetes, myocardial infarction (MI), or, in 3 of 5 cohorts, electrocardiogram (ECG) abnormalities, were excluded. SETTING AND PARTICIPANTS: In 18 US cities, a total of 72144 men aged 35 through 39 years and 270671 men aged 40 through 57 years screened (1973-1975) for the Multiple Risk Factor Intervention Trial (MRFIT); in Chicago, a total of 10025 men aged 18 through 39 years, 7490 men aged 40 through 59 years, and 6229 women aged 40 through 59 years screened (1967-1973) for the Chicago Heart Association Detection Project in Industry (CHA) (N = 366559). MAIN OUTCOME MEASURES: Cause-specific mortality during 16 (MRFIT) and 22 (CHA) years, relative risks (RRs) of death, and estimated greater life expectancy, comparing low-risk subcohorts vs others by age strata. RESULTS: Low-risk persons comprised only 4.8% to 9.9% of the cohorts. All 5 low-risk groups experienced significantly and markedly lower CHD and cardiovascular disease death rates than those who had elevated cholesterol level, or blood pressure, or smoked. For example, age-adjusted RRs of CHD mortality ranged from 0.08 for CHA men aged 18 to 39 years to 0.23 for CHA men aged 40 through 59 years. The age-adjusted relative risks (RRs) for all cardiovascular disease mortality ranged from 0.15 for MRFIT men aged 35 through 39 years to 0.28 for CHA men aged 40 through 59 years. The age-adjusted RR for all-cause mortality rate ranged from 0.42 for CHA men aged 40 through 59 years to 0.60 for CHA women aged 40 through 59 years. Estimated greater life expectancy for low-risk groups ranged from 5.8 years for CHA women aged 40 through 59 years to 9.5 years for CHA men aged 18 through 39 years. CONCLUSIONS: Based on these very large cohort studies, for individuals with favorable levels of cholesterol and blood pressure who do not smoke and do not have diabetes, MI, or ECG abnormalities, long-term mortality is much lower and longevity is much greater. A substantial increase in the proportion of the population at lifetime low risk could contribute decisively to ending the CHD epidemic.

Adult↗
PubMed1999

van der waals interactions in the Cl + HD reaction

The van der Waals forces in the entrance valley of the Cl + HD reaction are shown here to play a decisive role in the reaction's dynamics. Exact quantum mechanical calculations of reactive scattering on a potential energy surface without Cl-HD van der Waals forces predict that the HCl and DCl products will be produced almost equally, whereas the same calculations on a new ab initio potential energy surface with van der Waals forces show a strong preference for the production of DCl. This preference is also seen in crossed molecular beam experiments on the reaction. The study of chemical reaction dynamics has now advanced to the stage where even comparatively weak van der Waals interactions can no longer be neglected in calculations of the potential energy surfaces of chemical reactions.

Journal Article↗
PubMed1999

Shock melting of the canyon diablo impactor: constraints from nickel-59 contents and numerical modeling

Two main types of material survive from the Canyon Diablo impactor, which produced Meteor Crater in Arizona: iron meteorites, which did not melt during the impact; and spheroids, which did. Ultrasensitive measurements using accelerator mass spectrometry show that the meteorites contain about seven times as much nickel-59 as the spheroids. Lower average nickel-59 contents in the spheroids indicate that they typically came from 0.5 to 1 meter deeper in the impactor than did the meteorites. Numerical modeling for an impact velocity of 20 kilometers per second shows that a shell 1.5 to 2 meters thick, corresponding to 16 percent of the projectile volume, remained solid on the rear surface; that most of the projectile melted; and that little, if any, vaporized.

Journal Article↗
PubMed1999

Solid state NMR studies of hydrogen bonding in a citrate synthase inhibitor complex.

The ionization state and hydrogen bonding environment of the transition state analogue (TSA) inhibitor, carboxymethyldethia coenzyme A (CMX), bound to citrate synthase have been investigated using solid state NMR. This enzyme-inhibitor complex has been studied in connection with the postulated contribution of short hydrogen bonds to binding energies and enzyme catalysis: the X-ray crystal structure of this complex revealed an unusually short hydrogen bond between the carboxylate group of the inhibitor and an aspartic acid side chain [Usher et al. (1994) Biochemistry 33, 7753-7759]. To further investigate the nature of this short hydrogen bond, low spinning speed 13C NMR spectra of the CMX-citrate synthase complex were obtained under a variety of sample conditions. Tensor values describing the chemical shift anisotropy of the carboxyl groups of the inhibitor were obtained by simulating MAS spectra (233 +/- 4, 206 +/- 5, and 105 +/- 2 ppm vs TMS). Comparison of these values with our previously reported database and ab initio calculations of carbon shift tensor values clearly indicates that the carboxyl is deprotonated. New data from model compounds suggest that hydrogen bonds in a syn arrangement with respect to the carboxylate group have a pronounced effect upon the shift tensors for the carboxylate, while anti hydrogen bonds, regardless of their length, apparently do not perturb the shift tensors of the carboxyl group. Thus the tensor values for the enzyme-inhibitor complex could be consistent with either a very long syn hydrogen bond or an anti hydrogen bond; the latter would agree very well with previous crystallographic results. Two-dimensional 1H-13C heteronuclear correlation spectra of the enzyme-inhibitor complex were obtained. Strong cross-peaks were observed from the carboxyl carbon to proton(s) with chemical shift(s) of 22 +/- 5 ppm. Both the proton chemical shift and the intensity of the cross-peak indicate a very short hydrogen bond to the carboxyl group of the inhibitor, the C.H distance based upon the cross-peak intensity being 2.0 +/- 0.4 A. This proton resonance is assigned to Hdelta2 of Asp 375, on the basis of comparison with crystal structures and the fact that this cross-peak was absent in the heteronuclear correlation spectrum of the inhibitor-D375G mutant enzyme complex. In summary, our NMR studies support the suggestion that a very short hydrogen bond is formed between the TSA and the Asp carboxylate.

Acyl Coenzyme A↗
PubMed1999

Metyrapone alleviates ischemic neuronal damage in the gerbil hippocampus.

Transient forebrain ischemia was induced in gerbils, and the effect of a pre-ischemic treatment with metyrapone (100 mg/kg) on delayed neuronal death in hippocampal CA1 neurons was evaluated. The effect of metyrapone on the ischemic release of amino acids in the CA1 region was also examined by microdialysis. Hippocampal slices were used for the evaluation of the hypoxia-induced intracellular Ca2+ increase by microfluorometry. The metyrapone treatment morphologically improved the damage provoked by 3 min of ischemia, although it did not alleviate the damage by 5 min. Ischemia for 3 min produced a 306% increase in the glutamate concentration in perfusates, and metyrapone suppressed the peak value to 42% of that in the control group. The extent of the increase in fluorescence intensity by intracellular Ca2+ was lower by 16% in slices from metyrapone-treated animals than in controls 600 s after induction of hypoxia. The removal of Ca2+ from the perfusion medium suppressed the hypoxic Ca2+ increase, and the increase was further reduced in slices pretreated with metyrapone. The increase in the level of endogenous glucocorticoids, which occurs in cerebral ischemia, may aggravate ischemic neuronal damage.

Amino Acids↗
PubMed1999

Cr(IV) causes activation of nuclear transcription factor-kappa B, DNA strand breaks and dG hydroxylation via free radical reactions.

Electrophoretic mobility shift, DNA strand breakage assays and electron spin resonance (ESR) spin trapping were used to investigate the activation of nuclear transcription factor (NF)-kappa B, DNA strand breakage and 2'-deoxyguanosine hydroxylation induced by Cr(IV), as well the role of free radical reactions in these processes. Incubation of synthesized Cr(IV)-glutathione complex with cultured Jurkat cells resulted in activation of DNA binding activity of NF-kappa B. Cr(VI) is also able to induce NF-kappa B activation through Cr(V) and Cr(IV) intermediates generated during the reduction of Cr(VI) by the cells. Cr(III) did not cause observable NF-kappa B activation due to its inability to cross cell membranes. Cr(IV)-induced NF-kappa B activation is dose-dependent. Catalase inhibited the activation while superoxide dismutase enhanced it. The metal chelator, deferoxamine, and hydroxyl (.OH) radical scavengers, sodium formate and aspirin, also inhibited the NF-kappa B activation. Electrophoretic assays using lambda Hind III linear DNA showed that, in the presence of H2O2, Cr(IV) is capable of causing DNA strand breaks. Deferoxamine, sodium formate and aspirin inhibited the DNA strand breaks. HPLC measurements also show that .OH radical generated by the Cr(IV)-mediated reaction with H2O2 was capable of causing 2'-deoxyguanosine (dG) hydroxylation to generate 8-hydroxyguanosine (8-OHdG). The relative magnitude of 8-OHdG formation correlated with the generation of .OH radicals. ESR spin trapping measurements showed that reaction of Cr(IV) with H2O2 generated .OH radicals, which were inhibited by deferoxamine, sodium formate and aspirin. The results show that Cr(IV) can cause NF-kappa B activation, DNA strand breaks and dG hydroxylation through .OH radical-initiated reactions. This reactive chromium intermediate may play an important role in the mechanism of Cr(VI)-induced carcinogenesis. The results also suggest that the Cr(IV)-glutathione complex may be used as a model compound to study the role of Cr(IV) in Cr(VI) carcinogenicity.

Antioxidants↗
PubMed1999

Sepsis facilitates brain serotonin activity and impairs learning ability in rats.

Sepsis often provokes various neurological disorders. Because many neurologic symptoms are caused by changes in neurotransmissions, we investigated the relationship between behavioral alterations and changes in activities of the monoaminergic systems in rats. Sepsis was induced by cecal ligation and puncture. A step-through passive avoidance test was used for the behavioral evaluation. Passive avoidance retention in animals subjected to learning immediately before the septic or sham operation was examined after 24 or 48 h. Retention performance in animals subjected to learning 24 h after the operation was also examined after a further 24 h. Plasma concentrations of amino acids were determined 24 h after the operation. The activities of the brain monoaminergic systems were evaluated by ratios of metabolites to monoamines. Marked damage was found in the septic rats in the blood analysis 24 h after the operation. The plasma concentrations of tyrosine and arginine in the septic rats were decreased to 69% and 70% of those in the sham-operated animals, respectively. Retention performance was impaired in the septic rats when they were subjected to learning 24 h after the operation, but it was not impaired when animals were subjected to learning before the septic operation. The brain concentration of serotonin was increased in the cerebral cortex, striatum, and hippocampus 48 h after the septic operation, but not after 24 h. The concentration of 5-hydroxyindoleacetic acid, a metabolite of serotonin, was increased in the above three regions both 24 and 48 h after the operation, but not in the hypothalamus. Facilitation of the serotonergic activity in the telencephalon and hippocampus is suggested to be involved in the impairment of learning ability in sepsis.

Animals↗
PubMed1999

Large magnetoresistance of electrodeposited single-crystal bismuth thin films

Single-crystal bismuth thin films 1 to 20 micrometers thick were fabricated by electrodeposition and suitable annealing. Magnetoresistance up to 250 percent at 300 kelvin and 380,000 percent at 5 kelvin as well as clean Shubnikov-de Haas oscillations were observed, indicative of the high quality of these films. A hybrid structure was also made that showed a large magnetoresistive effect of 30 percent at 200 oersted and a field sensitivity of 0.2 percent magnetoresistance per oersted at room temperature.

Journal Article↗
PubMed1999

Resting heart rate is a risk factor for cardiovascular and noncardiovascular mortality: the Chicago Heart Association Detection Project in Industry.

In a prospective cohort study, associations of resting heart rate with risk of coronary, cardiovascular disease, cancer, and all-cause mortality in age-specific cohorts of black and white men and women were examined over 22 years of follow-up. Participants were employees from 84 companies and organizations in the Chicago, Illinois, area who volunteered for a screening examination. Participants included 9,706 men aged 18-39 years, 7,760 men aged 40-59 years, 1,321 men aged 60-74 years, 6,928 women aged 18-39 years, 6,915 women aged 40-59 years, and 1,151 women aged 60-74 years at the baseline examination in 1967-1973. Vital status was ascertained through 1992. For fatal coronary disease, multivariate-adjusted relative risks associated with a 12 beats per minute higher heart rate (one standard deviation) were as follows: for men aged 18-39 years, relative risk (RR) = 1.27 (95% confidence interval (CI) 1.08-1.48); for men aged 40-59 years, RR = 1.13 (95% CI 1.05-1.21); for men aged 60-74 years, RR = 1.00 (95% CI 0.89-1.12); for women aged 40-59 years, RR = 1.21 (95% CI 1.07-1.36); and for women aged 60-74 years, RR = 1.16 (95% CI 0.99-1.37). Corresponding risks for all fatal cardiovascular diseases were similar to those for coronary death alone. Deaths from cancer were significantly associated with heart rate in men and women aged 40-59 years. All-cause mortality was associated with higher heart rate in men aged 18-39 years (RR = 1.11, 95% CI 1.01-1.20), men aged 40-59 years (RR = 1.16, 95% CI 1.11-1.21), and women aged 40-59 years (RR = 1.20, 95% CI 1.13-1.27). Heart rate was not associated with mortality in women aged 18-39 years. In summary, heart rate was a risk factor for mortality from coronary disease, all cardiovascular diseases, and all causes in younger men and in middle-aged men and women, and for cancer mortality in middle-aged men and women.

Adult↗
PubMed1999

Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes.

Human telomerase consists of two essential components, telomerase RNA template (hTER) and telomerase reverse transcriptase (hTERT), and functions to synthesize telomere repeats that serve to protect the integrity of chromosomes and to prolong the replicative life span of cells. Telomerase activity is expressed selectively in germ-line and malignant tumor cells but not in most normal human somatic cells. As a notable exception, telomerase is expressed in human lymphocytes during development, differentiation, and activation. Recent studies have suggested that regulation of telomerase is determined by transcription of hTERT but not hTER. The highly regulated expression of telomerase in lymphocytes provides an opportunity to analyze the contribution of transcriptional regulation of hTERT and hTER. We report here an analysis of hTERT expression by Northern and in situ hybridization. It was found that hTERT mRNA is expressed at detectable levels in all subsets of human lymphocytes isolated from thymus, tonsil, and peripheral blood, regardless of the status of telomerase activity. hTERT expression is regulated as a function of lineage development, differentiation, and activation. Strikingly, however, telomerase activity in these cells is not correlated strictly with the levels of hTERT and hTER transcripts. The absence of correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT splice variants or to detectable inhibitors of telomerase activity. Thus, transcriptional regulation of hTERT is not sufficient to account for telomerase activity in human lymphocytes, indicating a likely role of posttranscriptional factors in the control of enzyme function.

B-Lymphocytes↗
PubMed1999

Interpreting age, period and cohort effects in plasma lipids and serum insulin using repeated measures regression analysis: the CARDIA Study.

Observed changes in health-related behaviours and disease risk factors may arise from physiological or environmental changes, or from biases due to sampling or measurement errors. We illustrate problems in the interpretation of such changes with longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Mean plasma cholesterol was 14 mg/dl higher in 27- than in 20-year-old black men cross-sectionally, but longitudinally it declined by 4 mg/dl during the 7 years. To sort out these contradictory assessments of the effect of age/passage of time, we estimated age and period effects under the assumptions that age effects are a smooth function of age independent of period, and that period effects are changes common to persons across all ages. Simple estimates the age effect, such as the cross-sectional age slopes, may be confounded by cohort effects, by interactions of time and age after baseline, or by the occurrence of non-linearities in response after baseline. We note examples of each potential type of bias. The data and background literature support the assumption that cohort effects do not seriously compromise interpretation for these variables in the CARDIA study. Strong secular decreases in plasma cholesterol, apparently due to population-wide dietary change, mask increases with ageing. Age increases in triglycerides are largely explained by increases in body fatness. For these data, we cautiously accept the cross-sectional age slope as an estimate of ageing and the age-matched time trend as an estimate of secular trend.

Adolescent↗
PubMed1999

Association of nonspecific minor ST-T abnormalities with cardiovascular mortality: the Chicago Western Electric Study.

CONTEXT: Minor electrocardiographic (ECG) ST-T abnormalities are common, but their prognostic importance has not been fully determined. OBJECTIVE: To examine associations of single (1 time only) and multiple (2 times only and > or =3 times) nonspecific minor ST-T abnormalities in 5 years with long-term mortality due to myocardial infarction (MI), coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in middle-aged men. DESIGN: Prospective cohort study (29-year follow-up after 5 annual examinations). SETTING AND PARTICIPANTS: A total of 1673 men employed at the Western Electric Company in Chicago, III, aged 40 to 55 years at entry, with no evidence of CHD and no major ECG abnormalities throughout the first 5-year period. MAIN OUTCOME MEASURES: Minor ST-T abnormalities identified from annual resting ECGs and mortality ascertained from death certificates. RESULTS: Of the 1673 men, 173 had evidence of isolated nonspecific minor ST-T segment abnormalities. During the follow-up period, there were 234 deaths due to MI, 352 deaths due to CHD, 463 deaths due to CVD, and 889 deaths due to all causes. For men with 3 or more annual recordings of minor ST-T abnormalities, risk of death due to MI, CHD, CVD, and all causes was significantly greater than for those with normal ECG findings. For men with 3 or more ECGs with minor ST-T abnormalities, relative risks (and 95% confidence intervals) adjusted for cardiovascular and other risk factors were 2.28 (1.16-4.49), 2.39 (1.39-4.12), 2.30 (1.44-3.68), and 1.60 (1.06-2.42), respectively, with a graded relationship between frequency of occurrence of ST-T abnormalities and mortality risk (linear trend, P< or =.007). CONCLUSIONS: Persistent, minor, nonspecific ST-T abnormalities are associated with increased long-term risk of mortality due to MI, CHD, CVD, and all causes; the higher the frequency of occurrence of minor ST-T abnormalities, the greater the risk. These data underscore the potential value of including nonspecific ECG findings in the overall assessment of cardiovascular risk.

Adult↗
PubMed1999

Evidence for heat shock protein immunity in a rat cardiac allograft model of chronic rejection.

BACKGROUND: The stress response to injury concept has been proposed as a mechanism of chronic rejection. This hypothesis has been tested with a rat cardiac allograft model in recipients pretreated with donor bone marrow (BM) cells. Chronic rejection is manifested in this BM group by obliterative arteriopathy and the epicardium and endocardium contains lymphocytic infiltrates resembling Quilty lesions. Pretreatment with a liver allograft (the orthotopic liver transplant [OLTx] group) is associated with an absence of chronic rejection in the transplanted heart. METHODS AND RESULTS: . Stress responses in the allograft were assessed by determining heat shock protein (hsp) expression by immunohistology of graft tissues and immunoblot analysis of stromal tissue lysates with monoclonal antibodies (mAb) to mammalian hsp60, the inducible hsp72, the constitutively expressed hsc73, and the grp78 C-terminal sequence KSEKDEL (grp78seq). Immunostaining showed clusters of grp78seq-positive cells in the inflammatory infiltrates of obliterated blood vessels and Quilty lesions in the BM group of cardiac allografts. Such grp78seq-positive cells were not seen in the OLTx group of heart allografts nor in syngrafts. Neither group showed significantly different graft myocyte staining of grp78 or hsp72, whereas hsp60 and hsc73 showed higher expression in the BM group and, to a lesser extent, the OLTx group. The increased expression of hsc73 was seen especially in the obliterated arteries and in myocytes nearby cellular infiltrates. Immunoblot analysis of graft stromal tissue lysates showed additional bands with mAb to hsp60 and hsc73 for the OLTx and especially the BM group. No significant bands were seen for hsp72 and grp78. Lymphocytes isolated from chronically rejecting allografts reacted with irradiated autologous spleen cells in the presence of mycobacterial hsp65 and interleukin-2. Culturing of graft-infiltrating cells with mycobacterial hsp71 and interleukin-2 yielded lymphocyte clones without alloreactivity, but with strong proliferative responsiveness to self-antigen-presenting cells and, only in the presence of mycobacterial hsp71 or murine grp78. This T-cell reactivity seemed to require intact hsp molecules because treatment of hsp71 with proteolytic enzymes, polymyxin, or ATP abrogated this induction of the stimulatory effect of self-antigen-presenting cells. These T cells are similar to the hsp-dependent, autoreactive lymphocytes cloned from acutely rejecting rat allografts. CONCLUSIONS: These findings support the concept that the pathogenesis of chronic rejection involves a stress response and the participation of graft-infiltrating autoreactive T cells that operate under hsp-dependent mechanisms.

Animals↗