Comparison of the computed tomography values of the bone fragment gap after sagittal split ramus osteotomy in mandibular prognathism with and without asymmetry.

The purpose of this study was to compare computed tomography (CT) Hounsfield unit values of bone fragment gaps after sagittal split ramus osteotomy (SSRO) in patients with and without asymmetry, and to evaluate differences between the deviated and non-deviated sides in asymmetric patients. Thirty-two patients who underwent a bilateral SSRO were included in this retrospective study. Patients were divided into symmetric and asymmetric groups by cephalometric analysis. CT values of the bone fragment gap were measured at 1 week and at 1 year after surgery. There were significant differences between CT values obtained at 1 week and at 1 year after surgery for all measurement points. However, there were no significant differences in CT values between symmetric and asymmetric patients at either 1 week or 1 year after surgery. Among asymmetric patients, there were no significant differences between the deviated and non-deviated sides at 1 week or 1 year after surgery. This study showed ossification of the bone fragments and adaptation to change the mandible form in patients with and without asymmetry following SSRO.

Changes in the computed tomography (pixel) value of mandibular ramus bone and fixation screws after sagittal split ramus osteotomy.

The purpose of this retrospective study was to evaluate the changes in computed tomography (CT) values of ramus bone and screws after sagittal split ramus osteotomy (SSRO) setback surgery. The subjects were 64 patients (128 sides) who underwent bilateral SSRO setback surgery. They were divided into six groups according to the fixation plate type used and the use or not of self-setting α-tricalcium phosphate (Biopex): group 1: titanium plate and screws; group 2: titanium plate and screws with Biopex; group 3: poly-l-lactic acid (PLLA) plate and screws; group 4: PLLA plate and screws with Biopex; group 5: uncalcined and unsintered hydroxyapatite particles and poly-l-lactic acid (uHA/PLLA) plate and screws; group 6: PLLA/uHA plate and screws with Biopex. CT values (pixel values) of the lateral cortex, medial cortex, osteotomy site, and screws were measured preoperatively, immediately after surgery, and 1 year postoperatively using horizontal CT images at the mandibular foramen taken parallel to the Frankfort horizontal plane. There were significant differences in the time-course change of pixel values for the lateral cortex (P<0.0001) and the osteotomy site (P<0.0001) among the six groups. This study suggests that the fixation plate type and use of bone alternative material may affect bone quality during the process of bone healing after SSRO.

Changes in occlusal function after orthognathic surgery in mandibular prognathism with and without asymmetry.

This study aimed to evaluate the postoperative changes in masticatory function in patients with jaw deformities with or without asymmetry treated by orthognathic surgery. Thirty female patients who underwent a Le Fort I osteotomy with sagittal split ramus osteotomy (SSRO) were enrolled. The patients were divided into symmetry and asymmetry groups. The bite force, occlusal contact area, and bite force balance were measured before and at 1, 3, and 6 months and 1 year after surgery; these measurements were compared statistically within and between the two groups. In the symmetry group, there was a significant difference in the preoperative bite force and the 1 month postoperative bite force (P=0.0033). In the asymmetry group, the bite force before surgery was significantly different from that at 1 month (P=0.0375) and at 1 year (P=0.0353) after surgery. Significant differences in the bite force were also observed between the following time points: 1 month and 1 year (P=0.0003), 3 months and 1 year (P=0.0034), and 1 month and 6 months (P=0.0486). The occlusal contact area, bite force, and occlusal balance tended to change after Le Fort I osteotomy with SSRO, with a significantly improved bite force in patients with asymmetry before surgery.

Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers.

Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.

Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling.

Pulmonary fibrosis is a progressive disorder whose molecular pathology is poorly understood. Here we developed an in-house cDNA microarray ("lung chip") originating from a lung-normalized cDNA library. By using this lung chip, we analyzed global gene expression in a murine model of bleomycin-induced fibrosis and selected 82 genes that differed by more than twofold intensity in at least one pairwise comparison with controls. Cluster analysis of these selected genes showed that the expression of genes associated with inflammation reached maximum levels at 5 days after bleomycin administration, while genes involved in the development of fibrosis increased gradually up to 14 days after bleomycin treatment. These changes in gene expression signature were well correlated with observed histopathological changes. The results show that microarray analysis of animal disease models is a powerful approach to understanding the gene expression programs that underlie these disorders.

Various scoring systems evaluating histologic features of chronic hepatitis C treated with interferon.

Various scoring systems for chronic hepatitis have been proposed; however, there is no standard scoring system for studies of interferon (IFN) therapy in patients with chronic hepatitis C. The aims of this study were to determine the most useful system reflecting histologic changes in biopsy specimens from complete responders and predicting the efficacy of IFN therapy. Patients with chronic hepatitis C were administered IFN-alpha for 6 months. Forty-six patients were included in this study and categorized as complete responders (n = 15), partial responders (n = 24), and nonresponders (n = 7) according to viral and biochemical responses to the therapy. Biopsy specimens obtained from each patient before and after treatment were evaluated under 3 different systems: Histological Activity Index (HAI), modified HAI, and Scheuer classification. Complete responders showed considerable improvement in both grade and stage on the modified HAI and Scheuer classifications. On the HAI, a considerable improvement was observed in grade but not in stage. No significant change was observed in partial responders or nonresponders on any system. Prediction of complete response was not possible under any system, but the pretreatment score reflecting piecemeal necrosis on any 1 of the 3 classifications and the fibrosis score on Scheuer classification were predictors of nonresponse. The modified HAI system and Scheuer classification were amply useful in evaluating histologic changes in complete responders. Scores higher than 4 of the categories reflecting piecemeal necrosis on any system and fibrosis scores of 3 or 4 on Scheuer classification predicted nonresponse to IFN therapy.

Autopsy case of alcoholic hepatitis and cirrhosis treated with corticosteroids and affected by Pneumocystis carinii and cytomegalovirus pneumonia.

A case of the very early phase of Pneumocystis carinii pneumonia in a human immunodeficiency virus (HIV)-negative man with alcoholic hepatitis and cirrhosis treated with steroids is presented. A 40-year-old man with a 10-year history of alcohol abuse was admitted to hospital with jaundice, fever and macrohematuria. Laboratory examinations revealed neutrophilic leukocytosis and a serum bilirubin level of 13.9 mg/dL. The serum bilirubin level rose to 28.5 mg/dL over 1 month. Prednisolone administered orally for 10 days produced a slight improvement in the jaundice and fever. After an interval of a week, it was resumed and maintained for 22 days (total dose, 1555 mg) until the patient died of a massive hemorrhage from ruptured vessels of a gastric ulcer. An autopsy disclosed P. carinii pneumonia in the lower lobe of the left lung, cytomegalovirus infection in both lungs and the esophagus, and esophageal candidiasis. To our knowledge, this is the first report of P. carinii pneumonia together with cytomegalovirus infection in an HIV-negative alcoholic patient. The present case suggests that a rare opportunistic infection such as P. carinii pneumonia might be caused by treating cirrhosis and alcoholic hepatitis with corticosteroids, even if only for a relatively short period.

[Complications of stress echocardiography].

BACKGROUND: Stress echocardiography is an established clinical testing method and is accurate for the detection of coronary artery disease. Despite its widespread use, the safety of stress echocardiography has not been sufficiently documented in Japanese laboratories. OBJECTIVES: The feasibility, safety, complications and side effects of stress echocardiography were assessed for detecting myocardial ischemia in patients with suspected coronary artery disease. METHODS: 1,866 patients who underwent dobutamine echocardiography(n = 897), exercise echocardiography(n = 722), and dipyridamole echocardiography(n = 247) were prospectively studied from November 1990 to April 2000. Dobutamine was administered intravenously at 5, 10, 20, 30, 40 micrograms/kg/min in 3-minute intervals. Exercise echocardiography used the supine ergometer, starting at 50 W and increasing gradually by 25 W at 3-minute intervals to the maximum of 150 W. Dipyridamole was administered intravenously at 0.14 mg/kg/min for 4 min. After a 4-minute observation period, the drug was re-administered at the same dose for 2 min. RESULTS: The most common side effects under each stress were ventricular premature beats in 34.1% (dobutamine echocardiography), ventricular premature beats in 14.4%(exercise), and headache in 24.3% (dipyridamole). Serious side effects occurred in one patient(0.05%). The case of acute myocardial infarction was caused by dipyridamole echocardiography, and the patient needed emergency coronary angioplasty. Seven patients needed other drug therapy for nonsustained ventricular tachycardia(one), paroxysmal supraventricular tachycardia(two), sinus bradycardia(three), and bronchial asthma(one). There was no incidence of death, shock, or ventricular fibrillation, sustained ventricular tachycardia or other conditions requiring inpatient observation during stress echocardiography. CONCLUSIONS: Stress echocardiography is a reasonable, safe method for determining myocardial ischemia, but may be associated with minor, self-limiting side effects.

Effect of PPAR activators on cytokine-stimulated cyclooxygenase-2 expression in human colorectal carcinoma cells.

Cyclooxygenase-2 (COX-2) expression is up-regulated in colorectal cancer tissue. Peroxisome proliferator-activated receptors (PPARs) are expressed in human colorectal tissue and activation of PPARs can alter COX-2 expression. In macrophages, activation of PPARs down-regulates COX-2 expression. We examined the effect of PPARalpha and PPARgamma ligands on untreated and TNF-alpha-induced COX-2 expression in the human colorectal epithelial cell line HT-29. The expression of PPARalpha and PPARgamma was confirmed in these cells. TNF-alpha, an inflammatory cytokine, increased COX-2 expression via the NFkappaB pathway. In the absence of TNF-alpha, WY14643 (PPARalpha activator) caused an increase, while BRL49653 (PPARgamma activator) did not alter COX-2 expression. When HT-29 cells were incubated with TNF-alpha and WY14643, a further increase in COX-2 expression was detected. Incubation with TNF-alpha and BRL49653 caused an additional twofold increase in COX-2 expression. Our results suggest that both PPARalpha signaling and TNF-alpha signaling increase COX-2 expression by independent pathways, while PPARgamma stimulates COX-2 expression by up-regulation of the TNF-alpha pathway.

Hyperventilation and cold-pressor stress echocardiography for noninvasive diagnosis of coronary artery spasm.

We report the usefulness of 2-dimensional echocardiography during the cold-pressor test immediately after hyperventilation for noninvasive diagnosis of coronary vasospasm in 43 patients with suspected vasospastic angina. The stress test consisted of hyperventilation for 6 minutes, followed by cold water pressor stress for 2 minutes under continuous electrocardiographic and echocardiographic monitoring. Coronary angiography with an intracoronary injection of acetylcholine was performed within 2 weeks after the stress test. Coronary spasm was observed in 33 patients by angiography. Multivessel spasm was diagnosed in 26 patients by stress echocardiography and in 23 patients by angiography. The stress-induced wall motion abnormalities occurred earlier than the ST-segment changes and chest pain. The wall motion abnormalities shown on the echocardiogram correlated well with the vascular territories of the coronary artery that had the spasm. The sensitivity, specificity, and diagnostic accuracy of hyperventilation and cold-pressor stress echocardiography for detecting vasospastic angina against coronary angiography with an intracoronary injection of acetylcholine were 91%, 90%, and 91%, respectively. However, the sensitivity, specificity, and diagnostic accuracy of hyperventilation and cold-pressor stress electrocardiography for detecting vasospastic angina were 48%, 100%, and 60%, respectively. No major side effects were observed during or after the stress test. Echocardiographic monitoring during the stress test detected spasm unaccompanied by either ST- segment changes or chest pain and revealed the location of multivessel coronary spasm. Hyperventilation and cold-pressor stress echocardiography is thus a noninvasive and useful tool for the diagnosis of vasospastic angina.

[Contrast agent improves diagnostic value of dobutamine stress echocardiography].

OBJECTIVES: Suboptimal endocardial definition reduces the diagnostic value of stress echocardiography for coronary artery disease, but intravenous infusion of a left ventricular contrast agent (Albunex) may enhance endocardial border delineation and improve the diagnostic value of dobutamine stress echocardiography. METHODS: Fifty-six patients, 38 with myocardial infarction, 16 with angina pectoris and two normal subjects, were enrolled in this study. Dobutamine was infused in scalar doses of 5 to 40 micrograms/kg/min. Intravenous infusion of Albunex (0.15 ml/kg) was administered at rest and during peak dobutamine stress during monitoring of the apical four-chamber view. The left ventricle in the apical four-chamber view was divided into six segments and an endocardial delineation score of 0 to 3 (none to excellent visualization) was given to each segment. RESULTS: Endocardial delineation score was increased after Albunex infusion from 2.0 to 2.3 in the basal-septal, 2.0 to 2.4 in the mid-septal, 1.1 to 1.8 in the apical-septal, 0.7 to 1.2 in the apical-lateral, 0.9 to 1.6 in the mid-lateral, and 1.2 to 1.9 in the basal-lateral segments during peak dobutamine administration. Endocardial border resolution in the lateral wall showed greater improvement than in the septal wall after Albunex infusion. Diagnostic values in the left anterior descending artery territory failed to improve with Albunex infusion (sensitivity 82% to 89%, specificity 94% to 89%, and accuracy 86% to 89%), whereas a higher diagnostic accuracy was noted in the left circumflex artery territory with Albunex compared to without Albunex (sensitivity 63% to 81%, specificity 88% to 98%, and accuracy 80% to 93%, p < 0.05). CONCLUSIONS: Contrast agent improves the diagnostic accuracy of dobutamine stress echocardiography in the left circumflex artery territory.

Can the proximal isovelocity surface area method calculate stenotic mitral valve area in patients with associated moderate to severe aortic regurgitation? Analysis using low aliasing velocity of 10% of the peak transmitral velocity.

To assess the ability of the proximal isovelocity surface area (PISA) method to accurately measure the stenotic mitral valve area (MVA), and to assess whether aortic regurgitation (AR) affects the calculation, we compared the accuracy of the PISA method and the pressure half-time (PHT) method for determining MVA in patients with and without associated AR by using two-dimensional echocardiographic planimetry as a standard. The study population consisted of 45 patients with mitral stenosis. Seventeen of the 45 patients had associated moderate-to-severe AR. The PISA method was performed using low aliasing velocity (AV) of 10% of the peak transmitral velocity, which provided the most accurate estimation of MVA when compared with planimetry. The maximal radius r of the PISA was measured from the orifice to blue-red aliasing interface. Using the PISA method, MVA was calculated as (2pir(2)) x theta / 180 x AV/Vmax, where theta was the inflow angle formed by mitral leaflets, AV was the aliasing velocity (cm/sec), and Vmax was the peak transmitral velocity (cm/sec). MVA by the PISA method correlated well with planimetry both in patients with AR (r = 0.90, P < 0.001, SEE = 0.17 cm(2)) and without AR (r = 0.92, P < 0.001, SEE = 0.16 cm(2)). However, MVA by the PHT method did not correlate as well with planimetry (r = 0.57, P < 0.05, SEE = 0.37 cm(2)) in patients with associated AR, and the PHT method produced a significant overestimation (24%) of MVA obtained by planimetry in these patients. We conclude that the PISA method allows accurate estimation of MVA and is not influenced by AR.

Expression of 15-lipoxygenase-1 is regulated by histone acetylation in human colorectal carcinoma.

15-Lipoxygenase-1 (15-LO-1) is expressed at higher levels in human colorectal tumors compared with normal tissue. 15-LO-1 is expressed in cultured human colorectal cells, but only after treatment with sodium butyrate (NaBT), which also stimulates apoptosis and cell differentiation. We examined the regulation of 15-LO-1 in human tissue and the colorectal carcinoma cell lines Caco-2 and SW-480 by treatment with histone deacetylase (HDAC) inhibitors: NaBT, trichostatin A (TSA) and HC toxin. Northern and western analysis showed that expression of 15-LO-1 was up-regulated by these HDAC inhibitors. Furthermore, HDAC inhibitors stimulated promoter activity of the 15-LO-1 gene approximately 12-to 21-fold using the -331/-23 region of the 15-LO-1 promoter, as measured with a luciferase-15-LO-1 promoter-reporter system, suggesting that 15-LO-1 is regulated at the transcriptional level by HDAC inhibitors. Histone proteins in colorectal cells were acetylated after treatment with HDAC inhibitors. Histone acetylation was also measured in human colorectal tissue and a correlation was observed between increased histone acetylation and 15-LO-1 expression. Thus, regulation of 15-LO-1 expression in colorectal tissues appears to occur by a novel and new mechanism associated with histone acetylation. Moreover, these results suggest that 15-LO-1 is a marker that reflects histone acetylation in colorectal carcinoma.

Pancreatoblastoma. Three original cases and review of the literature.

PURPOSE: To describe the characteristics of pancreatoblastoma. MATERIAL AND METHODS: We studied 3 cases of pancretoblastoma and reviewed another 59 cases. Parameters analyzed were tumor site, hemorrhage, capsule formation, necrosis, vascularity, production of alpha-fetoprotein (AFP), cystic changes and calcification. RESULTS: The diagnostic findings were as follows: pancreatic head origin (24/54, 44%), pancreatic body and tail origin (30/54, 56%), hemorrhage (16/17, 94%), capsule formation (24/26, 92%), necrosis (28/31, 90%), hypervascularity (10/14, 71%), production of AFP (19/28, 68%), cystic changes (11/16, 69%), and calcification (10/21, 48%). All neonatal cases demonstrated cystic changes. Three of them were patients with Beckwith-Wiedmann syndrome. The incidence of capsule formation and calcification was not related to the origin of the tumor. CONCLUSION: The most common features of pancreatoblastoma are hemorrhage, capsule formation and necrosis.

[Diagnosis of myocardial viability by exercise echocardiography].

This study determined whether the diagnosis of myocardial viability could be established on the basis of the contractile reserve during low level exercise with an ergometer using echocardiography. The study involved 22 patients with transmural old myocardial infarction who underwent exercise echocardiography, followed by coronary intervention after a mean 4 days. Exercise echocardiography was started from 50 W and stepped up by 25 W every 3 min up to a maximum of 150 W. Low level exercise was administered for 1 to 2 min at 50 W. A 16-segment model was used for the left ventricular wall motion, which was evaluated by five-grade scoring, ranging from normokinesis to dyskinesis. If patients showed improvement by one point or more in the score for segments of dyskinesis, akinesis, or severe hypokinesis on the exercise echocardiography, they were considered to have positive viability. The golden standard for the diagnosis of myocardial viability was that wall motion abnormalities before exercise echocardiography should be improved by one point or more after coronary intervention. Before exercise echocardiography, there were 152 segments showing wall motion abnormalities assessed as severe hypokinesis or more. After coronary intervention, improvement of the wall motion by one grade or more was found in 2 of the 18 segments (11%) for dyskinesis, in 38 of the 96 segments (40%) for akinesis, and in 22 of the 38 segments (58%) for severe hypokinesis; improvement for the segments of severe hypokinesis was significantly better than those for dyskinesis and akinesis. Out of 19 segments with akinesis before exercise echocardiography in which wall motion was improved during low level exercise, 16 segments (84%) showed improvement in wall motion after coronary intervention. Out of 77 segments with akinesis before exercise echocardiography in which no change or worsening was seen during low level exercise, 22 segments (29%) showed improved wall motion after coronary intervention. There were 38 segments with severe hypokinesis before exercise echocardiography; out of 12 segments in which wall motion was improved during low level exercise, 7 segments (58%) showed improved wall motion after coronary intervention. Out of 26 segments with severe hypokinesis before exercise echocardiography in which no change or worsening was seen during low level exercise, 11 segments (42%) showed improved wall motion after coronary intervention. Wall motion was improved after coronary intervention in 20 of 25 segments (80%) that showed the biphasic response, in 4 of 7 segments (57%) that showed improvement, in 14 of 43 segments (33%) that showed worsening, in 24 of 77 segments (31%) for no change; the biphasic response showed a significantly higher improvement compared to worsening or no change. If segments in which wall motion was improved during low level exercise are regarded as positive viability segments, occurrences of the sensitivity, specificity and diagnostic accuracy of myocardial viability were 50%, 84%, and 71%, respectively.

Epithelioid hemangioendothelioma with marked liver deformity and secondary Budd-Chiari syndrome: pathological and radiological correlation.

A case of malignant epithelioid hemangioendothelioma of the liver in a 48-year-old woman with severe portal hypertension and marked deformity of the liver is presented. This woman had a history of mild liver dysfunction since the age of 30 years, and abdominal distention, esophageal varices, splenomegaly and ascites since October 1996. Imaging examinations revealed liver deformity with severe atrophy of the left lobe and the anterior segment of the right lobe. Celiac arteriography showed narrowing and upward deviation of the proper hepatic artery, and occlusion of the left and right anterior hepatic arteries. Since March 1997, hepatic venography showed stenosis in the right hepatic vein truncus. Budd-Chiari syndrome was clinically diagnosed. She died in June 1997. The autopsy disclosed massive tumor embolism in the left and right anterior portal branches, few in the hepatic artery, and occlusion of the left and right anterior hepatic arteries. The extensive tumor embolism resulted in portal hypertension, and atrophy of the left lobe. The anterior segment of the right lobe was probably caused by the occlusion of both the hepatic arteries and the portal veins. The posterior segment of the right lobe, without massive tumor embolism in its portal branch, appeared hypertrophic.

Metabolic suppression of platelet-type 12-lipoxygenase in human uterine cervix with invasive carcinoma.

Several types of lipoxygenases with various functions occur in mammalian cells. Although the presence of 12-lipoxygenase activity has been reported in uterine tissues, neither its type nor its biological functions have yet been established. Moreover, the putative role of uterine 12-lipoxygenase in cervical cancer has not been addressed before. Homogenates of uterine tissues from women without cancer and from patients with invasive cervical carcinoma were incubated with (1-(14)C)-arachidonic acid under various conditions and the labelled reaction products were analyzed both by thin-layer chromatography and by high-pressure liquid chromatography. 12-Lipoxygenase protein was estimated by Western blot using anti-serum against recombinant human platelet-type 12-lipoxygenase. Highest concentrations and activities of 12-lipoxygenase were found in the exocervix. The formation of 12S-hydroxy-5Z,8Z,10E, 14Z-eicosatetraenoic acid (12-HETE) was stimulated by micromolar concentrations of 13S-hydroperoxy-9Z,11E-octadecadienoic acid, suggesting metabolic control of the 12-lipoxygenase activity via the hydroperoxide tone. Immunohistochemical investigation revealed that the enzyme is mainly located in the squamous epithelium, and is of platelet-type. Significantly lower values for the 12-HETE formation were found in samples from patients with invasive cervical carcinoma, whereas the amount of immunochemically detectable 12-lipoxygenase protein was unaltered. At the same time the expression levels of the bcl-2 gene were enhanced. Thus, it is concluded that during carcinogenesis the hydroperoxide-reducing capacity of the uterine cervix tissue is enhanced, possibly mediated by bcl-2 protein, and in turn metabolically suppresses the 12-lipoxygenase activity. Furthermore, the data suggest an anti-carcinogenic action of 12-lipoxygenase in human cervix, in contrast to its reported pro-carcinogenic action in breast cancer.

Regulation of 12-lipoxygenase in rat intestinal epithelial cells during differentiation and apoptosis induced by sodium butyrate.

We evaluated the expression and activity of rat 12-lipoxygenase (LO) in rat intestinal epithelial (RIE) cells during apoptosis and cell differentiation. Sodium butyrate (NaBT) treatment induced wild-type RIE (W-RIE) cells to undergo differentiation and apoptosis. Alkaline phosphatase (ALP) activity, a marker of cell differentiation, and DNA fragmentation, an index of apoptosis, were increased by NaBT treatment. Arachidonic acid was metabolized primarily to 12-hydroxyeicosatetraenoic acid (HETE) suggesting induction of 12-LO activity. In contrast, sense-RIE (S-RIE) cells engineered to overexpress COX-2 were resistant to apoptosis by treatment with 5 mM NaBT and NaBT did not induce 12-LO activity. The upregulation of 12-LO expression by NaBT in W-RIE cells was confirmed at both the transcriptional and translational level but 12-LO was undetectable in S-RIE cells following NaBT treatment. The expression of 12-LO mRNA in W-RIE cells occurs as early as 6 h after treatment and reaches maximum expression at 24 h following treatment. This inducible 12-LO was isolated by RT-PCR and identified as rat "leukocyte-type" 12-LO. The level of 12-LO expression in W-RIE cells was dependent on the concentration of NaBT and appears to reflect the extent of cell differentiation. NDGA, a lipoxygenase inhibitor, attenuated induction of ALP activity by NaBT treatment of W-RIE cells. These observations suggested that 12-LO is regulated by treatment with NaBT and is associated with cell differentiation in rat intestinal epithelial cells.

Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma.

BACKGROUND: Interleukin-10 (IL-10) has been implicated as an important modulator of lymphoid cells, and its sequence is homologous to an open reading frame in the Epstein-Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a representative tumor related to EBV infection. METHODS: The authors investigated the expression of IL-10 in 21 primary NPCs by using an immunohistochemical approach to examine its prognostic significance. RESULTS: IL-10 staining was positive in 12 of 21 primary NPCs (57%). There was no association between IL-10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between the negative expression and positive expression of IL-10 (P = 0.0348). Although 87.5% of the IL-10 negative group survived for 5 years, only 15.6% of IL-10 positive patients survived for that length of time by the Kaplan-Meier method. IL-10 expression was significant as an independent prognostic indicator of overall survival by multivariate analysis using the Cox proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS: The results imply that expression of IL-10 is a prognostic factor in patients with NPC and may prove valuable in selecting patients with NPC who are candidates for aggressive therapy.