Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 667 records · Page 37Linked to original sources

PubMed1998

Socioeconomic status and cancers of the female breast and reproductive organs: a comparison across racial/ethnic populations in Los Angeles County, California (United States).

OBJECTIVES: Despite the fact that socioeconomic status (SES) has been shown to have important implications in health related issues, population-based cancer registries in the United States do not routinely collect SES information. This study presents a model to estimate the SES of cancer patients in the registry database. METHODS: At the Los Angeles Cancer Surveillance Program (CSP), we developed a model to estimate each cancer patient's SES from aggregate measurements of the census tract of residence (n = 1,640) at time of diagnosis. We then applied the SES estimates to observe the relationship between SES and risk of cancers of the female breast and reproductive organs including cancers of the ovary, cervix uteri, and corpus uteri. The analyses were performed on the cumulative records (n = 127,819) of cancer patients diagnosed between 1972 and 1992 in Los Angeles County, California, for the mutually exclusive racial/ethnic groups of non-Hispanic Whites, Hispanic Whites, Blacks, Asians, and persons of other ethnic groups. RESULTS: We found SES is positively associated with female breast cancer, ovarian cancer, and cancer of the corpus uteri, but inversely associated with cervical cancer. These SES trends were quite consistent across age groups among non-Hispanic White women. Variations by race/ethnicity in the SES patterns were also found, with Asians exhibiting little association. CONCLUSIONS: Our model of measuring SES is sufficiently sensitive to capture the trends. Adopting the aggregate approach to measure SES in population-based registry data appears to be useful.

Adolescent↗

PubMed1998

S100 beta increases levels of beta-amyloid precursor protein and its encoding mRNA in rat neuronal cultures.

S100beta has been implicated in the formation of dystrophic neurites, overexpressing beta-amyloid precursor protein (betaAPP), in the beta-amyloid plaques of Alzheimer's disease. We assessed the effects of S100beta on cell viability of, neurite outgrowth from, and betaAPP expression by neurons in primary cultures from fetal rat cortex. S100beta (1-10 ng/ml) enhanced neuronal viability (as assessed by increased mitrochondrial activity and decreased lactic acid dehydrogenase release) and promoted neurite outgrowth. Higher levels of S100beta (100 ng/ml, but not 1 microg/ml) produced qualitatively similar, but less marked, effects. S100beta also induced increased neuronal expression of the microtubule-associated protein MAP2, an effect that is consistent with trophic effects of S100beta on neurite outgrowth. S100beta (10 and 100 ng/ml) induced graded increases in neuronal expression of betaAPP and of betaAPP mRNA. These results support our previous suggestion that excessive expression of S100beta by activated, plaque-associated astrocytes in Alzheimer's disease contributes to the appearance of dystrophic neurites overexpressing betaAPP in diffuse amyloid deposits, and thus to the conversion of these deposits into the diagnostic neuritic beta-amyloid plaques.

Amyloid beta-Protein Precursor↗

PubMed1998

Vergence eye movements elicited by stimuli without corresponding features.

We have observed quantitative depth perception with a dichoptic stimulus which possessed no contrast-defined binocular corresponding features (phantom stereogram). The depth perception can be the result of appreciation of a partial-occlusion situation depicted by the stimulus, or the result of activities of low-level disparity detectors which are capable of combining dissimilar local features in the stimulus. Although both mechanisms predict similar depth perception, they predict different vergence eye-movement outputs, especially in the vertical dimension. To identify the underlying mechanisms of the phantom stereopsis, we recorded vergence tracking eye movements to four types of dichoptic stimuli: (a) conventional stereogram with horizontal disparity (HD); (b) horizontal phantom stereogram (HP); (c) conventional stereogram with vertical disparity (VD); and (d) vertical phantom stereogram (VP). We found that HD, HP, and VD stimuli could elicit robust vergence tracking eye movements but VP stimulus could not. While the success of HP stimulus in eliciting vergence tracking may be explained by proximal vergence, the failure of VP stimulus in eliciting vergence tracking clearly indicates that phantom stereogram could not elicit coherent responses among low-level disparity detectors. Partial occlusion, therefore, has to play an important role in the depth perception from the phantom stereogram.

Data Interpretation, Statistical↗

PubMed1998

Inhibition of lung surfactant secretion by KN-62, a specific inhibitor of the calcium- and calmodulin-dependent protein kinase II.

A role of Ca(2+)- and calmodulin-dependent protein kinase II (CaMK II) in lung surfactant secretion was evaluated using KN-62, a specific inhibitor of CaMK II. KN-62 caused a dose-dependent inhibition of Ca2+ iononphore A23187-stimulated phosphatidylcholine (PC) secretion from cultured alveolar type II cells. Concentration effecting 50% inhibition was approximately 4 microM. However, KN-62 only slightly influenced PC secretion from type II cells stimulated by phorbol 12-myristate 13-acetate, terbutaline and ATP that are known to increase surfactant secretion via the protein kinase C and protein kinase A pathways. KN-62 also inhibited the activity of CaMK II in type II cells. A 55 kDa protein was detected in type II cells by Western blot analysis using an antibody against the beta-subunit of CaMK II. The results suggest that CaMK II participates in A23187-stimulated lung surfactant secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

The evolution of the type I interferons.

There are five recognized subtypes within the type I interferons (IFN), IFN-alpha, IFN-beta, IFN-delta, IFN-omega, and IFN-tau, although others may remain to be described, and the IFN-omega may have to be subdivided further because of their evident structural complexity. Together, they constitute an ancient family of intronless genes, possibly present in all vertebrates. THe IFNA/IFNB genes originated by duplication of a progenitor after the divergence of birds, most probably about 250 million years ago (MYA). The avian gene itself proceeded to duplicate to form a series of independent subtypes. The IFND, to date described only in the pig, arose from the IFNA lineage before the emergence of mammals about 180 MYA and might, therefore, be generally distributed in present day species. The IFNB, which occurs as a single gene in primates and rodents, have been duplicated in some other orders. Recent events have produced 10 or more genes in bovid species. The IFNA, which are clustered with the IFNW in humans and cattle, exist as multiple genes in all mammals so far examined as a result of a series of duplication events, some of which occurred recently and, therefore, independently in separate mammalian lineages. The IFNW diverged from the IFNA approximately 130 MYA, just prior to the emergence of mammals, and have continued to duplicate since then. The IFNT, which play a role in reproduction of ruminants, arose from an IFNW within the Artiodactyla suborder about 36 MYA and are found only in the suborder Ruminantia. These genes have also continued to duplicate to form an extensive family. Consequently, their involvement in early pregnancy is a feature of ruminants and not of other mammalian species.

Animals↗

PubMed1998

Responses of cultured rat trigeminal ganglion neurons to bitter tastants.

The initial steps in taste and olfaction result from the activation by chemical stimuli of taste receptor cells (TRCs) and olfactory receptor neurons (ORNs). In parallel with these two pathways is the chemosensitive trigeminal pathway whose neurons terminate in the oral and nasal cavities and which are activated by many of the same chemical stimuli that activate TRCs and ORNs. In a recent single unit study we investigated the responses of rat chorda tympani and glossopharnygeal neurons to a variety of bitter-tasting alkaloids, including nicotine, yohimbine, quinine, strychnine and caffeine, as well as capsaicin, the pungent ingredient in hot pepper. Here we apply many of these same compounds to cultured rat trigeminal ganglion (TG) neurons and measure changes in intracellular calcium [Ca2+]i to determine whether TG neurons will respond to these same compounds. Of the 89 neurons tested, 34% responded to 1 mM nicotine, 7% to 1 mM caffeine, 5% to 1 mM denatonium benzoate, 22% to 1 mM quinine hydrochloride, 18% to 1 mM strychnine and 55% to 1 microM capsaicin. These data suggest that neurons from the TG respond to the same bitter-tasting chemical stimuli as do TRCs and are likely to contribute information sent to the higher CNS regarding the perception of bitter/irritating chemical stimuli.

Animals↗

PubMed1998

SRF binding to SRE in the rat heart: influence of age.

One important promoter element at the 5' end of the c-fos gene is the serum response element (SRE). SRE is the site of attachment of the 67-kDa protein serum response factor (SRF) and several accessory proteins (Elk1, SAP1, SAP2/NET), termed the ternary complex factors. The binding of SRF to SRE plays an integral role in c-fos transcription and may occur independently of the association of the ternary complex factors. In the current study, we found that SRF protein expression was increased in the hearts of the old vs young adult rats in the basal condition. The hearts of old rats may have posttranslationally modified SRF proteins that are different compared to that of the young adults. The SRF increase was present both in the cytoplasm as well as in the nucleus in the old hearts. To test whether SRF protein levels in response to acute stress might be altered with age, we studied hearts of young adult and old rats during myocardial infarction. The young adult rat hearts responded to acute ischemic stress with an increase in both p62 and p67 SRF. The hearts of the old rats, however, did not exhibit a significant change in SRF protein expression. These findings demonstrate qualitative as well as quantitative age differences in SRF protein levels, both at baseline and following stimulation. The reduced SRF expression in response to acute cardiac ischemic stress in the old rats might contribute to the observed age-related decrease in the induction of immediate early genes such as c-fos in the heart.

Aging↗

PubMed1998

Induction of Th2 cell differentiation in the primary immune response: dendritic cells isolated from adherent cell culture treated with IL-10 prime naive CD4+ T cells to secrete IL-4.

A number of observations indicate that exposure to IL-4 is essential for the priming of Th2-type effector T cells and that exposure to IL-12 is essential for the priming of Th1-type effector T cells. However, the initial source of IL-4 in the early immune response has not been clearly identified. Dendritic cells (DC) are the most potent antigen-presenting cells (APC) in priming naive T cells. In this report, we show that DC exposed to IL-10 may play an important role in the priming of IL-4-secreting cells in the early immune response. DC isolated from splenic adherent cell cultures treated with rIL-10 (IL-10-DC) primed naive ovalbumin (OVA)-TCR transgenic T cells to secrete IL-4 upon re-stimulation with OVA and splenic APC. By contrast, DC isolated from rIL-12, rIL-4 or control treated cultures induced almost exclusively Th1-type effector T cells. IL-4 secretion was detected in the primary cultures of IL-10-DC plus naive CD4+ T cells and the priming of IL-4-secreting T cells by IL-10-DC was dependent on endogenous IL-4 production in the priming culture since anti-IL-4 neutralizing antibody completely abrogated the priming of IL-4-secreting cells. Anti-B7-2 but not anti-B7-1 inhibited the ability of IL-10-DC to prime T cells to secrete IL-4. Furthermore, the ability of IL-10 DC to prime for IL-4-secreting T cells was closely related to the down-regulation of CD40 ligand-mediated IL-12 p70 production by DC in the primary cultures and was markedly reduced by adding exogenous IL-12 to the priming cultures. Thus, our findings indicate that early immunologic events that drive Th2 differentiation involve the effects of IL-10 on DC.

Animals↗

PubMed1998

Differential inactivation of maturation-promoting factor and mitogen-activated protein kinase following parthenogenetic activation of bovine oocytes.

Bovine oocytes matured for 24 h (young) or 40 h (aged) were treated with calcium ionophore (A23187) alone or followed with 6-dimethylaminopurine (6-DMAP), a protein phosphorylation inhibitor, and were then assayed for histone H1 kinase and mitogen-activated protein kinase (MAPK) activities. Additionally, the changes in chromatin, meiotic spindle, and microfilament were assessed by immunofluoresence microscopy. In both young and aged oocytes, treatment with 6-DMAP following A23187 treatment abolished the activities of both H1 and MAPKs; the decline of H1 kinase preceded the decline in MAPK activity. However, A23187 treatment alone caused a slower decrease in H1 kinase activity and no evident MAPK alteration in young oocytes. In contrast, activities of both kinases decreased in aged oocytes after A23187 treatment, similar to the response in the combined treatments. The inactivation of MAPK was caused by dephosphorylation of MAP42/extracellular signal-regulated kinase 2 (ERK2) as detected by gel mobility shift in the Western blot assay. A23187 treatment of young oocytes led to chromosome separation and second polar body extrusion, but not pronuclear development, with the majority of the oocytes arrested at a transitional stage of metaphase to anaphase known as metaphase III (MIII). However, most of the A23187-treated aged oocytes developed to the pronuclear stage. When oocytes, regardless of age, were treated by A23187 plus 6-DMAP, bivalent chromosomes were clumped into a single mass, the spindle was disassembled, microtubule networks were distributed in the cytoplasm, and a pronucleus appeared. It is suggested that the decrease in H1 kinase activity is involved in the initiation of oocyte activation, i.e., the exit from metaphase II, whereas the decrease in MAPK activity correlates with onset of pronuclear formation. In conclusion, inactivation of maturation-promoting factor and MAPKs probably occurs via two independent processes, and the inactivation of both kinases is required for the metaphase II oocytes to progress through interphase. High MAPK activity might contribute to spindle stabilization, and inactivation of MAPK is associated with microtubular network formation in the cytoplasm.

Adenine↗

PubMed1998

Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group.

BACKGROUND: Isolated systolic hypertension occurs in around 8% of Chinese people aged 60 years or older. In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension. METHODS: All patients were initially started on masked placebo. After stratification for centre, sex and previous cardiovascular complications, alternate patients (n=1253) were assigned nitrendipine at 10-40 mg daily, with the addition of captopril at 12.5-50.0 mg daily or hydrochlorothiazide at 12.5-50.0 mg daily, or both, if a sufficient blood pressure fall was not obtained. In the remaining 1141 control patients, matching placebos were administered similarly. RESULTS: At entry, sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic, age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l. After 2 years of follow-up, sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group. The intergroup differences were 9.1 mmHg systolic (95% confidence interval 7.6-10.7 mmHg ) and 3.2 mmHg diastolic (95% confidence interval 2.4-4.0). Active treatment reduced total strokes by 38% (from 20.8 to 13.0 endpoints per 1000 patient-years, P=0.01), all-cause mortality by 39% (from 28.4 to 17.4 endpoints per 1000 patient-years, P=0.003), cardiovascular mortality by 39% (from 15.2 to 9.4 endpoints per 1000 patient-years, P=0.03), stroke mortality by 58% (from 6.9 to 2.9 endpoints per 1000 patient-years, P=0.02), and ail fatal and nonfatal cardiovascular endpoints by 37% (from 33.3 to 21.4 endpoints per 1000 patient-years, P=0.004). CONCLUSIONS: Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths, 39 strokes or 59 major cardiovascular endpoints.

Aged↗

PubMed1998

Chromosome 7 rearrangements in glioblastomas; loci adjacent to EGFR are independently amplified.

The first gene found to be amplified in human glioblastomas was EGFR at 7p12. More recently the MET gene at 7q31 was also reported amplified. We have studied chromosome 7 in a series of 47 glioblastomas by FISH, RFLP and microsatellite analysis. Four per cent (2/47) had 1 centromere, 26% (12/47) 2, 32% (15/47) 3, 4% (2/47) 4, and 34% (16/47) had subpopulations with variable numbers of chromosome 7 centromeres. In 25 of the 47 tumors (53%) the pattern of allelic imbalance observed at each informative locus was similar and in accord with the FISH data, indicating loss or gain of complete chromosome copies. In 32% of tumors (15/47) varying allelic imbalance was seen at different loci along the chromosome indicative of loss or gain of parts of chromosome 7 on a background of disomy, trisomy, tetrasomy, or polysomy. Amplification was studied in an extended series of 121 glioblastomas, and was seen at the 7p12 region in 47 tumors (39%). Forty-two tumors showed amplification of EGFR and 12 of these had extensive amplicons including a number of adjacent loci, always involving only 1 allele. The amplicons of 5 tumors (11%) did not include EGFR, indicating that other unidentified genes in the region are targeted for amplification. Amplification of MET was not found. The findings show that copy number changes of chromosome 7 are common and that a number of genes may be targeted for amplification at 7p12 in glioblastomas.

Alleles↗

PubMed1998

Mutational analysis of bean yellow dwarf virus, a geminivirus of the genus Mastrevirus that is adapted to dicotyledonous plants.

Bean yellow dwarf virus (BeYDV) is an atypical member of the geminivirus genus Mastrevirus that infects dicotyledonous plants. BeYDV DNA contains six open reading frames (ORFs) with the capacity to encode proteins in excess of 10 kDa. Two virion-sense ORFs (V1 and V2) and two complementary-sense ORFs (C1 and C2) have homologues in all mastreviruses, while ORFs C3 and C4 are not conserved. To investigate their functions, each of the ORFs has been truncated by either frame-shifting or the introduction of a stop codon. We demonstrate that an ORF V1 mutant replicated efficiently in Nicotiana tabacum protoplasts but was unable to systemically infect Phaseolus vulgaris and Datura stramonium, consistent with a role for V1 protein in virus movement. However, the mutant was able to systemically infect Nicotiana benthamiana although the onset of symptoms was appreciably delayed in comparison with wild-type virus. Disruption of ORF V2, encoding the coat protein, prevented systemic infection of all three hosts but the mutant replicated in protoplasts. Both ORF C1 and ORF C2 were essential for replication in protoplasts. Modification of the complementary-sense splice donor and acceptor sequences also prevented replication. Removal of the intron prevented systemic infection, although the intronless mutant was able to produce functional replication-associated protein (Rep) and replicated efficiently in protoplasts. ORFs C3 and C4 were not required for systemic infection. Our results indicate that four ORFs are spatially and functionally conserved in mastreviruses that infect both monocotyledonous and dicotyledonous plants.

Base Sequence↗

PubMed1998

High resolution genetic typing of the class II HLA-DRB1 locus using group-specific amplification and SSO-hybridisation in microplates.

The HLA-DRB1 locus is one of the most polymorphic HLA class II loci and rapid and accurate typing of this polymorphism is important both in bone-marrow transplantation, analysis of disease association and in forensic medicine. The allelic variation at DRB1 is characterized by combinations of a limited number of amino-acid motifs, reducing the resolution of a typing strategy based on a single PCR and subsequent analysis of polymorphic motifs. In the present paper we describe a strategy for typing of DRB1 based on eight allele-specific PCRs followed by sandwich hybridization to immobilized probes in a microplate format. The combined approach results in a rapid typing system with very high resolution. Using a rapid DNA extraction protocol, a complete HLA-DRB1 typing can be performed in less than a day.

Alleles↗

PubMed1998

A protein (M9) associated with monoclonal antibody-mediated agglutination of Mycoplasma gallisepticum is a member of the pMGA family.

A 62-kDa cell surface antigen (M9) of Mycoplasma gallisepticum PG31 that mediates antibody-induced agglutination of the organism was purified and subjected to N-terminal amino-acid sequencing. A 999-bp region of the cDNA encoding the M9 protein was generated by reverse transcription-PCR, and its nucleotide sequence was determined. PCR primers based on this sequence were used to screen a genomic DNA library of PG31. A full-length M9 protein-encoding gene was isolated and sequenced, revealing 96% nucleotide identity with the pMGA1.1 gene of M. gallisepticum S6. Sequence analyses of the M9 gene and flanking open reading frames that encode other pMGA family members suggest that a tandemly repeated GAA sequence may influence pMGA gene expression.

Amino Acid Sequence↗

PubMed1998

Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex.

GCN5, a putative transcriptional adapter in humans and yeast, possesses histone acetyltransferase (HAT) activity which has been linked to GCN5's role in transcriptional activation in yeast. In this report, we demonstrate a functional interaction between human GCN5 (hGCN5) and the DNA-dependent protein kinase (DNA-PK) holoenzyme. Yeast two-hybrid screening detected an interaction between the bromodomain of hGCN5 and the p70 subunit of the human Ku heterodimer (p70-p80), which is the DNA-binding component of DNA-PK. Interaction between intact hGCN5 and Ku70 was shown biochemically using recombinant proteins and by coimmunoprecipitation of endogenous proteins following chromatography of HeLa nuclear extracts. We demonstrate that the catalytic subunit of DNA-PK phosphorylates hGCN5 both in vivo and in vitro and, moreover, that the phosphorylation inhibits the HAT activity of hGCN5. These findings suggest a possible regulatory mechanism of HAT activity.

Acetyltransferases↗

PubMed1998

DNA-dependent protein kinase phosphorylation of IkappaB alpha and IkappaB beta regulates NF-kappaB DNA binding properties.

Regulation of the IkappaB alpha and IkappaB beta proteins is critical for modulating NF-kappaB-directed gene expression. Both IkappaB alpha and IkappaB beta are substrates for cellular kinases that phosphorylate the amino and carboxy termini of these proteins and regulate their function. In this study, we utilized a biochemical fractionation scheme to purify a kinase activity which phosphorylates residues in the amino and carboxy termini of both IkappaB alpha and IkappaB beta. Peptide microsequence analysis by capillary high-performance liquid chromatography ion trap mass spectroscopy revealed that this kinase was the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). DNA-PK phosphorylates serine residue 36 but not serine residue 32 in the amino terminus of IkappaB alpha and also phosphorylates threonine residue 273 in the carboxy terminus of this protein. To determine the biological relevance of DNA-PK phosphorylation of IkappaB alpha, murine severe combined immunodeficiency (SCID) cell lines which lack the DNA-PKcs gene were analyzed. Gel retardation analysis using extract prepared from these cells demonstrated constitutive nuclear NF-kappaB DNA binding activity, which was not detected in extracts prepared from SCID cells complemented with the human DNA-PKcs gene. Furthermore, IkappaB alpha that was phosphorylated by DNA-PK was a more potent inhibitor of NF-kappaB binding than nonphosphorylated IkappaB alpha. These results suggest that DNA-PK phosphorylation of IkappaB alpha increases its interaction with NF-kappaB to reduce NF-kappaB DNA binding properties.

3T3 Cells↗

PubMed1998

Differential expression of EGFR during early reparative phase of the gastric mucosa between young and aged rats.

Aging is associated with decreased reparative ability of the gastric mucosa. Our recent data suggest a role for epidermal growth factor receptor (EGFR) in the mucosal reparative processes. Thus we examined changes in EGFR tyrosine kinase activity as well as expression and subcellular localization of EGFR and its ligand transforming growth factor-alpha (TGF-alpha) in the gastric mucosa of young (4-mo-old) and aged (24-mo-old) Fischer 344 male rats during the early reparative phase after acute injury induced by 2 M NaCl. Within 240 min of injury, significant epithelial restitution was observed in the gastric mucosa of young but not of aged rats. Expansion of the neck region and initiation of foveolar cell migration could be seen within 45 min of injury in young rats but not until 90 min in aged rats. In young rats mucosal EGFR tyrosine kinase activity increased at 45 min after injury and subsequently fell to basal levels. Mucosal EGFR mRNA increased throughout the reparative phase as did content of the EGFR ligand TGF-alpha. In contrast, although the basal tyrosine kinase activity and levels of EGFR mRNA and TGF-alpha were elevated in the gastric mucosa of aged rats, injury did not cause increases in these parameters. Immunofluorescent localization suggests that internalization and/or degradation of EGFR may be higher in aged than in young rats. We suggest that diminished induction of EGFR tyrosine kinase activity and increased EGFR internalization after injury may in part be responsible for the age-related decrease in the reparative capacity of the gastric mucosa.

Aging↗

PubMed1998

Bcl-2 and Bax expression in adult rat hearts after coronary occlusion: age-associated differences.

It has been reported that programmed cell death (apoptosis) occurs during myocardial infarction. The influence of age on programmed cell death or DNA fragmentation after coronary occlusion has not been extensively characterized. To test the hypothesis that there are age-related differences in susceptibility to DNA fragmentation during ischemia-infarction, we studied DNA fragmentation in young adult and old male F344 rat hearts after acute coronary artery occlusion. Hearts were studied at 1, 3, and 5 h and 1 and 7 days after coronary ligation. The percentage of apoptotic cells was determined by the in situ end-labeling technique, and internucleosomal fragmentation (DNA laddering) pattern was also analyzed. Our results show that 1) DNA fragmentation began earlier and peaked earlier in the old compared with young adult hearts during infarction; 2) there was heightened expression of both Bcl-2 and Bax in the old hearts at baseline; and 3) the Bcl-2-to-Bax ratio was higher in the older heart after coronary ligation. These results suggest that, compared with the young adult heart, the aged heart may be more susceptible to ischemia-induced DNA fragmentation.

Aging↗