Biomedical subjects

T Sakai

Publications and source records attributed to T Sakai.

At least 127 records · Page 7Linked to original sources

PubMed2001

CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects.

PURPOSE: To predict the CYP2C19 genotype-dependence in anti-Helicobacter pylori (H. pylori) therapy when lansoprazole or rabeprazole was used instead of omeprazole as a proton pump inhibitor (PPI). METHODS: A comparative pharmacokinetic study with each PPI was designed as an open, randomized, and crossover study of 18 Japanese healthy volunteers who were classified into the homozygous, heterozygous extensive metabolizer and the poor metabolizer based on the CYP2C19 genotype determined by PCR-RFLP method. Each subject received a single oral dose of 20 mg omeprazole, 30 mg lansoprazole, or 20 mg sodium rabeprazole, with at least 1 week washout period between treatments. Plasma concentrations of PPIs and their metabolites were monitored until 12 h after medication. RESULTS: Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype. The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference. The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole. As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype. CONCLUSIONS: CYP2C19 genotype dependence will be found in the anti-H. pylori therapy even when lansoprazole is used as the PPI.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects.

PURPOSE: To evaluate the MDR1 genotype frequency in the Japanese population and to study the relationship between the MDR1 genotype and the pharmacokinetics of digoxin after single oral administration in healthy subjects. METHODS: The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg. RESULTS: It was found that 35.1 % (40/114) of subjects were homozygous for the wild-type allele (C/C). 52.6% (60/114) were compound heterozygotes with a mutant T-allele (C3435T) (C/T), and 12.3% (14/114) were homozygous for the mutant allele (T/T). There was no effect of gender or age on the distribution. The serum concentration of digoxin after a single oral administration increased rapidly, attaining a steady state in all subjects; however, it was lower in the subjects harboring the T-allele. AUC0-4 h values (+/-SD) were 4.11 +/- 0.57, 3.20 +/- 0.49. and 3.27 +/- 0.58 ng h/ml, respectively, with a significant difference between C/C and C/T or T/T. CONCLUSIONS: The serum concentration of digoxin after single oral administration was lower in the subjects harboring a mutant allele (C3435T) at exon 26 of the MDR1 gene.

Adult↗

PubMed2001

Roles of galactose and sulfate residues in sulfatides for their antagonistic functions in the blood coagulation system.

We previously reported that the sulfatide (galactosylceramide I3-sulfate) may have contradictory functions, namely both coagulant and anticoagulant roles in vivo: sulfatide induced giant thrombi formation when injected into rats with vein ligation, whereas no thrombi were formed when sulfatide was injected into rats without vein ligation. Rather it prolonged bleeding time. To investigate the structural features of sulfatide for both functions, a synthetic sulfatide (galactosylceramide I6-sulfate) which does not occur naturally, cholesterol 3-sulfate and ganglioside GM4 were examined together with naturally occurring sulfatide. Both sulfatides and cholesterol 3-sulfate induced giant thrombi in the rats with vein ligation within ten minutes of injection, although cholesterol 3-sulfate exhibited weaker coagulant activity than the sulfatides. On the contrary, both sulfatides significantly prolonged bleeding time but cholesterol 3-sulfate barely prolonged it when injected without vein ligation. GM4 exhibited neither coagulant nor anticoagulant activity. These results suggested that sulfate moiety in the sulfatides is essential for coagulant activity and that galactose residue enhances the activity, whereas both galactose and sulfate residues seem to be important for anticoagulant activity. This is because the sulfatides possess both residues but GM4 possesses galactose without sulfate and cholesterol 3-sulfate possesses sulfate without galactose. We previously reported that the possible mechanism of anticoagulation by sulfatide was due to its binding to fibrinogen, thereby inhibiting the conversion to fibrin. In this paper we reveal that both sulfatides inhibited thrombin activity independent of heparin cofactor II, thus providing evidence of another anticoagulation mechanism for the sulfatides.

Animals↗

PubMed2001

Beta2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol.

PURPOSE: To evaluate the beta2-adrenergic receptor (beta2AR) genotype frequency in the Japanese population and the relationship between beta2AR genotype at amino acid position 16 (beta2AR-16) and desensitization to beta2-agonist ex vivo. METHODS: The beta2AR genotypes at amino acid positions 16, 27, and 164 of 92 healthy Japanese subjects were determined by polymerase chain reaction-restriction fragment-length polymorphism. The relationship between the beta2AR-16 genotype and the desensitization to beta2-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50 microg, Meptin) was given orally for 5 days, and peripheral blood was obtained before and after 5 days of consecutive medications followed by the assessment of the intracellular cAMP levels in peripheral blood mononuclear cells after incubation with or without procaterol hydrochloride (0-1000 ng/mL). RESULTS: Allele frequency was Arg16:Gly16 = 46%:54%, Gln27: Glu27 = 92%:8%, and Thr164:Ile164 = 100%:0%, respectively. The cAMP levels were increased by incubation with procaterol hydrochloride, and the increase was suppressed after 5 days of consecutive medications. The suppression was more significant in the homozygote for Gly16 than the homozygote for Arg16. CONCLUSIONS: The desensitization to beta2-agonist was associated more frequently with the mutation at beta2AR-16 (Gly16).

Administration, Oral↗

PubMed2001

Expression of Set-alpha during morphogenesis of mouse lower first molar.

The detailed in situ expression pattern of the Set-alpha gene has been studied. Previously we showed that Set-alpha is a differentially expressed gene in the embryonic mouse mandible at day 10.5 (E10.5) gestational age. Cells expressing Set-alpha were widely distributed in both the epithelial and underlying ectomesenchymal cells at E10.5. At E12, they were slightly aggregated in an area where tooth germ of the lower first molar is estimated to be formed. At E13.5, Set-alpha was strongly expressed in the tooth germ. At the cap stage, Set-alpha was expressed in the enamel organ and dental papilla. At the bell stage, Set-alpha was distinctly expressed in the inner enamel epithelial and dental papilla cells facing the inner enamel epithelial layer, which were intended to differentiate into ameloblasts and odontoblasts, respectively. Interestingly, Set-alpha was also expressed in several embryonic craniofacial tissues derived from the ectoderm. This study is the first report that Set-alpha is distinctly expressed in the developing tooth germ, and suggests that Set-alpha plays an important role in both the initiation and the growth of the tooth germ, as well as in the differentiation of ameloblasts and odontoblasts.

Animals↗

PubMed2001

Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar.

This study examined the immunohistochemical detection of activated caspase-3, and its association with apoptosis, during tooth morphogenesis of the mouse lower first molar. The distribution of cells positive for caspase-3 closely corresponded with the localization of the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labelling (TUNEL)-positive apoptotic cells through the developmental course of tooth germs from embryo day 12 (E12) to E19, thus showing that the apoptosis occurring in the developing odontogenic tissue was induced by the activation of the caspase family. The specific distribution pattern of apoptotic cells in the developing odontogenic epithelial tissue from the initiation (E12) of tooth germ to the completion of tooth crown morphology (E19) also suggests that apoptotic events are related not only to a deletion of functionally suspended cells, but also participate in initiation and the completion of tooth morphogenesis. Electron microscopic examination revealed that apoptotic cells were present in the primary enamel knot, and these apoptotic cells were phagocytized by neighbouring odontogenic epithelial cells, thus indicating the prompt disposal of any dead cells by epithelial cells.

Animals↗

PubMed2001

Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis.

Fibronectin performs essential roles in embryonic development and is prominently expressed during tissue repair. Two forms of fibronectin have been identified: plasma fibronectin (pFn), which is expressed by hepatocytes and secreted in soluble form into plasma; and cellular fibronectin (cFn), an insoluble form expressed locally by fibroblasts and other cell types and deposited and assembled into the extracellular matrix. To investigate the role of pFn in vivo, we generated pFn-deficient adult mice using Cre-loxP conditional gene-knockout technology. Here we show that pFn-deficient mice show increased neuronal apoptosis and larger infarction areas following transient focal cerebral ischemia. However, pFn is dispensable for skin-wound healing and hemostasis.

Animals↗

PubMed2001

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.

Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.

Amino Acid Sequence↗

PubMed2001

Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals.

Polycyclic aromatic hydrocarbons (PAHs) are toxic chemicals released into the environment by fossil fuel combustion. Moreover, a primary route of human exposure to PAHs is tobacco smoke. Oocyte destruction and ovarian failure occur in PAH-treated mice, and cigarette smoking causes early menopause in women. In many cells, PAHs activate the aromatic hydrocarbon receptor (Ahr), a member of the Per-Arnt-Sim family of transcription factors. The Ahr is also activated by dioxin, one of the most intensively studied environmental contaminants. Here we show that an exposure of mice to PAHs induces the expression of Bax in oocytes, followed by apoptosis. Ovarian damage caused by PAHs is prevented by Ahr or Bax inactivation. Oocytes microinjected with a Bax promoter-reporter construct show Ahr-dependent transcriptional activation after PAH, but not dioxin, treatment, consistent with findings that dioxin is not cytotoxic to oocytes. This difference in the action of PAHs versus dioxin is conveyed by a single base pair flanking each Ahr response element in the Bax promoter. Oocytes in human ovarian biopsies grafted into immunodeficient mice also accumulate Bax and undergo apoptosis after PAH exposure in vivo. Thus, Ahr-driven Bax transcription is a novel and evolutionarily conserved cell-death signaling pathway responsible for environmental toxicant-induced ovarian failure.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

A possible role for lamivudine as prophylaxis against hepatitis B reactivation in carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Hepatitis B virus (HBV) reactivation, a well-known complication in immunosuppressed patients, can give rise to acute hepatitis and even fatal fulminant hepatitis. Three Japanese males with non-Hodgkin's lymphoma (NHL) who were carriers of HBV received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). To prevent HBV reactivation, all received oral lamivudine (150 mg/day), a nucleoside analogue, at the start of chemotherapy. All were treated at full-dose intensity, including corticosteroids, without modification of treatment regimens. All three patients completed the total course of chemotherapy and PBSCT, with no signs of HBV reactivation. Peripheral blood stem cell (PBSC) harvests and hematological recoveries after transplantation were not affected by lamivudine, which was continued for at least 16 weeks after transplantation. HBV-DNA and DNA polymerase levels remained negative/normal after discontinuation of lamivudine. Lamivudine effectively inhibits HBV replication and has few serious adverse effects, particularly those related to hematopoiesis. Thus, prophylactic use of lamivudine from initiation of chemotherapy deserves consideration in the treatment of HBV carriers who require immunosuppressive chemotherapy, and may prevent HBV reactivation.

Adult↗

PubMed2001

Successful non-myeloablative stem cell transplantation for a heavily transfused woman with severe aplastic anemia complicated by heart failure.

A 30-year-old Japanese woman weighing 35 kg with severe hemochromatosis due to multiple transfusions was referred to our clinic for treatment of severe aplastic anemia (SAA). The patient had heart failure with an ejection fraction of 36% requiring diuretics and a severe liver dysfunction with an indocyanine green clearance rate of 18%, as well as other transfusion-related complications such as chronic hepatitis due to hepatitis C virus and diabetes mellitus. She was treated with a non-myeloablative preparative regimen that included fludarabine monophosphate (Flu, 120 mg/m(2)), cyclophosphamide (CY, 1200 mg/m(2)) and antithymocyte globulin (ATG, 15 mg/kg) followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-matched sister. The regimen was well tolerated, and engraftment rapidly occurred without any therapy-related complications. Chimerism analysis on day 14 after transplant showed reconstitution with 100% donor cells. She no longer needed transfusion after day 23 and has been well in 90% Karnofsky status at 4 months post transplant. The clinical course of this patient indicates that this preparative regimen enables SAA patients with severe organ failure to safely undergo allogeneic stem cell transplantation.

Adult↗

PubMed2001

Plasma cytokine response to surgical stress in schizophrenic patients.

Schizophrenic patients are reported to have immunological dysfunction, however, the immune response to surgery in schizophrenic patients remains unclear. We measured plasma interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) before, during and after colectomy, hemicolectomy and sigmoidectomy in 25 chronic schizophrenic patients (Group S) and 25 control patients (Group C) using ELISA assays. We could find no significant difference in the baseline plasma concentrations of IL-6, IL-8 and TNF-alpha between Group S and Group C. Plasma IL-6 concentrations (32.1 (30.3) and 15.8 (9.6) pg/ml) in Group S at the end of the operation and 24 h after surgery were significantly lower than 76.9 (37.1) and 35.1 (21.5) pg/ml of Group C. Plasma IL-8 concentration (6.1 (2.8)) in Group S at the end of the operation was significantly lower than 8.7 (4.2) pg/ml of Group C. There were no significant changes in plasma TNF-alpha concentration throughout the study period in either group. Plasma cortisol concentrations of schizophrenic patients during surgery were significantly lower than those of control patients. The plasma IL-6 concentrations correlated with plasma cortisol concentrations in either group. We conclude that proinflammatory cytokine response to abdominal surgery is inhibited in schizophrenic patients.

Adult↗

PubMed2001

Granule-dependent killing of Toxoplasma gondii by CD8+ T cells.

Immunization of mice with live bradyzoites of a low-virulent Beverley strain of Toxoplasma gondii has been shown to increase CD8+ T-cell mediated immunity against a highly virulent RH strain. We found that preimmunization with an RH homogenate further enhanced this immunity. Using this model, we investigated the mechanism of CD8+ T-cell mediated protection against T. gondii infection. Splenic cells from mice immunized with RH homogenate and live bradyzoites stimulated apoptosis of RH-infected J774A.1 macrophages in vitro, and at the same time, the immunization significantly suppressed the proliferation of parasites within macrophages, as assessed by measuring 3H-uracil uptake by the parasites. Splenic cells from the immunized mice produced larger amounts of interferon-gamma (IFN-gamma) than did naive splenic cells; however, the production of nitric oxide (NO) by RH-infected macrophages was not enhanced. The elimination of CD8+ T cells from splenic cells significantly reduced their inhibitory action on parasite proliferation as well as their cytotoxic activity against RH-infected macrophages, but it did not affect the production of IFN-gamma. Treatment of CD8+ T-enriched splenic cells from the immunized mice with concanamycin A, but not an anti-Fas ligand monoclonal antibody, significantly reduced their anti-proliferative and killing capabilities, suggesting that the CD8+ T cells induced by immunization with RH antigen and live bradyzoites of the Beverley strain may exert protection against T. gondii infection at least in part through granule-dependent cytotoxic activities.

Animals↗

PubMed2001

A novel branching pattern of the superior mesenteric artery found in the bullfrog (Rana catesbeiana) amphibian.

The branching and distribution patterns of the superior mesenteric artery were studied in 10 adult bullfrogs (Rana catesbeiana) after injection of coloured latex solution into the vasculature. The abdominal digestive organs in the bullfrog were mainly supplied by the coeliac artery and the superior mesenteric artery, both of which arose as a common trunk, the coeliacomesenteric artery, from the abdominal aorta. The coeliac artery supplied the stomach, liver, gallbladder and the pancreas, whereas the first branch of the superior mesenteric artery was the splenic artery with other branches supplying the greater part of intestine. The apex of the intestinal loop was defined as the region supplied by the trunk of the superior mesenteric artery, and its intestinal branches constituted a 'nested formation' which had the following characteristics. (1) The branches of the trunk were distributed to both sides of the apex, and the distribution regions of younger branches were located more distant from the apex than those of older branches. (2) Two branches directed towards both sides of the trunk frequently made a common stem arising from the trunk. The second branch of the superior mesenteric artery constituted a secondary trunk and its distribution region could be defined as a secondary apex, since 1 of its branches also constituted a nested formation which was distributed to both sides of the primary and secondary apices. The intestinal branches of the superior mesenteric artery were divided into 4 types on the basis of their pattern of branching and course. It is suggested that the nested formation of the superior mesenteric artery in the bullfrog is a remnant of the vascular pattern of the tadpole, which possesses a double spiral mode of intestinal convolution, probably supplied by arteries with the nested formation in a latent form.

Animals↗

PubMed2001

FAT is a component of glomerular slit diaphragms.

BACKGROUND: Slit diaphragms are intercellular junctions of podocytes of the renal glomerulus. The molecular composition of slit diaphragms is still elusive. Slit diaphragms are characterized by the presence of a wide intercellular space. The morphological feature is shared by desmosomes and adherens junctions, which contain members of the cadherin superfamily. Thus, we have hypothesized that some components of slit diaphragms belong to the cadherin superfamily. Consequently, we have isolated cDNA encoding FAT from reverse-transcribed (RT) glomerular cDNA by homology polymerase chain reaction (PCR) using primers based on conserved sequences in cadherin molecules. FAT is a novel member of the cadherin superfamily with 34 tandem cadherin-like extracellular repeats, and it closely resembles the Drosophila tumor suppressor fat. METHODS: Expression of FAT was examined in glomeruli of the adult rat kidney by the ribonuclease protection assay and in situ hybridization. To localize the FAT protein in podocytes minutely, we prepared affinity-purified antibody against FAT by immunizing rabbits against an oligopeptide corresponding to the C-terminal 20 amino acids. RESULTS: Expression of FAT mRNA was detected in total RNA from glomeruli. In situ hybridization revealed significant signals in podocytes. Western blot analysis using solubilized glomeruli showed a single band, in which the molecular weight was more than 500 kD. Immunostaining of cultured epithelial cells from rat kidney (NRK52E) revealed FAT accumulation in cell-cell contact sites. In the glomerulus, FAT staining was observed distinctly along glomerular capillary walls. Double-label immunostaining using monoclonal antibody against slit diaphragms (mAb 5-1-6) showed identical localization of anti-FAT antibody and mAb 5-1-6. Furthermore, the double-label immunogold technique with ultrathin cryosections demonstrated that gold particles for FAT cytoplasmic domain were located at the base of slit diaphragms labeled by mAb 5-1-6 and that the cytoplasmic domain of FAT colocalized with ZO-1, a cytoplasmic component associated with slit diaphragms. CONCLUSION: The molecular structure of FAT and its colocalization with 5-1-6 antigen and ZO-1 indicate that FAT is a component of slit diaphragms.

Animals↗

PubMed2001

Hyperplastic vascular smooth muscle cells of the intrarenal arteries in angiotensin II type 1a receptor null mutant mice.

BACKGROUND: Angiotensin II (Ang II), which contracts vascular smooth muscle cells (VSMCs), has been reported to regulate VSMC growth. Recently formed transgenic mice without angiotensinogen or Ang II receptors showed vascular alterations. However, it is still unclear how their VSMCs alter. We explored the role of Ang II via the Ang II type 1a receptor (AT1a) in VSMCs in vivo using AT1a null mutant mice. METHODS: We analyzed the ultrastructure of the intrarenal arteries in AT1a null mutant mice that were homozygous for a targeted disruption of AT1a receptor gene using light and electron microscopy. RESULTS: The structural changes of the intrarenal arteries in AT1a null mutant mice showed the wall thickening, which in the interlobar, arcuate, and proximal interlobular arteries consisted of two additional populations of VSMCs, on the luminal and abluminal sides of the media. The luminal overpopulation of smooth muscle cells (SMCs) was arranged in a longitudinal direction separated by increased interposed elastic laminae. The abluminal overpopulation of SMCs ran in circumferential directions separated from the main population. The cytological structure of VSMCs in AT1a null mutant mice was smaller in size, contained more organelles for protein synthesis and secretion than in control mice, and had poorly developed contractile apparatus. CONCLUSIONS: The lack of AT1a signaling causes structural abnormalities in the renal vascular system and transforms the phenotype of VSMCs into cell proliferation, induces the escape of VSMCs from the circular mechanical integrity, and results in increased synthesis of extracellular matrices.

Animals↗

PubMed2001

The morbidity, time course and predictive factors for persistent post-thoracotomy pain.

After thoracotomy, patients often suffer from a persistent pain syndrome called post-thoracotomy pain. To elucidate morbidity, time course, and predictive factors for this syndrome, we analyzed follow-up data for 85 post-thoracotomy patients. We used a four-point scale to assess pain: none, slight, moderate and severe. Of 85 patients, 50 reported pain (39 slight, 11 moderate) one day after surgery. A year after surgery, the patients were polled using a simple questionnaire received by the mail. Sixty patients reported persistent pain (34 slight, 14 moderate, 12 severe) a month after surgery, and 35 patients reported persistent pain (33 slight, two moderate) around the time of the poll (1 year after surgery). Although pain deterioration was observed in 40% (34/85) of patients during month 1 after surgery, pain alleviation was seen in 48% (41/85) of patients during months 2-12. Stepwise regression analysis revealed that female gender and pain at postoperative day 1 were predictive for persistent pain both 1 month and 1 year after thoracotomy. Among 35 patients with persistent pain 1 year after surgery, 24 cases reported paresthesia-dysesthesia, and 14 cases reported hypoesthesia. The present data thus suggests that persistent pain is common and often severe 1 month after surgery but is alleviated after 1 year. Clinical time course and symptoms indicate that nerve impairment rather than simple nociceptive impact may be involved in this syndrome.

Aged↗

PubMed2001

High expression of CD34-positive sinusoidal endothelial cells is a risk factor for hepatocellular carcinoma in patients with HCV-associated chronic liver diseases.

CD34 has been widely used for the assessment of sinusoid-like neoangiogenesis in hepatocellular carcinoma (HCC). Recently, it was demonstrated that CD34-positive cells isolated from human peripheral blood differentiate into endothelial cells and contribute to neoangiogenesis in adults. We investigated the localization and the substantial role of CD34-positive endothelial cells in the liver with hepatitis C virus (HCV)--associated chronic liver diseases. Liver tissue sections obtained by biopsy from 56 patients with HCV-associated chronic liver diseases by were examined immunohistochemically using anti-CD34, anti-von Willebrand factor (vWF), and anti-vascular endothelial growth factor (VEGF) antibodies. CD34 was stained in the sinusoid, showing dotty, linear, semicircular, or circular patterns. However, sinusoidal expression of vWF was not substantially identified in the same specimens, indicating the existence of sinusoidal CD34-positive but vWF-negative endothelial cells. We classified these cells as CD34 LI and found that CD34 LI was correlated with the expression of VEGF. Among 34 patients with advanced-stage disease, the cumulative incidence of HCC was significantly higher in patients with CD34 LI >or= 12 (n = 16) than in those with CD34 LI < 12 (n = 18; P = .009). Moreover, among several clinicopathologic risk factors, CD34 LI could be recognized as an independently significant factor for development of HCC (relative risk, 7.36; P = .019). We conclude that CD34-positive endothelial cells are regulated by several factors, such as VEGF, and might play a substantial role in hepatocarcinogenesis. Furthermore, high expression of CD34-positive sinusoidal endothelial cells is a risk factor for HCC in patients with HCV-associated chronic liver diseases.

Adult↗