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Biomedical subjects

K Kawamura

Publications and source records attributed to K Kawamura.

At least 73 records · Page 4Linked to original sources
PubMed2000

Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice.

A cardiac homeobox-containing gene Csx/Nkx2-5, which is essential for cardiac development, is abundantly expressed in the adult heart as well as in the heart primordia. Targeted disruption of this gene results in embryonic lethality due to abnormal heart morphogenesis. To elucidate the role of Csx/Nkx2-5 in the adult heart, we generated transgenic mice which overexpress human Csx/Nkx2-5. The transgene was expressed abundantly in the heart and the skeletal muscle. mRNA levels of several cardiac genes including natriuretic peptides, CARP, MLC2v, and endogenous Csx/Nkx2-5 were increased in the ventricle of the transgenic mice. Electron microscopic analysis revealed that the ventricular myocardium of the transgenic mice had many secretory granules, which disappeared after administration of vasopressin. These results suggest that Csx/Nkx2-5 regulates many cardiac genes and induces formation of secretory granules in the adult ventricle.

Animals↗
PubMed2000

Histogenesis of the cerebral cortex in rat fetuses with a mutation in the Pax-6 gene.

The embryonic development of the cerebral cortex was histologically examined in rat homozygotes with a mutation of the Paired box (Pax)-6 gene, rat Small eye (rSey(2)/rSey(2)). Although the cerebral wall was thinner in rSey(2)/rSey(2) than in the wild type at embryonic day 16 (E16), cortical cells of mutants labeled with 5'-bromodeoxyuridine (BrdU) at E13 migrated as normal, settling in superficial layer at E16. Mitotic activity in the ventricular zone, estimated by immunoreactivity for proliferating cell nuclear antigen (PCNA), was also retained. On the other hand, after E20 cells were clustered in abnormally expanded ventricular and intermediate zones of the rSey(2)/rSey(2) cortex. Birthdating studies using BrdU revealed that most of these clustered cells were generated between E18 and E20. Most of clustered cells were immunoreactive for PCNA and highly polysialylated NCAM, while immunoreaction for neurofilament and microtubule-associated protein-2 (MAP-2) was hardly detected in the clusters. Furthermore, apoptosis detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) was rarely seen, suggesting that the clustered cells remain in an undifferentiating state, but not degenerated by the end of the gestational period. Considering that Pax-6 immunoreactivity was exclusively localized in the ventricular zone of the normal rat cortex throughout the fetal period, the present results suggest that Pax-6 is crucial for differentiation and migration of late-generated cortical neurons.

Animals↗
PubMed2000

On the nature of cell death during remodeling of hypertrophied human myocardium.

Cardiocyte loss during myocardial hypertrophy leads to progressive dysfunction in human hearts with chronic hemodynamic overload. The mechanism for such cell elimination is unknown. We examined lysosomal participation in cardiocytic degradation present in human cardiac biopsies, utilizing electron microscopic cytochemistry (acid phosphatase). Lysosomes were significantly increased in number (t-test, P<0.001) in 50 hemodynamically overloaded hearts (375+/-69, mean+/-s.e.m., per 5,000 microm(2) cardiocytic area; eight controls, 38+/-11). Secondary lysosomes were prominent near degenerative intracellular organelles in both hypertrophic and atrophic cardiocytes. Increased lysosomal and phagocytic activity in the cytoplasm without typical nuclear apoptosis resembled cytoplasmic degradation in developmental programmed cell death described in different tissues. We also demonstrated cardiocytic DNA degradation (in situ nick-end labeling) in autopsy hearts, including 299 nuclei normalized per 10(6) observed nuclei from five concentrically hypertrophied hearts, 1961 nuclei from five eccentrically hypertrophied hearts, and no positive nuclei in five controls. We postulate a chronic self-controlled cytoplasmic proteolysis in cardiocytes, not initially associated with either nuclear degradation or intercellular dehiscence but later possibly accompanied by apoptotic nuclear elimination, and leading to apoptotic cell death.

Acid Phosphatase↗
PubMed2000

Preclinical evaluation of [11C]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma1 receptors in the cat brain.

Our previous in vivo study with rats has demonstrated that 11C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) is a potential radioligand for mapping CNS sigmal receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [11C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [11C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma2 or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for signal receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [11C]SA4503 has the potential for mapping sigma1 receptor by PET.

Animals↗
PubMed2000

Myocardial integrated ultrasonic backscatter in patients with dilated cardiomyopathy: prediction of response to beta-blocker therapy.

BACKGROUND: Myocardial integrated backscatter (IB) imaging has been reported to be useful for ultrasonic tissue characterization and delineation of myocardial viability or fibrosis. beta-Blocker therapy has beneficial effects for patients with dilated cardiomyopathy (DCM), but there are no clear findings that indicate which patients with DCM will respond to this therapy. This study was performed to evaluate whether myocardial IB analysis can predict the response to beta-blocker therapy. METHODS AND RESULTS: We prospectively performed echocardiographic examination with IB analysis in 29 patients with DCM (20 men, 9 women) before starting bisoprolol therapy and in 15 normal subjects. Standard echocardiographic examination and IB analysis in the left ventricular wall in the 2-dimensional short-axis view were performed and the magnitude of cyclic variation (CV) of IB and calibrated myocardial IB intensity (subtracted pericardial) were obtained from the interventricular septum and the left ventricular posterior wall. Sixteen patients responded to bisoprolol therapy and 13 did not respond after 12 months of full-dose therapy. Calibrated myocardial IB intensity was lower in responders relative to nonresponders in both the interventricular septum (responders, -20.1 +/- 3.6 dB vs nonresponders, -9.8 +/- 5.1 dB, P <.0001; controls, -20.1 +/- 4.4 dB) and posterior wall (responders, -20.6 +/- 3.6 dB vs nonresponders, -14.6 +/- 4.2 dB, P =.0002; controls, -22.7 +/- 3.3 dB). Also, the lower the myocardial intensity in the interventricular septum or posterior wall, the better left ventricular systolic function improved after beta-blocker therapy. However, CV was lower in both DCM groups than in the controls, and CV in the interventricular septum was lower in nonresponders than in responders (responders, 4.0 +/- 4.1 dB vs nonresponders, -0.8 +/- 6. 1 dB, P <.02; controls, 8.3 +/- 2.4 dB). In addition, CV in the posterior wall showed no difference between the 2 DCM groups (responders, 5.6 +/- 1.3 dB vs nonresponders, 5.1 +/- 3.5 dB, P = not significant; controls, 9.6 +/- 2.5 dB). Also, the percent fibrosis on right ventricular endomyocardial biopsy specimens showed no distinctions between these 2 groups (responders, 25.1% +/- 16.1% vs nonresponders, 24.9% +/- 15.0%, P = not significant). CONCLUSIONS: These findings suggest that left ventricular myocardial IB data, especially IB intensity, provide useful information for predicting the response to beta-blocker therapy in patients with DCM. However, right ventricular endomyocardial biopsy findings do not appear to contribute to discriminating between the 2 groups.

Adrenergic beta-Antagonists↗
PubMed2000

Efficient HPLC separation of [11C]beta-CFT or [11C]beta-CIT from an N-desmethyl precursor on a semipreparative reversed phase ODS column.

HPLC separation of either [11C]beta-CFT or [11C]beta-CIT from the N-desmethyl precursor greatly depended on the ODS column used and the pH of the phosphate buffer in the mobile phase. The separation was accomplished on the semipreparative reversed phase ODS column without end-capping treatment over a pH ranging from 6.4 to 9.2, but failed on the end-capped ODS column. This suggests that the presence of residual silanol groups on the ODS is an important factor for the separation.

Carbon Radioisotopes↗
PubMed2000

In vivo evaluation of [(11)C]SA4503 as a PET ligand for mapping CNS sigma(1) receptors.

The potential of the (11)C-labeled selective sigma(1) receptor ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) was evaluated in vivo as a positron emission tomography (PET) ligand for mapping sigma(1) receptors in rats. SA4503 is known to have a high affinity (IC(50) = 17.4 nM) and a higher selectivity (sigma(1)/sigma(2) = 103) for the sigma(1) receptor. A high and increasing brain uptake of [(11)C]SA4503 was found. Pre-, co- and postinjection of cold SA4503 significantly decreased uptake of [(11)C]SA4503 in the brain, spleen, heart, lung, and kidney in which sigma receptors are present as well as in the skeletal muscle. In the blocking study with one of four sigma receptor ligands including haloperidol, (+)-pentazocine, SA4503, and (-)-pentazocine (in the order of their affinity for sigma(1) receptor subtype), SA4503 and haloperidol significantly reduced the brain uptake of [(11)C]SA4503 to approximately 30% of the control, but the other two benzomorphans did not. A high specific uptake of [(11)C]SA4503 by the brain was also confirmed by ex vivo autoradiography (ARG) and PET. Ex vivo ARG showed a higher uptake in the vestibular nucleus, temporal cortex, cingulate cortex, inferior colliculus, thalamus, and frontal cortex, and a moderate uptake in the parietal cortex and caudate putamen. Peripherally, the blocking effects of the four ligands depended on their affinity for sigma(1) receptors. No (11)C-labeled metabolite was detected in the brain 30 min postinjection, whereas approximately 20% of the radioactivity was found as (11)C-labeled metabolites in plasma. These results have demonstrated that the (11)C-labeled sigma(1) receptor ligand [(11)C]SA4503 has a potential for mapping sigma(1) receptors in the central nervous system and peripheral organs.

Animals↗
PubMed2000

Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells.

We investigated the antitumor effects induced by the production of interleukin-12 (IL-12) or IL-18, which influence the function of T helper type 1 cells, in murine colon carcinoma cells (Colon 26). Retrovirally transduced cells with IL-12 genes that encoded both p35 and p40 (Colon 26/IL-12) lost their tumorigenicity when inoculated subcutaneously or intraperitoneally into syngeneic immunocompetent mice. Moreover, the mice that had rejected the Colon 26/IL-12 cells generated protective immunity to wild-type (wt) cells when subsequently challenged. Colon 26 cells transduced with the IL-18 gene (Colon 26/IL-18) could not form subcutaneous tumors in immunocompetent mice, and the mice became resistant to inoculated wt cells. Immunohistochemical analysis revealed that the numbers of blood vessels in Colon 26/IL-12 or Colon 26/IL-18 tumors were markedly reduced, and that the expression of adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 increased on the endothelium in the stroma of Colon 26/IL-12 tumors. The loss of tumorigenicity of Colon 26/IL-12 or Colon 26/IL-18 cells was not observed in immunocompromised mice. However, the survival days of the immunocompromised mice inoculated with Colon 26/IL-12 but not Colon 26/IL-18 cells were significantly longer than those inoculated with wt cells. The secretion of cytokines that stimulate T helper type 1 cells from tumor cells can thereby induce an antitumor response. However, the effector cells involved in these antitumor effects could differentially migrate to the tumors, and the inhibition of angiogenesis may partially contribute to the antitumor responses observed.

Animals↗
PubMed2000

Expression of Escherichia coli uracil phosphoribosyltransferase gene in murine colon carcinoma cells augments the antitumoral effect of 5-fluorouracil and induces protective immunity.

Uracil phosphoribosyltransferase (UPRT) of Escherichia coli origin can convert 5-fluorouracil (5-FU), a chemotherapeutic agent widely used for solid tumors, to an active intermediate, 5-fluorouridine-5'-monophosphate, as mammalian orotate phosphoribosyltransferase does. To examine whether the E. coli UPRT gene expressed in tumor cells can confer increased sensitivity to 5-FU, we retrovirally transduced Colon 26 cells, a murine colon carcinoma cell line, with the UPRT gene (Colon 26/UPRT cells) and tested the in vivo antitumoral effect of 5-FU in syngeneic immunocompetent mice. After 5-FU administration, tumors of Colon 26/UPRT cells regressed, whereas those of wild-type cells were unaffected. The mice that once eliminated Colon 26/UPRT tumors after 5-FU treatment rejected wild-type cells that were subsequently inoculated but not irrelevant syngeneic tumor cells. This suicide gene/prodrug system was less efficient in nude mice, suggesting that mature alphabeta T cells play a role in the antitumoral effect. The cytotoxicity mediated by the bystander effect was marginal in this system, contrary to the herpes simplex virus-thymidine kinase gene/ganciclovir system. Therefore, expression of the UPRT gene in tumor cells followed by 5-FU administration is a possible strategy for cancer gene therapy, but potentiation of the bystander effect is required for its therapeutic application.

Adenocarcinoma↗
PubMed2000

Immunological responsiveness to interleukin-2-producing brain tumors can be restored by concurrent subcutaneous transplantation of the same tumors.

The central nervous system shows tolerance for activated host immune reactions, and this relative unresponsiveness may lessen the efficacy of an immunotherapy for brain tumors. Using interleukin-2 (IL-2)-producing 9L rat gliosarcoma cells (9L/IL-2), we examined whether secretion of IL-2 from subcutaneous (s.c.) and/or intracerebral (i.c.) tumors can elicit augmented immunological responses to brain tumors. Syngeneic rats could reject 9L/IL-2 cells inoculated s.c., but developed 9L/IL-2 brain tumors by i.c. inoculation. The growth of i.c. 9L/IL-2 tumors was, however, significantly retarded compared with that of i.c. wild-type tumors. The growth of i.c. wild-type tumors was significantly suppressed when the rats concurrently received 9L/IL-2 cells s.c. Moreover, most of the rats that were inoculated i.c. with 9L/IL-2 cells did not develop brain tumors when concurrently injected s.c. with 9L/IL-2 cells. Immunohistochemical analysis on i.c. 9L/IL-2 tumors, when the rats were concurrently inoculated s.c. with 9L/IL-2 cells, revealed that migration of CD4+ or CD8+ T cells, monocytes/microglias, and macrophages was markedly augmented to a similar level as found in the s.c. 9L/IL-2 tumors. These results showed that systemic immune responses to brain tumor were induced in an immunologically privileged site by concurrent s.c. inoculation of the same tumors that produce IL-2. The present study may also raise the possibility of a therapeutic strategy for brain tumors by the combinatory expression of IL-2 gene using s.c. immunization followed by direct gene transfer into brain tumors.

Animals↗
PubMed2000

Germ cell-specific heat shock protein 105 binds to p53 in a temperature-sensitive manner in rat testis.

Heat shock protein (HSP)105 is a testis-specific and HSP90-related protein. The aim of this study was to explore the functions of HSP105 in the rat testis. Signals of HSP105 were detected immunohistochemically in the germ cells and translocated from the cytoplasm to the nucleus at 2 days after experimental induction of cryptorchidism. In cultured testicular germ cells, a significant increase in the expression of HSP105 in response to heat stress (37 degrees C) was detected in the insoluble protein fractions. Several binding proteins were isolated from rat testis using a HSP105 antibody immunoaffinity column, and p53, the tumor suppressor gene product, was copurified with these. Furthermore, immunoprecipitation using antibodies to p53 led to coprecipitation of HSP105 together with p53 after culturing germ cells at 32.5 degrees C, but not at 37 or 42 degrees C. In conclusion, HSP105 is specifically localized in the germ cells and may translocate into the nucleus after heat shock. HSP105 is suggested to form a complex with p53 at the scrotal temperature, and dissociate from it at suprascrotal temperatures. At scrotal temperature, HSP105 may thus contribute to the stabilization of p53 proteins in the cytoplasm of the germ cells, preventing the potential induction of apoptosis by p53.

Animals↗
PubMed2000

Functional retinoid receptors in budding ascidians.

A homolog of retinoid X receptors (RXR), named PmRXR, was cloned from the budding ascidian, Polyandrocarpa misakiensis. Gel-shift assays revealed that PmRXR and a previously identified P. misakiensis retinoic acid receptor (PmRAR) formed a complex to bind vertebrate-type retinoic acid response element (RARE). Transfection assays were carried out using a reporter gene containing a RARE upstream of lacZ. Two chimeric effector genes were constructed by placing PmRXR and PmRAR cDNA fragments (containing the DNA-binding, ligand-binding and ligand-dependent transactivation domains) downstream of the human RXR alpha and RAR alpha cDNA (covering the N-terminal coding region), respectively. Each chimeric cDNA was ligated to a notochord-specific enhancer. In case the embryos were transfected with all three transgenes and treated with retinoic acid (RA), the reporter gene was activated in the notochord cells. The result suggests that the PmRXR/PmRAR complex functions as an RA-dependent transcriptional activator. The PmRXR mRNA was detected in a mesenchymal cell type, called glomerulocyte, in the developing Polyandrocarpa bud. As this cell type has been shown to express PmRAR mRNA, it seems possible that the PmRXR/PmRAR complex mediates RA signaling in this cell type to induce the expression of genes involved in the morphogenesis of the developing bud.

Amino Acid Sequence↗
PubMed2000

Increased digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy.

AIMS: Although increased digitalis-like immunoreactive substances have been found in cases of hypertension and heart failure, no information is available about digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy. We investigated digitalis-like immunoreactive substances in the plasma and biopsied specimens of patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: In 40 patients with hypertrophic cardiomyopathy (27 with the non-obstructive type and 13 with the obstructive type), the plasma concentration of digitalis-like immunoreactive substances was studied by fluorescence polarization immunoassay. Right ventricular endomyocardial biopsy specimens were analysed immunohistochemically, using a monoclonal antibody against digoxin. An increase in digitalis-like immunoreactive substances of more than 0.2 ng. ml(-1)in plasma was found in six of 27 patients with non-obstructive hypertrophic cardiomyopathy (22.2%) and five of 13 with obstructive hypertrophic cardiomyopathy (38.4%). Under light microscopy, positive staining against the antibody was observed heterogeneously on some cardiocytes. In non-obstructive hypertrophic cardiomyopathy, digitalis-like immunoreactive substances in the plasma correlated with the left atrial dimension and inversely with the cardiac index. In obstructive hypertrophic cardiomyopathy, plasma and myocardial digitalis-like immunoreactive substances were positively correlated; they also correlated with left ventricular end-diastolic pressures. Under electron microscopy, digitalis-like immunoreactive substances were detected at the sarcolemma in the free wall, T-tubules, intercalated discs and Z-bands of cardiocytes. CONCLUSIONS: Increased digitalis-like immunoreactive substances in plasma and cardiocytes, which may have been caused by pressure and/or volume overload, were found in patients with hypertrophic cardiomyopathy. Digitalis-like immunoreactive substances may act on the sarcolemma of cardiocytes and be transported into the cytoplasm.

Adult↗
PubMed2000

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients.

OBJECTIVE: To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN: Prospective, single-center, observational study. SETTING: University hospital operating room, intensive care unit. PATIENTS: Sixteen adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: None except cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. CONCLUSION: Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.

Adult↗
PubMed2000

Ovarian mucinous cystadenocarcinoma as a cause of Zollinger-Ellison syndrome: report of a case and review of the literature.

Gastrin producing ovarian tumor is a rare cause of the Zollinger-Ellison syndrome. We report the case of an ovarian carcinoma showing increased plasma gastrin concentration. A 60-yr-old woman presented with epigastric pain and diarrhea. Physical examination showed a large mass in the lower abdomen. Computed tomography revealed a large multilocular ovarian cyst. Upper gastrointestinal endoscopy examination showed multiple ulcerations of the stomach and duodenum. The plasma gastrin level was 1500 pg/ml. No tumors were found in the pancreas and duodenum, and salpingo-oophorectomy was performed. Histologic examination revealed a mucinous tumor of borderline malignant potential. Immunoperoxidase studies for gastrin showed many gastrin-producing cells within the epithelium of the tumor. There have been 11 cases (including our patient) of gastrin-producing ovarian tumor reported in the literature. We review here the relevant literature. Although ovarian gastrinoma is extremely rare, it should be considered as a possible cause of the Zollinger-Ellison syndrome in women.

Adenocarcinoma, Mucinous↗
PubMed2000

Enhanced hepatic lipid peroxidation in patients with primary biliary cirrhosis.

OBJECTIVE: The mechanisms responsible for hepatic injury have not been fully clarified in primary biliary cirrhosis (PBC). It has recently been suggested that hepatic lipid peroxidation may be involved in the pathogenesis of PBC. The aims of the current study were to determine whether patients with PBC have evidence of enhanced hepatic lipid peroxidation and to evaluate its relationship to clinicopathological features. METHODS: Immunohistochemical detection of 4-hydroxynonenal (HNE) protein adducts was performed in the liver biopsies of 20 patients with PBC. Histological stages of PBC were evaluated. Orcein or Victoria blue staining was performed for detection of copper-associated proteins. The size of bile ducts was defined as the smallest diameter between the subepithelial basement membranes. RESULTS: All 20 patients had immunodetectable HNE protein adducts in the cytoplasm of damaged, but also intact, biliary cells. The mean diameter of bile ducts with HNE protein adducts was smaller than those without the adducts (61.0 +/- 1.9 vs 122.5 +/- 24.4 microm, respectively, p < 0.01). Out of 20 patients, 6 (30%) also had immunodetectable HNE protein adducts in hepatocytes preferentially located around the portal tracts. Most of the patients with hepatocytic HNE protein adducts had copper-associated protein granules in hepatocytes around the portal tracts and were classified as histological stage 3, whereas all of the patients without the adducts lacked copper-associated protein granules and were classified as histological stage 1 or 2. The patients with hepatocytic HNE protein adducts had higher levels of serum total bilirubin than did those without the adducts (2.9 +/- 0.9 vs 0.7 +/- 0.1 mg/dl, respectively, p < 0.01). CONCLUSIONS: Hepatic lipid peroxidation can occur in PBC and may be an early event in bile duct destruction. At advanced stages of PBC, hepatocellular lipid peroxidation may play a role in hepatocyte injury during cholestasis.

Aldehydes↗