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Biomedical subjects

H Lim

Publications and source records attributed to H Lim.

At least 37 records · Page 2Linked to original sources
PubMed2001

Myocyte apoptosis and reduced SR gene expression precede the transition from chronically stunned to hibernating myocardium.

A systematic transition from chronic stunning to hibernation occurs as coronary flow reserve decreases to a critical level. Hibernating myocardium exhibits apoptosis-induced myocyte loss and a reduction in the expression of the sarcoplasmic reticulum (SR) Ca2+ ATPase but whether similar cellular changes occur in chronic stunning is unknown. Pigs with a chronic left anterior descending coronary artery (LAD) stenosis were studied one (n=9) or two (n=10) months after instrumentation. Anterior hypokinesis with normal levels of resting perfusion developed at each time-point, consistent with chronic stunning. After 1 month, sub-endocardial flow reserve was moderately reduced (adenosine/rest, LAD: 3.60+/-0.91 v Remote: 6.00+/-0.54, P<0.01) with no regional differences in SR protein expression, no increase in apoptosis (32+/-6 v 21+/-5 nuclei/10(6) myocyte nuclei, p-ns) and no regional myocyte loss (1976+/-44 v 1955+/-30 nuclei/mm2, p-ns). After 2 months, sub-endocardial flow reserve in chronically stunned myocardium was severely impaired (LAD: 1.41+/-0.21 v Remote: 5.59+/-0.96, P<0.01). There were small but significant reductions in LAD mRNA and protein levels for the SRCa2+ ATPase and phospholamban whereas calsequestrin was unchanged. In addition, regional myocyte apoptosis increased (127+/-24 v 55+/-9 nuclei/10(6) myocyte nuclei, P<0.01), resulting in the onset of myocyte loss (1293+/-50 v 1394+/-32 nuclei/mm2, P<0.01). Apoptosis-induced myocyte loss and reductions in SR protein expression are not invariably present in viable chronically dysfunctional myocardium. They are induced as the propensity of a region to develop reversible ischemia increases (as reflected by coronary flow reserve). The temporal progression indicates that alterations in SR protein expression and myocyte apoptosis precede the transition from chronically stunned to hibernating myocardium.

Animals↗
PubMed2001

Peanut challenge: a retrospective study of 140 patients.

BACKGROUND: Accurate diagnosis of peanut allergy is essential given that it is a lifelong and potentially fatal food allergy. Diagnosis relies on patient history, prick skin test (PST), and in many situations, food challenge. More information is required on the safety of food challenge and the informational value of a PST. OBJECTIVES: Primary: to assess the safety of peanut challenges. Secondary: to estimate the sensitivity, specificity, and the positive and negative predictive values of PST to peanut performed in those who underwent a peanut challenge. METHODS: A retrospective study of peanut challenges performed at a tertiary care paediatric hospital allergy clinic between January 1994 and November 1998. RESULTS: Of the 140 peanut challenges performed on 140 patients, 18 were positive. The most frequent adverse clinical effects of positive peanut challenges were: urticaria, oropharyngeal irritation, rhinitis, vomiting and abdominal pain. Among the 18 patients who had a positive result, 10 required medical treatment (antihistamines, +/- epinephrine, +/- salbutamol) to control the allergic reaction. The sensitivity, specificity, and the positive and negative predictive values of PST to peanut in this group of children undergoing a peanut challenge were 100%, 62.3%, 28.1% and 100%, respectively. CONCLUSIONS: Given the poor positive predictive value and specificity of PST, a peanut challenge is usually required to diagnose peanut allergy with certainty when the PST is positive. In cases of a clear history of anaphylaxis to peanut and a positive PST, challenges are unwarranted. When the history is strongly suggestive and the PST is borderline positive, i.e. 3 or 4 mm, peanut challenge is generally necessary to confirm the diagnosis. Given the excellent negative predictive value and sensitivity of PST, a blinded peanut challenge is usually unnecessary in the context of a negative PST except for patients with a history strongly suggestive of immediate hypersensitivity. These patients should be individually assessed for the need to undergo a blinded challenge. The peanut challenge is a useful and safe diagnostic tool when performed by qualified personnel under appropriate conditions.

Administration, Oral↗
PubMed2001

Airway responsiveness as a direct factor contributing to the dyspnoea perception in asthma.

It is not clear whether airway responsiveness is directly related to the perception of bronchoconstriction in asthma. The purpose of this study is to directly compare the perception of induced bronchoconstriction among the groups classified according to the degree of airway responsiveness. Two hundred and twenty-seven patients with the definitive or suspected asthma underwent a methacholine provocation test. During the test, the degree of dyspnoea was assessed by a modified Borg scale. The perception of induced bronchoconstriction was indicated by the slope in the linear regression analysis between changes in Borg score and the reduction in forced expiratory volume in 1 sec (FEV1) as a percentage of baseline value. The provocative concentration of methacholine resulting in 20% fall in FEV1 (PC20) was calculated. The degree of airway responsiveness to methacholine was categorized as moderate to severe airway hyper-responsiveness (AHR) if PC20 was < 1 mgml(-1), mild AHR if PC20 was > or =1 but < or =4 mgml(-1), borderline AHR if PC20 was >4 but < or =16 mgml(-1), and normal airway responsiveness (negative AHR) if PC20 was > 16 mgml(-1). Positive AHR was defined as PC20< or =4 mgml(-1). Another index of bronchial responsiveness (BR index) was calculated as the log [(% decline in FEV1/log final methacholine concentration as mg dl(-1)+10]. We found that the geometric mean of the slope was lower in subjects with positive AHR (0.12, n=115) than in subjects with negative AHR (0.17, n=72; P<0.01). The geometric mean of the slope in subjects with borderline AHR (0.14, n=40) was between the two groups. Furthermore, the slope was decreased in asthmatics with moderate to severe AHR compared with mild AHR (P <0.05), although the baseline FEV1 did not differ between the two groups. In multiple regression analysis, airway responsiveness expressed as BR index had a significant effect on the perception of bronchoconstriction. We conclude that the perception of bronchoconstriction is diminished in patients with AHR and the degree of airway responsiveness may be directly related to the perception of bronchoconstriction in asthmatic subjects.

Adolescent↗
PubMed2001

Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

We evaluated the expression of thymidylate synthase (TS) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients. TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil (5-FU) and doxorubicin-based adjuvant chemotherapy after curative resection. 65 patients (63%) had primary tumours with high TS expression (> or = 25% of tumour cells positive), and 38 patients (37%) demonstrated low TS expression (< 25% of tumour cells positive or no staining). High TS expression was associated with male gender (P = 0.002), poorly differentiated histology (P = 0.015), and mixed type in Lauren's classification (P = 0.027). There were no statistically significant differences in 4-year disease-free survival (60.0% vs. 57.2%, P = 0.548) and overall survival (59.6% vs. 59.3%, P = 0.792) between high-TS group and low-TS group. In conclusion, although high TS expression was associated with poorly differentiated histology and mixed type in Lauren's classification, it did not predict poor disease-free and overall survival in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy after curative resection. Further prospective studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary.

Adult↗
PubMed2001

Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced mr imaging versus combined helical CT during arterial portography and CT hepatic arteriography.

OBJECTIVE: The purpose of this study was to compare ferumoxides-enhanced MR imaging with combined helical CT during arterial portography and CT hepatic arteriography for preoperative detection of hepatocellular carcinomas. SUBJECTS AND METHODS: Twenty patients with 30 hepatocellular carcinomas underwent ferumoxides-enhanced MR imaging and combined helical CT during arterial portography and CT hepatic arteriography. The diagnosis was established by pathologic examination after surgical resection in 18 patients and by biopsy in two. The MR protocol included fast spin-echo with two echo times, T2(*)-weighted fast multiplanar gradient-recalled acquisition in the steady state, proton density-weighted fast multiplanar spoiled gradient-recalled echo, and T1-weighted fast multiplanar spoiled gradient-recalled echo images. The MR images of all sequences and the paired CT during arterial portography and CT hepatic arteriography images were independently evaluated by three radiologists on a segment-by-segment basis. Diagnostic accuracy was assessed with receiver operating characteristic analysis. RESULTS: The accuracies (A(z) values) of ferumoxides-enhanced MR imaging and combined CT during arterial portography and CT hepatic arteriography for all observers were 0.964 and 0.948, respectively. The mean sensitivities of MR imaging and CT were 93% and 91%, respectively. The differences were not statistically significant. The mean specificity of MR imaging (99%) was significantly higher than that of combined CT during arterial portography and CT hepatic arteriography (94%). CONCLUSION: Ferumoxides-enhanced MR imaging can be used successfully in place of combined CT during arterial portography and CT hepatic arteriography for the preoperative evaluation of patients with hepatocellular carcinomas.

Adult↗
PubMed2001

Oxidation of polycyclic aromatic hydrocarbons by ozone in the presence of sand.

A series of soil slurry experiments was performed to investigate the characteristics of PAHs removal by ozone in various conditions. Gaseous ozone was bottled into the aqueous phase in the presence of soil contaminated by PAHs. The effects of soil media, OH radical scavengers, ozone dosage, and humic acid were examined at the given experimental conditions. There exists a substantial difference in the removal of PAH according to the types of soil media tested. Baked sand showed the highest removal efficiency compared to the others. The descending order of removal rate was: BS > S > GB. This is considered to be due to the OH radical effect produced by catalytic reactions of ozone with the reactive site on the and. This is qualitatively proved by the experiment of scavenging OH radicals using tert-butanol. The comparison of half-lives of ozone in sand and glass bead columns further supports this hypothesis. It was found that about 22% of enhancement of phenanthrene destruction was accomplished by OH radicals produced by the catalytic ozone decomposition. The rate of ozone consumption for the phenanthrene oxidation was obtained as 1.88 mg/mgO3/min.

Catalysis↗
PubMed2001

Blood partition and protein binding of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378.

The blood partition of KR-31378 between plasma and blood cells and the factors influencing the binding of the drug to 4% human serum albumin (HSA) using an equilibrium dialysis technique were evaluated. KR-31378 reached an equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells concentration ratios were independent of initial rabbit blood concentrations of KR-31378, 1, 10 and 50 microg/ml; the values were in the range of 1.42-2.33. It took approximately 12-h incubation to reach an equilibrium between plasma and isotonic Søresen phosphate buffer of pH 7.4 containing 3% dextran ('the buffer'). The binding of KR-31378 to 4% HSA was dependent on HSA concentrations (the binding values were 25.3 and 32.0% for HSA concentrations of 2 and 5%, respectively), incubation temperature (the binding values were 48.8, 29.0 and 25.8% for 4, 22 and 37 degrees C, respectively), pHs of isotonic Sørensen phosphate buffer containing 3% dextran (the binding values were 17.7, 20.6, 22.8, 25.6 and 29.5% for buffer pHs of 5.8, 6.4, 7.0, 7.4 and 8.0, respectively) and alpha-1-acid glycoprotein (AAG) concentrations (the binding values were 25.6, 29.9, 34.4 and 50.3% for AAG concentrations of 0, 0.08, 0.16 and 0.32%, respectively).

Animals↗
PubMed2000

Regulation of cyclooxygenase-2 induction in the mouse uterus during decidualization. An event of early pregnancy.

The infertility phenotype of cyclooxygenase-2 (Cox-2)-deficient female mice establishes the important role of Cox-2 in pregnancy. Cox-2 deficiency results in defective ovulation, fertilization, implantation, and decidualization; the latter of which can be restored in part by the prostacyclin analog carbaprostacyclin. Uterine Cox-2 expression during early pregnancy shows distinct localization and kinetics in the uterine luminal epithelium and underlying stromal cells, suggesting that expression is tightly regulated. Several intracellular signaling cascades including ERK, p38, and JNK are implicated in vitro as critical components of regulated Cox-2 expression in response to mitogens, growth factors, and cytokines. We investigated the involvement of these signaling pathways during Cox-2 induction in vivo by monitoring uterine kinase activity after intraluminal application of a deciduogenic stimulus. Our results show that the ERK and p38 pathways are activated in uterine preparations as early as 5-min post-stimulation. ERK activation was sustained for several hours with a return to baseline levels by 4 h. p38 activation was rapid with a peak at 5-min post-stimulation and returned to near baseline levels after 45 min. Systemic administration of a MEK inhibitor completely inhibited ERK activation, but did not affect early (2 h) luminal epithelial or late (24 h) stromal Cox-2 expression and only modestly affected decidualization. In contrast, administration of a p38 inhibitor modestly inhibited early Cox-2 expression in the luminal epithelium, while dramatically diminishing late stromal expression. In parallel, induced stromal peroxisomal proliferator activated receptor-delta (PPARdelta) expression is blunted by p38 inhibition. p38 inhibition also significantly inhibited decidualization. These results suggest that p38, but not ERK, activation is required for induced Cox-2 and PPARdelta expression during decidualization. In addition, inhibition of p38 led to decreased decidualization suggesting that an intracrine prostanoid pathway consisting of Cox-2, prostacyclin, and PPARdelta is required for maintenance of early pregnancy.

Animals↗
PubMed2000

Mutational analysis of Lys65 of HIV-1 reverse transcriptase.

Amino acid Lys(65) is part of the highly flexible beta3-beta4 loop in the fingers domain of the 66 kDa subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Recent crystal data show that the epsilon-amino group of Lys(65) interacts with the gamma-phosphate of the bound deoxynucleoside triphosphate ('dNTP') substrate [Huang, Chopra, Verdine and Harrison (1998) Science 282, 1669-1675]. In order to biochemically define the function of RT Lys(65), we have used site-specific mutagenesis to generate RT with a variety of substitutions at this position, including K65E, K65Q, K65A and K65R. Kinetic analyses demonstrate that if Lys(65) in RT is substituted with an amino acid other than arginine the enzyme exhibits dramatic decreases in the binding affinity (K(m)) for all dNTP substrates, in RT catalytic efficiency (k(cat)/K(m)) and in the mutant enzyme's ability to carry out pyrophosphorolysis, the reverse reaction of DNA synthesis. The pH optimum for the DNA polymerase activity of K65E RT was 6.5, compared to 7.5 for the wild-type enzyme, and 8.0 for the K65R, K65A and K65Q mutants. Molecular modelling studies show that mutations of Lys(65) do not affect the geometry of the loop's alpha-carbon backbone, but rather lead to changes in positioning of the side chains of residues Lys(70) and Arg(72). In particular, Glu in K65E can form a salt bridge with Arg(72), leading to the diminution of the latter residue's interaction with the alpha-phosphate of the dNTP residue. This alteration in dNTP-binding may explain the large pH-dependent changes in both dNTP-binding and catalytic efficiency noted with the enzyme. Furthermore, the K65A, K65Q and K65E mutant enzymes are 100-fold less sensitive to all dideoxynucleoside triphosphate ('ddNTP') inhibitors, whereas the K65R mutation results in a selective 10-fold decrease in binding of ddCTP and ddATP only. This implies that mutations at position 65 in HIV-1 RT influence the nucleotide-binding specificity of the enzyme.

Binding Sites↗
PubMed2000

Dose-dependent pharmacokinetics of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378, in rats.

The dose-dependent pharmacokinetic parameters of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378, were evaluated after intravenous and oral administration, 10, 20, and 50 mg/kg, to rats. After intravenous administration of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (994 microg min/mL) was significantly greater than that at 10 (569 microg min/ml) and 20 (660 microg min/mL) mg/kg. This could be due to slower clearance (Cl) with increasing dosage (18.5, 14.6, and 10.2 mL/min/kg for 10, 20, and 50 mg/kg, respectively). The slower Cl with increasing dosage could be due to saturable metabolism of KR-31378 in rats and this could be supported by significantly slower Cl(nr) and significantly greater 24-h urinary excretion of the drug at 50 mg/kg than those at 10 and 20 mg/kg. After oral administration of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (1160 microg min/mL) was significantly greater than that at 10 (572 microg min/mL) and 20 (786 microg min/mL) mg/kg. Note that the AUCs were comparable (not significantly different) between intravenous and oral administration at each dosage, indicating that the absorption from gastrointestinal tract was almost complete and the first-pass (gastric, intestinal, and hepatic) effect was not considerable after oral administration to rats.

Analysis of Variance↗
PubMed2000

Molecular signaling in uterine receptivity for implantation.

Successful implantation is the result of an intimate 'cross-talk' between the blastocyst and uterus in a temporal and cell-specific manner. Thus, both the uterine and embryonic events must be examined to better understand this process. Although various aspects and molecules associated with these events have been explored, a comprehensive understanding of the implantation process is still very limited. In this review, we have highlighted the importance of the blastocyst's activity state and the receptive state of the uterus in determining the 'window' of implantation. In this context, we provide a testable scheme that signifies the important roles of various key molecules in embryo-uterine interactions during implantation.

Animals↗
PubMed2000

Phototesting and photopatch testing: when to do it and when not to do it.

Phototesting and photopatch testing are among the most important tests in the evaluation of photodermatoses, yet their use has been restricted to specialized centers. To assist clinicians interested in conducting these procedures and in updating their techniques, we asked 4 experts to comment on these tests in the context of diagnostic approach to the photosensitive patient. A list of photoallergens and a protocol for their use is provided.

Allergens↗
PubMed2000

The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children.

BACKGROUND: Peanut-allergic patients are affected by a condition which forces them and their families to exercise extreme dietary vigilance and experience constant uncertainty throughout their lives. OBJECTIVE: To compare the quality of life and family relations of children and adults with a peanut allergy to that of children and adults with a rheumatological disease. METHODS: Patients with a confirmed diagnosis of peanut allergy or a rheumatological disease completed (for children less than 18 years, by proxy) self-report questionnaires regarding the impact of their condition on their quality of life and family relations. A vertical visual analogue scale and the Impact on Family Questionnaire (IFQ) served as outcome measures. RESULTS: One hundred and fifty-three peanut-allergic children were compared with 69 children with a rheumatological disease while 37 peanut-allergic adults were compared with 42 adults with a rheumatological disease. The parents of peanut-allergic children, compared to the parents of children with a rheumatological disease, reported that their children had significantly more disruption in their daily activities. Furthermore, the parents of peanut-allergic children reported more impairment in the familial-social dimension of the IFQ. Conversely, adults with a chronic rheumatological disease reported more disruption in their family relations than peanut-allergic adults. CONCLUSION: Given the considerable disruption in daily activities and family relations reported by the parents of peanut-allergic children, accurate diagnosis of peanut allergy is essential. Our work should make health care professionals dealing with children with confirmed peanut allergy more aware of the support that these families may require. Furthermore, we hope to motivate food industries to offer more 'peanut free' products to decrease the dietary restrictions of these patients while minimizing their potential for accidental ingestion.

Adolescent↗
PubMed2000

Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal epithelium correlates with implantation failure in LIF-deficient mice.

Various mediators, including cytokines, growth factors, homeotic gene products, and prostaglandins (PGs), participate in the implantation process in an autocrine, paracrine, or juxtacrine manner. However, interactions among these factors that result in successful implantation are not clearly understood. Leukemia inhibitory factor (LIF), a pleiotropic cytokine, was shown to be expressed in uterine glands on day 4 morning before implantation and is critical to this process in mice. However, the mechanism by which LIF executes its effects in implantation remains unknown. Moreover, interactions of LIF with other implantation-specific molecules have not yet been defined. Using normal and delayed implantation models, we herein show that LIF is not only expressed in progesterone (P4)-primed uterine glands before implantation in response to nidatory estrogen, it is also induced in stromal cells surrounding the active blastocyst at the time of the attachment reaction. This suggests that LIF has biphasic effects: first in the preparation of the receptive uterus and subsequently in the attachment reaction. The mechanism by which LIF participates in these events was addressed using LIF-deficient mice. We observed that while uterine cell-specific proliferation, steroid hormone responsiveness, and expression patterns of several genes are normal, specific members of the EGF family of growth factors, such as amphiregulin (Ar), heparin-binding EGF-like growth factor (HB-EGF), and epiregulin, are not expressed in LIF(-/-) uteri before and during the anticipated time of implantation, although EGF receptor family members (erbBs) are expressed correctly. Furthermore, cyclooxygenase-2 (COX-2), an inducible rate-limiting enzyme for PG synthesis and essential for implantation, is aberrantly expressed in the uterus surrounding the blastocyst in LIF(-/-) mice. These results suggest that dysregulation of specific EGF-like growth factors and COX-2 in the uterus contributes, at least partially, to implantation failure in LIF(-/-) mice. Since estrogen is essential for uterine receptivity, LIF induction, and blastocyst activation, it is possible that the nidatory estrogen effects in the P4-primed uterus for implantation are mediated via LIF signaling. However, we observed that LIF can only partially resume implantation in P4-primed, delayed implanting mice in the absence of estrogen, suggesting LIF induction is one of many functions that are executed by estrogen for implantation.

Animals↗
PubMed2000

Changes in gallbladder motility in gastrectomized patients.

OBJECTIVES: Gastric resection may predispose gallstone formation. However, the mechanism has not been clearly understood. To evaluate the relationship between gastric resection and gallstone formation, we compared gallbladder(GB) motility in gastrectomized patients and control subjects. METHODS: We compared the GB volume and ejection fraction of the 46 gastrectomized patients with 37 healthy controls using real time ultrasonography. RESULTS: GB volume increased significantly in the gastrectomized group in fasting (30.2 +/- 13.9 ml). The GB volume after a fatty meal was greater in the gastrectomized group (12.6 +/- 6.4 ml) than in the control group (4.3 +/- 3.3 ml) (p < 0.01). A significant reduction of ejection fraction was found in gastrectomized patients (56.9 +/- 13.0%) in comparison with the control group (75.5 +/- 16.1%) (p < 0.01). The GB ejection fraction had a poor correlation to the postoperative period (r = 0.232). CONCLUSION: A gastrectomy appears to be a risk factor of GB dysmotility, which may play a major role in gallstone formation in gastrectomized patients.

Adult↗
PubMed1999

Profound apoptosis-mediated regional myocyte loss and compensatory hypertrophy in pigs with hibernating myocardium.

BACKGROUND: Myocyte apoptosis is seen in ischemic heart disease, but whether it can occur after reversible ischemia or independent of necrosis and replacement fibrosis is unknown. METHODS AND RESULTS: Pigs were instrumented with a stenosis of the left anterior descending coronary artery to chronically reduce coronary flow reserve over a period of 3 months. At this time, there was viable dysfunctional myocardium having the physiological features of hibernating myocardium. Resting subendocardial perfusion was reduced to 0.65+/-0.08 (mean+/-SEM) mL. min(-1). g(-1) in hibernating myocardium of instrumented pigs compared with 0.98+/-0.14 mL. min(-1). g(-1) in myocardium of sham-operated pigs (P<0.05). There was a critical limitation in subendocardial flow during vasodilation to 0.78+/-0.20 mL. min(-1). g(-1) in instrumented pigs versus 3. 24+/-0.50 mL. min(-1). g(-1) in sham-operated pigs (P<0.001). Histology revealed a regional reduction in myocyte nuclear density to 995+/-100 nuclei/mm(2) in hibernating myocardium from the instrumented group versus 1534+/-65 nuclei/mm(2) in myocardium from the sham-operated group (P<0.05), regional myocyte hypertrophy (myocyte volume per nucleus, 14 183+/-2594 in the instrumented group versus 9130+/-1301 microm(3) in the sham group; P<0.05), and minimal increases in connective tissue (5.8+/-0.9% in the instrumented group versus 3.0+/-0.2% in the sham group, P<0.05). Necrosis was not identified, but apoptosis was increased from 30+/-9 myocytes per 10(6) myocyte nuclei in myocardium from the sham group to 220+/-77 myocytes per 10(6) myocyte nuclei in hibernating myocardium (P<0.05). CONCLUSIONS: These findings indicate that reversible ischemia in an area of chronically reduced coronary flow reserve induces regional myocyte loss via an apoptotic mechanism. This may contribute to the progression of chronic coronary disease to heart failure and explain the lack of complete functional recovery after revascularization in hibernating myocardium.

Animals↗
PubMed1999

Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta.

We have demonstrated previously that cyclo-oxygenase-2 (COX2), the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs), is essential for blastocyst implantation and decidualization. However, the candidate PG(s) that participates in these processes and the mechanism of its action remain undefined. Using COX2-deficient mice and multiple approaches, we demonstrate herein that COX2-derived prostacyclin (PGI2) is the primary PG that is essential for implantation and decidualization. Several lines of evidence suggest that the effects of PGI2 are mediated by its activation of the nuclear hormone receptor PPARdelta, demonstrating the first reported biologic function of this receptor signaling pathway.

Animals↗